Promising Drug (promising + drug)

Distribution by Scientific Domains

Terms modified by Promising Drug

  • promising drug target

  • Selected Abstracts

    Interferon alpha receptors are important for antiproliferative effect of interferon-, against human hepatocellular carcinoma cells

    Bazarragchaa Damdinsuren
    Aim:, Interferon (IFN)-, is a promising drug for the prevention and treatment of hepatocellular carcinoma (HCC). We reported that responders to IFN-,/5-fluorouracil combination therapy expressed higher IFN alpha receptor (IFNAR)2 in tumor. Herein we studied involvement of IFNARs in response to IFN-, in HCC cells. Methods:, IFN-, sensitivity and expression of IFNARs were studied in six HCC cell lines (HuH7, PLC/PRF/5, HLE, HLF, HepG2, Hep3B) using growth-inhibitory and RT-PCR, Western blot assays. Short interfering RNAs (SiRNAs) against IFNAR1 and 2 were used to analyze the role of the IFNARs in IFN-,'s effect and signal transduction. Results:, The expressions of IFNAR1 and 2c mRNAs were higher in PLC/PRF/5 cells than those in other cell lines, and PLC/PRF/5 cells expressed abundant IFNAR2c on their cell membrane. When we examined the sensitivity of the HCC cell lines to the growth-inhibitory effect of IFN-,, PLC/PRF/5 exhibited a significant response, while the other cells were much more resistant. Knockdown of either IFNAR1 or 2 using siRNAs suppressed the IFN-,'s signal transduction (2.5-fold), and decreased the growth-inhibitory effect (down by 69.9% and 67.3%). Conclusion:, The results suggest that the expression of IFNAR1 and IFNAR2c independently are important for the antiproliferative effect of IFN-, in HCC cells. [source]

    ApoG2, a novel inhibitor of antiapoptotic Bcl-2 family proteins, induces apoptosis and suppresses tumor growth in nasopharyngeal carcinoma xenografts

    Zhe-Yu Hu
    Abstract Nasopharyngeal carcinoma (NPC) is a common malignant tumor in South China. It has been reported that overexpression of antiapoptotic Bcl-2 family proteins in NPC has caused the lack of long-term efficacy of conventional therapies. Apogossypolone (ApoG2), a novel small-molecule inhibitor of antiapoptotic Bcl-2 family proteins, has been discovered as the optimized derivative of gossypol. In this study, we found that in NPC cells, ApoG2 totally blocked the antiapoptotic function of Bcl-2 family proteins without affecting the expression levels of these proteins. ApoG2 selectively inhibited proliferation of 3 NPC cell lines (C666-1, CNE-1 and CNE-2) that highly expressed the antiapoptotic Bcl-2 proteins. This inhibitory activity was associated with release of cytochrome c, activation of caspase-9 and caspase-3 and apoptosis of sensitive NPC cells. However, ApoG2 had no obvious inhibitory effect on NPC cell line HONE-1, which expressed antiapoptotic Bcl-2 and Bcl-xL at a low level. We further found that ApoG2 effectively suppressed tumor growth of NPC xenografts in nude mice and enhanced the antitumor effect of CDDP (cisplatin) on NPC cells in vitro and in vivo. Immunohistochemical results showed that the expression of CD31 decreased after ApoG2 treatment, which suggested inhibition of angiogenesis in NPC xenografts. Our findings strongly suggest that ApoG2 may serve as a novel inhibitor of Bcl-2 family proteins and, by targeting these proteins, may become a promising drug for the treatment of NPC. © 2008 Wiley-Liss, Inc. [source]

    Vinylic telluride derivatives as promising pharmacological compounds with low toxicity

    V. C. Borges
    Abstract The aim of the present study was to evaluate pharmacological and toxicological properties of (Z)-2-(methylthio)-1-(butyltelluro)-1-phenylethene 1a, (Z)-1-(4-methylphenylsulfonyl)-2-(phenyltelluro)-2-phenylethene 1b, (Z)-2-(butyltelluro)-1-(benzylthio)-1-heptene 1c and (Z)-2-(phenylthio)-1-(butyltelluro)-1-phenylethene 1d. In vitro, vinylic telluride derivatives 1a, 1d and 1c were more effective in reducing lipid peroxidation than compound 1b. The maximal inhibitory effect of vinylic telluride derivatives on lipid peroxidation was in the following order: 1a = 1d > 1c > 1b. Compound 1b was more potent in inhibiting , -ALA-D activity (, -aminolevulinate dehydratase) than compounds 1c and 1d. Based on the in vitro properties presented by compounds 1a (an antioxidant) and 1b (a pro-oxidant), toxicological parameters were assessed in vivo and ex vivo in rats. Calculated LD50 of compounds 1a and 1b, administered by oral route, were 20.5 and 1.44 µmol kg,1, respectively. Compound 1b induced behavioral alterations in the open field test. Renal and spleenic , -ALA-D activities were inhibited in rats treated orally with compound 1a. Compound 1b stimulated , -ALA-D activity in liver and spleen of rats. Rats treated with compound 1b had increased hepatic, renal and spleenic lipid peroxidation. Renal and hepatic markers were not altered when compounds 1a and 1b were administered to rats at doses of around LD50, while compound 1a at high doses changed aspartate aminotransferase activity and urea levels. Based on in vitro results, this study demonstrated that compounds 1a and 1d are promising antioxidant compounds. Ex vivo data reinforce compound 1a as a promising drug for more detailed pharmacological studies. Copyright © 2008 John Wiley & Sons, Ltd. [source]

