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)

Some new S-dialkylarsenic compounds, S-dialkylarsino-3-mercapto-1,2-propanediol (3a-3d) and their derivatives (4a,4b), have been synthesized. They were screened at the National Cancer Institute (NCI) for their anticancer activity against a panel of about 60 human tumor cell lines. Most of them display anticancer activity having GI(50) and LC(50) values at low concentrations and are sensitive to leukemia, renal cancer and prostate cancer cell lines and in which the compound 3c is the most active.
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PMID:Synthesis of S-dialkylarsino-3-mercapto-1,2-propanediols and evaluation of their anticancer activity. 1728 25

The transcription factor nuclear factor-kappaB (NF-kappaB) has been shown to be constitutively activated in various human malignancies, including leukemia, lymphoma and a number of solid tumors. NF-kappaB regulates the transcriptional of genes important for tumor invasion, metastasis and chemoresistance. The sesquiterpene lactone parthenolide, an inhibition of NF-kappaB, has been used conventionally to treat migraines and inflammation. In this study, renal cancer cell lines OUR-10 and ACHN were used for in vitro experiments to evaluate growth-inhibitory effects of parthenolide. An OUR-10 xenograft model in nude mice was also used to investigate the in vivo growth-inhibitory effects of parthenolide. Apoptosis in response to treatment of OUR-10 cells with parthenolide was confirmed. Localization of NF-kappaB in response to parthenolide treatment was examined of by immunofluorostaining of OUR-10 cells with antibody against NF-kappaB p65 and by Western blot analysis of OUR-10 cell and tumor nuclear and cytosol fraction. Parthenolide effectively inhibited proliferation of cultured OUR-10 cells and triggered apoptosis in vitro. Subcutaneous injection or oral administration of parthenolide showed significant tumor growth inhibition in the xenograft model via decreased production of interleukin-8 (IL-8) or vascular endothelial growth factor (VEGF). Immunohistochemistry and Western blot analysis showed decreased nuclear localization of NF-kappaB and phosphorylated NF-kappaB protein and subsequently expression of MMP-9, Bcl-xL and Cox-2 in response to parthenolide treatment. These results indicate that parthenolide is a useful in the treatment of renal cell carcinoma and acts via inhibition of NF-kappaB.
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PMID:Sesquiterpene lactone parthenolide suppresses tumor growth in a xenograft model of renal cell carcinoma by inhibiting the activation of NF-kappaB. 1729 Mar 98

Following [2+3]-cyclocondensation reaction of 1,2,4-triazole-3(5)-thiol with N-arylmaleimides or with monochloroacetic acid and oxocompounds, N-(R-phenyl)-(6-oxo-5,6-dihydro[1,3]thiazol[3,2-b][1,2,4]triazol-5-yl)acetamides (1-5) and 5-ylidene-[1,3]thiazolo[3,2-b][1,2,4]triazol-6-ones (6-11) were synthesized as possible anticancer agents. Anticancer activity evaluation on the full panel of nearly 60 human cancer cell lines showed that synthesized compounds displayed this kind of activity on renal cancer, leukemia, colon cancer, breast cancer and melanoma cell lines. It was shown that 5-ylidene-[1,3]thiazolo[3,2-b][1,2,4]triazol-6-ones are characterized with more potent anticancer activity than respective amides. The structures of the compounds were determined by (1)H NMR, (13)C NMR and X-ray analysis.
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PMID:New 5-substituted thiazolo[3,2-b][1,2,4]triazol-6-ones: synthesis and anticancer evaluation. 1730 90

A series of 11 bis-indolylthiophenes of type 8-10 were obtained by cyclization of diketones 4 and 7 using Lawesson's reagent. Derivatives 8c, 9c, 9d, and 10c were selected to be evaluated in the full panel of about 60 human tumor cell lines derived from nine human cancer cell types and showed antiproliferative activity generally in the micromolar range. The most sensitive cell lines were: CCRF-CEM, MOLT-4, HL60 (TB), and RPMI-8226 of the leukemia subpanel, HT29 and HCC-2998 cell lines of the colon sub-panel, NCI-H522 of the non-small cell lung cancer sub-panel, LOX IMVI of the melanoma sub-panel, and UO-31 of the renal cancer sub-panel.
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PMID:Synthesis and antitumor properties of 2,5-bis(3'-indolyl)thiophenes: analogues of marine alkaloid nortopsentin. 1730 31

