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https://www.readbyqxmd.com/read/28943919/braf-v600e-mutation-is-not-associated-with-central-lymph-node-metastasis-in-all-patients-with-papillary-thyroid-cancer-different-histological-subtypes-and-preoperative-lymph-node-status-should-be-taken-into-account
#1
Si-Yang Dong, Rui-Chao Zeng, Lang-Ping Jin, Fan Yang, Xiang-Jian Zhang, Zhi-Han Yao, Xiao-Hua Zhang, Ou-Chen Wang
The association between central lymph node metastasis (LNM) and risk factors, including the presence of the BRAF mutation, BRAF(V600E), in patients with papillary thyroid cancer (PTC) requires further investigation. A potent risk factor that can indicate LNM in different histological subtypes of PTC and in different preoperative central lymph node statuses also requires further research. A total of 287 patients with PTC who accepted thyroidectomy were included in the present study. Clinicopathological data of these patients were reviewed to examine the risk factors for central LNM through univariate and multivariate analyses...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28943451/tubulin-binding-anticancer-polysulfides-induce-cell-death-via-mitotic-arrest-and-autophagic-interference-in-colorectal-cancer
#2
Esma Yagdi Efe, Aloran Mazumder, Jin-Young Lee, Anthoula Gaigneaux, Flavia Radogna, Muhammad Jawad Nasim, Christo Christov, Claus Jacob, Kyu-Won Kim, Mario Dicato, Patrick Chaimbault, Claudia Cerella, Marc Diederich
Polysulfanes show chemopreventive effects against gastrointestinal tumors. We identified diallyl tetrasulfide and its derivative, dibenzyl tetrasulfide (DBTTS), to be mitotic inhibitors and apoptosis inducers. Here, we translate their application in colorectal cancer (CRC). MALDI-TOF-MS analysis identified both compounds as reversible tubulin binders, validated by in cellulo α-tubulin degradation. BRAF(V600E)-mutated HT-29 cells were resistant to DBTTS, as evidenced by mitotic arrest for 48 h prior to apoptosis induction compared to KRAS(G12V)-mutated SW480/620 cells, which committed to death earlier...
September 21, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28940307/frequent-braf-mutations-suggest-a-novel-oncogenic-driver-in-colonic-neuroendocrine-carcinoma
#3
Kamran Idrees, Chandrasekhar Padmanabhan, Eric Liu, Yan Guo, Raul S Gonzalez, Jordan Berlin, Kimberly B Dahlman, R Daniel Beauchamp, Chanjuan Shi
BACKGROUND AND OBJECTIVES: The World Health Organization (WHO) 2010 has classified GI neuroendocrine neoplasms into neuroendocrine tumor (NET) and high-grade neuroendocrine carcinoma (NEC). The genetic underpinnings of NEC are poorly understood. The aim of the study was to perform genomic profiling of NEC to better characterize this aggressive disease. METHODS: We identified nine patients with colonic NEC between January 1, 2005 and June 30, 2013. Whole exome sequencing (WES) was performed on tumor DNA from two patients with ≥80% tumor cellularity and matched normal tissue available...
September 20, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28939657/first-line-dabrafenib-plus-trametinib-has-activity-in-braf-v600e-nsclc
#4
(no author information available yet)
Dabrafenib plus trametinib achieves responses in 64% of patients with metastatic BRAF(V600E) NSCLC.
September 22, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28938534/targeting-of-the-mapk-and-akt-pathways-in-conjunctival-melanoma-shows-potential-synergy
#5
Jinfeng Cao, Renier C Heijkants, Aart G Jochemsen, Mehmet Dogrusöz, Mark J de Lange, Pieter A van der Velden, Sjoerd H van der Burg, Martine J Jager, Robert M Verdijk
PURPOSE: Conjunctival melanoma (CM) is a rare but lethal form of cancer. Similar to cutaneous melanoma, CM frequently carries activating mutations in BRAF and NRAS. We studied whether CM as well as conjunctival benign and premalignant melanocytic lesions express targets in the mitogen-activated protein kinase (MAPK) and AKT pathways, and whether specific inhibitors can suppress CM growth in vitro. METHODS: 131 conjunctival lesions obtained from 129 patients were collected...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28937091/obstruction-of-braf-v600e-transcription-by-complementary-pna-oligomers-as-a-means-to-inhibit-braf-mutant-melanoma-growth
#6
J H Rothman, O Surriga, E de Stanchina, S D Vasudeva, G K Schwartz
Peptide nucleic acid (PNA) oligomers are DNA mimics, which are capable of binding gene sequences 1000-fold more avidly than complementary native DNA by strand invasion and effectively obstruct transcription. Irreversibly obstructing the transcription or replication of a gene sequence, such as BRAF(V600E), offers a potential route to specifically target the cancer cell itself. We have employed PNA oligomers to target BRAF(V600E) in a sequence-specific complementary manner. These PNAs have been modified by appending configurationally stabilizing cationic peptides in order to improve their cellular delivery and target avidity...
