http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2013 , Hindawi Publishing Corporation . All rights reserved. Thu, 23 May 2013 13:35:43 +0000 http://www.hindawi.com/journals/jsc/2013/537028/ AP1 (jun/fos) transcription factors (c-jun, junB, junD, c-fos, FosB, Fra-1, and Fra-2) are key regulators of epidermal keratinocyte survival and differentiation and important drivers of cancer development. Understanding the role of these factors in epidermis is complicated by the fact that each protein is expressed, at different levels, in multiple cells layers in differentiating epidermis, and because AP1 transcription factors regulate competing processes (i.e., proliferation, apoptosis, and differentiation). Various in vivo genetic approaches have been used to study these proteins including targeted and conditional knockdown, overexpression, and expression of dominant-negative inactivating AP1 transcription factors in epidermis. Taken together, these studies suggest that individual AP1 transcription factors have different functions in the epidermis and in cancer development and that altering AP1 transcription factor function in the basal versus suprabasal layers differentially influences the epidermal differentiation response and disease and cancer development. Richard L. Eckert, Gautam Adhikary, Christina A. Young, Ralph Jans, James F. Crish, Wen Xu, and Ellen A. Rorke Copyright © 2013 Richard L. Eckert et al. All rights reserved. Wed, 08 May 2013 08:10:43 +0000 http://www.hindawi.com/journals/jsc/2013/423829/ Ipilimumab, a fully human anti-cytotoxic T-lymphocyte antigen-4 monoclonal antibody that potentiates antitumor T-cell responses, has demonstrated improved survival in previously treated and treatment-naïve patients with unresectable stage III/IV melanoma. Survival benefit has also been shown in diverse patient populations, including those with brain metastases. In 2011, ipilimumab (3 mg/kg every 3 weeks for 4 doses) was approved by the Food and Drug Administration for unresectable or metastatic melanoma. Ipilimumab can induce novel response patterns for which immune-related response criteria have been proposed. irAEs are common but are usually low grade; higher grades can be severe and life-threatening. irAEs are usually manageable using established guidelines emphasizing vigilance and prompt intervention. This agent provides an additional therapeutic option in metastatic melanoma, and guidelines for management of adverse events facilitate clinical implementation of this new agent. Bartosz Chmielowski Copyright © 2013 Bartosz Chmielowski. All rights reserved. Mon, 29 Apr 2013 09:00:14 +0000 http://www.hindawi.com/journals/jsc/2013/452425/ To find clues about the mechanism by which kinase C epsilon (PKCε) may impart susceptibility to ultraviolet radiation (UVR)-induced development of cutaneous squamous cell carcinomas (SCC), we compared PKCε transgenic (TG) mice and their wild-type (WT) littermates for (1) the effects of UVR exposures on percent of putative hair follicle stem cells (HSCs) and (2) HSCs proliferation. The percent of double HSCs (CD34+ and α6-integrin or CD34+/CD49f+) in the isolated keratinocytes were determined by flow cytometric analysis. Both single and chronic UVR treatments (1.8 kJ/m2) resulted in an increase in the frequency of double positive HSCs in PKCε TG mice as compared to their WT littermates. To determine the rate of proliferation of bulge region stem cells, a 5-bromo-2′-deoxyuridine labeling (BrdU) experiment was performed. In the WT mice, the percent of double positive HSCs retaining BrdU label was % compared to % for the TG mice, an approximately 7-fold decrease. A comparison of gene expression profiles of FACS sorted double positive HSCs showed increased expression of Pes1, Rad21, Tfdp1 and Cks1b genes in TG mice compared to WT mice. Also, PKCε over expression in mice increased the clonogenicity of isolated keratinocytes, a property commonly ascribed to stem cells. Ashok Singh, Anupama Singh, Jordan M. Sand, Erika Heninger, Bilal Bin Hafeez, and Ajit K. Verma Copyright © 2013 Ashok Singh et al. All rights reserved. Mon, 22 Apr 2013 09:35:26 +0000 http://www.hindawi.com/journals/jsc/2013/632028/ Mouse models have informed us that p63 is critical for normal epidermal development and homeostasis. The p53/p63/p73 family is expressed as multiple protein isoforms due to a combination of alternative promoter usage and C-terminal alternative splicing. These isoforms can mimic or interfere with one another, and their balance ultimately determines biological outcome in a context-dependent manner. While not frequently mutated, p63, and in particular the ΔNp63 subclass, is commonly overexpressed in human squamous cell cancers. In vitro keratinocytes and murine transgenic and transplantation models have been invaluable in elucidating the contribution of altered p63 levels to cancer development, and studies have identified the roles for ΔNp63 isoforms in keratinocyte survival and malignant progression, likely due in part to their