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https://www.readbyqxmd.com/read/29456854/novel-braf-mutation-in-melanoma-a-case-report
#1
Serena Trubini, Alessandro Ubiali, Carlo Terenzio Paties, Luigi Cavanna
In melanoma, a number of specific genetic and genomic aberrations have been identified to be important in tumorigenesis. In particular, the mutant B-Raf proto-oncogene, Serine/Threonine kinase (BRAF) gene is the target of tailored therapy with kinase inhibitor molecules. Identification of the array of mutations in patients with melanoma will be useful in determining a genetic profile of the tumor with potential implications for treatment decisions. A rare aminoacidic insertion in codon 599 of the BRAF gene (c...
March 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29454849/escmid-study-group-for-infections-in-compromised-hosts-esgich-consensus-document-on-the-safety-of-targeted-and-biological-therapies-an-infectious-diseases-perspective-intracellular-signaling-pathways-tyrosine-kinase-and-mtor-inhibitors
#2
REVIEW
Mark Reinwald, Jose T Silva, Nicolas J Mueller, Jesús Fortún, Christian Garzoni, Johan W de Fijter, Mario Fernández-Ruiz, Paolo Grossi, Jose María Aguado
BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of therapies targeting different intracellular signaling pathways and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family...
February 15, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29453679/the-impact-of-timing-of-immunotherapy-with-cranial-irradiation-in-melanoma-patients-with-brain-metastases-intracranial-progression-survival-and-toxicity
#3
Rifaquat Rahman, Alfonso Cortes, Andrzej Niemierko, Kevin S Oh, Keith T Flaherty, Donald P Lawrence, Ryan J Sullivan, Helen A Shih
Immunotherapy (IT) is increasingly incorporated in the management of metastatic melanoma patients with brain metastases, but the impact of timing of IT with stereotactic radiosurgery (SRS) remains unclear. The aim of this study was to determine the temporal significance of IT in melanoma patients treated with cranial radiation therapy (RT) with respect to patterns of intracranial progression, overall survival (OS), and toxicity. We retrospectively reviewed consecutive melanoma patients with brain metastases undergoing cranial RT and IT between 2008 and 2015...
February 16, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29453361/heterogeneity-and-mutation-in-kras-and-associated-oncogenes-evaluating-the-potential-for-the-evolution-of-resistance-to-targeting-of-kras-g12c
#4
Vincent L Cannataro, Stephen G Gaffney, Carly Stender, Zi-Ming Zhao, Mark Philips, Andrew E Greenstein, Jeffrey P Townsend
Activating mutations in RAS genes are associated with approximately 20% of all human cancers. New targeted therapies show preclinical promise in inhibiting the KRAS G12C variant. However, concerns exist regarding the effectiveness of such therapies in vivo given the possibilities of existing intratumor heterogeneity or de novo mutation leading to treatment resistance. We performed deep sequencing of 27 KRAS G12-positive lung tumors to determine the prevalence of other oncogenic mutations within KRAS or within commonly mutated downstream genes that could confer resistance at the time of treatment...
February 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29428455/ophthalmic-findings-of-rosai-dorfman-disease
#5
Michael B Choi, Diva R Salomão, Wendy M Smith, Jose S Pulido, James A Garrity
PURPOSE: To describe the ophthalmic, pathologic, and BRAF V600E mutation status of Rosai-Dorfman Disease (RDD). DESIGN: Retrospective case series. METHODS: A retrospective review of all cases of RDD seen at Mayo Clinic from 1992 to 2016 identified patients with ophthalmic manifestations (n=8). Immunostain for BRAF and molecular studies for BRAFV600E mutation were performed on cases with tissue available. RESULTS: Of 76 patients with RDD, 15 had eye exams and, of those, 8 had ophthalmic manifestations (5 females and 3 males)...
February 8, 2018: American Journal of Ophthalmology
https://www.readbyqxmd.com/read/29426605/diversity-of-circulating-tumor-cells-in-peripheral-blood-detection-of-heterogeneous-braf-mutations-in-a-patient-with-advanced-melanoma-by-single-cell-analysis
#6
Yukiko Kiniwa, Kenta Nakamura, Asuka Mikoshiba, Yasuyuki Akiyama, Atsushi Morimoto, Ryuhei Okuyama
The advent of therapeutics targeting the MAPK signal pathway has led to great advances in the treatment of metastatic melanoma. However, a significant number of patients experience a short response and exhibit recurrence within several months after therapy, potentially related to mutation heterogeneity arising due to genetic and epigenetic instability of melanoma cells. Circulating tumor cells (CTCs) released from either primary or metastatic tumors are a non-invasive tool that could be used to characterise changes in tumors over time...
