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)

Acute myelogenous leukemia (AML) of the inbred Wistar/Furth (W/Fu) rat is pathophysiologically similar to human AML. Subcutaneous transplantation of 1.0 X 10(6) cells of a clonal tissue culture line of W/Fu AML into 6- to 8-week-old rats produced local myeloblastomas in 8--10 days which progressed to infiltration of regional nodes, replacement of greater than 90% of the bone marrow, ascites, and fatal peripheral blood leukemia with concomitant hyperlysozymemia. Single doses of adriamycin, daunomycin, actinomycin, cytosine arabinoside, or Cytoxan in rats with 1.0 cm myeloblastomas produced complete tumor regression while bu-sulfan, vinblastine, vincristine, dexamethasone, and Methotrexate was relatively ineffective. Responses were associated with delay in progression to peripheral blood leukemia and prolonged survival. Similar results were obtained following treatment of rats with already disseminated leukemia. The demonstration of response to drugs known active against human AML indicates that the W/Fu AML should be a valuable model for rapid evaluation of new chemotherapeutic agents for clinical use.
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PMID:Chemotherapeutic remissions in Wistar Furth rat acute myelogenous leukemia: a model for human AML. 6 30

The clinical and pathological features of 47 patients with Burkitt's lymphoma seen at the University of Baghdad Teaching Hospital over the years 1969-1977 are described. There were 30 males and 17 females with a mean age of 7.5 years. All patients presented with advanced disease; 44 were in Stage III and 3 in Stage IV, (1 with central nervous system involvement; 1 with bone-marrow involvement; 1 presented as acute leukaemia). The abdomen, with or without other sites, was involved in 42 patients. Thirty-four patients died within 18 months, 11 in the immediate post-operative period. Cyclophosphamide in variable dosages was administered to 29 patients with a good response in 15. The 3 patients with Stage IV disease died with poor response to therapy. Thus, in Iraq, a non-endemic area for the disease, Burkitt's lymphoma seems to have somewhat different clinical and pathological features from the endemic (African), or the rare, sporadic disease reported elsewhere.
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PMID:Burkitt's lymphoma in Iraq. Clinical and pathological study of forty-seven patients. 21 59

The treatment of central nervous system (CNS) involvement in human acute myelogenous leukemia (AML) presents a serious therapeutic dilemma. In an attempt to study the pathophysiology of this diseases in an animal model, the incidence and sites of detection of CNS leukemia were evaluated in inbred rats receiving chemotherapy for the transplantable WF AML. Eight of 100 rats with untreated WF AML demonstrated CNS leukemia at death with concomitant widespread visceral infiltrates, ascites, bone marrow involvement, and peripheral blood leukemia. Similarly, 6 of 120 rats (5%) failing to attain a complete remission following adriamycin. Cytoxan, or cytosine arabinoside chemotherapy demonstrated CNS leukemia in addition to systemic disease at death. In contrast, 70 of 75 rats (93.3%) achieving a complete remission subsequently relapsed in the CNS, either in combination with widespread systemic disease in 48 (64.0%) or with minimal evidence of systemic relapse in 22 (29.3%). There was a greater frequency of detectable cerebral compared to spinal cord infiltrates in relapsing rats. The WF AML appears to be a valuable model for study of the mechanism and ultimately the prevention of CNS relapse following chemotherapy in human AML.
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PMID:Central nervous system (CNS) relapse following chemotherapy of WF rat acute myelogenous leukemia: a model for human CNS leukemia. 26 15

The antileukemic activity of cis-diamminedichloroplatinum (PDD) was studied in rats bearing myelogenous leukemia RBA-Le. Clinical picture, changes in life-span, hematological indices and weight changes were used to assess the effectiveness of the therapy. Maximum effectiveness was noted when PDD was given in combination with Methotrexate (MTX) and Poly I:C, respectively. The mean life-span of the rats treated with PDD and MTX was prolonged to 37 days that is an increase of 147 percent of the control level. Furthermore 20 percent of the treated animals survived symptom-free for more than 60 days. Out of 20 animals receiving PDD in combination with Poly I:C 6 rats survived 60 days symptom-free. In remaining 14 animals who finally died on leukemia an 85 percent increase in life-span was noted. Only slight increase in life-span was recorded in those groups treated with PDD alone and in combination with Cyclophosphamide regardless of dosage schedule. The general toxicity of PDD therapy is discussed.
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PMID:Experimental chemotherapy of rat leukemia RBA-Le with cis-diamminedichloroplatinum. 27 Jun 16

Cyclophosphamide (CPM) chemotherapy (134 mg/kg) of L1210 leukemia is less efficient in mice previously immunodepressed by antithymocyte serum (ATS) than in non-ATS pretreated mice. On the other hand, administration of a higher dose of CPM (403 mg/kg), which kills a greater number of leukemic cells but induces an immunodepression, according to the skin graft test, results in a shorter survival time than does the administration of a lower dose of CPM (134 mg/kg), capable of killing fewer leukemic cells but not inducing such an immunodepression. Thus, it appears that: (1) the antileukemic effect of the same dose of a chemotherapeutic drug is less efficient in immunodepressed than in nonimmunodepressed hosts, and (2) calculation of the number of neoplastic cells killed by a given chemotherapy by extrapolation from the survival time may lead to erroneous conclusions.
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PMID:Effectiveness of murine leukemia chemotherapy according to the immune state: reconsideration of correlations between chemotherapy, tumour cell killing, and survival time. 30 90

