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)

Several classes of plant polyphenols namely, flavonoids, chalcones and coumarins exhibited varying degrees of inhibition on the cell proliferation of human colon adenocarcinoma cell line 220.1. At the highest concentration tested (100 microM), many of the chalcones showed > 100% growth inhibition and their order of potency was butein > 2'-hydroxychalcone > 2-hydroxychalcone > 2',6'-dihydroxy-4'-methoxychalcone > 2',4-dihydroxychalcone with IC50 values of 1.75, 6.2, 7.5, 17, 23 microM, respectively. Butein (the most potent chalcone) at 2 microM concentration inhibited the incorporation of 14C-labelled thymidine, uridine and leucine into the colon cancer cells whilst 5-fluorouracil (5-FU, a chemotherapeutic drug) at 50 microM concentration could significantly inhibit only the uridine incorporation. The mode of cytotoxic action of butein was different from 5-FU but may be similar to colchicine, a known HeLa cell inhibitor.
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PMID:Cytotoxic effect of butein on human colon adenocarcinoma cell proliferation. 803 70

533 patients with diagnosis of operable colorectal carcinoma were randomized to receive either a single course of portal infusion with Mitomycin-C (MMC) and 5-Fluorouracil (5-FU) starting immediately after operation, or no adjuvant treatment. Of these, 505 (94%) were evaluable. Over the median follow-up of 8 years, the adjuvant therapy reduced the risk of recurrence by 22% (Hazard ratio = 0.78%, 95% CI 0.61-0.99; P = 0.045). The relative reduction of relapse on death was similar in all subgroups (i.e. nodal status, localization). However, adjuvant portal chemotherapy proved to be most efficient in the subgroups of patients with tumor involvement of the regional lymph nodes (Dukes C) and of patients with colon cancer. Analysis of the pattern of relapse showed that most of the difference in overall and disease-free survival is to be attributed to a consistent reduction of all kinds of tumor recurrences (i.e. local relapses, liver metastases and/or other distant metastases) in the treated group, rather than to liver relapses alone. We conclude therefore, that part of significant benefit obtained for patients with operable colorectal carcinoma treated with a single course of adjuvant chemotherapy via the portal vein might be due to the additional systemic effects of the portal chemotherapy and further study of perioperative treatment with and without prolonged chemotherapy appears worthwhile.
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PMID:[Status of portal perfusion in colorectal cancer. Swiss Study Group for Clinical Cancer Research]. 808 6

A 58-year-old woman with colon cancer, who had received oral 5-FU over 17 months after right hemicolectomy, was diagnosed as having a recurrence of the disease with multiple pulmonary metastasis. She was treated for 5 days with a combination of continuous infusion of 5-FU 600 mg/m2/day, bolus injection of leucovorin (LV) 20 mg/m2/day, and intramuscular injection of interferon (IFN)-alpha-2a (6.0 x 10(6) U/day, repeated every 3 weeks. The chest X-ray after three cycles showed a decrease in size of metastatic lesions by 51%, indicating a partial response. Correspondingly, the serum levels of CEA and CA 19-9 significantly decreased. There were modest but tolerable side effects such as fever, nausea, diarrhea, stomatitis, and alopecia. The patient has been given oral UFT and LV after discharge, and is still alive with continued improvement of pulmonary lesions even 9 months after initial chemotherapy. Although the detailed synergistic mechanism of 5-FU and IFN has yet to be determined, the addition of IFN, as a biochemical modulator distinct from LV, to the combination of 5-FU and LV, appears to further potentiate the therapeutic efficacy and may be useful for advanced colorectal cancer.
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PMID:[A case of pulmonary metastasis from colon cancer successfully treated by 5-FU combined with leucovorin and interferon alpha-2a]. 823 93

