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)

Immunohistochemical study with various monoclonal antibodies against the mononuclear cell surface antigen was performed on the regional lymph nodes of gastric cancer through Avidin-Biotin Complex (ABC) method. In the paracortical area (P.C.) of those lymph nodes without the metastasis of gastric cancer, T cells were dominant, and OKT3 positive (OKT3+) cells and OKT4+ cells were diffusely present, while OKT8+ cells were occasionally recognized. In the sinus, subsets of the above T cells, and OKT9+ cells and OKT10+ cells were observed. In the germinal center (G.C.), mantle zone (M.Z.) and primary follicle (P.F.), which were B cell regions, OKIa1+ cells and Leu12+ cells were diffusely present. OKB7+ cells, OKT9+ cells, OKT10+ cells and Leu7+ cells were also noted in G.C.. Leu8+ cells were observed in M.Z. and P.F.. OKIa1+ cells were occasionally noted in P.C. and sinus. In the lymph nodes with the metastasis, decrease of OKT4+ cells and increase of OKT8+ cells were noted in comparison to the lymph nodes without the metastasis. Using the tissue double fluorescence staining method, it was found that about half of the OKT4+ cells were helper T cells. The majority of OKT8+ cells were identified as cytotoxic T cells or their precursors. By preoperative endoscopic administration of OK-432 or PSK into the tumor, the IL-2 receptor+ cells, or OKM1+ cells and OKT4+ cells increased in the regional lymph nodes and the antitumor activity was intensified.
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PMID:[Immunohistochemical study of the regional lymph nodes in gastric cancer]. 311 May 88

Tumor infiltrating lymphocytes (TIL) and lymph node lymphocytes (LNL) were thought to play an important role in local immunity against cancer. But the natural cytotoxicity (NC) of TIL and LNL was very weak, and was not augmented by beta-IFN. This low cytotoxicity was augmented by IL-2, and especially LNL were activated to have higher lymphokine activated killer (LAK) activity than that of PBL. So it was proven that TIL and LNL had an potential of immunological defence system. In order to bring out these potential, immunomodulators (OK-432, PSK) were injected intralesionally under endoscopy one week prior to surgery. The cytotoxicity of TIL and LNL was augmented by the intralesional injection of OK-432 or PSK. There was no significant difference in LAK activity of LNL among the OK-432-, PSK-injected group, and the control. The 2-year survival rate of the OK-432-injected group was much longer than that of the control. From above results, intralesional injection of immunomodulators was thought to be a promising candidate for the immunotherapy of gastric cancer.
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PMID:[The immune defense system in gastric cancer tissue, regional lymph node and spleen--aspects from subsets and functions of lymphocytes]. 408 22

Normal peripheral blood lymphocyte (PBL) from healthy donors, and splenic cells and tissues from patients with gastric cancers were implanted into the severe combined immunodeficient (SCID) mouse. The normal PBLs at 10(7) and 10(8)/mouse were implanted intraperitoneally (ip), and three to six splenic tissues with a size of 3 x 3 x 3 mm from gastric cancer patients were inoculated subcutaneously (sc) into the bilateral backs of the mice. The dissociated splenic cells were also administered ip and intravenously (iv). At 2, 4, 6 and 8 weeks after inoculation, mice were killed, and the human IgG and IgM were assessed by ELISA method. SCID mice with splenic cells and tissue revealed high human IgG and IgM levels from 2 weeks after inoculation, while the IgG levels in mice treated with PBLs were limited. When the tetanus toxoid was challenged to SCID mice reconstituted with splenic tissue, the anti-tetanus IgG was observed in 10 of 43 mice, showing the human B cell functions in the mice. Although the reconstitution of T cell surface marker in SCID mice was incomplete, OKT3, OKT4 and OKT8 surface markers were successfully observed in 10% to 20% SCID mice of which splenic cells were incubated with IL-2 or anti-CD3 monoclonal antibody. This model was thought to be adequate for evaluating human immunological functions of the patients with gastric cancer in vivo.
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PMID:[Reconstitution of human immune systems in severe combined immunodeficient mouse--with reference to the reconstituted with human splenic cells and tissues from patients with gastric cancer]. 766 52