Novel 6,11-dioxo-6,11-dihydro-benzo[f]pyrido[1,2-a]indole-12-carboxamide derivatives and the corresponding 7,10-dihydroxy analogues were designed in accordance with Moore's and Pindur's theory and synthesized based on the structural similarity with known antitumour agents such as ellipticine, daunorubicin, mitoxantrone and 9-aminoacridine-4 carboxamide derivatives. These compounds, including structural variations of the amide side chain, were evaluated in the NCI panel of human tumour cell lines, from which 6,11-dioxo-6,11-dihydro-benzo[f]pyrido[1,2-a]indole-(2-dimethylamino-ethyl)-12-carboxamide 11a was found to be the most potent agent within the series. It showed good selectivity towards leukaemia, colon and renal cancer cell lines, with significant GI50 values, from lower than 10 nM to 0.2 microM. Moreover, its cytotoxicity against the adriamicine-resistant breast tumour cell line at a concentration lower than 1 microM turned out to be higher than the values using the clinical anticancer agents, daunorubicin and mitoxantrone.
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PMID:Synthesis and in vitro cytotoxicity evaluation of novel naphthindolizinedione derivatives. 1731 60

In recent years the use of the microarray technology has allowed the identification of numerous cancer-related genes and proteins. Today anticancer drug discovery is mainly target driven, which requires the characterization of molecular targets in existing cell lines or xenograft models. However, this analysis is time consuming and labor intensive. In order to ease this bottleneck, we have established tissue microarrays of 41 human tumor cell lines on glass slides. The purpose of our study was to (a) establish a simple and efficient method for cell line microarray construction, (b) apply the resulting array to the profiling of cathepsin B and transferrin receptor by immunohistochemistry and (c) verify the results in separate Western blot analyses. Ten to twenty million (1-2 x 10(7)) cells were harvested without trypsinization and fixed with Bouin's solution containing 8% formalin. Cell pellets 2-5 mm in diameter were embedded in paraffin. Microarrays were assembled using a tissue arrayer. Pellet biopsies 0.6 cm in diameter were taken and arrayed in duplicate in a new recipient paraffin block. About 60 slides can be obtained from one block. Citrate buffer was used for antigen retrieval. Expression of cathepsin B was granular and located in the cytoplasm. High cathepsin B levels were detected in 2 melanomas (MEXF 514L and MEXF 276L) and in the renal cell line RXF 486L. Twenty-five cell lines showed only minimal positivity. Nine cell lines of leukemia and lymphoma, breast, ovarian, prostate and renal cancer origin were positive for the transferrin receptor, while 32 cell lines were negative. Western blotting confirmed the results obtained by immunohistochemistry. Using these cell line microarrays, cell lines overexpressing a target of interest can be selected for in vitro evaluation of specific inhibitors.
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PMID:Microarrays of 41 human tumor cell lines for the characterization of new molecular targets: expression patterns of cathepsin B and the transferrin receptor. 1734 87

In search of novel purine antimetabolites, a series of 8-substituted methylxanthine derivatives was prepared in order to explore their in vitro anticancer, anti-HIV-1 and antimicrobial activities. The target compounds include: 8-[(3-substituted-4-oxo-thiazolidin-2-ylidene)hydrazino]-1,3-dimethyl (or 1,3,7-trimethyl)-3,7-dihydropurine-2,6-diones 5a-e, 8-[(3,4-disubstituted 2,3-dihydrothiazol-2-ylidene)hydrazino]-1,3,7-trimethyl-3,7-dihydropurine-2,6-diones 6a-d and 8-(5-amino-3-arylpyrazol-1-yl)-1,3-dimethyl- (or 1,3,7-trimethyl)-3,7-dihydropurine-2,6-diones 7a-g. The in vitro anticancer results revealed that compound 5d exhibited a super sensitivity profile towards leukemia K-562 with a GI(50) value of <0.01 microM. Compound 7c showed significant activity against colon cancer HCT-15 and renal cancer CAKI-1 (GI(50) values of 0.47 and 0.78 microM, respectively). Compound 7a displayed high activity against colon cancer HCT-15 (GI(50 )= 0.8 microM). The anti-HIV-1 results indicated that compound 6b displayed a good reduction of viral cytopathic effect (56.69%). The antimicrobial results showed that compound 5a was four times more active than ampicillin against P. aerugenosa (MIC =or< 25 microg/mL), compound 5b had twice the activity of ampicillin, while compounds 5d, 7c and 7f were equipotent to ampicillin. On the other hand, compound 7a was equipotent to ampicillin against P. vulgaris (MIC = 50 microg/mL).
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PMID:Synthesis of some novel substituted purine derivatives as potential anticancer, anti-HIV-1 and antimicrobial agents. 1735 64

