Saprochaete clavata invasive infection: characterization, antifungal susceptibility, and biofilm evaluation of a rare yeast isolated in Brazil.

Rare emerging pathogens such as Saprochaete clavata are associated with invasive fungal diseases, high morbidity, mortality, rapidly fatal infections, and outbreaks. However, little is known about S. clavata infections, epidemiology, risk factors, treatment, biofilms, and disease outcomes. The objective of this study was to describe a new case of severe S. clavata infection in a patient diagnosed at a referral children's hospital in Brazil, including antifungal minimal inhibitory concentration, S. clavata biofilm characterization, and molecular characterization. The S. clavata isolated from an immunocompromised 11-year-old male patient was characterized using MALDI-TOF, Gram staining, scanning electron microscopy (SEM), and next generation sequencing (NGS) of genomic DNA. Biofilm production was also evaluated in parallel with determining minimal inhibitory concentration (MIC) and biofilm sensitivity to antifungal treatment. We observed small to medium, whitish, farinose, dry, filamentous margin colonies, yeast-like cells with bacillary features, and biofilm formation. The MALDI-TOF system yielded a score of ≥ 2,000, while NGS confirmed S. clavata presence at the nucleotide level. The MIC values (in mg L-1) for tested drugs were as follows: fluconazole = 2, voriconazole ≤ 2, caspofungin ≥ 8, micafungin = 2, amphotericin B = 4, flucytosine ≤ 1, and anidulafungin = 1. Amphotericin B can be active against S. clavata biofilm and the fungus can be susceptible to new azoles. These findings were helpful for understanding the development of novel treatments for S. clavata-induced disease, including combined therapy for biofilm-associated infections.

Saprochaete clavata invasive infection: characterization, antifungal susceptibility, and biofilm evaluation of a rare yeast isolated in Brazil

ABSTRACT Rare emerging pathogens such as Saprochaete clavata are associated with invasive fungal diseases, high morbidity, mortality, rapidly fatal infections, and outbreaks. However, little is known about S. clavata infections, epidemiology, risk factors, treatment, biofilms, and disease outcomes. The objective of this study was to describe a new case of severe S. clavata infection in a patient diagnosed at a referral children's hospital in Brazil, including antifungal minimal inhibitory concentration, S. clavata biofilm characterization, and molecular characterization. The S. clavata isolated from an immunocompromised 11-year-old male patient was characterized using MALDI-TOF, Gram staining, scanning electron microscopy (SEM), and next generation sequencing (NGS) of genomic DNA. Biofilm production was also evaluated in parallel with determining minimal inhibitory concentration (MIC) and biofilm sensitivity to antifungal treatment. We observed small to medium, whitish, farinose, dry, filamentous margin colonies, yeast-like cells with bacillary features, and biofilm formation. The MALDI-TOF system yielded a score of ≥ 2,000, while NGS confirmed S. clavata presence at the nucleotide level. The MIC values (in mg L-1) for tested drugs were as follows: fluconazole = 2, voriconazole ≤ 2, caspofungin ≥ 8, micafungin = 2, amphotericin B = 4, flucytosine ≤ 1, and anidulafungin = 1. Amphotericin B can be active against S. clavata biofilm and the fungus can be susceptible to new azoles. These findings were helpful for understanding the development of novel treatments for S. clavata-induced disease, including combined therapy for biofilm-associated infections.

