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Karin Kfir-Elirachman, Rona Ortenberg, Bella Vizel, Michal J Besser, Iris Barshack, Jacob Schachter, Yael Nemlich, Gal Markel
BRAF becomes constitutively activated in 50% to 70% of melanoma cases. CEACAM1 has a dual role in melanoma, including facilitation of cell proliferation and suppression of infiltrating lymphocytes, which are consistent with its value as a marker for poor prognosis in melanoma patients. Here we show that BRAFV600E melanoma cells treated with BRAF and MEK inhibitors (MAPKi) downregulate CEACAM1 mRNA and protein expression in a dose- and exposure time-dependent manners. Indeed, there is a significant correlation between the presence of BRAFV600E and CEACAM1 expression in melanoma specimens obtained from 45 patients...
March 17, 2018: Neoplasia: An International Journal for Oncology Research
Moozhan Nikpanah, Lauren Kim, S Mojdeh Mirmomen, Rolf Symons, Ioannis Papageorgiou, William A Gahl, Kevin O'Brien, Juvianee I Estrada-Veras, Ashkan A Malayeri
OBJECTIVES: To use magnetic resonance imaging (MRI) and computed tomography (CT) to define abdominal involvement in Erdheim-Chester disease (ECD), and to investigate the association between these findings and the BRAFV600E mutation. METHODS: This prospective study was performed on 61 ECD patients (46 men). The MRI and CT imaging studies were reviewed independently by two experienced radiologists. The association between BRAFV600E mutation and imaging findings was analysed using Fisher's exact test, and odds ratios with 95% confidence intervals...
March 19, 2018: European Radiology
A Campennì, R M Ruggeri, M Siracusa, S A Pignata, F Di Mauro, A Vento, F Trimarchi, S Baldari
PURPOSE: The aim of the present study was to evaluate the possible diagnostic role of the combined performance of BRAF mutation analysis and MIBI scintigraphy in papillary thyroid cancer (PTC) patients with incomplete bio-chemical response to first radioiodine therapy (RAIT) performed for thyroid remnant ablation. METHODS: The records of 15 PTC patients with bio-chemical incomplete response to first RAIT were retrospectively analyzed. BRAFV600E analysis on primary tumor samples was obtained in all cases along with neck ultrasonography and99m Tc-MIBI scintigraphy of the neck-thorax regions at first follow-up...
March 16, 2018: Journal of Endocrinological Investigation
O Awwad, F Coperchini, P Pignatti, M Denegri, S Massara, L Croce, C A Di Buduo, V Abbonante, A Balduini, L Chiovato, M Rotondi
PURPOSE: The AMPK-activator AICAR recently raised great interest for its anti-cancer properties. With specific regard to thyroid cancer, AICAR reduces cancer cell growth, invasion and metastasis. CXCL8, a chemokine with several recognized tumorigenic effects, is abundantly secreted in thyroid cancer microenvironment. The aim of this study was to investigate if AICAR could inhibit the basal and the TNFα-induced CXCL8 secretion in normal human thyroid cells (NHT) and in thyroid cancer cell lines TPC-1 and BCPAP (RET/PTC and BRAFV600e mutated, respectively)...
March 15, 2018: Journal of Endocrinological Investigation
Christian S Hinrichs
As oncogenes drive carcinogenesis and promote cancer cell survival, they are highly attractive therapeutic targets, and oncogene-targeting small molecules have achieved some clinical success. While many oncogenes are presently considered to be "druggable," tumors often acquire treatment resistance, and patients are rarely cured in response to oncogene-specific treatment. In this issue of the JCI, Veatch and colleagues describe a patient with metastatic acral melanoma who experienced a complete tumor response following infusion of tumor-infiltrating T cells that targeted multiple tumor antigens, including a BRAFV600E driver mutation...
