5 results on '"Alexis Exarhopoulos"'
Search Results
2. Phase II study of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma
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Patrick Y. Wen, Marek Ancukiewicz, Thomas Benner, Elizabeth R. Gerstner, Rakesh K. Jain, Emmanuelle di Tomaso, Alexis Exarhopoulos, Jay S. Loeffler, Kenneth S. Cohen, Scott R. Plotkin, A. Gregory Sorensen, Tracy T. Batchelor, Fred H. Hochberg, April F. Eichler, Percy Ivy, Marsha A. Moses, David N. Louis, Houng Chea, Jan Drappatz, and Dan G. Duda more...
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Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,medicine.drug_class ,Urinary system ,Phases of clinical research ,Antineoplastic Agents ,Tyrosine-kinase inhibitor ,Disease-Free Survival ,Cediranib ,chemistry.chemical_compound ,Young Adult ,Internal medicine ,Original Reports ,medicine ,Biomarkers, Tumor ,Humans ,Protein Kinase Inhibitors ,Aged ,medicine.diagnostic_test ,business.industry ,Brain Neoplasms ,Cancer ,Magnetic resonance imaging ,Middle Aged ,medicine.disease ,Vascular endothelial growth factor ,Endocrinology ,Receptors, Vascular Endothelial Growth Factor ,chemistry ,Quinazolines ,Biomarker (medicine) ,Female ,Neoplasm Recurrence, Local ,business ,Glioblastoma ,medicine.drug - Abstract
Purpose Glioblastoma is an incurable solid tumor characterized by increased expression of vascular endothelial growth factor (VEGF). We performed a phase II study of cediranib in patients with recurrent glioblastoma. Methods Cediranib, an oral pan-VEGF receptor tyrosine kinase inhibitor, was administered (45 mg/d) until progression or unacceptable toxicity to patients with recurrent glioblastoma. The primary end point was the proportion of patients alive and progression free at 6 months (APF6). We performed magnetic resonance imaging (MRI) and plasma and urinary biomarker evaluations at multiple time points. Results Thirty-one patients with recurrent glioblastoma were accrued. APF6 after cediranib was 25.8%. Radiographic partial responses were observed by MRI in 17 (56.7%) of 30 evaluable patients using three-dimensional measurements and in eight (27%) of 30 evaluable patients using two-dimensional measurements. For the 15 patients who entered the study taking corticosteroids, the dose was reduced (n = 10) or discontinued (n = 5). Toxicities were manageable. Grade 3/4 toxicities included hypertension (four of 31; 12.9%); diarrhea (two of 31; 6.4%); and fatigue (six of 31; 19.4%). Fifteen (48.4%) of 31 patients required at least one dose reduction and 15 patients required temporary drug interruptions due to toxicity. Drug interruptions were not associated with outcome. Changes in plasma placental growth factor, basic fibroblast growth factor, matrix metalloproteinase (MMP) -2, soluble VEGF receptor 1, stromal cell–derived factor-1α, and soluble Tek/Tie2 receptor and in urinary MMP-9/neutrophil gelatinase-associated lipocalin activity after cediranib were associated with radiographic response or survival. Conclusion Cediranib monotherapy for recurrent glioblastoma is associated with encouraging proportions of radiographic response, 6-month progression-free survival, and a steroid-sparing effect with manageable toxicity. We identified early changes in circulating molecules as potential biomarkers of response to cediranib. The efficacy of cediranib and the predictive value of these candidate biomarkers will be explored in prospective trials. more...
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- 2010
Catalog
3. Matrix metalloproteinases are elevated in the urine of patients with endometriosis
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Christian M. Becker, Andreas D. Ebert, Sylvia Mechsner, Gwendolyn Louis, Alexis Exarhopoulos, Marsha A. Moses, and David Zurakowski
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Adult ,medicine.medical_specialty ,Pathology ,Longitudinal study ,Endometriosis ,Urine ,Matrix metalloproteinase ,Lipocalin ,Gastroenterology ,Internal medicine ,medicine ,Humans ,Uterine Diseases ,Metalloproteinase ,integumentary system ,business.industry ,Case-control study ,Obstetrics and Gynecology ,medicine.disease ,Matrix Metalloproteinases ,Up-Regulation ,Reproductive Medicine ,Matrix Metalloproteinase 9 ,Case-Control Studies ,Biomarker (medicine) ,Matrix Metalloproteinase 2 ,Female ,business ,Biomarkers - Abstract
In a prospective, blinded, longitudinal study MMP-2, MMP-9, and MMP-9/neutrophil gelatinase-associated lipocalin were significantly more likely to be detected in the urine of patients with endometriosis than in controls. more...