A Covid-19 e as citocinas: uma revisão de literatura / Covid-19 and cytokines: a literature review / Covid-19 y citocinas: una revisión de la literatura

A COVID-19 surgiu em dezembro de 2019 na China, o contágio se espalhou rapidamente pelo mundo e já em março de 2020 a Organização Mundial da Saúde (OMS) declarou o surto como pandemia. A infecção causada por SARS-COV-2 mostrou-se com sintomatologia variada. Enquanto alguns infectados não tinham sintomas, outros apresentavam sinais que variam dos semelhantes a uma gripe, até uma possível evolução para síndrome do desconforto respiratório. Evidências indicam que, durante o curso da COVID-19 a rápida progressão e mortalidade pode ter sido associada à mecanismo hiperinflamatórios, com descontrole regulatório da produção de citocinas pró- inflamatórias, tanto em nível local, quanto sistêmico. Sendo assim, neste artigo revisamos a literatura sobre a COVID-19, seus aspectos epidemiológicos e clínicos, bem como a o papel das citocinas no contexto da infecção por SARS-CoV-2, já que a busca pelo entendimento dos mecanismos imunológicos que envolvem a COVID-19 e outras doenças de caráter inflamatório é de suma importância para o tratamento e o manejo de tais enfermidades.

COVID-19 emerged in December 2019 in China, the contagion spread rapidly around the world, and already in March 2020 the World Health Organization (WHO) declared the outbreak a pandemic. The infection caused by SARS-COV-2 was shown to have varied symptomatology. While some infected people had no symptoms, others showed signs ranging from flu-like to a possible evolution to respiratory distress syndrome. Evidence indicates that during the course of COVID-19 the rapid progression and mortality may have been associated with hyperinflammatory mechanisms, with regulatory uncontrolled production of pro-inflammatory cytokines at both local and systemic levels. Therefore, in this article we review the literature on COVID-19, its epidemiological and clinical aspects, as well as the role of cytokines in the context of SARS-CoV-2 infection, since the search for understanding the immunological mechanisms surrounding COVID-19 and other inflammatory diseases is of paramount importance for the treatment and management of such diseases.

El COVID-19 surgió en diciembre de 2019 en China, el contagio se extendió rápidamente por todo el mundo y ya en marzo de 2020 la Organización Mundial de la Salud (OMS) declaró el brote como pandemia. Se demostró que la infección causada por el SARS-COV-2 presentaba una sintomatología variada. Mientras que algunos infectados no presentaban síntomas, otros mostraban signos que iban desde similares a los de la gripe hasta una posible evolución a síndrome de dificultad respiratoria. Las pruebas indican que durante el curso del COVID-19 la rápida progresión y la mortalidad pueden haber estado asociadas a mecanismos hiperinflamatorios, con una producción descontrolada reguladora de citocinas proinflamatorias tanto a nivel local como sistémico. Por lo tanto, en este artículo revisamos la literatura sobre la COVID-19, sus aspectos epidemiológicos y clínicos, así como el papel de las citocinas en el contexto de la infección por SARS-CoV-2, ya que la búsqueda de la comprensión de los mecanismos inmunológicos que rodean la COVID-19 y otras enfermedades inflamatorias es de suma importancia para el tratamiento y la gestión de dichas enfermedades.

Clinical decision support analysis of a microRNA-based thyroid molecular classifier: A real-world, prospective and multicentre validation study.

BACKGROUND: The diagnosis of cancer in Bethesda III/IV thyroid nodules is challenging as fine-needle aspiration (FNA) has limitations, and these cases usually require diagnostic surgery. As approximately 77% of these nodules are not malignant, a diagnostic test accurately identifying benign thyroid nodules can reduce "potentially unnecessary" surgery rates. We have previously reported the development and validation of a microRNA-based thyroid classifier (mir-THYpe) with high sensitivity and specificity, which could be performed directly from FNA smear slides. We sought to evaluate the performance of this test in real-world clinical routine to support clinical decisions and to reduce surgery rates. METHODS: We designed a real-world, prospective, multicentre study. Molecular tests were performed with FNA samples prepared at 128 cytopathology laboratories. Patients were followed-up from March 2018 until surgery or until March 2020 (patients with no indication for surgery). The final diagnosis of thyroid tissue samples was retrieved from postsurgical anatomopathological reports. FINDINGS: A total of 435 patients (440 nodules) classified as Bethesda III/IV were followed-up. The rate of avoided surgeries was 52·5% for all surgeries and 74·6% for "potentially unnecessary" surgeries. The test achieved 89·3% sensitivity, 81·65% specificity, 66·2% positive predictive value, and 95% negative predictive value. The test supported 92·3% of clinical decisions. INTERPRETATION: The reported data demonstrate that the use of the microRNA-based classifier in the real-world can reduce the rate of thyroid surgeries with robust performance and support clinical decision-making. FUNDING: The São Paulo Research-Foundation (FAPESP) and Onkos.

