Multiparameter analysis of naevi and primary melanomas identifies a subset of naevi with elevated markers of transformation

Here we have carried out a multiparameter analysis using a panel of 28 immunohistochemical markers to identify markers of transformation from benign and dysplastic naevus to primary melanoma in three separate cohorts totalling 279 lesions. We have identified a set of eight markers that distinguish naevi from melanoma. None of markers or parameters assessed differentiated benign from dysplastic naevi. Indeed, the naevi clustered tightly in terms of their immunostaining patterns whereas primary melanomas showed more diverse staining patterns. A small subset of histopathologically benign lesions had elevated levels of multiple markers associated with melanoma, suggesting that these represent naevi with an increased potential for transformation to melanoma

Cytokine/chemokine profiles in squamous cell carcinoma correlate with precancerous and cancerous disease stage.

Actinic Keratosis (AK), Intraepidermal Carcinoma (IEC), and Squamous Cell Carcinoma (SCC) are generally considered to be advancing stages of the same disease spectrum. However, while AK often regress spontaneously, and IEC often regress in response to immune-activating treatments, SCC typically do not regress. Therefore, it is vital to define whether fundamental immunological changes occur during progression to SCC. Here we show that proinflammatory cytokine expression, chemokine expression, and immune cell infiltration density change during progression to SCC. Our findings suggest a switch from predominantly proinflammatory cytokine production to chemokine production is a key feature of progression from precancer to cancer. Together, these observations propose a model that can underpin current research and open new avenues of exploration into the clinical significance of these profiles with respect to immunotherapeutic or other treatment outcomes

Microneedle Enhanced Delivery of Cosmeceutically Relevant Peptides in Human Skin

Peptides and proteins play an important role in skin health and well-being. They are also found to contribute to skin aging and melanogenesis. Microneedles have been shown to substantially enhance skin penetration and may offer an effective means of peptide delivery enhancement. The aim of this investigation was to assess the influence of microneedles on the skin penetration of peptides using fluorescence imaging to determine skin distribution. In particular the effect of peptide chain length (3, 4, 5 amino acid chain length) on passive and MN facilitated skin penetration was investigated. Confocal laser scanning microscopy was used to image fluorescence intensity and the area of penetration of fluorescently tagged peptides. Penetration studies were conducted on excised full thickness human skin in Franz type diffusion cells for 1 and 24 hours. A 2 to 22 fold signal improvement in microneedle enhanced delivery of melanostatin, rigin and pal-KTTKS was observed. To our knowledge this is the first description of microneedle enhanced skin permeation studies on these peptides

Hitomi (ASTRO-H) X-ray Astronomy Satellite

The Hitomi (ASTRO-H) mission is the sixth Japanese x-ray astronomy satellite developed by a large international collaboration, including Japan, USA, Canada, and Europe. The mission aimed to provide the highest energy resolution ever achieved at E  >  2  keV, using a microcalorimeter instrument, and to cover a wide energy range spanning four decades in energy from soft x-rays to gamma rays. After a successful launch on February 17, 2016, the spacecraft lost its function on March 26, 2016, but the commissioning phase for about a month provided valuable information on the onboard instruments and the spacecraft system, including astrophysical results obtained from first light observations. The paper describes the Hitomi (ASTRO-H) mission, its capabilities, the initial operation, and the instruments/spacecraft performances confirmed during the commissioning operations for about a month

Advances and controversies in studying sunscreen delivery and toxicity

This review critically evaluates the sunscreen delivery and toxicity field. We chose to focus on approved sunscreens in this review. Optimal sunscreen use prevents skin cancer and photoageing but there is an important knowledge gap in sunscreen/skin interactions. Sunscreen delivery is a key for efficacy, but studying sunscreen delivery is not straightforward. We review the strengths and weaknesses of in vitro, excised skin and clinical approaches. Understanding positive and negative sunscreen effects on skin homeostasis is also challenging. The results in this field, especially in vitro testing, are controversial and experimental design varies widely which further supports disparities between some findings. We hypothesize that bias towards showing sunscreen toxicity to increase impact could be problematic. We explore that perception through a detailed review of experimental design, especially in cell culture models. Our conclusion is that emerging, non- and minimally invasive technologies are enabling new approaches to volunteer studies that could significantly improve knowledge of sunscreen delivery and interactions

