The kinetics and hydrodynamic properties of factor V-membrane interaction were characterized. Factor V bound to membranes containing acidic phospholipids with a high collisional efficiency. For membranes of 20% phosphatidyl-serine-80% phosphatidylcholine, an association rate constant of (1.13 +/- 0.10) X 10(8) M-1 s-1 was obtained. These membranes contained about 20 factor V binding sites per vesicle of 3.6 X 10(6) daltons. This association rate represented about a 30% collisional efficiency. Dissociation of factor V was measured by a fluorescence energy transfer method with a dissociation rate constant of 0.0055 s-1 at 10 degrees C. The equilibrium dissociation constant for binding to these membranes at 10 degrees C and 0.14 M ionic strength was 5 X 10(-11) M. Ionic strength, pH, calcium, and charge density in the membrane had large effects on the rate of factor V-membrane dissociation, indicating a strongly ionic interaction between protein and membrane. In contrast, the association rate was nearly insensitive to ionic strength. The membrane-binding properties were relatively unchanged after thrombin digestion of factor V or after long-term protein storage which resulted in loss of procoagulant activity. Other proteins of the prothrombinase reaction greatly decreased the rate of factor Va-membrane dissociation. At protein saturation, factor V increased the hydrodynamic radius of phospholipid vesicles by 11.4 nm. In contrast, factor Va increased the hydrodynamic vesicle radius by only about 5 nm. The mass of membrane-bound protein was comparable for both proteins.
BackgroundSince there is high local failure and poor survival for unresectable esophageal squamous cell carcinoma (ESCC), the necessity of elective node irradiation is controversial. The purpose of this study was to investigate the failure patterns and survival in patients with locally advanced ESCC receiving involved-field irradiation (IFI).MethodsA retrospective study was preformed on the clinical records of patients with locally advanced ESCC, who have received IFI with concurrent chemotherapy between January 2003 and January 2009. Comparing the target volume and first sites of failure, patterns of failure were defined as in-field, out-of-field regional lymph node and distant failure. The survivals were analyzed by different patterns of failure.ResultsEighty patients were included in our study. With a median follow-up of 52.6 months, failures were observed in 76 patients. In-field recurrence, distant metastasis, and out-of-field regional failure were seen in 53.75%, 41.25%, 30% patients, respectively. There were significant differences in OS for patients with and without in-field (median OS 14.2 vs.17.4 m, P = 0.01)or distant failure(13.2 vs.15.9 m, P ≤ 0.0001), but not for out-of-field regional lymph node failure(both 14.5 m, P = 0.665).ConclusionsThe solitary regional nodal failure of out-of-field was acceptable in advanced ESCC patients treated with IFI. In-field and distant failures remained the predominant patterns and negatively impacted survival more significantly. Further investigation is needed to establish the optimal radiotherapy field for these patients at advanced stage.
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