Academic literature on the topic 'BRAF35'
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Journal articles on the topic "BRAF35"
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Rugerio-Martínez, Claudia Ivette, Daniel Ramos, Abel Segura-Olvera, Nadia Mireya Murillo-Melo, Yessica Sarai Tapia-Guerrero, Raúl Argüello-García, Norberto Leyva-García, Oscar Hernández-Hernández, Bulmaro Cisneros, and Rocío Suárez-Sánchez. "Dp71 Point Mutations Induce Protein Aggregation, Loss of Nuclear Lamina Integrity and Impaired Braf35 and Ibraf Function in Neuronal Cells." International Journal of Molecular Sciences 23, no. 19 (October 6, 2022): 11876. http://dx.doi.org/10.3390/ijms231911876.
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Dystrophin Dp71 is the most abundant product of the Duchenne muscular dystrophy gene in the nervous system, and mutations impairing its function have been associated with the neurodevelopmental symptoms present in a third of DMD patients. Dp71 is required for the clustering of neurotransmitter receptors and the neuronal differentiation of cultured cells; nonetheless, its precise role in neuronal cells remains to be poorly understood. In this study, we analyzed the effect of two pathogenic DMD gene point mutations on the Dp71 function in neurons. We engineered C272Y and E299del mutations to express GFP-tagged Dp71 protein variants in N1E-115 and SH-SY5Y neuronal cells. Unexpectedly, the ectopic expression of Dp71 mutants resulted in protein aggregation, which may be mechanistically caused by the effect of the mutations on Dp71 structure, as predicted by protein modeling and molecular dynamics simulations. Interestingly, Dp71 mutant variants acquired a dominant negative function that, in turn, dramatically impaired the distribution of different Dp71 protein partners, including β-dystroglycan, nuclear lamins A/C and B1, the high-mobility group (HMG)-containing protein (BRAF35) and the BRAF35-family-member inhibitor of BRAF35 (iBRAF). Further analysis of Dp71 mutants provided evidence showing a role for Dp71 in modulating both heterochromatin marker H3K9me2 organization and the neuronal genes’ expression, via its interaction with iBRAF and BRAF5.
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Mi LEE, Young, and Wankee KIM. "Association of human kinesin superfamily protein member 4 with BRCA2-associated factor 35." Biochemical Journal 374, no. 2 (September 1, 2003): 497–503. http://dx.doi.org/10.1042/bj20030452.
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A large portion of human kinesin superfamily protein member 4 (KIF4) is associated with the nuclear matrix during the interphase, while a small portion is found in the cytoplasm. During mitosis, it is associated with chromosomes throughout the entire process. In the present study, we identified a protein that interacts with KIF4 using a yeast two-hybrid system, co-immunoprecipitation and co-fractionation. This protein is BRCA2-associated factor 35 (BRAF35) containing a non-specific DNA binding high-mobility-group domain and a kinesin-like coiled-coil domain. It appeared that the interaction between the two proteins occurs through their respective α-helical coiled-coil domains. The co-fractionation experiment revealed that KIF4 and BRAF35 were present in a complex of approx. 540 kDa. The composition and biological significance of this complex should be studied further.
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Hakimi, M. A., D. A. Bochar, J. Chenoweth, W. S. Lane, G. Mandel, and R. Shiekhattar. "A core-BRAF35 complex containing histone deacetylase mediates repression of neuronal-specific genes." Proceedings of the National Academy of Sciences 99, no. 11 (May 28, 2002): 7420–25. http://dx.doi.org/10.1073/pnas.112008599.
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Zanchetta, Melania E., Luisa M. R. Napolitano, Danilo Maddalo, and Germana Meroni. "The E3 ubiquitin ligase MID1/TRIM18 promotes atypical ubiquitination of the BRCA2-associated factor 35, BRAF35." Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1864, no. 10 (October 2017): 1844–54. http://dx.doi.org/10.1016/j.bbamcr.2017.07.014.
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Ceballos-Chavez, M., S. Rivero, P. Garcia-Gutierrez, M. Rodriguez-Paredes, M. Garcia-Dominguez, S. Bhattacharya, and J. C. Reyes. "Control of neuronal differentiation by sumoylation of BRAF35, a subunit of the LSD1-CoREST histone demethylase complex." Proceedings of the National Academy of Sciences 109, no. 21 (May 8, 2012): 8085–90. http://dx.doi.org/10.1073/pnas.1121522109.
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Lee, Belinda, Angelyn Anton, Margaret Lee, Rachel Wong, Phillip Parente, Jeremy David Shapiro, Desmond Yip, et al. "Examining progression-free survival in first- and second-line treatment for BRAF-mutant metastatic colorectal cancer (CRC)." Journal of Clinical Oncology 35, no. 4_suppl (February 1, 2017): 728. http://dx.doi.org/10.1200/jco.2017.35.4_suppl.728.
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728 Background: BRAF mutated (BRAFm) CRC represents ~10% of all CRC and is associated with significantly poorer prognosis. However, responses to chemotherapy do still occur. Some data suggest that the poor prognosis associated with BRAFm CRC is dominated by substantially poorer second line PFS (PFS2), whereas first line PFS (PFS1) was similar for both BRAFm and BRAF wildtype (BRAFwt) CRC. Using a large multicenter dataset, our study aimed to examine PFS1 and PFS2 in BRAFm versus BRAFwt CRC. Methods: Prospectively collected data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) database was interrogated. PFS was calculated and compared in patients with BRAFm versus BRAFwt CRC. Median survival was determined by the Kaplan-Meier method and compared using the log rank test. Results: TRACC identified 523 CRC patients with known BRAF mutation status, who received first-line chemotherapy: 53 (10%) were BRAFm, while 470 (90%) were BRAFwt. At the time of data analysis, only 231 (44%) CRC patients had received second-line chemotherapy, of which 21 (9%) were BRAFm and 210 (91%) were BRAFwt. PFS1 analyses demonstrated significantly poorer survival in the BRAFm population (Median 7.8mo versus 11.5mo, HR 1.72, p = 0.0026). PFS2 analyses revealed similar findings for the BRAFm population, albeit non-significant due to smaller numbers (Median 5.5mo versus 7.7mo, HR1.26, p = 0.44). Conclusions: Our study demonstrated that BRAFm CRC was associated with poorer PFS in both first- and second-line settings. Additional analyses will be performed to examine the impact of different treatment strategies and other clinicopathological features.
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Osterlund, Pia J., Emerik Osterlund, Aki Uutela, Päivi Halonen, Raija S. Kallio, Annika Ålgars, Tapio Salminen, et al. "Resectability, conversion and resections rates, and outcomes in RAS&BRAF wildtype (wt), RAS mutant (mt) and BRAFmt metastatic colorectal cancer (mCRC) subgroups in the prospective Finnish RAXO-study." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 3532. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.3532.
