Deep learning uncovers histological patterns of YAP1/TEAD activity related to disease aggressiveness in cancer patients.

Over the last decade, Hippo signaling has emerged as a major tumor-suppressing pathway. Its dysregulation is associated with abnormal expression of and -family genes. Recent works have highlighted the role of YAP1/TEAD activity in several cancers and its potential therapeutic implications.

Glycosylation profiling of triple-negative breast cancer: clinical and immune correlations and identification of LMAN1L as a biomarker and therapeutic target.

Introduction: Breast cancer (BC) is the most prevalent malignant tumor in women, with triple-negative breast cancer (TNBC) showing the poorest prognosis among all subtypes. Glycosylation is increasingly recognized as a critical biomarker in the tumor microenvironment, particularly in BC. However, the glycosylation-related genes associated with TNBC have not yet been defined.

Determinants of Demoralization Syndrome and Social Support Among Patients with Breast Cancer: A Cross-Sectional Study.

Objective: This study aimed to assess the determinants of demoralization syndrome among patients with breast cancer (BC) in the southwestern region of China.

Methods: This investigation constituted a single-center cross-sectional study in which 176 patients with BC were surveyed through a questionnaire covering the current status of demoralization syndrome and social support.

Results: Majority of patients with BC developed moderate-to-severe levels of demoralization.

Pro-inflammatory dietary pattern and the risk of female gout: sex-specific findings from three prospective cohort studies.

Objective: We aimed to determine whether a pro-inflammatory dietary pattern (mechanism-based diet) is associated with incident female gout among two large cohorts of US women.

Methods: We prospectively followed 79,104 women from Nurses' Health Study (NHS; 1984-2016) and 93,454 women from NHSII (1991-2017); 45,445 men from Health Professionals Follow-up Study (1986-2016) served as a comparison cohort. Validated food frequency questionnaires were used to calculate Empirical Dietary Inflammatory Pattern (EDIP; food-based index predictive of circulating inflammatory biomarkers) scores every 4-years.

The Efficacy of Oral Atorvastatin for Skin Toxicity in Breast Cancer Patients Undergoing Radiotherapy: A Randomized, Double-blind, Placebo-controlled Trial.

Introduction: Most Breast Cancer (BC) patients undergoing Radiotherapy (RT) are potentially susceptible to skin toxicity and prone to clinical symptom complaints. This study aimed to investigate the effect of oral Atorvastatin (ATV) administration on skin toxicity in BC patients undergoing RT.

Methods: One hundred BC patients were randomly assigned to oral ATV (40 mg) or placebo tablets two days before beginning the RT until the eighth week of the RT regimen was completed.

CDKN3 as a key regulator of G2M phase in triple-negative breast cancer: Insights from multi-transcriptomic analysis.

Triple-negative breast cancer (TNBC) remains a significant global health challenge, emphasizing the need for precise identification of patients with specific therapeutic targets and those at high risk of metastasis. This study aimed to identify novel therapeutic targets for personalized treatment of TNBC patients by elucidating their roles in cell cycle regulation. Using weighted gene co-expression network analysis (WGCNA), we identified 83 hub genes by integrating gene expression profiles with clinical pathological grades.

Adjusting for Ascertainment Bias in Meta-Analysis of Penetrance for Cancer Risk.

Multi-gene panel testing allows efficient detection of pathogenic variants in cancer susceptibility genes including moderate-risk genes such as ATM and PALB2. A growing number of studies examine the risk of breast cancer (BC) conferred by pathogenic variants of these genes. A meta-analysis combining the reported risk estimates can provide an overall estimate of age-specific risk of developing BC, that is, penetrance for a gene.

Integrating mitochondrial and lysosomal gene analysis for breast cancer prognosis using machine learning.

The impact of mitochondrial and lysosomal co-dysfunction on breast cancer patient outcomes is unclear. The objective of this study is to develop a predictive machine learning (ML) model utilizing mitochondrial and lysosomal co-regulators in order to provide a foundation for future studies focused on breast cancer (BC) patients' stratification and personalized interventions. Firstly, Differences and correlations of mitochondrial and lysosome related genes were screened and validated by differential analysis, copy number variation (CNV), single nucleotide polymorphism (SNPs) and correlation analysis.

Proteomic profiling identifies upregulation of aurora kinases causing resistance to taxane-type chemotherapy in triple negative breast cancer.

Nowadays, chemotherapy and immunotherapy remain the major treatment strategies for Triple-Negative Breast Cancer (TNBC). Identifying biomarkers to pre-select and subclassify TNBC patients with distinct chemotherapy responses is essential. In the current study, we performed an unbiased Reverse Phase Protein Array (RPPA) on TNBC cells treated with chemotherapy compounds and found a leading significant increase of phosphor-AURKA/B/C, AURKA, AURKB, and PLK1, which fall into the mitotic kinase group.

