Letetresgene Autoleucel in Advanced/Metastatic Myxoid/Round Cell Liposarcoma.

Purpose: The cancer/testis antigen New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a promising target in myxoid/round cell liposarcoma (MRCLS).

Methods: In this pilot study, we assessed the adoptive T-cell therapy NY-ESO-1cT letetresgene autoleucel (lete-cel) in patients with human leukocyte antigen (HLA)-A*02:01-, HLA-A*02:05-, and/or HLA-A*02:06-positive advanced/metastatic NY-ESO-1-expressing MRCLS. Patients underwent a reduced-dose (cohort 1) or standard-dose (cohort 2) lymphodepletion regimen (LDR).

Acute resistance to BET inhibitors remodels compensatory transcriptional programs via p300 coactivation.

Initial clinical trials with drugs targeting epigenetic modulators - such as bromodomain and extraterminal protein (BET) inhibitors - demonstrate modest results in acute myeloid leukemia (AML). A major reason for this involves an increased transcriptional plasticity within AML, which allows cells to escape the therapeutic pressure. In this study, we investigated immediate epigenetic and transcriptional responses following BET inhibition and could demonstrate that BET inhibitor-mediated release of BRD4 from chromatin is accompanied by an acute compensatory feedback that attenuates down-regulation, or even increases expression, of specific transcriptional modules.

Safety and Tolerability of Letetresgene Autoleucel (Lete-cel; GSK3377794): Pilot Studies in Patients With Advanced Non-Small Cell Lung Cancer.

Purpose: To evaluate safety, tolerability, and anti-tumor response of lete-cel, genetically modified autologous T-cells expressing a T-cell receptor specific for NY-ESO-1/LAGE-1a shared epitope, alone or in combination with pembrolizumab, in human leukocyte antigen HLA-A*02-positive (HLA-A*02:01-, HLA-A*02:05-, and/or HLA-A*02:06-) patients with New York esophageal squamous cell carcinoma 1 (NY-ESO-1)- and/or LAGE-1a-positive non-small cell lung cancer (NSCLC).

Experimental Design: Study 208749 was a single-arm study of lete-cel alone. Study 208471 was a multi-arm study of lete-cel alone or in combination with pembrolizumab in patients with advanced or recurrent NSCLC.

l-Securinine Induces ROS-Dependent Apoptosis on Pancreatic Cancer Cells via the PI3K/AKT/mTOR Signaling Pathway.

Accumulating evidence has shown that l-securinine can, in certain circumstances, suppress tumor development by elevating reactive oxygen species (ROS) levels. The current work set out to examine l-securinine's apoptotic effects on HuP-T3 cells as well as any potential underlying molecular mechanism(s) that could explain its action as an anticancer agent. In this study, we used 1.

Screening tools for diabetic foot ulcers: a narrative review.

The prevalence of diabetic foot ulcers (DFUs) is 4 to 10% among people with diabetes mellitus. DFUs are associated with increased morbidity and mortality as well as reduced quality of life and have a significant impact on overall healthcare expenditure. The main predisposing factors for DFU are diabetic neuropathy, peripheral arterial disease, and trauma.

Investigating the prognostic impact of NY-ESO-1 expression and HLA subtypes in metastatic synovial sarcoma.

Background: To better understand the importance of the New York esophageal squamous cell carcinoma 1 (NY-ESO-1) and human leukocyte antigen (HLA) subtypes in treatment decision-making, further investigation of their prevalence and prognostic impact among patients with metastatic synovial sarcoma (mSS) is needed.

Patients And Methods: This was a retrospective clinico-biological cohort study of adults with mSS. Patient data were collected from the French Sarcoma Group NetSARC database and supplemented by electronic medical records.

A Single Center, Randomized Controlled Trial on the Efficacy of Topical Application of ReGenerating Tissue Agents (RGTA) Technology in Diabetic Foot Ulcers.

Diabetic foot ulcers (DFUs) are a serious complication of diabetes mellitus. Clinical data from the use of ReGenerating Tissue Agents (RGTA) technology in patients with DFUs are scarce. The objective of this randomized controlled study was to evaluate the efficacy of RGTA technology in the management of DFUs.

The Association of Vitamin D Receptor Polymorphisms with COVID-19 Severity.

Background: Association studies of vitamin D receptor (VDR) polymorphisms with COVID-19 severity have produced inconsistent results in different populations. Herein we examined gene polymorphisms in a Caucasian Greek cohort of COVID-19 patients.

Methods: This was a case-control study in a tertiary university hospital in Greece including 137 COVID-19 patients with varying disease severities and 72 healthy individuals.

Risk factors for the in‑hospital and 1‑year mortality of elderly patients hospitalized due to COVID‑19‑related pneumonia.

Coronavirus disease 2019 (COVID-19) is characterized by poor outcomes and a high mortality rate, particularly among elderly patients. Since the beginning of the pandemic, an older age has been recognized as a critical risk factor for disease severity, with increasing mortality rates in each decade of life. This phenomenon may be a consequence of a poor previous health status, with a higher prevalence of pre-existing comorbidities and a higher degree of frailty.

Effects of Hypericin on Cultured Primary Normal Human Dermal Fibroblasts Under Increased Oxidative Stress.

Introduction: Wound healing is a dynamic process that begins with inflammation, proliferation, and cell migration of a variety of fibroblast cells. As a result, identifying possible compounds that may improve fibroblast cell wound healing capacity is crucial. Hypericin is a natural quinine that has been reported to possess a wide range of pharmacological profiles, including antioxidant and anti-inflammatory, activities.

Highlights from the 82 ADA Scientific Sessions and the 58 EASD Meeting on Diabetic Neuropathy.

