GILBERTO DE CASTRO JUNIOR

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Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder

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  • conferenceObject
    Canopy-1: Phase 3 Study of Canakinumab/Placebo
    (2020) FELIP, E.; JR, G. Castro; GREYSTOKE, A.; SOLOMON, B.; TAN, D. S. W.; GROHE, C.; PASSOS, V. Q.; DEUDON, S.; LOUVEAU, A. L.; ARTICUS, K.; JOHNSON, B.
  • conferenceObject
    Pembrolizumab (P) or P plus chemotherapy (C) versus EXTREME (E) as first-line (1L) therapy for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): analysis of KEYNOTE-048 by disease state.
    (2020) RISCHIN, Danny; HARRINGTON, Kevin Joseph; GREIL, Richard; SOULIERES, Denis; TAHARA, Makoto; CASTRO, Gilberto; PSYRRI, Amanda; BASTE, Neus; NEUPANE, Prakash C.; BRATLAND, Ase; FUEREDER, Thorsten; HUGHES, Brett Gordon Maxwell; MESIA, Ricard; NGAMPHAIBOON, Nuttapong; RORDORF, Tamara; ISHAK, Wan Zamaniah Wan; LIN, Jianxin; GUMUSCU, Burak; SWABY, Ramona F.; BURTNESS, Barbara
  • conferenceObject
    Radiation Pneumonitis in Patients with Interstitial Lung Disease and Lung Cancer: Report of 6 Cases
    (2020) FREITAS, L. V. de; SERRA, J. P.; NAJAS, G. F.; PRADO, G. F.; KAWASSAKI, A. M.; TAKAGAKI, T. Y.; GABRIELLI, F.; JUNIOR, G. C.; OLIVEIRA, M. R.; KAIRALLA, R. A.; BALDI, B. G.
  • article 5 Citação(ões) na Scopus
    Real-World Molecular Testing and Treatment Patterns in Brazilian Patients with Newly Diagnosed Locally Advanced or Metastatic NSCLC
    (2020) CRONEMBERGER, Eduardo; BALDOTTO, Clarissa; MARINHO, Felipe; MARCHI, Pedro De; ARAUJO, Luiz Henrique; FRANKE, Fabio; SALLES, Paulo; CALABRICH, Aknar; ALMEIDA, Thais; CUSTODIO, Marcelo Graziano; MARIA, Andre Santa; PEREIRA, Marcelo Horacio; CASTRO JR., Gilberto
    OBJECTIVES: To evaluate the molecular testing and treatment patterns in a retrospective cohort of newly diagnosed treatment-naive patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). METHODS: This is an observational retrospective cohort study conducted across 10 cancer centers in Brazil. Treatment-naive patients with locally advanced or metastatic NSCLC were enrolled from January to December 2014. The following data were collected from the medical records of patients from diagnosis until the last record (death, loss to follow-up, or the end of the maximum follow-up period): demographics; medical history; smoking status; disease characteristics; previous treatments; and molecular testing patterns and results. The overall survival (OS) was also estimated. Results: A total of 391 patients from 8 different Brazilian states were included, with a median age of 64.1 years (23.7-98.7), with most patients being males (60.1%). The smoking status of 74.2% of patients was a 'former' or 'current smoker'. Stage IV NSCLC at diagnosis was observed in 82.4% of patients, with 269 of them (68.8%) presenting adenocarcinoma (ADC). Among the stage IV ADC patients, 54.0% were referred for molecular testing. Among the patients with an available epidermal growth factor receptor (EGFR) mutation status, 31 (24.0%) were EGFR-positive. The first-line treatment was a platinum-based chemotherapy for 98 patients (25.1 %), while non-platinum-based regimens were used in 54 patients (13.8%). OS data were available for 370 patients, with a median OS of 10.8 months. Never smokers had a significantly higher median OS versus current or former smokers (14.6 versus 9.1 months; log-rank p=0.003). Among the patients for whom molecular testing data were available, those with EGFR-positive results had a longer median OS (34.6 versus 12.8 months; log-rank p=0.003). Conclusion: Our findings provide relevant information for prescribers and policy decision-makers by highlighting the unmet needs of patients and the importance of molecular testing in newly diagnosed locally advanced or metastatic lung adenocarcinoma. We also highlight the respective EGFR-tyrosine kinase inhibitor treatment when the result is positive and the areas in which further efforts are required to grant access to effective treatment.