March 12, 2018: Journal of Clinical Investigation
Benjamin H Durham
The systemic histiocytoses encompass a clinically heterogeneous group of disorders leading to tissue damage secondary to the accumulation and infiltration of pathological cells thought to be derived from the dendritic or monocytic lineages with accompanying inflammation. For decades, whether or not the histiocytoses were inflammatory or neoplastic disorders was unclear, and their cellular origins have long been obscure and heavily debated. However, the rise of the molecular era led to the discovery of recurrent BRAFV600E mutations in approximately 50% of patients with Langerhans cell and non-Langerhans cell histiocytoses, which provided the first convincing evidence that these are indeed histiocytic neoplasms...
March 8, 2018: Seminars in Cell & Developmental Biology
Nirmala Pandeya, Marina Kvaskoff, Catherine M Olsen, Adèle C Green, Susan Perry, Catherine Baxter, Marcia B Davis, Rohan Mortimore, Lorraine Westacott, Dominic Wood, Joe Triscott, Richard Williamson, David C Whiteman
A proportion of cutaneous melanomas display neval remnants on histologic examination. Converging lines of epidemiologic and molecular evidence suggest that melanomas arising from nevus precursors differ from melanomas arising de novo. In a large, population-based study comprising 636 cutaneous melanomas subjected to dermatopathology review, we explored the molecular, host and environmental factors associated with the presence of neval remnants. We found nevus-associated melanomas were significantly associated with younger age at presentation, non-brown eye color, trunk site, thickness <0...
March 7, 2018: Journal of Investigative Dermatology
Victoria Peyret, Magalí Nazar, Mariano Martin, Amado A Quintar, Elmer A Fernandez, Romina C Geysels, Cesar Fuziwara, María M Montesinos, Cristina A Maldonado, Pilar Santisteban, Edna T Kimura, Claudia G Pellizas, Juan P Nicola, Ana M Masini-Repiso
Emerging evidence suggests that unregulated Toll-like receptors (TLRs) signaling promotes tumor survival signals, thus favoring tumor progression. Here, the mechanism underlying TLR4 overexpression in papillary thyroid carcinomas (PTCs) mainly harboring the BRAFV600E mutation was studied. TLR4 was overexpressed in PTCs compared to non-neoplastic thyroid tissue. Moreover, paired clinical specimens of primary PTC and its lymph node metastasis showed a significant upregulation of TLR4 levels in the metastatic tissues...
March 9, 2018: Molecular Cancer Research: MCR
Sven-Martin Schlaffer, Michael Buchfelder, Robert Stoehr, Rolf Buslei, Annett Hölsken
A 6-year old patient presented with an intra and suprasellar cystic lesion accompanied with impairment of the hypothalamic-pituitary axis and partial hypopituitarism. The most likely cause of sellar lesions in this age group are adamantinomatous craniopharyngioma (adaCP) or Rathke´s cleft cysts (RCCs). AdaCP are characterized by CTNNB1 mutations accompanied with aberrant nuclear beta-catenin expression. RCC show neither nuclear beta-catenin expression nor BRAF mutation. The latter is a hallmark of papillary craniopharyngiomas (papCP) that exhibit remarkable histological similarity with metaplasia of RCC...
2018: Frontiers in Genetics
J Smeby, A Sveen, M A Merok, S A Danielsen, I A Eilertsen, M G Guren, R Dienstmann, A Nesbakken, R A Lothe
BACKGROUND: The prognostic impact of KRAS and BRAFV600E mutations in primary colorectal cancer (CRC) varies with microsatellite instability (MSI) status. The gene expression-based consensus molecular subtypes (CMS) of CRC define molecularly and clinically distinct subgroups, and represent a novel stratification framework in biomarker analysis. We investigated the prognostic value of these mutations within the CMS groups. PATIENTS AND METHODS: Totally 1197 primary tumors from a Norwegian series of CRC stage I-IV were analyzed for MSI and mutation status in hotspots in KRAS (codons 12, 13 and 61) and BRAF (codon 600)...
