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

A combined efficacy of the polyamine antimetabolites, alpha-difluoromethylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG) with two fluorinated pyrimidines was studied. DFMO, MGBG, 5-FU and 5'-deoxy-5-fluorouridine (5'-DFUR) were administered intraperitoneally to BALB/c nu/nu mice bearing xenotransplanted human gastric cancer for 5 consecutive days. Similar antitumor efficacies were observed in 3 groups treated with DFMO plus MGBG, DFMO, MGBG plus 5-FU as well as DFMO, MGBG plus 5'-DFUR. The two groups on 5-FU or 5'-DFUR alone did not differ in antitumor effects from the control, although reasonable levels of 5-FU were involved in tumor tissues. Hepatic and splenic 5-FU levels after 5-FU administration were significantly higher than those after 5'-DFUR, and marked decrease in mouse body weight was caused by 5-FU alone as well as 5-FU plus polyamine antimetabolites for 5 consecutive days. DNA biosynthesis and spermine levels in the tumor tissues on day 2 after cessation of the treatments dropped in 3 groups with DFMO plus MGBG, DFMO, MGBG plus 5'-DFUR as well as DFMO, MGBG plus 5-FU, while on day 6 there was little difference between the control and treated groups. These data suggest that combination with 5-FU or 5'-DFUR does not enhance the antitumor activity of polyamine antimetabolites by this experimental regimen.
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PMID:[Anticancer treatment with a combination of antimetabolites of polyamine and pyrimidine]. 293 57

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

Because of the limited effects of single-agent chemotherapy for solid tumors, combination therapy was employed in an attempt to enhance the clinical effects. Following our former report in which the combination effects of mitomycin C (MMC) and 5'-deoxy-5-fluorouridine (5'-DFUR) were clarified, combined applications of 4 drugs, vindesine (VDS), methotrexate (MTX), cisplatin (CDDP) and 5'-DFUR against 3 lines of human breast cancer (H-62, H-31, H-71), and one line each of gastric cancer (H-55) and colon cancer (H-110) xenografted into nude mice were evaluated in comparison with CAF (cyclophosphamide, adriamycin and 5-FU) therapy which is commonly used for breast cancer. Treatment was initiated in groups of 7 mice each when the mean tumor volume of subcutaneous tumors had reached about 100mm3, and the therapeutic effect was evaluated in terms of the inhibition rate (I.R.). A synergistic effect is said to exist when the combination therapy is superior to each single drug therapy at the maximal tolerated dose. Combination therapy with 3 drugs (VDS, CDDP and 5'-DFUR) or 4 drugs (VDS, CDDP, MTX and 5'-DFUR) achieved an I.R. of over 98%, i.e., a marked effect with tumor shrinkage, in 3 lines of tumors (H-55, H-31 and H-62). Moreover, remarkable effects were shown even in the other 2 lines which were insensitive to every single-agent therapy, the I.R. values being 85.7% (H-71) and 78.5% (H-110). A synergistic effect was obtained in 3 of the 5 lines examined. These combination therapies were histologically superior to therapies employing each single-drug therapy or CAF therapy. The side effects for combination of these 3 or 4 drugs evaluated by body weight loss were transient and equivalent to maximal dose of VDS or CDDP. Clinically, it is thought that these combined therapies of 3 or 4 drugs will bring about a considerable response in practice.
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PMID:[Combination chemotherapy with 3 or 4 drugs on human breast and gastrointestinal cancer xenografts in nude mice (II)]. 295 10

As a postoperative adjuvant chemotherapy for gastric cancer, we have administered a combination of NCS (Neocarzinostatin) and 5-FU (NF treatment method) and in this paper we have compiled the results obtained in patients who were treated for 5 years in an attempt to compare the 5-year survival rate with that of patients administered a combination of MMC and 5-FU (MF treatment group) and a control group administered no anticancer agents. As the selection of either NF or MF treatment was conducted on an annual basis, this study can be considered an historical controlled study. The results obtained are summarized as follows. On comparing the survival rate of the NF treatment group and the control group, the 5-year survival rate for all patients who underwent curative resection and all patients with histological stage III cancers and the curative resection PS (+) group, as well as the survival period of the non-resected patients, showed a statistically significant difference, indicating that the survival rate was higher in the NF group. On comparing the NF group and the MF group, although no statistically significant difference was observed between then based on a stratified analysis of all resected cases, histological stage differences and n.ps factors, etc., certain values tended to indicate a higher survival rate for the NF group. Moreover, the survival rate of the non-resected patients was more favorable in the NF group. These results confirm that NCS is useful for the treatment of stomach cancer and compares favorably with MMC. The appearance of side-effects was significantly lower in the NF group in comparison with the MF group and the number of patients who had to discontinue therapy was extremely low.
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PMID:[Postoperative adjuvant chemotherapy using NCS (neocarzinostatin) and 5-FU in the treatment of gastric cancer. First report--A comparison with the 5-year survival rate of patients undergoing combined therapy with MMC and 5-FU]. 296 Feb 67

Sequential chemotherapy with low-dose methotrexate (30 mg/body) and 5-FU (750 mg/m2) was undertaken in 16 patients with advanced gastric cancer. Following the chemotherapy, leucovorin (30 mg/body) was injected intravenously. These treatment were repeated weekly for two to eight weeks. Out of 16 patients, two partial remissions and two minor responses were obtained. The overall response rate was 12.5%. There were no cases of renal or hematologic toxicity. The only adverse effect was nausea. We concluded therefore, that sequential chemotherapy with low-dose methotrexate and 5-FU is a useful method for advanced gastric cancer.
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PMID:[Sequential chemotherapy with low-dose methotrexate and 5-fluorouracil in advanced gastric cancer]. 299 97

