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World Journal of Pediatrics 2024年第3期20卷 287-293页

作者： Dinesh Babu Somasundaram Andrew Maher sheeja aravindan Zhongxin Yu Brian MBesch Natarajan aravindan Department of Radiation Oncology University of Oklahoma Health Sciences CenterOklahoma CityOKUSA Stephenson Cancer Center Oklahoma CityOKUSA Department of Pathology University of Oklahoma Health Sciences CenterOklahoma CityOKUSA Radiation Biology Laboratory University of Oklahoma Health Sciences CenterBSEB 302F941 Stanton L.Young BoulevardOklahoma CityOK 73104USA

Progressive neuroblastomas(pNBs)that defy current intensive multimodal clinical therapy(IMCT)are a significant contributor to overall childhood cancer deaths[l].Neuroblastomas(NBs)that survive first-line IMCT actively evolve to acquire genetic and molecular rearrangements and display unparalleled plasticity and evolution,which causes frequent relapses in a rapidly accelerating timeline[2-4].

关键词： neuroblastoma clinical evolve

ALK expression,prognostic significance,and its association with MYCN expression in MYCN non-amplified neuroblastoma

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World Journal of Pediatrics 2022年第4期18卷 285-293页

作者： Dinesh Babu Somasundaram sheeja aravindan Nandita Gupta Zhongxin Yu Ashley Baker Natarajan aravindan Department of Radiation Oncology BMSB 311CRadiation Biology LaboratoryUniversity of Oklahoma Health Sciences Center940 Stanton L.Young BoulevardOklahoma CityOK 73104USA Stephenson Cancer Center Oklahoma CityOKUSA Plainsboro NJUSA Department of Pathology BMSB 311CRadiation Biology LaboratoryUniversity of Oklahoma Health Sciences Center940 Stanton L.Young BoulevardOklahoma CityOK 73104USA Department of Pediatrics University of Oklahoma Health Sciences CenterOklahoma CityOKUSA

Neuroblastoma(NB),the most common cancer at infancy,is derived from a selective sympathoadrenal lineage of the neural crest cells[1-3].The majority of NB is found in children younger than 5 years(median age:2 years)and is rare in children older than 10 *** NB accounts for only 5-6%of the childhood cancers,it heavily contributes(about 15%)to pediatric cancer deaths[4,5].

关键词： neuroblastoma MYCN cancer

MicroRNAs in neuroblastoma tumorigenesis,therapy resistance,and disease evolution

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Cancer Drug Resistance 2019年第4期2卷 1086-1105页

作者： Natarajan aravindan Karthikeyan Subramanian Dinesh Babu Somasundaram Terence S.Herman sheeja aravindan Department of Radiation Oncology University of Oklahoma Health Sciences CenterOklahoma CityOK 73104USA Stephenson Cancer Center Oklahoma CityOK 73104USA

Neuroblastoma(NB)deriving from neural crest cells is the most common extra-cranial solid cancer at *** originates within the peripheral sympathetic ganglia in adrenal medulla and along the midline of the ***,NB exhibits significant heterogeneity stretching from spontaneous regression to rapid progression to therapy ***(miRNAs,miRs)are small(19-22 nt in length)non-coding RNAs that regulate human gene expression at the post-transcriptional level and are known to regulate cellular signaling,growth,differentiation,death,stemness,and ***,the function of miRs in tumorigenesis,progression and resistance is of utmost importance for the understanding of dysfunctional cellular pathways that lead to disease evolution,therapy resistance,and poor clinical *** the last two decades,much attention has been devoted to understanding the functional roles of miRs in NB *** review focuses on highlighting the important implications of miRs within the context of NB disease progression,particularly miRs’influences on NB disease evolution and therapy *** this review,we discuss the functions of both the“oncomiRs”and“tumor suppressor miRs”in NB progression/therapy *** are the critical components to be considered during the development of novel miR-based therapeutic strategies to counter therapy resistance.

关键词： miRNAs progressive neuroblastoma therapy resistance oncomiRs tumor suppressor miRs tumor progression

Cancer stem cells in neuroblastoma therapy resistance

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Cancer Drug Resistance 2019年第4期2卷 948-967页

作者： Natarajan aravindan Drishti Jain Dinesh Babu Somasundaram Terence S.Herman sheeja aravindan Department of Radiation Oncology The University of Oklahoma Health Sciences CenterOklahoma CityOK 73104USA Department of Pathology The University of Oklahoma Health Sciences CenterOklahoma CityOK 73104USA Department of Anesthesiology The University of Oklahoma Health Sciences CenterOklahoma CityOK 73104USA Stephenson Cancer Center Oklahoma CityOK 73104USA

Neuroblastoma(NB)is the most common cancer of infancy and accounts for nearly one tenth of pediatric cancer *** mortality rate has been attributed to the>50%frequency of relapse despite intensive,multimodal clinical therapy in patients with progressive *** the disease’s heterogeneity and developed resistance,attaining a cure after relapse of progressive NB is highly challenging.A rapid decrease in the timeline between successive recurrences is likely due to the ongoing acquisition of genetic rearrangements in undifferentiated NB-cancer stem cells(CSCs).In this review,we present the current understanding of NB-CSCs,their intrinsic role in tumorigenesis,their function in disease progression,and their influence on acquired therapy resistance and tumor *** particular,this review focus on the intrinsic involvement of stem cells and signaling in the genesis of NB,the function of pre-existing CSCs in NB progression and therapy response,the formation and influence of induced CSCs(iCSCs)in drug resistance and tumor evolution,and the development of a CSC-targeted therapeutic approach.

关键词： Neuroblastoma therapy resistance cancer stem cells clonal selection drug resistance induced cancer stem cell