Therapeutic gold, silver, and platinum nanoparticles

There are an abundance of nanoparticle technologies being developed for use as part of therapeutic strategies. This review focuses on a narrow class of metal nanoparticles that have therapeutic potential that is a consequence of elemental composition and size. The most widely known of these are gold nanoshells that have been developed over the last two decades for photothermal ablation in superficial cancers. The therapeutic effect is the outcome of the thickness and diameter of the gold shell that enables fine tuning of the plasmon resonance. When these metal nanoparticles are exposed to the relevant wavelength of light, their temperature rapidly increases. This in turn induces a localized photothermal ablation that kills the surrounding tumor tissue. Similarly, gold nanoparticles have been developed to enhance radiotherapy. The high-Z nature of gold dramatically increases the photoelectric cross-section. Thus, the photoelectric effects are significantly increased. The outcome of these interactions is enhanced tumor killing with lower doses of radiation, all while sparing tissue without gold nanoparticles. Silver nanoparticles have been used for their wound healing properties in addition to enhancing the tumor-killing effects of anticancer drugs. Finally, platinum nanoparticles are thought to serve as a reservoir for platinum ions that can induce DNA damage in cancer cells. The future is bright with the path to clinical trials is largely cleared for some of the less complex therapeutic metal nanoparticle systems

Current and next generation topical anti-skin cancer therapeutics

Non-melanoma skin cancers are among the most commonly diagnosed skin cancers in the world. Ultraviolet radiation is a primary carcinogen resulting in UV induced mutations, loss of activity in tumour suppressor genes and the over expression of oncogenes in keratinocytes resulting in the development of skin malignancies. With the continued rising rate of non-melanoma skin cancer, topical therapies have become an established treatment method for effective lesion clearance. Current topical therapies include 5-fluorouracil, imiquimod, diclofenac, ingenol mebutate and photodynamic therapy. With high lesion recurrence rates still presenting as an issue following topical treatment, lack of drug selectivity for cancer cells, severe side effects from topical agent use and patient non-compliance due to prolonged treatment periods, new novel topical therapies need to be explored and developed. New therapies must target and clear both subclinical and clinically presenting skin cancers by interrupting the molecular mechanisms that induce and sustain the proliferation of neoplastic cells. Piperlongumine and EBC-46 are two naturally occurring small molecules which have demonstrated effective induction of cancer cell death. Piperlongumine, an amide isolated from the pepper, Piper longum, has demonstrated cancer cell death selectivity yet has no impact on healthy rapidly dividing primary cells. EBC-46 is a diterpene ester isolated from the seed of the fruit, Fontainea picrosperma. EBC-46 induces rapid inflammation and necrosis resulting in tumour ablation following intra-lesional injection. The development of Piperlongumine and EBC-46, as new topical agents offers a unique opportunity to further explore and exploit these selective properties for a more efficient and targeted approach to topical non -melanoma skin cancer treatment

Multiphoton microscopy applications in biology

This chapter provides an overview of basic principles of multiphoton microscopy, including a brief summary of how multiphoton microscopy fits within the arena of fluorescent microscopy techniques. The description of how multiphoton microscopy works is geared toward both the novice and experienced user. There are several examples of how multiphoton microscopy can be applied to the life sciences. Each example has a detailed section on the configuration of the device in context with the study focus. These applications include tracking fluorescent protein-expressing immune cells, drug-containing nanoparticles, metal nanoparticles, multiphoton microscopy, microendoscopy, and clinical multiphoton microscopy. Finally, the limitations and future of multiphoton microscopy are explored