Epidemiological Support for an Hypothesis for Melanoma Induction Indicating a Role for UVA Radiation

An hypothesis for melanoma induction is presented: UV radiation absorbed by melanin in melanocytes generates products that may activate the carcinogenic process. Products formed by UV absorption in the upper layers of the epidermis cannot diffuse down as far as to the melanocytes. Thus, melanin in the upper layer of the skin may be protective, while that in melanocytes may be photocarcinogenic. Observations that support this hypothesis include: (1) Africans with dark skin have a reduced risk of getting all types of skin cancer as compared with Caucasians, but the ratio of their incidence rates of cutaneous malignant melanoma to that of squamous cell carcinoma is larger than the corresponding ratio for Caucasians. (2) Albino Africans, as compared with normally pigmented Africans, seem to have a relatively small risk of getting cutaneous malignant melanomas compared to nonmelanomas. This is probably also true for albino and normally pigmented Caucasians. (3) Among sun-sensitive, poorly tanning persons, frequent UV exposures are associated with increased risk of melanoma, whereas among sun-resistant, well-tanning persons, increased frequency of exposure is associated with decreased melanoma risk. (4) It is likely that UVA, being absorbed by melanin, might have a melanoma-inducing effect. This is in agreement with some epidemiological investigations which indicate that sun-screen lotions may not protect sufficiently against melanoma induction. The relative latitude gradient for UVA is much smaller than that for UVB. The same is true for the relative latitude gradient of cutaneous malignant melanoma as compared with squamous cell carcinoma and basal cell carcinoma. Under the assumption that the average slopes of the curves relating incidence rates with fluences of carcinogenic UV radiation are similar for melanomas and nonmelanomas, these facts are in agreement with the assumption that UVA plays a significant role in the induction of melanomas in humans. This is in agreement with the experimental results with Xiphophorus.     

An Animal Model for Human Melanoma

Abstract— Experimental animal models that are directly relevant to human melanoma are lacking. We propose the Angora goat as a potentially useful field model with experimental potential and to this end have examined the prevalence and site distribution of all skin cancers in 28 Angora goat herds in Queensland, Australia. The prevalence of benign melanocytic lesions (lentigines) and their experimental induction by sunlight were also investigated. Among 1731 goats over 2 years of age, 139 malignant skin tumors were excised from 95 affected animals. The prevalence of squamous cell carcinoma (SCC) was 3.8% and of melanoma, 2.2%. Main site of occurrence of melanoma (83%) was the dorsal surface of the ear; in contrast SCC occurred mostly (84%) on the perineum. Lentigines were darker and more prevalent on the exposed compared with the unexposed surface of the ear in Angoras, analogous to the higher prevalence of nevi on the exposed compared with the less exposed inner surface of the arm in humans. Lentigines, which were also found on the perineum though lighter in color than on the dorsal ear, were absent in young animals under 3 months but were numerous in 1–3 year olds. Furthermore in an experimental substudy eight goats, having one flank repeatedly shorn and the contralateral flank left unshorn, revealed consistently more solar lentigines on the shorn flank ( P < 0.05) when both sides were examined after 9 months. Histopathological examination of paired skin biopsies from five of these goats also showed more abundant pigmentation in skin from the exposed, as compared with the unexposed flank. These findings indicate that sunlight induces tumors and lentigines in goats in a highly site-specific manner. The Angora goat model may suggest paradigms for explaining the site differences observed for human melanoma and may also be useful in the future clarification of molecular changes following carcinogenic levels of sun exposure.     

CD437 Reduces Metastatic Potential of Melanoma Cells

Moscow University Chemistry Bulletin - Synthetic retinoid CD437, an agonist of the retinoic acid receptor γ (RARγ), demonstrates high potential for cancer treatment in xenograft models....     

Identification of Dihydrolipoamide Dehydrogenase as Potential Target of Vemurafenib-Resistant Melanoma Cells

Background: Despite recent improvements in therapy, the five-year survival rate for patients with advanced melanoma is poor, mainly due to the development of drug resistance. The aim of the present study was to investigate the mechanisms underlying this phenomenon, applying proteomics and structural approaches to models of melanoma cells. Methods: Sublines from two human (A375 and SK-MEL-28) cells with acquired vemurafenib resistance were established, and their proteomic profiles when exposed to denaturation were identified through LC-MS/MS analysis. The pathways derived from bioinformatics analyses were validated by in silico and functional studies. Results: The proteomic profiles of resistant melanoma cells were compared to parental counterparts by taking into account protein folding/unfolding behaviors. Several proteins were found to be involved, with dihydrolipoamide dehydrogenase (DLD) being the only one similarly affected by denaturation in all resistant cell sublines compared to parental ones. DLD expression was observed to be increased in resistant cells by Western blot analysis. Protein modeling analyses of DLD’s catalytic site coupled to in vitro assays with CPI-613, a specific DLD inhibitor, highlighted the role of DLD enzymatic functions in the molecular mechanisms of BRAFi resistance. Conclusions: Our proteomic and structural investigations on resistant sublines indicate that DLD may represent a novel and potent target for overcoming vemurafenib resistance in melanoma cells.     

