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)

Thioredoxin (TRX) is a widely distributed Mr 13,000 protein with a redox-active dithiol/disulfide in the active site. The TRX system, consisting of TRX, TRX reductase, and NADPH, has an intracellular reducing capacity. Another reducing capacity, glutathione (GSH), can be associated with cis-diaminedichloroplatinum (cDDP) resistance. Therefore, we examined the involvement of TRX in cDDP resistance using two cell lines designated St/DDP and HT/DDP, which were established from the human gastric cancer cell line St-4 and the colon cancer cell line HT-29. St/DDP and HT/DDP were seven and five times as resistant to cDDP as their parental lines, and the expression of TRX in these variants was increased by 2.5- and 2-fold, respectively. The expression of TRX in the complete revertant cells of St/DDP was reduced as low as that in St-4 cells. TRX reductase activity was also increased in St/DDP and HT/DDP, suggesting that activation of the TRX system was associated with in vitro-acquired cDDP resistance. Because cDDP is the first-line drug against ovarian cancer, we examined the expression of TRX in 11 human ovarian cancer cell lines not treated with cDDP in vitro. Positive correlation between TRX expression and cDDP resistance was observed in these cell lines (r = 0.76, P = 0.007). This correlation was comparable to that between GSH content and cDDP resistance (r = 0.69, P = 0.019). These results suggest a possible involvement of TRX, as well as GSH, in cDDP resistance.
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PMID:Increased expression of thioredoxin/adult T-cell leukemia-derived factor in cisplatin-resistant human cancer cell lines. 981 87

Clinical studies performed by several groups suggest that platinum-DNA adduct--measured in malignant or non-malignant cells from cancer patients--may be an important marker for clinical biological effect of platinum-based chemotherapy. DNA repair is clearly an important effector of resistance to platinum-based DNA-damaging agents in tissue culture, although its role in effecting clinical resistance to these agents is not completely clear. In recent years, it has become apparent that DNA repair is an extremely complex process. Processes within DNA repair that may contribute to one or more drug resistance phenotypes include 0-6-alkytransferase activity, base excision repair, mismatch repair, nucleotide excision repair (NER), and gene specific repair. Clearly, several of these processes may concurrently show increased activity within any single cell, or tumor, at any one time. For platinum compounds, in vitro data clearly show that NER is the DNA repair pathway responsible for the repair of cisplatin-DNA damage. One critical gene within NER is ERCC1. Data exist in human ovarian cancer and in human gastric cancer that ERCC1 may be a useful marker for clinical drug resistance when platinum-based systemic chemotherapy is utilized. Although the data suggest that the relative ERCC1 mRNA level may be a good marker for NER activity in human ovarian cancer, it is unclear whether expression of this gene has any relationship to other pathways of DNA repair.
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PMID:Platinum-DNA adduct, nucleotide excision repair and platinum based anti-cancer chemotherapy. 986 Nov 96

Many studies have reported changes in the carbohydrate structure of serum glycoproteins in disease, but this information is often of limited value for understanding disease mechanisms because it is obtained with simple and/or indirect methodologies that determine only one structural feature. On the other hand, more detailed carbohydrate methodologies are time-consuming and require a lot of purified material. Using haptoglobin (Hp) as a model protein, a new procedure was devised that determined the oligosaccharide composition of very small amounts of Hp in a relatively short time. The Hp was purified by batch affinity-chromatography, oligosaccharides were removed with PNGase F, and the oligosaccharide composition of charged species was determined using HPAEC/PAD (Dionex carbohydrate analyser). The method was applied to the analysis of Hp from eight healthy individuals and 37 patients with different inflammatory diseases or cancers. Twenty-seven oligosaccharides were consistently detected, but the majority could not be identified. However, by calculating retention times relative to the sialylated biantennary peak (Neu5Ac(alpha)2-3/6Gal(beta)1-4GlcNAc(beta)1-2Man(alpha)1-6(Neu 5Ac(alpha)2-3/6Gal(beta)1-4GlcNAc(beta)1-2Man(alpha)1-3)Man(beta)1-4G lcNAc(beta)1-4GlcNAc) it was possible to compare profiles quantitatively. Although no peak was identified as disease-specific, characteristic and reproducible profiles were obtained. Particularly striking were reductions in the major peaks in Crohn's disease, rheumatoid arthritis, stomach cancer, accompanied by increases in unidentified peaks. Previous studies suggested that many of the unknown peaks were due to increased sialylation and fucosylation. Only small changes in patterns were observed for breast and ovarian cancer. The new procedure will be very useful in the characterization of oligosaccharide composition of glycoproteins in clinical specimens.
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PMID:Reproducible and sensitive determination of charged oligosaccharides from haptoglobin by PNGase F digestion and HPAEC/PAD analysis: glycan composition varies with disease. 988 48

