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braf performance

Michaël Duruisseaux, Anne McLeer-Florin, Martine Antoine, Sanaz Alavizadeh, Virginie Poulot, Roger Lacave, Nathalie Rabbe, Jacques Cadranel, Marie Wislez
Invasive mucinous lung adenocarcinoma (IMA) is a rare subtype of lung adenocarcinoma with no effective treatment option in advanced disease. KRAS mutations occur in 28-87% of the cases. NRG1 fusions were recently discovered in KRAS-negative IMA cases and otherwise negative for known driver oncogenes and could represent an attractive therapeutic target. Published data suggest that NRG1 fusions occur essentially in nonsmoking Asian women. From an IMA cohort of 25 French patients of known ethnicity, driver oncogenes EGFR, KRAS, BRAF, ERBB2 mutations, and ALK and ROS1 rearrangements presence were analyzed...
October 21, 2016: Cancer Medicine
Xiaoyan Kang, Nan Zhu, Xia Song
In recent years, targeted drugs occupy a pivotal position in the treatment of non-small cell lung cancer (NSCLC), drugs targeting epidermal growth factor receptor (EGFR) has been widely used in clinical practice, it is of milestone significance. V-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitors targeted at BRAF gene have obviously clinical efficacy to specific advantages populations with little side-effect, and be well tolerated. It is discovered recently that drug resistance also exists in BRAF inhibitors like other targeted drugs, the mechanism of drug resistance is being studied...
October 20, 2016: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
Zhen Huo, Tao Lu, Zhiyong Liang, Fan Ping, Jie Shen, Jingjing Lu, Wenbing Ma, Dachun Zhao, Dingrong Zhong
BACKGROUND: Isolated hypothalamic-pituitary Langerhans cell histiocytosis (HPLCH) is very rare. We investigated the clinicopathological characteristics, endocrine function changes, BRAF(V600E) mutations and treatments of isolated HPLCH. METHODS: We identified seven patients with isolated HPLCH by reviewing the clinical and pathological files in our hospital from 2007 to 2015. The clinical characteristics of the seven patients were retrospectively reviewed, especially the endocrine function changes...
October 19, 2016: Diagnostic Pathology
Lea Bottlaender, Marie Perier-Muzet, Véronique Lapras, Luc Thomas, Stephane Dalle
BRAF inhibitors (vemurafenib and dabrafenib) are nowadays commonly prescribed in BRAF-mutant metastatic melanoma and allow improvement of the overall survival and progression-free survival. They are, however, accompanied by many adverse effects which mainly affect the skin. We observed on computed tomographic scans in three different patients after 3 months of treatment, the onset of osteosclerotic lesions. In parallel, the computed tomographic scans showed a significant reduction in all of the previously identified metastases in all patients...
October 18, 2016: Melanoma Research
Seo Ki Kim, Inhye Park, Jung-Woo Woo, Jun Ho Lee, Jun-Ho Choe, Jung Han Kim, Jee Soo Kim
BACKGROUND: In the 2015 American Thyroid Association guidelines, either lobectomy or total thyroidectomy was recommended for thyroid cancer < 4 cm without extrathyroidal extension (ETE) and lymph node (LN) metastasis. Therefore, the purpose of this study was to investigate factors predictive of bilaterality in papillary thyroid carcinoma (PTC) patients with tumor size < 4 cm. METHODS: We retrospectively reviewed 3296 conventional PTC patients who underwent total thyroidectomy with central neck dissection and/or lateral neck dissection between January 2008 and June 2015...
October 17, 2016: Thyroid: Official Journal of the American Thyroid Association
Manojkumar Bupathi, Christina Wu
Colorectal cancer (CRC) is a heterogeneous disease for which the treatment backbone has primarily been cytotoxic chemotherapy. With better understanding of the involved molecular mechanisms, it is now known that there are a number of epigenetic and genetic events, which are involved in CRC pathogenesis. Specific biomarkers have been identified which can be used to determine the clinical outcome of patients beyond tumor staging and predict for treatment efficacy. Molecular testing is now routinely performed to select for patients that will benefit the most from targeted agents and immunotherapy...
