Datasets:

---

Gaborandi

/

breast_cancer_pubmed_abstracts

like 2

An Magnetic-Targeting Nano-Diagnosis and Treatment Platform for TNBC.

In this experiment, we constructed a magnetic targeting nano-diagnosis and treatment platform of doxorubicin (DOX) combined with iron nanoparticles, and explored their application value and mechanism in the treatment of Triple Negative Breast Cancer (TNBC), as well as its new diagnosis and treatment mode in Magnetic Resonance Imaging (MRI). Hollow mesoporous nanoparticles (HFON) were synthesized by solvothermal method, and loaded the drug DOX (DOXHFON) to treat TNBC. The experiments in vivo and in vitro were carried out according to the characteristics of the materials. In vitro experiments, the killing effect of the drug on cells was verified by cell viability CCK8, ROS generation level, LPO evaluation and flow cytometry the MRI effect and targeted anti-tumor therapy effect were studied by in vivo experiments then the tumor tissue sections were detected by Ki-67, CD31, ROS, LPO and TUNEL immunofluorescence detection HE staining and blood biochemical tests were used to evaluate the biosafety of the materials. Through a series of characterization tests, it is confirmed that the nano-materials prepared in this experiment have positive drug loading properties. MDA-MB-231 cells had great phagocytic ability to DOXHFON under Confocal Laser Scanning Microscope (CLSM). Experiments in vitro confirmed that DOX and Fe were released and concentrated in cells, and a large number of ROS production and induction of LPO were detected by DCFH-DA and C11-BODIPY probes in cells. Apoptosis experiments further confirmed that DOXHFON induced apoptosis, autophagy and ferroptosis. In the vivo experiment, the anti-tumor therapy effect of MAGNETDOXHFON group was the most significant, and in MRI also proved that the drug had great tendency and imaging ability in tumor tissue. The new magnetic targeting nano-diagnosis and treatment platform prepared in this experiment is expected to become a new treatment model for TNBC.

Diagnostic accuracy of contrast-enhanced ultrasound synchronized with shear wave elastography in the differential diagnosis of benign and malignant breast lesions a diagnostic test.

Breast cancer (BC) is one of the most common malignancies affecting women. Timely and accurate diagnosis is crucial for treatment and prognosis. Some studies have found that elastography combined with microperfusion characteristics, which are mostly described by contrast-enhanced ultrasound (CEUS), could help in the diagnosis of breast lesions. This study aimed to assess the diagnostic performance of CEUS synchronized with shear wave elastography (SWE) in discriminating between benign and malignant breast lesions by using real-time contrast elastography images to analyze shell elasticity and contrast intensity. A total of 26 pathologically confirmed breast lesions in 26 patients were retrospectively reviewed. Each patient underwent conventional B-mode ultrasound, CEUS, and then SWE data was obtained from a frame of image that was almost identical to the B-mode and CEUS images when acquiring time to peak (TTP). Breast lesions were evaluated based on the Breast Imaging Reporting and Data System (BI-RADS) and quantitative characteristics that describe the stiffness and intensity of contrast of the 1.0-3.0 mm shell region. Quantitative aspects of the inner lesions and shell on the elastogram included the maximum (Emax), mean (Emean), and minimum (Emin) Youngs moduli. Quantitative enhanced features included maximum (Imax) and mean (Imean) intensity. We took postoperative pathological results as the gold standard. Receiver operating characteristic (ROC) curves were used to compare the diagnostic efficacy of the 2 examination modalities, either alone or in combination. The age of the patients ranged from 23 to 76 years, with a 42.5-year average age. In all breast lesions, 19 were benign and 7 were malignant. SWE synchronized with CEUS can effectively improve the diagnostic performance of breast lesions, and Emean Imean and Emax Emean Imean of shell at 1.0 mm both had the highest area under the curve (AUC) of 0.86 95% confidence interval (CI) 0.67, 0.96, with the sensitivity and specificity of 71.43% and 89.47%, respectively. The combination of CEUS and SWE has a better diagnostic value in differentiating benign and malignant breast lesions compared to separate techniques.

Breast metastasis from endometrial clear cell carcinoma A case report and review of the literature.

Metastasis to the breast from extra-mammary malignancies are rare, accounting for less than 1% of all breast cancers. Endometrial cancer, a common gynecological malignancy, often spreads to the pelvis, abdominal lymph nodes, peritoneum or the lungs. Endometrial metastasis to the breast is extremely rare, and while there have been isolated case reports of endometrial serous carcinoma with breast metastasis, it has not been reported in the case of clear cell carcinoma. We present a rare case of a 70 year old Chinese lady who had a metastatic endometrial clear cell carcinoma with metastasis to the breast, mimicking an inflammatory breast cancer clinically. We reviewed the current literature and describe the challenges in differentiating primary from metastatic breast lesions, as well as clinical, radiological and histopathological features that may help to differentiate the two. Tumour metastasis to the breast

LAG-3

Immune checkpoint molecule lymphocyte-activating gene-3 (LAG-3), which is expressed on active lymphocytes, has proven to be associated with immunosuppression and cancer progression in a variety of solid tumors. However, the role of LAG-3 We searched PubMed, Embase, and EBSCO to identify the studies evaluating the association of LAG-3 Eight published studies involving 5,859 BC patients were incorporated into this meta-analysis. We noted that a high number of LAG-3 The infiltration of LAG-3

Real-life analysis of neoadjuvant-therapy-associated benefits for pathological complete response and survival in early breast cancer patients - role of trastuzumab in HER2 BC and platinum in TNBC.

Neoadjuvant therapy, which aims to achieve a pathological complete response (pCR) for better overall survival (OS) has several advantages for patients with early breast cancer (eBC) and subtypes of HER2-positive (HER2) and triple-negative breast cancer (TNBC). However, there has been no large-scale real-world investigation on the clinical outcomes associated with trastuzumab-based and platinum-based neoadjuvant treatments for patients with HER2 and TNBC, respectively. Taiwan Cancer Registry and National Health Insurance Research Database were utilized in this study. Patients diagnosed with clinically lymph-node-positive (LN) HER2 or TNBC were identified for analysis. Logistic regression and Cox proportional hazard models were employed to estimate the adjusted odds ratios (aOR) of achieving pCR and adjusted hazard ratios (aHR) of overall survival associated with treatment agents, respectively. A total of 1,178 HER2 eBC and 354 early TNBC patients were identified, respectively. Neoadjuvant trastuzumab significantly increased the pCR rates by 3.87-fold among HER2 patients. Trastuzumab-associated survival benefit was found in HER2 patients who achieved pCR (aHR 95% CI 0.30 0.11-0.84) but not in those without pCR (1.13 0.77-1.67). Among the TNBC patients, platinum was associated with a 1.6-fold increased pCR rate however, it did not improve OS regardless of pCR status. Trastuzumab improved pCR and OS for patients with HER2 subtype. Using platinum agents for TNBC patients increased pCR rates but was not linked to better survival. Optimal neoadjuvant anti-HER2 therapy for patients with HER2 eBC and the introduction of novel therapy for patients with TNBC should be considered.

Real-world effect of bevacizumab and eribulin on metastatic breast cancer using a propensity score matching analysis.

Bevacizumab and eribulin are novel agents for the treatment of HER2-negative metastatic breast cancer (MBC) however, the choice between bevacizumab and eribulin for MBC can be difficult. The present study aimed to compare two treatment strategies, eribulin followed by bevacizumab and paclitaxel (BEV PTX) versus BEV PTX followed by eribulin, to determine whether the order of administration affects the outcome of MBC in the real world. A total of 180 patients who started BEV PTX and eribulin treatment for HER2-negative MBC from August 2011 to June 2018 were selected. Of these, 84 patients were treated with both BEV PTX and eribulin sequentially. To evaluate the influence of the sequential order, the efficacy of BEV PTX followed by eribulin (B-E arm) was compared to treatment with the reverse sequence (E-B arm). The propensity score matching method (PSMA) was used to improve the robustness of the findings from the present study. A total of 60 cases analyzed received BEV PTX or eribulin as either first- or second-line treatment. In the entire cohort, the median time to failure of strategy (TFS) was 16.8 and 9.9 months in the B-E and E-B arms, respectively hazard ratio (HR)0.515, 95% CI 0.298-0.889, P0.017). A similar HR was derived from PSMA for TFS. Using PSMA, TFS was 16.9 and 9.9 months in the B-E and E-B arms, respectively (HR0.491, 95% CI 0.253-0.952, P0.031). These results suggested that when both bevacizumab and eribulin are administered, bevacizumab should be administered first and eribulin should be administered later to ensure the most effective use of each drug.

Circulating cervical cancer biomarkers potentially useful in medical attention (Review).

Cervical cancer (CC) is a public health problem worldwide, including Mexico. This type of cancer is the fourth most frequent in women worldwide in Mexico it is the second most common type in women after breast cancer. The diagnosis of CC is based mainly on Pap smears and colposcopy and the identification of molecular tools that serve as a support for these methods is urgent. Regarding this, differential expressions of specific circulating biomolecules has been detected and, based on this, they have been postulated as potential biomarkers for CC diagnosis, prognosis, andor to identify the response to treatments. Importantly, the combined analysis of these molecules considerably improves their efficacy as biomarkers and their potential use in the medical attention is promising.

Axillary chest wall solid-papillary carcinoma A case report on presentation and management.

Papillary breast carcinomas comprise <1% of all breast cancers. They are notorious among surgical pathologists for posing diagnostic difficulty, especially with small sample sizes, such as a core-needle biopsy and carry potential for overtreatment. Solid-papillary carcinoma is a subtype of papillary breast carcinomas that affects elderly females and generally has a favorable diagnosis in its in-situ form. This report focuses on the unique and clinically aggressive presentation and treatment of invasive solid-papillary carcinoma that was discovered along the axillary chest wall after an ipsilateral mastectomy for multifocal ductal carcinoma in situ.

Evaluation of probe-based ultra-sensitive detection of miRNA using a single-molecule fluorescence imaging method miR-126 used as the model.

This study proposed a new detection method of miRNA based on single-molecule fluorescence imaging, a method that has been successfully developed to measure the light signal of individual molecules labeled with proper fluorophores. We designed probes 1 and 2 to be labeled with Cy5 dye and BHQ2 quencher at the 3terminals, respectively. Probe 1 consisted of two parts, the longer part complementary to miR-126 and the shorter part complementary to probe 2. After hybridization, miR-126 bound to probe 1 by replacing probe 2 and assembled into a double-stranded DNA with probe 1. The abundance of miR-126 was quantified by detecting image spots of Cy5 dye molecules from probe 1miR-126 complexes. MiR-126 single-molecule imaging method showed high specificity and sensitivity for miR-126 with a detection limit of 50 fM. This method has good selectivity for miR-126 detection with 2.1-fold, 8.8-fold, and 26.9-41.3-fold higher than those of single-base mismatched miR-126, three-base mismatched miR-126 and non-complementary miRNAs (miR-221, miR-16, miR-143 and miR-141). The method to detect miR-126 was validated in breast cancer cell lines. Our single-molecule miRNA imaging showed high specificity and sensitivity for miRNAs. By changing the base pair sequence of the designed probes, our method would be able to detect different miRNAs.

Periodic-net an end-to-end data driven framework for diffuse optical imaging of breast cancer from noisy boundary data.

The machine learning (ML) approach plays a critical role in assessing biomedical imaging processes especially optical imaging (OI) including segmentation, classification, and reconstruction, intending to achieve higher accuracy efficiently. This research aims to develop an end-to-end deep learning framework for diffuse optical imaging (DOI) with multiple datasets to detect breast cancer and reconstruct its optical properties in the early stages. The proposed Periodic-net is a nondestructive deep learning (DL) algorithm for the reconstruction and evaluation of inhomogeneities in an inverse model with high accuracy, while boundary measurements are calculated by solving a forward problem with sourcesdetectors arranged uniformly around a circular domain in various combinations, including The results of image reconstruction on numerical and phantom datasets demonstrate that the proposed network provides higher-quality images with a greater amount of small details, superior immunity to noise, and sharper edges with a reduction in image artifacts than other state-of-the-art competitors. The network is highly effective at the simultaneous reconstruction of optical properties, i.e., absorption and reduced scattering coefficients, by optimizing the imaging time without degrading inclusions localization and image quality.

Contouring Collaborative for Consensus in Radiation Oncology (C3RO) is a crowdsourced challenge engaging radiation oncologists across various expertise levels in segmentation. An obstacle to artificial intelligence (AI) development is the paucity of multiexpert datasets consequently, we sought to characterize whether aggregate segmentations generated from multiple nonexperts could meet or exceed recognized expert agreement. Participants who contoured For all cases, the DSC values for Multiple nonexpert-generated consensus ROIs met or exceeded expert-derived acceptability thresholds. Five nonexperts could potentially generate consensus segmentations for most ROIs with performance approximating experts, suggesting nonexpert segmentations as feasible cost-effective AI inputs.

Ensemble Learning-Based Hybrid Segmentation of Mammographic Images for Breast Cancer Risk Prediction Using Fuzzy C-Means and CNN Model.

The research interest in this field is that females are not aware of their health conditions until they develop tumour, especially when breast cancer is concerned. The breast cancer risk factors include genetics, heredity, and sedentary lifestyle. The prime concern for the mortality rate among females is breast cancer, and breast cancer is on the rise, both in rural and urban India. Women aged 45 or above are more vulnerable to this disease. Images are more effective at depicting information as compared to text. With the advancement in technology, several computerized techniques have come up to extract hidden information from the images. The processed images have found their application in several sectors and medical science is one of them. Disease-like breast cancer affects most women universally and it happens due to the existence of breast masses in the breast region for the development of breast cancer in women. Timely breast cancer detection can also increase the rate of effective treatment and the survival of women suffering from breast cancer. This work elaborates the method of performing hybrid segmentation techniques using CLAHE, morphological operations on mammogram images, and classified images using deep learning. Images from the MIAS database have been used to obtain readings for parameters threshold, accuracy, sensitivity, specificity rate, biopsy rate, or a combination of all the parameters and many others under study.

Higher risk of cardiovascular mortality than cancer mortality among long-term cancer survivors.

Previous studies focused more on the short-term risk of cardiovascular (CV) death due to traumatic psychological stress after a cancer diagnosis and the acute cardiotoxicity of anticancer treatments than on the long-term risk of CV death. Time trends in the proportions of CV death (P For patients with cancer at all sites, the P CV death gradually outweighs cancer death as survival time increases for most patients with cancer. Both the cardio-oncologist and cardio-oncology care should be involved to reduce CV deaths in long-term cancer survivors.

Hypermethylated WASF2 tumor suppressive role in head and neck squamous cell carcinoma.

WASF2 regulates actin reorganization during cell migration. WASF2 has been identified as a regulator of the development of gastric cancer, breast cancer, and pancreatic cancer. But its regulatory mechanisms remain unknown. Also, its function was absent in head and neck squamous cell carcinoma (HNSCC). Consequently, we examined the effect of DNA methylation on aberrant WASF2 expression in HNSCC. TNMplot, TIMER, GSEA pathway analysis, and the Kaplan-Meier Plotter database were used to analyze the expression, function, and prognostic value of WASF2, as well as the correlation between WASF2 and infiltrating immune cells in HNSCC or pan-cancer analysis. WASF2 promoter methylation levels and the correlation between WASF2 expression and WASF2 promoter methylation in HNSCC were evaluated using the DNMIVD database. The effect of DNA methylation inhibitor on WASF2 expression was demonstrated in the GEO database. Finally, the TISIDB database determined the relationships between WASF2 methylation, immune cell infiltration, and immune inhibitors. WASF2 was significantly downregulated in HNSCC tissues where WASF2 promoter methylation was elevated. According to the GEO database, treatment with a DNA methylation inhibitor notably restored the mRNA expression of WASF2. WASF2 expression was also a favorable indicator of human papilloma virus (HPV)-positive HNSCC. Its level of promoter methylation had detrimental effects on patient survival. In addition, patients with elevated levels of WASF2 demonstrated active G2M regulation, TGF-β signaling, Kras signaling, fatty acid metabolism, and p53 pathways. WASF2 was positively associated with tumor-killing immune cells, while WASF2 methylation was positively related to immunosuppressive cells and immune-inhibitors. Hypermethylated WASF2 acted as a tumor suppressor of HNSCC by regulating tumor formation and immune imbalance.

