Telomere Protection in Stem Cells.

The natural ends of chromosomes resemble double-strand breaks (DSBs), which would activate the DNA damage response (DDR) pathway without the protection provided by a specialized protein complex called shelterin. Over the past decades, extensive research has uncovered the mechanism of action and the high degree of specialization provided by the shelterin complex to prevent aberrant activation of DNA repair machinery at chromosome ends in somatic cells. However, recent findings have revealed striking differences in the mechanisms of end protection in stem cells compared to somatic cells.

Phase II Study of Defactinib (VS6063) in Patients With Tumors With Loss: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol U.

Purpose: The NCI-MATCH trial assigned patients with solid tumors, lymphomas, or multiple myeloma to targeted therapies on the basis of identified genetic alterations from tumor biopsies. In preclinical models, ()-inactivated tumors display sensitivity to focal adhesion kinase (FAK) inhibition. The EAY131-U subprotocol evaluated the efficacy of defactinib, a FAK inhibitor, in patients with -altered tumors.

A large-scale proteomics resource of circulating extracellular vesicles for biomarker discovery in pancreatic cancer.

Pancreatic cancer has the worst prognosis of all common tumors. Earlier cancer diagnosis could increase survival rates and better assessment of metastatic disease could improve patient care. As such, there is an urgent need to develop biomarkers to diagnose this deadly malignancy.

Comparison of targeted next generation sequencing assays in non-small cell lung cancer patients.

Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer the mutational spectrum of which has been extensively characterized. Treatment of patients with NSCLC based on their molecular profile is now part of the standard clinical care. The aim of this study was firstly to investigate two different NGS-based tumor profile genetic tests and secondly to assess the clinical actionability of the mutations and their association with survival and clinicopathological characteristics.

Molecular profile of adult primary leptomeningeal gliomatosis aligns with glioblastoma, IDH-wildtype.

Adult primary leptomeningeal gliomatosis (PLG) is a rare, rapidly progressive and fatal disease characterized by prominent leptomeningeal infiltration by a glial tumor without an identifiable parenchymal mass. The molecular profile of adult PLG has not been well-characterized. We report the clinical, pathological, and molecular findings of six adult PLG patients (five males and one female), median age 58 years.

Genotype-phenotype associations in individuals with Diamond Blackfan anaemia.

Introduction: Diamond Blackfan anaemia (DBA) is a rare disorder characterized by failure of red blood cell production, congenital abnormalities and cancer predisposition, primarily caused by pathogenic germline variants in genes encoding ribosomal proteins.

Methods: We conducted a genotype-phenotype and outcome study of 121 patients with DBA spanning the 20-year history of the National Cancer Institute's Inherited Bone Marrow Failure Syndromes study. Patient phenotypes were compared by large versus small ribosomal protein genes, across genes with >5 cases (, , and ) and by type of pathogenic variants (hypomorphic versus null, large deletions versus others).

Representative Organ Doses from Computed Tomography (CT) Exams from a Large International Registry.

Estimation of absorbed organ doses used in computed tomography (CT) using time-intensive Monte Carlo simulations with virtual patient anatomic models is not widely reported in the literature. Using the library of computational phantoms developed by the University of Florida and the National Cancer Institute, we performed Monte Carlo simulations to calculate organ dose values for 9 CT categories representing the most common body regions and indications for imaging (reflecting low, routine, and high radiation dose examinations), stratified by patient age (in children) and effective diameter (in adults, using "diameter" as a measure of patient size). Our sample of 559,202 adult and 103,423 pediatric CT examinations was prospectively assembled between 2015-2020 from 156 imaging facilities from 27 healthcare organizations in 20 U.

Delphi technique for design and content validation by experts of a mobile app for self-care of breast cancer-related lymphedema.