October 2016: Journal of Gastrointestinal Oncology
Tyler Friedrich, Stephen Leong, Christopher H Lieu
Despite numerous breakthroughs in the understanding of colorectal cancer and identification of many oncogenic mutations, the treatment of metastatic colorectal cancer remains relatively more empiric than targeted. Testing for mutations in rat sarcoma virus (RAS) and rapidly growing fibrosarcoma (RAF) are routinely performed, though identification of these mutations currently offers little more than a negative predictive marker for response to EGFR inhibitor treatment and, in the case of RAF mutation, a poor prognostic indicator...
October 2016: Journal of Gastrointestinal Oncology
Asha Bonney, Michael Christie, Anne Beaty, Sebastian Lunke, Graham Taylor, Louis Irving, Daniel Steinfort
BACKGROUND: With the rapid development of genotype-guided therapies, molecular testing is becoming important in the management of lung cancer. Bronchoscopy is one of the most common investigations performed to diagnose and investigate lung cancer. Given the limited samples often produced by bronchoscopy, this study aims to evaluate the feasibility of performing molecular testing on cell blocks created from bronchoscope cytology brush tip washings (BTW). METHODS: Patients with positive brush cytology for tumour cells had cell blocks created from the BTW...
September 2016: Journal of Thoracic Disease
Wen-Chih Huang, Chien-Chen Tsai, Chih-Chieh Chan
BACKGROUND/PURPOSE: Cholangiocarcinoma (CC) is a fatal malignancy originating from biliary tracts and constitutes approximately 10-20% of hepatobiliary cancers. CC is characterized by a very poor prognosis. The definite molecular mechanisms leading to oncogenesis remain unclear. This study aimed to perform mutation analysis and copy number changes of KRAS and BRAF genes of CC in Taiwan. METHODS: A total of 182 cases of biliary tact CC were studied for point mutation and quantitative real-time polymerase chain reaction analysis of KRAS and BRAF genes...
October 10, 2016: Journal of the Formosan Medical Association, Taiwan Yi Zhi
Jan Franko, Qian Shi, Jeffrey P Meyers, Timothy S Maughan, Richard A Adams, Matthew T Seymour, Leonard Saltz, Cornelis J A Punt, Miriam Koopman, Christophe Tournigand, Niall C Tebbutt, Eduardo Diaz-Rubio, John Souglakos, Alfredo Falcone, Benoist Chibaudel, Volker Heinemann, Joseph Moen, Aimery De Gramont, Daniel J Sargent, Axel Grothey
BACKGROUND: Patients with peritoneal metastatic colorectal cancer have reduced overall survival compared with patients with metastatic colorectal cancer without peritoneal involvement. Here we further investigated the effect of the number and location of metastases in patients receiving first-line systemic chemotherapy. METHODS: We analysed individual patient data for previously untreated patients enrolled in 14 phase 3 randomised trials done between 1997 and 2008...
October 12, 2016: Lancet Oncology
Keisuke Goto, Daichi Maeda, Yukitsugu Kudo-Asabe, Takashi Hibiya, Akimasa Hayashi, Masashi Fukayama, Kenichi Ohashi, Akiteru Goto
AIMS: Hidradenoma papilliferum (HP) is a benign vulvar neoplasm that arises from anogenital mammary-like glands, and its morphology is similar to mammary intraductal papilloma. The aim of this study was to investigate oncogenic mutations involved in the tumourigenesis of HP. We focused specifically on PIK3CA and AKT1 mutations, which are both reported to be detected in 33% of mammary intraductal papillomas. METHODS: In total, seven HP cases were analysed. Clinicopathological analyses and immunohistochemistry for oestrogen receptor, p63, smooth muscle actin (SMA), p53 and β-catenin were performed...
