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2.  18F-FDG-PET/CT imaging in an IL-6- and MYC-driven mouse model of human multiple myeloma affords objective evaluation of plasma cell tumor progression and therapeutic response to the proteasome inhibitor ixazomib 
Blood Cancer Journal  2013;3(11):e165-.
18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) are useful imaging modalities for evaluating tumor progression and treatment responses in genetically engineered mouse models of solid human cancers, but the potential of integrated FDG-PET/CT for assessing tumor development and new interventions in transgenic mouse models of human blood cancers such as multiple myeloma (MM) has not been demonstrated. Here we use BALB/c mice that contain the newly developed iMycΔEμ gene insertion and the widely expressed H2-Ld-IL6 transgene to demonstrate that FDG-PET/CT affords an excellent research tool for assessing interleukin-6- and MYC-driven plasma cell tumor (PCT) development in a serial, reproducible and stage- and lesion-specific manner. We also show that FDG-PET/CT permits determination of objective drug responses in PCT-bearing mice treated with the investigational proteasome inhibitor ixazomib (MLN2238), the biologically active form of ixazomib citrate (MLN9708), that is currently in phase 3 clinical trials in MM. Overall survival of 5 of 6 ixazomib-treated mice doubled compared with mice left untreated. One outlier mouse presented with primary refractory disease. Our findings demonstrate the utility of FDG-PET/CT for preclinical MM research and suggest that this method will play an important role in the design and testing of new approaches to treat myeloma.
PMCID: PMC3880444  PMID: 24292417
GEMM (genetically engineered mouse model) of human cancer; preclinical cancer drug testing; plasma cell neoplasia
3.  Global Oral Health Inequalities 
Advances in Dental Research  2011;23(2):211-220.
The IADR Global Oral Health Inequalities Task Group on Dental Caries has synthesized current evidence and opinion to identify a five-year implementation and research agenda which should lead to improvements in global oral health, with particular reference to the implementation of current best evidence as well as integrated action to reduce caries and health inequalities between and within countries. The Group determined that research should: integrate health and oral health wherever possible, using common risk factors; be able to respond to and influence international developments in health, healthcare, and health payment systems as well as dental prevention and materials; and exploit the potential for novel funding partnerships with industry and foundations. More effective communication between and among the basic science, clinical science, and health promotion/public health research communities is needed. Translation of research into policy and practice should be a priority for all. Both community and individual interventions need tailoring to achieve a more equal and person-centered preventive focus and reduce any social gradient in health. Recommendations are made for both clinical and public health implementation of existing research and for caries-related research agendas in clinical science, health promotion/public health, and basic science.
PMCID: PMC3144035  PMID: 21490233
Dental caries; health inequalities; health disparities; implementation research; translational research
4.  Antiphospholipid syndrome associated with infections: clinical and microbiological characteristics of 100 patients 
Annals of the Rheumatic Diseases  2004;63(10):1312-1317.
Objective: To describe and analyse the clinical characteristics of 100 patients with antiphospholipid syndrome (APS) associated with infections.
Methods: Patients were identified by a computer assisted search (Medline) of published reports to locate all cases of APS published in English, Spanish, and French from 1983 to 2003. The bilateral Fisher exact test was used for statistics.
Results: 59 female and 41 male patients were identified (mean (SD) age, 32 (18) years (range 1 to 78)): 68 had primary APS, 27 had systemic lupus erythematosus, two had "lupus-like" syndrome, two had inflammatory bowel disease, and one had rheumatoid arthritis. APS presented as a catastrophic syndrome in 40% of cases. The main clinical manifestations of APS included: pulmonary involvement (39%), skin involvement (36%), and renal involvement (35%; nine with renal thrombotic microangiopathy, RTMA). The main associated infections and agents included skin infection (18%), HIV (17%), pneumonia (14%), hepatitis C (13%), and urinary tract infection (10%). Anticoagulation was used in 74%, steroids in 53%, intravenous immunoglobulins in 20%, cyclophosphamide in 12%, plasma exchange in 12%, and dialysis in 9.6%. Twenty three patients died following infections and thrombotic episodes (16 with catastrophic APS). Patients given steroids had a better prognosis (p = 0.024). The presence of RTMA and requirement for dialysis carried a worse prognosis (p = 0.001 and p = 0.035, respectively).
Conclusions: Various different infections can be associated with thrombotic events in patients with APS, including the potentially lethal subset termed catastrophic APS. Aggressive treatment with anticoagulation, steroids, and appropriate antibiotic cover is necessary to improve the prognosis.
PMCID: PMC1754783  PMID: 15361392

Results 1-4 (4)