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  • 1
    Electronic Resource
    Electronic Resource
    Randomized controlled study of postoperative adjuvant immunochemotherapy with Nocardia rubra cell wall skeleton (N-CWS) and Tegafur for gastric carcinoma (1986)
    Springer
    Cancer immunology immunotherapy 22 (1986), S. 148-154 
    Details
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We performed a randomized controlled study of postoperative adjuvant immunochemotherapy with Nocardia rubra cell wall skeleton (N-CWS) and Tegafur for gastric carcinoma between September 1979 and March 1983. A total of 309 patients were entered into this trial. Of the 309 patients, there were 98 evaluable patients in the chemotherapy group and 115 evaluable patients in the immunochemotherapy group. In both groups, Tegafur was given as chemotherapy at a daily dose of 400 to 800 mg, starting at 24–29 days after gastrectomy. In the immunochemotherapy group, 400 μg of N-CWS was injected i. d. within the 2nd postoperative week. It was given weekly during the first month and subsequently monthly for as long as practicable. The patients were surveyed for length of survival in March 1985. The postoperative survival rate was analyzed for all cases, and for patients with various histopathological stages of carcinoma for comparison between the two treatment groups. No statistical difference was detected between the two groups in terms of age, sex, surgical curabilities, or stage of carcinoma. The overall survival rate for all patients was significantly higher in the immunochemotherapy group than in the chemotherapy group (p〈0.05). With stage III plus IV disease, 53 patients from the chemotherapy group and 61 patients from the immunochemotherapy group were included for the analysis. As a consequence, a highly significant survival rate was observed in patients with stage III plus IV carcinoma in the immunochemotherapy group (p〈0.005) as compared to the chemotherapy group. The overall 5-year (1800 days) survival rate after surgical treatment was 60.2% for the chemotherapy group and 73.2% for the immunochemotherapy group. In patients with stage III plus IV disease, the 5-year survival rates of the two treatment groups were 28.8% and 52.4%, respectively. Accordingly, the 50% survival period of patients with stage III plus IV cancer was 1800 days or more in the immunochemotherapy group, whereas it was only 722 days in the chemotherapy group. These results emphasize the effectiveness of N-CWS as an adjuvant immunotherapeutic agent in postoperative gastric cancer patients. The main side effects of N-CWS were skin lesions in the injected sites and fever, but these were temporary and not serious.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00199130
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  • 2
    Electronic Resource
    Electronic Resource
    Lymphokine-activated suppressor (LAS) cells in patients with gastric carcinoma (1989)
    Springer
    Cancer immunology immunotherapy 28 (1989), S. 218-224 
    Details
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary T-cell-growth-factor (TCGF) activated peripheral blood lymphocytes (PBL), cultured for 14 days, showed killer cell activities against natural-killer resistant Daudi cells in a 4 h 51Cr-release assay. However, the effector cells obtained from patients with nonresectable carcinoma exhibited very much lower cytotoxicity to tumor cells. To analyze the mechanism of depression, we have attempted to examine suppressor cell activities of the TCGF-activated PBL. The assay for the suppressor cell activities was made by in vitro inhibition of cell-mediated cytotoxicity by incubating radiolabeled target tumor cells with lymphokine-activated killer (LAK) cells and TCGF-activated PBL. LAK cells were induced by cultivation with recombinant interleukin-2. TCGF-activated PBL, obtained from four out of ten patients with resectable carcinoma and nine out of ten patients with nonresectable carcinoma, significantly suppressed the LAK cell activities. However, this suppression was not observed in TCGF-activated PBL from ten normal healthy control subjects. TCGF-activated PBL with immunosuppressive reactivity were named lymphokine-activated suppressor (LAS) cells. To investigate the phenotypic characterization of TCGF-activated PBL, the cells were analyzed by two-color flow cytometry. TCGF preferentially expanded CD8+CD11− cells and decreased the growth of CD8+CD11+ cells in both normal healthy control subjects and gastric cancer (resectable and nonresectable) patients. Dominantly expressed CD8+CD11− cells on TCGF-activated PBL in patients — especially those with nonresectable gastric carcinoma — showed strong LAS cell activity, irrespective of the presence of killer cell activities of CD8+CD11− cells in TCGF-activated PBL from normal healthy control subjects. The results suggested the generation of CD8+CD11− LAS cells from cancer patients, and revealed that CD8+CD11− T-cells contained killer and/or suppressor cell function. In addition, it was found that the TCGF-activated PBL from gastric cancer patients were associated with an increased proportion of CD4+Leu8+, HLA-DR+CD8+ and HLA-DR+CD25+ cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00204992
