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)

By comparing gastric cancer tissues treated by the conventional hematoxylin and eosin (HE) staining and those by the chemical staining of immunohistologicals using monoclonal antibodies (MoAB) which recognize different carbohydrate antigens, the relation of cancer tissue patterns between the two staining methods was studied. Consequently, stainability was not seen in MoAB-FH4, AH6, FH6 and TKH2 in the cancer tissues where MoAB-SH1 responded to immunohistological staining. Likewise, each of MoAB-FH4, AH6, FH6 was found to have its own stain localization. The patterns made by immunohistological staining using MoAB showed so-called mosaicism even where the HE stain presented the same histologic form. Study of correlation between gastric cancer patterns and MoAB's localization revealed that localization of MoAB-SH1, AH6 and TKH2 was predominant in well differentiated adenocarcinoma. On the contrary, MoAB-FH4 and FH6, which are more specific, showed predominant localization in poorly differentiated adenocarcinoma of gastric cancers. Localization of MoAB-FH6 and AH6 increased as cancer grew from the early stage to the advanced stage. These results leads to this assumption: cancer, being of an isogenic carbohydrate structure at the initial stage when carcinoma in situ is generated, gains heterogeneity with the process of growth, differentiating into various directions and thus changing into a complicated carbohydrate structure.
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PMID:[Immunohistochemical studies on tumor associated carbohydrate antigens in gastric cancers of different histological stages]. 133 75

Leucovorin (LV), given intravenously the orally becomes 5, 10-methylene tetrahydrofolate in both cancer and normal cells. FdUMP which is an active metabolite of 5-FU binds tightly to thymidylate synthase in the presence of the cofactor 5, 10-methylene tetrahydrofolate. This interaction leads to potentiate the cytotoxic effect of 5-FU by prolonged inhibition of thymidylate synthase. Clinically, the combination of LV and 5-FU is given parenterally by two schedules; 5 consecutive days schedule and weekly schedule. Five 5 consecutive days-schedule is divided into 2 methods. One is a 200 mg/m2/day of LV by Machover, and the other is 20 mg/m2/day of LV by O'Connell. The weekly schedule is a 2-hour infusion of dl-LV (500 mg/m2) and iv bolus of 5-FU (600 mg/m2), given 1 hour after the beginning of LV infusion by Petrelli. A multicenter cooperative study in Japan was conducted to evaluate the clinical efficacy of LV and 5-FU using the weekly schedule by Petrelli. Response rates were 31.5% and 41.2% against advanced gastric and colorectal cancer respectively. Then, we carried out a randomized early phase II study using 250 mg/m2 of l-LV weekly (similar to the schedule of Petrelli's, armA) and 100 mg/m2 (similar to the schedule of Machover's, arm B) or 10 mg/m2 (similar to the schedule of O'Connell's, arm C) of l-LV for 5 consecutive days against gastric cancer. The response rate was 33.3% in arm A, 24.1% in arm B and no response in arm C. Toxicity was within acceptable limits, Toxic effects included diarrhea, stomatitis, anorexia and myelohypoplasia. Our data suggests that high-dose LV and 5-FU seems to be a very promising combination but, there was no responder using low dose (10 mg/m2) of l-LV schedule against gastric cancer patients.
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PMID:[High-dose leucovorin and 5-FU]. 162 51

In recent years the concept of metabolic modulation of fluoropyrimidines by leucovorin has been introduced clinically in patients with advanced colorectal cancer, breast cancer, gastric cancer and head and neck cancer among others. The concept of metabolic modulation was developed in the laboratory and employed clinically. Leucovorin is a noncytotoxic compound used to increase the therapeutic efficacy of 5-fluorouracil. Following 5-fluorouracil activation to 5-fluorodeoxyuridine monophosphates, its binding to thymidylate synthase is stabilized by the active cofactor, 5,10 methylene tetrahydrofolate and its polyglutamate forms. Under these conditions, both the extent and duration of inhibition of thymidylate synthase and consequently, DNA synthesis are more pronounced. The results of clinical trials (phase II and III) indicate that the response rates to 5-fluorouracil/leucovorin modulation are significantly higher than that of fluorouridine alone.
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PMID:Modulation of fluoropyrimidines by leucovorin: rationale and status. 183 38

