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Safety of GM-CT-01 With and Without 5-Fluorouracil in Patients With Solid Tumors

ABSTRACT: This is a Phase I, multi-center study of GM-CT-01, which has been shown to increase the anti-tumor activity of 5-fluorouracil in mice. The primary reason for doing the study is to determine the safety of GM-CT-01 given alone and in combination with therapeutical dosage of 5-Fluorouracil, in patients who have advanced cancer that can be measured by CT scan.

DISEASE(S): Lung Cancer,Colorectal Cancer,Prostate Cancer,Head And Neck Neoplasms,Head And Neck Cancer,Breast Cancer,Cancer

PROVIDER: 2008862 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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GM-CT-01 Plus 5-Fluorouracil as Third- or Fourth-Line Therapy for Metastatic Colorectal Cancer

Project description:This is a Phase II, multi-center study of GM-CT-01 which has been shown to increase the anti-tumor activity of 5-fluorouracil (5-FU) in mice. 5-FU is a chemotherapy drug commonly used in cancer patients. In this Phase II study, patients with colon cancer which has spread, despite treatment with approved therapies, will receive GM-CT-01 plus 5-FU in monthly cycles for at least 2 cycles or until their disease progresses.

| 2012793 | ecrin-mdr-crc

NK cell-derived GM-CSF is critical for enhancing pathological arthritis

Project description:GM-CSF is involved in immune complex (IC)-mediated arthritis. However, little is known about what is the cellular source of GM-CSF and how it is regulated during IC-mediated inflammation. Using novel GM-CSF reporter mice, we show that NK cells produce GM-CSF during an IC-mediated model of inflammatory arthritis. NK cells promoted STIA in a GM-CSF-dependent manner, as deletion of NK cells and selective removal of GM-CSF production by NK cells abrogated disease. Furthermore, we show that myeloid cell activation by GM-CSF is restrained by induction of JAK/STAT checkpoint inhibitor cytokine-inducible SH2-containing protein, CIS. Myeloid cells from CIS-deficient mice had exaggerated responses to GM-CSF, and these mice develop exacerbated STIA. Our data suggest that tissue NK cells may amplify joint inflammation in arthritis via GM-CSF production and thus represent a novel target in IC-mediated pathology. Endogenous CIS provides a key brake on signaling through the GM-CSF receptor and strategies that boost its function may provide an alternative anti-inflammatory approach.

2020-02-19 | PXD012794 | Pride

Identification of genes modulate by MLS000408882-01 and MLS000573813-01 in lung cancer cells

Project description:MLS000408882-01 and MLS000573813-01 were identified through a cell based screen that measures the reactivation of an epigenetically silenced transgene. MLS000408882-01 and MLS000573813-01 shows selectivity for cancer vs. normal cells affecting both transcriptional patterns and cell viability in a cancer specific manner.

2017-02-09 | GSE59077 | GEO

The gene expression upon dominant negative form of GAS2 (GAS2DN) in MEG-01 cells

Project description:GAS2DN could suppress the growth of chronic myeloid leukemia cells, including K562, MEG-01 and CD34+ cells from patients. In addition, GAS2DN inhibited the tumorigenic ability of MEG-01 cells in nude mice. To understand the molecular insight of this inhibitory effect of GAS2DN, global gene expression were performed. The control and GAS2DN-transduced MEG-01 cells were used for microarray analysis.

2013-07-25 | GSE49184 | GEO

Effect of ER-464195-01 on the gene expression in the intestine of mice.

Project description:Our previous study identified a small molecule, orally active ER-464195-01, inhibits the calreticulin binding to alpha integrins, and clearly suppresses the adherence ability of leukocytes. Our transcriptome analysis with the colon of dextran sodium sulfate (DSS)-treated mice reveals that the increased expression of pro-inflammatory genes was down-regulated by ER-464195-01. Male Balb/c mice (7 weeks) were allowed free access to distilled water (Otsuka Pharmaceutical). ER-464195-01 (10 mg/kg) or vehicle was orally administered once per day for 6 days.

