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.

Machine Learning-based Prognostic Subgrouping of Glioblastoma: A Multi-center Study.

Background: Glioblastoma is the most aggressive adult primary brain cancer, characterized by significant heterogeneity, posing challenges for patient management, treatment planning, and clinical trial stratification.

Methods: We developed a highly reproducible, personalized prognostication and clinical subgrouping system using machine learning (ML) on routine clinical data, MRI, and molecular measures from 2,838 demographically diverse patients across 22 institutions and 3 continents. Patients were stratified into favorable, intermediate, and poor prognostic subgroups (I, II, III) using Kaplan-Meier analysis (Cox proportional model and hazard ratios [HR]).

Higher expression of mir-31-5p is associated with reduced risk of head and neck keloid recurrence following surgical resection.

Objective: In this study, we aimed to evaluate mir-31-5p as a prognostic biomarker of keloid disease (KD) recurrence using a retrospective, treatment naïve, surgical cohort of head and neck KD cases from Henry Ford Health.

Methods: Using a tissue microarray, mir-31-5p expression was measured with miRNAscope, and mir-31-5p cell positivity was determined with QuPath. Logistic regression was used to test the association between mir-31-5p positive cells and KD recurrence at 1 year.

Cancer Clinical Trial Participation: A Qualitative Study of Black/African American Communities' and Patient/Survivors' Recommendations.

Background: Black/African Americans experience a disproportionate cancer burden and mortality rates. Racial/ethnic variation in cancer burden reflects systemic and healthcare inequities, cancer risk factors, and heredity and genomic diversity. Multiple systemic, socio-cultural, economic, and individual factors also contribute to disproportionately low Black/African American participation in cancer clinical trials.

Factors associated with breast lymphedema after adjuvant radiation therapy in women undergoing breast conservation therapy.

Purpose: Breast lymphedema after post-lumpectomy radiation therapy (RT) is poorly defined and difficult to treat. The aim of this study was to define the incidence of breast lymphedema and identify factors associated with the risk of developing breast lymphedema (BL) in women undergoing breast-conserving therapy.

Methods: A retrospective cohort study of patients with early-stage breast cancer who underwent breast-conserving surgery (lumpectomy) followed by RT between January 1, 2014 and July 31, 2019 at a single institution.

A diverse hidradenitis suppurativa cohort: A retrospective cross-sectional study of 13,130 patients from a large US health care system database from 1995 to 2022.

Background: Most epidemiological studies of hidradenitis suppurativa (HS) have described homogeneous patient populations.

Objective: To characterize demographics, modifiable health behaviors, and comorbidities of HS patients within a diverse cohort.

Methods: A retrospective cross-sectional study of 13,130 HS patients within a health care system was conducted.

Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.2.

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Zinc finger nuclease-mediated gene editing in hematopoietic stem cells results in reactivation of fetal hemoglobin in sickle cell disease.

BIVV003 is a gene-edited autologous cell therapy in clinical development for the potential treatment of sickle cell disease (SCD). Hematopoietic stem cells (HSC) are genetically modified with mRNA encoding zinc finger nucleases (ZFN) that target and disrupt a specific regulatory GATAA motif in the BCL11A erythroid enhancer to reactivate fetal hemoglobin (HbF). We characterized ZFN-edited HSC from healthy donors and donors with SCD.

BUB1 Inhibition Overcomes Radio- and Chemoradiation Resistance in Lung Cancer.

: Despite advances in targeted therapies and immunotherapies, traditional treatments like microtubule stabilizers (paclitaxel, docetaxel), DNA-intercalating platinum drugs (cisplatin), and radiation therapy remain essential for managing locally advanced and metastatic lung cancer. Identifying novel molecular targets could enhance the efficacy of these treatments. : We hypothesize that BUB1 (Ser/Thr kinase) is overexpressed in lung cancers and its inhibition will sensitize lung cancers to chemoradiation.

Present and Future of Immunotherapy for Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) lacks the expression of estrogen receptors (ERs), human epidermal growth factor receptor 2 (HER2), and progesterone receptors (PRs). TNBC has the poorest prognosis among breast cancer subtypes and is more likely to respond to immunotherapy due to its higher expression of PD-L1 and a greater percentage of tumor-infiltrating lymphocytes. Immunotherapy has revolutionized TNBC treatment, especially with the FDA's approval of pembrolizumab (Keytruda) combined with chemotherapy for advanced cases, opening new avenues for treating this deadly disease.

Development of an EGSnrc multi-leaf collimator component module and treatment head model for a low-field MRI linear accelerator.

Background: Monte Carlo (MC) modeling of MR-guided radiotherapy (MRgRT) treatment machines enables the characterization of photon/electron interactions in the presence of a magnetic field. The EGSnrc MC code system is a well-established system for radiation dose calculations. The multi-leaf collimator (MLC) component modules presently available within the EGSnrc MC code system do not include a model of the double-focused MLC available on a low-field (0.