September 22, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28936920/rescue-of-cell-cycle-progression-in-braf-v600e-inhibitor-resistant-human-melanoma-by-a-chromatin-modifier
#7
Antoni X Toress-Collado, Ramin Nazarian, Ali R Jazirehi
The BRAF(V600E)-specific inhibitor vemurafenib blocks mitogen-activated protein kinase pathway and induces cell cycle arrest at G0/G1 phase leading to apoptosis of melanomas. To gain an understanding of the dynamics of cell cycle regulation during vemurafenib therapy, we analyzed several vemurafenib-resistant human melanoma sublines derived from BRAF(V600E) harboring vemurafenib-sensitive parental lines. Vemurafenib provoked G0/G1 phase arrest in parental but not in vemurafenib-resistant sublines. We hypothesized that refractoriness of vemurafenib-resistant sublines to vemurafenib-mediated cell cycle inhibition can be partially rescued by the chromatin modifier suberoylanilide hydroxamic acid...
September 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28931215/berberine-could-inhibit-thyroid-carcinoma-cells-by-inducing-mitochondrial-apoptosis-g0-g1-cell-cycle-arrest-and-suppressing-migration-via-pi3k-akt-and-mapk-signaling-pathways
#8
Liang Li, Xingchun Wang, Rampersad Sharvan, Jingyang Gao, Shen Qu
Berberine, an important natural isoquinoline alkaloid from traditional Chinese medicine, is reported to exhibit multiple pharmacological properties, including anti-microbial, anti-diabetes, anti-obesity, anti-inflammatory and anti-carcinogenic activities. Although studies have shown that a wide range of carcinoma cells could be inhibited by berberine, few studies involved thyroid carcinoma. We therefore examined the effect of berberine on papillary thyroid carcinoma (PTC, the most common subtype) and anaplastic thyroid carcinoma (ATC, the most malignant and aggressive subtype)...
September 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28928829/braf-v600e-mutation-contributes-papillary-thyroid-carcinoma-and-hashimoto-thyroiditis-with-resistance-to-thyroid-hormone-a-case-report-and-literature-review
#9
Wanjia Xing, Xiaohong Liu, Qingqing He, Zongjing Zhang, Zhaoshun Jiang
Resistance to thyroid hormone (RTH) is a rare autosomal hereditary disorder characterized by increased serum thyroid hormone (TH) levels with unsuppressed or increased thyrotropin concentration. It remains unknown whether the coexistence of RTH with papillary thyroid carcinoma (PTC) and Hashimoto thyroiditis (HT) is incidental or whether it possesses a genetic or pathophysiological association. In the present study, a case of RTH with PTC and HT in an 11-year-old Chinese patient was examined and the clinical presentation of RTH with PTC was discussed...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28928360/tumor-associated-b-cells-induce-tumor-heterogeneity-and-therapy-resistance
#10
Rajasekharan Somasundaram, Gao Zhang, Mizuho Fukunaga-Kalabis, Michela Perego, Clemens Krepler, Xiaowei Xu, Christine Wagner, Denitsa Hristova, Jie Zhang, Tian Tian, Zhi Wei, Qin Liu, Kanika Garg, Johannes Griss, Rufus Hards, Margarita Maurer, Christine Hafner, Marius Mayerhöfer, Georgios Karanikas, Ahmad Jalili, Verena Bauer-Pohl, Felix Weihsengruber, Klemens Rappersberger, Josef Koller, Roland Lang, Courtney Hudgens, Guo Chen, Michael Tetzlaff, Lawrence Wu, Dennie Tompers Frederick, Richard A Scolyer, Georgina V Long, Manashree Damle, Courtney Ellingsworth, Leon Grinman, Harry Choi, Brian J Gavin, Margaret Dunagin, Arjun Raj, Nathalie Scholler, Laura Gross, Marilda Beqiri, Keiryn Bennett, Ian Watson, Helmut Schaider, Michael A Davies, Jennifer Wargo, Brian J Czerniecki, Lynn Schuchter, Dorothee Herlyn, Keith Flaherty, Meenhard Herlyn, Stephan N Wagner
In melanoma, therapies with inhibitors to oncogenic BRAF(V600E) are highly effective but responses are often short-lived due to the emergence of drug-resistant tumor subpopulations. We describe here a mechanism of acquired drug resistance through the tumor microenvironment, which is mediated by human tumor-associated B cells. Human melanoma cells constitutively produce the growth factor FGF-2, which activates tumor-infiltrating B cells to produce the growth factor IGF-1. B-cell-derived IGF-1 is critical for resistance of melanomas to BRAF and MEK inhibitors due to emergence of heterogeneous subpopulations and activation of FGFR-3...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28927118/mutations-in-braf-codons-594-and-596-predict-good-prognosis-in-melanoma
#11
Xiaowen Wu, Junya Yan, Jie Dai, Meng Ma, Huan Tang, Jiayi Yu, Tianxiao Xu, Huan Yu, Lu Si, Zhihong Chi, Xinan Sheng, Chuanliang Cui, Yan Kong, Jun Guo
