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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  • article 61 Citação(ões) na Scopus
    Lung cancer in Brazil
    (2018) ARAUJO, Luiz Henrique; BALDOTTO, Clarissa; CASTRO JR., Gilberto de; KATZ, Artur; FERREIRA, Carlos Gil; MATHIAS, Clarissa; MASCARENHAS, Eldsamira; LOPES, Gilberto de Lima; CARVALHO, Heloisa; TABACOF, Jaques; MARTINEZ-MESA, Jeovany; VIANA, Luciano de Souza; CRUZ, Marcelo de Souza; ZUKIN, Mauro; MARCHI, Pedro De; TERRA, Ricardo Mingarini; RIBEIRO, Ronaldo Albuquerque; LIMA, Vladmir Claudio Cordeiro de; WERUTSKY, Gustavo; BARRIOS, Carlos Henrique
    Lung cancer is one of the most incident types of cancer and a leading cause of cancer mortality in Brazil. We reviewed the current status of lung cancer by searching relevant data on prevention, diagnosis, and treatment in the country. This review highlights several issues that need to be addressed, including smoking control, patient lack of awareness, late diagnosis, and disparities in the access to cancer health care facilities in Brazil. We propose strategies to help overcome these limitations and challenge health care providers, as well as the society and governmental representatives, to work together and to take a step forward in fighting lung cancer.
  • article
    Repurposing NF kappa B and HDAC inhibitors to individually target cancer stem cells and non-cancer stem cells from mucoepidermoid carcinomas
    (2023) SILVA, Luan Cesar; BORGATO, Gabriell Bonifacio; WAGNER, Vivian Petersen; MARTINS, Manoela Domingues; SANTOS-SILVA, Alan Roger; JR, Gilberto de Castro; KOWALSKI, Luiz Paulo; SQUARIZE, Cristiane Helena; VARGAS, Pablo Agustin; CASTILHO, Rogerio Moraes
    Drug resistance remains a major obstacle in the treatment of mucoepidermoid carcinomas (MEC) lead-ing to tumor recurrence, disease progression, and metastasis. Emerging evidence suggests that drug resistance is mediated by the presence of a highly adaptative subpopulation of cancer cells known as cancer stem cells (CSC). We have previously reported that solid tumors use NFkB signaling as a chemotherapy-resistant mechanism. We have also shown that interfering with the epigenome of solid tumors is an effective strategy to control the popula-tion of CSC. Here, we sought to investigate the effects of the NFkB inhibitor emetine and the HDAC inhibitor SAHA on the biology of MEC CSC and assessed whether this combination therapy would favor the standard of care therapy comprised of the administration of Cisplatin (CDDP). Our findings suggested that the administration of low concen-trations of emetine and SAHA is more effective in disrupting CSC in MEC, while the administration of emetine in combination with CDDP constitutes an effective therapy to target non-CSC MEC tumor cells.
  • article 1 Citação(ões) na Scopus
    The importance of molecular characterization in lung cancer
    (2019) CASTRO JUNIOR, Gilberto de; HARADA, Guilherme; MELLO, Evandro Sobroza de
  • conferenceObject
    Phase 3 KEYNOTE-042 Study: Pembrolizumab vs Platinum-Based Chemotherapy as 1l Therapy for Advanced NSCLC with a PD-L1 TPS >= 1%
    (2018) LOPES, G.; WU, Y.; KUDABA, I.; KOWALSKI, D.; CHO, B.; TURNA, H.; CASTRO JR., G. De; SRIMUNINNIMIT, V.; LAKTIONOV, K.; BONDARENKO, I.; KUBOTA, K.; LUBINIECKI, G.; ZHANG, J.; KUSH, D.; MOK, T.