Diabetic neuropathy is one of the commonest diabetic complications. It affects 30-50% of people with diabetes mellitus (DM) and may cause severe pain and foot ulcers. Distal symmetric polyneuropathy and diabetic autonomic neuropathy are the main manifestations of diabetic neuropathy.

Effects of Advanced Glycation End Products Oxidative Stress on Beta Cells: Insights from and Studies and Update on Emerging Therapies.

Background: Protein, lipid, and nucleic acid glycation reactions begin and continue as a result of persistent hyperglycemia in patients with diabetes mellitus. Advanced glycated end products (AGEs) are a complex group of chemical moieties that are formed as a result of the glycation process and play an important role in the pathogenesis of diabetes mellitus. When AGEs interact with their cellular receptor (RAGE), numerous signaling pathways, including nuclear factor kappa-light-chainenhancer of activated B cells (NF-κB), c-Jun N-terminal kinase (JNK), and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), are activated, increasing oxidative stress.

Impact of Glucagon-like peptide 1 receptor agonists on peripheral arterial disease in people with diabetes mellitus: A narrative review.

Peripheral arterial disease (PAD) is a common macrovascular complication of diabetes mellitus (DM). Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) are among the latest class of antidiabetic medications that stimulate insulin synthesis and secretion and have been used for the management of type 2 DM. Apart from the effect on glycaemic control, GLP-1RAs also have a robust impact on weight reduction and have shown favorable effects on cardiovascular morbidity and mortality in cardiovascular outcome trials (CVOTs).

Safety and efficacy of letetresgene autoleucel alone or with pembrolizumab for relapsed/refractory multiple myeloma.

This pilot study assessed the safety and efficacy of letetresgene autoleucel (lete-cel; GSK3377794), a genetically modified autologous T-cell therapy targeting New York esophageal squamous cell carcinoma-1 (NY-ESO-1)/L antigen family member 1 isoform A (LAGE-1a)-positive myeloma cells, alone or in combination with pembrolizumab in patients with relapsed/refractory multiple myeloma. Eligible patients expressed NY-ESO-1 and/or LAGE-1a and either HLA-A∗02:01, ∗02:05, or ∗02:06. Patients received lete-cel single infusion alone (arm 1) or with pembrolizumab (arm 2).

Factors predicting poor outcomes of patients treated with tocilizumab for COVID‑19‑associated pneumonia: A retrospective study.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic is a significant global issue that has major implications for the healthcare system. The mortality rates associated with SARS-CoV-2 infection vary according to the geographical region and are associated with age, comorbidities and vaccination status. Organ damage is caused by the cytokine release syndrome, which plays a crucial role in the course of coronavirus disease 2019 (COVID-19) infection.

Biomarker correlates with response to NY-ESO-1 TCR T cells in patients with synovial sarcoma.

Autologous T cells transduced to express a high affinity T-cell receptor specific to NY-ESO-1 (letetresgene autoleucel, lete-cel) show promise in the treatment of metastatic synovial sarcoma, with 50% overall response rate. The efficacy of lete-cel treatment in 45 synovial sarcoma patients (NCT01343043) has been previously reported, however, biomarkers predictive of response and resistance remain to be better defined. This post-hoc analysis identifies associations of response to lete-cel with lymphodepleting chemotherapy regimen (LDR), product attributes, cell expansion, cytokines, and tumor gene expression.

Lipidomics Analysis of Free Fatty Acids in Human Plasma of Healthy and Diabetic Subjects by Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS).

Targeted analytical methods for the determination of free fatty acids (FFAs) in human plasma are of high interest because they may help in identifying biomarkers for diseases and in monitoring the progress of a disease. The determination of FFAs is of particular importance in the case of metabolic disorders because FFAs have been associated with diabetes. We present a liquid chromatography-high resolution mass spectrometry (LC-HRMS) method, which allows the simultaneous determination of 74 FFAs in human plasma.

Low concentrations of bisphenol A promote the activation of the mitochondrial apoptotic pathway on Beta-TC-6 cells via the generation of intracellular reactive oxygen species and mitochondrial superoxide.

Τhe natural history of type 2 diabetes mellitus is characterized by a progressive loss of pancreatic beta cell function and insulin resistance. Bisphenol A (BPA) is an endocrine-disrupting chemical that is used widely in industry; people are exposed to BPA and its products daily. Studies have delineated that BPA alters the function of pancreatic beta cells.

Diabetes mellitus and multiple myeloma; common features of two distinct entities.

Diabetes mellitus (DM) has attained the status of a global pandemic. Cardiovascular disease (CV) was the leading cause of morbidity in people with type 2 DM, however, a transition from CV to cancer as the leading contributor to DM related death has been observed lately. Multiple myeloma (MM) is the second most common haematological malignancy.

Immunogenicity of SARS-CoV-2 BNT162b2 Vaccine in People with Diabetes: A Prospective Observational Study.

The mRNA-based BNT162b2 vaccine has demonstrated high efficacy against severe SARS-CoV-2. However, data regarding immune response in people with diabetes mellitus (DM) after vaccination with the BNT162b2 vaccine are limited. In this prospective observational study, we examined humoral immune response in participants with and without DM after vaccination with the BNT162b2 mRNA vaccine.

The effect of vitamin D supplementation on mortality and intensive care unit admission of COVID-19 patients. A systematic review, meta-analysis and meta-regression.

Aims: The aim of this systematic review and meta-analysis was to investigate the effect of vitamin D supplementation on mortality and admission to intensive care unit (ICU) of COVID-19 patients.

Methods: A systematic search of PubMed, Google Scholar, Embase, Web of Science and medRxiv with terms relative to vitamin D supplementation and COVID-19 was conducted on 26 March 2021. Comprehensive Meta-Analysis software was used for the quantitative assessment of data and random-effects model was applied.