Tumor suppressor role of microRNA-1296 in triple-negative breast cancer.

Unlabelled: Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis, which lacks effective targeted therapies. There is an urgent need to better understand the underlying molecular mechanisms of TNBC aggressiveness and identify novel, efficient targets for therapeutic intervention.

Methods: miRNA qRT-PCR was used to determine the expression of miR-1296 in cell lines.

CYP1B1 promotes tumorigenesis via altered expression of CDC20 and DAPK1 genes in renal cell carcinoma.

Background: Cytochrome P450 1B1 (CYP1B1) has been shown to be up-regulated in many types of cancer including renal cell carcinoma (RCC). Several reports have shown that CYP1B1 can influence the regulation of tumor development; however, its role in RCC has not been well investigated. The aim of the present study was to determine the functional effects of CYP1B1 gene on tumorigenesis in RCC.

Predictors of clinical outcomes in acute decompensated heart failure: Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure outcome models.

Background: Patients hospitalized for acute decompensated heart failure (ADHF) are at high risk for early mortality and rehospitalization. Risk stratification of ADHF using clinically available data on admission is increasingly important to integrate with clinical pathways. Our goal was to create a simple method of screening patients upon admission to identify those with increased risk of future adverse events.

Advanced (stage D) heart failure: a statement from the Heart Failure Society of America Guidelines Committee.

We propose that stage D advanced heart failure be defined as the presence of progressive and/or persistent severe signs and symptoms of heart failure despite optimized medical, surgical, and device therapy. Importantly, the progressive decline should be primarily driven by the heart failure syndrome. Formally defining advanced heart failure and specifying when medical and device therapies have failed is challenging, but signs and symptoms, hemodynamics, exercise testing, biomarkers, and risk prediction models are useful in this process.

Protective association of colonoscopy against proximal and distal colon cancer and patterns in interval cancer.

Background: The protective effect of colonoscopy against proximal colorectal cancer is variable and depends on the detection and complete removal of precancerous polyps.

Objective: To estimate the efficacy of colonoscopy in a medical center with open-access screening colonoscopy since 1998.

Design: Nested case-control study with incidence density sampling.

Versican is a potential therapeutic target in docetaxel-resistant prostate cancer.

In the current study, we investigated a combination of docetaxel and thalidomide (DT therapy) in castration-resistant prostate cancer (CRPC) patients. We identified marker genes that predict the effect of DT therapy. Using an androgen-insensitive PC3 cell line, we established a docetaxel-resistant PC-3 cell line (DR-PC3).

Inactivation of bone morphogenetic protein 2 may predict clinical outcome and poor overall survival for renal cell carcinoma through epigenetic pathways.

We investigated whether impaired regulation of bone morphogenetic protein-2 (BMP-2) via epigenetic pathways is associated with renal cell carcinoma (RCC) pathogenesis. Expression and CpG methylation of the BMP-2 gene were analyzed using RCC cell lines, and 96 matched RCC and normal renal tissues. We also performed functional analysis using BMP-2 restored RCC cells.

The role of BPTF in melanoma progression and in response to BRAF-targeted therapy.

Background: Bromodomain PHD finger transcription factor (BPTF) plays an important role in chromatin remodeling, but its functional role in tumor progression is incompletely understood. Here we explore the oncogenic effects of BPTF in melanoma.

Methods: The consequences of differential expression of BPTF were explored using shRNA-mediated knockdown in several melanoma cell lines.

Amantadine extended release for levodopa-induced dyskinesia in Parkinson's disease (EASED Study).

ADS-5102 is a long-acting, extended-release capsule formulation of amantadine HCl administered once daily at bedtime. This study investigated the safety, efficacy, and tolerability of ADS-5102 in Parkinson's disease (PD) patients with levodopa-induced dyskinesia. This was a randomized, double-blind, placebo-controlled, parallel-group study of 83 PD patients with troublesome dyskinesia assigned to placebo or one of three doses of ADS-5102 (260 mg, 340 mg, 420 mg) administered daily at bedtime for 8 weeks.

Acute heart failure in the elderly: differences in clinical characteristics, outcomes, and prognostic factors in the VERITAS Study.

Background: Acute heart failure (HF) is common in the elderly, but the association of age with clinical outcomes and prognostic factors has not been examined thoroughly.

Methods And Results: We analyzed the clinical and laboratory characteristics and the outcomes of 1,347 patients with acute HF enrolled in the VERITAS trial. Subjects were subdivided based on their median age of 72 years.

Navigating toward research success in times of uncertainty: funding opportunities for early career investigators in nephrology.

There is considerable concern within the nephrology community about recent federal budget cuts and the decreasing availability of funds for research. This is especially difficult for junior investigators who are about to start a career as physician-scientists. Accordingly, it is imperative that resources other than federal funds be made available to these individuals during this most delicate yet crucial transition period.

Antitumor activity of miR-1280 in melanoma by regulation of Src.

MicroRNAs (miRNAs) play a key role in cancer progression by coordinately repressing target genes involved in cell proliferation, migration, and invasion. miRNAs regulate gene expression by repressing translation or directing sequence-specific degradation of complementary mRNA. Here, we report that expression of miR-1280 is significantly suppressed in human melanoma specimens when compared with nevi, and in human melanoma cell lines when compared with cultured normal human melanocytes.

Impact of rural residence and health system structure on quality of liver care.

Background: Specialist physician concentration in urban areas can affect access and quality of care for rural patients. As effective drug treatment for hepatitis C (HCV) becomes increasingly available, the extent to which rural patients needing HCV specialists face access or quality deficits is unknown. We sought to determine the influence of rural residency on access to HCV specialists and quality of liver care.