February 1, 2018: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29423503/association-between-circulating-tumor-dna-and-pseudoprogression-in-patients-with-metastatic-melanoma-treated-with-anti-programmed-cell-death-1-antibodies
#7
Jenny H Lee, Georgina V Long, Alexander M Menzies, Serigne Lo, Alexander Guminski, Kataraina Whitbourne, Michelle Peranec, Richard Scolyer, Richard F Kefford, Helen Rizos, Matteo S Carlino
Importance: Longitudinal circulating tumor DNA (ctDNA) has been shown to predict response and survival in patients with metastatic melanoma treated with anti-programmed cell death 1 (PD-1) antibodies. Pseudoprogression, defined as radiologic finding of disease progression prior to response, has been a challenge to clinicians. Objective: To establish whether ctDNA at baseline and up to week 12 of treatment can differentiate between the radiologic findings of pseudoprogression and true progression in patients with metastatic melanoma...
February 8, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29419849/braf-v600-mutation-profile-of-metastatic-melanoma-in-the-thrace-region-of-turkey
#8
Nuray Can, Ebru Taştekin, Tülin Deniz Yalta, Necdet Süt, Selma Korkmaz, Ufuk Usta, Fulya Öz Puyan, Ezgi Genç, Mert Cezik, Busem Binboğa Tutuğ, Osman Köstek, Hilmi Tozkir
OBJECTIVE: BRAF is the most common mutation in melanoma. The most common subtype is BRAF V600E, followed by V600K. Initially, the authors aimed to investigate whether clinicopathological features of melanoma are associated with BRAF mutations. We then aimed to present the relationships between the clinicopathological features and the mutated subtype (V600E vs V600K). MATERIAL AND METHOD: 61 patients with metastatic malignant melanoma (affecting the lymph node or other distant sites) were selected...
February 8, 2018: Türk Patoloji Dergisi
https://www.readbyqxmd.com/read/29416939/maturation-of-tertiary-lymphoid-structures-and-recurrence-of-stage-ii-and-iii-colorectal-cancer
#9
Florian Posch, Karina Silina, Sebastian Leibl, Axel Mündlein, Holger Moch, Alexander Siebenhüner, Panagiotis Samaras, Jakob Riedl, Michael Stotz, Joanna Szkandera, Herbert Stöger, Martin Pichler, Roger Stupp, Maries van den Broek, Peter Schraml, Armin Gerger, Ulf Petrausch, Thomas Winder
Tertiary lymphoid structures (TLS) are associated with favorable outcome in non-metastatic colorectal carcinoma (nmCRC), but the dynamics of TLS maturation and its association with effective anti-tumor immune surveillance in nmCRC are unclear. Here, we hypothesized that not only the number of TLS but also their composition harbors information on recurrence risk in nmCRC. In a comprehensive molecular, tissue, laboratory, and clinical analysis of 109 patients with stage II/III nmCRC, we assessed TLS numbers and degree of maturation in surgical specimens by multi-parameter immunofluorescence of follicular dendritic cell (FDC) and germinal center (GC) markers...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29416771/menopause-and-adipose-tissue-mir-19a-3p-is-sensitive-to-hormonal-replacement
#10
Reeta Kangas, Cristina Morsiani, Grazia Pizza, Catia Lanzarini, Pauliina Aukee, Jaakko Kaprio, Sarianna Sipilä, Claudio Franceschi, Vuokko Kovanen, Eija K Laakkonen, Miriam Capri
Tissue-specific effects of 17β-estradiol are delivered via both estrogen receptors and microRNAs (miRs). Menopause is known to affect the whole-body fat distribution in women. This investigation aimed at identifying menopause- and hormone replacement therapy (HRT)-associated miR profiles and miR targets in subcutaneous abdominal adipose tissue and serum from the same women. A discovery phase using array technology was performed in 13 women, including monozygotic twin pairs discordant for HRT and premenopausal young controls...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29416574/validation-of-the-graded-prognostic-assessment-for-melanoma-using-molecular-markers-melanoma-molgpa
#11
Carsten Nieder, Mandy Hintz, Angelika Bilger, Oliver Oehlke, Anca-Ligia Grosu
Background: It has been suggested to replace the diagnosis-specific graded prognostic assessment (DS-GPA, based on performance status and number of brain metastases) for patients with primary malignant melanoma with the new Melanoma-molGPA. The latter is a more complex assessment, which also includes BRAF mutation status, age and extracranial metastases. To test the performance of the Melanoma-molGPA, we performed a validation study of this new survival prediction tool. Methods: A retrospective analysis of patients treated at two different academic institutions was performed...
