Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009402 (colorectal cancer)
 53,228 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To define the influence of weight loss on the severity of metabolic abnormalities in patients with the same stage and primary site of cancer, hepatic glucose production (HGP) and nutritional status were determined in 44 patients with advanced, Stage D colorectal carcinoma and compared to values in seven cancer-free controls. The colorectal cancer patients were divided into three groups based upon percentage of ideal body weight. HGP was determined in all participants after an overnight fast by using a 3- or 4-h primed, continuous infusion of [6-3H]glucose. Fasting glucose, insulin, cortisol, thyroxine, triiodothyronine, and growth hormone values were also determined. Mean HGP was significantly elevated in colorectal carcinoma patients versus normal subjects (2.35 +/- 0.89 (SD) mg/kg/min versus 1.75 +/- 0.16; P less than 0.01). The most severely malnourished group (ideal body weight less than 90%) demonstrated the greatest increase in HGP (2.98 +/- 0.73 mg/kg/min). Growth hormone mean fasting levels were significantly elevated in the colorectal carcinoma population compared to the normal subjects (2.9 +/- 3.1 ng/ml versus 0.5 +/- 0.2; P less than 0.001). The most severely malnourished group also demonstrated the highest growth hormone levels. The rate of HGP was significantly correlated with fasting growth hormone levels (r = 0.71; P less than 0.001) and not significantly correlated to cortisol, insulin, thyroxine, triiodothyronine, or glucose levels in carcinoma patients. Thus, the elevation in HGP seen in patients with colorectal carcinoma is related to the severity of weight loss and is associated with elevations in fasting growth hormone.
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PMID:Relationship of hepatic glucose production to growth hormone and severity of malnutrition in a population with colorectal carcinoma. 231 2

Growth hormone (GH) is indispensable for the growth of animals and its biological activity is mediated by binding to the growth hormone receptor (GHR) [Harvey S, Scanes CG, Daughaday WH. Growth hormone. Boca Raton: CRC Press; 1995]. GHR is a transmembrane protein responsible for signal transduction upon GH binding. GH also binds to the growth hormone binding protein (GHBP) which is the soluble form of GHR extracellular domain existing in circulation. Actions of GHBP include prolongation of GH bioavailability and prevention of GH signaling system from over-stimulation. To date, little is known about the mechanisms generating the chicken GHBP (cGHBP). Elucidating the genomic structure of cGHR will provide insights into such underlying mechanisms. Using polymerase chain reaction and library screening methods, we have characterized the genomic organization of chicken GHR (cGHR). The full-length coding region of the cGHR transcript is composed of eight exons (exons 2-10), lacking a human homolog exon 3 and spans at least 71 kb on the genome. A novel transcript of size 1.2kb was isolated from chicken liver total RNA using 5' and 3' rapid cDNA ends amplification (RACE). It was generated by utilizing a previously unknown polyadenylation signal located at the intron 6. Semi-quantitative reverse transcription polymerase chain reaction showed that this transcript is widely expressed in a variety of tissues. This transcript has an open reading frame comprising 203 amino acids. In vitro binding assay using ELISA demonstrated that Escherichia coli expressed recombinant protein encoded by this transcript was able to bind with chicken GH. Hence, this transcript is a potential candidate for cGHBP.
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PMID:Cloning and characterization of chicken growth hormone binding protein (cGHBP). 1681 75

Growth hormone releasing hormone (GHRH) from hypothalamus nominatively stimulates growth hormone release from adenohypophysis. GHRH is also produced by cancers, acting as an autocrine/paracrine growth factor. This growth factor function is seen in lymphoma, melanoma, colorectal, liver, lung, breast, prostate, kidney, bladder cancers. Pituitary type GHRH receptors and their splice variants are also expressed in these malignancies. Synthetic antagonists of the GHRH receptor inhibit proliferation of cancers. Besides direct inhibitory effects on tumors, GHRH antagonists also enhance cytotoxic chemotherapy. GHRH antagonists potentiate docetaxel effects on growth of H460 non-small cell lung cancer (NSCLC) and MX-1 breast cancer plus suppressive action of doxorubicin on MX-1 and HCC1806 breast cancer. We investigated mechanisms of antagonists on tumor growth, inflammatory signaling, doxorubicin response, expression of drug resistance genes, and efflux pump function. Triple negative breast cancer cell xenografted into nude mice were treated with GHRH antagonist, doxorubicin, or their combination. The combination reduced tumor growth, inflammatory gene expression, drug-resistance gene expression, cancer stem-cell marker expression, and efflux-pump function. Thus, antagonists increased the efficacy of doxorubicin in HCC1806 and MX-1 tumors. Growth inhibition of H460 NSCLC by GHRH antagonists induced marked downregulation in expression of prosurvival proteins K-Ras, COX-2, and pAKT. In HT-29, HCT-116 and HCT-15 colorectal cancer lines, GHRH antagonist treatment caused cellular arrest in S-phase of cell cycle, potentiated inhibition of in vitro proliferation and in vivo growth produced by S-phase specific cytotoxic agents, 5-FU, irinotecan and cisplatin. This enhancement of cytotoxic therapy by GHRH antagonists should have clinical applications.
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PMID:Potentiating effects of GHRH analogs on the response to chemotherapy. 2564 97