October 14, 2016: Journal of Clinical Pathology
Hui Min Yang, Susan J Hsiao, David F Schaeffer, Chi Lai, Helen E Remotti, David Horst, Mahesh M Mansukhani, Basil A Horst
Anorectal melanoma is a rare disease that carries a poor prognosis. To date, limited genetic analyses confirmed KIT mutations as a recurrent genetic event similar to other mucosal melanomas, occurring in up to 30% of anorectal melanomas. Importantly, a subset of tumors harboring activating KIT mutations have been found to respond to c-Kit inhibitor-based therapy, with improved patient survival at advanced tumor stages. We performed comprehensive targeted exon sequencing analysis of 467 cancer-related genes in a larger series of 15 anorectal melanomas, focusing on potentially actionable variants based on gain- and loss-of-function mutations...
October 14, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Yanfang Zhang, Fang Sui, Jingjing Ma, Xiaojuan Ren, Haixia Guan, Qi Yang, Jing Shi, Meiju Ji, Bingyin Shi, Yue Sun, Peng Hou
CONTEXT: Although neuronal cell adhesion molecule (NrCAM) has been reported to be overexpressed in papillary thyroid cancer (PTCs), its role in this disease remains largely unclear. OBJECTIVES: The aim of this study was to explore the biological functions of NrCAM and its potential as a diagnostic marker and therapeutic target in thyroid cancer. EXPERIMENTAL DESIGN: Quantitative RT-PCR (qRT-PCR) was performed to evaluate mRNA expression of investigated genes...
October 12, 2016: Journal of Clinical Endocrinology and Metabolism
Rikhia Chakraborty, Thomas M Burke, Oliver A Hampton, Daniel J Zinn, Karen Phaik Har Lim, Harshal Abhyankar, Brooks Scull, Vijetha Kumar, Nipun Kakkar, David A Wheeler, Angshumoy Roy, Poulikos I Poulikakos, Miriam Merad, Kenneth L McClain, D Williams Parsons, Carl E Allen
Langerhans cell histiocytosis (LCH) is characterized by inflammatory lesions containing pathologic CD207+ dendritic cells with constitutively activated ERK. Mutually exclusive somatic mutations in MAPK pathway genes have been identified in approximately 75% of LCH cases, including recurrent BRAF-V600E and MAP2K1 mutations. In order to elucidate mechanisms of ERK activation in the remaining 25% of patients, we performed whole exome sequencing (WES, n=6), targeted BRAF sequencing (n=19) and/or whole transcriptome sequencing (RNA-seq, n=6) on 24 LCH patient samples lacking BRAF-V600E or MAP2K1 mutations...
October 11, 2016: Blood
Claudio Bellevicine, Roberta Sgariglia, Umberto Malapelle, Elena Vigliar, Mariantonia Nacchio, Giuseppe Ciancia, Markus Eszlinger, Ralf Paschke, Giancarlo Troncone
BACKGROUND: Fine-needle aspiration (FNA) cytology is accurate and cost-effective in the evaluation of thyroid nodules. Molecular techniques may contribute to risk stratification in indeterminate cases. Although next-generation sequencing (NGS) is a promising technique for the molecular testing of thyroid FNA specimens, thyroid-specific cancer gene panels are not commercially available. Conversely, the Ion AmpliSeq Cancer Hotspot Panel v2 (CHPv2), which includes the genes most frequently mutated in thyroid neoplasms, is commercially available and may represent an alternative to thyroid-specific panels...
