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leukemia breast cancer cell lines growth inhibitory effects reversed leukemia cell lines first show evidence thiaminase therapeutic potential demonstrating activity breast leukemia xenografts primary leukemia xenograft therefore explored metabolic effects thiaminase combination leukemia breast cell lines decreased oxygen consumption rate increased extracellular rate consistent inhibitory effect acute depletion activity pyruvate dehydrogenase dehydrogenase complexes effects reversed studies demonstrated intracellular depletion presence cleavage product thiaminase treated cells providing validation experimental procedures cell lines support thiaminase mediated suppression Interestingly thiaminase suppression another chain amino dehydrogenase showed different patterns two cell lines RS leukemia cells led increase substrates MCF breast cancer cells led decrease products analyses showed corresponding differences expression pathway enzymes partial protection thiaminase growth inhibition indicated inhibition may mechanism thiaminase mediated toxicity thiaminase mediated effects also reversed Thus studies demonstrate acute intracellular depletion recombinant thiaminase results metabolic changes dependent metabolism demonstrate previously role mTOR signaling regulation dependent metabolism current external funding sources study Introduction vitamin B enzymes involved critical metabolic processes involving energy production generation amino acid Despite requirement vitamin central processes role dependent enzymes cancer development treatment received little attention although recent review summarized potential importance cancer metabolism well established role cancer therapy small molecule relatively leading pathways could important anticancer targets However limitations small molecule inhibitors potential role anticancer therapeutic targets effective intracellular enzymes catalytic process allowing inhibition enzyme activity molecules designed bind intracellular substrates contrast intracellular activated phosphorylation remains bound enzyme complexes catalytic cycle little inhibitors complex challenge could potential targeting cancer therapy previously shown regulation transporter gene expression tumors compared normal tissues recently shown low diet onset mammary tumors mice effect high fat diet observations led hypothesis pathways altered part overall changes energy metabolism occurs cancer cells changes could produce metabolic could therapies aimed activities take novel exploration cancer studied cytotoxic activity bacterial enzyme thiaminase limitations small molecule |
instrument variability overall process variability Following normalization total protein assay log transformation minimum observed values compound two sample tests used identify differed significantly experimental groups entire data sets RS MCF cells statistical results included data tables Table analysis Cells treated thiaminase U ml hours Cells lysed triple lysis buffer mM pH mM NP sodium g ml protease inhibitors Roche phosphatase inhibitors Thermo Scientific amounts protein well separated gel followed transfer onto membranes membranes blocked incubated indicated primary antibodies C overnight appropriate secondary antibody added hour room temperature developed use West substrate Thermo Scientific according manufacturers protocol analyzed image software primary secondary antibodies used study listed follows PKM anti anti anti antibodies purchased Group Inc IL PKM anti antibodies Cell Signaling Technology anti antibodies obtained laboratories anti actin secondary antibodies obtained Sigma St Results antitumor activity thiaminase leukemia breast cancer tumor models shown Figure Figure Kaplan plot MCF subcutaneous xenografts treated thiaminase showing time endpoint pre defined tumor volume days treated cohort days treated cohort p Figure B RS subcutaneous xenografts show increase median days start treatment days p also previously shown evidence thiaminase activity breast cancer Figure C activity thiaminase shown primary human leukemia cells sensitive primary leukemia specimens appear specimens gene interest RS cell line also cell line Figure shows flow analysis bone marrow primary leukemia cell xenograft treated thiaminase demonstrating decrease leukemia cell proportion treatment studies along previous studies provided performing detailed examination metabolic effects thiaminase breast cancer cell line MCF RS leukemia cell line addition points comparison included selected studies two additional cell lines leukemia cells another leukemia cell line MCF non malignant breast cell line journal pone g Figure vivo evidence thiaminase anticancer activity Kaplan plot time pre defined tumor volume endpoint subcutaneous MCF breast cancer xenografts treated thiaminase units SC buffer control median time endpoint |
chain amino acid enzymes reactions produce substrates total phosphorylated subunit E E E respectively RS leukemia cells treated thiaminase C vs C vs R comparisons indicates p indicates p assay RS MCF cells treated increasing concentrations thiaminase control conditions medium contains also affected amino acids RS leukemia cells shown Figure products tyrosine lactate increased thiaminase treated cells Furthermore shown Figure B increased one pathway produces pathway approach took alteration chain amino acids examined possibility accumulation amino acid mediated growth inhibitory effects thiaminase drug inhibits enzyme alternative pathway would expected increase accumulation amino acid however alter dose response curves thiaminase either cell line data shown g Figure Effects thiaminase amino acid products tyrosine RS cells treatment thiaminase hours B thiaminase treatment showing accumulation C vs C vs R comparisons indicates p indicates p Discussion systematic difference cancer cells normal cells provides potentially therapeutic altered energy metabolism cancer cells known effect represents vitamin key two critical enzymes energy metabolism also two critical enzymes required formation cell phosphate regulates chain amino acids requires active transport cellular uptake previously shown regulation transporters human tumors suggesting tumors may nutritional could clinically regulation synthase acute leukemia bacterial enzyme enzyme thiaminase cleavage two molecules one conjugated type may phosphorylated depending substrate reaction Several forms thiaminase exist nature including plant animal bacterial forms enzyme thus example evolution even though role enzyme essential nutrient clear developed methods produce thiaminase enzyme shown preclinical xenograft models therapy directed dependent enzymes completely novel concept strategy potential treat leukemia breast cancer despite anti metabolite role thiaminase cause tumor responses dose determine responsible cytotoxic effects thiaminase examined effect enzyme cellular metabolism goal identifying critical responsible cytotoxicity setting acute Since thiaminase bacterial enzyme less ideal product identification specific pathway leads cytotoxicity could reveal alternative approach changes global biochemical profiles RS leukemia cells MCF breast cancer |
results suggest critical role P breast cancer progression identify P potential therapeutic target biomarker breast cancer progression Tumor microenvironment Breast cancer deposition Cancer progression Cell proliferation Background matrix important component tumor microenvironment plays critical roles cancer development major structural proteins form networks tumor tissue Cell collagen interaction controls variety cellular activities including proliferation migration invasion integrin domain receptor expression deposition associated tumor development progression Recent studies demonstrate increased collagen deposition enhance density mammary tissue important risk factor breast cancer development Type collagen identified prognosis marker associated cancer recurrence human breast cancer patients knockout mice reduced primary tumor formation growth enhancing collagen deposition inhibiting collagen degradation significantly enhances tumor initiation tumor growth addition cancer cell invasion usually occurs tumor stromal collagen collagen facilitate cell migration metastasis results indicate increased collagen expression deposition promotes breast cancer development progression enhancing tumor growth invasion Therefore inhibiting collagen synthesis deposition promising strategy suppress breast cancer progression biosynthesis process involves several post transcription modification enzymes one important members enzymes collagen formation residues X sequences within endoplasmic reticulum ER expression used marker collagen synthesis residues formed reaction essential triple formation collagen inhibiting activity blocks collagen synthesis deposition known collagen consisting two subunits two subunits subunit contains peptide substrate binding domain two catalytic sites enzyme subunits identified protein Three types collagen isoforms P P P identified human tissue P expressed cell types P mainly expressed endothelial cells P expression detected adult fetal tissues low levels compared P P Increased P expression detected many solid tumors including oral cavity squamous cell carcinoma papillary thyroid cancer breast cancer however function P cancer progression largely remains determined showed expression P collagen genes significantly correlated breast cancer development progression increased mRNA levels P associated poor prognosis breast cancer patients P treatment P inhibitor cell proliferation suppresses aggressive phenotypes tumor growth cancer metastasis |
established risk factor susceptibility lung cancer However people lung cancer smokers Lung cancer non smokers induced second hand smoke air present data showed significant difference year smoking status NSCLC cases controls suggested important role environmental factors development NSCLC could induce chronic inflammation lung microenvironment contributing pulmonary carcinogenesis smokers also data regarding inflammation lung cancer CR important molecule implicated immunity inflammation could protect host invasion exogenous derived cigarette smoking Genetic variant CR could alter gene function result inflammatory immune responses thereby modulating susceptibility lung cancer importantly observed potential interaction SNP rs G C smoking status suggesting gene environmental interaction plays prominent role susceptibility lung cancer present study limitation patients may representative total NSCLC patients large recruited one hospital addition due relatively small sample size case control studies still needed findings Conclusion conducted case control study Chinese subjects found SNP rs G C CR significantly associated lung cancer risk best knowledge study provides first evidence genetic variant CR rs G C smoking development lung cancer Methods Study subjects case control study consisted patients confirmed NSCLC cancer free controls subjects genetic Han Chinese Patients recruited January December Hospital China age gender stage however patients previous malignancy cancer ans excluded response rate patients controls randomly selected cancer free population nutritional survey conducted region selection criteria control subjects included individual history cancer ii frequency matched cases according gender age years iii region iv time period blood sample collection recruitment informed consent obtained subject participant collect detailed information demographic characteristics study approved institutional review board United University SNPs selection genotyping Based Chinese population data database used program select candidate SNPs r threshold minor allele frequency MAF greater Furthermore also added two potential functional polymorphisms rs rs Therefore included SNPs study represents common genetic variants Chinese population performed Beijing China using San CA USA used design PCR |
year disease free survival rate significant statistical differences year disease free survival rate p open thoracotomy Conclusions VATS approach safe feasible treatment terms survival rate metastatic lung cancer compared thoracotomy year disease free survival rate VATS group inferior open thoracotomy VATS approach could completely open thoracotomy authors support funding report Introduction considered beneficial treatment patient metastatic lung cancer whose primary tumor well controlled surgery year survival rates could achieved depending underlying primary cancer practice surgical approaches pulmonary metastases variable assisted thoracoscopic surgery VATS emerging technique many procedures previously required thoracotomy performed minimally invasive VATS VATS used treatment pulmonary metastases routine use VATS treatment metastatic lung cancer remains controversial VATS approach might equivalent oncological operation prospective study found nodules could detected thoracotomy missing VATS VATS approach provide outcome unknown based investigation VATS approach needed meta analysis achieve objective assessment published studies provide accurate comparison VATS thoracotomy metastatic lung cancer Methods PubMed databases performed July following search used metastatic lung cancer pulmonary metastases video assisted thoracic surgery thoracotomy comparative study searched reference relevant studies reviews meeting used Science Index cross reference studies met criteria Study studies included meta analysis based criteria follows clinical trials include full text paper published peer reviewed reports major thoracic surgery comparison efficacy VATS thoracotomy patients metastatic lung cancer similarity patients baseline characteristics Data extraction quality assessment Two independent assessed quality risk bias included trials follows studies include comparative group surgery form intervention excluded trials patients undergoing surgery primary lung cancer excluded studies video assisted thoracic surgery excluded overlap authors centers patient cohorts evaluated published literature recent report included studies published years excluded significant changes occurred evaluated quality assessment method two investigators resolved discussion consensus investigator final results reviewed two investigators Lin Jiang disease free survival defined date initial date recurrence Statistical sensitivity analyses meta analysis performed using |
b c V f b C b C b Chen L e f H MD g J MD h J MD R MD j MD g B MD k F MD l B MD b Medical Center Surgery Department Medicine University Medical Center Medicine Public Health University Medical Center Epidemiology University Medical Center Sciences University Medical Center Statistics Clinic Surgery University NC Surgery University Surgery General Hospital PA Surgery University Surgery University CA Surgery University St P H Department Surgery st South edu shared co first author Society Published Inc Background emission tomography FDG PET recommended diagnosis staging NSCLC analyses FDG PET diagnostic accuracy demonstrated sensitivity specificity respectively performed select centers potential bias study accuracy FDG PET NSCLC differences across sites national Z trial Methods eligible patients clinical stage N known suspected NSCLC enrolled Z trial baseline FDG PET diagnosis determined pathological examination FDG PET categorized four levels based description reported maximum standard uptake value FDG PET diagnostic accuracy calculated entire cohort differences based preoperative size site examined Results FDG PET results available participants enrolled sites Lung cancer prevalence FDG PET sensitivity CI specificity CI Positive negative predictive values respectively improved lesion size false positive scans negative scans occurred patients adenocarcinoma frequent mm sensitivity varied p specificity ranged p across participants Conclusions national surgical population clinical stage NSCLC FDG PET lung cancer performed poorly compared published studies Biol Biol Biology Netherlands x Research diagnostic prognostic value serum human related non small cell lung cancer Xu Zhang Yu Yu Li com Department Respiratory Medicine Chest Hospital Road China Clinical Center Respiratory Diseases China Access article distributed terms Creative Commons Attribution License permits use distribution reproduction medium provided original author source aim study explore diagnostic prognostic value serum human related KLK level non small cell lung cancer NSCLC Serum specimens patients w |
appropriate skin entry site successful placement needle location location basal portion around line needle tip mm depth avoid pulmonary vessels placed needle cm length lung parenchyma appropriate skin entry site parameters CT used study tube tube current thickness mm thickness speed connected mL needle hub confirm blood needle tip accurately located within location injected materials immediately removed needle CT scan measured distance skin entry needle tip depth needle tip post CT scan identified procedure related complications included leakage materials addition recorded extent shape density radio opacity MLM injection extent MLM defined maximum diameter radio shape radio opacity categorized groups small nodular nodular nodular recorded injection time measure time interval injection examinations successful localization lipiodol determined examination subsequently evaluated radio opacity MLM using X unit Medical Systems Netherlands post procedure session follow session hr Group hr Group B parameters tube tube current obtained images rabbit cm field view radio cm located near rabbit order estimate exact size lipiodol opacity recorded time examinations findings MLM size shape radio opacity Evaluation staining radio opacity assessed directly visible staining excised lung surface radio opacity MLM examinations using point scoring order compare localization ability MLM methylene blue percutaneous injection material injection materials assessed staining ability order evaluate staining ability reader reviewed images excised lung specimens obtained formalin staining point scores non visualization staining extensive dispersion made difficult find accurate locations acceptable available estimate locations dispersion excellent localized staining Fig maximum diameter staining extent lung surface measured calculated compared scores extent staining two materials findings radio opacity MLM evaluated using point scoring detectable radio opacity minimally increased opacity acceptable low density increased opacity excellent nodular increased opacity Fig compared average scores initial follow examinations considered score score appropriate localization staining radio opacity compared number appropriate excellent localization MLM methylene blue histopathologic examinations excised entire lungs used |
CT guided percutaneous injection material study supported grant Seoul National University College Medicine Research potential interest commercial involvement G H preoperative computed tomography guided localization video assisted thoracoscopic surgery pulmonary metastatic pulmonary nodules Ann Thorac Surg Chen Zhou J Zhang J Hu H X Zhang Chen H assisted thoracoscopic solitary pulmonary nodule resection CT guided localization cases report literature review Surg P G R P assisted thoracoscopic surgery pulmonary nodules preoperative computed tomography guided localization Eur J Surg K K J H K assisted thoracoscopic surgery small pulmonary nodules indications preoperative Chest JM Lee Kim Kim J Lee determining successful computed tomography guided localization lung nodules J Thorac Surg J technique localization pulmonary nodules thoracoscopic resection Chest E P assisted thoracoscopic resection small pulmonary nodule computed tomography guided localization system experience consecutive patients World J Surg Chen W Chen L Yang Chen Z G Zhang J novel technique localization small pulmonary nodules Chest pulmonary nodules using video assisted thoracic surgery Group Ann Thorac Surg AE Chen CS Smith localization technique thoracoscopic resection lung lesions children J Surg K H K small pulmonary nodules thoracoscopic resection injection lipiodol CT guidance Acad H R H thoracoscopic resection pulmonary nodule child J Med Imaging Oncol K K H guided small pulmonary lesions video assisted thoracic surgery Med J K K tomography guided injection pulmonary nodule thoracoscopic resection J Thorac Surg H H collagen long point marker small pulmonary nodules thoracoscopic Ann Thorac Surg PI GP blue stained blood needle localization thoracoscopic resection deep pulmonary nodules J Surg Hu J Zhang C Sun L small pulmonary nodules surgery J Surg B P CT guided pulmonary nodules methylene blue injections thoracoscopic Chest CT guided methylene blue thoracoscopic resection pulmonary nodules Eur J Surg CD W pulmonary nodules thoracoscopic surgery value percutaneous staining methylene blue J |
important environmental genetic factors lung adenocarcinoma cooking oil smoke passive smoking exposures implicated possible risk factors among Chinese women mainly based Chinese people traditional diet lifestyle social environment designed study evaluate association genetic variant environmental risk factors lung adenocarcinoma female non smokers date association ATM rs host susceptibility lung adenocarcinoma Chinese female non smokers well addressed ATM rs common polymorphism promoter ATM gene Studies shown site possibly may regulate ATM protein activity due regulation function promoter shown genes specific genotypes ATM may play important role carcinogenesis expression regulation alternative splicing ATM gene searched National Center Biotechnology Information database get allele frequency polymorphism data indicated frequency wild type allele G frequency variant allele Chinese Han population study results accordance data Kim et al evaluated role ATM rs lung cancer development Korean population first time significant association found polymorphism lung cancer risk P recruited lung cancer patients male cigarette smokers cigarette smoking might modulate risk lung cancer turn could association ATM rs lung cancer risk Besides gene environment interactions considered research et al suggested ATM rs associated lung cancer risk among never smokers AA vs GG CI association might modified passive smoking Although effect cigarette smoking study non smokers risk lung cancer among different histological types still needed Recently et al attention association ATM rs lung cancer susceptibility among smokers genotype frequency difference found lung cancer cases controls among smokers P studies combining current situation Chinese non smoking female lung adenocarcinoma incidence rate increasingly performed case control study elucidate association ATM rs lung adenocarcinoma risk best knowledge first study investigated whether ATM rs associated lung adenocarcinoma risk non smoking Han Chinese females results shown individuals exposure cooking oil fold increased risk developing lung adenocarcinoma P Similar significant associations observed previous studies Chinese non smoking females Experimental studies presented cooking could potential components |
emerging differences epidemiology biology therapy Chest lung cancer risk men women examination evidence J Natl Cancer Study risk factors lung cancer non smoking women et al Chinese food cooking lung cancer women J et al functional single nucleotide polymorphism promoter ATM associated Identification cooking oil Res study cooking oil Sci Identification N human lung adenocarcinoma cells exposed cooking oil conditions Chem Res et al cooking lung cancer risk Chinese women Cancer et al Lung cancer among Chinese women International Journal Cancer Wu et al Lung cancer among women China Br J Cancer Lung cancer air pollution Chinese cooking among women living Shanghai China Epidemiology PLoS One PLoS ONE PLoS ONE Public Science San USA Research Biology Genetics Genetic mutation Mutation types Cancer genetics Medicine Clinical research design studies Diagnostic medicine Pathology Clinical pathology evaluation Oncology Cancer detection diagnosis Cancer screening Cancer treatment drug treatment Clinical trials cancer treatment neoplasms Lung tumors Non small cell lung cancer Oncology agents Clinical Validation PCR Assay Detection EGFR Cell Lung Cancer EURTAC EGFR Mutation NSCLC EURTAC de n Chen Zhang F Wu Lin H Spain Medical Oncology Hospital Spain F Roche South San California United States America Roche Molecular Systems California United States America Pathology Department University Hospital de Spain Roche Molecular Systems California United States America Medical Center United States America E com Competing MS DC current Roche DC Roche former Roche Roche served Roche CM current former current Medical Oncology Hospital alter authors adherence PLOS ONE sharing data materials designed experiments experiments CM data DC CM reagents materials analysis tools CM MS DC paper CM MS DC e et al open access article distributed terms Creative Commons Attribution License permits unrestricted use distribution reproduction medium provided original author source EURTAC trial demonstrated tyrosine kinase inhibitor TKI erlotinib superior chemotherapy first line therapy |