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3532 Background: Outcomes of metastasectomy varies with RAS and BRAF-status, but the effect on resectability, conversion and resection rates has not been extensively studied. Methods: The prospective Finnish RAXO study (NCT01531621) included 1086 patients 2011-2018 (Osterlund et al TLRHE 2021, Isoniemi et al BJS 2021) of which 906 were included in this secondary endpoint analysis. Excluded had missing KRAS/ NRAS/ BRAF-V600E test, were untreatable or had an atypical BRAF mutation. We studied repeated centralized resectability assessment, conversion and resectability rates in mCRC, and overall survival (OS) after resection and/or local ablative therapy (LAT) and systemic therapy. Results: Included were 289 RAS& BRAFwt, 529 RASmt (overrepresented) and 88 BRAFmt, with median age 65.8/66.1/66.9 years. Demographics per RAS& BRAFwt, RASmt and BRAFmt showed significant differences in male proportion (68/61/39%), ECOG PS 2-3 groups (16/14/25%), primary tumour location (right colon 16/30/69%, left colon 47/34/17%, rectum 38/36/14%), but not for Charlson comorbidity index, BMI, resection of primary, synchronous presentation or adjuvant therapy (Bonferroni corrected Chi-square). Metastatic profile was different for liver (78/74/61% per RAS& BRAFwt, RASmt and BRAFmt), lung (24/35/28%) and peritoneal (15/15/32%) metastases, but not for lymph nodes or other sites, nor for number of metastatic sites (1 in 53/54/52%). Upfront resectability rates were different with 32/29/15% for RAS& BRAFwt, RASmt and BRAFmt, respectively, as were conversion rates with 16/13/7%, and resection/LAT rates with 45/37/17%, respectively. Kaplan-Meier median OS estimate in R0/1/2-resected and/or LAT group (n = 342) was 83/69/30 months for RAS& BRAFwt, RASmt and BRAFmt groups, respectively and 5-year OS-rates 67/60/24%, with Cox HR ref/1.53 (95% CI 1.04-2.25)/3.11 (1.49-6.49). In the “systemic therapy only” (n = 564) OS was 29/21/15 months and 5-year OS-rates 11/6/2% respectively, with HR ref/1.43 (1.15-1.76)/2.34 (1.73-3.17). Resection/LAT patients had improved OS over “systemic therapy only” patients in all subgroups, HR 5.74 (3.90-8.44)/5.06 (3.92-6.55)/2.89 (1.43-5.86). Conclusions: There were significant differences in resectability, conversion and resection/LAT rates according to RAS& BRAFwt, RASmt and BRAFmt status. OS was also significantly longer for RAS& BRAFwt versus either mutant. Resected/LAT had better OS than “systemic therapy alone” patients in all subgroups. Clinical trial information: NCT01531621.
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Braithwaite, Matthew, Christopher Duane Nevala-Plagemann, Kelsey Baron, Benjamin Haaland, Lisa M. Pappas, and Ignacio Garrido-Laguna. "Real-world outcomes of patients with BRAF-mutated mCRC treated in the United States." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 4030. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.4030.
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4030 Background: BRAF mutations portend a poor prognosis in metastatic colorectal cancer (mCRC). Recent trials have hypothesized that using more aggressive triplet-based chemotherapy regimens such as FOLFOXIRI in the frontline setting may improve outcomes in this patient population. In this study, we utilized real-world data to assess whether FOLFOXIRI is being used in the United States (US) and compared survival outcomes in BRAF mutated (BRAFmt) mCRC stratified by first line (1L) therapy. Methods: The nationwide Flatiron Health EHR-derived de-identified database was reviewed for patients diagnosed with mCRC between 2013 and 2018. Patients who had documented BRAF mutation testing and received a standard 1L therapy were included for analysis. Patients who did not have a visit or medication order within 90 days of metastatic diagnosis were excluded to ensure patients were engaged with care at the data-providing institution. Kaplan-Meier and Cox proportional hazard modeling were used to compare survival outcomes stratified by BRAF mutation status and 1L therapy received. Results: A total of 4,454 patients with documented BRAF mutational status were included, of which 3,988 (89.5%) were BRAF wild type (BRAFwt) and 466 (10.5%) were BRAFmt. Median OS was 15.4 months (mo) in the BRAFmt group compared to 28.1 mo in the BRAFwt group (HR 0.48, 95% CI 0.41- 0.56, p < 0.001). Only 3% (n = 16) of BRAFmt patients received 1L FOLFOXIRI +/- bevacizumab with a median OS of 13.8 mo compared to 15.5 mo in patients receiving a chemotherapy doublet (FOLFOX, CAPEOX, or FOLFIRI) +/- bevacizumab (95% CI 4.9 – not reached vs 14.3 – 19.0, p = 0.38). In BRAFmt patients, multivariate analysis (MVA) did not detect a significant improvement in OS with the use of FOLFIRI plus bevacizumab (HR 0.88, 95% CI 0.50-1.56, p = 0.67) or FOLFOX/CAPEOX plus bevacizumab (HR 0.89, 95% CI 0.59 – 1.34, p = 0.58) when compared to chemotherapy doublet alone. A MVA comparing 1L therapies in the BRAFwt group did not detect a significant improvement in OS with bevacizumab plus chemotherapy doublet compared to chemotherapy doublet alone. When stratified by 1L treatment regimen, similar proportions of BRAFmt patients received second line therapy. Conclusions: This analysis of real-world data confirms the negative prognostic impact of BRAF mutations in mCRC and suggests that FOLFOXIRI has not been widely adopted in the management of these patients in the US. We were unable to demonstrate any significant difference in OS of patients with BRAFmt mCRC based on type of 1L therapy received.
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Hernandez-Aya, Leonel Fernando, Matthew Burke, Jenna M. Collins, Dennis Earle, Melissa Hamilton, Beth L. Nordstrom, Ying Zhang, and Shivani Srivastava. "Real-world treatment patterns and clinical outcomes of advanced melanoma patients following disease progression on anti-PD-1-based therapy." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e22036-e22036. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e22036.
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e22036 Background: Despite the success of anti-programmed cell death-1 (PD-1) based therapies that prolong survival in advanced melanoma, some patients experience disease progression. Real-world treatment patterns and outcomes after progression on anti-PD-1 based regimens are unknown. Methods: Adults with advanced melanoma and a record of disease progression on anti-PD-1 treatment (alone or in combination) between 1 Sept 2014–31 Jan 2019 were selected from the Flatiron Health Oncology electronic medical record (EMR) database for this retrospective study. Index progression date was defined as an event where the treating clinician concluded in the patient record that there had been disease progression. The first subsequent therapy received was identified. Kaplan-Meier methods estimated overall survival (OS) with 95% confidence interval (CI) after the progression date. Analyses were run separately for BRAF mutant (mt) and wild type (wt). Results: Among 2,169 patients with advanced melanoma treated with an anti-PD-1, 213 BRAFmt and 302 BRAFwt had a record of progression following anti-PD-1 initiation and were included; an additional 82 BRAFmt and 138 BRAFwt were excluded due to death without a record of progression. Median age was 64 and 71 years, respectively; 27.7% and 9.9% had >1 line of therapy prior to the anti-PD-1. Among the BRAFmt patients who progressed on anti-PD-1, 94 (44.1%) received no subsequent therapy, 80 (37.6%) BRAF±MEK (± IO), and 16 (7.5%) anti-CTLA4 alone or with anti-PD-1 after progression on the initial anti-PD-1; 11% received other treatments with no clear pattern of care. Median (95% CI) OS from the index progression date for BRAFmt was 11.9 (8.2–16.9) months. In a subgroup of these BRAFmt patients with BRAF treatment prior to or during the first anti-PD-1 line (N = 65), 52.3% had no subsequent therapy and a median OS of 4.0 (2.7–7.5) months. Among the BRAFwt patients who progressed on anti-PD-1, 186 (61.6%) received no subsequent therapy, 46 (15.2%) received anti-CTLA4 alone or with anti-PD-1, 26 (8.6%) switched anti-PD-1s, and 15% received other treatments. Median (95% CI) OS for BRAFwt was 10.1 (8.8–12.5) months. Conclusions: In this real-world retrospective study, > 40% of BRAFmt and > 60% of BRAFwt patients did not initiate a new regimen after progression on anti-PD-1 therapy. Median OS after progression was < 1 year. This may be overestimated, as it excluded patients who died before progression was recorded in the EMR. These findings highlight a need for more effective treatments for advanced melanoma.
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Trunk, Andrew, Matthew Braithwaite, Christopher Nevala-Plagemann, Lisa Pappas, Benjamin Haaland, and Ignacio Garrido-Laguna. "Real-World Outcomes of Patients With BRAF-Mutated Metastatic Colorectal Cancer Treated in the United States." Journal of the National Comprehensive Cancer Network 20, no. 2 (February 2022): 144–50. http://dx.doi.org/10.6004/jnccn.2021.7059.
