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Extracellular vesicles (EVs) are mediators of the immune system response. Encapsulated in EVs, microRNAs can be transferred between cancer and immune cells. To define the potential effects of EVs originated from squamous cell carcinoma cells on immune system response, we performed microRNA profiling of EVs released from two distinct cell lines and treated dendritic cells derived from circulating monocytes (mono-DCs) with these EVs. We confirmed the internalization of EVs by mono-DCs and the down-regulation of microRNA mRNA targets in treated mono-DCs. Differences in surface markers of dendritic cells cultivated in the presence of EVs indicated that their content disrupts the maturation process. Additionally, microRNAs known to interfere with dendritic cell function, and detected in EVs, matched microRNAs from squamous cell carcinoma patients’ plasma: miR-17-5p in oropharyngeal squamous cell carcinoma, miR-21 in oral squamous cell carcinoma, miR-16, miR-24, and miR-181a circulating in both oral and oropharyngeal squamous cell carcinoma, and miR-23b, which has not been previously described in plasma of head and neck squamous cell carcinoma, was found in plasma from patients with these cancer subtypes. This study contributes with insights on EVs in signaling between cancer and immune cells in squamous cell carcinoma of the head and neck.

Made available in DSpace on 2022-04-29T08:41:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-04-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Background: Cancer is currently a major public health problem worldwide, with a marked increase of about 70% in the number of expected diagnosed cases over the next two decades. The amount of tobacco and alcohol consumed is calculated based on the subjective information provided by the user. Tobacco exposure can be assessed using the Fagerström Test for Cigarette Dependence (FTCD) and alcohol consumption by the Alcohol Use Disorder Identification Test (AUDIT). Materials and Methods: Forty-eight subjects answered the Fagerström, and AUDIT tests and we studied them as likely screening tools for oral cancer and their correlation with the expression of CYP1A1, GSTM1, GSTP1, and GSTT1 genes by the RT-qPCR method. Results: There were significant differences in the AUDIT score and CYP1A1 expression between cancer and control groups. Participants in advanced stages, whether due to tumor size or regional metastasis, showed significant differences in the duration of tobacco use, FTCD, AUDIT score, and CYP1A1 expression when compared to patients in early stages. Among subjects without cancer, we found a significant correlation between participant age and GSTP1 expression. Furthermore, the expression of GSTP1 was significantly correlated with the number of cigarettes smoked per day, duration of tobacco use, and FTCD. Conclusions: Questionnaires designed to evaluate the degree of tobacco and alcohol exposure and dependence combined with gene expression tests can be useful to assess the risk of developing oral cancer. Furthermore, raising the awareness of individuals regarding their degree of dependence and encouraging them to participate in cessation programs are important educational measures for the prevention of tobacco-related malignancies. Department of Bioscience and Oral Diagnosis Institute of Science and Technology of São José dos Campos São Paulo State University (Unesp) Faculdade de Ciências Médicas de São José dos Campos—Humanitas School of Medicine Anhembi Morumbi University Technology Research Center (NPT) Universidade Mogi das Cruzes Department of Head and Neck Surgery São Leopoldo Mandic College Department of Head and Neck Surgery Hospital Municipal Doutor Mário Gatti Department of Basic Sciences and Environment São Paulo University Department of Oral Pathology School of Dentistry São Paulo University Department of Bioscience and Oral Diagnosis Institute of Science and Technology of São José dos Campos São Paulo State University (Unesp) FAPESP: #2016/08633-0

Made available in DSpace on 2020-12-12T02:46:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Objective: The aim of this study was to evaluate the expression of DNA repair genes in cases of oral squamous cell carcinoma (OSCC). Study Design: Expression of the MLH1, MSH2, MLH3, ATM, MRE11A, XRCC1, and PMS2 genes was evaluated by reverse transcription–quantitative polymerase chain reaction in the OSCC group (32 patients) and the control group (15 patients). The groups were compared by using the Mann-Whitney test, with Bonferroni correction. Associations between gene expression levels and clinical data were explored by using Pearson's and Spearman's correlation coefficients, with P value less than. 05 indicating a significant difference. Results: The MLH1, MSH2, MLH3, ATM, MRE11A, XRCC1, and PMS2 genes were downregulated in the OSCC group compared with the control group, with significant values for MLH1 (P < .0001); MSH2 (P = .038); MLH3 (P < .0001); ATM (P < .0001); MRE11A (P < .0001); XRCC1 (P = .0004); and PMS2 (P = .008). Analysis of the correlation between gene expression and clinical data only revealed a significant negative correlation between age and expression of the PMS2 gene. Conclusions: Expression of the DNA repair genes MLH1, MSH2, MLH3, ATM, MRE11 AMRE11A, XRCC1, and PMS2 was reduced in OSCC. School of Dentistry Universidade Mogi das Cruzes School of Dentistry Brazcubas Educação Department of Biosciences and Oral Diagnosis Institute of Science and Technology São Paulo State University (UNESP) Department of Head and Neck Surgery São Leopoldo Mandic Medical School Department of Head and Neck Surgery Hospital Municipal Dr. Mário Gatti Department of Oral Pathology School of Dentistry University of São Paulo School of Medicine Anhembi Morumbi University São José dos Campos Department of Biosciences and Oral Diagnosis Institute of Science and Technology São Paulo State University (UNESP)

Oral cancer squamous cell carcinoma (OCSCC) mainly affects individuals aged between 50 and 70 years who consume tobacco and alcohol. Tobacco smoke contains hundreds of known toxic and carcinogenic molecules, and a few studies have sought to verify the relationship of such trace elements as risk or prognostic factors for head and neck cancer. We obtained 78 samples of tumor tissues from patients with OCSCC, and performed a qualitative elemental characterization using the micro X-Ray Fluorescence technique based on synchrotron radiation. We found the presence of magnesium, phosphorus, sulfur, chlorine, potassium, calcium, chromium, manganese, iron, zinc, cobalt, nickel, copper, arsenic and bromine in OCSCC samples. Magnesium, chlorine, chromium, manganese, nickel, arsenic and bromine are associated with smoking. We observed a significant association between relapse and chlorine and chromium. The presence of chlorine in the samples was an independent protective factor against relapse (OR = 0.105, CI = 0.01–0.63) and for best disease-free survival (HR = 0.194, CI = 0.04–0.87). Reporting for the first time in oral cancer, these results suggest a key relationship between smoking and the presence of certain elements. In addition, chlorine proved to be important in the context of patient prognosis and survival.

Cancer is currently a major public health problem worldwide, with a marked increase of about 70% in the number of expected diagnosed cases over the next two decades. The amount of tobacco and alcohol consumed is calculated based on the subjective information provided by the user. Tobacco exposure can be assessed using the Fagerström Test for Cigarette Dependence (FTCD) and alcohol consumption by the Alcohol Use Disorder Identification Test (AUDIT).Forty-eight subjects answered the Fagerström, and AUDIT tests and we studied them as likely screening tools for oral cancer and their correlation with the expression ofThere were significant differences in the AUDIT score andQuestionnaires designed to evaluate the degree of tobacco and alcohol exposure and dependence combined with gene expression tests can be useful to assess the risk of developing oral cancer. Furthermore, raising the awareness of individuals regarding their degree of dependence and encouraging them to participate in cessation programs are important educational measures for the prevention of tobacco-related malignancies.

The comparison of chemical and histopathological data obtained from the analysis of excised tumor fragments oral squamous cell carcinoma (OSCC) with the demographic and clinical evolution data is an effective strategy scarcely explored in OSCC studies. The aim was to analyze OSCC tissues for protein expression of enzymes related to oxidative stress and DNA repair and trace elements as candidates as markers of tumor aggressiveness and prognosis. Tumor fragments from 78 OSCC patients that had undergone ablative surgery were qualitatively analyzed by synchrotron micro-X-ray fluorescence for trace elements. Protein expression of SOD-1, Trx, Ref-1 and OGG1/2 was performed by immunohistochemistry. Sociodemographic, clinical, and histopathological data were obtained from 4-year follow-up records. Disease relapse was highest in patients with the presence of chlorine and chromium and lowest in those with tumors with high OGG1/2 expression. High expression of SOD-1, Trx, and Ref-1 was determinant of the larger tumor. Presence of trace elements can be markers of disease prognosis. High expression of enzymes related to oxidative stress or to DNA repair can be either harmful by stimulating tumor growth or beneficial by diminishing relapse rates. Interference on these players may bring novel strategies for the therapeutic management of OSCC patients.

