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- Impact of Sunscreens on Preventing UVR-Induced Effects in Nevi: In Vivo Study Comparing Protection Using a Physical Barrier vs Sunscreen. [JOURNAL ARTICLE]
- JAMA Dermatol 2013 May 8.:1-11.
IMPORTANCE Sun damage is the most important environmental factor associated with malignant melanoma. To address the health threat, as well as the economic burden, primary prevention and early detection are crucial.
OBJECTIVETo test the efficacy of a topical sunscreen in the prevention of UV-induced effects in nevi. DESIGN Prospective study of nevi protected by sunscreen vs a physical barrier. SETTING AND PATIENTS Twenty-three nevi from 20 patients attending a referral hospital. INTERVENTION Half of each nevus was protected by either a physical barrier or a sunscreen. Lesions were completely irradiated by a single dose of UV-B. MAIN OUTCOMES AND MEASURES In vivo examination before and 7 days after irradiation and histopathologic-immunopathologic evaluation after excision on the seventh day.
RESULTSThe most frequent clinical changes after UV radiation were pigmentation, scaling, and erythema; the most frequent dermoscopic changes were increased globules/dots, blurred network, regression, and dotted vessels. Both physical barrier-and sunscreen-protected areas showed some degree of these changes. More than 30% (7) of nevi did not show any change on clinical examination, and 18% (4) had no dermoscopic change. Immunohistopathologic differences between the halves of each nevus were demonstrable even when in vivo examination detected nothing. Parakeratotic scale, increased number and activation of superficial melanocytes, and keratinocyte proliferation were the most remarkable features. The only difference between both barriers was more enhanced melanocytic activation and regression features in the sunscreen group. No phenotypic features were found to predict a specific UV-B response.
CONCLUSIONSAND RELEVANCE Both physical barriers and sunscreens can partially prevent UV-B effects on nevi. Subclinical UV radiation effects, not always associated with visible changes, can develop even after protection. Sunscreens are not quite as effective as physical barriers in the prevention of inflammatory UV-B-induced effects.
- MicroRNA Assay for Accurate Histological Classification of Non-small Cell Lung Cancer Small Biopsy Samples Using Laser Microdissection. [JOURNAL ARTICLE]
- Chest 2012 Oct 1; 142(4_MeetingAbstracts):591A.
SESSION TYPE: Lung Cancer IIPRESENTED ON: Monday, October 22, 2012 at 04:00 PM - 05:30 PM
PURPOSE:NSCLC classification as squamous cell carcinoma (SCC) and non-SCC has clinical utility. With small biopsies, the accuracy of such classification using routine histological examination is ~85%. A new method using reverse transcription-PCR (RTPCR) to classify NSCLC by measuring miR-205 relative to RNU6B and miR-21 for a >95% classification accuracy has been described, but its routine use is limited by the need to use samples with at least 50% tumor content. We sought to simplify this method and to enhance its applicability to small biopsy samples with the use of laser microdissection.
METHODS:RNA levels were measured in quantification cycle values (Cq) or in moles to calculate miR-205 levels relative to RNU6B, or to both RNU6B and miR-21, in 36 non-SCC and 22 SCC resected and formalin-fixed tumor tissues using RTPCR and synthetic small RNA standards (training set). Values for miR-205 in laser microdissected tumor cells from small biopsy samples were similarly determined for a test set of 16 NSCLC cases with known histology after surgical resection using an optimized RNA extraction protocol.
RESULTS:Using the area under curve (AUC) statistic in receiver operator characteristics analysis of our training set, the molar ratio of miR-205 to RNU6B performed as well as Cq values of miR-205 compared to RNU6B and miR-21(AUC = 0.922; 95%CI = 0.853 - 0.991 vs. AUC = 0.943; 95% CI = 0.888 - 0.998; P>0.05). miR-205 levels could be measured in 15/16 samples in the test set; 13/15 (87%) were correctly predicted by either method. For four (31%) of the 13, histology of small biopsies had been deemed indeterminate.
CONCLUSIONS:Our study validates use of microRNA miR-205 level for accurate histological classification in NSCLC.
CLINICAL IMPLICATIONS:Such an assay may be useful to classify NSCLC when histology of small biopsy samples is indeterminable by routine means. Using molarity instead of Cq values, such an assay may be based on just two instead of three analytes and can be transferred to any microRNA expression platform.DISCLOSURE: The following authors have nothing to disclose: Samjot Dhillon, Santosh Patnaik, Eric Kannisto, Sai YendamuriNo Product/Research Disclosure InformationRoswell Park Cancer Institute, Buffalo, NY.
- Effect of Arginine-Rich Peptide Length on the Structure and Binding Strength of siRNA-Peptide Complexes. [JOURNAL ARTICLE]
- J Phys Chem B 2013 May 22.