March 5, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Natalie E Parks, Gaurav Goyal, Ronald S Go, Jay Mandrekar, W Oliver Tobin
Background: We describe the neuroradiologic features of a cohort of patients with Erdheim-Chester disease. Methods: We assessed patients at Mayo Clinic Rochester between January 1, 1990, and July 31, 2016, with pathologically confirmed Erdheim-Chester disease (n = 53). Results: Neuroimaging, including head CT (n = 17), brain MRI (n = 39), orbital MRI (n = 15), and spine MRI (n = 16), was available for 42 participants. Median age at diagnosis was 55 years (interquartile range 46-66) with higher male prevalence (33:20)...
February 2018: Neurology. Clinical Practice
Małgorzata Mackiewicz-Wysocka, Patrycja Czerwińska, Violetta Filas, Elżbieta Bogajewska, Agata Kubicka, Anna Przybyła, Ewelina Dondajewska, Tomasz Kolenda, Andrzej Marszałek, Andrzej Mackiewicz
Introduction: Twenty-five - fifty percent of skin melanomas arise from nevi. Melanocyte proliferation is activated by BRAF V600E , then is arrested, but single nevi transform to melanomas. p16 controls arrest, and p16 loss may promote transformation. Aim: To analyze BRAF V600E , p16 expression and melanocyte proliferation in dermal, compound and dysplastic nevi, cells of primary and metastatic melanoma in the Polish population. Material and methods: One hundred and thirty-two nevi (dermal, compound, dysplastic) and 41 melanomas ( in situ , primary, metastatic) were studied...
October 2017: Postȩpy Dermatologii i Alergologii
Kwon Joong Na, Hongyoon Choi
Although papillary thyroid cancer (PTC) is curable with excellent survival rate, patients with dedifferentiated PTC suffer the recurrence or death. As cancer immune escape plays a critical role in cancer progression, we aimed to investigate the relationship between differentiation and immune landscape of PTC and its implications for immunotherapy. Using the Cancer Genome Atlas data, we estimated the immune cell enrichment scores and overall immune infiltration, ImmuneScore, to characterize the immune landscape of PTC...
March 5, 2018: Endocrine-related Cancer
Ignazia Tusa, Sinforosa Gagliardi, Alessandro Tubita, Silvia Pandolfi, Carmelo Urso, Lorenzo Borgognoni, Jinhua Wang, Xianming Deng, Nathanael S Gray, Barbara Stecca, Elisabetta Rovida
Malignant melanoma is among the most aggressive cancers and its incidence is increasing worldwide. Targeted therapies and immunotherapy have improved the survival of patients with metastatic melanoma in the last few years; however, available treatments are still unsatisfactory. While the role of the BRAF-MEK1/2-ERK1/2 pathway in melanoma is well established, the involvement of mitogen-activated protein kinases MEK5-ERK5 remains poorly explored. Here we investigated the function of ERK5 signaling in melanoma...
February 27, 2018: Oncogene
Nicholas Forsythe, Alaa Refaat, Arman Javadi, Hajrah Khawaja, Jessica-Anne Weir, Heba Emam, Wendy L Allen, Frank Burkamp, Vlad Popovici, Puthen V Jithesh, Claudio Isella, Melissa J LaBonte, Ian G Mills, Patrick G Johnston, Sandra Van Schaeybroeck
BRAFV600E mutations occur in 10% of colorectal cancer (CRC) cases, are associated with poor survival and have limited responses to BRAF/MEK inhibition with or without EGFR inhibition. There is an unmet need to understand the biology of poor prognostic BRAFMT CRC. We have used differential gene expression and pathway analyses of untreated stage II and stage III BRAFMT (discovery set: n=31; validation set: n=26) CRC and an siRNA screen to characterize the biology underpinning the BRAFMT subgroup with poorest outcome...
