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https://www.readbyqxmd.com/read/28938534/targeting-of-the-mapk-and-akt-pathways-in-conjunctival-melanoma-shows-potential-synergy
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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/28920557/automated-microspect-microct-image-analysis-of-the-mouse-thyroid-gland
#9
Peng Cheng, Brynn Hollingsworth, Daniel Scarberry, Daniel Hueng-Yuan Shen, Kimerly Powell, Sean C Smart, John Beech, Xiaochao Sheng, Lawrence S Kirschner, Chia-Hsiang Menq, Sissy M Jhiang
<b>Background:</b> The ability of thyroid follicular cells to take up iodine enables the use of radioactive iodine (RAI) for imaging and targeted killing of RAI-avid thyroid cancer following thyroidectomy. To facilitate identifying novel strategies to improve <sup>131</sup>I therapeutic efficacy for patients with RAI refractory disease, it is desired to optimize image acquisition and analysis for preclinical mouse models of thyroid cancer. <b>Methods:</b> A customized mouse cradle was designed and used for microSPECT/CT image acquisition at 1 hour (t1) and 24 hours (t24) post-injection of <sup>123</sup>I, which mainly reflect RAI influx/efflux equilibrium and RAI retention in the thyroid, respectively...
September 16, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28919012/braf-v600e-and-braf-inactivating-mutations-in-nsclc
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
https://www.readbyqxmd.com/read/28895526/molecular-testing-for-lynch-syndrome-in-people-with-colorectal-cancer-systematic-reviews-and-economic-evaluation
#18
Tristan Snowsill, Helen Coelho, Nicola Huxley, Tracey Jones-Hughes, Simon Briscoe, Ian M Frayling, Chris Hyde
BACKGROUND: Inherited mutations in deoxyribonucleic acid (DNA) mismatch repair (MMR) genes lead to an increased risk of colorectal cancer (CRC), gynaecological cancers and other cancers, known as Lynch syndrome (LS). Risk-reducing interventions can be offered to individuals with known LS-causing mutations. The mutations can be identified by comprehensive testing of the MMR genes, but this would be prohibitively expensive in the general population. Tumour-based tests - microsatellite instability (MSI) and MMR immunohistochemistry (IHC) - are used in CRC patients to identify individuals at high risk of LS for genetic testing...
September 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28891408/adjuvant-dabrafenib-plus-trametinib-in-stage-iii-braf-mutated-melanoma
#19
Georgina V Long, Axel Hauschild, Mario Santinami, Victoria Atkinson, Mario Mandalà, Vanna Chiarion-Sileni, James Larkin, Marta Nyakas, Caroline Dutriaux, Andrew Haydon, Caroline Robert, Laurent Mortier, Jacob Schachter, Dirk Schadendorf, Thierry Lesimple, Ruth Plummer, Ran Ji, Pingkuan Zhang, Bijoyesh Mookerjee, Jeff Legos, Richard Kefford, Reinhard Dummer, John M Kirkwood
Background Combination therapy with the BRAF inhibitor dabrafenib plus the MEK inhibitor trametinib improved survival in patients with advanced melanoma with BRAF V600 mutations. We sought to determine whether adjuvant dabrafenib plus trametinib would improve outcomes in patients with resected, stage III melanoma with BRAF V600 mutations. Methods In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 870 patients with completely resected, stage III melanoma with BRAF V600E or V600K mutations to receive oral dabrafenib at a dose of 150 mg twice daily plus trametinib at a dose of 2 mg once daily (combination therapy, 438 patients) or two matched placebo tablets (432 patients) for 12 months...
September 10, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28884045/braf-mutation-in-colorectal-carcinomas-with-signet-ring-cell-component
#20
Serap Yalcin, Onder Onguru
OBJECTIVE: : Signet ring cell carcinoma is a rare subtype of colorectal carcinoma (CRC) with an associated BRAFV600E mutation. We investigated frequencies of BRAF mutation in 28 CRCs containing variable signet ring cell component and their relation with clinicopathologic parameters. METHODS: : According to the presence of signet ring cell component, tumors were categorized into groups as follows: 0%-9%, 10%-24%, 25%-49%, and >50%. Genomic DNA was isolated and analyzed for BRAF V600E gene mutation by polymerase chain reaction-restriction fragment length polymorphism...
August 2017: Cancer Biology & Medicine
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