Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of methotrexate (MTX) on the proliferative activity of cells in different phases of cell cycle has been studied. MTX (5 mg/kg) was injected i.p. 3 days after the inoculation of 5 X 10(6) leukemia cells, into F1 (DBA X C57 BL) mice. It was shown that MTX causes degeneration of cells, being in G1- as well as in S-phase at the time of drug injection. Incorporation of 3H-TdR was suppressed for a period ranging from 2 to 12 hr after MTX administration, which is demonstrated by the decrease in the number of grains per cell. The number of cells labeled after 3H-TdR injection was also sharply decreased during this period. For a period of 3 until 15 hr after MTX administration the mitotic index decreased significantly as a result of inhibition of DNA synthesis. The blocking of the G1-S transition was evident during 4 hr after MTX. Thereafter the G1-S transition proceeds at a rate which is practically equal to that for nontreated controls. MTX did not inhibit transition to mitosis of cells being in G2-phase and in a very late S-phase at the time of drug injection. The sensitivity of G1-cells to the cytocidal effect of MTX shows that for L1210 leukemia cells MTX can be classified as a cycle-specific drug killing both G1-and S-cells rather than S-phase specific agent with self-limitation.
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PMID:Effect of methotrexate on the cell cycle of L1210 leukemia. 94 29

Spleen cells from normal (C57BL/6 X DBA/2)F1 mice were sensitized in vitro for 5 days with irradiated C57BL/6 or DBA/2 parental stimulating cells. Effector cells were generated which specifically lysed 51Cr-labeled targets (leukemia or mitogen-stimulated lymphoid cells) H-2-matched with the parental genotype used for sensitization. The response of F1 spleen cells to the C57BL/6 parent was stronger and more reproducible than that to the DBA/2 parent. The kinetics of generation of effector cells were similar for the F1 anti-parent and an F1 anti-allogeneic response. However, the magnitude of the F1 anti-C57BL/6 cytotoxic response was considerably lower than the F1 response to allogeneic cells. The ratio of responder to stimulator cells in the cultures was more critical for the former than for the latter response. Several lots of fetal bovine serum were found to be adequate for supplementing the medium in the induction of J1 hybrid anti-parent and anti-allogeneic cytotoxic effector cells. Based on these and other studies, it would appear that the F1 hybrid anti-parent cytotoxic response provides an in vitro model of murine hemopoietic graft rejection in vivo. This response may be elicited by a mechanism distinct from T cell-mediated cytotoxicity and involve different subpopulations of spleen cells.
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PMID:In vitro induction of F1 hybrid anti-parent cell-mediated cytotoxicity. 95 51

The killing of the LR subline of the DBA/2J leukemia L1210/MTX by passive antibody was followed in vivo with 131I-iododeoxyuridine-labeled cells and whole-body measurement of retained radioactivity. The in vivo killing of LR cells was proportional to the in vitro 2-mercaptoethanol resistant titer, independent of the complement system, and radioresistant. Although a large percentage of the leukemic cells was killed in passively immunized mice, the protective effect of the passive antiserum was dependent on the active immune response of the host.
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PMID:Antibody-induced killing in vivo of L1210/MTX-R cells quantitated in passively immunized mice with 131I-iododeoxyuridine-labeled cells and whole-body measurement of retained radioactivity. 95 54

DBA/1 and DBA/2 mice infected with the Rauscher leukemia virus developed a biphasic erythroleukemia. Transitory regression of the disease was closely associated with the appearance of tumor-specific antibodies and the exacerbation was preceded by the gradual decrease of antibody titer. The antibody-dependent cellular cytotoxicity could be detected earlier, than the complement-dependent cytotoxicity. Moreover, in each case the titer of antibody-dependent cellular cytotoxicity was higher than that of complement-dependent cytotoxicity. The results suggest that the antibody-dependent cellular cytotoxicity is mainly responsible for the rejection of tumor cells.
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PMID:Immune response to rauscher virus-induced leukemia in DBA mice. I. Role of cellular and humoral immunity in spontaneous regression. 98 Jan 78