  • article 21 Citação(ões) na Scopus
    Exercise training reverses cancer-induced oxidative stress and decrease in muscle COPS2/ TRIP15/ALIEN
    (2020) ALVES, Christiano R. R.; NEVES, Willian das; ALMEIDA, Ney R. de; EICHELBERGER, Eric J.; JANNIG, Paulo R.; VOLTARELLI, Vanessa A.; TOBIAS, Gabriel C.; BECHARA, Luiz R. G.; FARIA, Daniele de Paula; ALVES, Maria J. N.; HAGEN, Lars; SHARMA, Animesh; SLUPPHAUG, Geir; MOREIRA, Jose B. N.; WISLOFF, Ulrik; HIRSHMAN, Michael F.; NEGRAO, Carlos E.; CASTRO JR., Gilberto de; CHAMMAS, Roger; SWOBODA, Kathryn J.; RUAS, Jorge L.; GOODYEAR, Laurie J.; BRUM, Patricia C.
    Objective: We tested the hypothesis that exercise training would attenuate metabolic impairment in a model of severe cancer cachexia. Methods: We used multiple in vivo and in vitro methods to explore the mechanisms underlying the beneficial effects induced by exercise training in tumor-bearing rats. Results: Exercise training improved running capacity, prolonged lifespan, reduced oxidative stress, and normalized muscle mass and contractile function in tumor-bearing rats. An unbiased proteomic screening revealed COP9 signalosome complex subunit 2 (COPS2) as one of the most downregulated proteins in skeletal muscle at the early stage of cancer cachexia. Exercise training normalized muscle COPS2 protein expression in tumor-bearing rats and mice. Lung cancer patients with low endurance capacity had low muscle COPS2 protein expression as compared to agematched control subjects. To test whether decrease in COPS2 protein levels could aggravate or be an intrinsic compensatory mechanism to protect myotubes from cancer effects, we performed experiments in vitro using primary myotubes. COPS2 knockdown in human myotubes affected multiple cellular pathways, including regulation of actin cytoskeleton. Incubation of cancer-conditioned media in mouse myotubes decreased F-actin expression, which was partially restored by COPS2 knockdown. Direct repeat 4 (DR4) response elements have been shown to positively regulate gene expression. COPS2 overexpression decreased the DR4 activity in mouse myoblasts, and COPS2 knockdown inhibited the effects of cancer-conditioned media on DR4 activity. Conclusions: These studies demonstrated that exercise training may be an important adjuvant therapy to counteract cancer cachexia and uncovered novel mechanisms involving COPS2 to regulate myotube homeostasis in cancer cachexia. (C) 2020 The Author(s).
  • conferenceObject
    Long-term outcomes from KEYNOTE-048: Pembrolizumab (pembro) alone or with chemotherapy (pembro plus C) vs EXTREME (E) as first-line (1L) therapy for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC)
    (2020) GREIL, R.; RISCHIN, D.; HARRINGTON, K. J.; SOULIERES, D.; TAHARA, M.; CASTRO, G. de; PSYRRI, A.; BASTE, N.; NEUPANE, P.; BRATLAND, A.; FUEREDER, T.; HUGHES, B. G. M.; SR., R. Mesia; NGAMPHAIBOON, N.; RORDORF, T.; ISHAK, W. Z. Wan; LIN, J.; SWABY, R. F.; GUMUSCU, B.; BURTNESS, B.
  • conferenceObject
    KEYNOTE-048: Progression after the next line of therapy following pembrolizumab (P) or P plus chemotherapy (P plus C) vs EXTREME (E) as first-line (1L) therapy for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).
    (2020) HARRINGTON, Kevin Joseph; RISCHIN, Danny; GREIL, Richard; SOULIERES, Denis; TAHARA, Makoto; CASTRO, Gilberto; PSYRRI, Amanda; BASTE, Neus; NEUPANE, Prakash C.; BRATLAND, Ase; FUEREDER, Thorsten; HUGHES, Brett Gordon Maxwell; MESIA, Ricard; NGAMPHAIBOON, Nuttapong; RORDORF, Tamara; ISHAK, Wan Zamaniah Wan; ZHANG, Yayan; GUMUSCU, Burak; SWABY, Ramona F.; BURTNESS, Barbara
  • article 33 Citação(ões) na Scopus
    Global prevalence of human papillomavirus-driven oropharyngeal squamous cell carcinoma following the ASCO guidelines: A systematic review and meta-analysis
    (2020) MARIZ, Bruno Augusto Linhares Almeida; KOWALSKI, Luiz Paulo; JR, William Nassib William; CASTRO, Gilberto de; CHAVES, Aline Lauda Freitas; SANTOS, Marcos; OLIVEIRA, Thiago Bueno de; ARAUJO, Anna Luiza Damaceno; NORMANDO, Ana Gabriela Costa; RIBEIRO, Ana Carolina Prado; BRANDAO, Thais Bianca; VARGAS, Pablo Agustin; LOPES, Marcio Ajudarte; SANTOS-SILVA, Alan Roger