Twenty-five patients with gastrointestinal tumors (stomach 13, colon 8, pancreas 2, liver 2) were treated with a combination chemotherapy regimen consisting of CDDP (30 mg/m2/day d 1, 2) and 5-FU (500 mg/m2/day d 1-3), repeated every 3 or 4 weeks. The patients comprised 14 males and 11 females with a median age of 50 years (range 24-69), and a median performance status of 80% (range 40-100%). Thirteen patients had had prior chemotherapy. Partial response was observed in 2 patients (colon and liver), which lasted for 2 months each, respectively. No objective response was observed in 11 patients evaluable for gastric cancer. Non-hematological toxicities were nausea (92%), vomiting (56%), proteinuria (17%), transient elevation of BUN (8%), and hepatotoxicity (11%). Leukopenia and thrombocytopenia were observed in 71% and 25%, respectively. However, these toxicities were mild to moderate, and generally well tolerated.
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PMID:[Combination chemotherapy of cis-diamminedichloroplatinum (CDDP) and 5-fluorouracil (5-FU) in gastrointestinal tumors]. 301 30

Three hundred and twenty-two patients with locally advanced (stages III and IVA) and disseminated (stage IVB) gastric cancer were included in a randomized trial to assess the effect of immunochemotherapy (BCG and 5-fluorouracil,5-FU). The survival of patients receiving chemoimmunotherapy was compared to chemotherapy (5-FU) or no further treatment (control) groups. Patients with stage III underwent radical surgery (subtotal or total resection), stage IVA palliative resection, while explorative laparotomy or bypass was performed in stage IVB. Patients with stage III and IVA receiving immunochemotherapy had significantly (p less than 0.05) prolonged survival in comparison to chemotherapy or control groups. Prolongation of survival was more pronounced in patients with diffuse type carcinoma than in patients with intestinal type of tumour according to Lauren's classification. The survival of patients receiving chemotherapy was somewhat shorter than that of the control group, but the differences were not statistically significant. There was no effect of either immunochemotherapy or chemotherapy in patients with stage IVB. No serious side effects of immunochemotherapy were noted. These results indicate that immunochemotherapy may be a safe form of adjuvant treatment in patients with operable gastric cancer.
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PMID:Postoperative immunochemotherapy (BCG + 5-FU) in advanced gastric cancer. 306 17

The combined effect of human interferons and chemotherapeutic agents on human gastric cancer cell lines and a human pancreatic cancer cell line was studied in vitro. Interferons, when used as a single drug, showed inhibitory effects in the order, gamma greater than beta greater than alpha. However, there was no significant difference between the effects of natural and recombinant interferon. In combination therapy, the chemotherapeutic agents should be administered first, followed by administration of interferon(s), since this method showed the most inhibitory effect. Low concentration of 5-FU (0.001-0.01 microgram/ml) or methotrexate (0.01-1 microgram/ml) was able to inhibit the growth of cell lines when combined with interferon. These results suggested that in clinical use, low amounts of chemotherapeutic agents followed by administration of interferon(s) could be available with minimum side effects and with more pronounced anticancer effects.
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PMID:[Antitumor effect of interferons with chemotherapeutic agents]. 308 Sep 64

UFT, a combination antitumor drug consisting of 1 part Futraful and 4 parts Uracil, was administered preoperatively to 10 patients with gastric cancer, 9 patients with colo-rectal cancer and 1 patient with hepatocellular carcinoma. A pharmacokinetic study was then carried out after oral administration of 600 mg per day of UFT, measuring Uracil, Futraful and 5-FU levels in serum and tumor tissue. Preoperative total doses of UFT for gastric cancer were 3.0-11.4 g, for colo-rectal cancer 3.6-16.8 g and for hepatocellular carcinoma 8.4 g. Side effects, mainly gastrointestinal symptoms, were observed in 3 cases. Abnormalities of liver function test, depression of serum protein and bone marrow damage were observed in 4 cases. 5-FU concentration in the tumor tissue was higher than 0.05 mu/g in 15 of 19 patients (79%). This suggested that 5-FU was maintained in the tumor tissue for a longer period. However, it also suggested that the concentration of Uracil in the tumor tissue corresponded to the total dose of UFT as did the degree of side effects.
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PMID:[Effects of preoperative administration of UFT in gastrointestinal cancer]. 308 Sep 66

A literature survey was conducted regarding adjuvant therapy for surgical cases of gastric cancer. A total of 66 papers published on a world wide basis in the 5 years from 1980 through 1984 were collected. Forty-three papers (65%) were published by Japanese researchers, of which only 17 were written in English. Adjuvant therapy was regarded as being effective in about 60% of the papers. The main drugs achieving effective adjuvant chemotherapy were mitomycin C (M), 5-FU (F), Tegafur, MF, and MFC(M+F+cytosine arabinoside). The cases yielding an effective result were mainly patients who had undergone radical surgery for stage II or III gastric cancer. The doses used for adjuvant chemotherapy were slightly less than the doses used for chemotherapy of advanced gastric cancer in internal medicine. The incidences of adverse effects of the adjuvant chemotherapy were almost the same as those encountered in internal medicine, and severe complications occasionally developed. Some recent reports observed that efficacy of adjuvant chemotherapy was increased by intensive therapy in the immediate postoperative period and by maintenance therapy over the long term.
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PMID:[Adjuvant therapy of gastric cancer in the literature from 1980-1984]. 308 97


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