Using the fixed-effect model, the author quantitatively estimated the risks of cancers of the colon, bladder, kidneys, and brain as well as non-Hodgkin's lymphoma and leukemia among firefighters. The risk of these six cancers was not markedly elevated when cohort mortality studies were considered. When all mortality studies were considered, however, there was a mild increase in risk for kidney cancer and non-Hodgkin's lymphoma, with a summary relative risk (sumRR) of 1.22 (95% confidence interval [CI] = 1.02-1.43) and 1.40 (95% CI = 1.20-1.60), respectively. A subcohort analysis based on duration of employment revealed that firefighters with 30 or more years of employment had a significantly increased mortality risk for colon cancer, sumRR of 1.51 (95% CI = 1.05-2.11); kidney cancer, sumRR of 6.25 (95% CI = 1.70-16.00); brain cancer, sumRR of 2.53 (95% CI = 1.27 7.07); and leukemia, sumRR of 2.87 (95% CI = 1.43-5.14). After firefighters had 40 or more years of employment, their risk of mortality was significantly increased for colon cancer, sumRR of 4.71 (95% CI = 2.03-9.27); kidney cancer, sumRR of 36.12 (95% CI = 4.03-120.42); and bladder cancer, sumRR of 5.7 (95% CI = 1.56-14.63). The risk for non-Hodgkin's lymphoma was elevated but not significantly so among firefighters with 20 or more years of employment, with sumRR of 1.72 (95% CI = 0.90-3.31). Kidney cancer risk was significantly elevated as early as the second decade of employment.
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PMID:Risk of cancer among firefighters: a quantitative review of selected malignancies. 1789 91

Sorafenib, a novel drug for metastatic renal cancer, has broad-spectrum activity against multiple tyrosine kinases, including Raf-1, vascular endothelial growth factor receptor and platelet-derived growth factor receptor. However, little is known about its effects on the immune system. In this report, we examine the effects of sorafenib on the proliferation and activation of human peripheral blood T cells, as well as its effects on T-cell-mediated immune response in mice. At concentrations similar to those used in patients, sorafenib inhibited the proliferation of primary human T cells in vitro. At more than 10 microM, sorafenib caused an irrecoverable inhibition of proliferation, even after drug withdrawal. In addition, sorafenib induced T-cell apoptosis at concentrations higher than 10 muM. sorafenib also caused G(0)/G(1) phase arrest, inhibition of CD25 and CD69 expression, interleukin-2 production and LCK phosphorylation in the T cells; all of these effects exhibited dose and time dependence. When tested against contact dermatitis in mice, sorafenib significantly reduced the ear swelling induced by picryl chloride. These findings suggest that sorafenib may cause the loss of T-cell immune response by inducing apoptosis and targeting LCK. This could potentially lead to immunosuppression in patients with cancer.
Leukemia 2008 Jun
PMID:Sorafenib inhibits activation of human peripheral blood T cells by targeting LCK phosphorylation. 1833 60

Fifty-one acylthioureas (ATUs) incorporating imidazolidine-2-thione or its upper cyclohomologue were prepared by parallel synthesis and evaluated against a high number of human cancer cell lines for antiproliferative activity. ATUs 1o (3,5-dichlorobenzoyl), 1s (2-furoyl), 3s (2-furoyl) and 1t (2-thenoyl) displayed activity against leukemia, melanoma LOX IMVI, non-small cell lung NCI-H522, renal 786-0, CAKI-1, SN12C, UO-31 and breast MCF7, MDA-MB-435, T-47D cancer cell lines in the 0.3-9.7 microM concentration range. Compound 14s exhibited selectivity for melanoma SK-MEL-5 (GI(50)<5 nM); 1s for leukemia MOLT-4 (GI(50): 300 nM); 1q, 3b and 3q for renal cancer UO-31 (GI(50): 70-200 nM); 8s, 9s for non-small cell lung cancer EKVX (GI(50): 300, 10 nM) and 3j for HOP-92 (GI(50): 700 nM) cell line.
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PMID:N-acylated and N,N'-diacylated imidazolidine-2-thione derivatives and N,N'-diacylated tetrahydropyrimidine-2(1H)-thione analogues: synthesis and antiproliferative activity. 1866 59


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