Profile and outcome of neuroblastoma with convertional chemotherapy in children older than one year: a 15-years experience.
ABSTRACT The clinical profile and outcome of neuroblastoma in 103 children, older than one-year is presented. 74 had Stage IV, 27 Stage III and one patient each had Stage I or II disease. Treatment included chemotherapy followed by surgical resection/debulking. Radiotherapy was administered to those with residual tumor. Chemotherapy consisted of OPEC (vincristine, cyclophosphamide, cisplatin and etoposide). The caretakers of 54 (52.4%) children either did not opt for or defaulted therapy, whilst 3 patients died before chemotherapy could be initiated. Of the remaining 46 patients, the tumor progressed during therapy in 19 (41.3%). Relapse of disease was documented in 22 (47.8%) cases. Merely 4 (8.7%) children are disease free for a period of 16.5+/-6.7 months. Majority of children presented with advanced disease and the outcome was dismal with conventional non-myloablative chemotherapy.
Article: Outcome of Neuroblastoma in India.[show abstract] [hide abstract]
ABSTRACT: OBJECTIVES: To assess the outcome of childhood neuroblastoma in India over the last 2 decades, identify management lacunae and suggest remedial measures. METHODS: A comprehensive search to identify literature addressing outcome of childhood neuroblastoma from India was performed. International Society of Paediatric Oncology and American Society of Clinical Oncology Annual-Meeting abstracts were hand searched to identify unpublished data. Clinico-demographic and outcome data was extracted. RESULTS: Outcome of approximately 700 patients has been published over the last 2 decades with predominantly small to moderate single center series from 6 cities. Primarily non-myeloablative multiagent chemotherapy protocols alongwith surgery, have been used for treatment. A large majority of patients had stage III/IV neuroblastoma. Limited diagnostic facilities were available at most centers. Survival outcome of 8.7 to 80 % has been reported with high death and relapse rates alongwith high incomplete control/disease progression and treatment abandonment. Few series have identified prognostic parameters. Few patients with high-risk disease have been adequately treated and cured. CONCLUSIONS: There is a clear need for replicating neuroblastoma outcomes at centers of excellence in other cancer centers, improving diagnostic and laboratory facilities, administering adequate and appropriate contemporary therapy, assessing disease response and improving supportive care. National data management infrastructure along with better financial and social support initiatives are key factors.The Indian Journal of Pediatrics 01/2013; · 0.72 Impact Factor
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ABSTRACT: Neuroblastoma is the most common cancer in infants and fourth most common cancer in children. Despite recent advances in cancer treatments, the prognosis of stage-IV neuroblastoma patients continues to be dismal which warrant new pharmacotherapy. A novel tetracyclic condensed quinoline compound, 8-methoxypyrimido [4',5':4,5]thieno(2,3-b) quinoline-4(3H)-one (MPTQ) is a structural analogue of an anticancer drug ellipticine and has been reported to posses anticancer property. Study on MPTQ on neuroblastoma cells is very limited and mechanisms related to its cytotoxicity on neuroblastoma cells are completely unknown. Here, we evaluated the anticancer property of MPTQ on mouse neuro 2a and human SH-SY5Y neuroblastoma cells and investigated the mechanisms underlying MPTQ-mediated neuro 2a cell death. MPTQ-mediated neuro 2a and SH-SY5Y cell deaths were found to be dose and time dependent. Moreover, MPTQ induced cell death reached approximately 99.8% and 90% in neuro 2a and SH-SY5Y cells respectively. Nuclear oligonucleosomal DNA fragmentation and Terminal dUTP Nick End Labelling assays indicated MPTQ-mediated neuro 2a cell death involved apoptosis. MPTQ-mediated apoptosis is associated with increased phosphorylation of p53 at Ser15 and Ser20 which correlates with the hyperphosphorylation of Ataxia-Telangiectasia mutated protein (ATM). Immunocytochemical analysis demonstrated the increased level of Bax protein in MPTQ treated neuro 2a cells. MPTQ-mediated apoptosis is also associated with increased activation of caspase-9, -3 and -7 but not caspase-2 and -8. Furthermore, increased level of caspase-3 and cleaved Poly (ADP Ribose) polymerase were observed in the nucleus of MPTQ treated neuro 2a cells, suggesting the involvement of caspase-dependent intrinsic but not extrinsic apoptotic pathway. Increased nuclear translocation of apoptosis inducing factor suggests additional involvement of caspase-independent apoptosis pathway in MPTQ treated neuro 2a cells. Collectively, MPTQ-induced neuro 2a cell death is mediated by ATM and p53 activation, and Bax-mediated activation of caspase-dependent and caspase-independent mitochondrial apoptosis pathways.PLoS ONE 01/2013; 8(6):e66430. · 3.73 Impact Factor
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ABSTRACT: A series of 2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazoles 9a-j were obtained via multistep synthesis from hydroxybenzophenones 4a-e. The cytotoxicity of compounds 9a-j was evaluated against human leukemia cell lines (K562 and CEM). The compounds exhibited moderate to good anti-cancer activity with compounds 9b and 9i having a chloro group exhibiting the best activity (IC50 = 10 μM). Compound 9i exhibited activity against both the cell lines and 9b only exhibited activity against CEM. Further, a lactate dehydrogenase (LDH) assay and DNA fragmentation studies of the compounds 9a-j were also performed.European journal of medicinal chemistry 03/2013; 63C:536-543. · 3.27 Impact Factor