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1.  Positron Emission Tomography and Neuropathologic Estimates of Fibrillar Amyloid-β in a Patient With Down Syndrome and Alzheimer Disease 
Archives of Neurology  2011;68(11):1461-1466.
Background
Down syndrome appears to be associated with a virtually certain risk of fibrillar amyloid-β (Aβ) pathology by the age of 40 and a very high risk of dementia at older ages. The positron emission tomography (PET) ligand florbetapir F18 has been shown to characterize fibrillar Aβ in the living human brain and to provide a close correlation with subsequent Aβ neuropathology in individuals proximate to and after the end of life. The extent to which the most frequently used PET ligands can be used to detect fibrillar Aβ in patients with Down syndrome remains to be determined.
Objectives
To characterize PET estimates of fibrillar Aβ burden in a Down syndrome patient very close to the end of life and to compare them with neuropathologic assessment made after his death.
Design/Methods
With the family’s informed consent, florbetapir PET was used to study a 55-year-old Down syndrome patient with Alzheimer disease near the end of life; his brain was donated for neuropathologic assessment when he died 14 days later. Visual ratings of cerebral florbetapir uptake were performed by trained readers who were masked to the patient’s diagnosis as part of a larger study, and an automated algorithm was used to characterize regional-to-cerebellar standard uptake value ratios in 6 cerebral regions of interest. Neuropathologic assessments were performed masked to the patient’s diagnosis or PET measurements.
Results
Visual ratings and automated analyses of the PET image revealed a heavy fibrillar Aβ burden in cortical, striatal, and thalamic regions, similar to that reported for patients with late-onset Alzheimer disease. This matched neuropathologic findings of frequent neuritic and diffuse plaques, as well as frequent amyloid angiopathy, except for neuropathologically demonstrated frequent cerebellar diffuse plaques and amyloid angiopathy that were not detected by the PET scan.
Conclusions
Florbetapir PET can be used to detect increased cerebral-to-cerebellar fibrillar Aβ burden in a Down syndrome patient with Alzheimer disease, even in the presence of frequent amyloid angiopathy and diffuse plaques in the cerebellum. Additional studies are needed to determine the extent to which PET could be used to detect and to track fibrillar Aβ and to evaluate investigational Aβ-modifying treatments in the presymptomatic and symptomatic stages of Alzheimer disease.
doi:10.1001/archneurol.2011.535
PMCID: PMC3346179  PMID: 22084131
2.  Examining the Incidence of Human Papillomavirus-Associated Head and Neck Cancers by Race and Ethnicity in the U.S., 1995–2005 
PLoS ONE  2012;7(3):e32657.
Background
Head and neck cancer (HNC) incidence, mortality and survival rates vary by sex and race, with men and African Americans disproportionately affected. Risk factors for HNC include tobacco and alcohol exposure, with a recent implication of human papillomavirus (HPV) in the pathogenesis of HNC. This study describes the epidemiology of HNC in the United States, examining variation of rates by age, sex, race/ethnicity and potential HPV-association.
Methods
We used the North American Association of Central Cancer Registries (NAACCR) Cancer in North America (CINA) Deluxe Analytic Data to analyze HNC incidence for 1995–2005 from forty population-based cancer registries. We calculated age-adjusted incidence rates and incidence trends using annual percent change by age, sex, race/ethnicity and HPV-association.
Results
Males and Non-Hispanic Blacks experienced greater HNC incidence compared to women and other race/ethnicity groupings. A significant overall increase in HNC incidence was observed among HPV-associated sites during 1995–2005, while non HPV-associated sites experienced a significant decline in HNC incidence. Overall, younger age groups, Non-Hispanic Whites and Hispanics experienced greater increases in incidence for HPV-associated sites, while HNC incidence declined for Non-Hispanic Blacks independent of HPV-association. In particular, for HPV-associated sites, HNC incidence for Non-Hispanic White males aged 45–54 increased at the greatest rate, with an APC of 6.28% (p<0.05). Among non HPV-associated sites, Non-Hispanic Black males aged 0–44 years experienced the greatest reduction in incidence (APC, −8.17%, p<0.05), while a greater decline among the older, 55–64 year age group (APC, −5.44%, p<0.05) occurred in females.
