9 research outputs found
Role of SLIT2 in the Activation of Breast Cancer-Associated Fibroblasts
Cancer-associated fibroblasts (CAF) are stromal cells that have been shown to regulate invasion and metastasis in various cancers including breast cancer. However, the molecular mechanism in breast cancer is not known. This project aims to analyze the role of tumor suppressor SLIT2 in regulating CAF differentiation in breast cancer. The level of SLIT2 mRNA was analyzed in human normal epithelial and breast adenocarcinoma cells by RT-PCR. SLIT2 protein expression in normal breast epithelial cells versus fibroblasts was compared by Western Blot technique. Results showed that SLIT2 mRNA is downregulated in breast adenocarcinoma cells compared to normal breast epithelial cells. Similarly, SLIT2 is overexpressed in normal fibroblasts versus normal epithelial cells. In addition, fibroblast cells were treated with conditioned media obtained from breast adenocarcinoma cells to induce myofibroblasts differentiation. SLIT2 and α-SMA (myofibroblasts marker) mRNA expression in myofibroblasts and fibroblasts was analyzed by RT-PCR. Results showed that the breast adenocarcinoma cell conditioned media enhanced α-SMA and downregulated SLIT2 in myofibroblasts. SLIT2 expression in patient samples was extracted from publicly available datasets (Oncomine and CBioportal). SLIT2 is significantly downregulated among invasive cancers. SLIT2 alterations were also investigated and compared to survival outcomes. Alteration(s) in SLIT2 gene and transcription correlates to lower survival compared to breast cancer patients without SLIT2 alterations. This study suggests use of CAF-secreted factors as a tool to develop novel strategy for targeting breast cancer cells. Complete understanding of the cell signaling mechanism between breast adenocarcinoma cells and cancer-associated fibroblasts could be utilized to develop therapeutic agents against breast cancer.ASC Undergraduate Research Scholarship AwardA five-year embargo was granted for this item.Academic Major: BiochemistryAcademic Major: Molecular Genetic
The Endosymbiotic relationship of Leguminosae (Fabaceae) and Rhizobium
This project will look at The Endosymbiotic Relationship of Leguminosae (Fabaceae) and Rizobioum. Endoysmbiosis Theory is the concept that mitochondria and chloroplasts are the result of years of evolution initiated by the endocytosis, (the process by which cells absorb material through their cell membrane) of bacteria and algae which, instead of becoming digested, became symbiotic.The mitochondria of eukaryotes evolved from aerobic bacteria, probably rickettsias, living within their host cell and the chloroplasts from cyanobacteria, also known as blue-green algae. Endoysmbiosis is a type of symbiosis in which one organism lives inside the body of another and both function as a single organism. comes from a Greek word meaning inside, with, and living. Endosymbiosis in biology is a subdivision of the more general concept, symbiosis, which refers to living beings of different species living together for most of the life history of a member of at least one of those species. *Rickettsia bacteria cause diseases such as typhus and Rocky Mt Spotted Fever.
Novel thermophilic cellulolytic isolates belonging to the phylum Chloroflexi
Current biofuel technologies utilize valuable foodstuffs, such as corn kernels and cane sugar, as sources of easily metabolized sugars. Microbes are used to ferment these sugars into bioethanol, a first-generation biofuel. However, in order to avoid diverting foodstuffs from the food supply, the development of second-generation biofuels technology is necessary. Second-generation biofuels are produced by converting structurally complex lignocellulosic biomass, such as agricultural and municipal wastes, to fermentable sugars or directly to biofuels.
