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Chemical Characterization of Honey and Its Effect (Alone as well as with Synthesized Silver Nanoparticles) on Microbial Pathogens and Human Cancer Cell Lines Growth.

The antibacterial, anticancer, and wound-healing effects of honey can vary according to the type, geographical region, honey bee species, and source of the flowers. Nanotechnology is an innovative and emerging field of science with an enormous potential role in medical, cosmetics, and industrial usages globally. Metal nanoparticles that derived from silver and range between 1 nm and 100 nm in size are called silver nanoparticles (AgNPs). Much advanced research AgNPs has been conducted due to their potential antibacterial and anticancer activity, chemical stability, and ease of synthesis. The purpose of the present study was to explore the physicochemical properties of honey and the potential to use forest honey to synthesize AgNPs as well as to appraise the nanoparticles antimicrobial and anticancer effects. Here, we used three different percentages of forest honey (20%, 40%, and 80%) as biogenic mediators to synthesize AgNPs at room temperature. The development of AgNPs was confirmed by color change (to the naked eye) and ultraviolet-visible spectroscopy studies, respectively. The absorbance peak obtained between 464 to 4720 nm validated both the surface plasmon resonance (SPR) band and the formation of AgNPs. Regarding the sugar profile, the contents of maltose and glucose were lower than the content of fructose. In addition, the results showed that the SPR band of AgNPs increased as the percentage of forest honey increased due to the elevation of the concentration of the bio-reducing agent. A bacterial growth kinetic assay indicated the strong antibacterial efficacy of honey with silver nanoparticles against each tested bacterial strain. Honey with nanotherapy was the most effective against hepatocellular carcinoma (HepG2) and colon cancer (HCT 116) cells, with IC

Carrot Intake and Risk of Developing Cancer A Prospective Cohort Study.

A prospectively followed Danish cohort of 55,756 citizens with an observation time upwards of 25 years was investigated for association between eating raw carrots on a regular basis and developing various adenocarcinoma-dominant cancers and leukemia. Mean age at inclusion was 56.2 years (SD 4.4 years), and 52% were females. A dose-dependent reduction in incidence was seen for cancer of the lung (HR 0.76, CI95% 0.66 0.87) and pancreas (HR 0.79, CI95% 0.61 1.03), as well as leukemia (HR 0.91, CI95% 0.68 1.21). Only for lung cancer was the association significant. In the case of pancreatic cancer, a possible type 1 error was present due to a low number of cancers. In cases of breast and prostate cancer, no association and no dose response were demonstrated. The association seen for lung and pancreatic cancer parallels that earlier demonstrated for large bowel cancer and indicates a cancer-protective effect from daily intake of raw carrots not limited to gastrointestinal adenocarcinomas. Processed carrots exhibited no effect. The preventive effect could be due to the polyacetylenic compounds falcarinol and falcarindiol in carrots, whereas carotene may not have an effect. The polyacetylenes are inactivated by heating, supporting our findings that only raw carrot intake has an effect. Indirect evidence for the cancer preventive effect of carrots in humans has reached a level where a prospective human trial is now timely.

Intermittent Fasting in Breast Cancer A Systematic Review and Critical Update of Available Studies.

Breast cancer (BC) is the most-frequent malignancy amongst women, whereas obesity and excess caloric consumption increase the risk for developing the disease. The objective of this systematic review was to examine the impact of intermittent fasting (IF) on previously diagnosed BC patients, regarding quality of life (QoL) scores during chemotherapy, chemotherapy-induced toxicity, radiological response and BC recurrence, endocrine-related outcomes, as well as IF-induced adverse effects in these populations. A comprehensive search was conducted between 31 December 2010 and 31 October 2022, using the PubMed, CINAHL, Cochrane, Web of Science, and Scopus databases. Two investigators independently performed abstract screenings, full-text screenings, and data extraction, and the Mixed Method Appraisal Tool (MMAT) was used to evaluate the quality of the selected studies. We screened 468 papers, 10 of which were selected for data synthesis. All patients were female adults whose age ranged between 27 and 78 years. Participants in all studies were women diagnosed with BC of one of the following stages I, II (HER2-), III (HER2-), IV, LUMINAL-A, LUMINAL-B (HER2-). Notably, IF during chemotherapy was found to be feasible, safe and able to relieve chemotherapy-induced adverse effects and cytotoxicity. IF seemed to improve QoL during chemotherapy, through the reduction of fatigue, nausea and headaches, however data were characterized as low quality. IF was found to reduce chemotherapy-induced DNA damage and augmented optimal glycemic regulation, improving serum glucose, insulin, and IGF-1 concentrations. A remarkable heterogeneity of duration of dietary patterns was observed among available studies. In conclusion, we failed to identify any IF-related beneficial effects on the QoL, response after chemotherapy or related symptoms, as well as measures of tumor recurrence in BC patients. We identified a potential beneficial effect of IF on chemotherapy-induced toxicity, based on markers of DNA and leukocyte damage however, these results were derived from three studies and require further validation. Further studies with appropriate design and larger sample sizes are warranted to elucidate its potential standard incorporation in daily clinical practice.

Narrow Leafed Lupin (

Breast cancer (BC) is the most widespread tumor in women and the second type of most common cancer worldwide. Despite all the technical and medical advances in existing therapies, between 30 and 50% of patients with BC will develop metastasis, which contributes to the failure of existing treatments. This situation urges the need to find more effective prevention and treatment strategies like the use of plant-based nutraceutical compounds. In this context, we purified three Narrow Leafed Lupin (NLL) β-conglutins isoforms using affinity-chromatography and evaluated their effectiveness in terms of viability, proliferation, apoptosis, stemness properties, and mechanism of action on both BC cell lines and a healthy one. NLL β-conglutins proteins have very promising effects at the molecular level on BC cells at very low concentrations, emerging as a potential natural cytotoxic agent and preserving the viability of healthy cells. These proteins could act through a dual mechanism involving tumorigenic and stemness-related genes such as SIRT1 and FoxO1, depending on the state of p53. More studies must be carried out to completely understand the underlying mechanisms of action of these nutraceutical compounds in BC in vitro and in vivo, and their potential use for the inhibition of other cancer cell types.

A Review of Different Types of Liposomes and Their Advancements as a Form of Gene Therapy Treatment for Breast Cancer.

Breast cancer incidence and mortality rates have increased exponentially during the last decade, particularly among female patients. Current therapies, including surgery and chemotherapy, have significant negative physical and mental impacts on patients. As a safer alternative, gene therapy utilising a therapeutic gene with the potential to treat various ailments is being considered. Delivery of the gene generally utilises viral vectors. However, immunological reactions and even mortality have been recorded as side effects. As a result, non-viral vectors, such as liposomes, a system composed of lipid bilayers formed into nanoparticles, are being studied. Liposomes have demonstrated tremendous potential due to their limitless ability to combine many functions into a system with desirable characteristics and functionality. This article discusses cationic, anionic, and neutral liposomes with their stability, cytotoxicity, transfection ability, cellular uptake, and limitation as a gene carrier suitable for gene therapy specifically for cancer. Due to the more practical approach of employing electrostatic contact with the negatively charged nucleic acid and the cell membrane for absorption purposes, cationic liposomes appear to be more suited for formulation for gene delivery and therapy for breast cancer treatment. As the other alternatives have numerous complicated additional modifications, attachments need to be made to achieve a functional gene therapy system for breast cancer treatment, which were also discussed in this review. This review aimed to increase understanding and build a viable breast cancer gene therapy treatment strategy.

Towards Developing Novel Prostate Cancer Recurrence Suppressors Acute Toxicity of Pseurotin A, an Orally Active PCSK9 Axis-Targeting Small-Molecule in Swiss Albino Mice.

The proprotein convertase subtilisin kexin type 9 (PCSK9) emerged as a molecular target of great interest for the management of cardiovascular disorders due to its ability to reduce low density lipoprotein (LDL) cholesterol by binding and targeting at LDLR for lysosomal degradation in cells. Preliminary studies revealed that pseurotin A (PsA), a spiro-heterocyclic γ-lactam alkaloid from several marine and terrestrial

Mushroom-Derived Compounds as Metabolic Modulators in Cancer.

Cancer is responsible for lifelong disability and decreased quality of life. Cancer-associated changes in metabolism, in particular carbohydrate, lipid, and protein, offer a new paradigm of metabolic hits. Hence, targeting the latter, as well as related cross-linked signalling pathways, can reverse the malignant phenotype of transformed cells. The systemic toxicity and pharmacokinetic limitations of existing drugs prompt the discovery of multi-targeted and safe compounds from natural products. Mushrooms possess biological activities relevant to disease-fighting and to the prevention of cancer. They have a long-standing tradition of use in ethnomedicine and have been included as an adjunct therapy during and after oncological care. Mushroom-derived compounds have also been reported to target the key signature of cancer cells in in vitro and in vivo studies. The identification of metabolic pathways whose inhibition selectively affects cancer cells appears as an interesting approach to halting cell proliferation. For instance, panepoxydone exerted protective mechanisms against breast cancer initiation and progression by suppressing lactate dehydrogenase A expression levels and reinducing lactate dehydrogenase B expression levels. This further led to the accumulation of pyruvate, the activation of the electron transport chain, and increased levels of reactive oxygen species, which eventually triggered mitochondrial apoptosis in the breast cancer cells. Furthermore, the inhibition of hexokinase 2 by neoalbaconol induced selective cytotoxicity against nasopharyngeal carcinoma cell lines, and these effects were also observed in mouse models. Finally, GL22 inhibited hepatic tumour growth by downregulating the mRNA levels of fatty acid-binding proteins and blocking fatty acid transport and impairing cardiolipin biosynthesis. The present review, therefore, will highlight how the metabolites isolated from mushrooms can target potential biomarkers in metabolic reprogramming.

Folic Acid Functionalized Diallyl Trisulfide-Solid Lipid Nanoparticles for Targeting Triple Negative Breast Cancer.

DATS (diallyl trisulfide), an anti-oxidant and cytotoxic chemical derived from the plant garlic, has been found to have potential therapeutic activity against triple-negative breast cancer (TNBC). Its hydrophobicity, short half-life, lack of target selectivity, and limited bioavailability at the tumor site limit its efficacy in treating TNBC. Overexpression of the Folate receptor on the surface of TNBC is a well-known target receptor for overcoming off-targeting, and lipid nanoparticles solve the limitations of limited bioavailability and short half-life. In order to overcome these constraints, we developed folic acid (FA)-conjugated DATS-SLNs in this research. The design of experiment (DoE) method was employed to optimize the FA-DATS-SLNs nanoformulation, which resulted in a particle size of 168.2 ± 3.78 nm and a DATS entrapment of 71.91 ± 6.27%. The similarity index between MCF-7 and MDA-MB-231 cell lines demonstrates that FA-DATS-SLNs are more therapeutically efficacious in the treatment of aggravating TNBC. Higher cellular internalization and efficient Bcl2 protein downregulation support the hypothesis that functionalization of the FA on the surface of DATS-SLNs improves anticancer efficacy when compared with DATS and DATS-SLNs. FA-functionalized DATS-SLNs have demonstrated to be a promising therapeutic strategy for TNBC management.

Ulvophyte Green Algae

Marine algae have excellent bioresource properties with potential nutritional and bioactive therapeutic benefits, but studies regarding

Impact of AgZnO Reinforcements on the Anticancer and Biological Performances of CAAgZnO Nanocomposite Materials.

In this study, an unpretentious, non-toxic, and cost-effective dissolution casting method was utilized to synthesize a group of anticancer and biologically active hybrid nanocomposite materials containing biopolymer cellulose acetate. Pristine ZnO and Ag

Studies on the Complexation of Platinum(II) by Some 4-Nitroisoxazoles and Testing the Cytotoxic Activity of the Resulting Complexes.

Two novel platinum(II) complexes (

Biosynthesized Silver Nanoparticles Using

In this study, we report the green synthesis of silver nanoparticles (AgNPs) from

Bioactive Clerodane Diterpenoids from the Leaves of

Ferritin-Coated SPIONs as New Cancer Cell Targeted Magnetic Nanocarrier.

Superparamagnetic iron oxide nanoparticles (SPIONs) may act as an excellent theragnostic tool if properly coated and stabilized in a biological environment, even more, if they have targeting properties towards a specific cellular target. Humanized

In Silico Study on the Interactions, Molecular Docking, Dynamics and Simulation of Potential Compounds from

Cancer is characterized by the abnormal development of cells that divide in an uncontrolled manner and further take over the body and destroy the normal cells of the body. Although several therapies are practiced, the demand and need for new therapeutic agents are ever-increasing because of issues with the safety, efficacy and efficiency of old drugs. Several plant-based therapeutics are being used for treatment, either as conjugates with existing drugs or as standalone formulations.

Icaritin Derivative IC2 Induces Cytoprotective Autophagy of Breast Cancer Cells via SCD1 Inhibition.

Breast cancer is one of the most prevalent malignancies and the leading cause of cancer-associated mortality in China. Icaritin (ICT), a prenyl flavonoid derived from the

Wnt Signaling Pathway Collapse upon β-Catenin Destruction by a Novel Antimicrobial Peptide SKACP003 Unveiling the Molecular Mechanism and Genetic Activities Using Breast Cancer Cell Lines.

