The Prostate
-
Dose escalation has resulted in improved biochemical control in patients with clinically localized prostate cancer treated with conformal external beam radiation (EBRT). Conformal dose distributions may also be achieved with brachytherapy. Therefore, biochemical control was evaluated for patients treated with combined external radiation therapy and low dose rate brachytherapy (EBRT + LDR). ⋯ These results support EBRT followed by brachytherapy boost as a safe and effective method for dose escalation in the treatment of prostate cancer.
-
We assessed the influence of sequential treatment of ionizing radiation followed by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on intracellular mechanisms of apoptosis of prostate tumor cells in vitro and in vivo. ⋯ The sequential treatment with irradiation followed by TRAIL can be used as a viable option to enhance the therapeutic potential of TRAIL in prostate cancer.
-
Early in the malignant transformation of prostate epithelial cells, the apoptotic response to androgen deprivation (AD) is lost and the principle response is a slowing of cell growth. In this study, we tested whether interruption of MDM2 function using antisense MDM2 oligonucleotide (AS) affects the apoptotic response of prostate cancer cells to AD. ⋯ Our results suggest that the apoptotic response of prostate cancer to AD is strongly influenced by MDM2 expression. Antisense MDM2 has broad potential as a therapeutic agent to sensitize prostate cancer cells to AD therapy by enhancing apoptotic cell death.
-
Review
Apoptotic impact of alpha1-blockers on prostate cancer growth: a myth or an inviting reality?
Pharmacological manipulation or genetic targeting of the major apoptosis regulators, such as bcl-2, caspases, and inhibitors of apoptosis (IAPs), represent clinically attractive avenues towards effective therapeutic strategies for advanced prostate cancer. A wealth of evidence established the alpha(1)-adrenoceptor antagonists to be clinically effective in relieving the symptoms associated with benign prostatic hyperplasia (BPH) by relaxing prostatic smooth muscle tone. This action alone however does not fully account for the long-term clinical response to these drugs in BPH patients. ⋯ This evidence challenges conventional knowledge of the mechanism of action of alpha(1)-adrenoceptor antagonists, and points to a new therapeutic value for these drugs by providing a differential molecular basis for their anti-tumor efficacy. The present review focuses on the characterization of the apoptotic/anti-angiogenic effect of quinazoline-based alpha(1)-adrenoceptor antagonists against prostate cancer cells and discusses the clinical significance of this action in the prevention and treatment of prostate cancer.
-
Apoptosis is a therapeutic target for the elimination of cancer cells. As elevations in ceramide levels induce apoptosis, there is much excitement about the use of agents that elevate ceramide levels as novel chemotherapeutic agents. Ceramidases are enzymes involved in degradation of ceramide and inhibition of ceramidase has been proposed as a mechanism to increase ceramide levels. This study provides the first insight into the effect of B13, an inhibitor of acid ceramidase, on human prostate cancer cell lines and xenografts. ⋯ Targeting ceramide pathways may be a novel treatment strategy for hormone refractory prostate cancer.