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Rev. biol. trop ; 70(1)dic. 2022.
Article in English | LILACS-Express | LILACS, SaludCR | ID: biblio-1387701


Abstract Introduction: The digestive tract of Neotropical cichlids has not been deeply studied, and it is a fundamental topic for understanding fish physiology, nutrition, trophic associations, and evolution. Objective: To describe anatomically and histologically the digestive tract of the Neotropical cichlid fish Cichlasoma dimerus and to immunolocalize the orexigenic peptide (Npy) along the intestine. Methods: We euthanized 14 adult individuals and fixed the organs in Bouin´s solution; we stained 7 μm thick paraffin sections for general description and with Alcian Blue (pH = 2.5, AB) and Periodic acid-Schiff (PAS) to identify acid or neutral glycoconjugates, respectively. Additionally, we performed immunohistochemistry for Npy in 3 adult individuals. We manually counted PAS- and AB-positive cells, and Npy-immunoreactive cells per fold. Results: There is a short oesophagus, a sac-like stomach, and a tubular intestine with two loops. The oesophagus has a stratified epithelium with a high density of PAS- and AB-positive goblet cells and striated muscle fibers in the tunica muscularis. The stomach mucosa is formed by simple columnar epithelium. The intestine has a simple columnar epithelium, with brush border and interspersed PAS- and AB-positive goblet cells, and Npy-immunoreactive cells. There is an ileorectal valve in the transition between the posterior intestine and the rectum. This last gut portion has goblet cells and a thicker tunica muscularis. Conclusions: C. dimerus shares features with other Neotropical cichlids, but the goblet cells and gastric glands distribution seems to be unique for the species. To our understanding, this is the first work to describe Npy-immunoreactive cells distribution in the intestine of a Neotropical cichlid fish.

Resumen Introducción: El tracto digestivo de los cíclidos neotropicales no ha sido profundamente estudiado y es un tema fundamental para entender la fisiología, nutrición, asociaciones tróficas y evolución de los peces. Objetivo: Describir anatómica e histológicamente el tracto digestivo del pez cíclido neotropical Cichlasoma dimerus e inmunolocalizar el péptido orexigénico (Npy) a lo largo del intestino. Métodos: Sacrificamos 14 individuos adultos y fijamos los órganos en solución de Bouin; teñimos secciones de parafina de 7 μm de espesor para una descripción general y con azul alcián (pH = 2.5, AB) y ácido periódico-Schiff (PAS) para identificar glicoconjugados ácidos o neutros, respectivamente. Además, en 3 individuos adultos se realizaron inmunohistoquímicas contra Npy. Contamos manualmente las células PAS y AB positivas, y las células inmunorreactivas a Npy por pliegue. Resultados: Hay un esófago corto, un estómago en forma de saco y un intestino con dos vueltas. El esófago tiene un epitelio estratificado con una alta densidad de células caliciformes PAS- y AB- positivas y fibras esqueléticas estriadas en las capas musculares. La mucosa del estómago está revestida por epitelio simple cilíndrico. El epitelio intestinal es simple cilíndrico con chapa estriada y células caliciformes PAS- y AB- positivas intercaladas, y células inmunorreactivas a Npy. Hay una válvula ileorrectal en la transición entre el intestino posterior y el recto. Esta última porción intestinal tiene células caliciformes y una túnica muscular más gruesa. Conclusiones: C. dimerus comparte características con otros cíclidos neotropicales, pero la distribución de las células caliciformes y las glándulas gástricas, serían rasgos propios de esta especie. A nuestro entender, este es el primer trabajo que describe la distribución de células inmunorreactivas a Npy en el intestino de un pez cíclido neotropical.

