Polymorphisms of the VDR gene are associated with presence of solar keratoses on the skin

Background Vitamin D has a range of biological effects including antiproliferative functions that are mediated through its receptors, encoded by the VDR gene. Objectives We investigated polymorphisms within the VDR gene for association with solar keratosis (SK), a biomarker for skin cancer, and examined interactions with skin phenotype. Methods Among participants of the community-based Nambour Skin Cancer Study, we genotyped 190 people with SKs and 190 without for ApaI, TaqI and FokI polymorphisms. Results We found a significant difference in genotype frequencies of the TaqI polymorphism between affected and unaffected populations (P = 0Æ008). The TT ⁄tt genotype group was associated with a twofold increase in odds of being affected by one or more SK. Individuals with fair skin and the TT ⁄tt genotype had about a sevenfold increase, whereas fair-skinned people with the Tt genotype had a fourfold increase in odds of being affected by SK. Individuals with the TT ⁄tt genotype who were prone to burn and not tan on acute sun exposure had about a sixfold increase in odds of SK. Fair-skinned people with VDR-Apa AA ⁄aa genotypes had about an eightfold increase in odds of being affected by SK compared with a fivefold increase in individuals with the Aa genotype and fair skin. Conclusions The trend for homozygote genotypes to increase the odds of SK suggests that intermediate VDR activity is important in protection or that the heterodimer formed by a heterozygous genotype may have an altered binding potential. Overall, these analyses indicate that VDR may be important in SK development.

Cytogenetic alterations in nonmelanoma skin cancer : a review

Since the advent of cytogenetic analysis, knowledge about fundamental aspects of cancer biology has increased, allowing the processes of cancer development and progression to be more fully understood and appreciated. Classical cytogenetic analysis of solid tumors had been considered difficult, but new advances in culturing techniques and the addition of new cytogenetic technologies have enabled a more comprehensive analysis of chromosomal aberrations associated with solid tumors. Our purpose in this review is to discuss the cytogenetic findings on a number of nonmelanoma skin cancers, including squamous- and basal cell carcinomas, keratoacanthoma, squamous cell carcinoma in situ (Bowen's disease), and solar keratosis. Through classical cytogenetic techniques, as well as fluorescence-based techniques such as fluorescence in situ hybridization and comparative genomic hybridization, numerous chromosomal alterations have been identified. These aberrations may aid in further defining the stages and classifications of nonmelanoma skin cancer and also may implicate chromosomal regions involved in progression and metastatic potential. This information, along with the development of newer technologies (including laser capture microdissection and comparative genomic hybridization arrays) that allow for more refined analysis, will continue to increase our knowledge about the role of chromosomal events at all stages of cancer development and progression and, more specifically, about how they are associated with nonmelanoma skin cancer.

Focussing on genomic and phenomic correlations in respiration of non-melanotic skin cancers

In recent years, with the development of techniques in modern molecular biology, it has become possible to study the genetic basis of carcinogenesis down to the level of DNA sequence. Major advances have been made in our understanding of the genes involved in cell cycle control and descriptions of mutations in those genes. These developments have led to the definition of the role of specific oncogenes and tumour suppressor genes in several cancers, including, for example, colon cancers and some forms of breast cancer. Work reported from our laboratory has led to the identification of a number of candidate genes involved in the development of non-melanotic skin cancers. In this chapter, we attempt to further explain the observed (phenomic) alterations in metabolic pathways associated with oxygen consumption with the changes at the genetic level.

Current status of pharmacogenomics testing for anti-tumor drug therapies : approaches to non-melanoma skin cancer

Skin cancer is one of the most commonly occurring cancer types, with substantial social, physical, and financial burdens on both individuals and societies. Although the role of UV light in initiating skin cancer development has been well characterized, genetic studies continue to show that predisposing factors can influence an individual's susceptibility to skin cancer and response to treatment. In the future, it is hoped that genetic profiles, comprising a number of genetic markers collectively involved in skin cancer susceptibility and response to treatment or prognosis, will aid in more accurately informing practitioners' choices of treatment. Individualized treatment based on these profiles has the potential to increase the efficacy of treatments, saving both time and money for the patient by avoiding the need for extensive or repeated treatment. Increased treatment responses may in turn prevent recurrence of skin cancers, reducing the burden of this disease on society. Currently existing pharmacogenomic tests, such as those that assess variation in the metabolism of the anticancer drug fluorouracil, have the potential to reduce the toxic effects of anti-tumor drugs used in the treatment of non-melanoma skin cancer (NMSC) by determining individualized appropriate dosage. If the savings generated by reducing adverse events negate the costs of developing these tests, pharmacogenomic testing may increasingly inform personalized NMSC treatment.

