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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Autor: SANTOS-SILVA, Alan Roger ×

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  • 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 130 Citação(ões) na Scopus
    Combining discovery and targeted proteomics reveals a prognostic signature in oral cancer
    (2018) CARNIELLI, Carolina Moretto; MACEDO, Carolina Carneiro Soares; ROSSI, Tatiane De; GRANATO, Daniela Campos; RIVERA, Cesar; DOMINGUES, Romenia Ramos; PAULETTI, Bianca Alves; YOKOO, Sami; HEBERLE, Henry; BUSSO-LOPES, Ariane Fidelis; CERVIGNE, Nilva Karla; SAWAZAKI-CALONE, Iris; MEIRELLES, Gabriela Vaz; MARCHI, Fabio Albuquerque; TELLES, Guilherme Pimentel; MINGHIM, Rosane; RIBEIRO, Ana Carolina Prado; BRANDAO, Thais Bianca; CASTRO JR., Gilberto de; GONZALEZ-ARRIAGADA, Wilfredo Alejandro; GOMES, Alexandre; PENTEADO, Fabio; SANTOS-SILVA, Alan Roger; LOPES, Marcio Ajudarte; RODRIGUES, Priscila Campioni; SUNDQUIST, Elias; SALO, Tuula; SILVA, Sabrina Daniela da; ALAOUI-JAMALI, Moulay A.; GRANER, Edgard; FOX, Jay W.; COLETTA, Ricardo Della; LEME, Adriana Franco Paes
    Different regions of oral squamous cell carcinoma (OSCC) have particular histopathological and molecular characteristics limiting the standard tumor-node-metastasis prognosis classification. Therefore, defining biological signatures that allow assessing the prognostic outcomes for OSCC patients would be of great clinical significance. Using histopathology-guided discovery proteomics, we analyze neoplastic islands and stroma from the invasive tumor front (ITF) and inner tumor to identify differentially expressed proteins. Potential signature proteins are prioritized and further investigated by immunohistochemistry (IHC) and targeted proteomics. IHC indicates low expression of cystatin-B in neoplastic islands from the ITF as an independent marker for local recurrence. Targeted proteomics analysis of the prioritized proteins in saliva, combined with machine-learning methods, highlights a peptide-based signature as the most powerful predictor to distinguish patients with and without lymph node metastasis. In summary, we identify a robust signature, which may enhance prognostic decisions in OSCC and better guide treatment to reduce tumor recurrence or lymph node metastasis.
  • article 3 Citação(ões) na Scopus
    Patient's perceptions of oral and oropharyngeal cancer diagnosis disclosure: communication aspects based on SPIKES protocol
    (2023) ALVES, Carolina G. B.; RIBEIRO, Ana Carolina Prado; BRANDAO, Thais Bianca; TONAKI, Juliana O.; PEDROSO, Caique Mariano; RIVERA, Cesar; EPSTEIN, Joel B.; MIGLIORATI, Cesar Augusto; KOWALSKI, Luiz Paulo; MAK, Milena Perez; CASTRO, Gilberto; LOPES, Marcio Ajudarte; SANTOS-SILVA, Alan Roger
    Objective. Breaking bad medical news is a complex task of clinical practice. The manner in which this is done has a significant impact on patients. This study aimed to assess patient's perceptions regarding oral and oropharyngeal cancer diagnosis disclosure according to the ""SPIKES"" protocol. Study Design. This cross-sectional study used a questionnaire with 21 SPIKES-based items. The questionnaire was administered to 100 patients with recently diagnosed oral and oropharyngeal squamous cell carcinoma who evaluated each item according to their preference and experience. Results. Nineteen items showed a significant difference between patient's preference and recalled experience. Eighteen of these items showed lower experience scores primarily related to the amount of information desired by patients, presence of a compan-ion, time to express feelings, and summary of information. Most patients preferred receiving as much information as possible about the diagnosis. However, only 35% reported that they had obtained sufficient information. Patients who were aware of can-cer diagnostic suspicion had better communication experiences. Conclusions. Protocols may be useful to guide health professionals to support patient-centered strategies to disclose oral cancer diagnoses. (Oral Surg Oral Med Oral Pathol Oral Radiol 2023;135:518-529)
