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

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)
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PMID:[Effects of TCGF (T-cell growth factor) on experimental malignant glioma-specific killer T-cell]. 660 19

The effect of intravenously injected tumor immune spleen cells on growth of 3 X 10(5) gliosarcoma T9 cells injected intradermally (ID) or intracerebrally (IC) into sublethally irradiated CDF rats was evaluated. Spleen cells from donor rats with sufficient immunity to reject 5 X 10(5) T9 cells inhibited the growth of T9 cells mixed with spleen cells in a ratio of 1:25 and injected ID, but could not act after intravenous transfer. However, donor rats which had rejected increasing T9 challenge doses up to 1 X 10(7) cells produced immune spleen cells which, upon IV transfer, could inhibit growth of ID T9 challenge but not of EB-679, an unrelated glioma, in recipient rats. Rejection of IC T9 challenge was also obtained after IV transfer, in recipients of such "hyperimmune" spleen cells, but was less (60% maximum) than that noted after ID T9 challenge (100% maximum). The removal of B cells from the transferred spleen cells did not affect the results, suggesting that the specific immunity was mediated by T cells. We conclude that the special immunological circumstances of tumors growing in the brain renders them less accessible to rejection by systemically transferred immune cells, but it is nevertheless possible to effect a significant incidence of rejection of syngeneic tumor growth in the brain by the intravenous transfer of hyperimmune spleen cells.
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PMID:Immunity to transplantable nitrosourea-induced neurogenic tumors. III. Systemic adoptive transfer of immunity. 661 Jul 26

The immune response of Wistar rats to the intracranial inoculum of 1 X 10(5) C-6 glioma cells was evaluated. The growth of these cells disrupted the blood-brain barrier by day 9. The rats with the implanted tumor cells died between three to four weeks following injection. No significant cell-mediated cytotoxicity against 51Cr labelled C-6 cells was seen in the short term (4 hours) cytotoxicity assay with spleen cells obtained from glioma-bearing rats at any stage of tumor growth. In the long term (18 hours) cytotoxicity assay, significant activity was detected using whole, adherent and nonadherent spleen cells from glioma-bearing rats at every assessment point during the growth of the tumor, but this cytotoxicity was also seen in normal rat splenocytes. The lack of cell mediated cytotoxicity above normal values was not due to a generalized immunosuppression since splenocytes from glioma bearers were found to have responses to Con A comparable to normal controls. However, normal or glioma-bearer splenocytes showed augmented cytotoxicity in the presence of serum obtained from rats bearing a glioma tumor starting by day 13 of tumor growth and rising in cytotoxic activity until death. This activity was not seen with normal serum. The glioma-bearer serum, though not cytotoxic to the C-6 cells alone, became cytotoxic with the addition of rabbit complement. These data indicate that the growth of intracranially implanted glioma cells in rats elicits primarily a humoral cytotoxic immunity without a significant cell-mediated immunity. This humoral immunity develops after the breakdown of the blood-brain barrier.
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PMID:The immunological response of Wistar rats to the intracranially implanted C-6 glioma cell line. 667 75

Cellular growth interactions were studied between neonatal human lung fibroblasts (NLF-13) and human tumor lines derived from carcinomas of the prostate (PC-3, DU145), bladder (J82), and endometrium (HEC-1A) and from a glioma (Hs 683t). NLF-13 were interacted with tumor cells in soft agar or agarose media using two experimental protocols. In one system, NLF-13 cells were grown as anchored monolayers proliferating under the tumor cell layer. In the second, NLF-13 were embedded directly (nonanchored) into the agar or agarose layer with the tumor cells. The results from both interaction systems were similar for all five tumor lines. Anchored NLF-13 caused a dose-dependent inhibition of tumor growth, whereas nonanchored cells produced a dose-dependent growth stimulation. A time exposure experiment indicated that tumor stimulation and inhibition were biphasic responses to NLF-13. It was concluded that low concentrations of a diffusible NLF-13 product(s) accelerated tumor growth, whereas high concentrations were inhibitory. Further, the production of the active NLF-13 substance(s) was positively correlated with NLF-13 growth rate. Tumor cell inhibition was irreversible after a 5-day exposure to proliferating NLF-13 cells. Another line of normal neonatal human lung fibroblasts (NLF-147) showed inhibitory properties similar to those described for NLF-13. However, preliminary studies with fibroblasts from the skin of a Down's syndrome neonate (DS-172) and from a human kidney tumor (KTF-130) have shown both these fibroblast types to have a reduced ability to inhibit tumor cell cultures (J82) compared to the neonatal lung fibroblasts (NLF-13 and NLF-147).
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PMID:Comparable growth regulation of five human tumor cell lines by neonatal human lung fibroblasts in semisolid culture media. 668 26

