Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intraperitoneal and pleural immunotherapy has been used as an effective therapy for malignancy. Recently we treated two patients with peritonitis and pleuritis due to cancer by intraperitoneal and pleural administration of IFN-gamma, OK-432 and antitumor agents. One patient with gastric cancer (stage IIIb) was treated with intraperitoneal administration of IFN-gamma and OK-432 in combination with intraarterial infusion of MMC, ADM, 5-FU and CDDP. Two months later, ascites and pleural fluid diminished. Another patient with ovarian carcinoma (stage IV), was administered IFN-gamma, OK-432 and CDDP into ascites with general medication of CDDP and Epi-ADM. Two months later, her ascites and tumor size decreased. This patient was treated with palaplatin every two months for the ten months and hysterosalpingecctomy and tumorectomy of Douglas pouch were performed at the sixteenth month. The histopathological examination of resection from this patient showed complete necrotic tissue of tumor. Endogenous cytokine therapy with intraperitoneal and pleural administration of IFN-gamma for priming and OK-432 for eliciting in combination with antitumor agents may be effective treatment for malignant peritonitis and pleuritis.
 ...
PMID:[Immunochemotherapy of carcinomatous peritonitis and pleuritis--report of 2 cases]. 132 10

Interleukin 8 (IL-8) is a novel cytokine which possesses neutrophil chemotactic and activating activities in addition to chemotactic activity for basophils and T lymphocytes. It has been shown that IL-8 is produced by a variety of human somatic cells including monocytes/macrophages, dermal fibroblasts, vascular endothelial cells, keratinocytes, mesangeal cells, and several types of tumor cell lines. We have examined here whether or not human gastric cancer cell lines produce IL-8 in vitro. The production of IL-8 protein was detected by enzyme-linked immunosorbent assay in the culture supernatants derived from eight of nine human gastric cancer cell lines stimulated with either interleukin 1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha), or TNF alpha plus interferon gamma (IFN gamma). In some of the gastric cancer cell lines such as MKN 45 and KATO, TNF alpha plus IFN gamma synergistically induced the production of IL-8. In MKN 45 cells, synergistic increase of the steady state level of IL-8 mRNA by TNF alpha plus IFN gamma was not inhibited by cycloheximide treatment. Scatchard analysis revealed that IFN gamma changed neither the number nor the affinity constant of TNF alpha binding sites on a gastric cancer cell line, suggesting that the synergism was a post-receptor event. Furthermore, synergistic induction of chloramphenicol acetyltransferase activity by TNF alpha plus IFN gamma was observed in MKN 45 that were transiently transfected with chimeric chloramphenicol acetyltransferase reporter genes driven by the transcriptional regulatory region of human IL-8 gene. Through the mutation of the regulatory region of the IL-8 gene, both AP-1- and NF-kB-like factor binding elements were presumed to be involved in conferring the responsiveness to TNF alpha plus IFN gamma. Moreover, gel retardation analyses revealed that TNF alpha and IFN gamma synergistically induced the binding of NF-kB like as well as AP-1 like proteins bound to these sites. These results indicated that IFN gamma synergistically enhanced TNF alpha-induced IL-8 production in a human gastric cancer cell line through synergistic activation of transcription factors without up-regulating TNF alpha receptor.
 ...
PMID:Tumor necrosis factor alpha and interferon gamma synergistically induce interleukin 8 production in a human gastric cancer cell line through acting concurrently on AP-1 and NF-kB-like binding sites of the interleukin 8 gene. 133 Oct 59

Transgenic animal technology has been useful for the direct demonstration of the tumorigenic potential of oncogenes in vivo. Over the past eight years a wide variety of oncogenes and proto-oncogenes from viral and cellular sources have been inserted into the germline of mice with subsequent development of neoplasia. Many of the published reports describe similarities between morphologic features of the transgenic mice tumors and those occurring naturally in humans. We discuss the morphologic features of selected transgenic models carrying viral genes and review their applicability to investigations directed toward understanding cancer in general and specifically gastric cancer, neurofibromatosis and leukemia. Examples of the impact of nutrition, interaction with growth factors and initiation with chemical carcinogens are presented. In one of the models functional similarities to the mechanism of oncogenesis in human T-cell leukemia virus type-1 (HTLV-1) lymphoma may exist with activation of cytokine production and subsequent autocrine stimulation. The transgenic model of proximal gastric cancer demonstrates features similar to those seen in carcinogen-induced neoplasia. These studies underscore the vast potential of transgenic models for inquiry into the genetic and epigenetic basis of human carcinogenesis. However, many features of transgenic cancer models differ from cancer in humans and the specific criteria for judging the value of transgenic models remain unclarified. For example, although the tumors arising in the HTLV-1 Tax transgenic mice show numerous similarities to human neurofibromatosis including development of lesions of the iris, the similarities do not necessarily extend to the molecular involvement of neurofibromatosis-1 (NF-1), a gene with structural and functional homology to GTPase activating proteins. Transgenic experiments of the future will ask questions beyond whether a particular gene is capable of initiating the neoplastic process. The ability to construct systems in vivo with a defined starting point that facilitate further controlled manipulation of events resulting in cancer provide great opportunities to dissect the various molecular pathways involved in such a process. Therefore, gene knockout experiments and disruption of gene function will further enhance our ability to understand the multi-factorial process of tumor development.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Transgenic models of human cancer. 166 87