Bisphenol A-Induced Cancer-Associated Adipocytes Promotes Breast Carcinogenesis Via CXCL12/AKT Signaling.

Bisphenol A (BPA), a commonly used plastic additive, is believed to cause obesity. As an environmental endocrine disruptor, BPA is closely associated with the onset and progression of BC. However, the molecular mechanisms underlying the promotion of breast cancer by BPA remain unclear.

Digital Profiling of Immune Biomarkers in Breast Cancer: Relation to Anthracycline Benefit.

Assessment of the tumor immune microenvironment can be used as a prognostic tool for improved survival and as a predictive biomarker for treatment benefit, particularly from immune modulating treatments including cytotoxic chemotherapy. Using Digital Spatial Profiling (DSP), we studied the tumor immune microenvironment of 522 breast cancer cases by quantifying 35 immune biomarkers on tissue microarrays from the MA.5 phase III clinical trial.

A promising future for breast cancer therapy with hydroxamic acid-based histone deacetylase inhibitors.

Histone deacetylases (HDACs) play a critical role in chromatin remodelling and modulating the activity of various histone proteins. Aberrant HDAC functions has been related to the progression of breast cancer (BC), making HDAC inhibitors (HDACi) promising small-molecule therapeutics for its treatment. Hydroxamic acid (HA) is a significant pharmacophore due to its strong metal-chelating ability, HDAC inhibition properties, MMP inhibition abilities, and more.

Enhancing early breast cancer detection with APE1-triggered oligonucleotide probes and graphene oxide: The impact of variable AP site modification on sensitivity and specificity.

There is a critical need for inclusive diagnostic platforms to enhance the accuracy of early breast cancer detection. Dysregulated microRNA-1246 (miR-1246), closely linked to the disease progression and recurrence, has emerged as a promising diagnostic and prognostic biomarker for BC. However, achieving simple, rapid, and ultrasensitive quantification of serum miRNAs remains significant challenge.

Liposomal Formulation of Hydroxychloroquine Can Inhibit Autophagy In Vivo.

Preclinical studies have shown that the anti-malarial drug hydroxychloroquine (HCQ) improves the anti-cancer effects of various therapeutic agents by impairing autophagy. These findings are difficult to translate in vivo as reaching an effective HCQ concentration at the tumor site for extended times is challenging. Previously, we found that free HCQ in combination with gefitinib (Iressa, ZD1839) significantly reduced tumor volume in immunocompromised mice bearing gefitinib-resistant JIMT-1 breast cancer xenografts.

Immunohistochemical Profiling of Histone Modification Biomarkers Identifies Subtype-Specific Epigenetic Signatures and Potential Drug Targets in Breast Cancer.

Breast cancer (BC) subtypes exhibit distinct epigenetic landscapes, with triple-negative breast cancer (TNBC) lacking effective targeted therapies. This study investigates histone biomarkers and therapeutic vulnerabilities across BC subtypes. The immunohistochemical profiling of >20 histone biomarkers, including histone modifications, modifiers, and oncohistone mutations, was conducted on a discovery cohort and a validation cohort of BC tissues, healthy controls, and cell line models.

Neoadjuvant Chemotherapy for T3 Tumors in the Era of Precision Medicine-Biology Is Still King.

Clinical T3 (cT3) breast cancer (BC) presents a challenge for achieving cosmetically acceptable breast conservation, and neoadjuvant chemotherapy (NAC) is commonly used for cytoreduction in these high-risk cancers. MammaPrint risk-of-recurrence and BluePrint molecular subtyping genomic signatures have demonstrated high accuracy in predicting chemotherapy benefits. Here, we examined the utility of MammaPrint/BluePrint for predicting pathological Complete Response (pCR) rates to NAC among 404 patients diagnosed with cT3 early-stage BC.

Association of Pregnancy Complications with Endometrial or Ovarian or Breast Cancer: A Case Control Study.

: The relationship between pregnancy complications and the risk of gynecological and breast cancer remains inconclusive, with limited research available. This study aimed to determine whether pregnancy complications, including preeclampsia, gestational diabetes mellitus (GDM), large for gestational age (LGA), or intrauterine growth restriction (IUGR) are associated with the development of endometrial cancer (EC), ovarian cancer (OC), or breast cancer (BC). : This was a population-based case-control study linked to the National Health Insurance Research Database from 2008 to 2020, using ICD codes to identify parous gynecological cases (n = 6714).

Lipopolymers as the Basis of Non-Viral Delivery of Therapeutic siRNA Nanoparticles in a Leukemia (MOLM-13) Model.

