Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have examined the effect of FK506 on the Adriamycin sensitivity of the multidrug resistant human chronic myelocytic leukemia cell line (K562/ADM). In K562/ADM cells, 1.0 microgram/ml FK506 reversed the resistance of Adriamycin, and increased the IC50 value for Adriamycin up to 17 fold. However, IC50 value for the parent cells (K562) increased only 1.5 fold. By cell cycle analysis, the accumulation in late S-G2M phase was confirmed on K562/ADM cells, treated with 1.0 microgram/ml FK506 and low-dose of Adriamycin. Cyclosporin A (CsA) could also restored the Adriamycin sensitivity in the K562/ADM cells, as previously reported. 1.0 microgram/ml FK506 as well as CsA significantly increased radioactive Adriamycin accumulation in K562/ADM cells and blocked [3H]azidopien photoaffinity labeling of P-glycoprotein. These results suggest that 1.0 microgram/ml FK506 could reverse the Adriamycin resistance in a MDR human leukemia cells through the interaction with P-glycoprotein.
 ...
PMID:FK506 reverses adriamycin resistance in a multidrug-resistant human leukemia cell line. 128 34

Utility of drug response modulators to increase therapeutic:toxic ratio of anticancer drugs in the treatment of refractory malignancies is becoming desirable. In this study, we have attempted to potentiate the tumor cell killing ability of Adriamycin (ADR) against chronic myeloid leukemia cells (CML), in the presence of vitamin K3. Cell growth was evaluated by the MTT assay and the 3H-thymidine incorporation inhibition assay. A highly significant (p less than 0.001) inhibition of cell survival and 3H-thymidine incorporation was effected in CML cells exposed to the combination of ADR and vitamin K3. When the CML cells were treated with ADR and vitamin K3 simultaneously, a greater fragmentation of the intact DNA was revealed as observed by the enhanced formation of DNA single strand breaks. Results demonstrate the therapeutic significance of employing vitamin K3 as an adjuvant in CML chemotherapy with ADR.
 ...
PMID:Single and combination treatment with vitamin K3 and adriamycin: in vitro effects on cell survival and DNA damage in human chronic myeloid leukemia cells. 177 Dec 99

A 20-year old patient is presented with generalized lymphadenopathy, splenomegaly, hyperleukocytosis and a bone marrow biopsy showing panmyelosis with predominance of immature granulocytes. Lymph node biopsy showed a histopathological feature that was diagnosed as a chronic granulocytic leukemia in blast crisis. The cell surface phenotype of these blast cells showed predominance of immature CD1+, CD7+ T lymphocytes. The T cell lineage was confirmed by DNA rearrangement studies. In addition, the patient showed erythrocytosis, arterial O2 saturation of 92% and thrombocytosis, characteristics of polycythemia vera. After chemotherapy, the patient relapsed with similar symptoms and lymph node cells of similar immature T phenotype. With a revised diagnosis of immature T cell lymphoma associated to a myeloproliferative disorder and polyglobulia, the patient received a combined treatment of Cyclophosphamide-Adriamycin-Vincristine-VM26-Prednisone. Two months later, the patient relapsed again. He received the first phase of induction of the BFM protocol, with partial clinical remission. Five months later, the patient returned with fever, polyadenopathy and splenomegaly. Lymph node cells showed again immature T cell phenotype. The patient was next treated with the m-BACOD scheme, with no response and progression of the disease and he died few days later due to massive bleeding and cardiorespiratory failure.
 ...
PMID:[T lymphoma of immature phenotype associated with polycythemia vera]. 182 May 2

The utilization of drug response modulators, based on their physico-chemical properties to augment the cytotoxic response of anticancer drugs is now gaining importance. We present in this communication, investigations performed to assess the antitumor activity of Adriamycin (ADR), on chronic myeloid leukemia (CML) cells, and the effect of bepridil, a calcium channel blocker on the ADR cytotoxicity. Inhibition of 3H-thymidine incorporation into DNA was used as an index of the cytotoxic effects of drugs when utilised alone or in combination. The combination of bepridil (1 and 5 micrograms/ml) and ADR (5 and 10 micrograms/ml) indicated a significant (P less than 0.001) enhancement in the DNA biosynthesis inhibition in CML cells, as compared to those samples exposed to ADR alone. The observed inhibition of DNA biosynthesis was found to be totally reversible, partially reversible and completely irreversible when the CML cells were exposed to bepridil alone, ADR alone and ADR plus bepridil, respectively. Bepridil was found to be highly lipid soluble at physiological pH, and this property could be responsible for the modulation of the ADR activity observed in this study. Results obtained, though preliminary due to the small sample size, clearly indicate a necessity for a detailed evaluation of bepridil effects, which would lead to higher therapeutic gains in anticancer chemotherapy in the clinic.
 ...
PMID:Bepridil enhances adriamycin-induced DNA biosynthesis inhibition in human myeloid leukemia cells. 209 38