transcriptional regulatory function. These findings can be extended to human cancers; for example, the novel recognition of NFκB/c-Rel as a downstream effector of p63 has identified a role for NFκB/c-Rel in human squamous cell cancers. These models will be critical in enhancing the understanding of the specific molecular mechanisms of cancer development and progression. Kathryn E. King, Linan Ha, Tura Camilli, and Wendy C. Weinberg Copyright © 2013 Kathryn E. King et al. All rights reserved. Tue, 16 Apr 2013 08:34:28 +0000 http://www.hindawi.com/journals/jsc/2013/929364/ Since the first description of the Merkel cell carcinoma by Cyril Toker in 1972, the number of studies has significantly increased over the last 4 decades. In this review, we will illustrate the historical background of the Merkel cell carcinoma beginning with the 19th century, the first description of the Merkel cell to the finding of the CK20 as a highly specific diagnostic marker and finally to the recently detected Merkel cell polyomavirus (MCPyV). Moreover, we will highlight the beginning of adjuvant therapeutic regimens with radiotherapy and chemotherapy and discuss the diagnostic work-up including imaging and histology of patients with Merkel cell carcinoma. Another very rapidly growing and interesting field of research is the development of patients' specific and tailored targeted therapy, in particular in patients with distant metastatic disease. Inamaria Erovic and Boban M. Erovic Copyright © 2013 Inamaria Erovic and Boban M. Erovic. All rights reserved. Thu, 21 Mar 2013 13:16:52 +0000 http://www.hindawi.com/journals/jsc/2013/684050/ Signal transducer and activator of transcription 3 (Stat3) is a cytoplasmic protein that is activated in response to cytokines and growth factors and acts as a transcription factor. Stat3 plays critical roles in various biological activities including cell proliferation, migration, and survival. Studies using keratinocyte-specific Stat3-deficient mice have revealed that Stat3 plays an important role in skin homeostasis including keratinocyte migration, wound healing, and hair follicle growth. Use of both constitutive and inducible keratinocyte-specific Stat3-deficient mouse models has demonstrated that Stat3 is required for both the initiation and promotion stages of multistage skin carcinogenesis. Further studies using a transgenic mouse model with a gain of function mutant of Stat3 (Stat3C) expressed in the basal layer of the epidermis revealed a novel role for Stat3 in skin tumor progression. Studies using similar Stat3-deficient and gain-of-function mouse models have indicated its similar roles in ultraviolet B (UVB) radiation-mediated skin carcinogenesis. This paper summarizes the use of these various mouse models for studying the role and underlying mechanisms for the function of Stat3 in skin carcinogenesis. Given its significant role throughout the skin carcinogenesis process, Stat3 is an attractive target for skin cancer prevention and treatment. Everardo Macias, Dharanija Rao, and John DiGiovanni Copyright © 2013 Everardo Macias et al. All rights reserved. Sun, 24 Feb 2013 09:42:39 +0000 http://www.hindawi.com/journals/jsc/2013/735282/ Nowadays, oncogene-directed therapy and immunotherapy represent the two most promising avenues for patients with metastatic melanoma. The recent oncogene-directed therapeutic, vemurafenib, usually produces high level of tumor shrinkage and survival benefits in many patients with B-RA mutant melanomas, although the fast and high degrees of responses are likely short-lived. Conversely, the newly-approved immunotherapeutic, ipilimumab, produces durable responses in patients presenting CTLA-4 T-cell surface protein. Nevertheless, the possible synergy in combining these two therapeutic strategies primarily rely on the rational design of medical protocols (e.g., sequence and timing of agent administration; drug selectivity; compatibility of combined therapies i.e., adoptive T cell or agents, i.e., MEK inhibitor trametinib, PD-1 and PDL-1 blockers). Improved therapeutic protocols shall overcome therapeutic limitations such as the (i) tolerability and safety (i.e., minimal toxic side-effects); (ii) progression free survival (e.g., reduced relapse disease frequency); (iii) duration response (i.e., decreased drug resistance). Eventually, multidisciplinary approaches are still requested (e.g., genomics for personalized medicine, nanomedicine to overcome low free-drug bioavailability and targeting, systematic search of “melanoma stem cells” to enhance the prognosis and develop more valuable theranostics). In this paper, I will mainly present and discuss the latest and promising treatments for advanced cutaneous melanomas. Farid Menaa Copyright © 2013 Farid Menaa. All rights reserved. Thu, 21 Feb 2013 12:59:18 +0000 http://www.hindawi.com/journals/jsc/2013/742925/ Exploitation of biological properties unique to cancer cells may provide a novel approach to overcome difficult challenges to the treatment of advanced