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- Achen, M G, et al.
(författare)
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Monoclonal antibodies to vascular endothelial growth factor-D block its interactions with both VEGF receptor-2 and VEGF receptor-3.
- 2000
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Ingår i: European Journal of Biochemistry. - 0014-2956 .- 1432-1033. ; 267:9
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Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial growth factor-D (VEGF-D), the most recently discovered mammalian member of the VEGF family, is an angiogenic protein that activates VEGF receptor-2 (VEGFR-2/Flk1/KDR) and VEGFR-3 (Flt4). These receptor tyrosine kinases, localized on vascular and lymphatic endothelial cells, signal for angiogenesis and lymphangiogenesis. VEGF-D consists of a central receptor-binding VEGF homology domain (VHD) and N-terminal and C-terminal propeptides that are cleaved from the VHD to generate a mature, bioactive form consisting of dimers of the VHD. Here we report characterization of mAbs raised to the VHD of human VEGF-D in order to generate VEGF-D antagonists. The mAbs bind the fully processed VHD with high affinity and also bind unprocessed VEGF-D. We demonstrate, using bioassays for the binding and cross-linking of VEGFR-2 and VEGFR-3 and biosensor analysis with immobilized receptors, that one of the mAbs, designated VD1, is able to compete potently with mature VEGF-D for binding to both VEGFR-2 and VEGFR-3 for binding to mature VEGF-D. This indicates that the binding epitopes on VEGF-D for these two receptors may be in close proximity. Furthermore, VD1 blocks the mitogenic response of human microvascular endothelial cells to VEGF-D. The anti-(VEGF-D) mAbs raised to the bioactive region of this growth factor will be powerful tools for analysis of the biological functions of VEGF-D.
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- Lee, Benjamin Y., et al.
(författare)
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Unmasking true signal/tumor information from ProstaScint scans
- 2004
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Ingår i: MEDICAL IMAGING 2004: IMAGE PROCESSING, PTS 1-3. - : SPIE - International Society for Optical Engineering. - 0819452831 ; , s. 1980-1990
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Konferensbidrag (refereegranskat)abstract
- Purpose: Improve tumor localization in In-111 ProstaScint SPECT scans through improved reconstruction and identification/removal of non-specific blood pool volumes using simultaneously acquired Tc-99m tagged red blood cell (RBC) SPECT scans. Methods: We chose 30 patients with a history of prostate cancer who had undergone CT/MR and simultaneous Tc-99m RBC/In-111 ProstaScint SPECT scans due to rising PSA. To estimate the impact of reconstruction methods on anatomic definition and artifacts, SPECT volume data sets were reconstructed using ordered set-expectation maximization (OS-EM) with varying numbers of iterations and subsets, and these were compared against each other and against standard filtered back projection (FBP) reconstruction. Non-blood pool bladder activity in the Tc-99m scans was suppressed prior to subtraction from the In-111 scans by using an averaging algorithm within an ellipsoid volume encompassing the bladder. Outside the ellipsoid volume, Tc-99m voxel values were subtracted from the corresponding In-111 voxels after normalization of the data sets based on peak activity within the descending aorta. Results: OS-EM reconstruction using 3 iterations and 45 subsets showed improved representation of anatomy compared with FBP. Bladder suppression reduced artifacts in the prostate bed. The subtraction method reduced the blood pool signal, confirmed visually by superimposition with matched CT/MR scans. Conclusions: OS-EM reconstruction together with bladder suppression and subtraction of the blood pool may help improve the specificity of ProstaScint SPECT interpretation and increase its utility in radiation therapy treatment planning.
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- Murphy, E, et al.
(författare)
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Increased serum cartilage oligomeric matrix protein levels and decreased patellar bone mineral density in patients with chondromalacia patellae.
- 2002
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 61:11, s. 981-985
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chondromalacia patellae is a potentially disabling disorder characterised by features of patellar cartilage degradation. OBJECTIVE: To evaluate markers of cartilage and bone turnover in patients with chondromalacia patellae. METHODS: 18 patients with chondromalacia patellae were studied. Serum cartilage oligomeric matrix protein (s-COMP) and bone sialoprotein (s-BSP) levels were measured by enzyme linked immunosorbent assay (ELISA) and compared with those of age and sex matched healthy control subjects. Periarticular bone mineral density (BMD) of both knee joints was assessed by dual energy x ray absorptiometry (DXA). RESULTS: s-COMP levels were significantly raised in all patients with chondromalacia patellae compared with healthy control subjects (p=0.0001). s-BSP levels did not differ significantly between the groups (p=0.41). BMD of the patella was significantly reduced in patients with chondromalacia patellae compared with the control subjects (p=0.016). In patients with bilateral chondromalacia patellae, BMD of the patella was lower in the more symptomatic knee joint (p=0.005). Changes in periarticular BMD were localised to the patella and were not present in femoral regions. Neither s-COMP (p=0.18) nor s-BSP (p=0.40) levels correlated with patellar BMD. CONCLUSIONS: Increased s-COMP levels, reflecting cartilage degradation, and reduced BMD localised to the patella may represent clinically useful markers in the diagnosis and monitoring of patients with chondromalacia patellae. Measures of cartilage degradation did not correlate with loss of patellar bone density, suggesting dissociated pathophysiological mechanisms.
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