Impacto da atividade física na qualidade de vida e sobrevida de idosos com câncer: uma revisão sistemática / Impact of physical activity on the quality of life of older adults with cancer: a systematic review

Objetivo: avaliar o impacto da atividade física (AF) em qualidade de vida (QV) e sobrevida (SV) de idosos com câncer. Método: revisão sistemática nas bases de dados Medline-Bireme, PubMed, Cochrane-Embase e SciELO. Os estudos passaram por critérios de seleção e análise, com base nas escalas de PRISMA e PEDro. Resultados:foram selecionados dez estudos ao final do processo, sete relacionados à QV e três relacionados à SV. Os resultados mostraram que intervenções realizadas após o diagnostico oncológico trazem benefícios para a QV, como aumento da funcionalidade, da força muscular, da densidade mineral óssea, da flexibilidade, do bem-estar e da massa magra. Houve também impacto positivo na SV. Conclusão: os resultados desta revisão sistemática ajudam a compreender que a prática de AF pode trazer benefícios tanto para a QV quanto para a SV de pessoas acima de 60 anos com diagnósticos oncológicos.(AU)

Objective: to evaluate the impact of physical activity (PA) on quality of life (QoL) and survival rate (SV) of the elderly with cancer. Method: systematic review in databases such as Medline-Bireme, PubMed, Cochrane-Embase, and SciELO. The studies underwent selection and analysis criteria, based on PRISMA and PEDro scales. Results: ten studies were selected at the end of the process, seven related to QoL and three related to SV. The results showed that interventions performed after cancer diagnosis bring benefits for QoL, such as increased functionality, muscle strength, bone mineral density, flexibility, well-being and lean mass. There was also a positive impact on SV. Conclusion: the results of this systematic review help to understand that PA can offer benefits for both QoL and SV of people over 60 years of age with cancer diagnosis.(AU)

Microbiome and oral squamous cell carcinoma: a possible interplay on iron metabolism and its impact on tumor microenvironment.

There is increasing evidence showing positive association between changes in oral microbiome and the occurrence of oral squamous cell carcinoma (OSCC). Alcohol- and nicotine-related products can induce microbial changes but are still unknown if these changes are related to cancerous lesion sites. In an attempt to understand how these changes can influence the OSCC development and maintenance, the aim of this study was to investigate the oral microbiome linked with OSCC as well as to identify functional signatures and associate them with healthy or precancerous and cancerous sites. Our group used data of oral microbiomes available in public repositories. The analysis included data of oral microbiomes from electronic cigarette users, alcohol consumers, and precancerous and OSCC samples. An R-based pipeline was used for taxonomic and functional prediction analysis. The Streptococcus spp. genus was the main class identified in the healthy group. Haemophilus spp. predominated in precancerous lesions. OSCC samples revealed a higher relative abundance compared with the other groups, represented by an increased proportion of Fusobacterium spp., Prevotella spp., Haemophilus spp., and Campylobacter spp. Venn diagram analysis showed 52 genera exclusive of OSCC samples. Both precancerous and OSCC samples seemed to present a specific associated functional pattern. They were menaquinone-dependent protoporphyrinogen oxidase pattern enhanced in the former and both 3',5'-cyclic-nucleotide phosphodiesterase (purine metabolism) and iron(III) transport system ATP-binding protein enhanced in the latter. We conclude that although precancerous and OSCC samples present some differences on microbial profile, both microbiomes act as "iron chelators-like" potentially contributing to tumor growth.