L.K. is a fellow in the Canadian Institutes of Health Research (CIHR) Strategic Training in Advanced Genetic Epidemiology (STAGE) programme and is supported by the CIHR Doctoral Research Award from the Frederick Banting and Charles Best Canada Graduate Scholarships (GSD-137441). Transdisciplinary Research for Cancer in Lung (TRICL) of the International Lung Cancer Consortium (ILCCO) was supported by the National Institutes of Health (U19-CA148127, CA148127S1). Genotyping for the TRICL-ILCCO OncoArray was supported by in-kind genotyping at Centre for Inherited Disease Research (CIDR) (26820120008i-0–6800068-1). Genotyping for the Head and Neck Cancer OncoArray performed at CIDR was funded by the US National Institute of Dental and Craniofacial Research (NIDCR) grant 1X01HG007780–0. CAPUA study was supported by FIS-FEDER/Spain grant numbers FIS-01/310, FIS-PI03–0365 and FIS-07-BI060604, FICYT/Asturias grant numbers FICYT PB02–67 and FICYT IB09–133, and the University Institute of Oncology (IUOPA), of the University of Oviedo and the Ciber de Epidemiologia y Salud Publica. CIBERESP, SPAIN. The work performed in the CARET study was supported by the National Institute of Health (NIH)/National Cancer Institute (NCI): UM1 CA167462 (PI: Goodman), National Institute of Health UO1-CA6367307 (PIs Omen, Goodman); National Institute of Health R01 CA111703 (PI Chen), National Institute of Health 5R01 CA151989 (PI Doherty). The Liverpool Lung Project is supported by the Roy Castle Lung Cancer Foundation. The Harvard Lung Cancer Study was supported by the NIH (National Cancer Institute) grants CA092824, CA090578 and CA074386. The Multiethnic Cohort Study was partially supported by NIH Grants CA164973, CA033619, CA63464 and CA148127. The work performed in MSH-PMH study was supported by the Canadian Cancer Society Research Institute (020214), Ontario Institute of Cancer and Cancer Care Ontario Chair Award to R.J.H. and G.L. and the Alan Brown Chair and Lusi Wong Programs at the Princess Margaret Hospital Foundation. The Norway study was supported by Norwegian Cancer Society, Norwegian Research Council. The work in TLC study has been supported in part the James & Esther King Biomedical Research Program (09KN-15), National Institutes of Health Specialized Programs of Research Excellence (SPORE) Grant (P50 CA119997) and by a Cancer Center Support Grant (CCSG) at the H. Lee Moffitt Cancer Center and Research Institute, an NCI designated Comprehensive Cancer Center (grant number P30-CA76292). The dataset(s) used for the analyses described were obtained from Vanderbilt University Medical Center’s BioVU, which is supported by institutional funding and by the Vanderbilt CTSA grant UL1 TR000445 from NCATS/NIH. Dr Melinda Aldrich is supported by the by NIH/National Cancer Institute 5K07CA172294. The Copenhagen General Population Study (CGPS) was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Herlev Hospital. The NELCS study: Grant Number P20RR018787 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). Kentucky Lung Cancer Research Initiative (KLCRI) was supported by the Department of Defense (Congressionally Directed Medical Research Program, U.S. Army Medical Research and Materiel Command Program) under award number: 10153006 (W81XWH-11–1-0781). Views and opinions of, and endorsements by the author(s) do not reflect those of the US Army or the Department of Defense. This research was also supported by unrestricted infrastructure funds from the UK Center for Clinical and Translational Science, NIH grant UL1TR000117 and Markey Cancer Center NCI Cancer Center Support Grant (P30 CA177558) Shared Resource Facilities: Cancer Research Informatics, Biospecimen and Tissue Procurement, and Biostatistics and Bioinformatics. The research undertaken by M.D.T., L.V.W. and M.S.A. was partly funded by the National Institute for Health Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. M.D.T. holds a Medical Research Council Senior Clinical Fellowship (G0902313). The Tampa study was funded by Public Health Service grants P01-CA68384 and R01-DE13158 from the National Institutes of Health. The University of Pittsburgh head and neck cancer case–control study is supported by US National Institutes of Health grants P50 CA097190 and P30 CA047904. The Carolina Head and Neck Cancer Study (CHANCE) was supported by the National Cancer Institute (R01CA90731). The Head and Neck Genome Project (GENCAPO) was supported by the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP; grants 04/12054–9 and 10/51168–0). The authors thank all the members of the GENCAPO team. This publication presents data from the Head and Neck 5000 study. The study was a component of independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (RP-PG-0707–10034). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Human papillomavirus (HPV) serology was supported by a Cancer Research UK Programme Grant, the Integrative Cancer Epidemiology Programme (grant number: C18281/A19169). The Alcohol-Related Cancers and Genetic Susceptibility Study in Europe (ARCAGE) was funded by the European Commission’s fifth framework programme (QLK1– 2001-00182), the Italian Association for Cancer Research, Compagnia di San Paolo/FIRMS, Region Piemonte and Padova University (CPDA057222). The Rome Study was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) awards IG 2011 10491 and IG 2013 14220 to S.B. and by Fondazione Veronesi to S.B. The IARC Latin American study was funded by the European Commission INCO-DC programme (IC18-CT97–0222), with additional funding from Fondo para la Investigacion Cientifica y Tecnologica (Argentina) and the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (01/01768–2). The IARC Central Europe study was supported by the European Commission’s INCO-COPERNICUS Program (IC15-CT98–0332), US NIH/National Cancer Institute grant CA92039 and World Cancer Research Foundation grant WCRF 99A28. The IARC Oral Cancer Multicenter study was funded by grant S06 96 202489 05F02 from Europe against Cancer; grants FIS 97/0024, FIS 97/0662 and BAE 01/5013 from Fondo de Investigaciones Sanitarias, Spain; the UICC Yamagiwa-Yoshida Memorial International Cancer Study; the National Cancer Institute of Canada; Associazione Italiana per la Ricerca sul Cancro; and the Pan-American Health Organization. Coordination of the EPIC study is financially supported by the European Commission (DG SANCO) and the International Agency for Research on Cancer.

Background Most patients with head and neck cancer receive nonsteroidal anti-inflammatory drugs concomitant with oncogenic treatment in order to control cardiovascular diseases and chronic inflammatory processes. Inflammation is closely related to neoplastic development and the release of inflammatory cytokines and chemokines represents a crucial event in this relationship. The aim of the present study was to evaluate the effect of acetylsalicylic acid (ASA) and celecoxib treatment in the gene expression pattern of cytokines and chemokines in squamous cell carcinoma (OSCC) cell lines. Materials and methods Cells were treated with plasmatic concentrations of ASA and celecoxib and were submitted to cell viability assay and immunoenzymatic assay to investigate interleukin 6 (IL6) production. Treated cells were collected and a gene expression array was performed using the reverse transcriptase-quantitative polymerase chain reaction. Results Both treatments provoked a discrete inhibitory effect on cell viability and modulated IL6 production. The mRNA expression of several cytokines, chemokines, chemokine receptors, and other chemotaxis-related genes were modulated after treatment with ASA and celecoxib. Conclusion Plasmatic doses of ASA and celecoxib altered the expression of IL6 and the gene expression of chemokines (ligands and receptors) and cytokines in a dose- and time-dependent manner.

