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INTRODUCTION: Hepatocellular carcinoma (HCC) carcinogenesis is not yet fully known. Insulin-like Growth Factor-1 Receptor (IGF-1R) can translocate to the nucleus and modulate cellular growth, possibly participating in HCC development and aggressiveness. This study aims to evaluate the immunoexpression of IGF-1R in HCC, the cellular compartment involved, and its association with clinicopathological parameters and clinical outcomes. METHODS: Liver specimens from 111 HCC patients who underwent liver transplantation or partial surgical resections at a Brazilian referral hospital center were studied. IGF-1R expression was determined by immunohistochemistry, clinical data were collected from medical records, and pathological parameters were obtained from path review. RESULTS: IGF-1R nuclear expression was higher in the tumor than in the adjacent cirrhosis (p < 0.001). The odds of IGF-1R expression in the nucleus compared to the membrane are lower in the cirrhosis condition than in the tumor, suggesting an increase in the prevalence of nucleus expression relative to the membrane from cirrhosis to tumor. There was an association between IGF-1R nuclear expression in HCC and the moderate/poor grade of histologic differentiation (p < 0.001). However, long-term clinical outcomes were not associated with IGF-1R nuclear expression. CONCLUSION: The data presented here suggest the role of IGF-1R in HCC progression and carcinogenesis as its expression increases in the nucleus relative to the membrane, from cirrhosis to tumor, and it was associated with a poorer differentiated tumor grade. Further research is awaited to fully understand the mechanisms underlying this association.
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ABSTRACT Introduction Hepatocellular carcinoma (HCC) is the most common primary malignant neoplasm in the liver. HCC develops gradually from multiple stages that control proliferation and apoptosis. In hepatocarcinogenesis, multiple signaling pathways were already described, such as the Hedgehog pathway (Hh). However, few studies have investigated the expression of Hh proteins as a potential prognostic factor in human HCC. This study aimed to investigate the expression of the Shh protein in HCC and to correlate with clinical and morphological prognostic characteristics of the tumor. Methods Immunohistochemical expression of Shh protein in tumor and cirrhotic parenchyma was performed in 36 HCC samples from patients who underwent liver transplantation at Clinical Hospital - UFMG. Correlation between the Shh tumor expression and etiology, number of nodules, size of the nodules, levels of alpha-fetus-protein (AFP), MELD score, tumor differentiation, and vascular invasion were performed. Results In our study, Shh protein labeling gradually increased from the normal to the cirrhotic and neoplastic parenchyma. Degree of tumor differentiation and vascular invasion were correlated with high Shh protein expression (p = 0.014 and p = 0.003, respectively). The other variables did not show a statistically significant correlation with Shh labeling. Conclusion Hedgehog pathway has importance in hepatocarcinogenesis. The immunohistochemical study of the Hh signaling pathway may have a promising role as a prognostic factor for HCC, especially due to the positive correlation between the Shh expression and the degree of tumor differentiation and invasion vascular.
RESUMO Introdução O carcinoma hepatocelular (CHC) é a neoplasia maligna primária mais comum no fígado. O CHC se desenvolve gradualmente a partir de múltiplos estágios que controlam a proliferação e a apoptose. Na hepatocarcinogênese, múltiplas vias de sinalização já foram descritas, como a via Hedgehog (Hh). No entanto, poucos estudos investigaram a expressão de proteínas Hh como um potencial fator prognóstico no CHC humano. Este estudo teve como objetivo investigar a expressão da proteína Shh no CHC e correlacionar com características prognósticas clínicas e morfológicas do tumor. Métodos A expressão imuno-histoquímica da proteína Shh em tumor e parênquima cirrótico foi realizada em 36 amostras de CHC de pacientes submetidos a transplante hepático no Hospital das Clínicas - UFMG. Correlação entre a expressão e etiologia do tumor Shh, número de nódulos, tamanho dos nódulos, níveis de proteína alfa-feto (AFP), pontuação MELD, diferenciação tumoral e invasão vascular foram realizadas. Resultados Em nosso estudo, a marcação da proteína Shh aumentou gradualmente do parênquima normal para o cirrótico e neoplásico. Grau de diferenciação tumoral e invasão vascular foram correlacionados com alta expressão da proteína Shh (p = 0,014 ep = 0,003, respectivamente). As demais variáveis não apresentaram correlação estatisticamente significativa com a marcação de Shh. Conclusão A via Hedgehog tem importância na hepatocarcinogênese. O estudo imuno-histoquímico da via de sinalização Hh pode ter um papel promissor como fator prognóstico para CHC, principalmente devido à correlação positiva entre a expressão de Shh e o grau de diferenciação tumoral e invasão vascular.
