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Labib R.M.,Childrens Cancer Hospital Egypt 57357 | Labib R.M.,Beni Suef University | Abdelrahim M.E.A.,Beni Suef University | Elnadi E.,Beni Suef University | And 3 more authors.
PLoS ONE | Year: 2016

Background: Rhabdomyosarcoma (RMS) is a small round blue cell malignant tumor, representing 7% of childhood malignancies, and over 50% of all soft tissue sarcomas. Cyclophosphamide (CPA) is a prodrug and is the mainstay of RMS treatment. CYP2B6 is a highly polymorphic drug metabolizing enzyme involved in CPA bioactivation. The influence of CYP2B6 single nucleotide polymorphisms (SNPs) on the survival of RMS is still unknown. Methods: We genotyped CYP2B6SNPs rs2279343, rs3745274, and rs3211371 by restriction fragment polymorphism (RFLP) after PCR amplification in a cohort of 73 pediatric RMS patients treated with CPA-based first line treatment. We then analyzed the association between those genotypes and survival outcome of RMS. Results: The frequencies of CYP2B6 rs2279343, rs3745274, and rs3211371 were 63%, 45.2%, and 5.5%, respectively. There was no association between rs3745274, rs3211371 genotypes and survival outcomes of RMS. However, the carriers of at least one mutant allele CYP2B6rs2279343 had significantly longer event-free survival (p-value = 0.03). Conclusion: Our results demonstrated that CYP2B6 rs2279343 may predict EFS in RMS patients and warrants future studies to clarify the pharmacogenetics of CPA in pediatrics. If validated, integration of genetic factors with clinical and molecular characteristics could be used for a composite algorithm to better stratify risk prior to treatment. © 2016 Labib et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Marcotte E.L.,University of Minnesota | Thomopoulos T.P.,National and Kapodistrian University of Athens | Infante-Rivard C.,McGill University | Clavel J.,University of Paris Pantheon Sorbonne | And 20 more authors.
The Lancet Haematology | Year: 2016

Background: Results from case-control studies have shown an increased risk of acute lymphoblastic leukaemia (ALL) in young children born by caesarean delivery, and prelabour caesarean delivery in particular; however, an association of method of delivery with childhood leukaemia subtypes has yet to be established. We therefore did a pooled analysis of data to investigate the association between childhood leukaemia and caesarean delivery. Methods: We pooled data from 13 case-control studies from the Childhood Leukemia International Consortium done in nine countries (Canada, Costa Rica, Egypt, France, Germany, Greece, Italy, New Zealand, and the USA) for births from 1970-2013. We analysed caesarean delivery overall and by indications that probably resulted in prelabour caesarean delivery or emergency caesarean delivery. We used multivariable logistic regression models, adjusted for child's birthweight, sex, age, ethnic origin, parental education, maternal age, and study, to estimate odds ratios (ORs) and 95% CIs for the risk of ALL and acute myeloid leukaemia (AML) in children aged 0-14 years at diagnosis. Findings: The studies provided data for 8780 ALL cases, 1332 AML cases, and 23 459 controls, of which the birth delivery method was known for 8655 (99%) ALL cases, 1292 (97%) AML cases, and 23 351 (>99%) controls. Indications for caesarean delivery were available in four studies (1061 ALL, 138 AML, and 1401 controls). The OR for all indications of caesarean delivery and ALL was 1·06 (95% CI 0·99-1·13), and was significant for prelabour caesarean delivery and ALL (1·23 [1·04-1·47]; p=0·018). Emergency caesarean delivery was not associated with ALL (OR 1·02 [95% CI 0·81-1·30]). AML was not associated with caesarean delivery (all indications OR 0·99 [95% CI 0·84-1·17]; prelabour caesarean delivery 0·83 [0·54-1·26]; and emergency caesarean delivery 1·05 [0·63-1·77]). Interpretation: Our results suggest an increased risk of childhood ALL after prelabour caesarean delivery. If this association is causal, maladaptive immune activation due to an absence of stress response before birth in children born by prelabour caesarean delivery could be considered as a potential mechanism. Funding: National Cancer Institute. © 2016 Elsevier Ltd.


