RARα/RXR synergism potentiates retinoid responsiveness in cutaneous T-cell lymphoma cell lines.

Retinoids, natural and synthetic derivatives of vitamin A, induce cellular changes by activating nuclear retinoic acid receptors (RAR) and retinoid X receptors (RXR). Although the ability of retinoids to govern gene expression is exploited clinically for cancer therapeutics, the full benefit of retinoid-based strategies is unrealized due to detrimental side effects. Delineating the receptors that prompt cellular outcomes is critical to advancing retinoid-based approaches. Here, we identify the receptors that evoke multiple responses in cutaneous T-cell lymphoma (CTCL). The data demonstrate that RARα drives integrin ß7-dependent adhesion and CCR9-mediated chemotaxis in CTCL cells. Of note, concomitant activation of RARα and RXR nuclear receptors yielded synergistic increases in adhesion and migration at concentrations where single agents were ineffective. As the established paradigm of retinoid action in CTCL is apoptosis and growth arrest, the role of RARα/RXR in these events was studied. As with adhesion and migration, RARα/RXR synergism prompted apoptosis and dampened CTCL cell proliferation. Strikingly, RARα/RXR synergism induced responses from CTCL cell lines previously reported to be unresponsive to retinoids. These data provide a novel framework that may further refine a proven CTCL therapy.

A 10-year review of outpatient skin biopsy results and skin cancer subtypes.

The results of skin biopsies over a 10 year period were reviewed from the outpatient dermatology clinic at the Brody School of Medicine in Greenville, North Carolina. This research was conducted because there are very few studies that characterize this information over a long-term horizon. The biopsy rate per patient encounter, the clinical reason for the biopsy, the biopsy outcomes, the distribution of cutaneous malignancies per encounter, and the distribution of the subtypes of basal cell carcinoma, squamous cell carcinoma, and melanoma were analyzed. Biopsy logs from January 1, 2001 to December 31, 2010 were reviewed. Our investigation found that 20% of patient encounters resulted in a biopsy. Of these biopsies, 87.9% were performed to rule out malignancy and 12.1% were completed on patients suspected of having inflammatory skin conditions. The basal cell carcinomas diagnosed in Greenville, NC have more aggressive histologic subtypes compared to other studies, whereas the squamous cell carcinomas and melanomas were less aggressive.

Information system technologies' role in augmenting dermatologists' knowledge of prescription medication costs.

OBJECTIVES: Despite the recent rising costs of once affordable dermatologic prescription medications, a survey measuring dermatologists' attitudes, beliefs, and knowledge of the cost of drugs they commonly prescribe has not been conducted. Awareness of drug costs is hindered by a lack of access to data about the prices of medicines. No surveys of physicians have addressed this issue by proposing new information system technologies that augment prescription medication price transparency and measuring how receptive physicians are to using these novel solutions in their daily clinical practice. Our research aims to investigate these topics with a survey of physicians in dermatology. METHODS: Members of the North Carolina Dermatology Association were contacted through their electronic mailing list and asked to take an online survey. The survey asked several questions about dermatologists' attitudes and beliefs about drug costs. To measure their knowledge of prescription medications, the National Average Drug Acquisition Cost was used as an authoritative price that was compared to the survey takers' price estimates of drugs commonly used in dermatology. Physicians' willingness to use four distinct information system technologies that increase drug price transparency was also assessed. RESULTS: Dermatologists believe drug costs are an important factor in patient care and believe access to price information would allow them to provide a higher quality of care. Dermatologists' knowledge of the costs of medicines they commonly prescribe is poor, but they want to utilize information system technologies that increase access to drug pricing information. CONCLUSIONS: There is an unmet demand for information system technologies which increase price transparency of medications in dermatology. Physicians and IT professionals have the opportunity to create novel information systems that can be utilized to help guide cost conscious clinical decision making.

Retinoids Bias Integrin Expression and Function in Cutaneous T-Cell Lymphoma.

Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of malignancies characterized by accumulation of malignant T-cells within the skin. Retinoids, metabolic derivatives, and synthetic analogs of vitamin A embody an effective CTCL therapy with over three decades of clinical use. The established mechanism of action is induction of growth arrest and apoptosis. However, the natural role of retinoids in T-cell biology is imprinting gut-homing properties by inducing integrin α4ß7 expression. How the natural role of retinoids relates to therapeutic effectiveness in CTCL has not been addressed and merits investigation. Here we provide evidence that retinoids, including Bexarotene, selectively induce CTCL lineages to increase integrin ß7 expression and function prior to growth arrest and apoptosis. Interestingly, augmented CTCL cell adhesion obtained with retinoid exposure was potently attenuated by 1,25-dihydroxyvitamin D3, a metabolic vitamin derivative involved in prompting immune cell skin homing. The integrin-dependent adhesion changes in CTCL cells occurred through synergistic activation of RAR and RXR nuclear receptors. These data explore the early cellular changes induced by retinoids that may be pivotal to sensitizing CTCL cells to growth arrest and apoptosis.