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)

This multi-center trial was carried out to assess the therapeutic potential of recombinant tumor necrosis factor (rTNF) as the first form of systemic therapy for advanced carcinomas of gastric and pancreatic origin. To be eligible patients were required to have no overt sign of coagulopathy and hepatic function studies with enzymes less than two times beyond the normal range. Twenty nine patients with gastric cancer and 26 with pancreatic cancer were entered from various institutions in the Southwest Oncology Group with 27 and 22, respectively, meeting eligibility criteria. Drug treatment consisted of rTNF (Genentech) given at a dose of 150 micrograms intravenously for five consecutive days every 3 weeks; 50% dose reduction was made for acute intolerance such as hypotension or severe fever and chills. Although eight patients with gastric cancer and five patients with pancreatic cancer received four or more courses of treatment, no objective antitumor responses were recorded. As in other trials common toxicities of rTNF included nausea and vomiting, chills and fever, hypotension, headache, myalgias, fatigue and malaise. However, in this trial, other toxicities became prominent: four episodes of symptomatic disseminated intravascular clotting occurred among patients with pancreatic cancer. Eleven with this disease and five with gastric cancer manifested laboratory findings of abnormal amounts of fibrin split products, and/or hypofibrinogenemia, and/or thrombocytopenia after treatment began. Other laboratory abnormalities that were commonly encountered included hyperglycemia, hypertriglyceridemia, anemia, neutropenia and an elevation in liver enzymes. We conclude that rTNF does not demonstrate antitumor efficacy against adenocarcinomas of the stomach and the pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High incidence of coagualopathy in phase II studies of recombinant tumor necrosis factor in advanced pancreatic and gastric cancers. 152

Preoperative endoscopic intratumoral injection (IT) of biological response modifiers (BRM), such as OK432, a compound composed of attenuated Streptococcus pyogens, in gastric cancer patients has been tried and this method has been improving the prognosis compared to surgical resection only. We tried to clarify this mechanism using experimental mouse system and demonstrated here the preoperative IT of OK432 significantly prolonged the survival and induced the tumor-specific cytotoxic T lymphocytes (CTL) in the spleen. By contrast, tumor necrosis factor (TNF) IT failed to prolong the survival and to induce specific CTL response, although it reduced primary tumor size significantly. To analyze why OK432 IT induce the systemic CTL response, viable tumor cells and infiltrating dish-adherent cells from the OK432 injected tumor mass were harvested and examined the class I and class II antigen expression by flow cytometer. Class I and class II antigen expression of the tumor cells remained unchanged, however, the class II positive dish-adherent cells markedly increased by OK432 pretreatment. As same in these results, histological finding in gastric cancer specimen has shown prominent increase of Langerhans cells, possessing potent antigen-presenting function and positive class II antigen, by OK432 pretreatment. Taken together, these findings strongly suggest that the increased class II positive antigen-presenting cells (APC) activity by OK432 IT augment the CTL response via cascade reaction and finally, resulted in anti-tumor efficacy in vivo.
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PMID:[Immunomodulating effect of intratumoral (IT) injection of biological response modifiers (BRM) on tumor-bearing hosts]. 223 Apr 39

We examined whether OK-432, a streptococcal preparation, could induce tumor necrosis factor in cancer patients. OK-432 was administered at a dose of 100 KE intratumorally to 4 advanced gastric cancer patients and 10KE intracavitary to 8 patients with malignant pleuroperitoneal effusion. The cytostatic activity of the sera and malignant effusions was assayed by the growth inhibition of L929 cells. OK-432 induced significant cytostatic activity in the sera and malignant effusions. The activity was partially neutralized by the monoclonal antibody against human recombinant tumor necrosis factor. These data suggest that OK-432 induces tumor necrosis factor in the sera and malignant effusions of cancer patients.
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PMID:Induction of tumor necrosis factor by administration of OK-432 in cancer patients. 356 Jan 94

