The Landscape of Circulating Tumor DNA (ctDNA) in Appendiceal Adenocarcinoma.

Purpose: Appendiceal adenocarcinoma (AA) is a rare malignancy with distinct histopathologic subtypes and a natural history with metastasis primarily limited to the peritoneum. Little is known about the molecular pathogenesis of AA relative to common tumors.

Experimental Design: We analyzed molecular data for patients within the Guardant Health database with appendix cancer (n = 718).

Differential expression of small RNAs in biofilm-producing clinical methicillin-susceptible recovered from human urine.

Bacterial small RNAs (sRNAs) play crucial roles in coordinating gene regulatory networks in various physiological processes, including biofilm formation. In this study, RNA sequencing was performed on biofilm ( = 4) and planktonic ( = 4) cells harvested at 10 h (pre-stationary phase of biofilm development) to identify biofilm-associated sRNAs in human methicillin-susceptible (MSSA) recovered from urine isolate. A total of 56 highly expressed sRNAs were identified with 15 overlapping sRNA genes (srn_9348, sprD, sRNA205, sRNA288, srn_2467, Sau-25, srn_2468, sRNA260, sRNA200, RsaE, sRNA397, Teg55, Teg60, RsaX05 and Teg140).

Molecular, Socioeconomic, and Clinical Factors Affecting Racial and Ethnic Disparities in Colorectal Cancer Survival.

Importance: Disparity in overall survival (OS) and differences in the frequency of driver gene variants by race and ethnicity have been separately observed in patients with colorectal cancer; however, how these differences contribute to survival disparity is unknown.

Objective: To quantify the association of molecular, socioeconomic, and clinical covariates with racial and ethnic disparities in overall survival among patients with colorectal cancer.

Design, Setting, And Participants: This single-center cohort study was conducted at a tertiary-level cancer center using relevant data on all patients diagnosed with colorectal cancer from January 1, 1973, to March 1, 2023.

Genetic variations of penicillin-binding protein 1A: insights into the current status of amoxicillin-based regimens for eradication in Malaysia.

Resistance towards amoxicillin in causes significant therapeutic impasse in healthcare settings worldwide. In Malaysia, the standard treatment regimen includes a 14-day course of high-dose proton-pump inhibitor (rabeprazole, 20 mg) with amoxicillin (1000 mg) dual therapy. The high eradication rate with amoxicillin-based treatment could be attributed to the primary resistance rates of amoxicillin being relatively low at 0%, however, a low rate of secondary resistance has been documented in Malaysia recently.

Serum Tumor Markers and Outcomes in Patients With Appendiceal Adenocarcinoma.

Importance: Serum tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA125) have been useful in the management of gastrointestinal and gynecological cancers; however, there is limited information regarding their utility in patients with appendiceal adenocarcinoma.

Objective: To assess the association of serum tumor markers (CEA, CA19-9, and CA125) with clinical outcomes and pathologic and molecular features in patients with appendiceal adenocarcinoma.

Design, Setting, And Participants: This is a retrospective cohort study at a single tertiary care comprehensive cancer center.

Implementing HLA-B*58:01 testing prior to allopurinol initiation in Malaysian primary care setting: A qualitative study from doctors' and patients' perspective.

Introduction: Allopurinol, the first-line treatment for chronic gout, is a common causative drug for severe cutaneous adverse reactions (SCAR). HLA-B*58:01 allele was strongly associated with allopurinol-induced SCAR in Asian countries such as Taiwan, Japan, Thailand and Malaysia. HLA-B*58:01 screening before allopurinol initiation is conditionally recommended in the Southeast-Asian population, but the uptake of this screening is slow in primary care settings, including Malaysia.

Loss of thymocyte competition underlies the tumor suppressive functions of the E2a transcription factor in T-ALL.

