Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Examples of collateral sensitivity, even in experimental tumor systems, remain few. Preliminary data from this laboratory indicated that certain tumor cells expressed increased sensitivity to cisplatin after exposure in vitro to x-irradiation. To further clarify whether the type of fractionated radiation procedure used clinically can induce hypersensitivities to certain antitumor drugs we have pre-exposed the human ovarian carcinoma cell line JA-T/P derived from a tumor from an untreated patient to fractionated x-irradiation (total dose 50 Gy) in vitro. The resultant subline JA-T/DXR-10 expressed collateral sensitivity to cisplatin (CDDP), methotrexate (MTX) and fluorouracil (5-FU), but not to acute x-irradiation. Hypersensitivity to CDDP was associated with decreased activity of DNA polymerase beta (3.5-fold, P less than .01), but unaltered glutathione metabolism. Pre-incubation with cyclosporin A or with 3-aminobenzamide significantly enhanced (twofold, P less than .01) CDDP-induced cytotoxicity in JA-T/P cells, but not in the DXR-10 subline. Consistent with MTX hypersensitivity dihydrofolate reductase activity was significantly decreased (2.9-fold, P less than .01). Despite collateral sensitivity to 5-FU, however, thymidylate synthase activity was increased (twofold, P less than .05) suggesting alternative mechanisms for 5-FU-induced cytotoxicity in these JA-T/DXR-10 cells. These data demonstrate that DNA repair and associated reduced folate metabolism can be modified not only by drugs but also by fractionated x-irradiation.
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PMID:Expression of collateral sensitivity to cisplatin, methotrexate, and fluorouracil in a human ovarian carcinoma cell line following exposure to fractionated x-irradiation in vitro. 155 59

A number of the studies on pharmacokinetics of fluorinated pyrimidines have been precisely reported. In mice bearing Ehrlich ascites carcinoma, 5-FU showed highest concentration in the lung and kidney immediately after i.v. administration of 5-FU, and in the liver, it showed rather lower concentration but for a longer period. 5-FU in blood was transferred into ascites fluid rapidly, and thus, the level of 5-FU in ascites fluid became higher than that in blood. FT is a masked compound of 5-FU, having a tetrahydrofuryl group. Drug metabolizing enzyme, natural degradation, and thymidine phosphorylase are considered to be responsible for the molecular conversion of FT into 5-FU. In order to increase the level of drug metabolizing enzyme, P450 in the liver of tumor bearers, of which P450 level was extremely lower as compared to normal individuals, phenobarbital was very effective from our previous experiment. Clinically, phenobarbital 200mg/day for 3 successive days was administered in prior to FT, and a better response was obtained than FT alone. Prevention from degradation of 5-FU in the liver by uracil kept higher level of 5-FU in blood. HCFU and 5'DFUR are also masked form of 5-FU and are converted to 5-FU in the liver.
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PMID:[Pharmacokinetic studies on fluorinated pyrimidine in cancer cell and tissue]. 155 91

The results of 4 pathologically proven advanced lung cancer patients treated by CT guided percutaneous intubation of chemotherapeutic agent into the tumor are reported. Multidrug chemotherapy using mitomycin, cisplatin, cyclophosphamide or 5-Fu was given in a total of 11 treatments. All patients had symptomatic improvement with tumor reduction. There was no incidence of pneumothorax and other side reactions were mild. The authors believe that direct intervention chemotherapy of lung cancer is an effective and safe treatment of choice in advanced cases.
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PMID:[CT guided direct intervention chemotherapy of lung cancer]. 157 13

A randomized study of the effects of methionine-deprived amino acid solution (AO-90) on the metabolism of 5-FU was performed in patients with advanced gastric or colorectal cancers. Continuous intravenous hyperalimentation with either AO-90 or conventional amino acid solution (control group) in combination with 5-FU was performed for 7 days preoperatively under the fasting condition. The administration of AO-90 showed a decreased level of serum methionine and resulted in the subsequent increased tendency in the intratumorous levels of both folic acid and methylene tetrahydrofolate compared to those of the control group. In the AO-90 group, the inhibition rate of thymidilate synthase in the tumor was significantly higher than that of the control group. These results indicate that AO-90 plays an important role in the metabolism of 5-FU and seems to contribute to the increased antitumor effect of 5-FU as a biochemical modulator.
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PMID:[Methionine-deprived amino acid solution-induced biochemical modulation of 5-FU and augmentation of the antitumor activity]. 158 Jun 36

