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91.
Telomerase expression strongly correlates with the grade of malignancy in glioma with inhibition illustrating a definite increase
in chemosensitivity. This study was designed to investigate the effects of a green tea derivative, epigallocatechin-3-gallate
(EGCG); together with either cisplatin or tamoxifen in glioma, and to investigate whether these effects are mediated through
telomerase suppression. EGCG showed a significant cytotoxic effect on 1321N1 cells after 24 h and on U87-MG cells after 72 h
(P < 0.001) without significantly affecting the normal astrocytes. Treatment with EGCG inhibited telomerase expression significantly
(P < 0.01) and enhanced the effect of cisplatin and tamoxifen in both 1321N1 (P < 0.01) and U87-MG (P < 0.001) cells. EGCG, as a natural product has enormous potential to be an anti-cancer agent capable of enhancing tumour
cell sensitivity to therapy. 相似文献
92.
Amal M. Mohamed Tarek F. Elwakil Ibrahim M. Taher Mohamed M. Elbarbary Hesham F. Kayed Hassan A. Hussein Ola M. Eid 《Cell and tissue research》2009,338(1):107-115
Cyclin D1 gene amplification has been reported to promote abnormal endothelial cell proliferation and angiogenesis; these
findings constantly present in proliferating haemangiomas. The present study was conducted to evaluate cyclin D1 gene amplification
by fluorescence in situ hybridization analysis in tissue biopsies of 22 proliferating haemangiomas from 20 infants. Two significant
correlations of cyclin D1 gene amplification with the early onset and the duplication of proliferating haemangiomas have been
observed. Moreover, a significant correlation (P≤0.05) has been found between the treatment parameters of proliferating haemangiomas with the amplified versus the normal
cyclin D1 gene. Proliferating haemangiomas with the amplified cyclin D1 gene required more frequent flashlamp pulsed dye laser
treatment sessions at the maximum dosimetry and more frequent intralesional steroid injections at the maximum dose/injection
but treatment outcomes were limited. The more frequent post-treatment complications among proliferating haemangiomas with
cyclin D1 gene amplification might be attributable not only to the associated more aggressive natural course, but also to
the higher treatment parameters needed for effective treatment. Within the limitations of the present study, cyclin D1 gene
amplification was seen for the first time in proliferating haemangiomas. We have found that the amplification of the cyclin
D1 gene can predict the more aggressive natural course of proliferating haemangiomas and the limited outcome and higher incidence
of complications after non–excision treatment modalities. The present findings reflect the possible usefulness of antisense
cyclin D1 to improve the therapeutic outcome of proliferating haemangiomas. 相似文献
93.
David V. Smil Sukhdev Manku Yves A. Chantigny Silvana Leit Amal Wahhab Theresa P. Yan Marielle Fournel Christiane Maroun Zuomei Li Anne-Marie Lemieux Alina Nicolescu Jubrail Rahil Sylvain Lefebvre Anthony Panetta Jeffrey M. Besterman Robert Déziel 《Bioorganic & medicinal chemistry letters》2009,19(3):688-692
In an effort to identify HDAC isoform selective inhibitors, we designed and synthesized novel, chiral 3,4-dihydroquinoxalin-2(1H)-one and piperazine-2,5-dione aryl hydroxamates showing selectivity (up to 40-fold) for human HDAC6 over other class I/IIa HDACs. The observed selectivity and potency (IC50 values 10–200 nM against HDAC6) is markedly dependent on the absolute configuration of the chiral moiety, and suggests new possibilities for use of chiral compounds in selective HDAC isoform inhibition. 相似文献
94.
Oscar M. Saavedra Ljubomir Isakovic David B. Llewellyn Lijie Zhan Naomy Bernstein Stephen Claridge Franck Raeppel Arkadii Vaisburg Nadine Elowe Andrea J. Petschner Jubrail Rahil Norman Beaulieu A. Robert MacLeod Daniel Delorme Jeffrey M. Besterman Amal Wahhab 《Bioorganic & medicinal chemistry letters》2009,19(10):2747-2751
The inhibitory activity of base-modified SAH analogues and the specificity of inhibiting human DNMT1 and DNMT3b2 enzymes was explored. The 6-amino group was essential while the 7-N of the adenine ring of SAH could be replaced by CH– without loss of activity against both enzymes. The introduction of small groups at the 2-position of the adenine moiety favors DNMT1 over DNMT3b2 inhibition whereas alkylation of the N6-amino moiety favors the inhibition of DNMT3b2 enzyme. 相似文献
95.
