Loss of STIM2, but not of STIM1, drives colorectal cancer metastasis through metabolic reprogramming and the ATF4 ER stress pathway.

The large amounts of calcium (Ca) stored in the endoplasmic reticulum (ER) and the controlled release of this Ca store into the cytosol regulate many cellular functions, and altered ER Ca homeostasis induces ER stress. Stromal-interacting molecules 1 and 2 (STIM1/2) are homologous ER-resident Ca sensors that synergistically activate cytosolic Ca influx through Orai channels to promote Ca-dependent changes in gene expression and ER Ca refilling. Here, we demonstrated that reduced abundance of STIM2, but not that of STIM1, was associated with poor prognosis in colorectal cancer (CRC).

Current challenges and potential opportunities for interception and prevention of head and neck cancer.

Globally, the incidence of head and neck squamous cell carcinoma (HNSCC) has increased over recent decades and is projected to continue to rise, largely driven by increases in oropharyngeal squamous cell carcinoma (OPSCC), which is linked to HPV infection. HPV infection is also involved in the development of other cancers (anogenital and cervical), and almost 100% of cervical cancer patients are positive for HPV. OPSCC is the most common HPV-associated cancer in men and has exceeded the incidence of cervical cancer cases in women in the USA.

Differential hepatic activation of mouse and human peroxisome proliferator-activated receptor-α by perfluorohexane sulfonate.

Exposure of perfluorohexane sulfonate (PFHxS) is associated with hepatomegaly and accumulation of lipids that may be mediated by nuclear receptors like peroxisome proliferator-activated receptor-α (PPARα), constitutive androstane receptor (CAR), or pregnane X receptor (PXR). This study tested the hypotheses that: (i) PFHxS causes changes in liver by activating PPARα, CAR, or PXR, and (ii) there is a species difference in PPARα activity by PFHxS. Wild-type, Ppara-null, and PPARA-humanized mice were fed either a control diet, or one containing 2.

Interferon-γ/Janus Kinase 1/STAT1 Signaling Represses Forkhead Box A1 and Drives a Basal Transcriptional State in Muscle-Invasive Bladder Cancer.

During progression, luminal muscle-invasive bladder cancer (MIBC) can transition to the aggressive basal-squamous (Ba/Sq) subtype. Reduced expression of forkhead box A1 (FOXA1) in the urothelium is a hallmark and driver of the Ba/Sq transcriptional state and squamous differentiation. Ba/Sq tumors are highly inflamed; however, the specific inflammatory pathways contributing to the Ba/Sq state are unknown.

Impact of SCN10A Polymorphism on Abdominal Pain Perception and Visceral Hypoalgesia in Crohn's Disease and Ulcerative Colitis.

Introduction: Hypoalgesic inflammatory bowel disease (IBD) may provide critical insights into human abdominal pain. This condition was previously associated with homozygosity for a polymorphism (rs6795970, A1073V; 1073 val/val ) related to Na v 1.8, a voltage-gated sodium channel preferentially expressed on nociceptors.

Clinical characterization of the silent chronic pancreatitis patient: a single-center retrospective cohort study.

Background: Silent chronic pancreatitis (SCP) is a poorly understood subtype of chronic pancreatitis (CP) in which individuals describe little to no abdominal pain. The risk factors for SCP are unclear, and it is unknown whether there are differences in the clinical outcomes of SCP and painful CP. We set out to investigate the clinical features of SCP and the risk factors associated with this condition.

Drp1 splice variants regulate ovarian cancer mitochondrial dynamics and tumor progression.

Aberrant mitochondrial fission/fusion dynamics are frequently associated with pathologies, including cancer. We show that alternative splice variants of the fission protein Drp1 (DNM1L) contribute to the complexity of mitochondrial fission/fusion regulation in tumor cells. High tumor expression of the Drp1 alternative splice variant lacking exon 16 relative to other transcripts is associated with poor outcome in ovarian cancer patients.

