Over expression of brain and acute leukemia,cytoplasmic and ETS-related gene is associated with poor outcome in acute myeloid leukemia

The high expression of brain and acute leukemia, cytoplasmic (BAALC) and ETS-related gene (ERG) has been reported to influence the outcome in acute myeloid leukemia (AML), but due to limited prospective studies, their role as prognostic factors is unclear. At diagnosis, the prognostic value of BAALC and ERG expression with respect to other cytogenetic and molecular markers was analyzed in 149 AML patients. Patients were divided into quartiles which resulted in the formation of four groups (G1–G4) based on expression values of BAALC and ERG and clinical response defined across groups. Groups with similar survival probabilities were merged together and categorized subsequently as high versus low expressers. Patients with high BAALC and ERG expression had significantly lower overall survival (OS; BAALC: p = 0.001 at 5 years 29.4% vs. 69.8%; ERG: p < 0.0001 at 5 years 4% vs. 50.4%) and disease-free survival (BAALC: p = 0.001 at 5 years 19.5% vs. 69.8%; ERG: p < 0.0001 at 5 years 4.2% vs. 47%). Patients were further stratified combining BAALC and ERG expression in an integrative prognostic risk score (IPRS). After a median follow-up of 54 months (95% CI 45–63 months) among survivors, IPRS for high versus low expressers was a significant predictor for OS (BAALC + ERG: 4% vs. 71.6%, p < 0.0001) and DFS (BAALC + ERG: 4.5% vs. 74.1%, p < 0.0001). In a multivariate model, IPRS of BAALC + ERG expression retained prognostic significance for OS (hazard ratio [HR] 2.96, 95%CI 1.91–4.59, p < 0.001) and DFS (HR 3.61, 95%CI 2.26–5.76, p < 0.001).     

Evidence for early and progressive ultrasonic vocalization and oromotor deficits in a PINK1 gene knockout rat model of Parkinson's disease

Parkinson's disease (PD) is a progressive neurodegenerative disease that leads to a wide range of motor and nonmotor deficits. Specifically, voice and swallow deficits manifest early, are devastating to quality of life, and are difficult to treat with standard medical therapies. The pathological hallmarks of PD include accumulation of the presynaptic protein α‐synuclein (αSyn) as well as degeneration of substantia nigra dopaminergic neurons. However, there is no clear understanding of how or when this pathology contributes to voice and swallow dysfunction in PD. The present study evaluates the effect of loss of function of the phosphatase and tensin homolog‐induced putative kinase 1 gene in rats (PINK1^–/–), a model of autosomal recessive PD in humans, on vocalization, oromotor and limb function, and neurodegenerative pathologies. Behavioral measures include ultrasonic vocalizations, tongue force, biting, and gross motor performance that are assayed at 2, 4, 6, and 8 months of age. Aggregated αSyn and tyrosine hydroxylase immunoreactivity (TH‐ir) were measured at 8 months. We show that, compared with wild‐type controls, PINK1^–/– rats develop 1) early and progressive vocalization and oromotor deficits, 2) reduced TH‐ir in the locus coeruleus that correlates with vocal loudness and tongue force, and 3) αSyn neuropathology in brain regions important for cranial sensorimotor control. This novel approach of characterizing a PINK1^–/– genetic model of PD provides the foundational work required to define behavioral biomarkers for the development of disease‐modifying therapeutics for PD patients. © 2015 Wiley Periodicals, Inc.     

Gallic Acid,an Active Constituent of Grape Seed Extract,Exhibits Anti-proliferative,Pro-apoptotic and Anti-tumorigenic Effects Against Prostate Carcinoma Xenograft Growth in Nude Mice