Despite progress in breast cancer treatment, the survival rate for patients with metastatic breast cancer remains low due to chemotherapeutic agent resistance and the lack of specificity of the current generation of cancer drugs. Our previous findings indicated that the antimicrobial peptide SKACP003 exhibited anticancer properties, particularly against the MCF-7, MDA-MB-231, and MDA-MB-453 breast cancer cell lines. However, the mechanism of SKACP003-induced cancer cell death is unknown. Here, we investigated the molecular mechanism by which SKACP003 inhibits the cell cycle, cell proliferation, and angiogenesis in breast cancer cell lines. The results revealed that all the breast cancer cell lines treated at their IC

The Cytotoxicity of Carbon Nanotubes and Hydroxyapatite, and Graphene and Hydroxyapatite Nanocomposites against Breast Cancer Cells.

Cancer is a current dreadful disease and the leading cause of death. Next to cardiovascular diseases, cancer is the most severe threat to human life and health. Breast cancer is the most common invasive cancer diagnosed in women. Each year about 2.3 million women are diagnosed with breast cancer. In consideration of the severity of breast cancer, herein we designed the biocompatible nanomaterials, CNTs-HAP and GR-HAP, through grafting of hydroxyapatite (HAP) to carbon nanotubes (CNTs) and graphene (GR) nanosheets. CNTs-HAP and GR-HAP have been tested for their cytotoxicity, growth and motility inhibitory effects, and their effects on the mesenchymal markers. All these demonstrated significant dose-dependent and time-dependent in vitro cytotoxicity against SUM-159 and MCF-7 breast cancer cell lines. The cell viability assay showed that the CNTs-HAP was more effective over SUM-159 cells than MCF-7 cells. It found that the increase in the concentration of GR-HAP has inhibited the clonogenic ability of breast cancer cells. The GR-HAP exhibited a substantial inhibitory effect on the cell motility of SUM-159 cell lines. It was investigated that the expression of vimentin (mesenchymal marker) was majorly reduced in SUM-159 cells by GR-HAP.

3D AFM Nanomechanical Characterization of Biological Materials.

Atomic Force Microscopy (AFM) is a powerful tool enabling the mechanical characterization of biological materials at the nanoscale. Since biological materials are highly heterogeneous, their mechanical characterization is still considered to be a challenging procedure. In this paper, a new approach that leads to a 3-dimensional (3D) nanomechanical characterization is presented based on the average Youngs modulus and the AFM indentation method. The proposed method can contribute to the clarification of the variability of the mechanical properties of biological samples in the 3-dimensional space (variability at the x-y plane and depth-dependent behavior). The method was applied to agarose gels, fibroblasts, and breast cancer cells. Moreover, new mathematical methods towards a quantitative mechanical characterization are also proposed. The presented approach is a step forward to a more accurate and complete characterization of biological materials and could contribute to an accurate user-independent diagnosis of various diseases such as cancer in the future.

Does the Pathologic Fracture Predict Severe Paralysis in Patients with Metastatic Epidural Spinal Cord Compression (MESCC)-A Retrospective, Single-Center Cohort Analysis.

Currently, there is uncertainty about the predictive factors for metastatic epidural spinal cord compression (MESCC) and consecutive symptomatology in tumor patients. Prognostic algorithms for identifying patients at risk for paralysis are missing. The influence of the pathologic fracture on the patients symptoms is widely discussed in the literature and we hypothesize that pathologic fractures contribute to spinal cord compression and are therefore predictive of severe paralysis. We tested this hypothesis in 136 patients who underwent surgery for spinal metastases. The most common primary cancers were prostate (24.3%, n 33), breast (11.0%, n 15), lung (10.3%, n 14), and cancer of unknown primary (10.3%, n 14). MESCC primarily affected the thoracic (77.2%, n 105), followed by the lumbar (13.2%, n 18) and cervical (9.6%, n 13) spine. Pathologic fractures occurred in 63.2% (n 86) of patients, mainly in osteolytic metastases. On the American spinal injury association (ASIA) impairment scale (AIS), 63.2% (n 86) of patients exhibited AIS grade D and 36.8% (n 50) AIS grade C-A preoperatively. The presence of a pathologic fracture alone did not predict severe paralysis (AIS C-A,

State of the Art in 2022 PETCT in Breast Cancer A Review.

Molecular imaging with positron emission tomography is a powerful and well-established tool in breast cancer management. In this review, we aim to address the current place of the main PET radiopharmaceuticals in breast cancer care and offer perspectives on potential future radiopharmaceutical and technological advancements. A special focus is given to the following the role of

Predictive Biomarkers for Response to Immunotherapy in Triple Negative Breast Cancer Promises and Challenges.

Triple negative breast cancer (TNBC) is a highly heterogeneous disease with a poor prognosis and a paucity of therapeutic options. In recent years, immunotherapy has emerged as a new treatment option for patients with TNBC. However, this therapeutic evolution is paralleled by a growing need for biomarkers which allow for a better selection of patients who are most likely to benefit from this immune checkpoint inhibitor (ICI)-based regimen. These biomarkers will not only facilitate a better optimization of treatment strategies, but they will also avoid unnecessary side effects in non-responders, and limit the increasing financial toxicity linked to the use of these agents. Huge efforts have been deployed to identify predictive biomarkers for the ICI, but until now, the fruits of this labor remained largely unsatisfactory. Among clinically validated biomarkers, only programmed death-ligand 1 protein (PD-L1) expression has been prospectively assessed in TNBC trials. In addition to this, microsatellite instability and a high tumor mutational burden are approved as tumor agnostic biomarkers, but only a small percentage of TNBC fits this category. Furthermore, TNBC should no longer be approached as a single biological entity, but rather as a complex disease with different molecular, clinicopathological, and tumor microenvironment subgroups. This review provides an overview of the validated and evolving predictive biomarkers for a response to ICI in TNBC.

Robustness of Breast Margins with Volumetric Modulated Arc Therapy without a Six-Degrees-of-Freedom Couch A Dosimetric Evaluation.

In our hospital, a TrueBeam linear accelerator and the PerfectPitch 6-degrees-of-freedom (6-DOF) couch (Varian), with 7 mm margins, are used for volumetric modulated arc therapy (VMAT) of breast cancer (BC). This study tested whether a 3-degrees-of-freedom (3-DOF) couch, i.e., without rotation compensation (such as the Halcyon couch), affected dose metrics. A total of 446 daily extended cone beam computed tomography (CBCT) data of 20 patients who received VMAT for BC were used to recalculate the treatment plans with the session registration (6-DOF) and a simulated matching with 3-DOF. The initial plan provided significantly better coverage for internal mammary chain and clavicular lymph node clinical target volumes (CTVs) than the 6-DOF and 3-DOF CBCT plans. The volumes receiving 110% of the prescribed dose (V110%) were increased for all CTVs with the 6-DOF and 3-DOF CBCT plans, but the difference was significant only for the breastchest wall CTV (

Long-Term Results after Autologous Breast Reconstruction with DIEP versus PAP Flaps Based on Quality of Life and Aesthetic Outcome Analysis.

(1) Background This work aimed to conduct a comparative study, providing long-term data about patient-reported outcome measures and donor site scar assessments, as well as an aesthetic evaluation of the reconstructed breasts in patients with DIEP versus PAP flap breast reconstruction. (2) Methods This prospective, single-center, matched cohort study included a total of 36 patients after DIEP and PAP flap breast reconstruction. The evaluation was carried out using the Breast-Q and POSAS questionnaire, as well as the Breast Aesthetic Scale for cosmetic analysis, by four plastic surgeons. (3) Results The postoperative Breast-Q evaluation revealed no significant differences between both patient groups for the categories of the physical well-being of the donor site, the physical well-being of the breast, and satisfaction with the breast. A scar evaluation of the donor site region showed equivalent results for the thigh and abdomen regions, concerning the overall opinion of the patients and the observers. There was no significant difference between both methods of reconstruction for all aspects of breast aesthetics. (4) Conclusions Similar results for donor site morbidity, scar quality, and the aesthetic outcome of the breasts in both the DIEP and PAP patient groups have been demonstrated. Hence, in those cases suitable for both types of reconstruction, the decision can be based on factors such as patients lifestyles, leisure activities, and preferences.

Triple-Negative Breast Cancer and Predictive Markers of Response to Neoadjuvant Chemotherapy A Systematic Review.

Around 40-50% of all triple-negative breast cancer (TNBC) patients achieve a pathological complete response (pCR) after treatment with neoadjuvant chemotherapy (NAC). The identification of biomarkers predicting the response to NAC could be helpful for personalized treatment. This systematic review provides an overview of putative biomarkers at baseline that are predictive for a pCR following NAC. Embase, Medline and Web of Science were searched for articles published between January 2010 and August 2022. The articles had to meet the following criteria patients with primary invasive TNBC without distant metastases and patients must have received NAC. In total, 2045 articles were screened by two reviewers resulting in the inclusion of 92 articles. Overall, the most frequently reported biomarkers associated with a pCR were a high expression of Ki-67, an expression of PD-L1 and the abundance of tumor-infiltrating lymphocytes, particularly CD8 T cells, and corresponding immune gene signatures. In addition, our review reveals proteomic, genomic and transcriptomic markers that relate to cancer cells, the tumor microenvironment and the peripheral blood, which also affect chemo-sensitivity. We conclude that a prediction model based on a combination of tumor and immune markers is likely to better stratify TNBC patients with respect to NAC response.

Ubiquitin-Related Modifier 1 (URM-1) Modulates Cx43 in Breast Cancer Cell Lines.

Gap-junction-forming connexins are exquisitely regulated by post-translational modifications (PTMs). In particular, the PTM of connexin 43 (Cx43), a tumor suppressor protein, regulates its turnover and activity. Here, we investigated the interaction of Cx43 with the ubiquitin-related modifier 1 (URM-1) protein and its impact on tumor progression in two breast cancer cell lines, highly metastatic triple-negative MDA-MB-231 and luminal breast cancer MCF-7 cell lines. To evaluate the subsequent modulation of Cx43 levels, URM-1 was downregulated in these cells. The transcriptional levels of epithelial-to-mesenchymal transition (EMT) markers and the metastatic phenotype were assessed. We demonstrated that Cx43 co-localizes and interacts with URM-1, and URMylated Cx43 was accentuated upon cellular stress. The significant upregulation of small ubiquitin-like modifier-1 (SUMO-1) was also observed. In cells with downregulated URM-1, Cx43 expression significantly decreased, and SUMOylation by SUMO-1 was affected. The concomitant expression of EMT markers increased, leading to increased proliferation, migration, and invasion potential. Inversely, the upregulation of URM-1 increased Cx43 expression and reversed EMT-induced processes, underpinning a role for this PTM in the observed phenotypes. This study proposes that the URMylation of Cx43 in breast cancer cells regulates its tumor suppression properties and contributes to breast cancer cell malignancy.

Targets Involved in the Anti-Cancer Activity of Quercetin in Breast, Colorectal and Liver Neoplasms.

Phytochemicals have long been effective partners in the fight against several diseases, including cancer. Among these, flavonoids are valuable allies for both cancer prevention and therapy since they are known to influence a large panel of tumor-related processes. Particularly, it was revealed that quercetin, one of the most common flavonoids, controls apoptosis and inhibits migration and proliferation, events essential for the development of cancer. In this review, we collected the evidence on the anti-cancer activity of quercetin exploring the network of interactions between this flavonol and the proteins responsible for cancer onset and progression focusing on breast, colorectal and liver cancers, owing to their high worldwide incidence. Moreover, quercetin proved to be also a potentiating agent able to push further the anti-cancer activity of common employed anti-neoplastic agents, thus allowing to lower their dosages and, above all, to sensitize again resistant cancer cells. Finally, novel approaches to delivery systems can enhance quercetins pharmacokinetics, thus boosting its great potentiality even further. Overall, quercetin has a lot of promise, given its multi-target potentiality thus, more research is strongly encouraged to properly define its pharmaco-toxicological profile and evaluate its potential for usage in adjuvant and chemoprevention therapy.

The Association of Integrins β3, β4, and αVβ5 on Exosomes, CTCs and Tumor Cells with Localization of Distant Metastasis in Breast Cancer Patients.

Integrins are cell adhesion receptors, which play a role in breast cancer invasion, angiogenesis, and metastasis. Moreover, it has been shown that exosomal integrins provide organotropic metastasis in a mouse model. In our study, we aimed to investigate the expression of integrins β3, β4, and αVβ5 on exosomes and tumor cells (circulating tumor cells and primary tumor) and their association with the localization of distant metastasis. We confirmed the association of exosomal integrin β4 with lung metastasis in breast cancer patients. However, we were unable to evaluate the role of integrin β3 in brain metastasis due to the rarity of this localization. We established no association of exosomal integrin αVβ5 with liver metastasis in our cohort of breast cancer patients. The further evaluation of β3, β4, and αVβ5 integrin expression on CTCs revealed an association of integrin β4 and αVβ5 with liver, but not the lung metastases. Integrin β4 in the primary tumor was associated with liver metastasis. Furthermore, an in-depth analysis of phenotypic characteristics of β4 tumor cells revealed a significantly increased proportion of E-cadherin and CD44CD24- cells in patients with liver metastases compared to patients with lung or no distant metastases.