Animals , Cichlids/anatomy & histology , Gastrointestinal Tract , Fishes
Rev. Odontol. Araçatuba (Impr.) ; 43(2): 25-28, maio-ago. 2022. ilus
Article in English | LILACS, BBO | ID: biblio-1361992


Benign fibrous histiocytoma (BFH) is a common mesenchymal lesion on the skin where it is better known as dermatofibroma. It mainly affects areas of the integument exposed to the sun. It can occur in the mucous membranes, being quite unusual in the oral cavity. This article presents a rare case of benign oral fibrous histiocytoma in childhood. An eleven-year-old male patient sought the stomatology clinic of the dentistry course at a reference university in northeastern Brazil, complaining of an asymptomatic increase in volume on the cheek, with an evolution of approximately two years. On intraoral examination, a lesion in the cheek mucosa was observed, measuring approximately 4 cm. The lesion had a nodular, circumscribed, reddish appearance, showing ulcerated areas covered by a yellowish pseudomembrane on its surface. The clinical diagnostic hypothesis was pleomorphic adenoma. Excisional biopsy was performed and, after morphological and immunohistochemical evaluation, the diagnosis of BFH was reached. Although it is a lesion with an excellent prognosis, BFH must be carefully analyzed for the differential diagnosis with malignant neoplasms that may have a mild appearance, such as fibrosarcoma or dermatofibrosarcoma. In addition, other benign lesions such as desmoplastic fibroblastoma, myofibroma, myopericytoma and nodular fasciitis may, in some histological sections, mimic the microscopic appearance of benign fibrous histiocytoma. In this reported case, immunohistochemical evaluation was essential to conclude the diagnosis of BFH(AU)

Humans , Male , Child , Histiocytoma, Benign Fibrous/diagnosis , Histiocytoma, Benign Fibrous
Int. j. morphol ; 40(3)jun. 2022.
Article in English | LILACS-Express | LILACS | ID: biblio-1385649


SUMMARY: Recent studies have shown that homeobox proteins play an important role in the formation and development of tissues and organs in the embryonic period. In our study, the distribution of Dlx-5 and TLX proteins, which are members of the homeobox family, in the testis, epididymis and ductus deferens ducts of some cat breeds were investigated. For this purpose, in the study, 18 testes younger than six months (immature) and older than one year (mature) were examined under a light microscope using an immunohistochemical method (indirect streptavidin-biotin complex). While it was determined that Dlx-5 and TLX1 proteins were expressed at varying levels in cells in immature and mature cat testicles, epithelial cells of ductus epididymis and ductus deferens, and smooth muscle cells of ductus deferens, no differences were observed between cat breeds. Dlx-5 immunoreactivity was more intense in the testes, epididymis and deferens ducts of immature and mature compared to TLX1. These results suggested that both proteins play important roles in the development of male feline genital organs and in the secretion and differentiation of cells, and also further observation of Dlx-5 expression suggested that this protein may be more effective than TLX1 in testicular development and physiological processes.

RESUMEN: Estudios recientes han demostrado que las proteínas homeobox juegan un papel importante en la formación y desarrollo de tejidos y órganos en el período embrionario. En nuestro estudio, se investigó la distribución de las proteínas Dlx-5 y TLX, que son miembros de la familia homeobox, en los testículos, en el epidídimo y en los conductos deferentes de algunas razas de gatos. En el estudio fueron examinados, 18 testículos de animales menores de seis meses (inmaduros) y mayores de un año (maduros) bajo un microscopio óptico utilizando un método inmunohistoquímico (complejo indirecto de estreptavidina-biotina). Si bien se determinó que las proteínas Dlx-5 y TLX1 se expresaron en niveles variables en las células de los testículos de gatos inmaduros y maduros, las células epiteliales del epidídimo y del conducto deferente y las células del músculo liso del conducto deferente, no se observaron diferencias entre las razas de gatos. La inmunorreactividad de Dlx-5 fue más intensa en los testículos, epidídimo y conductos deferentes de gatos inmaduros y maduros en comparación con TLX1. Estos resultados sugieren que ambas proteínas tienen un rol importante en el desarrollo de los órganos genitales felinos masculinos y en la secreción y diferenciación de células, y también la observación de la expresión de Dlx-5 sugirió que esta proteína puede ser más efectiva que TLX1 en el desarrollo testicular y en los procesos fisiológicos.