The modulation effects of cimetidine on the production of IL-2 and IFN-gamma by the peripheral blood mononuclear cells in 31 patients with gastric cancer and 32 normal subjects were studied. Their T lymphocyte subsets were also assayed. The IL-2 and IFN-gamma activity in patients were significantly lower than that in normal subjects (P < 0.01). Cimetidine could significantly promote IL-2 and IFN-gamma production. There was a significant negative correlation between OKT8 subsets and the activity of IL-2 and IFN-gamma (P < 0.01). The results showed that cimetidine could be used as an adjunct in the treatment of advanced neoplasm.
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PMID:[Modulation effect of cimetidine on the production of IL-2 and interferon-gamma in patients with gastric cancer]. 780 62

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

In this paper we investigate the reactivity pattern of T cells from stomach carcinoma patients against autologous tumour cells. T cells obtained from the tumour environment, tumour-draining lymph nodes and peripheral blood were cloned in 78 patients with stomach cancer and anti-tumour cytotoxic T lymphocytes (CTLs) precursor frequencies were assessed in each sample by using limiting dilution analysis. When tumour-specific CTLs were tested for specific T-cell killing by using only low doses of Interleukin 2 (100 U ml-1), a moderate rate of proliferation frequency of T cells (0.047) and specific cytotoxicity (12%) were observed in lymph node populations. When both IL-2 and autologous tumour cells in mixed lymphocyte tumour cultures (MLTCs) were used for stimulation, a dramatic increase in number (0.1) and in specific lytic activity (46%) could be measured. No effect or specific activity to tumour cells was observed with peripheral blood lymphocytes and tumour-infiltrating lymphocytes.
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PMID:Human stomach carcinoma-specific T cells derived from the tumour-draining lymph nodes. 798 Oct 54

The supernatant of a cell line of squamous cell carcinoma of the head and neck (SCCHN), PCI-50, was previously shown to induce activation, promote proliferation and increase antitumor cytotoxicity of freshly purified human natural killer (NK) cells and CD4+ T lymphocytes [Arch Otolaryngol Head Neck Surg (1994) in press]. This supernatant was found also to promote the growth of a variety of hematopoietic cell lines, including Jurkat, THP-1, K562, NK-92 or Epstein-Barr-virus-transformed B cell lines. The Jurkat cell line was selected as a reporter cell in an 18-h proliferation assay established to measure the growth-promoting activity of PCI-50 supernatant. The presence of soluble tumor-derived factors able to induce proliferation of Jurkat cells was demonstrated in the supernatant produced by several other SCCHN cell lines but not in that produced by a gastric cancer cell line (HR) or renal cell carcinoma line (5117G8). The growth-promoting PCI-50 supernatant was shown to contain 28 +/- 0.5 pg/ml interleukin-6 (IL-6) in vitro but was negative for interferon gamma, IL-1, IL-2, IL-4, tumor necrosis factor alpha, granulocyte/macrophage-colony-stimulating factor and IL-12. The addition of any of these recombinant cytokines to Jurkat cell cultures did not significantly promote growth, while PCI-50 supernatant was consistently growth-stimulatory. This supernatant neither enhanced intracellular Ca2+ concentration in Jurkat cells nor induced up-regulation of activation antigens on the cell surface, although it supported growth of Jurkat cells in the absence of IL-2. The growth-promoting activity in the PCI-50 supernatant was acid-labile at pH 2 for 4 h, heat-resistant at 96 degrees C for 1 h and sensitive to treatments with trypsin and pepsin. Preincubation of the PCI-50 producer cells with tunicamycin or cyclohexamide reduced the level of growth-promoting activity in the supernatant. A partial purification of this activity was achieved using Amicon filtration, chromatography on concanavalin-A-Sepharose and then a hydroxyapatite column and high-pressure liquid chromatography gel filtration. The partially purified glycoprotein had a molecular mass of 50-70 kDa, as determined by gel filtration.
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PMID:Proliferation of hematopoietic cell lines induced by a soluble factor derived from human squamous cell carcinomas of the head and neck. 800 Oct 29