Currently, biochemical modulation for 5-fluorouracil (5-FU) is one of the most successful chemotherapy for both colo-rectal and gastric cancer. The purpose of this study is to evaluate the significance of measuring intratumoral thymidylate synthetase (TS) and folate (FH4) levels as predictive parameters for the successful treatment. Samples were collected from 16 advanced colo-rectal and 21 advanced gastric cancer. TS and tetrahydrofolate levels in the specimens were measured by binding assay. Results showed that there were no significant difference in TS levels between the different pathologic types of carcinoma. On the other hand, well (3.94 +/- 1.75 p mol/g) and moderately (5.95 +/- 2.69 p mol/g) differentiated carcinoma showed lower FH4 levels compared to poorly differentiated carcinoma (9.58 +/- 5.27 p mol/g). In conclusion, biochemical modulation by cisplatin or leucovorin, which elevates intratumoral folate levels, is more needed for well and moderately differentiated carcinoma. Finally, measuring TS levels can also be important because two cases who responded to cisplatin/5-FU chemotherapy showed low TS levels compared to the others who had lower response.
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PMID:[The intratumoral levels of thymidylate synthetase and folate in gastric and colon cancer]. 967 79

We evaluated DNA polymorphisms in the thymidylate synthase (TS) and 5,10-methylene-tetrahydrofolate reductase (MTHFR) genes for an association with response and survival in locally advanced gastric cancer treated with 5-FU based preoperative chemotherapy (CTx). DNA of 238 patients (CTx-group: total n = 135, completely resected (R0) n = 102; without CTx: R0 n = 103) was isolated from blood or from nontumorous tissues. In the CTx-group, genotyping of the tandem repeat and the G/C polymorphism in the triple repeat in the promoter region of the TS gene and of the C677T polymorphism of the MTHFR gene was performed. None of the TS or MTHFR genotypes were associated with histopathological response and only the TS tandem repeat polymorphism was significantly related to survival (all patients n = 135, p = 0.002; R0 resected patients n = 102, p = 0.007; log-rank test). Multivariate analysis revealed ypN (p < 0.001) and the TS tandem repeat polymorphism as independent prognostic factors in the CTx-R0-group (p = 0.003). Analyzing the prognostic significance of the TS polymorphisms in the R0-group without CTx, TS genotypes were not significantly associated with survival. Comparing survival between R0 patients with and without CTx in the respective TS genotype groups of the tandem repeat polymorphism, a significant survival benefit for the patients with CTx was found for the 2rpt/2rpt (n = 49; p = 0.002) and 2rpt/3rpt genotypes (n = 99; p = 0.004), but not for the 3rpt/3rpt genotype (n = 57; p = 0.93). Patients' survival after CTx was associated with the TS tandem repeat polymorphism. CTx did not improve survival of patients with the 3rpt/3rpt genotype. Thus, a different therapy might be more appropriate for these patients.
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PMID:The thymidylate synthase tandem repeat promoter polymorphism: A predictor for tumor-related survival in neoadjuvant treated locally advanced gastric cancer. 1692 15

The CpG island methylator phenotype (CIMP+) of colorectal cancer (CRC) occurs predominantly in the proximal colon and is characterized by frequent hypermethylation of gene promoter regions. In this review, we present evidence suggesting CIMP+ represents the subgroup of colon cancers that are responsive to 5-fluorouracil (5-FU)-based treatments. CIMP+ has been associated with survival benefit from 5-FU in a clinical study of CRC, with additional evidence coming from studies on gastric cancer and tumor cell lines. Elevated concentrations of 5-10-methylene tetrahydrofolate (CH(2)FH(4)) occur in CIMP+ tumors and are probably due to low expression levels for gamma-glutamyl hydrolase (GGH). Clinical and in vitro work has previously shown that high CH(2)FH(4) and low GGH expression levels correlate with good response to 5-FU. Methylation-induced silencing of dihydropyrimidine dehydrogenase, the rate-limiting enzyme in 5-FU degradation, may also provide a link between CIMP+ and good response to 5-FU. The CIMP+-related phenotype referred to as microsatellite instability (MSI+) has been widely investigated as a predictive marker of response to 5-FU, with contradictory results. The interpretation of these studies is likely to be confounded by the fact that some MSI+ tumors occur in the background of CIMP+, but a significant proportion of others do not. Further studies on tumors from randomized clinical trials are required to confirm the value of CIMP+ and associated molecular features for the prediction of clinical outcome to 5-FU-based chemotherapy.
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PMID:Predicting clinical outcome of 5-fluorouracil-based chemotherapy for colon cancer patients: is the CpG island methylator phenotype the 5-fluorouracil-responsive subgroup? 1909 76