Proliferation and death were measured in cultures of mouse neuroblastoma N18TG -2 and rat glioma C6BU -1 cells when treated with up to 100 micron retinoidal butenolides (RB 1-6). The number of viable cells in each case was measured with various concentrations of the compounds, of which RB-3 (5-hydroxy-4-[2-(2,6,6,-trimethyl-l- cyclohex en-l-yl) ethenyl ]-2(5H)- furanone ) was the most potent in destroying the cells after 2 days' incubation. ED50 of RB-3 was about 5 X 10(-7) M for both types of cell. RB-3 was 80 times more potent than retinoic acid. Ten analogues of RB-3 had a similar inhibitory effect on DNA synthesis in N18TG -2 cells. The degenerative changes caused by RB-3 in C6BU -l cells were irreversible even when the cells were exposed to it for 2 h. Tumor weights of N18TG -2 cells that had been inoculated subcutaneously onto the backs of A/J mice were 30-40% lower than those of untreated controls after 14 days of single daily i.p. injections of RB-3 doses of 100 mg/kg of body weight. The results indicate that RB-3 is cytotoxic in murine tumor cells originating from the nervous system and has an inhibitory effect on neuroblastoma-tumor growth in mice.
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PMID:Cytotoxic action of retinoidal butenolides on mouse neuroblastoma and rat glioma cells. 672 42

Alkyl-lysophospholipids (ALP) and related derivatives inhibited the in vitro incorporation of [3H]thymidine into seven different permanent cell lines derived from rat brain tumors. The cytostatic effect of ALP was dependent on dosage and incubation time. Naturally occurring 2-lysophosphatidylcholine did not exhibit cytostatic effects; under these conditions, the incorporation rates of [3H]thymidine were generally more than 100% of the controls. The trypan blue dye exclusion test, which was used to assess severe cell damage, correlated with the extent that [3H]thymidine incorporation was inhibited by ALP. Preincubation of ALP (rac-1-octadecyl-lyso-glycero-3-phosphocholine) for more than 8 min with a tetrahydropteridine-dependent O-alkyl cleavage enzyme preparation from rat liver microsomes destroyed almost all of the cytotoxic properties of ALP when tested at a concentration that previously inhibited tumor growth by more than 50%. [3H]Thymidine incorporation rates were greater than 100% for astrocytoma cells incubated with ALP after exposure to the alkyl cleavage enzyme. Comparison of the microsomal activities of the tetrahydropteridine-dependent alkyl-cleavage enzyme present in astrocytoma 78-FR-G-299 cells and the pleomorphic glioma 78-FR-G-219/S4 cells to that found in normal skin fibroblasts and rat livers revealed a markedly reduced activity in the neoplastic cell lines. Moreover, those tumor cells that were more resistant to ALP cytotoxicity (pleomorphic glioma, 78-FR-G-219/S4) had a 3-fold higher tetrahydropteridine-dependent cleavage activity than a more cytotoxic sensitive line (astrocytoma cells, 78-FR-G-299). Our results indicate that the low-alkyl-cleavage enzyme activities in these neoplastic cells in comparison to normal cells might be a factor in explaining the relatively high cytotoxicity of ALP in tumor cells.
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PMID:Cytotoxicity of alkyl-lysophospholipid derivatives and low-alkyl-cleavage enzyme activities in rat brain tumor cells. 684 77

Known and unknown host factors determine the individual susceptibility to carcinogenic agents. Such factors may interact with either the phase of transformation (initiation) or with the phase of proliferation (promotion). Some of these factors have been recognized as potential determinants of the degree of susceptibility or resistance to cancer. Transformation may be impeded by a low rate of absorption of carcinogenic agents (barrier effect), by the availability of deactivating enzymes operative at several steps of the metabolism of carcinogenic agents, and by a high repair capability of DNA damage. Proliferation of transformed cells may be impeded or prevented by immune defense mechanisms and by maturation factors such as nerve growth factor (NGF), glia maturation factor, fibroblast growth factor, and others. NGF has already been shown to be capable of maturing anaplastic glioma cells (clone F98) and reducing their rate of growth. Rats treated with NGF following implantation of anaplastic glioma cells had a significantly decreased tumor growth rate and increased survival time. NGF administration to pregnant rats preceding exposure to ethylnitrosourea (ENU) (50 mg/kg, 21st day of gestation) or to offspring transplacentally exposed to ENU resulted in reduction of neurinoma development. The importance of NGF as a suppressing agent of neoplastic proliferation and as a prospective tumor therapeutic needs further exploration.
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PMID:Potential factors in carcinogenesis and tumor regression. 685 28

