RESUMO
Villin is an actin-binding protein found in a few normal adult epithelia, namely epithelial cells in the digestive and urogenital tracts. Moreover, villin production is maintained in malignant cells. We assumed that cell lysis and necrosis of solid tumors producing villin might result in villin release into blood. We analyzed the villin content of sera from 788 patients and controls using an enzyme-linked immunosorbent assay. Patients and controls were classified into healthy donors, patients with benign diseases of the gastrointestinal tract, patients with colorectal cancers, and patients with malignant nondigestive diseases. In the panel of sera analyzed, the sensitivity of the assay for colorectal cancers was 50.5%, and its overall specificity for malignant digestive tumors was 94.5%. Results were statistically analyzed comparing each group of sera with each other. We conclude that the presence of villin is indicative of a pathological state in the gastrointestinal tract (P less than 0.001). Finally, we followed villin levels after tumor resections (60 patients). We found that the villin level in sera remains low in remissions but is raised in recurrences. We suggest that the villin assay may have clinical utility as a diagnostic adjunct for adenocarcinoma of the gastrointestinal tract. It may also have some value in monitoring patients with advancing colorectal carcinomas after resection of these tumors.
Assuntos
Biomarcadores Tumorais/sangue , Proteínas de Transporte/sangue , Neoplasias Colorretais/diagnóstico , Proteínas dos Microfilamentos/sangue , Adulto , Antígeno Carcinoembrionário/análise , Neoplasias Colorretais/sangue , Doenças do Sistema Digestório/sangue , Doenças do Sistema Digestório/diagnóstico , Ensaio de Imunoadsorção Enzimática , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de NeoplasiaRESUMO
PURPOSE: To evaluate the safety, pharmacokinetics, and efficacy of three different dose levels of pegylated granulocyte colony-stimulating factor (Ro 25-8315) on progenitor cell mobilization and hematologic recovery in cancer patients. PATIENTS AND METHODS: Breast cancer patients (n = 36) were randomly assigned to receive before (part I) and after (part II) chemotherapy either a single-dose injection of Ro 25-8315 (20 microg/kg, n = 9; 60 microg/kg, n = 9; 100 microg/kg, n = 10) or a standard daily dose of filgrastim (part I, 10 microg/kg/d; part II, 5 microg/kg/d) (control group, n = 8). RESULTS: Overall, Ro 25-8315 was well tolerated. In part I, more progenitor cell mobilization was observed with Ro 25-8315 100 microg/kg. The peak of circulating CD34(+) cells was obtained at day +5 in the four groups, and the absolute neutrophil count (ANC) returned to less than 20 x 10(9)/L by day +15. In part II, high levels of circulating CD34(+) cells (> 20 cells/microL) were obtained in all four groups. The chemotherapy-induced neutropenia (< 1 x 10(9)/L) was similar in the four groups. Ro 25-8315 100 microg/kg was more effective than filgrastim in reducing the number of patients with an ANC less than 0.5 x 10(9)/L on day +12 after chemotherapy. CONCLUSION: A single injection of Ro 25-8315 100 microg/kg might be the optimal dose for steady-state peripheral-blood progenitor cell mobilization. A single injection of 20, 60, or 100 microg/kg could be as efficient as daily administration of filgrastim to correct chemotherapy-induced cytopenia. The optimal dose of Ro 25-8315 should be determined according to the planned chemotherapy regimen.