Heparin decomplexation experiments, as well as all-atom (AA) and coarse-grained (CG) molecular dynamics (MD) simulations were performed to determine the effect of the size of arginine(Arg)-rich peptides on the structure and binding strength of the siRNA-peptide complex. At a fixed peptide/siRNA mole ratio of 5:1 or 10:1, the siRNA complexes with peptides longer than 9 Arg residues are more easily decomplexed by heparin than are those with 9 Arg residues. At these mole ratios, peptides longer than 9 Arg residues have cationic/anionic charge ratios in excess of unity, and produce more weakly bound complexes than 9-Arg residue ones do. AA simulations of mixtures of peptides with a single siRNA show formation of an electrostatically-induced complex, and the longer peptides produce a larger complex, but with no significant increase in the number of Arg residues bound to the siRNA. Larger-scale CG-MD simulations show that multiple siRNAs can be linked together by peptides into a large complex, as observed in the experiments. The peptides longer than 9 residues, which at mole ratio 5:1 yield a peptide/siRNA charge ratio in excess of unity, include many non-interacting Arg residues, which repel each other electrostatically. This leads to a less dense complex than for 9-residue peptides, which can explain why these longer complexes are more easily decomplexed by heparin molecules, as observed in the experiments. The key role of the charge ratio is supported by simulations that show that at a mole ratio of 2.5 peptides per siRNA, the longer 18-residue peptide has a charge ratio of roughly unity, and also shows a tight complex, just as the 9-residue peptide does at a 5:1 mole ratio, where its charge ratio is also unity.
- Rapid multiplexed genotyping of simple tandem repeats using capture and high-throughput sequencing. [JOURNAL ARTICLE]
- Hum Mutat 2013 May 20.
Although simple tandem repeats (STRs) comprise ∼2% of the human genome and represent an important source of polymorphism, this class of variation remains understudied. We have developed a cost-effective strategy for performing targeted enrichment of STR regions that utilizes capture probes targeting the flanking sequences of STR loci, enabling specific capture of DNA fragments containing STRs for subsequent high-throughput sequencing. Utilizing a capture design targeting 6,243 STR loci <94bp and multiplexing eight individuals in a single Illumina HiSeq2000 sequencing lane we were able to call genotypes in at least one individual for 67.5% of the targeted STRs. We observed a strong relationship between (G+C) content and genotyping rate. STRs with moderate (G+C) content were recovered with >90% success rate, while only 12% of STRs with ≥80% (G+C) were genotyped in our assay. Analysis of a parent-offspring trio, complete hydatidiform mole samples, repeat analyses of the same individual, and Sanger sequencing-based validation indicated genotyping error rates between 7.6-12.4%. The majority of such errors were a single repeat unit at mono- or dinucleotide repeats. Altogether, our STR capture assay represents a cost-effective method that enables multiplexed genotyping of thousands of STR loci suitable for large scale population studies. This article is protected by copyright. All rights reserved.
- Taller plants have lower rates of molecular evolution. [Journal Article]
- Nat Commun 2013.:1879.
Rates of molecular evolution have a central role in our understanding of many aspects of species' biology. However, the causes of variation in rates of molecular evolution remain poorly understood, particularly in plants. Here we show that height accounts for about one-fifth of the among-lineage rate variation in the chloroplast and nuclear genomes of plants. This relationship holds across 138 families of flowering plants, and when accounting for variation in species richness, temperature, ultraviolet radiation, latitude and growth form. Our observations can be explained by a link between height and rates of genome copying in plants, and we propose a mechanistic hypothesis to account for this-the 'rate of mitosis' hypothesis. This hypothesis has the potential to explain many disparate observations about rates of molecular evolution across the tree of life. Our results have implications for understanding the evolutionary history and future of plant lineages in a changing world.
- Reticulin and NM23 Staining in the Interpretation of Lymph Nodal Nevus Rests. [Journal Article]
- Am J Dermatopathol 2013 Jun; 35(4):452-7.
: Melanocytic nevus rests in lymph nodes are a known diagnostic challenge, especially in patients with a history of melanoma. Reticulin and NM23 have been studied in this context. The pattern of reticulin staining in melanomas surrounds groups/nests of melanocytes but individual cells in benign nevi. NM23, a metastasis-suppressor gene, has an association with metastatic potential in melanomas and some carcinomas. Twenty-eight cases (14 cases of metastatic melanoma to lymph nodes and 14 cases of lymph node nevus rests, all confirmed with Melan-A staining) were stained with reticulin and NM23. The pattern of reticulin staining was reported as surrounding groups if staining was noted in approximately 5-10 melanocytes in greater than 50% of the lesion but was otherwise reported as surrounding individual melanocytes. Cytoplasmic staining was considered to represent reactivity for NM23. Reticulin staining around groups of melanocytes was identified in all 14 cases of metastatic melanoma. Regarding nodal nevus rest cases, 12 of 14 cases (86%) demonstrated staining around individual melanocytes, whereas in 2 cases, reticulin surrounded melanocytic groups. NM23 staining was equivocal in all cases. Reticulin staining reliably invests groups of melanocytes in cases of metastatic melanoma, whereas in nodal nevus rests, it predominantly surrounds individual melanocytes. NM23 demonstrated no discriminatory value in this analysis. In cases in which a collection of melanocytes is present within a lymph node, reticulin deposition around individual melanocytes supports a diagnosis of lymph nodal nevus rest.