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BACKGROUND: Hepatocarcinogenesis is a multistep process that lead to genetic changes in hepatocytes resulting in neoplasia. However, the mechanisms of malignant transformation seem to differ widely. To know carcinogenesis mechanisms is essential to develop new treatment and prevention methods. OBJECTIVE: The aim of this study is to analyze B-Raf protein immunoexpression in explants with hepatocellular carcinoma (HCC) related to hepatitis C (HCV), in adjacent cirrhotic tissue and in normal livers. We also associated the immunoexpression with known HCC related histopathogical prognostic features. METHODS: Livers from 35 patients with HCV related cirrhosis and HCC that underwent liver transplantation or hepatectomy at Clinical Hospital – UFMG and 25 normal livers from necropsy archives were studied. Tumors were classified according to: tumor size, vascular invasion and differentiation grade. B-Raf protein expression was determined by immunohistochemistry. RESULTS: B-Raf was strongly expressed in the HCV cirrhotic parenchyma cytoplasm of 17.1% cases and in 62.9% of HCC samples. Strong B-Raf protein staining was associated with tumor tissue (P<0.0001; OR=8.18 (2.62–26.63)). All normal livers showed weak or negative expression for B-Raf. There was no significant association among B-Raf scores and tumor differentiation grade (P=0.9485), tumor size (P=0.4427) or with vascular invasion (P=0.2666). CONCLUSION: We found B-Raf protein immunostaining difference in normal livers, in the areas of HCV cirrhosis and in the hepatocarcinoma. We did not find association between B-Raf expression and histopathological markers of tumor progression. Our data suggests that B-Raf may play an important role in initial HCC carcinogenesis. Larger studies are needed to validate these observations.
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Carcinoma Hepatocelular , Hepatite C , Neoplasias Hepáticas , Hepacivirus , Hepatite C/complicações , Humanos , Cirrose HepáticaRESUMO
ABSTRACT BACKGROUND: Hepatocarcinogenesis is a multistep process that lead to genetic changes in hepatocytes resulting in neoplasia. However, the mechanisms of malignant transformation seem to differ widely. To know carcinogenesis mechanisms is essential to develop new treatment and prevention methods. OBJECTIVE: The aim of this study is to analyze B-Raf protein immunoexpression in explants with hepatocellular carcinoma (HCC) related to hepatitis C (HCV), in adjacent cirrhotic tissue and in normal livers. We also associated the immunoexpression with known HCC related histopathogical prognostic features. METHODS: Livers from 35 patients with HCV related cirrhosis and HCC that underwent liver transplantation or hepatectomy at Clinical Hospital – UFMG and 25 normal livers from necropsy archives were studied. Tumors were classified according to: tumor size, vascular invasion and differentiation grade. B-Raf protein expression was determined by immunohistochemistry. RESULTS: B-Raf was strongly expressed in the HCV cirrhotic parenchyma cytoplasm of 17.1% cases and in 62.9% of HCC samples. Strong B-Raf protein staining was associated with tumor tissue (P<0.0001; OR=8.18 (2.62–26.63)). All normal livers showed weak or negative expression for B-Raf. There was no significant association among B-Raf scores and tumor differentiation grade (P=0.9485), tumor size (P=0.4427) or with vascular invasion (P=0.2666). CONCLUSION We found B-Raf protein immunostaining difference in normal livers, in the areas of HCV cirrhosis and in the hepatocarcinoma. We did not find association between B-Raf expression and histopathological markers of tumor progression. Our data suggests that B-Raf may play an important role in initial HCC carcinogenesis. Larger studies are needed to validate these observations.
RESUMO CONTEXTO: A hepatocarcinogênese é um processo de múltiplas etapas que leva a alterações genéticas nos hepatócitos, resultando em neoplasia. No entanto, os mecanismos da transformação maligna parecem diferir amplamente. Conhecer os mecanismos da carcinogênese é fundamental para o desenvolvimento de novos métodos de tratamento e prevenção. OBJETIVO: O objetivo deste estudo é analisar a imunoexpressão da proteína B-Raf em explantes de carcinoma hepatocelular (CHC), em tecido cirrótico relacionado à hepatite C adjacente e em fígados normais. Também analisamos a imunoexpressão com características histopatológicas prognósticas relacionadas ao CHC. MÉTODOS: Foram estudados fígados de 35 pacientes com CHC relacionado à cirrose por vírus C submetidos a transplante hepático ou hepatectomia no Hospital das Clínicas – UFMG e 25 fígados normais de arquivos de necropsia. Os tumores foram classificados de acordo com tamanho do tumor, invasão vascular e grau de diferenciação. A expressão de B-Raf foi determinada por imunohistoquímica. RESULTADOS: B-Raf foi fortemente expresso no citoplasma do parênquima cirrótico em 17,1% dos casos e em 62,9% das amostras de CHC. A forte expressão da proteína B-Raf foi associada ao tecido tumoral (P<0,0001; OR=8,18 (2,62–26,63)). Todos os fígados normais apresentaram expressão fraca ou negativa para B-Raf. Não houve associação significativa entre os escores B-Raf e o grau de diferenciação do tumor (P=0,9485), tamanho do tumor (P=0,4427) ou invasão vascular (P=0,26666). CONCLUSÃO: Encontramos diferença na imunoexpressão da proteína B-Raf em fígados normais, nas áreas de cirrose por HCV e no hepatocarcinoma. Não encontramos associação entre a expressão de B-Raf e marcadores histopatológicos de progressão tumoral. Nossos dados sugerem que o B-Raf pode desempenhar um papel importante na carcinogênese inicial do CHC. Estudos maiores são necessários para validar essas observações.
