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https://www.readbyqxmd.com/read/28077340/clinicopathological-characteristics-of-papillary-thyroid-cancer-in-children-with-emphasis-on-the-pubertal-status-and-association-with-brafv600e-mutation
#1
Şükran Poyrazoğlu, Rüveyde Bundak, Firdevs Baş, Gülçin Yeğen, Yasemin Şanlı, Feyza Darendeliler
OBJECTIVE: Papillary thyroid cancer (PTC) could behave differently in prepubertal than in pubertal children and between children and adults. BRAF gene activating mutations may associate with PTC by creating aberrant activation. We aimed to evaluate clinicopathological characteristics of PTC patients with emphasis on the pubertal status and investigate the association of BRAFV600E mutation with disease characteristics. METHODS: Medical records of 75 patients with PTC were reviewed retrospectively...
January 12, 2017: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/28075446/nf%C3%A2-%C3%AE%C2%BAb-inhibition-is-associated-with-opn-mmp%C3%A2-9-downregulation-in-cutaneous-melanoma
#2
Claudio Guarneri, Valentina Bevelacqua, Jerry Polesel, Luca Falzone, Patrizia S Cannavò, Demetrios A Spandidos, Grazia Malaponte, Massimo Libra
The development of cutaneous melanoma is influenced by genetic factors, including BRAF mutations and environmental factors, such as ultraviolet exposure. Its progression has been also associated with the involvement of several tumour microenvironmental molecules. Among these, nuclear factor‑κB (NF‑κB) has been indicated as a key player of osteopontin (OPN) and matrix metalloproteinase‑9 (MMP‑9) activation. However, whether NF‑κB plays a role in the development and progression of melanoma in association with the OPN/MMP‑9 axis according to the BRAFV600E mutation status has not been investigated in detail to date...
January 10, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28073844/fda-approval-of-nivolumab-for-the-first-line-treatment-of-patients-with-brafv600-wild-type-unresectable-or-metastatic-melanoma
#3
Julia A Beaver, Marc R Theoret, Sirisha Mushti, Kun He, Meredith Libeg, Kirsten Goldberg, Rajeshwari Sridhara, Amy E McKee, Patricia Keegan, Richard Pazdur
On November 23, 2015, the U.S. Food and Drug Administration approved nivolumab (OPDIVO®, Bristol Myers Squibb, Co.) as a single agent for the first-line treatment of patients with BRAFV600 wild-type, unresectable or metastatic melanoma. An international, double-blind, randomized (1:1) trial conducted outside of the U.S. allocated 418 patients to receive nivolumab 3mg/kg intravenously every 2 weeks (n=210) or dacarbazine 1000mg/m2 intravenously every 3 weeks (n=208). Patients with disease progression who met protocol-specified criteria (~25% of each trial arm) were permitted to continue with the assigned treatment in a blinded fashion until further disease progression is documented...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28058658/combination-treatment-of-patients-with-braf-mutant-melanoma-a-new-standard-of-care
#4
REVIEW
Ester Simeone, Antonio M Grimaldi, Lucia Festino, Vito Vanella, Marco Palla, Paolo A Ascierto
Raf-mitogen-activated protein kinase (Raf-MAPK) pathway inhibition with the BRAF inhibitors vemurafenib and dabrafenib, alone or in combination with a MEK inhibitor, has become a standard therapeutic approach in patients with BRAF-mutated metastatic melanoma. Both vemurafenib and dabrafenib have shown good safety and efficacy as monotherapy compared with chemotherapy. However, the duration of response is limited in the majority of patients treated with BRAF inhibitor monotherapy because of the development of acquired resistance...