  • article 53 Citação(ões) na Scopus
    Locally advanced oral squamous cell carcinoma patients treated with photobiomodulation for prevention of oral mucositis: retrospective outcomes and safety analyses
    (2018) BRANDAO, Thais Bianca; MORAIS-FARIA, Karina; RIBEIRO, Ana Carolina Prado; RIVERA, Cesar; SALVAJOLI, Joao Victor; LOPES, Marcio Ajudarte; EPSTEIN, Joel B.; ARANY, Praveen R.; CASTRO JR., Gilberto de; MIGLIORATI, Cesar Augusto; SANTOS-SILVA, Alan Roger
    The well-established clinical efficacy of photobiomodulation (PBM) therapy in management of oral mucositis (OM) is leading to increasing use in oncology care. This protection and enhanced repair of damage to mucosal tissue have led to the question of the potential effects of PBM therapy on pre-malignant and malignant cells. The purpose of this study was to examine the outcome of cancer therapy and incidence of tumor recurrence in locally advanced oral squamous cell carcinoma (OSCC) patients treated with PBM therapy for OM. A retrospective clinical analysis of 152 advanced OSCC patients treated with prophylactic PBM therapy for radiotherapy-induced OM from January 2009 to December 2014 was conducted. Of the 152 OSCC patients treated with PBM therapy in this study, 19 (12.5%) had stage III and 133 (87.5%) had stage IV tumors. Of these, 52 (34.2%) received initial treatment with surgery followed by adjuvant radiotherapy, 94 (61.8%) with exclusive chemoradiation, and 6 (4%) with induction chemotherapy followed by surgery and radiotherapy. After a mean follow-up of 40.84 (+/- 11.71) months, the overall survival and disease-free survival rates were 46.7 and 51.8%, respectively. Forty-five (29.6%) patients developed local-regional recurrence, 10 (6.57%) patients developed distant relapse, and 19 (12.5%) developed new (second) primary tumors. Clinicopathological features and survival outcomes in the PBM-treated patients were similar to previously published data for conventional treatments in patients with advanced OSCC. In this study, prophylactic use of PBM therapy did not impact treatment outcomes of the primary cancer, recurrence or new primary tumors, or survival in advanced OSCC patients.
  • article 7 Citação(ões) na Scopus
    Impact of radiation on tooth loss in patients with head and neck cancer: a retrospective dosimetric-based study
    (2021) GOMES-SILVA, Wagner; MORAIS-FARIA, Karina; RIVERA, Cesar; NAJAS, Gabriel Faria; MARTA, Gustavo Nader; VASCONCELOS, Karina Gondim Moutinho da Conceicao; CARVALHO, Heloisa de Andrade; CASTRO JR., Gilberto de; BRANDAO, Thais Bianca; EPSTEIN, Joel B.; SANTOS-SILVA, Alan Roger
    Objective. To characterize the dental adverse events after head and neck radiation therapy (HNRT) and to investigate the impact of regional radiation dose upon tooth loss outcomes. Study Design. A retrospective dosimetric-based analysis was conducted to assess dental events affecting post-HNRT extracted teeth and the impact of 3 different radiation doses ( 30 Gy, 30-60 Gy, and .001). The odds ratio for post-HNRT tooth extraction risk was approximately 3-fold higher for teeth exposed to 60 Gy (confidence interval, 1.56-5.35; P < .001), followed by an increased risk of delayed healing and osteoradionecrosis (ORN) in sites receiving doses above 50 Gy. Conclusions. Radiation caries was the major cause of dental extractions after HNRT, and the dosimetric analysis suggested that a high dose of radiation may negatively impact the dentition of survivors of head and neck cancer, increasing the risk of tooth loss and ORN. (Oral Surg Oral Med Oral Pathol Oral Radiol 2021;132:409-417)
  • 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 11 Citação(ões) na Scopus
    Oral leukoplakia and erythroplakia in young patients: a systematic review
    (2021) ROZA, Ana Luiza Oliveira Correa; KOWALSKI, Luiz Paulo; JR, William Nassib William; JR, Gilberto de Castro; CHAVES, Aline Lauda Freitas; ARAUJO, Anna Luiza Damaceno; RIBEIRO, Ana Carolina Prado; BRANDAO, Thais Bianca; LOPES, Marcio Ajudarte; VARGAS, Pablo Agustin; SANTOS-SILVA, Alan Roger