The antitumor activity of 46 cis-amineplatinum congeners was evaluated against L1210 leukemia in (C57BL/L X DBA/2)F1 mice. Several compounds in this series significantly prolonged the life-spans of mice with the leukemia. During the selection of the compound that yielded optimal activity [dichloro(1,2-diaminocyclohexane)platinum], the chlorides were substituted with various organic and inorganic anions. The aqueous solubility was greatly increased with retention of significant antileukemic activity. Most of the active compounds were synergistic with cyclophosphamide, and cure rates up to 80% were obtained with certain combinations.
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PMID:Antileukemic properties of organoplatinum complexes. 100 31

The possibility that C'3 participates in tumor rejection was investigated in DBA/2 mice previously immunized against L1210 leukemia and in Swiss mice previously immunized against Ehrlich's adenocarcinoma. In both the cases, animals treated with an appropriate dose of cobra venom factor to produce a C'3 depletion for some days after the tumor challenge, developed the neoplasia and had a mortality rate analogous to that of non-immunized animals. Studies on the peritoneal washing cells obtained at different times after the challenge revealed that in C'3 depleted immunized mice IgM are present on lymphocytes, macrophages and tumor cells, as in the immunized controls, but no contract between the cells and no macrophage phagocytosis were observed and the number of tumor cells increased progressively. These findings indicate that C'3 is critically involved in the rejection of the experimental tumors considered.
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PMID:C'3 participation in the rejection of some experimental tumors. 102 54

N-Trifluoroacetyladriamycin-14-valerate (AD 32), an analog of adriamycin, exhibits significantly greater antitumor activity than does adriamycin or daunorubicin in two experimental mouse tumor systems under similar assay conditions (C57BL X DBA/2 F1 male mice, agents administered i.p. each day for Days 1 to 4). Against the P388 leukemia at optimal dosages, AD 32 gave a +429% increase in median life-span with 3 of 5 60-day survivors compared to +132% for adriamycin (no 30-day survivors). In the L1210 leukemia system, AD 32 at several dosages consistently and reproducibly effected an increase in lifespan in excess of 445%, with a high percentage of 60+-day survivors compared to adriamycin (+42 to +54% ILS; no 30-day survivors). The reduced toxicity of AD 32 was evidenced by its optimal dose range, which is significantly greater than the lethal dose for 100% of mice of adriamycin, and by its lack of delayed toxicity. In vitro, AD 32 was somewhat less effective than was adriamycin in inhibiting the growth of CCRF-CEM cells; enzymatic conversion of AD 32 by cell-free culture medium was not observed. The unique growth-inhibitory properties of this analog indicate that the therapeutic effectiveness of the anthracycline antitumor antibiotics can be retained or enhanced by substitution on the glycosidic amino group.
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PMID:N-trifluoroacetyladriamycin-14-valerate, an analog with greater experimental antitumor activity and less toxicity than adriamycin. 105 22

