Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a previous clinical study, sequential methotrexate and 5-fluorouracil has shown improved efficacy for treating advanced gastric cancer of the poorly differentiated type. In this study, we investigated whether difference in the levels of thymidylate synthetase (TS) and thymidine kinase (TK) activities in gastric cancer tissue account for selectivity of the treatment. Activity of TS was higher in 19 cases of the poorly differentiated type than in 16 cases of the well differentiated type (P < 0.02), whereas TK activity was lower in the poorly differentiated type than in the well differentiated type (P < 0.01). Thus, the TS/TK ratio was significantly higher in poorly differentiated gastric cancers than in well differentiated cancers (P < 0.001). These results suggest that a greater dependence upon the de novo pathway of pyrimidine synthesis in poorly differentiated gastric carcinomas may enhance the efficacy of sequential methotrexate and 5-fluorouracil treatment.
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PMID:Activities of thymidylate synthetase and thymidine kinase in gastric cancer. 134 Dec 54

Mechanism of synergism and clinical results of methotrexate and 5-fluorouracil (MTX/5-FU) combination therapy for gastric cancer were studied. The response rate against poorly differentiated gastric cancers was 35% in this treatment. This treatment also showed a remarkable effect against cases with pleural and abdominal effusion caused by cancerous disseminations. A promising result was obtained by this treatment as neoadjuvant and postoperative chemotherapy against Borrmann type 4 gastric cancer. A greater dependence on the de novo pathway of pyrimidine synthesis against poorly differentiated gastric carcinoma, which was estimated by the fact that the thymidylate synthetase/thymidine kinase ratio was significantly higher in poorly differentiated gastric cancer than in well differentiated cancer, may potentiate therapeutic results of this treatment.
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PMID:[Mechanism of synergism and clinical results of sequential methotrexate and 5-fluorouracil in the treatment of gastric cancer]. 162 50

In tissues obtained from patients undergoing gastrectomy, the activities of 12 enzymes involved in pyrimidine nucleotide synthesis: cytidine triphosphate (CTP) synthetase, deoxycytidine monophosphate (dCMP) deaminase, thymidine monophosphate (dTMP) kinase, uridine (Urd), deoxycytidine (dCyd) and thymidine (dThd) kinases, Urd, deoxyuridine (dUrd) and dThd phosphorylases, cytidine (Cyd) and dCyd deaminases, and DNA polymerase were examined in the eight-well-differentiated and 12 poorly differentiated gastric cancer tissues and the ten normal tissues. These cases were clinically advanced and serosal invasions were evident. Activities of these enzymes were higher in the poorly differentiated tissues than the well differentiated type and in the normal tissues. Significant differences were noted between the poorly differentiated and well-differentiated types, in dTMP kinase (P less than 0.02), dThd kinase (P less than 0.05), dThd phosphorylase (P less than 0.01), and DNA polymerase (P less than 0.05). The authors' findings show that the level of pyrimidine nucleotide synthesis, in both de novo and salvage pathways, is higher in the poorly differentiated gastric cancer tissues than in the well-differentiated type and suggest that antitumor drugs have an increased susceptibility in cases of poorly differentiated gastric carcinoma.
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PMID:Pyrimidine nucleotide synthesis is more extensive in poorly differentiated than in well-differentiated human gastric carcinoma. 291 Apr 29

Antitumor therapies using polyamine antimetabolites combined with 1-(4-amino-2-methyl-5-pyrimidyl)methyl-3(2-chloroethyl)-3-nitrosourea (ACNU) or fluorinated pyrimidines for human gastric cancer xenotransplanted into nude mice were studied to determine inhibiting post-therapeutic regrowth of the tumor after cessation of antitumor treatments with polyamine antimetabolites alone. ACNU 20 mg/kg, fluorinated pyrimidine, 5-FU 52.8 mg/kg and 5'-deoxy-5-fluorouridine (5'-DFUR) 100 mg/kg as well as polyamine antimetabolites, alpha-difluoromethylornithine (DFMO) 1000 mg/kg and methylglyoxal-bis-guanylhydrazone (MGBG) 50 mg/kg were given intraperitoneally for 5 successive days. When DFMO and MGBG were combined with ACNU, the post-therapeutic regrowth was definitely inhibited, while combined treatments with 5-FU or 5'-DFUR did not inhibit the regrowth. Post-therapeutic DNA biosynthesis was suppressed in mice given DFMO, MGBG plus ACNU. On the contrary, in mice treated with DFMO, MGBG plus 5-FU or 5'-DFUR, suppression of DNA biosynthesis was not observed. Tumor tissue spermine levels in the DFMO, MGBG plus 5-FU or 5'-DFUR group remained unchanged, compared to those in the DFMO + MGBG group. In mice given DFMO, MGBG plus ACNU, however, spermine levels were markedly depressed; and the ACNU alone depressed also the tissue spermine levels. These different results between nitrosourea and fluorinated pyrimidines may relate to mechanisms of action of these antitumor drugs.
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PMID:Combined therapy of polyamine antimetabolites and antitumor drugs for human gastric cancer xenotransplanted into nude mice. 294 8

