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)

We studied the pharmacokinetics of the intraperitoneal administration of CPT-11 for four patients with peritoneal metastasis (2 gastric cancer cases, 2 colon cancer cases). CPT-11 was administrated in a dose of 40-60 mg and the intraperitoneal and serum levels of CPT-11, SN-38 and SN-38 glucuronized (SN-38 Glu) were measured periodically. Intraperitoneal therapy with CPT-11 was effective for the control of malignant ascites. No serious side effects were observed. The levels of CPT-11, SN-38 were no different 30 min afterwards the administration of CPT-11 either intraperitoneally or intravenously. The high concentration of CPT-11 was achieved with intraperitoneal therapy and a small fraction of CPT-11 changed into SN-38 in the abdominal cavity.
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PMID:[Pharmacokinetic study of the intraperitoneal administration of CPT-11 for patients with peritoneal seedings of gastric and colonic cancers]. 1170 65

This study evaluates the anti-tumor effect of cisplatin-loaded microspheres (CDDP-MS) against peritoneal carcinomatosis using human tumor xenografts. The incorporated CDDP was released from CDDP-MS for 3 weeks in vivo as well as in vitro. CDDP-MS at a dose of 35 mg/kg (at maximal tolerable dose (MTD)) showed effective anti-tumor activity (tumor growth inhibition rate (IR)=70.3%) against Li-7 (human liver cancer) xenografts transplanted into the peritoneal cavity. This procedure also resulted in increased life span (ILS (%)=47.2%), whereas CDDP dissolved in saline solution (CDDP-SOL) at a dose of 8 mg/kg (at MTD) was ineffective (IR=15.7%, ILS=2.6%). Likewise, CDDP-MS (35 mg/kg) significantly prolonged the mean survival time (ILS=50.8%) compared with a CDDP-SOL group (8 mg/kg) (ILS=13.1%) in the mice with Li-7 xenografts transplanted into the spleen. Furthermore, CDDP-MS showed markedly effective anti-tumor activity (IR=82.2%) against H-154 (human stomach cancer) xenografts, in which CDDP-SOL was effective (IR=69.5%) at the MTDs. The suppressive effect of CDDP-MS on accumulation of malignant ascites was intimately related to unchanged CDDP concentration in ascites. These results demonstrated that the administration of CDDP-MS resulted in an unchanged CDDP concentration in ascites, and induced a sustained tumor growth inhibition along with a prolonged survival time.
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PMID:Anti-tumor effect of intraperitoneal administration of cisplatin-loaded microspheres to human tumor xenografted nude mice. 1194 6

We report a case in which weekly paclitaxel (TXL) administration was effective for gastric cancer with malignant ascites. TXL (80 mg/m2) was infused over 1 hour after short premedication on an outpatient basis. Administration was continued for 3 weeks followed by 1 week rest. The patient was a 49-year-old woman who suffered from non-resectable gastric cancer, staged intraoperatively as having severe lymph node metastasis and malignant ascites. As an outpatient treatment, she was first treated with 5-fluorouracil combined with high-dose Leucovorin for 4 cycles. However, she complained of abdominal fullness and ascites, and received weekly TXL administration as the second line treatment. The ascites had completely disappeared 3 months after administration. The toxic events were anemia (grade 1) and alopecia (grade 2). No major adverse effects such as hypersensitivity reaction, leukopenia or peripheral neuropathy were observed.
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PMID:[Effective weekly paclitaxel administration for gastric cancer with malignant ascites--a case report]. 1235 53