B-Raf proto-oncogene serine/threonine kinase (BRAF) V600E is the most common kinase-activating mutation and is associated with poor prognosis in melanoma. However, the clinical significance of kinase-impairing mutations remains unclear. The present study aimed to analyze kinase-impairing mutations in BRAF codons 594 and 596 in non-Caucasian patients with melanoma and to investigate their possible clinical significance. To detect hotspot mutations, exon 15 of the BRAF gene was amplified using polymerase chain reaction in samples from 1,554 patients with melanoma...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28921583/associations-of-alcohol-intake-smoking-physical-activity-and-obesity-with-survival-following-colorectal-cancer-diagnosis-by-stage-anatomic-site-and-tumor-molecular-subtype
#12
Harindra Jayasekara, Dallas R English, Andrew Haydon, Allison M Hodge, Brigid M Lynch, Christophe Rosty, Elizabeth J Williamson, Mark Clendenning, Melissa C Southey, Mark A Jenkins, Robin Room, John L Hopper, Roger L Milne, Daniel D Buchanan, Graham G Giles, Robert J MacInnis
The influence of lifestyle factors on survival following a diagnosis of colorectal cancer (CRC) is not well established. We examined associations between lifestyle factors measured before diagnosis and CRC survival. The Melbourne Collaborative Cohort Study collected data on alcohol intake, cigarette smoking and physical activity, and body measurements at baseline (1990-94) and wave 2 (2003-07). We included participants diagnosed to 31 August 2015 with incident stage I-III CRC within 10-years post exposure assessment...
September 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28919012/braf-v600e-and-braf-inactivating-mutations-in-nsclc
#13
Rafael Rosell, Niki Karachaliou
No abstract text is available yet for this article.
September 8, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28919011/dabrafenib-plus-trametinib-in-patients-with-previously-untreated-braf-v600e-mutant-metastatic-non-small-cell-lung-cancer-an-open-label-phase-2-trial
#14
David Planchard, Egbert F Smit, Harry J M Groen, Julien Mazieres, Benjamin Besse, Åslaug Helland, Vanessa Giannone, Anthony M D'Amelio, Pingkuan Zhang, Bijoyesh Mookerjee, Bruce E Johnson
BACKGROUND: BRAF(V600E) mutation occurs in 1-2% of lung adenocarcinomas and acts as an oncogenic driver. Dabrafenib, alone or combined with trametinib, has shown substantial antitumour activity in patients with previously treated BRAF(V600E)-mutant metastatic non-small-cell lung cancer (NSCLC). We aimed to assess the activity and safety of dabrafenib plus trametinib treatment in previously untreated patients with BRAF(V600E)-mutant metastatic NSCLC. METHODS: In this phase 2, sequentially enrolled, multicohort, multicentre, non-randomised, open-label study, adults (≥18 years of age) with previously untreated metastatic BRAF(V600E)-mutant NSCLC were enrolled into cohort C from 19 centres in eight countries within North America, Europe, and Asia...
September 8, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28918044/targeted-disruption-of-v600e-mutant-braf-gene-by-crispr-cpf1
#15
Meijia Yang, Heng Wei, Yuelong Wang, Jiaojiao Deng, Yani Tang, Liangxue Zhou, Gang Guo, Aiping Tong
BRAF-V600E (1799T > A) is one of the most frequently reported driver mutations in multiple types of cancers, and patients with such mutations could benefit from selectively inactivating the mutant allele. Near this mutation site, there are two TTTN and one NGG protospacer-adjacent motifs (PAMs) for Cpf1 and Cas9 CRISPR nucleases, respectively. The 1799T > A substitution also leads to the occurrence of a novel NGNG PAM for the EQR variant of Cas9. We examined the editing efficacy and selectivity of Cpf1, Cas9, and EQR variant to this mutation site...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28916540/massive-reshaping-of-genome-nuclear-lamina-interactions-during-oncogene-induced-senescence
#16
Christelle Lenain, Carolyn A de Graaf, Ludo Pagie, Nils L Visser, Marcel de Haas, Sandra S de Vries, Daniel Peric-Hupkes, Bas van Steensel, Daniel S Peeper
Cellular senescence is a mechanism that virtually irreversibly suppresses the proliferative capacity of cells in response to various stress signals. This includes the expression of activated oncogenes, which causes Oncogene-Induced Senescence (OIS). A body of evidence points to the involvement in OIS of chromatin reorganization, including the formation of senescence-associated heterochromatic foci (SAHF). The nuclear lamina (NL) is an important contributor to genome organization and has been implicated in cellular senescence and organismal aging...