Cavitation (volume oscillations and collapse of gas bubbles), as generated by a co-administration of shockwaves (SW) and microbubbles (SWB), induces cytotoxicity in vitro. Moreover, cavitation potentiates the effects of Fluorouracil (FUra) on colon cancer cells. We aimed at reproducing such effects in vivo. A peritoneal carcinomatosis was induced in BDIX rats by intraperitoneal (IP) injection of DHDK12PROb cells. Cavitation was produced by various SW regimens (250 to 750SW) combined with bubbles (air/gelatin emulsion) infused through an IP catheter. In two consecutive experiments, microtumours (day 3 after cell injection) were submitted to various combinations of cavitation and/or Fluorouracil (FUra) and Cisplatinum (CDDP) at either high or low doses. After 30 days, 100% of control animals were dead or presented carcinomatosis with ascites, vs 60% after FUra 5 mg kg dy, day 4 through 8, and 0% after 250 SWB, day 4 and 6 + FUra 5 mg kg dy, day 4 through 8 (P < 0.001); similar differences were found with CDDP. Survival after low dose FUra + SWB was comparable to high dose FUra (25 mg kg dy day through 8) and was improved as compared to low-dose FUra alone. Only a high dose FUra + SWB schedule induced 40% long term (> 150 days) disease-free survival, but also a higher undesirable toxicity (40% toxic deaths within 1 month). It is concluded that cavitation is cytotoxic in vivo and that it potentiates the effects of FUra and CDDP in this animal model.
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PMID:In vivo effects of cavitation alone or in combination with chemotherapy in a peritoneal carcinomatosis in the rat. 831 2

Intermittent intra-arterial infusion chemotherapy (5-FU: 500 mg and carboplatin; 100 mg per week) using an implantable access was performed for 19 patients with unresectable liver metastasis of colon cancer (17 cases) and gastric cancer (2 cases). Survival time ranged from 12 to 641 days, and the average was 281.4 days with 50% survival at 276 days. Of 19 cases, one access was infected, two cases had catheter obstruction, and two cases had nausea and vomiting.
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PMID:[Intermittent intra-arterial infusion chemotherapy of 5-FU and carboplatin for unresectable liver metastases]. 837 11

A 72-year-old man underwent a radical operation for sigmoid colon cancer (well-differentiated adenocarcinoma, stage III) in 1989. Chest X-ray examination performed in September 1992 showed multiple nodular shadows in the lungs. A diagnosis of pulmonary metastasis was made from abnormally increased CEA and CA 19-9 and findings by chest tomography and CT scanning. There was no evidence of metastasis or recurrence in the liver, bone, brain or large intestine. He received three courses of bolus injections of leucovorin (30 mg/body) and 5-FU (500 mg/body), each over five consecutive days with a two-week rest period, and subsequently weekly at the same doses. CEA and CA 19-9 levels started to decrease after completion of the second course of consecutive treatment. In week 18 of chemotherapy, CEA and CA 19-9 levels dropped to 5.6 ng/ml and 32 U/ml from 66 ng/ml and 130 U/ml, respectively. Chest tomography and chest CT showed the disappearance or reduction in size of the nodules, with a reduction rate of 87.1%. Twenty-two weeks later, at this writing, there was no evidence of disease progression, and the patient was thus judged to be PR. He continues to receive chemotherapy at our outpatient clinic.
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PMID:[A case of postoperative pulmonary metastasis of colon cancer which responded to treatment with leucovorin and 5-FU]. 837 80

The effects of fluorouracil (5-FU) and interferon-gamma (IFN-gamma) on the regulation of thymidylate synthase (TS) gene expression were investigated in the human colon cancer H630 cell line. By Western immunoblot analysis, TS protein levels in H630 cells were increased 3-, 5.5-, 5-, and 2.5-fold after 8-, 16-, 24-, and 36-hr exposure to 1 microM 5-FU, respectively. When H630 cells were exposed to varying concentrations of 5-FU (0.3-10 microM) for 24 hr, increases in TS protein up to 5.5-fold were observed. A 24-hr exposure to 1 microM 5-FU resulted in a 4.5-fold increase in the level of TS protein, whereas in 5-FU/IFN-gamma-treated cells TS protein was increased by only 1.8-fold, compared with control cells. IFN-gamma treatment alone did not affect TS protein levels, relative to control. Northern blot analysis revealed no changes in TS mRNA levels when H630 cells were exposed either to 1 microM 5-FU for 8-36 hr, to varying concentrations of 5-FU (0.3-10 microM) for 24 hr, or to the combination of 5-FU and IFN-gamma. Pulse-labeling studies with [35S]methionine demonstrated a 3.5-fold increase in net synthesis of TS in cells treated with 1 microM 5-FU, whereas the level of newly synthesized TS increased only 1.5-fold in cells treated with 5-FU/IFN-gamma, compared with control cells. Pulse-chase studies revealed that the half-lives of TS protein in control and 5-FU-treated cells were equivalent. These findings demonstrate that the increase in TS protein after 5-FU exposure and the subsequent inhibitory effect of IFN-gamma on TS protein expression are both regulated at the post-transcriptional level.
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PMID:Regulation of thymidylate synthase in human colon cancer cells treated with 5-fluorouracil and interferon-gamma. 847 31