test p value PFS OS results EGFR PCR test positive patients differ significantly obtained patients enrolled EURTAC trial suggests EGFR PCR test positive patients representative EURTAC enrolled patients cases EGFR PCR test result mutation detected LDT two cases resolved LDT MPP three cases resolved EGFR PCR test one sample Sanger MPP agreement EGFR PCR test Sanger MPP Table patients treated erlotinib one patient achieved greater equal median PFS based LDT EGFR PCR test Comparison EGFR PCR test LDT results Among specimens valid results EGFR PCR test LDT OPA CI CI CI respectively Table Thus high concordance original LDT EGFR PCR test results Among specimens discordant results EGFR PCR test result confirmed MPP cases Table Table analysis EGFR PCR test LDT LDT Total N Mutation detected Mutation detected EGFR PCR test Mutation detected Mutation detected Total samples LDT results samples EGFR PCR test results excluded Positive percent agreement CI Negative percent agreement CI Overall percent agreement CI Comparison EGFR PCR test results Sanger specimens tested using EGFR PCR test Sanger sequencing gave valid results methods methods five EGFR PCR test Sanger sequencing OPA EGFR PCR test compared Sanger sequencing CI CI CI Table respectively Among discordant results EGFR PCR test Sanger sequencing MPP EGFR PCR test result cases Table Sanger sequencing detected one L R detected MPP failed detect exon deletions L R mutations confirmed MPP Four MPP results remaining four results Sanger range percent mutant alleles cases Sanger several specimens n estimated limit detection Sanger Table analysis EGFR PCR test Sanger sequencing Sanger sequencing Total N Mutation detected Mutation detected EGFR PCR test Mutation detected Mutation detected Total samples EGFR PCR test Sanger sequencing results excluded Positive percent agreement CI Negative percent agreement CI Overall percent agreement CI Discussion study supports feasibility performing retrospective clinical validation companion diagnostic prospective therapeutic |
Medicine University California San CA USA Department Health Sciences University USA Department Health Sciences University California CA USA Division Public Health Sciences Cancer Research Center USA School Public Health University BC V Z Department Health University DC USA Hospital Cancer Center Shanghai China E edu Copyright Cancer Research UK Cancer Research UK months original publication work licensed Creative Commons Attribution License view copy license visit Background widespread many environmental settings Since generally consistent evidence indicating reduced risks lung cancer associated exposure Methods updated study within cohort female workers Shanghai China compared exposure incident lung cancers cases diagnosed reference workers free lung cancer end follow applied Cox proportional hazards estimate trends adjusted age smoking cumulative exposures years separately time years since first exposure Results observed associations cumulative exposure lung cancer lag interval contrast analyses exposure time revealed elevated statistically significant relative risks highest three exposure exposures occurred years since first exposure Conclusions findings support protective effect possible lung cancer promotion increasing time since first exposure lung cancer epidemiology health Br J Cancer Br J Cancer Journal Cancer Nature Group Clinical Study multicentre randomised controlled trial lung cancer peer review supported quality improvement results improving lung cancer outcomes project lung cancer outcomes project results G K L R Clinical Department College London UK Clinical Unit NHS Information Centre Health Care AE UK Department Respiratory Medicine Hospital UK Department Respiratory Medicine Hospital B UK E uk Copyright Cancer Research UK Cancer Research UK months original publication work licensed Creative Commons Attribution License view copy license visit Background Results National Lung Cancer demonstrate variation outcomes review supported quality improvement shown reduce variation areas health care tested cancer multidisciplinary teams aim current study assess impact peer peer review visits supported quality improvement working lung cancer process outcome measures Methods lung cancer teams randomised care facilitate |
R G J J C intervention decrease related infections ICU N Engl J Med CM RA RJ NA JM randomized trial peer review UK National Chronic Pulmonary Disease Outcomes Project three year evaluation J Clin C MD J N L E K G ML J J E B Group Lung cancer survival stage diagnosis UK population based study J Health atlas shows large variations care England BMJ c c Study Figure diagram eligible trusts including screening follow Figure chart showing waiting times multidisciplinary team meeting first treatment consecutive small cell lung cancer patients following implementation quality improvement plan one intervention group Figure Mean change national lung cancer baseline P active vs controls n trusts control n trusts non intervention control non participants combined n trusts clinical nurse multidisciplinary team SCLC small cell lung cancer Figure Total patient questionnaire scores multidisciplinary team intervention group baseline pre end study post low score indicates better experience represents mean score intervention group maximum possible score questionnaire Table Quality improvement plan Quality improvement plan Number plans team effectiveness Diagnostic pathways Treatment pathways Access clinical nurse Clinical trial recruitment Patient experience Table Baseline national lung cancer indicators Control n n n P value Mean e Mean e Mean e Control vs intervention vs non participant control vs intervention Case meeting rate treatment Surgery cases SCLC present diagnosis clinical nurse team SCLC small cell lung cancer Data shown mean e proportion patients BMC Cancer BMC Cancer BMC Cancer Central Study Study protocol randomized controlled trial comparing Mindfulness Based treatment reducing psychological distress patients lung cancer partners study van GM B H van der Department University Medical Centre Netherlands Department Pulmonary Diseases University Medical Centre Netherlands Department Medical University Medical Centre Netherlands Department Epidemiology Health Technology Assessment University Medical Centre Netherlands Copyright et al Central Ltd et al |
physical role cognitive social three symptom fatigue pain nausea vomiting global health quality life scale array single item symptom measures role functioning global health physical functioning scale internal consistency varied except cognitive functioning scale varying reliability varied lung cancer questionnaire module designed supplement core questionnaire specific symptoms associated lung cancer pain side effects conventional radiotherapy loss item scale showed high internal consistency pain combined pain items core questionnaire pain showed high internal consistency Since C LC mainly focused physical symptoms added items consistency test reliability correlated self assessed dysfunction partners use item Care assess extent caregiving experienced also measure positive aspects caregiving item Care Assessment SE included consistency SE SE quality measure relationship included item Model Scale items measure enhance global items utilized form construct consistency varied related Scale Also scale included measure communication partners cancer contains items divided two open communication negative cancer measured consists items divided others nature activities internal consistency varied test reliability varied except nature related Functional Assessment Chronic Therapy Scale patients cost effectiveness evaluation carried perspective considering direct well indirect health costs Data costs collected using participants health care type care duration b cancer related absence work Unit cost estimates derived national manual cost health care reduced ability work estimated using costs method results estimate human approach Treatment costs MBSR calculated using activity based methods thus measuring actual resources time time patients used unit cost adjusted Unit cost estimates combined resource data obtain net cost per patient entire follow period measures Mindfulness examined item Mindfulness based factor analysis five measures allowed items different form factors providing integration independent led following five acting non experience non experience consistency varied among different related experience psychological symptoms including sensitive change based interventions found mediate relationship practice improvements psychological symptoms e g assessed Scale items divided six self v |
end stage disease J b e f PR symptoms lung cancer patients Health Kim PR MR symptoms people lung cancer effects social support caregiving burden N family caregivers lung cancer patients examination practical challenges Care Cancer health mental health life changes among family caregivers patients lung cancer Oncol U C P health significant others patients lung cancer C U JP Development quality relationship significant lung cancer patient perceived significant Eur J Oncol j LA symptoms lung cancer patients family caregivers influence family environment H processes psychological distress among head neck lung cancers H Effects relationship maintenance psychological distress adjustment among lung cancer Health G reactions lung cancer common often followed poor outcome Eur J J CH P G Treatment depression people lung cancer systematic review Lung Cancer j K J G C Phase II study outpatient palliative care intervention patients metastatic cancer J Clin Oncol MS P JH Quality life palliative cancer care results cluster randomized trial J Clin Oncol K R R CL system supporting palliative care patients nonsmall cell lung cancer Cancer JA RS ER Effect early palliative care chemotherapy use end life care patients metastatic non small cell lung cancer J Clin Oncol J living using body face stress pain illness New York JD Mindfulness Based Therapy depression new approach preventing relapse New York Press J H R effect Mindfulness Based Therapy anxiety depression adult cancer patients systematic review meta analysis J Clin K benefits cancer patients partners participating Mindfulness Based MBSR R J JC cancer meta analysis critical review role gender effects SE PR mental state practical method cognitive state J Res AB L E JC screening distress men prostate carcinoma Cancer CO X SM referral distress practice Cancer E death New York MBSR pathway complete RS W RP L based development assessment Mindfulness RP H |
following treatment scFvMTBHsp control proteins normal saline mouse model papillary ovarian cancer immune FVB NJ mice scFvMTBHsp prolonged free survival time compared saline n per group representative two independent experiments median survival Med days vs days mixture MTBHsp plus P scFv Med days scFvMTBHsp also prolonged overall survival time mice compared saline Med days vs days mixture MTBHsp plus P scFv Med days B mouse model mesothelioma immune C BL mice fusion protein prolonged free survival time compared saline treated mice n per group pooled two independent experiments Med days vs days mixture MTBHsp plus P scFv Med days fusion protein also prolonged overall survival time compared saline Med days vs days P values determined using log rank test p p p scFvMTBHsp enhances anti tumor CD cell responses ovarian tumor bearing mice investigate whether anti tumor effects scFvMTBHsp associated anti tumor effector CD cell responses stimulated ovarian tumor bearing FVB mice received different treatments CD cell MSLN negative control ex vivo analyzed cells production IFN B using flow cytometry previously showed expressed BR FVB cells designed H restricted MSLN peptide induce ovarian cancer specific cell response H q FVB mice demonstrated significantly greater anti CD cell responses scFvMTBHsp treated mice compared mice treated saline simple mixture MTBHsp plus P scFv measured IFN B production CD cells Figure B indicates scFvMTBHsp enhances anti tumor specific CD cell responses ovarian tumor bearing mice However significant difference seen number tumor infiltrating CD cells tumor infiltrating cells seen tumors mice different treatment groups indicating scFvMTBHsp may improve effector cell function rather number intratumoral CD cells Additional file Figure B Figure tumor specific CD cell functions tumor bearing mice following different treatments harvested mice treated scFvMTBHsp fusion protein mixture MTBHsp plus P scFv saline n per group stimulated peptide MSLN peptide Results reported difference |
cross presentation studies harvested animal injections obtained FVB mice via vein lysis using buffer R systems Small peritoneal membrane taken mice enzyme free cell buffer obtain mouse peritoneal cells test whether scFvMTBHsp MTBHsp binds MSLN expressing tumor cells non cancerous cells incubated BR FVB ovarian tumor cells L mesothelioma cells normal cells FVB mice including peritoneal cells g ml scFvMTBHsp g ml MTBHsp followed anti MTBHsp IgG International anti IgG BD APC analyzed tumor cells flow cytometry controls cells incubated reagents described except scFvMTBHsp MTBHsp confirm scFv portion fusion protein binds MSLN surface tumor cells scFvMTBHsp MTBHsp g ml recombinant human MSLN R Systems min adding cells fluorescence microscopy cells cultured stained g ml scFvMTBHsp g ml MTBHsp followed mouse anti MTBHsp dilution anti mouse Invitrogen dilution Cells observed using fluorescence microscope experiments tumor cells treated g ml C concentration ml h C water washed complete medium least times use Animal models tumor treatment cancer established p injection cancer cells BR FVB cells per mouse week old female FVB NJ mice previously described mice purchased laboratories established p injection L cells per mouse week old male C BL mice previously described ovarian tumors treated days BR FVB tumor cell p injections scFvMTBHsp g per mouse normal saline mixture MTBHsp plus P scFv followed treatments day intervals mesothelioma model C BL mice treated days L tumor cell injected p scFvMTBHsp g per mouse normal saline mixture MTBHsp plus P scFv Three subsequent doses administered day intervals thereafter survival studies observed mice daily weeks BR FVB cells week L cells Tumor consistently first evident via abdominal secondary malignant tumor bearing mice endpoint signs distress including rapid respiratory rate reduced activity progressive formation previously described investigation anti tumor cell responses ovarian tumor bearing mice sacrificed days final treatment studies performed manner blinded pro |
Huang Q K RA vivo cytotoxic lymphocyte heat shock protein fusion proteins maps domain CD cell independent Journal experimental medicine LA JM MM CS BR CA adjuvant effects heat shock protein result rapid prolonged activation antigen specific CD cells vivo J Cancer immunotherapy dendritic cells j F N CD cell dendritic cell vaccines requires antigen transfer endogenous antigen presenting cells one e journal pone K H G J J dendritic cell subsets improve cancer vaccines Current immunology j L H B R vivo targeting antigens dendritic cells via receptor improves cell vaccination Journal experimental medicine Wang B N Zhang L JM non mutated tumor antigen mature dendritic cells induces integrated immune response breast cancer mice Breast cancer research R Wang B JM human cancer antigen presented mouse immune system targeted CD receptor dendritic cells Ann N Acad Sci j x P E JL Cell responses glioma cells anti receptor antibody targeted activating gamma human dendritic cells Journal b e b e Wang CG LA Th cytokines C C chemokines maturation dendritic cells adjuvant function peptide binding fragment heat shock protein J mouse model molecular characterization brca associated ovarian carcinoma Cancer research Wu Z AB host cell recruitment diffuse malignant peritoneal mesothelioma Cancer microenvironment journal International Cancer Society R strategy CD cell FVB N rat mouse model breast cancer Cancer research Huang J E J JD MR F P Huang P doses treatment immunosuppressive tumor microenvironment enhance immunotherapy Natl Acad Sci USA RC K JJ dendritic cells whole tumor lysates mediate potent antitumor immune responses vitro vivo Natl Acad Sci USA B AR N Li Z PS Hsp promotes antigen presenting cell function cell tolerance vivo Nature medicine nm L Chang H antigen presenting cells antigen Science science CD C H RA L dendritic cells use receptors capture present antigens N |
resistant NSCLC tumor models AZD BEZ lung tumor tissues assessed evaluating Ki expression using immunohistochemical analyses observed active cell proliferation NCI H tumor model proliferation index Figure AZD BEZ slightly decreased percentage Ki positive tumor tissues proliferation respectively Figure treatment AZD BEZ markedly decreased percentage Ki positive tumor tissues consistent marked inhibition ERK AKT phosphorylation also found similar results NCI H NCI H tumor models Figure evaluate potential mechanism AZD BEZ gefitinib resistant NSCLC tumor tissues analyzed CD platelet endothelial cell adhesion molecule results showed BEZ significantly decreased vascular density three gefitinib resistant NSCLC tumors whereas AZD monotherapy effect upon lung tumor angiogenesis effects AZD BEZ markedly increased combined Figure B Figure Effects AZD BEZ expressions Ki CD B NCI NCI NCI H xenograft models three gefitinib resistant tumor xenograft models treated AZD BEZ h Day efficacy study tumor tissues group resected anti Ki anti CD antibodies N P vs vehicle group P vs vehicle group MEK PIK mTOR inhibitors effect caspase activities gefitinib resistant NSCLC tumor models order investigate whether AZD BEZ would induce apoptosis gefitinib resistant NSCLC tumor models activity caspase measured assay results showed AZD BEZ effect caspase activities three gefitinib resistant NSCLC tumor models Figure Figure Effects AZD BEZ activities caspase NCI NCI NCI H xenograft models three gefitinib resistant tumor xenograft models treated AZD BEZ h Day efficacy study tumor tissues group resected measured caspase protease kits N Discussion Although advances made cancer treatment development selective molecular targeted therapies several relevant issues optimal effective use remain Recent studies demonstrated EGFR TKI gefitinib erlotinib associated high response rate progression free survival patients EGFR mutant lung cancer agents however later relapse EGFR TKI resistance making urgent develop novel therapeutic agents overcome acquired resistance EGFR TKI Current clinical approaches resistance lung adenocarcinoma include mutant selective inhibitors EGFR combination |
V V Mean dose Gy dose Gy dose Gy Index Index plans used four five non compared nine ten photon plans Figure average number monitor units per field range range would average beam time per field versus photon proton plans respectively differences monitor units beam time statistically significant P Table journal pone g Figure Comparison distributions left photon right treatment plans journal pone Table Comparison treatment time photon proton plans P value Mean Mean Total monitor units N field time per field Discussion transmission beam proton therapy planning significant dose irradiation lung tumors concern power impact peak location planning requires fewer selection optimal beam allows minimal dose adjacent normal tissues tumor dose may improved local control rates showed Gy single fraction comparable Gy four fractions protocol easily achieved using proton photon plans patients study proton therapy allow even higher doses still established normal tissues may better tumor control requires investigation clinical setting Patients planned required fewer vs reduce total treatment time low dose outside tumor average monitor units per field plans fraction needed photon plans Table beam time per field plans compared photon plan second time estimate based dose rate however new proton centers may able achieve greater thereby reducing time factor decreasing treatment time less per field breath techniques may better greater number lung cancer patients lung function technique would minimize tumor motion e leading smaller overall irradiation volume would significant issue scanning proton therapy peak would require larger planning volume due various need taken account would require longer treatment time due use multiple proton change energy requires several least would required treatments modulated therapy may decrease treatment times compared multiple However cost larger volumes normal tissue receiving low doses radiation since beam patient use four five proton transmission shorter treatment times well lower dose body data normal tissues |
trial achieved primary feasibility objective treatment assignment within patients successfully determined protein levels patients eligible patients achieve assignment treatment versus observation within day time interval surgical resection time interval surgery assignment ranged days days patients patients specimens received day limit patients time interval reporting ranged days days median days patients successful assignment within day time interval surgical resection time reporting ranged days days median days reasons reporting results excess days failure expression values control specimens required processing specimens Overall time specimens reporting ranged day days median days mean days similar reported patients advanced NSCLC range day days median days mean days Survival Survival analyses performed patients accepted assignment treatment patients surveillance patients Patients treatment assignment consent thus could followed survival patients DFS events died disease recurrence cardiac disease without recurrence median follow among patients still time last follow months range months months patients cm risk reduction reported tumors measuring cm risk increase reported significant treatment related toxicity reported patients Treatment related deaths occur patients inclusion molecular markers predictive therapeutic efficacy adjuvant decision algorithms would greatly improve clinical benefit reduce toxicity patients NSCLC approach particularly patients stage disease parameters risks benefits knowledge least well defined Recent advances molecular diagnostics resulted improved outcomes patients whose tumors mutations oncogenic signal transduction molecules therapeutic agents Similarly platinum agents target DNA gemcitabine targets required cellular proliferation also essential cellular functions Although knowledge specific oncogenic mutations identified date ERCC RRM emerged promising predictors efficacy cisplatin gemcitabine respectively conducted phase trial treatment selection based levels protein expression ERCC RRM patients completely resected stage NSCLC tumor cm primarily establish feasibility also evaluate preliminary efficacy assessed year survival rates achieved primary goal demonstrating within group environment treatment assignment achieved patients within days weeks established initiation adjuvant therapy surgery patients NSCLC first feasibility However important note surgical practice usually medical |
