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)

Lipotropin (LPH) has been evaluated as a potential tumor marker using a sensitive beta melanocyte-stimulating hormone (beta MSH) radioimmunoassay. All 79 acetic acid extracts of carcinomas of lung, colon, stomach, esophagus and breast contained LPH in concentrations greater than blood; 61 of 79 extracts contained LPH in larger amounts than control tissues from patients without cancer. In a blind prospective study, plasma LPH was quantified in 107 patients admitted for work-up because of an abnormality on a chest roentgenogram. Thirty-one of 33 patients subsequently diagnosed as having benign lesions had plasma LPH within the 95 per cent confidence limits of normal subjects whereas 28 (36 per cent) of the 74 patients subsequently diagnosed histologically as having primary lung carcinoma had elevated levels. In control studies, 13 of 100 patients with chronic obstructive pulmonary disease had elevated plasma LPH levels; three of the 13 with elevated levels and four with normal levels have been diagnosed, during the two years of follow-up, as having lung carcinoma. In control studies of 23 patients with granulomatous lung disease, 22 had normal levels of LPH. In those with carcinoma of the colon elevated plasma LPH levels were observed in two of 21 untreated patients and in 11 of 61 patients receiving noncurative chemotherapy. Elevated plasma LPH levels were also observed in 10 of 59 patients with breast cancer, eight of 28 with pancreatic cancer, eight of 22 with gastric or esophageal cancer, six of 16 with renal cancer, four of eight with prostatic cancer, one of seven with cervical cancer and one of six with ovarian cancer. We conclude, an elevated LPH level is frequently observed in blood and tumor tissue from patients with various types of carcinoma.
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PMID:Ectopic production of lipotropin by cancer. 43 67

Derivatives of xanthenone-4-acetic acid (XAA) have been found to have similar activity to flavone-8-acetic acid against transplantable solid tumors. Some of these compounds were compared to flavone acetic acid (FAA) in their ability to induce cytokines as well as to mediate antitumor effects against murine renal cancer (Renca) and a mouse colon cancer (MCA-38). 5-Methyl-XAA and 5-chloro-XAA proved to be more potent than FAA on a mg/kg basis for induction of the genes for IFN alpha, IFN gamma, and TNF alpha, and for IFN and TNF activities in the sera of treated mice. These effects were sharply dose dependent. On the other hand, 7-methyl-XAA, which has no antitumor activity, did not induce these genes. In addition, 5-methyl-XAA and 5-chloro-XAA but not 7-methyl-XAA synergized with recombinant human interleukin-2 (rhIL-2) for the treatment of Renca and MCA-38. Doses of the active derivatives that failed to induce cytokines also exhibited no therapeutic synergy with rhIL-2. These results suggest that at least some of the antitumor effects of these XAA derivatives are related to their ability to induce cytokines.
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PMID:Cytokine induction and therapeutic synergy with interleukin-2 against murine renal and colon cancers by xanthenone-4-acetic acid derivatives. 147 76

This phase I study investigated flavone acetic acid (FAA) given as a 12-h intravenous infusion every 3 weeks in the absence of urinary alkalinisation. Cohorts of three patients were treated at doses of 7, 10 and 13 g/m2. One subject had colon cancer; 5, renal cancer; and 3, lung cancer. The Eastern Cooperative Oncology Group (ECOG) performance status was 0 in four patients, 1 in two subjects and 2 in three cases. The maximum tolerated dose was 13 g/m2. The dose-limiting toxicities were WHO grade 3 hypotension and grade 3 diarrhoea. Other toxicities included lethargy and dizziness, nausea, temperature fluctuation, myalgia and dry mouth, but no significant myelosuppression was encountered. One patient receiving 10 g/m2 for renal cancer showed a partial response that lasted for 3 months and included the resolution of pulmonary and cutaneous metastases. The pharmacokinetics showed large interpatient variability. At 12-16 h post-infusion, the plasma elimination profile entered a plateau phase, with frequent increases in concentration suggesting enterohepatic recycling. Neither peak FAA levels nor AUC values were dose-dependent at the doses studied. Peak plasma levels were 101-402 micrograms/ml and AUC (0-48 h) values were 75-470 mg ml-1 min. Plasma protein binding varied with total concentration. Two metabolites were detected in the plasma, and both also underwent apparent enterohepatic recycling. Repeat dosing resulted in decreases of up to 48% in peak levels and AUC values for FAA in three of six patients. Of the total FAA dose, 39%-77% was excreted in the urine as FAA or metabolites within 2 days. The dose recommended for further phase II studies is 10 g/m2.
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PMID:A phase I and pharmacokinetic study of 12-h infusion of flavone acetic acid. 155 Nov 73