COVID-19: The question of genetic diversity and therapeutic intervention approaches.

Coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2), is the largest pandemic in modern history with very high infection rates and considerable mortality. The disease, which emerged in China's Wuhan province, had its first reported case on December 29, 2019, and spread rapidly worldwide. On March 11, 2020, the World Health Organization (WHO) declared the COVID-19 outbreak a pandemic and global health emergency. Since the outbreak, efforts to develop COVID-19 vaccines, engineer new drugs, and evaluate existing ones for drug repurposing have been intensively undertaken to find ways to control this pandemic. COVID-19 therapeutic strategies aim to impair molecular pathways involved in the virus entrance and replication or interfere in the patients' overreaction and immunopathology. Moreover, nanotechnology could be an approach to boost the activity of new drugs. Several COVID-19 vaccine candidates have received emergency-use or full authorization in one or more countries, and others are being developed and tested. This review assesses the different strategies currently proposed to control COVID-19 and the issues or limitations imposed on some approaches by the human and viral genetic variability.

Larynx cancer: search for molecular markers

Introduction: Despite the advances in the understanding and treatment of the Larynx squamous cell carcinoma (LSCC), the survival has not changed in the last 30 years. Objective: In this study, we search for a better understanding of the pattern of genic expression of LSCC. Methods: Thirty-two tumor samples were collected from patients submitted to LSCC resection. The samples were submitted to cDNA microarray analysis to identify LSCC target. Results: The comparison of gene expression between early and advanced stages revealed 30 genes with significant differential expression. RT-qPCR validation experiments confirmed significant expression of only two genes (TMEM56 and SEC14L2) from eight selected. Comparing adjacent normal and tumor tissues, 69 genes showed statistically significant expression (mean ratio of 5.5), and 30 of them were up-regulated in tumor tissues. Gene expression validation by RT-qPCR showed SPRR2G and S100A7A as the most expressed in tumor tissue. Conclusion: The results demonstrate different pattern of expression, specially among tumor and non neoplastic tissue. The limitations to improve survival in larynx cancer justify studies focusing on search for molecular markers of prognosis and possible targeted therapy on LSCC.

Short telomere length in peripheral blood leukocytes in head and neck cancer: Findings in a Brazilian cohort.

BACKGROUND: Telomeres are specialized DNA structures that are critical to maintain cell homeostasis and to avoid genomic instability. Epidemiological studies have examined the association between leukocyte telomere length (LTL) and risk of cancers, but the findings remain conflicting. METHODS: Mean LTL was measured by quantitative PCR in 97 patients with head and neck cancer (HNC) and 262 healthy controls. The association between LTL and patients' clinical status, such as smoke, alcoholism, and overall survival, were also evaluated. RESULTS: The age-adjusted LTL was significantly shorter in patients with HNC in comparison to healthy controls (P = .0003). Patients with shortest LTL had an increased risk to develop HNC (P < 0.0001). No significant correlation was observed between LTL and patients' clinical features and personal habits. CONCLUSIONS: Our data support the hypothesis that LTL is a risk factor for HNC. The use of LTL as a biomarker can help physicians to identify high-risk individuals for HNC.

Molecular Classification of Thyroid Nodules with Indeterminate Cytology: Development and Validation of a Highly Sensitive and Specific New miRNA-Based Classifier Test Using Fine-Needle Aspiration Smear Slides.

