RESUMO
Gap junction intercellular communication (GJIC) is considered a key mechanism in the regulation of tissue homeostasis. GJIC structures are organized in two transmembrane channels, with each channel formed by connexins (Cxs). GJIC and Cxs expression alterations are related to the process of tumorigenesis in different cell types. Pituitary neuroendocrine tumors (PitNETs) represent 15-20% of intracranial neoplasms, and usually display benign behavior. Nevertheless, some may have aggressive behavior, invading adjacent tissues, and featuring a high proliferation rate. We aimed to assess the expression and relevance of GJIC and Cxs proteins in PitNETs. We evaluated the mRNA expression levels of Cx26, 32, and 43, and the protein expression of Cx43 in a series of PitNETs. In addition, we overexpressed Cx43 in pituitary tumor cell lines. At the mRNA level, we observed variable expression of all the connexins in the tumor samples. Cx43 protein expression was absent in most of the pituitary tumor samples that were studied. Moreover, in vitro studies revealed that the overexpression of Cx43 decreases cell growth and induces apoptosis in pituitary tumor cell lines. Our results indicate that the downregulation of Cx43 protein might be involved in the tumorigenesis of most pituitary adenomas and have a potential therapeutic value for pituitary tumor therapy.
Assuntos
Adenoma , Neoplasias Hipofisárias , Adenoma/genética , Linhagem Celular Tumoral , Transformação Celular Neoplásica , Conexina 43/genética , Conexinas/genética , Conexinas/metabolismo , Humanos , Neoplasias Hipofisárias/genética , RNA Mensageiro/genéticaRESUMO
Defining biomarkers for invasive pituitary neuroendocrine tumors (PitNETs) is highly desirable. The high mobility group A (HMGA) proteins are among the most widely expressed cancer-associated proteins. Indeed, their overexpression is a frequent feature of human malignancies, including PitNETs. We show that nonfunctioning PitNETs (NF-PitNETs) express significantly higher levels of HMGA1 than somatotropinomas (GHs) and corticotropinomas (ACTHs). Furthermore, HMGA2 expression was detected only in NF-PitNETs and was significantly higher in larger tumors than in smaller tumors. HMGA expression analysis generally focuses on nuclear staining. Here, cytoplasmic HMGA staining was also found. PitNETs displayed strong nuclear HMGA1 and strong cytoplasmic HMGA2 immunoreactivity. Interestingly, the HMGA1 and HMGA2 nuclear expression levels were significantly higher in invasive adenomas than in noninvasive adenomas. The highest levels of nuclear HMGA2 were found in GHs. In conclusion, we show that overexpression of nuclear HMGA proteins could be a potential biomarker of invasive PitNETs, particularly HMGA2 for GHs. HMGA2 might be a reliable biomarker for NF-PitNETs.
Assuntos
Regulação Neoplásica da Expressão Gênica , Proteína HMGA1a/genética , Proteína HMGA2/genética , Tumores Neuroendócrinos/genética , Neoplasias Hipofisárias/genética , Adolescente , Adulto , Idoso , Núcleo Celular/metabolismo , Feminino , Proteína HMGA1a/metabolismo , Proteína HMGA2/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Neoplasias Hipofisárias/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Adulto JovemRESUMO
Several studies have associated acromegaly with an increased risk of benign and malignant tumors. While simple and multinodular goiters are common findings in acromegaly, the prevalence of thyroid cancer is uncertain. The objective of this study was to estimate the prevalence of thyroid cancer in a series of acromegalic patients from three hospitals in northeast of Brazil. The methodology used included morphological, cytological and histological thyroid analysis of acromegalic patients and volunteers over 18 years, matched for age and sex and with nodule (s) ≥1 cm. The subjects of this study were 124 acromegalic patients, including 76 females (61.3%) and 48 men (38.7%), with a mean age 45.1 years. Results of the study showed that thyroid ultrasonography was normal in 31 cases (25%), 25 had diffuse goiter (20.1%), 67 had nodules (54%) and one agenesis of the right lobe (0.8%). Thirty-six patients underwent fine needle aspiration biopsy (FNAB) of their nodules and 9 cases of papillary cancer were found (7.2%). The control group consisted of 263 subjects, 156 females (59.3%) and 107 males (40.7%), mean age 44.7 years. In ultrasound assessment, 96 had nodules (36.5%). Of these, 13 were punctured and 2 cases of papillary carcinoma were found (0.7%). These results gave an odds ratio of 10.21 (p = 0.0011, 95% CI 2.17 to 48.01). These findings demonstrate an increased prevalence of thyroid cancer, statistically significant when compared to our control group. Thus, it is suggested that acromegalic patients should be routinely submitted to thyroid ultrasound evaluation, followed by FNAB of nodules when indicated.
