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)

A major problem associated with the chemosensitivity testing of fresh human tumour cells using the MTT assay is the contamination of nonmalignant cells in the tumour tissues. Highly purified fresh human gastric cancer cells could be obtained from 43 solid tumours and eight malignant ascites for the MTT assay. The success rate of the MTT assay was 87.9% (51 of the 58 cases), and the purity of tumour cells was greater than 90% after separation on Ficoll-Hypaque and Percoll discontinuous gradients in primary, or metastatic lesions, and also ascites. Cisplatin, mitomycin, and doxorubicin were more potent drugs than etoposide and 5-FU against gastric cancer cells. The chemosensitivity in differentiated cancer was equivalent to that in non-differentiated cancer. Twenty of the 51 patients with gastric cancer had evaluable lesions, and they received chemotherapy according to the results of the MTT assay using highly purified tumour cells. A clinical response was obtained in 12 of these 20 patients (response rate: 60.0%; five with complete response, seven with partial response).
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PMID:Chemosensitivity testing of fresh human gastric cancer with highly purified tumour cells using the MTT assay. 141 22

A new dosage form of cisplatinum (CDDP), lactic acid oligomer microspheres incorporating cisplatinum (CDDP-ms), is designed to slowly release 70% of contained CDDP. CDDP-ms's acute toxicity is as low as 57% of the toxicity of CDDP aqueous solution, and its therapeutic efficacy is statistically significantly strong as compared with that of CDDP aqueous solution, when examined with experimental peritoneal carcinomatosis induced by mouse M5076 ovarian sarcoma. Clinical trials were carried out in 10 patients with malignant ascites (gastric cancer 6, pseudomyxoma peritonei 2, colon cancer 1, pancreas cancer 1) and in one patient with pleural effusion (lung cancer). CDDP-ms at 100 mg/person in terms of CDDP was injected at bolus into the affected cavity. In the 10 patients with ascites, 7 responded completely, two partially and one did not respond. The patient with pleural effusion responded partially. The response rate was 91%. Five of the 11 patients complained of temporary nausea or vomiting. In 5 patients fever higher than 38 degrees C was seen. No other side effect such as kidney, nor liver-damage or blood cell count abnormality was noted.
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PMID:[Intracavitary microspheres incorporating cisplatinum in the treatment of malignant effusions--clinical trials]. 238 51

The tumor-infiltrating lymphocytes (TIL) were cultured with interleukin 2 (IL-2) to induce the cytotoxic T lymphocytes possessing autologous tumor-killing activity from 21 cancer patients (11 with solid tumor and 10 with malignant peritoneal or pleural effusions), and transferred into 7 patients as IL-2-activated TIL adoptively. The clinical application of activated TIL by adoptive transfer could result the complete regression of malignant pleural effusions in a patient with pancreatic cancer, and the nearly complete regression of malignant ascites in a patient with gastric cancer. The autologous tumor cells were isolated at the purity of more than 90% by Ficoll-Hypaque and Percoll discontinuous gradients, and then the TIL were cultured with IL-2 until 4 weeks. The optimal concentration of IL-2 was 1,500 IU/ml to obtain maximum proliferation and autologous tumor killing activity. The cytotoxic activities of activated TIL at 3 weeks-incubation was 72 +/- 15, 42 +/- 26, 27 +/- 21 and 22 +/- 15% against K562, Daudi, KATO-III and autologous tumor, respectively. By negative selection method, it was clarified that the killer cells recognizing autologous tumor consisted of CD4 or CD8 positive T lymphocyte in 43% of patients. The CD8 positive cells and CD56 positive cells increased, the CD4 positive cells and CD16 positive cells decreased by flow cytometry. The activated TIL could lyse not only cultured tumor cell lines, also other autologous tumor cells. The CD56+ cells were isolated by the Panning method, these cells could not lyse autologous tumor cells. Thus, it was indicated that the cytotoxic T lymphocytes recognizing autologous tumor could be generated from TIL and the adoptive immunotherapy of activated TIL was effective in cancer therapy.
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PMID:[Clinical application of adoptive immunotherapy by cytotoxic T lymphocytes induced from tumor-infiltrating lymphocytes]. 239 45

