Targeting YES1 enhances the efficacy of chemotherapy, targeted therapy and onco-immunotherapy.

YES1 (Yamaguchi sarcoma virus homolog 1), a non-receptor tyrosine kinase of the SRC family (SFK), has been abnormally amplified or mutated in several types of solid tumors. The alteration of YES1 impacted multiple biological processes, including promoting tumor progression and metastasis, especially, producing cancer therapy resistance via bypass pathways. Thus, YES1 can serve as a druggable target to overcome drug resistance and suppress tumor growth.

Analysis of TERT association with clinical outcome in meningiomas: a multi-institutional cohort study.

Background: TERT promoter mutation is a rare biomarker in meningiomas associated with aberrant TERT expression and reduced progression-free survival. Although high TERT expression is characteristic of tumours with TERT promoter mutations, it has also been observed in tumours with wildtype TERT promoters. This study aimed to investigate the prevalence and prognostic association of TERT expression in meningiomas.

Epigenetic modulation of BARD1 to enhance anti-VEGF therapy.

Despite the clinical use of anti-vascular endothelial growth factor (VEGF) antibodies (AVAs) in cancer therapy, resistance frequently develops, leading to disease progression. To address this, we identify a previously unknown role for breast cancer type 1 susceptibility protein (BRCA1)-associated RING domain 1 (BARD1) in modulating AVA sensitivity. Epigenetic modulation-via global and targeted DNA methylation-reveals BARD1 as a key regulator of angiogenesis.

Non-invasive bladder cancer detection: Identification of a urinary volatile biomarker panel using GC-MS metabolomics and machine learning.

Early detection of bladder cancer (BC) remains a major clinical challenge due to the limitations of current diagnostic methods, which are often invasive, expensive, or insufficiently sensitive, particularly for early-stage disease. Metabolomics approaches, when integrated with machine learning (ML) techniques, offer a powerful platform for identifying novel, non-invasive biomarkers. In this study, urinary volatile organic compounds (VOCs) were analysed from 87 BC patients and 90 age- and sex-matched cancer-free controls using headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME/GC-MS).

Gene actionability according to the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) in No Specific Molecular Profile (NSMP) endometrial cancer.

Background: The No Specific Molecular Profile (NSMP) subtype accounts for ∼30%-40% of endometrial cancer (EC), comprising a heterogeneous group of EC.

Patients And Methods: The primary outcome of this study was the prevalence of actionable genomic alterations in NSMP EC, classified according to the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of molecular Targets (ESCAT). Oncogenic and likely oncogenic alterations, pathways, and co-mutation patterns were reported.

Prospective assessment of prognostic significance of malignant peritoneal cytology in endometrial cancer: An NRG Oncology / Gynecologic Oncology Group study on GOG-210 protocol.

Objective: To examine the association between malignant peritoneal cytology and survival outcomes in endometrial cancer.

Methods: This was an ancillary analysis of prospectively collected surgical-pathological data in the NRG Oncology / Gynecologic Oncology Group study on GOG-210 protocol. The study population included 2383 patients with stage I-III endometrial cancer from 2003 to 2011.

Feasibility of Intravaginal Artesunate as an Adjuvant HPV & Cervical Precancer Treatment Among Women Living With HIV in Kenya: Study Protocol for a Phase II Clinical Trial.

IntroductionCervical cancer disproportionately affects women in low- and middle-income countries (LMICs), who account for 90% of deaths from the disease. Human papillomavirus (HPV) is responsible for 99% of cervical cancer cases. Women living with HIV (WLWH) have a higher risk of persistent HPV infection and a greater likelihood of developing cervical cancer.

Real-World Validation of the Purity Independent Subtyping of Tumors Classifier for Informing Therapy Selection in Pancreatic Ductal Adenocarcinoma.

Purpose: FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GnP) are the most commonly administered first-line (1L) regimens for advanced, nonresectable, pancreatic ductal adenocarcinoma (PDAC). In the absence of biomarkers to predict response, clinical covariates such as age and performance status are often used by clinicians to select optimal treatment regimens. Purity independent subtyping of tumors (PurIST) is a molecular subtyping algorithm that classifies tumors as classical or basal.