This study evaluated the influence of genetic polymorphism influencing drug metabolism on survival in taxane- and cisplatin-treated advanced gastric cancer (AGC). Peripheral blood samples from 207 AGC patients treated with first-line chemotherapy of taxane and cisplatin were used. We investigated polymorphisms that influenced the metabolism of taxane (ATP-binding cassette transporter B1 (ABCB1)), cisplatin (glutathione S-transferase M1 (GSTM1), glutathione S-transferase P1 (GSTP1), glutathione S-transferase T1 (GSTT1), excision repair cross complementing 1 (ERCC1), X-ray Cross Complementing group 3 (XRCC3), X-ray Cross Complementing group 4 (XRCC4), X-ray Cross Complementing group 1 (XRCC1), breast cancer (BRCA1)), and 5-fluorouracil (methylene tetrahydrofolate reductase (MTHFR), thymidylate synthase (TYMS)). A total of 207 patients were enrolled between May 2004 and Dec 2008, and 200 patients were analyzed. The overall response rate was 38.5%. Time to progression and overall survival time were 4.3 +/- 0.19 months and 11.9 +/- 1.05 months, respectively. There was no significant association between genetic polymorphism and response rate. However, the BRCA1 mutant TT homozygote was associated with significant prolongation of overall survival (hazard ratio [HR] = 0.43; 95% confidence interval [CI], 0.20-0.92; P = 0.03) and progression-free survival (HR = 0.51; 95% CI, 0.26-1.00; P = 0.05). Also, the XRCC1 194 CT genotype was associated with inferior overall survival, relative to the XRCC1 194 CC homozygotes (HR = 1.49; 95% CI, 0.11-2.07; P = 0.018).These findings suggest that BRCA1 TT and XRCC1 194 CT genotypes could be modest prognostic markers of AGC response in taxane- and cisplatin-treated patients.
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PMID:BRCA1 and XRCC1 polymorphisms associated with survival in advanced gastric cancer treated with taxane and cisplatin. 2033 23

The purpose of the present study is to test the validity of the steroid carcinogenesis hypothesis in humans by investigating the problem whether or not a cancer-specific change of the hormonal milieu emerges at a specified stage of life where the growth rate of cancer risk is at its zenith. A case-control study of 14 urinary steroid excretions was conducted for each of 3 human neoplasias. The identification and the size (in parenthesis) of the population units used in this study were,given as follows: a) the male gastric cancer group (421); b) the male control group (104); c) the female breast cancer group (245); d) the cervical cancer group (345); e) the female control group (127). Two kinds of steroid parameters were employed for the statistical analysis of hormonal data: a) the logarithm of a steroid excretion figure (mu g/day), as expressed by log x; b) the logarithm of a relative weight of a given steroid to tetrahydrocortisol, as expressed by log x/THF. The case-control difference for each parameter was expressed in terms of a t-value of Student's t-test. The steroid deviation profile was prepared for each neoplasia and for each of the log x data set and the log x/THF data set. The results obtained are as follows: a) the 2 steroid parameters (log x and log x/THF) for each of 14 urinary steroids were both subject to change with the progress of host age. The rate of age-dependent change was different for each steroid parameter and for each population unit. b) The above differential age dependency of the steroid parameters gave rise to a continual transition of the steroid deviation profile in the course of aging. c) The hormonal traits of male gastric cancer, female breast cancer and cervical cancer were described each as a complex of androgen depression and glucocorticoid stimulation (male gastric cancer), a sequential emergence of premenopausal progestin depression and postmenopausal predominance of glucocorticoid over androgen (female breast cancer), and a complex of androgen-glucocorticoid depression over progestin (cervical cancer). d) The emergence of the above cancer-specific steroid disorders chronologically coincided with the quasiexponential growth phase of cancer risk (and slow growth phase of cancer risk in postmenopausal breast cancer). e) The usefulness of the log x/THF type deviation profile for the assessment of the hormonal milieu of the host was verified by both theoretical approach to the problem and its application to the real data of a case-control study. f) The age dependent decline of androgens was generally much faster in their progressions than that of glucocorticoids - a finding to suggest the possibility that the production of a cancer-specific steroid deviation profile might have taken the form of the stress shift of Hans Selye, since both phenomena share depletion of gonadal steroids relative to glucocorticoid in common. The etiological relevancy of the 3 cancer-specific steroid changes to the geneses of 3 cancers:was discussed in the light of the experimental pathology studies in our laboratory as well as in other laboratories.
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PMID:The relation between the aging of the steroid generating system and the geneses of cancers of the stomach, the breast and the uterine cervix. 2159 38