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Background: BRAF mutations portend a poor prognosis in metastatic colorectal cancer (mCRC). Whether these patients may benefit from more aggressive frontline chemotherapy with a triplet regimen such as FOLFOXIRI remains unclear. We used real-world data from a cohort of patients in the United States to assess the BRAF testing rate, determine the prevalence of FOLFOXIRI use, and compare survival outcomes in mCRC, stratified by BRAF mutation status and first-line therapy. Methods: A nationwide electronic health record–derived deidentified database was reviewed for patients diagnosed with mCRC between 2013 and 2018. Those with documented BRAF mutation testing who received standard first-line therapy were included. Kaplan-Meier estimates with corresponding log-rank tests and Cox proportional hazards modeling compared survival outcomes stratified by BRAF status and first-line therapy. Results: Of 4,457 included patients, 3,991 (89.5%) had BRAF wild-type (BRAFwt) and 466 (10.5%) had BRAF-mutated (BRAFmt) mCRC. Median overall survival (OS) was 15.4 months in the BRAFmt group versus 28.1 months in the BRAFwt group (hazard ratio [HR], 0.48; 95% CI, 0.41–0.56; P<.001). Only 3% of patients with BRAF mutations received first-line FOLFOXIRI ± bevacizumab, with a median OS of 13.8 months compared with 15.5 months in those treated with doublet chemotherapy ± bevacizumab (P=.38). In patients with BRAF mutations, propensity-weighted analysis did not detect a significant improvement in OS with FOLFIRI + bevacizumab (HR, 0.90; 95% CI, 0.58–1.39; P=.63) or FOLFOX/CAPEOX + bevacizumab (HR, 0.81; 95% CI, 0.52–1.26; P=.35) versus doublet chemotherapy alone. In 2018, only 56% of patients diagnosed with mCRC had documented BRAF testing at any time. Conclusions: This real-world data analysis confirms the negative prognostic impact of BRAF mutations in mCRC and suggests that FOLFOXIRI has not been widely adopted in the United States. The proportion of patients with documented BRAF testing in this real-world population was low at 56%. We were unable to show any significant difference in OS of patients with BRAFmt mCRC based on the first-line therapy received.
Dissertations / Theses on the topic "BRAF35"
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Carson, Robbie. "Targeting acute resistance mechanisms inhibition in BRAFMT CRC." Thesis, Queen's University Belfast, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.695267.
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Colorectal cancer (GRG) is the 3rd common cancer, and second leading cause of cancer associated mortality. Oncogenic mutations in the BRAF gene results in an altered protein structure, leading to constitutively activated MAPK signalling. Beneficial treatment strategies for this poor prognostic subgroup of GRG patients have yet to be identified. Hence this objective of this study was to identify novel treatment strategies in BRAF mutant GRG models. Our data has shown that MEK inhibition results in acute expression of pSTAT3, regulated through the c-METI JAK signalling axis. Taking a combined approach of JAKlMEK, or c-MET/MEK inhibition we have shown that these combinations results in significant increased apoptosis in BRAFMT GRG, and have potential as novel combinations. Furthermore, we are the first to show that MEK inhibition results in increased expression of the caspase 8 inhibitor c-FLlP, as a mechanism of resistance to apoptosis induction. Using a gene silencing and small-molecule inhibitor approach, we have identified that combined c-FLlP/MEK inhibition is a novel treatment strategy that may provide benefit for this subgroup of GRG patients.
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Beleboni, Rafaela Cardoso [UNESP]. "Traços impressionistas nos contos de Menalton Braff." Universidade Estadual Paulista (UNESP), 2007. http://hdl.handle.net/11449/91603.
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beleboni_rc_me_arafcl.pdf: 472797 bytes, checksum: 62a22cf691cdd6b5eabee61469afea96 (MD5)Nossa pesquisa de Mestrado procura apontar a permanência de traços impressionistas nos contos do livro premiado pelo Jabuti, em 2000, À sombra do cipreste (1999), de Menalton Braff. Para mostrar a construção dessas marcas na produção literária de Braff, recorremos a conceitos da teoria semiótica, sobretudo àqueles relacionados ao modo de presença da enunciação. A partir disso, pudemos depreender determinados elementos impressionistas presentes, sobretudo, nos contos À sombra do cipreste, No dorso do granito, O banquete e Adágio Apassionato. Dessa forma, há, na obra, do ponto de vista temático, a percepção do tempo e os ritos da memória, a relação do homem com o seu passado e o seu resgate numa situação do presente. Do ponto de vista formal, vários traços aparecem pontilhados. Sendo assim, há descrições sensoriais que dão cor, formato, som, gosto e cheiro às tensões, às dúvidas, às crises interiores das personagens que, na sua maioria, são sujeitos à flor da pele. Dentre as figuras sensoriais, a visão é predominante, figurativizada ponto-a-ponto pelos efeitos cromáticos, pelo circuito construído pelos olhares do narrador ou das personagens, pelo jogo de luz e sombra, a macro-figura impressionista recorrente na obra. A imagem criada torna-se, por meio do uso recorrente de figuras de linguagem, sugestiva. Em vários casos, há o efeito de borrão pontilhado, que indefine o objeto descrito para depois defini-lo.No entanto, esta pesquisa não se limita a desenvolver essa discussão. Procuramos, ainda, investigar, nos enunciados dos contos, as projeções da enunciação, evidenciadas nas entrevistas realizadas com o autor. Nesse sentido, procuramos contemplar quatro instâncias: a nossa leitura crítica de contos literários; a leitura do artista sobre a própria produção artística; o confronto entre essas duas leituras; o olhar do ficcionista...
Our Master research tries to indicate the permanence of impressionist traces in the tales obtained from the book A sombra do cipreste (1999) by Menalton Braff, awarded by Jabuti in 2000. We have used the concepts of semiotics theory to show these marks in Braff's work, especially those related to the way of enunciation presence. From these concepts we were able to infer some impressionist's elements present, especially in the tales, A sombra do cipreste, No dorso do granito, O banquete e Adágio Apassionato. From that, there is in the masterpiece a thematic point of view, the perception of time and rite of memory and the relation between the man with his past and its rescue to the present. From a formal point of view, many dotted traces show up. So there are many sensorial descriptions that give, color, shape, sound, taste and smell to the tensions, doubts, the characters inner crises, which are extremely evident subjects. Among the sensorial figures the predominant view symbolized point to point by the chromatics effects, the view connection built among the narrator and the characters, and by the light and shadow game, the impressionist appealing macro-figure in the masterpiece. The created image becomes significant through the use of language figures. In many cases there is the effect called dotted stain, which turns the described object indefinable to determine it later. However, this research was not limited in developing this discussion. We also tried to investigate the projection of the enunciation in the tale proposition that became evident in interviews done with the author. In those circumstances, we tried to observe four instances: our critical reading of literary tales, the authors point of view about his own work, the confrontation between these two readings and the fictionist's view facing the critics to his work. The results obtained point to agreements... (Complete abstract click electronic access below)
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Beleboni, Rafaela Cardoso. "Traços impressionistas nos contos de Menalton Braff /." Araraquara : [s.n.], 2007. http://hdl.handle.net/11449/91603.
