The role of narratives in promoting vaccine confidence among Indigenous peoples in Canada, the United States, Australia, and New Zealand: a scoping review.

Background: Many Indigenous youth and young adults in Canada, the United States, Australia, and New Zealand have reported low vaccine confidence, which has been linked to lower vaccination rates for COVID-19, MMR, HPV, DTaP-IPV-Hib, and pneumococcal conjugate vaccines. Narrative-based health promotion approaches, including those focused on strengthening vaccine confidence, have been used in public health interventions. Scoping reviews have become increasingly valued for their rigorous and reproducible exploration of evidence in public health research.

Creating a Culturally Safe Online Data Collection Instrument to Measure Vaccine Confidence Among Indigenous Youth: Indigenous Consensus Method.

Background:  Participating in surveys can shape the perception of participants related to the study topic. Administering a vaccine hesitancy questionnaire can have negative impacts on participants' vaccine confidence. This is particularly true for online and cross-cultural data collection because culturally safe health education to correct misinformation is typically not provided after the administration of an electronic survey.

Clinical and research updates on the VISTA immune checkpoint: immuno-oncology themes and highlights.

Immune checkpoints limit the activation of the immune system and serve an important homeostatic function but can also restrict immune responses against tumors. Inhibition of specific immune checkpoint proteins such as the B7:CD28 family members programmed cell death protein-1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) has transformed the treatment of various cancers by promoting the anti-tumor activation of immune cells. In contrast to these effects, the V-domain immunoglobulin suppressor of T-cell activation (VISTA) regulates the steady state of the resting immune system and promotes homeostasis by mechanisms distinct from PD-1 and CTLA-4.

VISTA expression and patient selection for immune-based anticancer therapy.

V-domain Ig suppressor of T-cell activation (VISTA) is a B7 family member that plays key roles in maintaining T cell quiescence and regulation of myeloid cell populations, which together establish it as a novel immunotherapy target for solid tumors. Here we review the growing literature on VISTA expression in relation to various malignancies to better understand the role of VISTA and its interactions with both tumor cells and immune cells expressing other checkpoint molecules within the tumor microenvironment (TME). The biology of VISTA creates several mechanisms to maintain the TME, including supporting the function of myeloid-derived suppressor cells, regulating natural killer cell activation, supporting the survival of regulatory T cells, limiting antigen presentation on antigen-presenting cells and maintaining T cells in a quiescent state.

Activation of targetable inflammatory immune signaling is seen in myelodysplastic syndromes with SF3B1 mutations.

Background: Mutations in the splicing factor are commonly seen in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), yet the specific oncogenic pathways activated by mis-splicing have not been fully elucidated. Inflammatory immune pathways have been shown to play roles in the pathogenesis of MDS, though the exact mechanisms of their activation in splicing mutant cases are not well understood.

Methods: RNA-seq data from mutant samples was analyzed and functional roles of interleukin-1 receptor-associated kinase 4 ( isoforms were determined.

Innate immune mediator, Interleukin-1 receptor accessory protein (IL1RAP), is expressed and pro-tumorigenic in pancreatic cancer.

Advanced pancreatic ductal adenocarcinoma (PDAC) is usually an incurable malignancy that needs newer therapeutic targets. Interleukin-1 receptor accessory protein (IL1RAP) is an innate immune mediator that regulates activation of pro-inflammatory and mitogenic signaling pathways. Immunohistochemistry on tissue microarrays demonstrated expression of IL1RAP in majority of human PDAC specimens and in murine pancreatic tumors from K-Ras/p53/PDXCre (KPC) mice.

Association between medication adherence and non-drug healthcare utilisation and costs: a retrospective longitudinal cohort study among US women age 65 and older.

Objectives: To explore the association between hormone therapy (HT) adherence and non-drug healthcare utilisation and healthcare costs among patients with breast cancer.

Design: Retrospective longitudinal cohort study.

Setting: The US Medicare beneficiaries in the SEER-Medicare-linked database PARTICIPANTS: Women aged ≥ 65 with hormone-receptor positive breast cancer from 2007 through mid-2009 in the USA.