Introduction Immune cells contribute with mediators in the protein expression profile of the tumor microenvironment. Levels of plasminogen activator inhibitor-1 (PAI-1) are elevated in non-malignant inflammatory conditions; however, the association between PAI-1 expression and inflammation remains uncertain in oral squamous cell carcinoma (OSCC). This study aimed to investigate PAI-1 expression in mononuclear inflammatory cell infiltrate in OSCC and its role as a prognostic marker. Methods Samples were collected from patients with OSCC, treated surgically, and followed for 24 months after the procedure. Thirty-nine tumoral tissue were analyzed using immunohistochemistry. Correlation between protein expression, clinicopathological parameters, and the prognosis was investigated. Results Positive PAI-1 expression in mononuclear inflammatory cell infiltrate was significantly associated with lymph node status (p = 0.009) and with the cytoplasmic expression of vascular endothelial growth factor A (VEGFA) (p = 0.028). Multivariate analysis revealed weak PAI-1 expression as an independent marker for lymph node metastases, with approximately 8-fold increased risk compared to strong expression (OR = 8.60; CI = 1.54–48.08; p = 0.014). Conclusion Our results suggest that the strong PAI-1 expression in intratumoral inflammatory infiltrate is an indicator of a better prognosis for patients diagnosed with oral squamous cell carcinoma., Highlights • PAI-1 is a potential marker for lymph node metastasis in the OSCC with predictive potential of the marker under metastatic conditions.

Advanced salivary gland mucoepidermoid carcinoma (MEC) is a relentless cancer that exhibits resistance to conventional chemotherapy. As such, treatment for patients with advanced MEC is tipically radical surgery and radiotherapy. Facial disfigurement and poor quality of life are frequent treatment challenges, and many patients succumb to loco-regional recurrence and/or metastasis. We know that cancer stem-like cells (CSC) drive MEC tumorigenesis. The current study tests the hypothesis that MEC CSC are sensitive to therapeutic inhibition of mTOR. Here, we report a correlation between the long-term clinical outcomes of 17 MEC patients and the intratumoral expression of p-mTOR (p = 0.00294) and p-S6K1 (p = 0.00357). In vitro, we observed that MEC CSC exhibit constitutive activation of the mTOR signaling pathway (i.e., mTOR, AKT, and S6K1), unveiling a potential strategy for targeted ablation of these cells. Using a panel of inhibitors of the mTOR pathway, i.e., rapamycin and temsirolimus (mTOR inhibitors), buparlisib and LY294002 (AKT inhibitors), and PF4708671 (S6K1 inhibitor), we observed consistently dose-dependent decrease in the fraction of CSC, as well as inhibition of secondary sphere formation and self-renewal in three human MEC cell lines (UM-HMC-1,-3A,-3B). Notably, therapeutic inhibition of mTOR with rapamycin or temsirolimus induced preferential apoptosis of CSC, when compared to bulk tumor cells. In contrast, conventional chemotherapeutic drugs (cisplatin, paclitaxel) induced preferential apoptosis of bulk tumor cells and accumulation of CSC. In vivo, therapeutic inhibition of mTOR with temsirolimus caused ablation of CSC and downregulation of Bmi-1 expression (major inducer of stem cell self-renewal) in MEC xenografts. Transplantation of MEC cells genetically silenced for mTOR into immunodeficient mice corroborated the results obtained with temsirolimus. Collectively, these data demonstrated that mTOR signaling is required for CSC survival, and unveiled the therapeutic potential of targeting the mTOR pathway for elimination of highly tumorigenic cancer stem-like cells in salivary gland mucoepidermoid carcinoma.

Made available in DSpace on 2018-12-11T17:22:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-08-29 Background: Lymph node metastasis is one of the most important prognostic factors in head and neck squamous cell carcinomas (HNSCCs) and critical for delineating their treatment. However, clinical and histological criteria for the diagnosis of nodal status remain limited. In the present study, we aimed to characterize the proteomic profile of lymph node metastasis from HNSCC patients. Methods: In the present study, we used one- and two-dimensional electrophoresis and mass spectrometry analysis to characterize the proteomic profile of lymph node metastasis from HNSCC. Results: Comparison of metastatic and non-metastatic lymph nodes showed 52 differentially expressed proteins associated with neoplastic development and progression. The results reinforced the idea that tumors from different anatomical subsites have dissimilar behaviors, which may be influenced by micro-environmental factor including the lymphatic network. The expression pattern of heat shock proteins and glycolytic enzymes also suggested an effect of the lymph node environment in controlling tumor growth or in metabolic reprogramming of the metastatic cell. Our study, for the first time, provided direct evidence of annexin A1 overexpression in lymph node metastasis of head and neck cancer, adding information that may be useful for diagnosing aggressive disease. Conclusions: In brief, this study contributed to our understanding of the metastatic phenotype of HNSCC and provided potential targets for diagnostic in this group of carcinomas. Departamento de Biologia Molecular Faculdade de Medicina (FAMERP), Av. Brigadeiro Faria Lima, 5416, Vila São Pedro Departamento de Biologia Instituto de Biociências Letras e Ciências Exatas (IBILCE) Universidade Estadual Paulista (UNESP), R. Cristóvão Colombo, 2265 Instituto Do Câncer de São Paulo Octavio Frias de Oliveira - ICESP, Av. Dr. Arnaldo, 251 - Cerqueira César Faculdade Ceres (Faceres), Av. Anísio Haddad, 6751 Departamento de Estomatologia Faculdade de Odontologia Universidade de São Paulo, Av. Prof. Lineu Prestes, 2227 Instituto Do Câncer Arnaldo Vieira de Carvalho, R. Dr Cesário Mota Jr, 112 Departamento de Cirurgia de Cabeça e Pescoço Hospital Heliópolis, R. Cônego Xavier, 276 Departamento de Análises Clínicas Toxicológicas e Bromatológicas Faculdade de Ciências Farmacêuticas Universidade de São Paulo, Avenida do Café, s/n Departamento de Genética e Biologia Evolutiva Instituto de Biociências Universidade de São Paulo, R. do Matão, 321 Departamento de Biologia Instituto de Biociências Letras e Ciências Exatas (IBILCE) Universidade Estadual Paulista (UNESP), R. Cristóvão Colombo, 2265

Macrophages play a very important role in the conduction of several regenerative processes mainly due to their plasticity and multiple functions. In the muscle repair process, while M1 macrophages regulate the inflammatory and proliferative phases, M2 (anti‐inflammatory) macrophages direct the differentiation and remodelling phases, leading to tissue regeneration. The aim of this study was to evaluate the effect of red and near infrared (NIR) photobiomodulation (PBM) on macrophage phenotypes and correlate these findings with the repair process following acute muscle injury. Wistar rats were divided into 4 groups: control; muscle injury; muscle injury + red PBM; and muscle injury + NIR PBM. After 2, 4 and 7 days, the tibialis anterior muscle was processed for analysis. Macrophages phenotypic profile was evaluated by immunohistochemistry and correlated with the different stages of the skeletal muscle repair by the qualitative and quantitative morphological analysis as well as by the evaluation of IL‐6,TNF‐α and TGF‐β mRNA expression. Photobiomodulation at both wavelengths was able to decrease the number of CD68+ (M1) macrophages 2 days after muscle injury and increase the number of CD163+ (M2) macrophages 7 days after injury. However, only NIR treatment was able to increase the number of CD206+ M2 macrophages (Day 2) and TGF ‐β mRNA expression (Day 2, 4 and 7), favouring the repair process more expressivelly. Treatment with PBM was able to modulate the inflammation phase, optimize the transition from the inflammatory to the regeneration phase (mainly with NIR light) and improve the final step of regeneration, enhancing tissue repair.