Targeting Tyro3, Axl, and MerTK Receptor Tyrosine Kinases Significantly Sensitizes Triple-Negative Breast Cancer to CDK4/6 Inhibition.

Triple-negative breast cancer (TNBC) is the most aggressive subtype with high metastasis and mortality rates. Given the lack of actionable targets such as ER and HER2, TNBC still remains an unmet therapeutic challenge. Despite harboring high CDK4/6 expression levels, the efficacy of CDK4/6 inhibition in TNBC has been limited due to the emergence of resistance.

Association of medical comorbidities in obese subjects diagnosed with heparin-induced thrombocytopenia.

Objectives: Heparin-induced thrombocytopenia can occur in obese subjects. The medical comorbidities associated with obesity may contribute to the pathogenesis of this disease. It is unknown, however, which specific medical comorbidities and if higher odds of thrombosis are present in obese heparin-induced thrombocytopenia patients.

Acute kidney injury in hospitalized children with proteinuria: A multicenter retrospective analysis.

Background And Objective: Acute kidney injury (AKI) is a common complication in hospitalized pediatric patients. Previous studies focused on adults found that proteinuria detected during an admission urinalysis is fit to serve as an indicator for AKI and associated clinical outcomes. The objective of this study is to evaluate if proteinuria on the first day of hospital services in hospitalized children is associated with AKI, need for renal replacement therapy, shock and/or antibiotic use, critical care services, and all-cause mortality at 30 days, hypothesizing that it is associated with these outcomes.

Immune Responses in Oral Papillomavirus Clearance in the MmuPV1 Mouse Model.

Human papillomavirus (HPV)-induced oropharyngeal cancer now exceeds HPV-induced cervical cancer, with a noticeable sex bias. Although it is well established that women have a more proficient immune system, it remains unclear whether immune control of oral papillomavirus infections differs between sexes. In the current study, we use genetically modified mice to target CCR2 and Stat1 pathways, with the aim of investigating the role of both innate and adaptive immune responses in clearing oral papillomavirus, using our established papillomavirus (MmuPV1) infection model.

Lifestyle Factors and Silent Inflammatory Bowel Disease.

Introduction: Hypoalgesic or silent inflammatory bowel disease (IBD) is a poorly understood condition that has been associated with poor clinical outcomes. There is evidence that lifestyle factors, including diet, exercise, and substance use can influence inflammatory activity and symptoms in IBD. It is unclear, though, whether these issues impact pain experience in IBD.

Polysubstance use in inflammatory bowel disease is associated with increased risk of emergency department visits: a longitudinal study.

Background: Polysubstance use (PSU), the simultaneous use of 2 or more substances of abuse, is common in inflammatory bowel disease (IBD). Preliminary studies suggest it may be associated with poor outcomes. This prospective study evaluated the impact of PSU on disease activity and healthcare resource utilization in IBD.

27-year trends in incidence rates for testis cancer across a large statewide registry.

Purpose: To review 27-years of testicular cancer (TC) incidence data (1990-2017) within the state of Pennsylvania to better define incidence, geographic distribution, and trends over time.

Methods: The Pennsylvania Cancer Registry was reviewed for statewide and component county age-adjusted TC incidence rates and stage distribution. We reported annual percent changes (APCs) in age-adjusted rates.

Loss of STIM2 in colorectal cancer drives growth and metastasis through metabolic reprogramming and PERK-ATF4 endoplasmic reticulum stress pathway.

The endoplasmic reticulum (ER) stores large amounts of calcium (Ca), and the controlled release of ER Ca regulates a myriad of cellular functions. Although altered ER Ca homeostasis is known to induce ER stress, the mechanisms by which ER Ca imbalance activate ER stress pathways are poorly understood. Stromal-interacting molecules STIM1 and STIM2 are two structurally homologous ER-resident Ca sensors that synergistically regulate Ca influx into the cytosol through Orai Ca channels for subsequent signaling to transcription and ER Ca refilling.

