Emerging biomarkers of prostate cancer (Review).

Prostate cancer progression involves activation of signaling pathways controlling cell proliferation, apoptosis, anoikis, angiogenesis and metastasis. The current PSA-based test for the diagnosis of prostate cancer lacks sensitivity and specificity, resulting in missed diagnoses and unnecessary biopsies. Intense research efforts to identify serum and tissue biomarkers will expand the opportunities to understand the functional activation of cancer-related pathways and consequently lead to molecular therapeutic targeting towards inhibition of tumor growth. Current literature describes multiple biomarkers that indicate the properties of prostate cancer including its presence, stage, metastatic potential and prognosis. Used singly, assays detecting these biomarkers have their respective shortcomings. Several recent studies evaluating the clinical utilization of multiple markers show promising results in improving prostate cancer profiling. This review discusses the current understanding of biomarker signature cluster-based approaches for the diagnosis and therapeutic response of prostate cancer derived from panels of biomarker tests that provide a selective molecular signature characteristic of the tumor. As these signatures are robustly defined and their pathways are exhaustively dissected, prostate cancer can be more accurately diagnosed, characterized, staged and targeted with inhibitory antitumor agents. The growing promise surrounding the recent evidence in identifying and utilizing such biomarker panels, will lead to improvement in cancer prognosis and management of the therapeutic response of prostate cancer patients.

Apoptosis induction by doxazosin and other quinazoline alpha1-adrenoceptor antagonists: a new mechanism for cancer treatment?

Doxazosin and related, quinazoline-based alpha(1)-adrenoceptor antagonists can induce apoptosis in prostate and various other normal, benign, smooth muscle, endothelial and malignant cells. Such apoptosis-inducing effects occur independently of alpha(1)-adrenoceptor antagonism and typically require much high concentrations than those required for receptor occupancy. Several studies have invested efforts towards the elucidation of the molecular mechanisms underlying doxazosin-induced apoptosis. These include various tumor cells, cardiomyocytes, endothelial cells and bladder smooth muscle cells. While the high concentrations of doxazosin required to induce apoptosis challenge the use of this and related drugs for clinical optimization of apoptosis induction, such quinazoline structure may represent chemical starting points to develop more potent apoptosis-inducing agents free of alpha(1)-adrenoceptor antagonistic action and suitable for cancer treatment with minimal and well-tolerated side effects.

Intraoperative transfusion of 1 U to 2 U packed red blood cells is associated with increased 30-day mortality, surgical-site infection, pneumonia, and sepsis in general surgery patients.

BACKGROUND: Transfusion of packed red blood cells (PRBCs) increases morbidity and mortality in select surgical specialty patients. The impact of low-volume, leukoreduced RBC transfusion on general surgery patients is less well understood. STUDY DESIGN: The American College of Surgeons National Surgical Quality Improvement Program participant use file was queried for general surgery patients recorded in 2005 to 2006 (n = 125,223). Thirty-day morbidity (21 uniformly defined complications) and mortality, demographic, preoperative, and intraoperative risk variables were obtained. Infectious complications and composite morbidity and mortality were stratified across intraoperative PRBCs units received. Multivariable logistic regression was used to assess influence of transfusion on outcomes, while adjusting for transfusion propensity, procedure type, wound class, operative duration, and 30+ patient risk factors. RESULTS: After adjustment for transfusion propensity, procedure group, wound class, operative duration, and all other important risk variables, 1 U PRBCs significantly (p < 0.05) increased risk of 30-day mortality (odds ratio [OR] = 1.32), composite morbidity (OR = 1.23), pneumonia (OR = 1.24), and sepsis/shock (OR = 1.29). Transfusion of 2 U additionally increased risk for these outcomes (OR = 1.38, 1.40, 1.25, 1.53, respectively; p