Expression and localization of hypoxia proteins in prostate cancer: prognostic implications after radical prostatectomy.

OBJECTIVES: To uncover novel biomarkers that will help predict which patients are at risk and may guide future treatment decisions. A significant proportion of prostate cancer patients treated with radical prostatectomy will experience a recurrence of the disease. Given the substantial role of hypoxia in prostate cancer development and treatment, this investigation focuses on the Hypoxia Inducible Factor (HIF-1alpha) pathway. METHODS: A tissue microarray was constructed of prostate cancer tissue collected from 71 patients undergoing radical prostatectomy. The expression of proteins involved in the HIF-1alpha pathway was investigated by an immunohistochemical approach and correlated to clinical features including the time to biochemical recurrence. RESULTS: Expression of GLUT1 correlated significantly (P <.05) with a shorter time to biochemical recurrence after radical prostatectomy and was independent from the Gleason grade and stage of cancer. Furthermore, our studies revealed for the first time that accumulation of prolyl-4-hydroxylases 1 especially in the nucleus, is a significant indicator for a worse prognosis (P <.001). CONCLUSIONS: This study confirms the upregulation of proteins involved in the HIF-1alpha hypoxia pathway in prostate cancer cells, indicative of a hypoxic tumor state. Importantly, we report the identification of 2 novel markers, GLUT1 and prolyl-4-hydroxylases 1, with prognostic significance for patients undergoing radical prostatectomy.

DNA replication licensing and progenitor numbers are increased by progesterone in normal human breast.

Proliferation in the nonpregnant human breast is highest in the luteal phase of the menstrual cycle when serum progesterone levels are high, and exposure to progesterone analogues in hormone replacement therapy is known to elevate breast cancer risk, yet the proliferative effects of progesterone in the human breast are poorly understood. In a model of normal human breast, we have shown that progesterone increased incorporation of 5-bromo-2'-deoxyuridine and increased cell numbers by activation of pathways involved in DNA replication licensing, including E2F transcription factors, chromatin licensing and DNA replication factor 1 (Cdt1), and the minichromosome maintenance proteins and by increased expression of proteins involved in kinetochore formation including Ras-related nuclear protein (Ran) and regulation of chromosome condensation 1 (RCC1). Progenitor cells competent to give rise to both myoepithelial and luminal epithelial cells were increased by progesterone, showing that progesterone influences epithelial cell lineage differentiation. Therefore, we have demonstrated that progesterone augments proliferation of normal human breast cells by both activating DNA replication licensing and kinetochore formation and increasing bipotent progenitor numbers.

Haemostasis in laparoscopic partial nephrectomy: current status.

Laparoscopic partial nephrectomy (LPN) is increasingly performed all over the world. However, as in its open counterpart, achieving a satisfactory haemostasis may be challenging. Our goal is to describe the different methods employed to control bleeding during LPN. We performed a non-structured review of the literature on the different haemostatic methods used during LPN. The techniques and materials used are divided into two main groups: LPN with ischemia and LPN without ischemia. The techniques to achieve warm, cold and regional ischemia are described. Energy sources and sealants are discussed in the section on LPN without ischemia. Case selection is of capital importance in the choice the appropriate haemostatic tools for LPN. Some refinements, related to the nature of the laparoscopic procedure, are still required to reach an effective cold ischemia. A broad variety of energy sources have been tested in animal models and in human setting. Major disadvantages are tissue scarring, smoke creation and low progression speed. To date none has been demonstrated to be superior to the conventional suturing. Fibrin and thrombin promoters as bio-glues are an important adjuvant method during LPN. Bipolar current devices together with fibrin sealants or coagulation promoters are used in small peripheral tumors. In bigger or central tumors, additionally suturing over Surgicel bolsters, the most popular technique is to secure the suture by means of clips. The level of the recommendations is based on comparative cohorts. We conclude that haemostasis is achieved during LPN adapting the protocols used in open nephron sparing surgery to the laparoscopic approach. Renal ischemia and bolster sutures are still mandatory in complicated LPN while in case of small exophytic tumors a satisfactory haemostasis may be achieved by using only a sealant product.