We established a cell line (STKM-1) from tumor cells obtained from carcinomatous pleural effusion of a gastric cancer patient. The lymphocytes separated from her peripheral blood or pleural effusion were cryopreserved and immunological experiments were performed after the establishment of the cell line. They were treated with IL-2 or with both IL-2 and mitomycin C (MMC)-treated autologous STKM-1 cells. The cytolytic activity against STKM-1 cells was elevated in lymphocytes cultured with IL-2, and was more prominently augmented in lymphocytes cultured with both IL-2 and MMC-treated STKM-1 cells. The elevation in cytolytic activity was more marked with pleural effusion lymphocytes than with the peripheral blood lymphocytes. The results suggest that the lymphocytes obtained from the pleural effusion would be an excellent source for adoptive immunotherapy.
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PMID:Induction of cytolytic activity of lymphocytes from carcinomatous pleural effusion by IL-2 and autologous tumor cells. 801 49

The antitumor efficacy of IL-2 is limited to renal cancer and melanoma. Several cytokines have been associated with IL-2 in an attempt to improve its activity, without, however, any clear benefit. Recent experimental and clinical studies have suggested the possibility to manipulate the host biological response by immunomodulating neurohormones, such as the pineal hormone melatonin (MLT). On the bases of these considerations, we have designed a neuroimmunotherapeutic protocol with low-dose IL-2 subcutaneous therapy (3 million IU/day for 6 days/week for 4 weeks) plus MLT (40 mg/day orally, starting 7 days before IL-2) in advanced solid neoplasms other than renal cancer and melanoma, which are generally resistant to IL-2 alone. The study included 82 patients, 72 of whom showed distant organ metastases. Tumor histotypes were, as follows: non-small cell lung cancer: 19; hepatocarcinoma: 16; colon cancer: 15; gastric cancer: 11; cancer of pancreas: 11; breast cancer: 6; miscellaneous: 4. Objective tumor regression were achieved in 17/82 (21%) patients, consisting of CR in 4 (liver: 2; pancreas: 1; stomach: 1) and PR in 13 (lung: 4; liver: 4; stomach: 2; pancreas: 1; breast: 1; colon: 1). The median duration of response was 8+ months. A stabilization of disease was obtained in 30 patients, while the other 35 patients progressed. The lack of progression was associated with a significantly higher increase in lymphocyte and eosinophil mean number and with a significantly lower increase in neopterin mean levels. The treatment was well tolerated in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cancer immunotherapy with low-dose interleukin-2 subcutaneous administration: potential efficacy in most solid tumor histotypes by a concomitant treatment with the pineal hormone melatonin. 802 99

The advanced tumours of the digestive tract are generally less responsive to conventional chemotherapies. Moreover, preliminary results with IL-2 immunotherapy also seem to show a low efficacy. On the basis of our previous studies suggesting s synergistic action between IL-2 and some neurohormones, such as the pineal indole MLT, a clinical trial was performed to investigate the clinical efficacy and tolerability of an immunotherapy with IL-2 plus MLT in patients with advanced neoplasms of the digestive tract. The study included 35 patients (colorectal cancer: 14; gastric cancer: 8; hepatocarcinoma: 6; pancreas adenocarcinoma: 7). Distant organ metastases were present in 31/35 patients. MLT was given orally at a daily dose of 50 mg at 8.00 p.m., starting 7 days before IL-2, which was given subcutaneously at a dose of 3 million IU/day at 8.00 p.m. for 6 days/week for 4 weeks, corresponding to one cycle of immunotherapy. In nonprogressed patients, a second cycle was given after a 21-day rest period. A complete response was achieved in two patients (gastric cancer: 1; hepatocarcinoma: 1). Six other patients obtained a partial response: (gastric cancer: 2; hepatocarcinoma: 2; colon cancer: 1; pancreas cancer: 1). Therefore, the overall response rate was 8/35 (23%). Stable disease was obtained in 11/35 (31%) patients, whereas the remaining 16 patients (46%) progressed. The response rate was significantly higher in untreated patients than in those previously treated with chemotherapy. Toxicity was low in all patients, who received the treatment as a home therapy. This study shows that the immunotherapy with low-dose IL-2 plus the pineal hormone MLT is a new well tolerated and effective therapy of advanced tumours of the digestive tract, mainly in gastric cancer and hepatocarcinoma.
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PMID:Immunotherapy with subcutaneous low-dose interleukin-2 and the pineal indole melatonin as a new effective therapy in advanced cancers of the digestive tract. 851 25


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