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Wakefield C.E.,Center for Childrens Cancer and Blood Disorders
Journal of pediatric psychology | Year: 2010

OBJECTIVE: To review the results of any published research study examining the psychosocial functioning of children who have recently completed cancer treatment. METHODS: Five electronic databases were searched (from 1978 to 2008). Of 1,734 identified articles, 19 met all inclusion criteria. Four articles utilized a qualitative methodology, thirteen utilized a quantitative methodology, and two used mixed methods. RESULTS: Children may experience positive psychosocial outcomes on treatment completion, including high self-worth, good behavioral conduct, and improved mental health and social behavior. However, they may also experience significant negative outcomes, including lower levels of psychological well-being, mood, liveliness, self-esteem, and motor and physical functioning, as well as increased anxiety, problem behaviors, and sleeping difficulties. CONCLUSIONS: Completing treatment can be a psychologically complex time for children as they wait to make the transition from "cancer patient" to long-term "cancer survivor." Further high-quality research targeting the needs of these children is warranted.


Cheung B.B.,University of New South Wales | Marshall G.M.,University of New South Wales | Marshall G.M.,Center for Childrens Cancer and Blood Disorders
Current Cancer Drug Targets | Year: 2011

Following the discovery that defective retinoid signaling directly contributes to tumorigenesis, and, that retinoids have an anti-cancer effect in vitro and in vivo, retinoids have become part of the routine care in children with neuroblastoma at the stage of minimal residual disease. However, many patients still relapse following retinoid therapy, demonstrating the need for more effective retinoids and better assays to predict retinoid sensitivity in cancer cells. Recent evidence suggests that the copper metabolism gene, ATP7A, is retinoid-regulated and an important component of the retinoic acid receptor βRARβ anticancer effect in neuroblastoma cells. To highlight and further develop the concept of using ATP7A as a target in retinoid therapy, and combination therapy with copper chelators in neuroblastoma, the current literature and abstracts related to the clinical application of retinoids, the function of ATP7A and the clinical application of copper chelators are summarized. We propose that strategies targeting the copper export protein, ATP7A, in combination therapy with retinoids and copper depletion therapy, may have great therapeutic potential in the clinical treatment of neuroblastoma and other malignancies. © 2011 Bentham Science Publishers.


Tee A.E.L.,Childrens Cancer Institute Australia | Marshall G.M.,Childrens Cancer Institute Australia | Marshall G.M.,Center for Childrens Cancer and Blood Disorders | Liu P.Y.,Childrens Cancer Institute Australia | And 5 more authors.
Journal of Biological Chemistry | Year: 2010

We have demonstrated previously that the Myc oncoprotein blocks cancer cell differentiation by forming a novel transcriptional repressor complex with histone deacetylase and inhibiting gene transcription of tissue transglutaminase (TG2). Moreover, induction of TG2 gene transcription and transamidase activity is essential for the differentiating effects of retinoids in cancer cells. Here, we show that two structurally distinct TG2 protein isoforms, the full-length (TG2-L) and the short form (TG2-S), exert opposing effects on cell differentiation. Repression of TG2-L with small interfering RNA, which did not affect TG2-S expression, induced dramatic neuritic differentiation in neuroblastoma cells. In contrast, overexpression of TG2-S or a GTP-binding-deficient mutant of TG2-L (R580A), both of which lack the GTP-binding Arg-580 residue, induced neuroblastoma cell differentiation, which was blocked by an inhibitor of transamidase activity. Whereas N-Myc repressed and retinoid activated both TG2 isoforms, repression of TG2-L, but not simultaneous repression of TG2-L and TG2-S, enhanced neuroblastoma cell differentiation due to N-Myc small interfering RNA or retinoid. Moreover, suppression of vasoactive intestinal peptide (VIP) expression alone induced neuroblastoma cell differentiation, and VIP was up-regulated by TG2-L, but not TG2-S. Taken together, our data indicate that TG2-L and TG2-S exert opposite effects on cell differentiation due to differences in GTP binding and modulation of VIP gene transcription. Our findings highlight the potential importance of repressing the GTP binding activity of TG2-L or activating the transamidase activity of TG2-L or TG2-S for the treatment of neuroblastoma, and possibly also other Myc-induced malignancies, and for enhancing retinoid anticancer effects. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.


Cohen J.,Center for Childrens Cancer and Blood Disorders | Laing D.G.,University of Sydney
Supportive Care in Cancer | Year: 2012

Background The intensive conditioning regimens of a pediatric blood and marrow transplant (BMT) can limit voluntary intake leading to a risk of malnutrition. Poor dietary intake is likely multi-factorial with a change in taste and smell function potentially being one contributing factor limiting intake, though this is not well studied. This research aimed to assess the taste and smell function of a cohort of pediatric BMT patients. Methods A total of ten pediatric BMT patients (8-15 years) were recruited to this study. Smell function was assessed using a three-choice 16-item odour identification test. Taste function was assessed using five concentrations of sweet, sour, salty and bitter tastants. All tests were completed at admission to transplant and monthly until taste and smell function had normalised. Results At the 1-month post-transplant assessment, one third of participants displayed some evidence of taste dysfunction and one third smell dysfunction, but there was no evidence of dysfunction in any patient at the 2-month assessment. Conclusion Contrary to reports of long-term loss of taste and smell function in adults, dysfunction early in transplant was found to be transient and be resolved within 2 months posttransplant in children. Further research is required to determine the causes of poor dietary intake in this population. © Springer-Verlag 2012.


Lau D.T.,University of New South Wales | Hesson L.B.,University of New South Wales | Norris M.D.,University of New South Wales | Marshall G.M.,University of New South Wales | And 3 more authors.
Clinical Cancer Research | Year: 2012

Purpose: To characterize the clinical significance of promoter methylation in a cohort of primary neuroblastoma tumors and investigate the association between DNA methylation and clinical outcome. Experimental Design: A customized Illumina GoldenGate methylation assay was used to assess methylation status of 96 CpG sites within 48 candidate genes in primary neuroblastoma tumors obtained from 131 children diagnosed in Australia. Genes were selected on the basis of previous reports of altered DNA methylation in embryonal cancers. Levels of DNA methylation were validated in a subset of 48 patient samples using combined bisulfite restriction analysis (CoBRA) and bisulfite sequencing. A Cox proportional hazards model was used to investigate the association between promoter hypermethylation and the risk of relapse/death within 5 years of diagnosis, while adjusting for known prognostic factors including MYCN amplification, age, and stage at diagnosis. Results: Levels of promoter methylation of DNAJC15, neurotrophic tyrosine kinase receptor 1 or TrkA (NTRK1), and tumor necrosis factor receptor superfamily, member 10D (TNFRSF10D), were higher in older patients at diagnosis (P < 0.01), whereas higher levels of methylation of DNAJC15, NTRK1, and PYCARD were observed in patients with MYCN amplification (P < 0.001). In multivariate analysis, hypermethylation of folate hydrolase (FOLH1), myogenic differentiation-1 (MYOD1), and thrombospondin-1 (THBS1) remained significant independent predictors of poorer clinical outcome after adjusting for known prognostic factors (P ≤ 0.017). Moreover, more than 30% of patients displayed hypermethylation in 2 genes or more and were at least 2 times more likely to relapse or die (HR = 2.72, 95% confidence interval = 1.55-4.78, P = 0.001), independent of MYCN status, age, and stage at diagnosis. Conclusions: Our findings highlight the potential use of methylation profiling to identify additional prognostic markers and detect new therapeutic targets for selected patient subsets. ©2012 AACR.

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