March 2018: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/29413057/tumor-biomarker-testing-in-non-small-cell-lung-cancer-a-decade-of-change
#12
Paul A VanderLaan, Deepa Rangachari, Adnan Majid, Mihir S Parikh, Sidharta P Gangadharan, Michael S Kent, Danielle C McDonald, Mark S Huberman, Susumu S Kobayashi, Daniel B Costa
INTRODUCTION: Although a growing list of essential genomic/immune-based biomarkers are linked to approved non-small-cell lung cancer (NSCLC) therapies worldwide, few reports have detailed the evolution of NSCLC predictive biomarker assessment in routine clinical practice. METHODS: We retrospectively reviewed the first one thousand plus NSCLC patient specimens from our institution analyzed for predictive biomarkers from 2004 to 2017 and evaluated patterns of testing as well as correlation with clinical-pathologic characteristics...
February 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29407956/design-synthesis-mechanistic-and-histopathological-studies-of-small-molecules-of-novel-indole-2-carboxamides-and-pyrazino-1-2-a-indol-1-2h-ones-as-potential-anticancer-agents-effecting-the-reactive-oxygen-species-production
#13
Bahaa G M Youssif, Mostafa H Abdelrahman, Ahmed H Abdelazeem, Mohamed A Abdelgawad, Hussein M Ibrahim, Ola I A Salem, Mamdouh F A Mohamed, Laurent Treambleau, Syed Nasir Abbas Bukhari
A series of novel compounds carrying pyrazino[1,2-a]indol-1(2H)-one scaffold (5a-g) and their reaction intermediates, indole-2-carboxamides, (3a-g) were synthesized and evaluated for their ability to inhibit reactive oxygen species (ROS) generation, antioxidant activity and anticancer activity against a panel of cancer cell lines using MTT assay. The results showed that these compounds can inhibit ROS generation during the metabolic phase of phagocytosis in a dose-dependent manner where compounds 5d and 5e were the most potent samples with higher inhibitory activities (IC50 values 3...
January 25, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29406329/no-braf-v600e-mutation-identified-in-28-periocular-pyogenic-granuloma
#14
Guosheng Li, Emily Adams, James R Eshleman, Charles G Eberhart
PURPOSE: BRAF V600E mutations were recently identified in some pyogenic granulomas of skin, particularly lesions arising in patients with port wine stains. In this study, the authors analyzed BRAF gene status in 28 periocular pyogenic granulomas to determine its role in their pathogenesis. METHODS: Retrospective review of ophthalmic pathology archives from 2007 to 2016 was used to identify pyogenic granulomas of the conjunctiva, eyelid, and orbit. Three eyelid nevi were also analyzed as positive controls...
February 5, 2018: Ophthalmic Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/29405341/metastatic-melanoma-with-dedifferentiation-and-extensive-rhabdomyosarcomatous-heterologous-component
#15
Katelynn Campbell, Asangi R Kumarapeli, Neriman Gokden, Roni Michele Cox, Laura Hutchins, Jerad M Gardner
Melanoma may undergo dedifferentiation and sarcomatous transformation with loss of melanocytic markers. Dedifferentiated melanoma rarely forms true rhabdomyoblasts with skeletal muscle immunophenotype (rhabdomyosarcomatous heterologous component). A 52 year-old woman was diagnosed with invasive melanoma (Breslow depth 0.83 mm) of the upper back in 2012, treated by wide local excision only. In 2013, an axillary mass was excised to show metastatic melanoma with two morphologies: an epithelioid morphology expressing S100 and MART-1 and a spindled morphology with loss of melanocytic markers but strong expression of desmin...
February 5, 2018: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/29405038/systemic-treatments-for-metastatic-cutaneous-melanoma
#16
REVIEW
Sandro Pasquali, Andreas V Hadjinicolaou, Vanna Chiarion Sileni, Carlo Riccardo Rossi, Simone Mocellin
BACKGROUND: The prognosis of people with metastatic cutaneous melanoma, a skin cancer, is generally poor. Recently, new classes of drugs (e.g. immune checkpoint inhibitors and small-molecule targeted drugs) have significantly improved patient prognosis, which has drastically changed the landscape of melanoma therapeutic management. This is an update of a Cochrane Review published in 2000. OBJECTIVES: To assess the beneficial and harmful effects of systemic treatments for metastatic cutaneous melanoma...