Ping La Amal P. Fernando Zhi Wang Ameen Salahudeen Guang Yang Qing Lin Clyde J. Wright Phyllis A. Dennery 《The Journal of biological chemistry》2009,284(52):36302-36311
Zinc protoporphyrin IX (ZnPP), an endogenous heme analogue that inhibits heme oxygenase (HO) activity, represses tumor growth. It can also translocate into the nucleus and up-regulate heme oxygenase 1 (HMOX1) gene expression. Here, we demonstrate that tumor cell proliferation was inhibited by ZnPP, whereas tin protoporphyrin (SnPP), another equally potent HO-1 inhibitor, had no effect. Microarray analysis on 128 tumorigenesis related genes showed that ZnPP suppressed genes involved in cell proliferation and angiogenesis. Among these genes, CYCLIN D1 (CCND1) was specifically inhibited as were its mRNA and protein levels. Additionally, ZnPP inhibited CCND1 promoter activity through an Sp1 and Egr1 overlapping binding site (S/E). We confirmed that ZnPP modulated the S/E site, at least partially by associating with Sp1 and Egr1 proteins rather than direct binding to DNA targets. Furthermore, administration of ZnPP significantly inhibited cyclin D1 expression and progression of a B-cell leukemia/lymphoma 1 tumor in mice by preferentially targeting tumor cells. These observations show HO independent effects of ZnPP on cyclin D1 expression and tumorigenesis. 相似文献
96.
Amina Abdelaal Hassan Abd El-Ghaffar HosamEldeen Mohammad Zaghloul Noha El mashad Ehab Badran Amal Fathy 《Annals of clinical microbiology and antimicrobials》2009,8(1):1-8
Background
Tuberculosis is a growing international health concern. It is the biggest killer among the infectious diseases in the world today. Early detection of drug resistance allows starting of an appropriate treatment. Resistance to drugs is due to particular genomic mutations in specific genes of Mycobacterium tuberculosis(MTB). The aim of this study was to identify the presence of Isoniazid (INH) and Rifampicin(RIF) drug resistance in new and previously treated tuberculosis (TB) cases using DNA sequencing.Methods
This study was carried out on 153 tuberculous patients with positive Bactec 460 culture for acid fast bacilli.Results
Of the 153 patients, 105 (68.6%) were new cases and 48 (31.4%) were previously treated cases. Drug susceptibility testing on Bactec revealed 50 resistant cases for one or more of the first line antituberculous. Genotypic analysis was done only for rifampicin resistant specimens (23 cases) and INH resistant specimens (26 cases) to detect mutations responsible for drug resistance by PCR amplification of rpoB gene for rifampicin resistant cases and KatG gene for isoniazid resistant cases. Finally, DNA sequencing was done for detection of mutation within rpoB and KatG genes. Genotypic analysis of RIF resistant cases revealed that 20/23 cases (86.9%) of RIF resistance were having rpoB gene mutation versus 3 cases (13.1%) having no mutation with a high statistical significant difference between them (P < 0.001). Direct sequencing of Kat G gene revealed point mutation in 24/26 (92.3%) and the remaining 2/26 (7.7%) had wild type KatG i.e. no evidence of mutation with a high statistical significant difference between them (P < 0.001).Conclusion
We can conclude that rifampicin resistance could be used as a useful surrogate marker for estimation of multidrug resistance. In addition, Genotypic method was superior to that of the traditional phenotypic method which is time-consuming taking several weeks or longer. 相似文献97.
98.