To investigate the optimal dosage schedule for 5'-deoxy-5-fluorouridine (5'-DFUR), a randomized comparative study was performed in patients with inoperable or advanced gastric cancer. Eight hundred mg/m2/day of 5'-DFUR was administered in the continuous administration group, while in the intermittent administration group 1,400 mg/m2/day was given for 4 days followed by 3 days with no medication in a one-week cycle, making the total dose 5,600 mg/m2/week in both regimens. In both groups, 5'-DFUR was administered for more than 4 weeks. Overall response rate was 14.3% (3/21) for both administration methods. The response rate for the primary site was 9.5% (2/21) in the continuous administration group, and 14.3% (3/21) in the intermittent group. As to toxicity, the incidence of diarrhea was 26.7% in the continuous group and 4.2% in the intermittent group. Although there was no significant difference between these two dosage schedules in efficacy and toxicity, the lower incidence of diarrhea suggested the clinical usefulness of the intermittent administration method. This result emphasized the need to further studies to investigate the most appropriate dosage schedule for fluorinated pyrimidine derivatives.
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PMID:[Randomized comparison of continuous and intermittent oral administration of 5'-deoxy-5-fluorouridine in the treatment of advanced gastric cancer; a phase II trial by the Multi-institutional Cooperative Study Group]. 296 7

The chemotherapy of gastric carcinoma is at an important point in its evolution. Multiple studies with a variety of agents have demonstrated that combination chemotherapy appears to be superior to single-agent chemotherapy in regard to response rate but not survival rate. The typical single agent results in response rates of 20% or less, whereas the typical combination chemotherapy regimen results in response rates of 30% to 50%. The FAM (5-fluorouracil [5-FU], doxorubicin, mitomycin C) chemotherapy regimen, widely used during the last 10 years, produces partial responses (PRs) in 35% of patients. However, the overall complete response (CR) rate is only 2%. Long-term survival of patients with disseminated malignancy is only achieved when treatments produce CR of disease. Because available combination chemotherapy approaches to gastric cancer only produce PRs, it is not surprising that there has been no impact on patient survival from these approaches. There are several newer approaches that hold promise in the treatment of gastric cancer. For example, the role of cisplatin in gastric cancer has not been completely defined. A recent study of FAP (5-FU, doxorubicin, cisplatin) has reported a 50% response rate with a significant number of CRs. The FAP regimen needs further exploration. The drug triazinate appears to have activity in gastric cancer, and in combination with mitomycin C produces a 28% response rate in patients who had failed chemotherapy regimens containing fluorinated pyrimidine. Thus, the efficacy of this drug needs further exploration in stomach cancer therapy. There is no clear definition of the future role of hepatic arterial infusion in gastric cancer. There is no question that, in colon cancer, response rates with fluorinated pyrimidine alone or fluorinated pyrimidine with mitomycin C are in the range of 50% when hepatic arterial infusion is used. This approach needs to be explored in gastric cancer. Finally, the use of intraperitoneal (IP) therapy in patients with minimal disease should be explored, because a common form of relapse in carcinoma of the stomach is IP dissemination.
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PMID:Chemotherapy of advanced gastric cancer: present status, future prospects. 329 18

590-S is a new masked compound of 5-fluorouracil, the antimetabolic antitumor agent of the fluorinated pyrimidine group. The safe dose for the phase II study was determined during the phase I study to be 600 mg/m2/day, equivalent to 900 mg/body/day. The phase II study involving 24 institutions was performed for the treatment of gastro-intestinal cancer. A daily dose of 900 mg was given 3 times a day after meals for more than 4 weeks. The number of registered cases was 32 with stomach cancer, 17 with colo-rectal cancer and 8 with others. 4 of the 23 completed cases with stomach cancer were judged as PR, and the response rate was 19.0%. No response was found in the cases with colo-rectal cancer. Slight side effects were observed in 14 of the 44 evaluable cases. Most of these were gastro-intestinal disorders.
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PMID:[Phase II study of 590-S (1-phthalidyl-5-fluorouracil) in patients with gastrointestinal cancer. Tokyo Cancer Chemotherapy Cooperative Group]. 367 97

