Real-world evidence on the effectiveness and safety of gliclazide MR 60 mg in Bangladeshi patients with Type II diabetes during fasting: a sub-analysis from the global DIA-RAMADAN study.

Many Muslims with Type II diabetes (T2DM) fast during Ramadan, which can put them at increased risk of hypoglycemia. This sub-analysis of the global DIA-RAMADAN study assessed the effectiveness and safety of gliclazide modified release (MR) 60 mg in the Bangladeshi cohort. DIA-RAMADAN was an international, prospective, observational study conducted in adult T2DM patients intending to fast and receiving gliclazide MR 60 mg once daily for ≥90 days before Ramadan.

SRSF2 mutation reduces polycythemia and impairs hematopoietic progenitor functions in JAK2V617F-driven myeloproliferative neoplasm.

SRSF2 mutations are found in association with JAK2V617F in myeloproliferative neoplasms (MPN), most frequently in myelofibrosis (MF). However, the contribution of SRSF2 mutation in JAK2V617F-driven MPN remains elusive. To investigate the consequences of SRSF2 and JAK2 mutations in MPN, we generated Cre-inducible Srsf2Jak2 knock-in mice.

Interleukin-1 contributes to clonal expansion and progression of bone marrow fibrosis in JAK2V617F-induced myeloproliferative neoplasm.

Chronic inflammation is frequently associated with myeloproliferative neoplasms (MPN), but the role of inflammation in the pathogenesis of MPN remains unclear. Expression of the proinflammatory cytokine interleukin-1 (IL-1) is elevated in patients with MPN as well as in Jak2V617F knock-in mice. Here, we show that genetic deletion of IL-1 receptor 1 (IL-1R1) normalizes peripheral blood counts, reduces splenomegaly and ameliorates bone marrow fibrosis in homozygous Jak2V617F mouse model of myelofibrosis.

Inhibition of vascular adhesion protein-1 enhances the anti-tumor effects of immune checkpoint inhibitors.

Modulation of the immunosuppressive tumor microenvironment (TME) is essential for enhancing the anti-tumor effects of immune checkpoint inhibitors (ICIs). Adhesion molecules and enzymes such as vascular adhesion protein-1 (VAP-1), which are expressed in some cancers and tumor vascular endothelial cells, may be involved in the generation of an immunosuppressive TME. In this study, the role of VAP-1 in TME was investigated in 2 murine colon cancer models and human cancer cells.

Immune-resistant mechanisms in cancer immunotherapy.

Immune checkpoint inhibitors (ICI) such as PD-1/PD-L1 antibodies (Abs) and CTLA4 Abs and T cell-based adoptive cell therapies are effective for patients with various cancers. However, response rates of ICI monotherapies are still limited due to lack of immunogenic antigens and various immune-resistant mechanisms. The latter includes adaptive immune resistance that is caused by anti-tumor T cells (e.

An oncofetal antigen, IMP-3-derived long peptides induce immune responses of both helper T cells and CTLs.

Insulin-like growth factor II mRNA-binding protein 3 (IMP-3), an oncofetal antigen identified using genome-wide cDNA microarray analyses, is overexpressed in several malignancies. IMP-3-derived cytotoxic T lymphocyte (CTL) epitopes have been used for peptide-based immunotherapies against various cancers. In addition to CTLs, induction of tumor-associated antigen (TAA)-specific helper T (Th) cells is crucial for establishment of effective antitumor immunity.

Identification of glypican-3-derived long peptides activating both CD8 and CD4 T cells; prolonged overall survival in cancer patients with Th cell response.

In a recent phase I clinical trial, a vaccine consisting of glypican-3 (GPC3)-derived CTL epitopes was found to be safe and induced measurable immune and clinical responses in patients with hepatocellular carcinoma (HCC). The aim of this study was to identify GPC3-derived long peptides (GPC3-LPs) carrying promiscuous HLA class II-restricted T helper (Th) cell epitopes. Using a computer algorithm, we predicted GPC3-LPs that can bind to promiscuous HLA class II molecules.

Identification of immunogenic LY6K long peptide encompassing both CD4 and CD8 T-cell epitopes and eliciting CD4 T-cell immunity in patients with malignant disease.

Identification of peptides that activate both tumor-specific helper T (Th) cells and cytotoxic T lymphocytes (CTLs) are important for the induction of effective antitumor immune responses. We focused on a long peptide (LP) derived from lymphocyte antigen 6 complex locus K (LY6K) encompassing both candidate Th epitopes and a known CTL epitope. Using IFNγ ELISPOT assays as a marker of activated T cells, we studied the immunogenicity and cross-priming potential of LY6K-LP, assaying human immune cell responses in vitro and immunologic activities in HLA-A24 transgenic mice in vivo.

Differential host immune responses to epidemic and endemic strains of Shigella dysenteriae type I.

Shigella dysenteriae type 1 causes devastating epidemics in developing countries with high case-fatality rates in all age-groups. The aim of the study was to compare host immune responses to epidemic (T2218) and endemic strains of S. dysenteriae type 1.