RESUMO
Folate metabolism is essential for DNA synthesis and repair. Alterations in genes that participate in folate metabolism can be associated with several types of malignant neoplasms, including thyroid and breast cancer. In the present case-control study, we examined the association between methylenetetrahydrofolate reductase (MTHFR C677T, rs1801133) and methionine synthase (MTR A2756G, rs1805087) polymorphisms and risk for thyroid and breast cancer. Polymerase chain reaction-restriction fragment length technique was used to determine the specific genotypes in the genes of interest. Statistical analysis was performed by multiple logistic regression test. We found an association between MTHFR C677T polymorphism and risks to both thyroid (OR = 2.50; 95%CI = 1.15-5.46; P = 0.02) and breast cancer (OR = 2.53; 95%CI = 1.08-5.93; P = 0.03). Tobacco consumption and high body mass index were also associated with thyroid cancer. In addition, increased age (≥50 years) and alcohol consumption were found to be associated with breast cancer. Our results indicated that MTHFR C677T is significantly associated with thyroid and breast cancer risks. Thus, these factors may be used as potential prognostic markers for thyroid and breast cancers.
Assuntos
5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/genética , Neoplasias da Mama/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Neoplasias da Glândula Tireoide/genética , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/metabolismo , Adulto , Idoso , Brasil , Estudos de Casos e Controles , Feminino , Ferredoxina-NADP Redutase/genética , Ácido Fólico/metabolismo , Predisposição Genética para Doença , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Head and neck cancer (HNC) is a multifaceted and genomically complex disease and rapidly emerging preclinical and clinical studies have provided a broader landscape of signaling. It is being realized that intra-tumor heterogeneity, genetic and epigenetic mutations considerably challenge wide ranging therapeutics and patients frequently develop locoregional recurrences, second primary tumours and distant metastases. Using high-throughput technologies, it has been revealed that existence of different subpopulations of cells within tumor mass with different phenotypic and functional properties with distinct tumour-initiating potential is responsible to HNC resistance. In light of accumulating evidence reported in recent years, it is now known that different intracellular proteins and cell surface markers have been used to study CSCs. This review provides an overview of CSC biomarkers in HNC treatment and their potential as therapeutic targets in improving the diagnosis, prognosis and treatment of HNC patients for new therapeutic strategies with information about estimation of prognosis and treatment decision. Further studies regarding biomarkers are necessary to determine the specific role of CSCs in HNC which could be useful in development of new therapeutic strategies to eliminate CSCs and maximize clinical outcome. Furthermore, CD44 still need more research in HNC once the studies show contradictions. Studies using lineage tracing and deep sequencing will provide a comprehensive understanding of CSC model and extent to which it is accountable for resistance against therapeutics and carcinogenesis.
Assuntos
Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Células-Tronco Neoplásicas/patologia , Antígeno AC133 , Animais , Antígenos CD/metabolismo , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Resistencia a Medicamentos Antineoplásicos , Glicoproteínas/metabolismo , Neoplasias de Cabeça e Pescoço/genética , Ensaios de Triagem em Larga Escala , Humanos , Receptores de Hialuronatos/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Peptídeos/metabolismoRESUMO
The functional effect of the A>G transition at position 2756 on the MTR gene (5-methyltetrahydrofolate-homocysteine methyltransferase), involved in folate metabolism, may be a risk factor for head and neck squamous cell carcinoma (HNSCC). The frequency of MTR A2756G (rs1805087) polymorphism was compared between HNSCC patients and individuals without history of neoplasias. The association of this polymorphism with clinical histopathological parameters was evaluated. A total of 705 individuals were included in the study. The polymerase chain reaction-restriction fragment length polymorphism technique was used to genotype the polymorphism. For statistical analysis, the chi-square test (univariate analysis) was used for comparisons between groups and multiple logistic regression (multivariate analysis) was used for interactions between the polymorphism and risk factors and clinical histopathological parameters. Using univariate analysis, the results did not show significant differences in allelic or genotypic distributions. Multivariable analysis showed that tobacco and alcohol consumption (P < 0.05), AG genotype (P = 0.019) and G allele (P = 0.028) may be predictors of the disease and a higher frequency of the G polymorphic allele was detected in men with HNSCC compared to male controls (P = 0.008). The analysis of polymorphism regarding clinical histopathological parameters did not show any association with the primary site, aggressiveness, lymph node involvement or extension of the tumor. In conclusion, our data provide evidence that supports an association between the polymorphism and the risk of HNSCC.