Advanced gastric cancer is often accompanied by metastasis to the peritoneum, resulting in a high mortality rate. Mechanisms involved in gastric cancer metastasis have not been fully clarified because metastasis involves multiple steps and requires a combination of altered expressions of many different genes. Thus, independent analysis of any single gene would be insufficient to understand all of the aspects of gastric cancer peritoneal dissemination. In this study, we performed a global analysis of the differential gene expression of a gastric cancer cell line established from a primary main tumour (SNU-1) and of other cell lines established from the metastasis to the peritoneal cavity (SNU-5, SNU-16, SNU-620, KATO-III and GT3TKB). The application of a high-density cDNA microarray method made it possible to analyse the expression of approximately 21 168 genes. Our examinations of SNU-5, SNU-16, SNU-620, KATO-III and GT3TKB showed that 24 genes were up-regulated and 17 genes down-regulated besides expression sequence tags. The analysis revealed the following altered expression such as: (a) up-regulation of CD44 (cell adhesion), keratins 7, 8, and 14 (epitherial marker), aldehyde dehydrogenase (drug metabolism), CD9 and IP3 receptor type3 (signal transduction); (b) down-regulation of IL2 receptor gamma, IL4-Stat (immune response), p27 (cell cycle) and integrin beta4 (adhesion) in gastric cancer cells from malignant ascites. We then analysed eight gastric cancer cell lines with Northern blot and observed preferential up-regulation and down-regulation of these selected genes in cells prone to peritoneal dissemination. Reverse transcriptase-polymerase chain reaction confirmed that several genes selected by DNA microarray were also overexpressed in clinical samples of malignant ascites. It is therefore considered that these genes may be related to the peritoneal dissemination of gastric cancers. The results of this global gene expression analysis of gastric cancer cells with peritoneal dissemination, promise to provide a new insight into the study of human gastric cancer peritoneal dissemination.
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PMID:Differential gene expression profiles of gastric cancer cells established from primary tumour and malignant ascites. 1240 56

In this study, we performed a global analysis of the differential gene expression of a gastric cancer cell line established from a primary main tumor (SNU-1) and that of other cell lines established from the metastasis to the peritoneal cavity (KATO-III, SNU-5, SNU-719, MKN45P, HS39). The application of a high-density cDNA microarray method made it possible to analyze the expression of approximately 21,168 genes. Our examinations of KATO-III, SNU-5, SNU-719, MKN45P, and HS39 showed that several genes were up-regulated in addition to expression of sequence tags (ESTs). The analysis revealed altered up-regulation of CD44 (cell adhesion), CEA, 14-3-3, Ubiquitin A and several kinds of ESTs in gastric cancer cells from malignant ascites. We then analyzed these gastric cancer cell lines with Northern blots and observed preferential up-regulation of these selected genes in cells prone to peritoneal dissemination. RT-PCR confirmed that several genes selected by DNA microarray were also overexpressed in clinical samples of malignant ascites. It is therefore considered that these genes may be related to the peritoneal dissemination of gastric cancers. The results of this global gene expression analysis of gastric cancer cells with peritoneal dissemination promise to provide new insights into the study of human gastric cancer peritoneal dissemination.
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PMID:[Screening of novel biomarkers for the detection of intraperitoneally disseminated cancer cells using human cDNA microarray]. 1248 52

We treated a patient with inoperable advanced gastric cancer and malignant ascites by combination chemotherapy of TS-1 and biweekly paclitaxel (TXL). After two courses the ascites had disappeared and the primary tumor was reduced. TS-1 (80 mg/body/day) was administered for 21 days followed by 7 days rest and TXL (100 mg/body) was administered on days 1 and 14 as one course. The patient could not eat at the time of hospitalization, but at the time of the second course he could eat a full serving of rice porridge. Grade 2 anemia and leukopenia were the only adverse reactions observed; no major adverse reactions were observed. These results suggest that with TS-1 and TXL combination chemotherapy, patients with advanced gastric cancer can achieve a marked improvement in quality of life.
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PMID:[A patient with advanced gastric cancer that response remarkably to combination chemotherapy of TS-1 and biweekly paclitaxel (TXL)]. 1451 19