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- 2009
4. Endothelial Progenitor Cells as a Sole Source for Ex Vivo Seeding of Tissue-Engineered Heart Valves
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Virna L. Sales, Michael S. Sacks, Bret A. Mettler, David P. Martin, Elena Aikawa, Frederick J. Schoen, Marsha A. Moses, Alexis Exarhopoulos, John E. Mayer, George C. Engelmayr, and Joyce Bischoff
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CD31 ,Biomedical Engineering ,Bioengineering ,Matrix (biology) ,Biochemistry ,Biomaterials ,Tissue engineering ,medicine ,Animals ,Heart valve ,Progenitor cell ,Cells, Cultured ,Bioprosthesis ,Sheep ,Tissue Engineering ,Chemistry ,Stem Cells ,Endothelial Cells ,Original Articles ,Antigens, Differentiation ,Cell biology ,Endothelial stem cell ,medicine.anatomical_structure ,Gene Expression Regulation ,Heart Valve Prosthesis ,cardiovascular system ,Stem cell ,Ex vivo ,Biomedical engineering - Abstract
Purposes: We investigated whether circulating endothelial progenitor cells (EPCs) can be used as a cell source for the creation of a tissue-engineered heart valve (TEHV). Methods: Trileaflet valved conduits were fabricated using nonwoven polyglycolic acid/poly-4-hydroxybutyrate polymer. Ovine peripheral blood EPCs were dynamically seeded onto a valved conduit and incubated for 7, 14, and 21 days. Results: Before seeding, EPCs were shown to express CD31+, eNOS+, and VE-Cadherin+ but not α-smooth muscle actin. Histological analysis demonstrated relatively homogenous cellular ingrowth throughout the valved conduit. TEHV constructs revealed the presence of endothelial cell (EC) markers and α-smooth muscle actin+ cells comparable with native valves. Protein levels were comparable with native valves and exceeded those in unseeded controls. EPC-TEHV demonstrated a temporal pattern of matrix metalloproteinases-2/9 expression and tissue inhibitors of metalloproteinase activities comparable to that of native valves. Mechanical properties of EPC-TEHV demonstrated significantly greater stiffness than that of the unseeded scaffolds and native valves. Conclusions: Circulating EPC appears to have the potential to provide both interstitial and endothelial functions and could potentially serve as a single-cell source for construction of autologous heart valves. more...
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- 2009
5. Urinary metalloproteinases: noninvasive biomarkers for breast cancer risk assessment
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David Zurakowski, Margaret M. Lotz, Corrine Lenahan, Susan Schumer, Roopali Roy, Rochelle Scheib, Gwendolyn Louis, Carolyn C. Lamb, Judi Hirshfield-Bartek, Marsha A. Moses, Alexis Exarhopoulos, Virginia F. Borges, Ulla M. Wewer, Ankur Anand, Susan E. Pories, Sughra Raza, and Nina Isakovich more...
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Oncology ,medicine.medical_specialty ,Pathology ,Epidemiology ,Urinary system ,Lobular carcinoma ,ADAM12 Protein ,Breast Neoplasms ,Risk Assessment ,Atypical hyperplasia ,Breast cancer ,Internal medicine ,medicine ,Atypia ,Biomarkers, Tumor ,Humans ,Analysis of Variance ,Chi-Square Distribution ,business.industry ,Case-control study ,Area under the curve ,Membrane Proteins ,Middle Aged ,medicine.disease ,ADAM Proteins ,Logistic Models ,Matrix Metalloproteinase 9 ,Case-Control Studies ,Metalloproteases ,Female ,Risk assessment ,business ,Precancerous Conditions ,Carcinoma in Situ - Abstract
Matrix metalloproteinases (MMP) and a disintegrin and metalloprotease 12 (ADAM 12) can be detected in the urine of breast cancer patients and provide independent prediction of disease status. To evaluate the potential of urinary metalloproteinases as biomarkers to predict breast cancer risk status, urine samples from women with known risk marker lesions, atypical hyperplasia and lobular carcinoma in situ (LCIS), were analyzed. Urine samples were obtained from 148 women: 44 women with atypical hyperplasia, 24 women with LCIS, and 80 healthy controls. MMP analysis was done using gelatin zymography and ADAM 12 analysis was done via immunoblotting with monospecific antibodies and subsequent densitometric measurement. Positive urinary MMP-9 levels indicated a 5-fold risk of atypical hyperplasia and >13-fold risk of LCIS compared with normal controls. Urinary ADAM 12 levels were significantly elevated in women with atypical hyperplasia and LCIS from normal controls, with receiver operating characteristic curve analysis showing an area under the curve of 0.914 and 0.950, respectively. To assess clinical applicability, a predictive index was developed using ADAM 12 in conjunction with Gail risk scores for women with atypia. Scores above 2.8 on this ADAM 12-Gail risk prediction index score are predictive of atypical hyperplasia (sensitivity, 0.976; specificity, 0.977). Our data suggest that the noninvasive detection and analysis of urinary ADAM 12 and MMP-9 provide important clinical information for use as biomarkers in the identification of women at increased risk of developing breast cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1034–12) more...
- Published
- 2008
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