The antitumor activity of tumor necrosis factor (TNF) against various primarily cultured human cancer cells (32 cases) was investigated by the 51Cr cytotoxic release assay and the tumor stem cell assay. Over 50% sensitivity (the ratio to the cytotoxicity in L929 cells) was noted in 4 of 14 cases of gastric cancer (28.6%), 7 of 9 cases of leukemic cells (77.8%), and 1 case each of pancreatic carcinoma and ovarian cancer. Scarcely any sensitivity, however, was observed in 1 case of acute promyelocytic leukemia or in some of the gastric cancer cases. No correlation was observed between the histological type of the cancer and TNF sensitivity. The above results seem to confirm that TNF has significant antitumor activity against human cancer cells.
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PMID:Antitumor effect of tumor necrosis factor against various primarily cultured human cancer cells. 393 30

The antitumor activity of tumor necrosis factor (TNA) against various human cancer cells (32 cases) was investigated by 51Cr cytotoxic release assay and tumor stem cell assay. Over 50% sensitivity (the ratio of cytotoxicity for L929 cells) was shown by 4 of 14 cases of gastric cancer (28.6%), 7 of 9 cases of leukemic cells (77.8%), and 1 case each of pancreatic carcinoma and ovarian cancer. However, scarcely any sensitivity was shown by APL, a portion of the gastric cancer cells, normal lymphocytes or colony-forming cells tested. No correspondence was observed between the histological type of the cancer and TNF sensitivity. The above results seem to confirm the significant antitumor activity of TNF against human cancer cells.
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PMID:[Antitumor effect of the tumor necrosis factor against various types of human cancer cells]. 406 18

To determine the gene expression for tumor necrosis factor (TNF) alpha and its main site of production in gastric cancer patients, serum levels in the peripheral venous blood of 50 patients and the portal blood from 15 of these 50 patients were measured by enzyme-linked immunosorbent assay (ELISA). TNF gene expression in the peripheral blood mononuclear cells (PBMC) and in the surgically resected tissues was then studied in 16 patients by reverse transcription-polymerase chain reaction (RT-PCR) assay. Whereas TNF mRNA expression was detected in the PBMC from 13 of 16 gastric cancer patients (81.3%), it was detected in only one tumor tissue (6.3%). Preoperatively, TNF was detected in the serum from 13 of 50 patients (26.0%). In the portal blood sampled immediately after laparotomy, TNF was positive in 4 of 15 patients (26.7%). TNF gene expression was much more frequently detected in PBMC than in other resected tissues, and its expression was higher than in the serum. Various clinicopathological factors for gastric cancer were not related to the preoperative detection of TNF in the serum. It appears that TNF is produced mainly in PBMC but not in the cancer regions or the regional lymph nodes of gastric cancer patients. It is suggested that TNF is not always secreted even when TNF mRNA is expressed, and its preoperative production is not related to tumor progression.
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PMID:Gene expression for tumor necrosis factor alpha and its production in gastric cancer patients. 796 Nov 4

Nine gastric cancer patients with simultaneous liver metastases were given intermittent transarterial administration of chemotherapeutics (adriamycin, mitomycin C or 5-fluorouracil) and biological response modifiers (BRM; OK-432 and interleukin (IL) -2) after gastrectomy. In terms of direct antitumor effect on liver metastases, a partial response was observed in 4 of 9 cases (44%). In addition, the concentration of 3 kinds of cytokines such as IL-6, tumor necrosis factor (TNF) -alpha and interferon (IFN) -gamma in the peripheral blood sera was measured immediately before and after transarterial administration of agents. While the concentration of IL-6 increased by BRM, chemotherapeutics could not alter the level of IL-6. As for TNF-alpha and IFN-gamma, no particular changing pattern was observed after transarterial administration. Furthermore, natural killer (NK) activity of peripheral blood mononuclear cells was measured. Administration of either BRM or BRM in combination with chemotherapeutics caused a decrease in NK activity, whereas chemotherapeutics did not. Flow cytometric analysis using 3 kinds of monoclonal antibodies (Anti-CD16, CD56 and CD57) revealed that the proportion of subset of both highly activated NK cells (CD16+.CD56+.CD57-) and moderately activated NK cells (CD16+.CD56+.CD57+) reduced after administration of BRM.
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PMID:[Immunological effects of locoregional immunochemotherapy for liver metastases of gastric cancer]. 837 5

