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)

Although advanced gastrointestinal cancer is the most commonplace problem encountered by the medical oncologist, this group of diseases has proved exceedingly resistant to past chemotherapy efforts. 5-Fluorouracil (5-FU), accepted by some as standard treatment, had provided only infrequent, incomplete, and fleeting antitumor effects, which are probably more than counterbalanced by its gastrointestinal, mucocutaneous, and hematologic antihost effects. There is no evidence that any manipulation of route or schedule of administration provides any improvement in the therapeutic ratio of 5-FU. There is no evidence that this drug contributes to patient survival when used at any stage of any type of gastrointestinal carcinoma. The search for alternative single drugs to 5-FU has been disappointing. The nitrosoureas and Mitomycin C produce occasional regressions, but they do not match the meager effectiveness of 5-FU; and they, in addition, present the difficult problem of cumulative bone marrow suppression. Recent trials with combination regimens have given some indication that the long stalemate in chemotherapy of gastrointestinal cancer may be breaking. Substantial improvements in frequency of tumor regression have been recorded for gastric carcinoma with combinations of 5-FU and BCNU, 5-FU and methyl CCNU, and 5-FU, Mitomycin C, and cytosine arabinoside; for colorectal carcinoma, with the combination of 5-FU, methyl CCNU, and vincristine; and for carcinoid tumors and islet cell carcinomas, with the combination of 5-FU and Streptozotocin. There are also suggestion that such combination chemotherapy with response rates in the 30 to 50% range may produce increased survival when compared to the untreated patient and patients treated with single-drug regimens. While the accomplishments of chemotherapy for the gastrointestinal cancer patient remain less than spectacular there is nevertheless realistic hope that a respectable contribution can now be made to multidisciplinary efforts applied at a stage of disease with minimal tumor burden.
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PMID:Clinical management of advanced gastrointestinal cancer. 16 61

Over a period of 21 years 39 patients with gastrinoma were surgically treated. Thirty-three patients had total gastrectomy with two postoperative deaths, and 6 patients had a lesser procedure. The postoperative fasting gastrin levels remained elevated and did not always indicate the extent of tumor involvement. Further mobilization of tumor gastrin by provocative infusion of calcium gluceptate, 15 mg/kg of body weight, should be carried out routinely. A hepatic angiogram should be considered when the gastrin levels exceed 1,000 picograms per ml. Chemotherapy consisting of Tubercidin, Streptozotocin and 5-Fluorouracil was given to 5 patients with extensive gastrinoma. All patients felt better and gained from three to 35 pounds in weight. Since 60% of the patients died or have definite evidence of tumor activity it is assumed that the tumor growth was not inhibited and that it is malignant. Approximately 40% of the patients seem to do well despite modest elevations in gastrin levels suggesting that the retained tumor could be considered benign.
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PMID:Observations on the postoperative tumor growth behavior of certain islet cell tumors. 18 9

Thirty-seven patients with advanced or recurrent lung cancer were randomized to cytoxan (CTX) alone, COMF (CTX, oncovin, methotrecate and 5-FU) or AMCOF (adriamycin, methotrexate, CTX, oncovin and 5-FU) after receiving radiation therapy to primary and bulky tumor sites. Median survival was 3 months for CTX, 6 months for COMF and 14 months for AMCOF. Analysis of those with cell (small cell) carcinoma showed median survival of 8.5 months. Oat cell cases treated with CTX survived 5 months (8 patients) with COMF 7.5 months (15 patients) and with AMCOF 13 months (14 patients). The median survival of those with adenocarcinoma or epidermoid carcinoma treated with CTX survived 3 months, with COMF 6 months and with AMCOF 15.5 months. Toxicity was moderate though no life-theatening toxicity developed in spite of the protocol design of escalation to achieve some degree of hematologic toxicity in all patients.
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PMID:Combination modality therapy in lung cancer: a survival study showing beneficial results of AMCOF (adriamycin, methotrexate, cyclophosphamide, oncovin and 5-fluorouracil). 20 81

An in vivo model is described for assessing the antitumor activity of chemotherapeutic agents. Tumors derived from human colon carcinoma cell lines injected into antithymocyte serum (ATS) immunosuppressed mice were used. In this system, both antitumor effects and host toxicity can be quantitated, permitting calculation of a Therapeutic Index. Compared with other xenograft models, the present system is simple, experiments are completed in less than 2 weeks, and the use of cultured cell lines allows in vitro studies to be performed. The in vitro sensitivities of one colon cell line to 22 chemotherapeutic agents and of four cell lines to three agents is reported. Four drugs used in treating colon cancer (Mitomycin C, 5-FU, BCNU, and methyl-CCNU) show antitumor activity in vivo in this system. Each has a low therapeutic index. Further work with this model is indicated, with the goal of finding new drugs with high Therapeutic Indices.
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PMID:Chemotherapy of cell-line-derived human colon carcinomas in mice immunosuppressed with antithymocyte serum. 30 40

A renal cell endocarcinoma that arose spontaneously in a Wistar-Lewis rat has been used to screen various chemotherapeutic agents for effectiveness against this tumor. Of the agents so far tested, cyclophosphamide (Cytoxan) and vinblastine have displayed very considerable anti-tumor activity. Adriamycin was marginal, and fluorouracil (5-FU) and Cis-dichlorodiammine Platinum (II) were ineffective.
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PMID:A new animal model for testing the effectiveness of chemotherapeutic agents on renal adenocarcinoma. 40 Dec 84

