Direct intra-tumoral injection of zinc-acetate halts tumor growth in a xenograft model of prostate cancer

Intracellular levels of zinc have shown a strong inverse correlation to growth and malignancy of prostate cancer. To date, studies of zinc supplementation in prostate cancer have been equivocal and have not accounted for bioavailability of zinc. Therefore, we hypothesized that direct intra-tumoral injection of zinc could impact prostate cancer growth. In this study, we evaluated the cytotoxic properties of the pH neutral salt zinc acetate on the prostate cancer cell lines PC3, DU145 and LNCaP. Zinc acetate killed prostate cancer cell lines in vitro, independent of androgen sensitivity, in a dose-dependent manner in a range between 200 and 600 μM. Cell death occurred rapidly with 50% cell death by six hours and maximal cell death by 18 hours. We next established a xenograft model of prostate cancer and tested an experimental treatment protocol of direct intra-tumoral injection of zinc acetate. We found that zinc treatments halted the growth of the prostate cancer tumors and substantially extended the survival of the animals, whilst causing no detectable cytoxicity to other tissues. Thus, our studies form a solid proof-of-concept that direct intra-tumoral injection of zinc acetate could be a safe and effective treatment strategy for prostate cancer

Epigenetics as a mechanism driving polygenic clinical drug resistance

Aberrant methylation of CpG islands located at or near gene promoters is associated with inactivation of gene expression during tumour development. It is increasingly recognised that such epimutations may occur at a much higher frequency than gene mutation and therefore have a greater impact on selection of subpopulations of cells during tumour progression or acquisition of resistance to anticancer drugs. Although laboratory-based models of acquired resistance to anticancer agents tend to focus on specific genes or biochemical pathways, such 'one gene : one outcome' models may be an oversimplification of acquired resistance to treatment of cancer patients. Instead, clinical drug resistance may be due to changes in expression of a large number of genes that have a cumulative impact on chemosensitivity. Aberrant CpG island methylation of multiple genes occurring in a nonrandom manner during tumour development and during the acquisition of drug resistance provides a mechanism whereby expression of multiple genes could be affected simultaneously resulting in polygenic clinical drug resistance. If simultaneous epigenetic regulation of multiple genes is indeed a major driving force behind acquired resistance of patients' tumour to anticancer agents, this has important implications for biomarker studies of clinical outcome following chemotherapy and for clinical approaches designed to circumvent or modulate drug resistance

Metabolic flexibility as a major predictor of spatial distribution in microbial communities

A better understand the ecology of microbes and their role in the global ecosystem could be achieved if traditional ecological theories can be applied to microbes. In ecology organisms are defined as specialists or generalists according to the breadth of their niche. Spatial distribution is often used as a proxy measure of niche breadth; generalists have broad niches and a wide spatial distribution and specialists a narrow niche and spatial distribution. Previous studies suggest that microbial distribution patterns are contrary to this idea; a microbial generalist genus (Desulfobulbus) has a limited spatial distribution while a specialist genus (Methanosaeta) has a cosmopolitan distribution. Therefore, we hypothesise that this counter-intuitive distribution within generalist and specialist microbial genera is a common microbial characteristic. Using molecular fingerprinting the distribution of four microbial genera, two generalists, Desulfobulbus and the methanogenic archaea Methanosarcina, and two specialists, Methanosaeta and the sulfate-reducing bacteria Desulfobacter were analysed in sediment samples from along a UK estuary. Detected genotypes of both generalist genera showed a distinct spatial distribution, significantly correlated with geographic distance between sites. Genotypes of both specialist genera showed no significant differential spatial distribution. These data support the hypothesis that the spatial distribution of specialist and generalist microbes does not match that seen with specialist and generalist large organisms. It may be that generalist microbes, while having a wider potential niche, are constrained, possibly by intrageneric competition, to exploit only a small part of that potential niche while specialists, with far fewer constraints to their niche, are more capable of filling their potential niche more effectively, perhaps by avoiding intrageneric competition. We suggest that these counter-intuitive distribution patterns may be a common feature of microbes in general and represent a distinct microbial principle in ecology, which is a real challenge if we are to develop a truly inclusive ecology