Fifty cases of malignant ascites were studied to determine what factors influenced outcome after peritoneovenous shunt. There were 36 women and 14 men. The five most common tumor types were colon, breast, gastric, pancreatic, and unspecified adenocarcinoma. Multivariate analysis between those patients surviving longer than 7 weeks (n = 20) and those who died in less than 7 weeks (n = 30) showed that women did uniformly better than men, even excluding the "female malignancies" (P less than 0.01). An elevated white blood cell count (WBC) and low platelets also were strong predictors of poor outcome (P less than 0.5 for difference in means between the two groups). Patients with pancreatic cancer and ascites fared poorly (80% mortality by 7 weeks) as did those with colon cancer (73% mortality by 7 weeks). By contrast, 50 per cent of the patients with breast and gastric cancer lived more than 7 weeks. Twelve patients had a LaVeen shunt placed, compared with 38 who had a Denver shunt. Fifty per cent of the La Veen shunts failed, with a mean time to failure of 69 days (P less than 0.01). Shunt failure, however, had no influence on overall survival.
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PMID:Peritoneovenous shunt (PVS) for malignant ascites. An analysis of outcome. 274 27

Our previous method of adoptive immunotherapy using IL2-cultured autologous lymphocytes consists of (1) in vitro sensitization by sonicated autologous tumor extract, (2) the induction and proliferation of active CTL by crude IL2, and (3) the preadministration of OK-432 for the augmentation of the therapeutic effect. Here we describe a new method to augment the therapeutic effect of OK432-combined AIT. In BALB/c mice with advanced malignant ascites (MOPC 104E), serial therapy with OK-432, cyclophosphamide and AIT significantly prolonged the survival compared with other therapeutic schedules through synergism between host's effector cells induced by immuno-chemotherapy and transferred killer cells. Many patients with advanced malignancies, for example, unresectable gastrointestinal cancer, locally advanced breast cancer or lung metastases of breast cancer, respond to such immuno-chemo-lymphocytotherapy, while previous OK432-combined AIT was effective only in malignant pleural effusion or metastatic liver tumor from breast cancer or peritoneal dissemination of gastric cancer.
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PMID:[Experimental and clinical study of adoptive immunotherapy combined with preadministration of OK-432: a method to augment the therapeutic effect]. 278 79

Ascitic fluid from tumour patients (hepatoma, gastric cancer, gallbladder cancer, colorectal cancer, ovarian cancer) and from non-malignant diseases (liver cirrhosis, congestive heart failure) were compared with respect to their content of determinants of the fibrinolytic system, tissue-type plasminogen activator antigen (t-PAag) and activity (t-PAact), urokinase-type plasminogen activator antigen (u-PA) and plasminogen activator inhibitor activity (PAI). Furthermore, SDS-polyacrylamide slab-gel electrophoresis (SDS-PAGE) was performed to evaluate molecular weight distribution of the detectable fibrinolytic parameters. In malignant ascites, PAI activity was three to four times higher, and increased complex formation of PAI with t-PA could be demonstrated, compared with non-malignant ascitic fluid. Tissue-type plasminogen activator antigen and activity showed a similar concentration in ascites of both study groups. Urokinase-type plasminogen activator antigen was detectable neither in ascites of malignant nor in ascites of non-malignant origin. It is concluded that t-PA is the physiological plasminogen activator in ascites and that increased PAI levels followed by increased complex formation between t-PA and PAI might reflect a reaction of the peritoneum.
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PMID:Plasminogen activators and plasminogen activator inhibitor in malignant and non-malignant ascitic fluid. 285 12

We attempted to use CDDP for patients with advanced cancers of the gastrointestinal system by intra-arterial infusion, giving consideration to the side effects of CDDP. Of 19 cases treated with CDDP, 17 cases were evaluable. These 17 cases comprised 10 cases of gastric cancer, 1 of pancreatic cancer and 6 of colon cancer. Therapeutic effects were as follows. According to the criteria for judgement of solid cancers, there were 10 evaluable cases which comprised 1 case of PR, 2 of MR, 4 of NC and 3 of PD. According to the criteria for judgement of malignant ascites, there were 6 evaluable cases which comprised 4 effective and 2 non-effective cases. As to side effects, nausea and vomiting were observed in 10 cases, numbness in 1, fever in 1 and aggravation of diabetes in 2. From the above results, intra-arterial infusion of CDDP is considered to be an effective method for the treatment of advanced cancers of the gastrointestinal system, especially of malignant ascites.
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PMID:[Intra-arterial infusion of CDDP in advanced gastrointestinal cancer (combination of general chemotherapy)]. 395 80

