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

Suppressor cells capable of enhancing tumor growth in vivo and of abrogating a potential anti-tumor immunity in vitro are generated in C57BL/6 mice inoculated with the high-leukemogenic A-RadLV. Mice inoculated with low-leukemogenic D-RadLV do not develop suppressor cells but contain anti-tumor reactive lymphocytes that can inhibit in vivo tumor growth. Cyclophosphamide (CyF) treatment of mice inoculated with A-RadLV hampered suppressor cell function and rendered the animals' lymphocytes responsive to A-RadLV induced tumor cells in vitro. Administration of CyF also reduced leukemia incidence in mice inoculated with A-RadLV, but had no effect on leukemia induction by D-RadLV in irradiated mice. It is suggested that the high leukemogenic activity of A-RadLV depends on the virus' ability to recruit CyF-sensitive suppressor cells early in latency and that tumor progression in mice inoculated with D-RadLV is arrested due to the host immune response.
 ...
PMID:Suppressor and reactive lymphocytes in radiation leukemia virus (RadLV)-induced leukemogenesis. 622 81

Cyclophosphamide is the most commonly prescribed alkylating agent in clinical medicine. The usefulness of cyclophosphamide is often limited, however, by its propensity to cause hemorrhagic cystitis especially in children or patients receiving concomitant radiotherapy. Administration i.p. of cyclophosphamide at doses of 100 mg/kg or more to mice produced a significant increase in urinary bladder weight within 48 hr of treatment. The present studies demonstrate that disulfiram prevented cyclophosphamide-induced bladder damage when administered p.o. within 1 hr of cyclophosphamide treatment. Diethyldithiocarbamate, a sulfhydryl-containing metabolite of disulfiram, had identical uroprotective activity. Unlike disulfiram, diethyldithiocarbamate was effective only when administered 2 to 4 hr after cyclophosphamide. Disulfiram augmented slightly the antitumor activity of cyclophosphamide against L1210 murine leukemia in vivo when administered 30 min prior to cyclophosphamide. In contrast, diethyldithiocarbamate had no effect on the antitumor activity of cyclophosphamide when administered 4 hr after cyclophosphamide.
 ...
PMID:Effect of disulfiram (tetraethylthiuram disulfide) amd diethyldithiocarbamate on the bladder toxicity and antitumor activity of cyclophosphamide in mice. 629 38

We studied the basis of rejection of retrovirus-infected tumor cells in guinea pigs by evaluating host response to injection of mixtures containing retrovirus-infected tumor cells and, antigenically and biologically distinct, uninfected tumor cells (line 10). After intradermal injection, line 10 grew progressively, metastasized to regional lymph nodes, and led to death of animals; line 107C3 4070A, a murine leukemia virus-infected fibrosarcoma cell line, grew for approximately 1 week and then regressed. Growth of the line 10 hepatoma was suppressed when the hepatoma cells were mixed with viable 107C3 4070A cells before injection into strain 2 guinea pigs. Viable virus-infected 107C3 cells were more effective than irradiated virus-infected cells in suppressing line 10 growth; mixture of line 10 with murine leukemia virus 4070A alone did not inhibit line 10 growth. Suppression of growth of line 10 cells by admixed murine leukemia virus 4070A-infected cells was less effective in animals with established viral immunity. Cyclophosphamide inhibited suppression of line 10 at sites of injection of virus-infected cells. Infection of line 10 with murine leukemia virus in vitro required cocultivation of line 10 cells with murine leukemia virus-infected fibrosarcoma cells; virus alone did not lead to acquisition of murine leukemia virus antigens by line 10 cells.
 ...
PMID:Rejection of retrovirus-infected tumor cells in guinea pigs: effect on bystander tumor cells. 631 16