January 6, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28058082/on-chip-wavelength-multiplexed-detection-of-cancer-dna-biomarkers-in-blood
#5
H Cai, M A Stott, D Ozcelik, J W Parks, A R Hawkins, H Schmidt
We have developed an optofluidic analysis system that processes biomolecular samples starting from whole blood and then analyzes and identifies multiple targets on a silicon-based molecular detection platform. We demonstrate blood filtration, sample extraction, target enrichment, and fluorescent labeling using programmable microfluidic circuits. We detect and identify multiple targets using a spectral multiplexing technique based on wavelength-dependent multi-spot excitation on an antiresonant reflecting optical waveguide chip...
November 2016: Biomicrofluidics
https://www.readbyqxmd.com/read/28035401/acy-1215-accelerates-vemurafenib-induced-cell-death-of-braf-mutant-melanoma-cells-via-induction-of-er-stress-and-inhibition-of-erk-activation
#6
Ueihuei Peng, Zhihao Wang, Sa Pei, Yunchao Ou, Pengchao Hu, Wanhong Liu, Jiquan Song
BRAFV600E mutation is found in ~50% of melanoma patients and BRAFV600E kinase activity inhibitor, vemurafenib, has achieved a remarkable clinical response rate. However, most patients treated with vemurafenib eventually develop resistance. Overcoming primary and secondary resistance to selective BRAF inhibitors remains one of the most critically compelling challenges for these patients. HDAC6 has been shown to confer resistance to chemotherapy in several types of cancer. Few studies focused on the role of HDAC6 in vemurafenib resistance...
December 28, 2016: Oncology Reports
https://www.readbyqxmd.com/read/28031237/expression-profiling-of-a-human-thyroid-cell-line-stably-expressing-the-brafv600e-mutation
#7
Byoung-Ae Kim, Hyeon-Gun Jee, Jin Wook Yi, Su-Jin Kim, Young Jun Chai, June Young Choi, Kyu Eun Lee
BACKGROUND/AIM: The BRAF(V600E) mutation acts as an initiator of cancer development in papillary thyroid carcinoma (PTC). Gene expression changes caused by the BRAF(V600E) mutation may have an important role in thyroid cancer development. MATERIALS AND METHODS: To study genomic alterations caused by the BRAF(V600E) mutation, we made human thyroid cell lines that harbor the wild-type BRAF gene (Nthy/WT) and the V600E mutant-type BRAF gene (Nthy/V600E). RESULTS: Flow cytometry and western blotting showed stable transfection of the BRAF gene...
January 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/28009606/hobnail-variant-of-papillary-thyroid-carcinoma-clinicopathologic-and-molecular-evidence-of-progression-to-undifferentiated-carcinoma-in-2-cases
#8
José M Cameselle-Teijeiro, Irene Rodríguez-Pérez, Ricardo Celestino, Catarina Eloy, Magalí Piso-Neira, Ihab Abdulkader-Nallib, Paula Soares, Manuel Sobrinho-Simões
The hobnail variant (HV) of papillary thyroid carcinoma (PTC) is an unusual entity recently proposed as an aggressive variant of PTC. We describe the pathologic and molecular features of 2 cases of HV of PTC. Both tumors presented in stage III (pT3 pN1a M0). The first case was diagnosed in a 62-year-old man, whereas the second was in a 53-year-old woman. Both patients were treated with total thyroidectomy and radioactive iodine. The primary tumors showed a hobnail/micropapillary pattern in ≥50% of the neoplasm, and positivity for TTF-1, TTF-2, thyroglobulin (TG), cyclin D1, and p53...
December 22, 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28006055/association-of-dna-mismatch-repair-and-mutations-in-braf-and-kras-with-survival-after-recurrence-in-stage-iii-colon-cancers-a-secondary-analysis-of-2-randomized-clinical-trials
#9
Frank A Sinicrope, Qian Shi, Carmen J Allegra, Thomas C Smyrk, Stephen N Thibodeau, Richard M Goldberg, Jeffrey P Meyers, Kay L Pogue-Geile, Greg Yothers, Daniel J Sargent, Steven R Alberts
Importance: The association of biomarkers with patient survival after recurrence (SAR) of cancer is poorly understood but may guide management and treatment. Objective: To determine the association of DNA mismatch repair (MMR) status and somatic mutation in the B-Raf proto-oncogene (c.1799T>A [V600E]; BRAFV600E) or exon 2 of the KRAS proto-oncogene (KRAS) in the primary tumor with SAR in patients with stage III colon carcinomas treated with adjuvant chemotherapy...