September 15, 2017: Genome Research
https://www.readbyqxmd.com/read/28915656/patterns-and-clinical-significance-of-cervical-lymph-node-metastasis-in-papillary-thyroid-cancer-patients-with-delphian-lymph-node-metastasis
#17
Guibin Zheng, Hua Zhang, Shaolong Hao, Chengxin Liu, Jie Xu, Jinyao Ning, Guochang Wu, Lixin Jiang, Guojun Li, Haitao Zheng, Xicheng Song
Although the roles of Delphian lymph node (DLN) metastasis in papillary thyroid cancer (PTC) have been previously reported, there are still limited data on correlations of clinicopathologic factors with DLN metastasis and unique patterns of cervical node subsite metastasis in PTC patients with DLN metastasis. We retrospectively reviewed medical records of 320 patients with a diagnosis of PTC who underwent primary surgery. Clinicopathologic features and DLN metastasis patterns were analyzed for predicting extensive cervical lymph node metastasis...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28910894/-diagnostic-values-of-braf-v600e-mutation-analysis-and-bethesda-system-for-reporting-thyroid-cytopathology-in-thyroid-nodules-with-tirads-4-and-5
#18
Y Han, B W Zhao, S Y Li, J G Lyu, J D Shou, H S Xu, H Y Lou, L L Xu, L Gao, S X Xu, J Zhu
Objective: To evaluate the diagnostic efficacies of BRAF(V600E) testing and Bethesda system for reporting thyroid cytopathology (BSRTC) in thyroid nodules with thyroid imaging reporting and data system (TIRADS) category 4 and 5. Methods: A total of 187 thyroid nodules in 187 patients underwent the examinations of ultrasound-guided fine needle aspiration cytology (FNAC) and BRAF(V600E) mutation were analyzed retrospectively. Receive operating characteristic (ROC) curve was used to investigate the diagnostic values of both methods and the clinical application of BRAF(V600E) combined with BSRTC was evaluated...
September 7, 2017: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
https://www.readbyqxmd.com/read/28904173/impact-of-metastasectomy-in-the-multimodality-approach-for-braf-v600e-metastatic-colorectal-cancer-the-mayo-clinic-experience
#19
Benny Johnson, Zhaohui Jin, Mark J Truty, Rory L Smoot, David M Nagorney, Michael L Kendrick, Benjamin R Kipp, Axel Grothey
BACKGROUND: BRAF V600E mutations are present in 8%-10% of patients with metastatic colorectal cancer (mCRC) and portend poor prognosis. This study investigated the impact of metastasectomy for patients with BRAF V600E mCRC. Subjects, Materials, and Methods . Using prospective clinical and molecular data, patients with BRAF V600E mCRC were analyzed for clinical characteristics and survival. Statistical analyses utilized the Kaplan-Meier method, log-rank test, and Cox proportional hazard models...
September 13, 2017: Oncologist
https://www.readbyqxmd.com/read/28903326/distinct-clinicopathological-features-in-metanephric-adenoma-harboring-braf-mutation
#20
Anna Caliò, John N Eble, Ondrej Hes, Guido Martignoni, Saul E Harari, Sean R Williamson, Matteo Brunelli, Adeboye O Osunkoya, Lisha Wang, Eva Comperat, Antonio Lopez-Beltran, Mingsheng Wang, Shaobo Zhang, Kendra L Curless, Kristin M Post, Hsim-Yee Chang, Claudio Luchini, Lee Ann Baldrige, Gregory T MacLennan, Rodolfo Montironi, David J Grignon, Liang Cheng
BRAF mutation recently has been reported in metanephric adenoma. We sought to determine the clinical and morphologic features of BRAF-mutated metanephric adenoma and to correlate BRAF mutation with BRAF V600E immunohistochemical staining results. A series of 48 metanephric adenomas and 15 epithelial-predominant nephroblastomas were analyzed for the occurrence of BRAF mutation (BRAF V600E/V600E complex, BRAF V600D, BRAF V600K and BRAF V600R) using the BRAF RGQ PCR kit (Qiagen). Immunohistochemistry was performed using monoclonal mouse antibodies against p16(INK4) and VE1 (Spring Bioscience), recognizing the BRAF V600E mutant protein...
August 15, 2017: Oncotarget
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