  • article 1 Citação(ões) na Scopus
    EGFR Mutation Detection in Brazilian Patients With Non-Small-Cell Lung Cancer: Lessons From Real-World Data Scenario of Molecular Testing
    (2023) MONTELLA, Tatiane; ZALIS, Mariano; ZUKIN, Mauro; LIMA, Vladmir Claudio Cordeiro de; BALDOTTO, Clarissa; MARCHI, Pedro De; SALLES, Paulo; MATHIAS, Clarissa; BARRIOS, Carlos; KAWAMURA, Carolina; CALABRICH, Aknar; ARAUJO, Luiz Henrique; CASTRO, Gilberto; BUSTAMANTE, Carolina; MARIA, Andre Santa; REIS, Marcelo; FERREIRA, Carlos Gil
    PURPOSE There is a paucity of consistent data concerning genetic mutations in Brazilian patients with lung cancer. The aim of this study was to retrospectively analyze epidermal growth factor receptor (EGFR) mutations detected in a real-world scenario using a large cohort of Brazilian patients with non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS This was a cross-sectional, observational, descriptive study on the basis of a database of EGFR molecular analysis from tumor samples of patients with a confirmatory histopathological diagnosis of primary lung cancer. Specimens were collected from 2013 to 2017 and were tested using cobas, next-generation sequencing, and Sanger sequencing platforms. RESULTS A total of 7,413 tumor specimens were tested. The patients were predominantly women with a median age of 67.0 years. Patients with at least one mutation represented 24.2% of the total sample. Among the positive patients, the majority had just one mutation, but two or more simultaneous mutations were observed in 1.52% of patients. Exon 19 deletion was the most prevalent alteration in the sample (12.8%), followed by exon 21 L858R (6.9%) and exon 20 insertion (1.6%). All others were considered uncommon mutations and were observed in 18.5% of all mutated patients and 4.0% of the total sample (2.3%18.7% depending on the sequencing method). CONCLUSION This study examined the prevalence of EGFR mutations in Brazilian patients with NSCLC using different technologies, suggesting that the type of method used, directed or nondirected against specific mutations, influences the analysis, particularly for uncommon mutations, which will be missed by mutation-specific approaches such as cobas testing. Our estimates are the largest in Latin America and are consistent with previous reports from other parts of the world. Besides the variability in methods described here as technology incorporation advances in a nonhomogeneous manner, it is probably like the real-world clinical setting Brazilian oncologists face in their daily practice.
  • article 14 Citação(ões) na Scopus
    Metronomic oral cyclophosphamide plus prednisone in docetaxel-pretreated patients with metastatic castration-resistant prostate cancer
    (2015) BARROSO-SOUSA, Romualdo; FONSECA, Leonardo Gomes da; SOUZA, Karla Teixeira; CHAVES, Ana Carolina Ribeiro; KANN, Ariel Galapo; CASTRO JR., Gilberto de; DZIK, Carlos
    We evaluated the efficacy and safety of metronomic oral cyclophosphamide (CTX) and prednisone in metastatic castration-resistant prostate cancer (mCRPC) patients. We analyzed retrospectively patients with mCRPC previously treated with docetaxel, and who received metronomic CTX (from 50 mg PO daily to 150 mg PO, 14 days/7 days off) and prednisone 10 mg PO daily between September 2009 and April 2014 were analyzed. The primary endpoint was prostate-specific antigen (PSA) decrease >= 50 %. Secondary analysis included PSA decrease >= 30 %, time-to-treatment failure (TTF) and toxicity. Demographics and baseline characteristics were summarized using descriptive statistics. PSA response and adverse events were reported as relative rates. Kaplan-Meier estimates were calculated and plotted for time-to-event endpoints. Forty patients were evaluated. The median age was 69 years old (52-86), 12 (30.0 %) patients presented a Karnofsky performance status (KPS) of <80 %, and 34 (85 %) presented with bone with or without nodal metastases. Median pretreatment PSA was 192 ng/dL (7-2696 ng/dL). All patients were previously exposed to docetaxel, including 33 (82.5 %) with docetaxel-refractory disease. PSA response rate was achieved in eight (20.0 %) out of 40 patients. Additionally, PSA declines of >= 30 % occurred in 14 (35.0 %) patients. The median TTF was 3 months (95 % confidence interval 2.5-3.5). The treatment was well tolerated. Grade 3/4 lymphopenia was reported in 11 (27.5 %) patients and was the only grade 3-4 toxicity reported. Metronomic oral CTX showed activity and safety in docetaxel-pretreated mCRPC patients. This regimen deserves further investigation in this setting.