Clusterin is a biomarker of breast cancer prognosis and correlated with immune microenvironment.

It has been established that clusterin is involved in the invasion of immune cells in the tumor microenvironment, but it remains unknown how it promotes immune invasion in breast cancer. We used Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA) databases to assess the relation between expression of clusterin and immunoinfiltration-related marker genes. TIMER database was used to evaluate the expression of clusterin, and its relation to tumor immune invasion was examined. Based on Kaplan-Meier plotter database, we investigated the association between clusterin expression and prognosis in patients with cancer, and the impact of clinicopathological factors and cancer-related outcomes. Clusterin expression was markedly associated with prognosis of a variety of tumors, specifically breast cancer. Enhanced clusterin expression was markedly associated with molecular typing of breast cancer and expression of multiple markers related to specific immune cell subsets. These results indicate that clusterin is connected to prognosis of breast cancer patients and tumor immune cell infiltration. This demonstrates that clusterin may be a biomarker of immune cell recruitment into breast tumors and an important biomarker for immune cell infiltration consequently being a valuable prognostic factor in breast cancer patients.

Expression and clinical significance of undifferentiated embryonic cell transcription factor 1 in breast cancer.

At present, due to the heterogeneity of breast cancer, common tumor markers have certain limitations in clinical prognostic evaluation. This suggests an unmet need for markers to predict clinical outcomes and potentially guide targeted therapies. The present study sought to explore the expression level and clinical significance of undifferentiated embryonic cell transcription factor 1 (UTF1) in breast cancer. Immunohistochemistry (IHC) was used to detect the expression of UTF1 in 221 breast cancer samples. The clinical significance of UTF1 protein expression in breast cancer tissues was evaluated by combining clinicopathological parameters and UTF1 expression profile. We performed 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays to evaluate the effect of UTF1 on Bcap37 cell proliferation. Wound healing assay and transwell migration assay were used to evaluate the changes of cell invasion and migration ability, respectively. All experiments were performed with 3 biological replicates. Genomic differences after UTF1 overexpression were evaluated by RNA sequencing technology and the possible functions and regulatory mechanisms were elucidated. The findings showed that UTF1 expression level was significantly correlated with tumor size (P0.004), but not with patient age, tumor histological stage, lymph node metastasis, as well as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2), and Ki67 expression levels. Kaplan-Meier survival analysis and Cox proportional hazard model indicated that UTF1 expression was significantly associated with overall survival (OS) time of breast cancer patients. The median survival time of patients with high expression level of UTF1 was shorter compared with that of patients with low UTF1 expression level. The results of cell experiments showed that UTF1 overexpression could significantly promote the growth, proliferation, migration, and invasion of breast cancer cells. The RNA sequencing results showed that UTF1 was not only closely related to apoptosis genes, but also closely related to the nuclear factor (NF)-kappa B pathway. The findings of the current study indicate that UTF1 is involved in occurrence and tumor progression and is significantly associated with prognosis of breast cancer patients.

Targeting Education as a Barrier to Implement Hypofractionation Results of a Country-Wide Training Program.

Access to radiation therapy in low- and middle-income countries (LMICs) could be improved with modern hypofractionated radiation therapy schedules, although their adoption remains limited. We aimed to evaluate perceptions regarding hypofractionation and the effect of a dedicated curriculum in an LMIC. We developed a pilot e-learning hypofractionation curriculum focused on breast, prostate, rectal cancer, and high-grade glioma in Colombia. International educators taught 13 weekly, 90-minute sessions. Participants completed pre- and postcurriculum questionnaires regarding hypofractionation attitudes, 1 to 5 Likert-scale self-confidence, and practices for 12 clinical scenarios. Physicians responses were categorically scored 1 (for hypofractionation or ultrahypofractionation) or 0 (for conventional fractionation). We used the paired Across 19 cities in Colombia, 147 clinicians enrolled 61 radiation oncologists, 6 radiation oncology residents, 59 medical physicists, 18 physics residents, and 3 other staff. Among physicians, education was the greatest barrier to select hypofractionation, common in ultrahypofractionation for prostate (77.6%) and breast cancer (74.6%) and less common for moderate hypofractionation of prostate (61.2%) and breast cancer (52.2%). Additional perceived barriers included unfamiliarity with clinic protocols (7%-22%), clinical experience (5%-15%), personal preference (3%-16%), and lack of technology (3%-20%), with variation across different clinical settings. After the curriculum, paired (n 38) physicians selection of hypofractionation increased across all disease sites (mean aggregate score 6.212 vs 8.212, In an LMIC with a bundled payment system, lack of education and training was a perceived barrier for implementation of hypofractionation and ultrahypofractionation. A targeted e-learning hypofractionation curriculum increased participant confidence and selection of hypofractionated schedules.

Deep learning assisted holography microscopy for in-flow enumeration of tumor cells in blood.

Currently, detection of circulating tumor cells (CTCs) in cancer patient blood samples relies on immunostaining, which does not provide access to live CTCs, limiting the breadth of CTC-based applications. Here, we take the first steps to address this limitation, by demonstrating staining-free enumeration of tumor cells spiked into lysed blood samples using digital holographic microscopy (DHM), microfluidics and machine learning (ML). A 3D-printed module for laser assembly was developed to simplify the optical set up for holographic imaging of cells flowing through a sheath-based microfluidic device. Computational reconstruction of the holograms was performed to localize the cells in 3D and obtain the plane of best focus images to train deep learning models. We developed a custom-designed light-weight shallow Network dubbed s-Net and compared its performance against off-the-shelf CNN models including ResNet-50. The accuracy, sensitivity and specificity of the s-Net model was found to be higher than the off-the-shelf ML models. By applying an optimized decision threshold to mixed samples prepared

Elevated ADAM-like Decysin-1 (ADAMDEC1) expression is associated with increased chemo-sensitivity and improved prognosis in breast cancer patients.

Chemoresistance is problematic and its mechanisms are unclear in breast cancer. More predictive markers are urgently required. GSE32646, GSE34138, and GSE20271 were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) between chemosensitive and chemoresistant tumors. LinkedOmics was used to analyze ADAM-like Decysin-1 (ADAMDEC1) expression among patients with different clinical characteristics and detect co-expression genes for functional analysis. Tumor Immune Estimation Resource (TIMER) and an integrated repository portal for tumor-immune system interactions (TISIDB) were used to investigate the association between the target gene and the immune response. Gene Set Cancer Analysis (GSCA) was utilized to explore the related pathways of ADAMDEC1 and evaluate the correlation between the expression of ADAMDEC1 and drug sensitivity. RNA22, miRWalk, and miRmap were used to predict the upstream micro ribonucleic acids (miRNAs) regulating ADAMDEC1 expression, while DIANA-LncBase v2 was applied to predict the upstream long non-coding ribonucleic acids (lncRNAs). Kaplan-Meier curve analysis was applied to determine the survival time. We identified that ADAMDEC1 was upregulated among chemosensitive triple-negative breast cancer (TNBC) tissues in GSE32646, GSE34138, and GSE20271. Higher expression of ADAMDEC1 indicated longer survival in breast cancer. Next, we found that ADAMDEC1 was significantly related to the immune response in breast cancer through functional enrichment analysis and further meta-data validation. Moreover, we recognized that hsa-miR-4534 was the potential upstream miRNA regulating ADAMDEC1 expression and Taurine Up-Regulated 1 (TUG1) was the most likely upstream lncRNA of ADAMDEC1 and hsa-miR-4534. Finally, the correlation between ADAMDEC1 and chemosensitivity was confirmed through drug database analysis. Elevated ADAMDEC1 expression is associated with increased chemosensitivity and better prognosis in breast cancer patients.

Vitiligo-like lesions associated with ribociclib in a woman with metastatic breast cancer.

Cyclin-dependent kinase 46 inhibitors are new generation drugs that have recently been used in patients with hormone receptor-positive and human epidermal growth factor receptor 2-negativenegative metastatic breast cancer. Recent studies have shown that the use of cyclin-dependent kinase 46 inhibitors significantly improves the outcomes of these patients. The most common side effects of cyclin-dependent kinase 46 inhibitors are hematological toxicity, gastrointestinal side effects, and fatigue. We aimed to present a case of metastatic breast cancer who was treated with ribociclib and developed vitiligo-like lesions after treatment. A 56-year-old female patient was diagnosed with locally advanced hormone receptor ()human epidermal growth factor receptor 2 (-) breast cancer in May 2000. She was followed up with hormonal therapy after adjuvant chemotherapy and radiotherapy. The patient progressed with lung metastases in 2012. Ribociclib, anastrozole, and leuprolide acetate were started in November 2021 after multiple-line chemotherapy. After six cycles of ribociclib, vitiligo-like lesions that developed in the last 1 month were detected on the upper extremities, both hands, neck, chest, and upper back. The patient was referred to dermatology. Topical immunosuppressive therapy and oral corticosteroids were recommended. At the first and third-month follow-up examinations, vitiligo-like lesions were observed to persist. Vitiligo-like lesions are not a life-threatening side effect. However, it significantly affects the quality of life and disrupts the patients compliance with treatment. Cyclin-dependent kinase 46 inhibitors can inhibit cell division or cause premature cell death by acting on the melanocyte cell cycle.

Overall survival associated with CDK46 inhibitors in patients with HRHER2- metastatic breast cancer in the United States A SEER-Medicare population-based study.

Evidence on overall survival (OS) with cyclin-dependent kinase 4 and 6 (CDK46) inhibitors is generally limited to data from clinical trials or a few observational studies with limited generalizability to Medicare population. The aim of this study was to determine OS benefits associated with CDK46 inhibitors in older Medicare patients with hormone receptor (HR)-positive and human epidermal growth factor receptor-2 overexpressing (HER2-) metastatic breast cancer (MBC). In a retrospective cohort design, female patients aged ≥65 years with diagnosis of HRHER2- MBC from 2015 to 2017 who initiated first-line systemic therapy within 12 months of MBC diagnosis were selected from the Survey Epidemiology and End Results-Medicare database. The effect of treatment type (endocrine therapy ETCDK46 inhibitor vs. ET alone) on OS was analyzed using Kaplan-Meier methods and multivariable Cox regression models. Adjusted hazard ratio (aHR) and 95% CIs were estimated. A total of 630 eligible patients were identified (169 patients treated with ETCDK46 inhibitor and 461 patients treated with ET alone). In the Kaplan-Meier analysis, OS rate at 3 years after first-line treatment initiation was 73.0% for ETCDK46 inhibitor versus 49.1% for ET alone (log-rank p < .0001). In Cox regression analysis, first-line ETCDK46 inhibitor therapy was associated with 41% lower rate of mortality versus ET alone (aHR, 0.590 95% CI, 0.423-0.823). The findings of this real-world study demonstrate significant OS benefit associated with ETCDK46 inhibitor therapy over ET alone in an older Medicare population of patients with HRHER2- MBC, largely consistent with the evidence from clinical trials.

Self-assessment of a breast care nursing model within a Breast Unit learning process and keys to improving breast care.

To assess the adherence of a nursing care model in a multidisciplinary breast cancer unit in a tertiary hospital to the recommended competencies and quality indicators. Aligning the competencies of the breast care nurse with international recommendations for this role helps better fulfil patient needs, increases satisfaction and ensures continuity of care. Cohort study. Breast care nursing was assessed in all patients treated at the Functional Breast Unit from 1 July 2016 to 30 June 2017. Patients were followed for 1 year. Sociodemographic, clinical and pathological data, treatments performed and nursing interventions were collected. The strobe checklist has been used to report this study. We analysed nursing interventions carried out in 382 patients attended over 1 year in a multidisciplinary breast cancer unit. All patients with early disease had contact with the nurse at different times during their primary treatment. Only 58% of patients with advanced disease had contact with the nurse during their first year of illness. Moreover, first contact with the nurse was delayed by more than a week from diagnosis, the interval recommended by international guidelines. The nursing care model meets the core competencies defined for the breast care nurse in patients with early breast cancer, but the first visit should be organised earlier, and follow-up should extend beyond completion of primary treatment. This study evaluated the breast care nurse model in one breast cancer unit according to international guidelines. Nursing care adhered to most guideline requirements in patients with early breast cancer, but not in those with advanced disease. New models of care need to be developed for women with advanced breast cancer in order to achieve true patient-centred care. No contribution from the patient or the public because the data collected was entered into the clinical history by the health professionals of the Breast Unit as part of their usual clinical practice.

Five Cases of Breast Cancer Developed after Silicone Breast Implant.

We report 5 cases of breast cancer that developed after cosmetic augmentation using silicone breast implants. The chief complaints were breast tumor in 3 cases, skin change in 1 case, and nipple bleeding in 1 case. Intervals between silicone breast implants and breast cancer surgeries ranged from 10 to 31 years. The pTNM stages included were Stage 0, Ⅰ, ⅡA, ⅢB, and Ⅳ, respectively, and the subtypes included were 3 Luminal types and 2 Luminal-HER2 types. Silicone bag rupture was noted in 1 case, and all bags were removed during surgery. The breast cancer surgeries performed were four breast- conserving surgeries and one mastectomy. The follow-up period ranged between 1.8 and 14 years(mean 5.1 years). All cases survived, but 2 cases had recurrences the Stage ⅢB case experienced lung metastasis 2 years postoperatively and Stage Ⅳ case had induced pCR by chemotherapy postoperatively, but therapeutic self-interruption led to recurrences at the contralateral axillary nodes and contralateral breast and lung metastases 3 years postoperatively. Judging from limited reports of breast cancer after silicone breast implant in Japan, their incidence seems to be extremely low, and the incidence in our clinic during these 15 years(5 out of 1,851 primary breast cancers)is 0.27%.

Challenges to International Collaborative Clinical Research and Approval Disparities.

The standard treatment and prognosis of breast cancer are improving as because of international collaborative clinical research. Generally, the standard treatment for breast cancer in Japan is not different from that in the US, Europe or other Asian countries, however, some novel agents have not been developed or have been delayed. For example, no institution in Japan has participated in the clinical trials of sacituzumab-govitecan. Institutions in Japan participated in the clinical trial of alpelisib and neratinib, however, the development of these drugs was delayed due to the racial difference and lack of a company in charge. On the other hand, there are international collaborative trials that Japan has participated in or has taken the lead, such as POSITIVE trial, CREATE-X trial, and PATHWAY trial. There are many challenges for Japan to participate in or lead international collaborative trials with Europe, US, or Asia. It is necessary to build a network and infrastructure for international collaborative trials based on the cooperation between the institutions and clinical trial groups in the world.

Study on the correlation between B vitamins and breast cancer.

Relevant studies suggest that serum vitamin level is related to the risk of breast cancer, and dietary pattern and drug supplementation can significantly affect the level of vitamin in the body. Therefore, intervention of vitamin level in the body is expected to be a potential strategy to reduce the risk of breast cancer. However, the current epidemiological findings of serum vitamin levels and breast cancer risk are inconsistent, and the relationship between serum vitamin and breast cancer is still controversial. In this study, we compared the serum vitamin expression levels of healthy people, benign breast patients, and breast cancer patients, and evaluated the relationship between B vitamin levels and breast cancer risk. The study used liquid chromatography-tandem mass spectrometry to determine the serum vitamin levels of 520 people who attended Yunnan Cancer Hospital from September 2020 to December 2020. After screening by exclusion criteria, 38 patients with benign breast diseases, 87 patients with breast cancer and 91 healthy controls were finally included. The kruskal-wallis H test was used to compare the differences in serum vitamin levels of subjects. Χ The levels of VitB1 and VitB5 in the serum of breast cancer patients and patients with benign breast diseases were higher than those in the healthy control group, while the expression levels of VitB3 in breast cancer patients were lower than those in the healthy control group and the breast benign disease groups. The level of VitB1 was positively correlated with breast cancer risk. The VitB3 level was negatively correlated with breast cancer risk. The VitB5 level is not significantly related to the risk of breast cancer.

