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)

The protein-bound polysaccharide extracted from a fungus, PSK, has been used as a biological response modifier in the treatment of cancer patients in Japan for over 16 years. The administration of PSK to tumor-bearing rodents inhibited tumor growth and modulated immune responses. Recently, an in vitro study has revealed that PSK is a strong inducer of cytokine gene expression and production in human peripheral blood mononuclear cells (PBMC). To establish whether PSK has cytokine-inducing activities in vivo, we have orally administered PSK (1 g, the clinical dose) to 12 healthy volunteers and 9 gastric cancer patients who had undergone gastrectomy, and assessed the gene expression for cytokines in PBMC of each subject. As determined by the reverse-transcribed polymerase chain reaction method, the induction of gene expression for both tumor necrosis factor alpha and interleukin-8 (IL-8) was detected in PBMC from 5 of the 12 healthy volunteers (42%) and 4 of the 9 patients (44%). Furthermore, the concentration of serum IL-8 was elevated in 5 healthy volunteers given PSK orally, who had shown induction of IL-8 gene expression, as detected by enzyme-linked immunosorbent assay. These findings indicate that responsiveness of PBMC to PSK, in terms of gene expression and production of cytokines, varies among individuals. Thus, when using PSK to treat cancer patients, it seems advisable to select patients on the basis of their responsiveness to PSK. We speculate that the cytokines induced by PSK might mediate the immunoenhancing action of this agent in vivo.
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PMID:Induction of gene expression for immunomodulating cytokines in peripheral blood mononuclear cells in response to orally administered PSK, an immunomodulating protein-bound polysaccharide. 772 73

Nude mice bearing xenografts of the gastrin-responsive human gastric carcinoma MKN45 cell line were treated for 4 to 5 weeks with bombesin/gastrin-releasing-peptide(GRP) antagonist (RC-3095), somatostatin analogues RC-160 and SMS 201-995, or the combination of RC-3095 and RC-160. Tumor volumes and weights were reduced significantly to a similar extent by RC-160 and SMS 201-995, administered by daily s.c. injections at a dose of 100 micrograms/day. Bombesin/GRP antagonist RC-3095, given s.c. at a dose of 20 micrograms/day, had the greatest inhibitory effect on tumor growth. The combination of RC-3095 with RC-160 did not further potentiate the suppression of tumor growth. Histologically, the number of mitotic cels decreased significantly in the groups treated with RC-160 or the combination of RC-3095 with RC-160. Serum gastrin levels were significantly diminished in all treated groups. Therapy with RC-160 or the combination also significantly decreased levels of serum growth hormone. Receptor assays on tumor membranes showed that bombesin was bound to 2 classes of receptor sites, one with high affinity and low capacity, the other with low affinity and high capacity. Binding sites for epidermal growth factor (EGF) were down-regulated in tumor cells after treatment with RC-3095, RC-160 or the combination of RC-3095 with RC-160. In studies in vitro, both RC-160 and RC-3095 significantly inhibited the proliferation of MKN45 cells in culture as measured by cell number. These data demonstrate, for the first time, that the growth of human gastric cancer in nude mice can be inhibited not only by somatostatin analogues, but also by administration of modern bombesin/GRP antagonists, such as RC-3095.
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PMID:Inhibition of growth of MKN45 human gastric-carcinoma xenografts in nude mice by treatment with bombesin/gastrin-releasing-peptide antagonist (RC-3095) and somatostatin analogue RC-160. 791 Jan 53

Human CD3AK and LAK cells were prepared from peripheral blood mononuclear cells (PBMC) by culturing them in recombinant IL-2 (rIL-2, 30 mu/ml) and anti-CD3 monoclonal antibody, and in rIL-2 alone (300/ml), respectively. By MTT assay, it was found that the PBMC, when cultured in the presence of anti-CD3/rIL-2, proliferated more actively and persistently than PBMC cultured in the presence of rIL-2 alone. In vitro cytotoxicity assay showed that CD3AK cells had stronger killing activity against a poorly differentiated human gastric adenocarcinoma cell line MNK 45 than LAK cells did. Winn's assay at an E/T ratio of 20 carried out in nude mice also indicated that CD3AK cells were more effective than LAK cells in tumor growth inhibition. When the nude mice were inoculated with MNK 45 admixed with CD3AK, none of them developed tumor whereas those inoculated with either MNK 45 or MNK 45 admixed with LAK cells all developed tumor. The results indicate that CD3AK would be a better choice than LAK for the adoptive immunotherapy of human stomach cancer.
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PMID:[Experimental study of the anti-tumor activity of CD3AK against human gastric cancer cell line in vitro and in vivo]. 792 59