Characterization of Hormone Receptor and HER2 Status in Breast Cancer Using Mass Spectrometry Imaging.

Immunohistochemical evaluation of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 status stratify the different subtypes of breast cancer and define the treatment course. Triple-negative breast cancer (TNBC), which does not register receptor overexpression, is often associated with worse patient prognosis. Mass spectrometry imaging transcribes the molecular content of tissue specimens without requiring additional tags or preliminary analysis of the samples, being therefore an excellent methodology for an unbiased determination of tissue constituents, in particular tumor markers. In this study, the proteomic content of 1191 human breast cancer samples was characterized by mass spectrometry imaging and the epithelial regions were employed to train and test machine-learning models to characterize the individual receptor status and to classify TNBC. The classification models presented yielded high accuracies for estrogen and progesterone receptors and over 95% accuracy for classification of TNBC. Analysis of the molecular features revealed that vimentin overexpression is associated with TNBC, supported by immunohistochemistry validation, revealing a new potential target for diagnosis and treatment.

Evolution of Antiretroviral Drug Rilpivirine and Approach to Oncology.

Rilpivirine is an antiretroviral drug used to treat AIDS worldwide. The drug is a non-nucleoside reverse transcriptase inhibitor that halts the cDNA elongation process and, thus, the capacity of the HIV-1 virus to replicate. With the new wave of drug repurposing in recent years, rilpivirine has been studied in this regard. This drug is useful in Zika virus treatment, with in vivo results indicating regression in neuronal effects often associated with this infection. Several cancer types have also been researched, from breast to leukemia and pancreatic cancer, and rilpivirine has proved to have inhibitory effects in various cell lines with low concentrations, causing cellular death, apoptosis, and cell cycle arrest. The pathways are not yet established, but some works have hypothesized and demonstrated that rilpivirine causes inhibition of Aurora A kinase and has effects on the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway and the vascular endothelial growth factors-receptors (VEGFs-VEGFRs) pathway, which are known to be altered in cancer and tumors and can be targeted for cancer treatment. Further testing and clinical trials are needed, but this review demonstrates the potential of rilpivirines repurposing for cancer treatment.

Expression of RBMS3 in Breast Cancer Progression.

The aim of the study was to evaluate the localization and intensity of RNA-binding motif single-stranded-interacting protein 3 (RBMS3) expression in clinical material using immunohistochemical (IHC) reactions in cases of ductal breast cancer (in vivo), and to determine the level of RBMS3 expression at both the protein and mRNA levels in breast cancer cell lines (in vitro). Moreover, the data obtained in the in vivo and in vitro studies were correlated with the clinicopathological profiles of the patients. Material for the IHC studies comprised 490 invasive ductal carcinoma (IDC) cases and 26 mastopathy tissues. Western blot and RT-qPCR were performed on four breast cancer cell lines (MCF-7, BT-474, SK-BR-3 and MDA-MB-231) and the HME1-hTERT (Me16C) normal immortalized breast epithelial cell line (control). The Kaplan-Meier plotter tool was employed to analyze the predictive value of overall survival of

Harnessing the LdCsm RNA Detection Platform for Efficient microRNA Detection.

In cancer diagnosis, diverse microRNAs (miRNAs) are used as biomarkers for carcinogenesis of distinctive human cancers. Thus, the detection of these miRNAs and their quantification are very important in prevention of cancer diseases in human beings. However, efficient RNA detection often requires RT-PCR, which is very complex for miRNAs. Recently, the development of CRISPR-based nucleic acid detection tools has brought new promises to efficient miRNA detection. Three CRISPR systems can be explored for miRNA detection, including type III, V, and VI, among which type III (CRISPR-Cas10) systems have a unique property as they recognize RNA directly and cleave DNA collaterally. In particular, a unique type III-A Csm system encoded by

The Orphan GPR50 Receptor Regulates the Aggressiveness of Breast Cancer Stem-like Cells via Targeting the NF-kB Signaling Pathway.

The expression of GPR50 in CSLC and several breast cancer cell lines was assessed by RT-PCR and online platform (UALCAN, GEPIA, and R2 gene analysis). The role of GPR50 in driving CSLC, sphere formation, cell proliferation, and migration was performed using shGPR50 gene knockdown, and the role of GPR50-regulated signaling pathways was examined by Western blotting and Luciferase Assay. Herein, we confirmed that the expression of G protein-coupled receptor 50 (GPR50) in cancer stem-like cells (CSLC) is higher than that in other cancer cells. We examined that the knockdown of GPR50 in CSLC led to decreased cancer properties, such as sphere formation, cell proliferation, migration, and stemness. GPR50 silencing downregulates NF-kB signaling, which is involved in sphere formation and aggressiveness of CSLC. In addition, we demonstrated that GPR50 also regulates ADAM-17 activity by activating NOTCH signaling pathways through the AKTSP1 axis in CSLC. Overall, we demonstrated a novel GPR50-mediated regulation of the NF-κB-Notch signaling pathway, which can provide insights into CSLC progression and prognosis, and NF-κB-NOTCH-based CSLC treatment strategies.

Health Benefits of Coffee Consumption for Cancer and Other Diseases and Mechanisms of Action.

Coffee is one of the most widely consumed beverages worldwide, and epidemiology studies associate higher coffee consumption with decreased rates of mortality and decreased rates of neurological and metabolic diseases, including Parkinsons disease and type 2 diabetes. In addition, there is also evidence that higher coffee consumption is associated with lower rates of colon and rectal cancer, as well as breast, endometrial, and other cancers, although for some of these cancers, the results are conflicting. These studies reflect the chemopreventive effects of coffee there is also evidence that coffee consumption may be therapeutic for some forms of breast and colon cancer, and this needs to be further investigated. The mechanisms associated with the chemopreventive or chemotherapeutic effects of over 1000 individual compounds in roasted coffee are complex and may vary with different diseases. Some of these mechanisms may be related to nuclear factor erythroid 2 (Nrf2)-regulated pathways that target oxidative stress or pathways that induce reactive oxygen species to kill diseased cells (primarily therapeutic). There is evidence for the involvement of receptors which include the aryl hydrocarbon receptor (AhR) and orphan nuclear receptor 4A1 (NR4A1), as well as contributions from epigenetic pathways and the gut microbiome. Further elucidation of the mechanisms will facilitate the potential future clinical applications of coffee extracts for treating cancer and other inflammatory diseases.

MicroRNA and Messenger RNA Expression Profiles in Canine Mammary Gland Tumor.

Canine mammary gland tumor (CMT) is the most frequently diagnosed neoplasm in intact female dogs. As prognosis depends on the malignancy of tumors and metastasis levels, early and accurate diagnosis are crucial for prolongation of life expectancy. The genetic similarity of dogs with humans in addition to environmental and physiological similarities make them ideal models for the study of cancer. In this study, we analyzed differentially expressed microRNAs followed by RNA-Seq to investigate the alterations in mRNA levels based on the malignancy (benign, malignant) and the biopsy locations (tumors, surrounding normal tissues). We identified multiple breast cancer-related genes regardless of malignancy. We found cfa-miR-503 to be the only miRNA that showed altered expression in response to malignancy in CMTs. Although further validation is needed, cfa-miR-503 could be used as a potential diagnostic biomarker as well as a potential RNA-based anti-tumor drug in malignant CMTs.

Reactivity Graph Yields Interpretable IgM Repertoire Signatures as Potential Tumor Biomarkers.

Combining adaptive and innate immunity induction modes, the repertoire of immunoglobulin M (IgM) can reflect changes in the internal environment including malignancies. Previously, it was shown that a mimotope library reflecting the public IgM repertoire of healthy donors (IgM IgOme) can be mined for efficient probes of tumor biomarker antibody reactivities. To better explore the interpretability of this approach for IgM, solid tumor-related profiles of IgM reactivities to linear epitopes of actual tumor antigens and viral epitopes were studied. The probes were designed as oriented planar microarrays of 4526 peptide sequences (as overlapping 15-mers) derived from 24 tumor-associated antigens and 209 cancer-related B cell epitopes from 30 viral antigens. The IgM reactivity in sera from 21 patients with glioblastoma multiforme, brain metastases of other tumors, and non-tumor-bearing neurosurgery patients was thus probed in a proof-of-principle study. A graph representation of the binding data was developed, which mapped the cross-reactivity of the mixture of IgM (poly)specificities, delineating different antibody footprints in the features of the graph-neighborhoods and cliques. The reactivity graph mapped the major features of the IgM repertoire such as the magnitude of the reactivity (titer) and major cross-reactivities, which correlated with blood group reactivity, non-self recognition, and even idiotypic specificities. A correlation between an aspect of this image of the IgM IgOme, namely, small cliques reflecting rare self-reactivities and the capacity of subsets of the epitopes to separate the diagnostic groups studied was found. In this way, the graph representation helped the feature selection in its filtering step and provided reduced feature sets, which, after recursive feature elimination, produced a classifier containing 51 peptide reactivities separating the three diagnostic groups with an unexpected efficiency. Thus, IgM IgOme approaches to repertoire studies is greatly augmented when selfviral antigens are used and the data are represented as a reactivity graph. This approach is most general, and if it is applicable to tumors in immunologically privileged sites, it can be applied to any solid tumors, for instance, breast or lung cancer.

Breast Cancer From Pathophysiology to Novel Therapeutic Approaches 2.0.

Breast cancer (BC) is the most common malignancy in women worldwide ....

IRAK2 Downregulation in Triple-Negative Breast Cancer Cells Decreases Cellular Growth In Vitro and Delays Tumour Progression in Murine Models.

Breast cancer stem cells (BCSCs) are responsible for tumour recurrence and therapy resistance. We have established primary BCSC cultures from human tumours of triple-negative breast cancer (TNBC), a subgroup of breast cancer likely driven by BCSCs. Primary BCSCs produce xenografts that phenocopy the tumours of origin, making them an ideal model for studying breast cancer treatment options. In the TNBC cell line MDA-MB-468, we previously screened kinases whose depletion elicited a differentiation response, among which IRAK2 was identified. Because primary BCSCs are enriched in IRAK2, we wondered whether IRAK2 downregulation might affect cellular growth. IRAK2 was downregulated in primary BCSCs and MDA-MB-468 by lentiviral delivery of shRNA, causing a decrease in cellular proliferation and sphere-forming capacity. When orthotopically transplanted into immunocompromised mice, IRAK2 knockdown cells produced smaller xenografts than control cells. At the molecular level, IRAK2 downregulation reduced NF-κB and ERK phosphorylation, IL-6 and cyclin D1 expression, ERN1 signalling and autophagy in a cell line-dependent way. Overall, IRAK2 downregulation decreased cellular aggressive growth and pathways often exploited by cancer cells to endure stress therefore, IRAK2 may be considered an interesting target to compromise TNBC progression.

GRHL2 Regulation of GrowthMotility Balance in Luminal versus Basal Breast Cancer.

The transcription factor Grainyhead-like 2 (GRHL2) is a critical transcription factor for epithelial tissues that has been reported to promote cancer growth in some and suppress aspects of cancer progression in other studies. We investigated its role in different breast cancer subtypes. In breast cancer patients, GRHL2 expression was increased in all subtypes and inversely correlated with overall survival in basal-like breast cancer patients. In a large cell line panel, GRHL2 was expressed in luminal and basal A cells, but low or absent in basal B cells. The intersection of ChIP-Seq analysis in 3 luminal and 3 basal A cell lines identified conserved GRHL2 binding sites for both subtypes. A pathway analysis of ChIP-seq data revealed cell-cell junction regulation and epithelial migration as well as epithelial proliferation, as candidate GRHL2-regulated processes and further analysis of hub genes in these pathways showed similar regulatory networks in both subtypes. However, GRHL2 deletion in a luminal cell line caused cell cycle arrest while this was less prominent in a basal A cell line. Conversely, GRHL2 loss triggered enhanced migration in the basal A cells but failed to do so in the luminal cell line. ChIP-Seq and ChIP-qPCR demonstrated GRHL2 binding to CLDN4 and OVOL2 in both subtypes but not to other GRHL2 targets controlling cell-cell adhesion that were previously identified in other cell types, including CDH1 and ZEB1. Nevertheless, E-cadherin protein expression was decreased upon GRHL2 deletion especially in the luminal line and, in agreement with its selectively enhanced migration, only the basal A cell line showed concomitant induction of vimentin and N-cadherin. To address how the balance between growth reduction and aspects of EMT upon loss of GRHL2 affected in vivo behavior, we used a mouse basal A orthotopic transplantation model in which the GRHL2 gene was silenced. This resulted in reduced primary tumor growth and a reduction in number and size of lung colonies, indicating that growth suppression was the predominant consequence of GRHL2 loss. Altogether, these findings point to largely common but also distinct roles for GRHL2 in luminal and basal breast cancers with respect to growth and motility and indicate that, in agreement with its negative association with patient survival, growth suppression is the dominant response to GRHL2 loss.

VT68.2 An Antibody to Chondroitin Sulfate Proteoglycan 4 (CSPG4) Displays Reactivity against a Tumor-Associated Carbohydrate Antigen.

