Mental stress may have a negative impact on the immune state of cancer patients, in whom immunologic surveillance is essential for survival. This study investigated the immunological response of 19 patients with early-stage melanoma and a matched control group undergoing the Determination Stress Test before surgery. Cytokine and chemokine levels and lymphocyte subpopulations were measured at baseline and post-stress test time-points. Following the stress test lower levels of interleukin (IL)-6 were observed in the melanoma group compared with healthy volunteers (p = 0.044). IL-10 increased significantly in the control group 30 min after the stress test (p = 0.002) in comparison with the melanoma group (p = 0.407). CCL5/Rantes decreased significantly in the melanoma group, whereas CD16/CD56+ natural killer cells increased in both groups, with a sharp decrease below baseline after stress in the melanoma group (p = 0.001). This pilot study shows an altered immunological response to stressors in melanoma patients.
The PI3Kinase/Akt/mTOR pathway has important roles in cancer development for multiple tumor types, including UV-induced non-melanoma skin cancer. Immunosuppressed populations are at increased risk of aggressive cutaneous squamous cell carcinoma (SCC). Individuals who are treated with rapamycin, (sirolimus, a classical mTOR inhibitor) have significantly decreased rates of developing new cutaneous SCCs compared to those that receive traditional immunosuppression. However, systemic rapamycin use can lead to significant adverse events. Here we explored the use of topical rapamycin as a chemopreventive agent in the context of solar simulated light (SSL)-induced skin carcinogenesis. In SKH-1 mice, topical rapamycin treatment decreased tumor yields when applied after completion of 15 weeks of SSL exposure compared to controls. However, applying rapamycin during SSL exposure for 15 weeks, and continuing for 10 weeks after UV treatment, increased tumor yields. We also examined whether a combinatorial approach might result in more significant tumor suppression by rapamycin. We validated that rapamycin causes increased Akt (S473) phosphorylation in the epidermis after SSL, and show for the first time that this dysregulation can be inhibited in vivo by a selective PDK1/Akt inhibitor, PHT-427. Combining rapamycin with PHT-427 on tumor prone skin additively caused a significant reduction of tumor multiplicity compared to vehicle controls. Our findings indicate that patients taking rapamycin should avoid sun exposure, and that combining topical mTOR inhibitors and Akt inhibitors may be a viable chemoprevention option for individuals at high risk for cutaneous SCC.
The primary objective of our study was to update the prevalence of total body photography (TBP) utilization and the rationale for its implementation as an adjunctive screening measure by academic dermatologists across the USA, and investigate the emergence of total body digital photography (TBDP). Our secondary objective was to further examine how TBP/TBDP is being incorporated into the dermatology screening examination in academic pigmented lesion clinics. A questionnaire was mailed to 113 dermatology departments across the USA. About 43% (49/113) of surveyed departments responded. TBP was used by 67% (33/49) of the respondents. Of these respondents, 33% (11/33) used TBDP alone, 33% (11/33) used TBDP in combination with nondigitally based TBP, and 33% (11/33) used nondigital TBP with print photos. The three most frequently cited reasons for the use of full-body baseline photographs were that they reduced patient anxiety, led to fewer biopsies, and helped to find melanoma early in the curable stage. Respondents who did not use full body baseline photographs cited logistical constraints as the number one reason, followed by perceived lack of utility. In conclusion, our study shows that there is a significant number of academic dermatologists using TBP/TBDP. However, this study also shows that there are conflicting beliefs among academic dermatologists concerning the efficacy of TBP/TBDP. At this point with a documented growing trend in utilization of TBP, more studies are needed to evaluate the efficacy of this screening adjunct to diagnose melanoma early and positively impact survival because of early diagnosis.
Melanomas with poorly defined borders, lack of pigmentation, lentiginous extension, and location in cosmetically sensitive regions represent diagnostic and therapeutic challenges. Repeated surgical reexcisions are frequently required to achieve tumor-free margins. The use of reflectance mode confocal microscopy as an noninvasive method has shown to be a promising tool for diagnosing pigmented lesions in vivo.