Herbimycin A, a benzoquinonoid ansamycin antibiotic, is found to reduce intracellular phosphorylation by tyrosine protein kinase. The human chronic myelogenous leukemia cell line K562 expresses a structurally altered c-abl protein with tyrosine kinase activity. When K562 cells are induced to undergo erythroid differentiation by hemin, reduction in the intracellular level of tyrosine phosphorylation occurs. In order to understand the relationship between induction of differentiation and reduction of tyrosine phosphorylation by the c-abl gene product, the effect that herbimycin A, a selective inhibitor of intracellular tyrosine kinase activity, exerts on the differentiation of K562 cells was examined. Reduction of tyrosine phosphorylation in K562 cells by herbimycin A was observed within 1 h. Noncytotoxic concentrations of herbimycin A induced erythroid differentiation of K562 cells but not of murine erythroleukemia 745A cells. The other human myeloid leukemia cell lines (HL-60, THP-1, and U937) tested were not induced to undergo cell differentiation by this antibiotic. Herbimycin A and the other well-known inducers such as hemin, butyric acid, Adriamycin, and 1-beta-D-arabinofuranosylcytosine had additive or more than additive effects on induction of erythroid differentiation of K562 cells. With respect to inhibition of cell growth, the sensitivity of K562 cells to herbimycin A was highest in the human leukemia cell lines we tested. Noncytotoxic concentrations of herbimycin enhanced the antiproliferative effect of Adriamycin or 1-beta-D-arabinofuranosylcytosine on K562 cells. Combination therapy with herbimycin A and its derivatives may be considered for use in the treatment of some types of leukemia where tyrosine kinase activities are implicated as determinants of the oncogenic state.
 ...
PMID:Induction of erythroid differentiation of K562 human leukemic cells by herbimycin A, an inhibitor of tyrosine kinase activity. 291 Apr 52

Cancer chemotherapy combined with calcium-channel blockers was administered to seventeen evaluable patients with hematologic malignancy and solid tumor who became resistant to standard chemotherapies between November 1981 and June 1986 in Saitama Cancer Center. Nicardipine and diltiazem were used as the calcium-channel blockers, which were given orally or intravenously. Adriamycin and/or vinca alkaloids were mainly used as a cancer chemotherapy. Partial remission was attained in 3 of 6 patients with malignant lymphoma. Remission was attained in 2 of 7 patients with acute leukemia including acute transformation of chronic myelogenous leukemia (CML/BC), one complete remission with acute lymphocytic leukemia and one cytoreductive effect with CML/BC. One partial response and one minor response were obtained among 4 patients with solid tumor. The remission of these responders was of short duration. The most serious side effect caused by calcium-channel blockers was hypotension, which was dose-limiting and induced oliguria in 6 of 23 courses. In conclusion, the clinical impression obtained with regard to the effectiveness against chemotherapy-resistant malignancies of cancer chemotherapy combined with calcium-channel blockers was not good even though the overall remission rate was 41%.
 ...
PMID:[Cancer chemotherapy combined with a calcium antagonist in patients with hematologic malignancies and solid tumors resistant to standard chemotherapy]. 347 Nov 83

Adriamycin and mitoxantrone are known antitumor agents. The use of these agents is limited by their toxicity to normal body tissue. This paper shows that it is possible to achieve greater log cell-kill by using these drugs in combination with hyperthermia and diazepam. Experiments were carried out on 22 human chronic myeloid leukemia samples. 10 micrograms/ml adriamycin and 1 microgram/ml mitoxantrone were used in combination with hyperthermia 42 degrees C, for 3 h and 1 h respectively, with and without diazepam (1 microgram/ml). Inhibition of incorporation of radiolabeled nucleic acid precursor (3H-thymidine) in treated cells as compared to the untreated cells was used as a measure of cytotoxicity. The statistical evaluation of the data shows that the enhancement of drug cytotoxicity due to hyperthermia and diazepam is highly significant (p less than 0.001) in case of both the drugs.
 ...
PMID:In vitro modulation of adriamycin and mitoxantrone cytotoxicity by hyperthermia and diazepam, in human chronic myeloid leukemia cells. 347 31