This study was performed to investigate the direct effects of recombinant human tumor necrosis factor (rH-TNF) and recombinant human interleukin-2 (rH-IL-2), either alone or in combination, on the cytotoxicity of 5-FU measured by MTT assay against human gastric adenocarcinoma cell lines (MKN-28 and MKN-45), and also to determine the optimal schedule for their combination. The antitumor activity of rH-TNF was enhanced more than 42% by 10(2) U/ml of rH-IL-2. The enhancing effects of rH-TNF and rH-IL-2 on the cytotoxicity of 5-FU were evaluated in terms of Modification Index(MI), the MI value at 10 U/ml rH-TNF was 1.6; the MI at the same concentration of rH-TNF in the presence of 10(2) U/ml of rH-IL-2 was 2.1. These results demonstrated that the antitumor effect of 5-FU was enhanced 1.6 times by 10 U/ml of rH-TNF and further enhanced by the combined use of rH-TNF and rH-IL-2. The combined effect of equal concentrations of 5-FU and rH-TNF was superior or equivalent to that of 5-FU or rH-TNF alone. The sequence of 5-FU followed by rH-TNF and rH-IL-2 showed a higher inhibitory effect than the reverse sequence. This sequence combination seems worthy of further consideration for the treatment of gastric cancer.
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PMID:Combined effect of 5-fluorouracil and recombinant tumor necrosis factor against human gastric carcinoma cell lines. 871 99

To determine whether the liver plays an immunological role in certain extrahepatic disorders, we investigated the expression of interleukin (IL)-1 beta, IL-6, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha in 11 patients who had recovered from cholecystolithiasis, 12 patients with gastric cancer, 20 patients with chronic hepatitis, and 6 healthy controls. Cytokine mRNAs in the liver were detected by semiquantitative reverse transcribed-polymerase chain reaction. Serum cytokines and soluble IL-2 receptor (sIL-2R) were investigated by enzyme-linked immunosorbent assays. Increases in TNF-alpha, IL-6, IL-1 beta, and IFN-gamma mRNAs were found in the livers of patients with extrahepatic diseases. TNF-alpha and IL-6 peptides were increased in the sera of patients with gastric cancer. TNF-alpha in the sera and TNF-alpha mRNA in the liver were correlated in gastric cancer patients. Surprisingly, sIL-2R in the serum of gastric cancer patients was significantly higher than the level in healthy controls. Our findings suggest that the liver produces cytokines in reaction to extrahepatic lesions. Further, the increase in sIL-2R in gastric cancer patients indicates that malignancy may affect the immune network in vivo.
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PMID:Increased expression of cytokines in liver and serum in patients with extrahepatic diseases. 884 75

The purpose of this study was to determine the feasibility of a vaccine therapy using tumor necrosis factor (TNF) gene-transduced autologous tumor cells for the treatment of human gastrointestinal cancers, which tend to have lower immunogenicity than other cancers such as melanoma and renal cell carcinoma. We succeeded in establishing primary cultured tumor cells from 12/54 carcinomatous effusions (4 liver cancer patients, 5 gastric cancer patients, 1 pancreatic cancer patient, and 2 colon cancer patients) and in transducing the TNF gene to the tumor cells by using the retrovirus vector MFG-TNF. Even after irradiation, TNF production (0.3-3.5 U/ml per 10(6) cells per 72 hr) was confirmed for 10 of 12 transfectants, and the other two transduced cells were found to have approximately one TNF gene copy. In 7 of the 12 patients, the cytotoxic activity of killer cells to nontransduced autologous tumor cells incubated with these TNF gene transfectants was augmented. This activity was blocked with anti-HLA class I antibody or BrefeldinA (BFA), suggesting that the killer cells were cytotoxic T lymphocytes (CTL) and tumor antigens are presented with HLA class I molecules. Indeed, enhanced expression of HLA class I and/or ICAM-1 molecules on the surface of the TNF gene-transduced tumor cells were observed by fluorescence-activated cell sorting (FACS) analysis. Furthermore, natural killer (NK) and/or lymphokine-activated killer (LAK) activities determined by using K562 or Daudi cells as targets were also enhanced in some of these cases when they were incubated with TNF gene-transduced tumor cells. These findings indicate the feasibility of using TNF gene-transduced tumor cells as a vaccine in gastrointestinal cancer patients.
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PMID:Augmented antitumor effects of killer cells induced by tumor necrosis factor gene-transduced autologous tumor cells from gastrointestinal cancer patients. 889 81


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