Rev. Assoc. Med. Bras. (1992) ; 68(5): 680-684, May 2022. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1376198


SUMMARY Objective: The aim of this study was to evaluate the expression of endoglin and its correlation with histopathological and clinical findings in conjunctival nevi. Methods: The study included archival formalin-fixed, paraffin-embedded tissue sections of 44 patients with conjunctival nevi. Immunohistochemical staining for CD105 had been performed with monoclonal mouse antihuman CD105 antibodies. The intratumoral microvessel density for quantification of tumoral vascularization had been determined by this marker. Results: The expression of CD105 was positive in 30 (68.2%) cases. There was a statistically significant difference in the level of CD105 expression regarding the histological type of nevus (p=0.03) and intralesional cysts status (p=0.02). Spearman's rho (ρ −0.316) revealed a significant negative correlation between the expression of endoglin and the histological type of nevus (p=0.03) and between the expression of endoglin and the presence of intralesional cysts (ρ −0.380, p=0.01). Conclusion: This study suggests that endoglin could be a useful diagnostic and prognostic marker in differentiating between benign and malignant melanocytic ocular lesions.

Arq. gastroenterol ; 59(1): 58-64, Jan.-Mar. 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1374453


ABSTRACT Background Viral hepatitis C is a significant public health challenge. The disease may remain clinically silent in both acute and chronic forms, and chronic infections may progress to advanced disease such as cirrhosis and hepatocellular carcinoma, requiring costly treatment, compromising the patient's quality of life and even leading to death. For this reason, it is one of the most frequent indications for liver transplantation. Although treatment with direct-acting antivirals represents remarkable progress, many patients are still infected and even those who cleared the viral infection must be followed due to their previous hepatic lesions, especially regarding the disturbances of lobular architecture and the sanguineal and lymphatic vessels. Objective To assess immunohistochemical aspects of lymphatic sprouts and mature lymphatic vascularity with histological variables of liver injury attributable to hepatitis C virus (HCV) and fatty disease. Methods The present study included 72 liver biopsies of cases with chronic hepatitis C. Morphologic changes reflecting "staging" and "activity" were analyzed. Immunohistochemical reactions were performed with monoclonal antibody D2-40 anti-podoplanin. Major histological variables were also semiquantified so as to enable the search for possible associations among histological and Immunohistochemical criteria, as well as with genotypes 1 and 3 of HCV. Results Histological findings showed that the different degrees of strutural changes were well represented in this casuistic. Intralobular/parenchymal necro-inflammatory activity was predominantly mild to moderate. Most cases did not show major evidences of fatty disease, which was found significantly higher in cases infected with HCV genotype 3. The amount of portal lymphatic sprouts increased along with the progression of structural changes, maximal at cirrhosis. Portal lymphatic sprouts as well as portal mature lymphatic vessels also showed an increase parallel to the increase in the degree of portal/septal inflammatory infiltrate. In the present study, no significant association was found between the proportion of portal lymphatic sprouts or portal mature lymphatic vessels and the degree of periportal/periseptal activity. No significant relations were detected between lymphatic sprouts/mature vessels and periportal or parenchymal inflammatory activity, nor with infections due to HCV genotype 1 or 3. Conclusion Visualization and semiquantitation of sprouts and mature lymphatic vessels were clearly yielded by Immunohistochemical staining with monoclonal antibody D2-40. The amount of lymphatics was increased along fibrogenic process, significantly related to progression of liver disease and maximal at cirrhosis. No significant relations were detected with necro-inflammatory activity at interface or in the parenchyma.