Purpose  Gallic acid, a natural agent present in a wide-range of fruits and vegetables, has been of potential interest as an anti-cancer agent; herein, we evaluated its efficacy in androgen-independent DU145 and androgen-dependent-22Rv1 human prostate cancer (PCa) cells. Materials and Methods  Cell viability was determined by MTT and apoptosis by Annexin V-PI assays. In vivo anti-cancer efficacy was assessed by DU145 and 22Rv1 xenograft growth in nude mice given normal drinking water or one supplemented with 0.3% or 1% (w/v) gallic acid. PCNA, TUNEL and CD31 immunostaining was performed in tumor tissues for in vivo anti-proliferative, apoptotic and anti-angiogenic effects of gallic acid. Results  Gallic acid decreased cell viability in a dose-dependent manner in both DU145 and 22Rv1 cells largely via apoptosis induction. In tumor studies, gallic acid feeding inhibited the growth of DU145 and 22Rv1 PCa xenografts in nude mice. Immunohistochemical analysis revealed significant inhibition of tumor cell proliferation, induction of apoptosis, and reduction of microvessel density in tumor xenografts from gallic acid-fed mice as compared to controls in both DU145 and 22Rv1 models. Conclusion  Taken together, our findings show the anti-PCa efficacy of gallic acid and provide a rationale for additional studies with this naturally-occurring agent for its efficacy against PCa.     

Silibinin Suppresses Spontaneous Tumorigenesis in <Emphasis Type="BoldItalic">APC</Emphasis><Superscript>min/+</Superscript> Mouse Model by Modulating Beta-Catenin Pathway

Purpose  

Here we assessed whether silibinin, a nontoxic chemopreventive agent, inhibits spontaneous intestinal tumorigenesis in APC ^min/+ mouse model, a genetically predisposed animal model of human familial adenomatous polyposis (FAP).     

Rat sperm immobilisation effects of a protein from Ricinus communis (Linn.): an in vitro comparative study with nonoxynol‐9

Previous study conducted in our department showed that 50% ethanolic extract of the root of Ricinus communis possess reversible antifertility effect and a 62‐kDa protein (Rp) from this extract is responsible for the antifertility effects. In this study, we compared the spermicidal effect of this Rp with nonoxynol‐9 (N‐9) in vitro. The sperm immobilisation studies showed that 100 μg ml^?1 of Rp was able to immobilise the sperms completely within 30 s. Sperm revival test revealed that the spermicidal effect was irreversible. There was also a significant reduction in sperm viability and hypo‐osmotic swelling in Rp and N‐9 treated groups in comparison with the control. In Rp and N‐9 treated groups, the number of acrosome‐reacted cells was found to be high and also caused agglutination of the spermatozoa, indicating the loss of intactness of the plasma membrane, which was further supported by the significant reduction in the activity of membrane bound 5′‐nucleotidase, acrosomal acrosin. In short, the protein Rp possesses spermicidal activity in vitro and its effects are similar to that of nonoxynol 9.     

Chemopreventive efficacy of inositol hexaphosphate against prostate tumor growth and progression in TRAMP mice.

PURPOSE: Herein, for the first time, we evaluated the in vivo chemopreventive efficacy of inositol hexaphosphate (IP6), a major constituent of high-fiber diets, against prostate tumor growth and progression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. EXPERIMENTAL DESIGN: Beginning at 4 weeks of age, male TRAMP mice were fed 2% (w/v) IP6 in drinking water or only drinking water till 24 weeks of age, and then sacrificed. Prostate tissue was subjected to histopathologic analysis and to immunohistochemical analyses for proliferation and apoptosis. RESULTS: IP6 feeding did not show any adverse effect on fluid and diet consumption and body weight. There was a significant reduction (40%; P < 0.01) in lower urogenital tract weight in IP6-fed mice. IP6 inhibited prostate cancer progression at prostatic intraepithelial neoplasia stage and strongly reduced the incidence of adenocarcinoma (prostatic intraepithelial neoplasia/adenocarcinoma, 75:25% in the IP6 group versus 39:61% in the control group; P < 0.05). The incidences of well-differentiated and poorly differentiated adenocarcinomas in the IP6-fed group were reduced by 44% and 62%, respectively. Immunohistochemical analysis of prostate tissue showed a 26% decrease (P < 0.05) in proliferation cell nuclear antigen-positive cells and a 3.5-fold increase in apoptotic cells with no effect on Tag expression by IP6. CONCLUSIONS: These findings are both novel and highly significant in establishing for the first time that oral IP6, without any toxicity, suppresses prostate tumor growth and progression at the neoplastic stage, thereby reducing the incidence of adenocarcinoma through its antiproliferative and proapoptotic effects, and thus indicating that IP6 could have potential chemopreventive effects against human prostate cancer.