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  • 3
    Electronic Resource
    Electronic Resource
    Augmented human-tumor-cytolytic activity of peripheral blood lymphocytes and cells from a mixed lymphocyte / tumor culture activated by interleukin-12 plus interleukin-2, and the phenotypic characterization of the cells in patients with advanced carcinoma (1997)
    Springer
    Journal of cancer research and clinical oncology 123 (1997), S. 478-484 
    Details
    ISSN: 1432-1335
    Keywords: Key words IL-12 ; IL-2 ; LAK ; CTL ; Cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this study, we evaluated the ability of combination regimens of interleukin-12 (IL-12) and interleukin-2 (IL-2) to induce effective killer cells against human tumors in vitro, in peripheral blood lymphocytes (PBL) from 15 cancer patients and mixed lymphocyte/tumor culture (MLTC) cells from 16 cancer patients, and carried out a phenotypic analysis of the cells responsible for the lysis of the human tumors. The freshly prepared PBL were cultivated with IL-2 alone or IL-12/IL-2 for 10 days [lymphokine-activated killer (LAK) cell generation system]. The MLTC cells (PBL cultured with mitomycin-C-treated allogeneic G-415 tumor cells for 3 days) were further cultivated with IL-2 or IL-12/IL-2 for 7 days [cytotoxic T lymphocytes (CTL) generation system]. The cytolytic activities of the lymphoid cells cultivated with IL-12/IL-2 were significantly augmented in both the LAK and CTL generation systems, as compared with those of cells treated with IL-2 alone. In the LAK generation system, the cytolytic activities of the cells cultivated with IL-12/IL-2 were significantly decreased by the method of negative selection of CD11b+ or CD56+ cells using immunomagnetic beads. The CD8+-depleted cells showed a slight decrease of activity. The killer cell activities of the CD4+-depleted cells remained unchanged. In the CTL generation system, the activity was markedly reduced by the elimination of the CD8+ or CD11b+ or CD56+ cells. The combined data suggested that IL-12/IL-2-induced killer effector cells in the LAK generation system were mainly of the natural killer (NK) type, comprising CD8−CD11b+, CD8− CD16b+, CD3−CD56+, and partly possible CD8+ CD11b− T cells. CD8+CD11b− T cells mixed with cells of the NK type, comprising CD8−CD11b+, CD8− CD16b+ and CD3−CD56+ cells, were the population of killer effector cells induced by IL-12/IL-2 in the CTL generation system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050091
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  • 4
    Electronic Resource
    Electronic Resource
    Expression of costimulatory molecules, B7-1 and B7-2 on human gastric carcinoma (1998)
    Springer
    Journal of cancer research and clinical oncology 124 (1998), S. 383-388 
    Details
    ISSN: 1432-1335
    Keywords: Key words Costimulating molecule ; B7-1(CD80) ; B7-2(CD86) ; Gastric carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Costimulation of T cells via B7-1 and B7-2 molecules on a tumor has been shown to be important for eliciting cell-mediated antitumor immunity. We studied the surface expression of B7-1 and B7-2 in 24 cases of gastric carcinoma from the primary locus, 20 cases of metastatic carcinoma from malignant ascites, 20 cases of benign gastric mucosa and 7 gastric carcinoma cell lines by two-color flow cytometry with mAb CD80 and CD86. The B7-1 and B7-2 molecules were expressed by 6 cell lines, and 1 cell line showed the predominant expression of B7-2 but not B7-1. Almost all patients with primary gastric carcinoma and benign gastric mucosa showed high levels of expression of the B7-1 and B7-2, revealing approximately 40%–60% positive cells. However, the percentage of B7-1-positive cells of poorly differentiated primary carcinomas was significantly lower than that of well-differentiated carcinoma and normal mucosa (P〈0.01). Furthermore, all of the metastatic carcinoma cells revealed consistently very low or undetectable levels of expression of the B7-1 molecule, only 8% (mean) of cells being positive, despite showing higher levels of B7-2 expression. Thus, it seems likely that decreased or deleted expression of B7-1 correlates with the grade of tumor differentiation, tumor progression and metastasis. These results suggest that the B7-1 molecule on the gastric carcinoma bearing CD80+CD86+ is abrogated during tumor invasion and/or metastasis, and the tumor finally acquires the CD80−CD86+ phenotype. Consequently, inadequate B7-1 costimulation may contribute to the escape of tumors from destruction by the host's immune system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050187