December 22, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/27994058/signal-transducer-and-activator-of-transcription-1-plays-a-pivotal-role-in-ret-ptc3-oncogene-induced-expression-of-indoleamine-2-3-dioxygenase-1
#10
Sonia Moretti, Elisa Menicali, Nicole Nucci, Pasquale Voce, Renato Colella, Rosa Marina Melillo, Federica Liotti, Silvia Morelli, Francesca Fallarino, Antonio Macchiarulo, Massimo Santoro, Nicola Avenia, Efisio Puxeddu
Indoleamine 2,3-dioxygenase 1 (IDO1) is a single chain oxidoreductase that catalyzes tryptophan degradation to kynurenine. In cancer, it exerts an immunosuppressive function as part of an acquired mechanism of immune-escape. Recently, we demonstrated that IDO1 expression is significantly higher in all thyroid cancer histotypes compared to normal thyroid and that its expression levels correlate with T regulatory (Treg) lymphocyte densities in the tumor microenvironment. BRAFV600E- and RET/PTC3-expressing PcCL3 cells were used as cellular models for the evaluation of IDO1 expression in thyroid carcinoma cells and for the study of involved signal transduction pathways...
December 19, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27977682/perk-is-a-haploinsufficient-tumor-suppressor-gene-dose-determines-tumor-suppressive-versus-tumor-promoting-properties-of-perk-in-melanoma
#11
Dariusz Pytel, Yan Gao, Katarzyna Mackiewicz, Yuliya V Katlinskaya, Kirk A Staschke, Maria C G Paredes, Akihiro Yoshida, Shuo Qie, Gao Zhang, Olga S Chajewski, Lawrence Wu, Ireneusz Majsterek, Meenhard Herlyn, Serge Y Fuchs, J Alan Diehl
The unfolded protein response (UPR) regulates cell fate following exposure of cells to endoplasmic reticulum stresses. PERK, a UPR protein kinase, regulates protein synthesis and while linked with cell survival, exhibits activities associated with both tumor progression and tumor suppression. For example, while cells lacking PERK are sensitive to UPR-dependent cell death, acute activation of PERK triggers both apoptosis and cell cycle arrest, which would be expected to contribute tumor suppressive activity...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27974353/vegf-blockade-enhances-the-antitumor-effect-of-brafv600e-inhibition
#12
Valentina Comunanza, Davide Corà, Francesca Orso, Francesca Maria Consonni, Emanuele Middonti, Federica Di Nicolantonio, Anton Buzdin, Antonio Sica, Enzo Medico, Dario Sangiolo, Daniela Taverna, Federico Bussolino
The development of resistance remains a major obstacle to long-term disease control in cancer patients treated with targeted therapies. In BRAF-mutant mouse models, we demonstrate that although targeted inhibition of either BRAF or VEGF initially suppresses the growth of BRAF-mutant tumors, combined inhibition of both pathways results in apoptosis, long-lasting tumor responses, reduction in lung colonization, and delayed onset of acquired resistance to the BRAF inhibitor PLX4720. As well as inducing tumor vascular normalization and ameliorating hypoxia, this approach induces remodeling of the extracellular matrix, infiltration of macrophages with an M1-like phenotype, and reduction in cancer-associated fibroblasts...