melanoma. In order to develop melanoma-targeted chemothermoimmunotherapy, a melanogenesis substrate, N-propionyl-4-S-cysteaminylphenol (NPrCAP), sulfur-amine analogue of tyrosine, was conjugated with magnetite nanoparticles. NPrCAP was exploited from melanogenesis substrates, which are expected to be selectively incorporated into melanoma cells and produce highly reactive free radicals through reacting with tyrosinase, resulting in chemotherapeutic and immunotherapeutic effects by oxidative stress and apoptotic cell death. Magnetite nanoparticles were conjugated with NPrCAP to introduce thermotherapeutic and immunotherapeutic effects through nonapoptotic cell death and generation of heat shock protein (HSP) upon exposure to alternating magnetic field (AMF). During these therapeutic processes, NPrCAP was also expected to provide melanoma-targeted drug delivery system. Kowichi Jimbow, Yasue Ishii-Osai, Shosuke Ito, Yasuaki Tamura, Akira Ito, Akihiro Yoneta, Takafumi Kamiya, Toshiharu Yamashita, Hiroyuki Honda, Kazumasa Wakamatsu, Katsutoshi Murase, Satoshi Nohara, Eiichi Nakayama, Takeo Hasegawa, Itsuo Yamamoto, and Takeshi Kobayashi Copyright © 2013 Kowichi Jimbow et al. All rights reserved. Thu, 14 Feb 2013 14:49:02 +0000 http://www.hindawi.com/journals/jsc/2013/267474/ The management of lymph nodes in nonmelanoma skin cancer patients is currently still debated. Merkel cell carcinoma (MCC), squamous cell carcinoma (SCC), pigmented epithelioid melanocytoma (PEM), and other rare skin neoplasms have a well-known risk to spread to regional lymph nodes. The use of sentinel lymph node biopsy (SLNB) could be a promising procedure to assess this risk in clinically N0 patients. Metastatic SNs have been observed in 4.5–28% SCC (according to risk factors), in 9–42% MCC, and in 14–57% PEM. We observed overall 30.8% positive SNs in 13 consecutive patients operated for high-risk nonmelanoma skin cancer between 2002 and 2011 in our institution. These high rates support recommendation to implement SLNB for nonmelanoma skin cancer especially for SCC patients. Completion lymph node dissection following positive SNs is also a matter of discussion especially in PEM. It must be remembered that a definitive survival benefit of SLNB in melanoma patients has not been proven yet. However, because of its low morbidity when compared to empiric elective lymph node dissection or radiation therapy of lymphatic basins, SLNB has allowed sparing a lot of morbidity and could therefore be used in nonmelanoma skin cancer patients, even though a significant impact on survival has not been demonstrated. Marie-Laure Matthey-Giè, Ariane Boubaker, Igor Letovanec, Nicolas Demartines, and Maurice Matter Copyright © 2013 Marie-Laure Matthey-Giè et al. All rights reserved. Sun, 10 Feb 2013 11:23:37 +0000 http://www.hindawi.com/journals/jsc/2013/327150/ Merkel cell carcinoma (MCC) is a rare neuroendocrine skin tumor that typically occurs in elderly, immunosuppressed patients. Infection with Merkel cell virus (MCV) and immunosuppression play an important role in the development of MCC. Different staging systems make it difficult to compare the existing clinical data. Furthermore, there predominantly exist single case reports and case series, but no randomized controlled trials. However, it is necessary to develop further therapy options because MCC tends to grow rapidly and metastasizes early. In the metastatic disease, therapeutic attempts were made with various chemotherapeutic combination regimens. Because of the high toxicity of these combinations, especially those established in SCLC, and regarding the unsatisfying results, the challenge is to balance the pros and cons of chemotherapy individually and carefully. Up to now, emerging new therapy options as molecular-targeted agents, for example, pazopanib, imatinib, or somatostatin analogues as well as immunologicals, for example, imiquimod and interferons, also showed less success concerning the disease-free response rates. According to the literature, neither chemotherapy nor molecular-targeted agents or immunotherapeutic strategies have shown promising effects in the therapy of the metastatic disease of MCC so far. There is a great demand for randomized controlled studies and a need for an MCC registry and multicenter clinical trials due to the tumors curiosity. Laura Desch and Rainer Kunstfeld Copyright © 2013 Laura Desch and Rainer Kunstfeld. All rights reserved. Wed, 06 Feb 2013 09:33:08 +0000 http://www.hindawi.com/journals/jsc/2013/973123/ Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine tumor of the skin with a mortality rate of approximately 25% (Peloschek et al., 2010). Accurate assessment of nodal involvement in patients with MCC predicts significantly overall outcome (Smith et al., 2012 and Ortin-Perez et al., 2007). Due to the rarity of this highly aggressive disease, only a few imaging reports on MCC were published, and subsequently still to date no accepted imaging algorithm for MCC is available. For primary staging of