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)

Because the antigenic changes occurring after in vivo treatment of murine lymphoma cells with 5-(3,3-dimethyl-1-triazenyl)-1H-imidazole-4-carboxamide (DTIC) were suggested to result from DTIC-induced somatic mutation(s), quinacrine dihydrochloride, an antimutagenic compound, was tested for possible antagonistic activity related to this phenomenon. The increased immunogenicity of L1210Ha leukemia occurring at the first transplant generation of DTIC-treated histocompatible (BALB/cCr x DBA/2Cr)F1 male mice or the appearance of strong lymphoma-associated transplantation antigens at transplant generation 6 was prevented by simultaneous administration of quinacrine. However, the compound did not modify the antitumor or immunodepressive activity of DTIC in the mouse. We concluded that the selective antagonistic effect of quinacrine on DTIC-mediated immunogenic changes (DMIC) supported the hypothesis that the molecular mechanism of DMIC could be related to somatic mutation(s).
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PMID:Drug-mediated antigenic changes in murine leukemia cells: antagonistic effects of quinacrine, an antimutagenic compound. 692 22

Sequential treatment of mice with 5-(3,3'-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) and Cyclophosphamide (Cy) produced long-term inhibition of endogenous cells proliferation in the spleen and impairment of classical allograft response, similar to that obtainable with lethal total body irradiation. The growth of BALB/c bone marrow or of virus-induced LSTRA leukemia of BALB/c origin, was studied comparatively in drug-treated or irradiated histocompatible (BALB/c x DBA/2)F1 or allogeneic C3H/HeN hosts. No splenic resistance of Hh type against bone-marrow cells was detected in C3H recipients, either irradiated or drug-treated, confirming previous studies on the Hh susceptibility of C3H strain. In contrast, strong transplantation resistance was detected in the spleen, liver and lung of the same hosts, irradiated or drug-treated, and challenged with LSTRA cells. It follows that Hh-susceptible mice are competent for mounting a localized radioresistant and drug-resistant response, directed against a virus-induced lymphoma.
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PMID:Differential graft resistance of C3H mice pretreated with antitumor drugs against BALB/c bone marrow or lymphoma cells. 700 59

Tumor cells, treated in vivo with anticancer compounds, may acquire new antigenic specificities in addition to any original antigens associated with parental tumors. Treatment of mice carrying the parental leukemias L1210 Ha or L1210 Cr with leukemia cells antigenically altered by treatment with 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (L1210 Ha/DTIC and L1210 Cr/DTIC, respectively) was essentially ineffective in prolonging the life span of the animals. However, synergic therapeutic activity was exhibited by administration of L1210 Ha/DTIC cells plus 1,3-bis(2-chloroethyl)-1-nitrosourea in the treatment of the moderately immunogenic L1210 Ha leukemia and by the combination of L1210 Cr/DTIC cells and lymphocytes immune to L1210 Cr/DTIC administered with 1,3-lymphocytes immune to L1210 Cr/DTIC administered with 1,3-bis(2-chloroethyl)-1-nitrosourea in the treatment of the low immunogenic L1210 Cr leukemia. Early and advanced L1210 Cr-bearing mice showed marked increases in survival time and a significant number of tumor-free survivors on treatment with cyclophosphamide followed by transfer of lymphocytes immune to L1210 Cr/DTIC cells. When parental tumor cells were used as the immunogen, the therapeutic effect was diminished. Thus, in the current investigation, although immunotherapy per se was essentially ineffective, the immunochemotherapeutic modalities used were successful in markedly increasing the survival time of leukemic animals and resulted in an incidence of cures.
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PMID:Chemotherapy and immunotherapy of L1210 leukemic mice with antigenic tumor sublines. 701 35