    Investigation of ,2 -adrenoceptor subtype selectivity and organ specificity for bedoradrine (KUR-1246), a novel tocolytic beta-adrenergic receptor stimulant

    Yoshihito Inoue
    Abstract Objectives:, The aim of this study was to evaluate the beta-adrenergic receptor (,-AR) selectivity, organ specificity and efficacy of delaying the onset of spontaneous delivery of bedoradrine (KUR-1246), a novel uterine relaxant. Methods:, ,-AR selectivity was evaluated in terms of the amount of cyclic adenosine monophosphate produced by bedoradrine, ritodrine and isoprenaline in Chinese hamster ovary cells expressing human ,1 -, ,2 -AR or ,3 -AR. Inhibition of contractions of the atrium, trachea and proximal colon by bedoradrine were compared with those of the uterus in pregnant rats using an organ bath method. Finally, the delaying effect of bedoradrine on spontaneous labor was evaluated by an in vivo study using term pregnant rats. Results:, EC50 values of bedoradrine for cyclic adenosine monophosphate production in Chinese hamster ovary cells via ,1 -, ,2 - and ,3 -AR were 2400 ± 30, 2.9 ± 0.10 and 363 ± 3 nmol/L, respectively, indicating that bedoradrine had 832- and 126-fold higher selectivity for ,2 -AR than for ,1 - and ,3 -AR. EC50 values of bedoradrine for the uterus, atrium, trachea and proximal colon were 1.01 ± 0.27, 2300 ± 356, 1610 ± 299 and 219 ± 23.5 nmol/L, respectively. Thus, bedoradrine was 2280-, 1590- and 217-fold more specific for the uterus than for the atrium, trachea and proximal colon, respectively. Bedoradrine delayed the spontaneous delivery of 21-day-pregnant rats in a dose-dependent manner. Conclusions:, Bedoradrine is a promising drug for the treatment of preterm labor in obstetrical practice because it has better selectivity for ,2 -AR and specificity for the uterus than currently used agents and may effectively delay spontaneous delivery. [source]

    Rosiglitazone Inhibits Cell Proliferation by Inducing G1 Cell Cycle Arrest and Apoptosis in ADPKD Cyst-Lining Epithelia Cells

    Yawei Liu
    Many drugs inhibiting cell proliferation have been proved to be effective in slowing the disease progression in ADPKD. Recent evidence has suggested that peroxisome proliferator-activated receptor , (PPAR,) ligands have anti-neoplasm effects through inhibiting cell growth and inducing cell apoptosis in various cancer cells. In the present study, we examined the expression of PPAR, in human ADPKD kidney tissues and cyst-lining epithelial cell line, and found that the expression of PPAR, was greater in ADPKD kidney tissues and cyst-lining epithelial cell line than in normal kidney tissues and human kidney cortex (HKC) cell line. Rosiglitazone inhibited significantly proliferation of cyst-lining epithelial cells in a concentration- and time-dependent manner. These effects were diminished by GW9662, a specific PPAR, antagonist. Cell cycle analysis showed a G0/G1 arrest in human ADPKD cyst-lining epithelial cells with rosiglitazone treatment. Analysis of cell cycle regulatory proteins revealed that rosiglitazone decreased the protein levels of proliferating cell nuclear antigen, pRb, cyclin D1, cyclin D2 and Cdk4 but increased the levels of p21 and p27 in a dose-dependent manner. Rosiglitazone also induced apoptosis in cyst-lining epithelial cells, which was correlated with increased bax expression and decreased bcl-2 expression. These results suggest PPAR, agonist might serve as a promising drug for the treatment of ADPKD. [source]

    Alterations of the c-kit gene in testicular germ cell tumors

    CANCER SCIENCE, Issue 6 2003
    Yuji Sakuma
    Expression and gain-of-function mutation of the c-kit gene, that encodes a receptor tyrosine kinase (KIT), have been reported in mast cell tumors and gastrointestinal stromal tumors (GISTs). Among human testicular germ cell tumors (GCTs), seminomas and seminoma components of mixed GCTs have also been shown to express KIT, but only one study has found the c-kit gene mutation at exon 17 in seminoma. To elucidate the frequency and location of the c-kit gene mutation of testicular GCTs, we analyzed the whole coding region of the c-kit complementary DNA along with 4 mutational hot spots (exons 9, 11, 13 and 17) of the c-kit genomic DNA by polymerase chain reaction and direct sequencing. Somatic mutations were found in 4 pure seminomas of 34 testicular GCTs (11.8%). One mutation was found in exon 11 (W557R) and the others were observed in exon 17 (D816H and D816V). These types of mutations were reported in GISTs (W557R), seminoma (D816H) and mastocytosis (D816V) and were considered to be gain-of-function mutations, although there were no differences of any clinicopathological factors or outcome between patients with and without mutations. Additionally, we also demonstrated coexpression of Gly-Asn-Asn-Lys510,513 (GNNK)+ and GNNK- isoforms of the c-kit gene with dominance of the GNNK- transcript in all testicular GCTs. The mutations and/or preferential expression of GNNK- isoform of the c-kit gene might play an important role in the development of testicular GCTs, and these tumors may also be targets for STI571, which is a promising drug for advanced and metastatic GISTs. [source]

