Search

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

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

Hypermethylation in the promoter region has been associated with a loss of gene function that may give a selective advantage to neoplastic cells. In this study, the methylation pattern of genes CDKN2A (alias p14 , p14 ARF , p16 , p16 INK4a ), DAPK1 , CDH1 , and ADAM23 was analyzed in 43 samples of head and neck tumors using methylation-specific polymerase chain reaction. In the oropharynx, there was a statistically significant association between hypermethylation of the DAPK1 gene and the occurrence of lymph node metastases, and in the larynx there was statistically significant evidence of an association between hypermethylation of the ADAM23 gene and advanced stages of the tumors. Thus, a correlation was observed between hypermethylation of the promoter region of genes DAPK1 and ADAM23 and the progression of head and neck cancer.

Objetivo: O objetivo deste trabalho foi estudar a voz próximo à sua fonte produtora, as pregas vocais, através de um microfone miniaturizado de aparelho auditivo que foi adaptado para ser acoplado à extremidade de um fibrolaringoscópio, permitindo a captação da voz durante a laringoscopia direta. Forma de estudo: Experimental. Material e Método: A voz foi estudada em um grupo de 50 indivíduos, 25 homens e 25 mulheres sem doenças, através de um programa de análise acústica MDVP (Multi-Dimensional Voice Program) do laboratório de voz Computerized Speech Lab, Model 4300B, da Kay Elemetrics. Amostras de vogais sustentadas /a/, /i/ e /u/ foram captadas de três formas diferentes, primeiramente com um microfone comum externo a 15 cm da boca, em segundo lugar com o microfone especial na faringe a 1,5 cm acima das pregas vocais e por último com o microfone especial externamente a 2 cm da boca. Doze parâmetros acústicos relacionados a freqüência fundamental, amplitude e ruído de cada uma das vogais foram comparadas estatisticamente conforme à sua forma de captação. Resultados: Os resultados mostraram diferenças estatisticamente significativas entre a voz captada pelo microfone comum externo e o microfone especial, em relação à freqüência fundamental, aos parâmetros de variação de periodicidade de freqüência, amplitude e ruído. Conclusão: A diferença do som da fonte glótica do som da voz externa pode mostrar as modificações sofridas pela voz no decorrer da passagem pelo trato vocal.Aim: The aim of the present study is to examine the voice to its acoustic source - the vocal folds - with a miniature hearing-aid microphone coupled to the extremity of a laryngo-fiberscope allowing the voice to be captured during direct laryngoscopy. Study design: Experimental. Material and Method: The voice of 50 individuals - 25 males and 25 females bearing no pathologies - was collected by the Multi-Dimensional Voice Program (MDVP) by Kay Elemetrics’ Computerized Speech Lab 4300B Model. Samples of the sustained vowels /a/, /i/ and /u/ were picked up in three distinct ways. Firstly, by a common external microphone placed at 15 cm from the mouth. Secondly, a special microphone was placed on the pharynx 1.5 cm above the vocal folds. Lastly, the same special microphone was placed externally at 2 cm from the mouth. Twelve acoustic parameters regarding fundamental frequency, amplitude and noise of each and every vowel were compared statistically as to the way the voice was picked up. Results: Results show statistically significant differences between the voice picked up by the common external microphone and by the special one as regards to the fundamental frequency, frequency and amplitude variability and noise. Conclusion: The difference between the sound coming from the glottic source and the sound from the external voice shows alterations experienced by the voice during its passage through the vocal tract.

Background. The ultrasonic scalpel is a recently introduced device in head and neck surgery. Total thyroidectomy is the most common endocrine procedure performed by surgeons. Methods. This was an open, phase IV, multicenter, randomized controlled trial (RCT) that compared the use of an ultrasonic scalpel with a conventional technique in patients who underwent total thyroidectomy. The outcomes were surgi- cal complication rate, operative time, drainage volume, postop- erative pain, and costs. Results. In all, 261 patients were included in 11 centers. There was a mean difference of 17% of operative time in favor of the ultrasonic scalpel group. There were no differences in postoperative complications. There was a difference in costs of 14% in favor of the ultrasonic scalpel group, but it was not statistically significant. Conclusions. The use of an ultrasonic scalpel was as safe as that of the conventional technique and had the advantage of a shorter operative time and lower postoperative drainage. Costs were not different between groups. V C 2012 Wiley Period- icals, Inc. Head Neck 34: 805-812, 2012