results show adverse effect acute lung injury human lungs material potentially pathologic diagnosis target lesion due acute inflammation knowledge study indicated lipiodol methylene blue histopathologic diagnosis target lesions human lungs small amount material injection human lungs might create significant change underlying lung disease necessary avoid directly materials target lesion human lungs order avoid adverse effect injection materials underlying lung disease especially ground glass opacity nodule potential benign lesion several limitations study First included small number subjects Second overall localization success rate low complication rate high compared results previous studies due accurate percutaneous injection location depth small rabbit lung Third used mL manual administration materials lung parenchyma possible individual difference volume materials could evaluate complications pain material related could evaluate histopathologic changes effect underlying lung disease lung parenchyma experimental normal Finally evaluate successful localization true target lesion lung parenchyma criteria appropriate staining radio opacity clinical studies might provide MLM useful percutaneous injection material localization human lung conclusion MLM available percutaneous injection pulmonary localization results study showed MLM provides superior ability appropriate localization methylene blue research human lungs clarify availability MLM CT guided percutaneous injection material study supported grant Seoul National University College Medicine Research potential interest commercial involvement G H preoperative computed tomography guided localization video assisted thoracoscopic surgery pulmonary metastatic pulmonary nodules Ann Thorac Surg Chen Zhou J Zhang J Hu H X Zhang Chen H assisted thoracoscopic solitary pulmonary nodule resection CT guided localization cases report literature review Surg P G R P assisted thoracoscopic surgery pulmonary nodules preoperative computed tomography guided localization Eur J Surg K K J H K assisted thoracoscopic surgery small pulmonary nodules indications preoperative Chest JM Lee Kim Kim J Lee determining successful computed tomography guided localization lung nodules J Thorac Surg J technique localization pulmonary nodules thoracoscopic resection Chest E P assisted thoracoscopic |
therapeutic target Recently indicated CR G polymorphism plays critical role genetic susceptibility cancer population However association genetic variants CR risk lung cancer remains lung cancer common cancer terms incidence mortality NSCLC common subtype lung cancer less aggressive SCLC Although cigarette smoking risk factor lung cancer genetic characteristics account part variation lung cancer susceptibility Recently several genome wide association studies demonstrated common genetic variations associated susceptibility lung cancer Given involvement complement system innate immunity inflammatory response examination potential association genetic variation CR genes lung cancer warranted current study conducted case control study investigate association SNPs CR gene risk NSCLC effect interaction gene environment risk NSCLC Results characteristics frequency distributions select characteristics cases control subjects shown mean age SD years cancer patients years controls significant difference found mean age cases controls P significant difference proportion sex smoking status cases controls P P respectively However significant difference cases controls compared year P smokers year cases controls suggested cigarette smoking prominent risk lung cancer case patients diagnosed adenocarcinoma squamous cell carcinoma types including large cell carcinoma n mixed cell carcinoma n select characteristics cases control subjects n n P Sex Male Female Age status Non year sided test Association CR SNP NSCLC risk Total selected SNPs CR database among Chinese population analyzed rs polymorphism genotype distributions SNPs controls consistent Therefore excluded rs analysis order screen genetic variants susceptibility lung cancer candidate case control study consisting lung cancer patients cancer free controls shown Importantly genotype frequency one SNP rs G C cases found significantly different controls P multivariate regression model adjustment age gender smoking status used assess association rs G C polymorphism risk NSCLC results indicated rs CC genotype associated increased risk developing NSCLC CI compared GG genotype CR significantly associated risk NSCLC study population P frequencies among cases controls association non small cell lung |
controls suggested important role environmental factors development NSCLC could induce chronic inflammation lung microenvironment contributing pulmonary carcinogenesis smokers also data regarding inflammation lung cancer CR important molecule implicated immunity inflammation could protect host invasion exogenous derived cigarette smoking Genetic variant CR could alter gene function result inflammatory immune responses thereby modulating susceptibility lung cancer importantly observed potential interaction SNP rs G C smoking status suggesting gene environmental interaction plays prominent role susceptibility lung cancer present study limitation patients may representative total NSCLC patients large recruited one hospital addition due relatively small sample size case control studies still needed findings Conclusion conducted case control study Chinese subjects found SNP rs G C CR significantly associated lung cancer risk best knowledge study provides first evidence genetic variant CR rs G C smoking development lung cancer Methods Study subjects case control study consisted patients confirmed NSCLC cancer free controls subjects genetic Han Chinese Patients recruited January December Hospital China age gender stage however patients previous malignancy cancer excluded response rate patients controls randomly selected cancer free population nutritional survey conducted region selection criteria control subjects included individual history cancer ii frequency matched cases according gender age years iii region iv time period blood sample collection recruitment informed consent obtained subject participant collect detailed information demographic characteristics study approved institutional review board United University SNPs selection genotyping Based Chinese population data database used program select candidate SNPs r threshold minor allele frequency MAF greater Furthermore also added two potential functional polymorphisms rs rs Therefore included SNPs study represents common genetic variants Chinese population performed Beijing China using San CA USA used design PCR extension primers SNP information selected SNPs listed Table Table used study SNP ID st PCR primer sequences nd PCR primer sequences sequences rs G C rs G rs C rs G |
rs C rs C rs G rs G rs C rs C rs G rs C rs C Statistical analysis used test examine differences distributions demographic characteristics genotype frequencies cases controls NSCLC risk associated CR SNPs estimated odds ratios confidence intervals CI computed logistic regression model adjusted age gender smoking status appropriate considered current smokers year date cancer diagnosis NSCLC patients date interview controls number years determined indication cumulative cigarette dose level year per day years smokers categorized using th year value controls cut points e years statistical tests sided P significant level Statistical analyses done using SPSS version SPSS Inc IL Gene gene gene smoking interactions analyzed open resource software package version CR receptor Odds ratio CI interval SNP nucleotide polymorphism Competing interests authors declare competing financial interest Authors contributions drafted JR conducted genotyping CR JL LC collected clinical data analyzed data contributed research plan approved data authors read approved final manuscript work supported National Natural Sciences Foundation China Program New University Science Scientific Committee H Foundation National PR China GD function mediated cancer immunotherapy j MJ Cancer complement cascade Mol Cancer Res Liu structure genetic polymorphisms expression biological functions complement receptor type CR CD JM function complement receptors CR CD CR CD SW SF C q C b bind simultaneously CR support adhesion J C C R F GM complement receptor CR CD mediates inhibitory signals human lymphocytes Mol j J Z receptor type CD mediates inhibitory |
Nat Genet ng RJ JD V P N J P E V L V Chen C G G J Liu G F MB K L J susceptibility locus lung cancer maps receptor subunit genes q Nature nature Wang P E Wu X J Dong Q X Chen MR CI RS p p variants influence lung cancer risk Nat Genet ng JD RJ V P G N J P E V L V J F F MB L Chen C G MM Lung cancer susceptibility locus p Nat Genet ng MM JD role complement inflammatory diseases J Pathol JD targeted Nat TE biology Cancer complement Nat MM RA F C G JD antitumor immune response complement Nat ni MM JD complement good cancer patients new perspective old j Q Wang Sun Zhou Functional polymorphism UTR CR associated susceptibility nasopharyngeal carcinoma Oncol Rep JR Wang TG TE SM Risk non lymphoma association germline variation complement genes Br J j x Zhang Z Yu J Guo Wang H Zhang X smoking strongly association complement factor H variant risk lung cancer Cancer e e j R P X RS G L J Q innate immunity genes lung cancer risk China Mol Identification membrane glycoprotein C b receptor human B lymphocyte J Exp Med GP Second hand smoke human lung cancer Lancet Oncol JD study association air lung cancer incidence J Thorac Oncol E F B Smith Lung cancer workers exposed Health P PA P Wu G RS F C SC F L P smoke exposure risk lung cancer among never smokers pooled analysis two large studies Int J Cancer Lee G TC SM Chronic inflammation chronic obstructive pulmonary disease lung cancer Med b e c development lung cancer epidemiological evidence Rev Ther K K CA GP JC MD Z DR CG receptor gene variants |
studies sensitivity analysis performed compare year survival rate year disease free survival rate VATS open thoracotomy bias plot used explore bias plot trial size treatment effect used assess risk bias Results studies retrospective cohort studies met criteria included meta analysis total patients included six studies patients VATS group whereas open thoracotomy group evaluate survival rate search algorithm results search strategies selection criteria shown Fig patient characteristics evaluation index shown Table g Figure Identification studies inclusion Table Study V F Mean age years Assessment score OC Japan V V OC Netherlands OC UK V V OC USA V V OC V V OC Taiwan V V VATS thoracotomy reported OC observational cohort Assessment Survival studies documented year survival significant heterogeneity among six studies x P fixed effect model used combined result shown Fig CI p heterogeneity sample size sensitivity analyses conducted using larger sample sizes difference two surgical methods CI heterogeneity P studies reported year survival rate heterogeneity identified five studies x P random effect model adopted CI p Fig Three studies compared year survival rate CI p certain heterogeneity x P Fig g Figure year survival rate plot Odds year survival rate following VATS versus open thoracotomy metastatic lung cancer estimate individual trial corresponds middle horizontal line CI numbers events fraction total number randomized shown treatment groups sum statistics along summary represented middle solid test heterogeneity trials within subgroup given summary statistics g Figure year survival rate plot Odds year survival rate following VATS versus open thoracotomy metastatic lung cancer estimate individual trial corresponds middle horizontal line CI numbers events fraction total number randomized shown treatment groups sum statistics along summary represented middle solid test heterogeneity trials within subgroup given summary statistics g Figure year survival rate plot Odds year survival rate following VATS versus open thoracotomy metastatic lung cancer |
First cancer deaths included analysis year overall survival might account VATS comparable overall survival rate inferior disease free survival rate patients VATS group might lesions likely relapse lung leading inferior year disease free survival rate Third included studies early period VATS development technology complications prevented experience reported cases site recurrence associated VATS occurred number cases studied small observation period computed tomography far higher detection rate years small lesions accurately localized surgery success VATS advances imaging technology open thoracotomy less important latest VATS technology high definition resolution tip enables complete pleural cavity ensure VATS ideal method patients solitary relatively small peripheral lesions necessary therapeutic diagnostic procedure patients multiple lesions treated open thoracotomy VATS controversial study first meta analysis oncological outcome thoracoscopic surgery treatment metastatic lung cancer work observed VATS might promising treatment metastatic lung cancer randomized trials existing guide field metastatic lung cancer currently prospective randomized study different surgical strategies needed randomized controlled trials existing comparing VATS thoracotomy conducted observed sample size years covered studies limited small observational studies single institution case series total patients included two groups study period decade Two studies almost patients one study patients potential sources bias work Additional randomized controlled trials studies accessed would increased strength results bias language Conclusion meta analysis found patients metastatic lung cancer comparing VATS thoracotomy showed almost equivalent survival rates VATS open thoracotomy completely study large multicenter randomized trial comparing VATS thoracotomy would ideal Information Click additional data file References Pulmonary target J Thorac Oncol et al year survival pulmonary adult soft tissue sarcoma Cancer van van Pulmonary resection metastases colorectal origin Chest et al Long term results repeated surgical removal pulmonary metastases Ann Thorac Surg et al video assisted thoracic surgery treatment pulmonary metastases results prospective trial Ann Thorac Surg discussion et al Evaluation video assisted thoracoscopic surgery pulmonary metastases |
cases International Lung J Thorac Surg site metastasis complication thoracoscopic Eur J Surg Oncol site laparoscopic thoracoscopic procedures malignancy J Clin Oncol Pulmonary common practice based weak evidence Ann R Surg Engl et al Comparison median thoracotomy resection pulmonary metastases patients adult soft tissue Ann Thorac Surg et al recurrence incidence second primary tumors means video assisted thoracoscopic surgery VATS versus thoracotomy lung cancer J Thorac Surg site laparoscopic surgery review Surg et al CT guided localization lung lesions video assisted thoracoscopic surgery VATS J Med surgical approach pulmonary J Thorac Oncol et al surgery conventional open thoracotomy metastatic lung cancer Surg et al Long term survival thoracoscopic vs thoracotomy patients solitary pulmonary lesion Eur J Surg Oncol assisted versus open pulmonary Eur J Surg assisted thoracic surgery VATS safe alternative resection pulmonary metastases retrospective cohort study J Surg et al pulmonary metastases sarcoma patients benefit less invasive approach Ann Thorac Surg et al Management lung metastases colorectal cancer video assisted thoracoscopic surgery versus case matched study Thorac Surg Mol Cancer Res Mol Cancer Res Molecular cancer research MMP L J H K V V V N Department West University School Medicine Department West University School Medicine Department Statistics West University School Medicine Department Pathology West University School Medicine Cancer Center West University School Medicine author N address Department Cancer Center Medical Center West University School Medicine edu L R J contributed equally work protein established pro metastatic marker several cancers Nevertheless molecular mechanisms driven metastasis cancers remain ill defined using comprehensive breast cancer tissue microarray show increased levels protein significantly correlated transition carcinoma situ invasive carcinoma Similarly shown overexpression highly invasive cells Moreover expression crucial protease dependent mesenchymal invasion cancer cells primary site metastatic site sufficient suppress invasion tumor cells vitro vivo leading decreased circulating tumor cells lung metastases |
accuracy calculated entire cohort differences based preoperative size site examined Results FDG PET results available participants enrolled sites Lung cancer prevalence FDG PET sensitivity CI specificity CI Positive negative predictive values respectively improved lesion size false positive scans negative scans occurred patients adenocarcinoma frequent mm sensitivity varied p specificity ranged p across participants Conclusions national surgical population clinical stage NSCLC FDG PET lung cancer performed poorly compared published studies Biol Biol Biology Netherlands x Research diagnostic prognostic value serum human related non small cell lung cancer Xu Zhang Yu Yu Li com Department Respiratory Medicine Chest Hospital Road China Clinical Center Respiratory Diseases China Access distributed terms Creative Commons Attribution License permits use distribution reproduction medium provided original author source aim study explore diagnostic prognostic value serum human related KLK level non small cell lung cancer NSCLC Serum specimens patients NSCLC healthy controls collected concentration KLK measured enzyme linked assay ELISA concentration KLK NSCLC significantly higher compared controls P serum KLK levels decreased stage presence lymph node distant metastases regardless histology age sex cutoff point ng ml KLK showed good diagnostic performance NSCLC Univariate analysis revealed NSCLC patients serum high KLK longer overall survival OS progression free survival PFS low KLK HR P HR P Cox multivariate analysis indicated KLK independent prognostic indicator PFS OS HR P HR P KaplanMeier survival curves confirmed patients high KLK longer PFS OS P P respectively conclusion measurement KLK might useful diagnostic prognostic test NSCLC patients related Non small cell lung cancer issue copyright statement International Society Oncology Introduction Lung cancer leading cause cancer related death worldwide million deaths year Non small cell lung cancer NSCLC accounts total lung malignancies Although advances noninvasive methods improved ability detect lung cancer lung cancer patients present advanced stage disease little effective curative treatment year survival rates less |
Diagnostic value KLK NSCLC ROC curve analysis carried assess value KLK NSCLC area ROC curve confidence interval CI cutoff point ng ml defined normal value based mean value plus two standard deviation obtained healthy controls serum KLK sensitivity specificity accuracy positive predictive value negative predictive value Fig Fig ROC KLK diagnosis NSCLC Serum levels KLK among NSCLC patients healthy controls determined diagnostic KLK assessed ROC curves AUC value serum KLK levels clinicopathologic factors relationships KLK levels clinicopathologic factors lung cancer patients shown serum KLK levels differ significantly age P sex P histology P levels KLK significantly correlated tumor node metastasis TNM stage P lymph node metastases P distant metastases P clinicopathological factors NSCLC association KLK ng ml P year Male Female AC SCC TNM stage III Lymph node metastases metastases AC adenocarcinoma SCC squamous cell carcinoma Association serum KLK levels survival Finally determined whether baseline serum concentration KLK would prognostic marker NSCLC cutoff point ng ml selected patients KLK high low Univariate analysis showed serum KLK level significantly correlated OS P PFS P Univariate multivariate analysis KLK status regard PFS CI P CI P analysis KLK Low vs High Age vs Male vs Female AC vs SCC Stage III vs Lymph node metastases absent vs present metastases absent vs present Multivariate analysis KLK low vs high Age vs male vs Female AC vs SCC Stage III vs Lymph node metastases absent vs present metastases absent vs present HR hazard ratio CI confidence interval multivariate analysis high KLK found significantly associated longer PFS OS HR P P respectively KaplanMeier survival curves Fig demonstrate lung cancer patients high KLK substantially longer PFS OS P compared low KLK cancer expected disease stage found strongly associated decreased PFS OS univariate multivariate analyses P Fig KaplanMeier survival curves PFS OS patients KLK high low NSCLC |
apoptosis assayed cells blocking pathway shRNA knockdown small molecule inhibitors mice used determine vivo efficacy inhibitor Results cohorts activation signaling significantly associated classical subtype cell lines genetic knockdown produced minor effects cell survival knockdown significantly reduced proliferation induced extensive apoptosis inhibitor resulted limited cytotoxicity cells whereas inhibitor effective Importantly demonstrated specific vivo anti tumor activity xenograft models positive cell lines Conclusion studies demonstrate important role suggest inhibition novel potent strategy treat subset patients cell lung cancer J Korean Med Sci J Korean Med Sci Journal Korean Medical Science Korean Academy Medical Sciences Medical Imaging Evaluation Surgery Lee Kim Kim Dong Department Radiology Seoul Seoul National University Medical Center Seoul Korea Department Radiology Seoul National University Hospital Korea Department Radiology Seoul National University Hospital Seoul Korea Department Pathology Korea Correspondence Lee MD Department Radiology Seoul National University Hospital Korea ac Korean Academy Medical Sciences Access distributed terms Creative Commons Attribution Non License permits unrestricted non commercial use distribution reproduction medium provided original work properly cited localization necessary prior video assisted thoracoscopic surgery detection small located lung nodules compared localization ability mixture lipiodol methylene blue MLM mL methylene blue mL rabbit lungs CT guided percutaneous injections performed subjects MLM methylene blue measured extent staining excised lung evaluated localization ability point hr injections MLM radio opacity evaluated considered score acceptable excellent appropriate localization staining extent MLM significantly smaller methylene blue vs cm P MLM showed superior staining ability methylene blue vs P staining achieved subjects MLM methylene blue P acceptable excellent radio opacity MLM found subjects appropriate localization rate MLM use directly visible ability radio opacity MLM MLM provides superior pulmonary localization ability methylene blue Lung X Radiology Seoul National University College Medicine localization necessary video assisted thoracoscopic surgery VATS pulmonary nodules small distant detected failure nodules success thoracoscopic resection leads conversion thoracotomy |
estimate locations dispersion excellent localized staining Fig maximum diameter staining extent lung surface measured calculated compared scores extent staining two materials findings radio opacity MLM evaluated using point scoring detectable radio opacity minimally increased opacity acceptable low density increased opacity excellent nodular increased opacity Fig compared average scores initial follow examinations considered score score appropriate localization staining radio opacity compared number appropriate excellent localization MLM methylene blue histopathologic examinations excised entire lungs used final specimens lung tissues fixed neutral formalin embedded paraffin cut thick took record staining lung surface made covered center staining subjected hematoxylin eosin H E stain evaluate lung change evaluated presence absence neutrophil infiltration necrosis hemorrhage cell extent histopathologic finding estimated using visual scores focal diffuse change total area normal lung defined focal lung change total area replaced normal lung defined diffuse experienced eight years experience reviewed overall severity lung change defined total score adding visual scores histopathologic finding compared overall severity score MLM methylene blue well Group Group B Statistical analysis data expressed deviation SD unless otherwise stated average scores performed two test test used Fisher exact test compare number subjects subgroups linear association evaluated association extent lung change materials groups difference P values less statistical analysis performed available statistical software SPSS Statistics version NY USA characteristics records time interval injection examinations Among subjects included study successful CT guided percutaneous injections location lung achieved subjects Group Group B Three subjects died anesthesia Mean weight kg Group kg Group B depth needle tip cm range cm MLM cm range cm methylene blue P skin needle tip cm range cm MLM cm range cm methylene blue P CT guided percutaneous injections total number procedure related complications including leakage MLM MLM methylene blue complication rate MLM significantly higher methylene blue vs P post CT images extent radio opacity MLM |
