Carbonyl reductase as a significant predictor of survival and lymph node metastasis in epithelial ovarian cancer

We have recently reported a novel function for carbonyl reductase (CR), namely, its ability to modulate the metastatic potential of malignant mouse cells. Because there are currently no data addressing a similar function for CR in human cancers, the aim of this study was to assess a correlation between survival and metastasis, and CR level in epithelial ovarian cancer. Using anti-CR antibody, immunohistochemical staining was performed on 73 epithelial ovarian cancers, 13 borderline malignant tumours, and 25 benign ovarian tumours for a total of 111 specimens. The combined rate for strongly and weakly positive reactions for CR was 32.0% for benign tumours, 38.5% for borderline malignant tumours, and 61.6% for ovarian cancers. The CR-positive rate was 35.7% (weakly positive alone) for ovarian cancers with retroperitoneal lymph node (RLN) metastasis and 67.8% for those without RLN metastasis (P< 0.05). The 5-year survival rate was 62.7% for the patients with CR-negative cancer and 86.1% for those with CR-positive cancer (P< 0.05). The present results indicate that decreased CR expression in epithelial ovarian cancer is associated with RLN metastasis and poor survival.© 2001 Cancer Research Campaignhttp://www.bjcancer.co

Crowding Alone Cannot Account for Cosolute Effect on Amyloid Aggregation

Amyloid fiber formation is a specific form of protein aggregation, often resulting from the misfolding of native proteins. Aimed at modeling the crowded environment of the cell, recent experiments showed a reduction in fibrillation halftimes for amyloid-forming peptides in the presence of cosolutes that are preferentially excluded from proteins and peptides. The effect of excluded cosolutes has previously been attributed to the large volume excluded by such inert cellular solutes, sometimes termed “macromolecular crowding”. Here, we studied a model peptide that can fold to a stable monomeric β-hairpin conformation, but under certain solution conditions aggregates in the form of amyloid fibrils. Using Circular Dichroism spectroscopy (CD), we found that, in the presence of polyols and polyethylene glycols acting as excluded cosolutes, the monomeric β-hairpin conformation was stabilized with respect to the unfolded state. Stabilization free energy was linear with cosolute concentration, and grew with molecular volume, as would also be predicted by crowding models. After initiating the aggregation process with a pH jump, fibrillation in the presence and absence of cosolutes was followed by ThT fluorescence, transmission electron microscopy, and CD spectroscopy. Polyols (glycerol and sorbitol) increased the lag time for fibril formation and elevated the amount of aggregated peptide at equilibrium, in a cosolute size and concentration dependent manner. However, fibrillation rates remained almost unaffected by a wide range of molecular weights of soluble polyethylene glycols. Our results highlight the importance of other forces beyond the excluded volume interactions responsible for crowding that may contribute to the cosolute effects acting on amyloid formation

Loss of Heterozygosity at the CYP2D6 Locus in Breast Cancer: Implications for Germline Pharmacogenetic Studies

Controversy exists regarding the impact of CYP2D6 genotype on tamoxifen responsiveness. We examined loss of heterozygosity (LOH) at the CYP2D6 locus and determined its impact on genotyping error when tumor tissue is used as a DNA source

Spatiotemporally resolved imaging of streamer discharges in air generated in a wire-cylinder reactor with (sub)nanosecond voltage pulses

We use (sub)nanosecond high-voltage pulses to generate streamers in atmospheric-pressure air in a wire-cylinder reactor. We study the effect of reactor length, pulse duration, pulse amplitude, pulse polarity, and pulse rise time on the streamer development, specifically on the streamer distribution in the reactor to relate it to plasma-processing results. We use ICCD imaging with a fully automated setup that can image the streamers in the entire corona-plasma reactor. From the images, we calculate streamer lengths and velocities. We also develop a circuit simulation model of the reactor to support the analysis of the streamer development. The results show how the propagation of the high-voltage pulse through the reactor determines the streamer development. As the pulse travels through the reactor, it generates streamers and attenuates and disperses. At the end of the reactor, it reflects and adds to itself. The local voltage on the wire together with the voltage rise time determine the streamer velocities, and the pulse duration the consequent maximal streamer length

Isokinetic Shoulder Strength of Women Softball Players: A Pilot Study

The purpose of this pilot study was to provide isokinetic shoulder strength data on college women softball players. Ten women ranging in age from 18 to 21 years old were tested. The Cybex II+, U.B.X.T. and HUMAC system were utilized to test the strength of external rotators, internal rotators, horizontal abductors, and horizontal adductors at 90, 180, and 300 deg/sec. Mean peak torque values were consistently greater in the dominant arm but there were no statistically significant differences in agonist to antagonist ratios between arms. The ratios of external rotators to internal rotators were consistently 2:3 while the ratios of horizontal adductors to horizontal abductors ranged from 3:4 to 1:2 throughout the velocity spectrum. A weak positive correlation was found to exist between total body weight and horizontal abduction in the nondominant arm at 90 deg/sec and horizontal abduction in the dominant arm at 180 deg/sec