Made available in DSpace on 2013-08-28T14:07:40Z (GMT). No. of bitstreams: 1 WOS000278383600001.pdf: 960234 bytes, checksum: 9cd26a9750ec13e67eaf9019e1f48e7b (MD5) Made available in DSpace on 2013-09-30T18:12:07Z (GMT). No. of bitstreams: 2 WOS000278383600001.pdf: 960234 bytes, checksum: 9cd26a9750ec13e67eaf9019e1f48e7b (MD5) WOS000278383600001.pdf.txt: 69473 bytes, checksum: e718db9d53c8e8829f735f82524e401f (MD5) Previous issue date: 2010-05-04 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T14:00:48Z No. of bitstreams: 2 WOS000278383600001.pdf: 960234 bytes, checksum: 9cd26a9750ec13e67eaf9019e1f48e7b (MD5) WOS000278383600001.pdf.txt: 69473 bytes, checksum: e718db9d53c8e8829f735f82524e401f (MD5) Made available in DSpace on 2014-05-20T14:00:48Z (GMT). No. of bitstreams: 2 WOS000278383600001.pdf: 960234 bytes, checksum: 9cd26a9750ec13e67eaf9019e1f48e7b (MD5) WOS000278383600001.pdf.txt: 69473 bytes, checksum: e718db9d53c8e8829f735f82524e401f (MD5) Previous issue date: 2010-05-04 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Rede Proteoma do Estado de São Paulo Ludwig Institute for Cancer Research Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Background: The development and progression of cancer depend on its genetic characteristics as well as on the interactions with its microenvironment. Understanding these interactions may contribute to diagnostic and prognostic evaluations and to the development of new cancer therapies. Aiming to investigate potential mechanisms by which the tumor microenvironment might contribute to a cancer phenotype, we evaluated soluble paracrine factors produced by stromal and neoplastic cells which may influence proliferation and gene and protein expression.Methods: The study was carried out on the epithelial cancer cell line (Hep-2) and fibroblasts isolated from a primary oral cancer. We combined a conditioned-medium technique with subtraction hybridization approach, quantitative PCR and proteomics, in order to evaluate gene and protein expression influenced by soluble paracrine factors produced by stromal and neoplastic cells.Results: We observed that conditioned medium from fibroblast cultures (FCM) inhibited proliferation and induced apoptosis in Hep-2 cells. In neoplastic cells, 41 genes and 5 proteins exhibited changes in expression levels in response to FCM and, in fibroblasts, 17 genes and 2 proteins showed down-regulation in response to conditioned medium from Hep-2 cells (HCM). Nine genes were selected and the expression results of 6 down-regulated genes (ARID4A, CALR, GNB2L1, RNF10, SQSTM1, USP9X) were validated by real time PCR.Conclusions: A significant and common denominator in the results was the potential induction of signaling changes associated with immune or inflammatory response in the absence of a specific protein. Sch Med FAMERP, Dept Mol Biol, Sao Jose do Rio Preto, Brazil São Paulo State Univ UNESP, IBILCE, Dept Biol, Sao Jose do Rio Preto, Brazil Sch Med FAMERP, Dept Otorhinolaryngol & Head & Neck Surg, Sao Jose do Rio Preto, Brazil Univ São Paulo, Inst Biociencias, Dept Genet & Evolutionary Biol, São Paulo, Brazil Arnaldo Vieira de Carvalho Hosp, Dept Head & Neck Surg, São Paulo, Brazil Univ São Paulo, Sch Med, Dept Surg, Div Head & Neck Surg, BR-09500900 São Paulo, Brazil Heliopolis Hosp, Dept Head & Neck Surg, São Paulo, Brazil UNESP, Fac Engn Ilha Solteria, Dept Biol & Zootechny, Ilha Solteira, Brazil São Paulo State Univ UNESP, IBILCE, Dept Biol, Sao Jose do Rio Preto, Brazil UNESP, Fac Engn Ilha Solteria, Dept Biol & Zootechny, Ilha Solteira, Brazil FAPESP: 04/12054-9 FAPESP: 06/60162-0 FAPESP: 04/14846-0 FINEP: 01.07.0290.00

Laryngeal squamous cell carcinoma is very common in head and neck cancer, with high mortality rates and poor prognosis. In this study, we compared expression profiles of clinical samples from 13 larynx tumors and 10 non-neoplastic larynx tissues using a custom-built cDNA microarray containing 331 probes for 284 genes previously identified by informatics analysis of EST databases as markers of head and neck tumors. Thirty-five genes showed statistically significant differences (SNR > or = | 1.0 |, p< or =0.001) in the expression between tumor and non-tumor larynx tissue samples. Functional annotation indicated that these genes are involved in cellular processes relevant to the cancer phenotype, such as apoptosis, cell cycle, DNA repair, proteolysis, protease inhibition, signal transduction and transcriptional regulation. Six of the identified transcripts map to intronic regions of protein-coding genes and may comprise non-annotated exons or as yet uncharacterized long ncRNAs with a regulatory role in the gene expression program of larynx tissue. The differential expression of 10 of these genes (ADCY6, AES, AL2SCR3, CRR9, CSTB, DUSP1, MAP3K5, PLAT, UBL1 and ZNF706) was independently confirmed by quantitative real-time RT-PCR. Among these, the CSTB gene product has cysteine protease inhibitor activity that has been associated with an antimetastatic function. Interestingly, CSTB showed a low expression in the tumor samples analyzed (p