The Autophagy Receptor Adaptor p62 is Up‐regulated by UVA Radiation in Melanocytes and in Melanoma Cells

UVA (315–400 nm) is the most abundant form of UV radiation in sunlight and indoor tanning beds. However, much remains to be understood about the regulation of the UVA damage response in melanocytes and melanoma. Here, we show that UVA , but not the shorter waveband UVB (280–315 nm), up‐regulates adaptor protein p62 in an Nrf2‐ and reactive oxygen species (ROS )‐dependent manner, suggesting a UVA ‐specific effect on p62 regulation. UVA ‐induced p62 up‐regulation was inhibited by a mitochondria‐targeted antioxidant or Nrf2 knockdown. In addition, p62 knockdown inhibited UVA ‐induced ROS production and Nrf2 up‐regulation. We also report here a novel regulatory feedback loop between p62 and PTEN in melanoma cells. PTEN overexpression reduced p62 protein levels, and p62 knockdown increased PTEN protein levels. As compared with normal human skin, p62 was up‐regulated in human nevus, malignant melanoma and metastatic melanoma. Furthermore, p62 was up‐regulated in melanoma cells relative to normal human epidermal melanocytes, independent of their BRAF or NRAS mutation status. Our results demonstrated that UVA up‐regulates p62 and induces a p62‐Nrf2 positive feedback loop to counteract oxidative stress. Additionally, p62 forms a feedback loop with PTEN in melanoma cells, suggesting p62 functions as an oncogene in UVA ‐associated melanoma development and progression.     

An Application of Functional Analysis Method to the Potential of Electrical Double Layer for Spherical Micelles

With the help of the iterative method in functional analysis theory based on the Gouy–Chapman model in the colloid and interface chemistry an analytic solution of the potential of electrical double layer of spherical micelles has been obtained. This method has eliminated the restriction that the Poisson–Boltzmann equation, which represents the distribution of the potential in the double layer, can be solved only under the condition of zekT so far. The connections between the present results and those from Verwey and Overbeek's previous work have also been discussed. Our approach provides a simple but effective method for the calculation of the potential of electrical double layer under general potential condition.     

Importance of Methane Chemical Potential for Its Conversion to Methanol on Cu-Exchanged Mordenite

Copper-oxo clusters exchanged in zeolite mordenite are active in the stoichiometric conversion of methane to methanol at low temperatures. Here, we show an unprecedented methanol yield per Cu of 0.6, with a 90–95 % selectivity, on a MOR solely containing [Cu₃(μ-O)₃]²⁺ active sites. DFT calculations, spectroscopic characterization and kinetic analysis show that increasing the chemical potential of methane enables the utilization of two μ-oxo bridge oxygen out of the three available in the tricopper-oxo cluster structure. Methanol and methoxy groups are stabilized in parallel, leading to methanol desorption in the presence of water.     

Effect of UVA irradiance on photocatalytic and UVA inactivation of Bacillus cereus spores

The current study is the first to delineate the contribution of photocatalysis to inactivation of Bacillus cereus endospores on dry surfaces over a broad range (0–153 W/m²) of UVA irradiance. Inactivation of spores at low UVA irradiance (30 W/m²) was primarily due to photocatalysis, whereas at higher UVA irradiance inactivation was primarily due to UV alone. A linear relationship between UVA irradiance and the rate of spore inactivation was observed in the absence of photocatalyst. The rate of photocatalytic inactivation was non-linear with respect to UVA irradiance, exhibiting a maximum at 30 W/m².     