RESUMO Contexto A hepatite C é um relevante problema de saúde pública. A doença pode permanecer clinicamente silenciosa tanto na forma aguda como na crônica e as infecções crônicas podem progredir para doenças avançadas, tais como cirrose e carcinoma hepatocelular (CHC), requerendo tratamentos dispendiosos, comprometendo a qualidade de vida do paciente e até mesmo levando à morte. Por esta razão, é uma das indicações mais frequentes para o transplante hepático. Apesar da introdução do tratamento com antivirais de ação directa (AAD) representar um progresso notável, muitos pacientes não receberam o tratamento e continuam infectados, e mesmo aqueles que eliminaram a infecção viral devem ser seguidos devido às lesões hepáticas anteriores, especialmente no que diz respeito às alterações da arquitetura lobular e dos vasos sanguíneos e linfáticos. Objetivo Avaliar os aspectos imuno-histoquímicos dos brotos linfáticos e dos vasos linfáticos "maduros" com variáveis histológicas de lesão hepática atribuíveis ao vírus da hepatite C (VHC) e à doença gordurosa. Métodos O presente estudo incluiu 72 biópsias hepáticas em pacientes com hepatite C crônica. Foram analisadas alterações estruturais relativas a "estadiamento" e "atividade". Reações imuno-histoquímicas foram realizadas com anticorpo D2-40 anti-podoplanina. As principais variáveis histológicas também foram semiquantificadas, de modo a permitir a procura de possíveis associações entre os critérios histológicos e imunohistoquímicos, bem como com os genótipos 1 e 3 do VHC. Resultados Os achados histológicos mostraram que os diferentes graus de alterações estrutural estavam bem representados nesta casuística. A atividade necro-inflamatória lobular/parenquimatosa foi predominantemente leve à moderada. A maioria dos casos não apresentava grandes evidências de doença gordurosa, que foi encontrada significativamente mais elevada nos casos infectados com o genótipo 3 do VHC. A quantidade de brotos linfáticos portais aumentou com a progressão de alterações estruturais, sendo máxima na cirrose. Os brotos linfáticos portais, bem como os vasos linfáticos "maduros" portais também mostraram um aumento paralelo ao aumento do grau de infiltrado inflamatório portal/septal. No presente estudo, não foi encontrada qualquer associação significativa entre a proporção de brotos linfáticos portais ou vasos linfáticos maduros portais e o grau de atividade periportal/periseptal. Não foram detectadas relações significativas entre os brotos linfáticos/vasos maduros e a atividade inflamatória periportal ou atividade inflamatória parenquimatosa, nem com infecções devido ao genótipo 1 ou 3 do VHC. Conclusão A reação imunohistoquímica com anticorpo monoclonal D2-40 possibilitou a visualização e a semiquantitação de brotos e vasos linfáticos "maduros" nas amostras obtidas por biópsia hepática. A quantidade de linfáticos aumentou ao longo do processo fibrogênico, significativamente relacionada com a progressão da doença hepática e máxima na cirrose. Não foram detectadas relações significativas com a atividade necro-inflamatória periportal ou parenquimatosa.

Biomédica (Bogotá) ; 42(1): 196-206, ene.-mar. 2022. graf
Article in Spanish | LILACS | ID: biblio-1374518


Introducción. Las lesiones del nervio facial afectan la plasticidad a largo plazo en el hipocampo, así como la memoria de reconocimiento de objetos y la memoria espacial, dos procesos dependientes de esta estructura. Si bien se ha descrito una activación de la microglía en la corteza motora primaria asociada con esta lesión, no se conoce si ocurre algo similar en el hipocampo. Objetivo. Caracterizar en ratas el efecto de la lesión unilateral del nervio facial sobre la activación de células de la microglía en el hipocampo contralateral. Materiales y métodos. Se hicieron experimentos de inmunohistoquímica para detectar células de la microglía en el hipocampo de ratas sometidas a lesión irreversible del nervio facial. Los animales se sacrificaron en distintos momentos después de la lesión, para evaluar la evolución de la proliferación (densidad de células) y la activación (área celular) de la microglía en el tejido del hipocampo. Los tejidos cerebrales de los animales de control se compararon con los de animales lesionados sacrificados en los días 1,3, 7, 21 y 35 después de la lesión. Resultados. Las células de la microglía en el hipocampo de animales con lesión del nervio facial mostraron signos de proliferación y activación a los 3, 7 y 21 días después de la lesión. Sin embargo, al cabo de cinco semanas, estas modificaciones se revirtieron, a pesar de que no hubo recuperación funcional de la parálisis facial. Conclusiones. La lesión irreversible del nervio facial produce proliferación y activación temprana y transitoria de las células de la microglía en el hipocampo. Estos cambios podrían estar asociados con las modificaciones electrofisiológicas y las alteraciones comportamentales dependientes del hipocampo descritas recientemente.

