ABSTRACT
EphB4 is a member of the largest family of transmembrane receptor tyrosine kinases and plays critical roles in axonal pathfinding and blood vessel maturation. We wanted to determine the biological role of EphB4 in ovarian cancer. We studied the expression of EphB4 in seven normal ovarian specimens and 85 invasive ovarian carcinomas by immunohistochemistry. EphB4 expression was largely absent in normal ovarian surface epithelium, but was expressed in 86% of ovarian cancers. EphB4 expression was significantly associated with advanced stage of disease and the presence of ascites. Overexpression of EphB4 predicted poor survival in both univariate and multivariate analyses. We also studied the biological significance of EphB4 expression in ovarian tumour cells lines in vitro and in vivo. All five malignant ovarian tumour cell lines tested expressed higher levels of EphB4 compared with the two benign cell lines. Treatment of malignant, but not benign, ovarian tumour cell lines with progesterone, but not oestrogen, led to a 90% reduction in EphB4 levels that was associated with 50% reduction in cell survival. Inhibition of EphB4 expression by specific siRNA or antisense oligonucleotides significantly inhibited tumour cell viability by inducing apoptosis via activation of caspase-8, and also inhibited tumour cell invasion and migration. Furthermore, EphB4 antisense significantly inhibited growth of ovarian tumour xenografts and tumour microvasculature in vivo. Inhibition of EphB4 may hence have prognostic and therapeutic utility in ovarian carcinoma.
Subject(s)
Cystadenocarcinoma, Serous/metabolism , Ovarian Neoplasms/metabolism , Receptor, EphB4/metabolism , Adult , Aged , Aged, 80 and over , Animals , Apoptosis , Caspases/metabolism , Cell Line, Tumor , Cell Movement , Cystadenocarcinoma, Serous/pathology , Female , Gene Expression Regulation, Neoplastic , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Middle Aged , Neoplasm Invasiveness , Ovarian Neoplasms/pathology , Progesterone/pharmacology , Progestins/pharmacology , RNA, Small Interfering/therapeutic use , Receptor, EphB4/antagonists & inhibitors , Survival RateSubject(s)
Peptic Ulcer/diagnosis , Peptic Ulcer/pathology , Biopsy , Gastroscopy , Humans , PentagastrinABSTRACT
The present study analyzes a 7-year experience of two concurrent groups of patients, one with and one without coronary artery disease. These groups underwent aortic valve replacement within the same time frame. They had the same method of myocardial protection and type of valve substitute, and there was no postoperative anticoagulant therapy. There was no statistically significant difference in hospital and late mortality, or in actuarial survival of the two groups after 4 years. Bypass grafting in patients with coronary artery disease undergoing aortic valve replacement reverts these groups of patients to the longterm prognostic level of patients with isolated aortic valve disease undergoing aortic valve replacement.
Subject(s)
Coronary Disease/diagnosis , Osteopathic Medicine , Spine/physiopathology , Adult , Aged , Female , Humans , Male , Middle Aged , Palpation , Physical ExaminationABSTRACT
A European study involving 15 major centres shows that the surgical treatment of a perforated duodenal ulcer depends closely upon the underlying condition and the operative risk. The latter is determined on the basis of the age of the subject, the time since the perforation, and the chronicity of the ulcer as well as the possible concomitant existence of severe medical pathology. In the optimal situation, preference is given to suture of the perforation and supraselective vagotomy. When general conditions are poor, the tendency is for a more simple approach such as simple suture or even the Taylor Wangensteen method. Type B II gastric resection remains indicated where there is associated bleeding or in the presence of large non-suturable ulcers which cannot be dealth with by a Rives-type patch of epiploon.