lead large addition reported dispersion methylene blue throughout entire pleural surface intraoperative identification failure due severe failure rate reported use methylene blue results similar study indicate staining lung surface methylene blue study found dispersion methylene blue MLM lung parenchyma significantly smaller methylene blue cm vs cm P result lipiodol reduces spread methylene blue lung parenchyma score radio opacity MLM showed non visualization minimally increased opacity examinations means proportion lipiodol MLM time percutaneous injection small detected CT images also revealed subjects small radio opacity injection MLM suggests lipiodol methylene blue occurred preparation MLM lipiodol would result water soluble methylene blue mechanical two materials research required reduce non MLM time injection Previous studies reported availability mixture methylene blue materials collagen blood performed VATS resection day localization study evaluated localization ability MLM day localization hr well hr injection usually performed day surgery requires simultaneous use CT operating room always available next day localization reported several published MLM shows prolonged localization ability hr terms staining ability radio opacity localization ability advantage MLM study Due MLM one subject showed staining appropriate radio opacity required intraoperative examination detect MLM radiation exposure MLM would like use intraoperative avoid radiation exposure lead risk benefit patients risk detection failure thought important radiation exposure examinations showed lung changes specimens methylene blue MLM induced acute lung injury included neutrophil infiltration necrosis hemorrhage cell results study similar previous study et al showed lipiodol led acute lung injury described lipiodol histopathologic feature acute lung injury peripheral endothelial cell damage neutrophil infiltration necrosis hemorrhage alveolar wall macrophages alveolar space results extent lung change associated materials histopathologic features addition overall severity score lung change MLM different methylene blue P suggests MLM shows similar histopathologic effects lung parenchyma methylene blue overall severity score change higher Group B follow interval hr Group follow interval hr vs P |
pain material related could evaluate histopathologic changes effect underlying lung disease lung parenchyma experimental normal Finally evaluate successful localization true target lesion lung parenchyma criteria appropriate staining radio opacity clinical studies might provide MLM useful percutaneous injection material localization human lung MLM available percutaneous injection pulmonary localization results study showed MLM provides superior ability appropriate localization methylene blue research human lungs clarify availability MLM CT guided percutaneous injection material study supported grant Seoul National University College Medicine Research potential interest commercial involvement G H preoperative computed tomography guided localization video assisted thoracoscopic surgery pulmonary metastatic pulmonary nodules Ann Thorac Surg Chen Zhou J Zhang J Hu H X Zhang Chen H assisted thoracoscopic solitary pulmonary nodule resection CT guided localization cases report literature review Surg P G R P assisted thoracoscopic surgery pulmonary nodules preoperative computed tomography guided localization Eur J Surg K K J H K assisted thoracoscopic surgery small pulmonary nodules indications preoperative Chest JM Lee Kim Kim J Lee determining successful computed tomography guided localization lung nodules J Thorac Surg J technique localization pulmonary nodules thoracoscopic resection Chest E P assisted thoracoscopic resection small pulmonary nodule computed tomography guided localization system experience consecutive patients World J Surg Chen W Chen L Yang Chen Z G Zhang J novel technique localization small pulmonary nodules Chest pulmonary nodules using video assisted thoracic surgery Group Ann Thorac Surg AE Chen CS Smith localization technique thoracoscopic resection lung lesions children J Surg K H K small pulmonary nodules thoracoscopic resection injection lipiodol CT guidance Acad H R H thoracoscopic resection pulmonary nodule child J Med Imaging Oncol K K H guided small pulmonary lesions video assisted thoracic surgery Med J K K tomography guided injection pulmonary nodule thoracoscopic resection J Thorac Surg H H collagen long point marker small pulmonary nodules |
Chang National Health Research Taiwan E edu Competing authors competing interests exist designed experiments experiments data reagents materials analysis tools paper informed consent subjects Zhou e et al open access distributed terms Creative Commons Attribution License permits unrestricted use distribution reproduction medium provided original author source Background mutated ATM gene plays important role DNA double strand repair pathway nucleotide polymorphisms SNPs DNA repair genes suspected influence risk lung cancer study aimed investigate association ATM G rs polymorphism environmental risk factors risk lung adenocarcinoma Chinese female non smokers Methods hospital based case control study lung cancer patients matched cancer free controls conducted Information concerning demographic environmental risk factors obtained case control trained informed consent obtained ml venous blood collected subject biomarker testing nucleotide polymorphism determined using method Results study showed individuals ATM rs AA genotype increased risk lung adenocarcinoma compared carrying GA GG genotype adjusted odds ratios confidence interval CI P stratified analysis suggested increased risk associated ATM rs AA genotype individuals never exposed cooking oil adjusted CI P Conclusions ATM rs might associated risk lung adenocarcinoma Chinese non smoking females Furthermore ATM rs AA genotype might risk factor lung adenocarcinoma among female non smokers without cooking oil exposure study supported grant National Natural Science Foundation China grant National Natural Science Foundation China grant China Medical role study design data collection analysis decision publish preparation manuscript Introduction Lung cancer leading cause cancer related deaths worldwide China Although cigarette smoke major risk factor lung cancer fraction smokers develop disease suggesting host genetic susceptibility may play important role development lung cancer Recent genetic susceptibility studies lung cancer focused single nucleotide polymorphisms SNPs candidate genes among DNA repair genes increasingly studied critical role maintain genome integrity Genetic variations DNA repair genes thought affect DNA repair capacity DNA repair capacity may lead genetic instability carcinogenesis |
ages cases controls mean almost identical respectively cases female non smoking lung cancer patients statistically significant difference found cases controls terms age P P included non small cell lung cancer NSCLC patients small cell carcinoma patients NSCLC cases adenocarcinomas squamous cell carcinomas tumors variety different large cell carcinomas mixed cell carcinomas carcinomas Characteristics lung cancer cases controls P value Female Mean age years month type NSCLC cell carcinoma Small cell carcinoma test used compare frequency distributions demographic variables cases controls Association analysis observed genotype frequencies among control subjects agreement expected P distribution ATM rs genotypes among subjects displayed Table Using subjects ATM rs GG genotype reference group calculated heterozygous carriers GA genotype homozygous carriers AA genotype significant difference observed lung cancer cases controls test P order increase statistical power combined GA genotype AA genotype compare GG genotype dominant model combined GA genotype GG genotype compare AA genotype model results indicated individuals AA genotype significantly elevated risk lung adenocarcinoma compared carrying GG GA genotype CI P Table ATM rs genotypes lung cancer cases controls CI P overall n GG ref GA AA dominant NSCLC n GG ref GA AA dominant model model n GG ref GA AA dominant model model cell carcinoma n GG ref GA AA dominant model model P GA AA vs GG b AA vs GA GG c adjusted age data calculated logistic regression According results assumed ATM rs AA genotype might affect lung adenocarcinoma risk among non smoking Chinese females test hypothesis explore gene environment interaction adopted lung adenocarcinoma patients cancer free controls whose information environmental risk factors completely obtained smoke exposure cooking oil exposure passive smoking family history cancer controls included association analysis item environmental risk factors data incomplete screening lung adenocarcinoma cases cancer free controls eligible demographic variables environmental risk factors cases controls listed Table |
distribution demographic variables exposed group non exposed group b used compare frequency distribution demographic variables smoke exposure family history cancer passive smoking exposed group non exposed group several limitations current study First hospital based studies likely include controls non malignant lung diseases especially associated chronic inflammatory processes suspected factors lung cancer found may Second statistical power study may limited relatively small sample size subjects addition SNPs ATM gene pathway may involved risk lung adenocarcinoma gene gene interaction may offer association host genetic susceptibility lung adenocarcinoma risk study investigated association ATM rs polymorphism lung adenocarcinoma risk non smoking females population first time Meanwhile explored combined effects cooking oil exposure ATM rs polymorphism lung adenocarcinoma risk small sample size one SNP large scale studies gene gene gene environment interactions different population required validate findings Conclusions summary hospital based case control study showed ATM rs might associated risk lung adenocarcinoma Chinese non smoking females Furthermore ATM rs AA genotype might risk factor affecting lung adenocarcinoma among females without cooking oil exposure References odds smoking American journal public health DNA repair capacity lung cancer patients Cancer Res Genetic susceptibility lung cancer role DNA damage repair Cancer DNA damage induced activation ATM ATM dependent signaling pathways DNA cellular response DNA double strand mediators Cell Biol ATM activation DNA damage response Cell et al single gene product similar PI kinase Science many substrates functions ATM Nat Rev Mol Cell Biol Cell cycle cancer Nature et al First functional polymorphism promoter results decreased transcriptional activity Sp binding Biochem Res et al functional C promoter polymorphism influences gene expression melanoma cells via binding c transcription factor Mol De et al C G single nucleotide polymorphism gene promoter region transcriptional activity specific binding Sp transcription factor associated high blood pressure Italy J et al novel promoter polymorphism human gene |
mixed cohorts concluded similar results EURTAC trial randomized phase trial assess safety efficacy erlotinib compared standard platinum based chemotherapy first line treatment patient population advanced EGFR mutation detected NSCLC largely population European patients treated patients experienced significant improvements median PFS months vs months compared chemotherapy Patients erlotinib arm also higher percentage responses vs treat population trial submitted first line indication erlotinib EGFR mutated NSCLC patients majority activating EGFR mutations located exons recommend use anti EGFR TKIs first line therapy patients EGFR mutant advanced NSCLC based results pivotal clinical trials Recent recommendations identification EGFR mutations present exon deletions exon mutation L R account greater mutations guidelines testing method used however EGFR Mutation test approved recently FDA approved present retrospective analysis clinical validation study EGFR PCR test subset lung cancer specimens patients screened EURTAC trial EGFR PCR test demonstrated improved sample relative used EURTAC trial EGFR mutation screening single assay one day turn around time EGFR PCR test showed superior sensitivity specificity compared conventional Sanger sequencing Methods major study correlate clinical outcomes PFS subgroup available samples tested EGFR PCR test results entire EURTAC population compare performance EGFR PCR test original LDT Sanger sequencing using parallel MPP observed testing methods EURTAC trial patients hospitals Italy Spain screened using LDT study samples retrospectively analyzed approval specific approval clinical site written consent patients obtained prior study conduct phase NCT cases residual specimens available EGFR PCR test Figure single section least tumor content specimens used EGFR PCR test DNA existing extracted additional sections tested Sanger sequencing MPP Table demographics patients screened EURTAC trial LDT categorized patients tested tested EGFR PCR test Patients enrolled EURTAC trial selected using laboratory developed test validated Laboratory Oncology Hospital Spain consisting three study single PCR based assay detecting EGFR mutations used analytical performance assay described previously g Figure Flow samples study |
treatment arms months erlotinib arm CI months chemotherapy arm CI log rank test p value PFS OS results EGFR PCR test positive patients differ significantly obtained patients enrolled EURTAC trial suggests EGFR PCR test positive patients representative EURTAC enrolled patients cases EGFR PCR test result mutation detected LDT two cases resolved LDT MPP three cases resolved EGFR PCR test one sample Sanger MPP agreement EGFR PCR test Sanger MPP Table patients treated erlotinib one patient achieved greater equal median PFS based LDT EGFR PCR test Comparison EGFR PCR test LDT results Among specimens valid results EGFR PCR test LDT OPA CI CI CI respectively Table Thus high concordance original LDT EGFR PCR test results Among specimens discordant results EGFR PCR test result confirmed MPP cases Table Table analysis EGFR PCR test LDT LDT Total N Mutation detected Mutation detected EGFR PCR test Mutation detected Mutation detected Total samples LDT results samples EGFR PCR test results excluded Positive percent agreement CI Negative percent agreement CI Overall percent agreement CI Comparison EGFR PCR test results Sanger specimens tested using EGFR PCR test Sanger sequencing gave valid results methods methods five EGFR PCR test Sanger sequencing OPA EGFR PCR test compared Sanger sequencing CI CI CI Table respectively Among discordant results EGFR PCR test Sanger sequencing MPP EGFR PCR test result cases Table Sanger sequencing detected one L R detected MPP failed detect exon deletions L R mutations confirmed MPP Four MPP results remaining four results Sanger range percent mutant alleles cases Sanger several specimens n estimated limit detection Sanger Table analysis EGFR PCR test Sanger sequencing Sanger sequencing Total N Mutation detected Mutation detected EGFR PCR test Mutation detected Mutation detected Total samples EGFR PCR test Sanger sequencing results excluded Positive percent agreement CI Negative percent agreement CI Overall percent agreement CI |
sensitivity samples containing less mutant alleles compared agreement valid results EGFR PCR test Sanger sequencing n discordant cases confirmed MPP nine cases resulted mutation detected status EGFR PCR test would make patients eligible anti EGFR therapy sensitivity Sanger sequencing thus relatively low compared EGFR PCR test observed study Given EGFR mutation testing selecting specific therapies life cancers advanced NSCLC robust accurate assays rapid time preferred Recent quality studies mutation status standard panel tumors shown different clinical laboratories identify mutation status panel members even using similar testing assays involve mutation analysis tumor samples important factors contributing assay performance include validation reagents methodology laboratory experience appropriate involvement results present study indicate EGFR mutation test highly robust highly accurate companion diagnostic assay select patients treatment anti EGFR therapies erlotinib Information Table MPP Click additional data file Table samples EGFR PCR test LDT enrolled clinical trial LDT MD Click additional data file Table results discordant EGFR PCR LDT tests Click additional data file Table MPP results resolution analysis discordant specimens EGFR PCR test Sanger sequencing Click additional data file would like Yu contributions study References et al survival melanoma BRAF V E mutation N Engl J Med treatment ALK non small cell lung cancer success second decade molecular targeted therapy oncology new treatment option ALK positive non small cell lung cancer et al response crizotinib non small cell lung cancer patient IHC positive FISH negative ALK J Thorac Oncol e anti EGFR monoclonal antibodies KRAS et al Validation Diagnostic Detection KRAS Gene Patients Cancer Analysis CO Pathol Med et al chemotherapy nonsmall cell lung cancer mutated EGFR N Engl J Med et al carboplatin paclitaxel pulmonary adenocarcinoma N Engl J Med et al versus chemotherapy first line treatment patients advanced EGFR mutation positive non small cell lung cancer multicentre open label randomised phase study |
require ethical review Results One hundred trusts participate participate study one trusts data sufficient quality allow Two trusts provided joint multidisciplinary team allowing pairs multidisciplinary teams created One pair act pilot excluded analysis remaining pairs pairs trusts randomised intervention group remaining pairs formed control group study two trusts control group form one total number trusts control group Figure Quality improvement plans Two hundred medical professionals trusts participated review visits nine teams submitted total quality improvement plans issues identified quality improvement plans shown Table teams collected local data measure impact example data shown Figure identified small cell lung cancer chemotherapy area improvement introduced number changes diagnostic treatment pathways including small cell pathology reporting results multidisciplinary team lung nurse allow early oncology changes monitored using run chart demonstrated reduction time multidisciplinary team meeting chemotherapy treatment increase proportion small cell lung cancer patients receiving chemotherapy National lung cancer indicators Baseline indicators intervention control non participant groups similar Table mean change indicator baseline intervention control group shown Figure proportion patients receiving active anti cancer treatment intervention group increased compared controls mean difference CI P remaining indicators improved similarly intervention control groups Patient experience intervention group patient experience questionnaires patients multidisciplinary teams baseline rate patients trusts following intervention rate Baseline total scores low indicating high levels patient care received although statistically significant P variation results multidisciplinary team Figure particular proportion patients question find person diagnosis sufficient sensitivity care varied significantly P total questionnaire scores change significantly study P however variation multidisciplinary team reduced Figure Given study aimed standard lower performing trusts best performed post analysis five trusts baseline patient experience scores demonstrated mean total score improved significantly trusts P improvement group seen proportion patients question find person diagnosis sufficient sensitivity care increased P One multidisciplinary team group achieved improvement using baseline questionnaire results advanced course |
participation survey treated confidence take part survey affect care receive NHS way name address questionnaire information required information give questionnaire shared way allows identified complete survey long take questionnaire short take min complete every question questionnaire even every question first language understanding questions relative help complete questionnaire help questions contact local lung clinical nurse team select one question appropriate box space end survey work published standard license publish agreement months work become available license terms Creative Commons Attribution License B cancer survival many deaths Br J Cancer G L G N peer review quality improvement case study Lung Cancer Outcomes Project BMJ P R MD variations lung cancer care across UK far National Lung Cancer Clin Med Department Health National Cancer Patients England Health Care Information Centre National Lung Cancer Institute Healthcare Model RA DR JP Lung cancer survival England trends non small cell lung cancer survival duration National Lung Cancer Br J Cancer P K G W K W R E learning healthcare system surgery State Surgical Care Outcomes Assessment Program years Surgery National Institute Health Care Treatment Lung Cancer Clinical Clinical guidelines CG London UK P H B R R G J J C intervention decrease related infections ICU N Engl J Med CM RA RJ NA JM randomized trial peer review UK National Chronic Pulmonary Disease Outcomes Project three year evaluation J Clin C MD J N L E K G ML J J E B Group Lung cancer survival stage diagnosis UK population based study J Health atlas shows large variations care England BMJ c c Figure Study Figure diagram eligible trusts including screening follow Figure chart showing waiting times multidisciplinary team meeting first treatment consecutive small cell lung cancer patients following implementation quality improvement plan one intervention group Figure Mean change national lung cancer baseline |
patients lung cancer partners Methods parallel group randomized controlled trial conducted compare MBSR Lung cancer patients received still treatment partners recruited take place baseline post intervention three month follow primary outcome psychological distress e anxiety symptoms outcomes quality life patients caregiver partners relationship quality addition cost effectiveness ratio patients several process variables assessed Discussion trial provide information clinical cost effectiveness MBSR compared patients lung cancer partners registration NCT Mindfulness based stress reduction Lung cancer patients distress controlled trial Background estimated million deaths per year lung cancer leading cause death cancer worldwide best available treatment five year survival patients within first year diagnosis poor prognosis often caused late diagnosis presentation usually occurs lung cancer advanced Patients may develop symptoms like pain fatigue cough may undergo radical treatment including surgery radiotherapy lung cancer major impact psychological wellbeing patients family colleagues showed patients advanced lung cancer criteria disorders especially adjustment disorders patients successfully treated lung cancer met criteria minor major disorder prevalence rate anxiety symptoms among lung cancer patients ranges Compared patients cancer diagnoses lung cancer patients report highest rates distress resulting lower quality life especially partners patients lung cancer also psychological impact provide practical support also concerns including regarding course illness partner partners lung cancer patients report negative effects caregiving partners patients advanced lung cancer report high levels distress relationship patient partner also affected cancer shown partners report lower quality relationship diagnosis lung cancer numerous studies examined psychological distress lung cancer patients partners much research done distress groups addition available studies care needs cancer patients families focused care end life e g Recently studies demonstrated palliative care initiated early treatment improves quality life symptoms lung cancer patients importance care lung cancer patients partners early treatment rather life therapies past ten years MBSR become promising intervention cancer patients Mindfulness defined attention non way |