MCC, general recommendations have included ultrasonography, chest X-ray CT, and MRI, but recent articles show that the use of sentinel node and FDG-PET/PET-CT is gaining more and more importance. Elisabeth Enzenhofer, Philipp Ubl, Christian Czerny, and Boban M. Erovic Copyright © 2013 Elisabeth Enzenhofer et al. All rights reserved. Mon, 14 Jan 2013 15:35:21 +0000 http://www.hindawi.com/journals/jsc/2013/189342/ Background. The goal of this paper is to review contemporary multidisciplinary treatment with reference to Merkel cell carcinoma. Management of this rare but highly aggressive skin cancer is a complex undertaking that necessitates an understanding of its etiology, epidemiology, clinical presentation, and the coordinated work of several clinical specializations. Recent Findings. The contemporary literature employs a multidisciplinary approach to achieve the best patient's treatment. Conclusion. This paper presents an algorithm for contemporary management for the rare and aggressive Merkel cell carcinoma. Multidisciplinary approach in a tumor center provides high-quality care for patients with Merkel cell carcinoma. Sven Schneider, Dietmar Thurnher, and Boban M. Erovic Copyright © 2013 Sven Schneider et al. All rights reserved. Thu, 10 Jan 2013 18:55:30 +0000 http://www.hindawi.com/journals/jsc/2013/828329/ There is a need for effective “broad spectrum” therapies for metastatic melanoma which would be suitable for all patients. The objectives of Phase Ia/Ib studies were to evaluate the safety, pharmacokinetics, dosimetry, and antitumor activity of 188Re-6D2, a 188-Rhenium-labeled antibody to melanin. Stage IIIC/IV metastatic melanoma (MM) patients who failed standard therapies were enrolled in both studies. In Phase Ia, 10 mCi 188Re-6D2 were given while unlabeled antibody preload was escalated. In Phase Ib, the dose of 188Re-6D2 was escalated to 54 mCi. SPECT/CT revealed 188Re-6D2 uptake in melanoma metastases. The mean effective half-life of 188Re-6D2 was 12.4 h. Transient HAMA was observed in 9 patients. Six patients met the RECIST criteria for stable disease at 6 weeks. Two patients had durable disease stabilization for 14 weeks and one for 22 weeks. Median overall survival was 13 months with no dose-limiting toxicities. The data demonstrate that 188Re-6D2 was well tolerated, localized in melanoma metastases, and had antitumor activity, thus warranting its further investigation in patients with metastatic melanoma. M. Klein, M. Lotem, T. Peretz, S. T. Zwas, S. Mizrachi, Y. Liberman, R. Chisin, J. Schachter, I. G. Ron, G. Iosilevsky, J. A. Kennedy, E. Revskaya, A. W. de Kater, E. Banaga, V. Klutzaritz, N. Friedmann, E. Galun, G. L. DeNardo, S. J. DeNardo, A. Casadevall, E. Dadachova, and G. B. Thornton Copyright © 2013 M. Klein et al. All rights reserved. Thu, 10 Jan 2013 18:16:17 +0000 http://www.hindawi.com/journals/jsc/2013/325086/ Merkel cell carcinoma (MCC) is a rare cutaneous malignancy occurring mostly in older immunocompromized Caucasian males. A growing incidence of MCC has been reported in epidemiological studies. Treatment of MCC usually consists of surgical excision, pathological lymph node evaluation, and adjuvant radiotherapy. This paper reports the experience of a single tertiary center institution with 17 head and neck Merkel cell carcinoma patients. Median followup for the cohort was 37.5 months. After five years, recurrence-free survival, disease specific survival, and overall survival were 85%, 90%, and 83%, respectively. Our limited data support the use of adjuvant radiotherapy. We also report two cases of MCC located at the vestibule of the nose and two cases of spontaneous regression after diagnostic biopsy. About 40% of our patients were referred to our center for surgical revision and pathological lymph node evaluation. Increased awareness of MCC and an interdisciplinary approach are essential in the management of MCC. G. Morand, D. Vital, T. Pézier, D. Holzmann, M. Roessle, A. Cozzio, and G. F. Huber Copyright © 2013 G. Morand et al. All rights reserved. Wed, 26 Dec 2012 09:13:38 +0000 http://www.hindawi.com/journals/jsc/2012/249063/ TGFβ1 is a member of a large growth factor family including activins/inhibins and bone morphogenic proteins (BMPs) that have a potent growth regulatory and immunomodulatory functions in normal skin homeostasis, regulation of epidermal stem cells, extracellular matrix production, angiogenesis, and inflammation. TGFβ signaling is tightly regulated in normal tissues and becomes deregulated during cancer development in cutaneous SCC and many other solid tumors. Because of these diverse biological processes regulated by TGFβ1, this cytokine and its signaling pathway appear to function at multiple points during carcinogenesis with distinct effects. The mouse skin carcinogenesis model has been a useful tool to dissect the function of this pathway in cancer pathogenesis, with transgenic and null mice as well as small molecule inhibitors to alter the function of the TGFβ1 pathway and assess the