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Therapeutic modulation of the CD47-SIRPαaxis in the pediatric tumor microenvironment:working up an appetite

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cancer Drug Resistance 2020年第3期3卷 550-562页

作者： Ajay Gupta Cenny Taslim Brian P.Tullius Timothy P.Cripe Division of Hematology OncologyBlood and Marrow TransplantNationwide Children’s HospitalColumbusOH 43205USA. Center for Childhood cancer and Blood Diseases Nationwide Children’s HospitalColumbusOH 43205USA.

Evasion of immune surveillance is one of the hallmarks of cancer.Although the adaptive immune system has been targeted via checkpoint inhibition,many patients do not sustain durable remissions due to the heterogeneity of the tumor microenvironment,so additional strategies are needed.The innate immune system has its own set of checkpoints,and tumors have co-opted this system by expressing surface receptors that inhibit phagocytosis.One of these receptors,CD47,also known as the“don’t eat me”signal,has been found to be overexpressed by most cancer histologies and has been successfully targeted by antibodies blocking the receptor or its ligand,signal regulatory proteinα(SIRPα).By enabling phagocytosis via antigen-presenting cells,interruption of CD47-SIRPαbinding leads to earlier downstream activation of the adaptive immune system.Recent and ongoing clinical trials are demonstrating the safety and efficacy of CD47 blockade in combination with monoclonal antibodies,chemotherapy,or checkpoint inhibitors for adult cancer histologies.The aim of this review is to highlight the current literature and research on CD47,provide an impetus for investigation of its blockade in pediatric cancer histologies,and provide a rationale for new combination therapies in these patients.

关键词： CD47 SIRPα immunotherapy tumor microenvironment pediatric cancer innate immune system checkpoint inhibitor phagocytosis

Dodging the bullet: therapeutic resistance mechanisms in pediatric cancers

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cancer Drug Resistance 2019年第3期2卷 428-446页

作者： Nilay Shah Division of pediatric Hematology/Oncology/BMT Nationwide Children’s HospitalColumbusOH 43205USA Department of pediatrics The Ohio State University College of MedicineColumbusOH 43210USA.

While advances in the treatment of pediatric cancers have improved survival to>80%across all tumor types,drug resistance continues to limit survival for a considerable number of patients.We review the known mechanisms of resistance in pediatric cancers,including processes that impair conventional chemotherapies,newer classes of targeted small molecule antineoplastic drugs,and monoclonal antibodies.We highlight similarities and differences in treatment approach and resistance between pediatric and adult cancers.We also discuss newer areas of research into drug resistance,including extracellular and immune factors.

关键词： Tumor microenvironment drug efflux chemoresistance inhibition of apoptosis BCL2 pediatric cancer

Assessment of Psychological Distress among Parents of Children with cancer

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Open Journal of Psychiatry 2021年第4期11卷 229-247页

作者： Jihene Feki Fatma Baklouti Afef Khanfir Medical Oncology Department Habib Bourguiba Hospital University of Sfax Sfax Tunisia

Background and Aims: The diagnosis of pediatric cancer is a potentially traumatic event and a major source of psychological distress for parents. The aim of our study was to determine the prevalence and the risk factors of psychological distress among parents of children diagnosed with cancer. Methods: This is a descriptive study carried out on parents of children diagnosed with cancer and treated in the department of medical oncology at the Habib Bourguiba Hospital in Tunisia. Over a period of four months, from the beginning of December 2020 until the end of March 2021, forty-three parents (34 mothers and 9 fathers) were assessed, using psychometric scales of anxiety, depression and post-traumatic stress according to respectively to the Hamilton anxiety rating scale (HAM), the Beck Depression Inventory (BDI) and the Impact of Event Scale (IES-R). Results: Sixteen percent of the parents had scores indicating acute stress and 21% had scores indicating post-traumatic stress. Eighty six percent of the parents had mild to severe depression and 95% had minor to major anxiety. Post-traumatic stress and anxiety are significantly correlated with the female sex of parents. Significant correlations are also found between post-traumatic stress scores and symptoms of depression and anxiety. However, our study did not show a significant correlation between the others factors studied and the parents’ psychological distress. Conclusion: The prevalence of anxiety and depressive disorders was high among parents of children diagnosed with cancer and a significant correlation was found between stress and anxiety with the female sex of parents. Our results were similar to several studies although other risk factors for psychological distress in parents of children with cancer were described in the literature.