Characterisation of microvasulature changes after closed soft tissue trauma by contrast enhanced micro-CT imaging

INTRODUCTION It is known that the vascular morphology and functionality are changed following closed soft tissue trauma (CSTT) [1], and bone fractures [2]. The disruption of blood vessels may lead to hypoxia and necrosis. Currently, most clinical methods for the diagnosis and monitoring of CSTT with or without bone fractures are primarily based on qualitative measures or practical experience, making the diagnosis subjective and inaccurate. There is evidence that CSTT and early vascular changes following the injury delay the soft tissue tissue and bone healing [3]. However, a precise qualitative and quantitative morphological assessment of vasculature changes after trauma is currently missing. In this research, we aim to establish a diagnostic framework to assess the 3D vascular morphological changes after standardized CSTT in a rat model qualitatively and quantitatively using contrast-enhanced micro-CT imaging. METHODS An impact device was used for the application of a controlled reproducible CSTT to the left thigh (Biceps Femoris) of anaesthetized male Wistar rats. After euthanizing the animals at 6 hours, 24 hours, 3 days, 7 days, or 14 days after trauma, CSTT was qualitatively evaluated by macroscopic visual observation of the skin and muscles. For visualization of the vasculature, the blood vessels of sacrificed rats were flushed with heparinised saline and then perfused with a radio-opaque contrast agent (Microfil, MV 122, Flowtech, USA) using an infusion pump. After allowing the contrast agent to polymerize overnight, both hind-limbs were dissected, and then the whole injured and contra-lateral control limbs were imaged using a micro-CT scanner (µCT 40, Scanco Medical, Switzerland) to evaluate the vascular morphological changes. Correlated biopsy samples were also taken from the CSTT region of both injured and control legs. The morphological parameters such as the vessel volume ratio (VV/TV), vessel diameter (V.D), spacing (V.Sp), number (V.N), connectivity (V.Conn) and the degree of anisotropy (DA) were then quantified by evaluating the scans of biopsy samples using the micro-CT imaging system. RESULTS AND DISCUSSION A qualitative evaluation of the CSTT has shown that the developed impact protocols were capable of producing a defined and reproducible injury within the region of interest (ROI), resulting in a large hematoma and moderate swelling in both lateral and medial sides of the injured legs. Also, the visualization of the vascular network using 3D images confirmed the ability to perfuse the large vessels and a majority of the microvasculature consistently (Figure 1). Quantification of the vascular morphology obtained from correlated biopsy samples has demonstrated that V.D and V.N and V.Sp were significantly higher in the injured legs 24 hours after impact in comparison with the control legs (p<0.05). The evaluation of the other time points is currently progressing. CONCLUSIONS The findings of this research will contribute to a better understanding of the changes to the vascular network architecture following traumatic injuries and during healing process. When interpreted in context of functional changes, such as tissue oxygenation, this will allow for objective diagnosis and monitoring of CSTT and serve as validation for future non-invasive clinical assessment modalities.

The incidence and predictors of lower limb split skin graft failure and primary closure dehiscence in day case surgical patients

This project was an observational study of outpatients following lower limb surgical procedures for removal of skin cancers. Findings highlight a previously unreported high surgical site failure rate. Results also identified four potential risk factors (increasing age, presence of leg pain, split skin graft and haematoma) which negatively impact on surgical site healing in this population.

Skin cancer prevention and fashion – frontier bedfellows

Problem Queensland has the highest rates of skin cancer in the world, even after wide-ranging public programs promoting sun safety awareness. To-date, public awareness campaigns on the dangers of excessive sun exposure have been highly successful. For adolescents, however, where a significant amount of lifetime sun exposure occurs, perilous exposure still ensues, despite awareness of the risks. New frontier approaches are required to target this key audience cluster, for this significant national problem. Approach For the majority of adolescents, being part of a collective norm defines their visual, attitudinal and behavioural actions and fashion has been validated as one of the most powerful forces that can form, shape and bolster these norms. Considering clothing is the easiest method to limit the amount of skin exposed to UV, fashion (in its many subtle, yet influential guises) is proposed as an avenue to advance positive sun safe practices for adolescents. Through an action-led methodology, this research explores the potential of fashion, as one of the key parts of a complex equation, to be a prime driver to facilitate sun safety for adolescents. Findings This paper advocates that fashion, as distinguishable from clothing, has the potential to positively influence sun protective behaviour. The findings go further and recommend the use of fashion as a stealth driver for sun safety advancement, for adolescents in particular, via shifts in norms of beauty and targeted generational communication strategies. This frontier approach has the potential to significantly reduce risky sun exposure in adolescence.

Advances in skin cancer early detection and diagnosis

OBJECTIVES: To provide an overview of 1) traditional methods of skin cancer early detection, 2) current technologies for skin cancer detection, and 3) evolving practice models of early detection. DATA SOURCES: Peer-reviewed databased articles and reviews, scholarly texts, and Web-based resources. CONCLUSION: Early detection of skin cancer through established methods or newer technologies is critical for reducing both skin cancer mortality and the overall skin cancer burden. IMPLICATIONS FOR NURSING PRACTICE: A basic knowledge of recommended skin examination guidelines and risk factors for skin cancer, traditional methods to further examine lesions that are suspicious for skin cancer and evolving detection technologies can guide patient education and skin inspection decisions.

