A dual-reporter, diagnostic vector for prostate cancer detection and tumor imaging.

Detection of prostate-specific antigen (PSA) as a screening strategy for prostate cancer is limited by the inability of the PSA test to differentiate between malignant cancer and benign hyperplasia. Here, we report the use of a cancer-specific promoter, inhibition of differentiation-1 (Id1), to drive a dual-reporter system (Ad5/3-Id1-SEAP-Id1-mCherry) designed for detection of prostate cancer using a blood-based reporter-secreted embryonic alkaline phosphatase (SEAP) and tumor visualization using a fluorescent reporter protein, mCherry. In human prostate tumors, Id1 levels are correlated with increased Gleason grade and disease progression. To evaluate the performance of the dual-reporter system, a prostate cell panel with varying aggressive phenotypes was tested. Following infection with the Ad5/3-Id1-SEAP-Id1-mCherry vector, expression of the SEAP and mCherry reporters was shown to increase with increasing levels of cellular Id1. No correlation was observed between Id1 and PSA. To evaluate in vivo performance, flank tumors were grown in athymic male mice using three prostate cancer cell lines. Following intra-tumoral injection of the vector, tumors formed by cells with high Id1 had the greatest reporter expression. Interestingly, tumors with the lowest levels of Id1 and reporter expression produced the greatest amounts of PSA. These data support the use of Ad5/3-Id1-SEAP-Id1-mCherry as a predictor of prostate cancer malignancy and as a strategy for tumor localization.

Efficacy of the fixed 1.2% clindamycin phosphate, 0.025% tretinoin gel formulation (Velac) and a proprietary 0.025% tretinoin gel formulation (Aberela) in the topical control of facial acne.

BACKGROUND: A formulation containing agents affecting the non-inflammatory as well as the inflammatory lesions of acne vulgaris at the same time would be efficient, probably showing a high efficacy and possibly a considerable shortening of the duration of treatment. One single formulation would simplify drug administration thereby enhancing patient compliance and possibly leading to improved therapeutic results. In two studies this seems to have been corroborated for the fixed clindamycin phosphate-tretinoin gel formulation. OBJECTIVE: This study was designed to assess whether the recently developed fixed formulation of 1.2% clindamycin phosphate and 0.025% tretinoin in a gel base (Velac), further referred to as Clindamycin phosphate Tretinoin Gel is at least as effective as a proprietary 0.025% tretinoin gel formulation (Aberela, Janssen Cilag Ab, Sollentuna, Sweden; further defined as tretinoin) showing an additional anti-inflammatory effect in the treatment of moderate to severe acne vulgaris. METHODS: In a double-blind, randomised study 72 patients were treated with CTG and 73 with tretinoin gel in a once daily regimen for 12 weeks. Responses, irritation as well as possible systemic and other adverse effects were recorded after 4, 8 and 12 weeks of treatment and the improvement, compared to baseline, assessed in all included patients. An additional assessment of the safety parameters was carried out at week 2. Parameters of efficacy were the various acne lesion counts, the overall acne severity grade and the calculated totals of acne lesion counts. RESULTS: CTG was statistically significantly more effective than tretinoin at the P = 0.05 level in the papular and the total mean inflammatory lesion counts as well as in the estimated or calculated mean overall acne severity scores. CTG and tretinoin gel were equally effective in the remaining parameters: open and closed comedones, the calculated total mean comedone, the pustule as well as the nodule lesion counts. The onset of action was faster for CTG than for tretinoin gel and evident in all assessed parameters except in open comedone lesion counts. In the calculated total mean acne lesion counts, half of all acne lesions had disappeared by week 6 of treatment with CTG, whereas this was recorded at week 9 for tretinoin gel. No clinically relevant changes in the parameters of safety as a consequence of treatment were observed, although the burning component of irritation was shown to be significantly less for CTG than for tretinoin gel. The observed adverse effects were considered minor. Treatment had to be discontinued in five patients on CTG and three on tretinoin. CONCLUSION: The addition of clindamycin to tretinoin, as in CTG, enhances the comedolytic efficacy of tretinoin in moderate to severe acne of the face, maintaining at the same time its anti-inflammatory efficacy thus accelerating resolution of all types of acne lesions without affecting the safety of response to both components.

Nomograms for calculating the number of patients needed for a clinical trial with survival as an endpoint.

This paper presents nomograms for calculating the sample size for a clinical trial with survival as an endpoint. The nomograms are valid when survival is exponential and patients enter the study uniformly.