Overexpression of the epigenetic modifier metastasis-associated protein 1 (MTA1) is associated with aggressive human prostate cancer. The purpose of this study was to determine MTA1- targeted chemopreventive and therapeutic efficacy of pterostilbene, a natural potent analog of resveratrol, in pre-clinical models of prostate cancer. Here, we show that high levels of MTA1 expression in Pten-loss prostate cooperate with key oncogenes, including c-Myc and Akt among others, to promote prostate cancer progression. Loss-of-function studies using human prostate cancer cells indicated direct involvement of MTA1 in inducing inflammation and epithelial-to-mesenchymal transition. Importantly, pharmacological inhibition of MTA1 by pterostilbene resulted in decreased proliferation and angiogenesis and increased apoptosis. This restrained prostatic intraepithelial neoplasia (PIN) formation in prostate-specific Pten heterozygous mice and reduced tumor development and progression in prostate-specific Pten-null mice. Our findings highlight MTA1 as a key upstream regulator of prostate tumorigenesis and cancer progression. More significantly, it offers pre-clinical proof for pterostilbene as a promising lead natural agent for MTA1-targeted chemopreventive and therapeutic strategy to curb prostate cancer.

A recent advance in molecular typing for tracing the transmission of leprosy is the discovery of short tandem repeats (STRs) in Mycobacterium leprae. To substantiate polymorphic loci from STR as promising candidates for molecular typing tools in leprosy epidemiology, 44 STR loci including 33 microsatellites and 11 minisatellites were investigated among 27 laboratory strains by sequencing PCR products. Not all STRs were necessarily polymorphic. Thirty-two out of the 44 loci were polymorphic. Nine polymorphic loci were suitable for identifying genotypes according to the discriminatory capacity, stability, and reproducibility. All the strains were classified into independent genotypes by the selected nine loci. Three multicase households were subjected to molecular typing. M. leprae obtained from household cases showed identical copy numbers by TTC triplet alone, but the isolates from one family contact case were divided into different genotypes by adding eight other polymorphic loci. The combination of information from multiple loci allows increasing levels of discrimination and it is likely that the generation and documentation of data will result in the choice of a potential molecular typing tool for leprosy epidemiology.Mycobacterium leprae is an obligate intracellular parasite with tropism for macrophages and Schwann cells and the only species of mycobacteria to infect peripheral nerves (19). It causes leprosy, a chronic granulomatous infection of the skin and peripheral nerves with characteristic deformities and disability (1). It is generally accepted today that the worldwide implementation of standardized multidrug therapy for leprosy has decreased the number of registered leprosy cases from a peak of 10 to 15 million to a current total of less than 1 million. However, the annual confirmed new cases remain at 500,000 to 700,000. This continuing number suggests that effective multidrug therapy fails to disrupt the chain of leprosy transmission (26).Even though leprosy is one of the oldest recorded diseases, the source for M. leprae, the portal of its exit/entry, and the mode of transmission are still under investigation. Some regard human beings as a host for the bacteria, while others are still considering more possibilities. It was proposed that the nasal mucosa are the exit/entry pathway of M. leprae (9,17,18). In light of the transmission mode, human-to-human direct contact was first generally accepted (6, 16), with time as airborne (23), as vector-borne (14, 25) and as vehicle-borne (3, 12) routes from evidence that has been obtained. All the progress in leprosy epidemiology was helpful in understanding the chain of transmission, yet at the same time was overwhelming.In the past few years, studies focusing on leprosy transmission by molecular genotyping have shed new light on it (8,10,11,22,24,27,28). The most recent one was the report from Groathouse et al. (8). By in silico analysis, 44 promising polymorphic short tandem repeat (STR) sites, including both 33 microsatellite loci (repeat units of 1 to 5...

Metastasis-associated protein 1 (MTA1), a negative epigenetic modifier, plays a critical role in prostate cancer (PCa) progression. We hypothesized that MTA1 overexpression in primary tumor tissues can predict PCa aggressiveness and metastasis. Immunohistochemical staining of MTA1 was done on archival PCa specimens from University of Mississippi Medical Center and University of Iowa. We found that nuclear MTA1 overexpression was positively correlated with the severity of disease progression reaching its highest levels in metastatic PCa. Nuclear MTA1 overexpression was significantly associated with Gleason > 7 tumors in African Americans but not in Caucasians. It was also a predictor of recurrent disease. We concluded that MTA1 nuclear overexpression may be a prognostic indicator and a future therapeutic target for aggressive PCa in African American men. Our findings may be useful for categorizing African American patients with a higher probability of recurrent disease and metastasis from those who are likely to remain metastasis-free.