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)

Temozolomide (8-carbamoyl-3-methylimidazo[5,1d]-1,2,3,5-tetrazin-4-(3H)-one), an experimental antitumor agent which spontaneously decomposes to 5-(3,3-methyl-1-triazeno) imidazole-4-carboxamide, the active metabolite of the antineoplastic drug DTIC, causes erythroid differentiation of K562 leukemia cells. The increase in epsilon and gamma globin gene expression after temozolomide treatment does not appear to be due to drug-induced hypomethylation of the genes. In other genes containing many methylated sequences such as the proto-oncogenes c-myc and C-Ha-ras, temozolomide caused no detectable change in methylation. In contrast, in the same genes 5-aza-2'-deoxycytidine induced hypomethylation. Temozolomide caused DNA alkali-labile sites and an arrest of the cell cycle in G2 phase. Ethazolastone (its 3-ethylimidazo analogue) which does not cause differentiation of K562 produced no significant DNA damage and G2 phase blockade. DNA damage rather than hypomethylation may be responsible for induction of differentiation.
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PMID:Temozolomide induced differentiation of K562 leukemia cells is not mediated by gene hypomethylation. 266 Jul 97

Fibrinopeptide A (FPA) was systematically investigated in 74 patients with acute leukaemia at different stages of the disease (50 with non-lymphocytic leukaemia, ANLL; 24 with lymphocytic leukaemia, ALL). At diagnosis, 75% of the cases had high FPA levels (86% in ANLL and 54% in ALL) with significantly higher levels in ANLL than in ALL (13.4 vs 4.4 ng/ml; p less than 0.001). Patients with DIC (20 cases in ANLL and 1 case in ALL) had significantly higher levels (p less than 0.001). FPA levels were neither correlated with fibrinogen or FDP levels nor with blast cell count. During chemotherapy, median FPA did not show significant changes whereas, at the end of therapy, a return toward normality was generally observed both in ALL and ANLL apart from the group of patients with acute promyelocytic leukaemia. Among the 24 patients who entered post-remission follow-up (13 ANLL and 11 ALL), 10 cases out of the 11 relapsing (6/6 with ANLL and 4/5 with ALL) had increased FPA 1 to 2 months before the ascertainment of the relapse. However, 16% and 9% of the samples obtained on different occasions, respectively from ANLL and ALL cases in maintained first remission, showed FPA above the normal limit. This study demonstrates that subclinical activation of blood coagulation, as indicated by high FPA level, is common both in lymphocytic and non-lymphocytic leukemia and suggests that this phenomenon is related to disease activity.
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PMID:Clinical significance of fibrinopeptide A in acute lymphocytic and non-lymphocytic leukaemia. 276 77

The possible interference with 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC)-mediated chemical xenogenization (CX) by antiemetic drugs was studied. DTIC was given alone or in combination with either dexamethasone or metoclopramide plus orphenadrine hydrochloride plus diazepam to CD2F1 mice bearing the histocompatible L1210 leukemia. Tumor cells were collected from treated animals and inoculated into histocompatible untreated and drug-treated recipients, for eight transplant generations. More than 50% of intact hosts rejected tumor cells between the fourth and sixth transplant generation, independently of antiemetic treatments. Positive controls treated with DTIC plus quinacrine (QC) confirmed that this antimutagenic compound entirely abrogates CX. The present results point out that the antiemetic regimens investigated in this study do not prevent CX. Since DTIC treatment requires intensive antiemetic support in man, these data are of clinical relevance for CX-oriented immunochemotherapy protocols.
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PMID:Two antiemetic regimens do not impair chemical xenogenization induced in vivo by 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide. 279 Nov 88

A 24 year-old female was admitted because of hypermenorrhea and petechiae. The peripheral blood tests on admission were consistent with acute promyelocytic leukemia complicated with DIC. BHAC-DMP therapy was started along with platelet transfusions and heparin administration. On the day 9 of admission, on the contrary to the improvement of hematological data, the patient suffered from severe headache and nausea. The neurological examination revealed anisocoria. Right side chronic subdural hematoma was a diagnosis made by emergency CT scan and was treated with drainage of the hematoma. Post-operatively, the patient did well, and achieved complete remission on the day 43 of admission. Since intracranial hemorrhages due to DIC complicated with leukemia are often fatal, those patients are usually treated conservatively. However, as shown in this case report, some cases might have an indication for the neurosurgical operation. It is important to check conditions carefully whether the patient has an indication for the operation.
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PMID:[Successful treatment by a drainage of subdural hematoma in a case of intracranial hemorrhage due to DIC complicated with acute promyelocytic leukemia]. 279 98