The ocean sampling day consortium

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

The context and potential of epigenetics in oncology

Cancer has long been known to be a disease caused by alterations in the genetic blueprint of cells. In the past decade it has become evident that epigenetic processes have a function, at least equally important, in neoplasia. Epigenetics describes the mechanisms that result in heritable alterations in gene expression profiles without an accompanying change in DNA sequence. Genetics and epigenetics intricately interact in the pathogenesis of cancer (Esteller, 2007). In this review, we paint a broad picture of current understanding of epigenetic changes in cancer cells and reflect on the immense clinical potential of emerging knowledge of epigenetics in the diagnosis, prognostic assessment, treatment, and screening of cancer

Deep Sequencing Analyses of Low Density Microbial Communities: Working at the Boundary of Accurate Microbiota Detection

Introduction: Accurate analyses of microbiota composition of low-density communities (10 3 –10 4 bacteria/sample) can be challenging. Background DNA from chemicals and consumables, extraction biases as well as differences in PCR efficiency can significantly interfere with microbiota assessment. This study was aiming to establish protocols for accurate microbiota analysis at low microbial density. Methods: To examine possible effects of bacterial density on microbiota analyses we compared microbiota profiles of seria

Prevalence and age-of-onset distributions of DSM IV mental disorders and their severity among school going Omani adolescents and youths: WMH-CIDI findings

<p>Abstract</p> <p>Background</p> <p>There is a dearth of studies exploring the magnitude of mental disorders amongst adolescents and youths in the Arab world. To our knowledge, this phase 2 survey in Oman is the first nationally representative school-based study to determine the prevalence of DSM-IV mental disorders (lifetime and over the preceding 12 months), their age-of-onset distributions and determine their severity over the past 12 months using the World Mental Health-Composite International Diagnostic Interview, the WMH-CIDI, used for international comparison.</p> <p>Methods</p> <p>A total of 1,682 (91.61%) students out of 1836 students who formed the phase 2 random sub-sample of a multi-stage, stratified, random sampling design (phase 1), participated in the face-to-face structured interview using the Arabic-version of WMH-CIDI 3.0.</p> <p>Results</p> <p>The phase 1 results using the General Health Questionnaire (GHQ-12) and Child Depression Inventory (CDI) showed depressive symptoms to be 17% prevalent in the larger sample of 5409 adolescents and youths. Amongst the phase 2 respondents from this sample, 13.9% had at least one DSM IV diagnostic label. The lifetime prevalence of Major Depressive Disorder (MDD) was 3.0%; Bipolar Mood Disorder (BMD) was 1%, Specific phobia 5.8% and Social phobia 1.6%. The female gender was a strong predictor of a lifetime risk of MDD (OR 3.3, 95% CI 1.7-6.3, <it>p </it>= 0.000); Any Mood Disorders (OR 2.5, 95% CI 1.4-4.3, p = 0.002) and Specific Phobia (OR 1.5, 95% CI 1.0-2.4, p = 0.047). The severity of illness for cases diagnosed with 12 month DSM IV disorders was found to be 80% lower in females (OR 0.2, 95%CI 0.0-0.8). The estimates over the previous 12 month period when compared with the lifetime prevalence showed a 25% to 40% lower prevalence for MDD, Specific phobia, Social phobia, Any Anxiety Disorders (AAD) and Any Mood disorders (AMD) while the rate was 80% lower for Separation Anxiety Disorder/Adult Separation Anxiety (SAD/ASA). Mood disorders were significantly lower in the 14-16 age groups (70% lower) in comparison to the older age groups and AMD showed a linear increase in prevalence across increasing age groups (<it>p </it>= 0.035).</p> <p>Conclusion</p> <p>The implications of the present findings are not clear cut, however this study endorses the adult CIDI studies findings that mental disorders do begin earlier in life. The relatively lower prevalence of DSM IV depressive disorders cautions against any conclusive interpretation of the inflated results based on the exclusive study of the depressive symptoms alone in the same sample in the same time period. The female gender proved to be a strong predictor of lifetime risk of MDD, any mood disorder and specific phobia. Under-reporting by males or some other gender-specific factors may have contributed to such a discrepancy. The odds of the severity of illness for cases with 12 month DSM IV disorders were significantly lower in females.</p