Evaluating the psychometric properties of the Persian version of the Healthy Lifestyle Instrument for Breast Cancer Survivors (HLI-BCS).

Precise examination of breast cancer survivors lifestyles can lead to improved planning and implementation of care and counseling interventions to increase their survival rate and improve their quality of life. Therefore, a valid and reliable instrument needs to be developed. Therefore, the present study aimed to determine the psychometric properties of the Persian version of the Healthy Lifestyle Instrument for Breast Cancer Survivors (HLI-BCS). This methodological study was conducted on 420 Iranian breast cancer survivors between May and November 2022. Participants were selected using convenience sampling. The face, content, construct validity, convergent, and reliability of the Persian version of the HLI-BCS were assessed. After assessing face, content, and construct validity, the Persian version of the HLI-BCS with five factors and 20 items was provided. The total Cronbachs alpha and intra-class correlation coefficient (ICC) were calculated as 0.86 and 0.79, respectively, which were at acceptable levels. A healthy lifestyle in breast cancer survivors was observed to have strong and significant relationships with quality of life in general (p < 0.001, r 0.832), physical health (r 0.786), and mental health (r 0.809). The Persian version of the HLI-BCS has favorable properties, is consistent with the conditions of breast cancer survivors, and is valid and reliable. This version of the scale can provide adequate and precise information on the lifestyles of these patients.

Inhibition of MMPs supports amoeboid angiogenesis hampering VEGF-targeted therapies via MLC and ERK 12 signaling.

In the past decades studies on anti-tumoral drugs inhibiting matrix metalloproteinase (MMPs) were disappointing. Recently, we demonstrated that mature endothelial cells (ECs) and endothelial colony forming cells (ECFCs) can switch between invasion modes to cope with challenging environments, performing the amoeboid angiogenesis in the absence of proteases activity. We first set out to investigate by ELISA if the inhibitors of the main protease family involved in angiogenesis were differently expressed during breast cancer progression. We used Marimastat, a broad-spectrum MMP inhibitor, as a means of inducing amoeboid characteristics and studied VEGF role in amoeboid angiogenesis. Thus, we performed invasion and capillary morphogenesis assay, morphological, cell signaling and in vivo mouse studies. Our data showed that TIMP1, TIMP2, alpha2-antiplasmin, PAI-1 and cystatin increase in breast cancer serum of patients with primary cancer and lymph node positive compared to healthy women. In vitro results revealed that the most high-powered protease inhibitors able to induce amoeboid invasion of ECFCs were TIMP1, 2 and 3. Surprisingly, Marimastat promotes ECFC invasion and tubular formation in vitro and in vivo, inducing amoeboid characteristics. We observed that the combination of Marimastat plus VEGF doesnt boost neither cell invasion nor vessel formation capacity. Moreover, inhibition of VEGF activity with Bevacizumab in the presence of Marimastat confirmed that amoeboid angiogenesis is independent from the stimulus of the main vascular growth factor, VEGF. We underline the importance to consider the amoeboid mechanism of endothelial and cancer cell invasion, probably responsible for the failure of synthetic metalloproteinase inhibitors as cancer therapy and tumor resistance to VEGF-targeted therapies, to set-up new drugs to be used in cancer therapy.

Melatonin and 5-fluorouracil combination chemotherapy opportunities and efficacy in cancer therapy.

Combined chemotherapy is a treatment method based on the simultaneous use of two or more therapeutic agents it is frequently necessary to produce a more effective treatment for cancer patients. Such combined treatments often improve the outcomes over that of the monotherapy approach, as the drugs synergistically target critical cell signaling pathways or work independently at different oncostatic sites. A better prognosis has been reported in patients treated with combination therapy than in patients treated with single drug chemotherapy. In recent decades, 5-fluorouracil (5-FU) has become one of the most widely used chemotherapy agents in cancer treatment. This medication, which is soluble in water, is used as the first line of anti-neoplastic agent in the treatment of several cancer types including breast, head and neck, stomach and colon cancer. Within the last three decades, many studies have investigated melatonin as an anti-cancer agent this molecule exhibits various functions in controlling the behavior of cancer cells, such as inhibiting cell growth, inducing apoptosis, and inhibiting invasion. The aim of this review is to comprehensively evaluate the role of melatonin as a complementary agent with 5-FU-based chemotherapy for cancers. Additionally, we identify the potential common signaling pathways by which melatonin and 5-FU interact to enhance the efficacy of the combined therapy. Video abstract.

Preparation of chitosan nanoparticle containing recombinant CD44v antigen and evaluation of its immunization capacity against breast cancer in BALBc mice.

Breast tumors show heterogeneity containing cancer stem cells as a small subpopulation of a tumor mass. CD44 as a cancer stem cells antigen is abnormally expressed by carcinomas of epithelial origin. Also, overexpression of CD44 variable isoforms (CD44v) is associated with malignancy in breast cancer. In the present research, our objective was to evaluate the immunogenicity of prepared nanoparticles containing a novel recombinant CD44v (rCD44v) protein in the mouse model. CD44 gene was expressed in E. coli BL21 DE3 using the pET28a-CD44 vector. The expressed rCD44v protein was purified, encapsulated into the chitosan nanoparticles, and administered to BALBc mice. ELISA was used to evaluate the immunoglobulin levels of immunized animals. For challenge experiment, 2 × 10 The measured size of chitosan-rCD44v nanoparticles was 146.5 nm. Recombinant CD44v encapsulated by chitosan nanoparticles increases immunological responses via the adjuvant nature of chitosan nanoparticles. In the immunized mice, IgG and IgA titers were significantly increased. Tumor growth in injection and nano-injection test groups compared with the mice control groups displayed a significant reduction (P < 0.05). A high amount of splenocytes secreting IFNγ and IL-17 was seen in immunized mice with rCD44v (P < 0.05). Furthermore, a smaller size of lung metastases compared to the control mice groups was detected. The encapsulated rCD44v within the chitosan nanoparticles induced a significant immune response in mice and can establish significant protection against breast cancer. Therefore, it can be considered a vaccine candidate for breast cancer therapeutic modalities.

A reversible SRC-relayed COX2 inflammatory program drives resistance to BRAF and EGFR inhibition in BRAF

BRAF

The oncogenic roles and clinical implications of YAPTAZ in breast cancer.

Breast cancer (BC) is the most commonly diagnosed form of cancer and a leading cause of cancer-related deaths among women worldwide. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are homologous transcriptional coactivators and downstream effectors of Hippo signalling. YAPTAZ activation has been revealed to play essential roles in multiple events of BC development, including tumour initiation, progression, metastasis, drug resistance and stemness regulations. In this review, we will first give an overview of YAPTAZ-mediated oncogenesis in BC, and then systematically summarise the oncogenic roles of YAPTAZ in various BC subtypes, BC stem cells (BCSCs) and tumour microenvironments (TMEs). Based on these findings, we will further discuss the clinical implications of YAPTAZ-based targeted therapies in BC and the potential future direction.

Oncolytic T-VEC virotherapy plus neoadjuvant chemotherapy in nonmetastatic triple-negative breast cancer a phase 2 trial.

Talimogene laherparepvec (T-VEC) is an oncolytic virus hypothesized to enhance triple-negative breast cancer (TNBC) responses to neoadjuvant chemotherapy (NAC). This article describes the phase 2 trial of T-VEC plus NAC (ClinicalTrials.gov ID NCT02779855 ). Patients with stage 2-3 TNBC received five intratumoral T-VEC injections with paclitaxel followed by doxorubicin and cyclophosphamide and surgery to assess residual cancer burden index (RCB). The primary end point was RCB0 rate. Secondary end points were RCB0-1 rate, recurrence rate, toxicity and immune correlates. Thirty-seven patients were evaluated. Common T-VEC toxicities were fevers, chills, headache, fatigue and injection site pain. NAC toxicities were as expected. Four thromboembolic events occurred. The primary end point was met with an estimated RCB0 rate 45.9% and RCB0-1 descriptive rate 65%. The 2-year disease-free rate is equal to 89% with no recurrences in RCB0-1 patients. Immune activation during treatment correlated with response. T-VEC plus NAC in TNBC may increase RCB0-1 rates. These results support continued investigation of T-VEC plus NAC for TNBC.

Novel roles of RNA-binding proteins in drug resistance of breast cancer from molecular biology to targeting therapeutics.

Therapy resistance remains a huge challenge for current breast cancer treatments. Exploring molecular mechanisms of therapy resistance might provide therapeutic targets for patients with advanced breast cancer and improve their prognosis. RNA-binding proteins (RBPs) play an important role in regulating therapy resistance. Here we summarize the functions of RBPs, highlight their tremendously important roles in regulating therapy sensitivity and resistance and we also reveal current therapeutic approaches reversing abnormal functions of RBPs in breast cancer.

Rates of reoperation after breast conserving cancer surgery in Western Australia before and after publication of the SSO-ASTRO margins guideline.

A 2014 SSO-ASTRO guideline on surgical margins aimed to reduce unnecessary reoperation after breast conserving surgery (BCS). We investigate whether publication of the guideline was associated with a reduction in reoperation in Western Australia (WA). In this retrospective, population-based cohort study, cases of newly-diagnosed breast cancer were identified from the WA Cancer Registry. Linkage to the Hospital Morbidity Data Collection identified index BCS for invasive cancer between January 2009 and June 2018 (N 8059) and reoperation within 90 days. Pre-guideline (2009-2013) and post-guideline (2014-2018) reoperation proportions were compared, and temporal trends were estimated with generalised linear regression. The pre-guideline reoperation proportion was 25.8% compared with 21.7% post-guideline (difference -4.0% 95% CI -5.9, -2.2, p < 0.001, odds ratio OR 0.80 95% CI 0.72, 0.89, p < 0.001). Absolute reductions were similar for repeat BCS (16.3% versus 14.6% difference -1.8% 95% CI -3.4, -0.2, p 0.03) and conversion to mastectomy (9.4% versus 7.2% difference -2.2% 95% CI -3.4, -1.0, p < 0.001). Over the study period, there was an annual absolute change in reoperation of -0.8% (95% CI -1.2, -0.5, p < 0.001). Accounting for this linear trend, the difference in reoperation between time periods was -0.5% (95% CI -4.3, 3.3 p 0.81), reflecting a non-significant reduction in conversion to mastectomy. Comparisons of pre- versus post-guideline time periods in WA showed reductions in reoperation that were similar to international estimates however, an annual decline in reoperation predated the guideline. Analyses that do not account for temporal trends are likely to overestimate changes in reoperation associated with the guideline.

2022 New therapeutic practices in breast oncology.

In women, breast cancer is both the most common and the deadliest. In 2018, an estimated 58,459 new cases were diagnosed in France, and 12,146 patients died. While these figures are impressive, it should be borne in mind that patient survival after treatment for breast cancer has improved significantly and is now 87 % at five years (nearly nine out of ten women), up from 80 % in 1993. This progress is due to the different weapons available to patients and the development of new therapies such as immunotherapy or drug-conjugated antibodies. The classification of breast cancers is also evolving, in particular through the identification of biomarkers that enable the therapeutic strategy to be refined (PD-L1, BRCA…). New anti-HER2 molecules, such trastuzumab deruxtecan, have shown very promising therapeutic activity in patients with breast cancer with low HER2 expression. The search for the BRCA constitutional mutation helps to optimise management. The use of pembrolizumab in the metastatic setting is now possible in tumours expressing PD-L1 with a threshold expression of the PD-L1marker of CPS ≥ 10. In addition, late 2021early 2022 has provided evidence that collaboration between physicians and patient networks facilitates better access to treatment. This review presents advances in adjuvant and metastatic breast cancer presented at ASCO and ESMO in 2022.

An 80-Year-Old Woman With Dyspnea and a Lung Mass.

An 84-year-old woman presented to the interventional pulmonary clinic for evaluation of a right middle lobe lung mass. Her medical history was notable for atrial fibrillation on rivaroxaban and recurrent bilateral breast cancer that had required multiple lumpectomies, radiation, and chemotherapy. She is a former smoker of five-pack years. She underwent a right and left heart catheterization at an outside facility 2 months prior to her presentation for evaluation of dyspnea that showed minimal coronary artery disease but elevated pulmonary artery pressures of 5524 mm Hg. The procedure itself was complicated by hemoptysis that required hospital admission for observation. She underwent a chest radiography during her hospitalization (Fig 1) There was no recent imaging for comparison. She was seen by a pulmonologist as an outpatient and underwent bronchoscopy with BAL and bronchial brushing for concerns of malignancy. The results were not diagnostic. She was then referred to the interventional pulmonary service for further evaluation.

Breast Cancer Risk Assessment, Screening, and Primary Prevention.

This review provides an outline of a risk-based approach to breast cancer screening and prevention. All women should be assessed for breast cancer risk starting at age 18 with identification of modifiable and non-modifiable risk factors. Patients can then be stratified into average, moderate, and high-risk groups with personalized screening and prevention plans. Counseling on breast awareness and lifestyle changes is recommended for all women, regardless of risk category. High-risk individuals may benefit from additional screening modalities such as MRI and chemoprevention and should be managed closely by a multidisciplinary team.

Adenoid cystic carcinoma of the breast with late recurrence and high-grade transformation.

Breast cancers have broad histological subtypes with varied molecular expression, which determines the management. Although ductal and lobular breast carcinomas constitute the significant 90% of these tumours, other subtypes constitute about 10% of breast cancers. Adenoid cystic carcinoma (AdCC) is a salivary gland-type tumour described in breast, constituting less than 1% of all breast carcinomas. These tumours have a favourable prognosis and are surgically managed by either lumpectomy or mastectomy. Solid-basaloid and AdCC with high-grade transformation are the sporadic subtypes of AdCC, in addition to the classic type. We report a case of recurrent AdCC which was surgically managed by modified radical mastectomy initially and presented with recurrence and high-grade transformation 11 years later.

Prognosis-related metabolic genes in the development of colorectal cancer progress and perspective.

Colorectal cancer (CRC) is one of the most commonplace malignant tumors in the world. The occurrence and development of CRC are involved in numerous events. Metabolic reprogramming is one of the hallmarks of cancer and is convoluted and associated with carcinogenesis. Lots of metabolic genes are involved in the occurrence and progression of CRC. Study methods combining tumor genomics and metabolomics are more likely to explore this field in depth. In this mini-review, we make the latest progress and future prospects into the different molecular mechanisms of seven prognosis-related metabolic genes, we screened out in previous research, involved in the occurrence and development of CRC.

High-throughput method to analyze the cytotoxicity of CAR-T Cells in a 3D tumor spheroid model using image cytometry.

Solid tumors account for approximately 90% of all adult human cancers. As such, the development of novel cellular therapies has become of increasing importance to target solid tumor malignancies, such as prostate, lung, breast, bladder, colon, and liver cancers. One such cellular therapy relies on the use of chimeric antigen receptor T cells (CAR-T cells). CAR-T cells are engineered to target specific antigens on tumor cells. To date, there are six FDA-approved CAR-T cell therapies that have been utilized for hematologic B cell malignancies. Immune cell trafficking and immunosuppressive factors within the tumor microenvironment increase the relative difficulty in developing a robust CAR-T cell therapy against solid tumors. Therefore, it is critical to develop novel methodologies for high-throughput phenotypic and functional assays using 3D tumor spheroid models to assess CAR-T cell products against solid tumors. In this manuscript, we discuss the use of CAR-T cells targeted towards PSMA, an antigen that is found on prostate cancer tumor cells, the second most common cause of cancer deaths among men worldwide. We demonstrate the use of high-throughput, plate-based image cytometry to characterize CAR-T cell-mediated cytotoxic potency against 3D prostate tumor spheroids. We were able to kinetically evaluate the efficacy and therapeutic value of PSMA CAR-T cells by analyzing the cytotoxicity against prostate tumor spheroids. In addition, the CAR-T cells were fluorescently labeled to visually identify the location of the T cells as cytotoxicity occurs, which may provide more meaningful information for assessing the functionality of the CAR-T cells. The proposed image cytometry method can overcome limitations placed on traditional methodologies to effectively assess cell-mediated 3D tumor spheroid cytotoxicity and efficiently generate time- and dose-dependent results.