We successfully established a human gastric cancer cell line, HuGC-OOHIRA, from the ascites of a 60-year-old patient with advanced gastric cancer (poorly differentiated adenocarcinoma) complicated by peritonitis carcinomatosa and leukocytosis of unknown origin. Morphologically, the cells were polygonal and adhered weakly to the culture flask. They tended to pile up upon reaching confluence. Chromosome analysis revealed that the cell line has two modes of chromosome number, namely near diploidy and tetraploidy. Double minutes (DMs) were present in abundance in each cell. The doubling time was 25-30 hr. The cell line was successfully transplanted into nude mice, and their peripheral leukocyte counts increased in proportion to the growth of the tumors. At 2 weeks after the transplantation, the serum rG-CSF level was elevated to 2,893 pg/ml. The concentration of human G-CSF in the culture supernatants was an extraordinary high level of 145,380 pg/ml/day. Secretion of GM-CSF and IL-6 was also detected. The intracellular localization of the G-CSF was identified for the first time by immunofluorescence. Moreover, Northern blot analysis detected G-CSF mRNA in this cell line. Anti-recombinant human G-CSF serum suppressed the propagation of HuGC-OOHIRA cell line. Therefore, it is likely that the autocrine growth loop by G-CSF is present in this cell line. This cell line would be very useful for understanding both the cellular and molecular basis for the production of various cytokines such as G-CSF as well as cytokine-dependent tumor proliferation.
 ...
PMID:Establishment and characteristics of a gastric cancer cell line (HuGC-OOHIRA) producing high levels of G-CSF, GM-CSF, and IL-6: the presence of autocrine growth control by G-CSF. 754 2

Despite the fact that the inflammatory and immune responses have evolved to combat microorganisms, the present generation of inflammation researchers has evinced relatively little interest, with the exception of septic shock, in microbially-induced inflammation. This in spite of the fact that the Gram-negative cell wall constituent, lipopolysaccharide, has been widely used as a tool in inflammation research. The reason for such lack of interest has been due to the therapeutic efficacy of antibiotics which are the treatment of choice for infections and their inflammatory sequelae. However, this is likely to change within the next decade or so, with the relentless increase in the incidence of antibiotic-resistant strains of bacteria. This will return therapy to the stage where clinicians will have to treat the inflammatory symptoms of infection. Many of these symptoms are due to the stimulation of cytokine synthesis. The capacity of bacteria to induce cytokine synthesis has, until the past few years, centred exclusively on lipopolysaccharide. However, it has been established during the past 5-10 years that a range of other molecules, mainly associated with the surface of bacteria, have the capacity to induce cytokine production. Some of these are exquisitely potent stimulators of pro-inflammatory cytokine synthesis. The nature and mechanism of action of these various cytokine-inducing molecules, for which we have devised the name modulins, is the subject of this review. It is clear that bacteria still have many surprises for us, as exemplified by the recent discovery of the role played by Helicobacter pylori in gastritis, gastric ulceration and gastric cancer.
 ...
PMID:Modulins: a new class of cytokine-inducing, pro-inflammatory bacterial virulence factor. 765 92

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.
 ...
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