The First Study Evaluating the Safety of Pre-Surgery Administration of Metformin in Patients with Colorectal and other Gastrointestinal Cancers and Effect on Cancer Stem Cells.

Background: The cancer stem cell (CSC) hypothesis of tumor genesis suggests that unlike most cancer cells within tumor CSC resist chemotherapy and can regenerate various cell types in tumor thereby causing relapse. Hence drugs that selectively target CSC may offer great promise for cancer therapy especially when combined with chemotherapy. Current treatment options for colorectal cancer (CRC) and other gastrointestinal (GI) tumors rely on combination of surgical resection, cytotoxic and targeted drugs.

Fimepinostat (CUDC-907) in patients with relapsed/refractory diffuse large B cell and high-grade B-cell lymphoma: report of a phase 2 trial and exploratory biomarker analyses.

Fimepinostat (CUDC-907), a first-in-class oral small-molecule inhibitor of histone deacetylase and phosphatidylinositol 3-kinase, demonstrated efficacy in a phase 1 study of patients with relapsed/refractory (R/R) diffuse large and high-grade B-cell lymphomas (DLBCL/HGBL), particularly those with increased MYC protein expression and/or MYC gene rearrangement/copy number gain (MYC-altered disease). Therefore, a phase 2 study of fimepinostat was conducted in this patient population with 66 eligible patients treated. The primary end-point of overall response (OR) rate for patients with MYC-IHC ≥40% (n = 46) was 15%.

Cost sharing for breast cancer hormone therapy: How do dual eligible patients' copayment impact adherence.

Objective: To examine the different levels of copayment assistance and treatment adherence among Medicare and Medicaid dual eligible beneficiaries with breast cancer in the U.S.

Research Design: Propensity Score methodology was adopted to minimize potential selection bias from the nonrandom allocation of the treatment group (i.

Prospective Evaluation of Effect of Metformin on Activation of AMP-activated Protein Kinase (AMPK) and Disease Control in a Sub-group Analysis of Patients with GI Malignancies.

Background: Observational studies have demonstrated association of metformin with reduced cancer incidence and mortality in multiple cancer types, including gastrointestinal (GI) malignancies. Anti-neoplastic effects of metformin are believed through many mechanisms including activation of AMP-activated protein kinase, which controls mammalian target of rapamycin (mTOR) growth regulatory pathway.

Methods: In a pilot, delayed-start randomized study, non-diabetic patients with GI cancers were randomized to 2 arms, Stage 1: concurrent metformin (500mg twice daily) plus chemotherapy vs.

The impact of the introduction of generic aromatase inhibitors on adherence to hormonal therapy over the full course of 5-year treatment for breast cancer.

Background: High out-of-pocket costs (OOPCs) often are found to be inversely associated with adherence to medical treatment. The introduction of generic aromatase inhibitors (GAIs) significantly reduced the OOPCs of patients. The objective of the current study was to explore the impact of the introduction of GAIs on adjuvant hormone therapy (AHT) adherence over the full course of breast cancer treatment.

A phase I delayed-start, randomized and pharmacodynamic study of metformin and chemotherapy in patients with solid tumors.

Purpose: Metformin activates AMP-related pathways leading to inactivation of mammalian target of rapamycin (mTOR) and suppression of its downstream effectors, crucial for cancer growth. Epidemiologic studies showed a reduced incidence and improved survival in cancer patients. We conducted a prospective phase I study to assess the safety of metformin in combination with chemotherapy in patients with solid tumors.

Metformin, Diabetes, and Survival among U.S. Veterans with Colorectal Cancer.

Background: Metformin has been associated with improved colorectal cancer survival, but investigations are limited by small numbers of patients and confounding by diabetic severity. We examined the association between metformin use and overall survival (OS) in patients with diabetes and colorectal cancer in a large population of U.S.

Phase 1 trial of tivantinib in combination with sorafenib in adult patients with advanced solid tumors.

Purpose: This phase I study evaluated the safety, tolerability, maximum tolerated dose (MTD), and recommended phase II dose (RP2D) of tivantinib combined with sorafenib in patients with advanced solid tumors.