O Plano Nacional de Pós-Graduação recomenda que o Sistema Nacional de Pós-Graduação desenvolva estudos tendo em vista as necessidades e os interesses dos estudantes da educação básica. Buscando seguir esta diretriz, o Programa de Pós-Graduação em Ciências Odontológicas da Faculdade de Odontologia da Universidade de São Paulo estabeleceu uma parceria com instâncias gestoras da rede pública de educação no município de São Paulo, formulando e implementando o projeto Experimentando Ciência. O objetivo foi de aproximar os estudantes do ensino fundamental do conhecimento científico produzido na universidade, promovendo a popularização da ciência e da tecnologia. A partir da delimitação de um problema em sala de aula, quatro grupos de dez alunos, percorriam cinco laboratórios da faculdade, com o objetivo de levantar hipóteses, ensaiar e testar desenhos experimentais. Participaram, ao longo do ano de 2016, cinco escolas, perfazendo um total de 200 alunos. Os resultados foram apresentados em conjunto na forma de relatórios, relatos de experiência, e divulgados para a comunidade escolar, no sentido de compartilhar e multiplicar o conhecimento. De acordo com os relatos, os estudantes tiveram a oportunidade de ampliar o entendimento da ciência de forma prática, instigando a curiosidade pela pesquisa e despertando a percepção de que a educação superior é uma etapa possível de ser alcançada no ciclo educacional. Para a universidade, o projeto demonstrou a viabilidade e importância da articulação interdisciplinar e entre os diferentes níveis educacionais.

Made available in DSpace on 2018-12-11T17:23:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-01-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Objective The aim of this study was to evaluate the effect of chronic smoking on the expression profile of the repair genes MLH1, MSH2 and ATM in the normal oral mucosa of chronic smokers and never smokers. Materials and methods The sample consisted of thirty exfoliative cytology smears per group obtained from Smokers and Never Smokers. Total RNA was extracted and expression of the MLH1, MSH2 and ATM genes were evaluated by quantitative real-time and immunocytochemistry. The gene and protein expression data were correlated to the clinical data. Gene expression was analyzed statistically using the Student t-test and Pearson's correlation coefficient, with p

Radiographic examinations complement the anamnesis and physical exam with the purpose of reaching diagnosis, prognosis and treatment planning. In this case report, a 48 year-old male Caucasian patient was referred to an oral and maxillofacial surgeon by a general practitioner after a panoramic radiography for treatment planning; the implant surgery follow-up portrayed a multilocular radiolucent image at the left posterior mandible. Based solely on the panoramic radiography, the diagnostic hypothesis was ameloblastoma. The surgeon decided to perform an incisional biopsy. However, during the procedure, the professional noted that the lesion was easily detached from the adjacent bone and opted for the total removal of the lesion, thus altering its diagnostic hypothesis to central ossifying fibroma (COF). The histopathological result confirmed the diagnostic hypothesis provided by the surgeon, i.e. COF. Although multilocular presentation is not common, COF should be considered in the scope of multilocular radiolucent lesions of the jaws. In addition, computerized tomography imaging exam complemented by surgical and histopathological aspects should be considered for establishing the final diagnosis and conducting the therapeutic approach.

This article reports a case of oral mucosa lesions as the sole manifestation in Langerhans cell histiocytosis (LCH). This is a very uncommon manifestation of LCH since this disease preferably affects the bones with frequent involvement of the jaws. LCH may also involve other organs, particularly the lungs, liver, lymph nodes, and skin. The highlights of this report are the differential diagnosis, immunohistochemical analysis and, mostly, the therapeutic approach.

Natural triterpenes exhibit a wide range of biological activities. Since this group of secondary metabolites is structurally diverse, effects may vary due to distinct biochemical interactions within biological systems. In this work, we investigated the anticancer-related activities of the quinone-methide triterpene maytenin and its derivative compound 22-&beta, hydroxymaytenin, obtained from Maytenus ilicifolia roots cultivated in vitro. Their antiproliferative and pro-apoptotic activities were evaluated in monolayer and three-dimensional cultures of immortalized cell lines. Additionally, we investigated the toxicity of maytenin in SCID mice harboring tumors derived from a squamous cell carcinoma cell line. Both isolated molecules presented pronounced pro-apoptotic activities in four cell lines derived from head and neck squamous cell carcinomas, including a metastasis-derived cell line. The molecules also induced reactive oxygen species (ROS) and down-regulated microRNA-27a and microRNA-20a/miR-17-5p, corroborating with the literature data for triterpenoids. Intraperitoneal administration of maytenin to tumor-bearing mice did not lead to pronounced histopathological changes in kidney tissue, suggesting low nephrotoxicity. The wide-ranging activity of maytenin and 22-&beta, hydroxymaytenin in head and neck cancer cells indicates that these molecules should be further explored in plant biochemistry and biotechnology for therapeutic applications.

Receptor-interacting proteins are a family of serine/threonine kinases, which integrate extra and intracellular stress signals caused by different factors, including infections, inflammation and DNA damage. Receptor-interacting serine/threonine-protein kinase 2 (RIP-2) is a member of this family and an important component of the nuclear factor NF-kappa-B signaling pathway. The corresponding human gene RIPK2 generates two transcripts by alternative splicing, the full-length and a short transcript. The short transcript has a truncated 5’ sequence, which results in a predicted isoform with a partial kinase domain but able to transduce signals through its caspase recruitment domain. In this study, the expression of RIPK2 was investigated in human tissue samples and, in order to determine if both transcripts are similarly regulated at the transcriptional level, cancer cell lines were submitted to temperature and acid stresses. We observed that both transcripts are expressed in all tissues analyzed, with higher expression of the short one in tumor samples, and they are differentially regulated following temperature stress. Despite transcription, no corresponding protein for the short transcript was detected in tissues and cell lines analyzed. We propose that the shorter transcript is a noncoding RNA and that its presence in the cell may play regulatory roles and affect inflammation and other biological processes related to the kinase activity of RIP-2., Instituto de Biotecnologia y Biologia Molecular

Oral squamous cell carcinoma (OSCC) is an extremely aggressive disease associated with a poor prognosis. Previous studies have established that cancer stem cells (CSCs) actively participate in OSCC development, progression and resistance to conventional treatments. Furthermore, CSCs frequently exhibit a deregulated expression of normal stem cell signalling pathways, thereby acquiring their distinctive abilities, of which self-renewal is an example. In this study, we examined the effects of GLI3 knockdown in OSCC, as well as the differentially expressed genes in CSC-like cells (CSCLCs) expressing high (CD44high) or low (CD44low) levels of CD44. The prognostic value of GLI3 in OSCC was also evaluated. The OSCC cell lines were sorted based on CD44 expression; gene expression was evaluated using a PCR array. Following this, we examined the effects of GLI3 knockdown on CD44 and ESA expression, colony and sphere formation capability, stem-related gene expression, proliferation and invasion. The overexpression of genes related to the Notch, transforming growth factor (TGF)β, FGF, Hedgehog, Wnt and pluripotency maintenance pathways was observed in the CD44high cells. GLI3 knockdown was associated with a significant decrease in different CSCLC fractions, spheres and colonies in addition to the downregulation of the CD44, Octamer-binding transcription factor 4 (OCT4; also known as POU5F1) and BMI1 genes. This downregulation was accompanied by an increase in the expression of the Involucrin (IVL) and S100A9 genes. Cellular proliferation and invasion were inhibited following GLI3 knockdown. In OSCC samples, a high GLI3 expression was associated with tumour size but not with prognosis. On the whole, the findings of this study demonstrate for the first time, at least to the best of our knowledge, that GLI3 contributes to OSCC stemness and malignant behaviour. These findings suggest the potential for the development of novel therapies, either in isolation or in combination with other drugs, based on CSCs in OSCC.