Thirty patients with Philadelphia chromosome-positive lymphoid (20 patients) or undifferentiated (ten patients) chronic myelogenous leukemia in blast crisis were treated with 0.4 mg of vincristine by continuous intravenous infusion (CIV) daily for 4 days; (doxorubicin) 12 mg/m2 of Adriamycin (Adria Laboratories, Columbus, OH) by continuous intravenous infusion daily for 4 days; and 40 mg of decadron daily on days 1 through 4, 9 through 12, and 17 through 20 (VAD). Course 2 was given starting on day 24 with the addition of cyclophosphamide 1 g/22. Overall nine patients achieved complete remission (30%) and three attained a partial remission (10%), for an overall response rate of 40%. Four patients expired during induction whereas 14 had resistant disease. Response rate was significantly higher for patients with lymphoid compared to undifferentiated morphology (55% versus 10%; P = 0.05). In lymphoid blast crisis, Calla-positive disease was associated with a higher response rate compared to Calla-negative disease (75% versus 25%; P = 0.08). Eleven patients developed infections, and seven had fever without documented infections. The median overall survival was 29 weeks. Median survival was 43 weeks for patients achieving complete remission and 20 weeks for those with resistant disease. Remission duration was 39 weeks. After primary and salvage therapy, nine patients are alive, six of them in continuous remission for 19+ to 112+ weeks. The authors conclude that VAD chemotherapy is an effective regimen with acceptable toxicity in patients with lymphoid blast crisis especially those with Calla-positive disease. Alternate induction regimens for undifferentiated disease and for maintenance therapy are currently being investigated.
 ...
PMID:Therapy of lymphoid and undifferentiated chronic myelogenous leukemia in blast crisis with continuous vincristine and adriamycin infusions plus high-dose decadron. 347 15

Even patients with chronic myelogenous leukemia (CML) in blast crisis were treated with chemotherapy, followed by infusion of autologous bone marrow that had been collected during the chronic phase of the disease and cryopreserved at -198 degrees C. The mean age of the nine females and two males in this study was 34 years with an average duration of the chronic phase of the disease of 5.5 years. Seven out of the 11 patients had a splenectomy prior to intensive chemotherapy. The median survival of the first four patients who received 6-thioguanine, cytosine arabinoside, daunorubicin (TAD) chemotherapy was 2.6 weeks and no patient reachieved the chronic phase of CML. The second group of seven patients received more intensive chemotherapy (MAdHAT), which included melphalan 30 mg/m2 days 1, 2, and 3; Adriamycin 50 mg/m2 intravenously (iv) day 1, hydroxyurea 1500 mg/m2 by mouth for 5-7 days, cytosine arabinoside 100 mg/m2 continuous infusion for 5-7 days, and VM-26 100 mg/m2 iv on day 3. Six out of these seven patients reachieved chronic phase CML after bone marrow reinfusion. The median survival was 29.9 weeks for all patients and 33 weeks for the six patients who reachieved chronic phase CML. All patients subsequently died of recurrent blast crisis. There was no correlation between the time of bone marrow storage and the duration of subsequent chronic phase CML. These studies have shown that autologous bone marrow transplantation after high-dose chemotherapy can result in bone marrow engraftment with reestablishment of chronic phase CML, and prolongation of survival.
 ...
PMID:Autologous marrow transplantation for patients with chronic myelogenous leukemia (CML) in blast crisis. 636 1

Attempts to eliminate Philadelphia chromosome-positive cells during the treatment of chronic-phase chronic myelocytic leukemia (CML) have been largely unsuccessful, probably due to the lack of specificity of drugs which have been used. In an attempt to develop more specific therapy for CML, an assay for colony-forming units in culture was used to test for differences between CML blood and normal marrow progenitor cells. The following drugs, which have activity in acute nonlymphocytic leukemia, were tested over a range of concentrations achievable in vivo: Adriamycin; 1-beta-D-arabinofuranosylcytosine; aclacinomycin; m(4-acridinylamino)-3-methoxyphenyl methansulfamide; methylglyoxalbis(guanylhydrazone), and 5-azacytidine. [3H]Thymidine suicide indices were also determined. Normal marrow colony-forming units in culture tended to be more sensitive to all the drugs which were tested, although not of statistical significance. There was no difference in the suicide index between CML and normal colony-forming units in culture. It is concluded that the drugs which were tested are not likely to selectively kill CML progenitor cells while permitting normal hematopoietic elements to survive.
 ...
PMID:In vitro drug sensitivity studies of colony-forming units in culture in chronic myelocytic leukemia: lack of specificity between chronic-phase patients and normal donors. 658 67


1 2 Next >>