Background: Thyroid nodules can be identified in up to 68% of the population. Fine-needle aspiration (FNA) cytopathology classifies 20%-30% of nodules as indeterminate, and these are often referred for surgery due to the risk of malignancy. However, histological postsurgical reports indicate that up to 84% of cases are benign, highlighting a high rate of unnecessary surgeries. We sought to develop and validate a microRNA (miRNA)-based thyroid molecular classifier for precision endocrinology (mir-THYpe) with both high sensitivity and high specificity, to be performed on the FNA cytology smear slide with no additional FNA. Methods: The expression of 96 miRNA candidates from 39 benign/39 malignant thyroid samples, (indeterminate on FNA) was analyzed to develop and train the mir-THYpe algorithm. For validation, an independent set of 58 benign/37 malignant FNA smear slides (also classified as indeterminate) was used. Results: In the training set, with a 10-fold cross-validation using only 11 miRNAs, the mir-THYpe test reached 89.7% sensitivity, 92.3% specificity, 90.0% negative predictive value and 92.1% positive predictive value. In the FNA smear slide validation set, the mir-THYpe test reached 94.6% sensitivity, 81.0% specificity, 95.9% negative predictive value, and 76.1% positive predictive value. Bayes' theorem shows that the mir-THYpe test performs satisfactorily in a wide range of cancer prevalences. Conclusions: The presented data and comparison with other commercially available tests suggest that the mir-THYpe test can be considered for use in clinical practice to support a more informed clinical decision for patients with indeterminate thyroid nodules and potentially reduce the rates of unnecessary thyroid surgeries.

Saúde itinerante nos centros municipais de educação infantil do município de Guarapuava - PR; os desafios da promoção da saúde em crianças expostas a doenças parasitárias / Travelling health in the municipal kindergartens in the city of Guarapuava - PR; the challenges of health promotion in children exposed to parasitic diseases

A presença de enteroparasitoses em crianças em idade pré-escolar tem sido motivo de preocupação pelos órgãos de saúde principalmente devido ao impacto negativo sobre o crescimento e desenvolvimento intelectual dessas crianças. As infecções por parasitas intestinais podem levar a quadros de desnutrição e formas de gastroenterite crônica. O presente trabalho analisou crianças em idade pré-escolar frequentadoras de 11 unidades CMEIs (Centros Municipais de Educação Infantil) na cidade de Guarapuava-PR em 11 unidades. Foram estudadas 287 crianças e o índice de positividade para enteroparasitoses foi de 13,9%. A idade média das 287 crianças foi de 2,7 anos e a maioria das crianças analisadas foram domicialiadas em zona urbana 84,3% e somente 15,7% em zona rural, com média de filhos por família de 2,08 membros. A prevalência das parasitoses mostrou que G. duodenalis foi o protozoário mais isolado com 70,4%, seguido de Ascaris lumbricoides 6,8% o único helminto encontrado. Com relação à terapêutica empregada 20% das crianças tratadas com o fármaco albendazol continuaram apresentando exames positivos para os mesmos parasitas. Já com o fármaco benzoilmetronidazol todas as crianças apresentaram resultados negativos para presença de parasitas nas fezes. Os fatores de risco para enteroparasitoses indicaram que a presença da variável água tratada foi menor nos casos positivos. Nossos resultados mostraram que G. duodenalis foi o parasita mais isolado em crianças em idade pré-escolar.

The presence of enteroparasitoses in pre-school children has been a concern of health agencies mainly due to the negative impact on the growth and intellectual development of those children. Intestinal parasite infections can lead to malnutrition and chronic forms of gastroenteritis. The present study analyzed pre-school children attending 11 CMEIs (Municipal Kindergarten Schools) in the city of Guarapuava ­ PR. A total of 287 children were studied, resulting in a positive index for enteroparasitoses of 13.9%. The mean age of the 287 children was 2.7 years and most of the children analyzed were domiciled in urban areas (84.3%), with only 15.7% living in rural areas, with a mean number of children per family of 2.08. The parasite prevalence showed that G. duodenalis was the most frequently isolated protozoan, with 70.4%; followed by Ascaris lumbricoides with 6.8%, the only helminth found. Regarding therapy, 20% of the children treated with albendazole continued to present positive tests for the same parasites. When treated with benzoylmetronidazole, all children presented negative results for the presence of parasites in the faeces. The risk factors for enteroparasitoses showed that the variable treated water was lower in the positive cases. The results of this study showed that G. duodenalis was the most frequently parasite isolated in pre-school children.

