Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied whether lymphokine-activated killer (LAK) cells were capable of being induced in vitro from peripheral blood lymphocytes (PBL) of patients with malignant glioma, by using recombinant IL-2 (rIL-2). We then investigated whether they possessed anti-tumor efficacy against malignant gliomas (ONS-12, -20, -44). Human LAK cells were generated by placing 5 X 10(6) PBL into each well of 24-well plates (Corning) containing 2 ml of complete medium (CM) with 10 units of rIL-2 (TGP-3, provided by TAKEDA Chemical Industries, Ltd.). The CM consisted of RPMI 1640 with 0.1 mM nonessential amino acids, 1 microM sodium pyruvate, 5 X 10(-5) M 2-mercaptoethanol, 50 micrograms/ml gentamicin sulfate, 0.03% glutamine and 1% heat-inactivated human AB serum. The plates were incubated horizontally at 37 degrees C in a 5% CO2 atmosphere for 72-96 hours. The LAK cells were then harvested, washed three times with Hanks balanced solution, and resuspended in RPMI 1640 with 1% heat-inactivated human AB serum for the in vitro cytotoxicity assays. The anti-tumor cytotoxic activity of LAK cells was estimated in triplicate by 4-hr 51Cr release assays. The cytotoxic activity of the LAK cells against autogeneic ONS-44 glioma cells and PHA blasts was approximately 30% and a few %, respectively. The Natural Killer (NK) activity of the patient with ONS-44 glioma cells was equivalent to that of healthy subject.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[The anti-tumor efficacy of lymphokine-activated killer (LAK) cells induced in vitro from peripheral blood lymphocytes of patients with malignant glioma]. 308 95

We have studied the in vitro antitumor effectiveness of murine lymphokine-activated killer (LAK) cells induced by recombinant IL-2 (rIL-2). LAK cells were generated by placing 5 X 10(7) fresh C 57 BL/6 splenocytes (erythrocytes were lysed osmotically) in 10-cm (diameter) dishes (Falcon) containing 10 ml of complete medium (CM). The CM consisted of RPMI 1640 with 0.1 mM non-essential amino acids, 1 microM sodium pyruvate, 5 X 10(-5)M 2-mercaptoethanol, 50 micrograms/ml gentamicin sulfate, 0.03% glutamine, 10% heat-inactivated fetal calf serum (FCS) and 10 units/ml of rIL-2 (TGP-3, provided by TAKEDA Chemical Industries, Ltd). The dishes were incubated horizontally at 37 degrees C in a 5% CO2 atmosphere for 72-96 hr. The LAK cells were then harvested, washed three times, and resuspended in RPMI 1640 with 5% heat-inactivated FCS for the in vitro cytotoxicity assay. The antitumor cytotoxic activity of LAK cells was estimated in triplicate by 4 hr 51Cr release assays. The cytotoxic activity of LAK cells against syngeneic 203 glioma and normal syngeneic glioblasts was approximately 50% and a few %, respectively. The in vitro cytotoxicity of LAK cells against syngeneic EL-4 thymoma, allogeneic YAC-1 lymphoma and P-815 mastocytoma was 72%, 87% and 43%, respectively. Thus LAK cells have apparent tumor specificity in vitro and are easily generated. Fresh splenocytes of CBA/J mice were markedly lytic for natural killer (NK)-sensitive YAC-1 cells, but not for 203-glioma cells or NK-resistant P-815 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[The in vitro antitumor effectiveness of murine lymphokine-activated killer (LAK) cells induced by recombinant IL-2]. 348 67