work absence study period pt Mindfulness adherence study period pt pr Baseline measurement intervention measurement month follow measurement pt Patient pr State Hospital Scale C Quality Life Cancer LC Quality Life Lung Cancer Care SE Assessment Care Model Scale Mindfulness Scale Response Scale Scale stratified according setting stage disease curative versus palliative b baseline level anxiety symptoms anxiety depression score Hospital Scale versus c treatment MBSR treatment versus radiotherapy participation patient alone versus partner alone versus patient partner together using randomization website specifically designed study required data treatment nurse patient partner take place post intervention three month follow Participants access email address receive questionnaires online receive questionnaires paper along case contact participant complete minimum set outcome measures identify main reason MBSR used primarily based Mindfulness Based programme developed contains elements programme like education Moreover modifications made make intervention suitable patients lung cancer partners education addition communication exercise partners cancer added programme consists weekly hour sessions day session six seven home practice minutes days per week Participants receive set guided exercises home practice information home practice instructions week Table shows content MBSR programme per session MBSR extensive training MBSR advanced criteria Center Mindfulness University Medical School maintain regular personal practice trained assessed ensure levels met criteria MBSR classes trial receive weekly number sessions evaluate adherence Mindfulness Based Assessment Table MBSR programme per session session exercise pilot participating exercise one routine activity Mindfulness breath exercise demonstrate relationship focus breath breath events routine activity limits exercise demonstrate difference observation interpretation min breathing space events min breathing space distress focus breath body min breathing space stress reactions min breathing space distress focus breath body versus choice reaction difficult situation communication min breathing space min breathing space communication position communication exercise effect lung cancer partner min breathing space communication min breathing space stress day exercises |
lung cancer patients partners trial offer valuable information whether MBSR one available care contributes psychological distress MBSR Mindfulness based stress reduction controlled trial University Medical Centre Mindfulness based cognitive therapy mental state examination Hospital anxiety depression scale C Quality life cancer LC Quality life lung cancer impact profile perceived pressure care SE reaction assessment care derived self model scale sensitivity involvement list questionnaire scale response scale extended version event scale Competing interests authors declare competing interests Authors contributions authors contributed design study MD JP principal investigators study MS drafted paper modified supplemented authors MS MD involved participants MS take care study data collection RD contributed specifically statistical analysis plan contributed specifically design cost effectiveness evaluation authors read approved final manuscript publication history pre publication history paper accessed research funded Foundation Cancer Society number dr E Dr van der dr B F Center MM J E Global cancer statistics CA Cancer J Clin H disorders associated predictive factors patients unresectable nonsmall cell lung carcinoma longitudinal study Cancer CO K N K H successful treatment nonsmall cell lung carcinoma month follow study Cancer CO U R J CR depression patients lung cancer diagnosis findings population J Health K N K R impact informed consent hospitalized cancer patients study anxiety depression using Hospital scale Care Cancer NJ RA GP distress concerns elderly patients treated palliative radiotherapy lung cancer P RJ patients lung cancer prevalence risk factors derived quality life data J Clin Oncol J K B C prevalence psychological distress cancer site CO J E J L JH G J High levels untreated distress fatigue cancer patients Br J Cancer JA ER CM CD J Care Patients Non Small Cell Lung Cancer N Engl J Med AD Chang L PR depression among people lung cancer PA support depression caregivers patients end stage disease |
cancer mesothelioma cells heat shock protein Hsp potent immune activator stimulates monocytes DCs enhances DC aggregation maturation improves cross cells mediated DCs Methods fusion protein MSLN surface tumor cells measured flow cytometry fluorescence microscopy therapeutic efficacy fusion protein evaluated mouse models papillary ovarian cancer malignant mesothelioma received p treatments experimental control proteins post p injection tumor cells free overall survival time measured investigation anti tumor cell responses time matched study performed stimulated peptides IFN B generating CD CD cells detected flow cytometry examine role CD cells antitumor effect performed vivo CD cell depletion determined fusion protein increases DC maturation improves antigen presentation well cross presentation DCs Results demonstrated vitro scFvMTBHsp fusion protein bound tumor cells used study interaction scFv MSLN surface cells induced maturation bone marrow derived DCs Use fusion protein mouse models significantly enhanced survival tumor growth tumor specific CD cell dependent immune responses also demonstrated vitro vivo fusion protein enhanced antigen presentation cross presentation targeting tumor antigens towards DCs Conclusions new cancer immunotherapy potential cost effective applicable tumors Hsp chain variable fragment Cancer immunotherapy tumor model Background goal cancer immunotherapy stimulate immune system cancer cells strategies involve tumor antigen specific non specific activation immune system developed include dendritic cell DC vaccines cell therapy immune checkpoint blockade specific active immunotherapy expected strategy capacity induce therapeutic protective cell immunity Among various approaches DC vaccine considered promising treatment advanced cancer based ability DCs elements immune system DCs capture tumor antigens process antigens peptides secondary lymphoid ans present peptides na cells thus inducing anti tumor cellular immune responses DCs also activate B cells NK cells cells pre clinical clinical studies DCs means improve vaccine efficiency DCs ex vivo antigens administered patient example consists ex vivo activated peripheral blood cells including antigen presenting cells resulted significant survival benefit Phase III trials prostate cancer |
prolonged free overall survival time compared saline MTBHsp plus P scFv treated mice Figure B B Kaplan survival curves tumor bearing mice following treatment scFvMTBHsp control proteins normal saline mouse model papillary ovarian cancer immune FVB NJ mice scFvMTBHsp prolonged free survival time compared saline n per group representative two independent experiments median survival Med days vs days mixture MTBHsp plus P scFv Med days scFvMTBHsp also prolonged overall survival time mice compared saline Med days vs days mixture MTBHsp plus P scFv Med days B mouse model mesothelioma immune C BL mice fusion protein prolonged free survival time compared saline treated mice n per group pooled two independent experiments Med days vs days mixture MTBHsp plus P scFv Med days fusion protein also prolonged overall survival time compared saline Med days vs days P values determined using log rank test p p p scFvMTBHsp enhances anti tumor CD cell responses ovarian tumor bearing mice investigate whether anti tumor effects scFvMTBHsp associated anti tumor effector CD cell responses stimulated ovarian tumor bearing FVB mice received different treatments CD cell MSLN negative control ex vivo analyzed cells production IFN B using flow cytometry previously showed expressed BR FVB cells designed H restricted MSLN peptide induce ovarian cancer specific cell response H q FVB mice demonstrated significantly greater anti CD cell responses scFvMTBHsp treated mice compared mice treated saline simple mixture MTBHsp plus P scFv measured IFN B production CD cells Figure B indicates scFvMTBHsp enhances anti tumor specific CD cell responses ovarian tumor bearing mice However significant difference seen number tumor infiltrating CD cells tumor infiltrating cells seen tumors mice different treatment groups indicating scFvMTBHsp may improve effector cell function rather number intratumoral CD cells Additional file Figure B Figure tumor specific CD cell functions tumor bearing mice following different treatments |
response scFvMTBHsp treatment mediated tumor specific CD cells scFvMTBHsp stimulates maturation murine bone marrow derived dendritic cells order investigate immunological mechanisms involved scFvMTBHsp enhanced anti tumor immune response first examined scFvMTBHsp MTBHsp proteins used study could stimulate maturation bone marrow derived dendritic cells shown previous studies stimulated CD c g ml scFvMTBHsp amount MTBHsp g ml g ml used positive control determine whether maturation attributable contamination recombinant proteins used study also incubated ng ml equivalent amount found g ml scFvMTBHsp h incubation scFvMTBHsp MTBHsp induced DC maturation indicated increase expression CD CD CD MHC class II molecules comparison control cultures medium increased expression DC maturation markers comparable cells stimulated g ml contamination control showed addition ng ml effects scFvMTBHsp MTBHsp allowing us scFvMTBHsp MTBHsp specific effects effects Figure B scFvMTBHsp induces DC maturation promotes antigen presentation cross presentation CD c isolated form FVB NJ mice incubated h g ml scFvMTBHsp g ml MTBHsp g ml positive control ng ml contamination control thick lines medium solid stained CD c CD CD CD MHC II analyzed flow cytometry CD c DCs Data representative three independent experiments wells B Median fluorescence intensity protein stimulated normalized maintained medium Data expressed means SEM units P values determined using One ANOVA followed multiple comparison tests C cultured FVB NJ mice BR FVB cells alone BR FVB cells pre MTBHsp b scFvMTBHsp c incubated BR FVB tumor cell cells B IFN expressions CD CD CD CD cells analyzed flow cytometry Data three independent experiments wells pooled analyzed using One ANOVA followed multiple comparison tests Data presented mean SEM Representative flow data presented E scFvMTBHsp enhanced tumor cell vivo Results reported difference media alone stimulated cells expressed frequency parent CD CD CD CD cells P values determined using One ANOVA followed multiple comparison tests p p p p |
protein regulates surface expression phenotypic markers DC maturation Interestingly addition CD CD MHC class II molecules expression CD also enhanced indicating possible positive feedback loop involving CD signaling components promoting DC maturation scFvMTBHsp fusion protein also targets tumor cells towards DCs propose binding fusion protein tumor cells DCs improves phagocytosis parts tumor cells DCs therefore tumor antigen processed MHC class II MHC class molecules presented CD CD cells could explain observed augmentation tumor antigen presentation cross presentation fusion protein vitro may also explain observed increased anti CD cell responses scFvMTBHsp treated ovarian tumor bearing mice although directly targeted vitro findings vivo tumor cell study used fusion protein activate mature DCs skin cells DCs captured tumor cells tumor cell fragments established fusion protein lymphoid presented tumor antigens na cells cells recovered lymph node showed significantly enhanced responses stimulation range tumor antigens Conclusion study provides preclinical evidence supports protein based immunotherapy induces anti tumor immune responses normally require dendritic cell based approaches MSLN targeted MTBHsp fusion protein binds MSLN tumor cells activates including DCs DCs vivo profile processed tumor antigens promotes tumor antigen presentation cross presentation enhances tumor specific CD CD cell responses Figure study supports continued exploration novel fusion protein alone combination immune checkpoint inhibitors following conventional surgical reduction chemotherapy MSLN expressing cancers new approach could significantly increase time recurrence survival humans ovarian cancer mesothelioma effective second line treatment options limited Figure schematic model showing scFvMTBHsp fusion protein binds MSLN tumor cells activates antigen presenting cells thus promoting uptake tumor cells tumor cell fragments promoting tumor antigen presentation cross presentation well tumor specific CD CD cell responses Methods proteins plasmid encodes full length MTBHsp Dr Medical Academy plasmid scFv encodes scFv fragment specific MSLN recombinant P scFv protein generated purified yeast Dr Cancer Research Center University DNA fragment corresponding amino acid |
h C CO Cells placed collected washed stained following conjugated antibodies anti CD c anti CD anti CD BD anti CD anti MHC class II BD cells analyzed laser BD Biosciences vitro tumor antigen presentation assay BR FVB cells harvested treated C plated well round plate g ml scFvMTBHsp g ml MTBHsp pre incubation C h CD c ratio tumor cells DCs added wells plate incubated C h generation BR FVB cell cells FVB NJ mice p injection C treated BR FVB cells sacrificed mice days according approved animal protocol harvested cells isolated using Cell Kit II BR FVB cell cells added wells DC cell ratio hour co culture BR FVB cell DCs BR FVB cell cells cells harvested washed resuspended PBS FBS stained CD CD CD IFN analyzed laser BD Biosciences vivo C treated ovarian tumor cells BR FVB ovarian tumor cells harvested enzyme free cell buffer treated C described Cells pre incubated scFvMTBHsp g cells MTBHsp g cells PBS alone C h week old FVB mice left right injected l PBS tumor cells l PBS without pre incubation scFvMTBHsp MTBHsp mice fixed least h PBS formalin routinely embedded paraffin thick sections stained routinely H E staining tumor infiltrating cells mice paraformaldehyde PBS tumor nodules fixed PBS additional hours washed PBS C thick frozen sections stained rat anti mouse CD BD Biosciences dilution rat anti mouse dilution followed rabbit anti rat immunoglobulin dilution developed acquired microscope histopathological immunohistochemical samples reviewed cellular performed blinded manner Statistical analysis Statistical differences three experimental groups analyzed using One ANOVA followed multiple comparison tests mean group compared every group followed multiple comparison tests mean group compared control group Statistical differences two experimental groups analyzed using test Survival analyzed rank test software GraphPad Software used statistical analysis DC cell scFv chain antibody variable fragment MSLN |
mice spleen sections used positive controls CD cells clearly evident sections Scale bar B CD cells quantified randomized fields Click file Additional file Figure Validation vivo depletion CD cells FVB NJ mice injected p g anti CD matched rat IgG described Methods mice vein depletion CD cells examined flow cytometry analysis peripheral blood cells stained conjugated anti CD days tumor Representative results flow analyses mice per group reported percentage CD cells lymphocytes B CD cells mice treated IgG anti CD compared p Click file manuscript memory ovarian cancer authors support work C Cancer Research Program supported V College London thank Zhou technical Dr Huang useful Dr Dr technical advice Dr advice statistical analysis assistance schematic figure J cells therapeutic vaccines cancer Nature reviews Immunology G G Cancer immunotherapy age Nature nature DM Cancer immunotherapy age J Clin Oncol CS ER Small CH AC R Xu Study immunotherapy resistant prostate cancer New England journal medicine JD cancer treatment future policy New England journal medicine Chang K Molecular differentiation antigen present ovarian cancers Natl Acad Sci USA P C B C SD E JL SE overexpressed majority ductal adenocarcinomas pancreas identification new pancreatic cancer marker analysis gene expression Clinical cancer research journal American Association Cancer Research R expression human lung cancer Clinical cancer research journal American Association Cancer Research Tang Z role tumor progression targeted therapy cancer agents medicinal R RJ H Phase study P recombinant anti given V infusion patients expressing mesothelioma ovarian pancreatic cancers Clinical cancer research journal American Association Cancer Research RJ R Phase trial continuous infusion anti recombinant P Clinical cancer research journal American Association Cancer Research MJ JR JM JR P J C KD Flow isolation human antibodies surface display library Nature biotechnology L JA B N N Development vitro validation anti prevent CA dependent cell Cancer |
respectively Figure B Figure proliferative effects AZD BEZ NCI H NCI H NCI H gefitinib resistant cell lines Cells treated varying concentrations AZD BEZ B alone h ranged Mean SD n inhibition MEK PI K mTOR synergistic effect gefitinib resistant NSCLC cell lines growth vitro anti proliferative effect combining MEK PI K mTOR inhibitor measured NCI H NCI H NCI H cells calculating combination index CI according method using fixed dose ratio AZD BEZ introduced cell cultures respective IC NCI H NCI H NCI H cell lines h Cell growth cell lines markedly decreased following combination treatment multiple paired concentrations compared either single agent alone cells viability data processed get CI corresponding effective dose NCI H NCI H NCI H cell lines Figure software NCI H cell line following CI value obtained NCI H NCI H cell line CI values respectively CI results suggested AZD BEZ produce anti proliferative effect NCI H NCI H NCI H cell lines Figures C Figure effects AZD BEZ combination therapy cell viability NCI H NCI H B NCI H C cells treated AZD alone BEZ alone AZD BEZ combination h Results analyzed according method combination index CI values calculated using software Mean SD n Tumor growth inhibition effect MEK PI K mTOR inhibitors gefitinib resistant NSCLC tumor models order investigate tumor growth inhibition effect AZD BEZ vivo used AZD BEZ AZD plus BEZ treat NCI H NCI H NCI H subcutaneous tumor models respectively weeks shown Figure C treatment AZD weeks able inhibit tumor growth NCI H C value slightly inhibit tumor growth NCI H NCI H subcutaneous tumor models C values whereas BEZ treatment caused approximately reduction tumor growth three subcutaneous tumor models contrast combined treatments two drugs almost completely inhibited NCI H NCI H NCI H tumor growth end weeks therapy Figure |
early clinical trial evaluation clinical activity single agent rarely observed MEK inhibitors gefitinib resistant NSCLC patients benefit blocking individual pathway largely limited presence feedback loop PI K MEK example inhibition MEK pathway results activation PI K pathway PI K activation mediates resistance MEK inhibition study order feedback concurrent blockade two pathways tested antitumor effects detected providing phase clinical trials Moreover early signs clinical benefit reported advanced cancer retrospective analysis patients receiving agents target pathways mutations mutation EGFR associated resistance gefitinib common mechanisms tumor cells resistance targeted drugs Although EGFR TKIs including developed overcome mediated resistance gefitinib recent clinical trials failed show monotherapy EGFR TKIs benefits patients NSCLC refractory gefitinib may due least part low class compounds wild type mutant EGFR addition overexpression frequently observed tumors mutation monotherapy mutant selective EGFR TKI may sufficient inhibit growth tumors acquired resistance gefitinib findings suggest combination MEK TKI PIK mTOR TKI may effective controlling resistant tumors Many KRAS mutant cancer cells shown sensitive MEK inhibitors KRAS mutations detected lung cancers dependent upon histology suggesting subset lung cancers would likely highly sensitive AZD finding AZD effective one distinct KRAS mutant human lung cancer NCI H models supports hypothesis Although monotherapy AZD resulted antitumor effects lung cancer models antitumor effects apparent NCI H lung adenocarcinoma model increased antitumor efficacy observed model associated differences inhibitory effect p AKT signaling pathway NCI H NCI H lung tumors However additional studies needed elucidate phenomenon study evaluated therapy directed MEK PI K mTOR distinct gefitinib resistant NSCLC xenograft models MEK PI K mTOR inhibition resulted antitumor effects gefitinib resistance NSCLC models blocking key intracellular pathways controlling cell proliferation survival demonstrated vitro vivo PI K mTOR inhibition BEZ also suppressed lung tumor angiogenesis targeted MEK PI K mTOR activation lung tumors resulting substantial effects may due significantly reduced expression MMP tumors |
concluded combination selective MEK inhibitor PI K mTOR inhibitor effective suppressing growth gefitinib resistant tumors caused EGFR mutation MET amplification KRAS PIK CA mutation findings represent promising strategy treatment gefitinib resistant NSCLC provide strong basis design clinical trials purpose Competing interests authors declare competing interests Authors contributions conceived designed experiments HL performed experiments analyzed data HL wrote paper whole experimental work revised manuscript authors read approved manuscript J Yang P Q C Lung cancer China challenges interventions Chest MJ LA HL PA E report status cancer |
least dose including range position errors included mm standard scanning proton therapy created based motion tumor volume three using four computed tomography image data dose compared photon proton plans well total time would required treatment radiotherapy delivery time per beam estimated per second proton therapy scanning proton centers per photon plans treatment planning parameters photon proton plans analyzed two sided paired tests using version Institute Inc NC Results three tumors measured three proton plans excellent coverage volume received least dose including examined comparable photon plans received least dose normal tissues lower doses ans achieved proton plans compared photon plans fact near complete spinal cord heart possible selection beam g volume comparison ans risk comparison photon proton plans P value Mean Mean target volume cc N cord dose Gy bilateral Mean lung dose Gy V V Mean dose Gy dose Gy dose Gy Index Index plans used four five non compared nine ten photon plans Figure average number monitor units per field range range would average beam time per field versus photon proton plans respectively differences monitor units beam time statistically significant P Table g Figure Comparison distributions left photon right treatment plans Table Comparison treatment time photon proton plans P value Mean Mean Total monitor units N field time per field Discussion transmission beam proton therapy planning significant dose irradiation lung tumors concern power impact peak location planning requires fewer selection optimal beam allows minimal dose adjacent normal tissues tumor dose may improved local control rates showed Gy single fraction comparable Gy four fractions protocol easily achieved using proton photon plans patients study proton therapy allow even higher doses still established normal tissues may better tumor control requires investigation clinical setting Patients planned required fewer vs reduce total treatment time low dose outside tumor average monitor units per field plans |