Abdominal failure for colonic carcinoma patients following curative resection has been high in patients with advanced disease stage, particularly when increased numbers of lymph nodes are involved. Surgeons desire curative treatment for their patients, but they interpret local and regional lymph node recurrence as a failure of surgical resection. The effect of current adjuvant treatment protocols on modifying patterns of relapse, particularly in the abdomen, has not been well studied and is of interest to surgeons. We analyzed reported patterns of failure of patients with Stage C2 colon cancer from two colon cancer adjuvant treatment studies; 5-FU plus levamisole (SWOG 8591) and 5-FU, whole-abdominal radiation, and tumor boost. The total number of recurrences in SWOG 8591 at all sites was reduced. The percent of lung relapses was reduced from 34 per cent to 20 per cent in the treatment group, but the percentage of local relapse increased from 20 per cent in the observation group to 27 per cent in the 5-FU plus levamisole group. Similarly, the number of first relapses was fewer at a local site in the 5-FU plus levamisole group, but the percent of relapses at the local site was not reduced (18 vs. 22%). Advanced C2 patients who received regional treatment on 5FU and whole-abdominal radiation produced the lowest percent of local relapse (12%), suggesting a benefit for regional treatment. Further study of patterns of relapse after resection and adjuvant treatment in high risk C2 patients may lead to further progress in control of advanced, curative colon carcinoma.
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PMID:Patterns of recurrence for advanced colon cancer modified by whole abdominal radiation and chemotherapy. 865 49

There have been no life-prolonging effects of surgical adjuvant chemotherapy with 5-FU alone or in combination with chemotherapeutic drugs, so surgical resection has been considered a standard therapy for colorectal cancer. Recently, clinical trials of modulation therapy with 5-FU and leucovorin showed higher efficacies in advanced colorectal cancer, and significant prolongations of survival time and disease-free interval were reported in a randomized trial of 5-FU and leucovorin for postoperative adjuvant therapy of resected colon cancer. Moreover, in a scientifically well controlled randomized study with 5-FU and levamisole, the significance of this regimen for Dukes C colon cancer has been shown for standard adjuvant chemotherapy.
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PMID:[Progress of adjuvant chemotherapy in colon cancer]. 867 12

The relatively high response rate demonstrated with the use of continuous infusion 5-Fluorouracil (CIFU) 200 to 300 mg/m2 per day in disseminated colon cancer is the rationale behind a NCI-sponsored intergroup trial (INT 0153) for postoperative adjuvant therapy of stage III colon cancer. Because CIFU necessitates a significant reduction in the dose of the modulator leucovorin compared with bolus 5-FU, a pilot study of continuous infusion 5-FU in several doses with levamisole was conducted to determine any unexpected toxicity of this combination, and to assess completion rates of levamisole was conducted to determine any unexpected toxicity of this combination, and to assess completion rates of this dose intensive schedule. CIFU, scheduled as two 12-week cycles, was administered at 250 mg/m2 per day. Pending toxicity at the initial dose, CIFU was to be escalated (300 mg/m2) or de-escalated (200 mg/m2). All but one patient entered on this trial completed 24 weeks of adjuvant CIFU+levamisole. Eight patients (57%) completed 24 weeks of therapy with the 2-week scheduled break. One of these 8 patients required a dose reduction without interrupting the schedule. Six patients had toxicity from the CIFU, which obliged us to interrupt the schedule. Limiting toxicities were stomatitis and hand-foot syndrome. No dose-limiting hematologic toxicity was encountered. Three patients (21%) had catheter problems that required replacement. These data suggest that up to 30% of patients started on this regimen may require dose reduction, shorter infusion courses with rest breaks, or both to complete 24 weeks of adjuvant treatment in order to achieve desired dose intensity.
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PMID:A pilot trial of continuous infusion 5-fluorouracil with levamisole for adjuvant therapy of colon cancer. 880 55


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