The effects of adult thymectomy in C 57 BL/6 mice on in vivo and in vitro responses to syngeneic methylcholanthrene-induced glioma (203-glioma) were investigated in order to analyse the role of T cell subpopulation in relation to the antitumor immunity. The tumor growth in adult mice thymectomized 3 weeks before subcutaneous inoculation of tumor cells was significantly suppressed. On the other hand, in mice thymectomized 7 or 10 weeks before tumor cell inoculation, the tumor growth was enhanced resulting in shorter mean survival time. The cytotoxic activity of the regional lymph node T cells in the former mice was increased from the beginning after tumor cell inoculation with peak observed on day 14 and maintained for about 4 weeks, while it was extremely decreased in the latter mice. The marked enhancement of cytotoxic activity in the former mice is probably due to a reduced proportion of short-lived T lymphocyte population after adult thymectomy. In contrast, the low level of cytotoxic activity in the latter mice may be due to a gradual reduction of long-lived T lymphocyte population in addition to short-lived T lymphocyte population after adult thymectomy. The cytotoxic activity was specific for 203-glioma cells and almost completely eliminated with anti-Thy-1 monoclonal antibody and complement. The surface markers of these killer T cells were checked with the results that in normal mice Lyt-1-.2.3+ and Lyt-1+.2.3+ cells participate in cytotoxic reaction. In mice thymectomized 3-10 weeks before tumor cell inoculation, however, Lyt-1+.2.3+ killer T cells were not detected suggesting strongly that the progenitors of Lyt-1+.2.3+ killer T cells are short-lived cells in contrast to those of Lyt-1-.2.3+ killer T cells which survive more than 10 weeks after adult thymectomy. The tumor growth was also significantly suppressed by the intravenous adoptive transfer of sensitized lymphocytes obtained from mice thymectomized 3 weeks before tumor cell inoculation. This effect of tumor suppression was disappeared by the pretreatment of infused lymphocytes with anti-Thy-1 monoclonal antibody and complement. These evidences may suggest that in tumor bearing mice short-lived suppressor T cells or their precursors exist and regulate the growth and differentiation of killer T cells and that adult thymectomy affects immunoregulation, possibly by altering the generation of suppressor T cells.
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PMID:[Effects of adult thymectomy on the growth of 203-glioma in mice--analysis of T cell subpopulation in tumor immunology]. 698 37

The share of proliferating cells, the tumor growth fraction, was studied in 11 cases of glial tumors of the large hemispheres of man. The individual sensitivity of human glial tumors to irradiation was determined in 7 cases by the method of tumor growth in diffusion chambers. It was established that glioblastomas and dedifferentiated astrocytomas were characterized by a sufficiently high proliferative activity. The duration of the history of the disease and the period free of recurrences correlated with the value of the growth fraction in many cases. Gliomas, even of the same histostructure, differed considerably in the reaction to irradiation in some patients. The sensitivity of tumor cells to irradiation in growth in diffusion chambers does not depend on the proliferative activity of the initial tumors determined on operative material.
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PMID:[Experimental approaches in studying the biological properties and radiation sensitivity of human brain tumors]. 706 15

Tumors in vivo usually exhibit deceleratory rather than exponential growth kinetics. Deceleration results from a negative feedback inhibition of growth the effectiveness of which increases progressively with tumor size. A major obstacle to understanding the fine mechanisms of deceleratory growth has been the lack of a tissue culture system proven to exhibit these kinetics. Rat C6 glioma cells in culture enter a prolonged phase of deceleratory growth about 72 hr after subculture. As with tumor growth in vivo, the kinetics of the C6 deceleratory phase can be described with high accuracy by Gompertz, logistic, inverse cube root, and power functions. The least-squares correlation coefficients for the linearized forms of the rate equations for these functions were typically in the range of 0.75 to 0.90. During the deceleratory phase, the equilibrium growth rate of C6 cells is a monotonically decreasing function of population density at all observable densities, whether sub- or supraconfluent. Any change in density produces a compensatory change of opposite direction in the growth rate. To account for these relationships, a density-equilibrium hypothesis of C6 growth regulation is presented. The fine mechanisms responsible for this regulation do not involve medium or substratum depletion, production of conditioned medium factors, or the extracellular matrix. The development of growth deceleration appears to correlate with the extent of contact interactions between cells and their neighbors, indicating that deceleratory growth regulation is probably mediated by contact interactions. However, these interactions are fundamentally different from those postulated by the traditional contact inhibition theory. Confluency is irrelevant to the contact modulation which produces C6 growth deceleration. Any degree of contact, even at very sparse subconfluent densities, appears capable of exerting some degree of growth inhibition.
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PMID:Deceleratory growth by a rat glial tumor line in culture. 706 86


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