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1.  Examining Racial Differences in Diffuse Large B-Cell Lymphoma Presentation and Survival 
Leukemia & lymphoma  2013;54(2):268-276.
We performed a retrospective cohort analysis of 701 (533 White and 144 Black) patients with DLBCL treated at two referral centers in southern United States between 1981-2010. Median age of diagnosis for Blacks was 50 years vs. 57 years for Whites (p<0.001). A greater percentage of Blacks presented with elevated lactate dehydrogenase levels, B-symptoms, and performance status≥2. More Whites (8%) than Blacks (3%) had positive family history of lymphoma (p=0.048). There were no racial differences in the use of R-CHOP (52% Black vs. 47% White, p=0.73). While black race predicted worse survival among patients treated with CHOP (Hazard ratio [HR] 1.8, p<0.001), treatment with R-CHOP was associated with improved survival irrespective of race (HR 0.61, p=0.01). Future studies should examine biological differences that may underlie the observed racial differences in presentation and outcome.
PMCID: PMC4151307  PMID: 22800091
Diffuse large B-cell lymphoma; Race; Disparities; Outcomes; CHOP regimen; R-CHOP regimen
3.  The genetic landscape of mutations in Burkitt lymphoma 
Nature genetics  2012;44(12):1321-1325.
Burkitt lymphoma is characterized by deregulation of MYC, but the contribution of other genetic mutations to the disease is largely unknown. Here, we describe the first completely sequenced genome from a Burkitt lymphoma tumor and germline DNA from the same affected individual. We further sequenced the exomes of 59 Burkitt lymphoma tumors and compared them to sequenced exomes from 94 diffuse large B-cell lymphoma (DLBCL) tumors. We identified 70 genes that were recurrently mutated in Burkitt lymphomas, including ID3, GNA13, RET, PIK3R1 and the SWI/SNF genes ARID1A and SMARCA4. Our data implicate a number of genes in cancer for the first time, including CCT6B, SALL3, FTCD and PC. ID3 mutations occurred in 34% of Burkitt lymphomas and not in DLBCLs. We show experimentally that ID3 mutations promote cell cycle progression and proliferation. Our work thus elucidates commonly occurring gene-coding mutations in Burkitt lymphoma and implicates ID3 as a new tumor suppressor gene.
PMCID: PMC3674561  PMID: 23143597
4.  The SMAC mimetic RMT5265.2HCL induces apoptosis in EBV AND HTLV-I associated lymphoma cells by inhibiting XIAP and promoting the mitochondrial release of cytochrome C and Smac 
Leukemia Research  2012;36(6):784-790.
The inhibitors of apoptosis (IAP) are important regulators of apoptosis. However, little is known about the capacity of Smac mimetics (IAP inhibitor) to overcome virally-associated-lymphoma’s (VAL) resistance to apoptosis. Here, we explored the pro-apoptotic effect of a novel Smac mimetic, RMT5265.2HCL (RMT) in VAL cells. RMT improved the sensitivity to apoptosis in EBV- and to some extend in HTLV-1- but not in HHV-8-VAL. Furthermore, we identified that RMT promotes caspase 3 and 9 cleavage by inhibiting XIAP and inducing the mitochondrial efflux of Smac and cytochrome C. This investigation further support exploring the use of Smac inhibitors in VAL.
PMCID: PMC3331941  PMID: 22325366
XIAP; EBV; HTLV-1; HHV-8; lymphomas; Smac mimetics
6.  1,25(OH)2Vitamin D inhibits foam cell formation and suppresses macrophage cholesterol uptake in patients with type 2 diabetes 
Circulation  2009;120(8):687-698.
Cardiovascular disease is the leading cause of death among diabetics. Vitamin D deficiency is associated with increased risk of cardiovascular disease in this population. To determine the mechanism by which vitamin D deficiency mediates accelerated cardiovascular disease in patients with diabetes, we investigated the effects of active vitamin D on macrophage cholesterol deposition.
Methods and Results
We obtained macrophages from 76 obese, diabetic, hypertensive patients with vitamin D deficiency (25-hydroxyvitamin D < 80 nmol/L)(group A) and four control groups: obese, diabetic, hypertensive patients with normal vitamin D (group B, n=15), obese, non-diabetic, hypertensive patients with vitamin D deficiency (group C, n=25), and non-obese, non-diabetic, non-hypertensive patients with vitamin D deficiency (group D, n=10) or sufficiency (group E, n=10). The same patient’s macrophages from all groups were cultured in vitamin D-deficient or 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) supplemented media and exposed to modified low-density lipoprotein cholesterol. 1,25(OH)2D3 suppressed foam cell formation by reducing acetylated or oxidized low-density lipoprotein cholesterol uptake in diabetics only. Conversely, deletion of the vitamin D receptor in macrophages from diabetic patients accelerated foam-cell formation induced by modified LDL. 1,25(OH)2D3 downregulation of c-Jun N-terminal kinase activation reduced PPARγ expression, suppressed CD36 expression, and prevented oxLDL-derived cholesterol uptake. In addition, 1,25(OH)2D3 suppression of macrophage endoplasmic reticulum stress improved insulin signaling, downregulated SR-A1expression, and prevented oxLDL and AcLDL-derived cholesterol uptake.
These results identify reduced vitamin D receptor signaling as a potential mechanism underlying increased foam-cell formation and accelerated cardiovascular disease in diabetics.
PMCID: PMC3099646  PMID: 19667238
Nutrition; Diabetes mellitus; Atherosclerosis and Inflammation

Results 1-6 (6)