The anti-CSPG4 monoclonal antibodies (mAbs) have shown anti-tumor activity and therapeutic potential for treating breast cancer. In addition, CSPG4 is a dominant tumor-associated antigen that is also involved in normal-tissue development in humans. Therefore, the potential for off-tumor activity remains a serious concern when targeting CSPG4 therapeutically. Previous work suggested that glycans contribute to the binding of specific anti-CSPG4 antibodies to tumor cells, but the specificity and importance of this contribution are unknown. In this study, the reactivity of anti-CSPG4 mAbs was characterized with a peptide mimetic of carbohydrate antigens expressed in breast cancer. ELISA, flow cytometry, and microarray assays were used to screen mAbs for their ability to bind to carbohydrate-mimicking peptides (CMPs), cancer cells, and glycans. The mAb VT68.2 displayed a distinctly strong binding to a CMP (P10s) and bound to triple-negative breast cancer cells. In addition, VT68.2 showed a higher affinity for N-linked glycans that contain terminal fucose and fucosylated lactosamines. The functional assays demonstrated that VT68.2 inhibited cancer cell migration. These results define the glycoform reactivity of an anti-CSPG4 antibody and may lead to the development of less toxic therapeutic approaches that target tumor-specific glyco-peptides.

Pulsed Hypoxia Gradually Reprograms Breast Cancer Fibroblasts into Pro-Tumorigenic Cells via Mesenchymal-Epithelial Transition.

Hypoxia arises in most growing solid tumors and can lead to pleotropic effects that potentially increase tumor aggressiveness and resistance to therapy through regulation of the expression of genes associated with the epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET). The main goal of the current work was to obtain and investigate the intermediate phenotype of tumor cells undergoing the hypoxia-dependent transition from fibroblast to epithelial morphology. Primary breast cancer fibroblasts BrC4f, being cancer-associated fibroblasts, were subjected to one or two rounds of pulsed hypoxia (PH). PH induced transformation of fibroblast-shaped cells to semi-epithelial cells. Western blot analysis, fluorescent microscopy and flow cytometry of transformed cells demonstrated the decrease in the mesenchymal markers vimentin and N-cad and an increase in the epithelial marker E-cad. These cells kept mesenchymal markers αSMA and S100A4 and high ALDH activity. Real-time PCR data of the cells after one (BrC4fHyp1) and two (BrC4fHyp2) rounds of PH showed consistent up-regulation of TWIST1 gene as an early response and ZEB12 and SLUG transcriptional activity as a subsequent response. Reversion of BrC4fHyp2 cells to normoxia conditions converted them to epithelial-like cells (BrC4e) with decreased expression of EMT genes and up-regulation of MET-related OVOL2 and c-MYC genes. Transplantation of BrC4f and BrC4fHyp2 cells into SCID mice showed the acceleration of tumor growth up to 61.6% for BrC4fHyp2 cells. To summarize, rounds of PH imitate the MET process of tumorigenesis in which cancer-associated fibroblasts pass through intermediate stages and become more aggressive epithelial-like tumor cells.

Targeting the Retinoic Acid Pathway to Eradicate Cancer Stem Cells.

All-

Effective or Harmful-Evaluation of Locally Applied Antibiotics on Adipose Tissue during Lipofilling to the Breast-An In Vitro Study.

Lipofilling is a frequently used and safe procedure for breast reconstruction. One of the most feared complications is soft tissue infection following lipofilling. Because of this, some surgeons propose the practice of rinsing fat grafts with antibiotics. This study investigates the effect of antibiotic rinses on fat grafts in an in vitro model. Adipocytes and stem cells were isolated from fat tissue harvested during 24 lipofilling procedures and incubated with different doses of clindamycin or cefazolin. Cell viability, metabolism, proliferation, and differentiation capacities were analyzed by gross morphology, fluorescence staining, -(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid (MTT-), and Glyceraldehyde 3 Phosphate Dehydrogenase (G3PD)-assay as well as reactive oxygen species (ROS)-assay. Cefazolin and clindamycin led to significant reduction of cell viability of adipocytes. High doses of both antibiotics led to a rupture of adipocytes with visible free lipid droplets. Cell metabolism was significantly decreased after incubation with both antibiotics. There was a significant increase in ROS production. Exposure to clindamycin and cefazolin led to morphological changes in stem cells in a dose- and time-dependent manner. Furthermore, differentiation potential was significantly reduced. Antibiotic susceptibility testing, however, showed that low concentrations of antibiotics effectively inhibited bacterial growth in contaminated fat grafts. This study confirms that rinsing fat grafts with clindamycin or cefazolin not only overly prevents infection but also has cytotoxic and metabolic effects on adipocytes. Therefore, based on these results, the routine clinical application in high doses cannot be recommended.

Detection of Circulating Tumor Cell-Related Markers in Gynecologic Cancer Using Microfluidic Devices A Pilot Study.

The detection of circulating tumor cells (CTCs) is an emerging strategy for the early detection, prognostication, and identification of recurrent cancer. The clinical utility of CTC detection has been established, but few studies have employed this strategy for the detection of gynecologic cancers. Here, we present a novel, biochip-based microfluidic device for the detection of CTCs in gynecologic cancers. The study cohort included three patients with cervical cancer, eight with endometrial cancer, two with ovarian cancer, two with breast cancer, and one with vaginal small cell carcinoma. Four cancer type-specific molecular markers (PanCK, GATA3, HER2, and HE4), as well as CD13, were used for prognostication and recurrence detection, along with downstream genomic analysis. GATA3 and HER2 were markedly expressed in the patients with cervical cancer, and this expression was strongly correlated with the early detection of recurrent disease. All four molecular markers were expressed preoperatively in the patients with endometrial cancer, and the re-expression of different markers was observed at follow-up before recurrence was confirmed. CD13 was identified as an alternative prognostic marker for both cervical and endometrial cancer. Our pilot study indicated that the novel CTC detection system can be used for prognostication and early detection of disease recurrence, which needed further investigation.

Exploring the Biological Properties of Zn(II)

The design of artificial helicoidal molecules derived from metal ions with biological properties is one of the objectives within metallosupramolecular chemistry. Herein, we report three zinc helicates derived from a family of

Expression of CD22 in Triple-Negative Breast Cancer A Novel Prognostic Biomarker and Potential Target for CAR Therapy.

Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancer cases. Due to the lack of expression of well-known molecular targets estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), there is a need for more alternative treatment approaches in TNBC. Chimeric antigen receptor (CAR)-T cell-based immunotherapy treatment is one of the latest treatment technologies with outstanding therapeutic advances in the past decade, especially in the treatment of hematologic malignancies, but the therapeutic effects of CAR-T cells against solid tumors have not yet shown significant clinical benefits. Identification of highly specific CAR-T targets in solid tumors is also crucial for its successful treatment. CD22 is reported to be a multifunctional receptor that is mainly expressed on the surface of mature B-cells (lymphocytes) and is also highly expressed in most B-cell malignancies. This study aimed to investigate the expression of CD22 in TNBC. Bioinformatic analysis was performed to evaluate the expression of CD22 in breast carcinoma and normal tissues. RNA-seq data of normal and breast carcinoma patients were downloaded from The Cancer Genome Atlas (TCGA), and differential gene expression was performed using R language. Additionally, online bioinformatics web tools (GEPIA and TNM plot) were used to evaluate the expression of CD22 in breast carcinoma and normal tissues. Western blot (WB) analysis and immunofluorescence (IF) were performed to characterize the expression of CD22 in TNBC cell lines. Immunohistochemical (IHC) staining was performed on tumor specimens from 97 TNBC patients for CD22 expression. Moreover, statistical analysis was performed to analyze the association of clinical pathological parameters with CD22 expression. Correlation analysis between overall survival data of TNBC patients and CD22 expression was also performed. Differential gene expression analysis of TCGA data revealed that CD22 is among the upregulated differentially expressed genes (DEGs) with high expression in breast cancer, as compared to normal breast tissues. WB and IF analysis revealed high expression of CD22 in TNBC cell lines. IHC results also showed that approximately 62.89% (6197) of TNBC specimens were stained positive for CD22. Cell membrane expression of CD22 was evident in 23.71% (2397) of TNBC specimens, and 39.18% (3897) of TNBC specimens showed cytoplasmicmembrane expression, while 37.11% (3697) specimens were negative for CD22. Furthermore, significant associations were found between the size of tumors in TNBC patients and CD22 expression, which unveils its potential as a prognostic biomarker. No significant correlation was found between the overall survival of TNBC patients and CD22 expression. In conclusion, we demonstrated for the first time that CD22 is highly expressed in TNBC. Based on our findings, we anticipated that CD22 could be used as a prognostic biomarker in TNBC, and it might be a potential CAR-T target in TNBC for whom few therapeutic options exist. However, more large-scale studies and clinical trials will ensure its potential usefulness as a CAR-T target in TNBC.

Resveratrol Analogs and Prodrugs Differently Affect the Survival of Breast Cancer Cells Impairing EstrogenEstrogen Receptor αNeuroglobin Pathway.

Breast cancer is the first leading tumor in women in terms of incidence worldwide. Seventy percent of cases are estrogen receptor (ER) α-positive. In these malignancies, 17β-estradiol (E2) via ERα increases the levels of neuroglobin (NGB), a compensatory protein that protects cancer cells from stress-induced apoptosis, including chemotherapeutic drug treatment. Our previous data indicate that resveratrol (RSV), a plant-derived polyphenol, prevents E2ERα-induced NGB accumulation in this cellular context, making E2-dependent breast cancer cells more prone to apoptosis. Unfortunately, RSV is readily metabolized, thus preventing its effectiveness. Here, four different RSV analogs have been developed, and their effect on the ERαNGB pathway has been compared with RSV conjugated with highly hydrophilic gold nanoparticles as prodrug to evaluate if RSV derivatives maintain the breast cancer cells susceptibility to the chemotherapeutic drug paclitaxel as the original compound. Results demonstrate that RSV conjugation with gold nanoparticles increases RSV efficacy, with respect to RSV analogues, reducing NGB levels and enhancing the pro-apoptotic action of paclitaxel, even preventing the anti-apoptotic action exerted by E2 treatment on these cells. Overall, RSV conjugation with gold nanoparticles makes this complex a promising agent for medical application in breast cancer treatment.

Proteins Found in the Triple-Negative Breast Cancer Secretome and Their Therapeutic Potential.

The cancer secretome comprises factors secreted by tumors, including cytokines, growth factors, proteins from the extracellular matrix (ECM), proteases and protease inhibitors, membrane and extracellular vesicle proteins, peptide hormones, and metabolic proteins. Secreted proteins provide an avenue for communication with other tumor cells and stromal cells, and these in turn promote tumor growth and progression. Breast cancer is the most commonly diagnosed cancer in women in the US and worldwide. Triple-negative breast cancer (TNBC) is characterized by its aggressiveness and its lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and HER2, making it unable to be treated with therapies targeting these protein markers, and leaving patients to rely on standard chemotherapy. In order to develop more effective therapies against TNBC, researchers are searching for targetable molecules specific to TNBC. Proteins in the TNBC secretome are involved in wide-ranging cancer-promoting processes, including tumor growth, angiogenesis, inflammation, the EMT, drug resistance, invasion, and development of the premetastatic niche. In this review, we catalog the currently known proteins in the secretome of TNBC tumors and correlate these secreted molecules with potential therapeutic opportunities to facilitate translational research.

The Critical Impact of Sphingolipid Metabolism in Breast Cancer Progression and Drug Response.

Breast cancer is the second leading cause of cancer-related death in women in the world, and its management includes a combination of surgery, radiation therapy, chemotherapy, and immunotherapy, whose effectiveness depends largely, but not exclusively, on the molecular subtype (Luminal A, Luminal B, HER2 and Triple Negative). All breast cancer subtypes are accompanied by peculiar and substantial changes in sphingolipid metabolism. Alterations in sphingolipid metabolite levels, such as ceramides, dihydroceramide, sphingosine, sphingosine-1-phosphate, and sphingomyelin, as well as in their biosynthetic and catabolic enzymatic pathways, have emerged as molecular mechanisms by which breast cancer cells grow, respond to or escape therapeutic interventions and could take on diagnostic and prognostic value. In this review, we summarize the current landscape around two main themes 1. sphingolipid metabolites, enzymes and transport proteins that have been found dysregulated in human breast cancer cells andor tissues 2. sphingolipid-driven mechanisms that allow breast cancer cells to respond to or evade therapies. Having a complete picture of the impact of the sphingolipid metabolism in the development and progression of breast cancer may provide an effective means to improve and personalize treatments and reduce associated drug resistance.

The Effect of Silica Nanoparticles (SiNPs) on Cytotoxicity, Induction of Oxidative Stress and Apoptosis in Breast Cancer Cell Lines.

Breast cancer is one of the most common cancers in women. Silica nanoparticles (SiNPs) belong to the group of often-used nanoparticles in biomedical applications. The mechanisms of the cytotoxicity, apoptosis, and oxidative stress induced by the 5-15 nm SiNPs still remain unclear. The aim of the study was to evaluate the anti-cancer effect and mechanism of action of SiNPs in breast cancer cell lines. The breast cancer MDA-MB-231 and ZR-75-1 cell lines were analyzed using MTT assay, flow cytometry, and spectrophotometric methods. In this paper, we presented findings about the cytotoxicity, apoptosis, and oxidative stress in both breast cancer cell lines. We indicated that 5-15 nm SiNPs induced dose-dependent cytotoxicity in MDA-MB-231 and ZR-75-1 cells. Moreover, we demonstrated that the process of apoptosis in the studied cell lines was associated with a decrease in the mitochondrial membrane potential (ΔΨ

The Role of Different Types of microRNA in the Pathogenesis of Breast and Prostate Cancer.

