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https://www.readbyqxmd.com/read/28440781/immunohistochemical-detection-of-the-braf-v600e-mutation-in-papillary-thyroid-carcinoma-evaluation-against-real-time-polymerase-chain-reaction
#1
Miguel Paja Fano, Aitziber Ugalde Olano, Elena Fuertes Thomas, Amelia Oleaga Alday
INTRODUCTION: The BRAF V600E mutation is the most common genetic change in papillary thyroid carcinoma and is associated with a poorer clinical course. Usual methods for its study (DNA sequencing or molecular test based on PCR) are expensive and time-consuming. Recently, immunohistochemistry (IHC) for BRAF mutation has been introduced. OBJECTIVE: To compare the results of IHC and real time PCR (RT-PCR) in the detection of BRAF V600E mutation in papillary thyroid carcinoma...
February 2017: Endocrinol Diabetes Nutr
https://www.readbyqxmd.com/read/28438615/clinicopathological-immunohistochemical-and-mutational-analyses-of-pulmonary-enteric-adenocarcinoma-usefulness-of-satb2-and-%C3%AE-catenin-immunostaining-for-differentiation-from-metastatic-colorectal-carcinoma
#2
Jun Matsushima, Takuya Yazawa, Masaki Suzuki, Yoko Takahashi, Satoshi Ota, Takahiro Nakajima, Ichiro Yoshino, Tomoyuki Yokose, Toru Inoue, Kunimitsu Kawahara, Yukio Nakatani
Pulmonary enteric adenocarcinoma (PEA) is a rare variant of pulmonary adenocarcinoma; it is sometimes difficult to discriminate between PEA and metastatic colorectal carcinoma (MCRC) because of their morphological and immunohistochemical resemblance. Here, we conducted clinicopathological, immunohistochemical, and mutational analyses of PEA with special focus on its differentiation from MCRC. We comparatively analyzed eight surgically resected PEA tumors (7 patients) and 20 cases of MCRC. Patients were aged 43-77years (average age, 64...
April 21, 2017: Human Pathology
https://www.readbyqxmd.com/read/28438383/remitting-seronegative-symmetrical-synovitis-with-pitting-edema-rs3pe-syndrome-induced-by-nivolumab
#3
Marie-Léa Gauci, Barouyr Baroudjian, Pauline Laly, Isabelle Madelaine, Laetitia Da Meda, Laetitia Vercellino, Martine Bagot, Frédéric Lioté, Cécile Pages, Céleste Lebbé
INTRODUCTION: A new articular syndrome described as immunrelated side effect of immunotherapy: PD-1 inhibitors have revolutionized the treatment of advanced melanoma but are responsible for immune-related toxicity. We report a case of remitting seronegative symetrical synovitis with pitting edema (RS3PE) syndrome induced by nivolumab. CASE REPORT: A 80 year-old man with stage IV BRAF-wild type and NRAS exon 2-mutated melanoma was treated first line by nivolumab 3mg/kg every 2 weeks...
March 8, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/28438258/intraneural-glomus-tumor-of-uncertain-malignant-potential-and-with-braf-mutation-in-the-median-nerve-an-unusual-case
#4
Lars B Dahlin, Peter Scherman, Jack Besjakov, Eva Lindberg, David A Solomon, Andrew E Horvai, Arie Perry
A glomus tumor of uncertain malignant potential is defined as a glomus tumor with some, but not all, criteria for malignancy and without a known metastasis. Here, we present a rare example presenting in the median nerve in a 40-year-old woman with a long history of severely impaired left median nerve function. A large panel of immunohistochemical stains excluded other diagnoses, and the designation of a "uncertain malignant potential" was based on the high proliferative activity, the tumor size and location, and the lack of WHO malignancy criteria such as marked nuclear atypia, necrosis, or atypical mitoses...
April 25, 2017: Clinical Neuropathology
https://www.readbyqxmd.com/read/28435677/control-of-immune-cell-entry-through-the-tumour-vasculature-a-missing-link-in-optimising-melanoma-immunotherapy
#5
REVIEW
Lih Yin Tan, Carmela Martini, Zvi G Fridlender, Claudine S Bonder, Michael P Brown, Lisa M Ebert
Metastatic melanoma remains a fatal disease to many worldwide, even after the breakthrough introduction of targeted therapies such as BRAF inhibitors and immune checkpoint blockade therapies such as CTLA-4 and PD-1 inhibitors. With advances in our understanding of this disease, as well as the increasing data gathered from patient studies, the significance of the host immune response to cancer progression and response to treatment is becoming clear. More specifically, the presence of intratumoral CD8(+) cytotoxic T-cells correlates with better prognosis whereas the accumulation of monocytes/macrophages and neutrophils in the tumour is often associated with worse prognosis...