Timing genomic antigen loss in multiple myeloma treated with T-cell redirecting immunotherapies.

Genomic antigen loss is a recurring mechanism of resistance to chimeric antigen receptor T-cell (CAR-T) and T-cell engagers (TCE) in relapsed/refractory multiple myeloma (RRMM). Yet, it remains unclear whether these events are acquired under treatment or merely selected from pre-existing, undetectable clones. By leveraging chemotherapy mutational signatures as temporal barcodes within whole genome sequencing data, we could time genomic antigen escape in 4 out of 11 RRMM patients.

Impact of Human Epidermal Growth Factor Receptor 2 in Patients With Metastatic Colorectal Cancer Treated With Chemotherapy Plus Bevacizumab or Anti-EGFRs: Exploratory Analysis of Eight Randomized Trials.

Purpose: Human epidermal growth factor receptor 2 (HER2) amplification/overexpression (HER2-pos) is detected in 5% of wild-type metastatic colorectal cancers (mCRCs). Its prognostic/predictive role in terms of benefit from anti-EGFR/bevacizumab (bev) is debated. Similarly, the role of activating mutations (mut) is unclear.

Emerging role of ARHGAP29 in melanoma cell phenotype switching.

Rho GTPase-activating protein 29 (ARHGAP29) is an inhibitor of the Ras homolog family member A (RhoA)/Rho-associated protein kinase (ROCK) signaling pathway. Studies in non-melanoma cancer entities described that ARHGAP29 modulates the actin cytoskeleton, promoting tumor cell invasion. In melanoma, its function has been completely unknown.

Myeloid sarcoma shows a high frequency of mutations activating the MAPK/ERK pathway and association with clonal hematopoiesis.

Myeloid sarcoma (MS) is a mass-forming extramedullary manifestation of myeloid blasts, either in relation to an underlying acute myeloid leukemia (AML), another myeloid neoplasm (MN) or as a de novo occurrence. Data on the genetic profile of MS are sparse. In this study, 41 MS of 34 patients, including 7 de novo cases and 24 patients with antecedent or synchronous MN, were analyzed with targeted next-generation sequencing (NGS), RNA-based fusion detection, and gene expression profiling (GEP).

Incidental Cystadenomas of the Seminal Vesicle: An Institutional Series.

Cystadenoma of the seminal vesicle is a benign epithelial tumor composed of variably sized cysts, lined by bland epithelial cells, and surrounded by fibromuscular stroma. Considered rare and mostly described in case reports, affected patients are frequently described as presenting with obstructive urinary symptoms due to mass effect. Nonetheless, anecdotally, we have seen these tumors present more frequently as smaller, incidental lesions.

33 Unresolved Questions in Nanoscience and Nanotechnology.

Significant advances in science and engineering often emerge at the intersections of disciplines. Nanoscience and nanotechnology are inherently interdisciplinary, uniting researchers from chemistry, physics, biology, medicine, materials science, and engineering. This convergence has fostered novel ways of thinking and enabled the development of materials, tools, and technologies that have transformed both basic and applied research, as well as how we address critical societal challenges.

Evaluation of Neutrophil to Lymphocyte Ratio in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma Treated With a Combination of Cetuximab and Nivolumab in a Phase II Clinical Trial.

Objectives: We report on the biomarker analyses focusing on neutrophil-to-lymphocyte ratios (NLR) in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with combined cetuximab and nivolumab.

Methods: Data were obtained from a phase II trial (NCT03370276). Peripheral blood NLR was obtained at baseline (B-NLR) and on-treatment (OT-NLR; 1 mo from treatment initiation).

What's hidden in plain sight? Impact of clonal hematopoiesis on the risk and progression of non-hematologic cancers.

Clonal hematopoiesis (CH) is a frequently observed phenomenon in aging individuals without apparent illness and exhibits an increased prevalence in cancer patients. Mechanistic studies indicate that mutant immune cells alter the tumor microenvironment, leading to increased inflammation, blood vessel formation, and immune cell exhaustion. Paradoxically, these changes also preserve stem-like T-cell pools that can be utilized by immunotherapy.

Mast Cell Leukemia: Comprehensive Review of Literature With Current Insights and Updates on Management.