Gastric Cancer is one of the major leading causes of death by cancer worldwide, but the chemotherapeutics, one of the preferred approaches, bring about extensive side effects when systemically injected. In our work, doxorubicin-loaded pH and redox responsive hyperbranched poly(amidoamine)(h-PAMAM)-based vesicle was prepared to enhance anti-tumor efficacy of chemotherapeutic compounds. The doxorubicin (DOX) molecules were attached to PEGylated h-PAMAM by acid sensitive cis-aconityl linkage to form pH sensitive conjugate (PPCD), which self-assembled in THF into micelles. The resulted micelles were then crosslinked by disulfide bonds and transferred from THF into water to form vesicles, which could be disassembled into small-sized conjugates under the redox condition. The drug release profiles showed that the PPCD vesicle presented stimuli-triggered drug release in acidic and reducing environment, and lower DOX leakage under neutral condition. The in vitro cell assay reflected the rapid DOX release and significant tumor-cytotoxic effect of the PPCD vesicle. The in vivo anticancer activity and systematic toxicity studies showed that the PPCD vesicles had lower tissue toxicity with good antitumor effect. In brief, h-PAMAM-based PPCD vesicle provides a safe and effective drug delivery system for the therapy of gastric cancer.
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PMID:In vitro and in vivo evaluation of stimuli-responsive vesicle from PEGylated hyperbranched PAMAM-doxorubicin conjugate for gastric cancer therapy. 2723 96

BACKGROUND Serine hydroxymethyltransferase (SHMT) is the enzyme that catalyzes the reversible conversion of serine to glycine and tetrahydrofolate-bound one-carbon unit. Upregulation of SHMT2 has been observed in a variety of cancers, but the expression profile and clinical value of SHMT2 in gastric cancer (GC) are still unknown. MATERIAL AND METHODS In this study, SHMT2 expression was assessed in 130 patients with GC by immunohistochemistry (IHC). mRNA of SHMT2 in GC tissues and normal gastric epithelium was compared with qRT-PCR results. The correlations between SHMT2 and the clinicopathologic factors were analyzed with the chi-square test. Univariate analysis with Kaplan-Meier method was used to estimate the correlations between survival rate and clinicopathologic factors, including SHMT2. The independent prognostic biomarkers were confirmed by multivariate analysis using the Cox-regression hazard model. The function of SHMT2 in progression of GC was assessed by in vitro experiments. RESULTS The percentages of low and high expression of SHMT2 were 46.92% and 53.08%, respectively. SHMT2 mRNA in GC tissue was significantly higher than mRNA in the patient-paired adjacent tissues. In the clinical analysis, SHMT2 expression was notably associated with positive lymphatic invasion. High SHMT2 was also demonstrated to independently predict poor prognosis of GC. After silencing SHMT2, we proved that SHMT2 can promote proliferation and invasion of GC cells. CONCLUSIONS High SHMT2 promoted progression and was an independent prognostic biomarker of GC, suggesting that SHMT2 detection would be helpful for stratification of high-risk patients and thus directing personalized treatment.
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PMID:High Expression of Serine Hydroxymethyltransferase 2 Indicates Poor Prognosis of Gastric Cancer Patients. 3158 Nov 60


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