September 26, 2016: Cancer
Caterina Rebecchini, Antoine Nobile, Simonetta Piana, Rossella Sarro, Bettina Bisig, Sykiotis P Gerasimos, Chiara Saglietti, Maurice Matter, Laura Marino, Massimo Bongiovanni
Various histological variants of papillary thyroid carcinoma have been reported, some with clinical implications, some with peculiar, sometimes misleading morphologies. One of these rare and poorly characterized variants is papillary thyroid carcinoma with nodular fasciitis-like stroma, of which fewer than 30 cases have been documented, mostly as isolated reports. It is a dual tumor comprising a malignant epithelial proliferation that harbors typical features of conventional papillary thyroid carcinoma, admixed with a prominent mesenchymal proliferation resembling nodular fasciitis or fibromatosis...
October 7, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Magdalena Bodnar, Paweł Burduk, Paulina Antosik, Małgorzata Jarmuz-Szymczak, Malgorzata Wierzbicka, Andrzej Marszalek
BACKGROUND: The role of BRAF mutations in cancerogenesis has been demonstrated in several solid tumor types. However, in salivary gland tumors, this genetic alteration is very uncommon, and its role still remains unclear. Thus, the aim of this study was to analyze BRAF V600E (VE1) protein expression with BRAF mutation status in codon 600, in malignant and benign salivary gland tumors. METHODS: Studies were performed on archived formalin-fixed paraffin-embedded tissue sections derived from 95 patients who underwent surgery for tumors of the salivary gland...
September 28, 2016: Journal of Oral Pathology & Medicine
Tanja Dolinsek, Lara Prosen, Maja Cemazar, Tjasa Potocnik, Gregor Sersa
BACKGROUND: The aim of the study was to explore the effectiveness of electrochemotherapy (ECT) during the treatment of melanoma patients with BRAF inhibitors. Its effectiveness was tested on BRAF mutated and non-mutated melanoma cells in vitro and in combination with BRAF inhibitors. MATERIALS AND METHODS: ECT with bleomycin was performed on two human melanoma cell lines, with (SK-MEL-28) or without (CHL-1) BRAF V600E mutation. Cell survival was determined using clonogenic assay to determine the effectiveness of ECT in melanoma cells of different mutation status...
September 1, 2016: Radiology and Oncology
Reiko Satow, Tomomi Nakamura, Chiaki Kato, Miku Endo, Mana Tamura, Ryosuke Batori, Shiori Tomura, Yumi Murayama, Kiyoko Fukami
Insights into mechanisms of drug resistance could extend the efficacy of cancer therapy. To probe mechanisms in melanoma, we performed siRNA screening of genes which mediate the development of neural crest cells from which melanocytes are derived. Here we report the identification of ZIC5 as a mediator of melanoma drug resistance. ZIC5 is a transcriptional suppressor of E-cadherin expressed highly in human melanoma. ZIC5 enhanced melanoma cell proliferation, survival, drug resistance, in vivo growth and metastasis...
September 26, 2016: Cancer Research
Douglas B Johnson, Garrett M Frampton, Matthew J Rioth, Erik Yusko, Yaomin Xu, Xingyi Guo, Riley C Ennis, David Fabrizio, Zachary R Chalmers, Joel Greenbowe, Siraj M Ali, Sohail Balasubramanian, James X Sun, Yuting He, Dennie T Frederick, Igor Puzanov, Justin M Balko, Justin M Cates, Jeffrey S Ross, Catherine Sanders, Harlan Robins, Yu Shyr, Vincent Miller, Philip J Stephens, Ryan J Sullivan, Jeffrey A Sosman, Christine M Lovly
Therapeutic antibodies blocking programmed death-1 and its ligand (PD-1/PD-L1) induce durable responses in a substantial fraction of melanoma patients. We sought to determine whether the number and/or type of mutations identified using a next generation sequencing (NGS) panel available in the clinic were correlated with response to anti-PD-1 in melanoma. Using archival melanoma samples from anti-PD-1/PD-L1-treated patients, we performed hybrid capture-based NGS on 236-315 genes and T-cell receptor (TCR) sequencing on initial and validation cohorts from two centers...
September 26, 2016: Cancer Immunology Research
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