March 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28435463/design-and-development-of-fluorescent-vemurafenib-analogs-for-in-vivo-imaging
#6
Hannes Mikula, Shawn Stapleton, Rainer H Kohler, Claudio Vinegoni, Ralph Weissleder
Herein we describe fluorescent derivatives of vemurafenib to probe therapeutic BRAF inhibition in live cells and in vivo. The compounds were evaluated and compared by determining target binding, inhibition of mutant BRAF melanoma cell lines and live cell imaging. We show that vemurafenib-BODIPY is a superior imaging drug to visualize the targets of vemurafenib in live cells and in vivo in non-resistant and resistant melanoma tumors.
2017: Theranostics
https://www.readbyqxmd.com/read/28435391/programmed-cell-death-1-checkpoint-inhibitors-in-the-treatment-of-patients-with-advanced-melanoma
#7
REVIEW
Jacek Mackiewicz, Andrzej Mackiewicz
The treatment landscape of advanced melanoma has changed significantly following the discovery and marketing authorisation of immune checkpoints inhibitors. Ipilimumab (anti-CTLA-4) was the first one to be approved, and it. demonstrated long-term survival in about 20% of patients. Subsequently, anti-programmed cell death-1 (a-PD-1) antibodies (pembrolizuamb, nivolumab), inhibitors of PD-1/programmed cell death-1 ligand (PD1-L) synapse, showed higher clinical efficacy with lower toxicity comparing to ipilimumab...
2017: Contemporary Oncology Współczesna Onkologia
https://www.readbyqxmd.com/read/28433543/phenformin-inhibits-myeloid-derived-suppressor-cells-and-enhances-the-anti-tumor-activity-of-pd-1-blockade-in-melanoma
#8
Sun Hye Kim, Man Li, Sebastian Trousil, Yaqing Zhang, Marina Pasca di Magliano, Kenneth D Swanson, Bin Zheng
Biguanides, such as the diabetes therapeutics metformin and phenformin, have demonstrated antitumor activity both in vitro and in vivo. However, their potential effects on the tumor microenvironment are largely unknown. Here we report that phenformin selectively inhibits granulocytic myeloid-derived suppressor cells (G-MDSCs) in spleens of tumor bearing mice and ex vivo. Phenformin induces production of reactive oxygen species in G-MDSC, whereas the antioxidant N-acetylcysteine attenuates the inhibitory effects of phenformin...
April 19, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28433252/nrasq61r-immunohistochemistry-detects-both-nrasq61r-and-krasq61r-mutations-in-colorectal-cancer
#9
Jie-Yang Jhuang, Chang-Tsu Yuan, Yu-Lin Lin, Mei-Ling Cheng, Jau-Yu Liau, Jia-Huei Tsai
The NRASQ61R monoclonal antibody (clone sp174) is a mutation-specific antibody that is increasingly being used to detect the NRAS(Q61R) mutation in melanomas. This antibody has been reported to be highly correlated with the NRAS(Q61R) mutation status in melanomas and follicular neoplasms of the thyroid gland. However, its utility in colorectal carcinoma (CRC) has remained largely unknown. In this study, we assessed the sensitivity, specificity, and diagnostic utility of NRASQ61R immunohistochemistry in a cohort consisting of tissue sections of 113 CRCs, which were molecularly profiled for the KRAS, NRAS, and BRAF mutations...
April 19, 2017: Pathology
https://www.readbyqxmd.com/read/28433076/identification-of-ntrk3-fusions-in-childhood-melanocytic-neoplasms
#10
Lu Wang, Klaus J Busam, Ryma Benayed, Robert Cimera, Jiajing Wang, Ryan Denley, Mamta Rao, Ruth Aryeequaye, Kerry Mullaney, Long Cao, Marc Ladanyi, Meera Hameed
Spitzoid neoplasms are a distinct group of melanocytic tumors. Genetically, they lack mutations in common melanoma-associated oncogenes. Recent studies have shown that spitzoid tumors may contain a variety of kinase fusions, including ROS1, NTRK1, ALK, BRAF, and RET fusions. We report herein the discovery of recurrent NTRK3 gene rearrangements in childhood melanocytic neoplasms with spitzoid and/or atypical features, based on genome-wide copy number analysis by single-nucleotide polymorphism array, which showed intragenic copy number changes in NTRK3...