effects on cancer development. This paper will review data on changes in TGFβ1 signaling in human SCC primarily HNSCC and cutaneous SCC and different mouse models that have been generated to investigate the relevance of these changes to cancer. A better understanding of the mechanisms underlying the duality of TGFβ1 action in carcinogenesis will inform potential use of this signaling pathway for targeted therapies. Adam B. Glick Copyright © 2012 Adam B. Glick. All rights reserved. Thu, 20 Dec 2012 08:53:24 +0000 http://www.hindawi.com/journals/jsc/2012/825095/ Background. Advanced basal cell carcinoma (BCC) is often treated by surgery or X-ray therapy. The consequences of X-ray therapy on the patients’ health-related quality-of-life (HRQOL) have so far not been described. Objectives. To quantify quality of life in BCC patients before and after X-ray therapy compared with matched healthy controls. Materials. Twenty-five patients (mean age 69) with BCC completed the Dermatology Life Quality Index (DLQI) before and two weeks and three months after X-ray therapy and their results were compared with the DLQI scores for 25 matched controls. Results. Compared to the healthy controls the patients' DLQI score was significantly higher before and 2 weeks after X-ray therapy (; ). The patients' DLQI score decreased significantly from baseline to three months after X-ray therapy (), when it became similar to that of the healthy controls (). Three months after X-ray therapy eight patients had no skin reactions, 11 had slight atrophy, pigmentation change, and/or some hair loss, four had patch atrophy, moderate telangiectasia, and/or total hair loss. Conclusions. BCC has a negative effect on patients' quality of life. The study shows that HRQOL normalises shortly after X-ray therapy, despite minor skin manifestations. Jette Skiveren, Maria Rudkjaer Mikkelsen, Helle Daugbjerg, and Hans Christian Wulf Copyright © 2012 Jette Skiveren et al. All rights reserved. Wed, 19 Dec 2012 14:55:28 +0000 http://www.hindawi.com/journals/jsc/2012/943472/ Objective. To analyze the pattern of presentation of basal cell carcinoma (BCC) and margin status for excised specimens in the head and neck region. Study Design. Retrospective cross-sectional. Duration of Study. January 2009 to December 2011. Methodology. The database of the pathology department was searched to identify records of all malignant skin tumors that underwent standard excision with margins. Out of these records, tumors with a diagnosis of BCC in the head and neck region were retrieved and separated. Age, gender, anatomic location, pattern of tumor, and margin status were noted. Results. A total of 171 cases of BCC from various sites of head and neck were retrieved. Male to female ratio was 1.4 : 1. The age ranged from 22 to 90 years. Seventy-six cases presented on right side, 79 on left, and 16 were in the midline. Most common anatomical site was the nose followed by the cheek. Nodular lesions were the most common (46.2%) followed by pigmented variety (18.7%). Margins were clear in 77 (45.1%) cases, involved in 86 (50.2%) cases, and close in 8 (4.7%) cases. Conclusion. Nose was the most common site followed by the cheek. Nodular and pigmented varieties were the most frequent and margins were involved in more than fifty percent of the cases. Omer Sefvan Janjua and Sana Mehmood Qureshi Copyright © 2012 Omer Sefvan Janjua and Sana Mehmood Qureshi. All rights reserved. Tue, 18 Dec 2012 08:00:16 +0000 http://www.hindawi.com/journals/jsc/2012/571087/ What is the cellular origin of melanoma? What role do melanocyte stem cells (MSC) and other melanocyte precursors play in the development of melanoma? Are MSCs and other latent melanocyte precursors more susceptible to solar radiation? These and many other questions can be very effectively addressed using the zebrafish model. Zebrafish have a robust regenerative capability, permitting the study of how MSCs are regulated and recruited at specific times and places to generate the pigment pattern following fin amputation or melanocyte ablation. They can be used to determine the effects of environmental radiation on the proliferation, survival, repair, and differentiation of MSCs. Our lab is using zebrafish to investigate how UVA- (320–400 nm) and UVB- (290–320 nm) induced damage to MSCs may contribute to the development of melanoma. A review is given of MSCs in zebrafish as well as experimental techniques and drugs for manipulating MSC populations. These techniques can be used to design experiments to help answer many questions regarding the role of MSCs or melanocyte precursors in the formation of melanoma stem cells and tumors following exposure to UVA/UVB radiation. James D. Hoerter, Patrick Bradley, Alexandria Casillas, Danielle Chambers, Brandon Weiswasser, Lauren Clements, Sarah Gilbert, and Albert Jiao Copyright © 2012 James D. Hoerter et al. All rights reserved. Mon, 17 Dec 2012 14:38:45 +0000 http://www.hindawi.com/journals/jsc/2012/438502/ Reconstruction of periocular defects