Prostate cancer is the most common cancer in men. Advanced prostate cancer spreading beyond the gland is incurable. Identifying factors that regulate the spread of tumor into the regional nodes and distant sites would guide the development of novel diagnostic, prognostic, and therapeutic targets. The aim of our study was to examine the expression and biological role of EphB4 in prostate cancer. EphB4 mRNA is expressed in 64 of 72 (89%) prostate tumor tissues assessed. EphB4 protein expression is found in the majority (41 of 62, 66%) of tumors, and 3 of 20 (15%) normal prostate tissues. Little or no expression was observed in benign prostate epithelial cell line, but EphB4 was expressed in all prostate cancer cell lines to varying degrees. EphB4 protein levels are high in the PC3 prostate cancer cell line and several folds higher in a metastatic clone of PC3 (PC3M) where overexpression was accompanied by EphB4 gene amplification. EphB4 expression is induced by loss of PTEN, p53, and induced by epidermal growth factor/epidermal growth factor receptor and insulinlike growth factor-I/insulin-like growth factor-IR. Knockdown of the EphB4 protein using EphB4 short interfering RNA or antisense oligodeoxynucleotide significantly inhibits cell growth/viability, migration, and invasion, and induces apoptosis in prostate cancer cell lines. Antisense oligodeoxynucleotide targeting EphB4 in vivo showed antitumor activity in murine human tumor xenograft model. These data show a role for EphB4 in prostate cancer and provide a rationale to study EphB4 for diagnostic, prognostic, and therapeutic applications. (Cancer Res 2005; 65(11): 4623-32)

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Measurements provide the basis for monitoring and control of industrial processes as well as model development and validation. Therefore, systematic approaches are of great value to increase accuracy and reliability of measurements. In bioprocesses, linear conservation relations such as elements and enthalpy can be employed to relate conversion rates. In this work, a systematic approach has been applied to production scale fed‐batch yeast fermentations. The six data sets obtained from two industrial size bubble columns, one with 25 m3 volumes and the other with 100 m3 volumes, are analyzed for state estimation and error diagnosis. A statistical test is employed for error diagnosis. The serial elimination method is used to analyze and locate the source of errors. The conversion rates are calculated from primary measurements such as flow rates, temperatures, and concentrations. When available measurements are more than the degrees of freedom of the system, it is said that the system is redundant. The redundancy is, therefore, used for error detection and data reconciliation for the six data sets in this work. In addition to elemental balances, heat balance has been set up for the bubble columns, and metabolic heat production rate is employed as an additional measurement. The redundancy is employed for state estimation, and biomass concentration and specific growth rate have been estimated with great accuracy. The estimations can be further used for process monitoring and control. © 2006 American Institute of Chemical Engineers AIChE J, 2006

Increased VEGFR2 expression correlates with several features that predict progression of urothelial cancer, including disease stage and invasive phenotype. VEGF targeted therapy may enhance the efficacy of standard therapy for bladder cancer.

We have previously reported that high dietary salt exposure significantly increases daytime mean arterial pressure in spontaneously hypertensive rats (SHR) but not in normotensive Wistar-Kyoto (WKY) controls. In the present study, we used a telemetry monitoring system to evaluate the effects of high dietary salt exposure on diurnal variation of mean arterial pressure and heart rate in SHR and WKY rats. After implantation of a radio frequency transducer, SHR and WKY rats were maintained on either high (8%) or basal (1%) salt diets. Hemodynamic values were then analyzed for diurnal variation with the use of a nonlinear data-fitting program. After 2 weeks of dietary exposure, high salt-fed SHR had significantly greater 24-hour mean arterial pressure (156 +/- 3 mmHg) than SHR receiving basal (135 +/- 2 mmHg) and WKY rats receiving high (100 +/- 2 mmHg) or basal (100 +/- 1 mmHg) salt diets. Rhythm analysis indicated significant increases in both daytime and nighttime mean arterial pressure during high salt exposure in SHR. In WKY rats, high salt exposure increased nighttime but not daytime mean arterial pressure, with no net effect on 24-hour mean arterial pressure. High dietary salt exposure significantly decreased heart rate in both SHR and WKY rats, and it did not significantly alter the pattern of diurnal blood pressure or heart rate variation. These results indicate that WKY rats manifest an acute sensitivity to salt ingestion but have compensatory mechanisms sufficient to prevent sustained increases in mean arterial pressure; such mechanisms are lacking in SHR.

Purpose: Mesothelioma is a rare malignancy that is incurable and carries a short survival despite surgery, radiation, or chemotherapy.This study was designed to identify novel targets for diagnostic, prognostic, and therapeutic approaches. Experimental Design: The expression and functional significance of the receptor tyrosine kinase EphB4 was studied in vitro and in a murine model of mesothelioma. Results: EphB4 was highly expressed in mesothelioma cell lines and primary tumor tissues but not in normal mesothelium. Knockdown of EphB4 using small interfering RNA and antisense oligodeoxynucleotide showed reduction in cell survival, migration, and invasion. EphB4 knockdown initiated a caspase-8-mediated apoptosis and down-regulation of the antiapoptotic protein bcl-xl. EphB4 knockdown also resulted in reduced phosphorylation of Akt and down-regulation of matrix metalloproteinase-2 transcription. In addition, murine tumor xenograft studies using EphB4 oligodeoxynucleotides showed a marked reduction in tumor growth accompanied by a specific decline in EphB4 protein levels, reduced cell division, apoptosis in tumor tissue, and decreased microvascular density. Conclusions: EphB4 is expressed in mesothelioma, provides a survival advantage to tumor cells, and is therefore a potential novel therapeutic target.

SphK1 is upregulated in HNSCC, and inhibition of SphK1 sensitizes HNSCC to radiation-induced cytotoxicity.

We present the first implantable MEMS drug delivery device that includes an electrochemical bellows pump, refillable drug reservoir, and dual regulation valve. Multiple drug pump configurations were fabricated, assembled, and tested. Delivery of agents for cancer radiation reduction was demonstrated. In vivo chronic delivery of radiation sensitizing agents in the form of small interfering (siRNA)-gold nanorod complexes (nanoplexes) directly to tumors induced in mice was achieved. Radiation therapy in conjunction with active drug pumping by electrolysis actuation resulted in significant reduction of colon cancer tumor (HT29) size (~50%) over diffusion-based delivery and intravenous injections. To our knowledge, this is the first MEMS drug delivery pump suitable for safe, efficacious, and local delivery of short half-life siRNA in vivo.