Mesenchymal stem cell therapy: A promising cell‐based therapy for treatment of myocardial infarction 下载免费PDF全文
Ayman El‐Sayed Shafei Mahmoud Ahmed Ali Hazem G. Ghanem Ahmed I. Shehata Ahmed A. Abdelgawad Hossam R. Handal Kareem A. Talaat Ahmed E. Ashaal Amal S. El‐Shal 《The journal of gene medicine》2017,19(12)
For decades, mesenchymal stem (MSCs) cells have been used for cardiovascular diseases as regenerative therapy. This review is an attempt to summarize the types of MSCs involved in myocardial infarction (MI) therapy, as well as its possible mechanisms effects, especially the paracrine one in MI focusing on the studies (human and animal) conducted within the last 10 years. Recently, reports showed that MSC therapy could have infarct‐limiting effects after MI in both experimental and clinical trials. In this context, various types of MSCs can help cardiac regeneration by either revitalizing the cardiac stem cells or revascularizing the arteries and veins of the heart. Furthermore, MSCs could produce paracrine growth factors that increase the survival of nearby cardiomyocytes, as well as increase angiogenesis through recruitment of stem cell from bone marrow or inducing vessel growth from existing capillaries. Recent research suggests that the paracrine effects of MSCs could be mediated by extracellular vesicles including exosomes. Exosomal microRNAs (miRNAs) released by MSCs are promising therapeutic hotspot target for MI. This could be attributed to the role of miRNA in cardiac biology, including cardiac regeneration, stem cell differentiation, apoptosis, neovascularization, cardiac contractility and cardiac remodeling. Furthermore, gene‐modified MSCs could be a recent promising therapy for MI to enhance the paracrine effects of MSCs, including better homing and effective cell targeted tissue regeneration. Although MSC therapy has achieved considerable attention and progress, there are critical challenges that remains to be overcome to achieve the most effective successful cell‐based therapy in MI. 相似文献
99.
Amal A. Aloud Chinnadurai Veeramani Mohammed A. Alsaif Ahmed S. El Newehy Khalid S. Al-Numair 《Redox report : communications in free radical research》2017,22(6):290-300
Objective: To examine the effect of galangin on hyperglycemia-mediated oxidative stress in streptozotocin (STZ)-induced diabetic rats.Methods: Diabetes was induced by intraperitoneal administration of low-dose STZ (40?mg/kg body weight (BW)) into male albino Wistar rats. Galangin (8?mg/kg BW) or glibenclamide (600?µg/kg BW) was given orally, once daily for 45 days to normal and STZ-induced diabetic rats.Results: Diabetic rats showed significantly increased levels of plasma glucose, thiobarbituric acid reactive substances, lipid hydroperoxides, and conjugated dienes. The levels of insulin and non-enzymatic antioxidants (vitamin C, vitamin E, reduced glutathione) and the activity of enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase (GST)) were decreased significantly in diabetic control rats. These altered plasma glucose, insulin, lipid peroxidation products, enzymatic and non-enzymatic antioxidants ions were reverted to near-normal level after the administration of galangin and glibenclamide.Conclusion: The present study shows that galangin decreased oxidative stress and increased antioxidant status in diabetic rats, which may be due to its antidiabetic and antioxidant potential. 相似文献
100.
Poor drug solubility and dissolution rate remain to be one of the major problems facing pharmaceutical scientists, with approximately 40% of drugs in the industry categorised as practically insoluble or poorly water soluble. This in turn can lead to serious delivery challenges and poor bioavailability. The aim of this research was to investigate the effects of the surfactants, poloxamer 407 (P407) and caprol® PGE 860 (CAP), at various concentrations (0.1, 0.5, 1 and 3% w/v) on the enhancement of the dissolution properties of poorly water-soluble drug, naproxen, using in situ micronisation by solvent change method and freeze-drying. The extent at which freeze-drying influences the dissolution rate of naproxen microcrystals is investigated in this study by comparison with desiccant-drying. All formulations were evaluated and characterised using particle size analysis and morphology, in vitro dissolution studies, differential scanning calorimetry (DSC), and Fourier transform infra-red (FT-IR) spectroscopy. An increase in poloxamer 407 concentration in freeze-dried formulations led to enhancement of drug dissolution compared to desiccator-dried formulations, naproxen/caprol® PGE 860 formulations and untreated drug. DSC and FT-IR results show no significant chemical interactions between drug and poloxamer 407, with only very small changes to drug crystallinity. On the other hand, caprol® PGE 860 showed some interactions with drug components, alterations to the crystal lattice of naproxen, and poor dissolution profiles using both drying methods, making it a poor choice of excipient. 相似文献