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Orientador: Luiz Gonzaga MarchezanBanca: Arnaldo Cortina
Banca: Tânia Pellegrini
Resumo: Nossa pesquisa de Mestrado procura apontar a permanência de traços impressionistas nos contos do livro premiado pelo Jabuti, em 2000, À sombra do cipreste (1999), de Menalton Braff. Para mostrar a construção dessas marcas na produção literária de Braff, recorremos a conceitos da teoria semiótica, sobretudo àqueles relacionados ao modo de presença da enunciação. A partir disso, pudemos depreender determinados elementos impressionistas presentes, sobretudo, nos contos "À sombra do cipreste", "No dorso do granito", "O banquete" e "Adágio Apassionato". Dessa forma, há, na obra, do ponto de vista temático, a percepção do tempo e os ritos da memória, a relação do homem com o seu passado e o seu resgate numa situação do presente. Do ponto de vista formal, vários traços aparecem pontilhados. Sendo assim, há descrições sensoriais que dão cor, formato, som, gosto e cheiro às tensões, às dúvidas, às crises interiores das personagens que, na sua maioria, são sujeitos à flor da pele. Dentre as figuras sensoriais, a visão é predominante, figurativizada ponto-a-ponto pelos efeitos cromáticos, pelo circuito construído pelos olhares do narrador ou das personagens, pelo jogo de luz e sombra, a macro-figura impressionista recorrente na obra. A imagem criada torna-se, por meio do uso recorrente de figuras de linguagem, sugestiva. Em vários casos, há o efeito de borrão pontilhado, que indefine o objeto descrito para depois defini-lo.No entanto, esta pesquisa não se limita a desenvolver essa discussão. Procuramos, ainda, investigar, nos enunciados dos contos, as projeções da enunciação, evidenciadas nas entrevistas realizadas com o autor. Nesse sentido, procuramos contemplar quatro instâncias: a nossa leitura crítica de contos literários; a leitura do artista sobre a própria produção artística; o confronto entre essas duas leituras; o olhar do ficcionista... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Our Master research tries to indicate the permanence of impressionist traces in the tales obtained from the book A sombra do cipreste (1999) by Menalton Braff, awarded by Jabuti in 2000. We have used the concepts of semiotics theory to show these marks in Braff's work, especially those related to the way of enunciation presence. From these concepts we were able to infer some impressionist's elements present, especially in the tales, "A sombra do cipreste", "No dorso do granito", "O banquete" e "Adágio Apassionato". From that, there is in the masterpiece a thematic point of view, the perception of time and rite of memory and the relation between the man with his past and its rescue to the present. From a formal point of view, many dotted traces show up. So there are many sensorial descriptions that give, color, shape, sound, taste and smell to the tensions, doubts, the characters inner crises, which are extremely evident subjects. Among the sensorial figures the predominant view symbolized point to point by the chromatics effects, the view connection built among the narrator and the characters, and by the light and shadow game, the impressionist appealing macro-figure in the masterpiece. The created image becomes significant through the use of language figures. In many cases there is the effect called dotted stain, which turns the described object indefinable to determine it later. However, this research was not limited in developing this discussion. We also tried to investigate the projection of the enunciation in the tale proposition that became evident in interviews done with the author. In those circumstances, we tried to observe four instances: our critical reading of literary tales, the authors point of view about his own work, the confrontation between these two readings and the fictionist's view facing the critics to his work. The results obtained point to agreements... (Complete abstract click electronic access below)
Mestre
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Braff, Roseli Deienno [UNESP]. "Saramago, Braff e seus personagens duplos: uma análise comparativa." Universidade Estadual Paulista (UNESP), 2010. http://hdl.handle.net/11449/94006.
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Na leitura que fizemos dos romances O homem duplicado e Castelos de papel, guiou-nos o método comparativo de análise textual, tendo como norte a ideia de que o fato estético deve ser estudado à luz do fato histórico, em consonância com ele, e nunca dele apartado. Nessa linha de pensamento, constatamos que certo “ar do tempo” aproxima os autores José Saramago e Menalton Braff, que dialogam por meio da temática do duplo nas obras aqui investigadas. Nosso objetivo foi mostrar a existência dessa relação intertextual por meio da análise dos níveis temático, narrativo e discursivo dos romances, além do diálogo desses com a tradição literária. Ambos os autores fizeram uso, do ponto de vista da estrutura narrativa, de elementos característicos de outros gêneros, como a tragédia grega em O homem duplicado, e o drama em Castelos de papel. Além da temática do duplo, é a releitura do romance policial um dos pontos de contato mais evidente entre as duas obras, que se estruturam em torno de uma investigação. No entanto, os ficcionistas desmontam a velha fórmula: crime – investigação – desvendamento do enigma, e, na nova roupagem com que revestem esse subgênero, não há soluções tampouco culpados, mas indagações provocadoras – por essa razão a denominamos como falso romance policial. No nível temático, mostramos que o duplo como tema na literatura segue duas vertentes: o homogêneo, usualmente representado por gêmeos ou sósias idênticos, em que a identidade não é posta em questão, pois um mesmo personagem desempenha dois papéis; o heterogêneo, em que o usurpador ocupa uma forma definitiva, e tal divisão obriga o eu dilacerado a recuperar sua própria identidade. Tertuliano Máximo Afonso/ António Claro e Alberto Ribeiro/ sorveteiro são figuras do duplo heterogêneo. Exógeno, porque configurado extrinsecamente a ele, o duplicado de Tertuliano...
In our reading of the novels O homem duplicado and Castelos de papel, the comparative method of textual analysis has led us, with the idea that the aesthetic fact must be studied under the light of the historical fact, according to it and never separated from it. In this thought line, we verify that a certain “air of time” binds José Saramago and Menalton Braff in the sense of the dialogue through the way of the themes of the double, as presently in this investigated work. Our purpose was to show the existence of this intertextual relationship from the way of the analysis of the thematic, narrative and discursive levels of the novels, besides their dialogue with the literary tradition. Both the authors employed, under the point of view of narrative structure, characteristic elements of other genres, such as the Greek tragedy in O homem duplicado, and the drama in Castelos de papel. Besides the thematic of the double, it is the re-reading of the detective story one of the most evident contact points between both works that frame them around an investigation. However, the fictionists disassemble the old formula: crime − investigation − solving the enigma, and, in the new vesture in which they revest this subgenre, there are not solutions either guilty people, but provoking inquiries − due to this fact we regard them as false detective stories. In the thematic level, we show that the double as theme in literature follows two ways: the homogeneous one, habitually represented by twins or identical doubles, in which the identity is not questioned since the same character plays two roles; the heterogeneous one in which the usurper takes a definitive form, and such a division obliges the dilacerated I to pick up its own identity. Tertuliano/António Claro and Alberto/ice-cream peddler are characters of the heterogeneous double. Exogenous, because made up extrinsically to him... (Complete abstract click electronic access below)
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Braff, Roseli Deienno. "Saramago, Braff e seus personagens duplos : uma análise comparativa /." Araraquara : [s.n.], 2010. http://hdl.handle.net/11449/94006.
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Orientador: Luiz Gonzaga MarchezanBanca: Ana Luiza Silva Camarani
Banca: Caio Márcio Poletti Lui Gagliardi
Resumo: Na leitura que fizemos dos romances O homem duplicado e Castelos de papel, guiou-nos o método comparativo de análise textual, tendo como norte a ideia de que o fato estético deve ser estudado à luz do fato histórico, em consonância com ele, e nunca dele apartado. Nessa linha de pensamento, constatamos que certo "ar do tempo" aproxima os autores José Saramago e Menalton Braff, que dialogam por meio da temática do duplo nas obras aqui investigadas. Nosso objetivo foi mostrar a existência dessa relação intertextual por meio da análise dos níveis temático, narrativo e discursivo dos romances, além do diálogo desses com a tradição literária. Ambos os autores fizeram uso, do ponto de vista da estrutura narrativa, de elementos característicos de outros gêneros, como a tragédia grega em O homem duplicado, e o drama em Castelos de papel. Além da temática do duplo, é a releitura do romance policial um dos pontos de contato mais evidente entre as duas obras, que se estruturam em torno de uma investigação. No entanto, os ficcionistas desmontam a velha fórmula: crime - investigação - desvendamento do enigma, e, na nova roupagem com que revestem esse subgênero, não há soluções tampouco culpados, mas indagações provocadoras - por essa razão a denominamos como falso romance policial. No nível temático, mostramos que o duplo como tema na literatura segue duas vertentes: o homogêneo, usualmente representado por gêmeos ou sósias idênticos, em que a identidade não é posta em questão, pois um mesmo personagem desempenha dois papéis; o heterogêneo, em que o usurpador ocupa uma forma definitiva, e tal divisão obriga o eu dilacerado a recuperar sua própria identidade. Tertuliano Máximo Afonso/ António Claro e Alberto Ribeiro/ sorveteiro são figuras do duplo heterogêneo. Exógeno, porque configurado extrinsecamente a ele, o duplicado de Tertuliano... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: In our reading of the novels O homem duplicado and Castelos de papel, the comparative method of textual analysis has led us, with the idea that the aesthetic fact must be studied under the light of the historical fact, according to it and never separated from it. In this thought line, we verify that a certain "air of time" binds José Saramago and Menalton Braff in the sense of the dialogue through the way of the themes of the double, as presently in this investigated work. Our purpose was to show the existence of this intertextual relationship from the way of the analysis of the thematic, narrative and discursive levels of the novels, besides their dialogue with the literary tradition. Both the authors employed, under the point of view of narrative structure, characteristic elements of other genres, such as the Greek tragedy in O homem duplicado, and the drama in Castelos de papel. Besides the thematic of the double, it is the re-reading of the detective story one of the most evident contact points between both works that frame them around an investigation. However, the fictionists disassemble the old formula: crime − investigation − solving the enigma, and, in the new vesture in which they revest this subgenre, there are not solutions either guilty people, but provoking inquiries − due to this fact we regard them as false detective stories. In the thematic level, we show that the double as theme in literature follows two ways: the homogeneous one, habitually represented by twins or identical doubles, in which the identity is not questioned since the same character plays two roles; the heterogeneous one in which the usurper takes a definitive form, and such a division obliges the dilacerated I to pick up its own identity. Tertuliano/António Claro and Alberto/ice-cream peddler are characters of the heterogeneous double. Exogenous, because made up extrinsically to him... (Complete abstract click electronic access below)
Mestre
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Cheung, Lai-Kay Maggie. "Characterisation of ^L597V BRAF in cancer." Thesis, University of Leicester, 2013. http://hdl.handle.net/2381/28016.