Autologous brain tumor specific CTLs were induced from the patient's PBL by a mixed lymphocyte-tumor culture, and were maintained for more than 2 months in a medium containing exogenous IL-2. The autologous T cell line containing specific CTL was administered into the tumor-bed for the treatment of malignant glioma. In 2 cases out of 5, tumors regressed more than 50% in diameter. One of these patients is still alive now with full of his social activities, and it is 104 weeks after the initiation of the immunotherapy. Autologous T cell lines were safely administered in all cases without any complications nor toxicities.
 ...
PMID:Establishment of interleukin 2 dependent cytotoxic T lymphocyte cell line specific for autologous brain tumor and its intracranial administration for therapy of the tumor. 349 20

Lymphokine-activated killer cells (LAK) are cytolytic lymphocytes with the unique capacity of killing NK-resistant fresh human tumor cells in short-term assays. LAK appear to kill autologous tumors as well as TNP-modified self and allogeneic tumors with complete crossreactivity, both at the population and clonal level. Initial studies on the classification of LAK conclude that LAK are distinct from the classical NK and T-lymphocyte systems based on a number of criteria including surface phenotype, activation conditions, and spectrum of susceptible target cells. LAK kill rasoncogene-transfected fibroblasts in a manner similar to fresh tumors. As yet, the target cell determinant responsible for susceptibility to LAK lysis is unknown, but cell-surface proteins are definitely involved. Activation of LAK requires only IL-2, and is most efficient using serum-free conditions. Because interleukin-2 alone is sufficient for LAK activation, we have tested in vitro whether fresh PBL could be activated in the presence of tumor, as might be desired in vivo. LAK activation was greatly suppressed by tumor presence. LAK activation is also suppressed by hydrocortisone, but not cyclosporine A. Because of the above and other findings, we have initiated a clinical protocol to test whether LAK made from brain-tumor patients' PBL could eliminate residual glioma tumor cells. Autochthonous LAK, plus rIL-2 to maintain lytic ability, are injected during surgery. Preclinical studies in a rat glioma model have shown this approach to be safe. Eleven glioma patients have been injected intracerebrally with IL-2 and/or LAK with no immediate or long-term (14 months follow-up) adverse effects. Much work is needed to understand the LAK phenomenon and to resolve its potential usefulness in cancer therapy as well as its inherent biologic role.
 ...
PMID:Human lymphokine-activated killer cells (LAK cells) as a potential immunotherapeutic modality. 353 98

The efficacy of glioma-specific cytotoxic T-lymphocyte for a syngeneic murine malignant glioma (a 20-methylcholanthrene-induced ependymoblastoma, 203-glioma) was investigated. The cytotoxic clone (G-CTLL 1), established and expanded exponentially by T-cell growth factor, has retained target specificity for more than 6 months. In adoptive therapy and Winn assay, the in vivo antitumor activity of G-CTLL 1 was demonstrated against mice inoculated intracranially with 203-glioma cells. The therapeutic effects in adoptive immunotherapy were largely dependent on dose and time of i.v. administration, although the therapy was rather ineffective in condition of increased intracranial pressure due to the tumor growth. The mechanisms responsible for the in vivo protection were probably related to the killing activity of G-CTLL 1 or the tumor-specific production of immune interferon by G-CTLL 1.
 ...
PMID:Specific adoptive immunotherapy with tumor-specific cytotoxic T-lymphocyte clone for murine malignant gliomas. 660 88