An in vitro cell free assay system to measure phosphorylated products of 5-Fluorouracil is described. Total phosphorylated products and mono-, di and triphosphates of 5-Fluorouracil are measured along with the rate of fluorodeoxyuridylate generation. This assay has been applied to ten murine tumors and eight biopsy specimens from human breast adenocarcinomas. Phosphorylation patterns have been examined in murine tumors demonstrating in vivo sensitivity or resistance to 5-Fluorouracil. There are distinct differences in the patterns of phosphorylation between sensitive and resistant tumors. In a 5-Fluorouracil sensitive murine tumor, mono-, di and triphosphates are produced. In a resistant tumor only monosphophates are produced. Cell free supernatants from human breast tumors produce less total phosphorylation than murine tumors and some specimens produce only monophosphates whereas others produce mono-, di and triphosphates. Human tumors are in general more efficient producers of fluorodeoxyuridylate than murine tumors. These data suggest that resistance to 5-Fluorouracil may correlate with decreased concentration of di and triphosphates of 5-Fluorouracil in some murine tumors. Further experiences is required to demonstrate the value of this easily performed assay system in predicting clinical response to 5-Fluorouracil in man.
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PMID:Studies on mechanisms of 5-fluorouracil resistance in murine and human tumors. 42 Sep 47

In No. 13762 mammary adenocarcinoma, it has been shown that the combination of tumor infiltration with BCG and of subsequent surgery is more curative than either treatment modality alone. And the administration of postoperative systemic 5-fluorouracil (D-FU) is equally effective in eliminating the visceral metastasis and prolonging the host survival. In the experiments reported here, two other spontaneously metastasizing adenocarcinoma lines were similarly treated. Postoperative 5-FU chemotherapy, but not intralesional BCG, significantly improved survival duration of rats with SMT-2A mammary adenocarcinoma, but neither chemotherapy nor BCG immunotherapy was effective in the new colonic adenocarcinoma line.
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PMID:Effect of preoperative intralesional BCG and postoperative 5-FU chemotherapy in three adenocarcinoma lines in rats. 44 59

In vitro sensitivity of an established cell line from human urinary bladder cancer to various chemotherapeutic agents was determined by 14C-leucine incorporation into the target cells. Of 12 drugs tested, Carboquone, Neocarzinostatin, Actinomycin D, Adriamycin, Mitomycin C and Chromomycin A3 produced intensive cytotoxic effects, while Thio-Tepa, Bleomycin, 5-Fluorouracil and Vincirstine were less cytotoxic, Intravesical instillation of Carboquone, one of the most toxic agents in vitro, resulted in complete or partial tumor remission in 6 of 9 patients with bladder cancer. Prophylactic effects of periodic intravesical Carboquone were also indicated in 7 of 8 patients who had experienced recurring superficial bladder tumors.
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PMID:Chemosensitivity of human bladder cancer cells in long-term culture and clinical responses to the selected anticancer drug. 45 64

A phase II study of vindesine was carried out in 33 patients with colorectal cancer and nine patients with esophageal cancer. With the exception of six previously untreated patients with esophageal cancer, all others were refractory to 5-FU-containing regimens, w,hich included vincristine in ten patients. The initial dose of vindesine was 4 mg/m2 administered intravenously over 30 min every 2 weeks. Tumor regression less than 50% was set patients (six colorectal and two esophageal) achieved minor responses. Prior treatment with vincristine did not seem to influence response to vindesine. In general, the treatment with vindesine was well tolerated. The hematologic toxicity was acceptable and manifested mainly as moderate and transient neutropenia. The major nonhematologic toxicity was peripheral neuropathy, which became limiting. It occurred in 33% of patients who received two or more courses of vindesine. Because of the apparent antitumor activity and dose-limiting neurotoxicity of vindesine in this sutdy, further investigations of this compound should be conducted in combination chemotherapy programs for patients with metastatic gastrointestinal cancers.
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PMID:Phase II evaluation of vindesine in the treatment of colorectal and esophageal tumors. 45 86

Elevated serum levels of carcinoembryonic antigen (CEA) were found in 70% of 141 patients with advanced gastrointestinal (GI) cancers. Serial CEA measurements were performed on 70 patients before and during chemotherapy. The majority were treated with 5-FU and Methyl-CCNU (33 patients), 5-FU (19 patients), or 5-FU and mitomycin-C (8 patients). In 49 patients with colorectal carcinoma who had elevated serum CEA prior to chemotherapy, 18 had objective partial tumor remission, 16/18 (89%) showed definite decrease in CEA level, one had no change, and one had an increase CEA titer. Thirty-one patients had either stable disease (10 patients) or increasing disease (21 patients) while on chemotherapy. Of these patients four showed decrease in CEA, eight had no change, and 19 had increase in CEA levels as compared to pretreatment value. The survival of patients with a decrease in CEA during chemotherapy was statistically significant (p = .03) as compared to survival of those with no change or increasing CEA levels. In 21 patients with other GI cancers, the correlation between the clinical response and change in CEA level observed was not as definite as in patients with colorectal carcinoma.
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PMID:The value of serial carcinoembryonic antigen (CEA) in predicting response rate and survival of patients with gastrointestinal cancer treated with chemotherapy. 49 10


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