Introduction: Breast cancer-related lymphedema (BCRL) is a complication that requires lifelong control, with patients taking responsibility for self-care. Mobile applications (apps) can be an effective health education strategy to help manage BCRL by promoting collaborative learning environments in physical therapy. The objective of this study was to design and validate the content for the development of a mobile application for self-care in the health of the BCRL.

Epidemiology and clinical outcomes of childhood central nervous system cancers in a large low-middle income country pediatric oncology center: a report on 5051 kids.

Background: Central nervous system (CNS) tumors are the leading cause of cancer-related deaths in children. While most cases come from low-middle income countries (LMIC) where their prognosis is worse, few epidemiological studies are conducted in these regions.

Methods: We conducted a registry-based cohort study for childhood CNS tumors at Children's Cancer Hospital, Egypt (CCHE) over 15 years.

Determinants of tumor necrosis and its impact on outcome in patients with Localized osteosarcoma uniformly treated with a response adapted regimen without high dose Methotrexate- A retrospective institutional analysis.

Purpose: Response to neoadjuvant chemotherapy in form of tumor necrosis predicts outcome in osteosarcoma; although response-adapted treatment escalation failed to improve outcome among patients treated with high-dose methotrexate-based (HDMTx) chemotherapy. This study aimed to identify factors predicting tumor necrosis and its impact on survival among patients with non-metastatic osteosarcoma treated with a response-adapted non-HDMTx regimen.

Methods: A retrospective single-institutional study was conducted among non-metastatic osteosarcoma patients treated with neoadjuvant therapy between 2004-2019.

Initial experience of parenchyma-sparing liver resection with systematic selective hepatic vein reconstruction for colorectal metastases.

Objectives: This study aims to assess the feasibility and short-term and intermediate-term technical success rate of the concept of systematic selective hepatic vein (HV) reconstruction for parenchyma-sparing hepatectomies (PSHs) in patients with colorectal liver metastases (CRLM) in accordance with stage 2a of the IDEAL framework.

Design: The prospective case series of patients deemed eligible and operated on according to the concept.

Setting: All patients were treated by a single surgical team in three hospitals in Ukraine from June 2022 to November 2023.

Biophysical Characterization of a Novel Phosphopentomutase from the Hyperthermophilic Archaeon .

Phosphopentomutases catalyze the isomerization of ribose 1-phosphate and ribose 5-phosphate. , a hyperthermophilic archaeon, harbors a novel enzyme (PPM) that exhibits high homology with phosphohexomutases but has no significant phosphohexomutase activity. Instead, PPM catalyzes the interconversion of ribose 1-phosphate and ribose 5-phosphate.

Transcriptome and Temporal Transcriptome Analyses in Single Cells.

Transcriptome analysis in single cells, enabled by single-cell RNA sequencing, has become a prevalent approach in biomedical research, ranging from investigations of gene regulation to the characterization of tissue organization. Over the past decade, advances in single-cell RNA sequencing technology, including its underlying chemistry, have significantly enhanced its performance, marking notable improvements in methodology. A recent development in the field, which integrates RNA metabolic labeling with single-cell RNA sequencing, has enabled the profiling of temporal transcriptomes in individual cells, offering new insights into dynamic biological processes involving RNA kinetics and cell fate determination.

Tolerability and Preliminary Outcomes of Adjuvant T-DM1 in HER2-Positive Breast Cancer After Neoadjuvant Therapy: The ATD Study.

Background/objectives: HER2-positive breast cancer (HER2BC) is an aggressive subtype, with neoadjuvant treatment (NAT) aiming to achieve a pathological complete response (pCR) to improve long-term outcomes. Trastuzumab emtansine (T-DM1) has been established as the standard of care in the adjuvant setting for HER2BC patients who do not obtain pCR. The ATD study aimed to evaluate the real-world tolerability of T-DM1 in this setting.

Emerging Non-Breast Implant-Associated Lymphomas: A Systematic Review.