Micro ribonucleic acids (microRNAs or miRNAs) form a distinct subtype of non-coding RNA and are widely recognized as one of the most significant gene expression regulators in mammalian cells. Mechanistically, the regulation occurs through microRNA binding with its response elements in the 3-untranslated region of target messenger RNAs (mRNAs), resulting in the post-transcriptional silencing of genes, expressing target mRNAs. Compared to small interfering RNAs, microRNAs have more complex regulatory patterns, making them suitable for fine-tuning gene expressions in different tissues. Dysregulation of microRNAs is well known as one of the causative factors in malignant cell growth. Today, there are numerous data points regarding microRNAs in different cancer transcriptomes, the specificity of microRNA expression changes in various tissues, and the predictive value of specific microRNAs as cancer biomarkers. Breast cancer (BCa) is the most common cancer in women worldwide and seriously impairs patients physical health. Its incidence has been predicted to rise further. Mounting evidence indicates that microRNAs play key roles in tumorigenesis and development. Prostate cancer (PCa) is one of the most commonly diagnosed cancers in men. Different microRNAs play an important role in PCa. Early diagnosis of BCa and PCa using microRNAs is very useful for improving individual outcomes in the framework of predictive, preventive, and personalized (3P) medicine, thereby reducing the economic burden. This article reviews the roles of different types of microRNA in BCa and PCa progression.

Discrimination between Complete versus Non-Complete Pathologic Response to Neoadjuvant Therapy Using Ultrasensitive Mutation Analysis A Proof-of-Concept Study in

Neoadjuvant chemotherapy (NACT) for breast cancer (BC) often results in pathologic complete response (pCR), i.e., the complete elimination of visible cancer cells. It is unclear whether the use of ultrasensitive genetic methods may still detect residual BC cells in complete responders. Breast carcinomas arising in

Association of the Telomerase Reverse Transcriptase rs10069690 Polymorphism with the Risk, Age at Onset and Prognosis of Triple Negative Breast Cancer.

Telomerase reverse transcriptase (TERT) plays a key role in the maintenance of telomere DNA length. The rs10069690 single nucleotide variant, located in intron 4 of TERT, was found to be associated with telomere length and the risk of estrogen receptor-negative but not-positive breast cancer. This study aimed at analysis of the association of rs10069690 genotype and TERT expression with the risk, age at onset, prognosis, and clinically and molecularly relevant subtypes of breast cancer. Accordingly, rs10069690 was genotyped in a hospital-based case-control study of 403 female breast cancer patients and 246 female controls of a Central European (Austrian) study population, and the mRNA levels of TERT were quantified in 106 primary breast tumors using qRT-PCR. We found that in triple-negative breast cancer patients, the minor rs10069690 TT genotype tended to be associated with an increased breast cancer risk (OR, 1.87 95% CI, 0.75-4.71

Association between Poverty and Refraining from Seeking Medical Care during the COVID-19 Pandemic in Japan A Prospective Cohort Study.

This limited study examined how low household income affected avoidant behaviors to seek medical care during the pandemic. We investigated an association between household income below the relative poverty line and refraining from seeking medical care (RSMC) in a longitudinal study during the COVID-19 pandemic. We conducted an analysis of a population-based internet cohort in Japan. Individuals aged 20 to 79 years old living in Japan participated in the internet surveys between 2020 and 2021. The primary outcome was the RSMC of regular visits and new symptoms in 2021. A total of 19,672 individuals were included in the analysis. Household income below the relative poverty line in 2020 was significantly associated with refraining from seeking regular medical visits for men and women (for men, odds ratio 1.28 confidence interval 1.19, 1.83 for women, odds ratio 1.42 confidence interval 1.14, 1.82) in 2021, after accounting for RSMC in 2020. Relative poverty in 2020 was also associated with the RSMC of new symptoms among men (for males, odds ratio 1.32 confidence interval 1.05, 1.66) in 2021 after adjusting for covariates. The study suggested the need to alleviate the financial burden of vulnerable people seeking medical care and advocate for making necessary medical visits, even in a pandemic.

Safety of Combined Targeted and Helixor

Newer personalized medicines including targeted therapies such as PARP inhibitors and CDK 46 inhibitors have been shown to improve the survival of breast and gynaecological cancer patients. However, efficacy outcomes may be ham5pered by treatment discontinuation due to targeted therapy-related adverse drug reactions or resistance. Studies have suggested that add-on mistletoe ( The present study is a real-world data observational cohort study utilizing demographic and treatment data from the accredited national Network Oncology (NO) registry. The study has received ethics approval. The safety profile of targeted therapies with or without Helixor All stages of breast and gynecological cancer patients ( The present study is the first of its kind showing the applicability of Helixor

Comparison of Single Target-Controlled Infusion Pump-Delivered Mixed Propofol and Remifentanil with Two Target-Controlled Infusion Pumps-Delivered Propofol and Remifentanil in Patients Undergoing Breast Cancer Surgery-A Prospective Study.

Total intravenous anesthesia (TIVA) with remifentanil and propofol (RP) is considered to be an ideal type of general anesthesia (GA) for pediatric and adult patients undergoing medical procedures. However, delivery of an RP mixture by target-controlled infusion (TCI) for GA in surgical procedures has not been described. We investigated the merit of this approach for breast cancer surgery. Eighty-four patients (n 42 per group) were randomly allocated to propofol and remifentanil either delivered by separate TCI pumps (S group) or in an RP mixture by a single TCI pump (M group). Dosages were adjusted based on the bispectral index (BIS) and the analgesia nociception index (ANI). The primary outcomes were adequate anesthesia (BIS 40-60 and ANI 50-70, respectively), acceptable hemodynamic fluctuations (<30% of baseline) with less frequent TCI pump adjustments, bolus injections of anesthetics, and total consumption of anesthetics during the procedure. The secondary endpoints included time of emergence from anesthesia, patient satisfaction, postoperative pain, rescue with opioids, and adverse events. The characteristics of patients, hemodynamic parameters, BIS and ANI scores, duration of surgery, anesthesia, and emergence were not significantly different between groups. The adjustment frequency of TCI was significantly higher in the S group (3 (range 0-6) vs. 2 (0-6) times

Multivariate Pharma Technology Transfer Analysis Civilization Diseases and COVID-19 Perspective.

The importance of studying civilization diseases manifests itself in the impact of changing lifestyles, on the number of deaths and causes of death. Technology transfer plays an important role in the prevention and treatment of these diseases. Through this, it is possible to transfer new treatments and diagnostics to clinics and hospitals more quickly and effectively, which leads to better healthcare for patients. Technology transfer can also aid in the development of new drugs and therapies that can be effective in the treatment of civilization diseases. The paper aims to evaluate the technology transfer process in the field of civilization diseases, using COVID-19 as an example of a pandemic that requires quick development and transfer of technology. To achieve the assumed goal, we propose a multivariate synthetic ratio in the field of civilization diseases (SMTT-Synthetic Measure of Technology Transfer) to analyze data from the Global Data database. We used sub-measures like SMTTvalue (Synthetic Measure of Technology Transfervalue) and SMTTquantity (Synthetic Measure of Technology Transferquantity) to measure technology transfer and put the data into a graph. Our analysis focuses on 14 diseases over a period of 10 years (2012-2021) and includes nine forms of technology transfer, allowing us to create a tool for analysing the process in multiple dimensions. Our results show that COVID-19 is similar in terms of technology transfer to diseases such as diabetes, cardiovascular diseases, neurodegenerative diseases, and breast cancer, even though data for COVID-19 is available for only 2 years.

Encouraging and Reinforcing Safe Breastfeeding Practices during the COVID-19 Pandemic.

Promote safe breastfeeding during the pandemic. All participants were encouraged to request safe breastfeeding education from their prenatal provider. Pregnant mothers received appropriate breastfeeding and COVID-19 safe breastfeeding education in line with the CDCs COVID-19 breastfeeding guidelines. Data were obtained from 39 mothers attending Nashville General Hospital pediatric well-baby clinics (Group I from December 2019 to June 2020) and 97 pregnant women attending prenatal clinics (Group II from July 2020 to August 2021). The participants ages ranged from 15 to 45 years, with a mean of 27.5 ± 6.2. The women in both groups were similar in age, education, employment, and breastfeeding experience. They were equally unlikely to use face masks at home even while receiving guests or holding their babies. Although 121 (89.0%) women claimed face mask use while shopping, the rate for never doing so was 7 (18.0%) vs. 8 (8.3%) ( The mothers were not more knowledgeable regarding breastfeeding safely one year into the COVID-19 pandemic. Conflicting lay information can create healthy behavior ambivalence, which can be prevented by health professionals confidently advising mothers to wear face masks when breastfeeding, restricting visitors and outings, and accepting COVID-19 vaccination. This pandemic remains an open opportunity to promote and encourage breastfeeding to every mother as the default newborn feeding method.

Gauging the Changing Landscape Telehealth Perceptions among Hispanic Females with Breast Cancer.

During the COVID-19 pandemic, telehealth use rapidly grew while its uptake steadily increased in cancer care. Prior research has reported existing racial and ethnic disparities in telehealth, with Hispanics reporting lower rates of use compared to other major racialethnic groups. Our study examined the perceived benefits and challengesdisadvantages faced by Hispanic females diagnosed with breast cancer in San Diego County, California. In-depth interviews were conducted with 27 participants, who were mostly Spanish speaking. The recordings of the interviews were transcribed and translated from Spanish to English. Reflexive thematic analyses revealed both potential benefits and challenges of telehealth. The perceived benefits included logistic and financial aspects (such as convenience and timefinancial savings), faster access and longer duration spent with clinicians, the availability of family members, and the minimization of COVID-19 risk. The reported challengesdisadvantages of telehealth and the suggested strategies to address them focused on limitations in clinical care, diminished engagement with clinicians, difficulty accessing interpreter services, and technological access and challenges. The COVID-19 pandemic has greatly affected the landscape of how care is provided, with a greater shift to telehealth services. More research is needed to further examine the challenges of telehealth, particularly for groups that are disproportionately affected, to avoid the disruption of patients cancer care and to promote a better patient healthcare experience.

Quality of Life and Side Effects Management in Cancer Treatment-A Cross Sectional Study.

Cancer disease is a world problem which is increasing in its prevalence. Oncology patients have a multitude of symptoms derived from the treatments and from the disease itself that affect their quality of life to a greater or lesser extent. The aim of this study has been to discover the physical and psychological symptoms related to chemotherapy treatment in Spanish cancer patients in order to improve their quality of life. Symptoms from the previous week were taken into account and the Memorial Symptom Assessment Scale was used to measure the frequency, severity and associated distress of 32 symptoms. A total of 246 chemotherapy patients at the University Day Hospital in Salamanca completed the scale once while receiving chemotherapy treatment. A 95% confidence interval was considered. The most prevalent symptoms were a lack of energy (76.4%), anxiety (66.7%) and a dry mouth (60.6%). Lung cancer was the most prevalent cancer in men (26%) and breast cancer was the most prevalent cancer in women (72%). There is no consensus on which is the most prevalent symptom in this population and more studies will need to be carried out to determine the best treatment protocols. Symptoms prevalence knowledge could improve the patients care to prevent or avoid complications and to improve the cancer patients quality of life.

Coping Self-Efficacy and Its Relationship with Psychological Morbidity after Genetic Test Result Disclosure Results from Cancer-Unaffected

Women who are found to carry a

Framework for Adoption of Next-Generation Sequencing (NGS) Globally in the Oncology Area.

Radical new possibilities of improved treatment of cancer are on offer from an advanced medical technology already demonstrating its significance next-generation sequencing (NGS). This refined testing provides unprecedentedly precise diagnoses and permits the use of focused and highly personalized treatments. However, across regions globally, many cancer patients will continue to be denied the benefits of NGS as long as some of the yawning gaps in its implementation remain unattended. The challenges at the regional and national levels are linked because putting the solutions into effect is highly dependent on cooperation between regional- and national-level cooperation, which could be hindered by shortfalls in interpretation or understanding. The aim of the paper was to define and explore the necessary conditions for NGS and make recommendations for effective implementation based on extensive exchanges with policy makers and stakeholders. As a result, the European Alliance for Personalised Medicine (EAPM) developed a maturity framework structured around demand-side and supply-side issues to enable interested stakeholders in different countries to self-evaluate according to a common matrix. A questionnaire was designed to identify the current status of NGS implementation, and it was submitted to different experts in different institutions globally. This revealed significant variability in the different aspects of NGS uptake. Within different regions globally, to ensure those conditions are right, this can be improved by linking efforts made at the national level, where patients have needs and where care is delivered, and at the global level, where major policy initiatives in the health field are underway or in preparation, many of which offer direct or indirect pathways for building those conditions. In addition, in a period when consensus is still incomplete and catching up is needed at a political level to ensure rational allocation of resources-even within individual countries-to enable the best ways to make the necessary provisions for NGS, a key recommendation is to examine where closer links between national and regional actions could complement, support, and mutually reinforce efforts to improve the situation for patients.