Mast cell leukemia (MCL) is an exceedingly rare and aggressive variant of systemic mastocytosis (SM). MCL is classified as primary, occurring without prior mast cell (MC) disorders or secondary, from a pre-existing SM, and acute aggressive form with C-findings that indicate organ damage or chronic indolent form without organ damage. Of the cases, 60-65% are aleukemic with < 10% circulating MCs in the peripheral blood, and the rest of the cases are leukemic with > 10% MCs.

Polarization of Tumor Cells and Tumor-Associated Macrophages: Molecular Mechanisms and Therapeutic Targets.

Tumor-associated macrophages (TAMs) are prominent constituents of solid tumors, and their prevalence is often associated with poor clinical outcomes. These highly adaptable immune cells undergo dynamic functional changes within the immunosuppressive tumor microenvironment (TME), engaging in reciprocal interactions with malignant cells. This bidirectional communication facilitates concurrent phenotypic transformation: tumor cells shift toward invasive mesenchymal states, whereas TAMs develop immunosuppressive, pro-tumorigenic traits.

-cigarette market proportion by nicotine claims in the United States.

Objective: Nicotine concentration, form (salt vs. freebase), and type (synthetic vs. tobacco-derived) are key characteristics of e-cigarettes that manufacturers manipulate.

A soft-stiff patterned bioengineering model reveals kinase pathways driving directional cell migration in pulmonary arterial hypertension.

Directional cell migration by pulmonary arterial cells (PACs) is one of the important features of diseases involving arterial remodeling, such as pulmonary arterial hypertension (PAH), a disease that is often characterized by reduced arterial compliance and increased extracellular matrix (ECM) stiffening. However, there are no therapeutics that can halt the directional cell migration of PACs in PAH. The inability to identify drug targets or drugs against the directional cell migration during PAH pathogenesis stems from an incomplete understanding of the process and a lack of effective translational models for screening of candidate small molecules.

Isolated oral CD30+/CD4+ CAR+ T-cell lymphoma in long-term remission after radiotherapy.

A Chimeric Antigen Receptor (CAR) positive CD30+/CD4+ T-cell lymphoma (TCL) manifested as a single oral ulceration 22 months after treatment with tisagenlecleucel (tisa-cel), an anti-CD19 CAR T-cell based therapy. TCL showed lentiviral integration in ANKHD1-EIF4EBP3, loss of function of TET2, and NTRK1 copy number gain, suggesting that genetic alterations unrelated to insertional mutagenesis contributed to lymphomagenesis. The patient remains in remission two years after radiotherapy.

DNA2 enables growth by restricting recombination-restarted replication.

Nuclease-helicase DNA2 is a multifunctional genome caretaker that is essential for cell proliferation in a range of organisms, from yeast to human. Bi-allelic DNA2 mutations that reduce DNA2 concentrations cause a spectrum of primordial dwarfism disorders, including Seckel and Rothmund-Thomson-related syndromes. By contrast, cancer cells frequently express high concentrations of DNA2 (refs.

Rewiring of cortical glucose metabolism fuels human brain cancer growth.

The brain avidly consumes glucose to fuel neurophysiology. Cancers of the brain, such as glioblastoma, relinquish physiological integrity and gain the ability to proliferate and invade healthy tissue. How brain cancers rewire glucose use to drive aggressive growth remains unclear.

Evaluation of intraoperative blood pressure and intrinsic tumor features as predictors of pseudoaneurysm formation after partial nephrectomy: A case-control study.

Introduction: Renal artery pseudoaneurysm (RAP) is a life-threatening complication of partial nephrectomy (PN) with reported rates of 1% to 2%. No studies have reported on the association between intraoperative blood pressure (BP) and RAP.

Methods: We identified all PN patients in our system between 2010 and 2024 and identified those with RAP (cases).

A sensitive and specific non-invasive urine biomarker panel for prostate cancer detection.

Background: Prostate cancer (PCa) is one of the leading causes of cancer death in men. While prostate-specific antigen (PSA) testing is widely used for screening, its diagnostic accuracy is limited, often failing to distinguish between benign and malignant prostate conditions, underscoring the need for novel biomarkers with improved diagnostic performance. This study aimed to identify and validate a panel of urinary RNA biomarkers with improved diagnostic accuracy for PCa.