Influence of UVB,UVA and UVA1 irradiation on histamine release from human basophils and mast cells in vitro in the presence and absence of antioxidants

UV irradiation is widely used for the treatment of atopic eczema. In recent years, UVA1 phototherapy has gained increasing attention. This study analyzed the influence of different UV wavelengths--especially UVA1--on histamine release from human basophils and mast cells. The modulation of this parameter might be responsible for some of the therapeutic effects of UV irradiation. Enriched human basophils and human mast cells (HMC1 cell line) were irradiated with increasing doses of UVB, UVA and UVA1 in vitro. After irradiation, different stimulants were added to induce histamine release. In additional experiments, basophils were preincubated with superoxide dismutase, ascorbate or trolox to study the role of antioxidants in the modulation of histamine release after UV irradiation. UVA and UVA1 significantly inhibited histamine release from basophils and mast cells. UVB only had an inhibitory effect on mast cells. Preincubation with superoxide dismutase and ascorbate did not influence the inhibitory effect of UVA1 on basophil histamine release, whereas trolox decreased significantly the histamine release from nonirradiated basophils.     

Hydrothermally Stable Catalysts for the Removal of Emissions from Small-Scale Biofuel Combustion Systems

Catalytic oxidation of model pollutants, simulating the emissions from small-scale biofuel combustion systems, was studied over different fresh, aged and sulfur poisoned Pd-MeO/-alumina (Me = Ni, Ce and La) catalysts. Release of chlorine and restructuring of PdO particles was believed to cause activation of the Pd-MeO supported catalysts.     

Survey of UV Emissions from Sunbeds in the UK

Increased use of indoor tanning for cosmetic purposes has led to concerns for its impact on the risk of cutaneous cancers. The effects on UVR on skin depend on radiant dose, i.e. combination of irradiance and exposure duration. While a number of studies surveyed accessible emission from sunbeds, majority did not include the information on doses received during tanning sessions. Spectral irradiance of 195 sunbeds in five areas of the United Kingdom was measured in order to assess the radiant doses for comparison with the SED. Erythema weighted irradiance of more than 85% of all tested solaria exceeded 0.3 W m^?2, consistent with the findings of other studies. However, evaluation of radiant doses showed no evidence of increasing exposure per session in the United Kingdom in the last decade despite the increasing sunbed emission levels. Use of sunbeds for cosmetic purposes should be discouraged, with effective enforcement of the ban on under‐18 use, strict control on tanning duration and promotion of information on health risks of sunbed use. Such an integrated approach on safe equipment, safe use, and information should reduce the risk of detrimental impact of sunbed use on public health.     

Examination of Solar Simulators Used for the Determination of Sunscreen UVA Efficacy

The U.S. FDA recently proposed both in vivo and in vitro UVA efficacy tests for sunscreen products with the lower result used to establish the sunscreen's labeled UVA protection claim. The FDA stated their rationale for dual tests was concern that the in vivo test method overemphasizes UVA-2 (320–340 nm) photoprotection. We attribute FDA's observation to the relative lack, compared to sunlight, of UVA-1 (340–400 nm) radiation in the current JCIA UVA solar simulator specification, allowing the method to generate higher UVA protection factors than sunscreens will provide in sunlight. Our work is based upon comparisons of Air Mass 1.0 sunlight to variously filtered UVA solar simulators. Sources near the JCIA UVA-2/UVA limits (8–20%) had a goodness of fit to solar UVA of only 67–79%. We propose that instead of using ratios of UVA-2 to UVA the standard should be a goodness of fit to the UVA region of an Air Mass 1 solar reference spectrum. As the spectral distribution of solar UVA varies much less than UVB, sunlight of reasonable zenith angles of ≤60° will have similar spectral shapes and approximate risk spectrum. Goodness of fit to this spectrum will produce UVA protection values predictive to those actually achieved in sunlight of different zenith angles.     

SPME Analysis of Potential Attractants for Palm Weevils

Abstract

Solid-phase microextraction was applied for the analysis of a mixture of potential attractants for palm weevils, constituted by seven organic compounds. Various fibers, coated with different sorbent phases, were used in this study and the best results were obtained with the polydimethylsiloxane (PDMS)/divinylbenzene (DVB) and the Carboxen/PDMS fibers. A waiting time of 5 min before sampling was adequate for sample homogenisation and a sampling time of 30 min was used to obtain good extraction efficiencies. A complete desorption of the analytes into the injection port of the gas chromatograph was achieved with an injection time of 1 min. The detection limit of the method ranged from 0.29 to 156 ng/ml for the different components of the mixture, with a lower detection limit for the compounds with higher affinity for the fiber coating. This method was used in the analysis of volatiles released from a diffuser filled with the attractant mixture.     