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BRAF is a component of the RAF/MEK/ERK signalling cascade which controls fundamental cellular activities, including proliferation, cell survival, differentiation and motility. Deregulation of this pathway is common in cancer and ~7% of cancers have a mutation in BRAF. Leu597 is the fifth most commonly mutated residue in BRAF-mutated human cancers, and a substitution to a valine is one of only seven BRAF mutations that are found in both cancer and a group of developmental syndromes known as RASopathies. A major question is how the mutation can be associated with both diseases. In this study, using an autochthonous model and HEK 293[superscript T] cells, [superscript L597V]BRAF was shown to have weak kinase and MEK/ERK-inducing activity. It did not induce morphological transformation or foci formation, nor confer a growth advantage or induce early immortalisation. Therefore, the mutation was found not to be a driver oncogene. [superscript L597V]BRAF mutations are found to co-exist with other oncogenic mutations in human cancer. Using cells derived from a conditional knock-in mouse model, we showed that [superscript L597V]BRAF synergises with [superscript G12D]Kras to induce cell changes more reminiscent of the high activity mutant [superscript V600E]Braf. Double mutant [superscript L597V]BRAF and [superscript G12D]Kras cells have higher Braf and Craf kinase activity than single mutants, which translates to higher Mek/Erk activity to a similar level to [superscript V600E]Braf. These cells were more morphologically transformed than Braf[superscript +/L597V] and Kras[superscript +/G12D] cells alone. RAF inhibitors induced paradoxical activation of Erk in [superscript L597V]Braf-expressing cells, and this was shown to be through heterodimerisation and activation of Craf. These results caution against the use of RAF inhibitors in treatment of RASopathy and cancer patients with the [superscript L597V]BRAF mutation. Aged Braf[superscript +/L597V] mice developed some predisposition to tumour formation. The tumours were benign, and one out of eight tumours was heterozygous for [superscript Q61L]Hras. This supports the idea that [superscript L597V]BRAF is insufficient to induce cancer, but epistatically modifies other oncogenes to promote cancer progression by hyperactivation of the Erk pathway.
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Sugita, Juliana Sayuri. "ANÁLISE DA MUTAÇÃO V600E DO GENE BRAF EM MELANOMAS CUTÂNEOS PRIMÁRIOS." Pontifícia Universidade Católica de Goiás, 2012. http://localhost:8080/tede/handle/tede/2350.
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JULIANA SAYURI SUGITA INUMARU.pdf: 977119 bytes, checksum: dd9451c21f0c8b8df529c718c8cf5860 (MD5)
Previous issue date: 2012-08-24Melanoma comprises about 4% of skin cancers, however, more than 95% of stage IV melanoma patients will die within five years and most patients will succumb in a year. The most commonly mutated gene in melanoma is BRAF V600E mutation, described in 40-70% of cutaneous melanomas. This mutation results in the substitution of valine for glutamic acid in codon 600, resulting in the active form of the protein. The objective of this study was to investigate the frequency of BRAF V600E mutation in patients diagnosed with melanoma in Goiânia, as well as the possible associations between this mutation and clinical-pathological aspects of the cases analyzed. Seventy seven cases of melanoma from the Pathology Departament of Araújo Jorge Hospital, in Goiânia, Goiás were analized. Molecular analysis was performed by PCR and RFLP. Descriptive and comparative statistical analysis with Chi-square test were used in this study. The results demonstrated the presence of V600E mutation in 54 (70,1%) patients with cutaneous melanoma and no statistically significant association was found between the presence of mutation with other prognostics parameters such as age, gender, sun exposure, anatomic location, presence of metastasis, histological subtypes and histological parameters (Breslow thickness, presence of ulceration, signs of regression, lymphocytic infiltration and presence of satellites). Our results suggest that BRAF V600E mutation is a common event in melanomas and represents an important molecular target for therapeutic approaches in the treatment of this neoplasia.
O melanoma representa 4% das neoplasias malignas da pele, no entanto, mais de 95% dos pacientes com melanoma estágio IV irão morrer em cinco anos e a grande parte dos pacientes irá sucumbir em um ano. O gene mutado mais comumente no melanoma é o BRAF e a mutação V600E é descrita em 40 a 70% dos melanomas cutâneos. Tal mutação resulta na substituição da valina por ácido glutâmico no códon 600, resultando na forma ativa desta proteína. O objetivo desse estudo consistiu em investigar a frequência da mutação V600E do gene BRAF, em pacientes diagnosticados com melanoma em Goiânia, bem como as possíveis associações, entre tal mutação e os aspectos clinico-patológicos dos casos analisados. Para isso foram analisados 77 casos de melanoma do Setor de Anatomia Patológica do Hospital Araújo Jorge, em Goiânia, Goiás. A análise molecular foi realizada por PCR e RFLP. Análise estatística descritiva e comparativa com o teste Chi-quadrado foi usado neste estudo. A mutação V600E do gene BRAF foi encontrada em 54 (70,1%) pacientes portadores de melanoma cutâneo e nenhuma associação estatisticamente significativa foi detectada entre a presença de mutação com outros parâmetros prognósticos como idade, gênero, exposição solar, localização anatômica, presença de metástases, subtipo histológico e parâmetros histológicos (índice de Breslow, presença de ulceração, sinais de regressão, infiltração linfocitária e presença de satélites). Nossos resultados permitem concluir que a mutação V600E de BRAF é um evento comum nos melanomas e que representa um alvo molecular importante para as abordagens alvo dirigidas no tratamento desta neoplasia.
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Ngeow, Kao Chin. "Post-translational modifications of BRAF and MITF." Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:4f6ac084-55a7-4296-9a11-28af3979450d.
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Malignant melanoma is the deadliest and most aggressive form of skin cancer. Despite the development of targeted molecular therapies which specifically target oncogenic pathways in melanoma, melanoma remains highly refractory to treatment and prone to relapse. In order to develop more effective therapies, there is a need to investigate additional ways of manipulating aberrant molecular pathways in melanoma. To this end, we have identified novel sites of post-translational modifications in two oncogenic proteins that are known to play pivotal roles in driving melanoma tumorigenesis. We showed that BRAF, the most commonly mutated oncoprotein in melanoma, can be acetylated at K473 and K475 by the p300/CBP acetyltransferases. Importantly, acetylation of BRAF reduced its activity regardless of its mutational status at the commonly mutated V600 residue. We also identified a novel phosphorylation site targeted by GSK3 in microphthalmia-associated transcription factor (MITF), the melanocyte master regulator. GSK3 phosphorylation of S69, together with ERK-mediated phosphorylation of the nearby S73 residue, was found to promote MITF nuclear export via a previously undescribed nuclear export signal comprising of the S69, S73, M75, L78 and L80 residues. Importantly, phosphorylation-induced nuclear export was associated with reduced MITF activity, which may have important functional implications for melanocyte development and melanoma oncogenesis. In addition, we showed that the cyclin-dependent kinases CDK1 and CDK2 can also phosphorylate MITF at S73.
