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)

Lipids extracted from doxorubicin-resistant murine leukemia cells (P388/ADR) contained greater relative amounts of myristic and palmitoleic acids than lipids from sensitive cells (P388). This was seen in both the phospholipid and neutral lipid fractions under two nutritional conditions. Correspondingly in P388/ADR cells, myristic acid comprised a greater proportion of the products of the fatty acid synthetase system, and acyl-CoA 9-desaturase activity was transiently greater than in P388. Similar alterations in myristic acid synthesis were exhibited by DC3F/AD X, N417/VP-16, and P388/AZQ30U cells but not by CHRC5 or HL60/AR cells. This alterations was independent of alterations in the P180 glycoprotein and might be linked via the myristoylation of proteins to a different mechanism of drug resistance. Doxorubicin-resistant P388/ADR cells also exhibited a much higher rate of oxidative energy production.
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PMID:Differences in myristic acid synthesis and in metabolic rate for P388 cells resistant to doxorubicin. 208 96

This investigation was conducted to provide preclinical in vivo tumor response data collected under standardized conditions with a range of clinically useful drugs combined with type I (alpha/beta) or type II (gamma) interferon. Murine tumor models used were P388 leukemia, Meth A sarcoma, and B16 melanoma. Eleven cytotoxic drugs were studied. Interferon combinations with cytosine arabinoside provided consistent indications of activity greater than that of the respective single agents. Doxorubicin and cisplatin each prolonged the time to treatment failure, relative to single-agent results, when they were combined with gamma-interferon in the Meth A and B16 models. Interferon combinations with methotrexate, 6-mercaptopurine, 6-thioguanine, ampligen, suramin, 5-fluorouracil, cyclophosphamide, and vinblastine yielded no evidence of any positive therapeutic interactions under the conditions of this study.
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PMID:Evaluation of combinations of interferons and cytotoxic drugs in murine tumor models in vivo. 211 61

Datelliptium acetate (NSC 311152) is a water soluble analogue of ellipticine. It is a solid tumor selective compound. In vitro, in a disk diffusion, soft agar colony formation assay (25 micrograms/disk), the compound demonstrated solid tumor selectivity (compared to leukemia L1210) against colon adenocarcinoma 38 and pancreas ductal carcinoma 03. Upon intravenous administration, NSC 311152 was effective in vivo against a variety of murine solid tumors. Responses at maximum tolerated doses were: colon #07/A (T/C = 33%); 0.60 log cell kill), #38 [T/C = 0%; 4.2 log cell kill), colon #51/A (T/C = 2%; 1.2 log cell kill), undifferentiated colon #26/A (T/C = 38%; 0.4 log kill), mammary #16/C (T/C = 10%; 1.7 log cell kill), and pancreatic ductal carcinoma #03 (T/C = 0%; 80% cures through day 38). It was ineffective against pancreas #02 (T/C = 45%), mammary 17/A (T/C = 53%), and 17/A/ADR (T/C = 52%). At efficacious doses acute neurotoxicity (i.e. stupor and lethargy) and weight loss were noted (with rapid recovery from both toxicities). There were no delayed toxicities. The agent was slightly necrotizing and produced pain on SC injections. In lieu of its preclinical efficacy and toxicity profiles, we recommend further clinical investigation of this agent.
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PMID:Activity of datelliptium acetate (NSC 311152; SR 95156A) against solid tumors of mice. 217 44

Acute nonlymphocytic leukemia was diagnosed in a 1-year-old Rhodesian Ridgeback. Clinical signs of disease included weight loss, anorexia, lethargy, lymphadenopathy, splenomegaly, and hepatomegaly. Doxorubicin was administered IV on day 4 at a dosage of 30 mg/m2 of body surface, followed 2 days later by oral administration of cyclophosphamide at a dosage of 100 mg/m2. The cyclophosphamide was given for 4 consecutive days (days 8, 9, 10, and 11), but the WBC count did not respond. The dog was administered 500 ml of blood; but on day 12, it died. Necropsy was not performed, but the presumptive cause of death was related to leukostasis.
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PMID:Acute nonlymphocytic leukemia in a dog. 229 42

Pyrazine diazohydroxide (sodium salt, NSC 361456; PZDH) is a new antitumor drug with relatively broad activity in initial evaluations against murine leukemias, solid tumors, and two human tumor xenografts in vivo. The present studies were designed to address questions about PZDH activity on different treatment schedules, its activity against metastases, and the extent of its cross-resistance with established drugs. Human LOX amelanotic melanoma xenografts in athymic mice were used to explore schedule dependence and activity against natural metastases, and a series of drug-resistant murine leukemias provided an in vivo cross-resistance profile. Single-dose treatment and prolonged treatment provided equivalent therapeutic responses to PZDH by both the i.p. and i.v. routes in the i.p. LOX model. A s.c. LOX model resulting in spontaneous pulmonary metastases was adapted for bioassay and quantitation of the numbers of LOX cells killed by PZDH among both primary and metastatic cell populations. It was demonstrated that PZDH afforded about 2-log10 orders of magnitude greater cell kill among pulmonary metastases than against primary s.c. LOX tumors in the same mouse. Murine leukemias resistant to doxorubicin (ADR), vincristine (VCR), cisplatin (DDPt), methotrexate (MTX), N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU), and cyclophosphamide (CPA) were not cross-resistant to PZDH. However, both P388 and L1210 leukemia sublines resistant to melphalan (L-PAM) were cross-resistant to PZDH, suggesting that patients previously treated with L-PAM might have less likelihood of response to PZDH than those who had had no opportunity to develop L-PAM resistance. Although these observations should not be applied to clinical studies without due caution, they support clinical evaluation of PZDH as well as continued investigation of its molecular pharmacology.
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PMID:Schedule dependence, activity against natural metastases, and cross-resistance of pyrazine diazohydroxide (sodium salt, NSC 361456) in preclinical models in vivo. 231 Nov 70