Conclusions
This study provides evidence that HPV-associated tumors are disproportionately affecting certain age, sex and race/ethnicity groups, representing a different disease process for HPV-associated tumors compared to non HPV-associated tumors. Our study suggests that HPV tumor status should be incorporated into treatment decisions for HNC patients to improve prognosis and survival.
doi:10.1371/journal.pone.0032657
PMCID: PMC3308956  PMID: 22448226
3.  Probable Early-Onset Alzheimer's Disease in an Apolipoprotein E2 Homozygote 
Objective
To describe a case of early-onset Alzheimer's disease (AD) in an apolipoprotein (Apo) ∊2/∊2 homozygote.
Background
Apo ∊2/∊2 is the rarest of the ApoE genotypes, representing only 1.4% of the population. Cognitive decline in ApoE ∊2 homozygotes has rarely been reported. Case Report/Methods: We report a 58-year-old Apo ∊2/∊2 female who meets clinical criteria for probable AD as confirmed by neuropsychological testing, positron emission/computed tomography scan, CSF analysis and genetic screening for known mutations.
Results
The clinical course is typical of AD, with progressive cognitive and functional decline.
Conclusion
Clinically confirmed early-onset AD is atypical in ApoE2 homozygotes but can occur.
doi:10.1159/000320589
PMCID: PMC2992638  PMID: 20975270
Alzheimer's disease; Apolipoprotein E2; Homozygote; Positron emission tomography scan; Neuropsychological assessment; Cerebrospinal fluid analysis
4.  Flexible heteroarotinoid (Flex-Het) SHetA2 inhibits angiogenesis in vitro and in vivo 
Investigational new drugs  2008;27(4):304-318.
Summary
Flexible heteroarotinoids (Flex-Hets) compounds regulate growth, differentiation and apoptosis in cancer cells. The hypothesis of this study was that the lead Flex-Het, SHetA2, inhibits angiogenesis by blocking cytokine release from cancer cells. SHetA2 altered secretion of thrombospondin-4 (TSP-4), vascular endothelial growth factor A (VEGF) and fibroblast growth factor (bFGF) proteins from normal and cancerous ovarian and renal cultures. Thymidine phosphorylase (TP) expression was inhibited in cancer, but not normal cultures. Endothelial tube formation was stimulated by conditioned media from cancer but not normal cultures, and SHetA2 reduced secretion of this angiogenic activity. SHetA2 directly inhibited endothelial cell tube formation and proliferation through G1 cell cycle arrest, but not apoptosis. Recombinant TP reversed SHetA2 anti-angiogenic activity. SHetA2 inhibition of in vivo angiogenesis was observed in Caki-1 renal cancer xenografts. In conclusion, SHetA2 inhibits angiogenesis through alteration of angiogenic factor secretion by cancer cells and through direct effects on endothelial cells.
doi:10.1007/s10637-008-9175-7
PMCID: PMC2701494  PMID: 18802666
Angiogenesis; Vascular endothelial growth factor; Thymidine phosphorylase; Basic fibroblast growth factor; Thrombospondin 4; Heteroarotinoid
5.  Flexible heteroarotinoid (Flex-Het) SHetA2 inhibits angiogenesis in vitro and in vivo 
Investigational New Drugs  2008;27(4):304-318.
Summary
Flexible heteroarotinoids (Flex-Hets) compounds regulate growth, differentiation and apoptosis in cancer cells. The hypothesis of this study was that the lead Flex-Het, SHetA2, inhibits angiogenesis by blocking cytokine release from cancer cells. SHetA2 altered secretion of thrombospondin-4 (TSP-4), vascular endothelial growth factor A (VEGF) and fibroblast growth factor (bFGF) proteins from normal and cancerous ovarian and renal cultures. Thymidine phosphorylase (TP) expression was inhibited in cancer, but not normal cultures. Endothelial tube formation was stimulated by conditioned media from cancer but not normal cultures, and SHetA2 reduced secretion of this angiogenic activity. SHetA2 directly inhibited endothelial cell tube formation and proliferation through G1 cell cycle arrest, but not apoptosis. Recombinant TP reversed SHetA2 anti-angiogenic activity. SHetA2 inhibition of in vivo angiogenesis was observed in Caki-1 renal cancer xenografts. In conclusion, SHetA2 inhibits angiogenesis through alteration of angiogenic factor secretion by cancer cells and through direct effects on endothelial cells.
doi:10.1007/s10637-008-9175-7
PMCID: PMC2701494  PMID: 18802666
Angiogenesis; Vascular endothelial growth factor; Thymidine phosphorylase; Basic fibroblast growth factor; Thrombospondin 4; Heteroarotinoid

Results 1-5 (5)