Introduction: Facial nerve injury induces changes in hippocampal long-term synaptic plasticity and affects both object recognition memory and spatial memory consolidation (i.e., hippocampus-dependent tasks). Although facial nerve injury-associated microglíal activation has been described regarding the primary motor cortex, it has not been ascertained whether something similar occurs in the hippocampus. Peripheral nerve injury- associated microglíal changes in hippocampal tissue could explain neuronal changes in the contralateral hippocampus. Objective: To characterize the effect of unilateral facial nerve injury on microglíal proliferation and activation in the contralateral hippocampus. Materials and methods: Immunohistochemical experiments detected microglíal cells in the hippocampal tissue of rats that had undergone facial nerve injury. The animals were sacrificed at specific times after injury to evaluate hippocampal microglíal cell proliferation (cell density) and activation (cell area); sham-operated animals were compared to lesioned animals sacrificed 1,3, 7, 21, or 35 days after injury. Results: Facial nerve-injured rats' hippocampal microglíal cells proliferated and adopted an activated phenotype 3- to 21-days post-lesion. Such modifications were transient since the microglíal cells returned to their resting state five weeks after injury, despite the injury's irreversible nature. Conclusions: Facial nerve injury causes the transient proliferation and activation of microglíal cells in the hippocampus. This finding might partly explain the morphological and electrophysiological changes described for CA1 pyramidal neurons and the impairment of spatial memory consolidation which has previously been observed in facial nerve-injured rats.

Facial Nerve , Hippocampus , Rats , Immunohistochemistry
Medicina UPB ; 41(1): 91-95, mar. 2022. Ilus, tab
Article in Spanish | LILACS, COLNAL | ID: biblio-1362719


El angiosarcoma es un tumor vascular maligno poco frecuente. Constituye menos del 2% de todos los sarcomas. Existen varias formas clínicas, una es la producida después de radioterapia, en pacientes que fueron tratadas por un cáncer de mama, con cirugía conservadora y radioterapia. Se presenta como un sarcoma de alto grado, localizado en la piel o en el tejido subcutáneo y, ocasionalmente, el parénquima mamario. El único tratamiento curativo es la cirugía, con tendencia a la recurrencia y a hacer metástasis hematógena, el pronóstico es malo, con alta tasa de mortalidad.

Angiosarcoma is a rare malignant vascular tumor. It constitutes less than 2% of all sarcomas. There are several clinical forms; the one produced after radiation therapy is that associated with patients who were treated for breast cancer with conservative surgery and radiation therapy. It presents as a high-grade sarcoma located on the skin or the subcutaneous tissue and, occasionally, the breast parenchyma. The only curative treatment is surgery, with a tendency to recurrence and visceral hematogenous metastasis, with a poor prognosis and a high mortality rate.

El angiossarcoma é um tumor vascular maligno pouco frequente. Constitui menos de 2% de todos os sarcomas. Existem várias formas clínicas, uma é a produzida depois da radioterapia, em pacientes que foram tratadas por um câncer de mama, com cirurgia conservadora e radioterapia. Se apresenta como um sarcoma de alto grau, localizado na pele ou no tecido subcutâneo e, ocasionalmente, o parênquima mamário. O único tratamento curativo é a cirurgia, com tendência à recorrência e a fazer metástasehematogênica, o prognóstico é mau, com alta taxa de mortalidade.