Head and neck cancer remains a morbid and often fatal disease and at the present time few effective molecular markers have been identified. The purpose of the present work was to identify new molecular markers for head and neck squamous cell carcinoma (HNSCC). We applied methylation-sensitive arbitrarily primed PCR (MS/AP-PCR) to isolate sequences differentially methylated in HNSCC. The most frequently hypermethylated fragment we found maps close to a cytosine guanine dinucleotide (CpG) island on chromosome 9q33.2, and hypermethylation of this CpG island was associated with transcriptional silencing of an alternative transcript of the LHX6 gene. Using combined bisulfite restriction analysis (COBRA), hypermethylation of this fragment was detected in 13 of 14 (92.8%) HNSCC cell lines studied and 21 of 32 (65.6%) primary tumors, whereas little or no methylation was seen in 10 normal oral mucosa samples. We extended this investigation to other cancer cell lines and methylation was found in those derived from colon, breast, leukemia and lung, and methylation was also found in 12/14 primary colon tumors. These findings suggest that differentially methylated (DIME)-6 hypermethylation is a good cancer marker in HNSCC as well as in other kinds of neoplasias and confirm the importance of searching for markers of epigenetic dysregulation in cancer.

Univ Estadual Paulista, Inst Biociencias Letras & Ciencias Exatas, Dept Biol, BR-15054 Sao Jose do Rio Preto, Brazil

Head and neck squamous cell carcinoma is a disease associated with tobacco and alcohol abuse. There is evidence that the oncogenic human papillomavirus (HPV) may also be a risk for upper aerodigestive tract cancers. High-risk HPVs encode two early proteins, E6 and E7, that can bind to p53 and pRb, respectively, and induce its degradation or inactivation. The TP53 gene has a single polymorphism at codon 72 of exon 4 that encodes either arginine (Arg) or proline (Pro). The purpose of this study was to evaluate the role of HPV infection and TP53 polymorphism in head and neck cancer. We analyzed 50 tumors, as well swabs of oral mucosa from 142 control individuals, with a polymerase chain reaction technique. The prevalence of HPV in controls was 10.6% and in cancer specimens 16%. The frequency distribution of genotypes in controls was 50% Arg/Arg, 43% Arg/Pro and 7% Pro/Pro; in tumors, it was 52% Arg/Arg, 32% Arg/Pro, and 16% Pro/Pro. Contrary to the results of some studies on cervical cancer, no association between any TP53 genotype or allele and the development of head and neck cancer was observed, regardless of HPV status, except for the Pro/Pro genotype, which is associated with the absence of HPV. The arginine allele appears to protect against head and neck cancers. Also, the data showed that HPV infection results in no increased risk of developing head and neck tumors.

Objetivo: O objetivo deste trabalho foi estudar a voz próximo à sua fonte produtora, as pregas vocais, através de um microfone miniaturizado de aparelho auditivo que foi adaptado para ser acoplado à extremidade de um fibrolaringoscópio, permitindo a captação da voz durante a laringoscopia direta. Forma de estudo: Experimental. Material e Método: A voz foi estudada em um grupo de 50 indivíduos, 25 homens e 25 mulheres sem doenças, através de um programa de análise acústica MDVP (Multi-Dimensional Voice Program) do laboratório de voz Computerized Speech Lab, Model 4300B, da Kay Elemetrics. Amostras de vogais sustentadas /a/, /i/ e /u/ foram captadas de três formas diferentes, primeiramente com um microfone comum externo a 15 cm da boca, em segundo lugar com o microfone especial na faringe a 1,5 cm acima das pregas vocais e por último com o microfone especial externamente a 2 cm da boca. Doze parâmetros acústicos relacionados a freqüência fundamental, amplitude e ruído de cada uma das vogais foram comparadas estatisticamente conforme à sua forma de captação. Resultados: Os resultados mostraram diferenças estatisticamente significativas entre a voz captada pelo microfone comum externo e o microfone especial, em relação à freqüência fundamental, aos parâmetros de variação de periodicidade de freqüência, amplitude e ruído. Conclusão: A diferença do som da fonte glótica do som da voz externa pode mostrar as modificações sofridas pela voz no decorrer da passagem pelo trato vocal. Aim: The aim of the present study is to examine the voice to its acoustic source - the vocal folds - with a miniature hearing-aid microphone coupled to the extremity of a laryngo-fiberscope allowing the voice to be captured during direct laryngoscopy. Study design: Experimental. Material and Method: The voice of 50 individuals - 25 males and 25 females bearing no pathologies - was collected by the Multi-Dimensional Voice Program (MDVP) by Kay Elemetrics’ Computerized Speech Lab 4300B Model. Samples of the sustained vowels /a/, /i/ and /u/ were picked up in three distinct ways. Firstly, by a common external microphone placed at 15 cm from the mouth. Secondly, a special microphone was placed on the pharynx 1.5 cm above the vocal folds. Lastly, the same special microphone was placed externally at 2 cm from the mouth. Twelve acoustic parameters regarding fundamental frequency, amplitude and noise of each and every vowel were compared statistically as to the way the voice was picked up. Results: Results show statistically significant differences between the voice picked up by the common external microphone and by the special one as regards to the fundamental frequency, frequency and amplitude variability and noise. Conclusion: The difference between the sound coming from the glottic source and the sound from the external voice shows alterations experienced by the voice during its passage through the vocal tract.

Univ Estadual Paulista, Dept Biol, IBILCE, UNESP, BR-15054000 Sao Jose do Rio Preto, SP, Brazil