Medical devices used for functional or esthetic purposes improve health and quality of life; however, they are not risk-free. Anaplastic large-cell lymphoma (ALCL), associated with breast implants, is a well-known and recognized distinct lymphoma entity. More recently, additional lymphomas have been reported in relation to prosthesis other than breast implants, as these allow the pericyte to develop into a clone that undergoes a maturation process, progressing toward full malignancy.

Gut Microbiome Changes After Neoadjuvant Chemotherapy and Surgery in Patients with Gastric Cancer.

Background/objectives: Neoadjuvant chemotherapy (NAC) followed by radical gastrectomy is the current standard approach for locally advanced gastric cancer (GC) in the West. Both NAC and gastrectomy can significantly influence the gut microbiome, potentially leading to clinically significant changes. However, no longitudinal studies to date support this hypothesis.

Retrospective-Prospective Observational Study of Italian Patients Treated in Melanoma Adjuvant Cohort MAP-MADAM (Maximing ADjuvAnt MAP): Interim Analysis.

: Dabrafenib and trametinib (D + T) have been approved for the treatment of stage III melanoma with BRAF V600E V600K mutations in an adjuvant setting, based on the results from the COMBI-AD trial. To provide early access to this combination therapy prior to its commercial availability in Italy, a Managed Access Program (MAP) was run in Italy from June 2018 to December 2019. : The MADAM (Maximing ADjuvAnt MAP) study is an Italian retrospective-prospective observational study that included patients who received at least one dose of D + T through the MAP.

Pathobiological Features and Therapeutic Opportunities Linked to TNF Family Member Expression in Classic Hodgkin Lymphoma.

The tumor necrosis factor (TNF) family, which includes 19 ligands and 29 receptors, influences cellular proliferation, differentiation, and apoptosis. The TNF family plays a crucial role in the pathogenesis of Hodgkin lymphoma (HL), particularly through its influence on the tumor microenvironment (TME). Hodgkin Reed-Sternberg (HRS) cells, the hallmark of classic HL (cHL), exhibit overexpression of TNF receptor family members such as CD30 and CD40.

Characterization of Somatostatin Receptor 2 Gene Expression and Immune Landscape in Sinonasal Malignancies.

Olfactory neuroblastoma (ONB), sinonasal undifferentiated carcinoma (SNUC), and sinonasal neuroendocrine carcinoma (SNEC) are rare malignancies arising from the sinonasal tract with limited therapeutic options. The expression of the somatostatin receptor 2 gene (), which is expressed in other neuroendocrine neoplasms and is therapeutically actionable, has been reported in these tumors. Here, we analyzed gene expression and its associations with genomic features, established biomarkers predicting of immune response, and the tumor immune microenvironment in a cohort of ONB, SNUC, and SNEC tumor samples (26, 13, and 8 samples, respectively) from a real-world database.

Comparing Outcomes of Open and Robot-Assisted Inguinal Lymphadenectomy for the Treatment of cN2 Squamous Cell Carcinoma of the Penis: A Retrospective Single-Center Analysis.

Background: Inguinal lymph node (LN) dissection (iLND) is mandatory in cN2 penile squamous cell carcinoma (PSCC). Open iLND (OIL) is often omitted due to the high rate of complications. A minimally invasive approach may reduce morbidity; however, evidence supporting its role to treat bulky nodes is limited.

WNT and TGF-Beta Pathway Alterations in Early-Onset Colorectal Cancer Among Hispanic/Latino Populations.

Background/objectives: One of the fastest-growing minority groups in the U.S. is the Hispanic/Latino population.

Masked Image Modeling Meets Self-Distillation: A Transformer-Based Prostate Gland Segmentation Framework for Pathology Slides.

Detailed evaluation of prostate cancer glands is an essential yet labor-intensive step in grading prostate cancer. Gland segmentation can serve as a valuable preliminary step for machine-learning-based downstream tasks, such as Gleason grading, patient classification, cancer biomarker building, and survival analysis. Despite its importance, there is currently a lack of a reliable gland segmentation model for prostate cancer.