T lymphocyte acute lymphoblastic leukemia (T-ALL) is frequently associated with increased expression of the E protein transcription factor inhibitors TAL1 and LYL1. In mouse models, ectopic expression of TAL1 or LYL1 in T cell progenitors, or inactivation of E2A, is sufficient to predispose mice to develop T-ALL. How E2A suppresses thymocyte transformation is currently unknown.

Sustained Disease Control in Immune Checkpoint Blockade Responders with Microsatellite Instability-high Colorectal Cancer after Treatment Termination.

Unlabelled: Immune checkpoint inhibitors improve survival in patients with mismatch repair deficiency/microsatellite instability-high (MSI-H) colorectal cancer. The recurrence outcomes following discontinuation of immunotherapy after prolonged disease control have not been definitively reported in large series. Records from patients with advanced MSI-H colorectal cancer from The University of Texas - MD Anderson Cancer Center who received immunotherapy between 2014 and 2022 and stopped after prolonged clinical benefit were reviewed.

The Clinical Significance of CEA, CA19-9, and CA125 in Management of Appendiceal Adenocarcinoma.

Importance: Serum tumor markers CEA, CA19-9, & CA125 have been useful in the management of gastrointestinal and gynecological cancers, however there is limited information regarding their utility in patients with appendiceal adenocarcinoma.

Objective: Assessing the association of serum tumor markers (CEA, CA19-9, and CA125) with clinical outcomes, pathologic, and molecular features in patients with appendiceal adenocarcinoma.

Design: This is a retrospective study with results reported in 2023.

TGF-β Promotes the Postselection Thymic Development and Peripheral Function of IFN-γ-Producing Invariant NKT cells.

IFN-γ-producing invariant NKT (iNKT)1 cells are lipid-reactive innate-like lymphocytes that are resident in the thymus and peripheral tissues where they protect against pathogenic infection. The thymic functions of iNKT1 cells are not fully elucidated, but subsets of thymic iNKT cells modulate CD8 T cell, dendritic cell, B cell, and thymic epithelial cell numbers or function. In this study, we show that a subset of murine thymic iNKT1 cells required TGF-β-induced signals for their postselection development, to maintain hallmark TGF-β-induced genes, and for expression of the adhesion receptors CD49a and CD103.

A phase I trial of the pan-ERBB inhibitor neratinib combined with the MEK inhibitor trametinib in patients with advanced cancer with EGFR mutation/amplification, HER2 mutation/amplification, HER3/4 mutation or KRAS mutation.

Purpose: Aberrant alterations of ERBB receptor tyrosine kinases lead to tumorigenesis. Single agent therapy targeting EGFR or HER2 has shown clinical successes, but drug resistance often develops due to aberrant or compensatory mechanisms. Herein, we sought to determine the feasibility and safety of neratinib and trametinib in patients with EGFR mutation/amplification, HER2 mutation/amplification, HER3/4 mutation and KRAS mutation.

Quantitative control of Ets1 dosage by a multi-enhancer hub promotes Th1 cell differentiation and protects from allergic inflammation.

Multi-enhancer hubs are spatial clusters of enhancers present across numerous developmental programs. Here, we studied the functional relevance of these three-dimensional structures in T cell biology. Mathematical modeling identified a highly connected multi-enhancer hub at the Ets1 locus, comprising a noncoding regulatory element that was a hotspot for sequence variation associated with allergic disease in humans.

Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101): First-in-Human Clinical Trial in Patients with Advanced Metastatic Cancer.

IMA101 is an actively personalized, multi-targeted adoptive cell therapy (ACT), whereby autologous T cells are directed against multiple novel defined peptide-HLA (pHLA) cancer targets. HLA-A*02:01-positive patients with relapsed/refractory solid tumors expressing ≥1 of 8 predefined targets underwent leukapheresis. Endogenous T cells specific for up to 4 targets were primed and expanded in vitro.

Loss of thymocyte competition underlies the tumor suppressive functions of the E2a transcription factor in T lymphocyte acute lymphoblastic leukemia.

