Expression profile of 58As9 cells upon PLEKHA5 knockdown
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE163063 | GEO | 2020/12/12
REPOSITORIES: GEO
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Project description:Peritoneal carcinomatosis is a frequent finding in patients with primary gastric cancer, and it is associated with a poor prognosis. A major mechanism in peritoneal carcinomatosis is the dissemination of cancer cells into the abdominal cavity, mainly in diffuse gastric adenocarcinoma. The features that enable diffuse primary gastric tumours to develop peritoneal dissemination have been little investigated and are only incompletely understood. We therefore compared the gene expression profile in patients with diffuse primary gastric cancer with and without peritoneal carcinomatosis. Specimens from consecutive gastric cancer patients with and without peritoneal carcinomatosis were investigated using oligonucleotide microarrays. Keywords: Disease state analysis
2008-01-31 | GSE8657 | GEO
Project description:Although peritoneal dissemination is a major obstacle in treating diffuse-type GC patients, the mechanism is still unclear. To address this phenomenon from the viewpoint of molecular biology, we established a highly peritoneal-metastatic cell line, 60As6, from a diffuse-type GC derived cell line, HSC-60, through a six-times iterative in vivo selection consisting of an orthotopic inoculation of the tumor cells and the isolation of highly-metastatic ones from the ascites of immunodeficient mice. To assess the biological differences between HSC-60 and 60As6 cells, we compared gene expression profiles for both cell lines by microarray analysis. Down-regulation of three gastric pit cell differentiation markers and some cytokeratins were found in 60As6. By contrast, several stem cell markers were up-regulated in this cell line. The expression profile suggests that 60As6 has a strong mensencymal phenotype, which is a characteristic of epithelial cell-derived CSCs.
2014-12-31 | GSE53276 | GEO
Project description:Diffuse-type gastric carcinoma is a poor-prognostic cancer with high expression of transforming growth factor (TGF)-β and thick stromal fibrosis. However, detailed investigations on the roles of TGF-β signaling in diffuse-type gastric carcinoma have not been performed. We generated two diffuse-type gastric carcinoma cell lines, dominant-negative TGF-β type II receptor expressing cells (2MLN-dnTβRII) and GFP-expressing cells (2MLN-GFP). Cells were subcutaneously or orthotopically injected into nude mice. Although dnTβRII did not affect the growth of OCUM-2MLN in vitro, it accelerated the growth of subcutaneously or orthotopically transplanted tumors in vivo. By microarray analysis, we found gene expression of TSP-1, an angiogenic inhibitor, was down-regulated in dnTβRII tumors. This results suggested disruption of TGF-β signaling in diffuse-type gastric carcinoma cells leads to alteration of tumor microenvironment and acceleration of tumor growth. We generated two OCUM-2MLN-derived gastric carcinoma cell lines; 2MLN-dnTβRII, which expresses dominant negative form of TβRII, and control 2MLN-GFP, which expresses GFP. The transplanted tumors of these cell lines were subjected to gene expression analysis with Affymetrix U133 plus2 arrays.
2011-12-30 | E-GEOD-12336 | biostudies-arrayexpress
Project description:Diffuse-type gastric carcinoma is a poor-prognostic cancer with high expression of transforming growth factor (TGF)-β and thick stromal fibrosis. However, detailed investigations on the roles of TGF-β signaling in diffuse-type gastric carcinoma have not been performed. We generated two diffuse-type gastric carcinoma cell lines, dominant-negative TGF-β type II receptor expressing cells (2MLN-dnTβRII) and GFP-expressing cells (2MLN-GFP). Cells were subcutaneously or orthotopically injected into nude mice. Although dnTβRII did not affect the growth of OCUM-2MLN in vitro, it accelerated the growth of subcutaneously or orthotopically transplanted tumors in vivo. By microarray analysis, we found gene expression of TSP-1, an angiogenic inhibitor, was down-regulated in dnTβRII tumors. This results suggested disruption of TGF-β signaling in diffuse-type gastric carcinoma cells leads to alteration of tumor microenvironment and acceleration of tumor growth.
2011-12-30 | GSE12336 | GEO
Project description:High-grade serous ovarian carcinoma (HGSOC) typically remains undiagnosed until advanced stages when peritoneal dissemination has already occurred. Here, we sought to identify HGSOC-specific alterations in DNA methylation and assess their potential to provide sensitive and specific detection HGSOC at its earliest stages.
2020-08-06 | GSE155760 | GEO
Project description:Hepatocyte growth factor (HGF) signaling through its receptor Met has been implicated in hepatocellular carcinoma tumorigenesis and progression. Met interaction with integrins is shown to modulate the downstream signaling to Akt and ERK (extracellular-regulated kinase). In this study, we developed a mechanistically detailed systems biology model of HGF/Met signaling pathway that incorporated specific interactions with integrins to investigate the efficacy of integrin-binding peptide, AXT050, as monotherapy and in combination with other therapeutics targeting this pathway. Here we report that the modeled dynamics of the response to AXT050 revealed that receptor trafficking is sufficient to explain the effect of Met-integrin interactions on HGF signaling. Furthermore, the model predicted patient-specific synergy and antagonism of efficacy and potency for combination of AXT050 with sorafenib, cabozantinib, and rilotumumab. Overall, the model provides a valuable framework for studying the efficacy of drugs targeting receptor tyrosine kinase interaction with integrins, and identification of synergistic drug combinations for the patients.
Model is encoded by Johannes and submitted to BioModels by Ahmad Zyoud.