February 6, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29398453/updated-molecular-testing-guideline-for-the-selection-of-lung-cancer-patients-for-treatment-with-targeted-tyrosine-kinase-inhibitors-guideline-from-the-college-of-american-pathologists-the-international-association-for-the-study-of-lung-cancer-and-the-association
#17
Neal I Lindeman, Philip T Cagle, Dara L Aisner, Maria E Arcila, Mary Beth Beasley, Eric Bernicker, Carol Colasacco, Sanja Dacic, Fred R Hirsch, Keith Kerr, David J Kwiatkowski, Marc Ladanyi, Jan A Nowak, Lynette Sholl, Robyn Temple-Smolkin, Benjamin Solomon, Lesley H Souter, Erik Thunnissen, Ming S Tsao, Christina B Ventura, Murry W Wynes, Yasushi Yatabe
CONTEXT: In 2013, an evidence-based guideline was published by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology to set standards for the molecular analysis of lung cancers to guide treatment decisions with targeted inhibitors. New evidence has prompted an evaluation of additional laboratory technologies, targetable genes, patient populations, and tumor types for testing. OBJECTIVE: To systematically review and update the 2013 guideline to affirm its validity; to assess the evidence of new genetic discoveries, technologies, and therapies; and to issue an evidence-based update...
January 23, 2018: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/29396809/molecular-testing-of-nodules-with-a-suspicious-or-malignant-cytologic-diagnosis-in-the-setting-of-non-invasive-follicular-thyroid-neoplasm-with-papillary-like-nuclear-features-niftp
#18
Kyle C Strickland, Markus Eszlinger, Ralf Paschke, Trevor E Angell, Erik K Alexander, Ellen Marqusee, Matthew A Nehs, Vickie Y Jo, Alarice Lowe, Marina Vivero, Monica Hollowell, Xiaohua Qian, Tad Wieczorek, Christopher A French, Lisa A Teot, Edmund S Cibas, Neal I Lindeman, Jeffrey F Krane, Justine A Barletta
Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is an indolent thyroid tumor characterized by frequent RAS mutations and an absence of the BRAF V600E mutation commonly seen in classical papillary thyroid carcinoma (cPTC). The ability to differentiate potential NIFTP/follicular variant of papillary thyroid carcinoma (FVPTC) from cPTC at the time of fine-needle aspiration (FNA) can facilitate conservative management of NIFTP. The aim of the current study was to investigate how molecular testing may add to cytologic assessment in the pre-operative differentiation of potential NIFTP/FVPTC and cPTC...
February 2, 2018: Endocrine Pathology
https://www.readbyqxmd.com/read/29396253/updated-molecular-testing-guideline-for-the%C3%A2-selection-of-lung-cancer-patients-for-treatment-with-targeted-tyrosine-kinase-inhibitors-guideline-from-the-college-of-american-pathologists-the%C3%A2-international-association-for-the-study-of-lung-cancer-and-the%C3%A2-association
#19
Neal I Lindeman, Philip T Cagle, Dara L Aisner, Maria E Arcila, Mary Beth Beasley, Eric Bernicker, Carol Colasacco, Sanja Dacic, Fred R Hirsch, Keith Kerr, David J Kwiatkowski, Marc Ladanyi, Jan A Nowak, Lynette Sholl, Robyn Temple-Smolkin, Benjamin Solomon, Lesley H Souter, Erik Thunnissen, Ming S Tsao, Christina B Ventura, Murry W Wynes, Yasushi Yatabe
CONTEXT: In 2013, an evidence-based guideline was published by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology to set standards for the molecular analysis of lung cancers to guide treatment decisions with targeted inhibitors. New evidence has prompted an evaluation of additional laboratory technologies, targetable genes, patient populations, and tumor types for testing. OBJECTIVE: To systematically review and update the 2013 guideline to affirm its validity; to assess the evidence of new genetic discoveries, technologies, and therapies; and to issue an evidence-based update...
January 23, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29389234/duration-of-anti-programmed-death-1-therapy-in-advanced-melanoma-how-much-of-a-good-thing-is-enough
#20
Nikhil I Khushalani
The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice...
February 1, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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