December 14, 2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27936049/clinicopathological-features-and-prognosis-of-papillary-thyroid-microcarcinoma-for-surgery-and-relationships-with-the-brafv600e-mutational-status-and-expression-of-angiogenic-factors
#13
Chenlei Shi, Yong Guo, Yichen Lv, Abiyasi Nanding, Tiefeng Shi, Huadong Qin, Jianjun He
OBJECTIVE: To investigate the clinicopathological characteristics of papillary thyroid microcarcinoma (PTMC) for surgery by comparing the difference between PTMC and larger papillary thyroid carcinoma (LPTC). METHODS: We analyzed the differences in the clinicopathological characteristics, prognosis, B-type RAF kinase (BRAF)V600E mutational status and expression of angiogenic factors, including pigment epithelium-derived factor (PEDF), Vascular Endothelial Growth Factor (VEGF), and hypoxia-inducible factor alpha subunit (HIF-1α), between PTMC and LPTC by retrospectively reviewing the records of 251 patients with papillary thyroid carcinoma, 169 with PTMC, and 82 with LPTC (diameter >1 cm)...
2016: PloS One
https://www.readbyqxmd.com/read/27900869/-evaluation-of-five-years-of-treatment-of-erdheim-chester-disease-with-anakinra-case-report-and-overview-of-literature
#14
Zdeněk Adam, Hana Petrášová, Zdeněk Řehák, Renata Koukalová, Marta Krejčí, Luděk Pour, Eva Vetešníková, Aleš Čermák, Sabina Ševčíková, Petr Szturz, Zdeněk Král, Jiří Mayer
: Erdheim-Chester disease is a histiocytic neoplasm of diseases from the group of non-Langerhans-cell histiocytoses, formed by infiltrates of foamy histiocytes. These pathological histiocytes produce pro-inflammatory cytokines. Therefore Erdheim-Chester disease is called inflammatory histiocytary neoplasm. The disease is accompanied by clinical symptoms of systemic inflammatory response, i.e. B symptoms. Imaging examinations detect typical osteosclerotic changes affecting diaphyses and metaphyses of the lower long bones and fibrotic changes which affect the aorta wall and the vessels leading from it...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27898473/histopathological-and-clinical-findings-in-cutaneous-manifestation-of-erdheim-chester-disease-and-langerhans-cell-histiocytosis-overlap-syndrome-associated-with-the-brafv600e-mutation
#15
Julia Liersch, J Andrew Carlson, Jörg Schaller
The overlap of Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis (LCH) is more common than it was generally accepted. Both diseases seem to be linked by a mutation in oncogenic BRAFV600E, probably an early event which occurs in bone marrow progenitor cells. In this article are described the clinical and histological findings in 2 cases of ECD-LCH overlap syndrome bearing the BRAFV600E mutation in both ECD and LCH lesions in bone and skin. In one case, lesions of ECD and LCH were situated directly site-to-site in the same bone section leading to the assumption of a common myeloid precursor cell for these diseases...
November 23, 2016: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/27883956/efficacy-of-braf-inhibitors-in-asian-metastatic-melanoma-patients-potential-implications-of-genomic-sequencing-in-braf-mutated-melanoma
#16
Hee Kyung Kim, Sunyoung Lee, Kyung Kim, Mi Hwa Heo, Hansang Lee, Jinhyun Cho, Nayoung K D Kim, Woongyang Park, Su Jin Lee, Jung Han Kim, Kee-Taek Jang, Sang-Hee Choi, Jeeyun Lee
BACKGROUND: The BRAF inhibitors vemurafenib and dabrafenib are currently the standard treatment for metastatic melanoma with BRAF V600 mutations. However, given the rarity of noncutaneous melanoma, including acral and mucosal subtypes, the efficacy of BRAF inhibitors for this subset of patients has not been extensively investigated. Acquired resistance generally appears 6 to 8 months after treatment with a BRAF inhibitor, and the mechanism of resistance is not well established. METHODS: We examined treatment outcomes for patients diagnosed with metastatic melanoma and treated with BRAF inhibitors at Samsung Medical Center between April 2013 and December 2015...
