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Melanoma in situ

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https://www.readbyqxmd.com/read/28714990/an-approach-to-suppress-the-evolution-of-resistance-in-braf-v600e-mutant-cancer
#1
Yaohua Xue, Luciano Martelotto, Timour Baslan, Alberto Vides, Martha Solomon, Trang Thi Mai, Neelam Chaudhary, Greg J Riely, Bob T Li, Kerry Scott, Fabiola Cechhi, Ulrika Stierner, Kalyani Chadalavada, Elisa de Stanchina, Sarit Schwartz, Todd Hembrough, Gouri Nanjangud, Michael F Berger, Jonas Nilsson, Scott W Lowe, Jorge S Reis-Filho, Neal Rosen, Piro Lito
The principles that govern the evolution of tumors exposed to targeted therapy are poorly understood. Here we modeled the selection and propagation of an amplification in the BRAF oncogene (BRAF(amp)) in patient-derived tumor xenografts (PDXs) that were treated with a direct inhibitor of the kinase ERK, either alone or in combination with other ERK signaling inhibitors. Single-cell sequencing and multiplex fluorescence in situ hybridization analyses mapped the emergence of extra-chromosomal amplification in parallel evolutionary trajectories that arose in the same tumor shortly after treatment...
July 17, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28711897/studying-risk-factors-for-skin-cancer-development
#2
Оlena О Оshyvalova
INTRODUCTION: In most countries with a population of mainly European origin, non-melanoma skin carcinoma incidence rate has increased over the last decade. Understanding of what is the best way to identify people at high risk for skin cancer development will help to optimize the strategy for prevention and treatment tactics. Aim of the research involves studying risk factors for skin cancer development in patients with cutaneous squamous cell carcinoma and squamous cell carcinoma in situ (cSCC and SCCis correspondingly) and patients with actinic keratosis (AK)...
2017: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28711085/risk-factors-for-positive-or-equivocal-margins-after-wide-local-excision-of-1345-cutaneous-melanomas
#3
Christopher J Miller, Thuzar M Shin, Joseph F Sobanko, John M Sharkey, John W Grunyk, Rosalie Elenitsas, Emily Y Chu, Brian C Capell, Michael E Ming, Jeremy R Etzkorn
BACKGROUND: Positive or equivocal margins after wide local excision (WLE) complicate surgical management of cutaneous melanoma. OBJECTIVE: To identify the frequency of and risk factors for positive or equivocal margins after WLE of cutaneous melanoma. METHODS: Retrospective, single-center, cross-sectional study of 1345 consecutive melanomas treated with WLE. RESULTS: The overall frequency of positive or equivocal margins was 4...
August 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28698757/new-safety-margins-for-melanoma-surgery-nice-possibility-for-drinking-of-just-that-cup-of-coffee
#4
Georgi Tchernev, Anastasiya Atanasova Chokoeva
BACKGROUND: The American Joint Committee on Cancer (AJCC's) skin melanoma surgical treatment recommendations from 2011 are characterised by a prima facie "freedom of choice" regarding how extensive should be the excisions for melanomas with tumour thickness up to 2 mm and melanoma in situ. It is unclear why the recommended surgical security margins vary between 0.5 and 1 cm for melanoma in situ, whereas for melanomas with a tumour thickness of up to 1.99 mm, the range of variation is also between 1 and 2 cm, without specifying when the surgical field should be broader and, narrower, accordingly...
June 15, 2017: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28692464/melanocytes-pattern-in-the-normal-nail-with-special-reference-to-nail-bed-melanocytes
#5
Christophe Perrin, Jean-F Michiels, Julien Boyer, Damien Ambrosetti
Previous studies of the density of melanocytes in the normal nail bed have had conflicting results. This is unfortunate because knowing the normal values might help the difficult distinction between a benign subungual melanotic macule and an early melanoma in situ. Five specimens of normal nail unit were analyzed. On hematoxylin and eosin-stained sections the melanocytes were undetectable. We defined the melanocyte count (MC) as the number of melanocytes per 1-mm stretch of nail epithelium. The mean MC for nail matrix was 6...
