Galectin-3 secreted by triple-negative breast cancer cells regulates T cell function.

Triple-negative breast cancer (TNBC) is an aggressive subtype that accounts for 10-15 % of breast cancer. Current treatment of high-risk early-stage TNBC includes neoadjuvant chemo-immune therapy. However, the substantial variation in immune response prompts an urgent need for new immune-targeting agents.

TNBC-derived Gal3BP/Gal3 complex induces immunosuppression through CD45 receptor.

A preliminary study investigating immunotherapy strategies for aggressive triple negative breast cancer (TNBC) revealed an overexpression of genes involved in the release of extracellular vesicles (EVs). Proteins expressed by EVs play a role in reprogramming the tumor microenvironment and impeding effective responses to immunotherapy. Galectin 3 (Gal3), found in the extracellular space of breast cancer cells, downregulates T-cell receptor expression.

Caregiver Perspectives on Pain Sensitivity and Pain Experience in Rett Syndrome.

Background: Although delayed or decreased responses to pain are commonly reported among caregivers of individuals with Rett syndrome (RTT), previous studies in relatively small samples have documented that caregivers are concerned about pain, particularly due to gastrointestinal and musculoskeletal conditions.

Aims: The purpose of the current study was to investigate in detail caregivers' perceptions of pain sensitivity, as well as the types, severity, and effect of pain experienced by individuals with RTT in a larger sample than previous studies.

Methods: A total of 51 caregivers (mostly mothers) participated in the study, which involved standardized questionnaires and interviews.

Comparison of efficacy and frequency of akathisia and dystonia between olanzapine, metoclopramide and prochlorperazine in ED headache patients.

Study Objective: To compare the efficacy and frequency of akathisia and dystonia between the dopamine antagonist headache medications olanzapine, metoclopramide and prochlorperazine.

Methods: This was a retrospective observational cohort study of patients presenting to a large urban level one trauma center between 2010 and 2018. Inclusion criteria was age ≥ 18 who presented to the emergency department with a chief complaint of headache who received either olanzapine, metoclopramide or prochlorperazine.

BNT162b2 Booster Vaccination Induced Immunity against SARS-CoV-2 Variants among Hemodialysis Patients.

The emergence of new SARS-CoV-2 variants, which evade immunity, has raised the urgent need for multiple vaccine booster doses for vulnerable populations. In this study, we aimed to estimate the BNT162b2 booster effectiveness against the spread of coronavirus variants in a hemodialysis population. We compared humoral and cell-mediated immunity in 100 dialysis patients and 66 age-matched volunteers, before and 2-3 weeks following the first booster vaccine dose.

Downregulation of CD45 Signaling in COVID-19 Patients Is Reversed by C24D, a Novel CD45 Targeting Peptide.

CD45, the predominant transmembrane tyrosine phosphatase in leukocytes, is required for the efficient induction of T cell receptor signaling and activation. We recently reported that the CD45-intracellular signals in peripheral blood mononuclear cells (PBMCs) of triple negative breast cancer (TNBC) patients are inhibited. We also reported that C24D, an immune modulating therapeutic peptide, binds to CD45 on immune-suppressed cells and resets the functionality of the immune system via the CD45 signaling pathway.

On the Track of New Endoscopic Alternatives for the Treatment of Selected Gastric GISTs-A Pilot Study.

: GISTs (Gastrointestinal stromal tumors) are the most common mesenchymal gastrointestinal tract tumours and are mainly located in the stomach. Their malignant potential depends on size, location, and type. Endoscopic techniques are a less invasive modality for patients not eligible for surgery.

A novel role for an old target: CD45 for breast cancer immunotherapy.

Breast cancer subtypes have not shown significant response to current immunomodulatory therapies. Although most subtypes are treatable, triple negative breast cancer (TNBC), an aggressive highly metastatic cancer, comprising 10-20% of breast cancers, remains an unmet medical need. New strategies are needed in order to overcome flaws in the responsiveness to current TNBC therapies.

Caregiver-Reported Pain Management Practices for Individuals With Cerebral Palsy.

Objective: To investigate types and intensity of pain experienced by individuals with cerebral palsy (CP) and common pain-relieving approaches used by caregivers.

Design: The approach was cross-sectional, using standardized interviews.

Setting: Individuals with CP were recruited from a specialty health care hospital.

The Effect of Depression and Rurality on Diabetes Control.

Background: Having depression and living in a rural environment have separately been associated with poor diabetes outcomes, but there little is known about the interaction between the 2 risk factors. This study investigates the association of depression and rurality with glycemic control in adults, as well as their interaction.

Methods: This is a repeated cross-sectional study with data collected from 2010 to 2017 (n = 1,697,173 patient-year observations), comprising a near-complete census of patients with diabetes in Minnesota.

Chemotherapy Controls Metastasis Through Stimulatory Effects on GRP78 and Its Transcription Factor CREB3L1.