Analysis of Potential Energy Surface for Butanone Isomerization

The potential energy surfaces for butanone isomerization have been investigated by density function theory calculation. Six main reaction pathways are confirmed using the intrinsic reaction coordinate method, and the corresponding isomerization products are 1-buten-2-ol, 2-buten-2-ol, butanal or 1-buten-l-ol, methyl 1-propenyl ether, methyl allyl ether, and ethyl vinyl ether, respectively. Among them, there are three pathways through butylene oxide, indicating butylene oxide is an important intermediate product during butanone isomer ization. The calculated vertical ionization energies of the reactant and its products are in a good agreement with the experimental values available. From the consideration for the relative energies Of transition states and the number of high-energy barriers we infer that the reaction pathway butanone-＊l-buten-2-ol---2-buten-2-oi is the most competitive. The obtained results are informative for future studies on isomerization of ketone molecules.     

Kinetic Analysis of Apoptosis Induction in Human Cell Lines by UVA and 8-MOP

Whereas previous studies have indicated that DNA damage as a result of 8-methoxypsoralen (8-MOP) and UVA treatment leads to cell death, this study establishes the minimum concentrations of 8-MOP and UVA necessary to induce apoptosis in human T-lymphocytic and mono-cytic cell lines. In order to assess apoptosis, we used fluorescent microscopy to examine changes in light scattering as well as internucleosomal DNA fragmentation. Generation of a dose response curve showed that the minimum combination of UVA and 8-MOP that was necessary to induce greater than background levels of apoptosis within 24 h of treatment was 0.5 J/cm² UVA and 12.5 ng/mL of 8-MOP. A striking observation was that UVA alone at doses 1.0 J/cm², but not 8-MOP alone (6300 ng/mL), induced significant apoptosis in the Sup-T1 cell line within 24 h. Although the percentage of apoptotic Sup-T1 cells induced by UVA alone was not as great as that of 8-MOP and UVA in combination, a highly significant correlation between the product of the concentration of 8-MOP (ng/mL) times the dose of UVA (J/ cm²) and the percentage of apoptotic cells was observed. This correlation provides an important tool for studying the relationship of UVA-induced DNA damage to apoptosis induction. Moreover, it will provide a means by which early events in the apoptotic pathway can be dissected.     

Formation of Cyclobutane Thymine Dimers from UVA Photosensitization of Pyridopsoralen Monoadducted DNA

The present report provides evidence that thymine dimerization can be UVA photosensitized at a tetranucleotide, 5′-TATT-3′, by a 7-methyl-pyrido(3, 4-c)psoralen monoadduct in DNA. The efficiency of the photoprocess depends on the tetranucleotide flanking sequences. These results demonstrate that one DNA lesion can originate the contiguous formation of a second type of lesion and emphasize the sequence-specific response to interaction of drugs with DNA. Results are related to the sensitivity of DNA to 1, 10-phenanthroline-cuprous ion complex nucleolytic activity and discussed in terms of the major role of local deformability of DNA in interaction with ligands.     

均三唑并噻二唑:重要的潜在药物结构单元

均三唑并噻二唑是一类重要的稠杂环化合物,其衍生物具有抗菌、消炎、抗肿瘤、抗结核、酶抑制作用、调节植物生长等多种生物活性。本文按照均三唑并噻二唑类化合物呈现的不同生物活性进行分类,综述了近年来该类化合物在上述领域的研究进展。     

An ab initio Study of Intermolecular Potential for Ne-HBr Complex

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Impedance Analysis of Single Melanoma Cells in Microfluidic Devices

The electrical impedance analysis of single cells can provide information on cells’ pathological condition in various environments. Cell electrical properties are affected by factors such as the location, adhesion, and size of the cell. The proposed microfluidic device captures a single cell, maintains growth conditions, and allows single‐melanoma‐cell impedance to be measured using an impedance analyzer and a function generator. The rate of impedance variation (ROIV) can be used to determine cell growth conditions. Cellular apoptosis affects cell size and membrane surface area, and thus the electrical properties of cells. At 24 h without Antrodia cinnamomea (AC) addition, ROIV was 15.23 %, 17.04 %, and 12.60 % at temperatures of 34 °C, 37 °C, and 40 °C, respectively. At 24 h and 37 °C, ROIV was 17.04 %, 40.37 %, and 45.02 % for AC concentrations of 0, 20, and 40 µL/mL, respectively. The results show that the cell impedance variation of cells cultured without AC is much lower than that of cells cultured with AC. Regarding cellular morphology, with AC addition, the cells shrank obviously after 24 h, whereas they barely shrank without AC addition.     

Analysis of the Properties of Carbon Nanotubes from Distribution Maps of Molecular Electrostatic Potential

The electronic structure and stereochemical structure of some types of carbon nanotubes were investigated by quantum-chemical methods. It was found that the "zigzag" configurations have significant dipole moments and are characterized by dimorphism, reflected in the existence of symmetrical and unsymmetrical states.