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  • 1
    ISSN: 1436-2813
    Keywords: clonogenic assay ; hyperthermia ; anticancer agents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Utilizing a clonogenic assay, the effects of hyperthermia and selected chemotherapeutic drugs on growth of cells from malignant effusions were studied. Fourteen of 25 samples obtained from 25 patients with various carcinomas formed at least 30 colonies per plate. Exposure of the cells to heat at 42°C for 1 hr before the plating slightly inhibited the colony growth. The drugs, adriamycin (AM) and mitomycin C (MMC), were tested at 3 different concentrations. When the cells were treated with these two drugs for 1 hr at 42°C, the percent of surviving colonies was significantly decreased, as compared to findings at 37°C, in both groups, at 3 different concentrations. The combination of drugs and hyperthermia appeared to function synergistically in one-third of such cases. These results suggest that cells from malignant effusions in patients with various carcinomas were more sensitive to AM or MMC, under condition of a higher temperature (42°C).
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1436-2813
    Keywords: cell-mediated cytotoxicity ; regional lymph nodes ; gastric carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The cell-mediated cytotoxic activities of cells from the perigastric lymph nodes (LNC) were assayed in patients with gastric carcinoma. These activities were compared with those of the peripheral blood mononuclear cells (PBM), and also with the LNC of patients with benign lesions. The capacity of LNC to be converted to cytotoxic cells in mixed cell culture was significantly impaired in the cancer patients as compared to that of either the PBM from the same patients, or the LNC from patients with benign lesions. The natural killer cell (NK) activity of LNC was significantly lower than that of the PBM in both groups of patients. The cytotoxic activity induced by phytohemagglutinin activation (PAK) in the LNC from patients with carcinoma, as well as from those with benign lesions was also significantly decreased, when compared to that of the PBM, although the ability of LNC to produce interleukin 2 (IL 2) was significantly increased. The ability of these cells to generate cytotoxicity after activation with IL 2 (LAK) was therefore examined, and a decreased capacity in LNC was observed. These results indicated that the ability of T cells in LNC to develop into cytotoxic cells in patients with gastric carcinoma was impaired, and that the nonspecific cytotoxicity, including NK or PAK, as well as LAK activity, was essentially low in the perigastric lymph nodes.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0851
    Keywords: Key words Apoptosis ; Antibody-dependent cell-mediated cytotoxicity ; Monocyte ; 17-1A ; Interferon γ
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Antibody-dependent cell-mediated cytotoxicity (ADCC) has been considered to be one of the main effector mechanisms by which unconjugated monoclonal antibody (mAb) 17-1A can exert an antitumor effect in vivo. Since the apoptotic pathway as well as the necrotic pathway have been shown to be utilized in various cytotoxic effector mechanisms, we investigated the role of apoptosis in ADCC mediated by monocytes (ADMC) using mAb 17-1A as an antibody and the human colorectal carcinoma cell line, COLO205, as target cells in vitro. The implications of the apoptosis during ADMC was demonstrated by means of both a DNA fragmentation assay and a TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay. Furthermore, interferon γ (IFNγ) was also found to enhance the induction of apoptosis significantly. The addition of superoxide dismutase did not reduce the level of the apoptosis, although superoxide anion (O2 –) was observed to be produced. However, the release of tumor necrosis factor α (TNFα) was significantly enhanced during ADMC, while, in addition, apoptosis was significantly inhibited by the addition of anti-TNFα antibody. These findings indicated that apoptosis might be implicated in ADMC with mAb 17-1A, which was augmented by IFNγ, while, in addition, TNFα may also be one of the major mediators of apoptosis.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Cancer immunology immunotherapy 24 (1987), S. 259-262 
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of mitomycin C (MMC) on the generation of cell-mediated cytotoxicity in primary stimulation culture of human peripheral blood mononuclear cells (PBM) with the B lymphoblastoid Raji cell line were assessed. The cell-mediated cytotoxicity induced in culture was significantly augmented when MMC was added to cultures on day −1 to day 3 for 24 h at concentrations of 2.5×10−2 μg/ml and 2.5×10−3 μg/ml. To identify the cell populations affected by MMC, PBM were separated by adherence to plastic after treatment with MMC for 24 h (day −1). The two populations were recombined with untreated separated cells and stimulated with antigen. The ability to develop an augmented cell-mediated cytotoxicity was associated with the adherent cell fraction of MMC-treated PBM. Therefore, the ability of MMC-treated adherent cells to produce interleukin 1 (IL 1) was examined. Significantly higher levels of IL 1 were produced by treated cells as compared to untreated adherent cells. The results appear to indicate that the selective effects of MMC on the adherent cell fraction, especially the modification of IL 1 production, may be involved in the mechanisms of MMC-induced augmented cell-mediated cytotoxicity.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of mitomycin C administration on the generation of cytotoxic cells, induced by in vitro activation of peripheral blood mononuclear cells (PBM) with interleukin-2, was studied in patients with various carcinomas. The ability of PBM to generate lymphokine-activated killer (LAK) cell activity against Raji cell targets was significantly augmented 5 and 7 days after a single intravenous dose of 12 mg/m2 mitomycin C, when compared to that of PBM obtained before mitomycin C injection. Further, LAK cell activity against autologous tumor cells was also significantly increased after the drug administration. The distribution of lymphocyte subsets exhibited a significant increase in the percentage of CD3+ cells after injection, with the elevation of the CD4/CD8 ratio. Furthermore, the proportion of the CD4+ Leu8+ subpopulation, which identifies inducers of suppression, was significantly reduced. Thus, the decrease in the proportion of suppressor-inducer subsets of PBM might be at least partially, responsible for the augmented generation of LAK cells after mitomycin C administration.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0851