In vivo treatment of mouse leukemia L1210 with DTIC can induce new antigens on tumor cells that are not detectable on parental cells and that are transmissible as a genetic character. Moreover, L1210/DTIC is rejected by syngeneic hosts. The aim of this study was to investigate whether DTIC selects pre-existing immunogenic clones rather than inducing ex novo new antigenic determinants and to verify the number of induced antigens. L1210 leukemia was cloned in vitro and 4 clones were treated in vivo with DTIC. All the treated clones displayed antigenic properties since they were rejected by syngeneic hosts. Cytotoxic T lymphocytes (CTL) activated against one DTIC clone could recognize and lyse the relevant target. One of these DTIC-modified clones (L4/DTIC) was recloned and the subclones were tested in vivo and in vitro. Two out of six subclones were rejected by syngeneic hosts. CTL specific against these two clones were able to recognize and lyse all the other clones to different degrees. The degree of susceptibility to lysis did not correlate with the capability to evoke an immune response in vivo. Based on these findings we conclude that DTIC does not select pre-existing clones but modifies the tumor cells antigenically, and that the antigenicity induced by DTIC in a cloned tumor line is due to the presence of common antigens shared to different degrees with treated cells.
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PMID:Induction of new antigenic properties on DTIC-treated L1210 clones. 326 23

New antigenic specificities, not detectable on parental cells, have been induced by many investigators in mouse lymphomas by treatment with the antitumor agent 5(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC). The antigens are transmissible, after withdrawal of the drug treatment, as an inheritable character. The mechanism of induction, the molecular nature, and the number of the new antigenic specificities have not been completely elucidated. Four clones from murine leukemia L1210 isolated and expanded in vitro were treated in vivo with DTIC and the new sublines were studied in detail. The four drug-treated sublines studied exhibited strong immunogenicity since they were rejected by syngeneic animals. Immunosuppressed animals challenged with 10(7) A/DTIC or P/DTIC cells were reciprocally protected by the adoptive transfer of spleen cells from donors that had rejected a lethal challenge of A/DTIC or P/DTIC clone. In a similar fashion, the adoptive transfer of spleen cells obtained from animals that had rejected the Q/DTIC or the R/DTIC clones protected immunosuppressed mice challenged with Q/DTIC or R/DTIC cells. No antitumor activity was observed in cross-protective schedules other than those indicated. It was been concluded that (a) the L1210 leukemia line does not have antigenic cells, (b) four DTIC-treated clone sublines were rejected by compatible hosts, and (c) two mutually exclusive sets of antigens were expressed in four antigenic clone sublines.
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PMID:Adoptive immunity in mice challenged with L1210/DTIC clones. 354 66

Decarbazine (DTIC) is reported to exhibit enhanced clinical toxicity and increased antitumor activity in vitro when exposed to light. Since it was unclear whether light exposure enhanced DTIC antitumor activity or local toxic effects in vivo, a series of experiments was performed in mice given DTIC solutions exposed to light for 2 hours at room temperature. Adenocarcinoma 07/A was implanted by trocar in adult female BALB/c mice. DTIC (50 and 100 mg/kg) was given ip three times per week for 2 weeks. Both drug doses significantly inhibited tumor growth. However, there was no significant difference between light-exposed and -protected drug treatments. In vitro clonogenic assays in L1210 leukemia and Chinese hamster ovary (CHO) cells demonstrated that DTIC cytotoxicity was not increased with light exposure (0.8 J/m2/sec). Both cell lines showed a dose-response relationship to DTIC after 1- or 6-hour exposures in the presence or absence of light. Normal dehaired BALB/c mice were given single intradermal injections of 0.5, 1.75, 5.0, or 10 mg of DTIC in 0.05 ml of saline. Dose-dependent skin ulceration was produced at the 1.75-, 5.0-, and 10.0-mg dose levels. Again, there was no consistent statistical difference in skin ulceration between treatments using light-exposed and -protected DTIC vials. However, when mice were exposed to light following intradermal DTIC, increased skin toxicity was produced (P less than 0.05 by Student-Neuman-Keuls multiple range test). A number of potential local antidotes to DTIC skin ulceration were found to be ineffective. These included: L-cysteine, dimethyl sulfoxide, hyaluronidase, hydrocortisone, and 0.9% saline. Sodium thiosulfate (0.3 M) significantly reduced DTIC skin ulcers as did pre-exposure of DTIC to S-9 rat liver enzymes and NADPH. Neither mild skin heating nor cooling reduced DTIC ulcerations. DTIC appears to synergize with light in vivo to produce increased toxicity. Patients receiving DTIC should avoid intense light exposure after drug injection. However, elaborate precautions to prevent light exposure of DTIC solutions during preparation or injection appear to be unnecessary.
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PMID:Experimental dacarbazine antitumor activity and skin toxicity in relation to light exposure and pharmacologic antidotes. 381 94