    Mycophenolate mofetil in uveitis

    P NERI
    Purpose To review the current Literature and to describe the experience of a tertiary referral centre on the use of mycophenolate mofetil (MMF) treatment in uveitis. Methods The current literature is reviewed and the experience of a tertiary referral centre is reported. Results The long-lasting remission in several systemic diseases, such as Crohn's disease, severe atopic dermatitis, Wegener's granulomatosis and microscopic polyangioitis, rheumatoid arthritis, pemphigus vugaris, and psoriasis, have been proven. Recent publications have have recently confirmed the satisfactory control of uveitis with MMF in a large cohort of patients. Moreover, the long-term control of cystoid macular oedema (CMO) unresponsive to the traditional therapy has been described, as well as for the choroidal neovascularization (CNV). Conclusion Non-infectious uveitis is one of the leading causes of visual impairment in ophthalmology. Steroids can control such disease, even though a long-term treatment is not recommended: several complications, such as high blood sugar level, osteoporosis, blood cell abnormalities, cataract and glaucoma, can occur. MMF is a reversible, non competitive, selective inhibitor of the de-novo pathway of purine synthesis; mycophenolic acid has a strong effect to Type II isoform of inosine monophosphate dehydrogenase enzyme, providing a stronger cytostatic effect on lymphocytes than on other cells types, with minor action to Type I expressed in most other cells. The specific action of MMF on selected targets makes it a promising drug for the control of non-infectious intraocular inflammations. [source]

    Comparative activity of linezolid against staphylococci and enterococci isolated in Italy

    S. Stefani
    The activity of linezolid, a new oxazolidinone, was tested against 862 Gram-positive cocci isolated in Italy and compared with the activities of 12 antibiotics. Overall, MIC90s for linezolid (2,4 mg/L) indicated an in vitro activity comparable to that of vancomycin in methicillin-resistant Staphylococcus aureus (4 mg/L), S. epidermidis (2 mg/L) and methicillin-susceptible strains. Enterococcus faecalis strains were susceptible to linezolid (MIC90 2,4 mg/L), glycopeptides and , -lactams. In E. faecium, only glycopeptides (MIC90 2 mg/L) and linezolid (MIC90 2 mg/L) were active. Linezolid was the only drug active against two strains of Enterococcus showing a VanA phenotype. Owing to its antibacterial profile, linezolid represents a promising drug for the treatment of Gram-positive infections. [source]

    Lithium treatment in Aarhus: contributions and controversies through half a century

    Per Vestergaard
    In 1954 the first of several hundred publications on the use of lithium for treatment of affective disorders, lithium's unwanted effects, and its pharmacology was authored at the Aarhus University Psychiatric Hospital, the majority with Professor, now emeritus, Mogens Schou playing the principal part. The early part of this long series of papers highlights the pharmacology of lithium with its renal excretion, low therapeutic index, and ensuing risk of intoxication, the prophylactic effect not only against manic episodes but also the depressive ones and finally the long-term renal structural and functional impairment. Later papers present the problems related to lithium's lower effectiveness in routine clinical use, the problems of non-adherence, the dose effect relationships, and the problems inherent to establishing effective treatment service delivery. The present priority of the Aarhus lithium group is the simple large scale pragmatic effectiveness studies in which, together with domestic and foreign collaborators, we compare the long-term effectiveness of lithium with new promising drugs with mood stabilizing properties. The story of treatment with lithium in aarhus highlights important steps in the development of effective and comprehensive treatments for bipolar patients. [source]

    Glycogen synthase kinase 3 (GSK-3) inhibitors as new promising drugs for diabetes, neurodegeneration, cancer, and inflammation

    Ana Martinez
    Abstract Glycogen synthase kinase 3 (GSK-3) was initially described as a key enzyme involved in glycogen metabolism, but is now known to regulate a diverse array of cell functions. Two forms of the enzyme, GSK-3, and GSK-3,, have been previously identified. Small molecules inhibitors of GSK-3 may, therefore, have several therapeutic uses, including the treatment of neurodegenerative diseases, diabetes type II, bipolar disorders, stroke, cancer, and chronic inflammatory disease. As there is lot of recent literature dealing with the involvement of GSK-3 in the molecular pathways of different diseases, this review is mainly focused on the new GSK-3 inhibitors discovered or specifically developed for this enzyme, their chemical structure, synthesis, and structure,activity relationships, with the aim to provide some clues for the future optimization of these promising drugs. © 2002 Wiley Periodicals, Inc. Med Res Rev, 22, No. 4, 373,384, 2002; Published online in Wiley InterScience ( DOI 10.1002/med.10011 [source]