We reported a case of metastatic liver cancer from rectal carcinoma, which was successfully treated by systemic continuous 5-Fluorouracil and intermittent Mitomycin C chemotherapy. A 70-year-old male with rectosigmoid carcinoma was admitted to our hospital. Abdominal CT and echography revealed solid mass in the liver. He underwent low anterior resection and infuse-a-port was inserted because of arterial infusion chemotherapy for metastatic liver cancer. 5-FU (250 mg per day) was infused continuously and MMC at the dose of 8 mg for one time in a week was administered. Two months later, hepatic tumor disappeared and the serum CEA level also normalized. At this writing, the patient is alive and well and complete remission has been obtained for more than 10 months.
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PMID:[A case report of complete remission of liver metastasis from rectal carcinoma treated with intra-arterial infusion chemotherapy]. 158 Jun 47

The prognosis of colon cancer after curative resection is mainly related to the onset of metastases, and especially of liver metastases. In order to prevent metastatic recurrences, the value of adjuvant medical therapy is widely admitted. The aim of the present review was to analyse the conclusions of the main recent randomized trials assessing the comparative value of different adjuvant protocols. The results obtained using either classic systemic infusion or intraportal infusion, which is mainly used with the intent of preventing liver metastases, are reported. At term of this review, we conclude that: adjuvant chemotherapy using combined drugs (5-Fluorouracil + Methyl CCNU, 5-Fluorouracil + Oncovin) did not prove to be more active than 5-FU alone. the beneficial action of a combined 5-FU + Levamisole regimen has been clearly demonstrated for patients with a Dukes C tumor. intraportal adjuvant therapy has been shown to be effective for patients with Dukes B tumors in only one limited trial but this remains to be confirmed. On the basis of the present data, new adjuvant programs using combined chemotherapeutic and immunotherapeutic compounds, and combined systemic and regional infusion, can be envisaged.
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PMID:[Does an efficacious adjuvant treatment exist in resected colonic carcinoma?]. 158 19

From 1981 to 1987, 81 patients with localized, unresectable carcinoma of the pancreas were treated at Thomas Jefferson University Hospital with a combination of intraoperative Iodine-125 implantation, external beam radiation, and peri-operative systemic chemotherapy. Fifty patients had Stage II disease and 31 patients had Stage III disease. Radioactive Iodine-125 seeds were implanted intraoperatively into the tumor to deliver a minimum peripheral dose of 12,000 cGy over one year. This was followed by external beam radiation (50-55 Gy) and systemic chemotherapy (5-FU, Mitomycin-C +/- CCNU). Incidence of peri-operative mortality was 5% (4/81). Early morbidity was observed in 34% of patients and late complications in 32%. A median survival of 12 months and 2- and 5-year survival rates of 21% and 7% were observed. The determinate 2- and 5-year survival rates were 28% and 13%, respectively. The overall 2- and 5-year survival rates with Stage II disease were 27% and 8% and for Stage III disease, 13% and 3%, respectively (p less than 0.05). The determinate 2- and 5-year survival rates were 34% and 19% for Stage II and 19% and 5% for Stage III disease, respectively (p = 0.08). Local control of disease was achieved in 71% of patients. This combined modality approach appears to have achieved satisfactory local control of primary cancer and long term survival of selected patients.
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PMID:Long-term results of combined modality treatment with I-125 implantation for carcinoma of the pancreas. 158 51