Mixed exposure to phthalates and organic UV filters affects Childrens pubertal development in a gender-specific manner.

Previous studies showed phthalates and UV filters are endocrine-disruptive and associated with puberty. However, few studies have examined effects of mixed exposure. Six phthalate metabolites and 12 organic UV filters were detected among 223 school-age children. Puberty development was evaluated at baseline and after 18 months of follow-up. Ordered logistic regression models, least absolute shrinkage and selection operator (LASSO) regression and quantile-based g-computation (qgcomp) were used to evaluate relationships between phthalate metabolites or UV filters exposure and pubertal development. Six phthalate metabolites and 5 UV filters were detectable in urine samples. In boys, BP-3 and 4-MAP were negatively associated with genital (ORBP-3 0.52, (0.27, 0.93), OR4-MAP 0.45, (0.25, 0.74)) and pubic hair development (ORBP-30.24, (0.05, 0.76), OR4-MAP0.24, (0.05, 0.77)). In girls, MEP levels were associated with advanced breast development (OR 1.29, (1.04, 1.64)). LASSO regression identified BP-3, 4-MAP, and OD-PABA for inverse associations with pubertal development in boys. MEP was related to an increase in girls breast development (OR 1.64, (1.08, 2.63)). Overall mixture was related to a 70% reduction in boys genital development stage, with a larger effect size than a single chemical in qgcomp. Mixed exposure was associated with girls earlier puberty onset (OR 2.61, (1.06, 6.42)). Our results suggested higher levels of phthalate metabolites and UV filters were associated with delayed pubertal development in boys but with earlier puberty in girls. Higher effect size of joint exposure than single chemicals suggested phthalates and UV filters might have synergistic effects on puberty and distort adolescent endocrine function together.

Ganoderma lucidum extract promotes tumor cell pyroptosis and inhibits metastasis in breast cancer.

Regulation of tumor cell death is a fundamental mechanism for tumor treatment. However, most tumors are resistant to cell death. Triggering inflammatory cell death, pyroptosis, may provide a new view of enhancing tumor cell death. Here we report a new role of Ganoderma lucidum extract (GLE) in pyroptotic cell death. Treatment with GLE (50-200 μgmL) significantly elevated reactive oxygen species (ROS) levels and caused pyroptotic cell death in breast cancer cells. Mechanistically, GLE activates caspase 3 and further cleaves the gasdermin E (GSDME) protein to form pores on the cell membrane, releasing massive amounts of inflammatory factors in breast cancer cells. We also showed that GLE enhanced antitumor immune responses by substantially increasing the subsets of natural killer (NK) and CD8

Preparation of hyaluronic acid-loaded Harmine polymeric micelles and in vitro effect anti-breast cancer.

To prepare hyaluronic acid-loaded Harmine polymeric micelles with CD The carboxyl group on hyaluronic acid is coupled to the amino group on 3,5-bis(trifluoromethyl)benzylamine by an amidation reaction. And the polymeric micelles self-assemble to encapsulate the Harmine in a hydrophobic core, characterized the polymer micelles by IR, The prepared polymer micelles had a uniform particle size of about 200 nm, good dispersion, PDI < 0.3, encapsulation rate up to 87%, drug loading of 4.12±0.03%, and negative charge. Hyaluronidase has a good enzymatic effect on polymeric micelles, with a hemolysis rate of less than 1%. It showed some dose-dependent toxicity to both MDA-MB-231 and MCF-7, with increased uptake of polymer micelles by CD

Homologous recombination deficiency prediction using low-pass whole genome sequencing in breast cancer.

Homologous recombination repair deficiency (HRD) results in a defect in DNA repair and is a frequent driver of tumorigenesis. Poly(ADP-ribose) polymerase inhibitors (PARPi) or platinum-based therapies have increased theraputic effectiveness when treating HRD positive cancers. For breast cancer and ovairan cancer HRD companion diagnostic tests are commonly used. However, the currently used HRD tests are based on high-depth genome sequencing or hybridization-based capture sequencing, which are technically complex and costly. In this study, we modified an existing method named shallowHRD, which uses low-pass whole genome sequencing (WGS) for HRD detection, and estimated the performance of the modified shallowHRD pipeline. Our shallowHRD pipeline achieved an AUC of 0.997 in simulated low-pass WGS data, with a sensitivity of 0.981 and a specificity of 0.964 and achieved a higher HRD risk score in clinical BRCA-deficient breast cancer samples (p 5.5 × 10

Decision regret in breast cancer patients after adjuvant radiotherapy.

Breast cancer patients often engage in shared decision-making to select an individualized treatment regimen from multiple options. However, dissatisfaction with treatment outcomes can lead to decision regret. We evaluated decision regret and physical and psychological well-being among breast cancer patients who underwent adjuvant radiotherapy and explored their associations with patient, tumor, treatment, and symptom characteristics. This cross-sectional study involved retrospectively obtaining clinical data and data collected through interviews carried out as part of regular long-term medical aftercare. Decision regret regarding the radiotherapy was assessed using the Ottawa Decision Regret Scale, physical and psychological well-being were assessed using the PROMIS Global Health-10 questionnaire, and patients were asked about their treatment outcomes and symptoms. The questionnaire was administered 14 months to 4 years after completion of radiotherapy. Of the 172 included breast cancer patients, only 13.9% expressed high decision regret, with most patients expressing little or no decision regret. More decision regret was associated with volumetric modulated arc therapy, chest wall irradiation, use of docetaxel as a chemotherapy agent, lymphangiosis carcinomatosa, new heart disease after radiotherapy, and lower psychological well-being. Although most patients reported little or no decision regret, we identified several patient, treatment, and symptom characteristics associated with more decision regret. Our findings suggest that psychological well-being influences patients satisfaction with therapy decisions, implying that practitioners should pay special attention to maintaining psychological well-being during shared decision-making and ensuring that psychological assessment and treatment is provided after cancer therapy to deal with long-term effects of radiotherapy.

Impact of preoperative brachytherapy followed by radical hysterectomy in stage IB2 (FIGO 2018) cervical cancer An analysis of SENTICOL I-II trials.

The goal of this study was to compare the outcomes of preoperative brachytherapy followed by radical surgery versus radical surgery alone in cervical cancer with tumor between 2 and 4 cm (FIGO 2018 IB2). SENTICOL I and SENTICOL II were two French prospective multicentric trials evaluating sentinel node biopsy in early-stage cervical cancer between 2005 and 2012. Preoperative brachytherapy (low-dose rate or pulse-dose rate at the dose of 60Gy) could be performed 6 to 8 weeks prior to the radical hysterectomy, at the discretion of each center. SENTICOL I and SENTICOL II cohorts were retrospectively analysed to compare the outcomes of preoperative brachytherapy or upfront surgery in patients with IB2 cervical tumor. A total of 104 patients were included 55 underwent upfront radical hysterectomy and 49 underwent preoperative brachytherapy followed by radical hysterectomy. Patients with preoperative brachytherapy were more likely to have no residual disease (71.4% vs. 25.5%, p < 0.0001) and to be defined as low risk according to Sedlis criteria (83.3% vs. 51.2%, p < 0.0001). Adjuvant treatments were required less frequently in case of preoperative brachytherapy (14.3% vs. 54.5%, p < 0.0001). Patients with preoperative brachytherapy experienced more postoperative complications grade ≥ 3 (24.5% vs. 9.1%, p 0.03). Patients with preoperative brachytherapy had better 5-year disease-free survival compared to patients who underwent surgery alone, 93.6% and 74.4% respectively (p 0.04). Although preoperative brachytherapy was significantly associated with more severe postoperative complications, better pathologic features were obtained on surgical specimens and led to a better 5-year disease-free survival in IB2 cervical cancer.

Analysis of radiomic features derived from post-contrast T1-weighted images and apparent diffusion coefficient (ADC) maps for breast lesion evaluation A retrospective study.

Breast cancer is the most common malignancy among women, and its diagnosis relies on medical imaging and the invasive, uncomforted biopsy. Recent advances in quantitative imaging and specifically the application of radiomics has proved to be a very promising technique, facilitating both diagnosis and therapy. The purpose of this study is to assess radiomic features derived from post-contrast T1w Magnetic Resonance Imaging (MRI) sequences and Apparent Diffusion Coefficient (ADC) maps for the evaluation of breast pathologies. MRI data from 52 women were retrospectively reviewed, involving 54 breast lesions, both malignant and benign. Diffusion Weighted Imaging (DWI) was applied as a standard MRΙ protocol, including dynamic contrast-enhanced (DCE) MRΙ in all cases. All patients were examined on a 1.5T MRI scanner, and 216 features were initially extracted from DCE-MRI images. Histological analysis of the breast lesions was performed, and a comparative analysis of the results was carried out to assess the accuracy of the method. Following surgery and histological analysis, 30 lesions were found to be malignant and 24 benign. Implementation of a Machine Learning (ML) classification algorithm with 5-fold cross-validation resulted in a sensitivity of 70%, specificity of 66%, Negative Predictive Value of 82% and overall accuracy of 67% in differentiating malignancy from benevolence. Texture analysis and ML methodology based on the first post-contrast dynamic sequences and ADC maps may be employed to differentiate between malignant and benign breast lesions, offering a promising new tool for diagnostic analysis. The results of this study will enhance knowledge around application and performance of radiomics in breast MRI, thus helping MRI radiographers who use AI-enabled technologies to better delineate the pros and cons of these procedures.

Compatible-domain Transfer Learning for Breast Cancer Classification with Limited Annotated Data.

Microscopic analysis of breast cancer images is the primary task in diagnosing cancer malignancy. Recent attempts to automate this task have employed deep learning models whose success has depended on large volumes of data, while acquiring annotated data in biomedical domains is time-consuming and may not always be feasible. A typical strategy to address this is to apply transfer learning using pre-trained models on a large natural image database (e.g., ImageNet) instead of training a model from scratch. This approach, however, has not been effective in several previous studies due to fundamental differences between natural and medical images. In this study, for the first time we proposed the idea of using a compatible data set of histopathological images to classify breast cancer cytological biopsy specimens. Despite intrinsic differences between histopathological and cytological images, we demonstrate that the features learned by deep networks during the pre-training procedure are compatible with those obtained throughout fine-tuning process. To thoroughly investigate this assertion, we explore three different strategies for training as well as two different approaches for fine-tuning deep learning models. By comparing the obtained results with those of previous state-of-the-art research conducted on the same data set, we demonstrate that the proposed method boasts of improved classification accuracy by 6% to 17% compared to the studies which were based on traditional machine learning techniques, and also enhanced accuracy by roughly 7% compared to those who utilized deep learning methods, eventually achieving 98.73% validation accuracy and 94.55% test accuracy. Exploring different training scenarios also revealed that using a compatible dataset has helped to elevate the classification accuracy by 3.0% compared to the typical approach of using ImageNet. Experimental results show that our approach, despite using a very small number of training images, has achieved performance comparable to that of experienced pathologists and has the potential to be applied in clinical settings.

Adherence Disparities and Utilization Trends of Oncotype DX Assay A National Cancer Database Study.

Oncotype Dx (ODX) is a genetic assay that analyzes tumor recurrence risk and provides chemotherapy recommendations for T1-T2 stage, hormone receptor-positive, human epidermal growth factor receptor-negative, and nodal-negative breast cancer patients. Despite its established validity, the utilization of this assay is suboptimal. The study aims to evaluate factors that are associated with adherence rate with the testing guidelines and examine changes in utilization trends. This is a retrospective study, utilizing data from the National Cancer Database from 2010 to 2017. Patients who met the ODX testing guidelines were first evaluated for testing adherence. Secondly, all patients who underwent ODX testing were assessed to evaluate the trend in ODX utilization. A total of 429,648 patients met the criteria for ODX, and 43.4% of this population underwent testing. Advanced age, racial minorities, low-income status, well-differentiated tumor grade, uninsured status, and treatment at community cancer centers were associated with a decreased likelihood of receiving ODX in eligible patients. Additionally, a notable amount of testing was performed on patients who did not meet the ODX testing criteria. Among the 295,326 patients that underwent ODX testing, 16.6% of patients were node-positive and 1.8% had T3 or T4 stage tumors. A considerable number of patients who were eligible for ODX did not receive it, indicating potential barriers to care and disparities in breast cancer treatment. ODX usage has been expanded to broader patient populations, indicating more research is needed to validate the effectiveness of the assay in these patient groups.

Integrated SERS-Vertical Flow Biosensor Enabling Multiplexed Quantitative Profiling of Serological Exosomal Proteins in Patients for Accurate Breast Cancer Subtyping.

Protein profiles of exosomes (EXOs) in clinical samples of cancer patients have become a promising diagnostic and therapeutic biomarker. However, simultaneous quantitative analysis of multiple exosomal proteins of interest remains challenging. To address the unmet need, we develop a paper-based surface-enhanced Raman spectroscopy (SERS)-vertical flow biosensor, named iREX (integrated Raman spectroscopic EXO) biosensor, for multiplexed quantitative profiling of exosomal proteins in clinical serum samples of patients. Utilizing this iREX biosensor, we are able to quantitatively profile MUC1, HER2 and CEA in EXO samples derived from various breast cancer cell subtypes. The results show discriminative expression profiles of the three exosomal proteins in these cell subtypes, which allows for accurate diagnosis and molecular subtyping of breast cancer. We further validate the clinical utility of the iREX biosensor for simultaneous quantitative analysis of MUC1, HER2 and CEA in patients blood serums, thereby aiding in noninvasive breast cancer subtyping and longitudinal treatment monitoring. Our iREX biosensor integrating the SERS detection in a vertical flow diagnostic device offers great advantages of high sensitivity, molecular specificity, powerful multiplexing capability, and high diagnostic accuracy. We believe that the iREX biosensor could be a promising clinical tool for comprehensive analysis of exosomal proteins in clinical samples for personalized diagnosis and precise management of breast cancer.

Single-Cell Analysis of Unidirectional Migration of Glioblastoma Cells Using a Fiber-Based Scaffold.

Glioblastoma (GBM) is a malignant incurable brain tumor in which immature neoplastic cells infiltrate brain tissue by spreading along nerve fibers. The aim of the study was to compare the migration abilities of glioma cells with those of other cancer cells and elucidate the migratory profiles underlying the differential migration of glioma cells using a fiber-based quantitative migration assay. Here, wound healing and transwell assays were used to assess cell mobility in four cell lines U87-MG glioblastoma cells, MDA-MB-231 breast cancer cells, HCT116 colorectal cancer cells, and MKN45 gastric cancer cells. We also assessed cell mobility using a fiber model that mimics nerve fibers. Time-lapse video microscopy was used to observe cell migration and morphology. The cytoskeleton arrangement was assessed in the fiber model and compared with that in the conventional cell culture model. The conventional evaluation of cell migration ability revealed that the migration ability of breast cancer and glioblastoma cell lines was higher than that of colon cancer and gastric cancer cell lines. The fiber model confirmed that the glioblastoma cell line had a significantly higher migration ability than other cell lines. Tubulin levels were significantly higher in the glioblastoma cells than in other cell lines. In conclusion, the developed fiber-based culture model revealed the specific migratory profile of GBM cells during invasion.

Mitochondrial genome in sporadic breast cancer A case control study and a proteomic analysis in a Sinhalese cohort from Sri Lanka.

Breast cancer is the commonest malignancy in women and the majority occurs sporadically with no hereditary predisposition. However, sporadic breast cancer has been studied less intensively than the hereditary form and to date hardly any predictive biomarkers exist for the former. Furthermore, although mitochondrial DNA variants have been reported to be associated with breast cancer, findings have been inconsistent across populations. Thus we carried out a case control study on sporadic breast cancer patients and healthy controls of Sinhalese ethnicity (N 60 matched pairs) in order to characterize coding region variants associated with the disease and to identify any potential biomarkers. Mitochondrial genome was fully sequenced in 30 pairs and selected regions were sequenced in the remaining 30 pairs. Several in-silico tools were used to assess functional significance of the variants observed. A number of variants were identified among the patients and the controls. Missense variants identified were either polymorphisms or rare variants. Their prevalence did not significantly differ between patients and the healthy controls (matched for age, body mass index and menopausal status). MT-CYB, MT-ATP6 and MT-ND2 genes showed a higher mutation rate. A higher proportion of pre-menopausal patients carried missense and pathogenic variants. Unique combinations of missense variants were seen within genes and these occurred mostly in MT-ATP6 and MT-CYB genes. Such unique combinations that occurred exclusively among the patients were common in obese patients. Mitochondrial DNA variants may have a role in breast carcinogenesis in obesity and pre-menopause. Molecular dynamic simulations suggested the mutants, G78S in MT-CO3 gene and T146A in MT-ATP6 gene are likely to be more stable than their wild type counterparts.