  • article 13 Citação(ões) na Scopus
    Cephaeline is an inductor of histone H3 acetylation and inhibitor of mucoepidermoid carcinoma cancer stem cells
    (2022) SILVA, Luan Cesar; BORGATO, Gabriell Bonifacio; WAGNER, Vivian Petersen; MARTINS, Manoela Domingues; ROCHA, Guilherme Zweig; LOPES, Marcio Ajudarte; SANTOS-SILVA, Alan Roger; CASTRO JUNIOR, Gilberto de; KOWALSKI, Luiz Paulo; NOR, Jacques E.; SQUARIZE, Cristiane H.; CASTILHO, Rogerio Moraes; VARGAS, Pablo Agustin
    Aim To evaluate the potential use of Cephaeline as a therapeutic strategy to manage mucoepidermoid carcinomas (MEC) of the salivary glands. Material and Methods UM-HMC-1, UM-HMC-2, and UM-HMC-3A MEC cell lines were used to establish the effects of Cephaeline over tumor viability determined by MTT assay. In vitro wound healing scratch assays were performed to address cellular migration while immunofluorescence staining for histone H3 lysine 9 (H3k9ac) was used to identify the acetylation status of tumor cells upon Cephaeline administration. The presence of cancer stem cells was evaluated by the identification of ALDH enzymatic activity by flow cytometry and through functional assays using in vitro tumorsphere formation. Results A single administration of Cephaeline resulted in reduced viability of MEC cells along with the halt on tumor growth and cellular migration potential. Administration of Cephaeline resulted in chromatin histone acetylation as judged by the increased levels of H3K9ac and disruption of tumorspheres formation. Interestingly, ALDH levels were increased in UM-HMC-1 and UM-HMC-3A cell lines, while UM-HMC-2 showed a reduced enzymatic activity. Conclusion Cephaeline has shown anti-cancer properties in all MEC cell lines tested by regulating tumor cells' viability, migration, proliferation, and disrupting the ability of cancer cells to generate tumorspheres.
  • article 17 Citação(ões) na Scopus
    BRAF mutations in non-small cell lung cancer: has finally Janus opened the door?
    (2016) CAPARICA, Rafael; CASTRO JR., Gilberto de; GIL-BAZO, Ignacio; CAGLEVIC, Christian; CALOGERO, Raffaele; GIALLOMBARDO, Marco; SANTOS, Edgardo S.; RAEZ, Luis E.; ROLFO, Christian
    B-Raf mutations occur in about 1-2% of non-small cell lung cancers (NSCLC). These mutations generate a permanent activation of the mitogen activated protein kinase (MAPK) pathway, which promotes tumor growth and proliferation. In the present review, we discuss B-Raf mutation epidemiology, diagnostic methods to detect B-Raf mutations, the role of B-Raf as a driver mutation and a potential therapeutic target in NSCLC. The results of clinical trials involving B-Raf or MAPK pathway inhibitors for the treatment of NSCLC are also discussed. Clinical trials evaluating B-Raf inhibitors in BRAF mutated NSCLC patients have shown promising results, and larger prospective studies are warranted to validate these findings. Enrollment of these patients in clinical trials is an interesting strategy to offer a potentially more effective and less toxic targeted therapy.
