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1.  Prognostic significance of interleukin-6 single nucleotide polymorphism genotypes in neuroblastoma: rs1800795 (promoter) and rs8192284 (receptor) 
Purpose
Neuroblastoma is a childhood cancer of the sympathetic nervous system and many patients present with high risk disease. Risk stratification, based on pathology and tumor-derived biomarkers, has improved prediction of clinical outcomes, but overall survival rates remain unfavorable and new therapeutic targets are needed. Some studies suggest a link between interleukin-6 and more aggressive behavior in neuroblastoma tumor cells. Therefore, we examined the impact of two IL-6 single nucleotide polymorphisms (SNP) on neuroblastoma disease progression.
Experimental design
DNA samples from 96 high risk neuroblastoma patients were screened for two SNP that are known to regulate the serum levels of IL-6 and the soluble IL-6 receptor (IL-6R), rs1800795 and rs8192284 respectively. The genotype for each SNP was determined in a blinded fashion and independent statistical analysis was performed to determine SNP-related event free survival (EFS) and overall survival (OS) rates.
Results
The rs1800795 IL-6 promoter SNP is an independent prognostic factor for EFS and OS in -high risk neuroblastoma patients. In contrast, the rs8192284 IL-6 receptor SNP revealed no prognostic value.
Conclusions
The rs1800795 SNP (-174 IL-6 (G>C) represents a novel and independent prognostic marker for both EFS and OS in high risk neuroblastoma. Since the rs1800795 SNP (-174 IL-6 (G>C) has been shown to correlate with production of IL-6, this cytokine may represent a target for development of new therapies in neuroblastoma.
doi:10.1158/1078-0432.CCR-08-2953
PMCID: PMC2740837  PMID: 19671870
2.  Fracture Prevalence and Relationship to Endocrinopathy in Iron Overloaded Patients with Sickle Cell Disease and Thalassemia 
Bone  2008;43(1):162-168.
Transfusional iron overload leads to gonadal failure and low bone mass in patients with thalassemia (Thal). However, gonadal failure is rarely reported in transfused patients with sickle cell disease (SCD) and the literature regarding fracture prevalence in SCD is limited. The objective of this study was to assess self-reported fracture prevalence and its relationship to endocrinopathy in transfused Thal or SCD subjects and compare to non-transfused subjects with SCD (NonTxSCD). Eligibility was based on age ≥12 years and liver iron concentration ≥ 10 mg/g dry wt or serum ferritin ≥ 2000 ng/mL (Thal or TxSCD) or for NonTxSCD, ferritin < 500 ng/mL. Data were collected by patient interview and chart review at 31 clinical centers in the U.S., Canada and the U.K. 152 subjects with Thal (52% Male; 25.6±0.7 yrs), 203 subjects with TxSCD (44% Male, 24.7 ±0.9 years: Mean ± SE), and 65 NonTxSCD (50% Male, 22.2 ±1.3 yrs) were enrolled. Overall, male subjects with Thal were more likely to have sustained a fracture in their lifetime (51%) compared to TxSCD (28%) or NonTxSCD (32%) (p=0.005). There was no difference in fracture prevalence among women (Thal: 26%, TxSCD 17%, NonTxSCD: 16%). Fracture was most frequently reported in the upper extremities (53.3% of all fractures) while spine and pelvic fractures were relatively common for such a young cohort: 10.6%. Though overall fracture prevalence was not distinctly different from published healthy cohorts, fewer fractures occurred during the adolescent years. In multivariate analysis, the significant predictors of fracture prevalence were Thal diagnosis (Odds Ratio: 2.3; 1.2–4.6; 95%CI), male gender (OR: 2.6; 1.5–4.5), hypothyroidism (OR: 3.3; 1.1–9.8) and age (OR: 1.1; 1.03–1.08). These data suggest that despite similar iron burden, transfused patients with Thal are at greater risk for fracture than subjects with SCD. Male subjects with Thal and hypothyroidism are at particular risk for fracture, in contrast, transfused subjects with SCD had no greater risk of fracture compared to non-transfused SCD. Though ethnic differences in fracture risk cannot be ignored, endocrinopathy is rare in TxSCD which may also provide some protection from fracture.
doi:10.1016/j.bone.2008.03.003
PMCID: PMC2500183  PMID: 18430624
Fracture; Endocrinopathy; Iron Overload; Thalassemia; Sickle Cell Disease
3.  Nothing but NET: A review of norepinephrine transporter expression and efficacy of 131I-mIBG therapy 
Pediatric Blood & Cancer  2014;62(1):5-11.
Neuroblastoma is unique amongst common pediatric cancers for its expression of the norepinephrine transporter (NET), enabling tumor-selective imaging and therapy with radioactive analogues of norepinephrine. The majority of neuroblastoma tumors are avid for 123I-metaiodobenzaguanidine (mIBG) on imaging, yet the therapeutic response to 131I-mIBG is only 30% in clinical trials, and off-target effects cause short- and long-term morbidity. We review the contemporary understanding of the tumor-selective uptake, retention, and efflux of meta-iodobenzylguanidine (mIBG) and strategies currently in development for improving its efficacy. Combination treatment strategies aimed at enhancing NET are likely necessary to reach the full potential of 131I-mIBG therapy.
doi:10.1002/pbc.25200
PMCID: PMC4237663  PMID: 25175627
meta-iodobenzylguanidine; neuroblastoma; norepinephrine transporter

Results 1-3 (3)