RESUMO
PURPOSE: The incidence and prognosis of Pacific Islanders with gastric cancer is not well documented as previous studies have often aggregated this population with Asians. The purpose of our study was to describe patient and tumor characteristics, as well as prognostic factors of Pacific Islanders with gastric cancer. METHODS: Patients diagnosed with gastroesophageal junction or gastric adenocarcinoma between 2000 and 2014 were identified in the tumor registry of the largest hospital in Hawaii. Overall survival of Asians, Whites, and Pacific Islanders were calculated using the Kaplan-Meier method and log-rank test. Cox proportional hazards regression models were constructed to assess predictors of survival adjusting for clinical and pathological factors. RESULTS: A total of 615 patients were included in the final analysis. Pacific Islanders were found to present at a younger age, were more often uninsured or had Medicaid insurance, and were diagnosed with a higher stage of cancer compared to their Asian and White counterparts. Pacific Islanders were less likely to undergo surgery even after adjusting for stage. Race was a prognostic factor and survival was lowest among Pacific Islanders, but only if the model was unadjusted for treatment. CONCLUSIONS: We present an analysis of the largest cohort of Pacific Islander gastric cancer patients. Pacific Islanders have different sociodemographic characteristics and inferior survival compared to Asian patients and should be independently studied.
Assuntos
Neoplasias Gástricas , Povo Asiático , Estudos de Coortes , Humanos , Incidência , Modelos de Riscos Proporcionais , Neoplasias Gástricas/terapia , Estados UnidosRESUMO
Protein S (PS) is an anticoagulant plasma protein whose deficiency is associated with increased risk of venous thrombosis. PS directly inhibits thrombin generation by the blood coagulation pathways by several mechanisms, including by binding coagulation factors (F) Va and Xa. To identify PS sequences that mediate inhibition of FVa activity, antibodies and synthetic peptides based on PS sequence were prepared and employed in plasma coagulation assays, purified component prothrombinase assays, binding assays, and immunoblots. In the absence of activated protein C, monoclonal antibody (Mab) S4 shortened FXa-induced clotting in normal plasma but not in PS-depleted plasma. Mab S4 also blocked PS inhibition of FVa-dependent prothrombinase activity in purified component assays in the absence or presence of phospholipids and inhibited binding of PS to immobilised FVa. Epitope mapping identified N-terminal region residues 37-67 of PS as this antibody's epitope. A peptide representing PS residues 37-50 inhibited FVa-dependent prothrombinase activity in a non-competitive manner, with 50% inhibition observed at 11 µM peptide, whereas a peptide with a D-amino acid sequence of 37-50 was ineffective. FVa, but not FXa, bound specifically to the immobilised peptide representing residues 37-50, and the peptide inhibited binding of FVa to immobilised PS. These data implicate PS residues 37-50 as a binding site for FVa that mediates, at least in part, the direct inhibition of FVa-dependent procoagulant activity by PS.