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Moosavi, Mohammad Amin,Yazdanparast, Razieh,Lotfi, Abbas Korean Society for Biochemistry and Molecular Biol 2006 Journal of biochemistry and molecular biology Vol.39 No.5
Since differentiation therapy is one of the promising strategies for treatment of leukemia, universal efforts have been focused on finding new differentiating agents. In that respect, we used guanosine 5'-triphosphate (GTP) to study its effects on K562 cell line. GTP, at concentrations between 25-200 ${\mu}M$, inhibited proliferation (3-90%) and induced 5-78% increase in benzidine-positive cells after 6-days of treatments of K562 cells. Flow cytometric analyses of glycophorine A (GPA) showed that GTP can induce expression of this marker in more mature erythroid cells in a time- and dose-dependent manner. These effects of GTP were also accompanied with inhibition of DNA synthesis (measured by [$^3H$]-thymidine incorporation) and early S-phase cell cycle arrest by 96 h of exposure. In contrast, no detectable effects were observed when GTP administered to unstimulated human peripheral blood lymphocytes (PBL). However, GTP induced an increase in proliferation, DNA synthesis and viability of mitogen-stimulated PBL cells. In addition, growth inhibition and differentiating effects of GTP were also induced by its corresponding nucleotides GDP, GMP and guanosine (Guo). In heat-inactivated medium, where rapid degradation of GTP via extracellular nucleotidases is slow, the anti-proliferative and differentiating effects of all type of guanine nucleotides (except Guo) were significantly decreased. Moreover, adenosine, as an inhibitor of Guo transporter system, markedly reduced the GTP effects in K562 cells, suggesting that the extracellulr degradation of GTP or its final conversion to Guo may account for the mechanism of GTP effects. This view is further supported by the fact that GTP and Guo are both capable of impeding the effects of mycophenolic acid. In conclusion, our data will hopefully have important impact on pharmaceutical evaluation of guanine nucleotides for leukemia treatments.
Moosavi, Mohammad Amin,Yazdanparast, Razieh,Sanati, Mohammad Hasan Korean Society for Biochemistry and Molecular Biol 2005 Journal of biochemistry and molecular biology Vol.38 No.4
3-hydrogenwadaphnin (3-HK) is a new daphnane-type diterpene ester isolated from Dendrostellera lessertii with strong anti-tumoral activity in animal models and in cultures. Here, prolonged effects of this new agent on proliferation and viability of several different cancerous cell lines were evaluated. Using [$^3H$]thymidine incorporation, it was found that the drug inhibited cell proliferation and induced G1/S cell cycle arrest in leukemic cells 24 h after a single dose treatment. The cell viability of Jurkat cells was also decreased by almost 10%, 31% and 40% after a single dose treatment (7.5 nM) at 24, 48 and 72 h, respectively. The drug-treated cells were stained with acridine orange/ethidium bromide to document the chromatin condensation and DNA fragmentation. These observations were further confirmed by detection of DNA laddering pattern in the agarose gel electrophoresis of the extracted DNA from the treated cells. Treatment of K562 cells with the drug at 7.5, 15 and 30 nM caused apoptosis in 25%, 45% and 65% of the cells, respectively. Exogenous addition of $25-50\;{\mu}M$ guanosine and/or deoxyguanosine to the cell culture of the drug-treated cells restored DNA synthesis, released cell arrest at G1/S checkpoint and decreased the apoptotic cell death caused by the drug. These observations were not made using adenosine. However, the drug effects on K562 cells were potentiated by hypoxanthine. Based on these observations, perturbation of GTP metabolism is considered as one of the main reasons for apoptotic cell death by 3-HK.
Moosavi, Mohammad Amin,Yazdanparast, Razieh,Lotfi, Abbas Korean Society for Biochemistry and Molecular Biol 2006 Journal of biochemistry and molecular biology Vol.39 No.6
Recently, we have reported that 3-hydrogenkwadaphnin (3-HK), a diterpene ester isolated from Dendrostellera lessertii (Thymealeaceae), is very effective against leukemia cell lines without any detectable effects on normal cells (Moosavi et al., 2005b). In this study, we report that 3-HK induces $G_1$ cell-cycle arrest, differentiation and apoptosis in APL NB4 cell line. Indeed, the drug between 24 to 96 h induced 7-65% growth inhibition of NB4 cells. Cell viability was also decreased by 2-55% between 24 to 96 h treatments with the drug, respectively. These effects of the drug were also dose-dependent. According to flow cytomtry results, 3-HK (15 nM) induced a significant G1-arrest up to 24 h which was consequently followed with appearance of sub-$G_1$ peak at 72 to 96 h. Hoechst 33258 staining and DNA fragmentation assays confirmed the occurrence of apoptosis among the treated cells. On the other hand, NBT reducing assay, Wright-Giemsa staining, phagocytic activity and expression of cell surface markers (CD11b and CD14) confirmed that the inhibition of proliferation is associated with differentiation especially toward macrophage-like morphology. Interestingly, 3-HK at 5 and 10 nM enhanced the effects of all-trans retinoic acid (ATRA) in NB4 cells. Based on these results, 3-HK might become an ideal candidate for treatment of APL patients pending full exploration of its biological functions.
Breast Cancer Screening Barriers from the Womans Perspective: a Meta-synthesis
Azami-Aghdash, Saber,Ghojazadeh, Morteza,Sheyklo, Sepideh Gareh,Daemi, Amin,Kolahdouzan, Kasra,Mohseni, Mohammad,Moosavi, Ahmad Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.8
Background: The principal aim of health service providers in the field of breast cancer is to detect and treat lesions at an appropriate time. Therefore, identification of barriers to screening can be very helpful. The present study aimed to systematically review the qualitative studies for extracting and reporting the barriers of screening for breast cancer from the womans perspective. Materials and Methods: In this systematic review; Pubmed, Google Scholar, Ovid Scopus, Cochrane Library, Iranmedex, and SID were searched using the keywords: screening barriers, cancer, qualitative studies, breast and their Persian equivalents, and the needed data were extracted and analyzed using an extraction table. To assess the quality of the studies, the Critical Appraisal Skills Programme (CASP) tool was used. Results: From 2,134 related articles that were found, 21 articles were eventually included in the study. The most important barriers from the point of view of 1,084 women were lack of knowledge, access barriers (financial, geographical, cultural), fear (of results and pain), performance of service providers, women's beliefs, procrastination of screening, embarrassment, long wait for getting an appointment, language problems, and previous negative experiences. Articles' assessment score was 68.9. Conclusions: Increasing women's knowledge, reducing the costs of screening services, cultural promotion for screening, presenting less painful methods, changing beliefs of health service providers, provision of privacy for giving service, decreasing the waiting time, and providing high quality services in a respectful manner can be effective ways to increase breast cancer screening.