Previous studies have demonstrated that the passive therapy of Friend murine leukemia virus (F-MuLV)-induced disease with chimpanzee anti-F-MuLV serum is accompanied by the development of host antiviral humoral and cellular immunity, the latter measurable in adoptive transfer protocols and by the ability of serum-protected mice to resist virus rechallenge. The present study was designed to further examine the contribution of various compartments of the host immune system to serum therapy itself, as well as to the acquired antiviral immunity that develops in serum-protected mice, through the use of naturally immunocompromised animals [e.g., nude athymic mice and natural killer (NK)-deficient beige mutant mice] or mice treated with immunoabrogating agents such as sublethal irradiation, cyclophosphamide [Cytoxan (Cy)], cortisone, and 89Sr. The studies in nude mice indicate that while mature T-cells are not needed for effective serum therapy, they do appear to be necessary for the long-term resistance of serum-protected mice to virus rechallenge and for the generation of the cell population(s) responsible for adoptive transfer of antiviral immunity. Furthermore, this acquired resistance is not due to virus neutralization by serum antibodies since antibody-negative, Cy-treated, serum-protected mice still reject the secondary virus infection. Lastly, while the immunocompromise systems examined did effect various host antiviral immune responses, none of them, including the NK-deficient beige mutation, significantly diminished the efficacy of the passive serum therapy of F-MuLV-induced disease.
 ...
PMID:Immunotherapy of murine leukemia. VIII. Efficacy of passive serum therapy of Friend leukemia virus-induced disease in immunocompromised mice. 633 92

The activity of the in vitro active cyclophosphamide metabolite ASTA Z 7557 against pluripotent hemopoietic stem cells (CFU-S), in vitro myeloid precursor cells (CFU-C) and clonogenic leukemic cells (LCFU-S) was evaluated in a rat model for human acute myelocytic leukemia (BNML). LCFU-S were most sensitive (D0 = 10.9 X 10(-6) M), followed by CFU-C (D0 = 16.4 X 10(-6) M), while CFU-S were least sensitive (D0 = 22.1 X 10(-6) M). Per cell population there were considerable variations in response when identical drug concentrations were tested in different experiments under the same standardized conditions. Furthermore, the concentration of leukemic cells in a normal marrow cell suspension appeared to correlate with the cytotoxic action of the drug against leukemia. A decreased cytotoxicity was already observed in mixtures containing 1 leukemic cell per 10 normal marrow cells. The implications of these findings in the BNML model for human autologous bone marrow transplantation are discussed.
 ...
PMID:Toxicity of ASTA Z 7557 (INN mafosfamide) to normal- and leukemic stem cells: implications for autologous bone marrow transplantation. 638 83

Cyclophosphamide (CY) was tested in combination with the thalictrum alkaloid named thaliblastine (TBL) for therapeutic activity against early Lewis lung carcinoma and early L1210 leukemia in mice. TBL alone had no activity whereas therapy with CY and TBL was significantly better than with CY alone. The therapeutic potentiation resulting from the combination of CY and TBL is apparently due to the different mechanisms of action and the pharmacological behavior of the two agents.
 ...
PMID:Enhancement of antitumor effect of cyclophosphamide by thaliblastine in Lewis lung carcinoma and L1210 leukemia in mice. 644 22

Virus-induced leukemia was inoculated into histocompatible or allogeneic hosts pretreated with 5-(3,3'-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) + Cyclophosphamide (Cy), which abrogate endogenous cell proliferation and T-dependent graft responses, but not selected "natural resistance" (NR) activities. Marked impairment of lymphoma cell growth occurred mainly in the spleen of allogeneic mice with respect to that of histocompatible controls. Tumor inhibition was still present when lymphoma challenge was performed on day + 3 after Cy administration. Parallel studies on "natural killer" (NK) activity in vitro or in vivo showed that complete abrogation of the NK function was detectable on day + 3 or + 6 after Cy treatment. It was concluded that in vivo inhibition of lymphoma growth in mice pretreated with DTIC + Cy could be a drug-resistant NR at least in part distinguishable from the NK function.
 ...
PMID:Natural resistance of mice pretreated with 5-(3,3'-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) + cyclophosphamide (Cy) against virus-induced lymphoma cells. 648 Jan 92