The NF1 gene, a putative tumor suppressor gene, contains a GAP related domain (GRD) which accelerates hydrolysis of ras-bound GTP to GDP, thereby converting the ras oncogene from its active to inactive form. Two forms of the NF1 GRD transcript (Type I and Type II) are differentially expressed in neuroectodermal tumor tissue relative to differentiated neural cells, and in gastric cancer cell lines relative to normal stomach mucosa. We measured relative expression of NF1 Type II and Type I isoforms in cultured normal and malignant human ovarian surface epithelial cells(HOSE) and in invasive and borderline ovarian tumor tissue. We demonstrated an 11-fold increase in Type II:Type I ratio in 7 HOSE cultures relative to eight ovarian cancer cell lines. Our findings indicate a significant decrease in Type II isoform expression and increase in Type I expression in ovarian cancer cells and tumor tissue relative to HOSE cells. We also demonstrate an increase in Type II:Type I ratio, and a decrease in cell proliferation rate in three ovarian cancer cell lines on treatment with retinoic acid. We propose that differential expression of the NF1 Type I and Type II isoforms is related to cellular differentiation in ovarian epithelial cancer and strategies based on alteration in NF1 isoform expression may have therapeutic potential in ovarian malignancies.
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PMID:Differential expression of NF1 type I and type II isoforms in sporadic borderline and invasive epithelial ovarian tumors. 992 41

A case-control study nested within a large cohort, the American Cancer Society Cancer Prevention Study-1, was conducted to test associations between a family history of cancer and cancer mortality in women. By using logistic regression, the authors analyzed family history, as reported by 429,483 women enrolled in 1959, relative to subsequent mortality through 1972 from cancer within and across multiple sites. The associations between family history and cancer mortality were generally stronger within cancer sites than across cancer sites. Within-site associations were found for breast cancer (odds ratio (OR) = 1.9), colorectal cancer (OR = 1.6), stomach cancer (OR = 1.9), and lung cancer (OR = 1.7). Across-site associations were observed for a family history of 1) breast cancer as a risk factor for ovarian cancer mortality (OR = 1.6), 2) stomach cancer as a risk factor for ovarian cancer mortality (OR = 1.5), and 3) uterine cancer as a risk factor for pancreatic cancer mortality (OR = 1.6). A general pattern of positive associations was observed between a family history of cancer at several sites and subsequent death from pancreatic cancer. These findings support the growing body of evidence from cancer genetics suggesting that inherited cancer-susceptibility genes increase the risk for cancer at many sites and are not specific to cancer risk within a single site.
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PMID:Influence of a family history of cancer within and across multiple sites on patterns of cancer mortality risk for women. 1006 5

The antitumor effects of FK317, a novel substituted dihydrobenzoxazine, were evaluated using human tumor xenografts (small cell lung cancer, non-small cell lung cancer, stomach cancer, colon cancer, pancreatic cancer, breast cancer, cervical cancer and ovarian cancer). Tumor growth-inhibitory effects and the effective dose-range of FK317 were much stronger and broader, respectively, than those of reference drugs such as mitomycin C, adriamycin, cisplatin, taxol and irinotecan. Furthermore, the body weight decrease and myelosuppression in FK317-treated mice were less than in the animals given any of the reference drugs. To explain this tumor selectivity, the distribution of FK317 was investigated after dosing tumor-bearing mice with the 14C-labelled compound. The concentration of FK317 in tumor tissues was relatively low, and long tumor retention was not observed. However, thin-layer chromatographic separation revealed that the radioactivity in the tumor resided mainly in strongly cytotoxic metabolites, while that in other tissues resided mainly in non-cytotoxic metabolites. These results suggest that FK317 shows strong antitumor activity without side effects, and one reason for this is its specific metabolite pattern. FK317 is now undergoing phase I clinical trials.
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PMID:FK317, a novel substituted dihydrobenzoxazine, exhibits potent antitumor activity against human tumor xenografts in nude mice. 1008 92

To determine the role of the Wilms' tumor gene WT1 in tumorigenesis of solid tumors, expression of the WT1 gene was examined in 34 solid tumor cell lines (four gastric cancer cell lines, five colon cancer cell lines, 15 lung cancer cell lines, four breast cancer cell lines, one germ cell tumor cell line, two ovarian cancer cell lines, one uterine cancer cell line, one thyroid cancer cell line, and one hepatocellular carcinoma cell line) by means of quantitative reverse transcriptase-polymerase chain reaction. WT1 gene expression was detected in three of the four gastric cancer cell lines, all of the five colon cancer cell lines, 12 of the 15 lung cancer cell lines, two of the four breast cancer cell lines, the germ cell tumor cell line, the two ovarian cancer cell lines, the uterine cancer cell line, the thyroid cancer cell line, and the hepatocellular carcinoma cell line. Therefore, of the 34 solid tumor cell lines examined, 28 (82%) expressed WT1. Three cell lines expressing WT1 (gastric cancer cell line AZ-521, lung cancer cell line OS3, and ovarian cancer cell line TYK-nu) were further analyzed for mutations and/or deletions in the WT1 gene by means of single-strand conformation polymorphism analysis. However, no mutations or deletions were detected in the region of the WT1 gene ranging from the 3' end of exon 1 to exon 10 (the WT1 gene consists of 10 exons) in these three cell lines. Furthermore, when AZ-521, OS3, and TYK-nu cells were treated with WT1 antisense oligomers, the growth of these cells was significantly inhibited in association with a reduction in WT1 protein levels. Furthermore, constitute expression of the transfected WT1 gene in cancer cells inhibited the antisense effect of WT1 antisense oligomer on cell growth. These results indicated that the WT1 gene plays an essential role in the growth of solid tumors and performs an oncogenic rather than a tumor-suppressor gene function.
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PMID:Expression of the Wilms' tumor gene WT1 in solid tumors and its involvement in tumor cell growth. 1018 90