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  • 5
    Electronic Resource
    Electronic Resource
    Phenotypic analysis of nylon-wool-adherent suppressor cells that inhibit the effector process of tumor cell lysis by lymphokine-activated killer cells in patients with advanced gastric carcinoma (1994)
    Springer
    Journal of cancer research and clinical oncology 120 (1994), S. 240-247 
    Details
    ISSN: 1432-1335
    Keywords: Suppressor cells ; Nylon-wool-adherent cells ; Lymphokine-activated killer cells ; Gastric carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The causes of down-regulation of cytotoxic immune responses in cancer patients have not been fully evaluated. We previously demonstrated that T-cell-growth-factor-activated peripheral blood lymphocytes (PBL) with the surface phenotype CD8+ CD11b−, from patients with widespread metastasis of gastric carcinoma, inhibited the effector process of lymphokine-activated-killer(LAK)-cell-mediated cytolysis. In this study, we examined suppressor cell activity in freshly prepared PBL from 18 patients with advanced gastric carcinoma, and 10 normal healthy individuals. The suppressor cell activity was assayed by recording whether or not PBL inhibited directly the effector process of LAK cell cytotoxicity. Most of the PBL suspensions from cancer patients showed that they contained a population of cells that can directly inhibit the effector phase of tumor cell lysis of the cytotoxic cells. To analyze further the PBL responsible for the suppression, the cells were passed over a nylon-wool column. Nylon-wool-adherent cells significantly augmented the suppression, while the cells passing through abrogated the suppressive effect. Most nylon-wool-adherent cells from 10 normal healthy controls did not inhibit the cytotoxic reaction. To determine further the suppressor-effector population in nylon-wool-adherent cells, negative-selection studies using CD8-, CD4- or CD11b-coated magnetic beads, and positive-selection studies using CD8- or CD4-coated magnetic beads were performed. Finally the results suggest that the suppressor-effector cells comprise at least two different surface phenotypes: CD8+ T and CD8−CD11b+ cells. The possible role of CD4+ T cells and HLA-DR+ LeuM3+ macrophages as suppressor cells was ruled out in nylon-wood-adherent cells. CD8+ T and possibly CD8−CD11b+ cells apparently suppressed the efferent limb of the antitumor immunity. The selective immune suppression mediated by these cells may partly be concerned with escape mechanisms of gastric carcinoma from the host immune surveillance system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01372563
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  • 6
    Electronic Resource
    Electronic Resource
    Augmented human-tumor-cytolytic activity of peripheral blood lymphocytes and cells from a mixed lymphocyte/tumor culture activated by interleukin-12 plus interleukin-2, and the phenotypic characterization of the cells in patients with advanced carcinoma (1997)
    Springer
    Journal of cancer research and clinical oncology 123 (1997), S. 478-484 
    Details
    ISSN: 1432-1335
    Keywords: IL-12 ; IL-2 ; LAK ; CTL ; Cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this study, we evaluated the ability of combination regimens of interleukin-12 (IL-12) and interleukin-2 (IL-2) to induce effective killer cells against human tumors in vitro, in peripheral blood lymphocytes (PBL) from 15 cancer patients and mixed lymphocyte/tumor culture (MLTC) cells from 16 cancer patients, and carried out a phenotypic analysis of the cells responsible for the lysis of the human tumors. The freshly prepared PBL were cultivated with IL-2 alone or IL-12/IL-2 for 10 days [lymphokine-activated killer (LAK) cell generation system]. The MLTC cells (PBL cultured with mitomycin-C-treated allogeneic G-415 tumor cells for 3 days) were further cultivated with IL-2 or IL-12/IL-2 for 7 days [cytotoxic T lymphocytes (CTL) generation system]. The cytolytic activities of the lymphoid cells cultivated with IL-12/IL-2 were significantly augmented in both the LAK and CTL generation systems, as compared with those of cells treated with IL-2 alone. In the LAK generation system, the cytolytic activities of the cells cultivated with IL-12/IL-2 were significantly decreased by the method of negative selection of