Use of Ultrasound and Ki-67 Proliferation Index to Predict Breast Cancer Tumor Response to Neoadjuvant Endocrine Therapy.

Prediction of tumor shrinkage and pattern of treatment response following neoadjuvant endocrine therapy (NET) for estrogen receptor positive (ER), Her2 negative (Her2-) breast cancers have had limited assessment. We examined if ultrasound (US) and Ki-67 could predict the pathologic response to treatment with NET and how the pattern of response may impact surgical planning. A total of 103 postmenopausal women with ER, HER2- breast cancer enrolled on the FELINE trial had Ki-67 obtained at baseline, day 14, and surgical pathology. A total of 70 patients had an US at baseline and at the end of treatment (EOT). A total of 48 patients had residual tumor bed cellularity (RTBC) assessed. The US response was defined as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). CR or PR on imaging and ≤70% residual tumor bed cellularity (RTBC) defined a contracted response pattern. A decrease in Ki-67 at day 14 was not predictive of EOT US response or RTBC. A contracted response pattern was identified in one patient with CR and in sixteen patients (33%) with PR on US. Although 26 patients (54%) had SD on imaging, 22 (85%) had RTBC ≤70%, suggesting a non-contracted response pattern of the tumor bed. The remaining four (15%) with SD and five with PD had no response. Ki-67 does not predict a change in tumor size or RTBC. NET does not uniformly result in a contracted response pattern of the tumor bed. Caution should be taken when using NET for the purpose of downstaging tumor size or converting borderline mastectomylumpectomy patients.

Understanding Patient Experience with Outpatient Cancer Rehabilitation Care.

Understanding patient experience is key to optimize access and quality of outpatient cancer rehabilitation (physical or occupational therapy, PTOT) services. We performed a retrospective mixed-method analysis of rehabilitation medical record data to better understand patient experience and aspects of care that influenced experience. From the medical record, we extracted case characteristics, patient experience data (Net Promoter Survey Patients (n 383) were 60.51 ± 12.02 years old, predominantly women with breast cancer (69.2%), and attended 14.23 ± 12.37 visits. Most were promoters (92%) NPS score was 91.4. Patients described two experiences (themes) that influenced their likelihood to recommend rehabilitation (1) feeling comfortable with the process and (2) observable improvement in healthfunctioning, and described attributes of clinic staff, environment and clinical care that influenced themes. Likelihood to recommend rehabilitation was associated with achieving the minimal clinical important difference on a PRO ( Patients who received specialized cancer PTOT were highly likely to recommend rehabilitation. Feeling comfortable with the rehabilitation process and making observable improvements in health andor functioning influenced likelihood to recommend. Rehabilitation providers should leverage the findings of this study optimize access to and quality of cancer rehab services.

Patients Perspectives of Interprofessional Collaboration in Breast Cancer Unit.

Interprofessional teamwork provides significant benefits for patients. However, qualitative research on interprofessional collaboration in the breast cancer unit is uncommon. Therefore, a qualitative study was conducted to assess the perceptions of outpatient breast cancer patients regarding interprofessional collaboration in the breast care unit of an Indonesian referral center hospital. The teamwork involved in the interprofessional collaboration included breast cancer specialists, pharmacists, and nurses. In this study, in-depth interviews were performed with nine breast cancer outpatients. All interviews were audio recorded, transcribed verbatim, and analyzed using thematic analysis. The findings were divided into two categories to gather breast cancer patients viewpoints on interprofessional collaboration (1) obstacle components to interprofessional collaboration incompleteness of health personnel, no justification from health personnel, no knowledge of patients about health professionals, no involvement of patients in the therapy decision making (2) enabling elements patient-oriented, patient expectations, collaboration among healthcare personnel, patient participation in interprofessional collaboration, health personnel responsibilities, comprehensive hospital services. Respondents assumed interprofessional collaboration positively. However, several obstacles must be overcome to implement interprofessional collaboration in a breast care setting effectively. The research findings can be utilized to establish interprofessional collaborations aimed at improving quality healthcare in breast cancer units.

Metformin Therapy and Breast Cancer Incidence in the Hail Region.

Metformin is a drug used to treat patients with type 2 diabetes, especially those who suffer from obesity. It is also used in the treatment of women with polycystic ovary syndrome (PCOS). This disease is related to insulin resistance and multiplied blood sugar ranges. Furthermore, it has been established that the use of metformin improves the menstrual cycles and ovulation rates of these women. A structured questionnaire was conducted to determine the prevalence of breast cancer among women using metformin in the Hail region. The incidence of breast cancer among women using metformin in the Hail region is very low. Thus, it can be said that breast cancer cases declined among diabetics taking metformin. This means that metformin use is associated with a lower risk of breast cancer in women with type 2 diabetes, even in cases where these women have a family history of breast cancer. According to previous findings, metformin has been linked to lower breast cancer risk in women with type 2 diabetes. Furthermore, the findings of this study corroborate the literature on this subject by indicating that there is a substantial connection between metformin use and a lower risk of breast cancer in women with type 2 diabetes. However, further in vitro and in vivo experiments are crucial to investigate the protective effect of metformin against breast cancer and to confirm our findings.

Cancer of the Cervix in Bulgaria Epidemiology of a Crisis.

Eastern Europe continues to have the highest rates of cancer of the uterine cervix (CUC) and human papillomavirus (HPV) infection in Europe. The aim of this study was to investigate CUC trends in Bulgaria in the context of a lack of a population-based screening program and a demographic crisis. This was a retrospective study of 7861 CUC patients who were registered in the Bulgarian National Cancer Registry (BNCR) between 2013 and 2020 and followed up with until March 2022. We used descriptive statistics and modeling to assess temporal trends in new CUC incidence rates and identify factors associated with survival. Bulgarias population has decreased by 11.5% between 2011 and 2021. The CUC incidence rate decreased from 29.5100,000 in 2013 to 23.2100,000 in 2020 but remains very high. The proportion of patients diagnosed in earlier stages of CUC has decreased over time. Up to 19% of patients with CUC in Bulgaria are diagnosed between the age of 35 and 44 years. The median survival was 101.5 months, with some improvement in later years (adjusted HR 0.83 for 2017-2020). In countries with well-established population-based screening, CUC is nowadays considered a rare disease. However, it is not considered rare in Bulgaria. Population-based screening starting at an earlier age is the fastest way to improve outcomes.

The Effects of the Ukrainian Conflict on Oncological Care The Latest State of the Art.

The COVID-19 pandemic has dramatically affected all aspects of the patients pathway to cancer diagnosis and subsequent treatment. Our main objective was to evaluate the status of cancer trials in Ukraine as of September 2022. Initially, we examined with a narrative review the state of breast, colorectal, and cervical cancer population-based screening. Subsequently, we assessed each trial status for the years 2021 and 2022. Estimates of participation in breast and cervical cancer screening are different from region to region. Moreover, regarding cervical cancer screening, extremely different participation estimates were reported 73% in 2003 vs. <10% 2020. Our data show that from 2014 to 2020, despite the pandemic, cancer trials in Ukraine significantly increased from 27 to 44. In 2021 no trials were completed in fact, we observed that out of 41 trials, 8 were active not recruiting, 33 were recruiting, and 0 were completed or terminated. In 2022 in Ukraine, for oncological pathologies, only 3 trials were registered, while in 2021, 41 trials were registered. The suspension of trials regarded above all concern hematological tissue (66.7%) and the genitourinary tract (60%). Our work has highlighted how the areas most affected by the conflict present criticalities in oncological care.

Ultrastructural Analysis of Cancer Cells Treated with the Radiopharmaceutical Radium Dichloride (

The use of alpha-particle (α-particle) radionuclides, especially

RUNX1 Is Regulated by Androgen Receptor to Promote Cancer Stem Markers and Chemotherapy Resistance in Triple Negative Breast Cancer.

Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype for which no effective targeted therapies are available. Growing evidence suggests that chemotherapy-resistant cancer cells with stem-like properties (CSC) may repopulate the tumor. The androgen receptor (AR) is expressed in up to 50% of TNBCs, and AR inhibition decreases CSC and tumor initiation. Runt-related transcription factor 1 (RUNX1) correlates with poor prognosis in TNBC and is regulated by the AR in prostate cancer. Our group has shown that RUNX1 promotes TNBC cell migration and regulates tumor gene expression. We hypothesized that RUNX1 is regulated by the AR and that both may work together in TNBC CSC to promote disease recurrence following chemotherapy. Chromatin immunoprecipitation sequencing (ChIP-seq) experiments in MDA-MB-453 revealed AR binding to

Transcriptomic and Functional Evidence That miRNA193a-3p Inhibits Lymphatic Endothelial Cell (LEC) and LEC MCF-7 Spheroid Growth Directly and by Altering MCF-7 Secretome.

MicroRNA 193a-3p (miR193a-3p) is a short non-coding RNA with tumor suppressor properties. Breast cancer (BC) progression is governed by active interaction between breast cancer cells, vascular (V)lymphatic (L) endothelial cells (ECs), and BC secretome. We have recently shown that miR193a-3p, a tumor suppressor miRNA, inhibits MCF-7 BC cell-driven growth of VECs via direct antimitogenic actions and alters MCF-7 secretome. Since LEC-BC cross-talk plays a key role in BC progression, we investigated the effects of miR193a-3p on MCF-7 secretome and estradiol-mediated growth effects in LECs and LEC MCF-7 spheroids, and delineated the underlying mechanisms. Transfection of LECs with miR193a-3p, as well as secretome from MCF-7 transfected cells, inhibited LEC growth, and these effects were mimicked in LEC MCF-7 spheroids. Moreover, miR193a-3p inhibited ERK12 and Akt phosphorylation in LECs and LEC MCF-7 spheroids, which are importantly involved in promoting cancer development and metastasis. Treatment of LECs and LEC MCF-7 spheroids with estradiol (E2)-induced growth, as well as ERK12 and Akt phosphorylation, and was abrogated by miR193a-3p and secretome from MCF-7 transfected cells. Gene expression analysis (GEA) in LEC MCF-7 spheroids transfected with miR193a-3p showed significant upregulation of 54 genes and downregulation of 73 genes. Pathway enrichment analysis of regulated genes showed significant modulation of several pathways, including interferon, interleukincytokine-mediated signaling, innate immune system, ERK12 cascade, apoptosis, and estrogen receptor signaling. Transcriptomic analysis showed downregulation in interferon and anti-apoptotic and pro-growth molecules, such as IFI6, IFIT1, OSA12, IFITM1, HLA-AB, PSMB89, and PARP9, which are known to regulate BC progression. The cytokine proteome array of miR193a-3p transfected MCF secretome and confirmed the upregulation of several growth inhibitory cytokines, including IFNγ, Il-1a, IL-1ra, IL-32, IL-33, IL-24, IL-27, cystatin, C-reactive protein, Fas ligand, MIG, and sTIM3. Moreover, miR193a-3p alters factors in MCF-7 secretome, which represses ERK12 and Akt phosphorylation, induces pro-apoptotic protein and apoptosis in LECs, and downregulates interferon-associated proteins known to promote cancer growth and metastasis. In conclusion, miR193a-3p can potentially modify the tumor microenvironment by altering pro-growth BC secretome and inhibiting LEC growth, and may represent a therapeutic molecule to target breast tumorscancer.

Systemically Identifying Triple-Negative Breast Cancer Subtype-Specific Prognosis Signatures, Based on Single-Cell RNA-Seq Data.

Triple-negative breast cancer (TNBC) is a highly heterogeneous disease with different molecular subtypes. Although progress has been made, the identification of TNBC subtype-associated biomarkers is still hindered by traditional RNA-seq or array technologies, since bulk data detected by them usually have some non-disease tissue samples, or they are confined to measure the averaged properties of whole tissues. To overcome these constraints and discover TNBC subtype-specific prognosis signatures (TSPSigs), we proposed a single-cell RNA-seq-based bioinformatics approach for identifying TSPSigs. Notably, the TSPSigs we developed mostly were found to be disease-related and involved in cancer development through investigating their enrichment analysis results. In addition, the prognostic power of TSPSigs was successfully confirmed in four independent validation datasets. The multivariate analysis results showed that TSPSigs in two TNBC subtypes-BL1 and LAR, were two independent prognostic factors. Further, analysis results of the TNBC cell lines revealed that the TSPSigs expressions and drug sensitivities had significant associations. Based on the preceding data, we concluded that TSPSigs could be exploited as novel candidate prognostic markers for TNBC patients and applied to individualized treatment in the future.

A Medical Image Segmentation Method Based on Improved UNet 3 Network.

In recent years, segmentation details and computing efficiency have become more important in medical image segmentation for clinical applications. In deep learning, UNet based on a convolutional neural network is one of the most commonly used models. UNet 3 was designed as a modified UNet by adopting the architecture of full-scale skip connections. However, full-scale feature fusion can result in excessively redundant computations. This study aimed to reduce the network parameters of UNet 3 while further improving the feature extraction capability. First, to eliminate redundancy and improve computational efficiency, we prune the full-scale skip connections of UNet 3. In addition, we use the attention module called Convolutional Block Attention Module (CBAM) to capture more essential features and thus improve the feature expression capabilities. The performance of the proposed model was validated by three different types of datasets skin cancer segmentation, breast cancer segmentation, and lung segmentation. The parameters are reduced by about 36% and 18% compared to UNet and UNet 3, respectively. The results show that the proposed method not only outperformed the comparison models in a variety of evaluation metrics but also achieved more accurate segmentation results. The proposed models have lower network parameters that enhance feature extraction and improve segmentation performance efficiently. Furthermore, the models have great potential for application in medical imaging computer-aided diagnosis.

