Association Between Antibodies That Bind Epstein-Barr Virus (EBV) gp350 and gH/gL and Shedding of EBV in Saliva From Nasopharyngeal Carcinoma Multiplex Family Members in Taiwan.

Elevated levels of Epstein-Barr virus (EBV) gp350 and gH/gL antibodies have been associated with a lower risk of developing nasopharyngeal carcinoma (NPC), although the evidence remains inconclusive and unexplained. We conducted a longitudinal study within a high-risk Taiwanese cohort, analyzing total immunoglobulin against EBV-gp350 and -gH/gL in blood and EBV DNA shedding in saliva. Contrary to our hypothesis-that elevated levels of antibodies previously shown to be associated with a lower NPC risk should result in a decrease in EBV shedding in saliva-higher anti-gp350 antibodies at baseline were significantly associated with detectable EBV DNA in saliva at follow-up (odds ratio [OR], 1.

NANO-LM: An updated scorecard for the clinical assessment of patients with leptomeningeal metastases.

Background: There are no validated tools for the clinical neurological assessment of patients with leptomeningeal metastases (LM). However, clinical examination during the course of the disease guides medical management and is part of response assessment in clinical trials. Because neuroimaging may not always be obtained owing to rapid clinical deterioration, clinical neurological assessment of LM is essential, and standardization Is important to minimize rater disagreement.

DrugFormer: Graph-Enhanced Language Model to Predict Drug Sensitivity.

Drug resistance poses a crucial challenge in healthcare, with response rates to chemotherapy and targeted therapy remaining low. Individual patient's resistance is exacerbated by the intricate heterogeneity of tumor cells, presenting significant obstacles to effective treatment. To address this challenge, DrugFormer, a novel graph-augmented large language model designed to predict drug resistance at single-cell level is proposed.

Worse Wilms' Tumor Outcomes Associated With Chemical Complementarity for Multiple T-Cell Receptor CDR3-CMV Epitope Pairs.

Background/aim: Wilms' tumors are pediatric renal tumors that generally have a good prognosis and outcomes. Viral illnesses have been linked to development of neoplasms and should be considered as a factor that could modulate overall survival.

Materials And Methods: We considered recently developed adaptive immune receptor, genomics and bioinformatics approaches to assess the potential impact of cytomegalovirus (CMV) infections in Wilms' tumor.

Adaptive Immune Receptor Distinctions Along the Colorectal Polyp-Tumor Timelapse.

Introduction: Colorectal cancer (CRC) is the third-most common cancer diagnosed worldwide, with 1.85 million new cases per year. While mortality has significantly decreased due to preventive colonoscopy, only 5% of polyps identified progress to cancer.

Structural basis for FN3K-mediated protein deglycation.

Protein glycation is a universal, non-enzymatic modification that occurs when a sugar covalently attaches to a primary amine. These spontaneous modifications may have deleterious or regulatory effects on protein function, and their removal is mediated by the conserved metabolic kinase fructosamine-3-kinase (FN3K). Despite its crucial role in protein repair, we currently have a poor understanding of how FN3K engages or phosphorylates its substrates.

Phase I/II trial of plinabulin in combination with nivolumab and ipilimumab in patients with recurrent small cell lung cancer (SCLC): Big ten cancer research consortium (BTCRC-LUN17-127) study.

Background: Plinabulin is a GEF-H1 releasing agent with an immune-enhancing function. We report results from a multicenter Phase I/II study (NCT03575793) assessing plinabulin in combination with nivolumab and ipilimumab for the treatment of recurrent SCLC.

Methods: In Phase I, patients were enrolled using a 3 + 3 design to determine dose-limiting toxicities (DLTs) and recommended Phase 2 dose (RP2D).

Urachal and Nonurachal Adenocarcinomas of the Urinary Bladder: A Comprehensive Genomic Profiling Study.

Purpose: Although both urachal (U) and nonurachal (NU) bladder adenocarcinomas (adenoCas) share several histologic similarities, they differ in location and sometimes in therapeutic options. We analyzed the differences in genomic alterations (GAs) between these tumor entities, with the aim of identifying potential therapeutic targets for clinical trials.

Materials And Methods: Overall, 133 U and 328 NU adenoCas were analyzed.

Strain-release driven reactivity of a chiral SuFEx reagent provides stereocontrolled access to sulfinamides, sulfonimidamides, and sulfoximines.

Efforts aimed at enriching the chemical and structural diversity of small molecules have invigorated synthetic exploration in the last two decades. Spatially defined molecular functionality serves as the foundation to construct unique chemical space to further advance discovery science. The chiral SuFEx reagent t-BuSF provides a modular platform for the stereocontrolled bifunctionalization of sulfur.

Amplification of autoimmune organ damage by NKp46-activated ILC1s.

In systemic lupus erythematosus, loss of immune tolerance, autoantibody production and immune complex deposition are required but not sufficient for organ damage. How inflammatory signals are initiated and amplified in the setting of autoimmunity remains elusive. Here we set out to dissect layers and hierarchies of autoimmune kidney inflammation to identify tissue-specific cellular hubs that amplify autoinflammatory responses.

Macrophage-mediated myelin recycling fuels brain cancer malignancy.

Tumors growing in metabolically challenged environments, such as glioblastoma in the brain, are particularly reliant on crosstalk with their tumor microenvironment (TME) to satisfy their high energetic needs. To study the intricacies of this metabolic interplay, we interrogated the heterogeneity of the glioblastoma TME using single-cell and multi-omics analyses and identified metabolically rewired tumor-associated macrophage (TAM) subpopulations with pro-tumorigenic properties. These TAM subsets, termed lipid-laden macrophages (LLMs) to reflect their cholesterol accumulation, are epigenetically rewired, display immunosuppressive features, and are enriched in the aggressive mesenchymal glioblastoma subtype.

