Eleven adult sheep were divided into three groups. Baseline arterial blood samples were taken with the sheep standing and breathing room air. They were then anesthetized and placed in right (group one), left (group two), or dorsal (group three) recumbency. Arterial blood samples were taken at 30, 60, 90, and 120 minute intervals during anesthesia, and 15 minutes after the discontinuation of halothane in oxygen.Anesthetic induction resulted in an increase in arterial oxygen (PaoZ) and carbon dioxide (Paco,) tensions and a decrease in arterial pH (pHa) and base excess (BE). During anesthetic maintenance, no positional effects were noted, and pHa and BE increased in all groups. With the termination of anesthesia and the animals breathing room air, pHa increased, and Paoz and Paco, decreased; BE was elevated in group two when compared to group three. Only BE had returned to control values 15 minutes after halothane was discontinued.
Nucleoside diphosphate kinase A (NDPK-A), encoded by the nm23-H1 gene, acts as a metastasis suppressor in certain human tumors such as breast carcinoma. However, evidence also points to NDPK-A functioning as a metastasis promoter in other human tumors including neuroblastoma. In fact, amplification and overexpression of nm23-H1 as well as S120G mutation of NDPK-A (NDPK-AS120G) have been detected in 14% to 30% of patients with advanced stages of neuroblastoma. To test whether NDPK-A promotes neuroblastoma metastasis, we established stable transfectants and an orthotopic xenograft animal model from the human neuroblastoma NB69 cell line. We demonstrate that overexpressed NDPK-A or NDPK-AS120G increased both incidence and colonization of neuroblastoma metastasis in animal lungs without significantly affecting primary tumor development. In vitro, these metastasis-associated NDPK-A aberrations abrogated retinoic acid-induced neuronal differentiation while increasing cloning efficiency, cell survival, and colony formation of NB69 derivatives. Furthermore, NDPK-AS120G reduced cell adhesion and increased cell migration. Compared with its wild-type, NDPK-AS120G appears more effective in promoting neuroblastoma metastasis. Our results provide the first evidence that NDPK-A behaves as a metastasis promoter at least in human neuroblastoma derived from NB69 cells. The findings not only suggest a prognostic value of NDPK-A in neuroblastoma patients but also caution NDPK-A-targeted treatment for patients with different tumor types.
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