CD11b+ or CD56+ cells using immunomagnetic beads. The CD8+-depleted cells showed a slight decrease of activity. The killer cell activities of the CD4+-depleted cells remained unchanged. In the CTL generation system, the activity was markedly reduced by the elimination of the CD8+ or CD11b+ or CD56+ cells. The combined data suggested that IL-12/IL-2-induced killer effector cells in the LAK generation system were mainly of the natural killer (NK) type, comprising CD8−CD11b+, CD8− CD16b−, CD3−CD56+, and partly possible CD8+ CD11b−T cells. CD8+ CD11b−T cells mixed with cells of the NK type, comprising CD8−CD11b+, CD8− CD16b− and CD3−CD56+ cells, were the population of killer effector cells induced by IL-12/IL-2 in the CTL generation system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01192201
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  • 7
    Electronic Resource
    Electronic Resource
    Expression of intercellular adhesion molecule 1 (ICAM-1) during the development of invasion and/or metastasis of gastric carcinoma (1992)
    Springer
    Journal of cancer research and clinical oncology 118 (1992), S. 609-614 
    Details
    ISSN: 1432-1335
    Keywords: HLA class I ; HLA-class II ; ICAM-1 ; TIL ; Gastric carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In this study, using two-color flow-cytometric analysis, we examined the expression of histocompatibility locus antigens (HLA) classes I and II, and intercellular adhesion molecule 1 (ICAM-1) in 10 cases of normal gastric mucosa, 13 cases of primary carcinoma on the stomach, 16 cases of metastatic carcinoma from malignant ascites in patients with gastric carcinoma and 14 samples of their cultured carcinoma cells. Compared with normal gastric mucosa, HLA class I were highly expressed in a considerable number of tumor cells in each experimental group. The expression of HLA class II tended to reduce in the order of normal gastric mucosa, primary gastric carcinoma and peritoneal-effusion-associated carcinoma. Altogether, 85.7% of cases of cultured tumor cells showed abrogation and loss of HLA class II. The ICAM-1 molecule was not detected on normal gastric epithelial cells. In few cases, carcinoma cells from large volumes of tumor located in the stomach showed detectable amounts of ICAM-1. On the other hand, all of the metastatic carcinoma cells from peritoneal effusions showed a high level of expression of the ICAM-1 molecule. The expression of ICAM-1 on adenocarcinoma cells was maintained and/or augmented by in vitro cultivation with tumor-infiltrating lymphocytes (TIL). Furthermore, twocolor fluorescence-activated cell sorting analysis of TIL revealed that significant correlation was observed between the expression of ICAM-1 and the degree of TIL, composed mainly of CD3+ T cells including CD8+ CD11b−, CD8+CD28+, CD8+S6F1+ and CD4+Leu8+, and CD57+CD16− and CD57+CD16+ NK cells, and HLA-DR+LeuM3+ macrophages.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01211806
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  • 8
    Electronic Resource
    Electronic Resource
    Expression of epidermal growth factor receptor and CD44 splicing variants sharing exons 6 and 9 on gastric and esophageal carcinomas: a two-color flow-cytometric analysis (1999)
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 47-54 
    Details
    ISSN: 1432-1335
    Keywords: Key words Gastric carcinoma ; Esophageal carcinoma ; Epidermal growth factor receptor (EGFR) ; CD44 splicing variant isoforms (CD44v6 ; CD44v9) ; Flow cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Quantitative analysis based on the percentage of positive cells by two-color flow cytometry was used to quantify the surface expression of epidermal growth factor receptor (EGFR), and exons v6 and v9 of CD44 splice variants on tumor. Almost all patients with primary gastric and esophageal carcinomas, and benign mucosa of the stomach and esophagus showed usually high levels of EGFR expression, a mean of approximately 60% of cells being positive. Metastatic gastric carcinoma showed significantly higher levels of EGFR expression, a mean of 80% of cells being positive. Reduced expression of EGFR was observed in irradiated esophageal carcinoma. Adenocarcinomas, including primary and metastatic lesions, or cancer cell lines of the stomach revealed consistently very low or undetectable levels of expression of exon v6 of the CD44 variant (CD44v) protein. However, CD44v containing exon v9 could be detected in normal gastric epithelium and primary gastric carcinoma as well as in six adenocarcinoma cell lines. Exon v9 is significantly overexpressed on metastatic adenocarcinoma cells obtained from malignant ascites. On the other hand, normal squamous epithelium and primary squamous cell carcinoma (SCC) of the esophagus, and two SCC cell lines showed coexpression of exons v6 and v9 of CD44v. The expression of the CD44v6 molecule was significantly reduced in the irradiated primary SCC, although CD44v9 expression on the primary SCC remained unchanged after the radiation therapy. These results suggest that up-regulation of EGFR and CD44v9 molecules on gastric carcinomas, especially metastatic adenocarcinomas, shows tumor growth and tumor progression. In addition, down-regulation of EGFR and CD44v6 molecules on irradiated esophageal carcinoma may be involved in the mechanisms suppressing tumor growth and metastatic potential.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050241