Lesion selection by melanoma high-risk consumers during skin self-examination using mobile teledermoscopy

Mobile teledermatoscopy (MTD) for the early detection of skin cancer uses smartphones with dermatoscope attachments to magnify, capture, and transfer images remotely.1 Using the asymmetry–color variation (AC) rule, consumers achieve dermoscopy sensitivity of 92.9% to 94.0% and specificity of 62.0% to 64.2% for melanoma.2 This pilot randomized trial assessed lesions of concern selected by consumers at high risk of melanoma using MTD plus the AC rule (intervention, n = 10) or the AC rule alone (control, n = 12) during skin self-examination (SSE). Also measured were lesion location patterns, lesions overlooked by participants, provisional clinical diagnoses, likelihood of malignant tumor, and participant pressure to excise lesions.

Skin cancer detection by one click - are we any closer?

To the editor...

Characterisation of a human skin equivalent model to study the effects of ultraviolet B radiation on keratinocytes

The incidences of skin cancers resulting from chronic ultraviolet radiation (UVR) exposure are on the incline both in Australia and globally. Hence, the cellular and molecular pathways associated with UVR-induced photocarcinogenesis urgently need to be elucidated, in order to develop more robust preventative and treatment strategies against skin cancers. In vitro investigations into the effects of UVR (in particular the highly-mutagenic UVB wavelength) have, to date, mainly involved the use of cell culture and animal models. However, these models possess biological disparities to native skin, which to some extent have limited their relevance to the in vivo situation. To address this, we characterised a 3-dimensional, tissue-engineered human skin equivalent (HSE) model (consisting of primary human keratinocytes cultured on a dermal-derived scaffold) as a representation of a more physiologically-relevant platform to study keratinocyte responses to UVB. Significantly, we demonstrate that this model retains several important epidermal properties of native skin. Moreover, UVB-irradiation of the HSE constructs was shown to induce key markers of photodamage in the HSE keratinocytes, including the formation of cyclobutane pyrimidine dimers, the activation of apoptotic pathways, the accumulation of p53 and the secretion of inflammatory cytokines. Importantly, we also demonstrate that the UVB-exposed HSE constructs retain the capacity for epidermal repair and regeneration following photodamage. Together, our results demonstrate the potential of this skin equivalent model as a tool to study various aspects of the acute responses of human keratinocytes to UVB radiation damage.

Interventions to decrease skin cancer risk in outdoor workers : update to a 2007 systematic review

BACKGROUND: Outdoor workers are at high risk of harmful ultraviolet radiation exposure and are identified as an at risk group for the development of skin cancer. This systematic evidence based review provides an update to a previous review published in 2007 about interventions for the prevention of skin cancer in outdoor workers. RESULTS: This review includes interventions published between 2007-2012 and presents findings about sun protection behaviours and/or objective measures of skin cancer risk. Six papers met inclusion criteria and were included in the review. Large studies with extended follow-up times demonstrated the efficacy of educational and multi-component interventions to increase sun protection, with some higher use of personal protective equipment such as sunscreen. However, there is less evidence for the effectiveness of policy or specific intervention components. CONCLUSIONS: Further research aimed at improving overall attitudes towards sun protection in outdoor workers is needed to provide an overarching framework.

Tissue viability imaging of skin microcirculation following exposure to whole body cryotherapy (-110°C) and cold water immersion (8°C)

Cryotherapy is currently used in various clinical, rehabilitative, and sporting settings. However, very little is known regarding the impact of cooling on the microcirculatory response. Objectives: The present study sought to examine the influence of two commonly employed modalities of cryotherapy, whole body cryotherapy (WBC; -110°C) and cold water immersion(CWI; 8±1°C), on skin microcirculation in the mid- thigh region. Methods: The skin area examined was a 3 × 3 cm located between the most anterior aspect of the inguinal fold and the patella. Following 10 minutes of rest, 5 healthy, active males were exposed to either WBC for 3 minutes or CWI for 5 minutes in a randomised order. Volunteers lay supine for five minutes after treatment, in order to monitor the variation of red blood cell (RBC) concentration in the region of interest for a duration of 40 minutes. Microcirculation response was assessed using a non-invasive, portable instrument known as a Tissue Viability imaging system. After a minimum of seven days, the protocol was repeated. Subjective assessment of the volunteer’s thermal comfort and thermal sensation was also recorded. Results: RBC was altered following exposure to both WBC and CWI but appeared to stabilise approximately 35 minutes after treatments. Both WBC and CWI affected thermal sensation (p < 0.05); however no betweengroup differences in thermal comfort or sensation were recorded (p > 0.05). Conclusions: As both WBC and CWI altered RBC, further study is necessary to examine the mechanism for this alteration during whole body cooling.