- Electrochemical detection of the amino-substituted naphthalene compounds based on intercalative interaction with hairpin DNA by electrochemical impedance spectroscopy. [JOURNAL ARTICLE]
- Biosens Bioelectron 2013 Apr 15.:238-243.
The amino-substituted naphthalene compounds, such as 1,8-diaminonaphthalene (1,8-DANAP), 2,3-diaminonaphthalene (2,3-DANAP), 1,5-diaminonaphthalene (1,5-DANAP), 1-naphthylamine (1-NAP) and 2-naphthylamine (2-NAP), were investigated by electrochemical impedance spectroscopy (EIS), which was based on the interaction with hairpin DNA immobilized on the gold electrodes. Upon hairpin DNA interacting with the target chemicals, the charge transfer resistance (RCT) of the hairpin DNA films was significantly decreased and the charge transfer resistance change (ΔRCT) decreased in a sequence of ΔRCT 1,8-DANAP>ΔRCT 2,3-DANAP>ΔRCT 1,5-DANAP>ΔRCT 1-NAP>ΔRCT 2-NAP. The ΔRCT changes were due to the difference in the binding constant (KSV) of the target chemicals to DNA. In addition, the interaction mechanism was further explored using 1,8-DANAP as a model analyte by fluorescence spectra, Raman spectroscopy, differential pulse voltammetry (DPV) and EIS, correspondingly. The results demonstrated that the amino-substituted naphthalene compounds intercalated into "stem" appearing in the hairpin DNA. Moreover, the hairpin DNA sensor exhibited high sensitivity to the amino-substituted naphthalene compounds with the detection limit of nano-mole, and maintained high selectivity over other selected environmental pollutants. Finally, the DNA sensor was challenged in natural water sample with a recovery of 96-102%, which offered a platform for prospective future development of a simple, rapid, sensitive and low-cost assay for the detection of target aromatic amine pollutants.
- Malignant melanoma developed on a congenital melanocytic nevus with lymph node metastasis in a 19-month-old boy. [Journal Article]
- Turk J Pediatr 2012 Jul-Aug; 54(4):432-5.
Although rare, malignant melanoma occurs in children. The risk of degeneration of a congenital melanocytic nevus into a melanoma is approximately 0.7%. We report a case of malignant melanoma that developed on a congenital melanocytic nevus in a 19-month-old boy. The child was treated by surgical resection, superficial parotidectomy, and modified radical neck dissection with adjuvant therapy. The follow-up has been 24 months without metastasis. Early clinical detection, fast histological confirmation, prompt surgery, and adjuvant therapy are the only means to achieve a long survival period for children suffering from malignant melanoma.
- INFLAMMATORY LINEAR VERRUCOUS EPIDERMAL NEVUS: WHY A COMBINED LASER THERAPY. [JOURNAL ARTICLE]
- J Cosmet Laser Ther 2013 May 21.
ABSTRACTInflammatory linear verrucous epidermal nevus (ILVEN) is a benign cutaneous hamartoma, and more precisely an uncommon variant of the verrucous epidermal nevus. In our case report we describe an ILVEN female patient, resistant to previous treatments but responsive to a combined laser therapy, 10,600-nm CO2 laser and Fractional CO2 laser, with good and longstanding results. A complete resolution of the lesion was observed at the 9-month follow-up. The application of lasers has been reported in literature over recent years for resolving ILVEN lesions. Based on our clinical experience, 10,600-nm CO2 pulsed laser therapy seems to be the best treatment and Fractional CO2 laser treatment can be regarded as a very promising technique to combine with CO2 laser for reducing pigment modifications and endowing a more youthful appearance to the treated areas.
- Clonal BRAF Mutations in Melanocytic Nevi and Initiating Role of BRAF in Melanocytic Neoplasia. [JOURNAL ARTICLE]
- J Natl Cancer Inst 2013 May 20.
BRAF(V600E) mutations are frequent in melanomas originating from intermittently sun-exposed skin and also in common acquired melanocytic nevi, suggesting that BRAF mutation is an early event in melanocytic neoplasia. All neoplastic melanocytes within such a nevus would be expected to carry the BRAF mutation, and thus we evaluated the frequency of cells with BRAF(V600E) mutations within acquired nevi by droplet digital polymerase chain reaction. In BRAF-mutant nevi the number of BRAF mutant alleles equaled the number of wild-type (WT) alleles in the neoplastic cell population, consistent with a fully clonal heterozygous BRAF mutation. The allelic ratio of BRAF(V600E) to BRAF(WT) in the eight VE1-positive nevi, adjusted for degree of stromal contamination, ranged from 0.84 to 1.12 with an average ratio of 1.01. This was confirmed by immunohistochemistry with an antibody specific for BRAF(V600E), which uniformly labeled the neoplastic cells without any evidence of heterogeneity. We found BRAF(V600E) mutations in the melanocytic nevi to be fully clonal, strongly suggesting that BRAF-activating mutations typically are early initiating events in melanocytic neoplasia.