Identification of fluorescence in situ hybridization assay markers for prediction of disease progression in prostate cancer patients on active surveillance.

BACKGROUND: Prostate Cancer (PCa) is the second most prevalent cancer among U.S. males. In recent decades many men with low risk PCa have been over diagnosed and over treated. Given significant co-morbidities associated with definitive treatments, maximizing patient quality of life while recognizing early signs of aggressive disease is essential. There remains a need to better stratify newly diagnosed men according to the risk of disease progression, identifying, with high sensitivity and specificity, candidates for active surveillance versus intervention therapy. The objective of this study was to select fluorescence in situ hybridization (FISH) panels that differentiate non-progressive from progressive disease in patients with low and intermediate risk PCa. METHODS: We performed a retrospective case-control study to evaluate FISH biomarkers on specimens from PCa patients with clinically localised disease (T1c-T2c) enrolled in Watchful waiting (WW)/Active Surveillance (AS). The patients were classified into cases (progressed to clinical intervention within 10 years), and controls (did not progress in 10 years). Receiver Operating Characteristic (ROC) curve analysis was performed to identify the best 3-5 probe combinations. FISH parameters were then combined with the clinical parameters ─ National Comprehensive Cancer Network (NNCN) risk categories ─ in the logistic regression model. RESULTS: Seven combinations of FISH parameters with the highest sensitivity and specificity for discriminating cases from controls were selected based on the ROC curve analysis. In the logistic regression model, these combinations contributed significantly to the prediction of PCa outcome. The combination of NCCN risk categories and FISH was additive to the clinical parameters or FISH alone in the final model, with odds ratios of 5.1 to 7.0 for the likelihood of the FISH-positive patients in the intended population to develop disease progression, as compared to the FISH-negative group. CONCLUSIONS: Combinations of FISH parameters discriminating progressive from non-progressive PCa were selected based on ROC curve analysis. The combination of clinical parameters and FISH outperformed clinical parameters alone, and was complimentary to clinical parameters in the final model, demonstrating potential utility of multi-colour FISH panels as an auxiliary tool for PCa risk stratification. Further studies with larger cohorts are planned to confirm these findings.

Survivorship, tunneling and feeding behaviors of Coptotermes formosanus (Isoptera: Rhinotermitidae) in response to 2'-acetonaphthone-treated sand.

In laboratory tests, 2'-acetonaphthone was incorporated into sand at different concentrations (4.16-200 mg kg(-1)) and evaluated for survivorship, feeding and tunneling effects on the Formosan subterranean termite, Coptotermes formosanus Shiraki. 2'-Acetonaphthone at 8.33 mg kg(-1) sand significantly reduced survivorship (89-94%), tunnel area (68-91%) and food consumption (84-100%) compared with the control. Most of the dead workers were found at the release point and a few had traveled to the surface of the treated sand. Malformed workers (< or =27%) with an unexpected symptom of molting failure were observed, particularly at the lowest concentration tested (4.16 mg kg(-1)). In choice assays, threshold concentration for significant reduction in survivorship, tunnel construction in treated sand and food consumption in the treated-sand side was 8.33mg kg(-1) with termites collected from New Orleans, LA and 35.0 mg kg(-1) for those from Lake Charles, LA. Termites actively fed and tunneled in the untreated sand, whereas 2'-acetonaphthone at 140mg kg(-1) completely inhibited consumption of food placed on the treated sand.

Toxicity and behavioral effects of nootkatone, 1,10-dihydronootkatone, and tetrahydronootkatone to the formosan subterranean termite (Isoptera: Rhinotermitidae).

Toxicity and behavioral effects of nootkatone and two of its derivatives, 1,10-dihydronootkatone and tetrahydronootkatone, to Coptotermes formosanus Shiraki were investigated on workers from two different colonies by using topical application assays, repellency assays, and sand barrier assays. The acute toxicity of the nootkatones on workers from both colonies increased as the saturation of the molecule increased, but the difference was significant for only one colony. The results of the repellency assays showed a similar trend of efficiency; the threshold concentration for significant repellency was four-fold higher in nootkatone treatments (50 ppm) than in the reduced derivatives 1,10-dihydronootkatone or tetrahydronootkatone (12.5 ppm). In sand barrier assays, a concentration of 100 ppm of any of the three chemicals significantly reduced termite survival, tunnel building, and food consumption after a 12-d exposure. Termites preexposed to 100 ppm nootkatone-treated sand and placed in containers without nootkatone for 15 d continued to exhibit abnormal feeding and digging behaviors; survivorship, tunneling, and feeding activities were significantly reduced by 83.5, 63.2, and 95.4%, respectively. Termites pretreated for 12 d at concentrations of 50 and 75 ppm nootkatone and tetrahydronootkatone returned to normal digging activity after they were removed from the treatments, but their feeding activity was significantly reduced.

Toxicity, repellency, and horizontal transmission of fipronil in the formosan subterranean termite (Isoptera: Rhinotermitidae).

Toxicity of fipronil was evaluated against field-collected Coptoteres formosanus Shiraki. In topical application assays, fipronil was highly effective against both workers and soldiers at very low doses. Acute toxicity after 24 h was significantly greater in workers than in soldiers. The LD50s were 2.59- and 2.91-fold greater with soldiers than with workers from the two tested colonies. The LD50s of fipronil at 72 h after treatment were <2.0 ng/insect, with no significant differences regarding the tested workers/soldiers or colonies. Treated soldiers placed with untreated workers significantly increased worker mortality. However, there was no significant horizontal transmission of fipronil from treated workers to untreated soldiers. Fipronil at rates of 0.063% or less showed no repellency, whereas sand treatments of 0.125% fipronil were repellent to termite workers.