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)

Poly (2-azaadenylic acid) [(aza2A)n] and poly(2-azainosinic acid [(aza2I)n], two newly synthesized analogues of (A)n and (I)n, in which CH-2 of the purine ring is replaced by a nitrogen atom, have been evaluated in various biological assay systems. (Aza2A) n formed a complex with (U)n and (br5U)n, and (aza2I)n formed a complex with (C)n and (br5C)n, but these complexes were markedly destabilized relative to the corresponding (A)n or (I)n complexes. The (aza2A)n-and (aza2I)n-derived complexes failed to stimulate the production of interferon in primary rabbit kidney cells and human diploid fibroblasts, under conditions (A)n. (U)n, (I)n. (C)n and (I)n. (br5C)n induced high amounts of interferon. both (aza2A)n and (aza2I)n exerted a marked inhibitory effect on the endogenous RNA directed DNA polymerase (reverse transcriptase) activity associated with murine leukemia virus. They caused a relatively mild inhibition of complement activity in an hemolytic assay system.
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PMID:Biologic activities of poly (2-azaadenylic acid) and poly (2-azainosinic acid). 7 66

24 cases of adult acute leukaemia, of which 21 were evaluable, were treated in irreversible relapse with high-dose piperazinedione and supralethal total-body irradiation (T.B.I.) in conjunction with autologous marrow transplantation (A.B.M.T.). The grafted marrow cells had been collected and stored in liquid nitrogen at the time of remission. In 12 patients the marrow cells were fractionated on discontinuous albumin gradients in an attempt to separate normal cells from residual leukaemic cells. 11 patients achieved complete remission (C.R.); 7 other patients had signs of engraftment but died before C.R. The median remission duration was 4 months (2-14). 6 of 9 acute myeloblastic leukaemia patients, in whom bone-marrow transplantation was the first treatment of relapse, achieved C.R. 4 of 5 patients with acute lymphoblastic leukaemia, whose bone-marrow cells were collected during first remission, reached C.R. Autologous bone-marrow transplantation is a valuable first treatment for acute myeloblastic leukaemia in relapse and acute lymphoblastic leukaemia in second relapse.
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PMID:Autologous bone-marrow transplantation in relapsed adult acute leukaemia. 8 5

Methotrexate analogues, in which an additional nitrogen atom is inserted between the phenyl ring and the carbonyl group of the side chain, were prepared by photochemical methods. The compounds were less inhibitory toward dihydrofolate reductase and thymidylate synthetase derived from Lactobacillus casei than was methotrexate. They were also less cytotoxic against human lymphoblastic leukemia cells (CCRF-CEM). In vivo against L-1210 leukemia in mice, the aza homologue of methotrexate showed significant antitumor activity (%ILS = 55%) compared to methotrexate (%ILS = 88%).
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PMID:Methotrexate analogues. 12. Synthesis and biological properties of some aza homologues. 10 16

Folic acid analogues containing an additional nitrogen atom between the phenyl ring and the carbonyl group of the side chain were synthesized. None of the compounds showed significant inhibitory activity against human lymphoblastic leukemia cells (CCRF-CEM) in culture or against Lactobacillus casei (ATCC 7469) growth. Against L1210 leukemia in mice, the aza homologue of folic acid, 4, and the aspartic acid analogue, 14, showed no increase in life span over control animals. These compounds were more toxic in vivo than the corresponding methotrexate analogues. Compound 4 supported the growth of Streptococcus faecium (ATCC 8043), and its tetrahydro derivative supported the growth of Pediococcus cerevisiae (ATCC 8081). These results strongly suggest that 4 can substitute for folate derivatives as cofactors for serine transhydroxymethylase, thymidylate synthetase, and dihydrofolate reductase.
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PMID:Synthesis of aza homologues of folic acid. 10 17

Six patients with chronic granulocytic leukaemia (CGL) in transformation were treated with cytotoxic drugs or cytotoxic drugs plus total body irradiation, followed by infusion of reconstituted autologous peripheral blood cells that had been collected from them at diagnosis and stored in liquid nitrogen for up to 58 months. In four cases the blood and bone-marrow appearances were rapidly restored to those of typical chronic-phase disease. In three of these patients transformation recurred at 74, 32, and 26 weeks respectively. One patient was still in second chronic phase at eight weeks. One of the patients who entered a second transformation was restored to a third chronic phase by further treatment with cytotoxic drugs and a second autograft. Cryopreserved autologous blood cells may thus restore some patients with CGL in transformation to chronic-phase disease and so may help to prolong life.
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PMID:Cryopreserved peripheral blood cells functioning as autografts in patients with chronic granulocytic leukaemia in transformation. 28 22