Alfaar A.S.,Childrens Cancer Hospital Egypt 57357 | Alfaar A.S.,Charité - Medical University of Berlin | Nour R.,Childrens Cancer Hospital Egypt 57357 | Bakry M.S.,Childrens Cancer Hospital Egypt 57357 | And 16 more authors.
International Ophthalmology | Year: 2016

Research on childhood diseases represents a great global challenge. This challenge is maximized in both childhood cancer disciplines and developing world. In this paper, we aim at describing our institution experience in starting a structured childhood cancer research program in one of the developing countries in a short time based on philanthropic efforts. We used retinoblastoma as an example for what was conducted in this program. Starting in 2008, this program included improving clinical practice and its related supporting services besides developing new research services that both complement the clinical activities and pave the way towards creating a research foundation in the country. Results included developing hospital standard treatment protocols, developing national clinical trials, joining international consortia for childhood cancers clinical trials, developing data collection tools and real-time analytics, establishing a biobanking facility, and developing highly qualified team for conducting clinical, epidemiologic, and translational research studies. Moreover, this effort resulted in improving both clinical practice and patients’ awareness nationally. This model can be used for other startup facilities that aim at finding answers for their national health problems in low-resource setting. © 2016 Springer Science+Business Media Dordrecht


El Mesallamy H.O.,Ain Shams University | Rashed W.M.,Childrens Cancer Hospital Egypt 57357 | Hamdy N.M.,Ain Shams University | Hamdy N.,Cairo University
Journal of Cancer Research and Clinical Oncology | Year: 2014

Purpose: High-dose methotrexate (HD-MTX) is a cornerstone antineoplastic drug in most treatment protocols of pediatric acute lymphoblastic leukemia (ALL). Among the membrane efflux transporters of MTX, the human breast cancer resistant protein is the second member of the G subfamily of ATP-binding cassette (ABC) efflux pump (ABCG2). A single-nucleotide polymorphism (SNP) in ABCG2, the exchange of C to A at position 421, represents 13 % in the Middle Eastern population. We studied the effect of this SNP on the plasma levels of HD-MTX in Egyptian pediatric ALL. Methods: Two hundred ALL patients were recruited from Children's Cancer Hospital Egypt-57357, and all were treated according to the St Jude Total XV protocol. Determination of plasma MTX levels was done at 23, 42 and 68 h. Genotyping of C421A of ABCG2 was done by polymerase chain reaction-restriction fragment length polymorphism. Results: We found 14.5 % of the variant allele of the ABCG2 C421A SNP. The statistical association between ABCG2 421C>A SNP and the cutoff toxic plasma level of 24 h HD-MTX infusion at different time points tested was not statistically significant. There was no statistical significance between steady-state plasma concentration in patients with and without with this SNP. Conclusion: To date, this is the largest study on Egyptian ALL patients for this SNP. This study shows that there is no effect of ABCG2 421C>A on plasma concentrations of HD-MTX. Replacing candidate gene association studies with genome-wide studies of HD-MTX is now mandatory and is part of our research blueprint. © 2014 Springer-Verlag.


Gad A.Z.,Childrens Cancer Hospital Egypt 57357 | Gad A.Z.,American University in Cairo | El-Naggar S.,Childrens Cancer Hospital Egypt 57357 | Ahmed N.,Childrens Cancer Hospital Egypt 57357 | Ahmed N.,Baylor College of Medicine
Cytotherapy | Year: 2016

Over the last two decades, harnessing the power of the immune system has shown substantial promise. Specifically, the successes that chimeric antigen receptor (CAR) T cells achieved in the treatment of hematologic malignancies provided a concrete platform for further development in solid tumors. Considering that the latter contribute more than three quarters of cancer-related deaths in humans makes it clear that solid tumors represent the larger medical challenge, but also the larger developmental promise in the market. In solid tumors though, the more is achieved the more challenges are unveiled. The mere fact that engineered T cells are personalized therapies rather than a mass product has been a main constraint for clinical outspread. Further, the complexity of the hostile solid tumor microenvironment, antigenic diversity and dynamicity and the presence of a tenacious stem cell population rendered the effective development to the clinic questionable. In this article we shed light on the importance of a realistic understanding of challenges faced in solid tumors and some very innovative efforts to overcome these challenges in a manner that paves a pragmatic yet realistic road toward effective development at the discovery level and beyond. © 2016 International Society for Cellular Therapy


Kamal S.,Childrens Cancer Hospital Egypt 57357 | Abbassi M.,Cairo University | Abouelnaga S.A.,Outreach | Agha A.,Cairo University
European Journal of Oncology Pharmacy | Year: 2014