Strong and heritable increase of immunogenicity of L1210 Ha leukemia has been obtained in vitro following multiple treatments with 5-(3,3'-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC), metabolically activated by mouse liver preparations (MLP) containing liver microsomes. The DTIC-treated leukemia (L1210D line) or the control line treated with MLP alone (L1210N line) showed comparable growth kinetics in vitro. However, progressive increase of immunogenicity occurred in leukemic cells in the course of in vitro treatments with DTIC plus MIP, but not with MLP alone, as evidenced by comparative studies on transplantation immunity elicited in BALB/c x DBA/2 F1 mice by graded inocula of L1210D or L1210N leukemia cells. In vitro experiments confirmed that metabolic transformation of DTIC is required for increasing tumor immunogenicity. In fact, L1210Ha cells became highly immunogenic when treated with DTIC in intact mice but not in animals metabolically depressed by CCl4. Immunochemotherapy experiments based on the antigenic cross-reactivity between the L1210D line and the original L1210Ha leukemia showed that i.p. administration of L1210D cells followed by 1,3-bis(2-chloroethyl)-1-nitrosourea treatment afforded marked protection in mice inoculated intracerebrally with the parental lymphoma. The present findings could provide an adequate in vitro technique for developing further studies on DTIC-mediated immunogenic changes of tumors, including human cancer cells growing in tissue culture.
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PMID:In vitro generation of a highly immunogenic subline of L1210 leukemia following exposure to 5-(3,3'-dimethyl-1-triazeno)imidazole-4-carboxamide. 701 15

A mouse of monoclonal cell line (L1) was produced by fusing the mouse myeloma P3X63/Ag8 with CD2F1 spleen cells immunized with a highly immunogenic subline of L1210 leukaemia (L1210/DTIC). A very few positive clones (1%) were isolated and one of these was chosen for detailed study. The monoclonal antibody L1 is an IgM immunoglobulin strongly reacting in a complement-dependent cytotoxicity assay against L1210/Cr leukaemia and its more or less immunogenic sublines. The specificity of the L1 antibody against L1210 leukaemia was studied by extensive screening with normal adult and foetal tissues, lymphoid tissues from several independent strains and a panel of the most common experimental tumours, to all of which it was unreactive. Attempts at immunotherapy were carried out in DBA/2 mice challenged with L1210 leukaemia and treated with L1 (ascites) and complement. Although the in vitro cytotoxic titre of ascites fluid from mice bearing hybridoma was very high (10(-7)), no therapeutic effect was obtained in vivo.
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PMID:Characterization of a monoclonal antibody to L1210 leukaemia. 707 34

Seven patients presenting with DIC in association with acute promyelocytic and myelomonocytic leukaemia were treated with intensive chemotherapy (IC), intensive platelet support (IPS) and continuous heparinization (CH), or IC + CH but minimal platelet support (MPS), or no chemotherapy, no heparin or MPS. All four patients who received IC + IPS + CH achieved remission (survival time: 516, 400+, 371 and 368 days). The remaining three patients died early (survival time: 11, 7 and 3 days). The results suggest that a combination of IC + IPS + CH is essential in the management of leukaemia-related DIC.
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PMID:Management of leukaemia-associated disseminated intravascular coagulation (DIC). 718 47

Previous studies showed that treatment of mice with 5(3,3'-dimethyl-1-triazeno)-amidazole-4-carboxamide (DTIC) plus cyclophosphamide (Cy) produce profound depression of classical allograft responses and impairment of endogenous cell proliferation similar to that detectable in lethally-irradiated mice. However efficient localized graft resistance was found in the spleen of drug-treated hybrid or allogeneic mice challenged with lymphoma cells. The present report describes the genetic patterns of this type of natural resistance [hereafter called drug-resistant inhibition of tumors (DRIT) in various tumor-host combinations DRIT was evaluated measuring the extent of 125I-5-iodo-2'-deoxyuridine (125IUdR) uptake in the spleen and liver of leukemic hosts. The results of the experiments performed with two H-2d (i.e. L1210 and LSTRA), one H-2b (i.e. L5MF-22) and one H-2a (i.e. LAF-17) lymphomas inoculated into drug-treated recipients pointed out that: (a) tumor cell proliferation was markedly inhibited in the spleen and weakly or not impaired in the liver of D end Hh-1-incompatible euthymic or nude mice responder for the hh system; (b) no resistance was found in the spleen and liver of Hh-1-compatible B10.A (2R) mice against L5MF-22 lymphoma or of SJL recipients genetically non-responder for the Hh system, against LSTRA cells; (c) splenic resistance against L1210 leukemia was detectable in Hh-compatible B10.A or B10.A (5R) mice; (d) splenic and liver resistance was found in Hh-incompatible but genetically Hh non-responder SJL or C3H mice against L5MF-22 or LSTRA lymphomas, respectively. These results showed that the genetic patterns of the DRIT system parallels the Hh-type immunity in certain tumor-host combinations [(a) and (b)] but not in others [(a) and (d)], as previously detected in lethally-irradiated mice. It is concluded that genetically-controlled lymphoma graft resistance can be retained by mice treated with high doses of antitumor drugs, capable of abrogating classical T-dependent transplantation immunity.
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PMID:Transplantation resistance of drug-treated allogeneic mice against murine lymphomas--II. Studies with various tumor-host combinations. 733 20