    Objective. The aim of this study was to estimate the frequency of oral leukoplakia and oral erythroplakia in young patients. Study Design. The systematic review was based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and performed in the following electronic databases: PubMed, Scopus, and Embase. The studies included were cross-sectional, cohort, and diagnostic, which provided with clinical and microscopic data of patients younger than 40 years. The Critical Appraisal Checklist for Prevalence Studies from the Joanna Briggs Institute and the Quality Assessment Tool for Diagnostic Accuracy Studies were used to assess the risk of bias. Results. Five studies met eligibility criteria and were included. The total number of patients from the studies was 1246, of which 115 were young patients (9.2%) with oral leukoplakia as the only oral potentially malignant disorder reported. Oral epithelial dysplasia was identified in 40 cases (34.7%), of which 8 (6.9%) presented malignant transformation. Conclusions. The frequency of oral leukoplakia is low in young patients. Observational studies are necessary for understanding oral leukoplakia and other oral potentially malignant disorders in younger patients.
  • 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
    Head and neck radiotherapy does not increase gelatinase (metalloproteinase-2 and-9) expression or activity in teeth irradiated in vivo
    (2017) GOMES-SILVA, Wagner; RIBEIRO, Ana Carolina Prado; CASTRO JUNIOR, Gilberto de; SALVAJOLI, Joao Victor; PALMIER, Natalia Rangel; LOPES, Marcio Ajudarte; ROCHA, Marcelo Marques; GOES, Mario Fernando de; BRANDAO, Thais Bianca; SANTOS-SILVA, Alan Roger
    Objective. Recent studies suggested that head and neck radiotherapy increases active forms of matrix metalloproteinases (MMPs) in the dentin-enamel junction (DEJ), leading to enamel delamination and radiation-related caries. This study aimed to assess the expression and activity of the gelatinases MMP-2 and MMP-9 in the DEJ and dentin-pulp complex tissues of teeth irradiated in vivo. Study Design. Thirty-six teeth were studied, including 19 irradiated and 17 non-irradiated controls. In situ zymography was used to investigate the gelatinolytic activity in the micromorphologic components of enamel, DEJ, dentin-pulp complex, and caries. Immunohistochemical analysis was conducted on the demineralized samples to assess MMP-2 and MMP-9 expression levels in the DEJ, dentin-pulp complex components, and caries. Results. No statistically significant differences were detected between groups in gelatinolytic activity or in MMP-2 expression levels (P > .05). Odontoblast MMP-9 expression was reduced in the irradiated group (P = .02). Conclusions. The study rejected the hypothesis that MMP-2 and MMP-9 would be overexpressed or more activated in the DEJ and dentin-pulp complex of irradiated teeth. Direct effects of radiation should not be regarded as an independent factor for explaining radiation-related caries onset and progression.
  • article 7 Citação(ões) na Scopus
    Impact of pandemic COVID-19 outbreak on oral mucositis preventive and treatment protocols: new perspectives for extraoral photobiomodulation therapy
    (2020) FARIA, Karina Morais; GOMES-SILVA, Wagner; KAUARK-FONTES, Elisa; BONFIM-ALVES, Carolina Guimaraes; KOWALSKI, Luiz Paulo; PRADO-RIBEIRO, Ana Carolina; VECHIATO-FILHO, Aljomar Jose; LOPES, Marcio Ajudarte; MARTA, Gustavo Nader; JR, Gilberto de Castro; LEME, Adriana Franco Paes; MIGLIORATI, Cesar Augusto; SANTOS-SILVA, Alan Roger; BRANDAO, Thais Bianca
    This communication discusses the current challenges of oral mucositis (OM) management during the pandemic COVID-19 outbreak and reflects about an extraoral photobiomodulation protocol as an optimal alternative for preventing and treating OM in advanced cancer patients while minimizing the risk of infection by avoiding intraoral manipulation.