Eleven patients with chemotherapeutically pretreated advanced gastric cancer were treated in a phase II study with a combination of 5-fluorouracil (5-FU) and Leucovorin (LV, folinic acid). 5-FU (1,200 mg/m2) and LV (100 mg/m2) were given as a parallel continuous intravenous infusion over 48 h every 2 weeks for at least 8 weeks. Toxicity and response rates were evaluated. Results show that this chemotherapeutic regimen is well tolerable, without any side effects exceeding WHO grade 1 toxicity, but that it has no considerable effects on tumor growth. None of the patients achieved disease remission. In 8 out of the 11 study patients therapy had to be discontinued prematurely because of disease progression. Therefore we conclude that the studied protocol of 5-FU/LV as second-line treatment of advanced gastric cancer although well tolerable is not effective.
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PMID:Continuous 5-fluorouracil and leucovorin as a second-line therapy for advanced gastric carcinoma. 797 Apr 94

We recently established epidermal growth factor (EGF) receptor-hyperproducing human gastric cancer xenografts in nude mice. The present study was designed to examine whether the growth of a xenograft having 1,098 +/- 276 fmol/mg protein of EGF receptor would either be stimulated by the administration of EGF or inhibited by the removal of the submandibular glands (sialoadenectomy) which contain a large amount of EGF. A miniosmotic pump containing 2 micrograms or 20 micrograms of EGF was implanted on the back of the animals in the EGF stimulation experiments. The tumor growth was stimulated by the administration of EGF (P < 0.01), and the doubling time of the tumor was reduced relative to the controls (P < 0.01). Both the mitotic indices and the bromodeoxyuridine (BrdU)-labeling indices of the tumor were higher than those of the controls (P < 0.01). Tumor growth inhibited by the sialoadenectomy (P < 0.05) while the tumor doubling time was prolonged compared with the sham-operated mice (P < 0.05). These results suggest that the growth of a human gastric cancer xenograft may be modulated by EGF.
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PMID:Stimulatory effect of EGF and inhibitory effect of sialoadenectomy on growth of an EGF receptor-hyperproducing human gastric cancer xenograft in nude mice. 798 44

Serum cathepsin B levels and urinary excretion of cathepsin B in the patients with gastric cancer were significantly higher than those in the control non-cancer patients. Moreover, cancer tissue cathepsin B content was significantly higher than that in the normal tissue. After radical curative operations for gastric cancers, both serum cathepsin B levels and urinary excretion of cathepsin B were restored to the control values. These results suggest a possible role of lysosomal enzyme, cathepsin B in the pathogenesis of tumor growth, and also suggest that these parameters might be possible indicators for tumor malignancy.
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PMID:Serum cathepsin B levels, urinary excretion of cathepsin B and tissue cathepsin B content in the patients with gastric cancer. 803 Dec 15

We investigated the effect of bombesin/gastrin-releasing peptide (GRP) antagonist RC-3095 and other analogs on the growth of Hs746T human gastric cancer cells implanted in nude mice or cultured in vitro and on the binding of bombesin to its receptors. Nude mice bearing xenografts of the Hs746T cell line received s.c. injections of RC-3095 (10 micrograms twice daily) or the vehicle (control) for 21 days. Administration of antagonist RC-3095 inhibited the growth of Hs746T tumors. Treatment with RC-3095 produced a significant decrease in tumor volume, prolonged the tumor volume doubling time from 3.6 days to 5.1 days, and decreased the tumor growth rate by 76.9%. The tumor growth delay time in mice treated with RC-3095 was 2.8 days. Treatment with RC-3095 also decreased the final tumor weight by 88.3% and reduced DNA and protein contents in tumors by 91.5% and 89.5%, respectively, as compared to controls. The presence of specific receptors for bombesin/GRP was investigated on the crude membranes of implanted tumors of Hs746T cells. Saturation binding assays showed that the binding of [125I-Tyr4]bombesin to the membranes was saturable and reversible. Scatchard analysis indicated the presence of a single class of binding sites with a high affinity (Kd = 0.24 +/- 0.07 nM) and a low binding capacity (Bmax = 57.0 +/- 0.9 fmol/mg protein). In displacement studies, the binding of [125I-Tyr4]bombesin was inhibited in a dose-dependent manner by unlabelled bombesin(1-14), [Tyr4]-bombesin and GRP (14-27), but not by structurally unrelated peptides. Synthetic bombesin/GRP antagonists RC-3095, RC-3110, and RC-3950-II were all able to inhibit effectively the binding of [125I-Tyr4]bombesin to the membranes of Hs746T cells. RC-3950-II showed a higher binding affinity for bombesin receptors than RC-3095 or RC-3110. Addition of the non-hydrolyzable guanine-nucleotide analog GTP [S] to the binding buffer caused a significant reduction in the amount of [125I-Tyr4]bombesin bound to the cells, indicating that the bombesin receptor is coupled to a G-protein. In cell cultures, bombesin significantly stimulated the growth of Hs746T cells in vitro as shown by an increase in the uptake of [3H]thymidine. Bombesin antagonist RC-3095 could effectively inhibit the bombesin-stimulated growth of Hs746T cells in cultures. These observations suggest that bombesin/GRP may act as growth factors through specific receptors present on the membranes of Hs746T cells. Bombesin/GRP antagonists appear to nullify the effects of bombesin/GRP and may be useful for the treatment of gastric cancers.
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PMID:Bombesin antagonists inhibit in vitro and in vivo growth of human gastric cancer and binding of bombesin to its receptors. 804 17