February 26, 2018: Molecular Cancer Therapeutics
Sandeep S Joshi, Shunlin Jiang, Emmanual Unni, Stephen R Goding, Tao Fan, Paul A Antony, Thomas J Hornyak
Heat shock protein 90 (HSP90) is a molecular chaperone which stabilizes client proteins with important roles in tumor growth. 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of HSP90 ATPase activity, occupies the ATP binding site of HSP90 causing a conformational change which destabilizes client proteins and directs them towards proteosomal degradation. Malignant melanomas have active RAF-MEK-ERK signaling which can occur either through an activating mutation in BRAF (BRAFV600E) or through activation of signal transduction upstream of BRAF...
2018: PloS One
Maria Gonzalez-Cao, Clara Mayo de Las Casas, Nuria Jordana Ariza, Jose L Manzano, Miguel Á Molina-Vila, Virtudes Soriano, Teresa Puertolas, Ariadna Balada, Ainara Soria, Margarita Majem, Clara Montagut, Eva Muñoz, Delvys Rodriguez-Abreu, Elisabeth Perez, Almudena Garcia, Javier Cortes, Ana Drozdowskyj, Niki Karachaliou, Rafael Rosell
Serial analysis of BRAF mutations in circulating-free DNA (cfDNA) could be of prognostic value in melanoma patients. We collected blood samples from 63 advanced BRAFV600E/K melanoma patients and determined BRAFV600E/K status in cfDNA using a quantitative 5'-nuclease PCR-based assay. Levels of BRAF mutation in pre-cfDNAs were associated significantly with tumour burden, progression-free survival and overall survival. Changes in BRAF status in cfDNA after initiation of treatment (early-cfDNA) had a significant correlation with outcome...
February 23, 2018: Melanoma Research
Michele Maio, Karl Lewis, Lev Demidov, Mario Mandalà, Igor Bondarenko, Paolo A Ascierto, Christopher Herbert, Andrzej Mackiewicz, Piotr Rutkowski, Alexander Guminski, Grant R Goodman, Brian Simmons, Chenglin Ye, Yibing Yan, Dirk Schadendorf
BACKGROUND: Systemic adjuvant treatment might mitigate the high risk of disease recurrence in patients with resected stage IIC-III melanoma. The BRIM8 study evaluated adjuvant vemurafenib monotherapy in patients with resected, BRAFV600 mutation-positive melanoma. METHODS: BRIM8 was a phase 3, international, double-blind, randomised, placebo-controlled study that enrolled 498 adults (aged ≥18 years) with histologically confirmed stage IIC-IIIA-IIIB (cohort 1) or stage IIIC (cohort 2) BRAFV600 mutation-positive melanoma that was fully resected...
February 21, 2018: Lancet Oncology
Jonathan D Wasserman, Nelly Sabbaghian, Somayyeh Fahiminiya, Rose Chami, Ozgur Mete, Meryl Acker, Mona K Wu, Adam Shlien, Leanne de Kock, William D Foulkes
Context: Papillary thyroid carcinoma (PTC) is a common malignancy in adolescence and is molecularly and clinically distinct from adult PTC. Mutations in the DICER1 gene are associated with thyroid abnormalities including multinodular goitre and differentiated thyroid carcinoma. Objective: In this study, we sought to characterize the prevalence of DICER1 variants in paediatric PTC, specifically in tumours without conventional PTC oncogenic alterations. Patients: Patients (n = 40) who underwent partial or total thyroidectomy and who were <18 years of age at the time of surgery were selected...
February 21, 2018: Journal of Clinical Endocrinology and Metabolism
Ankush Bhatia, Gary Ulaner, Raajit Rampal, David M Hyman, Omar Abdel-Wahab, Benjamin H Durham, Ahmet Dogan, Neval Ozkaya, Mario E Lacouture, Julio Hajdenberg, Chezi Ganzel, Eli L Diamond
No abstract text is available yet for this article.
February 22, 2018: Haematologica
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