Made available in DSpace on 2018-12-11T17:37:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-08-01 Objective: The aim of this study was to evaluate the epigenetic changes in the process of oral carcinogenesis by screening the methylation of repair genes in chronic smokers. Design: Two groups were formed: Group 1: 16 smokers with consumption of 20 cigarettes/day for at least 10 years; and Group 2: 10 non-smoking. Exfoliative cytology of the tongue was performed, and the extracted DNA was treated by enzymes. The PCR Array System performed methylation screening to evaluate 22 DNA repair genes, and the results were validated by RT-qPCR for each gene with methylation levels ≥10%. Results: Highest percentages of methylation were observed for MLH3 and XRCC1 genes (11–20% methylation) and in one case for MRE11A and PMS2 (>50% methylation). Statistical analysis showed significant differences in the expression of the genes MRE11A (p = 0.0002), PMS2(p = 0.0068), XRCC1 (p = 0.0080) and MLH3 (0.0057) between the two groups. Conclusion: The effects of chronic smoking on oral mucosa led to the methylation of genes MRE11A PMS2, XRCC1 and MLH3, but resulted in a reduction of gene expression of MRE11A and PMS2, which showed ≥50% methylation. These results provide evidence that smoking cause methylation and reduced expression of repair genes. Department of Biosciences and Oral Diagnosis São Paulo State University (Unesp) Institute of Science and Technology University Braz Cubas, Mogi das Cruzes Universidade de Mogi das Cruzes, Mogi das Cruzes Angiogenesis Research Laboratory Department of Cariology Restorative Sciences and Endodontics University of Michigan School of Dentistry Heart Institute University Hospital Medical School Universidade de São Paulo Department of Oral Pathology School of Dentistry University of Sao Paulo Department of Biosciences and Oral Diagnosis São Paulo State University (Unesp) Institute of Science and Technology

Background: In oral squamous cell carcinoma (OSCC), the HIF-1 complex promotes the expression of genes involved in specific mechanisms of cell survival under hypoxic conditions, such as plasminogen activator inhibitor-1 (PAI-1), carbonic anhydrase 9 (CAIX), and vascular endothelial growth factor A (VEGFA). The study aimed to investigate the presence and prognostic value of PAI-1, CAIX, and VEGFA in OSCC. Materials and Methods: Immunohistochemistry was used to analyze the expressions of these proteins in 52 tumoral tissue samples of patients with OSCC, surgically treated and followed by a minimum of 24 months after surgery. The correlations between protein expressions and clinicopathological parameters and prognosis were analyzed. Results: Positive PAI-1 membrane expression was significantly associated with local disease relapse (P = .027). Multivariate analysis revealed that the positive PAI-1 membrane expression is an independent marker for local disease relapse, with approximately 14-fold increased risk when compared to negative expression (OR = 14.49; CI = 1.40-150.01, P = .025). Strong PAI-1 cytoplasmic expression was significantly associated with the less differentiation grade (P = .027). Strong CAIX membrane expression was significantly associated with local disease-free survival (P = .038). Positive CAIX cytoplasmic expression was significantly associated with lymph node affected (P = .025) and with disease-specific survival (P = .022). Multivariate analysis revealed that the positive CAIX cytoplasmic expression is an independent risk factor for disease-related death, increasing their risk approximately 3-fold when compared to negative expression (HR = 2.84; CI = 1.02-7.87, P = .045). Positive VEGFA cytoplasmic expression was significantly associated with less differentiation grade (P = .035). Conclusion: Our results suggest a potential role for these expressions profiles as tumor prognostic markers in OSCC patients

Objetivos: Avaliar variáveis associadas à necessidade do uso de prótese dos pacientes com necessidades especiais (PNE) do Centro de Especialidades Odontológicas da Estância Hidromineral de Poá (CEO-Poá). Materiais e métodos: A amostra total foi composta por 514 PNE do CEO-Poá, e a variável dependente foi a necessidade de uso de prótese estabelecida entre janeiro de 2011 e dezembro de 2016. As variáveis foram gênero, idade, diagnóstico principal, quantidade de medicação utilizada usualmente e aspectos comportamentais e foram compiladas do prontuário físico para o formulário eletrônico desenvolvido para este estudo. Dados foram tabulados e analisados. Resultados: Foram encaminhados 88 indivíduos (17,11%) à reabilitação protética. Prevaleceu o gênero feminino e o avanço da idade aumentou a necessidade de uso de prótese, de forma semelhante à população geral. O diagnóstico principal foi uma variável influenciadora, a maioria (47,72%) apresentou alterações sistêmicas, seguido de deficiência física (18,18%) e distúrbios psiquiátricos (11,36%). Quanto ao comportamento, todos indivíduos foram atendidos em âmbito ambulatorial, a maioria (71,59%) já havia recebido anestesia em tratamentos anteriores, e apenas 7,95% precisou de condicionamento psicológico. Grande parte dos PNE (89,77%) chegou a receber e utilizar as próteses. Conclusões: O diagnóstico principal e variáveis do perfil comportamental foram influenciadores na necessidade de próteses dos PNE do CEO-Poá. Gênero e idade igualmente influenciam a indicação, assim como na população em geral. Esse estudo poderá nortear a implementação de projetos tanto no setor privado como no público. Objectives: To evaluate variables associated with the need of denture by patients with special needs attending the Dental Specialty Center (DSC) in Poá, São Paulo, Brazil. Materials and methods: The total sample consisted of 514 patients, treated at the DSC-Poá, and the dependent variable was need of denture established between January 2011 and December 2016. The analyzed variables were gender, age, main diagnosis, amount of medication used, and behavioral aspects. The physical records were compiled to an electronic form specially developed for this study. Data were tabulated and analyzed. Results: Eighty-eight patients (17.11%) were referred to prosthetic rehabilitation. The female gender prevailed and the need for denture increased with age, in a similar manner as in the general population. Main diagnosis was a relevant variable, with the majority (47.72%) presenting systemic alterations, followed by physical deficiency (18.18%) and psychiatric disorders (11.36%). Regarding the behavior, all individuals were attended as outpatients, the majority (71.59%) had already received anesthesia in previous treatments, and only 7.95% required psychological conditioning. Most of the patients with special needs (89.77%) came to receive and use the prostheses. Conclusions: Main diagnosis and behavioral profile variables influenced the denture indication for those patients at the DSC-Poá. Gender and age also influence indication, as seen in the general population. This study may guide the implementation of projects both in private and public sectors.

The leptin gene product is released into the blood stream, passes through the blood-brain barrier, and finds the leptin receptor (LEPR) in the central nervous system. This hormone regulates food intake, hematopoiesis, inflammation, immunity, differentiation, and cell proliferation. The LEPR Gln223Arg polymorphism has been reported to alter receptor function and expression, both of which have been related with prognostics in several tumor types. Furthermore, several studies have shown a relationship between the Gln223Arg polymorphism and tumor development, and its role in oral and oropharyngeal squamous cell carcinoma is now well understood. In this study, 315 DNA samples were used for LEPR Gln223Arg genotyping and 87 primary oral and oropharyngeal squamous cell carcinomas were used for immunohistochemical expression analysis, such that a relationship between these and tumor development and prognosis could be established. Homozygous LEPR Arg223 was found to be associated with a 2-fold reduction in oral and oropharyngeal cancer risk. In contrast, the presence of the Arg223 allele in tumors was associated with worse disease-free and disease-specific survival. Low LEPR expression was found to be an independent risk factor, increasing the risk for lymph node metastasis 4-fold. In conclusion, the Gln223Arg polymorphism and LEPR expression might be valuable markers for oral and oropharyngeal cancer, suggesting that LEPR might serve as a potential target for future therapies.

Sodium hypochlorite has been used as an endodontic irrigant since 1936, when Walker used it as Sodium Chlorine. Since then it has became the most well acceptable endodontic irrigant. During the last few years many studies have reported the importance of pH control. Objective: This study evaluates the inflammatory response of some endodontic irrigations solutions in the subcutaneous connective tissue of mice. Material and methods: Thirty-six mice were obtained from the Biomedical Sciences Institute at the University of São Paulo. Their backs were divided into four quadrants and each quadrant was injured with an 8 mm punch. Three of these wounds were submitted to differents solutions, while the fourth was used as a control. This experiment was done in triplicate. After the irrigation of the wounds, the mice were sacrificed at 3, 7 and 14days. The samples were fixed on 10% formalin and histologically analyzed after hematoxylin and eosin staining. Results: At 14 days all wounds were covered with epithelium with a mild inflammatory infiltrate in the subjacent connective tissue, except for the group that employed 5% sodium hypochlorite at pH 11. Conclusion: The greatest the pH and concentration of sodium hypochlorite solutions, the most toxic they are.