Assuntos
5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/genética , Carcinoma de Células Escamosas/genética , Neoplasias de Cabeça e Pescoço/genética , Polimorfismo Genético/genética , Carcinoma de Células Escamosas/enzimologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Neoplasias de Cabeça e Pescoço/enzimologia , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Fatores de RiscoRESUMO
The functional effect of the A>G transition at position 2756 on the MTR gene (5-methyltetrahydrofolate-homocysteine methyltransferase), involved in folate metabolism, may be a risk factor for head and neck squamous cell carcinoma (HNSCC). The frequency of MTR A2756G (rs1805087) polymorphism was compared between HNSCC patients and individuals without history of neoplasias. The association of this polymorphism with clinical histopathological parameters was evaluated. A total of 705 individuals were included in the study. The polymerase chain reaction-restriction fragment length polymorphism technique was used to genotype the polymorphism. For statistical analysis, the chi-square test (univariate analysis) was used for comparisons between groups and multiple logistic regression (multivariate analysis) was used for interactions between the polymorphism and risk factors and clinical histopathological parameters. Using univariate analysis, the results did not show significant differences in allelic or genotypic distributions. Multivariable analysis showed that tobacco and alcohol consumption (P < 0.05), AG genotype (P = 0.019) and G allele (P = 0.028) may be predictors of the disease and a higher frequency of the G polymorphic allele was detected in men with HNSCC compared to male controls (P = 0.008). The analysis of polymorphism regarding clinical histopathological parameters did not show any association with the primary site, aggressiveness, lymph node involvement or extension of the tumor. In conclusion, our data provide evidence that supports an association between the polymorphism and the risk of HNSCC.
Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , /genética , Carcinoma de Células Escamosas/genética , Neoplasias de Cabeça e Pescoço/genética , Polimorfismo Genético/genética , Estudos de Casos e Controles , Carcinoma de Células Escamosas/enzimologia , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Neoplasias de Cabeça e Pescoço/enzimologia , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Fatores de RiscoRESUMO
Vascular endothelial growth factor (VEGF) is one of the most potent endothelial cell mitogens and plays a critical role in angiogenesis. Polymorphisms in this gene have been evaluated in patients with several types of cancer. The objectives of this study were to determine if there was an association of the -1154G/A polymorphism of the VEGF gene with head and neck cancer and the interaction of this polymorphism with lifestyle and demographic factors. Additionally, the distribution of the VEGF genotype was investigated with respect to the clinicopathological features of head and neck cancer patients. The study included 100 patients with histopathological diagnosis of head and neck squamous cell carcinoma. Patients with treated tumors were excluded. A total of 176 individuals 40 years or older were included in the control group and individuals with a family history of neoplasias were excluded. Analysis was performed after extraction of genomic DNA using the real-time PCR technique. No statistically significant differences between allelic and genotype frequencies of -1154G/A VEGF polymorphism were identified between healthy individuals and patients. The real-time PCR analyses showed a G allele frequency of 0.72 and 0.74 for patients and the control group, respectively. The A allele showed a frequency of 0.28 for head and neck cancer patients and 0.26 for the control group. However, analysis of the clinicopathological features showed a decreased frequency of the A allele polymorphism in patients with advanced (T3 and T4) tumors (OR = 0.36; 95 percentCI = 0.14-0.93; P = 0.0345). The -1154A allele of the VEGF gene may decrease the risk of tumor growth and be a possible biomarker for head and neck cancer. This polymorphism is associated with increased VEGF production and may have a prognostic importance.
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas/genética , Predisposição Genética para Doença , Neoplasias de Cabeça e Pescoço/genética , Polimorfismo Genético/genética , Biomarcadores Tumorais/genética , Fator A de Crescimento do Endotélio Vascular/genética , Brasil , Estudos de Casos e Controles , Frequência do Gene , Genótipo , Estilo de Vida , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , Estudos Prospectivos , Fatores de RiscoRESUMO
Vascular endothelial growth factor (VEGF) is one of the most potent endothelial cell mitogens and plays a critical role in angiogenesis. Polymorphisms in this gene have been evaluated in patients with several types of cancer. The objectives of this study were to determine if there was an association of the -1154G/A polymorphism of the VEGF gene with head and neck cancer and the interaction of this polymorphism with lifestyle and demographic factors. Additionally, the distribution of the VEGF genotype was investigated with respect to the clinicopathological features of head and neck cancer patients. The study included 100 patients with histopathological diagnosis of head and neck squamous cell carcinoma. Patients with treated tumors were excluded. A total of 176 individuals 40 years or older were included in the control group and individuals with a family history of neoplasias were excluded. Analysis was performed after extraction of genomic DNA using the real-time PCR technique. No statistically significant differences between allelic and genotype frequencies of -1154G/A VEGF polymorphism were identified between healthy individuals and patients. The real-time PCR analyses showed a G allele frequency of 0.72 and 0.74 for patients and the control group, respectively. The A allele showed a frequency of 0.28 for head and neck cancer patients and 0.26 for the control group. However, analysis of the clinicopathological features showed a decreased frequency of the A allele polymorphism in patients with advanced (T3 and T4) tumors (OR = 0.36; 95%CI = 0.14-0.93; P = 0.0345). The -1154A allele of the VEGF gene may decrease the risk of tumor growth and be a possible biomarker for head and neck cancer. This polymorphism is associated with increased VEGF production and may have a prognostic importance.