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merante, boschin isabella. "MUTAZIONI BRAF NEL CARCINOMA PAPILLARE DELLA TIROIDE." Doctoral thesis, Università degli studi di Padova, 2010. http://hdl.handle.net/11577/3426979.
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Introduction
The papillary thyroid carcinoma (PTC) represents the majority of the differentiated thyroid cancers and its treatment is still debate considering the rare preoperative informations on the prognosis.
Aim
We proposed to assess the prognostic value of BRAF V600E mutation in PTC in view of a better therapeutic approach in terms of surgical and radiometabolic treatment.
Materials and methods
We considered 136 cases of PTC, between October 2008 and September 2009, subdivided in BRAF + and BRAF - and we compared these 2 groups on the basis of sex, age, histothype, TNM, size of the lesion, extracapsular extension, node metastases, multifocality, postoperative Tg level. BRAF V600E mutation analysis was performed, in parallel to classic cytology, in thyroid citoaspirates of 266 patients subdivided in the 5 cytodiagnostic cathegories (THY1, THY2, THY3, THY4, THY5) and subsequently underwent to thyroidectomy+/- node dissection. For each cytodiagnostic cathegory we considered the definitive histological diagnosis of PTC and the presence of BRAFV600E mutation.
Results
The BRAFV600E mutation is associated to age, histological variant of PTC, stages in patients with age>45 years. The prevalence of BRAF V600E mutation among histologically diagnosed PTC patients was 69% and it improved the FNAC diagnostic sensitivity from 84% to 88%.
Conclusions
The BRAF V600E mutation analysis increases the sensitivity of cytology and it represents an useful adjuvant tool in presurgical characterization of thyroid nodules. There is an association between the BRAFV600E mutation and clinicopathological characteristics of the CPT such as age, histological variant and stages.Introduzione Il carcinoma papillare della tiroide (CPT) è il più frequente delle neoplasie tiroidee e il suo trattamento rimane per alcuni aspetti controverso, soprattutto per le scarse informazioni preoperatorie sul livello di aggressività del tumore stesso. Scopo dello studio Questo studio si propone di verificare il ruolo prognostico della mutazione BRAFV600E e di conseguenza la ricaduta di tale mutazione sul trattamento in termini di estensione dell’intervento chirurgico e terapia radioiodometabolica. Materiali e metodi Abbiamo considerato 136 casi di CPT all’esame istologico e li abbiamo distinti in 2 gruppi BRAF + e BRAF– confrontandoli sulla base delle seguenti variabili: sesso, età, istologia definitiva, diametro della lesione, stadiazione, metastasi linfonodali, infiltrazione della capsula, Tireoglobulina (Tg) nel follow up. Abbiamo inoltre ricercato la mutazione BRAFV600E su agoaspirato tiroideo in 266 casi sottoposti a intervento chirurgico di tiroidectomia totale +/- dissezione linfonodale tra ottobre 2008 e settembre 2009 distinti nelle 5 categorie citodiagnostiche (THY1, THY2, THY3, THY4, THY5) e per ciascuna categoria abbiamo verificato la diagnosi istologica di CPT distinguendo i casi BRAF + e BRAF –. Risultati La prevalenza di BRAF mutato nei pazienti operati con diagnosi istologica di CPT è risultata pari a 69%. La mutazione BRAFV600E si è associata a una maggior età, ad una minore frequenza di istotipo papillare variante follicolare e una più elevata frequenza di variante a cellule alte, ad una prevalenza degli stadi 3 e 4 nei pazienti di età > 45 anni. La ricerca di mutazione BRAFV600E ha incrementato la sensibilità della sola citologia dall’84 all'88%. Conclusioni Si conferma una associazione statisticamente significativa tra la presenza di mutazione in BRAF e caratteristiche clinico patologiche più aggressive del CPT, quali età più elevata, varianti istologiche a prognosi peggiore (variante tall cell), stadio più avanzato di malattia. La ricerca di mutazioni BRAF migliora la sensibilità della sola indagine citologica, in particolare in nodi la cui diagnosi citologica possa essere non conclusiva.
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Silva, Rosana Correa da. "ANÁLISE DA MUTAÇÃO V600E DO GENE BRAF E DETECÇÃO IMUNO-HISTOQUÍMICA DA PROTEÍNA BRAF EM CARCINOMAS PAPILÍFEROS DE TIREÓIDE." Pontifícia Universidade Católica de Goiás, 2012. http://localhost:8080/tede/handle/tede/2345.
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Previous issue date: 2012-03-28Papillary carcinomas are the most common tumors of the thyroid, corresponding to 80% of all tumors that affect the gland. In such tumors, a common mutation at the BRAF gene has been detected, comprising a nucleotide transversion, T1799A, at the exon 15 of gene. This mutation has been identified in about 50 % of the thyroid papillary carcinomas (TPC). Clinical and experimental studies have demonstrated important associations between BRAF mutations and different TPC clinical factors related to tumor progression, invasion and recurrence. The objective of this study was to analise BRAF protein expression, by using immunohistochemistry, and V600E BRAF mutations in a group of patients with thyroid papillary carcinoma. BRAF protein expression and V600E BRAF mutations were compared to TPC clinical and pathological aspects. The study group comprised 116 TPC patients that were selected at the Pathology Department of Hospital Araujo Jorge, in Goiânia. BRAF immunohistochemical analysis employed a labeled polymer peroxidase method and primary BRAF monoclonal antibody (clone F-7), Santa Cruz Biotechnology Inc. BRAF V600E molecular analysis was carried by PCR (Polimerase Chain Reaction) associated to RFLP (Restriction Fragment Length Polymorphism). Statistical analysis was performed by using univariate analysis (Chi-square test with Yates correction, and Fischer). Our results indicated that BRAF overexpression was detected in 54 TPC cases (46.0%), while BRAF V600E mutation was detected in 74 TPC cases (63.8%). Significant associations were detected between BRAF overexpression with distant metastasis (p=0.001) and tumor extrathyroidal extensions (p=0.0183). BRAF V600E mutations were significantly associated with lymph nodes methastasis (p=0.0385) and BRAF protein overexpression (p=0.0063).
Os carcinomas papilíferos são os tumores mais comuns da tireóide, sendo responsáveis por 80% de todos os cânceres da glândula. Nesses tumores, uma mutação comum no gene BRAF tem sido observada, compreendendo a transversão do nucleotídeo T1799A, localizado no exon 15, verificada em 50% dos carcinomas papilíferos de tireóide (CPT). Essa mutação acarreta a substituição do aminoácido valina na posição 600 da proteína, por ácido glutâmico, sendo assim designada V600E. Estudos experimentais e clínicos têm mostrado uma associação entre a mutação do gene BRAF e diferentes parâmetros clínicos de progressão, invasão e recorrência no CPT. O objetivo deste estudo foi detectar os níveis da proteína BRAF utilizando o método de imuno-histoquímica, e avaliar a mutação V600E do gene BRAF em um grupo de pacientes com carcinoma papilífero de tireóide. A detecção imuno-histoquímica da proteína BRAF e a mutação V600E do gene BRAF, foram comparadas em relação aos aspectos clínico-patológicos dos tumores. O grupo de estudo incluiu 116 pacientes com carcinoma papilífero de tireóide, selecionados no Setor de Anatomia Patológica do Hospital Araújo Jorge, em Goiânia-GO. A análise imuno-histoquímica utilizou o método da imunoperoxidase associada a polímeros e o anticorpo BRAF (clone F-7) Santa Cruz Biotechnology Inc. A análise molecular da mutação V600E do gene BRAF foi realizada por meio de PCR (reação em cadeia da polimerase) e RFLP (polimorfismo de comprimento de fragmentos de restrição). As análises estatísticas incluiram o teste do Chi-quadrado com correção de Yates e o teste exato de Fisher. Nossos resultados mostraram que a hiperexpressão de BRAF foi detectada em 54 casos (46%) e a mutação V600E do gene BRAF em 74 casos (63,8%). Dentre as associações investigadas, resultados significativos foram observados entre a hiperexpressão da proteína BRAF e extensão extra-tireoideana do tumor (p=0,0183). A presença da mutação V600E do gene BRAF foi associada as metástases linfonodais (p=0,0385) e à hiperexpressão da proteína BRAF (p=0,0063).