Objective. Possible differences in splicing variants of TGIF1 in oral squamous cell carcinoma (OSCC) have not yet been reported. This study analyzed the expression levels of different splicing variants of the TGIF1 gene in OSCC compared with nontumoral epithelium (NT) and the relationship with clinical-pathologic features of tumors. Study Design. Forty-eight frozen samples of OSCC and 17 of NT were analyzed using quantitative reverse transcription polymerase chain reaction. Results. TGIF1v2 and v8 are overexpressed in OSCC, whereas TGIF1v5 is underexpressed when compared with NT. Low TGIF1v8 expression was correlated with lower cellular differentiation, positive blood vascular invasion, advanced pathologic stage, and positive vascular lymphatic invasion of OSCC. TGIF1v8 is also related to overall survival over time, with lower values associated with an increased risk of cancer-related death. Conclusions. These data suggest that alternative splicing of TGIF1 is deregulated in OSCC, with overexpression of some splicing variants, especially TGIF1v8, which is associated with advanced stages of OSCC. (Oral Surg Oral Med Oral Pathol Oral Radiol 2013;116:614-625)

Objective Oral non-Hodgkin lymphomas (NHLs) are an extensive group of malignant lymphoid cell neoplasms that are the second most common group of oral cancers. Subtyping NHL is important to plan for appropriate treatment, and the analysis of clonality is in many instances used for helping in the diagnosis of NHL. Thus, the aim of this study was to analyze immunoglobulin heavy chain (IgH) gene rearrangement in a series of oral B cell lymphomas to investigate the sensitivity of seminested polymerase chain reaction (snPCR). Study Design Paraffin embedded tissue samples from 16 cases of oral B cell lymphomas were retrieved and subjected to snPCR to investigate the IgH gene rearrangement. Results The results showed monoclonal IgH rearrangement in 85.7% of the cases studied, as represented by finding one band within the expected range of amplification. Conclusions This study found that snPCR is a consistent method for the detection of gene rearrangement in paraffin-embedded tissue.

Oral manifestations of common variable immunodeficiency (CVID) are rare, have rarely been studied and have given controversial results. There are few data about IgA, IgG, and IgM antibody salivary levels in the literature, and there are few papers about the clinical impact of antibody deficiencies and CVID on the oral health of such patients. The aim of this study was to measure serum and salivary IgA, IgG, and IgM levels in CVID participants and controls, and to associate immunoglobulin levels with caries and periodontal disease. This was a case-control study involving 51 CVID individuals and 50 healthy controls. All participants underwent examination for dental caries and periodontal disease. Blood and whole saliva samples were collected on the same day of the oral examination. Serum IgA, IgM, and IgG levels were measured by turbidimetry and salivary IgA, IgM, and IgG titers were assessed by enzyme-linked immunosorbent assay. Incidences of caries and gingivitis were significantly higher in the CVID group than in the control group (p0.05 for both). Although CVID was associated with increased susceptibility to caries and gingivitis, it was not associated with low salivary levels of IgA and IgM. Resumo As manifestações orais em pacientes com imunodeficiência comum variável (ICV) têm sido pouco estudadas e com resultados variados. Há escassos dados na literatura sobre os níveis de IgA, IgG e IgM na saliva, e pouco se sabe sobre o impacto clínico da deficiência destes anticorpos sobre a saúde bucal de pacientes com ICV. O objetivo deste estudo foi medir os níveis séricos e salivares de IgA, IgG e IgM em indivíduos com ICV e controles, e associar os níveis de imunoglobulinas com cárie e doença periodontal. Este foi um estudo de caso-controle, envolvendo 51 indivíduos ICV e 50 controles saudáveis. Todos os participantes foram examinados para cárie e doença periodontal. As amostras de sangue e saliva foram coletadas no mesmo dia do exame intraoral. Os níveis de IgA, IgM e IgG foram medidos por turbidimetria, e os títulos salivares de IgA, IgM e IgG foram avaliados através método imunoenzimático (ELISA). As incidências de cáries e gengivite foram significativamente maiores no grupo ICV do que no grupo controle (p0,05 para ambos). Embora ICV foi associado com um aumento da susceptibilidade à cárie e gengivite, não estava associado com baixos níveis salivares de IgA e IgM.

We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10(-8)), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10(-9)). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10(-6)) than in HPV-negative (OR = 0.75, P = 0.16) cancers. Genotyping performed at the Center for Inherited Disease Research (CIDR) was funded through the U.S. National Institute of Dental and Craniofacial Research (NIDCR) grant 1X01HG007780-0. Genotyping for shared controls with the Lung OncoArray initiative was funded through the grant X01HG007492-0. Corina Lesseur undertook this work during the tenure of a Postdoctoral Fellowship awarded by the International Agency for Research on Cancer. The funders did not participate in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. We acknowledge all of the participants involved in this research and the funders and support. We thank Dr. Leticia Fernandez (Instituto Nacional de Oncologia y Radiobiologia, La Habana, Cuba) for her contribution to the IARC ORC multicenter study. We are also grateful to Sergio Koifman (Escola Nacional de Saúde Pública, Rio de Janeiro, Brazil) for his contribution to the IARC Latin America multicenter study (Sergio Koifman passed away in May 2014) and to Xavier Castellsagué from the ARCAGE Barcelona Center who recently passed away (June 2016). The University of Pittsburgh head and neck cancer case-control study is supported by National Institutes of Health grants P50 CA097190 and P30 CA047904. The Carolina Head and Neck Cancer Study (CHANCE) was supported by the National Cancer Institute (R01-CA90731). The Head and Neck Genome Project (GENCAPO) was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Grant numbers 04/12054-9 and 10/51168-0). The authors thank all the members of the GENCAPO team. The HN5000 study was funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (RP-PG-0707-10034), the views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The Toronto study was funded by the Canadian Cancer Society Research Institute (020214) and the National Cancer Institute (U19 CA148127) and the Cancer Care Ontario Research Chair. The alcohol-related cancers and genetic susceptibility study in Europe (ARCAGE) was funded by the European Commission’s 5th Framework Program (QLK1-2001-00182), the Italian Association for Cancer Research, Compagnia di San Paolo/FIRMS, Region Piemonte, and Padova University (CPDA057222).The Rome Study was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) IG 2011 10491 and IG2013 14220 to SB, and Fondazione Veronesi to SB. The IARC Latin American study was funded by the European Commission INCO-DC programme (IC18-CT97-0222), with additional funding from Fondo para la Investigacion Cientifica y Tecnologica (Argentina) and the Fundação de Amparo à Pesquisa do Estado de São Paulo (01/01768-2). The IARC Central Europe study was supported by European Commission’s INCO-COPERNICUS Program (IC15-CT98-0332), NIH/National Cancer Institute grant CA92039, and the World Cancer Research Foundation grant WCRF 99A28.The IARC Oral Cancer Multicenter study was funded by: grant S06 96 202489 05F02 from Europe against Cancer; Grants FIS 97/0024, FIS 97/0662, and BAE 01/5013 from Fondo de Investigaciones Sanitarias, Spain; UICC Yamagiwa-Yoshida Memorial International Cancer Study; National Cancer Institute of Canada; Italian Association for Research on Cancer; and the Pan American Health Organization. The coordination of EPIC study is financially supported

Approximately 300 homeobox loci were identified in the euchromatic regions of the human genome, of which 235 are probable functional genes and 65 are likely pseudogenes. Many of these genes play important roles in embryonic development and cell differentiation. Dysregulation of homeobox gene expression is a frequent occurrence in cancer. Accumulating evidence suggests that as genetics disorders, epigenetic modifications alter the expression of oncogenes and tumor suppressor genes driving tumorigenesis and perhaps play a more central role in the evolution and progression of this disease. Here, we described the current knowledge regarding homeobox gene DNA methylation in human cancer and describe its relevance in the diagnosis, therapeutic response and prognosis of different types of human cancers.