Assuntos
Acromegalia/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia , Acromegalia/complicações , Acromegalia/diagnóstico , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/etiologiaRESUMO
BACKGROUND: Subarachnoid S(+)-ketamine is a matter of much debate as the results regarding its toxicity are contradictory. OBJECTIVES: Our objective was to investigate possible histopathological alterations after subarachnoid administration of different doses of preservative-free S(+)-ketamine to dogs. STUDY DESIGN: A randomized, blind, prospective experimental study. SETTING: Center for Research on Pain at the Federal University of Maranhão, Brazil. METHODS: Sixteen adult mongrel dogs of both sexes, each weighing 11 to 20 kg were divided into 3 groups: Group I (n=6), 0.7 mg/kg-1 S(+)-ketamine; Group II (n=6), 0.5 mg/kg-1 S(+)-ketamine, and a control group, Group III, (n=4), 0.9% NaCl. All substances were administered in one mL volume doses. The animals were kept in captivity for 2 weeks; after this period, they were put down and lumbar and sacral portions of the spinal cords were removed for histological examination using conventional light microscopy. RESULTS: There were histological alterations in the spinal cords of the test subjects in the control group. Comparison showed significant histological abnormalities in Groups I and II when compared to the control group, including gliosis, axonal edema, central chromatolysis, lymphocyte infiltration and fibrous thickening of the dura mater. LIMITATIONS: Test subjects received only a single dose each. The observation period was not very long, less than a month. CONCLUSIONS: Subarachnoid administration of S(+)-ketamine without preservative caused histological lesions on the spinal cord and meninges in the dogs studied. S(+)-ketamine should not be given to clinical patients in this way until further evaluation of the significance of this toxicity has been conducted.
Assuntos
Analgésicos/toxicidade , Ketamina/toxicidade , Degeneração Neural/induzido quimicamente , Conservantes Farmacêuticos , Medula Espinal/efeitos dos fármacos , Espaço Subaracnóideo/efeitos dos fármacos , Animais , Aracnoidite/induzido quimicamente , Aracnoidite/patologia , Cães , Dura-Máter/efeitos dos fármacos , Dura-Máter/patologia , Feminino , Fibrose , Injeções Espinhais/efeitos adversos , Injeções Espinhais/métodos , Masculino , Modelos Animais , Degeneração Neural/patologia , Conservantes Farmacêuticos/efeitos adversos , Medula Espinal/patologia , Vasculite/induzido quimicamente , Vasculite/patologiaRESUMO
OBJETIVO: analisar alterações macroscópicas e histológicas que ocorrem com o uso da sinvastatina em endometriose experimental em ratas. MÉTODOS: quarenta ratas da linhagem Wistar foram submetidas à técnica de autotransplante uterino em mesentério. Após três semanas, 24 ratas desenvolveram endometriose experimental grau III e foram divididas em dois grupos: Sinvastatina (dado 20 mg/kg/dia via oral) e Controle (dado cloreto de sódio a 0,9 por cento na quantidade de 1 mL/100 g de peso corpóreo via oral), que receberam gavagem durante 14 dias seguido de morte. Os volumes dos implantes foram calculados [4pi (comprimento/2) x (largura/2) x (altura/2)/3] nas intervenções cirúrgicas e após a morte dos animais. Os autotransplantes foram retirados, corados com a hematoxilina-eosina e analisados à microscopia de luz. Foram usados o teste de Mann-Whitney para amostras independentes e o teste de Wilcoxon para amostras relacionadas. Para avaliação histológica, foi usado o teste exato de Fisher, adotando-se nível de significância de 5 por cento. RESULTADOS: a diferença entre os volumes médios iniciais dos autotransplantes nos dois grupos foi insignificante (p=1,00), e, entre os volumes médios finais, significante (p=0,04). Houve aumento significativo (p=0,01) entre os volumes médios iniciais e finais do Grupo Controle e redução insignificante no Grupo Sinvastatina (p=0,95). Histologicamente (p=0,64), o Grupo Sinvastatina (n=9) mostrou a parede epitelial moderadamente preservada em sete casos (77,80 por cento) e dois casos com camada epitelial bem preservada (22,2 por cento), e o Grupo Controle (n=12) com sete casos (58,30 por cento) moderadamente preservados e cinco casos (41,70 por cento) bem preservados. CONCLUSÕES: a sinvastatina impediu o crescimento dos focos de endometriose experimental. São promissores os estudos com uso da sinvastatina por período mais prolongado.
PURPOSE: to analyze the macroscopic and histological changes that occur with the use of sinvastatin in experimental endometriosis in female rats. METHODS: forty Wistar female rats were submitted to the technique of uterine self-transplant in mesenterium. After three weeks, 24 of them developed experimental endometriosis grade III, and were divided in two groups: one group received sinvastatin orally (20 mg/kg/day) and the other (control group) received 0.9 percent of sodium chloride orally (1 mL/100 g of body weight/day). Both groups received gavage for 14 days, followed by death. The implant volume was calculated [4pi (lenght/2) x (width/2) x (height/2)/3] at the surgical intervention and after the animals death. The self-transplants were removed, dyed with hematoxylin-eosin and analyzed by light microscopy. The Mann-Whitneys test was used in the independent samples and the Wilcoxons test for the related samples. The Fishers exact test was used for the histological evaluation, with a significance level of 5 percent. RESULTS: the difference between groups of the initial average volumes of the self-transplants was not significant (p=1.00), but became significant for the final average volumes (p=0.04). There was a significant increase (p=0.01) between the initial and final average volumes in the control group, and a no significant decrease in the sinvastatin group (p=0.95). Histologically, the sinvastatin group (n=9) presented seven cases (77.8 percent) of moderately preserved and two cases (22.2 percent) of well preserved epithelial wall, while the control group (n=12) presented seven cases (58.3 percent) of moderately preserved and five cases (41.7 percent) of well preserved epithelial wall. CONCLUSIONS: sinvastatin prevented the growth of experimental endometriosis. Studies with sinvastatin for longer periods are promising.