June 19, 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28685596/amelanotic-lentigo-maligna-melanoma-mohs-surgery-as-the-definitive-treatment-of-an-invisible-tumour
#6
Marisa Grace Ponzo, Richard Ian Crawford, Irèn Kossintseva
Amelanotic lentigo maligna melanoma represents <2% of melanomas. Diagnosis is delayed owing to the lack of lesion pigmentation and advanced disease at presentation. Excision with appropriate margins is the treatment standard, but the starting point for such margins is often unclear. We describe 2 patients with amelanotic melanoma treated by Mohs micrographic surgery (MMS) that would not have been cleared by wide local excision alone and provide an extensive review of the literature. Both patients presented with histologic diagnoses of malignant melanoma, one with a barely perceptible biopsy site scar on the left infraorbital cheek/lower eyelid (Breslow 1...
July 1, 2017: Journal of Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/28679643/endogenous-heat-shock-protein-induction-with-or-without-radiofrequency-ablation-or-cryoablation-in-patients-with-stage-iv-melanoma
#7
Evidio Domingo-Musibay, James M Heun, Wendy K Nevala, Matthew Callstrom, Thomas Atwell, Evanthia Galanis, Lori A Erickson, Svetomir N Markovic
LESSONS LEARNED: Percutaneous thermal ablation combined with in situ granulocyte-macrophage colony-stimulating factor cytokine therapy was technically feasible and well tolerated.No significant clinical or immunologic responses were seen. BACKGROUND: Melanoma tumor-derived heat-shock proteins (HSPs) and HSP-peptide complexes can elicit protective antitumor responses. The granulocyte-macrophage colony-stimulating factor (GM-CSF) chemokine can also promote uptake and processing by professional antigen presenting cells (APCs)...
July 5, 2017: Oncologist
https://www.readbyqxmd.com/read/28677156/connexin-43-upregulation-by-dioscin-inhibits-melanoma-progression-via-suppressing-malignancy-and-inducing-m1-polarization
#8
Yu Kou, Liyan Ji, Haojia Wang, Wensheng Wang, Hongming Zheng, Juan Zou, Linxin Liu, Xiaoxiao Qi, Zhongqiu Liu, Biaoyan Du, Linlin Lu
Connexin 43 (Cx43), a vital gap junction protein in tumor microenvironment (TME), is a novel molecular target for melanoma chemotherapeutics due to its tumor suppressive function. Dioscin, an herbal steroidal saponin, exerts anti-tumor effects while the underlying mechanism is unclear. Using WB, FACS, and immunofluorescence methodologies, we found dioscin significantly activated the transcription and translation of Cx43 via the retinoid acid signaling pathway and simultaneously enhanced the transporting function of Cx43...
July 5, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28670252/cd207-langerin-positive-dendritic-cells-in-invasive-and-in-situ-cutaneous-malignant-melanoma
#9
Grzegorz Dyduch, Katarzyna E Tyrak, Anna Glajcar, Joanna Szpor, Krzysztof Okoń
INTRODUCTION: Dendritic cells are crucial for cutaneous immune response. Their role in melanoma progression is however a matter of controversy. MATERIAL AND METHODS: The number of dendritic cells within epidermis and in peri- and intratumoral location was analyzed using CD207 immunostain in 17 cases of in situ and 25 case of invasive melanoma. RESULTS: Average peritumoral CD207+ cells count was 22.88 for all cases, 17.94 for in situ lesions and 26...
June 2017: Postȩpy Dermatologii i Alergologii
https://www.readbyqxmd.com/read/28668077/variation-of-mutant-allele-frequency-in-nras-q61-mutated-melanomas
#10
Zofia Hélias-Rodzewicz, Elisa Funck-Brentano, Nathalie Terrones, Alain Beauchet, Ute Zimmermann, Cristi Marin, Philippe Saiag, Jean-François Emile
BACKGROUND: Somatic mutations of BRAF or NRAS activating the MAP kinase cell signaling pathway are present in 70% of cutaneous melanomas. The mutant allele frequency of BRAF V600E (M%BRAF) was recently shown to be highly heterogeneous in melanomas. The present study focuses on the NRAS Q61 mutant allele frequency (M%NRAS). METHODS: Retrospective quantitative analyze of 104 NRAS mutated melanomas was performed using pyrosequencing. Mechanisms of M%NRAS imbalance were studied by fluorescence in situ hybridization (FISH) and microsatellite analysis...
