The pro-tumoral and anti-tumoral roles of EphA4 on T regulatory cells and tumor associated macrophages during HNSCC tumor progression.

Unlabelled: Head and Neck Squamous Cell Carcinoma (HNSCC) is a deadly cancer with poor response to targeted therapy, largely driven by an immunosuppressive tumor microenvironment (TME). Here we examine the immune-modulatory role of the receptor tyrosine kinase EphA4 in HNSCC progression. Within the TME, EphA4 is primarily expressed on regulatory T cells (Tregs) and macrophages.

Health disparities among incarcerated populations: a crucial laboratory and pathology review.

Background: The United States notoriously has one of the highest rates of incarceration in the world, yet scant attention to the health care needs of those incarcerated exists within laboratory medicine and pathology training and education. This article explores health disparities among incarcerated and released individuals regarding diagnostic laboratory testing and pathology services.

Methods: A literature search was conducted for articles published between 2002 and 2023 using keywords including "healthcare," "incarcerated," "laboratory services," "pathology services," and "health insurance for prisoners.

Sensory nerve release of CGRP increases tumor growth in HNSCC by suppressing TILs.

Background: Perineural invasion (PNI) and nerve density within the tumor microenvironment (TME) have long been associated with worse outcomes in head and neck squamous cell carcinoma (HNSCC). This prompted an investigation into how nerves within the tumor microenvironment affect the adaptive immune system and tumor growth.

Methods: We used RNA sequencing analysis of human tumor tissue from a recent HNSCC clinical trial, proteomics of human nerves from HNSCC patients, and syngeneic orthotopic murine models of HPV-unrelated HNSCC to investigate how sensory nerves modulate the adaptive immune system.

Polymorphonuclear myeloid-derived suppressor cells and phosphatidylinositol-3 kinase gamma are critical to tobacco-mimicking oral carcinogenesis in mice.

Background: Oral squamous cell carcinoma (OSCC) is a devastating disease most often associated with tobacco consumption that induces a field of mutations from which a tumor arises. Identification of ways to prevent the emergence of cancer in high-risk patients is an ultimate goal for combatting all types of cancer, including OSCC.

Methods: Our study employs a mouse model of tongue carcinogenesis induced by tobacco carcinogen mimetic, 4-nitroquinoline 1-oxide (4NQO), to establish tongue dysplasia and OSCC.

The next phase in patient safety education: Towards a standardized, tools-based pathology patient safety curriculum: ' .

Patient safety education is a mandated Common Program Requirement of the Accreditation Council for Graduate Medical Education and for the Royal College of Physicians and Surgeons of Canada in all medical residency and fellowship programs. Although many hospitals and healthcare environments have general patient safety education tools for trainees, few to none focus on the unique training milieu of pathologists, including a mix of highly automated and manual error-prone processes, frequent multiplicity of events, and lack of direct patient relationships for error disclosure. We established a national Association of Pathology Chairs-Program Directors Section Workgroup focused on patient safety education for pathology trainees entitled Training Residents in Patient Safety (TRIPS).

Nontuberculous Mycobacterial Infection of Larynx and Cervical Trachea.

Objectives: To present a patient with the first case of NTM (nontuberculous mycobacteria) infection of the larynx extending to cervical trachea, and the first case of subglottic stenosis associated with an NTM infection.

Methods: Case report and review of the literature.

Results: A 68-year-old female with history of prior smoking, gastroesophageal reflux disease, asthma, bronchiectasis, and tracheobronchomalacia presented with a 3-month history of shortness of breath, exertional inspiratory stridor, and hoarseness.

A phase I/Ib trial and biological correlate analysis of neoadjuvant SBRT with single-dose durvalumab in HPV-unrelated locally advanced HNSCC.

Five-year survival for human papilloma virus-unrelated head and neck squamous cell carcinomas remain below 50%. We assessed the safety of administering combination hypofractionated stereotactic body radiation therapy with single-dose durvalumab (anti-PD-L1) neoadjuvantly (n = 21) ( NCT03635164 ). The primary endpoint of the study was safety, which was met.

Occult Malignancy in Adult Tonsillectomy for Benign Indication.

Objective: National pathology guidelines recommend full pathologic analysis for all adult tonsillectomy specimens. We evaluated the available data on occult malignancy in adult tonsillectomy for benign indication, and created a screening system to reduce the risk of missed malignancies if routine histopathologic examination were to be discontinued.