The major technological hurdle limiting the mass production of second-generation biofuels is the difficulty in efficiently converting structurally complex lignocellulosic materials to fermentable sugars or directly to biofuels. The discovery of novel thermophilic microorganisms and enzymes that have high activities or broad substrate ranges on plant polymers addresses this challenge
Immune-checkpoint expression in Epstein-Barr virus positive and negative plasmablastic lymphoma: a clinical and pathological study in 82 patients
International audiencePlasmablastic lymphoma is a rare and aggressive diffuse large B-cell lymphoma commonly associated with Epstein-Barr virus co-infection that most often occurs in the context of human immunodeficiency virus infection. Therefore, its immune escape strategy may involve the upregulation of immune-checkpoint proteins allowing the tumor immune evasion. However, the expression of these molecules was poorly studied in this lymphoma. We have investigated 82 plasmablastic lymphoma cases of whom half were Epstein-Barr virus positive. Although they harbored similar pathological features, Epstein-Barr virus positive plasmablastic lymphomas showed a significant increase in MYC gene rearrangement and had a better 2-year event-free survival than Epstein-Barr virus negative cases (P=0.049). Immunostains for programmed cell death-1, programmed cell death-ligand 1, indole 2,3-dioxygenase and dendritic cell specific C-type lectin showed a high or moderate expression by the microenvironment cells in 60%–72% of cases, whereas CD163 was expressed in almost all cases. Tumor cells also expressed programmed cell death-1 and its ligand in 22.5% and 5% of cases, respectively. Both Epstein-Barr virus positive and negative plasmablastic lymphomas exhibited a high immune-checkpoint score showing that it involves several pathways of immune escape. However, Epstein-Barr virus positive lymphomas exhibited a higher expression of programmed cell death-1 and its ligand in both malignant cells and microenvironment as compared to Epstein-Barr virus negative cases. In conclusion, plasmablastic lymphoma expresses immune-checkpoint proteins through both malignant cells and the tumor microenvironment. The expression of programmed cell death-1 and its ligand constitutes a strong rationale for testing monoclonal antibodies in this often chemoresistant disease
Gut-resident CX3CR1hi macrophages induce tertiary lymphoid structures and IgA response in situ
Intestinal mononuclear phagocytes (MPs) are composed of heterogeneous dendritic cell (DC) and macrophage subsets necessary for the initiation of immune response and control of inflammation. Although MPs in the normal intestine have been extensively studied, the heterogeneity and function of inflammatory MPs remain poorly defined. We performed phenotypical, transcriptional, and functional analyses of inflammatory MPs in infectious Salmonella colitis and identified CX3CR1(+) MPs as the most prevalent inflammatory cell type. CX3CR1(+) MPs were further divided into three distinct populations, namely, Nos(2+)CX3CR1(lo), Ccr(7+)CX3CR1(int) (lymph migratory), and Cxcl(13+)CX3CR1(hi) (mucosa resident), all of which were transcriptionally aligned with macrophages and derived from monocytes. In follow-up experiments in vivo, intestinal CX3CR1(+) macrophages were superior to conventional DC1 (cDC1) and cDC2 in inducing Salmonella-specific mucosal IgA. We next examined spatial organization of the immune response induced by CX3CR1(+) macrophage subsets and identified mucosa-resident Cxcl73(+) CX3CR1(hi) macrophages as the antigen-presenting cells responsible for recruitment and activation of CD4(+) T and B cells to the sites of Salmonella invasion, followed by tertiary lymphoid structure formation and the local pathogen-specific IgA response. Using mice we developed with a floxed Ccr7 allele, we showed that this local IgA response developed independently of migration of the Ccr7(+)CX3CR1(int) population to the mesenteric lymph nodes and contributed to the total mucosal IgA response to infection. The differential activity of intestinal macrophage subsets in promoting mucosal IgA responses should be considered in the development of vaccines to prevent Salmonella infection and in the design of anti-inflammatory therapies aimed at modulating macrophage function in inflammatory bowel disease
Kallotenue papyrolyticum gen. nov., sp. nov., a cellulolytic and filamentous thermophile that represents a novel lineage (Kallotenuales ord. nov., Kallotenuaceae fam. nov.) within the class Chloroflexia
Rhesus iPSC Safe Harbor Gene-Editing Platform for Stable Expression of Transgenes in Differentiated Cells of All Germ Layers
A multiprotein supercomplex controlling oncogenic signalling in lymphoma
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