In vitro evaluation of dioscin and protodioscin against ER-positive and triple-negative breast cancer.

Womens breast cancer is one of the most significant healthcare issues for the human race that demands a proactive strategy for a cure. In this study, the cytotoxic activity (MTT assay) of two natural steroidal compounds, protodioscin and dioscin, against two major subtypes of human breast cancer estrogen receptor-positive (ER-positive)MCF-7 and triple-negative breast cancer (TNBC)MDA-MB-468), was assessed. The clonogenic capacity was evaluated using the clonogenic assay. Oxidative stress was determined by measuring the formation of malondialdehyde and H2O2 and the assessment of total antioxidant enzyme activities (SOD, GPx, GR, and TrxR). Protodioscin and dioscin were highly cytotoxic against the tested cell lines (1.53 μM <IC50< 6 μM) with low cytotoxicity on normal cells (PBMC IC50 ≥ 50 μM). Interestingly, these compounds were responsible for a substantial decrease in the clonogenic capacity of both cell lines. Moreover, dioscin was able to reduce the cell motility of the invasive breast cancer cells (MDA-MB-468). At the molecular level, the two treatments resulted in an increase of reactive oxygen species. Notably, both compounds were responsible for decreasing the enzymatic activities of glutathione reductase and thioredoxin reductase. On the basis of such considerations, protodioscin and dioscin may serve as promising natural compounds to treat TNBC and ER-positive breast cancer through the induction of oxidative stress.

pH-Redox-Responsive Nanodroplet Combined with Ultrasound-Targeted Microbubble Destruction for the Targeted Treatment of Drug-Resistant Triple Negative Breast Cancer.

Multiple drug resistance (MDR) exists in divergent cancers including triple negative breast cancer (TNBC) and partly results in the resistance to many first-line anti-cancer agents, bringing a big challenge to TNBC management. To develop novel TNBC therapeutics, in our study, a hyaluronic acid (HA)-carboxymethyl chitosan (CMC) conjugate linked via a disulfide-bond (HA-SS-CMC, HSC) was synthesized to fabricate nanodroplets (NDs). The NDs encapsulating doxorubicin (DOX) and perfluorohexane (DOX-HSC-NDs) were prepared via a homogenizationemulsification strategy and exhibited not only high biocompatibility but also noticeable tumor cell targeting ability and dual pHredox responsiveness. Besides, DOX-HSC-NDs can be used as a contrast-enhanced ultrasound imaging agent for specific tumor imaging. DOX-HSC-NDs in combination with ultrasound targeted microbubble destruction could improve intracellular drug aggregation and retention of MDR cells and work against multiple mechanisms of drug resistance through synergistic strategies, including up-regulating the reactive oxygen species (ROS) level, promoting apoptosis, and scavenging glutathione, while reducing the expression levels of P-glycoprotein and inhibiting the epithelial-mesenchymal transition. This combination strategy showed protective effects against TNBC in both MDA-MB-231ADR cells and tumor-bearing mice. Our study for the first time developed and reported the ultrasound-augmented HSC-NDs as the DOX nanocarrier and provided scientific evidence to support the future application of DOX-HSC-NDs as a potential TNBC therapy.

Counselling of path

path

Differential Protein Citrullination in Human ER- and ER Tumor and Adjacent Healthy Breast Tissue.

Post-translational modification of arginine to citrulline is catalyzed by members of the peptidylarginine deiminase (PAD) family. Dysregulation of this catalysis is a significant driver of the pathogenesis of numerous inflammatory diseases, including cancer. However, dysregulation of PAD activity has not been examined in breast cancer with respect to hormone receptor status. In this study, we measured PAD enzyme levels using Western blotting and investigated protein citrullination using a mass spectrometry-based proteomics approach in primary estrogen receptor negative (ER-) or positive (ER) breast tumor and matched adjacent normal tissue. Our findings reveal 72 and 41 citrullinated proteins in ER- tumor and adjacent healthy tissue, respectively, where 20 of these proteins are common between the two groups. We detected 64 and 49 citrullinated proteins in ER tumor and adjacent healthy tissue, respectively, where 32 proteins are common. Interestingly, upon comparison of ER- and ER tumor tissue, only 32 citrullinated proteins are shared between the two and the rest are unique to the tumors receptor status. Using the STRING database for protein-protein interaction network analysis, these proteins are involved in protein-folding events (i.e., heat shock proteins) in ER- samples and blood-clotting events (i.e., fibulin) in ER samples. Constituents of the extracellular matrix structure (i.e., collagen and fibrinogen) were found in both. Herein, we establish evidence that supports the role of this unique post-translational modification in breast cancer biology. Finally, to aid drug discovery against citrullination, we developed a liquid chromatography-ultraviolet method to measure PAD enzymatic activity and optimized glucagon-like peptide II to quantitatively measure the ability of PADs to citrullinate its substrate.

Stabilization of E-cadherin adhesions by COX-2GSK3β signaling is a targetable pathway in metastatic breast cancer.

Metastatic progression of epithelial cancers can be associated with epithelial-mesenchymal-transition (EMT) including transcriptional inhibition of E-cadherin (CDH1) expression. Recently, EM plasticity (EMP) and E-cadherin-mediated, cluster-based metastasis and treatment resistance have become more appreciated. However, the mechanisms that maintain E-cadherin expression in this context are less understood. Through studies of inflammatory breast cancer (IBC) and a 3D tumor cell emboli culture paradigm, we discovered that COX-2 (PTGS2), a target gene of CEBPd (CEBPD), or its metabolite prostaglandin E2 (PGE2) promotes protein stability of E-cadherin, β-catenin and p120 catenin through inhibition of GSK3β. The COX-2 inhibitor celecoxib downregulated E-cadherin complex proteins and caused cell death. Co-expression of E-cadherin and COX-2 was seen in breast cancer patients with poor outcome and, along with inhibitory GSK3β phosphorylation, in patient-derived xenografts (PDX) including triple negative breast cancer (TNBC). Celecoxib alone decreased E-cadherin protein expression within xenograft tumors, though CDH1 mRNA levels increased, and reduced circulating tumor cell (CTC) clusters, and in combination with paclitaxel attenuated or regressed lung metastases. This study uncovered a mechanism by which metastatic breast cancer cells can maintain E-cadherin-mediated cell-cell adhesions and cell survival, suggesting that some patients with COX-2E-cadherin breast cancer may benefit from targeting of the PGE2 signaling pathway.

Assessment of Phase 3 Randomized Clinical Trials Including Patients With Leptomeningeal Disease A Systematic Review.

This systematic review examines the proportion of patients with leptomeningeal disease included in phase 3 randomized clinical trials for patients with metastatic breast cancer, lung cancer, and melanoma.

High-multiplex tissue imaging in routine pathology-are we there yet

High-multiplex tissue imaging (HMTI) approaches comprise several novel immunohistological methods that enable in-depth, spatial single-cell analysis. Over recent years, studies in tumor biology, infectious diseases, and autoimmune conditions have demonstrated the information gain accessible when mapping complex tissues with HMTI. Tumor biology has been a focus of innovative multiparametric approaches, as the tumor microenvironment (TME) contains great informative value for accurate diagnosis and targeted therapeutic approaches unraveling the cellular composition and structural organization of the TME using sophisticated computational tools for spatial analysis has produced histopathologic biomarkers for outcomes in breast cancer, predictors of positive immunotherapy response in melanoma, and histological subgroups of colorectal carcinoma. Integration of HMTI technologies into existing clinical workflows such as molecular tumor boards will contribute to improve patient outcomes through personalized treatments tailored to the specific heterogeneous pathological fingerprint of cancer, autoimmunity, or infection. Here, we review the advantages and limitations of existing HMTI technologies and outline how spatial single-cell data can improve our understanding of pathological disease mechanisms and determinants of treatment success. We provide an overview of the analytic processing and interpretation and discuss how HMTI can improve future routine clinical diagnostic and therapeutic processes.

Association of sexual attitudes with sexual dysfunction and sexual distress among Chinese breast cancer survivors a cross-sectional study.

Little is known about sexual dysfunction and sexual distress in Chinese female breast cancer survivors (BCSs), and their associations with physical variables, psychological factors, body image, and sexual attitudes. A cross-sectional study of 341 BCSs was performed with the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised (FSDS-R). Associations between physical variables, psychological factors, body image, sexual attitudes, sexual dysfunction, and sexual distress were evaluated using logistic regression, adjusted for confounding factors. We found that 75.37% and 18.48% of BCSs reported sexual dysfunction and sexual distress during the past month, respectively. Attitudes toward sexual behavior such as sexual activity may impede disease recovery, sexual activity may cause cancer recurrence or metastasis, and sexual activity may weaken treatment effects were significantly associated with an increased likelihood of reporting sexual dysfunction and sexual distress. Body image disruption such as felt physically less attractive as a result of your disease or treatment was significantly associated with the experience of sexual distress. Sexual dysfunction and sexual distress are common issues in Chinese BCSs. Sexual misconception likely contributes to sexual dysfunction and sexual distress, and body image has a significantly negative association with sexual distress in BCSs. Interventions targeting sexual attitudes and body image might be important to address BCSs sexual issues and improve their overall sexual health.

Hypoxia-induced YAP activation and focal adhesion turnover to promote cell migration in mesenchymal TNBC cells.

Hypoxia is commonly characterized by malignant tumors that promote the aggressiveness and metastatic potential of cancer. Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, with approximately 46% capacity related to distant metastasis. Transcriptional factor yes-associated protein (YAP), a core component of the Hippo pathway, is associated with poor prognosis and outcome in cancer metastasis. Here, we explored the effect of hypoxia-mediated YAP activation and focal adhesions (FAs) turnover in mesenchymal TNBC cell migration. We characterized the effect of hypoxia on YAP in different breast cancer cell lines using a hypoxia chamber and CoCl Hypoxia-induced YAP nuclear translocation is significantly observed in normal breast epithelial cells, non-TNBC cells, mesenchymal TNBC cells, but not in basal-like TNBC cells. Functionally, we demonstrated that YAP activation was required for hypoxia to promote mesenchymal TNBC cell migration. Furthermore, hypoxia induced the localization of FAs at the leading edge of mesenchymal TNBC cells. In contrast, verteporfin (VP), a YAP inhibitor, significantly reduced the migration and the recruitment of nascent FAs at the cell periphery under hypoxia conditions, which only showed in mesenchymal TNBC cells. Our data support the hypothesis that YAP is novel factor and positively responsible for hypoxia-promoting mesenchymal TNBC cell migration. Our findings provide further evidence and outcomes to help prevent the progression of TNBC.

HER2-low status may predict poor neoadjuvant chemotherapy response in HR-negative breast cancer a real-world multicenter study.

We aimed to investigate the impact of human epidermal growth factor receptor 2 status (human epidermal growth factor receptor 2-low versus human epidermal growth factor receptor 2-zero) on pathological response to neoadjuvant chemotherapy and survival outcomes in early-stage breast cancer. Patients with primary invasive breast cancer received neoadjuvant chemotherapy between July 2018 and July 2021 were identified from six hospitals. The primary efficacy end-point was total pathological complete response. The second short-term efficacy end-points include breast pathological complete response, axillary lymph nodes pathological complete response and the score of Miller-Payne grade. Long-term efficacy end-point was disease-free survival. 429 patients with human epidermal growth factor receptor 2 negative invasive tumors were included, 267 (62.24%) had human epidermal growth factor receptor 2-low tumors. Hormone receptor-positive patients had a higher percentage of human epidermal growth factor receptor 2-low tumors compared to hormone receptor-negative patients (71.97% versus 42.14%). The pathological response rate was significantly lower in human epidermal growth factor receptor 2-low tumors than in human epidermal growth factor receptor 2-zero tumors for total patients in univariate analysis, including the rates of total pathological complete response (5.2% versus 14.2%), breast pathological complete response (6.4% versus 17.3%), nodes pathological complete response (26.3% versus 37.7%) and MP4-5 (21.2% versus 33.8%). Subgroup analysis showed that the rates of total pathological complete response, breast pathological complete response and MP4-5 were also significantly lower in human epidermal growth factor receptor 2-low tumors versus human epidermal growth factor receptor 2-zero tumors in both univariate and multivariate analysis in hormone receptor-negative subgroup. With the median follow-up of 24 months, disease-free survival was comparable between these two subgroups (P 0.816). Our results demonstrate that human epidermal growth factor receptor 2-low tumors achieved a significantly lower pathological complete response rate with conventional chemotherapy than those with human epidermal growth factor receptor 2-zero tumors, especially for hormone receptor-negative group. Large, randomized, prospective studies are needed to confirm our data and further evaluate the prognostic value of human epidermal growth factor receptor 2-low expression.

Homologous repair deficiency-associated genes in invasive breast cancer revealed by WGCNA co-expression network analysis and genetic perturbation similarity analysis.

Homologous repair deficiency (HRD) causes double-strand break repair to be impeded, which is a common driver of carcinogenesis. However, the therapeutic and prognostic potential of HRD in invasive breast cancer (BRCA) has not been fully explored using comprehensive bioinformatics analysis. HRD score was defined as the unweighted sum of LOH, TAI, and LST scores and obtained from the previous study according to Theo A et al. To characterize BRCA tumor microenvironment (TME) subtypes, ConsensusClusterPlus R package was used to conduct unsupervised clustering. The xCell algorithm was utilized for tumor composition analysis to estimate the TME in TCGA-BRCA. A WGCNA analysis was conducted to uncover the gene coexpression modules and hub genes in the HRD-related gene module of BRCA. The functional enrichment study was carried out using Metascape. A novel analysis pipeline, Genetic Perturbation Similarity Analysis (GPSA), was used to explore the single-gene perturbation closely related to HRD based on 3048 stable knockdownknockout cell lines. The prognostic variables were evaluated using univariate COX analysis. Kaplan-Meier (KM) survival analysis was performed to assess the prognostic potential of HRD score. Receiver operator characteristic (ROC) curve was utilized to judge the diagnostic utility. Drug sensitivity was estimated through the R package oncoPredict and Genomics of Drug Sensitivity in Cancer (GDSC) database. XSum algorithm was performed to screen the candidate small molecule drugs based on the connectivity map (CMAP) database. Low HRD score suggested a better prognosis in BRCA patients. The tumor with low HRD score had considerably greater degree of infiltration of stromal cells and infiltration of immunocytes was significantly enhanced in the high HRD score group. Using WGCNA, ten co-expression modules were obtained. The turquoise module and 25 hub genes were identified as the most correlated with HRD in BRCA. Functional enrichment analysis revealed that the turquoise gene module was mainly concentrated in the cell cycle pathways. Candidate HRD-related gene signatures (MELK) were screened out through WGCNA and GPSA analysis pipeline and then validated on independent validation sets. A small molecule drug (Clofibrate) that has the potential to reverse the increase of high HRD score was screened out to improve oncological outcomes in BRCA. Molecular docking suggested MELK to be one of possible molecular targets in the Clofibrate treatment of BRCA. Based on bioinformatic analysis, we fully explored the therapeutic and prognostic potential of HRD in BRCA. A novel HRD-related gene signature (MELK) were identified through the combination of WGCNA and GPSA analysis. In addition, we detailed the TME landscape in BRCA and identified four unique TME subtypes in group with high or low HRD score group. Moreover, Clofibrate were screened out to improve oncological outcomes in BRCA by reversing the increase of high HRD score. Thus, our study contributes to the development of personalized clinical management and treatment regimens of BRCA.

