15 research outputs found

    PIK3CA mutation in HPV-associated OPSCC patients receiving deintensified chemoradiation

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    PIK3CA is the most frequently mutated gene in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). Prognostic implications of such mutations remain unknown. We sought to elucidate the clinical significance of PIK3CA mutations in HPV-associated OPSCC patients treated with definitive chemoradiation (CRT). Seventyseven patients with HPV-associated OPSCC were enrolled on two phase II clinical trials of deintensified CRT (60 Gy intensitymodulated radiotherapy with concurrent weekly cisplatin). Targeted next-generation sequencing was performed. Of the 77 patients, nine had disease recurrence (two regional, four distant, three regional and distant). Thirty-four patients had mutation( s) identified; 16 had PIK3CA mutations. Patients with wild-type-PIK3CA had statistically significantly higher 3-year disease-free survival than PIK3CA-mutant patients (93.4%, 95% confidence interval [CI] = 85.0% to 99.9% vs 68.8%, 95% CI = 26.7% to 89.8%; P=.004). On multivariate analysis, PIK3CA mutation was the only variable statistically significantly associated with disease recurrence (hazard ratio = 5.71, 95% CI = 1.53 to 21.3; P=.01). PIK3CA mutation is associated with worse diseasefree survival in a prospective cohort of newly diagnosed HPV-associated OPSCC patients treated with deintensified CRT

    Oncogenic Signaling Pathways in The Cancer Genome Atlas

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    Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFb signaling, p53 and beta-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy

    Quantitative analysis of shoot development and branching patterns in Actinidia

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    Qualidade de goiaba-serrana em resposta à temperatura de armazenamento e ao tratamento com 1-metilciclopropeno Fruit quality of feijoas in response to storage temperature and treatment with 1-methylcyclopropene

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    Os objetivos deste trabalho foram caracterizar a fisiologia e avaliar os efeitos da temperatura e da aplicação de 1-metilciclopropeno (1-MCP) na qualidade pós-colheita de frutos de goiaba-serrana (Acca selowiana), em acessos do banco ativo de germoplasma da Empresa de Pesquisa Agropecuária e Extensão Rural de Santa Catarina. Os frutos foram colhidos na maturação comercial. Os genótipos Brasil (acesso 387) e Uruguai (acesso 454) foram avaliados quanto ao comportamento respiratório e de produção de etileno a 20ºC, e taxas respiratórias e alterações na cor da casca a 0, 5, 10, 20 e 30ºC. O genótipo Brasil (acesso 242) foi avaliado quanto ao amadurecimento a 4ºC, após tratamento com 1-MCP (0, 500 e 1.500 ppb). Os genótipos Brasil (acesso 387) e Uruguai (acesso 454) apresentaram comportamento climatérico, com picos de produção de etileno e de taxa respiratória aos 8 e 12 dias de armazenamento a 20ºC, respectivamente. Não houve diferença significativa entre as taxas respiratórias e de produção de etileno entre os genótipos, nessa temperatura. Houve aumento substancial na taxa respiratória em ambos os genótipos, com o aumento de 0 para 30ºC, com coeficiente metabólico de 3,5 aproximadamente. Com o aumento na temperatura, houve maior alteração na cor verde da epiderme, em frutos do tipo Brasil, e maior escurecimento da epiderme, em frutos do tipo Uruguai. Frutos do genótipo Brasil (acesso 242), tratados com 1-MCP e armazenados a 4ºC, apresentaram retardamento no amadurecimento.<br>The objectives of this work were to characterize the postharvest physiology and to evaluate the effects of temperature and treatment with 1-methylcyclopropene (1-MCP) on the postharvest quality of fruits of feijoa (Acca selowiana) accessions from the germplasm bank of Empresa de Pesquisa Agropecuária e Extensão Rural de Santa Catarina. Fruits were harvested at commercial maturity. The genotypes Brasil (accession no. 387) and Uruguai (accession no. 454) were evaluated for respiration and ethylene production at 20ºC, and respiration rates and skin color alterations at 0, 5, 10, 20, 30ºC. The genotype Brasil (accession no. 242) was evaluated for ripening at 4ºC, after treatment with 1-MCP (0, 500 and 1,500 ppb). Brasil (accession no. 387) and Uruguai (accession no. 454) exhibited a climacteric pattern, with a peak of ethylene evolution and respiration rate at the 8th and 12th days of storage at 20ºC, respectively. There was no significant difference for respiration rates and ethylene evolution between these genotypes at this temperature. There was a substantial increase of respiration rate in both genotypes with the increase in temperature from 0 to 30ºC, with a metabolic coefficient of approximately 3.5. With the increase in temperature, fruits of the genotype Brasil showed the greatest change of skin green color, while fruits of the genotype Uruguai exhibited the greatest darkening of skin. Feijoa fruits of genotype Brasil (accession no. 242) had delayed ripening when treated with 1-MCP and stored at 4ºC
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