In view of the similarity of clinicopathological features between reactive lesions of the oral cavity, the objective of the present study was to investigate the density of MCs (mast cells) and microvessels in a series of these lesions. Thirty-seven cases of reactive lesions including fibrous hyperplasia (FH, n=10), inflammatory fibrous hyperplasia (IFH, n=10), peripheral giant cell lesion (PGCL, n=10) and lobular capillary hemangioma (LCH, n=7) were investigated using immunohistochemistry for mast cell tryptase and CD34. For comparative purposes, central giant cell lesions (CGCL, n=5) were included. A higher MC density was observed in LCH (37.01), while CGCL exhibited the lowest density (n=8.14). There was a significant difference in MC density when all reactive lesions were compared to CGCL (p=0.001). The largest mean density of microvessels was observed in LCH (n=21.69). The smallest number was observed in CGCL (n=6.24). There was a significant difference in microvessel density when the reactive lesions were compared to CGCL (p=0.003). There was a significant and direct correlation between the density of MCs and microvessels only for IFH (p=0.048) and CGCL (p=0.005). A significant and direct correlation between the mean density of MCs and microvessels was observed when the reactive lesions were analyzed as a whole (p=0.005). Our results suggest that mast cells contribute to the connective tissue framework and angiogenic function, as well as the development, of reactive lesions of the oral cavity, including FH, IFH, LCH and PGCL.

Made available in DSpace on 2013-09-27T14:53:41Z (GMT). No. of bitstreams: 1 WOS000302298800023.pdf: 3718799 bytes, checksum: ab1d1250d6755fa013895445741e109a (MD5) Previous issue date: 2012-04-01 Made available in DSpace on 2013-09-30T19:24:42Z (GMT). No. of bitstreams: 1 WOS000302298800023.pdf: 3718799 bytes, checksum: ab1d1250d6755fa013895445741e109a (MD5) Previous issue date: 2012-04-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T14:04:49Z No. of bitstreams: 1 WOS000302298800023.pdf: 3718799 bytes, checksum: ab1d1250d6755fa013895445741e109a (MD5) Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T14:04:49Z No. of bitstreams: 1 WOS000302298800023.pdf: 3718799 bytes, checksum: ab1d1250d6755fa013895445741e109a (MD5) Made available in DSpace on 2014-05-20T14:04:49Z (GMT). No. of bitstreams: 1 WOS000302298800023.pdf: 3718799 bytes, checksum: ab1d1250d6755fa013895445741e109a (MD5) Previous issue date: 2012-04-01 Made available in DSpace on 2014-05-20T14:04:49Z (GMT). No. of bitstreams: 1 WOS000302298800023.pdf: 3718799 bytes, checksum: ab1d1250d6755fa013895445741e109a (MD5) Previous issue date: 2012-04-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T14:04:49Z No. of bitstreams: 1 WOS000302298800023.pdf: 3718799 bytes, checksum: ab1d1250d6755fa013895445741e109a (MD5) Made available in DSpace on 2014-05-20T14:04:49Z (GMT). No. of bitstreams: 1 WOS000302298800023.pdf: 3718799 bytes, checksum: ab1d1250d6755fa013895445741e109a (MD5) Previous issue date: 2012-04-01 Made available in DSpace on 2014-05-20T14:04:49Z (GMT). No. of bitstreams: 1 WOS000302298800023.pdf: 3718799 bytes, checksum: ab1d1250d6755fa013895445741e109a (MD5) Previous issue date: 2012-04-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Objective. The objective of this study was to evaluate the immunolocalization of bone morphogenetic protein 2 (BMP-2) after autogenous block grafting covered or not with an e-PTFE membrane.Study Design. Forty-eight rats were divided into 2 groups, autogenous block graft (B) and autogenous block graft + e-PTFE membrane (MB), and were evaluated by immunohistochemistry at baseline and 3, 7, 14, 21, and 45 days.Results. The largest number of positive cells in the recipient bed was observed after 3 days in both groups. At the graft border, the largest number of positive cells was seen after 7 days in group B and after 14 days in group MB. The highest proportion of staining in the graft was observed after 3 days in group B and after 21 days in group MB.Conclusions. High proportions of stain were related to intense revascularization and osteogenesis. Except for the interface, BMP-2 staining occurred later in group MB than in group B in all structures analyzed. (Oral Surg Oral Med Oral Pathol Oral Radiol 2012;113:533-541) Univ São Paulo, Dept Stomatol, São Paulo, Brazil Univ Estadual, UNESP, Fac Odontol, Dept Diag & Surg, Paulista, Brazil Universidade Federal de Santa Catarina (UFSC), Dept Pathol, Florianopolis, SC, Brazil Univ Estadual, UNESP, Fac Odontol, Dept Diag & Surg, Paulista, Brazil FAPESP: 00/11085-7

Made available in DSpace on 2019-09-12T16:57:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2012 Objective. The purposes of this study were to assess clinical, histopathological and immunohistochemical features of 22 oral neurofibromas (NFs) and discuss with previously described literature, addressing the main aspects regarding the differential diagnosis. Materials and methods. Immunohistochemical reactions included S-100, CD34, GLUT-1, EMA, Ki-67, p53 and Collagen IV and histochemical reactions for Alcian blue. Results. Clinically, the preferential location was the maxillary bones, tongue and buccal mucosa. Microscopically, widely spread spindle-shaped cells with scant cytoplasm and elongated nuclei were observed. Immunostaining revealed that the tumor cells weakly expressed GLUT-1, Collagen IV, Ki-67 and p53. They were variably positive for CD34, S-100 protein and membrane epithelial antigen (EMA). Conclusions. The different types of nerve sheath cells observed in the present series reinforce the presence of heterogeneous population in NFs. The strong positivity for S-100 suggests that the lesions were more composed by S-100-positive Schwann cells than other cells. Besides, the high number of CD34-positive cells suggests that this marker can be useful for the differential diagnosis of NFs against PEN, traumatic neuromas and Schwannomas. Finally, the low immunostaining for p53 and Ki-67 may indicate that NFs massively composed by S-100-positive Schwann cells present low potential of aggressiveness and malignant transformation. [Campos, Marcia Sampaio] Universidade de Taubaté (Unitau), Dept Dent Oral Pathol Oral Med, BR-12020330 Taubate, SP, Brazil [Fontes, Alexandra; Marocchio, Luciana Sassa; Nunes, Fabio Daumas; Orsini Machado de Sousa, Suzana Cantanhede] Univ Sao Paulo, Sch Dent, Dept Stomatol Oral Pathol, Sao Paulo, Brazil