Functionalized Fluorescent Nanostructures Generated from Self-Assembly of a Cationic Tripeptide Direct Cell-Selective Chemotherapeutic Drug Delivery.

Nanodrug delivery systems (NDDs) capable of conveying chemotherapeutics directly into malignant cells without harming healthy ones are of significant interest in the field of cancer therapy. However, the development of nanostructures with the requisite biocompatibility, inherent optical properties, cellular penetration ability, encapsulation capability, and target selectivity has remained elusive. In an effort to develop cell-selective NDDs, we have synthesized a cationic tripeptide Boc-Arg-Trp-Phe-OMe (

SAMD9 Promotes Postoperative Recurrence of Esophageal Squamous Cell Carcinoma by Stimulating MYH9-Mediated GSK3ββ-Catenin Signaling.

Recurrence is a challenge to survival after the initial treatment of esophageal squamous cell carcinoma (ESCC). But, its mechanism remains elusive and there are currently no biomarkers to predict postoperative recurrence. Here, the possibility of sterile alpha motif domain-containing protein 9 (SAMD9) as a predictor of postoperative recurrence of ESCC is evaluated and the molecular mechanisms by which SAMD9 promotes ESCC recurrence are elucidated. The authors found that the high level of SAMD9 is correlated with postoperative recurrence and poor prognosis of ESCC. Overexpression of SAMD9 promotes tumor stemness, angiogenesis, and EMT, while downregulation of SAMD9 reduced these phenotypes. Mechanistically, it is found that SAMD9 stimulated ubiquitination-mediated glycogen synthase kinase-3 beta (GSK-3β) degradation by interaction with myosin-9 (MYH9) and TNF receptor-associated factor 6 (TRAF6), which in turn activated Wntβ-catenin pathway. Further, the authors demonstrated that silencing SAMD9 inhibited lung metastasis and tumor formation in vivo. Finally, the authors found that silencing MYH9 or β-catenin, or overexpressing GSK-3β inhibited SAMD9-stimulated ESCC cell stemness, EMT, angiogenesis, metastasis, and tumorigenicity. Together, the findings indicate that the SAMD9MYH9GSK3ββ-catenin axis promotes ESCC postoperative recurrence and that SAMD9 is a crucial target for ESCC therapy. Additionally, SAMD9 has the potential as a predictor of postoperative recurrence in ESCC.

The pan-cancer analysis of the oncogenic role of FAM72A as a BRCA prognostic biomarker and immunotherapeutic target.

In this study, we first comprehensively investigated the expression profile, mutation status, and survival analysis of FAM72A as well as the correlation between FAM72A and DNA damage repair, methylation, and cell stemness analysis using bioinformatics techniques. In addition, we also analyzed the relationship between FAM72A and immune cell infiltration and pathway enrichment. The role of FAM72A in breast cancer (BC) was so conspicuous that we analyzed the prognostic significance and clinicopathological parameters relevance of FAM72A in BC. We also validated biological functions by applying in vitro experiments. FAM72A was highly expressed in 26 types of a total of 31 cancers, while it expressed low levels in only five cancers. FAM72A expression was relative to clinical stages in nine cancers and has a significant difference in disease-free survival among 31 kinds of cancers. In addition, FAM72A has negatively correlated with cancer-associated fibroblast and endothelial cells in BC but positively correlated with follicular helper T cells. Univariate and multivariate cox regression analyses identified T, N, M, age, and FAM72A expression as independent influences on BC prognosis, so we created a nomogram to predict patient survival benefits. In in vitro experiments, we verified that downregulation of FAM72A not only inhibited cell proliferation, colony formation, cell migration, cell invasion, and G2M cell cycle transition but also promoted apoptosis of breast invasive carcinoma cells. Our study discovered FAM72A as a clinically meaningful biomarker for prognostic predicting and a guiding target for immune treatment in BC.

3D bioprinting of dECMGelQCSnHAp hybrid scaffolds laden with mesenchymal stem cell-derived exosomes to improve angiogenesis and osteogenesis.

Craniofacial bone regeneration is a coupled process of angiogenesis and osteogenesis, which, associated with infection, still remains a challenge in bone defects after trauma or tumor resection. 3D tissue engineering scaffolds with multifunctional-therapeutic properties can offer many advantages for the angiogenesis and osteogenesis of infected bone defects. Hence, in the present study, a microchannel networks-enriched 3D hybrid scaffold composed of decellularized extracellular matrix (dECM), gelatin (Gel), quaterinized chitosan (QCS) and nano-hydroxyapatite (nHAp) (dGQH) was fabricated by an extrusion 3D bioprinting technology. And enlightened by the characteristics of natural bone microstructure and the demands of vascularized bone regeneration, the exosomes (Exos) isolated from human adipose derived stem cells as angiogenic and osteogenic factors were then co-loaded into the desired dGQH

Breast cancer-related mortality in Central and Eastern Europe years of life lost and productivity costs.

Breast cancer (BC) poses a public health challenge as the most commonly diagnosed cancer among women globally. While BC mortality has declined across Europe in the past three decades, an opposite trend has been reported in some transitional European countries. This analysis estimates the mortality burden and the cost of lost productivity due to BC deaths in nine Central and Eastern Europe (CEE) countries Bulgaria, Croatia, Czech Republic, Hungary, Poland, Romania, Serbia, Slovakia, and Slovenia, that have defied the favorable cancer mortality trends. These estimates may provide relevant evidence to aid decision-makers in the prioritization of BC-targeted policies. The human capital approach (HCA) was used to estimate years of life lost (YLL) and productivity losses due to premature death from BC (ICD-10 code C50 Malignant neoplasm of breast). YLL and present value of future lost productivity (PVFLP) were calculated using age and gender-specific mortality, wages, and employment rates. Data were sourced from the World Health Organization (WHO), Eurostat, and the World Bank. In 2019, there were 19,726 BC deaths in the nine CEE countries. This study estimated BC deaths resulted in 267,184 YLL. Annual PVFLP was estimated to be €85 M in Poland, €46 M in Romania, €39 M in Hungary, €21 M in Slovakia, €18 M in Serbia, €16 M in Czech Republic, €15 M in Bulgaria, €13 M in Croatia, and €7 M in Slovenia. Premature death from BC leads to substantial YLL and productivity losses. Lost productivity costs due to premature BC-related mortality exceeded €259 million in 2019 alone. The data modeled provide important evidence toward resource allocation priorities for BC prevention, screening, and treatment that could potentially decrease productivity losses. Careful consideration should be given to BC-specific policies, such as surveillance programs and the availability of new treatments in CEE countries to decrease the medical and financial burden of the disease.

A consensus approach Understanding the support needs of women in Newport West, Wales, to participate in breast screening.

Breast screening is an effective way to improve the early detection of breast cancer and reduce mortality. Unfortunately, low uptake of screening is often reported. This study aimed to explore the support needs of women residing in Newport West, Wales, to participate in breast screening. Group Concept Mapping, a structured participatory consensus approach, was used as the method. Participants completed three activities either online or offline brainstorming to generate statements, sorting statements into themed categories rating statements for perceived importance and accessibility (easy to get). Thirty-seven participants from seven ethnic groups took part. Sixty-three statements (items of support) were generated and sorted into seven conceptually similar clusters (themes) (Trusting that I will be respected Reassurance about my experience Accessibility and convenience Practical support Addressing cultural diversity Information tailored to individual needs Raising awareness and understanding of breast screening). The Trusting that I will be respected cluster was rated most important, while the Practical support cluster was rated least accessible. Some disparity between responses was found based on ethnicity, language, disability and previous attendance of breast screening. Women require a range of support to participate in breast screening. The results highlight the importance of ensuring women feel and are respected, instilling trust in the staff performing the screening, offering reassurance about positive experiences of breast screening and providing practical support, especially individualizedtargeted support for people who do not speak andor read English and those with a disability. The public contributed to the development of the information sheet, consent form, recruitment and data collection method.

The roles of 68Ga-PSMA PETCT and 18F-FDG PETCT imaging in patients with triple-negative breast cancer and the association of tissue PSMA and claudin 1, 4, and 7 levels with PET findings.

Aim of study is to compare the results of Gallium-68-prostate-specific membrane antigen (68Ga-PSMA) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography(PET)computed tomography (CT), to evaluate the correlation between PET findings and the level of PSMA, Claudin (Clau) 1, 4, and 7 receptors obtained by immunohistochemical (IHC) analysis, and to determine potential predictive and prognostic values in TNBC. Forty-seven lesions of 42 subjects diagnosed TNBC both underwent PETCT scan for preoperative stagingrestaging were prospectively included study. PSMA, Clau 1, 4, and 7 expressions were IHC evaluated from the biopsy samples of the primary tumor (PT). Maximum standardized uptake value(SUV max) of the PT, lymph node, and distant organ metastases (DOMs) on 18F-FDG and 68Ga-PSMA PETCT were compared with PSMA, Clau 1, 4, and 7 receptor expressions. IHC analyses on 29 BC lesions to demonstrate Clau expression showed 86% (2529) Clau 1, 86% (2529) Clau 4, 45% (1329) Clau 7, and 48% (1429) PSMA-positive. The mean DOM (SUVmax) was 15.5 ± 11.6 for 18F-FDG and 6.0 ± 2.9 for 68Ga-PSMA. Axial diameter of BC PT had a significant positive correlation with 18F-FDG SUVmax, 68Ga-PSMA SUVmax, and PSMA scores. BC lesions 68Ga-PSMA SUVmax had a significant negative correlation with the Ki-67 index. Axial diameter of the primary tumor had significant negative correlation with Clau 7 scores (r -0.409, P 0.034). Absence of Clau 1 expression found to significantly increase the rate of DOM (100% vs. 28%) (P 0.014). All patients with axillary lymph node (ALN) metastases (n 17, 100%) exhibited Clau 4 positivity (P 0.021). The presence of PSMA expression observed to significantly increase the rate of ALN metastases (64.7% vs. 25%) (P 0.035). Confirming PSMA expression with PET imaging would be significant as PSMA, a theranostic agent, may be a considerable potential agent for radionuclide treatment strategies, in addition to its additional diagnostic contribution to FDG, especially in patients with metastatic TNBC, which is an aggressive, heterogeneous disease.

Isolation, Characterization and Anticancer Activity of Secondary Metabolites from Verbascum speciosum.

Two iridoid glucosides aucubin (1) and ajugol (2), and two phenyl ethanoids, verbascoside (3) and poliumoside (4) were isolated from the methanol extract of the aerial parts of Verbascum speciosum and used to study about their anticancer activity for the first time. The structures of all compounds were elucidated using spectroscopic data (IR, 1D and 2D NMR, LC-MS TOF). In addition, the antiproliferative activities of aucubin (1) and verbascoside (3) were tested against A-549 (human lung cancer), HT-29 (human colon cancer), MDA-MB-453 (human breast cancer), and 3T3-L1 (mouse fibroblast) cell lines by XTT assay. According to the results, both compounds exhibited dose-dependent cytotoxic activity on all the cell lines, but 3 was more potent against all the cell lines with its lower IC50 values when compared to 1, and again 3 showed the strongest activity (IC50 40.63 μgml) and highest selectivity index (SI4.27) against A-549 cells. This is the first report of the isolation of 1 and 3 from the Verbascum speciosum plant and investigation of their cytotoxic effects against diverse cancer cell types.

Screening for breast and cervical cancer among OST patients a qualitative study of barriers and suggested interventions to increase participation.

Women with current or previous drug use are at risk of poor breast and cervical cancer outcomes. While screening is known to decrease cancer mortality, screening participation is sparsely investigated among drug dependent women. The aim of this study was to explore experiences of breast and cervical cancer screening-including barriers and suggested interventions to promote increased participation-among women in opioid substitution treatment (OST). Three focus group interviews were conducted at one OST clinic in Malmö, Sweden. The interviews were moderated by OST staff, assisted by a researcher. A descriptive qualitative analysis was carried out using a template analysis approach, employing a model of healthcare access to organize the description of barriers. The 11 participants reported several barriers to screening access, affecting the perceived need of screening and the opportunities to seek and reach screening services. Some barriers appear to be specific to women with previous or current drug use. Suggested interventions were moral and practical support, integratedspecialized delivery of screening services, and enhanced screening invitation procedures. The study findings provide insight to difficulties with screening compliance among women with current or previous drug use, and provide a knowledge base for quantitative and intervention studies.

Novel albumin-binding photodynamic agent EB-Ppa for targeted fluorescent imaging guided tumour photodynamic therapy.

The targeted and novel albumin-binding strategy has been attractive in the field of cancer therapy. Herein, we have developed an organic small molecule-based photosensitizer, Evans Blue-Pyropheophorbide-alpha (EB-Ppa), to treat solid tumors with extremely high photodynamic therapeutic efficiency, which is stable in serum-containing aqueous media and can effectively accumulate in the tumor site due to the enhanced permeability and retention (EPR) effect. Particularly, after the photodynamic therapeutic treatment with EB-Ppa, all breast tumors (4T1 cell line) xenografted in nude mice shrink fast due to the singlet oxygen generated by EB-Ppa with laser irradiation. Furthermore, EB-Ppa shows negligible toxicity in major organs. These results demonstrate that EB-Ppa presents the great potential of photodynamic therapy for efficient tumor treatment.

Design, synthesis, anticancer and

In this research the synthesis, characterization, anticancer and the cytotoxicity assessments of novel 8-caffeinyl-triazolylmethoxy hybrid conjugates have been described. These compounds are the first caffeine-1,2,3-triazolyl hybrid molecules that structurally are composed of three compartments comprising caffeinyl, 1,2,3-triazolyl and

ESGOESHREESGE Guidelines for the fertility-sparing treatment of patients with endometrial carcinoma

How should fertility-sparing treatment of patients with endometrial carcinoma be performed Forty-eight recommendations were formulated on fertility-sparing treatment of patients with endometrial carcinoma. The standard surgical treatment of endometrial carcinoma consisting of total hysterectomy with bilateral salpingo-oophorectomy drastically affects the quality of life of patients and creates a challenge for clinicians. Recent evidence-based guidelines of the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy Oncology (ESTRO) and the European Society of Pathology (ESP) provide comprehensive guidelines on all relevant issues of diagnosis and treatment in endometrial carcinoma in a multidisciplinary setting. While addressing also work-up for fertility preservation treatments and the management and follow-up for fertility preservation, it was considered relevant to further extend the guidance on fertility-sparing treatment. A collaboration was set up between the ESGO, the European Society of Human Reproduction and Embryology (ESHRE) and the European Society for Gynaecological Endoscopy (ESGE), aiming to develop clinically relevant and evidence-based guidelines focusing on key aspects of fertility-sparing treatment in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide. ESGOESHREESGE nominated an international multidisciplinary development group consisting of practising clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (11 experts across Europe). To ensure that the guidelines are evidence-based, the literature published since 2016, identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgement was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 95 independent international practitioners in cancer care delivery and patient representatives. The multidisciplinary development group formulated 48 recommendations in four sections patient selection, tumour clinicopathological characteristics, treatment and special issues. Of the 48 recommendations, none could be based on level I evidence and only 16 could be based on level II evidence, implicating that 66% of the recommendations are supported only by observational data, professional experience and consensus of the development group. These recommendations provide guidance to professionals caring for women with endometrial carcinoma, including but not limited to professionals in the field of gynaecological oncology, onco-fertility, reproductive surgery, endoscopy, conservative surgery and histopathology, and will help towards a holistic and multidisciplinary approach for this challenging clinical scenario. All costs relating to the development process were covered from ESGO, ESHRE and ESGE funds. There was no external funding of the development process or manuscript production. G.S. has reported grants from MSD Italia S.r.l., advisory boards for Storz, Bayer, Astrazeneca, Metronic, TESARO Bio Italy S.r.l and Johnson Johnson, and honoraria for lectures from Clovis Oncology Italy S.r.l. M.G. has reported advisory boards for Gedeon Richter and Merck. The other authors have reported no conflicts of interest.

Knowledge, attitudes, and behaviors toward fertility preservation in patients with breast cancer A cross-sectional survey of physicians.