following excision of cutaneous malignancy can present difficulties for oculofacial and reconstructive surgeons. The intricate anatomy of the eyelids and face requires precise restoration in order to avoid postoperative functional anesthetic concerns. Various reconstructive procedures based on common principles, location and size of the defect, can be applied to achieve restoration with the best possible functional and aesthetic outcomes. Scott M. Hayano, Katherine M. Whipple, Bobby S. Korn, and Don O. Kikkawa Copyright © 2012 Scott M. Hayano et al. All rights reserved. Thu, 13 Dec 2012 19:01:40 +0000 http://www.hindawi.com/journals/jsc/2012/147863/ Skin squamous cell carcinoma (SCC), the most common cancer in the USA, is a growing problem with the use of tanning booths causing sun-damaged skin. Antiproliferative effects of curcumin were demonstrated in an aggressive skin cancer cell line SRB12-p9 ( compared to control). Topical formulation was as effective as oral curcumin at suppressing tumor growth in a mouse skin cancer model. Curcumin at 15 mg administered by oral, topical, or combined formulation significantly reduced tumor growth compared to control (). Inhibition of pAKT, pS6, p-4EBP1, pSTAT3, and pERK1/2 was noted in SRB12-p9 cells post-curcumin treatment compared to control (). Inhibition of pSTAT3 and pERK1/2 was also noted in curcumin-treated groups in vivo. IHC analysis revealed human tumor specimens that expressed significantly more activated pERK () and pS6 () than normal skin samples. This is the first study to compare topical curcumin to oral curcumin. Our data supports the use of curcumin as a chemopreventive for skin SCC where condemned skin is a significant problem. Prevention strategies offer the best hope of future health care costs in a disease that is increasing in incidence due to increased sun exposure. Kunal Sonavane, Jeffrey Phillips, Oleksandr Ekshyyan, Tara Moore-Medlin, Jennifer Roberts Gill, Xiaohua Rong, Raghunatha Reddy Lakshmaiah, Fleurette Abreo, Douglas Boudreaux, John L. Clifford, and Cherie-Ann O. Nathan Copyright © 2012 Kunal Sonavane et al. All rights reserved. Thu, 13 Dec 2012 16:11:09 +0000 http://www.hindawi.com/journals/jsc/2012/286480/ Background. Basal cell carcinoma (BCC) is the most prevalent skin cancer. Because of its highly vascular characteristic, it is amendable to treatment with pulse dye laser (PDL). The goal of this study is to determine the safety and efficacy of PDL therapy for mostly facial BCCs. Materials and Methods. Sixteen men and thirteen women (29 total) with 39 biopsy-proven BCCs were treated with 1–4 PDL (595 nm) therapies at 2–4-week intervals. The treatment parameters included pulse energy of 15 J/cm 2, pulse length of 3 millisecond, with no dynamic cooling, and 7 mm spot size. The age of the patients was 30–90 years (mean 73 years). Response rates were evaluated by the clinical assessments with mean followup of 11 months. Results. Twenty-four patients with thirty-two tumors reached at least three months followup: 24/32 (75%) tumors with complete resolution (mean 3 treatment sessions); 5/32 (16%) tumors recurred; 3/32 (9%) tumors with incomplete responses after four treatments. Minimal side effects and discomfort were experienced by the patients with PDL therapy. Conclusion. PDL is a safe, tolerable, and moderately effective method of treating various BCCs. The ideal niche and standardized settings for PDL treatment of BCCs are yet to be determined. Norman Minars and Marianna Blyumin-Karasik Copyright © 2012 Norman Minars and Marianna Blyumin-Karasik. All rights reserved. Thu, 13 Dec 2012 08:49:40 +0000 http://www.hindawi.com/journals/jsc/2012/437502/ The key to improved prognosis for melanoma is early detection and diagnosis, achieved by skin surveillance and secondary prevention (screening). However, adherence to screening guidelines is low, with population-based estimates of approximately 26% for physician-based skin cancer screening and 20–25% for skin self-examination. The recent proliferation of melanoma detection “e-Health” tools, digital resources that facilitate screening in patients often outside of the clinical setting, may offer new strategies to promote adherence and expand the proportion and range of individuals performing skin self-examination. The purpose of this paper is to catalog and categorize melanoma screening e-Health tools to aid in the determination of their efficacy and potential for adoption. The availability and accessibility of such tools, their costs, target audience, and, where possible, information on their efficacy, will be discussed with potential benefits and limitations considered. While e-Health tools targeting melanoma screening are widely available, little has been done to formally evaluate their efficacy and ability to aid in overcoming screening barriers. Future research needs to formally evaluate the potential role of e-Health tools in melanoma prevention. Abhilasha Tyagi, Kimberly Miller, and Myles Cockburn Copyright © 2012 Abhilasha Tyagi