ABSTRACT
OBJECTIVES: Cyclin D1 is important for pancreatic cancer growth. Our aim was to determine the effects of cyclin D1 inhibition on the growth of established pancreatic tumors. METHODS: PANC-1 cells harboring cyclin D1 antisense cDNA in a tetracycline-inducible vector system were prepared. The effects of cyclin D1 inhibition after tumor development were characterized in a mouse model. RESULTS: In vitro removal of tetracycline induced cyclin D1 antisense cDNA expression and inhibited cyclin D1 expression and cyclin D1-associated kinase activity as well as anchorage-dependent and -independent growth. After establishment of xenograft tumors in the presence of tetracycline (2 mg/mL) in the drinking water, animals were assigned to either control (tetracycline remained in the drinking water) or to the group without tetracycline for which tetracycline was removed from the drinking water. Tumor growth was significantly inhibited after removal of tetracycline. Microscopic analysis revealed that the area of central necrosis was significantly increased in the group without tetracycline paralleled by a reduction of the vital peripheral area of proliferating cells. CONCLUSIONS: Our results confirmed that cyclin D1 plays an important role in the growth of pancreatic cancer cells and may be an attractive molecular target for the treatment of human pancreatic cancer.
Subject(s)
Cell Proliferation , Cyclin D1/metabolism , DNA, Antisense/biosynthesis , Genetic Therapy/methods , Pancreatic Neoplasms/therapy , Tetracycline/pharmacology , Animals , Cell Line, Tumor , Cyclin D1/genetics , DNA, Antisense/genetics , Female , Gene Expression Regulation/drug effects , Genes, Reporter , Humans , Mice , Mice, Nude , Necrosis , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Time Factors , Transfection , Tumor Burden , Xenograft Model Antitumor AssaysABSTRACT
In elective open infrarenal aortic aneurysm repair the surgical approach and the use of epidural anesthesia (EDA) may determine patients' outcome. Hence we analyzed our results after elective open aneurysm repair in the light of the surgical approach and the use of EDA. Retrospective analysis of a prospective data base. From December 2005 to April 2008, 125 patients with infrarenal aortic aneurysm underwent elective open repair. Patients were divided into four groups: retro- and transperitoneal approach with and without epidural anesthesia (RP+/-EDA and TP+/-EDA). In terms of age, sex, aneurysm diameter, ASA score and clamping time all groups were comparable. In the retroperitoneal groups significantly more tube grafts were implanted (63 vs. 27; P=0.001). The rate of surgical complications did not differ between the groups. The RP+EDA group had the lowest rate of postoperative assisted mechanical ventilation (5.1% vs. 35.7%; P=0.002) and medical complications (17.9% vs. 42.8%; P=0.032). Concerning frequency of surgical complications, the retroperitoneal incision was comparable to the transperitoneal approach in infrarenal aortic reconstruction. Supplementation with EDA resulted in a decreased rate of postoperative assisted mechanical ventilation and in lower morbidity rates.