Books on the topic "BRAF35"
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Haf braf. [Talybont, Ceredigion]: Y Lolfa, 2010.
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Cowley, Joy. Gwenu'n braf. (Walton-on-Thames): (Nelson), 1991.
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Pizer, Abigail. Mae'n ddiwrnod braf. Llandysul: Gomer, 1993.
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Cowley, Joy. Mae nofio'n braf. Pontypridd: Uned Iaith Genedlaethol Cymru, 1992.
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Tina, Macnaughton, and Sioned Lleinau, eds. Un diwrnod braf. Llandysul: Gwasg Gomer, 2010.
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Light, John. Mae'n braf allan. Swindon: Child's Play, 1990.
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Sullivan, Ryan J., ed. BRAF Targets in Melanoma. New York, NY: Springer New York, 2015. http://dx.doi.org/10.1007/978-1-4939-2143-0.
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Hustad, Thomas P. Born to play: The Ruby Braff discography and directory of performances. Lanham, Md: Scarecrow Press, 2012.
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Born to play: The Ruby Braff discography and directory of performances. Lanham, Md: Scarecrow Press, 2012.
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Braff, Richard E. The Braff silent short film working papers: Over 25,000 films, 1903-1929, alphabetized and indexed. Jefferson, N.C: McFarland & Co., 2002.
Find full textBook chapters on the topic "BRAF35"
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Furlan, Daniela, and Nora Sahnane. "BRAF." In Encyclopedia of Pathology, 1–3. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-319-28845-1_5150-1.
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Furlan, Daniela, and Nora Sahnane. "BRAF." In Endocrine Pathology, 91–93. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-62345-6_5150.
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Mose, Stephan, Stephan Mose, Brandon J. Fisher, Iris Rusu, Charlie Ma, Lu Wang, Larry C. Daugherty, et al. "BRAF-V600E." In Encyclopedia of Radiation Oncology, 63. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/978-3-540-85516-3_733.
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Mose, Stephan, Stephan Mose, Brandon J. Fisher, Iris Rusu, Charlie Ma, Lu Wang, Larry C. Daugherty, et al. "BRAF Inhibitors." In Encyclopedia of Radiation Oncology, 63. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/978-3-540-85516-3_744.
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Brummer, Tilman. "BRaf-Signaling." In Encyclopedia of Cancer, 598–604. Berlin, Heidelberg: Springer Berlin Heidelberg, 2017. http://dx.doi.org/10.1007/978-3-662-46875-3_704.
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Shih, Helen. "BRAF in NSCLC." In Targeted Therapies in Lung Cancer: Management Strategies for Nurses and Practitioners, 39–49. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-16550-5_5.
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Brummer, Tilman. "BRAF Somatic Alterations." In Encyclopedia of Cancer, 604–8. Berlin, Heidelberg: Springer Berlin Heidelberg, 2017. http://dx.doi.org/10.1007/978-3-662-46875-3_705.
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Daud, Adil, and Boris C. Bastian. "Beyond BRAF in Melanoma." In Therapeutic Kinase Inhibitors, 99–117. Berlin, Heidelberg: Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/82_2011_163.
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McCoppin, Holly H. "Cutaneous Reactions to BRAF Inhibitors." In Cutaneous Drug Eruptions, 341–51. London: Springer London, 2015. http://dx.doi.org/10.1007/978-1-4471-6729-7_32.
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Cooper, Zachary A., Zain Ahmed, and Jennifer A. Wargo. "Combination BRAF-Directed Therapy and Immunotherapy." In Cancer Drug Discovery and Development, 163–82. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-2143-0_8.
Full textConference papers on the topic "BRAF35"
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Li, Ying-Ying, Niramol Savaraj, Chunjing Wu, Shumei Chen, Medhi Wangpaichitr, Macus T. Kuo, and Lynn G. Feun. "Abstract 2900: Biochemical alterations in BRAF inhibitor (BRAFi) resistant melanoma cells increase their vulnerability to arginine deprivation." In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-2900.
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Banjin, Maja, Amina Jalovčić, and Velda Smajlbegović. "CILJANA TERAPIJA I METASTATSKI MELANOM." In Okrugli sto s međunarodnim učešćem "Melanom". Akademija nauka i umjetnosti Bosne i Hercegovine, 2018. http://dx.doi.org/10.5644/pi2019.180.02.
Full textAbstract:
Melanom je globalni zdravstveni problem s kontinuiranim porastom u incidence. Rezultati tretmana metastatskog melanoma su, do skorašnjih napredovanja u terapijama, bili slabi, s medijanom ukupnog preživljavanja (OS) od 7,5 mjeseci i petogodišnjom stopom preživljavanja 6%. U kliničkim istraživanjima za metastatski melanom, selektivni inhibitori BRAF gena, vemurafenib i dabrafenib, pokazali su značajnu antitumorsku aktivnost i poboljšanje u OS i PFS kada se porede s dakarbazinom. Međutim, skoro će svaki pacijent tretiran BRAF inhibitorima imati progresiju bolesti, a tumori pokazuju reaktivacije MAPK puta u vrijeme pojave rezistencije. Specifična BRAF inhibicija vodi ka paradoksalnoj aktivaciji ćelija s RAS divljim “wild” genom uzvodno u MAPK putu i iz tih razloga vodi rezistenciji na terapiju, ćelijskoj proliferaciji i povećanoj stopi RAS kožnog toksiciteta. Pretklinički podaci sugerisali su da inhibitori MEK gena u MAPK putu mogu da zaustave rast i isprovociraju ćelijsku smrt kod nekih BRAF pozitivnih melanomskih tumora. Selektivni inhibitori MEK1 i MEK2 su cobimetinib i trametinib. Kombinovanjem BRAF+MEK inhibicije postiže se produženje terapijskog odgovora, odgađanje rezistencija i smanjuje pojava novih kutanih SCC/KA udruženih s BRAF inhibicijom. Kombinacija dabrafenib+ trametinib i vemurafenib+cobimetinib odobrena je za pacijente s neresktabilnim ili metastatskim melanomom s tumorima koji imaju mutaciju na BRAF genu. Klinička vrijednost intermitentne terapije za sada nije definisana. Podaci iz kliničkih istraživanja sugerišu da selekcionirani pacijenti mogu imati benefit od terapije uprkos razvijanju novih metastaza. Uvođenje ovih terapija u adjuvantno područje može dodatno poboljšati ishod i liječenje ove bolesti.
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Kandolf Sekulović, Lidija. "TOXICITIES OF TARGETED THERAPY AND IMMUNE-RELATED ADVERSE DRUG REACTIONS OF IMMUNOTHERAPY IN THE TREATMENT OF METASTATIC MELANOMA." In Okrugli sto s međunarodnim učešćem "Melanom". Akademija nauka i umjetnosti Bosne i Hercegovine, 2018. http://dx.doi.org/10.5644/pi2019.180.04.
