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)

KW-2083 [7-n-(p-hydroxyphenyl)-mitomycin C] is a new mitomycin C (MMC) derivative. Its myelotoxicity was compared with that of MMC by using colony-forming unit-spleen (CFU-S) from the femurs of C57BL/6 mice. As a result, it was estimated that the intensity of myelotoxicity of MMC was four times greater than that of KW-2083. Based on this data, a clinical trial of KW-2083 was conducted in 24 cases with various types of advanced solid tumors. KW-2083 was administered by i.v. injection at a dose of 40 mg/body every week. Out of 15 evaluable cases, a case of ovarian cancer showed a partial response. One case of each of ovarian cancer and gastric cancer showed minor response. However, as with mitomycin C, the dose-limiting toxicity of KW-2083 was leukopenia and thrombocytopenia. Other toxicities encountered were nausea, vomiting, anorexia, phlebitis and hepatic dysfunction. There were no cases with renal toxicity. Plasma concentration of KW-2083 was bioassayed in 3 cases who received 40 mg/body as an i.v. bolus injection. Plasma concentration-time curves fitted to a one-compartment model and half-life values averaged 27.6 min. The effective and low toxic dose schedules of KW-2083 should be investigated further.
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PMID:[A clinical trial of a new mitomycin C derivative, KW-2083 (7-N-(p-hydroxyphenyl)-mitomycin C)]. 403 9

The antitumor activity of tumor necrosis factor (TNA) against various human cancer cells (32 cases) was investigated by 51Cr cytotoxic release assay and tumor stem cell assay. Over 50% sensitivity (the ratio of cytotoxicity for L929 cells) was shown by 4 of 14 cases of gastric cancer (28.6%), 7 of 9 cases of leukemic cells (77.8%), and 1 case each of pancreatic carcinoma and ovarian cancer. However, scarcely any sensitivity was shown by APL, a portion of the gastric cancer cells, normal lymphocytes or colony-forming cells tested. No correspondence was observed between the histological type of the cancer and TNF sensitivity. The above results seem to confirm the significant antitumor activity of TNF against human cancer cells.
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PMID:[Antitumor effect of the tumor necrosis factor against various types of human cancer cells]. 406 18

Among 4,184 patients with cancer of the esophagus, 55 second primary cancers were observed, whereas 64 were expected [relative risk (RR) = 0.86]. The absence of an excess risk of alcohol- and tobacco-related cancers was not anticipated. A significant 19% deficit of second cancers was found among 30,843 patients with stomach cancer. Cancer of the rectum, kidney, and lung all occurred significantly below expectation. An excess risk of ovarian cancer (RR = 1.9) was seen in women. Reasons for these findings are not entirely clear. Cancer of the small intestine is rare, and despite a relatively short survival expectation, a moderate excess of second cancers was seen among 868 patients (36 vs. 26.8). Only cancers of the liver and gallbladder were significantly elevated, and the possibility of misclassified metastases is discussed. Colon cancer is one of the most common cancers in Denmark, and 29,490 patients with this disease were at slightly lower risk for development of second cancer (RR = 0.96; 95% confidence interval = 0.9-1.0) than the general Danish population, excluding secondary colon cancers. Esophageal, stomach, and liver cancers occurred less frequently than expected. That cancers of the uterine corpus and ovary were significantly increased supports the notion that common risk factors, such as diet and endogenous hormones, influence the development of these cancers. A significant 23% deficit of second cancers was also found among 26,597 patients with cancer of the rectum, excluding secondary rectal cancer. Significant deficits were seen for cancers of the stomach (RR = 0.5), lung (RR = 0.8), and brain (RR = 0.5), and for multiple myeloma (RR = 0.4). The likelihood of underreporting of second cancers, especially of the digestive system, is discussed. However, cancer of sites previously reported to be associated with rectal cancer, e.g., the colon, breast, and uterus, did not occur below expectation. Cancers of the liver and biliary tract occurred in 4,453 patients; their average survival was only 1 year. Except for a slight excess of cancer of the ovary (5 vs. 1.6), the risk of second cancer development for all sites was consistent with unity (RR = 0.90). The risk of second cancers among 7,752 persons with cancer of the pancreas was not greater than expected (88 vs. 85.2). Males were at significant risk of kidney cancer (RR = 3.2), whereas females showed elevated rates of cancers of the uterine corpus (RR = 3.2) and ovary (RR = 3.1). No site occurred significantly below expectation.
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PMID:Second cancer following cancer of the digestive system in Denmark, 1943-80. 408 3

