Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The MAC 16 is a transplantable murine carcinoma of the colon producing extensive weight loss in tumour-bearing animals. The weight loss is proportional to the size of the tumour and occurs without a reduction in food intake when compared with non tumour-bearing control mice. Weight loss produced by the MAC 16 tumour is accompanied by hypoglycaemia which becomes more extensive as the tumour mass increases. In order to understand the mechanism of the cachexia produced by the MAC 16 tumour the rate of substrate utilization and CO2 formation from both glucose and palmitate has been compared in vitro, with other colon carcinoma cell lines known not to produce cachexia as well as a range of murine and human tumour cell lines. The rate of glucose consumption, lactate production and CO2 formation from both glucose and palmitate is much higher for the MAC 16 than for the other tumour cells. For all cell lines in vitro the consumption of glucose exceeds that of palmitate by a factor of 10(3). Excessive consumption of glucose by the MAC 16 tumour may account for the hypoglycaemic effect on the host. The level of 3 oxo acid CoA transferase, an initiator of ketone body utilization, was found to be much lower in the MAC 16 tumour than non-involved colon. This suggests that the tumour may not be able to metabolize ketone bodies effectively.
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PMID:Metabolic substrate utilization by a tumour cell line which induces cachexia in vivo. 377 4

The antitumor activities of novel 1-[1-(4-aminobenzoyl)-2,3-dihydro-1H-indol-6-sulfonyl]-4-phenyl-imidazolidin-2-ones were studied to determine the potential of these compounds as antitumor candidates. The agents studied were: DW2143 (1-[1-(4-aminobenzoyl)-2,3-dihydro-1H-indol-6-sulfonyl]-4-phenyl-imidazolidin-2-one), a racemic mixture, and DW2282 [(4S)-1-[1-(4-aminobenzoyl)-2,3-dihydro-1H-indol-6-sulfonyl]-4-phenyl-imidazolidin-2-one], an S-isomer. DW2143 and DW2282 suppressed the in vitro growth of tumor cells at lower concentrations than doxorubicin, but tumor specificity was not observed between the compounds. These compounds when administered orally were not active in syngeneic models of murine Colon 26 adenocarcinoma and L1210 leukemia. However, DW2143 suppressed the growth of SW620 (human colon cancer) and NCI-H23 (human lung cancer) cells in nude mice, inhibiting tumor growth by 87 and 67%, respectively. DW2282 was a more potent inhibitor of SW620 tumor cell growth in nude mice and was also lower in toxicity than DW2143. Moreover, DW2282 did not produce a series of toxic symptoms caused by the aniline metabolites of sulfonylureas, including hypoglycemia. These results suggest that DW2282, an S-isomer, could be a novel antitumor candidate with higher specificity and lower toxicity than other orally active sulfonylureas.
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PMID:A novel stereo-selective sulfonylurea, 1-[1-(4-aminobenzoyl)-2,3-dihydro-1H-indol-6-sulfonyl]-4-phenyl-imidazolidin-2-one, has antitumor efficacy in in vitro and in vivo tumor models. 1214 99

We review the case of a 74-year-old patient with advanced colon cancer who suffered recurrent bouts of hypoglycemia. A state of inappropriate, non-suppressed hyperinsulinism in the presence of severe hypoglycemia was diagnosed. We finally discuss the known mechanisms behind fasting hypoglycemia in patients with advanced cancer, the diagnosis, and possible treatments of this rare paraneoplastic endocrine complication.
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PMID:Paraneoplastic hyperinsulinism and secondary hypoglycaemia in a patient with advanced colon cancer: a rare association. 1835 Jun 40

Non-islet cell tumor hypoglycemia (NICTH) is a paraneoplastic syndrome characterized by persistent, severe hypoglycemia with a wide variety of solid tumors. It is considered to cause hypoglycemia by increasing the insulin-like bioactivity of the circulating insulin-like growth factor (IGF) system, however, the precise mechanism of hypoglycemia remains unclear. In this manuscript, we report on a patient suffering from NICTH caused by a small cell carcinoma of the colon. This is the first report focusing on the role of bioactive IGFs for this pathological condition. First, we demonstrated that the IGF signal pathway has been activated in this tumor in an autocrine and/or paracrine manner using immunohistochemical analysis. Second, we confirmed that bioactive IGFs in the patient's serum were increased using a modified kinase receptor activation assay, thus bioactive IGFs (mainly IGF-2) could be considered to play a major pathogenic role in enhanced hypoglycemic insulin-like activity. Third, increased IGF bioactivity in the patient's serum was completely inhibited by an anti-IGF neutralizing antibody in vitro. These results suggest that neutralization of bioactive IGFs might become a novel therapeutic strategy for NICTH to relieve the hypoglycemic symptoms together with the tumor suppressive effect.
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PMID:Bioactive insulin-like growth factors as a possible molecular target for non-islet cell tumor hypoglycemia. 2553 94

A 45-year-old man was referred to our hospital and found to have a tubular adenocarcinoma of the descending colon with multiple liver metastases. During hospitalization, the patient suffered recurrent hypoglycemic attacks that required intravenous 50% glucose infusion. He was diagnosed with non-islet cell tumor hypoglycemia (NICTH) because the colon cancer tissue obtained by biopsy was strongly stained for insulin-like growth factor-II (IGF-II) by immunohistochemistry. He received chemotherapy with oxaliplatin, 5-FU and leucovorin (FOLFOX) plus bevacizumab (Bmab), and showed a partial response. As the metastatic lesions decreased in size, the hypoglycemic attacks gradually disappeared. Subsequently, he received outpatient chemotherapy and maintained a high quality of life for about 10 months. Western blot analysis of IGF-II in serum at the time of admission showed a high-molecular-weight form of IGF-II, which was considered to have caused hypoglycemia. This patient presents a very rare case of colorectal cancer associated with NICTH syndrome due to production of high-molecular-weight IGF-II by cancer cells. It is important to investigate IGF-II expression in cancer tissues for establishing the diagnosis of NICTH in cases with intractable hypoglycemia complicated by advanced cancer.
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PMID:Insulin-like growth factor II-producing metastatic colon cancer with recurrent hypoglycemia. 2560 15

The use of sodium-glucose cotransporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes is steadily increasing. SGLT2 inhibitors are associated with weight loss, lowering of blood pressure, and low hypoglycemia risk along with beneficial cardiovascular and renoprotective effects. In view of the increasing use of SGLT2i, physicians must be aware of their adverse effects. Euglycemic diabetic ketoacidosis (euDKA) is a well-recognized adverse effect of SGLT2i. We present here a case of euglycemic diabetic ketoacidosis secondary to dapagliflozin use in a type 2 diabetic patient with colon cancer. To the best of our knowledge, this is first report of SGLT2 inhibitor-associated euDKA in a patient with underlying colon cancer.
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PMID:Euglycemic Diabetic Ketoacidosis Secondary to Dapagliflozin in a Patient with Colon Malignancy. 3119 10