Flavone 8-acetic acid (FAA) is a new experimental antitumor drug with activity against various murine and human solid tumors in vitro and in vivo. We previously demonstrated that FAA suppressed the growth of a human colon cancer cell line (HCT-116). In this study we investigated the effect of FAA on human peripheral blood (PBL) and human colonic lamina propria lymphocyte (LPL) DNA synthesis. Our results show that FAA inhibited DNA synthesis in PBL and LPL in a dose-dependent fashion. In addition, FAA inhibited the activity of the intracellular enzyme, ornithine decarboxylase (ODC), in stimulated PBL and LPL. FAA did not inhibit phorbol ester (PDB) and calcium ionophor(ionomycin)-stimulated LPL DNA synthesis. These results suggest that FAA alters DNA synthesis of human peripheral and colonic mucosal lymphocytes. We postulate that FAA may affect the human peripheral and mucosal immune system.
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PMID:Flavone acetic acid suppresses human peripheral blood lymphocyte and human colonic lamina propria lymphocyte DNA synthesis. 239 38

We report a prospective evaluation of three human, continuous colorectal cancer cell lines and a new semiautomated radiometric technique (Bactec system) as a primary screening procedure for cytotoxic compounds with activity against cancer of the large bowel. COLO 320DM, Ht-29, and the metastatic OM-1 colon cancer cell line that have previously been shown to yield clinically relevant information in terms of drug sensitivity patterns in humans were all tested against 11 new compounds currently being investigated in phase I or early phase II clinical trials. Our results suggest that trimetrexate, DUP-785, didemnin B, and flavone-8-acetic acid may be clinically effective for the treatment of colorectal cancer.
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PMID:Application of a new preclinical drug screening system for cancer of the large bowel. 334 63

Plasminogen activator content was determined quantitatively in extracts of 23 pairs of surgically removed colon tumors and adjacent normal mucosa specimens. The activator content averaged 4.4 times higher in the tumor samples than in the corresponding normal tissue. Polyps removed with the adenocarcinomas gave values intermediate between those for tumors and those for the normal mucosae. The enzyme content of the group of tumors that showed invasive propagation or metastatic spread was significantly higher (P < 0.05) than was the enzyme content of the group not manifesting these conditions. Activator activity of the tumor extracts was completely inhibited by rabbit antibody formed against human urokinse. The activity of the normal mucosae was variably inhibited, suggesting the presence of several kinds of activator in normal tissues. The activator from the normal tissues could be separated into a completely refractory fraction and a completely inhibitable fraction by means of an affinity column made of Sepharose-linked, rabbit antiurokinase antibody. The activator, eluted from this column with 1 M acetic acid in 0.5 M NaCl (pH 2.2), was highly purified and had an isoelectric point of 8.6, as does authentic urokinase. The details of the isoelectric profile of the two, however, differed. The data are discussed in relation to earlier studies on the fibrinolytic system in colon cancer.
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PMID:Plasminogen activator content of human colon tumors and normal mucosae: separation of enzymes and partial purification. 693 Dec 52

Two cases of liver metastasis from colon cancer were treated by percutaneous ethanol (PEI) and acetic acid (PAI) injection for the recurrent lesion after surgery. Case 1 was a 60-year-old female who received sigmoidectomy with partial hepatectomy, and intraarterial 5-FU infusion was done after surgery. One year later, recurrence of liver tumor was detected, and PEI and PAI were performed for the metastatic lesions of the liver. Tumor regression and histopathological examination revealed coagulative necrosis. The patient died of lung metastasis 2 years and 10 months after treatment. Case 2 was a 58-year-old-male with ascending colon cancer and liver metastasis, who received surgery, and chemotherapy with intraarterial 5-FU infusion was continued. Four months later, recurrence of liver metastasis with elevation of serum CEA was noted. The patient received PEI three times and CEA decreased. Re-operation of hepatectomy revealed complete necrosis at the site of PEI. The patient has been alive for 1 year and 6 months with a new recurrence in the liver and is receiving repeated PEI therapy. PEI and PAI seem to be useful for the treatment of unresectable liver metastasis.
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PMID:[Percutaneous ethanol and acetic acid injection for liver metastasis from colon cancer--two case reports]. 957 76