Our previous study using a cDNA microarray demonstrated that positive identification of differently expressed genes among gastric cancer cells involved in peritoneal dissemination could be accomplished. One of these genes with overexpression is inositol 1, 4, 5-trisphosphate receptor type 3 (IP3R3). IP3R3 is an intracellular Ca2+ release channel responsible for mobilizing stored Ca2+. Three different receptor types have been molecularly cloned, and their genes have been classified into a family. But the role of the IP3 signaling pathway in the peritoneal dissemination of gastric cancers is still unclear. In this study, IP3R3 is overexpressed in gastric cancer cell lines established from malignant ascites, but weakly expressed in gastric cancer cell lines established from primary tumor as well as in normal gastric epithelial cells. IP3R1 and 2 are expressed only weakly or not at all in these cells. The antagonist of IP3R, 2-APB, inhibited cell proliferation and induced apoptosis of gastric cancer cells from malignant ascites at concentrations of 100 nM to 100 microM in a dose dependent manner. Conversely, 2-APB showed a weak effect on other gastric cancer cells established from primary tumors (SNU1), lymph node metastases or liver metastases (MKN1 or 74), methothelial cell lines Met5A and myeloid leukemia cell HL60 cells. This suggests that this inhibitory effect depends on the level of IP3R3 expression. As cells that express IP3R3 mRNA (i.e., pancreatic aciner cells) are known to have a secretory function in which IP3/Ca2+ signaling has been shown to be involved, IP3R3 may be a prerequisite for secretion in gastric cancer cells. These results indicate that IP3R3 may be specifically involved in gastric cancer peritoneal dissemination and that IP3R3 may be a molecular target of the peritoneal dissemination of gastric cancer. Its antagonist, 2-APB, may thus be useful for the treatment of gastric cancer, especially for peritoneal dissemination.
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PMID:[Possible involvement of inositol 1, 4, 5-trisphosphate receptor type 3 (IP3R3) in the peritoneal dissemination of gastric cancers]. 1461 19

Our previous study using cDNA microarray showed that differentially expressed genes among gastric cancer cells involved in peritoneal dissemination could be positively identified. One of these genes, which is overexpressed, is inositol 1,4,5-trisphosphate receptor type 3 (IP3R3). IP3R3 is responsible for the intracellular Ca2+ release channel and for mobilizing stored Ca2+. Three different receptor types have been molecularly cloned and their genes have been classified into a family. However, the role of the IP3 signaling pathway in the peritoneal dissemination of gastric cancer is still unclear. In the study presented here, the IP3R3 is showed to be overexpressed in gastric cancer cell lines established from malignant ascites, but weakly expressed in a gastric cancer cell line established from primary tumor as well as normal gastric epithelial cells. IP3R1 and 2 are only weakly or not expressed in these cells. The antagonist of IP3R, 2APB, inhibited cell proliferation and induced apoptosis in gastric cancer cells from malignant ascites at concentrations of 100 nM to 100 microM in a dose-dependent manner. On the other hand, 2APB showed a weak effect on other gastric cancer cells established from primary tumors (SNU1), lymph node metastases or liver metastases (MKN1 or 74), methothelial cell lines Met5A and myeloid leukemia HL60 cells. This suggests that this inhibitory effect depends on the level of IP3R3 expression. As cells which express IP3R3 mRNA (i.e. pancreas ascinar cells) are known to have a secretory function in which IP3/Ca2+ signaling has been shown to be involved, IP3R3 may be a prerequisite for secretion of an enzyme, such as protease, in gastric cancer cells. These results indicate that IP3R3 may be specifically involved in gastric cancer peritoneal dissemination and that IP3R3 may be a molecular target of the peritoneal dissemination of gastric cancer. Its antagonist, 2APB, may thus be useful for the specific treatment of peritoneal dissemination of gastric cancer.
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PMID:Possible involvement of inositol 1,4,5-trisphosphate receptor type 3 (IP3R3) in the peritoneal dissemination of gastric cancers. 1466 65