July 1, 2017: BMC Dermatology
https://www.readbyqxmd.com/read/28663910/raman-active-components-of-skin-cancer
#11
Xu Feng, Austin J Moy, Hieu T M Nguyen, Jason Zhang, Matthew C Fox, Katherine R Sebastian, Jason S Reichenberg, Mia K Markey, James W Tunnell
Raman spectroscopy (RS) has shown great potential in noninvasive cancer screening. Statistically based algorithms, such as principal component analysis, are commonly employed to provide tissue classification; however, they are difficult to relate to the chemical and morphological basis of the spectroscopic features and underlying disease. As a result, we propose the first Raman biophysical model applied to in vivo skin cancer screening data. We expand upon previous models by utilizing in situ skin constituents as the building blocks, and validate the model using previous clinical screening data collected from a Raman optical fiber probe...
June 1, 2017: Biomedical Optics Express
https://www.readbyqxmd.com/read/28659278/pathologists-diagnosis-of-invasive-melanoma-and-melanocytic-proliferations-observer-accuracy-and-reproducibility-study
#12
Joann G Elmore, Raymond L Barnhill, David E Elder, Gary M Longton, Margaret S Pepe, Lisa M Reisch, Patricia A Carney, Linda J Titus, Heidi D Nelson, Tracy Onega, Anna N A Tosteson, Martin A Weinstock, Stevan R Knezevich, Michael W Piepkorn
Objective To quantify the accuracy and reproducibility of pathologists' diagnoses of melanocytic skin lesions.Design Observer accuracy and reproducibility study.Setting 10 US states.Participants Skin biopsy cases (n=240), grouped into sets of 36 or 48. Pathologists from 10 US states were randomized to independently interpret the same set on two occasions (phases 1 and 2), at least eight months apart.Main outcome measures Pathologists' interpretations were condensed into five classes: I (eg, nevus or mild atypia); II (eg, moderate atypia); III (eg, severe atypia or melanoma in situ); IV (eg, pathologic stage T1a (pT1a) early invasive melanoma); and V (eg, ≥pT1b invasive melanoma)...
June 28, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28650644/combination-of-plant-virus-nanoparticle-based-in-situ-vaccination-with-chemotherapy-potentiates-antitumor-response
#13
Karin L Lee, Abner A Murray, Duc H T Le, Mee Rie Sheen, Sourabh Shukla, Ulrich Commandeur, Steven Fiering, Nicole F Steinmetz
Immunotherapeutics are gaining more traction in the armamentarium used to combat cancer. Specifically, in situ vaccination strategies have gained interest because of their ability to alter the tumor microenvironment to an antitumor state. Herein, we investigate whether flexuous plant virus-based nanoparticles formed by the potato virus X (PVX) can be used as an immunotherapeutic for in situ vaccine monotherapy. We further developed dual chemo-immunotherapeutics by incorporating doxorubicin (DOX) into PVX yielding a dual-functional nanoparticle (PVX-DOX) or by coadministration of the two therapeutic regimes, PVX immunotherapy and DOX chemotherapy (PVX+DOX)...
June 26, 2017: Nano Letters
https://www.readbyqxmd.com/read/28646613/novel-tmc8-splice-site-mutation-in-epidermodysplasia-verruciformis-and-review-of-hpv-infections-in-patients-with-the-disease
#14
E Imahorn, Z Yüksel, I Spoerri, G Gürel, C Imhof, Z N Saraçoğlu, A E Koku Aksu, P L Rady, S K Tyring, W Kempf, P H Itin, B Burger
BACKGROUND: Epidermodysplasia verruciformis (EV) is a genodermatosis leading to infections with cutaneous HPV, persistent plane warts and a high rate of non-melanoma skin cancer (NMSC). Biallelic loss-of-function mutations in TMC6 and TMC8 are known to be causative. OBJECTIVE: The aim of this study was to report EV-causing mutations in four patients with EV and to give an overview of all described EV patients. PATIENTS AND METHODS: We investigated four patients with classical features of EV from two families...
June 24, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28645508/merkel-cell-carcinoma-melanoma-metastatic-mimics-of-breast-cancer
#15
REVIEW
Megan L Troxell
Merkel cell carcinoma and melanoma can each occur primarily in breast skin, or metastasize to the breast. The breast is a rare site of metastasis of essentially any and every type of tumor, including carcinomas, sarcomas, and hematolymphoid neoplasms, and 10-30% of breast metastases may represent the initial presentation of disease. Although metastases generally recapitulate histologic features of the primary tumor, they are diagnostically challenging given their rarity and morphologic overlap with breast carcinoma, including special types of breast cancer...
