Low-Dose Eribulin Promotes NK Cell-Mediated Therapeutic Efficacy in Bladder Cancer.

Unlabelled: Despite its immunogenic nature, bladder cancer (BCa) responds sub-optimally to FDA-approved immunotherapy.

Background/objectives: We have previously shown that natural killer (NK) cells are major contributors to overall patient survival in BCa. In our efforts to identify clinically approved agents that enhance NK cell activation, we identified eribulin, a microtubule destabilizer primarily used in breast cancer.

Perioperative Immune Checkpoint Blockade for Muscle-Invasive and Metastatic Bladder Cancer.

Checkpoint inhibitors offer promise in treating muscle-invasive and metastatic bladder cancer, but the optimal timing of their administration-neoadjuvant or adjuvant-remains unclear. To determine the efficacy of combining checkpoint inhibition with standard cisplatin-based chemotherapy, we conducted a phase II trial of neoadjuvant anti-PD-1 (αPD-1) and anti-CTLA-4 (αCTLA-4), in combination with cisplatin-gemcitabine, for patients with muscle-invasive bladder cancer prior to radical cystectomy. In addition, a novel murine model of spontaneous metastatic bladder cancer was used to compare the efficacy of neoadjuvant versus adjuvant anti-PD-L1 (αPD-L1) treatment.

Checkpoint Inhibitors in Urothelial Carcinoma-Future Directions and Biomarker Selection.

Context: Several recent phase 2 and 3 trials have evaluated the efficacy and toxicity of checkpoint inhibitor (CPI) therapy for urothelial carcinoma (UC) in the metastatic, localized muscle-invasive UC (MIUC), upper tract UC, and non-muscle-invasive bladder cancer (NMIBC) disease state.

Objective: To assess the outcomes and toxicity of CPIs across the treatment landscape of UC and contextualize their application to current real-world treatment.

Evidence Acquisition: We queried PubMed, Web of Science, and EMBASE databases and conference abstracts to identify prospective trials examining CPIs in UC.

KLRF1, a novel marker of CD56 NK cells, predicts improved survival for patients with locally advanced bladder cancer.

Background: Bladder tumor-infiltrating CD56 NK cells are more tumor cytotoxic than their CD56 counterparts. Identification of NK cell subsets is labor-intensive and has limited utility in the clinical setting. Here, we sought to identify a surrogate marker of bladder CD56 NK cells and to test its prognostic significance.

A RET::GRB2 fusion in pheochromocytoma defies the classic paradigm of RET oncogenic fusions.

The RET kinase receptor is a target of mutations in neural crest tumors, including pheochromocytomas, and of oncogenic fusions in epithelial cancers. We report a RET::GRB2 fusion in a pheochromocytoma in which RET, functioning as the upstream partner, retains its kinase domain but loses critical C-terminal motifs and is fused to GRB2, a physiological RET interacting protein. RET::GRB2 is an oncogenic driver that leads to constitutive, ligand-independent RET signaling; has transforming capability dependent on RET catalytic function; and is sensitive to RET inhibitors.

Effects of Mycobacterium bovis Calmette et Guérin (BCG) in oncotherapy: Bladder cancer and beyond.

The Mycobacterium bovis Bacillus Calmette et Guérin (BCG) vaccine was generated in 1921 with the efforts of a team of investigators, Albert Calmette and Camille Guérin, dedicated to the determination to develop a vaccine against active tuberculosis (TB) disease. Since then, BCG vaccination is used globally for protection against childhood and disseminated TB; however, its efficacy at protecting against pulmonary TB in adult and aging populations is highly variable. Due to the BCG generated immunity, this vaccine later proved to have an antitumor activity; though the standing mechanisms behind are still unclear.

Bladder tumor ILC1s undergo Th17-like differentiation in human bladder cancer.

Purpose: Human innate lymphoid cells (hILCs) are lineage-negative immune cells that do not express rearranged adaptive antigen receptors. Natural killer (NK) cells are hILCs that contribute to cancer defense. The role of non-NK hILCs in cancer is unclear.

Genotype-Phenotype Features of Germline Variants of the TMEM127 Pheochromocytoma Susceptibility Gene: A 10-Year Update.

Purpose: This work aimed to evaluate genotype-phenotype associations in individuals carrying germline variants of transmembrane protein 127 gene (TMEM127), a poorly known gene that confers susceptibility to pheochromocytoma (PHEO) and paraganglioma (PGL).

Design: Data were collected from a registry of probands with TMEM127 variants, published reports, and public databases.

Main Outcome Analysis: Clinical, genetic, and functional associations were determined.

The Use of FRAX in Identifying Women Less Than 65 Years Needing Bone Mineral Density Testing.

The purpose of this study is to determine if the United States Preventive Services Task Force (USPSTF) screening guideline for osteoporosis identifies women under the age of 65 with osteoporosis needing bone mineral density (BMD) testing. If the Fracture Risk Assessment Tool (FRAX) tool fails to identify women under the age of 65 with undiagnosed osteoporosis, then diagnosis and treatment are delayed, potentially leading to increased fractures and morbidity. Another aim of this study is to characterize women under the age of 65 with osteoporosis that FRAX fails to identify and provide descriptive data on our study population.

Reciprocal fine-tuning of progesterone and prolactin-regulated gene expression in breast cancer cells.

Progesterone and prolactin are two key hormones involved in development and remodeling of the mammary gland. As such, both hormones have been linked to breast cancer. Despite the overlap between biological processes ascribed to these two hormones, little is known about how co-expression of both hormones affects their individual actions.

Fibroblast growth factor (FGF)-21 based therapies: A magic bullet for nonalcoholic fatty liver disease (NAFLD)?

: Fibroblast growth factor (FGF) 21 is a member of the FGF19 sub-family of signaling molecules. They have been found to act at the localized paracrine/autocrine and systemic endocrine levels because of their extracellular matrix and co-receptor protein binding characteristics. While the molecule circulates systemically, it has specificity conferred by a co-factor binding protein β-Klotho which is preferentially expressed in hepatic and adipose tissues.

Urinary Diversion Disparity Following Radical Cystectomy for Bladder Cancer in the Hispanic Population.

Objective: To determine if disparities in quality of surgical care exist between Hispanics and non-Hispanics undergoing radical cystectomy for bladder cancer.

Materials And Methods: An observational cohort study was conducted retrospectively on patients who underwent radical cystectomy for urothelial carcinoma of the bladder at our institution between January 2005 and July 2018. Data was collected on demographic, clinical, and pathological characteristics of patients, including self-reported ethnicity.

Intratumoral CD56 natural killer cells are associated with improved survival in bladder cancer.

Background: Natural killer (NK) cells are effective at killing tumors in a non-MHC restricted manner and are emerging targets for cancer therapy but their importance in bladder cancer (BC) is poorly defined. NK cells are commonly subdivided into populations based on relative surface expression of CD56. Two major subsets are CD56 and CD56 NK cells.

Interferon-Stimulated Genes Are Transcriptionally Repressed by PR in Breast Cancer.

The progesterone receptor (PR) regulates transcriptional programs that drive proliferation, survival, and stem cell phenotypes. Although the role of native progesterone in the development of breast cancer remains controversial, PR clearly alters the transcriptome in breast tumors. This study identifies a class of genes, Interferon (IFN)-stimulated genes (ISGs), potently downregulated by ligand-activated PR which have not been previously shown to be regulated by PR.