Materials And Methods: A standard 3 + 3 dose escalation design was used. At the RP2D, expansion cohorts in 5 tumor types could be enrolled.

Discovery of novel drugs for promising targets.

Background: Once a promising drug target is identified, the steps to actually discover and optimize a drug are diverse and challenging.

Objective: The goal of this study was to provide a road map to navigate drug discovery.

Methods: Review general steps for drug discovery and provide illustrating references.

Diabetes, metformin use, and colorectal cancer survival in postmenopausal women.

Background: Observational studies have associated metformin use with lower colorectal cancer (CRC) incidence but few studies have examined metformin's influence on CRC survival. We examined the relationships among metformin use, diabetes, and survival in postmenopausal women with CRC in the Women's Health Initiative (WHI) clinical trials and observational study.

Methods: 2066 postmenopausal women with CRC were followed for a median of 4.

Oncology drug development and approval of systemic anticancer therapy by the U.S. Food and Drug Administration.

Background: Regulatory approval of oncology drugs is the cornerstone of the development process and approval characteristics shape eventual utilization. Approval trends and characteristics provide valuable information for drug developers and regulators and ultimately affect clinicians and patients.

Methods: Indication characteristics were tabulated for drugs approved by the U.

MG98, a second-generation DNMT1 inhibitor, in the treatment of advanced renal cell carcinoma.

Background: In carcinogenesis, methylation of DNA promoter regions results in inactivation of tumor-suppressing genes. MG98 was designed to inhibit DNA methyltransferases enzyme 1 production.

Methods: This multicenter study explored two schedules of MG98 with Interferon-α-2β to identify schedule and dose for patients with metastatic RCC.

Mocetinostat for relapsed classical Hodgkin's lymphoma: an open-label, single-arm, phase 2 trial.

Background: The prognosis of patients with relapsed Hodgkin's lymphoma, especially those who relapse after stem-cell transplantation, is poor, and the development of new agents for this patient population is an unmet medical need. We tested the safety and efficacy of mocetinostat, an oral isotype-selective histone deacetylase inhibitor, in patients with relapsed classical Hodgkin's lymphoma.

Methods: Patients with relapsed or refractory classical Hodgkin's lymphoma aged 18 years or older were treated with mocetinostat administered orally three times per week, in 28-day cycles.

The class-I HDAC inhibitor MGCD0103 induces apoptosis in Hodgkin lymphoma cell lines and synergizes with proteasome inhibitors by an HDAC6-independent mechanism.

Inhibition of histone deacetylase 6 (HDAC6)-dependent aggresome function by pan HDAC inhibitors was recently reported to be a key mechanism underlying the synergistic activity between proteasome inhibitors and HDAC inhibitors in a variety of tumour types. Because these combinations induce significant thrombocytopenia in vivo, we examined whether less toxic, isotype-selective HDAC inhibitors may still synergize with proteasome inhibitors, and if so, by what mechanisms. Here, we showed that the class I HDAC inhibitor, MGCD0103, has a potent antiproliferative activity in Hodgkin lymphoma (HL) cell lines.

Phase II study of the histone deacetylase inhibitor MGCD0103 in patients with previously treated chronic lymphocytic leukaemia.

MGCD0103, an orally available class I histone deacetylase (HDAC) inhibitor, was examined for pre-clinical activity in chronic lymphocytic leukaemia (CLL). A phase II clinical trial was performed, starting at a dose of 85 mg/d, three times per week. Dose escalation to 110 mg or the addition of rituximab was permitted in patients without a response after two or more cycles.

Histone deacetylase inhibitors in cancer therapy: new compounds and clinical update of benzamide-type agents.

Histone deacetylase (HDAC) inhibitors constitute a novel and growing class of anticancer agents that function by altering intracellular patterns of histone acetylation, the so-called epigenetic "histone code," thereby producing changes in cell cycle arrest, differentiation, and/or apoptosis in tumor cells. This overview describes the chemistry and preliminary characterization of recently disclosed molecules in three major classes of HDAC inhibitors: hydroxamic acids, 2-amino- benzanilides, and cyclic peptides. In addition, results from recent clinical trials on isotype-selective HDAC inhibitors are reviewed.