Project description:Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) frequently complicates combined anti-retroviral therapy (ART) and anti-tubercular therapy in HIV-1 co-infected tuberculosis (TB) patients. The immunopathological mechanism underlying TB-IRIS is incompletely defined. Differential transcript abundance in PBMC from IRIS and control patients stimulated with heat killed H37Rv was determined by microarray Blood samples were collected during longitudinal observational studies of TB-IRIS patients and controls (both groups HIV-infected patients placed on antiretroviral treatment). PBMC were stimulated with heat killed H37Rv and RNA extracted.
Project description:Endometrial cancer is the most commonly diagnosed gynecologic malignancy in women after breast, lung and colorectal cancer. Despite numerous scientific advances, the incidence and mortality rate of endometrial cancer is on the rise. Considerable research effort has therefore been placed on understanding the pathogenesis of this disease to combat this growing issue. There is now emerging evidence to suggest a putative role for dysregulation of the renin angiotensin system (RAS) and in particular the (pro)renin receptor ((P)RR), in the ontogenesis of endometrial cancer. Support for this notion arises from previous literature implicating (P)RR in cancer pathophysiology (e.g., breast cancer and pancreatic carcinoma) by virtue of its role in proliferation, angiogenesis, fibrosis, migration and invasion. In view of these data, we aimed to investigate the functional role of (P)RR in human endometrial cancer progression and development. To this end, we employed an siRNA-mediated knock down approach to abrogate (P)RR expression in the immortalized endometrial epithelial cell lines; Ishikawa, AN3CA and HEC-1A to explore the role of (P)RR in cellular proliferation and cellular viability. To further extend these analyses we also carried out a sophisticated proteomic screen, that investigated the potential pathways via which (P)RR is acting in endometrial cancer physiology. These data confirmed that (P)RR is critical for endometrial cell cancer development, contributing to both its proliferative capacity and in the maintenance cell viability. This is likely mediated through proteins such as MGA, SLC4A7, SLC7A11 or DHRS2, which were reduced following (P)RR knockdown. These putative protein interactions/pathways, which rely on the presence of (P)RR, are likely to contribute to endometrial cancer progression and could therefore, represent several novel therapeutic targets in the treatment of this cancer. Finally we contend that (P)RR, in its soluble form (s(P)RR) in blood, may have substantial potential as a novel biomarker for cancer diagnosis and prognosis prediction going forward.
Project description:c-myc-3'RR mice prone to develop Burkitt lymphoma (BL) were crossed with p53+/- mice in order to obtain c-myc-3'RR/p53+/- mice. These mice develop a wider spectrum of lymphoma including BL, mantle cell lymphoma (MCL) and plasma cell lymphoma (PCL). Transcriptoma analysis of these lymphomas is investigated in these arrays.
Project description:Mantle cell lymphoma (MCL) is a B cell malignancy characterized by a monoclonal proliferation of lymphocytes with co-expression of CD5, CD43 but not CD23. We have developed two murine models of MCL-like lymphoma. Breeding Cdk4R24C mice (a knock-in strain that express a Cdk4 protein resistant to inhibition by p16INK4a and other INK4 family members) with c-myc-3’RR transgenic mice (prone to develop aggressive Burkitt lymphoma-like lymphoma) leads in c-myc/Cdk4R24C mice to development of clonal blastoid MCL-like lymphoma. Breeding p53+/- mice with c-myc-3’RR transgenic mice lead to the development of several mature B cell lymphomas including MCL. In this study we compare MCL transcriptomas of c-myc-3'RR/Cdk4R24C mice and c-myc-3'RR/p53+/- mice.
Project description:Mantle cell lymphoma (MCL) is a B cell malignancy characterized by a monoclonal proliferation of lymphocytes with co-expression of CD5, CD43 but not CD23. We have developed two murine models of MCL-like lymphoma. Breeding Cdk4R24C mice (a knock-in strain that express a Cdk4 protein resistant to inhibition by p16INK4a and other INK4 family members) with c-myc-3’RR transgenic mice (prone to develop aggressive Burkitt lymphoma-like lymphoma) leads in c-myc/Cdk4R24C mice to development of clonal blastoid MCL-like lymphoma. Breeding p53+/- mice with c-myc-3’RR transgenic mice lead to the development of several mature B cell lymphomas including MCL. In this study we compare MCL transcriptomas of c-myc-3'RR/Cdk4R24C mice and c-myc-3'RR/p53+/- mice. B splenocytes from 2 c-myc/Cdk4R24C lymphoma mice and 2 c-myc-3'RR/p53+/- mice were investigated
Project description:Most individuals infected with Mycobacterium tuberculosis can control the infection by forming and maintaining TB granulomas at the local infection foci. However, when the chronic infection (also known as latency) becomes active, the caseous center of TB granuloma enlarges, and it liquefies and cavitates, ultimately releasing bacilli into airway. Deciphering how genes are regulated within TB granulomas will help to understand the granuloma biology. Therefore, we performed genome-wide microarray on caseous human pulmonary TB granulomas and compared with normal lung tissues.
Project description:In this study, we used zebrafish embryos as a model system to investigate the toxic effects of MC-RR on early development and try to elucidate the underlying developmental toxicological mechanisms in a global view at posttranscriptional level. Altered expression pattern of miRNAs in embryos treated with MC-RR was detected by miRNA microarray.