May 31, 2017: Seminars in Diagnostic Pathology
https://www.readbyqxmd.com/read/28640877/identification-of-c-ebp%C3%AE-as-a-novel-target-of-the-hpv8-e6-protein-regulating-mir-203-in-human-keratinocytes
#16
Anna M Marthaler, Marta Podgorska, Pascal Feld, Alina Fingerle, Katrin Knerr-Rupp, Friedrich Grässer, Hans Smola, Klaus Roemer, Elke Ebert, Yoo-Jin Kim, Rainer M Bohle, Cornelia S L Müller, Jörg Reichrath, Thomas Vogt, Magdalena Malejczyk, Sławomir Majewski, Sigrun Smola
Patients suffering from Epidermodysplasia verruciformis (EV), a rare inherited skin disease, display a particular susceptibility to persistent infection with cutaneous genus beta-human papillomavirus (beta-HPV), such as HPV type 8. They have a high risk to develop non-melanoma skin cancer at sun-exposed sites. In various models evidence is emerging that cutaneous HPV E6 proteins disturb epidermal homeostasis and support carcinogenesis, however, the underlying mechanisms are not fully understood as yet. In this study we demonstrate that microRNA-203 (miR-203), a key regulator of epidermal proliferation and differentiation, is strongly down-regulated in HPV8-positive EV-lesions...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28619614/rapid-ex-vivo-examination-of-mohs-specimens-using-optical-coherence-tomography
#17
D Rashed, D Shah, A Freeman, R J Cook, C Hopper, C M Perrett
BACKGROUND: Mohs micrographic surgery (MMS) is an effective treatment for certain non-melanoma skin cancers. Optical coherence tomography (OCT) is a biomedical imaging modality that permits high-resolution imaging of the epidermis and dermis with the potential to detect both healthy tissue and tumour. OCT may also provide a means of detecting and differentiating between the various histological subtypes of basal cell carcinomas (BCC) in vivo. OBJECTIVE: The aim of this prospective ex vivo study was to evaluate the efficacy of OCT in recognising healthy and pathological margins of excised BCC lesions and detecting different BCC subtypes...
June 12, 2017: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/28614272/quantification-of-microrna-21-and-microrna-125b-in-melanoma-tissue
#18
Anne Wandler, Rikke Riber-Hansen, Henrik Hager, Stephen J Hamilton-Dutoit, Henrik Schmidt, Boye S Nielsen, Magnus Stougaard, Torben Steiniche
Although microRNAs (miRNAs) have emerged as potent mediators of melanoma development and progression, a precise understanding of their oncogenic role remains unclear. In this study, we analysed formalin-fixed and paraffin-embedded tissues from two separate melanoma cohorts and from a series of benign melanocytic nevi. Using three different quantification methods [array analysis, quantitative PCR (qPCR) and in-situ hybridization (ISH) quantified by digital image analysis], we found considerable miRNA dysregulation in tumours...
June 13, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28609317/characteristics-of-melanoma-in-japan-a-nationwide-registry-analysis-2011-2013
#19
Taro Tomizuka, Kenjiro Namikawa, Takahiro Higashi
The distribution and incidence of melanoma vary among different races and ethnic groups. This study aimed to investigate the characteristics of cutaneous melanoma, mucosal melanoma, uveal melanoma, and melanoma of unknown primary (MUP) origin in a Japanese population. We studied these four types of melanoma in patients registered in Hospital Based Cancer Registries in Japan from 2011 to 2013. A total of 5566 patients with melanoma were identified. The distribution of sex, age, primary site, and clinical stage was analyzed...
June 12, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28601390/frequency-of-and-risk-factors-for-tumor-upstaging-after-wide-local-excision-of-primary-cutaneous-melanoma
#20
Jeremy R Etzkorn, John M Sharkey, John W Grunyk, Thuzar M Shin, Joseph F Sobanko, Christopher J Miller
BACKGROUND: Detecting a more advanced stage of the primary melanoma after wide local excision and reconstruction can complicate patient counseling about prognosis, management of surgical margins, and indications for sentinel lymph node biopsy. OBJECTIVE: To identify the frequency of and risk factors associated with upstaging after wide local excision of primary melanoma. METHODS: Retrospective, single center, cross-sectional study of 1332 consecutive in situ to stage T4a melanomas treated with wide local excision...
August 2017: Journal of the American Academy of Dermatology
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