Octreotide in the Prevention of Diarrhea in Patients Receiving Irinotecan for Metastatic Colon Cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Diarrhea,Colorectal Cancer,Colorectal Neoplasms
PROVIDER: 2005313 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Previous studies have shown that treatment with the somatostatin analogue octreotide LAR causes regression of gastric ECL-cell carcinoids in patients with hypergastrinaemia due to chronic atrophic gastritis, reducing both the number and size of tumours. The main objective of the present study was to examine the molecular mechanisms behind the antiproliferative effect of octreotide in the oxyntic mucosa on a genome wide scale. Female Sprague-Dawley rats were dosed with octreotide LAR and control group were given the LAR vehicle for 21 days. Serum gastrin levels were measured and tissue samples for histology and RNA extraction collected from the oxyntic mucosa. Histomorphological examination showed a significant decrease in the number of gastric glands, cells per gland and length of glands, indicating a negative effect of octreotide on growth of the oxyntic mucosa. Further immunohistochemical studies showed a tendency towards increased apoptosis and decreased proliferation in the group receiving octreotide. Affymetrix GeneChip microarrays were used to detect differentially expressed genes. Many regulated genes could be related to regulation of apoptosis, fewer to proliferation, and the largest group of regulated genes was transcriptional factors several of which may be involved in regulation of growth. Control studies using quantitative real-time RT-PCR showed a high degree of consistency of the microarray results. In conclusion, octreotide exerts a negative effect on growth of the oxyntic mucosa, and extensive gene expression changes relevant to growth regulation can be detected. Keywords: regulation, proliferation, Affymetrix GeneChip, qRT-PCR, immunohistochemistry.
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Project description:Previous studies have shown that treatment with the somatostatin analogue octreotide LAR causes regression of gastric ECL-cell carcinoids in patients with hypergastrinaemia due to chronic atrophic gastritis, reducing both the number and size of tumours. The main objective of the present study was to examine the molecular mechanisms behind the antiproliferative effect of octreotide in the oxyntic mucosa on a genome wide scale. Female Sprague-Dawley rats were dosed with octreotide LAR and control group were given the LAR vehicle for 21 days. Serum gastrin levels were measured and tissue samples for histology and RNA extraction collected from the oxyntic mucosa. Histomorphological examination showed a significant decrease in the number of gastric glands, cells per gland and length of glands, indicating a negative effect of octreotide on growth of the oxyntic mucosa. Further immunohistochemical studies showed a tendency towards increased apoptosis and decreased proliferation in the group receiving octreotide. Affymetrix GeneChip microarrays were used to detect differentially expressed genes. Many regulated genes could be related to regulation of apoptosis, fewer to proliferation, and the largest group of regulated genes was transcriptional factors several of which may be involved in regulation of growth. Control studies using quantitative real-time RT-PCR showed a high degree of consistency of the microarray results. In conclusion, octreotide exerts a negative effect on growth of the oxyntic mucosa, and extensive gene expression changes relevant to growth regulation can be detected. Experiment Overall Design: RNA from eigth animals (controls that received the LAR-vehicle) were pooled to produce a control affymetrix chip. Six animals (treatmentgroup) were given octreotide LAR and RNA from two and two animals were pooled to produce three affymetrix chips for comparison to the controlchip.
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