Global role of IGF2BP1 in controlling the expression of Wnt/β-catenin-regulated genes in colorectal cancer cells.

Wnt/β-catenin signaling controls cell division and lineage specification during embryonic development, and is crucial for stem cells maintenance and gut tissue regeneration in adults. Aberrant activation of Wnt/β-catenin signaling is also essential for the pathogenesis of a variety of malignancies. The RNA-binding protein IGF2BP1 is a transcriptional target of Wnt/β-catenin signaling, normally expressed during development and often reactivated in cancer cells, where it regulates the stability of oncogenic mRNA.

Sexually dimorphic effect of H-ferritin genetic manipulation on survival and tumor microenvironment in a mouse model of glioblastoma.

Purpose: Iron plays a crucial role in various biological mechanisms and has been found to promote tumor growth. Recent research has shown that the H-ferritin (FTH1) protein, traditionally recognized as an essential iron storage protein, can transport iron to GBM cancer stem cells, reducing their invasion activity. Moreover, the binding of extracellular FTH1 to human GBM tissues, and brain iron delivery in general, has been found to have a sex bias.

Alternative splice variants of the mitochondrial fission protein /Drp1 regulate mitochondrial dynamics and tumor progression in ovarian cancer.

Aberrant mitochondrial fission/fusion dynamics have been reported in cancer cells. While post translational modifications are known regulators of the mitochondrial fission/fusion machinery, we show that alternative splice variants of the fission protein Drp1 () have specific and unique roles in cancer, adding to the complexity of mitochondrial fission/fusion regulation in tumor cells. Ovarian cancer specimens express an alternative splice transcript variant of Drp1 lacking exon 16 of the variable domain, and high expression of this splice variant relative to other transcripts is associated with poor patient outcome.

Lifestyle Factors Associated with Abdominal Pain in Quiescent Inflammatory Bowel Disease.

Background: Lifestyle factors, including diet, exercise, substance use, and sexual activity, have been shown to influence risk of inflammation and complications in inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Little is known about their potential role in abdominal pain generation in IBD.

Aims: We performed this study to evaluate for relationships between lifestyle factors and abdominal pain in quiescent IBD (QP-IBD).

Abdominal pain is associated with an increased risk of future healthcare resource utilization in inflammatory bowel disease.

Background: Numerous factors influence healthcare resource utilization (HRU) in inflammatory bowel disease (IBD). We previously demonstrated an association between the presence of certain IBD-related symptoms and HRU. We conducted a longitudinal study to identify the clinical variables and IBD-related symptoms predictive of HRU.

Urothelium-Specific Expression of Mutationally Activated Pik3ca Initiates Early Lesions of Noninvasive Bladder Cancer.

Although approximately 70% of bladder cancers are noninvasive and have high recurrence rates, early-stage disease is understudied. The lack of models to validate the contribution of molecular drivers of bladder tumorigenesis is a significant issue. Although mutations in PIK3CA are frequent in human bladder cancer, an in vivo model for understanding their contribution to bladder tumorigenesis is unavailable.

Odds of Cardiometabolic Diseases and Medications in Children With Cerebral Palsy.

Introduction/objectives: Individuals with cerebral palsy may be at risk of obesity, but outcomes and risk factors are understudied. The study objectives are to evaluate the frequency of body mass index (BMI) weight categories of individuals with cerebral palsy and the odds of cardiometabolic-specific diseases and medications. We hypothesize subjects with cerebral palsy and an increased body mass index will have higher odds of cardiometabolic specific diseases and medications.

Potential Early Markers for Breast Cancer: A Proteomic Approach Comparing Saliva and Serum Samples in a Pilot Study.

Breast cancer is the second leading cause of death for women in the United States, and early detection could offer patients the opportunity to receive early intervention. The current methods of diagnosis rely on mammograms and have relatively high rates of false positivity, causing anxiety in patients. We sought to identify protein markers in saliva and serum for early detection of breast cancer.