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  • 9
    Electronic Resource
    Electronic Resource
    Transforming growth factor-alpha (TGF α)-producing gastric carcinoma with acanthosis nigricans: An endocrine effect of TGF α in the pathogenesis of cutaneous paraneoplastic syndrome and epithelial hyperplasia of the esophagus (1997)
    Springer
    Journal of gastroenterology 32 (1997), S. 71-77 
    Details
    ISSN: 1435-5922
    Keywords: acanthosis nigricans ; transforming growth factor-alpha (TGF α) ; epidermal growth factor (EGF) receptor ; gastric carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A case of well-differentiated adenocarcinoma (Borrmann type 3) of the stomach in a 76-year-old man associated with the typical skin manifestations of acanthosis nigricans and with multiple protruding lesions showing epithelial hyperplasia of the esophagus is reported. The advanced tumor was located in the cardiac region of the stomach, and measured approximately 8cm in diameter, with partial invasion to the esophagus. The associated cutaneous lesions were characterized by hyperpigmentation and by protruding verrucous papules on the torso, head, face, neck, upper extremities, perineum, and inguinal region. Histologically, the protruding skin lesions showed keratinocytes proliferation throughout the epidermis, resulting in diffhyperkeratosis, papillomatosis, and acanthosis of the skin. Immunohistological analysis showed coexpression of transforming growth factor alpha (TGF-a) and epidermal growth factor (EGF) receptors in the tumor from the stomach. It is reasonable to conclude from this evidence that gastric carcinoma cells secrete TGF α in an autocrine for auto-stimulation. EGF receptor expression was also noted on the papillomatous hyperplasia of the cutaneous lesion. Serum level of TGF α, determined by an enzyme-linked immunosorbent assay, was high (144pg/ml; normal, 22.0 ±16pg/ml (Mean±SD)). Serum TGF α abruptly decreased to 49pg/ml on day 7 after the total gastrectomy, and then gradually increased to 77pg/ml within 28 days. Amelioration of the cutaneous lesions and the protruding lesions in the esophagus was observed after surgical resection of the gastric carcinoma. This suggests that the TGF α stimulates the proliferation of keratinocytes involved with EGF receptor. Large amounts of circulating TGF α in the blood over a long period released by the primary tumor seem to act as an endocrine-like mechanism causing epidermal and esophageal epithelial cells to proliferate. There is a possible link in the pathogenesis of the acanthosis nigricans as a cutaneous paraneoplastic syndrome, and epithelial hyperplasia of the esophagus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01213299
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  • 10
    Electronic Resource
    Electronic Resource
    Venous tumor thrombosis and cavernous transformation of the portal vein in a patient with gastric carcinoma (1995)
    Springer
    Journal of gastroenterology 30 (1995), S. 529-533 
    Details
    ISSN: 1435-5922
    Keywords: tumor thrombosis ; portal vein ; gastric carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A case of extensive extra-and intrahepatic portal tumor thrombosis, with no metastatic foci in liver parenchyma, secondary to advanced gastric carcinoma in a 69-year-old man is reported. The portal tumor thrombosis was characterized by enlargement of the thrombosed segment of the vein, decreased density mass without intraluminal enhancement of the involved vein, nonvisualization of the portal venous branch in the involved lobe, and the so-called cavernous transformation of the portal vein. The surgically resected gastric specimen showed Borrmann type 3 advanced papillary adenocarcinoma. The portal tumor thrombus is presumed to have arisen from vascular invasion in the primary foci of gastric carcinoma, and then to have permeated the portal vein without invasion of liver parenchyma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02347573
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