Factors of coagulation and fibrinolysis have been evaluated in 15 patients with untreated acute nonlymphoblastic leukaemia (ANLL). 10 patients had major bleeding (MB) and 6 had laboratory signs of DIC. 5 patients went into complete remission (CR). Antithrombin III (AT III) was decreased in 7 patients, antiplasmin (AP) in 9, fibronectin (FN) in 6 and factor XIII in 4/12. The ratio between factor VIIIR:Ag and factor VIII:C was over 2.0 in 11 patients, and high values were especially seen in patients with MB and patients with DIC. Spontaneous proteolytic activity, measured with S-2288 was increased in 3 patients who all had MB, and none of whom achieved CR. 2 patients with promyelocytic leukaemia (M3) had low fibrinogen and AP, high FDP and normal AT III, speaking for primary fibrinolysis, which in addition to proteolytic enzymes in the blast cells are important contributing factors regarding MB in ANLL.
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PMID:Factors and inhibitors of blood coagulation and fibrinolysis in acute nonlymphoblastic leukaemia. 385 83

The procoagulant cellular activity (PCA) of intact and lysed leukaemic cells was evaluated at diagnosis in 23 patients with acute non-lymphoid leukaemia (ANLL). The leukaemic cells of all 13 patients having DIC feature (excess of fibrin monomers, serum FDP and plasma fibrino-peptide A) showed a significant (P less than 0.0001) increase of PCA, while a pattern similar to that of normal granulocytes and lymphomonocytes was observed in the remaining 10 patients without evidence of DIC. When the patients were subdivided according to the FAB cytological classification, features of DIC and increased PCA were demonstrated in 3/3 M3 patients, 5/6 M5 patients and only in 5/14 remaining patients. These findings indicate that in ANLL patients: (1) the increased PCA of leukaemic cells is closely related to the occurrence of DIC; (2) the increased PCA seems related to the differentiation line and maturation level of the leukaemic cells.
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PMID:Procoagulant cellular activity and disseminated intravascular coagulation in acute non-lymphoid leukaemia. 397 70

A panel of murine monoclonal antibodies (MAbs) was produced by fusing NS-0 myeloma cells with spleen cells of a BALB/c X DBA/2 F1 mouse hyperimmunized against a highly immunogenic subline of the L1210 leukemia obtained by in vivo treatment of the L1210 parental line with the antitumor drug 5-(3,3'-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC). Among the 52 MAbs produced 16 (anti-D) were specifically cytotoxic in a complement-dependent cytotoxicity assay for the drug-altered subline and the others (anti-L) also cross-reacted with the L1210 parental leukemia. Six anti-D and three anti-L MAbs were selected for detailed studies of tissue specificity. In quantitative absorption experiments the antigens defined by these antibodies could not be detected on cells from normal mouse tissues (lung, liver, kidney, heart, spleen, and thymus). The reactivities of both anti-D and anti-L MAbs against a panel of L1210/DTIC sublines obtained at different times were assayed. The results showed that the antigenic specificities defined by anti-L MAbs were expressed on almost every L1210/DTIC subline while the anti-D MAbs detected antigenic structures specific for the L1210/DTIC used for the immunization. None of the MAbs tested cross-reacted with the L5178Y lymphoma or with its DTIC-altered sublines. The failure of anti-D MAbs to cross-react with cells from other L1210/DTIC sublines supports the hypothesis that the immunological alterations induced by the DTIC treatment are the consequence of mutagenic activity of the drug. On the other hand the presence of anti-L antigens on the cells of every L1210 subline indicates that the DTIC alteration is not accompanied by a loss of the tumor-associated antigen from the L1210 leukemia.
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PMID:Monoclonal antibodies to the L1210 murine leukemia cell line and to a drug-altered subline. 405 6


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