Targeting INMT and interrupting its methylation pathway for the treatment of castration resistant prostate cancer.

Background: Castration-resistant prostate cancer (CRPC) is associated with a very poor prognosis, and the treatment of which remains a serious clinical challenge.

Methods: RNA-seq, qPCR, western blot and immunohistochemistry were employed to identify and confirm the high expression of indolethylamine N-methyltransferase (INMT) in CRPC and the clinical relevance. Chip assay was used to identify Histone-Lysine N-Methyltransferase (SMYD3) as a major epigenetic regulator of INMT.

A Constitutive Intrinsic Inflammatory Signaling Circuit Composed of miR-196b, Meis2, PPP3CC, and p65 Drives Prostate Cancer Castration Resistance.

Androgen deprivation therapy is the most effective treatment for advanced prostate cancer, but almost all cancer eventually becomes castration resistant, and the underlying mechanisms are largely unknown. Here, we show that an intrinsic constitutively activated feedforward signaling circuit composed of IκBα/NF-κB(p65), miR-196b-3p, Meis2, and PPP3CC is formed during the emergence of castration-resistant prostate cancer (CRPC). This circuit controls the expression of stem cell transcription factors that drives the high tumorigenicity of CRPC cells.

Expression and function of SIRT6 in muscle invasive urothelial carcinoma of the bladder.

SIRT6, a member of the class III histone deacetylase, has been shown to inhibit glycolysis and promote DNA double strand break repairs. Despite of its proposed tumor suppressor role, no significant differences in SIRT6 mRNA levels among normal bladder urothelium, non-muscle invasive, and muscle invasive urothelial carcinoma were noted in the two largest bladder cancer gene expression datasets available in Oncomine. We therefore studied the expression and function of SIRT6 in muscle invasive urothelial carcinoma of the bladder.

Prostate Cancer Chemoprevention Targeting High Risk Populations: Model for Trial Design and Outcome Measures.

Inspite of the large number of promising nutrient-derived agents demonstrating promise as potential chemopreventive agents, most have failed to prove effectiveness in clinical trials. Critical requirements for moving nutrient-derived agents to recommendation for clinical use include adopting a systematic, molecular-mechanism based approach and utilizing the same ethical and rigorous methods such as are used to evaluate other pharmacological agents. Preliminary data on a mechanistic rationale for chemoprevention activity as observed from epidemiological, in vitro and preclinical studies, phase I data of safety in high-risk cohorts are required to inform design of phase II clinical trials.

Bladder cancer: a review of non-muscle invasive disease.

Background: Bladder cancer is one of the most common cancers affecting men and women and thus has a profound impact on health care. The majority of patients (75%) with newly diagnosed urothelial tumors have non-muscle invasive disease confined to the bladder mucosa or the lamina propria.

Methods: The authors review the literature as well as recently published clinical guidelines regarding the bladder cancer risk and causative factors, diagnostic and pathologic evaluation, prognostic variables, and management strategies for patients with non-muscle invasive bladder cancer.

Premalignant and malignant prostate lesions: pathologic review.

Background: High-grade prostatic intraepithelial neoplasia (HGPIN) is currently the only recognized premalignant lesion of prostatic carcinoma.

Methods: This review article discusses HGPIN, its link to prostatic adenocarcinoma, and the significance of its presence on needle biopsy. The criteria and clinical impact of the diagnosis of atypical small acinar proliferation on needle biopsy are reviewed.