The immunogenicity of leukemia L1210 in DBA/2 Ha and 6C3HED lymphosarcoma tumor cells in C3H/f mice was significantly increased after treatment with V. cholerae neuraminidase. DBA/2 Ha and C3H/f mice repeatedly immunized with neuraminidase-treated tumor cells rejected subsequent challenge of 10(7) or 10(6) untreated tumor cells, respectively. Based on the 51Cr microcytotoxicity assay, both strains of mice showed strong complement-dependent antibody titers and cell-mediated immunity. Sera and splenic lymphocytes from immunized C3H/f mice neutralized the tumorigenicity of 6C3HED lymphosarcoma and protected the recipient C3H/f mice against the disease. Immune lymphocytes pretreated with anti-theta sera lost their ability to neutralize the tumorigenicity of lymphosarcoma, and they failed to be stimulated by T-cell mitogens. We studied the effectiveness of chemoimmunotherapy in DBA/2 Ha mice with leukemia L1210. A single near optimal dose of BCNU 2 days after implantation of 10(6) tumor cells increased the survival time. A single immunization with 2 X 10(7) neuraminidase-treated L1210 tumor cells 4 days after cytoreductive therapy increased survival and resulted in cures for 50% of animals. Immunization of mice with neuraminidase-treated tumor cells and MER produced indefinite survival in a larger percentage of mice than did either treatment alone. AKR mice with spontaneous leukemia treated with combination chemotherapy sustained an 180% increase in life-span. Combination chemotherapy plus immunization with neuraminidase-treated syngeneic or allogeneic (Gross virus-induced) E2G leukemia cells were highly effective in prolonging the life-span of the immunized leukemic AKR mice. The experimental data led to clinical trials in acute myelocytic leukemia with neuraminidase-treated a-logeneic myeloblasts. Patients with acute myelocytic leukemia were randomized into two groups after remission induction. The median remission duration of patients on sustaining chemotherapy alone was 19 weeks (8 patients), whereas six of nine patients who received neuraminidase-treated allogeneic myeloblasts remain in remission 79-132 weeks. Statistical analysis of the remission duration and survival of patients who received chemoimmunotherapy versus the control group shows highly significant differences.
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PMID:Therapeutic effectiveness of neuraminidase-treated tumor cells as an immunogen in man and experimental animals with leukemia. 106 51

Friend virus induces a leukemia characterized by the proliferation of neoplastic hematopoietic cells believed to be erythroid precursors. In vitro studies were conducted with spleen cells from mice with terminal Firend leukemia in order to determine their capacity for leukocytic differentiation. Spleen cells were obtained from leukemic DBA/2 mice 1 to 2 days before anticipated death and cultured in the presence or absence of colony-stimulating activity (CSA). Growth in liquid culture in dissusion chambers was dependent on CSA and resulted in the generation of normally differentiated granulocytes and macrophages. Colony formation in agar was also dependent on CSA, and the cloning efficiency of leukemic spleen cells was found to be approximately 10 times normal. The colonies formed were composed of leukocytes, which appeared morphologically normal. Total in vitro colony-forming units per leukemic spleen exceeded normal by more than 300-fold, but cells elaborating CSA were decreased. Although it is uncertain whether the stem cells stimulated by CSA are "normal" or leukemic," it is clear that Friend leukemia has profound effects on the proliferation and differentiation of nonerythroid stem cells.
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PMID:Granulocytic stem cells in Friend leukemia. 108 68

Rauscher virus causes in inbred Balb/c mice a rapidly progressing hyperacute, in C57B1/10Sn mice an incipient, spontaneously healing leukaemia. In DBA/1 and DBA/2 mice the appearance of leukaemia is followed by a partial remissions then by an exacerbation of the disease. The infection in C57B1/10Sn, DBA/1 and DBA/2 mice results in a significant tumour-specific immune response. Inhibition of the immune response is followed by an increased progression of leukaemia in DBA/1 and DBA/2 mice only. It is assumed that in C57B1/10Sn mice the remission of incipient leukaemia is associated with a resistance determined in the target cells, whereas in DBA/1 and DBA/2 mice the remission is due to a tumour-specific immune response. As in animals treated with anti-lymphocyte and anti-thymocyte serum the course of the disease runs proportionally to the degree of the inhibition of the immune response, the tumour-specific antibodies play a decisive role in the elimination of the tumour cells. In Balb/c, DBA/1 and DBA/2 mouse strains failing to exhibit a spontaneous reversion of the tumour cells, the appearance of a significant tumour-specific immune response depends on the resistance against the helper component of the Rauscher virus complex.
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PMID:The effect of anti-lymphocyte and anti-thymocyte serum on the pathogenesis of Rauscher leukaemia in inbred mouse strains. 108 32


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