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Ym155 Inhibits Neuroblastoma Cell migration and Survival <i>in Vitro</i>and Tumor Growth and metastatic Burden in a Pre-Clinical model

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Journal of Cancer Therapy 2014年第13期5卷 1289-1302页

作者： Heather m. Calderone Akshita Dutta Lauren Smith Alexandra Eckardt Ping Zhao Giselle Saulnier Sholler Laboratory for Translational Neuroblastoma Research Van Andel Research Institute Grand Rapids USA Pediatric Oncology Translational Research Program Helen DeVos Children’s Hospital Grand Rapids USA michigan State University College of medicine Grand Rapids USA

Background: Neuroblastoma exhibits a high incidence of chromosomal translocations, the most common being the gain of a portion of the long arm of chromosome 17. This region includes the gene birc5/survivin, which is highly upregulated in neuroblastoma and correlates with poor prognosis. Survivin is a member of the inhibitor of apoptosis family of proteins and is involved in tumor cell survival and migration. Ym155 is a small molecule inhibitor of survivin transcription and has shown efficacy in several cancer model systems both?in vitro?and?in vivo. Procedure: Cells were treated with Ym155 and effects on migration, invasion, and apoptosis signaling were investigated?in vitro. Tumor burden was assessed in xenografted mice by measuring tumor volume and liver metastases. Results: Treatment with Ym155 caused a dose-dependent decrease in survivin expression and induction of apoptosis. Lower concentrations of Ym155 reduced cell migration and invasion by 15% - 50% which varied by cell line. In a xenograft model, Ym155 treatment inhibited tumor growth by 25% - 70%, reduced metastatic burden in the liver by 50%, and prolonged animal survival. Conclusion: The data suggest Ym155 as a possible therapeutic agent for metastatic neuroblastoma.

关键词： Neuroblastoma Ym155 Survivin metastasis Apoptosis

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Development and quality of bovine embryos produced in vitro using growth factor supplemented serum-free system

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Open Journal of Animal Sciences 2011年第3期1卷 97-105页

作者： Arindam Dhali Vahida m. Anchamparuthy Steve P. Butler Isis K. mullarky Ronald E. Pearson Frank C. Gwazdauskas 不详

The influence of a growth factor supplemented serum-free system on the development, gene expression, and cryotolerance of in vitro pro- duced bovine embryos was investigated. To assess the embryo development and gene ex- pression in blastocysts, abattoir-derived oo- cytes (obtained from 3 - 10 or mm follicles) were matured and fertilized in serum-free media and cultured in synthetic oviductal fluid sup- plemented with fetal bovine serum (FBS, 4%), epidermal growth factor (EGF, 10 ng/mL), insulin like growth factor-1 (IGF-1, 100 ng/mL), stem cell factor (SCF, 50 ng/mL) or combinations of the growth factors. Expressions of selected gene transcripts were relatively quantified in the d 8 blastocysts. To assess the cryotolerance, d 4 morulae (derived from 3 - 10 mm follicles and cultured with the supplementation of FBS or combinations of the growth factors) were vitri- fied, thawed and cultured (with respective sup- plementations). Total cell number and DNA frag- mentation in blastocysts derived from the vitri- fied morulae were assessed through TUNEL assay. The rate (%) of cleavage, blastocyst and expanded/hatched blastocyst did not differ among the culture medium supplementations within the follicle size of 3 - 10 mm (range 65.1 ± 4.3 - 75.4 ± 3.9;22.4 ± 3.9 - 36.4 ± 3.6;and 11.2 ± 2.9 - 23.3 ± 3.2, respectively) or mm (range 59.3 ± 4.2 - 74.5 ± 3.7;15.0 ± 3.5 - 28.7 ± 4.5;and 9.3 ± 2.8 - 17.3 ± 2.7, respectively). Nevertheless, significantly lower (P mentations were observed for the oocytes derived from mpared to 3 - 10 mm follicles. The expression patterns of BCL-2, BAX, HSP1A1, GJA1 and birc5 tran- scripts varied significantly (P birc5 in the blastocysts derived from 3 - 10 mm follicles. Following thaw and culture, the development (%) of vitrified morulae into expanded/hatched blastocysts was lower (P mentation of growth fac- tors compared to FBS. In contrast,

关键词： IVF Growth Factors Embryo Development Gene Expression Cryotolerance Bovine

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