To achieve a cure for metastatic breast cancer, further understanding of molecular drivers of the metastatic cascade is essential. Currently, chemotherapy regimens include doxorubicin and paclitaxel which act in part by inducing the unfolded protein response (UPR). The master regulator of the UPR, glucose regulated protein 78 (GRP78), localizes on the surface of tumor cells and is associated with metastatic disease.

Optimal Endoscopic Resection Technique for Selected Gastric GISTs. The Endoscopic Suturing System Combined with ESD-a New Alternative?

In terms of therapeutic management, gastrointestinal stromal tumors (GISTs) seem to be the most difficult group of subepithelial gastrointestinal lesions (SELs). Despite various treatment option, choice of optimal management remains a dilemma in daily practice. Our aim was to evaluate a new hybrid resection technique of gastric GISTs type III as a modality of endoscopic full-thickness resection.

GRP78 expression in peripheral blood mononuclear cells is a new predictive marker for the benefit of taxanes in breast cancer neoadjuvant treatment.

Background: Breast cancer treatment is tailored to the specific cancer subtype. Often, systemic treatment is given prior to surgery. Chemotherapy induces significant endoplasmic reticulum (ER) stress-mediated cell death and upregulation of 78-kDa glucose-regulated protein (GRP78).

Characterization of Cellular Sources and Circulating Levels of Extracellular Vesicles in a Dietary Murine Model of Nonalcoholic Steatohepatitis.

Circulating extracellular vesicles (EVs) are a novel and emerging biomarker for nonalcoholic steatohepatitis (NASH). It has been demonstrated that total circulating EVs and hepatocyte-derived EVs are elevated in male mice with diet-induced NASH. How hepatocyte-derived EVs change over time and other cellular sources of EVs in NASH have not been determined.

Peptide Binding Glucose Regulated Protein 78 Improves Type 1 Diabetes by Preventing Pancreatic β Cell Apoptosis.

Background And Objectives: Diabetes Type 1 is characterized by hyperglycemia due to reduced insulin secretion that results from the death of pancreatic β cells. It was suggested that endoplasmic reticulum (ER) stress is associated with the autoimmune-mediated β cell destruction. Glucose regulated protein 78 (GRP78) functions as a key regulator to maintain the ER function.

Cell surface GRP78: A potential marker of good prognosis and response to chemotherapy in breast cancer.

The 78-kDa glucose-regulated protein (GRP78) is a stress induced heat shock protein which, under limiting conditions, functions as a cell surface signaling receptor. Tumor cells are considered to be subjected to a physiologically stressful microenvironment due to their excessive growth. The role of GRP78 in tumor survival has been of notable interest.

Pharmacological induction of cell surface GRP78 contributes to apoptosis in triple negative breast cancer cells.

Breast cancer tumor with triple-negative receptors (estrogen, progesterone and Her 2, receptors) is the most aggressive and deadly subtype, with high rates of disease recurrence and poor survival. Here, we show that induction in cell surface GRP78 by doxorubicin and tunicamycin was associated with CHOP/GADD153 upregulation and increase in apoptosis in triple negative breast cancer tumor cells. GRP78 is a major regulator of the stress induced unfolded protein response pathway and CHOP/GADD153 is a pro-apoptotic transcription factor associated exclusively with stress induced apoptosis.

The presence of anti-GRP78 antibodies in the serum of patients with colorectal carcinoma: a potential biomarker for early cancer detection.

Background: The identification of new biomarkers is required for early diagnosis of colorectal carcinoma patients (CRC), since about 20% of these patients are initially diagnosed with a distant metastatic disease. GRP78, a heat shock protein, functions also as a cell surface signaling receptor of cells under physiological stress. GRP78 was found to be expressed on the cell surface of various tumor cells.

Colon cancer cells expressing cell surface GRP78 as a marker for reduced tumorigenicity.

Background: The glucose regulated heat shock protein 78 (GRP78) is a central regulator of ER (endoplasmic reticulum) stress due to its pro-survival property. Up regulated GRP78 expression in tumor cells has been correlated with aggressive malignancies whereas some reports have predicted an improved prognosis. Over-expression of GRP78 in the ER promotes its localization to the cell surface on several cell types including tumor cells.

Peptide-binding GRP78 protects neurons from hypoxia-induced apoptosis.

Brain ischemia has major consequences leading to the apoptosis of astrocytes and neurons. Glucose-regulated protein 78 (GRP78) known for its role in endoplasmic reticulum stress alleviation was discovered on several cell surfaces acting as a receptor for signaling pathways. We have previously described peptides that bind cell surface GRP78 on endothelial cells to induce angiogenesis.

Endothelial cell surface vimentin binding peptide induces angiogenesis under hypoxic/ischemic conditions.

We have previously identified several angiogenic peptides that bind cell surface proteins by screening a phage display peptide library on human umbilical endothelial cells exposed to hypoxic conditions. In this study we describe one of the selected peptides, SP. We found by protein precipitation of endothelial cell lysates that the 12 amino acid SP peptide binds cell surface vimentin.