T lymphocyte acute lymphoblastic leukemia (T-ALL) is frequently associated with increased expression of the E protein transcription factor inhibitors TAL1 and LYL1. In mouse models, ectopic expression of Tal1 or Lyl1 in T cell progenitors or inactivation of E2a, is sufficient to predispose mice to develop T-ALL. How E2a suppresses thymocyte transformation is currently unknown.

The phenotypes and genotypes associated with biofilm formation among methicillin-susceptible Staphylococcus aureus (MSSA) isolates collected from a tertiary hospital in Terengganu, Malaysia.

Methicillin-susceptible Staphylococcus aureus (MSSA) is an important nosocomial pathogen worldwide. This study aims to investigate the in vitro biofilm-forming ability of clinical MSSA isolated from various sources in the main public tertiary referral hospital in Terengganu, Malaysia and to detect the presence of biofilm-associated and regulatory genes among these isolates. A total of 104 MSSA isolates [pus (n = 75), blood (n = 24), respiratory secretions (n = 2), eye (n = 2), and urine (n = 1)] were investigated for slime production and biofilm formation using Congo red agar and crystal violet microtitre plate, respectively.

Survival improvement for patients with metastatic colorectal cancer over twenty years.

Over the past two decades of successive clinical trials in metastatic colorectal cancer (CRC), the median overall survival of both control and experimental arms has steadily improved. However, the incremental change in survival for metastatic CRC patients not treated on trial has not yet been quantified. We performed a retrospective review of 1420 patients with de novo metastatic CRC who received their primary treatment at the University of Texas M.

Bintrafusp alfa, an anti-PD-L1:TGF-β trap fusion protein, in patients with ctDNA-positive, liver-limited metastatic colorectal cancer.

Background: Identification of circulating tumor DNA (ctDNA) following curative intent therapies is a surrogate for microscopic residual disease for patients with metastatic colorectal cancer (mCRC). Preclinically, in micrometastatic microsatellite stable (MSS) CRC, increased TGF-β signaling results in exclusion of anti-tumor cytotoxic T cells from the tumor microenvironment. Bintrafusp alfa (BA) is a bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor ("TGF-β trap") and anti-PD-L1 antibody.

Association of Prediagnosis Obesity and Postdiagnosis Aspirin With Survival From Stage IV Colorectal Cancer.

Importance: The potential relationship between obesity and colorectal cancer (CRC) outcome is poorly understood in patients with late-stage disease. Increased body mass index may negate aspirin use for cancer prevention, but its role as a factor on the effectiveness of postdiagnosis aspirin use is unclear.

Objective: To evaluate how prediagnosis obesity and postdiagnosis aspirin use may be associated with overall survival in patients with late-stage colorectal cancer.

Development of a universal thoracic enhanced recover after surgery protocol for implementation across a diverse multi-hospital health system.

Background: Implementation of enhanced recovery after surgery (ERAS) pathways for patients undergoing anatomic lung resection have been reported at individual institutions. We hypothesized that an ERAS pathway can be successfully implemented across a large healthcare system including different types of hospital settings (academic, academic-affiliated, community).

Methods: An expert panel with representation from each hospital within a healthcare system was convened to establish a thoracic ERAS pathway for patients undergoing anatomic lung resection and to develop tools and analytics to ensure consistent application.

Phase II study of durvalumab (anti-PD-L1) and trametinib (MEKi) in microsatellite stable (MSS) metastatic colorectal cancer (mCRC).

Background: Monotherapy with immune checkpoint blockade is ineffective for patients (pts) with microsatellite stable (MSS) metastatic colorectal cancer (mCRC). This study investigates whether the combination of trametinib (T) with durvalumab (D) can alter the immune tumor microenvironment (TME) by successfully priming and activating T-cells.

Methods: Open-label, single-center, phase II trial with primary endpoint of immune-related response rate for combination of T+D in refractory MSS mCRC pts (NCT03428126).