The triangulation arrangement of one nitrogen and two oxygen atoms proposed as a requirement for antileukemic activity involving a "common receptor-complement feature" has been reevaluated specifically as it applies to nucleosides. This re-evaluation has resulted in a rejection of the "receptor-complement feature" as a working model for the a priori design of nucleosides as compounds active against leukemia L-1210.
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PMID:Evaluation of a common receptor-complement concept for predicting the antileukemic activity of nucleosides. 29 Oct 63

Cancer chemotherapy has developed rapidly over the last twenty years. The majority of patients with cancer die from metastatic disease, so the major therapeutic advance now must be better systemic therapy. From its early beginning in the 1940's with oestrogen therapy for prostatic cancer, nitrogen mustards in the lymphomas, and folic acid antagonists in childhood leukaemia, there are now between thirty and forty active anti-cancer agents in clinical use. The main clinical pharmacological points of the major agents are briefly reviewed, together with their main dose-limiting toxic effects and their activity as single agents. Clinical chemotherapy has developed by the introduction of newer agents from the drug screening programmes and a better understanding of the scheduling to avoid serious toxicity. Although drug-resistance is still a major problem, by combining different active agents there has been a dramatic improvement in survival of patients with selected tumours. More recently, treatment of patients early, before they have gross clinical recurrence, has already shown some benefit in pre-menopausal patients with carcinoma of the breast and in patients with osteosarcoma. The limitations of clinical measurements in monitoring therapy are clear, and a major improvement could well be realised if therapy could be monitored on the basis of quantitative markers. The clinical impact of cancer chemotherapy has already been dramatic in drug-sensitive tumours, but these only contribute a small proportion of the total. Some of the common tumours fall into the group that are relatively drug sensitive where the lives of patients can be prolonged, but there is still a significant fraction of tumours which are insensitive to existing drugs and which will probably require the development of newer agents before chemotherapy can make any impact on the survival of patients with these tumours.
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PMID:The current role of cancer chemotherapy. 36 Nov 39

Peripheral blood lymphocytes (PBL) from normal human donors were sensitized in vitro against allogeneic human acute myelocytic leukemia (AML) cells by means of an unidirectional mixed lymphocyte-tumor cell culture (MLTC) technique. The cytotoxic responsiveness of the sensitized lymphocytes, as determined in vitro by the 51Cr-release assay, varied among individual lymphocyte donors and was greatly dependent on the sensitization culture conditions. Induction of cytotoxic effector cells was augmented appreciably by adding to the cultures minute amounts of the immunopotentiating agent MER-BCG. Responding lymphocytes and stimulating leukemia cells cryopreserved for several weeks in liquid nitrogen were as effective as fresh cells in generating effector lymphocytes; the cytotoxic capacity of already sensitized lymphocytes was fully retained by cryopreservation. The implications of these findings for possible clinical employment of in vitro sensitized lymphocytes in adoptive immunotherapy of cancer are discussed.
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PMID:In vitro induction of cytotoxic effector cells against human neoplasms. I. Sensitization conditions and effect of cryopreservation on the induction and expression of cytotoxic responses to allogeneic leukemia cells. 38 44

Eight of fifteen Fluorenone-Azomethines without alkylating function have been found effective against the leukemia L 1210. Little modifications concerning the structure of the compounds caused loss of effectiveness. It seems remarkably that one corresponding derivative with a nitrogen mustard group (4) was ineffective. Correlations between chemical structure and biological effect have not yet been found.
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PMID:[Cancerostatic effect of some fluorenone azomethines tested against leukemia L 1210 (author's transl)]. 44 28

The condensation of alkylenediamines with quinizarin or with 2,3-dihydro-1,4,5,8-tetrahydroxy-9,10-anthracenedione, followed by oxidation, gave 1,4-bis[aminoalkyl)amino]-9,10-anthracenediones. Some of these compounds and their 2,3-dihydro derivatives were markedly active against both leukemias and solid tumors in mice. Activity was maximal with 5,8-dihydroxylation and 1,4-bis[(2-aminoethyl)amino] substitution, in which the terminal nitrogen atoms were either unsubstituted (compound 50) or carried 2-hydroxyethyl groups (compound 40), indicating the importance of hydrophilicity. Against B-16 melanoma, 50 gave greater than 433% increase in median life span (ILS) with 7/10 80-day survivors. Against P-388 leukemia, 40 gave greater than 500% ILS with 4/5.60-day survivors; its efficacy and therapeutic index equaled or surpassed those of adriamycin, cyclophosphamide, daunorubicin, methotrexate, or 5-fluorouracil. Against L-1210 leukemia, B-16 melanoma, and colon tumor 26, 40 was generally as effective or more effective than adriamycin and is now undergoing preclinical toxicological evaluation.
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PMID:Antitumor agents. 1. 1,4-Bis[(aminoalkyl)amino]-9,10-anthracenediones. 49 May 45


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