In spite of recent advances in the early diagnosis of gastric cancer by mass screening, gastric stump cancers following gastrectomy are still diagnosed at a highly advanced stage, and the surgical results remain very poor. Involvement of the fourth level lymph node stations, local peritoneal carcinomatosis and tumor growth invading the neighboring organs are frequently observed in advanced stump cancers. With the aim of achieving complete resection of these tumors, left upper abdominal evisceration (LUAE) + R4 gastrectomy was performed in 29 patients (Group B) with stump cancer as a radical surgical procedure. The survival of these patients was compared with that of 74 patients (Group A) who underwent total gastrectomy with or without pancreaticosplenectomy. Duration of surgery blood loss, and incidence of postoperative complications were similar with the two methods. When the survival rates were compared, the 5-year-survival rate in stage IV cases was higher for Group B than for Group A. LUAE + R4 gastrectomy is a rational technique for the surgical treatment of stage IV gastric stump cancer.
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PMID:A new surgical technique (left upper abdominal evisceration) for advanced carcinoma of the gastric stump. 805 99

We evaluated killer cell activity and suppressor cell activity as the indicators of immunological function of spleen cells in rats implanted with N-methyl-N'-nitro-N-nitrosoguanidine-induced cancer. The effect of splenectomy on tumor growth was also investigated. Splenectomy was performed 2 (early stage of tumor growth), 5 (intermediate stage), or 8 weeks (late stage) after tumor implantation. The mean survival time of rats splenectomized at the early or intermediate stage of tumor growth was shorter than that of sham-operated rats, while that of rats splenectomized at the late stage was longer than controls. Natural killer (NK) and Cytotoxic T lymphocyte (CTL) activity of spleen lymphocytes of tumor-bearing rats were increased during the intermediate stage of tumor growth and then were declined during the late stage, while suppressor cell activity showed progressive increase after tumor implantation. The results of Winn assay showed that most of the splenic effector cells during the intermediate stage were T-lymphocytes, and some were NK cells. Furthermore suppressor macrophages and suppressor T-lymphocytes were increased in spleen lymphocytes of rats in the late stage of tumor growth. These results suggest that preservation of the spleen may be beneficial in the treatment of gastric cancer at the early and intermediate stage but that splenectomy is necessary for the advanced stage of cancer.
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PMID:[Changes in immunological function of spleen in rats implanted with N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric cancer]. 807 84

The mortality rate of gastric cancer in the Chinese population has reached a plateau. The main prognostic factor for gastric adenocarcinoma is recognized as tumor stage. Recently, abnormalities in DNA content have been considered as a new prognostic factor. Whether abnormal DNA content can be used as a prognostic tool for Chinese patients with gastric cancer is unknown. To investigate this relation DNA ploidy and prognosis of gastric cancer patients were studied using paraffin-embedded specimens. A group of 104 newly diagnosed and surgically resected gastric cancer specimens obtained from January 1984 to December 1986 were examined for DNA content by flow cytometry. The quality of flow cytometry was acceptable with a mean coefficient of variance of 5.45. The results showed that 38 cases (36.5%) had DNA aneuploidy; 42 cases had metastatic lymph nodes with enough tumor cells, and 31.0% of these cases had DNA aneuploidy. DNA aneuploidy of primary tumors was correlated to lymph node metastasis and patient's age, whereas DNA aneuploidy of metastatic lymph nodes was significantly correlated to the serosal invasion of the gastric wall at the primary site. The important parameters for prognosis were curability of surgical resection, serosal invasion, tumor size, and distant metastasis. DNA aneuploidy of both primary tumors or metastatic lymph nodes appeared to be unrelated to the prognosis of gastric adenocarcinoma in Chinese patients. We therefore propose that DNA aneuploidy of gastric cancer is associated with tumor growth but not biologic aggressiveness.
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PMID:DNA ploidy and biologic aggressiveness of gastric adenocarcinoma in Chinese. 809 87


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