To determine the clinical usefulness of the autopsy in elderly patients, we studied a total of 231 autopsies performed during 1986 and 1995 at Jikeikai hospital. Autopsies were done after 231 of 609 deaths (38%). The autopsy rate in our hospital fell from 63% in 1986 to 17% in 1995. Most primary causes of deaths as established by clinicians before autopsy were pulmonary, neoplastic, and cardiovascular diseases. The probability of a major unexpected finding at autopsy was higher in acute pneumonia, acute myocardial infarction, and cerebrovascular disease. No primary pathological cause of death was established by pathologists at autopsy in 13 cases (The clinical diagnoses in those patients were acute pneumonia in 5 patients, acute myocardial infarction in 2 patients, sepsis in 2 patients, bronchiale asthma, cerebral infarction, uremia, gastrointestinal bleeding each in 1 patient.) The mean age of these 13 patients was higher by 5 years than the age of the group as a whole. This indicate that elderly patients have many complications and that these deaths were caused by many small changes that were not be detected at autopsy. Latent cancer was found in 23 cases (12%): thyroid and colon cancer in 6 patients each, gastric cancer in 4, prostate cancer in 3, ovarian cancer in 2, and other cancers (renal, uterine, lung, urethral, pancreatis and liver) each 1 in patient.
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PMID:[Clinical usefulness of the autopsy in elderly patients]. 1021 66

This review summarizes the results reported in preclinical and clinical trials of three novel anticancer drugs developed and tested in Japan. In phase II trials, Irinotecan, a semisynthetic analog of camptothecin, has yielded response rates exceeding 20% in non-small-cell lung cancer, small-cell lung cancer, breast cancer, gastric cancer, colorectal cancer, ovarian cancer, uterine cervical cancer, and non-Hodgkini's lymphoma. It was modestly active on pancreatic cancer and was not active on acute leukemias. Dose-limiting toxicities were leukopenia and diarrhea, and other major toxicities were nausea, vomiting, and alopecia. Amrubicin, a totally synthetic anthracycline, exhibited both higher efficacy on human tumor xenografts and cardiotoxicity milder than that of doxorubicin in preclinical studies. The dose-limiting toxicity in phase I trials was leukopenia. In phase II trials, amrubicin has shown activity equivalent to that of doxorubicin on non-Hodgkin's lymphoma, response rates exceeding 20% on non-small-cell lung cancer, and a response rate of 78.8% on untreated extensive-stage small-cell lung cancer. S-1 is an oral formulation consisting of ftorafur (an analog of 5-fluorouracil), 5-chloro-2, 4-dehydropyrimidine, which inhibits degradation of 5-fluorouracil, and potassium oxonate, which reduces gastrointestinal toxicity, at a molar ratio of 1:0.4:1. In phase I trials, dose-limiting toxicities (myelosuppression and gastrointestinal toxicities) were judged to be milder than those induced by UFT (ftorafur plus uracil). The response rates obtained in phase II trials were 40-49% on advanced gastric cancer, 35.5% on colorectal cancer, 37.5% on head and neck cancer, and 40.7% on breast cancer.
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PMID:Novel anticancer drugs in Japan. 1023 66

Recently, the PTEN/MMAC1 gene encoding a protein phosphatase (PP) and the PPP2R1B gene encoding a regulatory subunit of PP2A have been identified as being genetically altered in several types of human cancers, indicating that aberrations of intracellular signaling pathways via PPs are involved in human carcinogenesis. Here we report genetic alterations of the PPP1R3 gene located at chromosome 7q31, which encodes regulatory subunit 3 of PP1, in various types of human cancers. Mutations of the PPP1R3 gene were detected in 5 of 33 (15%) non-small cell lung cancer cell lines and 2 of 38 (5%) primary non-small cell lung cancers and were also observed in cell lines derived from a small cell lung cancer, an ovarian cancer, a colorectal cancer, and a gastric cancer. Mutations were widely dispersed in the coding region of the PPP1R3 gene. Three of the 11 detected mutations were nonsense mutations, whereas the remaining ones were missense mutations, most of which caused substitutions of evolutionarily conserved amino acids. These findings suggest that PPP1R3 alteration plays a role in the development of human cancers and that PPP1R3 could act as a tumor suppressor gene.
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PMID:Alterations of the PPP1R3 gene in human cancer. 1048 48


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