Renova Retin-A
The cytostatic effect of 9-cis-retinoic acid, tretinoin, and isotretinoin on three different human bladder cancer cell lines in vitro.

Laaksovirta S, Rajala P, Nurmi M, Tammela TL, Laato M.

Division of Urology, Tampere University Hospital, Finland.

Retinoids have been shown to have activity in both preclinical and clinical bladder cancer studies but their exact role in its treatment and prevention remains obscure. In this study cytostatic activity of a novel 9-cis-retinoic acid (9-cis-RA) was compared with two other retinoids: tretinoin and isotretinoin, in three different bladder cancer cell lines: RT4 (well differentiated), 5637 (moderately differentiated) and T24 (poorly differentiated). The three retinoids were incubated at concentrations of 0.3, 3 and 30 microg/ml with bladder cancer cells in microtitre plates for 3 and 6 days. The cytostatic effect was estimated by using luminometric measuring of ATP activity of viable cells in suspension. Compared with the older retinoids, tretinoin and isotretinoin, the highest concentration of 9-cis-RA had a cytostatic efficacy in all three bladder cancer cell lines tested. A clear dose response relationship was observed in isotretinoin-treated cultures after 6 days and in all 9-cis-RA-treated cultures. Tretinoin was either ineffective or had a stimulating effect on poorly differentiated tumour cells. To conclude, isotretinoin and 9-cis-RA had a cytostatic effect on human bladder cancer cells in vitro. However, the possibility of stimulating cancer growth at small doses, at least with tretinoin, and toxicity at high doses must be considered when planning clinical trials.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10092149&dopt=Abstract tretinoin Retin-A Renova



Renova Retin-A
Tretinoin-iontophoresis in atrophic acne scars.

Schmidt JB, Donath P, Hannes J, Perl S, Neumayer R, Reiner A.

Department of Dermatology, Institute of Clinical Pathology, University of Vienna Medical School, Austria.

BACKGROUND: Atrophic acne scars are a frequent problem after acne. Hitherto, mainly invasive treatment measures were possible. In a recent paper, we demonstrated the positive effects of iontophoresis with 0.025% tretinoin gel vs. estriol 0.03%. OBJECTIVE: In this further study, the recording of the clinical effects of iontophoresis with 0.025% tretinoin gel in atrophic acne scars was supplemented by immunohistochemistry investigations of collagen I and III, proliferation markers, and the estimation of epidermal thickness. METHODS: The treatment was performed twice weekly in 32 volunteer patients for a period of 3 months by application of the substance under a constant direct current of 3 mA for 20 min. Skin biopsies prior to and at the end of treatment were performed in 32 voluntary patients in order to investigate collagen I/III and proliferation markers by immunohistochemistry methods. RESULTS: Clinically, at the end of treatment, in 94% of patients a significant decrease in the scar depth was observed. Neither epidermal thickness nor proliferation markers revealed a significant increase at the end of treatment. Furthermore, collagen I and collagen III showed no common trend, as expressed statistically by a lack of significance. In some cases, increases in collagen III became evident at the end of treatment. CONCLUSIONS: Tretinoin-iontophoresis is an effective, noninvasive treatment of atrophic acne scars without causing disturbing side-effects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10192170&dopt=Abstract tretinoin Retin-A Renova



Renova Retin-A
Can transforming growth factor-beta1 and retinoids modify the activity of estradiol and antiestrogens in MCF-7 breast cancer cells?.

Czeczuga-Semeniuk E, Anchim T, Dzieciol J, Dabrowska M, Wolczynski S.

Department of Gynaecological Endocrinology, Medical University of Bialystok, Bialystok, Poland. czeczuga wp.pl

Retinoic acid and transforming growth factor-beta (TGF-beta) affect differentiation, proliferation and carcinogenesis of epithelial cells. The effect of both compounds on the proliferation of cells of the hormone sensitive human breast cancer cell line (ER+) MCF-7 was assessed in the presence of estradiol and tamoxifen. The assay was based on [3H]thymidine incorporation and the proliferative activity of PCNA- and Ki 67-positive cells. The apoptotic index and expression of the Bcl-2 and p53 antigens in MCF-7 cells were also determined. Exogenous TGF-beta1 added to the cell culture showed antiproliferative activity within the concentration range of 0.003-30 ng/ml. Irrespective of TGF-beta1 concentrations, a marked reduction in the stimulatory action of estradiol (10(-9) and 10(-8) M) was observed whereas in combination with tamoxifen (10(-7) and 10(-6) M) only 30 ng/ml TGF-beta1 caused a statistically significant reduction to approximately 30% of the proliferative cells. In further experiments we examined the effect of exposure of breast cancer cells to retinoids in combination with TGF-beta1. The incorporation of [3H]thymidine into MCF-7 cells was inhibited to 52 +/- 19% (control =100%) by 3 ng/ml TGF-beta1, and this dose was used throughout. It was found that addition of TGF-beta1 and isotretinoin to the culture did not decrease proliferation, while TGF-beta1 and tretinoin at low concentrations (3 x 10(-8) and 3 x 10(-7) M) reduced the percentage of proliferating cells by approximately 30% (67+/-8% and 67+/-5%, P<0.05 compared to values in the tretinoin group). Both retinoids also led to a statistically significant decrease in the stimulatory effect of 10(-9) M estradiol, attenuated by TGF-beta1. In addition, the retinoids in combination with TGF-beta1 and tamoxifen (10(-6) M) caused a further reduction in the percentage of proliferating cells. Immunocytochemical analysis showed that all the examined compounds gave a statistically significant reduction in the percentage of cells with a positive reaction to PCNA and Ki 67 antigen. TGF-beta1, isotretinoin and tretinoin added to the culture resulted in the lowest percentage of PCNA positive cells. However, the lowest fraction of Ki 67 positive cells was observed after addition of isotretinoin. The obtained results also confirm the fact that the well-known regulatory proteins Bcl-2 and p53 play an important role in the regulation of apoptosis in the MCF-7 cell line, with lowered Bcl-2 expression accompanying easier apoptotic induction. The majority of the examined compounds act via the p53 pathway although some bypass this important proapoptotic factor.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15448735&dopt=Abstract tretinoin Retin-A Renova



Renova Retin-A
Is prior authorization of topical tretinoin for acne cost effective?

Feldman SR, Fleischer AB Jr, Chen GJ.

Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1071, USA. sfeldman wfubmc.edu

OBJECTIVE: To determine whether prior authorization of topical tretinoin for acne is in the best interest of health insurers and, if so, to determine the optimal prior authorization age for topical tretinoin. STUDY DESIGN: A retrospective, cross-sectional study of data from the National Ambulatory Medical Care Survey was performed. PATIENTS AND METHODS: We performed a sensitivity analysis using published data on the age distribution for topical tretinoin prescriptions for acne and nonacne indications to estimate the cost of topical tretinoin and the cost of performing prior authorizations as a function of the prior authorization age. RESULTS: A prior authorization age of 25 for topical tretinoin is not cost effective for health insurers. If prior authorization is required, an age threshold of 35 or older is most cost effective. The total cost of topical tretinoin (the sum of the drug costs plus the prior authorization costs) changes little with changes in the prior authorization age; if the prior authorization age is set too low, total costs increase (because the number of prior authorizations increase). CONCLUSIONS: Prior authorization for topical tretinoin is of no great benefit to insurers. As the prior authorization age decreases, the cost of requiring prior authorization increases. Eliminating prior authorization altogether would result in at most a small increase in costs and would be balanced by the benefits to both patients and physicians.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10387385&dopt=Abstract tretinoin Retin-A Renova