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Predisposição Genética para Doença , Neoplasias de Cabeça e Pescoço/genética , Polimorfismo Genético/genética , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , Estudos Prospectivos , Fatores de RiscoRESUMO
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.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Metilação de DNA , Neoplasias de Cabeça e Pescoço/metabolismo , Proteínas de Homeodomínio/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Sequência de Bases , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Cromossomos Humanos Par 9 , Primers do DNA , DNA de Neoplasias/sangue , Neoplasias de Cabeça e Pescoço/genética , Humanos , Proteínas com Homeodomínio LIM , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de TranscriçãoRESUMO
OBJECTIVE: To estimate the prevalence of deafness in children 3-6 years old in day-care centers of São José do Rio Preto, SP, Brazil. METHODS: We used free-field audiometry to screen 103 children from 8-selected day-care centers. Children with abnormal examination results were referred to the speech therapy outpatient service to undergo pure-tone conventional audiometry. We adopted the WHO classification for degree of deafness. RESULTS: Audiometric dysfunctions were present in 10 children (9.70%; SD=0.96) with one boy showing left ear mild conductive hearing loss (mean LE=35 dB), while 9 children (8.73%; SD=2.78) showed alterations in air-conduction threshold in 4000, 6000 or 8000 sharp frequencies. Out of 102 children (99.03%; SD=0.96), 55 boys (53.39%; SD=4.9) and 47 girls (45.64%; SD=4.9) presented no hearing loss according to the WHO criteria. CONCLUSIONS: The prevalence of 9.7% audiometric dysfunctions found in this study indicates that deafness prevention programs should be organized.
RESUMO
This study describes the selective removal of cell and cell residues from small and large diameter blood vessels for the preparation of tubular collagen:elastin matrices intended for small diameter vascular prosthesis. The results showed that total or partially devitalized collagen:elastin matrices may be conveniently prepared without denaturation of the collagen:elastin matrix with a high degree of preservation of the proteins. The efficiency of cell removal and the extent collagen and elastic fiber preservation were dependent on the segment and the type of blood vessel under study, with arteries characterized by a higher susceptibility of cell removal and better preservation of the collagen-elastin matrix.
Assuntos
Bioprótese , Prótese Vascular , Vasos Sanguíneos , Colágeno , Elastina , Preservação de Tecido/métodos , Álcalis , Animais , Aorta Abdominal , Materiais Biocompatíveis , Vasos Sanguíneos/citologia , Varredura Diferencial de Calorimetria , Corantes , Reagentes de Ligações Cruzadas , Dimetil Sulfóxido , Cães , Eletrofisiologia , Artéria Femoral , Veia Femoral , Artéria Ilíaca , Veia Ilíaca , Microscopia Eletrônica de Varredura , Desenho de Prótese , Solventes , Artérias Torácicas , Veia Cava Inferior , Veia Cava SuperiorRESUMO
Surgical control of severe epistaxis is usually reserved for cases refractory to more conservative techniques. We present our experience with intraoral ligation of the maxillary artery as it courses through the buccal fat pad before it enters the pterygopalatine fossa and branches posterior to the maxilla. This technique has been found useful in the control of nasal hemorrhage as well as an adjunct to other surgical procedures, such as removal of benign and malignant neoplasms involving the maxilla and paranasal sinuses. This technique was used for ligation of the maxillary artery in 20 patients. The artery was readily identified in some cases, but required more extensive dissection in others; therefore, an anatomic study in 18 preserved and fresh cadaver specimens was undertaken to investigate the variability of the maxillary artery in the region of the buccal fat pad. There appeared to be significant variation in the distance from the buccal mucosal incision site, as well as variation in the relationship to the pterygoid muscles. This relationship to the pterygoids explains the occasional difficulty in locating the artery for ligation. This technique represents a reasonable alternative to the more traditional transantral approach to ligation of the maxillary artery, as long as the surgeon understands the anatomy of the region, its variations, and where the artery may be located if not immediately apparent. No major complications have been experienced.
Assuntos
Artéria Maxilar/cirurgia , Adulto , Epistaxe/cirurgia , Humanos , Ligadura/métodos , Masculino , Artéria Maxilar/anatomia & histologia , Pessoa de Meia-Idade , RecidivaRESUMO
Congenital lop ear is a malformation secondary to an autosomal dominant mendelian factor. This anomaly may be surgically corrected as early as the preschool age. The surgical technique presented is derived from many sources with some personal modifications. It consists of cartilage excision and incision and the use of horizontal mattress sutures. The surgical procedure is organized into six steps. This technique is easy to learn and useful in the training or residents. The complications of otoplasty are discussed.