The immunoregulatory effects of TCGF (T-cell growth factor) on the generation and growth of syngeneic murine malignant glioma (20-methylcholanthrene-induced 203-glioma)-specific killer T-cell were investigated in C57BL/6 adult mice in order to clarify the immunopotential usefulness for anti-tumor local adoptive immunotherapy against malignant brain tumor. TCGF was prepared and assayed. Briefly, 5 x 10(6) ml mouse spleen cells were cultured with 2 microgram/ml concanavalin A in RPMI-1640 medium supplemented with 2% fetal calf serum for 24 hours. Culture supernatants were concentrated by ammonium sulphate precipitation (55 to 80% saturation) and purified by gel filtration (Sephadex G-100, a molecular weight from 30 to 36,000 daltons) and ion exchange chromatography (DEAE-cellulose, elution with 0.15 M in NaCl at ph 7.4). The purified TCGF had no IFN activity. Assays for TCGF was performed for quantitative analysis using 203-glioma-specific killer T cell clone (G-CTLL), which was obtained by limiting dilution method (0.3 cells/well in 96 well microtiter plate) and maintained for over 6 months in the presence of TCGF. Titer (U/ml) of TCGF was defined as the quantity of TCGF required to obtain one-half of the maximal stimulation of G-CTLL proliferation assay. It was confirmed that the specific killer T-cell against 203-glioma was generated in mice after intracranial as well as subcutaneous inoculation of the tumor cells. The killer T-cell activity of spleen cells, however, began to be severely impaired 2 weeks after intracranial inoculation concurrently with the increased intracranial pressure due to developing the tumor growth. Sensitized lymphocytes obtained from intracranial and subcutaneous tumor-bearing mice were assessed for CTL (cytotoxic T-lymphocyte) activity in MLTC (mixed lymphocyte-tumor cell culture) for 18 hours by microcytotoxicity assay. The specific cytotoxicity against 203-glioma cells was enhanced when sensitized lymphocytes from intracranial and subcutaneous tumor-bearing mice were pre-cultured with optimal TCGF (20 U/ml) for over 5 days. After the treatment of sensitized lymphocytes with anti-Thy-1 monoclonal antibody and complement, however, the specific cytotoxicity of sensitized lymphocytes was eliminated almost completely. Therefore, it was thought that TCGF possesses immunoregulatory effects of enhancement of killer T-cell activity. On the contrary, TCGF had no influence on normal T lymphocytes and the growth of 203-glioma cells in vitro.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Effects of TCGF (T-cell growth factor) on experimental malignant glioma-specific killer T-cell]. 660 19

The purposes of the current study were: (1) to investigate the immunoregulatory effects of T-cell growth factor (TCGF) on the activation and differentiation of syngeneic cytotoxic T lymphocyte (CTL) populations generated against a 20-methylcholanthrene-induced ependymoblastoma, 203-glioma, in C57BL/6 mice; and (2) to determine whether the glioma-specific CTL clone (G-CTLL) could be established by TCGF, and whether the in vivo efficacy of the cloned cells could be rendered more effective in adoptive therapy. It was found that TCGF largely allows the CTL populations to proliferate and thus can activate the depressed cytotoxic activity in tumour-bearing mice. Two lines of G-CTLL were successfully obtained by the limiting dilution technique. The G-CTLL retained a TCGF-dependent proliferative growth and a marked cytotoxic activity with target specificity for over 18 months, characterized by a surface phenotype of Lyt-1-.2.3+, Lyt-2 antibody blocking of cytotoxicity and the production of immune interferon in response to mitogen and tumour antigen. In the Winn assay and the adoptive transfer assay, the therapeutic effects were detected in intracranially inoculated tumours in mice. The in vivo efficacy was dependent on the dose of G-CTLL and on the time of the intravenous administration, although the transfer was inversely ineffective in conditions of increased intracranial pressure. The mechanism responsible for the in vivo effect was probably due to the adoptive immunity and/or the tumour-specific interferon production of G-CTLL.
 ...
PMID:Specific adoptive immunotherapy of malignant glioma with long-term cytotoxic T lymphocyte line expanded in T-cell growth factor. Experimental study and future prospects. 661 23