Treatment with daunorubicin-DNA (DNR-DNA) or adriamycin-DNA (ADM-DNA) has been evaluated in acute lymphoblastic leukemia of childhood (ALL), acute nonlymphoblastic leukemia (ANLL) and bronchogenic carcinoma (BC). The Five-year survival rate in 69 children with ALL was 73.7% when ADM-DNA was introduced in the treatment and 38% with DNR-DNA (P = 0.03). A randomization between free DNR and DNR-DNA for remission induction in 26 patients with ANLL has shown that the drugs were of equivalent effectiveness. The one-year survival rate was 66% for the DNR group and 64% for the DNR-DNA group. In 59 patients with BC, a randomized trial between ADM-DNA and cyclophosphamide-vinblastine (CTX-VLB) did not show an advantage in favor of one of these treatments. In anaplastic BC (51 patients), there was no difference in survival rate or remission rate between patients treated with ADM or ADM-DNA. No cardiotoxicity was noted among the patients treated with the complexed drugs. ADM-DNA and DNR-DNA are as effective as the free drugs. Cardiotoxicity appears to be reduced.
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PMID:Clinical trials with daunorubicin-DNA and adriamycin-DNA in acute lymphoblastic leukemia of childhood, acute nonlymphoblastic leukemia, and bronchogenic carcinoma. 38 79

Monotherapy of early rat leukemia L 5222 with 5 X 100 mg/kg EDU over 48 h yielded no increase in lifespan as compared to untreated controls. Combination therapy of advanced L 5222 with EDU and CPA in four different schedules results in no increase in life-span as compared to treatment with CPA only. DNA histogrms of preterminal L 5222 revealed no synchronizing effect of EDU.
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PMID:[No increase in chemotherapeutic effectiveness of cyclophosphamide (CPA) in rat leukemia L 5222 by 5-ethyl-2'-deoxyuridine (EDU) (author's transl)]. 58 56

In two patients with acute leukaemia, the development of progressive interstitial pulmonary fibrosis was observed following chemotherapy with BCNU, Cytoxan and Ara-C. The x-ray changes were accompanied by restrictive changes of pulmonary function and, later on, by severe hypoxia. Serologic tests did not reveal infection with cytomegaly virus or mycoplasma pneumoniae. These findings, together with reports in the literature, suggest a toxic effect of BCNU on the lung. The combination with Cyclophosphamide may contribute to this toxic reaction.
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PMID:[Progressive pulmonary fibrosis during combination chemotherapy with BCNU (author's transl)]. 65 38

Antileukemia sera with "directed" specificity are produced by immunization of rabbits with mouse leukemia cells admixed with normal antigen blocking (NAB) serum. Addition of NAB serum to the leukemia cells inhibits production of antibodies to normal cell components and directs specificity toward leukemia cell antigens. The resulting antileukemia serum (ALK-NABS) was not sufficiently potent to produce more than moderate therapy in the standard L1210 leukemia therapy assay. When given together with noncurative doses of cyclophosphamide (CTX), ALK-NABS acts synergistically. It is most effective when given early after injection of the leukemia cells and prior to injection of CTX. Daily repeated injections of a given dose are more effective than a single injection of that dose. Most important, small doses of ALK-NABS produce a significant prolongation of lifespan in conjunction with CTX. Results of therapy for BW-A leukemia with ALK-NABS in conjunction with CTX were negative.
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PMID:Passive immunotherapy for mouse leukemias with antisera of "directed" specificity: synergism with the action of cyclophosphamide. 92 53

2,5-Piperazinedione, 3,6-bis(5-chloro-2-piperidyl)-,dihydrochloride (NSC-135758) selectively inhibits DNA synthesis in L1210/0 leukemia and in cyclophosphamide-resistant L1210 (L1210/CPA). Melphalan (L-PAM) inhibits nucleic-acid synthesis but not protein synthesis in L1210/0 and L1210/CPA. CPA selectively inhibits DNA synthesis in L1210/0 but does not inhibit DNA synthesis in L1210/CPA. NSC-135758 is as active in vivo against L1210/CPA and BCNU-resistant L1210 (L1210/BCNU) as it is against L1210/0. It is inactive against ic implanted L1210/0. These data clearly indicate important differences in the biologic activity of this compound compared to either CPA or BCNU. L-PAM is similar to NSC-135758 in activity against L1210/CPA and L1210/BCNU.
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PMID:Studies with 2,5-piperazinedione, 3,6-bis(5-chloro-2-piperidyl)-,dihydrochloride. III. Biochemical and therapeutic effects in L1210 leukemias sensitive and resistant to alkylating agents: comparison with melphalan, cyclophosphamide, and BCNU. 101 68


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