MiR-199a and miR-497 are associated with better overall survival due to increased chemosensitivity in diffuse large b-cell lymphoma patients

Micro-RNAs (miRNAs) are short non-coding single-stranded RNA molecules regulating gene expression at the post-transcriptional level. miRNAs are involved in cell development, differentiation, apoptosis, and proliferation. miRNAs can either function as tumor suppressor genes or oncogenes in various important pathways. The expression of specific miRNAs has been identified to correlate with tumor prognosis. For miRNA expression analysis real-time PCR on 81 samples was performed, including 63 diffuse large B-cell lymphoma (DLBCL, 15 of germinal center B-cell like subtype, 17 non germinal center B-cell, 23 transformed, and eight unclassified) and 18 controls, including nine peripheral B-cells, 5 germinal-center B-cells, four lymphadenitis samples, and 4 lymphoma cell lines (RI-1, SUDHL4, Karpas, U2932). Expression levels of a panel of 11 miRNAs that have been previously involved in other types of cancer (miR-15b_2, miR-16_1*, miR-16_2, miR-16_2*, miR-27a, miR-27a*, miR-98-1, miR-103a, miR-185, miR-199a, and miR-497) were measured and correlated with clinical data. Furthermore, cell lines, lacking miR-199a and miR-497 expression, were electroporated with the two respective miRNAs and treated with standard immunochemotherapy routinely used in patients with DLBCL, followed by functional analyses including cell count and apoptosis assays. Seven miRNAs (miR-16_1*, miR-16_2*, miR-27a, miR-103, miR-185, miR-199, and miR-497) were statistically significantly up-regulated in DLBCL compared to normal germinal cells. However, high expression of miR-497 or miR-199a was associated with better overall survival (p = 0.042 and p = 0.007). Overexpression of miR-199a and miR-497 led to a statistically significant decrease in viable cells in a dose-dependent fashion after exposure to rituximab and various chemotherapeutics relevant in multi-agent lymphoma therapy. Our data indicate that elevated miR-199a and miR-497 levels are associated with improved survival in aggressive lymphoma patients most likely by modifying drug sensitivity to immunochemotherapy. This functional impairment may serve as a potential novel therapeutic target in future treatment of patients with DLBCL

Translin and Trax differentially regulate telomere-associated transcript homeostasis

Translin and Trax proteins are highly conserved nucleic acid binding proteins that have been implicated in RNA regulation in a range of biological processes including tRNA processing, RNA interference, microRNA degradation during oncogenesis, spermatogenesis and neuronal regulation. Here, we explore the function of this paralogue pair of proteins in the fission yeast. Using transcript analysis we demonstrate a reciprocal mechanism for control of telomere-associated transcripts. Mutation of tfx1(+) (Trax) elevates transcript levels from silenced sub-telomeric regions of the genome, but not other silenced regions, such as the peri-centromeric heterochromatin. In the case of some sub-telomeric transcripts, but not all, this elevation is dependent on the Trax paralogue, Tsn1 (Translin). In a reciprocal fashion, Tsn1 (Translin) serves to repress levels of transcripts (TERRAs) from the telomeric repeats, whereas Tfx1 serves to maintain these elevated levels. This reveals a novel mechanism for the regulation of telomeric transcripts. We extend this to demonstrate that human Translin and Trax also control telomere-associated transcript levels in human cells in a telomere-specific fashion

Human germ/stem cell-specific gene TEX19 influences cancer cell proliferation and cancer prognosis

Table of cancer data sets analyzed. (DOCX 14 kb

Propuesta de rediseño del sistema de abastecimiento de agua potable, para el Barrio Camilo Ortega, Municipio de Managua, en el período 2011-2031

El agua es el principal elemento para la supervivencia humana, por eso existe una gran relación entre el agua y la salud, los que son dos elementos que contribuyen al sostenimiento y a la calidad de la vida. La disponibilidad y calidad del agua determinan el grado de salud e higiene en cualquiera sociedad. La presente Tesis Monográfica titulada “Propuesta de rediseño del Abastecimiento de agua potable, para el Bo. Camilo Ortega, Municipio de Managua, Mayo 2011 a Mayo 2031” para optar por la titulación de Ingeniero Civil. Del 100% de las aguas, sólo un 2% equivalen a agua dulce, las cuales al pasar por un corto proceso de tratamiento y cloración puede ser consumida, lo que provoca una disputa por el vital líquido, debido a que cada comunidad por muy pequeña que sea, requiere de un servicio mínimo de abastecimiento de agua potable. El mayor aporte de las aguas dulces, lo hacen las aguas subterráneas las cuales eran relativamente libres de contaminación y particularmente útiles para uso doméstico. Hoy, salvo en raros casos, el agua como se encuentra en la naturaleza, no puede ser utilizada directamente para el consumo humano ni para usos industriales, dado que no es lo suficientemente pura biológicamente ni químicamente, debido a residuos y sustancias contaminantes arrojados por el ser humano a diario

Meta-analysis of expression of l(3)mbt tumor-associated germline genes supports the model that a soma-to-germline transition is a hallmark of human cancers

Evidence is starting to emerge indicating that tumorigenesis in metazoans involves a soma-to-germline transition, which may contribute to the acquisition of neoplastic characteristics. Here, we have meta-analyzed gene expression profiles of the human orthologs of Drosophila melanogaster germline genes that are ectopically expressed in l(3)mbt brain tumors using gene expression datasets derived from a large cohort of human tumors. We find these germline genes, some of which drive oncogenesis in D. melanogaster, are similarly ectopically activated in a wide range of human cancers. Some of these genes normally have expression restricted to the germline, making them of particular clinical interest. Importantly, these analyses provide additional support to the emerging model that proposes a soma-to-germline transition is a general hallmark of a wide range of human tumors. This has implications for our understanding of human oncogenesis and the development of new therapeutic and biomarker targets with clinical potential

Development of a bioinformatic analytical approach to identify novel human cancer testis Gene candidates

The identification of tumour antigens (TAs) represents an ongoing challenge to the development of novel cancer diagnostic, prognostic and therapeutic strategies. A group of proteins, the cancer testis (CT) antigens are promising targets for such clinical applications. Their encoding genes show expression restricted to the immunologically privileged testes but their expression is also found in cells with a cancerous phenotype. To facilitate and automate the identification of novel CT genes, bioinformatic analytical pipelines based on publicly available microarray and expressed sequence tag (EST) data were developed and implemented as web tools to support wider application. Human germline-associated datasets were generated and the developed screening pipelines were subsequently used to analyse these datasets, leading to the identification of a. novel cohort of meiosis-speci fic genes, the meiCT genes that exhibit t he characteristics of CT genes and may have oncogenic features. In general, frequent germline gene expression found in cancer could reflect a soma-to-germline transformation occurring in human cells in the course of the development of cancer. The expression of germline-specific genes, in particular of meiotic genes, could lead to the production of proteins that cause oncogenic events and thus contribute to tumorigenesis and to the acquisition of tumour characteristics.EThOS - Electronic Theses Online ServiceGBUnited Kingdo