Fertility is an important issue for young women with breast cancer, but studies about physicians knowledge, attitudes, and practices toward fertility preservation (FP) are largely based on Western populations and do not reflect recent international guidelines for FP. In this international study, we aimed to assess the knowledge, attitudes, and practices of physicians from South Korea, other Asian countries, and Latin America toward FP in young women with breast cancer, and identify the related barriers. The survey was conducted anonymously among physicians from South Korea, other Asian countries, and Latin America involved in breast cancer care between November 2020 and July 2021. Topics included knowledge, attitudes, and perceptions toward FP practice behaviors barriers and participant demographics. We grouped related questions around two main themes-discussion with patients about FP, and consultation and referral to a reproductive endocrinologist. We analyzed the relationships between main questions and other survey items. A total of 151 physicians completed the survey. Most participants overall knowledge about FP was good. More than half of the participants answered that they discussed FP with their patients in most cases, but that personnel to facilitate discussions about FP and the provision of educational materials were limited. A major barrier was time constraints in the clinic (52.6%). Discussion, consultations, and referrals were more likely to be performed by surgeons who primarily treated patients with operable breast cancer (FP discussion odds ratio OR 2.90 95% confidence interval CI 1.24-6.79 FP consultation and referral OR 2.98 95% CI 1.14-7.74). Participants knowledge and attitudes about FP were significantly associated with discussion, consultations, and referrals. Physicians from South Korea, other Asian countries, and Latin America are knowledgeable about FP and most perform practice behaviors toward FP well. Physicians knowledge and favorable attitudes are significantly related to discussion with patients, as well as consultation with and referral to reproductive endocrinologists. However, there are also barriers, such as limitations to human resources and materials, suggesting a need for a systematic approach to improve FP for young women with breast cancer.

Efficacy and safety results by menopausal status in monarchE adjuvant abemaciclib combined with endocrine therapy in patients with HR, HER2-, node-positive, high-risk early breast cancer.

Abemaciclib is the first and only cyclin-dependent kinases 4 and 6 inhibitor approved for adjuvant treatment of hormone receptor-positive (HR), human epidermal growth factor receptor 2-negative (HER2-), node-positive, and high-risk early breast cancer (EBC), with indications varying by geography. Premenopausal patients with HR, HER2- tumors may have different tumor biology and treatment response compared to postmenopausal patients. We describe the efficacy and safety of abemaciclib plus endocrine therapy (ET) for the large subgroup of premenopausal patients with HR, HER2- EBC in monarchE. Randomized patients (11) received adjuvant ET with or without abemaciclib for 2 years plus at least 3 additional years of ET as clinically indicated. Patients were stratified by menopausal status (premenopausal Among randomized patients, 2451 (43.5%) were premenopausal and 3181 (56.4%) were postmenopausal. The choice of ET for premenopausal patients varied considerably between countries. Treatment benefit was consistent across menopausal status, with a numerically greater effect size in premenopausal patients. For premenopausal patients, abemaciclib with ET resulted in a 42.2% and 40.3% reduction in the risk of developing IDFS and DRFS events, respectively. Absolute improvement at 3 years was 5.7% for IDFS and 4.4% for DRFS rates. Safety profile for premenopausal patients was consistent with the overall safety population. Abemaciclib with ET demonstrated clinically meaningful treatment benefit for IDFS and DRFS

Indian Data on HER2 Fluorescence In Situ Hybridization in Invasive Breast Cancer with Immunohistochemically Equivocal Results As Per 2018 ASCOCAP Guidelines.

Biren Parikh

Her2 Status Discrepancy Between Core Needle Biopsy and Surgically Resected Mastectomy Specimen A Clinical Case.

The biomarker concordance between core needle biopsy (CNB) and surgical specimen (SS), in breast cancer, has long been a matter of discussion because of its influence on oncologic treatment choice. Particularly, human epidermal growth factor receptor 2 (Her2) status is quite important, because of the impact on breast cancer classification and target therapy. Many factors could influence the difference in biomarker status between samples, such as the technic itself, sample procedures and intratumoral heterogeneity. Neoadjuvant chemotherapy (NAC) can also contribute to this variation and should be taken into consideration. We report a clinical case of a 33-year-old man who was diagnosed with right breast cancer, initially Her2 negative in the CNB. Therefore, the NAC was completed without anti-Her2 treatment. Later, after the mastectomy, revision of the SS was found to be positive for Her2, after the silver in situ hybridization (SISH) technique. Consequently, the patient lost the chance of doing anti-Her2 therapy in the neoadjuvant setting, reducing his possibility to achieve a complete pathologic response and later jeopardizing his clinical outcome.

Breast to Brain A Case Report and Literature Review of Leptomeningeal Carcinomatosis.

Breast cancer is widely known as the most common cancer in women in the United States. If left untreated, it can have detrimental effects. If the breast cancer is aggressive in nature, it can metastasize to the lymph nodes, bones, liver, lungs, and brain. A rare location of metastasis is the leptomeninges, specifically the pia and arachnoid matter. This term is coined as leptomeningeal carcinomatosis. Its diagnosis can be challenging to make as patients can present with non-specific symptoms. We present the case of an elderly female with a prior history of breast cancer that was treated with 12 cycles of chemotherapy with paclitaxel, radiation to her left axilla, and daily anastrozole for 3 years who came into the emergency department for worsening confusion, urinary incontinence, and difficulty ambulating. Cerebral spinal fluid obtained from a lumbar puncture supported a diagnosis of leptomeningeal carcinomatosis.

Correction to The DNA repair function of BCL11A suppresses senescence and promotes continued proliferation of triple-negative breast cancer cells.

This corrects the article DOI 10.1093narcanzcac028..

Obesity and endocrine-related cancer The important role of IGF-1.

Obesity is increasingly becoming a global epidemic of concern and is considered a risk factor for several endocrine-related cancers. Moreover, obesity is associated with cancer development and poor prognosis. As a metabolic abnormality, obesity leads to a series of changes in insulin, IGF-1, sex hormones, IGFBPs, and adipokines. Among these factors, IGF-1 plays an important role in obesity-related endocrine cancers. This review describes the role of obesity in endocrine-related cancers, such as prostate cancer, breast cancer and pancreatic cancer, focusing on the mechanism of IGF-1 and the crosstalk with estrogen and adipokines. In addition, this review briefly introduces the current status of IGF-1R inhibitors in clinical practice and shows the prospect of IGF-1R inhibitors in combination with other anticancer drugs.

When Breast Cancer Survivorship Discourse Doesnt Work Reflections From a Patient.

Within this narrative, I document my experiences with breast cancer. On 2 separate occasions, diagnoses did not qualify me for survivor identity within the current interpretation of breast cancer survivorship discourse. Yet each time, I underwent treatments that were necessary, but physically and emotionally difficult. I briefly discuss how breast cancer survivorship discourse is interpreted, including how this discourse has benefitted women, but also, the challenges in survivorship discourse adoption (including how the current survivorship definition differs). I then discuss my struggles in feeling like I could not assume breast cancer survivorship discourse, including the confusion and despair, as well as feeling ineligible for support groups. Briefly, one suggestion for change is made.

Integrating multi-type aberrations from DNA and RNA through dynamic mapping gene space for subtype-specific breast cancer driver discovery.

Driver event discovery is a crucial demand for breast cancer diagnosis and therapy. In particular, discovering subtype-specificity of drivers can prompt the personalized biomarker discovery and precision treatment of cancer patients. Still, most of the existing computational driver discovery studies mainly exploit the information from DNA aberrations and gene interactions. Notably, cancer driver events would occur due to not only DNA aberrations but also RNA alternations, but integrating multi-type aberrations from both DNA and RNA is still a challenging task for breast cancer drivers. On the one hand, the data formats of different aberration types also differ from each other, known as data format incompatibility. On the other hand, different types of aberrations demonstrate distinct patterns across samples, known as aberration type heterogeneity. To promote the integrated analysis of subtype-specific breast cancer drivers, we design a splicing-and-fusing framework to address the issues of data format incompatibility and aberration type heterogeneity simultaneously. To overcome the data format incompatibility, the splicing-step employs a knowledge graph structure to connect multi-type aberrations from the DNA and RNA data into a unified formation. To tackle the aberration type heterogeneity, the fusing-step adopts a dynamic mapping gene space integration approach to represent the multi-type information by vectorized profiles. The experiments also demonstrate the advantages of our approach in both the integration of multi-type aberrations from DNA and RNA and the discovery of subtype-specific breast cancer drivers. In summary, our splicing-and-fusing framework with knowledge graph connection and dynamic mapping gene space fusion of multi-type aberrations data from DNA and RNA can successfully discover potential breast cancer drivers with subtype-specificity indication.

Reconstructive types effect the prognosis of patients with tumors in the central and nipple portion of breast cancer An analysis based on SEER database.

The impact of different types of reconstruction, including tissue reconstruction, implant reconstruction and combined reconstruction, on patient survival were not illustrated completely. We tried to investigate the impact of patient survival between different types of reconstruction. We enrolled 6271 patients with tumors in the central and nipple portion of breast cancer from the Surveillance, Epidemiology, and End Results database. Factors associated with survival were identified by Cox regression analyses. The mortality rates per 1,000 person-years were calculated and compared. Survival curves were produced by Kaplan-Meier analyses using log-rank tests and cox proportional hazards regression quantified the risk of survival. Reconstructive types, region, insurance, race, marial status, grade, stage, ER status, PR status, HER-2 status and chemotherapy were significant prognostic factors associated with breast cancer-specific survival. The breast cancer mortality rates per 1,000 person-years for patients with tissue, implant and combined group were 26.01,21.54 and 19.83 which showed a downward trend. The HR of implant and combined reconstruction adjusted for demographic, pathological, and therapeutic data was 0.82 (95% CI 0.67-1.00, p0.052) and 0.73(95% CI0.55-0.97, p0.03) compared with tissue reconstruction. Breast cancer-related mortality between implant reconstruction and autologous tissue reconstruction showed no significantly different, but the risk of BCSS of compound reconstruction was lower than tissue reconstruction.

Strategies for five tumour markers in the screening and diagnosis of female breast cancer.

This study evaluated the diagnostic value of different combinations of five commonly used tumour markers and screened the best combination of tumour markers. Regression analysis was used to evaluate 185 patients with suspected breast cancer admitted to Mianyang Central Hospital from January 2020 to December 2021. The differences of five tumour markers between a breast cancer group and a benign lesion group were analysed. The sensitivity and specificity of five tumour markers were compared. Of 185 patients with suspected breast cancer, 108 patients had breast cancer and 77 patients had benign breast tumours. The detection results of carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199) and carbohydrate antigen 153 (CA153) in patients with breast cancer were significantly higher than those in patients with benign breast tumours. In the analysis of the single-detection results of tumour markers, CEA had the highest sensitivity (23.94%), CA153 had the highest specificity (96.43%), AFP had the highest accuracy (47.66%) and CA153 had the highest area under the curve (AUC) value (0.727). With the increase of parallel indicators, the sensitivity, accuracy and AUC value increased in turn, and the increase was obvious in the front. The increase began to slow down after the three parallel indicators. Among the different combinations of three parallel detections of breast cancer tumour markers, the highest sensitivity was AFP CEA CA153 (83.46%), the highest accuracy was AFP CEA CA153 and AFP CA153 CA125 (80.25%), and the highest AUC was CEA CA125 CA199 (0.922). AFP, CA153 and CA199 are recommended for clinical diagnosis of breast cancer. In routine physical examination and early breast cancer screening, the optimal combination of AFP CEA CA153 three parallel tests is recommended.

High-resolution synthesis of high-density breast mammograms Application to improved fairness in deep learning based mass detection.

Computer-aided detection systems based on deep learning have shown good performance in breast cancer detection. However, high-density breasts show poorer detection performance since dense tissues can mask or even simulate masses. Therefore, the sensitivity of mammography for breast cancer detection can be reduced by more than 20% in dense breasts. Additionally, extremely dense cases reported an increased risk of cancer compared to low-density breasts. This study aims to improve the mass detection performance in high-density breasts using synthetic high-density full-field digital mammograms (FFDM) as data augmentation during breast mass detection model training. To this end, a total of five cycle-consistent GAN (CycleGAN) models using three FFDM datasets were trained for low-to-high-density image translation in high-resolution mammograms. The training images were split by breast density BI-RADS categories, being

Chromatin Regulator-Related Gene Signature for Predicting Prognosis and Immunotherapy Efficacy in Breast Cancer.

Many studies have found that chromatin regulators (CRs) are correlated with tumorigenesis and disease prognosis. Here, we attempted to build a new CR-related gene model to predict breast cancer (BC) survival status. First, the CR-related differentially expressed genes (DEGs) were screened in normal and tumor breast tissues, and the potential mechanism of CR-related DEGs was determined by function analysis. Based on the prognostic DEGs, the Cox regression model was applied to build a signature for BC. Then, survival and receiver operating characteristic (ROC) curves were performed to validate the signatures efficacy and identify its independent prognostic value. The CIBERSORT and tumor immune dysfunction and exclusion (TIDE) algorithms were used to assess the immune cells infiltration and immunotherapy efficacy for this signature, respectively. Additionally, a novel nomogram was also built for clinical decisions. We identified 98 CR-related DEGs in breast tissues and constructed a novel 6 CR-related gene signature (ARID5A, ASCL1, IKZF3, KDM4B, PRDM11, and TFF1) to predict the outcome of BC patients. The prognostic value of this CR-related gene signature was validated with outstanding predictive performance. The TIDE analysis revealed that the high-risk group patients had a better response to immune checkpoint blockade (ICB) therapy. A new CR-related gene signature was built, and this signature could provide the independent predictive capability of prognosis and immunotherapy efficacy for BC patients.

Assessment of Knowledge and Awareness About Breast Self-Examination Among University Female Students in Saudi Arabia.

This study aims to evaluate the knowledge and awareness of female university students in Saudi Arabia about breast self-examination (BSE). From January to March 2022, an online self-administered questionnaire covering socio-demographic data and BSE Knowledge was distributed to female students enrolled in Saudi universities. The survey link was disseminated online and through student leaders. Mann-Whitney and Kruskal-Wallis tests were used to determine associations between the categorical variables and the BSE knowledge scores. Logistic regression was used to report the best predictor(s) for BSE knowledge. Among 668 respondents, 65.5% were aged between 20 and 24 years, 47.8% were taking health-related courses, 69.2% were from urban localities, and 90.6% had no family history of breast cancer. Only 4.2% showed adequate knowledge about BSEs. Students studying in health sciences had a significantly better BSE knowledge score (p 0.01). Moreover, 26.5% knew that a BSE has to be completed each month, and a similar percentage of students were aware that a BSE should not be completed during the menstrual cycle. Approximately half of the students knew that 20 years old is the recommended age to start BSEs. Seventy-two percent were aware that they must look for abnormal breast changes and the importance of feeling the axillary area when performing a BSE. Additionally, 55.2% were aware that most breast masses are detected by women themselves. Saudi female students knowledge about BSEs is inadequate. It is advisable that BSE knowledge and practice be incorporated into the curriculum of middle and high schools, as well as university students programs.

S100A9 promotes glycolytic activity in HER2-positive breast cancer to induce immunosuppression in the tumour microenvironment.