Activities of pyrimidine nucleoside phosphorylase in brain tumors were measured and their relationship to a clinical course of the patients was investigated. Pyrimidine nucleoside phosphorylase is said to exist more quantitatively in malignant tumors such as Sarcoma 180, Ehrlich ascites carcinoma, Walker 256, and hepatoma, and very little in normal tissues. In brain tumors the activities were measured by bioassay and compared to that of Sarcoma 180. When the activity of Sarcoma 180 was expressed to be 100%, those of brain tumors were as follows: ten cases of normal brain less than 8.5; six cases of glioblastoma 39.3 +/- 30.7; five cases of astrocytoma 22.0 +/- 13.8; five cases of meningioma 22.4 +/- 13.7; two cases of oligodendroglioma 8.1 and 11.3; two cases of sarcoma 94.3 and 145.4; chordoma 48.0; ependymoblastoma 3.7; plexus papilloma 22.5; parotid cancer 43.4; ten cases of metastatic brain tumors from lung cancer 61.5 +/- 41.6; two cases from breast cancer 28.0 and 68.8; that from thyroid cancer 10.0; that from gastric cancer 13.5; malignant melanoma 77.2. In 12 cases of gliomas (glioblastoma, astrocytoma, oligodendroglioma) the mean activity was highest in glioblastoma (39.3), followed by astrocytoma (22.0) and oligodendroglioma (9.7). The postoperative survival time became shorter in gliomas with the higher activities. In metastatic brain tumors from lung, breast, and gastric cancer, the average time from the diagnosis of primary cancer to brain metastasis was shorter in cases with high activities and longer in cases with low activities.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Activities of pyrimidine nucleoside phosphorylase in brain tumors and antitumor effect of 5'-DFUR]. 622 41

A Phase II study of a new fluorinated pyrimidine (TAC-278) was performed in 14 institutions from May 1980 to April 1981. 400-1200 mg of TAC-278 was orally administered in 2 to 4 divided doses every day for more than 4 weeks. Selection of patients and evaluation of clinical response were done according to the criteria for "Evaluation of Clinical Effects of Chemotherapy on Solid Tumors" by Koyama and Saito. A total of 188 patients were entered in the study and 96 of them were evaluable. Partial responses were observed in 9.4% (9/96) of the evaluated cases. Stomach cancer and colorectal cancer showed partial responses in 10.8% (4/37) and 20% (5/25), respectively. As for side effects, slight gastrointestinal symptoms (loss of appetite, nausea and vomiting etc.) were found in 24% and CNS-symptoms such as dizziness and disorientation were observed in approximately 8% of the patients.
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PMID:[Phase II study of a new fluorinated pyrimidine, ethyl (+/-)-t-6-butoxy-5-fluoro-2, 4-dioxohexahydropyrimidine-r-5-carboxylate (TAC-278)]. 718 76

Pyrimidine nucleoside phosphorylase (PyNPase) activity was measured in gastric cancer tissue from 25 patients who underwent resections of gastric cancer. The relation between the activity and host and tumor factors in gastric cancer was studied, and the following results were obtained. 1. PyNPase activity was 128.3 +/- 99.5 in cancer tissue and 37.2 +/- 23.1 in non-cancer tissue. The level was significantly higher in cancer tissue (p < 0.0001). 2. With respect to host factors, the PyNPase activity tended to be high in patients in whom cell-mediated immune response was maintained. 3. With respect to tumor factors, the values tended to be high in patients who were positive for lymph vessel and venous invasion, and positive for lymph node metastasis. 5'-deoxy-5-fluorouridine(5'-DFUR) is an anticancer agent which manifests antitumor effects when it is transformed into 5-FU by PyNPase. When this agent is administered to gastric cancer patients, it can be expected to be more effective in the above types of patients because of its characteristics.
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PMID:[Study on pyrimidine nucleoside phosphorylase (PyNPase) activity in resected tissues of patients with gastric cancer]. 766 71


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