Expression of cancer/testis antigens MAGE-A, MAGE-C1, GAGE and CTAG1B in benign and malignant thyroid diseases.

Despite considerable advances in the understanding of thyroid gland biology, correctly diagnosing thyroid nodules and treating high-grade thyroid carcinoma remains challenging. Cancer/testis (CT) antigens have emerged as potential diagnostic tools as well as targets of potential cancer vaccinations. In the present study, a total of 117 patients who underwent surgical therapy for thyroid disease were available for analysis. The expression levels of melanoma-associated antigen (MAGE) A, MAGE-C1/CT7, cancer/testis antigen 1B (CTAG1B) and G antigen (GAGE) were analyzed by immunohistochemistry. None of the CT antigens were expressed in the normal thyroid or goiter. In papillary and follicular carcinoma, MAGE-A was present in 8.1% of cases, GAGE in 10.8% and CT/7MAGE-C1 and CTAG1B in 2.7% each. In medullary carcinoma, CT antigen expression was as follows: MAGE-A in 42.9% of patients; MAGE-C1/CT7 in 46.5%; GAGE in 92.9%; and CTAG1B in 3.6%. A statistically significant association was observed between the expression of G MAGE-C1/CT7 and patient gender as well as patient clinical stage (P=0.029 and 0.031, respectively). In poorly differentiated and anaplastic carcinoma cases, CT antigen expression was as follows: MAGE-A in 61.8% of cases; MAGE-C1 in 57.1%; GAGE in 66.7%; and CTAG1B in 14.4%. There was a statistically significant association between expression of GAGE and gender (P=0.043). However, there was no association between CT antigen expression and patient survival in any of the tumor entities analyzed. The current study identified a distinct expression pattern of CT antigens in malignant thyroid tumors indicating that CT antigens have the potential to outperform existing thyroid cancer biomarkers. The prevalence of CT antigens in high-grade carcinomas suggests that they serve an important biological role within malignant tumors.

HOX genes: potential candidates for the progression of laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is a very aggressive cancer, considered to be a subtype of the head and neck squamous cell carcinoma (HNSCC). Despite significant advances in the understanding and treatment of cancer, prognosis of patients with LSCC has not improved recently. In the present study, we sought to understand better the genetic mechanisms underlying LSCC development. Thirty-two tumor samples were collected from patients undergoing surgical resection of LSCC. The samples were submitted to whole-genome cDNA microarray analysis aiming to identify genetic targets in LSCC. We also employed bioinformatic approaches to expand our findings using the TCGA database and further performed functional assays, using human HNSCC cell lines, to evaluate viability, cell proliferation, and cell migration after silencing of selected genes. Eight members of the homeobox gene family (HOX) were identified to be overexpressed in LSCC samples when compared to normal larynx tissue. Quantitative RT-PCR analysis validated the overexpression of HOX gene family members in LSCC. Receiver operating characteristic (ROC) statistical method curve showed that the expression level of seven members of HOX gene family can distinguish tumor from nontumor tissue. Correlation analysis of clinical and gene expression data revealed that HOXC8 and HOXD11 genes were associated with the differentiation degree of tumors and regional lymph node metastases, respectively. Additionally, siRNA assays confirmed that HOXC8, HOXD10, and HOXD11 genes might be critical for cell colony proliferation and cell migration. According to our findings, several members of the HOX genes were overexpressed in LSCC samples and seem to be required in biological processes involved in tumor development. This suggests that HOX genes might play a critical role in the physiopathology of LSCC tumors.

Gene expression analysis of laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignancies of the head and neck tumors Zhang et al., 2013 [1]). Previous studies have associated its occurrence with social activities, such as tobacco and alcohol consumption (Hashibe et al., 2007a [2]; Hashibe et al., 2007b [3]; Shangina et al., 2006 [4]). Here, we performed a genome-wide gene expression profiling in thirty-one patients positively diagnosed for LSCC, in order to investigate new targets involved in tumorigenesis.