    Keywords: Key words Cytokine ; Quantitative RT-PCR ; Interleukin-2 ; Interleukin-1 ; Tumor necrosis factor α
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  After activation with interleukin-2 (IL-2), peripheral blood mononuclear cells (PBMC) have been reported to induce the expression of mRNA coding various cytokines, including interleukin(IL)-1α, -1β and tumor necrosis factor α (TNFα). We examined the cytokine mRNA expression of PBMC following treatment with IL-2 in vitro and in vivo by a quantitative method using the reverse transcription/polymerase chain reaction (RT-PCR). After stimulating PBMC with IL-2 in vitro, peak levels of IL-1α mRNA were reached between 3 h and 12 h, and thereafter declined. The IL-1β expression increased, with levels peaking at 1–6 h and, had decreased by 96 h. The expression of TNFα was elevated both 1–3 h and 24–48 h after stimulation. The peak levels of IL-1α and -1β mRNA and the early elevation of TNFα mRNA mainly accounted for the cytokine mRNA expression in adherent cells; however, the late induction of TNFα mRNA was observed in nonadherent cells. In patients with advanced carcinoma, the IL-1α and -1β mRNA expression were elevated after IL-2 treatment for 5 consecutive days, while the expression of TNFα mRNA also increased. These results indicate that the quantitative RT-PCR method appears to be useful for analyzing the cytokine mRNA expression of PBMC after treatment with IL-2.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1436-2813
    Keywords: postoperative immunodepression ; interleukin 2 ; immunological restoration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Effect of exogenous interleukin 2 (IL 2) on the postoperative depression of cell-mediated immune responsein vitro was studied in 8 patients with benign lesion and 11 patients with various carcinoma, undergoing major surgical procedures. When peripheral blood mononuclear cells (PBM) were obtained from patients 3 days after surgery, the proliferative response of PBM in mixed lymphocyte culture (MLC) was significantly decreased, as compared to that before operation. The depressed proliferative response was significantly increased and improved to the preoperative level, when exogenous IL 2 was added at a concentration of 50 per cent in culture. The defective generation of cytotoxic cells in MLC 3 days after operation was also significantly augmented and improved to the preoperative range by addition of 25 per cent IL 2 in culture. IL 2 produced minimal increase in these responses when PBM were obtained preoperatively. There was no significant difference between each value in these responses obtained from patients with benign lesion and carcinoma. These results show that PBM from patients who had undergone major surgery were responsive to exogenous IL 2. The postoperative depression of cell-mediated immune response may be reversible with exogenous IL 2.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1436-2813
    Keywords: cell-mediated cytotoxicity ; spleen cells ; interleukin 2 ; activated killer cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The cell-mediated cytotoxic activities of cells from the spleens (SP cells) of patients with gastric carcinoma were assayed in comparison with the activities of peripheral blood mononuclear cells (PBM cells) from the same patients, and from patients with benign lesions. The natural killer cell (NK) activity of the SP cells and their capacity to generate allogeneic cytotoxicity in mixed lymphocyte culture (MLC) were very similar to those of the PBM cells. The cytotoxic activity of SP cells induced by alloactivation in MLC, however, was significantly higher than that of the PBM cells from the same patient as well as from patients with benign lesions. The production of interleukin 2 (IL 2) and the ability to induce cytotoxic cells after activation with IL 2 (LAK) were therefore examined. Both the ability to produce IL 2 and to generate LAK cells were shown to be significantly increased in SP cells when compared to PBM cells. These results indicate that the spleen may be a potential reservoir for the precursors of these activated killer cells in patients with gastric carcinoma. Furthermore, it may play an important role in the defence against tumors in these patients.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1436-2813
    Keywords: adjuvant therapy ; combination chemo-immunotherapy ; advanced gastric carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A chemo-immunotherapy program was designed on the basis of our clinical findings, which revealed that the ability to generate cell-mediated cytotoxicity was remarkably augmented after adriamycin (AM) administration in cancer patients. Twenty patients with stage IV gastric carcinoma who had undergone noncurative resections were treated with the above regimen that consisted of active immunotherapy with autologous tumor cells, in combination with 30 mg of AM, given 7 days before the immunization, followed by long-term tegafur (FT) and immunomodulators. The survival of these patients was compared to that of 3 other groups of patients, namely; 30 patients treated with another chemo-immunotherapy regimen which comprised autologous tumor cells in combination with several anticancer drugs followed by long-term FT and immunomodulators (CCI1), 17 patients treated with mitomycin C followed by long-term FT and immunomodulators (CI), and 24 patients with comparable histories (HC). The first treatment group had significantly improved survival, as compared to the HC group (p〈0.01) and the survival tended also to be more favorable, when compared to the CCIl group (p〈0.2) or the CI group (p〈0.2). Moreover, the survival rate at 9 months was significantly higher than that of either the CCI1 group (p〈0.01) or the CI group (p〈0.01).
    Type of Medium: Electronic Resource
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