Crosstalk between Medulloblastoma Cells and Endothelium Triggers a Strong Chemotactic Signal Recruiting T Lymphocytes to the Tumor Microenvironment

Cancer cells can live and grow if they succeed in creating a favorable niche that often includes elements from the immune system. While T lymphocytes play an important role in the host response to tumor growth, the mechanism of their trafficking to the tumor remains poorly understood. We show here that T lymphocytes consistently infiltrate the primary brain cancer, medulloblastoma. We demonstrate, both in vitro and in vivo, that these T lymphocytes are attracted to tumor deposits only after the tumor cells have interacted with tumor vascular endothelium. Macrophage Migration Inhibitory Factor (MIF)” is the key chemokine molecule secreted by tumor cells which induces the tumor vascular endothelial cells to secrete the potent T lymphocyte attractant “Regulated upon Activation, Normal T-cell Expressed, and Secreted (RANTES).” This in turn creates a chemotactic gradient for RANTES-receptor bearing T lymphocytes. Manipulation of this pathway could have important therapeutic implications

Co-Depletion of Cathepsin B and uPAR Induces G0/G1 Arrest in Glioma via FOXO3a Mediated p27Kip1 Upregulation

Cathepsin B and urokinase plasminogen activator receptor (uPAR) are both known to be overexpressed in gliomas. Our previous work and that of others strongly suggest a relationship between the infiltrative phenotype of glioma and the expression of cathepsin B and uPAR. Though their role in migration and adhesion are well studied the effect of these molecules on cell cycle progression has not been thoroughly examined.Cathepsin B and uPAR single and bicistronic siRNA plasmids were used to downregulate these molecules in SNB19 and U251 glioma cells. FACS analysis and BrdU incorporation assay demonstrated G0/G1 arrest and decreased proliferation with the treatments, respectively. Immunoblot and immunocyto analysis demonstrated increased expression of p27(Kip1) and its nuclear localization with the knockdown of cathepsin B and uPAR. These effects could be mediated by alphaVbeta3/PI3K/AKT/FOXO pathway as observed by the decreased alphaVbeta3 expression, PI3K and AKT phosphorylation accompanied by elevated FOXO3a levels. These results were further confirmed with the increased expression of p27(Kip1) and FOXO3a when treated with Ly294002 (10 microM) and increased luciferase expression with the siRNA and Ly294002 treatments when the FOXO binding promoter region of p27(Kip1) was used. Our treatment also reduced the expression of cyclin D1, cyclin D2, p-Rb and cyclin E while the expression of Cdk2 was unaffected. Of note, the Cdk2-cyclin E complex formation was reduced significantly.Our study indicates that cathepsin B and uPAR knockdown induces G0/G1 arrest by modulating the PI3K/AKT signaling pathway and further increases expression of p27(Kip1) accompanied by the binding of FOXO3a to its promoter. Taken together, our findings provide molecular mechanism for the G0/G1 arrest induced by the downregulation of cathepsin B and uPAR in SNB19 and U251 glioma cells

Major prospects for exploring canine vector borne diseases and novel intervention methods using 'omic technologies

Canine vector-borne diseases (CVBDs) are of major socioeconomic importance worldwide. Although many studies have provided insights into CVBDs, there has been limited exploration of fundamental molecular aspects of most pathogens, their vectors, pathogen-host relationships and disease and drug resistance using advanced, 'omic technologies. The aim of the present article is to take a prospective view of the impact that next-generation, 'omics technologies could have, with an emphasis on describing the principles of transcriptomic/genomic sequencing as well as bioinformatic technologies and their implications in both fundamental and applied areas of CVBD research. Tackling key biological questions employing these technologies will provide a 'systems biology' context and could lead to radically new intervention and management strategies against CVBDs

<i style="">Tacca leontopetaloides</i> (Linn.) O. Kuntze (Taccaceae) – A new record to the flora of Rajasthan

512-514Tacca leontopetaloides (Linn.) O. Kuntze (Family-Taccaceae) is first time collected from Sitamata Wildlife Sanctuary in southern Rajasthan. Morphological features, time of flowering and fruiting, ecological notes and illustrations of this species have been provided. No other genus of the family is recorded from Rajasthan, hence, it is a new record of this family and genus both

<i>Senna uniflora </i>(Mill.) Irwin & Barneby (Caesalpiniaceae)ó A new record for Rajasthan

525-527Senna uniflora (Mill.) Irwin & Barneby belonging to the family Caesalpiniaceae has been recorded for the first time from Mangrol and Laxmipura villages, 24km away in the South East of Chittorgarh, Rajasthan. The specimens were found growing along road sides intermingled with Senna tora (Linn.) Roxb. Morphological features, time of flowering-fruiting, ecological notes and key characters of this species have been reported in present paper

Some traditional ethnomedicinal plants of southern Rajasthan

471-474 An extensive survey of southern part of Rajasthan including Chittorgarh, Udaipur, Banswara and Dungarpur districts was made to document the traditional knowledge of medicinal plants used by tribal communities. Tribals like Bhil, Damor, Garasia, Kalbelia, Kathodia and Meena are residing in this area. These people and their medicine men and women have valuable information about properties and medicinal uses of plants. An attempt has been made to document the ethnomedicinal plants being used traditionally by the tribals with their local name, methods of administration and precautions. Information on 31 species, belonging to 31 genera and 22 families has been presented. </smarttagtype

Some ethnomedicinal plants used by the <i>Garasia</i> tribe of district Sirohi, Rajasthan

354-357The paper enumerates the ethnomedicinal uses of 35 plant species belonging to 34 genera and 27 families used by the Garasia tribe of Sirohi district in Rajasthan. Information on the medicinal uses gathered from the tribals together with their botanical identity, local name and mode of administration are presented

Some ethnomedicinal plants of Southern Rajasthan

169-172 An extensive survey of southern part of Rajasthan, which includes Chittorgarh, Udaipur, Banswara and Dungarpur districts was made to document the traditional knowledge of medicinal plants used by tribal communities.Tribals like Bhil, Damor, Garasia, Kalbelia, Kathodia and Meena are residing in the area. These people and their medicine men and women have valuable information about properties and medicinal uses of plants. In the paper, an attempt has been made to document 31 plant species, belonging to 31 genera and 22 families being used traditionally by the tribals. </smarttagtype