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  • Mitomycin C  (3)
  • Cytotoxic T lymphocytes Tumor-rejection antigen  (1)
  • 1
    ISSN: 1432-0851
    Keywords: Key words MAGE-3 ; Peptide ; Cytotoxic T lymphocytes Tumor-rejection antigen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The antigenic peptides encoded by tumor-rejection antigen genes, MAGE-1 and -3, have been identified, and various methods have been utilized for the in vitro induction of MAGE-specific, cytotoxic T lymphocytes (CTL) from peripheral blood mononuclear cells (PBMC) using synthetic peptides. However, all of these methods are technically demanding and thus have a relatively limited usefulness. We herein report a simple and efficient method for the in vitro induction of specific CTL by using the HLA-A2-restricted MAGE-3 peptide from the PBMC of a healthy donor. CTL responses could thus be efficiently induced from unseparated PBMC by stimulation with freshly isolated, peptide-pulsed PBMC as antigen-presenting cells and by using interleukin-7 and keyhole limpet hemocyanin for the primary culture. The induced CTL could thus recognize and lyse not only HLA-A2 target cells pulsed with the peptide but also HLA-A2 tumor cells expressing MAGE-3, in an HLA-class-I-restricted manner. This simple method may, therefore, become a useful tool for investigating the potential peptides for tumor antigens as well as for developing various immunotherapeutic approaches for human malignant tumors.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0851
    Keywords: Eosinophilia ; Antitumor response ; Interleukin-2 ; Mitomycin C ; Advanced carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary On the basis of our clinical findings that the ability of cancer patients to generate lymphokine-activated killer cells became markedly augmented after mitomycin C administration, we designed a treatment regimen comprising mitomycin C 12 mg/m2, i.v. on day 1 and recombinant interleukin-2 700 U/m2 (8000 IU/kg), i.v. every 12 h from day 4 through day 8. The treatment course was repeated at almost 7-day intervals. Altogether 33 patients with advanced carcinoma, including mainly gastrointestinal carcinoma, were treated with this regimen. Of these, 10 had a partial response (PR) and 4 had a minor response (MR). Since eosinophil counts peaked 1 day after either the first or second course of the therapy, the posttreatment values were compared to each pretreatment level, with regard to the clinical antitumor response to this treatment. When patients who showed PR were defined as responders, absolute eosinophil counts and the percentages of eosinophils in responders after both the first and second courses of the therapy were significantly greater than each pretreatment value or the posttreatment level in nonresponders. Further, these findings were almost identical, when both PR and MR were considered to be a true remission and therefore patients who exhibited PR or MR were defined as responders, although the difference between posttreatment levels of eosinophils in responders and nonresponders was not significant at the second course. These results indicate that eosinophilia induced by this treatment correlates with the clinical response to this therapy.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0851
    Keywords: Immunohistochemistry ; Lymphocyte subsets ; Tumor-infiltrating lymphocyte ; Mitomycin C ; Gastric carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The intensity of lymphoid cell infiltration and distribution of lymphocyte subsets in tumors were investigated immunohistochemically on tumor tissues obtained from 11 patients with gastric carcinoma, who had been treated with mitomycin C (MMC), 12 mg/m2, i.v. 5 days before operation. The results were compared with those obtained from 24 untreated patients as controls. In the tumor tissues from pretreated patients, the intensity of lymphoid infiltration was not significantly different from that of untreated patients. However, high-grade infiltration of CD4+ cells was observed in 55% of pretreated patients, whereas only 8% of control patients exhibited the high-grade infiltration (P 〈0.02). Since the CD8+ cell infiltration was not significantly altered, the ratio of CD4+ to CD8+ cells was more frequently estimated to be more than 1 in patients pretreated with MMC, as compared to untreated controls (P 〈0.02). Further, CD25+ cells in pretreated tumor tissues were more predominant than those in control tumor tissues (P 〈0.05). These results suggest that MMC administration induces these alterations in lymphocyte subsets in tumor tissue in patients with gastric carcinoma.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0851
    Keywords: Cytotoxic activity ; Phenotypic analysis ; Peripheral blood mononuclear cell ; Interleukin-2 ; Mitomycin C ; Clinical response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We previously found that the ability of peripheral blood mononuclear cells (PBM) of cancer patients to generate lymphokine-activated killer (LAK) cells became remarkably augmented after mitomycin C administration. On the basis of the clinical finding, we designed a treatment regimen comprised of 12 mg/m2 mitomycin C i. v. on day 1 and 700 U/m2 recombinant interleukin-2 (IL-2) i.v. every 12 h from day 4 through day 8. Of 25 patients with advanced carcinoma, 9 had a partial response and 3 had a minor response. Cytotoxic cell function, including natural killer activity, lymphokine-activated killer (LAK) activity, and the ability to generate LAK cells, and lymphocyte subsets in PBM was measured 1 day before and after either the first or second course of this therapy. The relationship between these parameters and the clinical antitumor response to this treatment was examined. Although the cytotoxic activities were significantly augmented after either the first or second treatment course, no positive correlation was observed between the changes in these cytotoxic activities and the clinical response to this therapy, when patients who either showed a partial response or whose disease remission was partial or minor were defined as responders. Further, phenotypic analysis showed a significant increase in CD2+, CD3+ CD4+ and CD4+Leu8− cells after the firs course, and CD25+ cells after either the first or second course of this treatment. The precentages of CD2+ and CD25+ cells were significantly elevated only in responders but not in nonresponders, suggesting the increase in these subsets was related to clinical response.
    Type of Medium: Electronic Resource
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