Using mice BDF1 it has been shown that the period of retention of Doxorubicin (Dx) is shorter in the leukemia P388 cells with induced antibiotic resistance (P388/Dx) as compared to P388 cells sensitive to Dx. Administration of Verapamil (Vp) to animals leads to an increase of Dx concentration in the leukemia P388/Dx cells during a 240 min observation period. Vp promotes the therapeutic effect of Dx on P388/Dx bearing mice. It can be suggested that the mechanism of Vp action consists in the damaged Dx elimination from cells with induced resistance, since Vp doesn't change the period of circulation of the antibiotic in the blood plasma of mice.
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PMID:Verapamil effect on the accumulation of doxorubicin in the leukemia P388 cells with induced antibiotic resistance. 233 61

Three cases of pulmonary atypical mycobacteriosis (AM) were reported. Two cases were associated with lung cancer in which the diagnosis of malignancy was difficult and delayed by the coexistence of AM. The third was a case of adult T-cell leukemia (ATL) which manifested during the course of AM. In case 1 (73 years, male) and case 2 (86 years, male), chest roentgenogram abnormalities as well as clinical symptoms were considered to be caused by mycobacteriosis because of positive smear of acid-fast bacilli in sputa on admission. Therefore it took four months and three months respectively for final diagnosis of lung cancer. The autopsy of case 1 revealed a poorly differentiated adenocarcinoma with coexisting foci of squamous cell carcinoma in right lower lung, and granulomatous inflammations with caseating necroses in right mid and lower lungs. M. avium complex was cultured from sputum on admission, and also a high titer of HTLV-I antibody was demonstrated. In case 2 malignant cells were detected in sputa (class V), however his general condition did not allow an aggressive anticancer chemotherapy and he died of malignancy with complication of thromboangiitis obliterans on right lower leg. Case 3 was a 76-year-old male who had been diagnosed as lung AM for more than two years. His chest radiography showed bilateral infiltrative shadows with frequent positive cultures of M. avium complex (more than 100 colonies) from sputum. A generalized lymphadenopathy including right hilar lymph node on chest X-ray film was followed by the presence of atypical lymphocytes in peripheral blood and the elevation of HTLV-I antibody in serum. Four months later he died with hypercalcemia and renal failure in spite of chemotherapy (CPM + VCR + ADR + PLS). The above cases suggest that AM as well as tuberculosis should be considered when pulmonary infiltrates were observed in malignant patients, especially in patients with retrovirus infections.
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PMID:[Three cases of pulmonary atypical mycobacteriosis associated with lung cancer and adult T-cell leukemia]. 237 33

Pyrindamycins A(1) and B(2) exhibited stronger cytotoxic activities than doxorubicin towards murine and human tumor cell lines and especially towards doxorubicin-resistant cells. Pyrindamycins A and B were also active in vivo against P388/ADR, a multidrug-resistant tumor cell line. Intracellular accumulation of pyrindamycins A and B in P388/ADR was the same as in P388. These antibiotics strongly inhibited DNA synthesis compared with RNA or protein synthesis. They showed significant therapeutic effects towards murine leukemia, but not to solid tumors.
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PMID:Antitumor activity of pyrindamycins A and B. 253 Nov 36

Accumulation of the dye rhodamine 123 was characterized by fluorescence in murine leukemia P388 cells and the Adriamycin-resistant subline, P388/ADR. Dye uptake by P388 cells was a slow, temperature-sensitive process, and involved binding at relatively hydrophobic and heterogeneous loci. Dye uptake by P388/ADR cells was temperature-insensitive, a steady state was quickly achieved, and the fluorescence emission spectrum suggested a relatively hydrophilic dye-binding site. Treatment of P388/ADR cells with verapamil resulted in enhanced accumulation of dye at hydrophobic loci. The fluorescence studies suggest that this dye may not reach the cytoplasm of P388/ADR cells, a result which may have implications with regard to the mechanism of multidrug resistance.
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PMID:Exploring multidrug resistance using rhodamine 123. 263 27

To improve the ability of flow cytometry to detect multidrug-resistant cells, we studied the extent to which cell volume heterogeneity accounts for the variance of intracellular daunorubicin (DNR) content. For P388 murine or HL-60 human leukemia cells exposed to DNR (1 micrograms/ml, 60 min), log intracellular DNR content varied in direct proportion to log cell volume measured by flow cytometry, with a correlation coefficient of .9. This relationship was confirmed by cell sorting based on intracellular DNR content with subsequent volume determination of the sorted cells. Normalization of intracellular DNR content for cell volume (thus obtaining intracellular DNR concentration) was accomplished by subtracting log cell volume from log intracellular DNR content for each cell. This resulted in a 34% decrease (range 23-58%) in standard deviation compared to DNR content measurements without volume normalization for all cell types tested. Following exposure to DNR (as above), intracellular DNR content of drug-sensitive P388 or HL-60 cells measured by flow cytometry was 12- and 8-fold greater than that of the multidrug-resistant sublines P388/ADR and HL-60/AR, respectively. However, because of the variance of intracellular DNR content, the predictive value of flow-cytometric determination of intracellular DNR content as a discriminant assay for detecting the frequency of drug-resistant cells in a mixed population was acceptable only when the frequency of resistant cells in the population exceeded 10%. In contrast, volume normalization of intracellular DNR content enhanced the ability of the flow-cytometric assay to discriminate resistant cells by 10-fold for P388 cells and 100-fold for HL-60 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Improvement of flow-cytometric detection of multidrug-resistant cells by cell-volume normalization of intracellular daunorubicin content. 271 7


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