关键词： pediatric cancer Parents Anxiety Depression Post Traumatic Stress

Detection and quantifi cation of extracellular microRNAs in medulloblastoma

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Journal of cancer Metastasis and Treatment 2015年第1期1卷 67-75页

作者： Tarek Shalaby Giulio Fiaschetti Sylvain Baulande Nicolas U.Gerber Martin Baumgartner Michael A.Grotzer Department of Oncology University Children’s Hospital Zurich8032 ZurichSwitzerland Department of Biology PartnerChip CEAGénopole Campus 291000ÉvryFrance.

Aim:Medu lloblastoma(MB)is the most common malignant brain tumor in children.The crucial role of extracellular-microRNAs(ex-miRNAs)in cancer has been widely recognized;however,their role in MB remains unknown.This study aimed to investigate MB-driven ex-miRNAs.Methods:Microarray analysis was used to disclose the identity and quantity of key miRNAs excreted in culture-medium(CM)of 3 human MB cell lines and cere brospinal fl uid(CSF)of brain tumors(including MB)and leukemia patients.MiRNA expression was validated by quantitative reverse transcription polymerase chain reaction.Results:We have demonstrated that the 3 MB cell lines tested commonly expressed 1,083 miRNAs in their spent CM.Among them,57 miRNAs were specifi c to the CM of metastasis-related cell lines which represents the aggressive group 3 and group 4 MB subtypes.A signifi cant number(1,254)of ex-miRNAs were identifi ed in the CSF of a MB patient.Eighty-six of these miRNAs were found to be differentially expressed in this patient’s CSF compared with controls.Interestingly,3 metastasis-associated miRNAs over-represented in CM of metastasis-related MB cell lines were found to be significantly enriched in the CSF of the MB patient.Conclusion:Although more samples are required to fully verify these results,our work provides the first evidence for the presence of a signifi cant amount of miRNAs excreted extracellularly by MB cells and raises the possibility that,in the near future,miRNAs could be probed in CSF of MB patients and serve as novel biological markers.

关键词： Medulloblastoma extracellular-microRNA pediatric cancer

Spectrum of pediatric Malignancies: An Observational Single Center Study from Western India

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Journal of Oncology Research 2021年第2期3卷 28-32页

作者： Aditi Mittal Kanu Neemawat Sandeep Jasuja Anushree Chaturvedi Department of Medical oncology SMS Medical College and attached HospitalJaipurIndia Department of Pathology SMS Medical College and attached HospitalJaipurIndia Department of Medical Oncology Apex Super-specialty HospitalVaranasiIndia

cancer is a leading cause of death for children and adolescent worldwide.The cure rates in low middle-income countries are dismal(20%)in comparison to high income countries(80%).The first move is to assemble precise data on epidemiology of pediatric cancer across the country and its region wide variation.This study attempts to provide spectrum of pediatric malignancies from a tertiary care hospital in the state of Rajasthan,India.A total of 140 cases were studied retrospectively over a period of two years(April 2018-March 2020).Patients,0-18 years of age that are diagnosed as a case of malignancy were included in this study.The records of these patients were retrieved and analyzed.Patients were stratified in 4 groups;0-4 years,5-9 years,10-14 years and 15-18 years.Most of the patients fell in 15-18 year group(35.7%),followed by 5-9 year group(28.5%).Majority of cases,67.8%were male.The male to female ratio is 2.1:1.Leukemia(40%)was the most common malignancy followed by lymphoma,retinoblastoma and malignant bone tumors.Acute lymphoblastic leukemia comprises majority(35/56)of leukemia.Retinoblastoma was predominant malignancy amongpediatric malignancies at one of the largest tertiary care hospitals in Rajasthan,which is important in the planning and evaluation of health strategies.As we lack a dedicated pediatric cancer registry,such epidemiological studies play a significant part for this small but distinguished group of patients.

关键词： pediatric cancer Epidemiology Leukemia Tertiary health care