The effect of a single injection of Pasteur BCG on the growth of a myelocytic leukemia transplantable in the Brown Norway rat (BNML) was studied. BCG (3.0 mg i.v.) caused a 6-fold increase in spleen weight with marked granuloma formation. After aspecific immunostimulation the TD50 for leukemic cells increased from 38.8 to 302.2 cells. Cyclophosphamide (100 mg/kg) given 48 h prior to BCG did not influence the anti-tumor immune response. However, cyclophosphamide injected after BCG partly abolished its activity. After high-dose chemo-radiotherapy of leukemic rats BCG significantly hampered the outgrowth of residual leukemic cells. Relapse from leukemia could even be avoided completely when BCG was injected after cyclophosphamide (100 mg/kg) and total body irradiation (7.0 Gy) followed by isologous bone marrow transplantation. These results are discussed in relation with the tumor load at the time of maximal immunostimulation. Finally, the data are extrapolated to those of the many controversial clinical studies.
 ...
PMID:BCG treatment of residual disease in acute leukemia: studies in a rat model for human acute myelocytic leukemia (BNML). 657 94

Cyclophosphamide (CY) has been shown to modulate a number of immune responses. In the present study, we have examined the effect of CY on human natural killer (NK) cells in vitro. Lymphocytes from six normal volunteers were cultured alone or with CY in the medium containing human AB plasma, and their cytotoxicity was assessed against cells of K562. The results demonstrated that lymphocytes when cultured with CY had 154 to 333% increase in NK cell activity as compared to lymphocytes that were cultured in the absence of CY. Similarly, CY markedly boosted the cytotoxic activity of lymphocytes from two healthy donors against cells from cultured B-leukemia 3163. Maximal augmentation occurred in cultured lymphocytes that expressed low levels of effector NK activity. Lymphocytes from 13 of 15 children with acute leukemia in remission when cultured alone had no reactivity to autologous leukemia cells. In the presence of CY, lymphocytes from eight of 15 of these patients developed cytotoxicity against autologous leukemia cells. CY was effective in augmenting NK cell activity at concentrations ranging from 7.5 to 60 micrograms/ml. Maximal potentiation of NK cell activity was induced after 8 hr of treatment with CY, although the increase in NK activity was started within 2 hr of incubation with CY. CY-activated NK cells were found in glass wool- and nylon wool-nonadherent cells. Treatment of lymphocytes with CY did not increase the extracellular levels of interferon. The results of this study demonstrate that CY can activate NK cells in vitro. The possible mechanisms of CY-induced augmentation of NK cell activity are discussed.
 ...
PMID:Augmentation of human natural killer cell activity by cyclophosphamide in vitro. 658 41

ASTA-Z-7557, an in vitro active metabolite of cyclophosphamide, has recently been introduced to purge autologous bone marrow grafts of patients with AML. The rationale of this approach assumes a relatively higher sensitivity of leukemic cells to the drug as compared to that of normal marrow precursors. We have investigated in direct comparison the sensitivity to ASTA-Z-7557 of normal bone marrow progenitors (GM-CFC and BFU-E) and clonogenic leukemic cells (L-CFC). Normal bone marrow cells and purified leukemic blast cells were exposed to varying concentrations of the drug. Dose-response relationships did not indicate a selective cytotoxic susceptibility of L-CFC to ASTA-Z-7557. The recovery of bone marrow precursors following exposure to ASTA-Z-7557 depended on the cell concentration during exposure and was higher for 2 X 10(7) cells/ml than for 1 X 10(6)/ml. To mimic minimal residual leukemia cell mixtures of 95% irradiated normal bone marrow cells with 5% leukemic blast cells were exposed to ASTA-Z-7557. In this mixture killing of L-CFC was largely decreased. These data suggest that in vitro incubation of autologous bone marrow grafts of patients with minimal residual leukemia with ASTA-Z-7557 might not offer a therapeutic advantage.
 ...
PMID:No preferential sensitivity of clonogenic AML cells to ASTA-Z-7557. 659 Sep 37


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>