The genes for interleukin (IL)-2, interferon (IFN)-gamma, or both IL-2 and IFN-gamma were introduced into a mouse fibroblast cell line (LM) expressing defined major histocompatibility complex determinants (H-2k). The cytokine-secreting cells were then co-transplanted with the Gl261 murine glioma cell line (H-2b) into syngeneic C57BL/6 mice that differed at the major histocompatibility complex from the cytokine-secreting cells. The period of survival of mice with glioma treated with IL-2- or IL-2/IFN-gamma-secreting allogeneic cells was significantly prolonged (P < 0.025) relative to the survival of mice receiving equivalent numbers of tumor cells alone or mice with glioma treated with nonsecreting fibroblast (LM) cells. Gliomas in the treated mice had an extensive lymphocytic cell infiltrate. Using a 51Cr release assay, the specific release of isotope from labeled Gl261 cells co-incubated with spleen from mice injected with the glioma cells and IL-2-secreting fibroblasts was higher (P < 0.001) than the release from glioma cells co-incubated with spleen cells from nonimmunized mice. Significantly higher levels of release (P < 0.005) were found in the group immunized with fibroblasts secreting both IL-2 and IFN-gamma. Based upon the effect of monoclonal antibodies for T-cell subsets on the antiglioma response, the immunity was mediated predominantly by natural killer/lymphokine-activated killer cells.
 ...
PMID:Fibroblasts genetically engineered to secrete cytokines suppress tumor growth and induce antitumor immunity to a murine glioma in vivo. 775 55

The humoral interactions between three malignant glioma early-passage cell cultures and in vitro interleukin (IL)-1 alpha- and IL-2-activated autologous peripheral blood mononuclear cells (PBMC's) were investigated, employing standard and modified (separated by permeable membranes) mixed lymphocyte tumor cell (MLTC) cultures. In modified MLTC's, glioma cells clearly inhibit proliferation of PBMC's (up to 60%), whereas lymphokine-activated PBMC's enhance glioma cell growth up to 12-fold, as determined by 3H-thymidine incorporation assays. Glioma cells produce both stimulatory (IL-6) and inhibitory proteins (transforming growth factor-beta) for PBMC's. Lymphokine-activated PBMC's secrete IL-1 alpha, IL-2, IL-4, IL-6, interferon-gamma, and tumor necrosis factor-alpha, which may modulate glioma cell proliferation. None of these cytokines stimulated glioma cells as intensely as modified MLTC systems. These observations indicate that in vitro lymphokine-activated PBMC's, although suppressed by humoral glioma-derived factors, may enhance glioma cell proliferation with soluble factors secreted into the culture medium. The authors conclude that glioma-lymphocyte growth regulatory networks include stimulatory and inhibitory factors from both cell populations, which may modulate tumor progression. These observations may have relevance for adoptive immunotherapy in patients with gliomas.
 ...
PMID:In vitro studies of cytokine-mediated interactions between malignant glioma and autologous peripheral blood mononuclear cells. 793 92

The effects of 5 different growth factors [EGF, PDGF(bb), TGF-alpha, bFGF and IL-2] were studied on tumour spheroids obtained from 5 different human glioma cell lines (U-251MG, D-263MG, D-37MG, D-54MG, GaMG). The expression of EGF and PDGF receptors as well as the endogenous production of TGF-alpha and PDGF were studied by Northern blot analyses. After growth-factor-exposure, tumour spheroid volume growth, and directional cell migration from the spheroids were studied. In addition, tumour-cell invasion was studied in vitro, where foetal rat-brain aggregates were used as a target for the tumour cells. In all the assays a common stimulator for most of the cell lines was EGF. The other growth factors had a more heterogeneous stimulatory effect. Tumour-cell invasion, cell growth and cell migration are biological properties which are not necessarily related to each other. This may explain why the tumours often responded differently to the growth factors in the various assay systems. Two of the cell lines studied were non-invasive (U-251MG, D-263MG). It is shown that these were stimulated both in the directional migration assay and in the spheroid-volume-growth assay. However, their non-invasive behaviour was not influenced by the growth factors studied.
 ...
PMID:Heterogeneous response to the growth factors [EGF, PDGF (bb), TGF-alpha, bFGF, IL-2] on glioma spheroid growth, migration and invasion. 831 9


<< Previous 1 2 3 4 5 6 7 Next >>