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to cause apoptosis in several cell lines including transformed chicken embryo fibroblasts and human colon cancer cells. We herein report the apoptotic effect of NSAIDs in a non-transformed cell line derived from the rat gastric mucosa, RGMI (rat gastric mucosa cell first). 1-[p-Chlorobenzoyl]-5-methoxy-2-methylindole-3-acetic acid (indomethacin) and sodium 2-(2,6-dichloroanilino)phenylacetate (sodium diclofenac), potent and non-selective inhibitors of cyclooxygenase, were found to induce DNA fragmentation in RGM1 cells in a time- and concentration-dependent manner. The expression of mRNA for cyclooxygenase-2 was hardly detected in the intact cells but was clearly enhanced when the cells were incubated with the two NSAIDs. In contrast, the expression of mRNA for cyclooxygenase-1 was constitutive and was never affected by NSAIDs. The effect of [3,4-di(4-methoxyphenyl)-5-isoxazolyl] acetic acid (mofezolac), a potent and highly preferential inhibitor of cyclooxygenase-1, and N-[2-(cyclohexyloxy)-4-nitrophenyl]methanesulphonamide (NS-398), a selective inhibitor of cyclooxygenase-2, on DNA fragmentation and cyclooxygenase-2 mRNA expression was weak compared to the effect of indomethacin or sodium diclofenac. The DNA fragmentation induced by sodium diclofenac was hardly affected by the exogenous addition of 16,16-dimethyl prostaglandin E2 but was inhibited by caspase inhibitors such as Ac-YVAD-CHO and Ac-DEVD-CHO. The present data provide the first evidence that NSAIDs, such as indomethacin and sodium diclofenac, cause apoptotic DNA fragmentation in cultured gastric mucosal cells, and also indicate the involvement of caspases rather than the inhibition of cellular prostaglandin synthesis in the apoptotic process.
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PMID:Induction of apoptotic DNA fragmentation by nonsteroidal anti-inflammatory drugs in cultured rat gastric mucosal cells. 985 95

The distinct melatonin rhythm with higher concentrations during the darktime was found in plasma of both control patients and patients with colorectal carcinoma. Moderate surgery did not induce any changes in plasma melatonin levels, but a pronounced increase in both the day- and nighttime melatonin concentrations was found after surgical treatment for colon cancer. The melatonin content in the tumor tissue did not differ from that in the proximal and the distal parts of the resected gut, which were without signs of malignant changes. Neither concentrations of serotonin nor 5-hydroxyindole acetic acid differed among analyzed parts of the gut. Daytime melatonin concentrations in gut tissue (314.7 +/- 87.8 pg/g of wet tissue) were more than ten times higher than the daytime levels in circulation. It was hypothesized that increased levels of this hormone in the gastrointestinal tract may play an important protective role against the development of colorectal cancer via stimulation of the immune system, protection against free radicals, and interaction with fatty acid uptake and metabolism.
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PMID:Melatonin content in plasma and large intestine of patients with colorectal carcinoma before and after surgery. 1053 66

The short-chain fatty acid (SCFA) butyrate is produced via anaerobic bacterial fermentation within the colon and is thought to be protective in regard to colon carcinogenesis. Although butyrate (C4) is considered the most potent of the SCFA, a variety of other SCFA also exist in the colonic lumen. Butyrate is thought to exert its cellular effects through the induction of histone hyperacetylation. We sought to determine the effects of a variety of the SCFA on colon carcinoma cell growth, differentiation and apoptosis. HT-29 or HCT-116 (wild-type and p21-deleted) cells were treated with physiologically relevant concentrations of various SCFA, and histone acetylation state was assayed by acid-urea-triton-X gel electrophoresis and immunoblotting. Growth and apoptotic effects were studied by flow cytometry, and differentiation effects were assessed using transient transfections and Northern blotting. Propionate (C3) and valerate (C5) caused growth arrest and differentiation in human colon carcinoma cells. The magnitude of their effects was associated with a lesser degree of histone hyperacetylation compared with butyrate. Acetate (C2) and caproate (C6), in contrast, did not cause histone hyperacetylation and also had no appreciable effects on cell growth or differentiation. SCFA-induced transactivation of the differentiation marker gene, intestinal alkaline phosphatase (IAP), was blocked by histone deacetylase (HDAC), further supporting the critical link between SCFA and histones. Butyrate also significantly increased apoptosis, whereas the other SCFA studied did not. The growth arrest induced by the SCFA was characterized by an increase in the expression of the p21 cell-cycle inhibitor and down-regulation of cyclin B1 (CB1). In p21-deleted HCT-116 colon cancer cells, the SCFA did not alter the rate of proliferation. These data suggest that the antiproliferative, apoptotic and differentiating properties of the various SCFA are linked to the degree of induced histone hyperacetylation. Furthermore, SCFA-mediated growth arrest in colon carcinoma cells requires the p21 gene.
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PMID:The effects of short-chain fatty acids on human colon cancer cell phenotype are associated with histone hyperacetylation. 1198 30


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