A Novel Nomogram Based on Imaging Biomarkers of Shear Wave Elastography, Angio Planewave Ultrasensitive Imaging, and Conventional Ultrasound for Preoperative Prediction of Malignancy in Patients with Breast Lesions.

Several studies have demonstrated the difficulties in distinguishing malignant lesions of the breast from benign lesions owing to overlapping morphological features on ultrasound. Consequently, we aimed to develop a nomogram based on shear wave elastography (SWE), Angio Planewave Ultrasensitive imaging (Angio PLUS (AP)), and conventional ultrasound imaging biomarkers to predict malignancy in patients with breast lesions. This prospective study included 117 female patients with suspicious lesions of the breast. Features of lesions were extracted from SWE, AP, and conventional ultrasound images. The least absolute shrinkage and selection operator (Lasso) algorithms were used to select breast cancer-related imaging biomarkers, and a nomogram was developed based on six of the 16 imaging biomarkers. This model exhibited good discrimination (area under the receiver operating characteristic curve (AUC) 0.969 95% confidence interval (CI) 0.928, 0.989) between malignant and benign breast lesions. Moreover, the nomogram also showed demonstrated good calibration and clinical usefulness. In conclusion, our nomogram can be a potentially useful tool for individually-tailored diagnosis of breast tumors in clinical practice.

A Systematic Review of Application Progress on Machine Learning-Based Natural Language Processing in Breast Cancer over the Past 5 Years.

Artificial intelligence (AI) has been steadily developing in the medical field in the past few years, and AI-based applications have advanced cancer diagnosis. Breast cancer has a massive amount of data in oncology. There has been a high level of research enthusiasm to apply AI techniques to assist in breast cancer diagnosis and improve doctors efficiency. However, the wise utilization of tedious breast cancer-related medical care is still challenging. Over the past few years, AI-based NLP applications have been increasingly proposed in breast cancer. In this systematic review, we conduct the review using preferred reporting items for systematic reviews and meta-analyses (PRISMA) and investigate the recent five years of literature in natural language processing (NLP)-based AI applications. This systematic review aims to uncover the recent trends in this area, close the research gap, and help doctors better understand the NLP application pipeline. We first conduct an initial literature search of 202 publications from Scopus, Web of Science, PubMed, Google Scholar, and the Association for Computational Linguistics (ACL) Anthology. Then, we screen the literature based on inclusion and exclusion criteria. Next, we categorize and analyze the advantages and disadvantages of the different machine learning models. We also discuss the current challenges, such as the lack of a public dataset. Furthermore, we suggest some promising future directions, including semi-supervised learning, active learning, and transfer learning.

Diagnostic Usefulness of Diffusion-Weighted MRI for Axillary Lymph Node Evaluation in Patients with Breast Cancer.

This study aimed to determine whether apparent diffusion coefficient (ADC) and morphological features on diffusion-weighted MRI (DW-MRI) can discriminate metastatic axillary lymph nodes (ALNs) from benign in patients with breast cancer. Two radiologists measured ADC, long and short diameters, long-to-short diameter ratio, and cortical thickness and assessed eccentric cortical thickening, loss of fatty hilum, irregular margin, asymmetry in shape or number, and rim sign of ALNs on DW-MRI and categorized them into benign or suspicious ALNs. Pathologic reports were used as a reference standard. Statistical analysis was performed using the Mann-Whitney U test and chi-square test. Overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of DW-MRI were calculated. The ADC of metastatic ALNs was 0.905 × 10

Clinical Evidence of Circulating Tumor DNA Application in Aggressive Breast Cancer.

Breast cancer is clinically and biologically heterogeneous and is classified into different subtypes according to the molecular landscape of the tumor. Triple-negative breast cancer is a subtype associated with higher tumor aggressiveness, poor prognosis, and poor response to treatment. In metastatic breast cancer, approximately 6% to 10% of new breast cancer cases are initially staged IV (de novo metastatic disease). The number of metastatic recurrences is estimated to be 20-30% of all existing breast tumor cases, whereby the need to develop specific genetic markers to improve the prognosis of patients suffering from these deadly forms of breast cancer. As an alternative, liquid biopsy methods can minutely identify the molecular architecture of breast cancer, including aggressive forms, which provides new perspectives for more precise diagnosis and more effective therapeutics. This review aimed to summarize the current clinical evidence for the application of circulating tumor DNA in managing breast cancer by detailing the increased usefulness of this biomarker as a diagnostic, prognostic, monitoring, and surveillance marker for breast cancer.

Classifying Breast Cancer Metastasis Based on Imaging of Tumor Primary and Tumor Biology.

The molecular classification of breast cancer has allowed for a better understanding of both prognosis and treatment of breast cancer. Imaging of the different molecular subtypes has revealed that biologically different tumors often exhibit typical features in mammography, ultrasound, and MRI. Here, we introduce the molecular classification of breast cancer and review the typical imaging features of each subtype, examining the predictive value of imaging with respect to distant metastases.

Optimized S-Curve Transformation and Wavelets-Based Fusion for Contrast Elevation of Breast Tomograms and Mammograms.

For the purpose of accuracy in detection and diagnosis, Computer-Aided Diagnosis (CAD) is preferred by radiologists for the analysis of Breast Cancer. However, the presence of noise, artifacts, and poor contrast in breast images during acquisition highlights the need for sophisticated enhancement techniques for the proper visualization of region-of-interest (ROI). In this work, contrast elevation of breast mammographic and tomographic images is performed with an improved S-Curve transform using the Particle Swarm Optimization (PSO) algorithm. The enhanced images are assessed using dedicated quality metrics such as the Enhancement Measure (EME) and Absolute Mean Brightness Error (AMBE) measurement. Although the enhancement techniques help in attaining better images, certain features relevant for diagnosis purposes are removed during the enhancement process, creating contradictions for radiological interpretation. Hence, to ensure the retention of diagnostic features from original breast tomograms and mammograms, a Discrete Wavelet Transform (DWT)-based fusion approach is incorporated, which fuses the original and contrast-enhanced images (with optimized s-curve transformation function) using the maximum fusion rule. The fusion performance is thereafter measured using the Image Quality Index (IQI), Standard Deviation (SD), and Entropy (E) as fusion metrics.

Expression of the Immunohistochemical Markers CK5, CD117, and EGFR in Molecular Subtypes of Breast Cancer Correlated with Prognosis.

Molecular-based subclassifications of breast cancer are important for identifying treatment options and stratifying the prognosis in breast cancer. This study aimed to assess the prognosis relative to disease-free survival (DFS) and overall survival (OS) in patients with triple-negative breast cancer (TNBC) and other subtypes, using a biomarker panel including cytokeratin 5 (CK5), cluster of differentiation 117 (CD117), and epidermal growth factor receptor (EGFR). This cohort-case study included histologically confirmed breast carcinomas as cohort arm. From a total of 894 patients, 572 patients with early breast cancer, sufficient clinical data, and archived tumor tissue were included. Using the immunohistochemical markers CK5, CD117, and EGFR, two subgroups were formed one with all three biomarkers negative (TBN) and one with at least one of those three biomarkers positive (non-TBN). There were significant differences between the two biomarker subgroups (TBN versus non-TBN) in TNBC for DFS (

Contribution of Outpatient Ultrasound Transvaginal Biopsy and Puncture in the Diagnosis and Treatment of Pelvic Lesions A Bicenter Study.

The use of transvaginal ultrasound guided biopsy and puncture of pelvic lesions is a minimally invasive technique that allows for accurate diagnosis. It has many advantages compared to other more invasive (lower complication rate) or non-invasive techniques (accurate diagnosis). Furthermore, it offers greater availability, it does not radiate, enables the study of pelvic masses accessible vaginally with ultrasound control in real time, and it is possible to use the colour Doppler avoiding puncturing large vessels among others. The main aim of the work is to describe a standardized ambulatory technique and to determine its usefulness. This is a retrospective study of ultrasound transvaginal punctures (core needle biopsies and cytologies) and drainages of pelvic lesions performed on an outpatient basis during the last two years. The punctures were made with local anesthesia, under transvaginal ultrasound guidance with an automatic or semi-automatic 18G biopsy needle with a length of 20-25 cm and a penetration depth of 12 or 22 mm. The material obtained was sent for anatomopathological, cytological andor microbiological study if necessary. A total of 42 women were recruited in two centers. Fifty procedures (nine punctures, seven drains, and 34 biopsies) were performed. In five cases the punction and drain provided clinical relief in benign pelvic masses. Regarding material of the biopsies performed, 15 were vaginal in women previously histerectomized, finding 10 carcinomas, eight were ovarian tumours in advanced stages or peritoneal carcinomatosis obtaining the appropriate histology in each case, seven were suspicious cervical biopsies finding carcinomas in five of them, three were myometrial biopsies including one breast carcinoma metastasis in the miometrium and a benign placental nodule, and a periurethral biopsy was performed on a woman with a history of endometrial cancer confirming recurrence. The pathological diagnosis was satisfactory in all cases, confirming the nature of the lesion (25 malignant-ten vaginal recurrences of previous gynaecological cancers, eight cases of primary ovarianperitoneal carcinoma, four new diagnosis of cervical malignant masses, one cervical metastasis of lymphoma, one periurethral recurrence of endometrial carcinoma and one recurrence of breast cancer in the myometrium-and 23 benign). The tolerance was excellent and no complications were detected. The ambulatory ultrasound transvaginal puncture and drainage technique is useful for obtaining a sample for pathological and microbiological diagnosis with excellent tolerance that can be used to rule out the recurrence of malignant lesions or progression of the disease, diagnose masses not accessible to gynecological exploration (vaginal vault, myometrium or cervix) and for early histologic diagnosis in cases of advanced peritoneal carcinomatosis or ovarian carcinoma as well as drainage and cytological study of cystic pelvic masses.

Prone versus Supine FDG PETCT in the Staging of Breast Cancer.

Supine 18FFluorodeoxyglucose (FDG) positron emission technologycomputed tomography (PETCT) is a commonly used modality for the initial staging of breast cancer, and several previous studies have shown superior sensitivity and specificity of prone FDG PETCT in comparison to its supine counterpart. This retrospective study included 25 females with breast cancer referred for staging. They underwent supine FDG PETCT followed by prone FDG PETCT. The outcomes were number of primary breast lesions, anatomical site of FDG-avid lymph nodes (LNs), and number and type of bone lesions, with SUVmax of all corresponding parameters. Performance was superior in prone acquisition compared to supine acquisition, with the respective results 29 vs. 22 breast tumor lesions detected, 62 vs. 27 FDG-avid axillary LNs detected, sensitivity of 68% vs. 57%, specificity of 64% vs. 53%. The detection rate of axillary LNs in the prone position was significantly higher (

A Novel Medical Image Enhancement Algorithm for Breast Cancer Detection on Mammography Images Using Machine Learning.

Mammography is the most preferred method for breast cancer screening. In this study, computer-aided diagnosis (CAD) systems were used to improve the image quality of mammography images and to detect suspicious areas. The main contribution of this study is to reveal the optimal combination of various pre-processing algorithms to enable better interpretation and classification of mammography images because pre-processing algorithms significantly affect the accuracy of segmentation and classification methods. In this study, the effect of combinations of different preprocessing methods in differentiating benign and malignant breast lesions was investigated. All image processing algorithms used for lesion detection were used in the mini-MIAS database. In the first step, label information and pectoral muscle resulting from the acquisition of mammography images were removed. In the second step, median filter (MF), contrast limited adaptive histogram equalization (CLAHE), and unsharp masking (USM) algorithms with different combinations of the resolution and visibility of images are increased. In the third step, suspicious regions are extracted from the mammograms using the k-means clustering technique. Then, features were extracted from the obtained ROIs. Finally, feature datasets were classified as normalabnormal, and benignmalign (two class classification) using Machine Learning algorithms. Test performance measures of the classification methods were examined. In both classifications made in the study, lower classification performance values were obtained when the CLAHE algorithm was used alone as a pre-processing method compared to other pre-processing combinations. When the median filter and unsharp masking algorithms are added to the CLAHE algorithm, the performance of the classification methods has increased. In terms of classification success, Support Vector Machines, Random Forest, and Neural Networks showed the best performance. It was found by comparing the performances of the classification methods that different preprocessing algorithms were effective in detecting the presence of breast lesions and distinguishing benign and malignant.

Development of an Artificial Intelligence-Based Breast Cancer Detection Model by Combining Mammograms and Medical Health Records.