GSK-3β in Dendritic Cells Exerts Opposite Functions in Regulating Cross-Priming and Memory CD8 T Cell Responses Independent of β-Catenin.

GSK-3β plays a critical role in regulating the Wnt/β-catenin signaling pathway, and manipulating GSK-3β in dendritic cells (DCs) has been shown to improve the antitumor efficacy of DC vaccines. Since the inhibition of GSK-3β leads to the activation of β-catenin, we hypothesize that blocking GSK-3β in DCs negatively regulates DC-mediated CD8 T cell immunity and antitumor immunity. Using CD11c-GSK-3β conditional knockout mice in which GSK-3β is genetically deleted in CD11c-expressing DCs, we surprisingly found that the deletion of GSK-3β in DCs resulted in increased antitumor immunity, which contradicted our initial expectation of reduced antitumor immunity due to the presumed upregulation of β-catenin in DCs.

RCC1 regulation of subcellular protein localization via Ran GTPase drives pancreatic ductal adenocarcinoma growth.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy, with limited therapeutic options. Here, we evaluated the role of regulator of chromosome condensation 1 (RCC1) in PDAC. RCC1 functions as a guanine exchange factor for GTP-binding nuclear protein Ran (Ran) GTPase and is involved in nucleocytoplasmic transport.

Cellular indexing of transcriptomes and epitopes (CITE-Seq) in hidradenitis suppurativa identifies dysregulated cell types in peripheral blood and facilitates diagnosis via machine learning.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by painful nodules, abscesses, and scarring, predominantly affecting intertriginous regions and it is often underdiagnosed. This study aimed to utilize single cell RNA and cell-surface protein sequencing (CITE-Seq) to delineate the immune composition of circulating cells in Hidradenitis suppurativa (HS) peripheral blood compared to healthy controls. CITE-Seq was used to analyze the gene and protein expression profiles of peripheral blood mononuclear cells (PBMCs) from 9 HS and 29 healthy controls.

American Radium Society Appropriate Use Criteria on Cardiac Toxicity Prevention and Management After Thoracic Radiotherapy.

Introduction: The multidisciplinary American Radium Society Thoracic Committee was assigned to create appropriate use criteria on cardiac toxicity prevention and management for patients undergoing radiotherapy.

Methods: A systematic review of the current literature was conducted. Case variants of patients with thoracic malignancies undergoing radiation were created based on presence or absence of cardiovascular risk factors and treatment-related risks assessed by dose exposure to the heart and cardiac substructures.

Appropriate Use Criteria (AUC) for the Management of Non-Small Cell Lung Cancer in a Central/Ultra-Central Location: Guidelines from the American Radium Society.

Introduction: Definitive radiation therapy is considered standard therapy for medically inoperable early-stage NSCLC. Nevertheless, for patients with tumors located near structures such as the proximal tracheobronchial tree, esophagus, heart, spinal cord, and brachial plexus, the optimal management regimen is controversial. The objective was to develop expert multidisciplinary consensus guidelines on managing medically inoperable NSCLC located in a central or ultracentral location relative to critical organs at risk.

Proceedings of the 1st biannual bridging the gaps in lung cancer conference.

Lung cancer is the leading cause of cancer death in the US and globally. The mortality from lung cancer has been declining, due to a reduction in incidence and advances in treatment. Although recent success in developing targeted and immunotherapies for lung cancer has benefitted patients, it has also expanded the complexity of potential treatment options for health care providers.

Devimistat (CPI-613) With Modified Fluorouarcil, Oxaliplatin, Irinotecan, and Leucovorin (FFX) Versus FFX for Patients With Metastatic Adenocarcinoma of the Pancreas: The Phase III AVENGER 500 Study.

Purpose: Metastatic pancreatic adenocarcinoma (mPC) remains a difficult-to-treat disease. Fluorouarcil, oxaliplatin, irinotecan, and leucovorin (FFX) is a standard first-line therapy for mPC for patients with a favorable performance status and good organ function. In a phase I study, devimistat (CPI-613) in combination with modified FFX (mFFX) was deemed safe and exhibited promising efficacy in mPC.

BRCA Status Dictates Wnt Responsiveness in Epithelial Ovarian Cancer.

Unlabelled: The association of BRCA1 and BRCA2 mutations with increased risk for developing epithelial ovarian cancer is well established. However, the observed clinical differences, particularly the improved therapy response and patient survival in BRCA2-mutant patients, are unexplained. Our objective is to identify molecular pathways that are differentially regulated upon the loss of BRCA1 and BRCA2 functions in ovarian cancer.