Locoregional administration of the streptococcal preparation OK-432 is effective in treating malignant ascites from gastric cancer. In order to enhance the efficacy, we conducted a pilot study of locoregional immunotherapy for malignant ascites using host-oriented doses of OK-432. Moreover, action mechanisms of OK-432 were further explored in view of the T-helper type 1 (Th1)-Th2 concept. Gastric cancer patients with cytologically determined malignant ascites were locoregionally administered with OK-432. The dose of OK-432 was selected according to the delayed-type hypersensitivity (DTH) reaction levels to OK-432. Cytokine production profiles of ascites cells were determined using whole ascites assay by stimulation with OK-432. IL-10 mRNA expression was analyzed using RT-PCR. It was found that a positive clinical response was observed in 37 of the 51 (73%) patients with the DTH-oriented approach, showing a significantly higher efficacy than traditional dosage methods using empirical doses (31/58, 53%) (p=0.0487). The DTH-oriented administration of OK-432 produced adverse effects such as fever elevation (p<0.0001) and abdominal pain (p=0.0013) to a significantly lesser extent compared with the traditional treatment. Analysis of the action mechanism of OK-432 revealed that the DTH reaction in responders (19+/-6 mm) was stronger than that in non-responders (6+/-4 mm) (p<0.0001). Tumor necrosis factor (TNF)-alpha production of ascites cells was also higher in responders (3943+/-1247 pg/ml) than in non-responders (1217+/-939 pg/ml) (p=0.0002). There was a significant positive correlation (p=0.0085) between the levels of DTH reaction and TNF-alpha production of ascites cells, but not of blood cells. Responders appeared to polarize on the Th1 axis when clinical responses were plotted on Th1-Th2 dimensions according to the cytokine production profiles of TNF-alpha, IFN-gamma, IL-4 and IL-6 of ascites cells. In vitro culture with IL-2 of ascites cells after OK-432 administration demonstrated an almost clonal expansion of CD4+ lymphocytes, which produced TNF-alpha and IFN-gamma, but did not produce IL-4 or IL-6. IL-10 mRNA expression was detectable in ascites cells from non-responders before treatment. These results suggest that the DTH-oriented locoregional administration of OK-432 may be both effective and less toxic in treating malignant ascites from gastric cancer, showing a possibility of the tailored immunotherapy for malignant ascites. Th1 dysfunction exists in the microenvironment of malignant ascites from gastric cancer, in which IL-10 may, in part, play a role. The up-regulation of Th1 responses by OK-432 may result in positive clinical responses. The DTH reaction to OK-432 may be a useful tool not only for predicting clinical response but also for selecting the optimal dose of OK-432.
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PMID:Locoregional immunotherapy of malignant ascites from gastric cancer using DTH-oriented doses of the streptococcal preparation OK-432: Treatment of Th1 dysfunction in the ascites microenvironment. 1501 Aug 36

To understand the molecular mechanism associated with gastric carcinogenesis, we identified genes expressed in gastric cancer cell lines and tissues. Of 97,609 high-quality ESTs sequenced from 36 cDNA libraries, 92,545 were coalesced into 10,418 human Unigene clusters (Build 151). The gene expression profile was produced by counting the cluster frequencies in each library. Although the profiles of highly expressed genes varied greatly from library to library, those genes related to cell structure formation, heat shock proteins, the glycolysis pathway, and the signaling pathway were highly represented in human gastric cancer cell lines and in primary tumors. Conversely, the genes encoding immunoglobulins, ribosomal proteins, and digestive proteins were down-regulated in gastric cancer cell lines and tissues compared to normal tissues. The transcription levels of some of these genes were confirmed by RT-PCR. We found that genes related to cell adhesion, apoptosis, and cytoskeleton formation were particularly up-regulated in the gastric cancer cell lines established from malignant ascites compared to those from primary tumors. This comprehensive molecular profiling of human gastric cancer should be useful for elucidating the genetic events associated with human gastric cancer.
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PMID:Gene cataloging and expression profiling in human gastric cancer cells by expressed sequence tags. 1517 56


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