Artificial intelligence (AI)-based computational models that analyze breast cancer have been developed for decades. The present study was implemented to investigate the accuracy and efficiency of combined mammography images and clinical records for breast cancer detection using machine learning and deep learning classifiers. This study was verified using 731 images from 357 women who underwent at least one mammogram and had clinical records for at least six months before mammography. The model was trained on mammograms and clinical variables to discriminate benign and malignant lesions. Multiple pre-trained deep CNN models to detect cancer in mammograms, including X-ception, VGG16, ResNet-v2, ResNet50, and CNN3 were employed. Machine learning models were constructed using k-nearest neighbor (KNN), support vector machine (SVM), random forest (RF), Artificial Neural Network (ANN), and gradient boosting machine (GBM) in the clinical dataset. The detection performance obtained an accuracy of 84.5% with a specificity of 78.1% at a sensitivity of 89.7% and an AUC of 0.88. When trained on mammography image data alone, the result achieved a slightly lower score than the combined model (accuracy, 72.5% vs. 84.5%, respectively). A breast cancer-detection model combining machine learning and deep learning models was performed in this study with a satisfactory result, and this model has potential clinical applications.

Proof-of-Concept Study of an Alpha-Fetoprotein-Derived Peptide for the Management of Canine Mammary Cancer.

Novel, well-tolerated drugs are needed for the management of canine mammary cancer. Many of these cancers are promoted in their growth by estrogen. Alpha-fetoprotein (AFP) is a ubiquitous mammalian protein that has anti-estrogenic properties. AFPep (the anti-estrogenic site of AFP) has been developed into a readily synthesizable drug. AFPep has been shown to have anti-mammary cancer activity in several models of this disease, both in cell culture and in rodents. The purpose of the study reported herein was to determine the tolerability of AFPep in normal and tumor-bearing dogs. AFPep was given to dogs via both parenteral and oral routes in a single application and in repeated daily doses. Full clinical chemistry and hematology values were determined before and after drug administration. Blood levels of the drug were achieved in dogs that had been previously found to be oncostatic in rodents. No changes in clinical chemistry, hematology, and clinical behaviors were found in dogs following drug administration. The data support the further development of AFPep for clinical use against canine mammary cancer.

Enhancer Clusters Drive Type I Interferon-Induced TRAIL Overexpression in Cancer, and Its Intracellular Protein Accumulation Fails to Induce Apoptosis.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine produced and secreted by immune cells in response to an infection, often in response to interferon (IFN) stimulation. In cancer, it has also been shown that IFN stimulates the production of TRAIL, and it has been proposed that this TRAIL can induce apoptosis in an autocrine or paracrine manner in different cancer cells. Yet, the mechanism mediating TRAIL upregulation and the implications of TRAIL as an apoptotic molecule in cancer cells are still poorly understood. We show here that in certain cancer cells, TRAIL is upregulated by enhancer clusters, potent genomic regulatory regions containing densely packed enhancers that have combinatorial and additive activity and that are usually found to be associated with cancer-promoting genes. Moreover, we found that TRAIL upregulation by IFNα is mediated by these enhancer clusters in breast and lung cancer cells. Surprisingly, IFNα stimulation leads to the intracellular accumulation of TRAIL protein in these cancer cells. Consequently, this TRAIL is not capable of inducing apoptosis. Our study provides novel insights into the mechanism behind the interferon-mediated upregulation of TRAIL and its protein accumulation in cancer cells. Further investigation is required to understand the role of intracellular TRAIL or depict the mechanisms mediating its apoptosis impairment in cancer cells.

CDK46 Inhibitors in Pancreatobiliary Cancers Opportunities and Challenges.

Existing treatment strategies for pancreatobiliary malignancies are limited. Nowadays, surgery is the only path to cure these types of cancer, but only a small number of patients present with resectable tumors at the time of diagnosis. The notoriously poor prognosis, lack of diverse treatment options associated with pancreaticobiliary cancers, and their resistance to current therapies reflect the urge for the development of novel therapeutic targets. Cyclin-dependent kinase 46 (CDK46) inhibitors have emerged as an attractive therapeutic strategy in a number of cancers since their approval for treatment in patients with ERHER- breast cancer in combination with antiestrogens. In this article, we discuss the therapeutic potential of CDK46 inhibitors in pancreatobiliary cancers, notably cholangiocarcinoma and pancreatic ductal adenocarcinoma.

Prediction of the Malignancy of a Breast Lesion Detected on Breast Ultrasound Radiomics Applied to Clinical Practice.

The study aimed to evaluate the performance of radiomics features and one ultrasound CAD (computer-aided diagnosis) in the prediction of the malignancy of a breast lesion detected with ultrasound and to develop a nomogram incorporating radiomic score and available information on CAD performance, conventional Breast Imaging Reporting and Data System evaluation (BI-RADS), and clinical information. Data on 365 breast lesions referred for breast US with subsequent histologic analysis between January 2020 and March 2022 were retrospectively collected. Patients were randomly divided into a training group (

Changes in Expression of Tumor Suppressor Gene RKIP Impact How Cancers Interact with Their Complex Environment.

Tumor microenvironment (TME) is the immediate environment where cancer cells reside in a tumor. It is composed of multiple cell types and extracellular matrix. Microenvironments can be restrictive or conducive to the progression of cancer cells. Initially, microenvironments are suppressive in nature. Stepwise accumulation of mutations in oncogenes and tumor suppressor genes enables cancer cells to acquire the ability to reshape the microenvironment to advance their growth and metastasis. Among the many genetic events, the loss-of-function mutations in tumor suppressor genes play a pivotal role. In this review, we will discuss the changes in TME and the ramifications on metastasis upon altered expression of tumor metastasis suppressor gene RKIP in breast cancer cells.

Genomic Prostate Score A New Tool to Assess Prognosis and Optimize Radiation Therapy Volumes and ADT in Intermediate-Risk Prostate Cancer.

Genomic classifiers such as the Genomic Prostate Score (GPS) could help to personalize treatment for men with intermediate-risk prostate cancer (I-PCa). In this study, we aimed to evaluate the ability of the GPS to change therapeutic decision making in I-PCa. Only patients in the intermediate NCCN risk group with Gleason score 3 4 were considered. The primary objective was to assess the impact of the GPS on risk stratification NCCN clinical and genomic risk versus NCCN clinical risk stratification alone. We also analyzed the predictive role of the GPS for locally advanced disease (≥pT3) and the potential change in treatment strategy. Thirty patients were tested for their GPS between November 2018 and March 2020, with the median age being 70 (45-79). Twenty-three patients had a clinical T1 stage. Eighteen patients were classified as favorable intermediate risk (FIR) based on the NCCN criteria. The median GPS score was 39 (17-70). Among the 23 patients who underwent a radical prostatectomy, Gleason score 3 4 was found in 18 patients. There was a significant correlation between the GPS and the percentage of a Gleason grade 4 or higher pattern in the surgical sample correlation coefficient r 0.56 95% CI 0.2-0.8

Computational Pathology for Breast Cancer and Gynecologic Cancer.

Advances in computation pathology have continued at an impressive pace in recent years ....

2,2-Diphenethyl Isothiocyanate Enhances Topoisomerase Inhibitor-Induced Cell Death and Suppresses Multi-Drug Resistance 1 in Breast Cancer Cells.

We previously reported that phenethyl isothiocyanate (PEITC), a dietary-related compound, can rescue mutant p53. A structure-activity relationships study showed that the synthetic analog 2,2-diphenylethyl isothiocyanate (DPEITC) is a more potent inducer of apoptosis than natural or synthetic ITCs. Here, we showed that DPEITC inhibited the growth of triple-negative breast cancer cells (MDA-MB-231, MDA-MB-468, and Hs578T) expressing hotspot p53 mutants, structural (p53

Traffic-Related Air Pollution and Breast Cancer Risk A Systematic Review and Meta-Analysis of Observational Studies.

Current evidence of an association of breast cancer (BC) risk with air pollution exposure, in particular from traffic exhaust, remains inconclusive, and the exposure assessment methodologies are heterogeneous. This study aimed to conduct a systematic review and meta-analysis on the association between traffic-related air pollution (TRAP) and BC incidence (PROSPERO CRD42021286774). We systematically reviewed observational studies assessing exposure to TRAP and BC risk published until June 2022, available on MedlinePubMed and Web of Science databases. Studies using models for assessing exposure to traffic-related air pollutants or using exposure proxies (including traffic density, distance to road, etc.) were eligible for inclusion. A random-effects meta-analysis of studies investigating the association between NO

Impact of Surgical Care Bundle on Surgical Site Infection after Non-Reconstructive Breast Cancer Surgery A Single-Centre Retrospective Comparative Cohort Study.

Surgical-site infections (SSIs) are the commonest cause of healthcare-related infections. Although a surgical care bundle (SCB), defined as a group of preventative measures, is effective in reducing SSIs, it has not been well documented in breast cancer surgery. We aimed to investigate the impact of SCB on SSI. A single-centre retrospective comparative cohort study between 2016 and 2020 was carried out. An SCB including eight different measures was implemented in October 2018 at Sahlgrenska University Hospital, Sweden. Patients who underwent non-reconstructive breast cancer surgery were included for analysis. The primary endpoint was SSI within 30 days after surgery. Overall, 10.4% of patients (100958) developed SSI. After SCB implementation, the overall SSI rate reduced from 11.8% to 8.9% ( The implementation of a SCB could reduce the incidence of SSI in breast cancer surgery.

Tumour Growth Models of Breast Cancer for Evaluating Early Detection-A Summary and a Simulation Study.

With the advent of nationwide mammography screening programmes, a number of natural history models of breast cancers have been developed and used to assess the effects of screening. The first half of this article provides an overview of a class of these models and describes how they can be used to study latent processes of tumour progression from observational data. The second half of the article describes a simulation study which applies a continuous growth model to illustrate how effects of extending the maximum age of the current Swedish screening programme from 74 to 80 can be evaluated. Compared to no screening, the current and extended programmes reduced breast cancer mortality by 18.5% and 21.7%, respectively. The proportion of screen-detected invasive cancers which were overdiagnosed was estimated to be 1.9% in the current programme and 2.9% in the extended programme. With the help of these breast cancer natural history models, we can better understand the latent processes, and better study the effects of breast cancer screening.

PETCT with Fibroblast Activation Protein Inhibitors in Breast Cancer Diagnostic and Theranostic Application-A Literature Review.

Growing studies have recently reported on the promising application of radiolabeled-fibroblast activation protein inhibitors (FAPIs) as diagnostic and therapeutic agents in various oncological populations. To exclusively evaluate the current evidence on the diagnostic and therapeutic role of FAPI radiotracers in patients with breast cancer (BC), a narrative review of the available literature was performed. A search algorithm from PubMedMEDLINE, based on the combination of PET OR positron emission tomography and FAPI and cancer, with a last update in February 2022, was applied. From 233 identified articles, 33 studies conducted in BC patients and with available data on PET imaging or radiolabeled-FAPI therapy were finally considered, for a total of 191 patients. Despite some clinical and methodological heterogeneity among the reviewed articles,

The Rochester Modified Magee Algorithm (RoMMa) An Outcomes Based Strategy for Clinical Risk-Assessment and Risk-Stratification in ER Positive, HER2 Negative Breast Cancer Patients Being Considered for Oncotype DX

Multigene genomic profiling has become the standard of care in the clinical risk-assessment and risk-stratification of ER 355 patients with an ODX recurrence score, and at least five years of follow-up or a BC recurrence were included in the study. All patients received either Tamoxifen or an aromatase inhibitor. None of the patients received adjuvant systemic chemotherapy. There was no significant difference in the risk of recurrence in similar risk categories (very low risk, low risk, and high risk) between the average Modified Magee score and ODX recurrence score with the chi-square test of independence ( Our study further reinforces that BC patients can be confidently stratified into lower and higher-risk recurrence groups using the Magee equations

Exosome-Transmitted tRF-16-K8J7K1B Promotes Tamoxifen Resistance by Reducing Drug-Induced Cell Apoptosis in Breast Cancer.

Tamoxifen resistance remains a challenge in hormone receptor-positive (HR) breast cancer. Recent evidence suggests that transfer ribonucleic acid (tRNA)-derived fragments play pivotal roles in the occurrence and development of various tumors. However, the relationship between tRNA-derived fragments and tamoxifen resistance remains unclear. In this study, we found that the expression of tRF-16-K8J7K1B was upregulated in tamoxifen-resistant cells in comparison with tamoxifen-sensitive cells. Higher levels of tRF-16-K8J7K1B were associated with shorter disease-free survival in HR breast cancer. Overexpression of tRF-16-K8J7K1B promotes tamoxifen resistance. Moreover, extracellular tRF-16-K8J7K1B could be packaged into exosomes and could disseminate tamoxifen resistance to recipient cells. Mechanistically, exosomal tRF-16-K8J7K1B downregulates the expression of apoptosis-related proteins, such as caspase 3 and poly (ADP-ribose) polymerase, by targeting tumor necrosis factor-related apoptosis-inducing ligand in receptor cells, thereby reducing drug-induced cell apoptosis. Therapeutically, the inhibition of exosomal tRF-16-K8J7K1B increases the sensitivity of breast cancer cells to tamoxifen in vivo. These data demonstrate that exosomal tRF-16-K8J7K1B may be a novel therapeutic target to overcome tamoxifen resistance in HR breast cancer.

Response to Ovarian Stimulation for Urgent Fertility Preservation before Gonadotoxic Treatment in

Elevation of Cytoplasmic Calcium Suppresses Microtentacle Formation and Function in Breast Tumor Cells.

Cytoskeletal remodeling in circulating tumor cells (CTCs) facilitates metastatic spread. Previous oncology studies examine sustained aberrant calcium (Ca