Full textAbstract:
Targeted therapy and immunotherapy changed the treatment landscape for metastatic melanoma, which is chemotherapy resistant cancer. In pre-innovation era, the overall survival of patients with metastatic melanoma was 6 months, while today 5-year overall survival rate of 34% (and 50% in good prognostic groups) is evident. However, both treatments have their side effects, and cutaneous are the most frequent. Treating physicians in oncology centres, but also primary care specialists, need to be aware of their spectrum which differs for each class of drug: BRAF inhibitors, MEK inhibitors and immunotherapy with anti-PD1 and anti-CTLA4. While BRAF inhibitors have the most prominent adverse effects which are class specific, there are also drug-specific adverse effects. For example, vemurafenib causes photosensitivity, which is not specific for dabrafenib, while dabrafenib induces pyrexia, that occurs much less frequently with other BRAF inhibitors. Cutaneous rash and cutaneous neoplasms which develop due to paradoxical activation of RAS signalling are described with BRAF inhibitor monotherapy. These side-effects are much less common in combination therapy with BRAF and MEK inhibitor, but MEK inhibitor itself causes characteristic acneiform eruption, and serous retinopathy. Immune related adverse drug reactions are a hallmark of the immune checkpoint inhibitor immunotherapy, which can affect every organ system, and most commonly skin, lungs and gastrointestinal system, with differential frequencies recorded with anti-CTLA4 therapy and anti PD-1 therapy. Skin reactions most frequently include pruritus and eczematous reactions, as well as vitiligo-like hypopigmentation, which is linked Melanom 45 to the better response to treatment. In this review, frequent and rare side effects are presented, as well as the current algorithms for their treatment.
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Amaria, Rodabe N., Van A. Trinh, Jun Gu, Susan McIntyre, Carlos Torres Cabala, Rinata Simien, Adi Diab, et al. "Abstract 3640: Treatment strategies using anti-PD1/PD-L1 (anti-PD) and BRAF/MEK inhibitor (BRAFi) therapy: a retrospective study comparing sequential vs. concurrent administration in BRAF-mutated metastatic melanoma (BMMM)." In Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.am2018-3640.
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Sachett, Mariana Linhares, GIANCARLLO DANEZI FELIN, GIULLIANO DANEZI FELIN, CAROLLINA DANEZI FELIN, and FELLIPE DANEZI FELIN. "GENÉTICA MOLECULAR DO MELANOMA MALÍGNO: UM ALVO TERAPÊUTICO." In I Congresso Nacional de Pesquisas e Estudos Genéticos On-line. Revista Multidisciplinar em Saúde, 2022. http://dx.doi.org/10.51161/geneticon/9012.
Full textAbstract:
Introdução: O melanoma maligno corresponde a 4% das neoplasias malignas da pele e é responsável por 90% dos óbitos por câncer nesse sítio primário. A alta mortalidade torna seu estudo altamente relevante. Até por volta de 2011, as estratégias antineoplásicas disponíveis para o melanoma avançado eram limitadas. Objetivos: Elucidar a importância da genética molecular na escolha do tratamento antineoplásico do melanoma maligno. Metodologia: Revisão de literatura através de pesquisa de artigos realizada na base de dados MEDLINE, via PubMed, utilizando-se os seguintes termos DeCS/ MeHS: "melanoma" [AND] “molecular targeted therapy" [AND] "immunotherapy”. Ao usar os filtros “textos completos” e “1 ano” foram encontrados 36 resultados. Após aplicados os critérios de inclusão (texto completo, 1 ano e adequação a temática proposta) e de exclusão (todos que não atendessem aos critérios de inclusão e artigos duplicados), foram selecionados 9 artigos para compor essa revisão. Realizada a extração dos dados e análise para redação da revisão. Resultados: Aproximadamente 50% dos melanomas malignos exibem mutação BRAF, enquanto que 20% apresentam mutação NRAS e mais raramente, mutação cKit. A identificação do tipo de mutação associada ao melanoma é de extremo valor, pois é capaz de direcionar para uma forma distinta de terapia alvo molecular (TAM) e ou imunoterapia (IMT), em especial nos casos avançados. Melanomas metastáticos com mutação BRAF tem indicação terapêutica do uso de TAM combinada com utilização de inibidores BRAF e inibidores MEK, devendo ainda ser associada a IMT através dos inibidores do checkpoint imunológico (anti-PD-1 e anti-CTLA-4). Conclusão: Através dessa revisão de literatura foi possível identificar que as bases genéticas e moleculares que compõem o genótipo maligno do melanoma, determinam novas promissoras terapias adjuvantes, o que inclui a TAM e a IMT para casos avançados. Portanto, foi possível elucidar a importância da genética molecular do melanoma para o seu tratamento oncológico adequado. Adicionalmente, foi possível reconhecer que a TAM e a IMT são indicações limitadas ao melanoma metastático com mutação BRAF detectada, permanecendo as incertezas em relação aos casos que não são avançados e que exibem mutações detectadas.
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Al Hashmi, Muna, Konduru Sastry, Lee Silcock, Lotfi Chouchane, Valentina Mattei, Barbara Seliger, Ena Wang, Francesco Marincola, and Sara Tomei. "Differential Responsiveness to Braf Inhibitors of Melanoma Cell Lines Braf V600e-Mutated." In Qatar Foundation Annual Research Conference Proceedings. Hamad bin Khalifa University Press (HBKU Press), 2016. http://dx.doi.org/10.5339/qfarc.2016.hbpp2578.
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Paoluzzi, Luca, Douglas Hanniford, Elena Sokolova, Iman Osman, Farbod Darvishian, Jinhua Wang, James E. Bradner, and Eva Hernando. "Abstract 3522: BET and BRAF inhibitors act synergistically against BRAF mutant melanoma." In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-3522.
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Xing, Feng, Yogindra Persaud, Christine Pratilas, Manickam Janakiraman, Qing‐Bai She, Cailian Liu, Igor Dolgalev, et al. "Abstract B87: Genomic complexity and BRAF/MEK‐dependence in V600E BRAF mutant melanoma." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Nov 15-19, 2009; Boston, MA. American Association for Cancer Research, 2009. http://dx.doi.org/10.1158/1535-7163.targ-09-b87.
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Delgado-Goni, Teresa, Slawomir Wantuch, Paul Workman, Richard Marais, Martin Leach, and Mounia Beloueche-Babari. "Abstract 1130: Unveiling the metabolic response of BRAF mutant melanoma cells to BRAF inhibition." In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-1130.
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Lutterbach, Bart, Chris Ware, Lenora Davis, Qing Zhang, Leigh Zawel, John Reilly, and Bo-Sheng Pan. "Abstract 1065: Growth factor-mediated resistance to BRAF/MEK inhibitors in BRAF mutant melanoma." In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-1065.
Full textReports on the topic "BRAF35"
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Ragunathan, Yoithapprabhunath Thuckanaickenpalayam, Srichinthu Kenniyan Kumar, Deepak Gupta, Diksha Singh, Swetha Pasupuleti, and Madhavan Nirmal Ramdas. Effectiveness of Neoadjuvant Molecular-Targeted Chemotherapy in Ameloblastoma - A Systematic Review. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, June 2022. http://dx.doi.org/10.37766/inplasy2022.6.0018.
Full textAbstract:
Review question / Objective: The aim of this article is to obtain an in-depth review of ameloblastoma tumor to determine the available level of evidence and the possible benefit of targeted therapeutics for the treatment of BRAF V600E mutation in ameloblastoma tumor. Condition being studied: Ameloblastoma is an epithelium-derived odontogenic tumour that evolved since the prehistoric era. Ameloblastoma is unique among the odontogenic neoplasms occurring in the jaws, because of its locally invasive behaviour and high recurrence rate. Facial asymmetry, displacement of teeth, malocclusion, and pathologic fractures are some of the asymmetrical features that ameloblastoma is known to cause. If left untreated, they often lead to wide tissue destruction and deformity. For the treatment of ameloblastomas, conventional chemotherapy and radiation have been unexplored or contraindicated and to date, wide surgical resection is the only treatment of choice for ameloblastoma tumours, resulting in post-treatment compromised quality of life in the individuals.