Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Valproic acid combined with cisplatin-based chemoradiation in locally advanced head and neck squamous cell carcinoma patients and associated biomarkers

Texto completo
Autor(es):
Mostrar menos -
Mak, Milena Perez [1] ; Pasini, Fatima Solange [2] ; Diao, Lixia [3] ; Teixeira Garcia, Fabyane O. [2] ; Takahashi, Tiago Kenji [1] ; Nakazoto, Denyei [1] ; Martins, Renata Eiras [1] ; Almeida, Cristiane Maria [1] ; Vamondes Kulcsar, Marco Aurelio [4] ; Lamounier, Valdelania Aparecida [1] ; Nunes, Emily Montosa [2] ; de Souza, Isabela Cristina [2] ; Taveira Garcia, Marcio Ricardo [5] ; Amadio, Alex Vieira [1] ; Siqueira, Sheila Aparecida C. [6] ; Longo Snitcovsky, Igor Moyses [2] ; Sichero, Laura [2] ; Wang, Jing [4] ; de Castro Jr, Gilberto
Número total de Autores: 19
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Dept Med Oncol, Inst Canc Estado Sao Paulo, Hosp Clin, Fac Med, Av Dr Arnaldo, 251 12th Floor, BR-01246000 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Ctr Translat Invest Oncol, Inst Canc Estado Sao Paulo, Hosp Clin, Fac Med, Av Dr Arnaldo, 251 12th Floor, BR-01246000 Sao Paulo, SP - Brazil
[3] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, 1400 Pressler St Floor 4, FCT4-6000, Houston, TX 77030 - USA
[4] Univ Sao Paulo, Head & Neck Surg Dept, Inst Canc Estado Sao Paulo, Hosp Clin, Fac Med, Av Dr Arnaldo, 251 12th Floor, BR-01246000 Sao Paulo, SP - Brazil
[5] Univ Sao Paulo, Dept Radiol, Inst Canc Estado Sao Paulo, Hosp Clin, Fac Med, Av Dr Arnaldo, 251 12th Floor, BR-01246000 Sao Paulo, SP - Brazil
[6] Univ Sao Paulo, Dept Pathol, Hosp Clin, Fac Med, Av Dr Eneas Carvalho Aguiar 255, BR-05403000 Sao Paulo, SP - Brazil
Número total de Afiliações: 6
Tipo de documento: Artigo Científico
Fonte: ECANCERMEDICALSCIENCE; v. 14, DEC 15 2020.
Citações Web of Science: 0
Resumo

Background: Cisplatin-based chemoradiation (CCRT) offers locally advanced head and neck squamous cell carcinoma (LAHNSCC) patients high local control rate, however, relapses are frequent. Our goal was to evaluate if association of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, with CCRT improved response rate (RR) and associated biomarkers. Methods: This phase II trial included patients with unresectable locally advanced (LA) oropharynx (OP) squamous cell carcinoma. CCRT began after 2 weeks of VPA (P1). Primary goal was RR at 8 weeks after chemoradiation (CRT)+VPA (P2). Biomarkers included microRNA (miR) polymerase chain reaction (PCR)-array profiling in plasma compared to healthy controls by two-sample t-test. Distribution of p-values was analysed by beta-uniform mixture. Findings were validated by real-time PCR quantitative polymerase chain reaction (qPCR) for selected miRs in plasma and saliva. p16, HDAC2 and RAD23 Homolog B, Nucleotide Excision Repair Protein (HR23B) tumour immunohistochemistry were evaluated. Results: Given significant toxicities, accrual was interrupted after inclusion of ten LA p16 negative OP patients. All were male, smokers/ex-smokers, aged 41-65 and with previous moderate/high alcohol intake. Nine evaluable patients yielded a RR of 88%. At false discovery rate of 5%, 169 miRs were differentially expressed between patients and controls, including lower expression of tumour suppressors (TSs) such as miR-31, -222, -let-7a/b/e and -145. miR-let-7a/e expression was validated by qPCR using saliva. A HDAC2 H-score above 170 was 90% accurate in predicting 6-month disease-free survival. Conclusions: VPA and CRT offered high RR; however, with prohibitive toxicities, which led to early trial termination. Patients and controls had a distinct pattern of miR expression, mainly with low levels of TS miRs targeting Tumor protein P53 (TP53). miR-let-7a/e levels were lower in patients compared to controls, which reinforces the aggressive nature of such tumours (NCT01695122). (AU)

Processo FAPESP: 15/01584-1 - Expressão de HDAC2 e HR23B no tumor primário e modulação de acetilação de histonas em células mononucleares circulantes de pacientes portadores de carcinoma epidermoide de boca e orofaringe sob tratamento com quimiorradioterapia e ácido valproico
Beneficiário:Alex Vitorio Amadio
Linha de fomento: Bolsas no Brasil - Iniciação Científica
Processo FAPESP: 14/26965-5 - Avaliação da eficácia de ácido valproico combinado ao tratamento padrão de quimiorradioterapia concomitante baseada em cisplatina, em pacientes portadores de carcinoma epidermoide de cabeça e pescoço localmente avançado
Beneficiário:Gilberto de Castro Junior
Linha de fomento: Auxílio à Pesquisa - Regular