MANCR lncRNA Modulates Cell-Cycle Progression and Metastasis by Cis-Regulation of Nuclear .

A significant number of the genetic alterations observed in cancer patients lie within nonprotein-coding segments of the genome, including regions coding for long noncoding RNAs (lncRNAs). LncRNAs display aberrant expression in breast cancer (BrCa), but the functional implications of this altered expression remain to be elucidated. By performing transcriptome screen in a triple negative BrCa (TNBC) isogenic 2D and 3D spheroid model, we observed aberrant expression of >1000 lncRNAs during BrCa progression.

T-cell Responses to Individualized Neoantigen Therapy mRNA-4157 (V940) Alone or in Combination with Pembrolizumab in the Phase 1 KEYNOTE-603 Study.

mRNA-4157 (V940) is an individualized neoantigen therapy targeting up to 34 patient-specific tumor neoantigens to induce T-cell responses and potentiate antitumor activity. We report mechanistic insights into the immunogenicity of mRNA-4157 via characterization of T-cell responses to neoantigens from the first-in-human, phase 1, KEYNOTE-603 study (NCT03313778) in patients with resected non-small cell lung cancer (Part A: 1-mg mRNA-4157, n = 4) or resected cutaneous melanoma (Part D: 1-mg mRNA-4157 + 200-mg pembrolizumab, n = 12). Safety, tolerability, and immunogenicity were assessed.

Mechanism and rational combinations with GP-2250, a novel oxathiazine derivative, in ovarian cancer.

Background: GP-2250, a novel analog of taurultam (TRLT), has emerged as a potent anti-neoplastic drug; however, the mechanisms underlying its effects are not well understood. Here, we investigated the mechanism of action and the biological effects of GP-2250 using in vitro and in vivo models.

Methods: We carried out a series of in vitro (MTT assay, Annexin V/PI assay, colony formation assay, reverse-phase protein array [RPPA], and HRLC/IC analysis) to determine the biological activity of GP-2250 and investigate the mechanism of action.

Concurrent substance use among cancer patients with and without a history of cannabis use since cancer diagnosis at an NCI-Designated Cancer Center in Florida.

Background: Although substance use may have adverse impacts on cancer outcomes, little is known regarding patterns of concurrent substance use with cannabis among cancer patients. Our objective was to examine predictors of concurrent substance use with cannabis among cancer patients since their cancer diagnosis and explore perceptions of cannabis among these patients.

Methods: Patients treated at a National Cancer Institute-designated comprehensive cancer center were invited to participate in an electronic survey regarding medical cannabis from August to November 2021.

Management of gastrointestinal stromal tumor and acute appendicitis during pregnancy: A case report.

Gastrointestinal stromal tumors (GISTs) are neoplasms of neural cells in the gastrointestinal tract; they typically develop in older adults, with less than 10% of cases presenting among patients under the age of 40. This report describes the clinical course and management of a 28-year-old woman with a history of irritable bowel syndrome (IBS) who presented with acute upper abdominal pain. Surgical pathology confirmed a diagnosis of metastatic GIST.

Lower Weight-Based Mycophenolate Mofetil Dosing is Associated with Superior Outcomes after Haploidentical Hematopoietic Cell Transplant with Post-transplant Cyclophosphamide.

Mycophenolate mofetil (MMF) is commonly included in post-transplant cyclophosphamide (PTCy) based graft-versus-host disease (GVHD) prophylaxis after haploidentical (haplo) hematopoietic cell transplant (HCT). In the non-PTCy setting, higher MMF dose/kg has been shown to reduce rates of acute graft-versus-host disease (GVHD). When used in conjunction with PTCy, MMF is dosed at 15 mg/kg three times daily up to a maximum dose of 3 g/day.

Chemical complementarity of tumor resident, T-cell receptor CDR3s and renalase-1 correlates with increased melanoma survival.

Overexpression of the secretory protein renalase-1 negatively impacts the survival of melanoma and pancreatic cancer patients, while inhibition of renalase-1 signaling drives tumor rejection by promoting T-cell activation. Thus, we investigated the chemical complementarity between melanoma-resident, T-cell receptor (TCR) complementarity-determining region 3 (CDR3) amino acid sequences (AAs) and the renalase-1 protein. Increasing complementarity of TCR CDR3s to renalase-1 AAs, as assessed by a chemical complementarity scoring algorithm, was associated with improved overall survival (OS) in melanoma patients.

Structural Racism Conceptualization and Operationalization for Research for the U.S. HIV Epidemic: Findings from a Scoping Review and Implications for Advancing Research for Structural Interventions.

In the U.S., inequities by race/ethnicity in health outcomes, such as in the HIV epidemic, are long standing but have come to the forefront during the COVID-19 pandemic.

Sacituzumab Govitecan Demonstrates Efficacy across Tumor Trop-2 Expression Levels in Patients with Advanced Urothelial Cancer.

Purpose: Human trophoblast cell surface antigen 2 (Trop-2) is a protein highly expressed in urothelial cancer (UC). Sacituzumab govitecan (SG) is a Trop-2-directed antibody drug conjugate with a hydrolysable linker and a potent SN-38 payload. This study explored Trop-2 expression in tumors treated with SG in cohorts 1 to 3 (C1-3) from the TROPHY-U-01 study and evaluated whether efficacy was associated with Trop-2 expression.