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OBJECTIVE: This article aims to alert health professionals for cancer screening in the face of the possibility of new waves of disease. METHODS: A narrative review was conducted through a search in MEDLINE, Lilacs, Chinese Biomedical Literature Database, and international medical societies publications. RESULTS: Breast cancer: in high-risk patients (confirmed familial cancer syndrome or with high-risk tools scores), clinicians should act according to usual recommendations; in average-risk individuals, consider screening with mammography with a longer time span (maximum of two years). Cervical cancer: women turning 25 years old who have already been immunized and with no previous Pap test can have the test postponed during the pandemic; if there is no previous dose of Human Papillomavirus vaccination, initiation of screening should be recommended following a more rigid approach for COVID prevention; in women over 30 years of age who have never participated in cervical screening, the first screening exam is also essential. Colorectal cancer: if the individual is at elevated risk for familial cancer, the screening with colonoscopy according to usual recommendations should be supported; if at average risk consider screening with Fecal Occult Blood Test. Prostate cancer: there is a trend to postpone routine prostate cancer screening until the pandemic subsides. CONCLUSIONS: The decision to keep cancer screening must be discussed and individualized, considering the possibility of new waves of COVID-19.
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COVID-19 , Neoplasias Colorretais , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias da Próstata , Neoplasias do Colo do Útero , Adulto , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Programas de Rastreamento , Antígeno Prostático Específico , SARS-CoV-2 , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controleRESUMO
SUMMARY OBJECTIVE: This article aims to alert health professionals for cancer screening in the face of the possibility of new waves of disease. METHODS: A narrative review was conducted through a search in MEDLINE, Lilacs, Chinese Biomedical Literature Database, and international medical societies publications. RESULTS: Breast cancer: in high-risk patients (confirmed familial cancer syndrome or with high-risk tools scores), clinicians should act according to usual recommendations; in average-risk individuals, consider screening with mammography with a longer time span (maximum of two years). Cervical cancer: women turning 25 years old who have already been immunized and with no previous Pap test can have the test postponed during the pandemic; if there is no previous dose of Human Papillomavirus vaccination, initiation of screening should be recommended following a more rigid approach for COVID prevention; in women over 30 years of age who have never participated in cervical screening, the first screening exam is also essential. Colorectal cancer: if the individual is at elevated risk for familial cancer, the screening with colonoscopy according to usual recommendations should be supported; if at average risk consider screening with Fecal Occult Blood Test. Prostate cancer: there is a trend to postpone routine prostate cancer screening until the pandemic subsides. CONCLUSIONS: The decision to keep cancer screening must be discussed and individualized, considering the possibility of new waves of COVID-19.
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Humanos , Masculino , Feminino , Adulto , Neoplasias da Próstata , Neoplasias Colorretais , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Infecções por Papillomavirus , Vacinas contra Papillomavirus , COVID-19 , Programas de Rastreamento , Antígeno Prostático Específico , Detecção Precoce de Câncer , SARS-CoV-2Assuntos
Infecções por Coronavirus , Diagnóstico Tardio , Neoplasias/diagnóstico , Pandemias , Pneumonia Viral , Betacoronavirus , COVID-19 , Humanos , SARS-CoV-2Assuntos
Humanos , Pneumonia Viral , Infecções por Coronavirus , Diagnóstico Tardio , Pandemias , Neoplasias/diagnóstico , Betacoronavirus , SARS-CoV-2 , COVID-19RESUMO
The proteolytic fraction (P1G10) from Vasconcellea cundinamarcensis, displays gastric protective and healing activities in different skin lesions in mice and human. In an excisional model, this fraction accelerates resolution of lesions and modulates inflammatory mediators. Based on these data, we assessed its anti-inflammatory activity in murine colitis model, induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) adopted by its physiopathological similarity with human colitis. Twenty four hours after colitis induction followed by three days of treatment, P1G10 at 0.3 and 3.0 mg/Kg induced 30% increase in body weight (p < 0.0001) and ~80% reduction in colon macroscopic damage score (p < 0.05) compared to the untreated TNBS-induced colitis group. Histological analyses showed that 0.3 mg/Kg P1G10 reduced the inflammatory profile and tissue damage (47%, p < 0.05) when it was proteolytically active. Compared to TNBS group, 0.3 mg/Kg P1G10 reduced MPO activity (80%, p < 0.01), MCP-1 (47%, p < 0.05) and TNF-α (50%, no significant) and increased IL-10 (330%, p < 0.001) levels in the supernatant of colonic tissue homogenate. P1G10 treatment also reduced COX-2 expression (60%, p < 0.05) and metalloprotease-2 activity (39%, p < 0.05) while increased globet cell density (140%, p < 0.01), that contributes to mucus layer protection in colonic tissue. Taken together, these findings suggest that low doses of active P1G10 promotes lesion resolution, at least in part by its anti-inflammatory activity, in TNBS-colitis model.