The purpose of this study was to investigate the correlation between S100 calcium binding protein A9 (S100A9), tumour glycolysis and tumour infiltrating lymphocytes (TIL) in human epidermal growth factor receptor 2 (HER2) - positive breast cancer (BRCA). A total of 667 BRCA patients in Xiangya Hospital of Central South University were enrolled in this study. Haematoxylin and eosin (HE) staining were used to count TIN in tissues. Human breast cancer cell lines (SK-BR-3 cells and BT474 cells) were transfected with S100A9 specific small interfering RNA (siRNA). The expressions of S100A9, glycolytic enzymes and lymphocyte markers were detected by immunohistochemistry (IHC) staining, Western blot and immunofluorescence. Lactate production, glucose consumption and the extracellular acidification rate (ECAR) were detected to assess glycolysis activity. S100A9 was significantly overexpressed in HER2 cases. The expressions of phosphoglycerol kinase 1 (PGK1), lactate dehydrogenase A (LDHA) and enolase α (ENO1) were significantly up-regulated in S100A9 dominant tissues. The expressions of PGK1, LDHA and ENO1 detected in S100A9 silenced cell lines were significantly down-regulated. Moreover, S100A9 silencing significantly altered lactate production, glucose uptake and ECAR levels in HER2 cell lines. Co-expression of S100A9 and c-Myc was detected in HER2 tissues. The absence of S100A9 greatly hindered β-catenin expression in cell lines, which later induced the phosphorylation of c-Myc.The amount of TILs in cases with abundant S100A9 and LDHA was much greater than in cases with low S100A9 levels and poorer LDHA. TIL deficiency and elevated S100A9 intensity are factors affecting the survival rate of HER2 BRCA cases. S100A9 overexpression upregulated the glycolysis activity of tumour cells through the c-Myc-related pathway, suppressing lymphocyte infiltration in the tumour stroma, affecting the efficacy of immune regulation and long-term survival of patients.

Deep-learning based breast cancer detection for cross-staining histopathology images.

Hematoxylin and eosin (HE) staining is the gold standard for tissue characterization in routine pathological diagnoses. However, these visible light dyes do not exclusively label the nuclei and cytoplasm, making clear-cut segmentation of staining signals challenging. Currently, fluorescent staining technology is much more common in clinical research for analyzing tissue morphology and protein distribution owing to its advantages of channel independence, multiplex labeling, and the possibility of enabling 3D tissue labeling. Although both HE and fluorescent dyes can stain the nucleus and cytoplasm for representative tissue morphology, color variation between these two staining technologies makes cross-analysis difficult, especially with computer-assisted artificial intelligence (AI) algorithms. In this study, we applied color normalization and nucleus extraction methods to overcome the variation between staining technologies. We also developed an available workflow for using an HE-stained segmentation AI model in the analysis of fluorescent nucleic acid staining images in breast cancer tumor recognition, resulting in 89.6% and 80.5% accuracy in recognizing specific tumor features in HE- and fluorescent-stained pathological images, respectively. The results show that the cross-staining inference maintained the same precision level as the proposed workflow, providing an opportunity for an expansion of the application of current pathology AI models.

Peripheral neuropathy, onycholysis and health-related quality of life in womens with breast cancer treated with taxanes. Prospective longitudinal study..

Peripheral neuropathy and onycholysis are adverse events produced by taxanes in breast cancer that persist even after the end of treatment and negatively influence quality of life. The objectives of the study were to describe these side effects and the degree of involvement and relating them to the drug doses received. Prospective, cross-sectional study of in 50 womens dignosed of breast cancer, treated with docetaxel and paclitaxel in Hospital Universitario Miguel Servet in Zaragoza (Aragón, Spain). CTCAE v.5.0 scale and Semes Weinsten test were used to evaluate peripheral neuropathy and onycholysis. ECOG scale was performed to measure the health-related quality of life. Study variables were evaluated before-during treatment and 1 and 6 months after finish treatment. Statistical analysis was performed using Jamovi 1.2®. For the relationship of the qualitative variables, the chi-square, Fishers exact test, Mcs test were used. Nemar and the Odds Ratio test. Effects were considered significant if p<0.05. 43 subjects were included. During treatment the 9.8 presented motor neuropathy and 12.2% sensitive neuropathy, 37.2% onycholisis in upper extremities and 39.5% in lower extremities (χ Taxanes have a negative impact on the health-related quality of life in patients, even 6 months after finishing treatment due to the peripheral neuropathy and onycholysis that they cause. La neuropatía periférica y la onicólisis son eventos adversos producidos por los taxanos en el cáncer de mama, que perduran incluso habiendo finalizado el tratamiento e influyendo negativamente en la calidad de vida. Los objetivos del estudio fueron describir estos efectos secundarios, midiendo el grado de afectación, y relacionarlos con las dosis de fármaco recibidas. Se realizó un estudio observacional, longitudinal prospectivo con muestreo consecutivo inicial de concuenta mujeres con cáncer de mama en tratamiento con docetaxel yo paclitaxel en el Hospital Universitario Miguel Servet de Zaragoza (Aragón, España). Para la valoración de la neuropatía periférica (motora y sensitiva) se utilizó la escala CTCAE v.5.0 y el test de Semmes Weinsten. La valoración de la calidad de vida relacionada con la salud se midió mediante la escala ECOG. Se realizaron valoraciones previo-durante-post y a los 6 meses de haber finalizado el tratamiento. El análisis estadístico se realizó mediante Jamovi 1.2®. Para la relación de las variables cualitativas se utilizó la chi-cuadrado, el test exacto de Fisher, el test de Mc.Nemar y el test de Odds Ratio. Los efectos se consideraron significativos si p<0,05. Se incluyeron finalmente 43 mujeres. Durante el tratamiento, el 9,8% presentó neuropatía motora y el 12,2% neuropatía sensitiva, el 37,2% onicólisis en extremidades superiores y el 39,5% en inferiores (χ Los taxanos repercuten negativamente en la calidad de vida de las mujeres incluso a los seis meses tras finalizar el tratamiento debido a la neuropatía periférica y la onicólisis que provocan.

Contralateral lymph node metastasis in recurrent ipsilateral breast cancer with Lynch syndrome a locoregional event.

Contralateral axillary lymph node metastasis (CALNM) in breast cancer (BC) is considered a distant metastasis, marking stage 4cancer. Therefore, it is generally treated as an incurable disease. However, in clinical practice, staging and treatment remain controversial due to a paucity of data, and the St. Gallen 2021 consensus panel recommended a curative approach in patients with oligometastatic disease. Aberrant lymph node (LN) drainage following previous surgery or radiotherapy is common. Therefore, CALNM may be considered a regional event rather than systemic disease, and a re-sentinel procedure aided by lymphoscintigraphy permits adequate regional staging. Here, we report a 37-year-old patient with Lynch syndrome who presented with CALNM in an ipsilateral relapse of a moderately differentiated invasive ductal BC (ER 90%, PR 30%, HER2 negative, Ki-67 25%, microsatellite stable), 3 years after the initial diagnosis. Lymphoscintigraphy detected a positive sentinel LN in the contralateral axilla despite no sign of LN involvement or distant metastases on FDG PETCT or MRI. The patient underwent bilateral mastectomy with sentinel node dissection, surgical reconstruction with histological confirmation of the CALNM, left axillary dissection, adjuvant chemotherapy, and anti-hormone therapy. In addition to her regular BC follow-up visits, the patient will undergo annual colonoscopy, gastroscopy, abdominal, and vaginal ultrasound screening. In January 2023, the patient was free of progression for 23 months after initiation of treatment for recurrent BC and CALNM. This case highlights the value of delayed lymphoscintigraphy and the contribution of sentinel procedure for local control in the setting of recurrent BC. Aberrant lymph node drainage following previous surgery may be the underlying cause of CALNM. We propose that CALNM without evidence of systemic metastasis should be considered a regional event in recurrent BC, and thus, a curative approach can be pursued. The next AJCC BC staging should clarify the role of CALNM in recurrent BC to allow for the development of specific treatment guidelines.

Tamoxifen induces radioresistance through NRF2-mediated metabolic reprogramming in breast cancer.

Recently, we reported that tamoxifen-resistant (TAM-R) breast cancer cells are cross-resistant to irradiation. Here, we investigated the mechanisms associated with tamoxifen-induced radioresistance, aiming to prevent or reverse resistance and improve breast cancer treatment. Wild-type ERα-positive MCF7 and ERα-negative MDA-MB-231 breast cancer cells and their TAM-R counterparts were analyzed for cellular metabolism using the Seahorse metabolic analyzer. Real-time ROS production, toxicity, and antioxidant capacity in response to H TAM-R cells exhibited decreased oxygen consumption and increased glycolysis, suggesting mitochondrial dysfunction. However, this did not explain radioresistance, as cells without mitochondria (Rho-0) were actually more radiosensitive. Real-time measurement of ROS after tamoxifen and H Mechanisms underlying tamoxifen-induced radioresistance are linked to cellular adaptations to persistently increased ROS levels, leading to cells with chronically upregulated antioxidant capacity and glycolysis. Pharmacological inhibition of antioxidant responses re-sensitizes breast cancer cells to irradiation.

Evaluation and comparison of different breast cancer prognosis scores based on gene expression data.

Breast cancer is one of the three most common cancers worldwide and is the most common malignancy in women. Treatment approaches for breast cancer are diverse and varied. Clinicians must balance risks and benefits when deciding treatments, and models have been developed to support this decision-making. Genomic risk scores (GRSs) may offer greater clinical value than standard clinicopathological models, but there is limited evidence as to whether these models perform better than the current clinical standard of care. PREDICT and GRSs were adapted using data from the original papers. Univariable Cox proportional hazards models were produced with breast cancer-specific survival (BCSS) as the outcome. Independent predictors of BCSS were used to build multivariable models with PREDICT. Signatures which provided independent prognostic information in multivariable models were incorporated into the PREDICT algorithm and assessed for calibration, discrimination and reclassification. EndoPredict, MammaPrint and Prosigna demonstrated prognostic power independent of PREDICT in multivariable models for ER-positive patients no score predicted BCSS in ER-negative patients. Incorporating these models into PREDICT had only a modest impact upon calibration (with absolute improvements of 0.2-0.8%), discrimination (with no statistically significant c-index improvements) and reclassification (with 4-10% of patients being reclassified). Addition of GRSs to PREDICT had limited impact on model fit or treatment received. This analysis does not support widespread adoption of current GRSs based on our implementations of commercial products.

CD1C is associated with breast cancer prognosis and immune infiltrates.

The tumor microenvironment (TME) in breast cancer plays a vital role in occurrence, development, and therapeutic responses. However, immune and stroma constituents in the TME are major obstacles to understanding and treating breast cancer. We evaluated the significance of TME-related genes in breast cancer. Invasive breast cancer (BRCA) samples were retrieved from the TCGA and GEO databases. Stroma and immune scores of samples as well as the proportion of tumor infiltrating immune cells (TICs) were calculated using the ESTIMATE and CIBERSORT algorithms. TME-related differentially expressed genes (DEGs) were analyzed by a protein interaction (PPI) network and univariate Cox regression to determine CD1C as a hub gene. Subsequently, the prognostic value of CD1C, its response to immunotherapy, and its mechanism in the TME were further studied. In BRCA, DEGs were determined to identify CD1C as a hub gene. The expression level of CD1C in BRCA patients was verified based on the TCGA database, polymerase chain reaction (PCR) results, and western blot analysis. Immunohistochemical staining (IHC) results revealed a correlation between prognosis, clinical features, and CD1C expression in BRCA. Enrichment analysis of GSEA and GSVA showed that CD1C participates in immune-associated signaling pathways. CIBERSORT showed that CD1C levels were associated with tumor immune infiltrating cells (TILs), such as different kinds of T cells. Gene co-expression analysis showed that CD1C and the majority of immune-associated genes were co-expressed in BRCA. In renal cell carcinoma, patients with a high expression of CD1C had a better immunotherapy effect. CD1C is an important part of the TME and participates in immune activity regulation in breast tumors. CD1C is expected to become a prognostic marker and a new treatment target for breast cancer.

The profiles of miR-4510 expression level in breast cancer.

MicroRNA that is abnormally produced in breast cells can disrupt biological processes, which can lead to cancer. This study aims to screen differentially expressed genes (DEGs) and ncRNAs (DEncRNAs) in the formalin-fixed paraffin-embedded (FFPE) tissues of breast cancer (BC) as compared with the normal adjacent tissues (NAT), and identify miR-4510 as a novel biomarker of BC. This study looked at differentially expressed genes (DEGs) using MACE-Seq and differentially expressed ncRNAs (DEncRNAs) using the small RNA-Seq. Real-time qPCR was used to determine the level of expression of miR-4510. In this study, MACE-Seq results showed that 26,795 genes, with a p-value < 0.05, were differentially expressed in BC paraffin tissues as compared with NAT. Small RNA-Seq results revealed that 1326 ncRNAs, with a p-value < 0.05, were differentially expressed. We confirmed that miR-4510 was significantly down-expressed (p-value 0.001) by qRT-PCR in the paraffin tissue of 120 BC patients. Based on eleven computational prediction programs, TP53, TP53INP1, MMP11, and COL1A1 for the miR-4510 were identified as miR-4510 targets. The MACE-seq result showed that the gene of TP53 (p-value 0.001) and TP53INP1 (p-value 0.02) was significantly down-regulated, but the gene of MMP11 (p-value 0.004) and COL1A1 (p-value 0.0001) was significantly over-expressed in 20 paired specimens of the BC and NAT. We discovered that a single SNP inside the miR-4510 binding site occurred only in BC, in which Guanine (G) changed into Adenine (A). Two SNPs outside the miR-4510 binding site occurred, and Guanine (G) in both BC and NAT was changed into Thymine (T), as compared to the reference sequence (RefSeq). Overall, our results suggested that miR-4510 functions as a tumor suppressor in the BC. Mir-4510 may act as a tumor suppressor, however additional experimental data is needed to corroborate these assumptions and can be exploited as a biomarker for BC.

Cuproptosis p53-regulated metabolic cell death

Cuproptosis is a novel type of copper-induced cell death that primarily occurs in cells that utilize oxidative phosphorylation as the main metabolic pathway to produce energy. Copper directly associates with the lipoylated proteins of the tricarboxylic acid cycle, leading to the disulfide-bond-dependent aggregation of these lipoylated proteins, destabilization of the iron-sulfur cluster proteins, and consequent proteotoxic stress. Cancer cells prefer glycolysis (Warburg effect) to oxidative phosphorylation for producing intermediate metabolites and energy, thereby achieving resistance to cuproptosis. Interestingly, the tumor suppressor p53 is a crucial metabolic regulator that inhibits glycolysis and drives a metabolic switch towards oxidative phosphorylation in cancer cells. Additionally, p53 regulates the biogenesis of iron-sulfur clusters and the copper chelator glutathione, which are two critical components of the cuproptotic pathway, suggesting that this tumor suppressor might play a role in cuproptosis. Furthermore, the possible roles of mutant p53 in regulating cuproptosis are discussed. In this essay, we review the recent progress in the understanding of the mechanism underlying cuproptosis, revisit the roles of p53 in metabolic regulation and iron-sulfur cluster and glutathione biosynthesis, and propose several potential mechanisms for wild-type and mutant p53-mediated cuproptosis regulation.

METTL3 stabilization by PIN1 promotes breast tumorigenesis via enhanced m

Methyltransferase-like 3 (METTL3) is the catalytic subunit of the N

Targeting BAP1 with small compound inhibitor for colon cancer treatment.

BRCA1-associated protein-1 (BAP1) is a ubiquitin C-terminal hydrolase domain-containing deubiquitinase. The gene encoding BAP1 is mutated in various human cancers, including mesothelioma, uveal melanoma and renal cell carcinoma. BAP1 plays roles in many cancer-related cellular functions, including cell proliferation, cell death, and nuclear processes crucial for genome stability, such as DNA repair and replication. While these findings suggest that BAP1 functions as a tumor suppressor, recent data also suggest that BAP1 might play tumor-promoting roles in certain cancers, such as breast cancer and hematopoietic malignancies. Here, we show that BAP1 is upregulated in colon cancer cells and tissues and that BAP1 depletion reduces colon cancer cell proliferation and tumor growth. BAP1 contributes to colon cancer cell proliferation by accelerating DNA replication and suppressing replication stress and concomitant apoptosis. A recently identified BAP1 inhibitor, TG2-179-1, which seems to covalently bind to the active site of BAP1, exhibits potent cytotoxic activity against colon cancer cells, with half-maximal inhibitory concentrations of less than 10 μM, and inhibits colon tumor growth. TG2-179-1 exerts cytotoxic activity by targeting BAP1, leading to defective replication and increased apoptosis. This work therefore shows that BAP1 acts oncogenically in colon cancer and is a potential therapeutic target for this cancer. Our work also suggests that TG2-179-1 can be developed as a potential therapeutic agent for colon cancer.