| 2 | Approaches to identifying drug resistance mechanisms to clinically relevant treatments in childhood rhabdomyosarcoma显示文摘Aim:Despite aggressive multiagent protocols,patients with metastatic rhabdomyosarcoma(RMS)have poor prognosis.In a recent high-risk trial(ARST0431),25% of patients failed within the first year,while on therapy and 80% had tumor progression within 24 months.However,the mechanisms for tumor resistance are essentially unknown.Here we explore the use of preclinical models to develop resistance to complex chemotherapy regimens used in ARST0431.Methods:A Single Mouse Testing(SMT)protocol was used to evaluate the sensitivity of 34 RMS xenograft models to one cycle of vincristine,actinomycin D,cyclophosphamide(VAC)treatment.Tumor response was determined by caliper measurement,and tumor regression and event-free survival(EFS)were used as endpoints for evaluation.Treated tumors at regrowth were transplanted into recipient mice,and the treatment was repeated until tumors progressed during the treatment period(i.e.,became resistant).At transplant,tumor tissue was stored for biochemical and omics analysis.Results:The sensitivity to VAC of 34 RMS models was determined.EFS varied from 3 weeks to>20 weeks.Tumor models were classified as having intrinsic resistance,intermediate sensitivity,or high sensitivity to VAC therapy.Resistance to VAC was developed in multiple models after 2-5 cycles of therapy;however,there were examples where sensitivity remained unchanged after 3 cycles of treatment.Conclusion:The SMT approach allows for in vivo assessment of drug sensitivity and development of drug resistance in a large number of RMS models.As such,it provides a platform for assessing in vivo drug resistance mechanisms at a“population”level,simulating conditions in vivo that lead to clinical resistance.These VAC-resistant models represent“high-risk”tumors that mimic a preclinical phase 2 population and will be valuable for identifying novel agents active against VAC-resistant disease. | Samson Ghilu Christopher L.Morton Angelina V.Vaseva Siyuan Zheng Raushan T.Kurmasheva Peter J.Houghton | 2022 | Cancer Drug Resistance2022，5，1： | 0 |
| 3 | Morphotaxonomy and seasonal distribution of planktonic and benthic Prorocentrales in Karachi waters,Pakistan Northern Arabian Sea显示文摘Morphotaxonomy and seasonal abundance of dinoflagellates of the genera Prorocentrum and Mesoporos(Prorocentrales) were studied from nutrient-rich waters,Karachi Harbor and the mouth of the Manora Channel,Pakistan during May 2002-July 2003.Using both light and scanning electron microscopy,13 species of Prorocentrales were identified according to cell shape,size,ornamentation of thecal plates,and architecture of apical platelets,apical pore area,marginal pores,and intercalary bands.P.sigmoides,P.arcuatum,P.scutellum,P.donghaiense,P.balticum,P.minimum,P.emarginatum,P.lima,P.faustiae,and Mesoporos perforatus constitute new records for sindh coast of Pakistan.The most abundant species were P.minimum/P.balticum(4.5×103 cells/L),P.micans(1.1×103 cells/L),P.gracile/P.sigmoides(2.5×102 cells/L) and P.donghaiense(6.6×103 cells/L) at temperatures of 29-31℃ and salinities of 35-40.Maximum abundance was observed in winter and lower abundance in summer.There was no significant change in the distribution of species between stations except for the benthic species which occurred close to Karachi Harbor waters.Significant positive correlations were observed between Prorocentrum spp.and temperature(R 2 =0.27) and negative correlations with salinity(R 2 =-0.32) except for P.minimum and P.emarginatum which has negative correlation with temperature(R 2 =-0.24) and positive with salinity(R 2 =0.08,0.19).The finding of potential okadaic-acid producing species of benthic Prorocentrum call for monitoring for possible human health problems in this region. | Sonia MUNIR Zaib-un-nisa BURHAN Tahira NAZ P.J.A.SIDDIQUI Steve L.MORTON | 2013 | Chinese Journal of Oceanology and Limnology2013，31，2： | 0 |
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