Small interfering RNA (siRNA) therapy in acute myeloid leukemia (AML) is a promising strategy as the siRNA molecule can specifically target proteins involved in abnormal cell proliferation. The development of a clinically applicable method for delivering siRNA molecules is imperative due to the challenges involved in effectively delivering the siRNA into cells. We investigated the delivery of siRNA to AML MOLM-13 cells with the use of two lipid-substituted polyethyleneimines (PEIs), a commercially available reagent (Prime-Fect) and a recently reported reagent with improved lipid substitution (PEI1.

The Immunohistochemical Prognostic Value of Nuclear and Cytoplasmic Silent Information Regulator 1 Protein Expression in Saudi Patients with Breast Cancer.

Background: The mammalian NAD-dependent deacetylase sirtuin-1 family (named also silent information regulator or SIRT family, where NAD stands for "nicotinamide adenine dinucleotide" (NAD)) appears to have a dual role in several human cancers by modulating cell proliferation and death. This study examines how SIRT1 protein levels correlate with clinicopathological characteristics and survival outcomes in patients with breast cancer.

Methods: A total of 407 BC formalin-fixed paraffin-embedded (FFPE) samples were collected from King Abdulaziz University Hospital, Saudi Arabia.

Tumor-Infiltrating Lymphocytes and Neutrophils and Their Location in Canine Mammary Neoplasms with a Solid Arrangement: A Prognostic Factor?

In canine mammary neoplasms, greater inflammation is associated with higher histological grade, lymphatic invasion, and metastases. This retrospective study assessed the density of peri- and intratumoral tumor-infiltrating lymphocytes (TILs), tumor-associated neutrophils (TANs), and CD3 and CD79 lymphocytes in canine mammary neoplasms with a solid arrangement, and associated such data with histological types, immunophenotype, prognostic factors, cyclooxygenase-2 (Cox-2) expression and overall and cancer-specific survival. Sixty-one neoplasms with a solid arrangement were classified as malignant myoepitheliomas (6/9.

IL-1β in Neoplastic Disease and the Role of Its Tumor-Derived Form in the Progression and Treatment of Metastatic Prostate Cancer.

Since its discovery, IL-1β has taken center stage as a key mediator of a very broad spectrum of diseases revolving around immuno-mediated and inflammatory events. Predictably, the pleiotropic nature of this cytokine in human pathology has led to the development of targeted therapeutics with multiple treatment indications in the clinic. Following the accumulated findings of IL-1β's central modulatory role in the immune system and the implication of inflammatory pathways in cancer, the use of IL-1β antagonists was first proposed and then also pursued for oncology disorders.

Enhanced Lung Cancer Survival Prediction Using Semi-Supervised Pseudo-Labeling and Learning from Diverse PET/CT Datasets.

Objective: This study explores a semi-supervised learning (SSL), pseudo-labeled strategy using diverse datasets such as head and neck cancer (HNCa) to enhance lung cancer (LCa) survival outcome predictions, analyzing handcrafted and deep radiomic features (HRF/DRF) from PET/CT scans with hybrid machine learning systems (HMLSs).

Methods: We collected 199 LCa patients with both PET and CT images, obtained from TCIA and our local database, alongside 408 HNCa PET/CT images from TCIA. We extracted 215 HRFs and 1024 DRFs by PySERA and a 3D autoencoder, respectively, within the ViSERA 1.

MET Activation in Lung Cancer and Response to Targeted Therapies.

The hepatocyte growth factor receptor (MET) is a receptor tyrosine kinase (RTK) that mediates the activity of a variety of downstream pathways upon its activation. These pathways regulate various physiological processes within the cell, including growth, survival, proliferation, and motility. Under normal physiological conditions, this allows MET to regulate various development and regenerative processes; however, mutations resulting in aberrant MET activity and the consequent dysregulation of downstream signaling can contribute to cellular pathophysiology.

Necroptosis-Related Gene Signature Predicts Prognosis in Patients with Advanced Ovarian Cancer.

This study aimed to construct a risk score (RS) based on necroptosis-associated genes to predict the prognosis of patients with advanced epithelial ovarian cancer (EOC). EOC data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) series 140082 (GSE140082) were used. Based on known necroptosis-associated genes, clustering was performed to identify molecular subtypes of EOC.

Prognostic Factors in Therapy Regimes of Breast Cancer Patients with Brain Metastases: A Retrospective Monocentric Analysis.

Breast cancer patients who develop brain metastases have a high mortality rate and a massive decrease in quality of life. Approximately 10-15% of all patients with breast cancer (BC) and 5-40% of all patients with metastatic BC develop brain metastasis (BM) during the course of the disease. However, there is only limited knowledge about prognostic factors in the treatment of patients with brain metastases in breast cancer (BMBC).