4'-epi-doxorubicin (4'-epi-DX) is a new anthracycline antibiotic. It differs from doxorubicin (DX) by the epimerization of the OH group in position 4' of the aminosugar moiety, and was synthesized in an effort to find agents with a superior therapeutic index to the parent compound doxorubicin (DX). 4'-epi-doxorubicin binds to DNA and inhibits nucleic acid synthesis and function. The antitumor activity of 4'-epi-DX in several experimental tumors (Leukemias L 1210, P 388, Gross Leukemia, Sarcoma 180 ascitic and solid, C3H/HE mammary carcinoma) is similar to that of DX. However, 4'-epi-doxorubicin has greater antitumor activity than doxorubicin in Lewis lung carcinoma, MS-2 sarcoma lung metastasis, and human melanoma in athymic mice. In chronic toxicity studies there were no qualitative differences between 4'-epi-DX and DX; quantitatively, however, 4'-epi-DX was less toxic. In different experimental models 4'-epi-DX has been shown to be less cardiotoxic than its parent compound. In chronic toxicity studies in the rabbit, histopathologic findings revealed the same pattern of cardiotoxicity for both drugs but less marked with 4'-epi-DX. Distribution studies in mice with tumors showed a lower concentration of 4'-epi-DX in the heart, spleen and kidneys; the hepatobiliary metabolism and excretion of 4'-epi-DX investigated in the rat, indicated that the new analogue was more extensively metabolized than the parent compound. Pharmacokinetics of 4'-epi-DX in humans showed a multiexponential decrease of plasma levels; the same pattern was observed for the metabolite 13-OH epidoxorubicinol but with lower concentrations than the unchanged drug. A high plasma clearance (0.9-1.41/min), a terminal half-life of about 30-40 hr and a large volume of distribution were the main pharmacokinetic characteristics of 4'-epi-DX. A reduction of the dose appears to be appropriate in patients with liver function impairment. Phase II studies with 4'-epi-DX have indicated that the drug produces a pattern of acute toxicity, including acute cardiac toxicity, qualitatively similar to that of DX at identical doses but quantitatively lower, with particular regard to leukopenia and gastrointestinal toxicity. The range of single active doses is between 60 and 90 mg/m2, the most frequently employed doses schedules being 75 or 90 mg/m2 i.v. every 3 weeks. 4'-epi-DX has shown activity in a variety of tumors such as breast carcinoma, soft tissues sarcomas, NH lymphomas, leukemias, ovarian cancer and gastric cancer. Preliminary evidence of activity has been found in melanoma, rectal cancer and pancreatic cancer suggesting a broad spectrum of activity. As to chronic cardiac toxicity up to now only 2 mild to moderate and reversible CHF have been observed at doses of 1120 and 1235 mg/m2 in about 700 treated patients. Specific and comparative studies are in progress: preliminary findings from a randomized comparison of 4'-epi-DX vs DX in breast cancer indicated that 4'-epi-DX may have a lower cumulative cardiotoxicity.
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PMID:4'-epi-doxorubicin, a new analogue of doxorubicin: a preliminary overview of preclinical and clinical data. 634 72

A clinical study on human lymphoblastoid interferon (HLBI) in various advanced malignant diseases was performed. HLBI was administered to a total of 25 patients with various advanced malignant diseases in order ot investigate antitumor effect and toxicity. The diseases evaluated were as follows: 8 multiple myeloma (MM), 2 chronic lymphocytic leukemia (CLL), 2 adult T cell leukemia (ATL), 1 acute lymphocytic leukemia (ALL), 8 breast cancer, 3 gastric cancer and 1 ovarian cancer. Twenty-three patients received either 3 million or 6 million units of HLBI by daily intramuscular injection or every other day. One patient with ATL received 18 million units of HLBI by i. v. daily and 1 patient with ALL received 30.32 million units of HLBI i. v. daily. Tumor regression (PR) was observed in 2 patients with MM, each one patient with ATL and ALL, respectively. Major toxicities were pyrexia, myelosuppression, general malaise and G.I. toxicity. Several patients showed abnormality of hepatic or renal function. Two patients who received HLBI for more than a year developed cardiac toxicity.
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PMID:[Clinical trial of human lymphoblastoid interferon on advanced malignancy]. 635 2

Sixty-six patients with advanced solid tumors were treated with 4'-epi-doxorubicin at a dose of 90 mg/m2 by rapid IV injection every 21 days until the disease had progressed or to a maximum cumulative dose of 540 mg/m2. Myelosuppression, nausea and vomiting, and alopecia were the almost frequent side effects, but their incidence seemed lower than that after a comparable dosage of doxorubicin. After a cumulative dose of 540 mg/m2 a significant decrease of QRS complex deflection on the electrocardiogram was detected, but no case of congestive heart failure was observed. Partial remission and minor remission were achieved, respectively, in nine (15%) and five (9%) out of 59 evaluable patients for a median duration of 6 months. Partial remission occurred in anthracycline-sensitive tumors like breast cancer (4 of 13), lung cancer (1 of 17), head and neck cancer (1 of 8), gastric cancer (2 of 4), and ovarian cancer (1 of 1).
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PMID:A phase-II clinical trial of 4'-epi-doxorubicin in advanced solid tumors. 658 36