et al. All rights reserved. Thu, 13 Dec 2012 08:37:43 +0000 http://www.hindawi.com/journals/jsc/2012/680410/ Merkel cell carcinoma (MCC), a highly aggressive skin tumour with increasing incidence, is associated with the newly discovered Merkel cell polyomavirus (MCPyV). Studies on MCC and MCPyV as well as other risk factors have significantly increased our knowledge of MCC pathogenesis, but the cells of origin, which could be important targets in future therapies, are still unknown. Merkel cells (MCs), the neuroendocrine cells of the skin, were believed to be at the origin of MCC due to their phenotypic similarities. However, for several reasons, for example, heterogeneous differentiation of MCCs and postmitotic character of MCs, it is not very likely that MCC develops from differentiated MCs. Skin stem cells, probably from the epidermal lineage, are more likely to be cells of origin in MCC. Future studies will have to address these questions more directly in order to identify the physiological cells which are transformed to MCC cells. Thomas Tilling and Ingrid Moll Copyright © 2012 Thomas Tilling and Ingrid Moll. All rights reserved. Sun, 02 Dec 2012 18:01:15 +0000 http://www.hindawi.com/journals/jsc/2012/231693/ Background. While it is established that the incidence of cutaneous melanoma has risen over time in the United States, the incidence trend for mucosal melanoma of the head and neck (MMHN) is unknown. Methods. We used the Surveillance, Epidemiology, and End Results (SEER) database to determine incidence trends for MMHN from 1987 to 2009 in the United States. We determined annual percent change (APC) by weighted least squares and joinpoint regression analysis. Results. MMHN incidence increased from 1987 to 2009 (APC 2.4%; ). Nasal cavity lesions increased in incidence (APC 2.7%; ) over this duration, while the incidence of non-nasal cavity lesions remained stable. The highest rate of increase was in white females ages 55 to 84 (APC 5.1%; ). Conclusions. The incidence of MMHN in the United States has been rising since 1987. This trend is driven primarily by increased incidence of nasal cavity melanomas. David M. Marcus, Rebecca P. Marcus, Roshan S. Prabhu, Taofeek K. Owonikoko, David H. Lawson, Jeffrey Switchenko, and Jonathan J. Beitler Copyright © 2012 David M. Marcus et al. All rights reserved. Wed, 28 Nov 2012 11:39:26 +0000 http://www.hindawi.com/journals/jsc/2012/981308/ Cutaneous melanoma, a type of skin tumor originating from melanocytes, often develops from premalignant naevoid lesions via a gradual transformation process driven by an accumulation of (epi)genetic lesions. These dysplastic naevi display altered morphology and often proliferation of melanocytes. Additionally, melanocytes in dysplastic naevi show structural mitochondrial and melanosomal alterations and have elevated reactive oxygen species (ROS) levels. For this study we performed genome-wide expression and proteomic analysis of melanocytes from dysplastic naevus (DNMC) and adjacent normal skin (MC) from 18 patients. Whole genome expression profiles of the DNMC and MC of each individual patient subjected to GO-based comparative statistical analysis yielded significantly differentially expressed GO classes including “organellar ribosome,” “mitochondrial ribosome,” “hydrogen ion transporter activity,” and “prefoldin complex.” Validation of 5 genes from these top GO classes revealed a heterogeneous differential expression pattern. Proteomic analysis demonstrated differentially expressed proteins in DNMC that are involved in cellular metabolism, detoxification, and cytoskeletal organization processes, such as GTP-binding Rho-like protein CDC42, glutathione-S-transferase omega-1 and prolyl 4-hydroxylase. Collectively these results point to deregulation of cellular processes, such as metabolism and protein synthesis, consistent with the observed elevated oxidative stress levels in DNMC potentially resulting in oxidative DNA damage in these cells. Linda Gao, Frans A. van Nieuwpoort, Jacoba J. Out-Luiting, Paul J. Hensbergen, Femke A. de Snoo, Wilma Bergman, Remco van Doorn, and Nelleke A. Gruis Copyright © 2012 Linda Gao et al. All rights reserved. Sun, 25 Nov 2012 11:18:25 +0000 http://www.hindawi.com/journals/jsc/2012/404615/ The incidence of melanoma continues to increase year on year. With better surgical techniques and medical management, greater numbers of organ transplants are being performed annually with much longer graft survival. The authors review our current understanding of the incidence of melanoma amongst organ transplant recipients, outcomes compared to the immunocompetent population, and management strategies in this burgeoning group. Faisal R. Ali and John T. Lear Copyright © 2012 Faisal R. Ali and John T. Lear. All rights reserved. Sun, 25 Nov 2012 08:48:01 +0000 http://www.hindawi.com/journals/jsc/2012/823534/ The current study characterizes the mitosis-associated histone dual modification on the core of histone H3: trimethylation of histone H3 lysine 79 