In vivo treatment of leukemic mice with the antitumor agent 5-(3,3'-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) results in early increase of tumor-associated immunogenicity which is expected to evoke host-versus-graft responses. However, transplantation immunity is severely impaired in DTIC-treated mice due to the immunodepressant activity of the drug. It follows that the DTIC-mediated increase of tumor immunogenicity effect cannot be of therapeutic value in ordinary conditions. In the present report, we describe the results of studies aimed at restoring immunocompetence of DTIC-treated mice by means of adoptive transfer of syngeneic lymphoid cells. Infusion of spleen cells into DTIC-treated mice failed to restore graft responsiveness even in allogeneic tumor-host combinations. However, when DTIC treatment was followed by administration of cytotoxic alkylating agents such as cyclophosphamide (CY) or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), graft responsiveness was partially restored upon adoptive transfer of syngeneic splenocytes. (BALB/c X DBA/2) F1 (hereafter called CD2F1) mice bearing leukemia L1210 Ha were treated as follows: (a) DTIC for increasing the immunogenicity of the leukemic cells; (b) CY or BCNU; and (c) adoptive transfer of CD2F1 lymphocytes. The results showed that: (a) DTIC alone or DTIC plus spleen cells produced little or no increase in survival times with respect to untreated controls; (b) DTIC plus CY or BCNU increased survival times to a larger extent; and (c) the adoptive transfer of lymphocytes produced marked protection of leukemic mice when the hosts had been pretreated with DTIC plus CY or BCNU but not with CY or BCNU without DTIC. These data may provide a model for exploiting DTIC-induced increase of tumor immunogenicity for immunochemotherapeutic regimens.
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PMID:Drug-mediated increase of tumor immunogenicity in vivo for a new approach to experimental cancer immunotherapy. 744 13

Eleven patients with chronic subdural hematoma (CSDH) with bleeding tendency (BT) were surgically treated in the last 12 years. To study the clinical problem of CSDH with BT, 11 surgical cases were divided into 3 groups, Group A; CSDH with primary BT (1 case of hemophilia A), Group B; CSDH with BT secondary to a basic disease (3 cases of leukemia, 2 cases of malignant tumor with DIC, 1 case of chronic renal failure and 1 case of liver cirrhosis), Group C; CSDH with BT by anticoagulants (warfarin) (2 cases of replacement of mitral valve, 1 case of A-C bypass). Evacuation of the hematoma was performed by means of one or two burr holes with irrigation of the hematoma cavity and a drainage tube was placed in the subdural space. The outcome was excellent in Groups A and C. In Group B, two patients with DIC due to gastric cancer and prostatic cancer died, and 3 patients with leukemia recovered dramatically from CSDH, but the poor course of the disease itself resulted in death. The outcome of other patients in Group B was excellent. Since CSDH with BT is often fatal, those patient had usually been treated conservatively. However, from this analysis, we stress that CSDH with BT should be surgically treated after checking the blood conditions carefully to determine whether or not the patient has need for surgery.
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PMID:[Chronic subdural hematoma with bleeding tendency; clinical analysis of 11 surgical cases]. 784 20

Pathologies of serial sections of 9 temporal bones from 6 patients without caloric response were studied. The patients died of epipharyngeal cancer, middle ear cancer, chronic renal failure with DIC, pancreatic cancer with DIC, multiple brain metastasis of pancreatic cancer, and leukemia. Under light microscopy, 8 ears showed pathologies in the vestibular end organs and the nerves. Possible causes of the lack of caloric responses in the 8 ears were endolymphatic hemorrhage, labyrinthitis, leukemic infiltration in the labyrinth, degeneration or disappearance of the vestibular sensory cells, reduction in the number of vestibular nerve fibers, and/or brainstem lesions. The remaining one ear did not show abnormal findings in the vestibular end organs or the nerves, but the patient had brainstem lesions. Four types of temporal bone pathologies were observed according to the lesion site responsible for the lack of caloric response; i) sensory type, ii) neural type, iii) mixed type and iv) central type.
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PMID:Temporal bone pathology in patients without caloric response. 787 14


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