    Objectives: to provide accurate information about the global prevalence of human papillomavirus (HPV) in oropharyngeal squamous cell carcinomas (OPSCC). Material and methods: a systematic review was performed using three main electronic databases. Studies were independently assessed by two reviewers based on established eligibility criteria, to identify the prevalence of HPV-driven OPSCC following criteria defined by the American Society of Clinical Oncology. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. Statistical software MedCalc was used to perform meta-analyses. Results: from 2215 records found, 15 were included, reporting data from 6009 patients (time period range: 1980-2016), distributed in 11 countries. Eleven studies were considered as presenting low risk, and four as moderate risk of bias. Using proportion meta-analysis, pooled prevalence of HPV-driven OPSCC was 44.8 % (95 %CI: 36.4-53.5 %; i(2) = 97.6 %), with the highest rates in New Zealand (74.5 %; 95 %CI: 60.9-85.3 %), and the lowest in Brazil (11.1 %; 95 %CI: 4.5-21.5 %). HPV prevalence was similar between males (45.7 %; 95 %CI: 36.5-55.0 %; i(2) = 96.4 %) and females (42.2 %; 95 %CI: 34.3- 50.5 %; i(2) = 85.4 %). Mean/median age ranged from 59.1-67.1 years in the HPV-negative group, and from 55.7-63.5 years in the HPV-positive group. There was an overall discordance between testing by p16 (49.4 %; 95 %CI, 38.2-60.5 %; i(2) = 96.2 %) and p16+ISH/PCR (44.7 %; 95 %CI, 33.5-56.2 %; i(2) = 96.4 %). Conclusion: Overall pooled prevalence of HPV-driven OPSCC was approximately 45 %, with similar distribution among males and females. Double p16/HPV-DNA/RNA testing may be considered to increase specificity and prognostic accuracy.
  • article 12 Citação(ões) na Scopus
    Lung Cancer and the COVID-19 pandemic: Recommendations from the Brazilian Thoracic Oncology Group
    (2020) BALDOTTO, Clarissa; GELATTI, Ana; ACCIOLY, Arthur; MATHIAS, Clarissa; MASCARENHAS, Eldsamira; CARVALHO, Heloisa; FARONI, Lilian; ARAUJO, Luiz Henrique; ZUKIN, Mauro; GADIA, Rafael; TERRA, Ricardo Mingarini; HADDAD, Rui; LIMA, Vladmir Cordeiro de; CASTRO-JUNIOR, Gilberto de
    New cases of the novel coronavirus disease 2019 (COVID-19), also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continue to rise worldwide following the declaration of a pandemic by the World Health Organization (WHO). The current pandemic has completely altered the workflow of health services worldwide. However, even during this critical period, patients with other diseases, like cancer, need to be properly treated. A few reports have shown that mortality due to SARS-CoV-2 is higher in elderly patients and those with other active comorbidities, including cancer. Patients with lung cancer are at risk of pulmonary complications from COVID-19, and as such, the risk/benefit ratio of local and systemic anticancer treatment has to be considered. For each patient, several factors, including age, comorbidities, and immunosuppression, as well as the number of hospital visits for treatment, can influence this risk. The number of cases is rising exponentially in Brazil, and it is important to consider the local characteristics when approaching the pandemic. In this regard, the Brazilian Thoracic Oncology Group has developed recommendations to guide decisions in lung cancer treatment during the SARS-CoV-2 pandemic. Due to the scarcity of relevant data, discussions based on disease stage, evaluation of surgical treatment, radiotherapy techniques, systemic therapy, follow-up, and supportive care were carried out, and specific suggestions issued. All recommendations seek to reduce contagion risk by decreasing the number of medical visits and hospitalization, and in the case of immunosuppression, by adapting treatment schemes when possible. This statement should be adjusted according to the reality of each service, and can be revised as new data become available.
  • article 7 Citação(ões) na Scopus
    Valproic acid combined with cisplatin-based chemoradiation in locally advanced head and neck squamous cell carcinoma patients and associated biomarkers
    (2020) MAK, Milena Perez; PASINI, Fatima Solange; DIAO, Lixia; GARCIA, Fabyane O. Teixeira; TAKAHASHI, Tiago Kenji; NAKAZOTO, Denyei; MARTINS, Renata Eiras; ALMEIDA, Cristiane Maria; KULCSAR, Marco Aurelio Vamondes; LAMOUNIER, Valdelania Aparecida; NUNES, Emily Montosa; SOUZA, Isabela Cristina de; GARCIA, Marcio Ricardo Taveira; AMADIO, Alex Vieira; SIQUEIRA, Sheila Aparecida C.; SNITCOVSKY, Igor Moyses Longo; SICHERO, Laura; WANG, Jing; JR, Gilberto de Castro
    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).