December 2016: Translational Oncology
https://www.readbyqxmd.com/read/27881018/a-different-prognostic-value-of-brafv600e-mutation-positivity-in-different-age-groups-of-patients-with-papillary-thyroid-cancer
#17
E Takacsova, R Kralik, I Waczulikova, K Zavodna, J Kausitz
The aim of retrospective single-center study was to assess the prognostic value of BRAFV600E mutation positivity (BRAFV600E+) on disease persistence/recurrence in patients with papillary thyroid cancer (PTC). A total of 199 patients having had initial surgery with neck dissection in our hospital between 6/2009-6/2012 were included in the cohort. Excluded were patients with unifocal microcarcinoma ≤1cm. BRAFV600E mutation was tested from formalin-fixed paraffin-embedded surgicaly removed tumors. All included patients were postoperatively treated with radioiodine...
November 24, 2016: Neoplasma
https://www.readbyqxmd.com/read/27863426/quantification-of-tumor-derived-cell-free-dna-cfdna-by-digital-pcr-digpcr-in-cerebrospinal-fluid-of-patients-with-brafv600-mutated-malignancies
#18
Parisa Momtaz, Elena Pentsova, Omar Abdel-Wahab, Eli Diamond, David Hyman, Taha Merghoub, Daoqi You, Billel Gasmi, Agnes Viale, Paul B Chapman
Tumor-derived cell free DNA (cfDNA) can be detected in plasma. We hypothesized that mutated BRAF V600 cfDNA could be quantified in the cerebrospinal fluid (CSF) of patients with central nervous system (CNS) metastases. We collected CSF from patients with BRAF V600E or K-mutated melanoma (N=8) or BRAF V600E mutated Erdheim-Chester Disease (ECD) (N=3) with suspected central nervous system (CNS) involvement on the basis of neurological symptoms (10/11), MRI imaging (8/11), or both. Tumor-derived cfDNA was quantified by digital PCR in the CSF of 6/11 patients (range from 0...
November 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27846237/integrated-genomics-identifies-mir-32-mcl-1-pathway-as-a-critical-driver-of-melanomagenesis-implications-for-mir-replacement-and-combination-therapy
#19
Prasun J Mishra, Pravin J Mishra, Glenn Merlino
AIMS: Cutaneous malignant melanoma is among the deadliest human cancers, broadly resistant to most clinical therapies. A majority of patients with BRAFV600E melanomas respond well to inhibitors such as vemurafenib, but all ultimately relapse. Moreover, there are no viable treatment options available for other non-BRAF melanoma subtypes in the clinic. A key to improving treatment options lies in a better understanding of mechanisms underlying melanoma progression, which are complex and heterogeneous...
2016: PloS One
https://www.readbyqxmd.com/read/27846054/sequencing-treatment-in-brafv600-mutant-melanoma-anti-pd-1-before-and-after-braf-inhibition
#20
Douglas B Johnson, Eirini Pectasides, Emily Feld, Fei Ye, Shilin Zhao, Romany Johnpulle, Ryan Merritt, David F McDermott, Igor Puzanov, Donald Lawrence, Jeffrey A Sosman, Elizabeth Buchbinder, Ryan J Sullivan
Novel agents targeting immune checkpoint molecules or mutated BRAF are active therapeutic options for patients with BRAF-mutant melanoma. However, the most effective first-line treatment and the optimal sequencing of these agents have not been well characterized. To explore this, we retrospectively assessed 114 patients from 4 centers with advanced, BRAF-mutant melanoma who received anti-programmed cell death-1 (PD-1)/PD-L1 antibodies. We evaluated clinical outcomes, including objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) to initial and subsequent therapies in patients that received anti-PD-1 first (n=56) versus those that received BRAF±MEK inhibitors (BRAFi) first (n=58)...
January 2017: Journal of Immunotherapy
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