In order to evaluate the biological response after intraperitoneal administration of OK-432 and CDDP, we studied the changes of cytokine levels in ascitic fluid. A total of 53 gastric cancer patients were included in this study. OK-432 20KE was administered in 7 patients and CDDP was administered in 4 patients intraperitoneally during operation. The IL-6, IL-8, TNF-alpha and sTNF RI levels in ascitic fluid were measured from 0 to 5 postoperative day. These results were compared with those obtained from the control groups (42 patients). The ascitic level of IL-6 increased immediately after operation, then gradually decreased. The elevations of IL-6 from 0 to 5 postoperative day were remarkably higher in the OK-432 treated group, and those on 0 and 1 postoperative days were remarkably lower in CDDP treated group than in the control group. Similarly, the ascitic level of IL-8 elevated soon after operation and then decreased gradually. In the OK-432 treated group, the ascitic level of IL-8 was significantly higher than in the control group from 0 to 2 postoperative day. Ascitic TNF-alpha was detectable only in the ascites soon after operation in the OK-432 treated group. The ascitic level of sTNF RI peaked on 2 postoperative day in the control and the OK-432 treated group and 1 postoperative day in the CDDP treated group. There were no significant differences between these groups.
 ...
PMID:[Changes of cytokine levels in ascitic fluid after intraperitoneal administration of OK-432 or CDDP]. 794 71

To investigate the role of group II phospholipase A2(PLA2) in cancer, we examined the expression and secretion of group II PLA2 in response to the stimulation of interleukin 6(IL-6) in human gastric cancer cells in vitro. Group II PLA2 determined by a specific radioimmunoassay was constitutively produced in culture supernatant of KATO III (signet ring cell carcinoma) and MKN28 (well differentiated adenocarcinoma). This production in KATO III significantly increased with a treatment of IL-6, whereas that in MKN28 remained at a same level. Moreover, the quantitation by reverse transcription-polymerase chain reaction(RT-PCR) demonstrated the IL-6 inducible overexpression of group II PLA2 mRNA in KATO III. This transcription was mediated by NF-IL6, the same as in hepatocytes. These results suggest two possible mechanisms of group II PLA2 production by cancer cells in vivo, that is, cytokine-induced production and constitutive production.
 ...
PMID:Group II phospholipase A2 in invasive gastric cancer cell line is induced by interleukin 6. 811 91

In order to evaluate the biological response after intraperitoneal administration of OK-432, we studied the changes of cytokine levels in ascitic fluid. In 6 advanced gastric cancer patients with peritoneal dissemination or extensive lymph node metastases, OK-432 20 KE was administered intraperitoneally during operation and the IL-6, IL-8 and IFN-gamma levels in ascitic fluid were measured from 0 to 5 postoperative days. These results were compared with those obtained from non-OK-432 administered control groups (17 cases). The ascitic level of IL-8 increased immediately after operation and gradually decreased. In the OK-432 treated group, the elevation of IL-8 on 0 and 1 postoperative days was remarkable, and there were statistically significant differences with the control group. Similarly, the ascitic level of IL-6 elevated soon after operation and then decreased gradually. In the OK-432 treated group, the ascitic level of IL-6 was significantly higher than in the control group after 3 postoperative days. There were no differences in changes of ascitic IFN-gamma levels between the groups. From these results, IL-6 and IL-8 appeared to be induced in ascitic fluid by intraperitoneal administration of OK-432.
 ...
PMID:[Changes in cytokine levels in ascitic fluid after intraperitoneal administration of OK-432]. 837 2

Human peripheral blood monocytes cocultured with tumour cells were used as an in vitro model of in situ interactions between tumour-infiltrating macrophages and the tumour. Tumour cells stimulated de novo expression of the human tumour necrosis factor alpha (TNF) gene in monocytes and caused the release of TNF into the culture supernatant. A group of 14 patients with stage IVA gastric cancer receiving adjuvant chemotherapy (5-FU, Adriamycin, mitomycin C: FAM) or immunochemotherapy (BCG+FAM) was investigated for the ability of monocytes to produce TNF in vitro upon stimulation with tumour cells or purified protein derivative of tuberculin (PPD). Patients were followed at biweekly intervals, i.e. before each instillation of BCG epicutaneously over a period of 10 weeks. It was found that monocytes of some patients receiving BCG at the end of the observation period had an enhanced ability to produce TNF following stimulation with tumour cells. In contrast, such production was not substantially altered during the study period in patients on chemotherapy. PPD-induced TNF production was much weaker and was not significantly changed during this observation time. We infer that BCG immunotherapy may induce the subtle changes in some cancer patients that lead to an increased interaction between monocytes and tumour cells and result in enhanced production of cytokine(s) with antitumour properties.
 ...
PMID:Tumour-cell-induced production of tumour necrosis factor by monocytes of gastric cancer patients receiving BCG immunotherapy. 842 10


1 2 3 4 5 6 7 8 9 10 Next >>