2018-04-11 | GSE109728 | GEO

Furfurilactobacillus rossiae strain:DSM 15814T, GM-S1_998, GM-S2_998, GM-S3_998

Project description:Furfurilactobacillus rossiae strain:DSM 15814T, GM-S1_998, GM-S2_998, GM-S3_998 Genome sequencing and assembly

| PRJNA531157 | ENA

ER-464195-01 regulates the expression of inflammation-related genes in DSS-treated mice

Project description:We identified a small molecule, orally active ER-464195-01, inhibits the calreticulin binding to alpha integrins, and clearly suppresses the adherence ability of leukocytes. Our transcriptome analysis with the colon of dextran sodium sulfate (DSS)-treated mice reveals that the increased expression of pro-inflammatory genes was down-regulated by ER-464195-01. Purpose: To gain insight into the molecular mechanisms underlying the prevention of DSS-induced colitis conferred by treatment of ER-464195-01, we performed a comprehensive analysis of ER-464195-01-mediated gene expression changes in DSS-induced colitis using RNA sequencing (RNA-Seq). Methods: Male Balb/c mice (7 weeks) were allowed free access to distilled water (Otsuka Pharmaceutical) containing 2% DSS (molecular weight: 36,000–50,000; ICN Biomedicals) for 6 days to induce colitis. ER-464195-01 (10 mg/kg) or vehicle was orally administered once per day for 6 days. Results: To investigate differentially expressed genes (false discovery rate (FDR) p<0.05, fold change >2) among three groups, we performed pairwise comparisons of RNA-Seq data using the CLC Genomics Workbench software. In comparison with the control, 5,570 (3,483 up- and 2,087 down-regulated) unique genes were significantly changed in the DSS-induced colitis group. Meanwhile, the data set of DSS-induced colitis with ER-464195-01 groups revealed significant changes in 1,808 (837 up- and 971 down-regulated) genes as compared with DSS alone. Notably, of 3,483 genes up-regulated by the DSS treatment, 894 transcripts of which were overlapped with 971 genes down-regulated genes by ER-464195-01.

2018-04-11 | GSE98407 | GEO

Priestia megaterium strain:GM-4 | isolate:GM-4

Project description:Priestia megaterium strain:GM-4 | isolate:GM-4 Genome sequencing

| PRJNA1192332 | ENA

Gene expression profiling of mature dendritic cells from mice s. c. treated with GM-CSF-gene transduced LLC cells (LLC/SeV/GM) or control cells (LLC, LLC/SeV/GFP)

Project description:Irradiated granulocyte macrophage-colony stimulating factor (GM-CSF)-transduced autologous tumor cells induce substantial antitumor immunity through the maturation and migration of dendritic cells (DCs). However, little is known about the key molecules involved in GM-CSF-sensitized DCs (GM-DCs) in tumor draining lymph nodes (TDLNs). We initially confirmed that mice subcutaneously injected with poorly immunogenic syngeneic Lewis lung carcinoma (LLC) cells transduced with Sendai virus encoding GM-CSF (LLC/SeV/GM) significantly rejected the tumor growth. Using microarray expression profiling, we obtained a large number of gene expression data files from GM-DCs and control DCs in TDLNs, and subjected them to network-based cluster analysis and unexpectedly unraveled the expression levels of type I IFNs-related genes specifically expressed in plasmacytoid DCs (pDC) were robustly up-regulated in GM-DCs. In vivo depletion assay showed that pDC-depleted mice treated with subcutaneous LLC/SeV/GM cells abrogated the antitumor effects observed in control mice. Moreover combination use of imiquimod for TLR7 triggering on pDC with irradiated LLC/SeV/GM cells induced a significant therapeutic antitumor effect with marked induction of CD9+ pDC with antitumor phenotype, whereas other control mice groups had only minimal to-modest antitumor responses, implicating that this combined vaccine strategy using imiquimod could be promising for improvement of GM-CSF-induced antitumor immunity.

2013-09-30 | GSE43169 | GEO

Proteomic analysis of GM-CSF and M-CSF polarized bone marrow derived macrophages

Project description:Bone marrow cells were isolated, primed with M-CSF (M-BMDM) or GM-CSF (GM-BMDM) and cultured for 7 days. The proteomic difference between GM-BMDM and M-BMDM were analyzed to describe the phenotye and function of two types of macrophages.

2023-03-29 | PXD041180 |

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