  • article 81 Citação(ões) na Scopus
    Meta-Analysis of First-Line Therapies in Advanced Non-Small-Cell Lung Cancer Harboring EGFR-Activating Mutations
    (2014) HAALAND, Benjamin; TAN, Pui San; CASTRO JR., Gilberto de; LOPES, Gilberto
    Introduction: Tyrosine kinase inhibitors gefitinib, erlotinib, and afatinib have been compared with chemotherapy as first-line therapies for patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor-activating mutations. This meta-analysis compares gefitinib, erlotinib, afatinib, and chemotherapy. Methods: Literature search was performed using relevant keywords. Direct and indirect meta-estimates were generated using log-linear mixed-effects models, with random effects for study. Study-to-study heterogeneity was summarized using I-2 statistics and predictive intervals (PIs). Results: Literature search yielded eight randomized phase 3 clinical trials comparing gefitinib, erlotinib, or afatinib with chemotherapy as first-line therapy in patients with advanced non-small-cell lung cancer during the last 5 years. Hazard ratio meta-estimates for progression-free survival were for gefitinib versus chemotherapy 0.44 (95% confidence interval [CI] 0.31-0.63; 95% PI, 0.22-0.88), erlotinib versus chemotherapy 0.25 (95% CI, 0.15-0.42; 95% PI, 0.11-0.55), afatinib versus chemotherapy 0.44 (95% CI, 0.26-0.75; 95% PI, 0.20-0.98), erlotinib versus gefitinib 0.57 (95% CI, 0.30-1.08; 95% PI, 0.24-1.36), afatinib versus gefitinib 1.01 (95% CI, 0.53-1.92; 95% PI, 0.41-2.42), and erlotinib versus afatinib 0.56 (95% CI, 0.27-1.18; 95% PI, 0.22-1.46). Results for overall response rate and disease control rate were similar. There was no evidence that gefitinib, erlotinib, or afatinib improved overall survival compared with chemotherapy. Conclusion: Gefitinib, erlotinib, and afatinib out-performed chemotherapy in terms of progression-free survival, overall response rate, and disease control rate. Differences among gefitinib, erlotinib, and afatinib were not statistically significant.
  • article 45 Citação(ões) na Scopus
    Health-Related Quality of Life in KEYNOTE-010: a Phase II/III Study of Pembrolizumab Versus Docetaxel in Patients With Previously Treated Advanced, Programmed Death Ligand 1-Expressing NSCLC
    (2019) BARLESI, Fabrice; GARON, Edward B.; KIM, Dong-Wan; FELIP, Enriqueta; HAN, Ji-Youn; KIM, Joo-Hang; AHN, Myung-Ju; FIDLER, Mary Jo; GUBENS, Matthew A.; CASTRO JR., Gilberto de; SURMONT, Veerle; LI, Qiao; DEITZ, Anne C.; LUBINIECKI, Gregory M.; HERBST, Roy S.
    Introduction: In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1-expressing (tumor proportion score >= 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here. Methods: Patients were randomized 1:1:1 to pembrolizumab 2 or 10 mg/kg every 3 weeks or docetaxel 75 mg/m(2) every 3 weeks. HRQoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLC) Core 30 (C30), EORTC QLQ-Lung Cancer 13 (LC13), and EuroQoL-5D. Key analyses included mean baseline-to-week-12 change in global health status (GHS)/quality of life (QoL) score, functioning and symptom domains, and time to deterioration in a QLQ-LC13 composite endpoint of cough, dyspnea, and chest pain. Results: Patient reported outcomes compliance was high across all three instruments. Pembrolizumab was associated with better QLQ-C30 GHS/QoL scores from baseline to 12 weeks than docetaxel, regardless of pembrolizumab dose or tumor proportion score status (not significant). Compared with docetaxel, fewer pembrolizumab-treated patients had ""deteriorated"" status and more had ""improved"" status in GHS/QoL. Nominally significant improvement was reported in many EORTC symptom domains with pembrolizumab, and nominally significant worsening was reported with docetaxel. Significant prolongation in true time to deterioration for the QLQ-LC13 composite endpoint emerged for pembrolizumab 10 mg/kg compared to docetaxel (nominal two-sided p = 0.03), but not for the 2-mg/kg dose. Conclusions: These findings suggest that HRQoL and symptoms are maintained or improved to a greater degree with pembrolizumab than with docetaxel in this NSCLC patient population.