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:26:26Z No. of bitstreams: 0 Made available in DSpace on 2014-05-27T11:26:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-04-01 The search for molecular markers to improve diagnosis, individualize treatment and predict behavior of tumors has been the focus of several studies. This study aimed to analyze homeobox gene expression profile in oral squamous cell carcinoma (OSCC) as well as to investigate whether some of these genes are relevant molecular markers of prognosis and/or tumor aggressiveness. Homeobox gene expression levels were assessed by microarrays and qRT-PCR in OSCC tissues and adjacent non-cancerous matched tissues (margin), as well as in OSCC cell lines. Analysis of microarray data revealed the expression of 147 homeobox genes, including one set of six at least 2-fold up-regulated, and another set of 34 at least 2-fold down-regulated homeobox genes in OSCC. After qRT-PCR assays, the three most up-regulated homeobox genes (HOXA5, HOXD10 and HOXD11) revealed higher and statistically significant expression levels in OSCC samples when compared to margins. Patients presenting lower expression of HOXA5 had poorer prognosis compared to those with higher expression (P=0.03). Additionally, the status of HOXA5, HOXD10 and HOXD11 expression levels in OSCC cell lines also showed a significant up-regulation when compared to normal oral keratinocytes. Results confirm the presence of three significantly upregulated (>4-fold) homeobox genes (HOXA5, HOXD10 and HOXD11) in OSCC that may play a significant role in the pathogenesis of these tumors. Moreover, since lower levels of HOXA5 predict poor prognosis, this gene may be a novel candidate for development of therapeutic strategies in OSCC. Department of Oral Pathology School of Dentistry University of São Paulo, Av. Prof. Lineu Prestes 2227, Cidade Universitária, 05508-000 São Paulo Department of Head and Neck Surgery School of Medicine University of São Paulo, Av. Dr. Arnaldo 455, Cerqueira César, 01246903 São Paulo Head and Neck Surgery Division Heliópolis Hospital Complex, Rua Cônego Xavier 276, Sacomã, 04231-030 São Paulo Department of Head and Neck Surgery Arnaldo Vieira de Carvalho Cancer Institute, Rua Dr Cesário Motta Junior 112, Vila Buarque, 01221020 São Paulo Department of Molecular Biology São José do Rio Preto School of Medicine, Av. Brigadeiro Faria Lima 5416-Vila São Pedro, 15090-000 São José do Rio Preto Department of Genetics and Evolutionary Biology Institute of Biosciences University of São Paulo, R. do Matão, travessa 14 321, Cidade Universitária, 05508-090 São Paulo Department of Genetics Biosciences Institute University of São Paulo, Rua do Matão, trav. 14 321, Cidade Universitária, 05508-090 São Paulo School of Medicine USP, São Paulo Albert Einstein Jewish Teaching and Research Institute (IIEP), São Paulo School of Medicine of São José do Rio Preto São José Dos Campos Dental School UNESP Cancer Institute Arnaldo Vieira de Carvalho, São Paulo School of Dentistry USP, São Paulo Heliópolis Hospital, São Paulo School of Medicine of Ribeirão Preto USP School of Public Health USP, São Paulo University of Vale do Paraíba, São José dos Campos School of Medicine UNIFESP, São Paulo Faculty of Pharmaceutical Sciences of Ribeirão Preto USP, SP São José Dos Campos Dental School UNESP

Objective: The present work aimed to present a brief review of literature on the most relevant prognostic factors to the clinical prognosis of patients with oral cancer considering the experience with clinical cases treated at our Oral Center. Method: An analytic and thematic literature review was performed through the PubMed and SciELO database articles. Texts were searched in the English and Portuguese medical literature, which were published from 1980 to 2009. The following key-words were used: prognostic factors, prognostic indicators, oral cancer prognosis, and oral cancer recurrence. Were included articles that addressed squamous cell carcinoma, since it is the most prevalent oral cancer, as well as clinical features, imaging procedures, clinical stage, recurrence rates, and aggressive behavior related to the most significant prognostic factors such as patient age, tumor location, tumor thickness and TNM classification. Were excluded articles whose approaches were related to laboratorial and experimental tests and involving tumor markers or molecular indicators of oral cancer. Results: From a total of 15.542 articles, twenty-three were selected after criteria application, and it was observed that lesions located in areas with difficult surgical access and with greater blood or lymphatic circulation (such as the tongue) have a worse prognosis; greater tumor thickness and TNM staging are associated with worst outcomes. Conclusion: Therefore, each member of the multidisciplinary group which assists OSCC patients must comprehend this pathology and its prognostic factors in order to become able to prevent, recognize and control the oral cancer. DESCRIPTORS: Oral Cancer. Prognostic. Diagnosis.

Objective Variations in genes that are critical for tooth formation may contribute to the tooth agenesis. MMPs are potential candidate genes for dental alterations based on the roles they play during embryogenesis. The aim of this study was to investigate the possible association between MMP1, MMP3, and MMP20 and tooth agenesis. Methods One hundred sixty-seven nuclear families from two different populations were analysed, 116 from Brazil and 51 from Turkey. Probands had at least one congenitally missing tooth. DNA samples were obtained from blood or saliva samples and genotyping was performed using TaqMan chemistry. In addition, Mmp20 was selected for quantitative real-time polymerase chain reaction analysis with SYBR Green I Dye in mouse tooth development. Results Associations between tooth agenesis and MMP1 (p = 0.007), and MMP20 (p = 0.03) were found in Brazilian families. In the total dataset, MMP20 continued to be associated with tooth agenesis (p = 0.01). Mmp20 was not expressed during the initial stages of tooth development. Conclusion Our findings provide evidence that MMP1 and MMP20 play a role in human tooth agenesis.

IntroductionOral lichen planus (OLP) is an idiopathic chronic mucocutaneous disease with a wide range of clinical manifestations, including white reticular patches, erosive/ulcerative and atrophic lesions, both associated with intense symptomatology. Topical corticosteroids are commonly used as standard therapy. However, patients frequently present relapses after the discontinuation of treatment as well as developing resistance to corticosteroid therapy. Photobiomodulation (PBM) has been shown to be a potential therapeutic tool to treat inflammatory disorders, including OLP. The aim of this study was to compare the efficacy of PBM (660 nm) with corticosteroid therapy with clobetasol propionate 0.05% for the treatment of OLP.Methods and analysisForty-four patients with symptomatic and histopathological diagnosis of OLP will be randomised into two experimental groups in a double-blind manner: control group (n=22): clobetasol propionate 0.05%+placebo PBM, and experimental group (n=22): PBM (λ=660 nm, power 100 mW, radiant exposure: 177 J/cm2and 0.5J per point)+placebo gel. Laser will be applied 2×/week for 1 month and clobetasol propionate three times a day for 30 days and the same for placebo treatments. The primary variable (pain) and the secondary variables (clinical score, evaluation of functional scores, clinical resolution, OLP recurrence, quality of life and anxiety and depression) will be evaluated at the baseline, once a week during treatment (depending on the variables) and after 30 days and 60 days of follow-up. Pain will be evaluated using visual analogue scale and clinical characteristics will be scored using the Thongprasom Index. The quality of life and anxiety and depression will be evaluated by Oral Health Impact Profile-14 questionnaire and by Hospital Anxiety and Depression Scale for anxiety scale, respectively. The serum and salivary levels of interleukin (IL)-6, IL-10, IL-1β, INF-γ and tumour necrosis factor-α will be evaluated by ELISA at baseline and at the end of treatment.Ethics and disseminationThis protocol was approved (#2.375.410) by the Nove de Julho University (UNINOVE) Research Ethics Committee. The data gathered using this protocol will be published in a peer-reviewed journal.Trial registration numberNCT03320460.

Previous studies indicated that patients with atherosclerosis are predominantly infected by human cytomegalovirus (HCMV), but rarely infected by type 1 Epstein-Barr virus (EBV-1). In this study, atheromas of 30 patients who underwent aortocoronary bypass surgery with coronary endartherectomy were tested for the presence of these two viruses. HCMV occurred in 93.3% of the samples and EBV-1 was present in 50% of them. Concurrent presence of both pathogens was detected in 43.3% of the samples.

Aims Jumonji Domain-Containing 1A (JMJD1A) protein promotes demethylation of histones, especially at lysin-9 of di-methylated histone H3 (H3K9me2) or mono-methylated (H3K9me1). Increased levels of H3 histone methylation at lysin-9 (H3K9) is related to tumor suppressor gene silencing. JMJD1A gene target Adrenomeduline (ADM) has shown to promote cell growth and tumorigenesis. JMJD1A and ADM expression, as well as H3K9 methylation level have been related with development risk and prognosis of several tumor types. Methods and results We aimed to evaluate JMJD1A, ADM, H3K9me1 and H3K9me2expression in paraffin-embedded tissue microarrays from 84 oral and oropharyngeal squamous cell carcinoma samples through immunohistochemistry analysis. Our results showed that nuclear JMJD1A expression was related to lymph node metastasis risk. In addition, JMJD1A cytoplasmic expression was an independent risk marker for advanced tumor stages. H3K9me1 cytoplasmic expression was associated with reduced disease-specific death risk. Furthermore, high H3K9me2 nuclear expression was associated with worse specific-disease and disease-free survival. Finally, high ADM cytoplasmic expression was an independent marker of lymph node metastasis risk. Conclusion JMJD1A, H3K9me1/2 and ADM expression may be predictor markers of progression and prognosis in oral and oropharynx cancer patients, as well as putative therapeutic targets.