and simultaneous phosphorylation of H3 threonine 80 (H3K79me3T80ph). Through the use of protein and microscopy-based techniques, we find that H3K79me3T80ph shares a similar spatial and temporal regulation as H3S10ph but additionally requires methyltransferase activity. In addition, we find that Aurora kinase activity is necessary for the catalysis of H3K79me3T80ph in vivo. Finally, our analysis of H3K79me3T80ph using a tissue microarray indicates that H3K79me3T80ph marks a subset of primary cutaneous melanomas with metastatic potential indicating that H3K79me3T80ph may identify a subset of invasive melanomas with a more aggressive clinical behaviour. Danielle R. Martinez, Hunter W. Richards, Qiushi Lin, Carlos A. Torres-Cabala, Victor G. Prieto, Jonathan L. Curry, and Estela E. Medrano Copyright © 2012 Danielle R. Martinez et al. All rights reserved. Tue, 20 Nov 2012 11:06:59 +0000 http://www.hindawi.com/journals/jsc/2012/563829/ Merkel cell carcinoma of the head and neck (MCCHN) presents a clinical challenge due to its aggressive natural history, unpredictable lymphatic drainage, and high degree of treatment related morbidity. Histological examination of the regional lymph nodes is very important in determining the optimal treatment and is usually achieved by sentinel lymph node biopsy. Radiotherapy plays a critical role in the treatment of most patients with MCCHN. Surgery with adjuvant radiotherapy to the primary tumour site is associated with high local control rates. If lymph nodes are clinically or microscopically positive, adjuvant radiotherapy is indicated to decrease the risk of regional recurrence. The majority of locoregional recurrences occur at the edge or just outside of the radiation field, reflecting both the inherent radiosensitivity of MCC and the importance of relatively large volumes to include “in-transit” dermal lymphatic pathways. When surgical excision of the primary or nodal disease is not feasible, primary radiotherapy alone should be considered as a potentially curative modality and confers good loco-regional control. Concurrent chemoradiotherapy is well tolerated and may further improve outcomes. Justin Lee, Ian Poon, Judith Balogh, May Tsao, and Elizabeth Barnes Copyright © 2012 Justin Lee et al. All rights reserved. Mon, 12 Nov 2012 08:51:45 +0000 http://www.hindawi.com/journals/jsc/2012/621968/ Germ cell protein expression in melanoma has been shown to correlate with malignancy, severity of disease and to serve as an immunologic target for therapy. However, very little is known about the role that germ cell proteins play in cancer development. Unique germ cell pathways include those involved in immortalization, genetic evolution, and energy metabolism. There is an ever increasing recognition that within tumors there is a subpopulation of cells with stem-cell-like characteristics that play a role in driving tumorgenesis. Stem cell and germ cell biology is intertwined. Given the enormous potential and known expression of germ cell proteins in melanoma, it is possible that they represent a largely untapped resource that may play a fundamental role in tumor development and progression. The purpose of this paper is to provide an update on the current value of germ cell protein expression in melanoma diagnosis, prognosis, and therapy, as well as to review critical germ cell pathways and discuss the potential roles these pathways may play in malignant transformation. Ashley M. Rosa, Nitika Dabas, Diana M. Byrnes, Mark S. Eller, and James M. Grichnik Copyright © 2012 Ashley M. Rosa et al. All rights reserved. Thu, 08 Nov 2012 10:25:23 +0000 http://www.hindawi.com/journals/jsc/2012/673291/ We have reported previously that daily intravenous infusions of a soluble nanobiotechnological complex, polyhemoglobin-tyrosinase [polyHb-Tyr], can suppress the growth of murine B16F10 melanoma in a mouse model. In order to avoid the need for daily intravenous injections, we have now extended this further as follows. We have prepared two types of biodegradable nanocapsules containing [polyHb-Tyr]. One type is to increase the circulation time and decrease the frequency of injection and is based on polyethyleneglycol-polylactic acid (PEG-PLA) nanocapsules containing [polyHb-Tyr]. The other type is to allow for intratumoural or local injection and is based on polylactic acid (PLA) nanocapsules containing [polyHb-Tyr]. Cell culture studies show that it can inhibit the proliferation of murine B16F10 melanoma cells in the “proliferation model”. It can also inhibit the attachment of murine B16F10 melanoma cells in the “attachment model.” This could be due to the action of tyrosinase on the depletion of tyrosine or the toxic effect of tyrosine metabolites. The other component, polyhemoglobin (polyHb), plays a smaller role in nanocapsules containing [polyHb-Tyr], and this is most likely by its depletion of nitric oxide needed for melanoma cell growth. Yun Wang and Thomas M. S. Chang Copyright © 2012 Yun Wang and Thomas M. S. Chang. All rights reserved.