Assessment of MLL methyltransferase gene expression in larynx carcinoma.

Larynx cancer is the second most common type of cancer among all head and neck cancers. Deregulation of epigenetic effectors, including altered expression of histone methyltransferases from the MLL (mixed lineage leukemia) family, have been reported in many cancer types, yet little is known concerning their involvement in larynx cancer. Our objective was to determine the expression profile of MLL genes in larynx carcinoma and normal adjacent tissues and correlate this profile to tumor characteristics. We analyzed the expression profile of 5 MLL genes in 13 cases of larynx carcinoma and their adjacent non-tumor tissues using quantitative real-time PCR. MLL3 was significantly downregulated in tumor samples compared to their normal counterparts, and all MLL genes showed decreased expression in advanced tumors compared to tumors in the initial stage. Altered expression in a single MLL gene was associated with a similar alteration in the other MLL genes, revealing a strong correlation of expression in each individual patient. In conclusion, MLL genes may have similar transcriptional control, and decreased expression of these genes may contribute to larynx cancer progression.

Human papillomavirus (HPV) 16 and the prognosis of head and neck cancer in a geographical region with a low prevalence of HPV infection.

BACKGROUND: The role of human papillomavirus (HPV) on head and neck squamous cell carcinoma (HNSCC) survival in regions with low HPV prevalence is not yet clear. We evaluated the HPV16 infection on survival of HNSCC Brazilian patient series. METHODS: This cohort comprised 1,093 HNSCC cases recruited from 1998 to 2008 in four Brazilian cities and followed up until June 2009. HPV16 antibodies were analyzed by multiplex Luminex assay. In a subset of 398 fresh frozen or paraffin blocks of HNSCC specimens, we analyzed for HPV16 DNA by L1 generic primer polymerase chain reaction. HNSCC survival according to HPV16 antibodies was evaluated through Kaplan-Meier method and Cox regression. RESULTS: Prevalence of HPV16 E6 and E6/E7 antibodies was higher in oropharyngeal cancer than in other head and neck tumor sites. HPV16 DNA positive in tumor tissue was also higher in the oropharynx. Seropositivity for HPV16 E6 antibodies was correlated with improved HNSCC survival and oropharyngeal cancer. The presence of HPV16 E6/E7 antibodies was correlated with improved HNSCC survival and oropharyngeal cancer survival. The death risk of oropharyngeal squamous cell carcinoma patients HPV16 E6/E7 antibodies positive was 78 % lower than to those who test negative. CONCLUSION: Oropharyngeal squamous cell carcinoma is less aggressive in the HPV16 E6/E7 positive serology patients. HPV16 E6/E7 antibody is a clinically sensible surrogate prognostic marker of oropharyngeal squamous cell carcinoma.

Significant differences in demographic, clinical, and pathological features in relation to smoking and alcohol consumption among 1,633 head and neck cancer patients.

OBJECTIVE: As a lifestyle-related disease, social and cultural disparities may influence the features of squamous cell carcinoma of the head and neck in different geographic regions. We describe demographic, clinical, and pathological aspects of squamous cell carcinoma of the head and neck according to the smoking and alcohol consumption habits of patients in a Brazilian cohort. METHODS: We prospectively analyzed the smoking and alcohol consumption habits of 1,633 patients enrolled in five São Paulo hospitals that participated in the Brazilian Head and Neck Genome Project - Gencapo. RESULTS: The patients who smoked and drank were younger, and those who smoked were leaner than the other patients, regardless of alcohol consumption. The non-smokers/non-drinkers were typically elderly white females who had more differentiated oral cavity cancers and fewer first-degree relatives who smoked. The patients who drank presented significantly more frequent nodal metastasis, and those who smoked presented less-differentiated tumors. CONCLUSIONS: The patients with squamous cell carcinoma of the head and neck demonstrated demographic, clinical, and pathological features that were markedly different according to their smoking and drinking habits. A subset of elderly females who had oral cavity cancer and had never smoked or consumed alcohol was notable. Alcohol consumption seemed to be related to nodal metastasis, whereas smoking correlated with the degree of differentiation.