radiation oncology biology et al Radiation Therapy Oncology Group Phase Study Body Radiation Therapy Patients Stage Non Small Cell Lung Cancer International journal radiation oncology biology et al management respiratory motion radiation oncology report Group Medical body radiation therapy clinically challenging cases located stage non small cell lung cancer International journal radiation oncology biology et al randomized phase III comparison standard dose Gy versus high dose Gy chemoradiotherapy without stage III non small cell lung cancer Results radiation dose Journal Clinical Oncology Cancer Cancer Cancer X Ltd UK phase group adjuvant trial using biomarker based decision algorithm patients stage non small cell lung cancer NCT MD PhD G MD MS MD MD C MD C PhD PhD Zheng MD PhD J MD W PhD R MD Cancer Institute University MD Cancer Center Statistical Center University California California City California H Lee Cancer Center Cancer Research Clinical Oncology Program Ann author MD PhD Cancer Institute R Authors Cancer published Inc behalf American Cancer Society open access terms Creative Commons Attribution License permits use distribution medium provided original work properly cited use non commercial modifications made group adjuvant phase trial patients completely resected stage non small cell lung cancer tumor measuring cm designed assess feasibility preliminary efficacy patients therapy observation using based decision algorithm least sampling recommended lymph node good performance status adequate function formalin fixed paraffin embedded tumor specimen required repair cross group ERCC RRM analyzed using immunofluorescence based situ automated quantitative image analysis categorized high low using cutoff values Patients high ERCC RRM assigned observation others cycles cisplatin gemcitabine defined treatment assignment within days surgery patients estimate year survival Treatment assignment met feasibility criteria eligible patients patients year disease free overall survival rates respectively Protein levels RRM within previously established range ERCC levels slightly lower expected significantly correlated correlation coefficient |
scan chest adequate bone marrow liver renal function performance status provide smoking history Patients prior malignancy prior radiation chest significant according good medical practice excluded Patients registered trial within days surgery Tumor specimens retrieved central laboratory analyzed situ tumor levels ERCC RRM using immunofluorescence based automated quantitative analysis method cutoff levels determined patients stage disease ERCC RRM used specimens high low marker Fig appropriate therapeutic assignment statistical center participating therapeutic center however specific protein levels treatment center assignment based biomarker categories stratification parameters used diagram trial shown Patients high levels biomarkers received active surveillance patients low levels one biomarkers received cycles cisplatin dose mg day gemcitabine dose g days every days protocol included dose treatment addition targeted cytotoxic agents therapy maintenance permitted Gene Expression Analysis study required collection formalin fixed paraffin embedded tumor blocks therapy However local tissue block sections could submitted done reference laboratory investigators V Z Z measuring thickness placed glass slides situ quantification performed automated quantitative analysis method PM version Inc New CT previously described primary antibody detection ERCC clone F product code G H RRM R generated rabbit conjugated peptide specific N terminal RRM column New image data captured digital camera fluorescence microscope analyzed adjusted range full sections evaluated specimen multiple mm analyzed obtain representative level protein expression number dependent suitable areas tumor cells ranged median targets included tissue microarray control specimens triplicate control purposes Statistical Analysis primary objective current study feasibility biomarker based treatment assignment group setting true success rate biomarker based treatment assignment would considered feasible true success rate would feasible eligible patients successfully assigned treatment active monitoring within days surgery would considered evidence feasibility design power using exact test sided type error included year disease free survival DFS patients accepted treatment assignment subset patients received adjuvant chemotherapy However would comparison made treatment arms |
Institute version cancer DFS defined time date enrollment disease recurrence death due cause estimated according Kaplan method Cox regression model fit time surgery enrollment evaluate effect DFS natural log transformation applied raw protein measurement data correlation coefficient used test associations comparison baseline characteristics assigned treatment groups performed using Fisher exact test categorical variables test rank sum test continuous variables multivariable logistic model evaluate baseline factors treatment assignment fit using selection Median ERCC RRM expression levels compared using sample rank test percentage patients ERCC RRM compared rate using test statistical analyses performed using statistical software version Institute Inc NC significance level used analyses Patient Characteristics ensure adequate sample size eligible patients biomarker specific subgroups total patients registered April April participating sites Four patients lymph node sampling tumor measuring cm provides characteristics eligible patients Patient Disease Characteristics Patients P Accepted P N N N N N Age Median Mean Sex Female Male Non b b American Asian c c Stage disease cm cm performance status loss status Current quit e e adenocarcinoma P values shown sided b versus c versus loss versus e using exact test distribution assignment chemotherapy observation patients patients respectively significantly different P Fisher exact test expected rates patients patients respectively Based protein levels patients number low ERCC low RRM patients patients low ERCC high RRM patients high ERCC low RRM patients high ERCC RRM significantly different prior results P Fisher exact test respectively investigated whether treatment arm assignment varied patients smoking status histology age sex comparisons statistically significant associations found However multivariable logistic model found patients adenocarcinoma P potentially stage disease P likely assigned adjuvant chemotherapy ie likely low levels ERCC RRM One patients assigned observation patients assigned chemotherapy choice consent statistically significant difference patient characteristics accepted treatment assignment trial achieved primary feasibility objective treatment assignment within patients |
months range months months patients cm risk reduction reported tumors measuring cm risk increase reported significant treatment related toxicity reported patients Treatment related deaths occur patients inclusion molecular markers predictive therapeutic efficacy adjuvant decision algorithms would greatly improve clinical benefit reduce toxicity patients NSCLC approach particularly patients stage disease parameters risks benefits knowledge least well defined Recent advances molecular diagnostics resulted improved outcomes patients whose tumors mutations oncogenic signal transduction molecules therapeutic agents Similarly platinum agents target DNA gemcitabine targets required cellular proliferation also essential cellular functions Although knowledge specific oncogenic mutations identified date ERCC RRM emerged promising predictors efficacy cisplatin gemcitabine respectively conducted phase trial treatment selection based levels protein expression ERCC RRM patients completely resected stage NSCLC tumor cm primarily establish feasibility also evaluate preliminary efficacy assessed year survival rates achieved primary goal demonstrating within group environment treatment assignment achieved patients within days weeks established initiation adjuvant therapy surgery patients NSCLC first feasibility However important note surgical practice usually medical time initial therapeutic planning rather complete recovery substantially reduces time available molecular testing initiation adjuvant treatment found difference P community sites time surgery specimens reference laboratory community sites patients median days range days days sites patients median days range days days time specimen reporting median days range day days similar previous experience international trial patients advanced NSCLC median days range day days Based observations conclude current process routine specimen reference laboratory requires substantial improvements facilitate implementation based therapeutic decision making example developing National Cancer Institute project Lung Cancer Identification patients epidermal growth factor receptor mutated anaplastic lymphoma kinase ALK NSCLC targeted therapy need carefully consider issues results adjuvant trials retrospective staging project patients stage disease complete surgical resection reported year DFS rates rates patients stage disease corresponding year OS rates patients stage disease patients stage disease stage disease |
among trials cannot account differences study populations eligibility staging criteria data collection analysis spectrum protein levels ERCC RRM significant correlation levels molecules distribution patients gene expression categories current study consistent previous experience However current analysis method biomarker evaluation ie antibody based assessment situ protein levels suitable general clinical implementation several reasons First ERCC multiple isoforms cannot specifically available reagents isoform appears involved platinum induced DNA damage repair Second monoclonal antibody F consistently used ERCC protein expression analysis second protein common ERCC observation may account highly dependent performance antibody may explain significantly lower ERCC values current study compared prior results Third protein levels RRM particular degree ERCC appear influenced specimen processing procedures used collection sites Finally although method immunofluorescence based quantitative detection molecules well specimens analyzed processed simultaneously considerable variability specimens need processed individually extended period time required real time patient decision making However important note biochemical cell biological evidence ERCC RRM predictive molecules platinum gemcitabine efficacy remains small number recent clinical trials used ERCC therapeutic decision making include randomized phase trials patients advanced stage NSCLC published NCT NCT adjuvant trials yet published phase trial Surgical Therapy Stage NSCLC NCT ongoing phase trial International trial Results first trial NCT demonstrated improvement patient survival however authors raised possibility false negative result survival internal control group second trial NCT third trial NCT early discovery ERCC isoforms specificity problems F antibody fourth trial using ERCC tumor synthase mRNA expression levels treatment assignment compared cisplatin based control treatment OS primary endpoint planned patients Results trials help feasibility technical issues mentioned results current study demonstrated feasibility biomarker based decision algorithm group environment patients resected NSCLC identified current practice evaluation treatment patients may present rapid molecular based decision making Although efficacy data emerged trial specifically measure platinum induced DNA damage repair must developed clinical trials use agents |
JA patients gland carcinoma without conjunctival invasion JA H BP RC CL carcinoma personal experience cases j JA H BP RC CL carcinoma region review j Wu X Radiation therapy local control eyelid cell carcinoma report two cases review literature Surg Wang JR PC SC PK Chen MS eyelid tumours Taiwan R K beam therapy approach mucosal melanoma head neck pilot study Int J Oncol Biol j R R beam therapy unresectable malignancies nasal cavity Int J Oncol Biol j J gland carcinoma NA AA carcinomas clinicopathologic study cases five year follow data Pathol C C H carcinoma eyelid considering Br J carcinoma Lin DM carcinoma eyelid neck metastasis Head Neck Surg j carcinoma eyelid Acad E CD de V P Treatment conjunctival squamous cell carcinoma fluorouracil Br J RP CD treatment neoplasia G B Treatment outcomes metastatic cell carcinoma eyelid Int J j x J curative radiation therapy carcinoma eyelid Int J Oncol Biol j RP JJ PM gland carcinoma second malignancy following radiation therapy patients bilateral Cancer CO P J Thorac Oncol J Thorac Oncol Journal thoracic oncology publication International Association Study Lung Cancer Phase Study Patients Cell Lung Cancer J MD MD MD MD PhD MS PhD MD University California School Medicine Comprehensive Cancer Center California Cancer Center Portland University Comprehensive Cancer Center State University University San California correspondence MD University California School Medicine Comprehensive Cancer Center CA edu Copyright International Association Study Lung Cancer COX overexpression associated poor prognosis nonsmall cell lung cancer NSCLC may promote resistance epidermal growth factor receptor inhibitors randomized phase trial evaluated novel COX inhibitor combination erlotinib biomarker selected patients Patients stage IV NSCLC previously treated platinum based chemotherapy randomized mg day plus mg day erlotinib AP E placebo plus erlotinib P E day cycles disease progression toxicity primary endpoint time progression |
Japan e u ac jp Published University Press Access distributed terms Creative Commons Attribution licence permits non commercial reproduction distribution work medium provided original work altered transformed way work properly cited commercial use contact com family Japanese multiple members developed lung cancer Using whole exome sequencing identified novel germline mutation transmembrane domain human epidermal growth factor receptor gene G novel somatic mutation V E also detected transmembrane domain one lung adenocarcinomas transmembrane domain considered responsible subsequent activation family downstream signaling pathways performed functional analyses G V E proteins stable wild type protein G V E activated Akt addition activated p thought promote cell proliferation lung adenocarcinoma findings strongly suggest mutations transmembrane domain may oncogenic causing lung adenocarcinomas lung cancers rare among human malignancies Recent studies reported germline mutations epidermal growth factor receptor EGFR gene development lung cancer lung adenocarcinomas germline EGFR mutation carry secondary somatic EGFR mutations including exon deletion exon L R mutation family Japanese multiple members developed lung cancer III year old woman multiple lung adenocarcinomas bilateral lungs light year history smoking left lower multiple lung adenocarcinomas age years II never also multiple lung adenocarcinomas pulmonary two tumors performed II purpose diagnosis pleural found surgery multiple lesions removed partial III histological examination resected tumors II revealed adenocarcinoma situ minimally invasive adenocarcinoma whereas histological findings pleural indicated mucus containing adenocarcinoma III contained various subtypes adenocarcinoma including mucinous adenocarcinoma situ invasive mucinous adenocarcinoma addition normal lung parenchyma obtained III revealed small lesions presence changes throughout lung Supplementary available online analyses EGFR exons KRAS well immunohistochemical staining ALK protein resected tumors indicated genetic alterations genes chart suggested lung cancer dominant manner chart Japanese family multiple members developed lung cancer indicate men women respectively numbers bottom member indicate age time death time analysis line shows family members III multiple lung adenocarcinomas arrow |
mutations restricted tyrosine kinase domain According Cancer accessed genetic mutation reported type cancer Interestingly previous study reported mutation transmembrane domain V E rat gene corresponds V E human homolog induced oncogenic transformation addition vivo experiments showed V E mutation contributed stability resulting dysregulated receptor activation subsequent cell transformation Furthermore novel mutations located within motif X Ser X variant GG like motif N terminal portion transmembrane domain critically related C performed functional analysis mutant proteins found degradation protein administration G V E compared wild type Supplementary indicating higher stability mutant proteins wild type protein addition results protein kinase array indicated activation Akt p data shown Indeed Akt known activated kinase leads increased cell growth survival Also activation p shown contribute viability lung adenocarcinoma cells derived never light smokers western blot analysis Akt p successfully confirmed upregulation Akt p expression mutant Supplementary B G alteration might cause lung cancer studied investigated whether aggregation cancer ans could seen found II II developed renal gastric cancers respectively however also lung cancer reason types clinically apparent rarely found unclear G germline mutation may ans lung study limitations First potential mutation transmembrane domain confirmed models transgenic mice Second mutations lung cancers may limitation cases even targeting therapies similar types mutation developed identified novel germline mutation transmembrane domain lung adenocarcinomas mutation transmembrane domain may possible cause lung adenocarcinomas study supported Scientific Research Science Technology Japan H J conceived project K K K performed experiments H J N K K collected samples assisted experiments H K K K analyzed data H K F prepared manuscript input authors F project authors interest References susceptibility lung cancer may associated drug resistance mutation EGFR Nat Genet germline mutation EGFR V patient multiple lung adenocarcinomas family members lung cancer Ann Thorac Surg lung adenocarcinoma caused EGFR V line mutation J Clin Oncol |
However molecular mechanisms regulate miRNA biogenesis still largely unknown Recent studies shown transcription factors TFs regulate expression protein encoding genes also miRNA biogenesis RNA polymerase II dependent transcription Several TFs including p c HIF directly miRNA promoters regulate miRNA transcription reported protein Sp belongs specificity protein like family first TF identified mammalian cells Sp contains three type zinc DNA binding motifs GC rich promoter sequences Sp regulates coding genes encoding cyclin p cip E cadherin Sp genes involved variety physiological processes including cell cycle progression cell migration Sp also regulates expression noncoding genes Sp forms complex B miR b expression recruitment histone HDAC HDAC leukemia thereby contributes growth leukemia cells Sp also forms complex HDAC miR expression hepatocellular carcinoma contributes cell proliferation migration addition Sp activator miR c miR miR expression However studies assessed whether Sp regulates expression miRNAs involved lung tumorigenesis accumulation Sp required lung tumor growth investigation Sp mediated miRNA regulation needed study showed Sp suppressed FOXO expression via post transcriptional regulation elucidate whether miRNAs involved process used systematic screening approach identify Sp regulated miRNAs identified novel Sp regulated miRNA miR lung cancer cells demonstrated Sp downregulated FOXO expression upregulating miR expression results show miR functions enhance cancer cell proliferation acts tumor suppressor inhibit cancer metastasis Sp regulates miR expression previous studies demonstrated Sp involved induced lung tumorigenesis Using cDNA microarray analysis found Sp increased oncogene expression decreased tumor suppressor gene expression present study initially used software analyze promoters identified miRNAs According database human genome contains miRNA genes investigated whether Sp regulation miRNAs First screened upstream kb sequences miRNAs Using program identified miRNAs contained potential binding sites Sp Sp upregulated lung cancer expression target genes altered next examined expression miRNAs lung cancer According previous studies expression patterns miRNAs differed significantly lung cancer tissue normal lung tissue Supplementary Table |
growth monitored vivo miRZip contains gene signal miRZip expressing cells lower miRZip control cells Furthermore tumor volume tumor weight also lower miRZip mice miRZip mice N per group E results suggest miR overexpression facilitates lung tumor growth vivo Sp inhibits FOXO expression inducing miR expression investigate molecular mechanism underlying miR mediated cancer cell proliferation studied important miR target gene FOXO FOXO expression higher cells stably expressing miRZip control cells miR expression enhanced luciferase activity vector containing UTR FOXO B indicating miR downregulated FOXO expression determine whether Sp downregulated FOXO expression miR Sp expressed cells stably expressing miRZip C Overexpression Sp reduced FOXO protein expression miRZip stable cells increased FOXO levels miRZip expressing cells different effect Sp regulation FOXO expression FOXO miR Sp miRZip miRZip viruses infected H h individually FOXO level studied Western blotting anti FOXO antibodies miR level studied stem loop RT PCR B FOXO UTR transfected miRZip miRZip stably expressed H cells h cells harvested luciferase activity assays C doses Sp infected miRZip miRZip stably expressed H cells h FOXO level studied Western blotting using anti FOXO antibodies panel results three independent experiments shown panel b level statistical significance determined test p p Therefore investigated relationship Sp miR context FOXO regulation expression Sp FOXO patients lung cancer examined Figure normal tissue samples Sp levels low FOXO levels high tumor tissue samples two Sp expression patterns e high low Sp expression identified Samples higher Sp levels exhibited lower FOXO levels whereas samples lower Sp levels exhibited higher FOXO levels suggesting correlation Sp FOXO levels lung specimen Figure levels FOXO Sp lung cancer cell lines H CL CL studied Figure B levels Sp expression accompanied lower levels FOXO expression CL cells lower levels Sp expression accompanied higher levels FOXO expression H CL cells suggesting correlation Sp FOXO expression lung tumorigenesis |
migration activities H cells x expressing miRZip miRZip studied Transwell miRZip miRZip stably expressed H cells x l PBS injected lateral vein mice weeks mice number pulmonary tumor nodules calculated fixation lungs h panel number pulmonary metastatic tumor nodules counted panel b E FOXO miR H cells knockdown miRZip respectively migration cells x studies Transwell panel addition cell lysates harvested FOXO miR knockdown cells Western blotting using antibodies N cadherin catenin vimentin FOXO panel b respectively F map genes miRZip miRZip microarray data red color represents genes upregulated green color represents genes downregulated level statistical significance determined test p p p recent studies showed Sp increased growth lung cancer cells inhibits metastatic activity present study found Sp accumulated early stages cancer positively regulated miR gene expression FOXO expression thereby promote cancer cell growth addition decreased levels Sp late stages cancer increased expression FOXO N cadherin leading cancer metastasis Clinical samples lung cancer patients stage IV used study Sp level IHC staining anti Sp antibodies B diagram Sp regulates miR FOXO expression early late stages lung cancer progression Sp functions transcriptional activator p target genes HDACs Sp several types cancer including lung cancer understanding Sp transcriptional regulatory network may provide novel insights molecular treatment lung cancer previous studies lung cancer found Sp highly upregulated early stages cancer progression partially regulated late stages previous studies also showed regulation Sp protein stability phosphorylation contributed expression early late stages cancer respectively activation Notch pathway might activate ERK Sp thus Sp early stages cancer late stages Sp could leading recruitment E RNF followed degradation clarify molecular mechanism underlying gene regulation Sp used microarray analysis assess gene expression induced lung tumor transgenic mice identified genes potentially regulated Sp However genes conserved Sp binding motif within promoter region suggesting another regulatory mechanism involved Sp mediated gene regulation |