4'-0-tetrahydropyranyladriamycin hydrochloride (THP-ADM) is a new anthracycline derivative. The antitumor activity of THP-ADM was tested on 51 human tumor samples representing ten different tumor types in in vitro colony assay method. Tested tumors were: 26 cases of ovarian cancer, 8 cases of breast cancer, 6 cases of colorectal cancer, 3 cases of endometrial cancer, 2 cases each with gastric cancer and sarcoma, and another 4 cases. An in vitro colony assay was done in soft agar as described by Hamburger & Salmon. The criteria for in vitro sensitivity was defined as a 70 percent or greater reduction in the number of colonies after a 1-h exposure to drugs. The selected concentrations of THP-ADM for assay were 0.05, 0.5, and 1.0 micrograms/ml. The sensitivity rates for THP-ADM in each dose were: 0.05 micrograms/ml (7/19, 37%), 0.5 micrograms/ml (10/51, 20%), and 1.0 micrograms/ml (12/19, 63%). In vitro sensitivity of adriamycin (0.04 micrograms/ml) was simultaneously tested in 49 cancer patients. Five out of 25 ovarian cancer patients (20%) showed responses to adriamycin and an overall response rate was 12% (6/49). These data indicate that THP-ADM has an antitumor activity against various cancers and it is comparable to that of adriamycin.
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PMID:Activity of 4'-0-tetrahydropyranyladriamycin hydrochloride (THP-ADM) in a human tumor cloning system. 668 22

A phase II clinical trial of a new anthracycline, 4'-O-tetrahydropyranyladriamycin (THP-ADM), was performed in thirty-one patients with advanced malignant tumors refractory to standard chemotherapies. The dosage of THP-ADM was 40 mg/m2 by iv bolus injection repeated every 3 weeks. Of 3 evaluable patients with non-Hodgkin's lymphoma, one achieved partial remission. A minor response was noted in one out of 7 patients with gastric cancer and one out of 5 patients with ovarian cancer. Leukopenia less than 4 X 10(3)/cmm and thrombocytopenia less than 100 X 10(3)/cmm were seen in 81% and 19% of cases, respectively. Mild gastrointestinal toxicities including nausea and vomiting and anorexia were observed in about one third of the patients. Mild hair loss occurred in 2 patients (6%). No ECG abnormalities on clinical sign of cardiotoxicity were seen.
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PMID:[Phase II study of 4'-O-tetrahydropyranyladriamycin(THP-ADM)]. 669 55

Colony forming ability of solid tumor cells was studied in a tumor colony assay (human tumor stem cell assay). In 50 cases of solid tumors, cloning efficiencies of 5 X 10(5) cells plated were as follows: breast cancer 12/12 (100%), colon cancer 10/11 (91%), ovarian cancer 9/9 (100%), sarcomas 7/9 (78%), gastric cancer 3/6 (50%), endometrial cancer 2/2 and pancreatic cancer 1/1. An overall cloning efficiency was 88% (44/50) and this rate is higher than those reported in literatures. Ovarian cancer showed the highest plating efficiency of 0.07% (number of colonies/number of cells plated X 100%) in various solid tumors tested. Subsequently, plating efficiencies of colon and breast cancer were 0.03 and 0.01%, respectively. In the cases of sarcomas and gastric cancer, low plating efficiencies were seen (0.008%, 0.003%). The overall rate succeeded colony growth of solid tumors was somewhat higher in enzymatically treated tumor cells, that is, cloning efficiencies in mechanical and enzymatic methods were 85 and 90%, respectively. The enzymatic disaggregation is an advantageous method in gastric cancer and sarcomas. Various solid tumors can be formed colonies in soft agar and chemosensitivity test using in vitro colony assay is expected in solid tumors.
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PMID:[Colony formation of solid tumors in in vitro colony assay (human tumor stem cell assay)]. 676 97

The effects of chemotherapy for lung metastasis in 284 cancer patients using various anti-tumor drugs, including classic ones and modern active agents for the past 18 years, were presented. Lung metastasis for lung cancer was excluded. The response was achieved in cervical carcinoma of the uterus (17/62, 27%), endometrial carcinoma of the uterus (1/7, 14%), colorectal cancer (6/39, 15%), breast cancer (5/28, 18%) and stomach cancer (4/28, 14%). A high response was achieved in myosarcoma (5/12, 42%), testicular cancer (5/11, 45%) and also in ovarian cancer (3/10, 30%). Though there were few cases, a high response was achieved in malignant melanoma (2/3), choriocarcinoma (2/4) and esophageal cancer (1/3). In total patients the response rate was 20%. In these cases a complete response was achieved in 4 cervical cancers; one testicular cancer, ovarian cancer, esophageal cancer and renal cancer, respectively. However, the effect was temporary and no longterm survivor was observed except for one case of renal cancer treated continuously with interferon (3 X 10(6) units daily) and showing complete remission after 7 months of therapy. The effect of chemotherapy for lung metastasis was compared between nodular metastasis (NM) and lymphagiosis carcinomatosa (LC). In cervical carcinoma of the uterus, the response rate in NM (39%) was higher than in LC (11%). However, no difference was observed in breast cancer (NM 15%, LC 13%) nor in stomach cancer (NM 13%, LC 18%).
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PMID:[Chemotherapy for metastatic lung cancer]. 687 21


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