May 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28431353/discovery-of-potential-anticancer-multi-targeted-ligustrazine-based-cyclohexanone-and-oxime-analogs-overcoming-the-cancer-multidrug-resistance
#11
Gao-Feng Zha, Hua-Li Qin, Bahaa G M Youssif, Muhammad Wahab Amjad, Maria Abdul Ghafoor Raja, Ahmed H Abdelazeem, Syed Nasir Abbas Bukhari
The drug research and development nowadays is focusing on multi-target drugs. In the treatment of cancer, therapies using drugs inhibiting one numerous targets signify a novel viewpoint. In comparison with traditional therapy, multi-targeted drugs directly aim cell subpopulations which are involved in progression of tumor. The current study comprises the synthesis of 34 novel ligustrazine-containing α, β-unsaturated carbonyl-based compounds and oximes. The growth of 5 various cancer cell types was strongly inhibited by ligustrazine-containing oximes as revealed by biological evaluation...
April 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28430287/dysembryoplastic-neuroepithelial-tumour-insight-into-the-pathology-and-pathogenesis
#12
Iwona Sontowska, Ewa Matyja, Jacek Malejczyk, Wieslawa Grajkowska
<i>Dysembryoplastic neuroepithelial tumour (DNT) is categorized as a benign glioneuronal neoplasm affecting children and young adults with chronic epileptic seizures. It is characterized by predominant intracortical localization and nodular architecture. Dysembryoplastic neuroepithelial tumour usually demonstrates a distinctive morphological pattern with a specific glioneuronal element but occasionally, its morphological picture is heterogeneous and unspecific. Thus, considering the morphology of DNT, three different histopathological subtypes are distinguished: simple, complex, and non-specific and diffuse...
2017: Folia Neuropathologica
https://www.readbyqxmd.com/read/28429715/mapping-clinicopathological-entities-within-colorectal-mucinous-adenocarcinomas-a-hierarchical-clustering-approach
#13
Charly Liddell, Laure Droy-Dupré, Sylvie Métairie, Fabrice Airaud, Christelle Volteau, Stéphane Bezieau, Christian L Laboisse, Jean-François Mosnier
The aim of this study was to interrogate the heterogeneity of colorectal mucinous adenocarcinomas. This study is based on hierarchical clustering approach combining clinicopathological and molecular patterns known to be relevant to oncogenesis and therapeutic management of patients with colorectal carcinoma, ie, microsatellite instability, O6-methylguanine-DNA methyltransferase (MGMT) status, KRAS, and BRAF mutations and wnt signaling pathway activation. Comparison of the study group of 60 mucinous adenocarcinomas defined according to World Health Organization classification with control group of 136 colorectal adenocarcinomas successively removed shows higher frequency of BRAF and KRAS mutations and microsatellite instability-high status and lower frequency of wnt signaling pathway activation in mucinous adenocarcinomas...
April 21, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28429064/simple-and-cost-effective-liquid-chromatography-mass-spectrometry-method-to-measure-dabrafenib-quantitatively-and-six-metabolites-semi-quantitatively-in-human-plasma
#14
Svante Vikingsson, Jan-Olof Dahlberg, Johan Hansson, Veronica Höiom, Henrik Gréen
Dabrafenib is an inhibitor of BRAF V600E used for treating metastatic melanoma but a majority of patients experience adverse effects. Methods to measure the levels of dabrafenib and major metabolites during treatment are needed to allow development of individualized dosing strategies to reduce the burden of such adverse events. In this study, an LC-MS/MS method capable of measuring dabrafenib quantitatively and six metabolites semi-quantitatively is presented. The method is fully validated with regard to dabrafenib in human plasma in the range 5-5000 ng/mL...
April 20, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28427252/long-non-coding-rna-braf-activated-non-coding-rna-as-a-potential-novel-molecular-biomarker-for-metastasis-and-prognosis-in-various-cancers
#15
Anbang He, Song Feng, Zhicong Chen, Yuhan Liu, Hongbing Mei
No abstract text is available yet for this article.
