RESUMO
The present study aimed to compare levels of VEGFR2 and MMP-9 among control, epithelial dysplasia (ED) and oral squamous cell carcinoma (OSCC) groups. We analyzed 48 patients with oral leukoplakia (OL), 20 patients with OSCC and 21 patients without OL and OSCC. Immunohistochemistry of VEGFR2 and MMP9 were performed and compared among groups. Analysis of tissue immunolocalization of VEGFR2 and MMP-9 assumed non-parametrical distribution and comparison between groups was performed using the Mann-Whitney and Kruskal-Wallis statistical tests. VEGFR2 and MMP9 immunoexpression appeared to correlate with the degree of dysplasia and was observed to increase in lesions with more severe dysplasia as compared to those with lower degrees of dysplasia. Immunoreactivity of MMP-9 was lower in the OL samples compared to the OSCC samples (p = 0.004). We observed no difference in VEGFR2 protein levels between OL and OSCC samples. A positive correlation was found between VEGFR2 and MMP-9 in OL samples (r = +0.452, p = 0.001), however, no correlation was found in OSCC samples (r = -0.042, p = 0.861). In conclusion, the results of the current study suggest that expression of MMP9 and VEGFR2 is associated with ED grading and MMP9 levels are increased in OSCC.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Leucoplasia/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Mucosa Bucal/metabolismo , Neoplasias Bucais/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Adulto , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Leucoplasia/patologia , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Neoplasias Bucais/patologia , Gradação de TumoresRESUMO
This study aimed to evaluate the association between several different aspects of disease in head and neck squamous cell carcinoma (HNSCC): morphological grading, Ki67 proliferation index (PI), invasive front, adjacent non-malignant mucosa (ANMM), recurrence and overall survival of the patients. Sixty-four fully reviewed and followed-up patients with primary HNSCC were matched according to recurrence of the lesion and placed in one of two groups of 32 cases. Chi-square and Fisher's exact tests were used to analyze the clinicopathological parameters between both groups of patients. Association between Ki67 PI and clinicopathological parameters was also analyzed through chi-square and Fisher's exact tests with the binary logistic regression model used as a multivariate analysis. In addition, survival analysis was also performed. Our results showed that high-risk dysplasia in ANMM and high Ki67 PI in ANMM of HNSCC exhibited a higher risk of tumor recurrence. Survival analysis showed that T3/T4 tumor sizes and high Ki67 PI were significantly associated with an increase in the risk of death in multivariate analysis. Our results revealed that high-risk dysplasia and high Ki67 PI of the ANMM are parameters which are indicative of tumor recurrence. Furthermore, T3/T4 tumor sizes and high Ki67 PI in the invasive front appear to be important prognostic tools for HNSCC.
Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Antígeno Ki-67/metabolismo , Mucosa Bucal/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Brasil/epidemiologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Proliferação de Células , Terapia Combinada , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/metabolismo , Recidiva Local de Neoplasia , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Recent work has provided compelling evidence that increased levels of acetylcholine (ACh) can be protective in heart failure, whereas reduced levels of ACh secretion can cause heart malfunction. Previous data show that cardiomyocytes themselves can actively secrete ACh, raising the question of whether this cardiomyocyte derived ACh may contribute to the protective effects of ACh in the heart. To address the functionality of this non-neuronal ACh machinery, we used cholinesterase inhibitors and a siRNA targeted to AChE (acetylcholinesterase) as a way to increase the availability of ACh secreted by cardiac cells. By using nitric oxide (NO) formation as a biological sensor for released ACh, we showed that cholinesterase inhibition increased NO levels in freshly isolated ventricular myocytes and that this effect was prevented by atropine, a muscarinic receptor antagonist, and by inhibition of ACh synthesis or vesicular storage. Functionally, cholinesterase inhibition prevented the hypertrophic effect as well as molecular changes and calcium transient alterations induced by adrenergic overstimulation in cardiomyocytes. Moreover, inhibition of ACh storage or atropine blunted the anti-hypertrophic action of cholinesterase inhibition. Altogether, our results show that cardiomyocytes possess functional cholinergic machinery that offsets deleterious effects of hyperadrenergic stimulation. In addition, we show that adrenergic stimulation upregulates expression levels of cholinergic components. We propose that this cardiomyocyte cholinergic signaling could amplify the protective effects of the parasympathetic nervous system in the heart and may counteract or partially neutralize hypertrophic adrenergic effects.
Assuntos
Cardiomegalia/metabolismo , Miócitos Cardíacos/metabolismo , Acetilcolina/metabolismo , Acetilcolinesterase/genética , Acetilcolinesterase/metabolismo , Animais , Atropina/farmacologia , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Isoproterenol/farmacologia , Camundongos , Antagonistas Muscarínicos/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Óxidos de Nitrogênio/metabolismo , Fenilefrina/farmacologia , RNA Interferente Pequeno , RatosRESUMO
OBJECTIVE: To investigate the DNMT3B (C46359T) polymorphism and immunoexpression of DNMT3b and DNMT1 in oral lichen planus (OLP) compared to a control group. METHODS: We aimed to investigate the DNMT3B (C46359T) polymorphism and immunoexpression of DNMT3b and DNMT1 in OLP (n = 32), comparing it with oral mucosa (control; n = 24). The DNMT3B (C46359T) polymorphism was analyzed using the RFLP-PCR and DNMT1, and DNMT3a proteins were identified using immunohistochemistry. We also compared the DNMT3B expression in OLP and oral inflammatory fibrous hyperplasia (OIFH), another oral inflammatory disease. Differences between the groups were determined by specific statistical analyses. RESULTS: The CT genotype of DNMT3B was associated with OLP development (p = 0.012). Increased expression of DNMT3B and DNMT1 was observed in OLP compared to the control group (p = 0.014 and p = 0.001, respectively). A significant increase in DNMT3B protein levels was observed in the genotype CT in DNMT3B (C46359T) polymorphisms (p = 0.045). No DNMT3B expression differences between OLP and OIFH were observed. CONCLUSIONS: Our data show that the DNMT3B (C46359T) polymorphism is associated with OLP development. Furthermore, increased expression of the enzyme DNMT3B, an epigenetic-associated protein, is present in OLP.