Introduction: Valproic acid (VPA) is a broad-spectrum anticonvulsant drug. The risk of seizures varies by tumour type and its location in the brain. Post-operative seizure prophylaxis after brain tumour resection is still controversial.Methods: A prospective study of paediatric brain tumour patients was performed to evaluate the effect of VPA on post-operative seizure prophylaxis. The patients were monitored for a period of 3 months post-operatively to determine whether VPA was effective in prophylaxis from seizures.Results: Eligible patients were 120 and for the retrospective arm were 62. Post-operatively, a total of 15 patients had seizures, 3 patients in the VPA group with an onset of 12, 15 and 60 days, and 12 patients in the non-VPA group with an average onset of 23 days. Comparing the incidence of seizures post-operatively using Fisher's exact test, the difference between the two groups was not statistically significantly different (p = 0.0714).Conclusion: Although VPA tended to reduce the incidence of seizure events and to delay the onset of seizures post-operatively in brain tumour patients, the difference did not reach statistical significance. Further studies are needed to investigate this difference on a larger number of patients to examine whether the difference observed is real, to investigate the anticancer effect of VPA and to investigate the prophylactic potential of other new generation antiepileptic drugs (AEDs). On the other hand, effort needs to be done to routinely monitor the side effects and seizure severity scale. Further studies need to validate the scales to be used. © 2014 Pharma Publishing and Media Europe. All rights reserved.


Zekri W.,Childrens Cancer Hospital Egypt 57357 | Zekri W.,Cairo University | Yehia D.,Childrens Cancer Hospital Egypt 57357 | Yehia D.,Cairo University | And 13 more authors.
Journal of the Egyptian National Cancer Institute | Year: 2015

Clear cell sarcoma of the kidney (CCSK) accounts for 2-5% of all pediatric renal malignancies, and is known for its propensity to metastasize to bone and other sites. We are reporting two cases with bilateral CCSK that were diagnosed at our institution. One patient initially presented with bilateral renal masses, as well as pulmonary, hepatic and bone metastasis; while other present only with bilateral masses with no evident distant metastasis. Both patients received aggressive neo-adjuvant chemotherapy to decrease tumor size. One patient completed his designated treatment and initially showed complete remission (CR); eventually suffering from relapse. The other patient's tumor progressed during the course of chemotherapy. Both cases manifested brain dissemination at the time of relapse or progression. This emphasizes the importance of staging stratification in CCSK. This also illustrates CCSK's ability to metastasize to bone and other sites including the brain (a primary relapse site in our cases). © 2015 The Authors.


PubMed | Childrens Cancer Hospital Egypt 57357
Type: | Journal: International ophthalmology | Year: 2016

Research on childhood diseases represents a great global challenge. This challenge is maximized in both childhood cancer disciplines and developing world. In this paper, we aim at describing our institution experience in starting a structured childhood cancer research program in one of the developing countries in a short time based on philanthropic efforts. We used retinoblastoma as an example for what was conducted in this program. Starting in 2008, this program included improving clinical practice and its related supporting services besides developing new research services that both complement the clinical activities and pave the way towards creating a research foundation in the country. Results included developing hospital standard treatment protocols, developing national clinical trials, joining international consortia for childhood cancers clinical trials, developing data collection tools and real-time analytics, establishing a biobanking facility, and developing highly qualified team for conducting clinical, epidemiologic, and translational research studies. Moreover, this effort resulted in improving both clinical practice and patients awareness nationally. This model can be used for other startup facilities that aim at finding answers for their national health problems in low-resource setting.


PubMed | Childrens Cancer Hospital Egypt 57357
Type: | Journal: Clinical and translational medicine | Year: 2015

Low grade gliomas are the most common brain tumor in children. Tandem duplication involving the KIAA1549 and the BRAF kinase genes results in a gene fusion that has been recently characterized in a subset of low grade glioma While there is no clear evidence that the KIAA1549-BRAF gene fusion has an effect on prognosis, it is an attractive target for therapy development and as a diagnostic tool.In the current study we examine the prevalence of KIAA1549-BRAF gene fusion in pediatric patients diagnosed with low grade glioma in the Egyptian population and its relationship to clinical and histological subtypes. Sixty patients between the ages of 1 to 18 years were analyzed for the presence of KIAA1549-BRAF fusion gene products using reverse transcription-PCR and sequencing. The clinicopathologic tumor characteristics were then analyzed in relation to the different fusion genes.KIAA1549-BRAF fusion genes were detected in 56.6% of patients. They were primarily associated with pilocytic astrocytoma (74.2%) and pilomyxoid astrocytoma (60%). Translocation 15-9 was the most common, representing (55.8%) of all positive samples followed by 16-9 (26.4%) and 16-11 (8.8%). Pilocytic astrocytomas presented primarily with 15-9 (32.2%), 16-9 (25.8%) and 16-11 (6.4%) while pilomyxoid astrocytomas presented with 15-9 (46.6%), 16-9 (6.6%) and 16-11 (6.6%) translocations.Gene fusion is found to be significantly increased in cerebellar pilocytic astrocytoma tumors. Furthermore, 15-9 was found to have a higher incidence among our cohort compared to previous studies. While most of the gene fusion positive pilomyxoid astrocytomas were 15-9, we find the association none significant.

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