June 2017: Minerva Medica
https://www.readbyqxmd.com/read/28427158/the-varied-distribution-and-impact-of-ras-codon-and-other-key-dna-alterations-across-the-translocation-cyclin-d-subgroups-in-multiple-myeloma
#16
Caleb K Stein, Charlotte Pawlyn, Shweta Chavan, Leo Rasche, Niels Weinhold, Adam Corken, Amy Buros, Pieter Sonneveld, Graham H Jackson, Ola Landgren, Tariq Mughal, Jie He, Bart Barlogie, P Leif Bergsagel, Faith E Davies, Brian A Walker, Gareth J Morgan
We examined a set of 805 cases that underwent DNA sequencing using the FoundationOne Heme (F1H) targeted sequencing panel and gene expression profiling. Known and likely variant calls from the mutational data were analyzed for significant associations with gene expression defined translocation cyclin D (TC) molecular subgroups. The spectrum of KRAS, NRAS, and BRAF codon mutations varied across subgroups with NRAS mutations at Q61 codon being common in hyperdiploid (HRD) and t(11;14) myeloma while being rare in MMSET and MAF...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426905/acantholytic-dyskeratotic-acanthoma-a-possible-skin-adverse-event-of-vemurafenib-treatment
#17
Takaya Komori, Atsushi Otsuka, Yo Kaku, Tetsuya Honda, Kenji Kabashima
Acantholytic dyskeratotic acanthoma (ADA) is a solitary small papule that is pathologically characterized by dyskeratosis with acantholytic acanthosis (1). Vemulafenib is a specific inhibitor of BRAF protein kinase with V600E mutation and is administered to treat metastatic melanoma. Various skin adverse events associated with vemurafenib, including acantholysis and flare up of Darier's disease, have been reported (2, 3). Here we report a case of ADA that developed during vemulafenib treatment for metastatic melanoma...
April 20, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28425764/braf-v600e-mutant-papillary-craniopharyngioma-dramatically-responds-to-combination-braf-and-mek-inhibitors
#18
Ashley Roque, Yazmin Odia
We present a patient with BRAF-V600E mutant papillary craniopharyngioma successfully treated with combination BRAF (dabrafenib 150 mg twice daily) and MEK (trametinib 2 mg daily) inhibitors after her unresectable tumor proved refractory to radiation. Serial brain MRIs and PET revealed marked tumor reduction with gradual neurological improvement and permanent panhypopituitarism.
April 2017: CNS Oncology
https://www.readbyqxmd.com/read/28424871/final-analysis-of-the-randomised-peak-trial-overall-survival-and-tumour-responses-during-first-line-treatment-with-mfolfox6-plus-either-panitumumab-or-bevacizumab-in-patients-with-metastatic-colorectal-carcinoma
#19
Fernando Rivera, Meinolf Karthaus, J Randolph Hecht, Isabel Sevilla, Frédéric Forget, Gianpiero Fasola, Jean-Luc Canon, Xuesong Guan, Gaston Demonty, Lee S Schwartzberg
PURPOSE: To report planned final overall (OS) and progression-free survival (PFS) analyses from the phase II PEAK trial (NCT00819780). METHODS: Patients with previously untreated, KRAS exon 2 wild-type (WT) metastatic colorectal cancer (mCRC) were randomised to mFOLFOX6 plus panitumumab or bevacizumab. The primary endpoint was PFS; secondary endpoints included OS, objective response rate, duration of response (DoR), time to response, resection and safety. Treatment effect by tumour RAS status was a prespecified objective...
April 19, 2017: International Journal of Colorectal Disease
https://www.readbyqxmd.com/read/28424412/fbxw7-missense-mutation-a-novel-negative-prognostic-factor-in-metastatic-colorectal-adenocarcinoma
#20
Krittiya Korphaisarn, Van Karlyle Morris, Michael J Overman, David R Fogelman, Bryan K Kee, Kanwal Pratap Singh Raghav, Shanequa Manuel, Imad Shureiqi, Robert A Wolff, Cathy Eng, David Menter, Stanley R Hamilton, Scott Kopetz, Arvind Dasari
BACKGROUND: FBXW7 functions as a ubiquitin ligase tagging multiple dominant oncogenic proteins and commonly mutates in colorectal cancer. Data suggest missense mutations lead to greater loss of FBXW7 function than other gene aberrations do. However, the clinicopathologic factors and outcomes associated with FBXW7 missense mutations in metastatic colorectal cancer (mCRC) have not been described. METHODS: Data were obtained from mCRC patients whose tumors were evaluated by next-generation sequencing for hotspot mutations at The University of Texas MD Anderson Cancer Center...
April 5, 2017: Oncotarget
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