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)

Two new boron compoumds, dihydroxy(oxybiguanido) boron (iii) hydrochloride monohydrate (HB) and guanidine biboric acid adduct (GB) were used in this study to observe the antitumor effect. Leukemic blast cells isolated from chronic myeloid leukemia (CML) patients showed significant cell growth inhibition within twentyfour hours. IC50 of GB and HB was 2mg/ml. The metabolically active cells were found to be inhibited by drug treatment as assessed by MTT test. Inhibition of 3H Thymidine incorporation also supported the above result. In this study we investigated the molecular mechanisms by which HB and GB induce apoptosis in immature blast cells.
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PMID:Boron compounds against human leukemic cells. 1187 44

Three new boron compounds, dihydroxy (oxybiguanido) boron (iii) hydrochloride monohydrate (HB), guanidine biboric acid adduct (GB) and hydroxosalicyl hydroxomato boron (iii) (SHB) were studied to observe their antineoplastic effect, if any. Leukemic cells isolated from acute lymphatic leukaemia (ALL) patients and chronic myeloid leukaemia patients (CML) and myeloid leukemia cell lines (HL 60 and U-937) showed cell growth inhibition after treatment with the boron compounds. MTT assay showed that the growth of metabolically active cells was inhibited by treatment with these drugs. The molecular mechanism by which SHB induced apoptosis in immature blast cells was also investigated by ladder formation in gel electrophoresis.
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PMID:Antineoplastic effect of new boron compounds against leukemic cell lines and cells from leukemic patients. 1238 77

The differentiation induction of K562 chronic myelogenous leukemia (CML) cells by crambescidin 800, a pentacyclic guanidine alkaloid isolated from a marine sponge, was examined. Crambescidin 800 increased hemoglobin production in K562 cells at concentrations of 0.15-1 microM and arrested the cell cycle of K562 cells at the S-phase. The expression of p21 was detected after 24-h treatment with crambescidin 800, and an increase of the expression was observed after 48-h treatment, but there was no remarkable change in the expression level of p27. This evidence indicates that crambescidin 800 induced the differentiation of K562 cells into erythroblasts accompanied by cell cycle arrest at the S-phase. Furthermore, crambescidin 800 induced a morphological change with neurite outgrowth in Neuro 2A cells at a 0.03-0.1 microM concentration.
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PMID:Erythroid differentiation in K562 chronic myelogenous cells induced by crambescidin 800, a pentacyclic guanidine alkaloid. 1533 Jan 79

Platelet aggregation profiles were studied in chronic myelogenous leukemia patients who were undergoing hydroxyurea therapy. Nitric oxide (NO) generation induced by hydroxyurea was measured from the altered aggregatory response, in which the platelet suspension exhibits a de-aggregatory behaviour. NO caused platelet de-aggregation by generation of cyclic guanidine monophosphate through the activation of soluble guanylate cyclase (SGC). The fact that the observed response is specific to NO was confirmed by the reversal of the de-aggregatory behaviour in the presence of (1)H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of SGC. Among the subjects studied, one subset showed an hydroxyurea-induced de-aggregatory effect that was inhibited by ODQ, whereas another subset did not show any such effect. The observed inter-individual variability in platelet aggregometric response after the ingestion of drugs may be an indicator for NO generation from hydroxyurea, and this may help to explain the drug efficacy encountered in such cases.
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PMID:Platelet aggregation profile as a marker of hydroxyurea bioavailability through nitric oxide generation in chronic myelogenous leukemia. 1669 May 34

Oligodeoxynucleic acid (21-mer) containing both negatively charged phosphate and positively charged ribonucleic guanidine linkages (RNG/DNA chimera) have been synthesized. DNA binding characteristics and nuclease resistance of RNG/DNA chimeras have been evaluated. Using the bcr-abl oncogene (cause of chronic myeloid leukemia) as a target, the binding of a 21-mer RNG/DNA chimera that includes six RNG's is more than 103.5 stronger than the binding of 21-mer composed solely of DNA.
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PMID:Incorporation of positively charged ribonucleic guanidine linkages into oligodeoxyribonucleotides: Development of potent antisense agents. 1835 46

Phenformin's recently demonstrated efficacy in melanoma and Gleevec's demonstrated anti-proliferative action in chronic myeloid leukemia may lie within these drugs' significant pharmacokinetics, pharmacodynamics and structural homologies, which are reviewed herein. Gleevec's success in turning a fatal leukemia into a manageable chronic disease has been trumpeted in medical, economic, political and social circles because it is considered the first successful targeted therapy. Investments have been immense in omics analyses and while in some cases they greatly helped the management of patients, in others targeted therapies failed to achieve clinically stable recurrence-free disease course or to substantially extend survival. Nevertheless protein kinase controlling approaches have persisted despite early warnings that the targeted genomics narrative is overblown. Experimental and clinical observations with Phenformin suggest an alternative explanation for Gleevec's mode of action. Using 13C-guided precise flux measurements, a comparative multiple cell line study demonstrated the drug's downstream impact on submolecular fatty acid processing metabolic events that occurred independent of Gleevec's molecular target. Clinical observations that hyperlipidemia and diabetes are both reversed in mice and in patients taking Gleevec support the drugs' primary metabolic targets by biguanides and statins. This is evident by structural data demonstrating that Gleevec shows pyridine- and phenyl-guanidine homology with Phenformin and identical phenylcarbamoyl structural and ligand binding homology with Lipitor. The misunderstood mechanism of action of Gleevec is emblematic of the pervasive flawed reasoning that genomic analysis will lead to targeted, personalized diagnosis and therapy. The alternative perspective for Gleevec's mode of action may turn oncotargets towards metabolic channel reaction architectures in leukemia and melanoma, as well as in other cancers.
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PMID:Structural homologies between phenformin, lipitor and gleevec aim the same metabolic oncotarget in leukemia and melanoma. 2841 52