cell proliferation Sp overexpression also cancer cell growth post modifications affect protein function overexpressed proteins might completely processed could affect function Previous studies melanoma hepatocellular carcinoma indicated miR enhanced tumor metastasis However data shown indicated miR knockdown altered cell morphology increased migration invasion activities addition miR knockdown increased N cadherin levels suggesting miR promotes mesenchymal epithelial transition MET Previous studies shown enhances E cadherin catenin complex lung cancer cells Sp miR regulates lung cancer needs addressed future studies Finally miR levels lower CL cells CL cells resulting increased metastatic activity CL data suggest miR inhibits lung cancer metastasis previous study indicated Sp regulated late stages lung cancer progression Therefore late stages lung tumorigenesis miR expression regulated compared expression early stages led tumor metastasis least part increase FOXO expression still clear miR different roles different types cancer study Although found FOXO involved miR mediated lung cancer progression FOXO knockdown completely effects miR knockdown suggesting genes regulated miR contribute inhibition metastasis miR determined expression profile miR regulated genes Many metastasis related genes induced miR knockdown cells including CD CD cell membrane involved cell migration various cancer types Recent studies also showed tumor cells high CD expression maintained lung cancer drug resistance Another metastasis related gene induced miR knockdown membrane proteins E cadherin previous study showed combined Wnt pathway activation increased incidence lung cancer formation Given also involved activation Wnt pathway Sp miR might Wnt pathway addition also involves cancer metastasis showed miR Sp activated miRNA whose expression increased lung cancer miR lung cancer growth also suppressor lung cancer metastasis Cell culture transfection Human lung cancer cell lines H CL cultured modified medium Invitrogen CA human fibroblasts cultured Invitrogen human bronchial epithelial cells B cultured Thermo Scientific IL culture contained fetal bovine serum U ml G sodium g ml Invitrogen Cells cultured CO |
binding sites mutations site C G F CCA CTC CC R AG site C G F CCA CTC C R G performed PCR using plaque forming unit DNA polymerase Technologies Santa CA immunoprecipitation assay protocol performed described previously Briefly fixed complex mg normal rabbit IgG anti H anti Sp antibodies DNA analyzed PCR primer sequences promoter miR PCR analyses follows F CTC GG R CA primer sequences promoter miR PCR analyses follows F CTC G R primer sequences promoter p PCR analyses follows F CT R CCA GA DNA affinity assay DNA miR CCA CT miR GG p end complementary assay performed g labeled probe cell extract ml buffer mM mM pH mM mM mM incubation h complexes incubated l Sigma h complexes washed three times buffer Clinical specimens patients lung adenocarcinoma Human clinical specimens used study approved Clinical Research Ethics Committee Medical Center National Cheng University Taiwan surgical resection National Cheng University Hospital specimens patients lung adenocarcinomas collected immunohistochemical analysis RT PCR Western blotting shRNA production purchased Sp FOXO shRNA National Taiwan Taiwan miRZip miRZip System Biosciences CA obtained Research Center Clinical Medicine National Cheng University Hospital protocol described cells cotransfected g plasmid R g plasmid G g shRNA using h h incubation containing viral ps harvested filtered mm activated cell miRZip miRZip stable expression H cells washed PBS fixed cold ethanol overnight Cells washed cold PBS X min treatment g ml MD h cells stained g ml propidium iodide Sigma room temperature h Finally cells analyzed flow BD Biosciences NJ study animal experiment approved Animal Care Use Committee National Cheng University Female mice purchased National Laboratory Animal Center Taiwan miRZip miRZip stable expression H cells cells l PBS back mice IHC experimental process IHC performed described previous study Briefly blocked histological sections stained anti Sp anti FOXO antibodies |
seeded cm cultured h linear wound cellular created cell using tip cell washed PBS remove incubation CO h area migration light microscope evaluation Transwell migration assay cell migration assay performed using Transwell system mm size filter membrane Cells serum free DMEM wells cell serum free DMEM lower wells DMEM containing fetal bovine serum incubation h CO lower side filter membrane fixed stained cells counted microscope quantified J software National Health MD vivo metastasis assay miRZip miRZip stable expression H cells PBS vein injection total x cells ml PBS injected lateral vein mice weeks excised lungs fixed h Finally number pulmonary metastatic nodules surface lung counted analysis Total RNA extracted using miRZip miRZip stable expression H cells analysis performed Group Taiwan data analyzed using Bioinformatics work supported National Cheng University project Program World Research together B B obtained National Science Taiwan Supplementary Data available online including Supplementary References AP transcriptional gene regulation genome wide studies Cell Mol Life Sci CM Van neuronal post transcriptional Genes SD transcriptional regulation cancer progression control alternative splicing translation J Cell EC RNAs complementary UTR sequence motifs mediate negative post transcriptional regulation Nat Genet target recognition regulatory functions Cell H R E DNA methylation microRNA dysregulation cancer Mol Oncol Chen PS JL cancer J Sci F E oncogene KRAS targeted miR c U R J analysis microRNA expression lung cancer Int J Cancer AA NA ML Expression Serum Patients Lung Cancer Pulmonary Cell Biochem F Center MM J E Global cancer statistics CA Cancer J Clin R TG N Genetics biomarkers lung cancer treatment Lancet C K K DA JA enzyme associated non small cell lung cancer NSCLC recurrence metastasis J Jiang F potential biomarkers human solid tumors Cancer U G lung cancer microRNA signatures cancer prognosis Cancer J R Molecular pathways cancer Clin Cancer Res |
least subjects per clinic see calculations statistics first patients GP patient give permission contact taking part smoking cessation research possible genetic risk testing fact addressed Figure flow diagram recruitment principal investigator patient would like week smoking cessation clinic would test genetic susceptibility development lung cancer principal investigator Group B subjects Group test subjects confirm smoking cessation sessions full patient information consent form information slightly different group B Non test subjects within group practice nurse smoking cessation exclusion criteria criteria years smoking daily ii criteria years years smoking less daily history major depression conditions serious terminal illness cancers etc Patients would excluded due interactions used treatment choice smoking cessation Patients smoke less day patients genetic test take part research study referred practice nurse smoking cessation cessation group subjects subjects expressed interest genetic test gene based estimation susceptibility lung cancer participate see referral group B subjects subjects participate smoking cessation programme e proportion clinic recorded subjects first session research clinic asked principal investigator consent form concerns protocol explained full information consent form Group Group B different health centre Clinic fact health risks smoking including lung cancer option gene based test calculation lung cancer susceptibility subjects Clinic B given fact health risks smoking including lung cancer without reference gene based test principal investigator responsible fact gene based test Clinic fact Clinic B NHS lead smoking cessation B using NHS smoking cessation guidelines principal investigator medical centre session includes new near patient test salivary nicotine metabolite name session patients given advice therapies smoking cessation patients course contact GP followed seven weekly sessions follow session six months Figure adherence smoking cessation monitored weekly carbon measurements breath test principal investigator involved clinic gene based test determining subjects COPD practice records history session Participants smokers smokers cough use COPD even GP records Group B subjects month follow |
Subsequently principal investigator report back clinic patients estimated lung cancer risks session ensure balance control clinic principal investigator also Clinic B sessions see flow eight week clinic month follow clinic smoking cessation status carbon breath test score recorded feedback questionnaire used assess efficacy various components administered followed patients month follow session NHS principal investigator cessation rate assessed verified carbon breath salivary tests details see flow project Flow chart duration trial Flow chart project start week b Flow chart project week good eight week free smoking cessation clinic would expected regular NHS smoking cessation clinic month follow clinic may challenging consider essential take time study participants receive three Group B subjects month follow unable quit gene based test stage taking test test requires subjects within minutes prior sample taken within minutes water nurse taking sample take care avoid contact collection tip avoid DNA acid contamination package end carefully remove end collection tip inside times press tip taking sample tip ml tube end sample tube label onto sample label requires trial code subject test sample collection kept room temperature immediately necessary tubes containing C instructions samples Ltd material around tube place tube provided kit back per instructions containing sample tube box box Using service provided samples Science Park GA Patients asked form clearly test give estimation cancer risk test still development one copy form investigators one patient result test Lung cancer susceptibility calculated using test formula Lung cancer score number susceptible genotypes number protective genotypes positive family history past history COPD age years old laboratory reports include scores explanation scores risk category see subject aged years report also include score risk category would apply subject still age years questionnaires questionnaires slightly different groups questionnaire B questionnaire b contain direct reference gene based test Patients eight weeks six months complete questionnaires hand practice |
related diseases smoking cessation outcomes systematic review meta analysis Control Smith SM U contributing time taken symptoms lung cancer cross study SC SC G L CM online genetic test results among smokers related patients lung cancer pilot study Cancer RP R C Wu L GD GD TE Functional variants antioxidant genes smokers COPD normal lung function RP RJ P GD COPD prevalence increased lung cancer independent age sex smoking history Eur J RP RJ BA MJ GD R GD Lung cancer susceptibility model based age family history genetic variants PLoS ONE e journal pone RP RJ BA GD GWAS SNPs COPD Lung Cancer Lung Cancer Validation Study J Care Med RP RJ BA MJ GD R GD gene based risk score lung cancer susceptibility smokers ex smokers Med J RP RJ BA MJ GD Lung cancer gene associated COPD triple possible effect Eur J CM G P G J genetic susceptibility feedback smoking cessation program American smokers low Cancer SC SE C E MJ J Genetic Lung Cancer Risk Phase II J Health de screening loss lung function help smokers give Br J G R Effect smoking quit rate patients lung age quit randomised control trial BMJ bmj RJ RP B GD Lung cancer risk testing enhances uptake quit rates randomly recruited smokers gene based risk test J Care Med RJ RP B GD Gene based lung cancer risk score triggers smoking cessation randomly recruited smokers J Care Med West R series London Health Press RP RJ Smith cessation potential role risk assessment tools triggers Review Med J E details Clinical Lung Cancer Detection Study L C J feedback brief long term smoking outcomes comparison smokers without lung impairment Patient j SE C impact genetic testing smokers lung cancer risk J Health E NHS smoking services services delivery monitoring guidance |
initially present stage IV disease develop distant metastases several months diagnosis still lower five year survival rate Recently range systemic chemotherapy expanded targeted therapy including epidermal growth factor receptor EGFR vascular endothelial growth factor VEGF inhibitor therapies used advanced CRC patients increasing patient survival However CRC patients respond poorly targeted therapy despite presenting positive results targeted therapy specific mutation studies One possible explanation therapeutic failure tumor heterogeneity several studies reported possess genotype phenotype including KRAS p BRAF Therefore characteristics primary tumor site corresponding metastatic need improve management CRC patients metastatic diseases Furthermore understanding clinicopathological characteristics advanced CRC important development improvement systemic therapies Since et al first described cancer microenvironment seed theory growing evidence cancer associated might affect cancer cells contribute cancer progression main components cancer microenvironment lymphatic vessels inflammatory cells cancer associated fibroblasts CAFs current method activity cancer tissue assess density MVD lymphatic vessel density LVD respectively MVD proposed marker cancer associated angiogenesis identify patients high risk recurrence poor various cancers including CRC however prognostic correlation angiogenesis CRC still controversial Similar angiogenesis LVD received interest means lymphatic metastasis survival role tumor progression still unclear prominent component CAFs consistently activated affect many aspects tumor initiation invasion progression studies suggested CAFs may inhibit tumor progression studies proposed CAFs may promote progression prostate breast skin cancers context CRC et al suggested smooth muscle actin expressing CAFs might useful indicator poor prognosis However results restricted stage II III addition cancer cells genetic alterations CAFs demonstrated including loss instability genetic mutations Recently genetic inactivation PTEN CAFs reported breast cancer patients et al identified PTEN loss stromal fibroblasts resulted extensive extracellular matrix remodeling angiogenesis characteristic tumor progression However expression loss PTEN clinical significance investigated colorectal cancer patients aim study investigate characteristics including CAFs advanced CRC patients Additionally assessed intratumoral heterogeneity primary tumor primary tumor distant metastasis |
H L using light microscopy improve accuracy results Fig CRC cells considered internal negative controls large vessels considered internal positive controls CD layer medium large vessels considered internal positive controls Samples showing staining internal negative positive controls considered non excluded analysis using CS instrument Technologies Inc CA magnification Subsequently analyzed using Analysis v algorithm Technologies MVD LVD calculated positive mucosa positive area CAFs mm calculated areas staining staining g Representative sections four tumor locations stained CD antibodies Statistical analysis test Fisher exact test sided non continuous variables analysis continuous variables used compare parameter respect CRC site according clinicopathologic features correlation continuous variables analyzed using correlation coefficient determine best cut continuous variables predicting patient survival method performed using R program overall survival curves plotted using Kaplan product limit method significance differences curves determined using log rank test univariate multivariate regression analysis performed using Cox proportional hazards model determine hazard ratios P values less considered statistically significant statistical analysis excluding test performed SPSS statistics NY USA Results cancer associated according examined tumor locations clinicopathological characteristics advanced CRC patients described CRC patients synchronous metastases aggressive features including larger tumor size advanced pN stage presence venous invasion patients metastasis p characteristics advanced colorectal cancers Total P value n n n Age median range Sex Male Female colon colon primary tumor grade Low grade High grade stage N stage N N N invasion invasion heterogeneous values LVD MVD area shown Fig LVD highest center primary cancers median interquartile range IQR site lymph node metastases distant metastases MVD lower distant metastases median IQR primary cancer lymph node metastases area CAFs lowest distant metastases median IQR site center lymph node metastases addition stromal characteristics varied relation metastatic examined MVD LVD higher lung metastases liver lymph nodes p Fig However amounts CAFs consistent among different metastatic ans p |
including liver lung peritoneal distant lymph nodes metastatic ans examined LVD MVD highest lung previous study KRAS rate also significantly higher matched lung metastases matched metastatic ans underlying mechanism known could primary high LVD MVD produce lung metastases however results indicated LVD MVD center primary cancers lower patients lung metastases data shown may due physiological characteristics metastatic ans interactions cancer cells microenvironment within metastatic characteristics cancer cell clones lung metastasis However technical sampling errors also may possible thus large scale studies required Although numerous studies demonstrate association tumor microenvironment characteristics survival prognostic impacts MVD LVD still controversial studies presented active angiogenesis represented high MVD LVD associated poor prognosis aggressive clinicopathologic factors Recent meta analysis demonstrated LVD significantly associated disease free survival overall survival studies reported statistical significance MVD LVD survival et al reported high MVD LVD related better survival consecutive series liver metastases results based patients advanced disease distant metastasis showed high MVD LVD related improved survival might patients study confirmed distant metastasis could influence even delivery chemotherapeutic drug tumor However study limitations terms survival analysis enrolled CRC patients available resected cancer tissues primary tumors corresponding metastatic tumors advanced CRC patients metastatic diseases included far advanced cases enrolled Therefore might influenced survival results studies demonstrated anti effect fibroblasts However become clear CAFs contribute progression cancer prognostic significance various cancers also raised furthermore several studies observed genetic alterations CAFs PTEN loss CAFs observed breast cancer prognostic association suggested observed PTEN loss CAFs CRC patients frequently observed corresponding distant metastases suggested CAFs cancer cells altered gene expression Moreover loss PTEN expression CAFs distant metastases significantly correlated survival patients knowledge first results showing PTEN loss CAFs CRC patients Although research required might prognostic factor CRC patients large cohort advanced CRC patients synchronous distant metastasis demonstrated regional heterogeneity stromal microenvironment factors according tumor location |
J Cancer Tumor angiogenesis invasive breast carcinoma N Engl J Med et al Prognostic significance count colorectal cancer J Clin Oncol et al quantification primary colorectal carcinoma immunohistochemical study Br J Cancer lymphatic vessel density vascular endothelial growth factor C expression early stage squamous cell carcinoma Clin Cancer Res et al analysis markers predicting metastasis human gastric carcinoma lymph nodes Int J Cancer lymphatic vessels case identity J Natl Cancer Cell cell communication carcinogenesis Increased invasion metastasis BL melanoma inhibition response C BL mice Cancer Res conversion human stromal cell activation Natl Acad Sci U et al fibroblasts present invasive human breast carcinomas promote tumor growth angiogenesis elevated secretion Cell et al associated fibroblasts direct tumor progression initiated human epithelium Cancer Res et al predict disease recurrence colorectal cancer Clin Cancer Res alternative carcinogenesis pathway instability colorectal cancer Br J Cancer et al somatic mutations PTEN TP breast carcinomas Nat Genet et al stromal fibroblasts suppresses mammary epithelial tumours Nature van et al features outcome advanced colorectal cancer patients synchronous vs metastases Br J Cancer classification tumours digestive system et al anization Cancer Press Tissue array methods high clinicopathologic research Cancer Res et al transient EMT linked loss membranes indicates metastasis poor survival colorectal cancer Park epithelial mesenchymal transition cancer stem cell like phenotypes independent prognostic value gastric cancer Pathol de tumour environment heterogeneity therapeutic response Nature et al metastatic pattern according KRAS mutational status site specific KRAS status patients colorectal cancer BMC Cancer De et al Stage colorectal carcinoma VEGF immunohistochemical expression density correlation clinical outcome et al analysis vascular density area colorectal carcinoma using different markers comparison clinicopathologic prognostic factors Biol et al meta analysis relationship lymphatic density survival patient colorectal cancer et al vessel density density growth factor expression colorectal cancer Dis architecture colorectal carcinomas liver metastases |
expression limited number adult lung cells monitored X staining marker K V Four weeks later cells form small clusters However SPC alveolar type II cells able form lesions progressed adenomas adenocarcinomas contrast induction K V expression lung cells infection ps generated regions except proximal junction primarily made CC cells progressed form benign adenomas However alveolar exclusively made SPC cells progressed yield malignant adenocarcinomas infection induced inflammatory primarily made B cells inflammatory response essential development K adenomas generation SPC lesions Finally activation K V embryonic development control promoter CC SPC adenomas results taken together different types lung cells generate benign lesions response K Ras oncogenic signals However adult mice SPC cells able yield malignant adenocarcinomas inflammation mouse model non small cell lung cancer lung stem cells J Clin Oncol J Clin Oncol Journal Clinical Oncology X American Society Clinical Oncology Statistics Oncology Evaluation Tumor Response Using RECIST Data Tumor J J J J Clinic College NY European Research Treatment Cancer author J MD Division Statistics Clinic First St SW e edu American Society Clinical Oncology sought test validate predictive utility tumor response complete response CR partial response PR v stable disease SD v progressive disease PD disease control rate CR PR SD v PD tumor response CR PR v others using cut points PR PD data guide Response Evaluation Tumors RECIST version used Methods Data trials patients metastatic breast cancer nonsmall cell lung cancer colorectal cancer randomly training validation data sets pairs cut points PR PD considered PR decrease PD increase RECIST Cox proportional hazards models analyses weeks stratified study number lesions fewer three v three adjusted average baseline tumor size used assess impact overall survival OS Model assessed using concordance index c index Results RECIST cut points demonstrated predictive ability similar PR PD cut points tumor type similar predictive performance |