Twelve patients with malignant ascites caused by gastric cancer were treated with intraperitoneal injections of a streptococcal preparation, OK-432. All had resolution of the ascites after OK-432 treatment. Neutrophils, macrophages, and lymphocytes increased in number in ascitic fluid samples. Some of the OK-432-induced inflammatory cells were attached to tumor cells. The absolute number of tumor cells decreased as the number of infiltrating inflammatory cells increased. Infiltrating lymphocytes were mainly E rosette-forming cells. Infiltrating macrophages were in an activated state. The infiltrating neutrophils, lymphocytes, and macrophages could inhibit DNA synthesis of the patient's own tumor cells in the ascitic fluid after OK-432 injection, but not before the injection. These results indicate that OK-432-induced neutrophils, lymphocytes, probably T cells, and activated macrophages may play an important role in tumor cell destruction in ascites. Moreover, as the number of tumor cells decreased, the ascitic fluid protein levels decreased. Decrease of the ascitic fluid protein level may suppress further accumulation of ascitic fluid, and the low protein level in ascitic fluid is likely to facilitate the reabsorption of the fluid into the bloodstream.
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PMID:New approach to management of malignant ascites with a streptococcal preparation, OK-432. II. Intraperitoneal inflammatory cell-mediated tumor cell destruction. 660 Aug 54

The pharmacokinetic studies of intraperitoneal cisplatin (CDDP) for gastric cancer were discussed elsewhere, but those studies were investigated in patients with ascites. The purpose of this study is to compare the difference in pharmacokinetics between patients with malignant ascites and those curatively resected without ascites. One hundred mg of CDDP and 300 ml of saline were administered intraperitoneally for 9 curatively resected patients by catheter just after operation, and the same doses of CDDP were administered for 3 advanced or recurrent patients with ascites just after removal of whole fluid. Blood samples were corrected at 6 points after administration. Results were as follows: The 0-t area under the curve (AUC) and the Cmax of both total and free CDDP in the patients without ascites was higher than in the patients with ascites. The 0-infinity AUC and MRT of the ascites patients were higher than in the patients without ascites. These data suggest that intraperitoneal CDDP chemotherapy for gastric cancer as an adjuvant setting is more effective than chemotherapy for advanced malignant ascites patients.
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PMID:[Pharmacokinetic study of intraperitoneal cisplatin chemotherapy for gastric cancer as an adjuvant setting]. 757 52

Despite recent advances in cellular immunotherapy of cancer, the effectiveness of this type of treatment is limited only to some types of cancer. This study was performed to generate tumor-specific cytotoxic T lymphocytes (CTL) for the treatment of gastric cancer and to find the optimal culture conditions for this CTL, because most immune effector cells used in the previous trials were non-specific killers. Lymphocytes were isolated from tumors, tumor-draining lymph nodes, malignant ascites and peripheral blood of 29 patients with gastric cancer. Lymphocytes from each source were then cultured for three weeks under one or more of the following conditions: 1) 50 U/ml of rIL-2; 2) 50 U/ml of rIL-2 + irradiated (6,000 rad) fresh autologous tumor cells (in vitro sensitization - IVS); 3) 1,000 U/ml of rIL-2; 4) 1,000 U/ml of rIL-2 + IVS. The study found that 1,000 U/ml of rIL-2 generated higher cytotoxicity against allogeneic tumor targets than 50 U/ml of rIL-2 (p < 0.05). However, neither the concentration of rIL-2, lymphocyte source, nor IVS produced any significant differences in cytotoxicity against fresh autologous tumor cell targets. The data suggested that immune effector cells for gastric cancer could be generated efficiently, but it was difficult to produce CTL specific for autologous tumor cells of gastric cancer using a low concentration of rIL-2 and/or in vitro sensitization with autologous irradiated tumor cells.
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PMID:In vitro generation of immune effector cells from tumor-associated lymphocytes of human gastric cancer. 765 4


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