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M12-28: MRX34 Biomarker study in animals bearing HuH7 orthotopic liver tumors [Affymetrix]

ABSTRACT: To identify direct tumor mRNA targets of miR-34a, tumor RNAs isolated from whole tumors from animals treated with negative control and MRX34 HuH7 cells were surgically implanted into the livers of Nod/Scid mice and allow to grow for multiple weeks. Once serum AFP levels reached levels consistent with tumor growth of ~80-100 mg, animals were subjected to a single IV injection of MRX34. Twenty-four hours later animals were sacrificed, tumors resected and RNA isolated for subsequent microarray analysis.

ORGANISM(S): Homo sapiens

SUBMITTER: Christopher Daige

PROVIDER: E-GEOD-58800 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Systemic delivery of a miR34a mimic as a potential therapeutic for liver cancer.

Daige Christopher L CL Wiggins Jason F JF Priddy Leslie L Nelligan-Davis Terri T Zhao Jane J Brown David D

Molecular cancer therapeutics 20140722 10

miR34a is a tumor-suppressor miRNA that functions within the p53 pathway to regulate cell-cycle progression and apoptosis. With apparent roles in metastasis and cancer stem cell development, miR34a provides an interesting opportunity for therapeutic development. A mimic of miR34a was complexed with an amphoteric liposomal formulation and tested in two different orthotopic models of liver cancer. Systemic dosing of the formulated miR34a mimic increased the levels of miR34a in tumors by approximat ...[more]

PMID: 25053820

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MRX34 Biomarker study in animals bearing Hep3B orthotopic liver tumors

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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M12-8: MRX34 Biomarker study in animals bearing Hep3B orthotopic liver tumors [Illumina]

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Regulation of dendritic cell genes by alpha fetoprotein

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siRNA Administration Against AFP Inhibits Hepatocellular Carcinoma Proliferation in Vitro and Progression in Mice

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M12-8: MRX34 Biomarker study in animals bearing Hep3B orthotopic liver tumors [Illumina]

Project description:To identify direct tumor mRNA targets of miR-34a, tumor RNAs isolated from whole tumors from animals treated with negative control and MRX34

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M12-28: MRX34 Biomarker study in animals bearing HuH7 orthotopic liver tumors [Affymetrix]

Project description:To identify direct tumor mRNA targets of miR-34a, tumor RNAs isolated from whole tumors from animals treated with negative control and MRX34

2014-11-05 | GSE58800 | GEO

siRNA Administration Against AFP Inhibits Hepatocellular Carcinoma Proliferation in Vitro and Progression in Mice

Project description:Increased ?-fetoprotein (AFP) levels have been reported to predict a poor prognosis in hepatocellular carcinoma (HCC). We assessed the mechanism of AFP involvement in the progression of HCC and determined whether AFP could be a molecular target. We used human HCC cell lines to assess proliferation and apoptosis response to exogenous AFP. We introduced AFP small interfering RNA (siRNA) into HCC cell lines to examine whether it could inhibit cell proliferation and anti-apoptotic properties. The effects of systemically introduced AFP siRNA were assessed using a tumor xenotransplantation model. The effects of AFP on gene expression in HCC cell lines and human HCC specimens were examined. Exogenous AFP induced cell proliferation dose-dependently and inhibited apoptosis induced by 5-fluorouracil (5-FU) in all cell lines examined. AFP siRNA inhibited the proliferation of AFP-producing HCC cell lines and induced apoptosis in co-cultures with 5-FU. Tumor sizes in mice treated with AFP siRNA were significantly smaller than those in controls. AFP siRNA administration in mice induced a low proliferation index and a high apoptosis index in tumors. cDNA microarray analysis, reverse transcription-polymerase chain reaction (RT-PCR), and Western blot using HepG2 and HLE cells with AFP showed that AFP reduced expression of genes related to apoptosis (DFFB) and tumor suppression (NDRG2). Expression of these molecules was also suppressed in human HCC tissues that overexpress AFP. AFP is not only a passive tumor marker, but also an active tumor stimulator through several mechanisms. AFP siRNA introduction may be of possible therapeutic use for HCC. Keywords: Genetic modification Two-condition experiment, Control vs. AFP-stimulated cells.

2008-12-30 | E-GEOD-12307 | biostudies-arrayexpress

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2016-01-08 | E-GEOD-76628 | biostudies-arrayexpress

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