This report updates findings from two National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trials conducted to evaluate the worth of systemic therapy for the treatment of node-negative breast cancer patients. In trial B-13, 737 women with estrogen receptor (ER)-negative tumors treated by sequential methotrexate and fluorouracil (MTX----5-FU) followed by leucovorin were compared with a control group treated by surgery alone. Findings for all patients through 5 years of follow-up indicate a 27% reduction in treatment failure as a result of MTX----5-FU (76% vs 67%). While patients 49 years old or less and 50 years old or more benefited significantly from MTX----5-FU, the effect on disease-free survival (DFS) was greatest in those 50 years or older, where a 50% reduction in treatment failure occurred (86% vs 72%). A 69% reduction in mortality resulting from MTX----5-FU was observed in the older group (95% vs 84%). Trial B-14 compared placebo with tamoxifen (TMX) in 2844 patients with ER-positive tumors. As originally reported, findings through 5 years of follow-up indicate a significant reduction (36%) in treatment failure as a result of the TMX (82% vs 72%). Improvement in DFS was highly significant in both age groups. In patients 49 years old or younger, there was a 44% reduction in DFS (81% vs 66%) and, in those 50 years old or more, a 31% reduction (82% vs 74%). A Cox proportional hazards model failed to indicate a benefit from MTX----5-FU and TMX in all patient subgroups. Both therapies reduced local-regional and distant recurrence, as well as breast tumor recurrence following lumpectomy. Updated findings from trials B-13 and B-14 continue to support our conclusions that (a) no subgroups of node-negative patients that we examined have such a good outcome as to preclude the use of effective systemic therapy in their treatment and (b) despite the benefits observed from MTX----5-FU and TMX, no subgroup of patients was so affected as to preclude use of a particular subgroup in assessing other therapy regimens in additional clinical trials. The identification and evaluation of markers to determine which patients should receive systemic therapy are of the highest priority. At present, however, the use of markers for therapeutic decision making regarding individual patients is tenuous.
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PMID:Systemic therapy in node-negative patients: updated findings from NSABP clinical trials. National Surgical Adjuvant Breast and Bowel Project. 162 17

Tumor-tissue platinum levels and major pharmacokinetic parameters were determined in 11 patients with head and neck squamous cancer (HNSC) who were given cisplatin (50 mg/m2 daily x 2 days) and 5-fluorouracil (5-FU; 1000 mg/m2, continuous infusion x 5 days) either i.a. or i.v. The plasma peak platinum concentrations (cmax) and the areas under the curve for total platinum concentration versus time (AUC) during i.a. infusions were lower than the i.v. cmax (mean, 1.92 +/- 0.28 and 4.08 +/- 2.80 mg/l, for i.a. and i.v. infusions, respectively) and AUC values (mean, 22.55 +/- 4.96 and 40.66 +/- 10.71 mg h-1 l-1 for i.a. and i.v. treatment, respectively), suggesting a first-passage extraction of the drug by the tumor mass during i.a. infusion. However, no statistically significant difference was found in platinum tumor concentrations after i.a. administration versus i.v. infusion. The lack of a difference in tumor platinum concentrations between the i.a. and the i.v. administration routes might be explained either by a relatively high blood supply to the tumor area, enabling efflux of the surplus free platinum from the tissue, or by the delay between drug infusion and biopsy. After three cycles of i.a. treatment good tumor remission was obtained with minimal local toxicity. Larger clinical studies testing the advantages of the i.a. administration route over i.v. infusion appear to be necessary.
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PMID:Pharmacokinetics and tumor concentration of intraarterial and intravenous cisplatin in patients with head and neck squamous cancer. 162 71

People with deficient cell-mediated immunity have an increased susceptibility to viral infections and certain cancers, particularly non-Hodgkin's lymphomas and cancers of the skin and anogenital region. These are linked to viral origins. Anogenital neoplasms in immunodeficient patients show a strong association with HPV infection; often occur at relatively young ages; involve multifocal locations; and tend to persist, recur, and progress rapidly, despite standard therapy. Because standard therapy of anogenital HPV lesions and neoplasia is often not effective in immunodeficient patients (and others with an anogenital neoplastic syndrome), special treatment is required. 5-Fluorouracil chemosurgery, followed by maintenance 5-fluorouracil therapy, is often effective and provides field suppression against recurrent HPV infection and neoplasia, with minimal damage to affected organs. After removal of all detectable HPV and neoplastic lesions, immunodeficient patients require close surveillance of the entire anogenital tract. Immunodeficient patients are an in vivo human laboratory in which to study the natural history of HPV and its oncogenic effects on the anogenital tract. The theory of HPV oncogenesis is supported by the evidence gathered from these patients.
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PMID:Anogenital papillomavirus infection and neoplasia in immunodeficient women: an update. 164 9


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