crizotinib response retrieved patient records least partial response treatment defined according Response Evaluation Tumors criteria e least decrease sum target lesions study evaluated classified service evaluation College Research Ethics Committee review sections protease pretreatment steps overnight available ALK dual color probe Molecular Tissue sections underwent nuclei Results analyzed interpreted accordance probe manufacturers instructions Non ALK showed yellow signals ALK appeared red green signals isolated red signal recommended cutoff used samples positive negative ALK nuclei additional five sections cut per case Three used immunohistochemical assays remaining two negative controls assays using monoclonal antibodies F ALK Abcam F assay performed using amplification step specified manufacturers protocol assays performed using conventional based staining amplification antibodies conditions employed given Table Assay stained sections examined without knowledge FISH status two independently proportion intensity immunohistochemical staining assigned consensus intensity staining recorded scale negative weak moderate strong stain due least partly signal amplification step visual intensity scoring antibody different e g moderate degree intensity seen stain would usually interpreted strong section stained proportion malignant cells staining positive recorded per estrogen receptor scoring breast cancer scale score intensity proportion also derived Statistical Analysis Statistical analyses performed using IC package according manufacturers recommendations Representative FISH images shown Figure positive cases showed greater cells ALK genes Three cases classified biopsy samples positively FISH signals cases FISH negative Representative fluorescence situ hybridization images showing normal signals nuclei multiple separated red signals B Three representative excision specimens adenocarcinoma Case negative three immunohistochemical assays F assay shows relatively high background signal amplification step positive three immunohistochemical assays clear cytoplasmic staining markedly reduced signal seen ALK assays case typical probably related absence amplification Case demonstrates cases show strong staining using non assays signal observed negative controls intensity staining three antibodies varied Fig B IHC assess three cases material two FISH negative one FISH positive |
test IHC result recent studies compare various immunohistochemical assays FISH detection ALK study et al identify FISH positive IHC negative cases explain two cases identifying co mutations oncogenes thereby tumor ALK one insufficient tumor material accurate IHC assessment et al compared assay using antibody FISH specimens achieved sensitivity specificity comparable findings small biopsy cases sensitivity specificity current study detected two false negative cases positive FISH negative three IHC assays combination two possible might represent tumors expressing ALK protein detectable levels false positive FISH result absence ALK protein despite presence ALK DNA tumors respond crizotinib might represent failure IHC assay poor antigen insufficient material another technical error case crizotinib therapy would still likely effective study includes seven cases positive FISH results data response crizotinib showed least partial response crizotinib therapy assessed Response Evaluation Tumors criteria single case showed response one two false Thus one case IHC test would predicted response specimen FISH interpretation difficult cells showed ALK signals fusion plus red green probes fusion plus isolated red signal Therefore seems possible represents technical failure FISH assay case excision specimen showed cells signals also shown mutation second gene PCR testing demonstrated loss exon endothelial growth factor receptor described another study characterized two false negative cases Thus tumors may well oncogene ALK kinase activity would consistent ALK protein expression IHC would expected best predictor response tyrosine kinase inhibitor therapy cases essential identify characterize false negative cases received crizotinib therapy addition seems likely IHC guide treatments false positive cases express high levels ALK genetic lesions current FISH assay Although identified false positives e FISH negative IHC positive cases sensitivity may FISH small number FISH negative cases study Several studies identified rare cases FISH detectable IHC confirmed reverse PCR cases would expected respond crizotinib recent study shows least one novel FISH indeed drive malignant phenotype |
J Thorac Oncol e e P J New response evaluation criteria solid tumours revised RECIST guideline version Eur J Cancer CI PA ALK lung adenocarcinoma multicenter comparison immunohistochemistry situ hybridization Pathol CM C J C reliable screening tool identification ALK non small cell lung carcinoma antibody dependent J Thorac Oncol SW use ALK immunohistochemistry FISH optimal detection ALK lung adenocarcinomas J Thorac Oncol B J Detection ALK positive non small cell lung cancers specimens high accuracy clone J Thorac Oncol Br J Cancer Br J Cancer Journal Cancer Nature Group Clinical Study phase II multicentre study ziv aflibercept combination cisplatin pemetrexed patients previously untreated advanced metastatic non squamous non small cell lung cancer aflibercept cisplatin pemetrexed NSCLC Chen H R J W J R J R R N B J W C J Liu L Gao B H Department Medicine Park Cancer Institute NY USA Oncology Clinical Research Center W St USA Department Medicine University School Medicine Cancer Institute Dr CA USA Department Oncology Comprehensive Cancer Center St G MD USA Department Medicine Cancer Center School Medicine Medical Center USA Cancer CO USA Department Medicine Hospital University University G Inc Road NY USA E Copyright Cancer Research UK Cancer Research UK months original publication work licensed Creative Commons Attribution License view copy license visit Background study evaluated efficacy safety ziv aflibercept combination cisplatin pemetrexed non small cell lung cancer NSCLC Methods single arm multicentre phase II trial enrolled patients previously untreated locally advanced metastatic non squamous NSCLC Patients received intravenous ziv aflibercept mg kg pemetrexed mg cisplatin mg every days six cycles administration ziv aflibercept continue disease progression toxicity cause co primary end points objective response rate ORR progression free survival PFS sample size patients Results study three confirmed two suspected cases posterior syndrome total patients enrolled Median age years |
PFS added cisplatin gemcitabine although OS significantly prolonged secondary end point case et al non squamous histology cisplatin pemetrexed active combination chemotherapy et al thus combinations platinum pemetrexed bevacizumab anti strong interest first line treatment advanced metastatic non squamous NSCLC et al b aflibercept NJ USA NY USA recombinant fusion protein consisting human VEGF receptor extracellular domains portion human immunoglobulin aflibercept binds VEGF acting high affinity ligand prevent binding endogenous receptor thereby inhibiting VEGF induced angiogenesis preclinical models et al cells expressing high levels highly susceptible blockade ziv aflibercept et al addition ziv aflibercept binds growth factor VEGF B could potentially inhibit cancer invasion Studies investigated ziv aflibercept single agent combination chemotherapeutic agents treatment various types cancers et al et al de et al et al August ziv aflibercept approved US FDA use metastatic colorectal cancer based results trial Van et al phase II study using ziv aflibercept monotherapy demonstrated objective responses pretreated patients advanced adenocarcinoma lung et al improvement response PFS OS observed combination docetaxel second line treatment NSCLC et al report results phase II trial ziv aflibercept combination cisplatin pemetrexed patients advanced metastatic non squamous NSCLC study conducted phase trial using regimen ziv aflibercept cisplatin pemetrexed et al phase trial determined recommended dose ziv aflibercept mg kg every days used current phase II trial aimed evaluate efficacy safety ziv aflibercept combination cisplatin pemetrexed first line treatment advanced metastatic NSCLC Materials methods Patients eligible study histologically confirmed untreated locally advanced metastatic NSCLC disease per Response Evaluation Tumors RECIST criteria et al Patients squamous histology lesions excluded Patients years age older Oncology Group performance status PS adequate bone marrow renal hepatic functions calculated creatinine clearance ml min Patients excluded study brain central nervous system metastases blood pressure BP mm blood pressure mm bleeding evidence active bleeding recent significant cardiovascular conditions |
patients enrolled participating sites across United States January December patient demographics Median age years male PS evaluation Treatment exposure dose modifications patients received least one dose three study drugs median days treatment range days seven patients completed four cycles combination treatment median range cycles pemetrexed range cycles cisplatin administered median dose intensity range mg per week pemetrexed range mg per week cisplatin dose pemetrexed cisplatin completed six cycles ziv aflibercept median dose intensity ziv aflibercept mg kg per week close planned intensity mg kg per week treatment disease progression AEs others including consent investigator patients least one cycle delayed patients least dose modification ziv aflibercept pemetrexed cisplatin events five patients experienced treatment adverse event grade patients experienced serious common nausea fatigue hypertension common grade patients respectively common nine patients experienced least one grade eight patients mostly patient experienced least one abnormal value grade commonly patients died clinical cutoff study died due disease progression two due pneumonia December five patients experienced neurological symptoms including altered mental status four one two four patients Three patients brain MRI consistent B MRI negative two patients three patients diagnosed women aged years respectively One three patients study history hypertension three patients experienced elevated BP two patients reduced therapy one patient decreased baseline ml min one cycle decreased ml min four cycles diagnosed one two five cycles ziv aflibercept respectively Two patients recovered one died due disease progression resolution information available two three patients one suspected case systemic concentrations free ziv aflibercept within range patients treatment cohort phase study using regimen N five patients experienced mild diagnosed et al cases observed ziv aflibercept clinical development programme rate observed study much higher previously reported e patients treated ziv aflibercept monotherapy combination chemotherapy product insert result study Patients remained study updated safety information regarding addition continued close monitoring |
baseline antibody end treatment visit patient completed six cycles combination treatment without dose delay reduction grade AEs stable disease one negative baseline positive visit patient experienced minutes start ziv aflibercept infusion day second cycle Study drug patient PK parameters profile different negative patients probably formation Discussion aflibercept tested single agent combination chemotherapy treatment NSCLC et al et al basis activity safety profile conducted current phase II study explore efficacy ziv aflibercept first line setting Similar trials et al et al et al study designed test three drug regimen including anti angiogenesis agent case ziv aflibercept cisplatin pemetrexed addition maintenance therapy single agent ziv aflibercept intended benefits delay development resistance approach first tested phase dose study used regimen ziv aflibercept cisplatin pemetrexed patients advanced solid tumours et al study population representative patients advanced NSCLC Overall median ziv aflibercept dose intensity similar planned intensity dose pemetrexed cisplatin study higher pemetrexed cisplatin arm respectively phase III trial et al PK ziv aflibercept study similar observed phase study mean observed terminal independent ziv aflibercept dose ziv aflibercept alter pemetrexed PK Development rare event leading reduced drug concentration one patient experienced therapeutic proteins potential however severe reactions rare Although study early two co primary end points ORR median PFS months accordance first line NSCLC studies et al et al slightly less regimens another anti VEGF agent et al et al However statistical power test primary hypothesis ziv aflibercept would enhance efficacy standard chemotherapy NSCLC predict degree VEGF blockade vivo currently available studies identified increased production possible marker VEGF inhibition animal data indicate VEGF inhibition including ziv aflibercept modulates via increased hepatic synthesis et al also associated increased NSCLC et al reduced Wu Therefore study explored whether increase observed previously could presence chemotherapy would correlate anti activity trend towards increase change level found small subset patients |
ziv aflibercept combination standard chemotherapy et al likely development may regimen dependent rather dose schedule dependent posterior syndrome described brain syndrome frequently related hypertension fluid possibly cytotoxic effects immunosuppressive agents vascular et al Risk factors include female sex hypertension renal dysfunction et al well anticancer agents diagnosed women associated combination regimens gemcitabine commonly associated Treatment including cisplatin without concomitant anti VEGF therapy associated et al whereas pemetrexed study literature three cases diagnosed women may related anticancer interaction inducing altered endothelial dysfunction decrease VEGF signalling increases risk including bevacizumab sunitinib sorafenib ziv aflibercept suggesting class effect toxicity et al Clinical features neurological symptoms characterized altered mental status visual systemic signs hypertension variable ranging hours month therapy Lee et al findings brain MRI demonstrate bilateral agent treatment hypertension renal indicated usually always clinically phase II study designed evaluate ziv aflibercept combination cisplatin pemetrexed patients untreated advanced metastatic non squamous NSCLC However three confirmed two suspected cases led early trial reason increased incidence might related increased BP Although ORR median PFS accordance first line NSCLC studies combination ziv aflibercept cisplatin pemetrexed NSCLC efforts identify predictive biomarkers anti VEGF agents warranted study supported thank patients participated study also thank participating study sites investigators research staff work published standard license publish agreement months work become available license terms Creative Commons Attribution License Liu Gao Inc remaining authors declare interest J P PA R R Van E analysis anti VEGF class adverse events three double placebo controlled phase III trials IV aflibercept J Clin Oncol syndrome part fundamental imaging clinical features J SE AB JR JH Clinical course advanced non small cell lung cancer patients hypertension treatment bevacizumab combination carboplatin paclitaxel J Clin Oncol de Chang SM MR TF K J F AB Chen MD Phase II study aflibercept recurrent malignant glioma North American Tumor Study |
Van E J R H J P van GA V J J R C aflibercept fluorouracil improves survival phase III randomized trial patients metastatic colorectal cancer previously treated oxaliplatin based regimen J Clin Oncol C Zhang L posterior syndrome cancer Oncol Rep KaplanMeier curve PFS N Median PFS months CI B MRI patient diagnosed increased signal areas restricted diffusion cortex regions near regions arrows focal enhancing lesions suggest metastatic disease Baseline demographics N Age years Median years Age years category N N Male Female N American Asian American American performance status N Oncology Group Summary common NCI grade N grades N Grade N Number patients common NCI grade loss Blood creatinine increased pain peripheral treatment adverse events Mean observed parameters free ziv aflibercept aflibercept N Mean Day CL l per day per kg V l kg C max mg l C last mg l max Day last Day Day mg l Day area concentration curve time zero CL clearance last positive plasma concentration plasma concentration mean time time last positive plasma concentration time required reach plasma concentration observed half life volume distribution state PLoS One one Public Science San USA Research Biology Molecular Cell Biology Signaling Signaling Medicine Oncology Cancer Research Immune Tumor Cancer Cancer Cancer Treatment Gene Therapy Lung Tumors p catenin Lung Cancer Cells E cadherin Effect p ctn EMT Lung Cancer Zhang Zhao Jiang Zhang Zhao Wu Xu Wang Department Pathology First Affiliated Hospital College Medical Sciences China Medical University China Department Radiology First Affiliated Hospital China Medical University China University E com Competing authors competing interests exist designed experiments experiments data reagents materials analysis tools paper e Zhang et al open access distributed terms Creative Commons Attribution License permits unrestricted use distribution reproduction medium provided original author source epithelial mesenchymal transition EMT important process tumor development |
expression p ctn correlated expression E cadherin vimentin lymph node metastasis immunohistochemistry detected expression levels p ctn E cadherin vimentin lung cancer cells Western blot screened cell lines expressing low high levels p ctn E cadherin membrane cytoplasm expression EMT related molecules cell invasion also investigated knockdown endogenous p ctn overexpression transfection p ctn plasmids cells Materials Methods Materials study conducted approval institutional review board China Medical University consent given participants information stored hospital database specimens used study clinical investigations conducted according expressed Samples collected cases squamous cell lung cancer lung adenocarcinoma diagnosed First Affiliated Hospital China Medical University China samples male female patients average age years samples classified according lung tumor histological criteria World Health anization squamous cell lung carcinoma cases lung carcinoma cases cases highly differentiated eight poorly differentiated Lymph node metastases present cases selected cases lymph node metastases compare metastatic nodules primary tumor Tumor staging performed according tumor node metastasis TNM staging system International Cancer cases stage III cases stage patients received radiotherapy chemotherapy operation given standard treatment following surgery samples fixed formalin embedded paraffin stained hematoxylin eosin pathological analysis diagnosis Cell culture human bronchial epithelial HBE cells H H H cell lines obtained American Type USA SPC cell lines purchased Shanghai Cell Chinese Academy Science human lung ADC cell lines purchased Shanghai Co Ltd stored Department Pathology Medical University Cells cultured Invitrogen CA USA containing fetal serum Invitrogen ml Sigma St USA mg ml Sigma construction transfection Expression plasmids p ctn isoforms Dr B Department Cancer Biology University School Medicine USA described previously p ctn siRNA Co Ltd China used experiments follows si h cells transfected p ctn siRNA plasmids expressing p ctn isoforms using Invitrogen CA Germany according manufacturer instructions paraffin embedded samples cut thick sections bronchial epithelium present tumor slides used internal positive control |
incubation labeled secondary antibody goat anti mouse labeled goat anti rabbit IgG cat E E San CA USA nuclei propidium iodide microscopy performed using TE microscope NY USA microscopy performed using laser scanning microscope NY USA cell invasion assay cell invasion assays performed according manufacturer instructions USA l cell suspension cells added upper chamber lower chamber medium containing fetal serum upper lower chamber separated membrane cells incubated h C CO medium cells fixed min stained hematoxylin Sigma filter numbers cells lower surface membrane five different fields magnification counted randomly using E microscope mean calculated data obtained experiment repeated three times Statistical analysis statistical analyses performed using SPSS SPSS Inc IL USA software test used analyze immunohistochemistry data independent samples test used examine transwell experimental data P values considered statistically significant Results expression p ctn positively correlates E cadherin expression negatively correlates vimentin expression lymph node metastasis bronchial epithelial tissues showed p ctn membrane proportion lung cancer tissues expressing p ctn membrane significantly lower p ctn cytoplasmic expression E cadherin expressed membrane normal bronchial epithelium tissues rate positive expression decreased negative expression significantly increased E cadherin lung cancer tissues negatively expressed normal bronchial epithelial tissues rate positive expression increased lung cancer tissue appears lung cancer tissues cytoplasmic nuclear localization p ctn express vimentin comparison localization versus nuclear localization p ctn showed increased lymph node metastasis comparison localization Statistical analysis showed localization p ctn closely related E cadherin expression vimentin expression lymph node metastasis P words p ctn membrane expression positively correlated E cadherin expression negatively correlated vimentin expression lymph node metastasis B meanwhile p ctn cytoplasmic expression negatively correlated E cadherin expression positively correlated vimentin expression lymph node metastasis C g analysis p ctn E cadherin vimentin localization NSCLC E cadherin p ctn membrane positive vimentin negative normal bronchial epithelial cells |
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Biomedical Text Publication Classification Dataset
Overview
This dataset contains text data for classifying biomedical publications. Each sample is stored in a separate text file, with features space-separated on a single line. The dataset is structured to be compatible with Lumina AI's Random Contrast Learning (RCL) algorithm via the PrismRCL application or API.
Dataset Structure
The dataset is organized into the following structure:
Cancer_Documents_Classification/ train_data/ category_1/ sample_0.txt sample_1.txt ... category_2/ sample_0.txt sample_1.txt ... test_data/ category_1/ sample_0.txt sample_1.txt ... category_2/ sample_0.txt sample_1.txt ...
Note: All text file names must be unique across all category folders.
Features
- Tabular Data: Each text file contains space-separated values representing the features of a sample.
- Categories: There are multiple categories, each represented by a separate folder based on the type of publication.
Usage (not pre-split; optimal parameters)
Here is an example of how to load the dataset using PrismRCL:
C:\PrismRCL\PrismRCL.exe chisquared rclticks=15 boxdown=0 channelpick=5 data=C:\path\to\Cancer_Documents_Classification_mm testsize=0.1 savemodel=C:\path\to\models\mymodel.classify log=C:\path\to\log_files stopwhendone
Explanation of Command:
C:\PrismRCL\PrismRCL.exe: Path to the PrismRCL executable for classificationchisquared: Specifies Chi-squared as the training evaluation methodrclticks=15: Sets the number of RCL iterations during training to 15boxdown=0: Configuration parameter for training behaviorchannelpick=5: RCL training parameterdata=C:\path\to\Cancer_Documents_Classification_mm: Path to the complete dataset for Cancer Documents Classificationtestsize=0.1: Specifies that 10% of the data should be used for testingsavemodel=C:\path\to\models\mymodel.classify: Path to save the resulting trained modellog=C:\path\to\log_files: Directory path for storing log files of the training processstopwhendone: Instructs PrismRCL to end the session once training is complete
License
This dataset is licensed under the Creative Commons Attribution 4.0 International License. See the LICENSE file for more details.
Original Source
This dataset was originally sourced from the Kaggle Dataset Repository. Please cite the original source if you use this dataset in your research or applications.
Additional Information
The data values have been prepared to ensure compatibility with PrismRCL. No normalization is required as of version 2.4.0. ```
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