Significant differe nces in demographic, clinical, and pathological features in relation to smoking and alcohol consumption among 1,633 head and neck cancer patients

OBJECTIVE: As a lifestyle-related disease, social and cultural disparities may influence the features of squamous cell carcinoma of the head and neck in different geographic regions. We describe demographic, clinical, and pathological aspects of squamous cell carcinoma of the head and neck according to the smoking and alcohol consumption habits of patients in a Brazilian cohort. METHODS: We prospectively analyzed the smoking and alcohol consumption habits of 1,633 patients enrolled in five São Paulo hospitals that participated in the Brazilian Head and Neck Genome Project - Gencapo. RESULTS: The patients who smoked and drank were younger, and those who smoked were leaner than the other patients, regardless of alcohol consumption. The non-smokers/non-drinkers were typically elderly white females who had more differentiated oral cavity cancers and fewer first-degree relatives who smoked. The patients who drank presented significantly more frequent nodal metastasis, and those who smoked presented less-differentiated tumors. CONCLUSIONS: The patients with squamous cell carcinoma of the head and neck demonstrated demographic, clinical, and pathological features that were markedly different according to their smoking and drinking habits. A subset of elderly females who had oral cavity cancer and had never smoked or consumed alcohol was notable. Alcohol consumption seemed to be related to nodal metastasis, whereas smoking correlated with the degree of differentiation. .

Expression of cancer-testis antigens MAGE-A4 and MAGE-C1 in oral squamous cell carcinoma.

BACKGROUND: Tumor markers are genes or their products expressed exclusively or preferentially in tumor cells and cancer-testis antigens (CTAs) form a group of genes with a typical expression pattern expressed in a variety of malignant neoplasms. CTAs are considered potential targets for cancer vaccines. It is possible that the CTA MAGE-A4 (melanoma antigen) and MAGE-C1 are expressed in carcinoma of the oral cavity and are related with survival. METHODS: This study involved immunohistochemical analysis of 23 patients with oral squamous cell carcinoma (SCC) and was carried out using antibodies for MAGE-A4 and MAGE-C1. Fisher's exact test and log-rank test were used to evaluate the results. RESULTS: The expression of the MAGE-A4 and MAGE-C1 were 56.5% and 47.8% without statistical difference in studied variables and survival. CONCLUSION: The expression of at least 1 CTA was present in 78.3% of the patients, however, without correlation with clinicopathologic variables and survival.

Expression of MAGE-A4 and MAGE-C1 tumor-associated antigen in benign and malignant thyroid diseases.

BACKGROUND: A subset of thyroid tumors characterized by a follicular growth pattern can represent a serious diagnosis. Immunohistochemistry and molecular pathology for genetic profiling have been used in an attempt to resolve some of these issues. METHODS: Tumor tissue samples of thyroid were obtained from 70 patients who underwent surgical therapy. They were divided into 4 groups: 20 adenomatous goiters, 10 follicular adenomas, 24 papillary carcinomas, and 16 follicular carcinomas. Immunohistochemical analysis was carried out using antibodies for MAGE-A4 (melanoma antigen-encoding gene A4) and MAGE-C1 (melanoma antigen-encoding gene C1). RESULTS: Standard histologic analysis and immunohistochemistry analysis of MAGE-A4 and MAGE-C1 expression were performed in all patients. The antigens examined were not expressed in any of the tissues. CONCLUSIONS: The malignant degeneration of normal tissues is a multifactorial process, varying considerably both among tumor types and among individual patients. The present study showed that there was no immunolabeling of the MAGE-A4 and MAGE-C1 antigens.