Genistein inhibits prostate cancer cell growth by targeting miR-34a and oncogenic HOTAIR.

Objective: Genistein is a soy isoflavone that has antitumor activity both in vitro and in vivo. It has been shown that genistein inhibits many type of cancers including prostate cancer (PCa) by regulating several cell signaling pathways and microRNAs (miRNAs). Recent studies suggest that the long non-coding RNAs (lncRNAs) are also involved in many cellular processes.

Nonresponse to interferon-α based treatment for chronic hepatitis C infection is associated with increased hazard of cirrhosis.

Background: The long-term consequences of unsuccessful interferon-α based hepatitis C treatment on liver disease progression and survival have not been fully explored.

Methods And Findings: We performed retrospective analyses to assess long-term clinical outcomes among treated and untreated patients with hepatitis C virus in two independent cohorts from a United States Veterans Affairs Medical Center and a University Teaching Hospital. Eligible patients underwent liver biopsy during consideration for interferon-α based treatment between 1992 and 2007.

Hrk mediates 2-methoxyestradiol-induced mitochondrial apoptotic signaling in prostate cancer cells.

Prostate cancer is one of the most prevalent cancers in males and ranks as the second most common cause of cancer-related deaths. 2-methoxyestradiol (2-ME), an endogenous estrogen metabolite, is a promising anticancer agent for various types of cancers. Although 2-ME has been shown to activate c-Jun-NH2-kinase (JNK) and mitochondrial-dependent apoptotic signaling pathways, the underlying mechanisms, including downstream effectors, remain unclear.

Genistein up-regulates tumor suppressor microRNA-574-3p in prostate cancer.

Genistein has been shown to inhibit cancers both in vitro and in vivo, by altering the expression of several microRNAs (miRNAs). In this study, we focused on tumor suppressor miRNAs regulated by genistein and investigated their function in prostate cancer (PCa) and target pathways. Using miRNA microarray analysis and real-time RT-PCR we observed that miR-574-3p was significantly up-regulated in PCa cells treated with genistein compared with vehicle control.

MicroRNA-182-5p promotes cell invasion and proliferation by down regulating FOXF2, RECK and MTSS1 genes in human prostate cancer.

Recently miR-182 has been reported to be over-expressed in prostate cancer (PC) tissues, however detailed functional analysis of miR-182-5p has not been carried out. The purpose of this study was to: 1. analyze the function of miR-182-5p in prostate cancer, 2.

Inhibition of PTEN gene expression by oncogenic miR-23b-3p in renal cancer.

Background: miR-23b is located on chromosome number 9 and plays different roles in different organs especially with regards to cancer development. However, the functional significance of miR-23b-3p in renal cell carcinoma (RCC) has not been reported.

Methods And Results: We measured miR-23b-3p levels in 29 pairs of renal cell carcinoma and their normal matched tissues using real-time PCR.

Genistein suppresses prostate cancer growth through inhibition of oncogenic microRNA-151.

Genistein has been shown to suppress the growth of several cancers through modulation of various pathways. However, the effects of genistein on the regulation of oncogenic microRNA-151 (miR-151) have not been reported. In this study, we investigated whether genistein could alter the expression of oncogenic miR-151 and its target genes that are involved in the progression and metastasis of prostate cancer (PCa).

Up-regulation of microRNA-21 correlates with lower kidney cancer survival.

Background: MicroRNA-21 is up-regulated in a variety of cancers like, breast, colorectal, lung, head and neck etc. However, the regulation of miR-21 in renal cell carcinoma (RCC) has not yet been studied systematically.

Methods And Results: We measured miR-21 levels in 54 pairs of kidney cancers and their normal matched tissues by real-time PCR.

MicroRNA-34a modulates c-Myc transcriptional complexes to suppress malignancy in human prostate cancer cells.

MicroRNA-34a (miR-34a), a potent mediator of tumor suppressor p53, has been reported to function as a tumor suppressor and miR-34a was found to be downregulated in prostate cancer tissues. We studied the functional effects of miR-34a on c-Myc transcriptional complexes in PC-3 prostate cancer cells. Transfection of miR-34a into PC-3 cells strongly inhibited in vitro cell proliferation, cell invasion and promoted apoptosis.

Diet, microRNAs and prostate cancer.

MicroRNAs (miRNAs) constitute an evolutionarily conserved class of small non-coding RNAs that are endogenously expressed with crucial functions in fundamental cellular processes such as cell cycle, apoptosis and differentiation. Disturbance of miRNA expression and function leads to deregulation of basic cellular processes leading to tumorigenesis. A growing body of experimental evidence suggests that human tumors have deregulated expression of microRNAs, which have been proposed as novel oncogenes or tumor suppressors.

Restoring erectile function by antioxidant therapy in diabetic rats.

Purpose: Diabetes mediates an increase in reactive oxygen species that can lead to impaired endothelial function, decreased smooth muscle in the diabetic corpus cavernosum and increased apoptosis. We hypothesized that antioxidant therapy may restore erectile function by inhibiting apoptosis in diabetic rat crura.

Materials And Methods: A total of 40 male Sprague-Dawley rats were randomized to 5 groups of 8 each, including healthy controls, rats with diabetes, and rats with diabetes with the antioxidant tempol (4-hydroxytetramethyl-piperidine-1-oxyl) (Sigma-Aldrich), with insulin, and with tempol and insulin.