2020-03-20 | MODEL2003200001 | BioModels
Project description:Specificity protein 1 (SP1) is an essential transcription factor regulating multiple cancer-related genes. Since aberrant expression of SP1 was known to be related to cancer development and progression, we focused on SP1 expression in gastric carcinoma and its correlation with disease outcomes. We discovered a different relationship between SP1 expression and patient survival in intestinal- and diffuse-type gastric cancer. In diffuse-type gastric cancer, patient survival decreased as SP1 expression increased (P < 0.05) in accordance with previously published papers, whereas the lack of SP1 expression in intestinal-type gastric cancer was correlated significantly with poor survival (P < 0.05). When SP1 downregulation was forced in high SP1 expressor intestinal-type gastric cell line MKN28 with siRNA, both migration and invasion were increased but cell proliferation was decreased. In accordance with these results, microarray data in siRNA-transfected MKN28 showed that genes inhibiting migration were downregulated and the expression of genes negatively facilitating proliferation was increased. Both migration and invasion, however, in low SP1 expressor intestinal-type gastric cell line AGS were decreased by forced SP1 expression. In contrast to intestinal-type, in diffuse-type gastric cell line SNU484, high SP1 expressor, both migration and invasion were decreased by siRNA. Contrary to previous studies, which did not reflect differences between the 2 histological types, our results showed that low expression of SP1 is involved in cancer progression and metastasis, and has a different effect on intestinal-type compared to diffuse-type gastric adenocarcinoma. 2 samples for MKN28 cells: si-SP1 against si-control and dyeswap of it upon 72 hour
2012-01-01 | E-GEOD-34792 | biostudies-arrayexpress
Project description:Objective Cancer immunotherapy aims to unleash the immune system's potential against cancer cells, providing sustained relief for tumors responsive to immune checkpoint inhibitors (ICIs). While promising in gastric cancer (GC) trials, the efficacy of ICIs diminishes in the context of peritoneal dissemination. Our objective is to identify strategies to enhance the impact of ICI treatment specifically for cases involving peritoneal dissemination in GC. Design The therapeutic efficacy of anti-PD1, CTLA4 treatment alone, or in combination, was assessed using the YTN16 peritoneal dissemination tumor model mice. Peritoneum and peritoneal exudate cells were collected for subsequent analysis. Immunohistochemical staining, flow cytometry, and bulk RNA-sequence analyses were conducted to evaluate the tumor microenvironment (TME). A JAK inhibitor (JAKi) was introduced based on the pathway analysis results. Results Anti-PD1 and anti-CTLA4 combination treatment (dual ICI treatment) demonstrated therapeutic efficacy in certain mice, primarily mediated by CD8+ T cells. However, in mice resistant to dual ICI treatment, even with CD8+ T cell infiltration, most of the T cells exhibited exhaustion phenotype. Notably, resistant tumors displayed abnormal activation of the JAK-STAT pathway compared to the untreated group, with observed infiltration of macrophages, neutrophils, and Tregs in the TME. The concurrent administration of JAKi rescued CD8+ T cells function and reshaped the immunosuppressive TME, resulting in enhanced efficacy of the dual ICI treatment. Conclusion Dual ICI treatment exerts its anti-tumor effects by increasing tumor- specific CD8+ T cell infiltration, and the addition of JAKi further improves ICI resistant by reshaping the immunosuppressive TME.
2024-05-28 | GSE250238 | GEO
Project description:Gastric cancer, a leading cause of cancer related deaths, is a heterogeneous disease, with little consensus on molecular subclasses and their clinical relevance. We describe four molecular subtypes linked with distinct patterns of molecular alterations, disease progression and prognosis viz. a) Microsatellite Instable: hypermutated intestinal subtype tumors occurring in antrum, best overall prognosis, lower frequency of recurrence (22%), with liver metastasis in 23% of recurred cases b) Mesenchymal-like: diffuse tumors with worst prognosis, a tendency to occur at an earlier age and highest recurrence (63%) with peritoneal seeding in 64% of recurred cases, low frequency of molecular alterations c) TP53-inactive with TP53 loss, presence of focal amplifications and chromosomal instability d) TP53-active marked by EBV infection and PIK3CA mutations. The key molecular mechanisms and associated survival patterns are validated in multiple independent cohorts, to provide a consistent and unified framework for further preclinical and clinical research. ACRG Gastric cohort: microarray profiles from 300 gastric tumors from gastric cancer patients.
2015-04-17 | E-GEOD-62254 | biostudies-arrayexpress
Project description:Specificity protein 1 (SP1) is an essential transcription factor regulating multiple cancer-related genes. Since aberrant expression of SP1 was known to be related to cancer development and progression, we focused on SP1 expression in gastric carcinoma and its correlation with disease outcomes. We discovered a different relationship between SP1 expression and patient survival in intestinal- and diffuse-type gastric cancer. In diffuse-type gastric cancer, patient survival decreased as SP1 expression increased (P < 0.05) in accordance with previously published papers, whereas the lack of SP1 expression in intestinal-type gastric cancer was correlated significantly with poor survival (P < 0.05). When SP1 downregulation was forced in high SP1 expressor intestinal-type gastric cell line MKN28 with siRNA, both migration and invasion were increased but cell proliferation was decreased. In accordance with these results, microarray data in siRNA-transfected MKN28 showed that genes inhibiting migration were downregulated and the expression of genes negatively facilitating proliferation was increased. Both migration and invasion, however, in low SP1 expressor intestinal-type gastric cell line AGS were decreased by forced SP1 expression. In contrast to intestinal-type, in diffuse-type gastric cell line SNU484, high SP1 expressor, both migration and invasion were decreased by siRNA. Contrary to previous studies, which did not reflect differences between the 2 histological types, our results showed that low expression of SP1 is involved in cancer progression and metastasis, and has a different effect on intestinal-type compared to diffuse-type gastric adenocarcinoma.
2012-01-01 | GSE34792 | GEO