Study Design: Retrospective chart review and systematic review of the literature.

Matrix metalloproteinases cleave membrane-bound PD-L1 on CD90+ (myo-)fibroblasts in Crohn's disease and regulate Th1/Th17 cell responses.

Increased T helper (Th)1/Th17 immune responses are a hallmark of Crohn's disease (CD) immunopathogenesis. CD90+ (myo-)fibroblasts (MFs) are abundant cells in the normal (N) intestinal mucosa contributing to mucosal tolerance via suppression of Th1 cell activity through cell surface membrane-bound PD-L1 (mPD-L1). CD-MFs have a decreased level of mPD-L1.

Expression of Programmed Death-Ligand 1 by Human Colonic CD90 Stromal Cells Differs Between Ulcerative Colitis and Crohn's Disease and Determines Their Capacity to Suppress Th1 Cells.

Background And Aims: The role of programmed cell death protein 1 (PD-1) and its ligands in the dysregulation of T helper immune responses observed in the inflammatory bowel disease (IBD) is unclear. Recently, a novel concept emerged that CD90 colonic (myo)fibroblasts (CMFs), also known as stromal cells, act as immunosuppressors, and are among the key regulators of acute and chronic inflammation. The objective of this study was to determine if the level of the PD-1 ligands is changed in the IBD inflamed colonic mucosa and to test the hypothesis that changes in IBD-CMF-mediated PD-1 ligand-linked immunosuppression is a mechanism promoting the dysregulation of Th1 cell responses.

Pancreatic neuroendocrine tumor in a patient with a TSC1 variant: case report and review of the literature.

The majority of pancreatic neuroendocrine tumors (PNETs) are sporadic while 10-15% are attributable to one of several familial cancer syndromes. Hereditary forms are more commonly associated with Multiple Endocrine Neoplasia Type I and von Hippel Lindau Syndrome. However, patients with Tuberous sclerosis complex also have an increased incidence of PNETs.

Altered protein levels in the isolated extracellular matrix of failing human hearts with dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is associated with extensive pathological cardiac remodeling and involves numerous changes in the protein expression profile of the extracellular matrix of the heart. We obtained seven human, end-stage, failing hearts with DCM (DCM-failing) and nine human, nonfailing donor hearts and compared their extracellular matrix protein profiles. We first showed that the DCM-failing hearts had indeed undergone extensive remodeling of the left ventricle myocardium relative to nonfailing hearts.

Blockade of MK2 is protective in inflammation-associated colorectal cancer development.

Chronic inflammation is a risk factor for colorectal cancer. The MAPK-activated protein kinase 2 (MK2) pathway controls multiple cellular processes including p38-dependent inflammation. This is the first study to investigate the role of MK2 in development of colitis-associated colon cancer (CAC).

Anti-G-CSF treatment induces protective tumor immunity in mouse colon cancer by promoting protective NK cell, macrophage and T cell responses.

Granulocyte colony-stimulating factor (G-CSF) is a cytokine that is highly expressed in human and mouse colorectal cancers (CRC). We previously reported that G-CSF stimulated human CRC cell growth and migration, therefore in this study we sought to examine the therapeutic potential of anti-G-CSF treatment for CRC. G-CSF is known to mobilize neutrophils, however its impact on other immune cells has not been well examined.

Metastatic peritoneal mesothelioma in the setting of recurrent ascites: a case report.

Malignant peritoneal mesothelioma is uncommon but rapidly fatal with a median survival of less than 1 year. The diagnosis of this entity is often delayed because of the nonspecific presenting symptoms and nonspecific cytological features of the mesothelial cells in the peritoneal fluids. A 72-year-old man who had no known history of exposure to asbestos and had longstanding refractory ascites thought to be secondary to alcoholic cirrhosis was found to have widespread metastatic malignant mesothelioma involving the lung, liver, pancreas, peritoneal, and pelvic wall, skin and subcutaneous tissue.

Soy isoflavones exert differential effects on androgen responsive genes in LNCaP human prostate cancer cells.

The high consumption of soy isoflavones in Asian diets has been correlated to a lower incidence of clinically important cases of prostate cancer. This study characterized the effects of a soy-derived isoflavone concentrate (ISF) on growth and gene expression profiles in the LNCaP, an androgen-sensitive human prostate cancer cell line. ISF caused a dose-dependent decrease in viability (P < 0.