Humans , Female , Breast Neoplasms , Radiotherapy , Breast , Subcutaneous Tissue , Parenchymal Tissue , Neoplasm Metastasis
Braz. J. Vet. Res. Anim. Sci. (Online) ; 59: e188941, fev. 2022. ilus
Article in English | LILACS, VETINDEX | ID: biblio-1380208


Canine Distemper is a disease caused by Canine morbillivirus (CM), a pantropic virus that can affect the central nervous system (CNS), causing demyelination. However, the pathogenesis of this lesion remains to be clarified. Brain samples of 14 naturally infected dogs by CM were analyzed to evaluate the presence of oxidative stress and demyelination. RT-PCR assay was performed to confirm a diagnosis of canine distemper in the brain, immunohistochemistry anti-CM was used to localize the viral proteins in the tissue, and anti-4-hydroxy-2-nonenal (4-HNE) was a marker of a product of lipid peroxidation. The results showed the presence of viral proteins in the demyelinated area with the presence of 4-HNE. Our results suggest that the CM virus infection causes oxidative stress leading to lipid peroxidation, which causes tissue damage and demyelination. In conclusion, oxidative stress plays a significant role in canine distemper pathogenesis in the CNS.(AU)

A cinomose canina é uma doença causada pelo Morbilivírus canino (CM), um vírus pantrópico que pode afetar o sistema nervoso central (SNC), causando desmielinização. No entanto, a patogênese dessa lesão não está totalmente esclarecida. RT-PCR e imuno-histoquímica foram realizadas para confirmação do diagnóstico de cinomose em amostras de encéfalo de 14 cães naturalmente infectados. Após confirmação, foi realizada uma avaliação do estresse oxidativo por imuno-histoquímica com uso de anti-4-hidroxi-nonenal (4HNE) como marcador de produtos resultantes da peroxidação lipídica. Os resultados sugerem que a infecção pelo CM causa estresse oxidativo no tecido, levando a peroxidação lipídica, a qual causa danos ao tecido, culminando com desmielinização. Conclui-se que o estresse oxidativo tem papel importante na patogênese da cinomose canina no sistema nervoso central.(AU)

Animals , Biomarkers/metabolism , Central Nervous System Infections/veterinary , Distemper/diagnosis , Dogs/virology , Immunohistochemistry/instrumentation , Lipid Peroxidation/drug effects , Demyelinating Diseases/veterinary , Morbillivirus/pathogenicity , Oxidative Stress/physiology , Reverse Transcriptase Polymerase Chain Reaction/instrumentation , Cerebrum/virology
Surg. cosmet. dermatol. (Impr.) ; 14: e20220065, jan.-dez. 2022.
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1370005


O linfoma cutâneo difuso de grandes células B, tipo perna, compreende uma neoplasia rara, agressiva e de mau prognóstico. Corresponde a 10-20% dos linfomas cutâneos de células B e afeta principalmente membros inferiores de mulheres idosas. Relatamos o caso de mulher de 81 anos, com nódulos e tumorações dolorosos, de crescimento rápido na perna esquerda. Os achados histopatológicos e a imuno-histoquímica, associados à ausência de comprometimento extracutâneo no estadiamento, concluíram o diagnóstico de linfoma cutâneo difuso de grandes células B, tipo perna. A raridade, a clínica e a epidemiologia típicas e a excelente resposta ao tratamento motivaram este relato

Cutaneous diffuse large B-cell lymphoma, leg type, is a rare, aggressive, and poorly prognostic neoplasm. It corresponds to 10-20% of cutaneous B-cell lymphomas and mainly affects the lower limbs of older women. We report the case of an 81-year-old woman with painful, fast-growing nodules and tumors in her left leg. Histopathological and immunohistochemical findings, associated with the absence of extra-cutaneous involvement during staging, concluded the diagnosis of cutaneous diffuse large B-cell lymphoma, leg type. The rarity of this limphoma, its typical clinic and epidemiology, and the excellent response to treatment motivated this report

J. Bras. Patol. Med. Lab. (Online) ; 58: e4482022, 2022. tab
Article in English | LILACS-Express | LILACS | ID: biblio-1375689


ABSTRACT Introduction In Brazil, 8,000 new cases of childhood cancer are estimated each year, whose causes are still little known, although some have genetically determined factors. Approximately 70% of human cancers have alterations in the TP53 gene, which encodes the protein responsible for inhibiting the disordered growth of cells exposed to injuries. However, the frequency of alterations in the expression of TP53 in childhood cancers in Brazil remains poorly known. Objective To evaluate the expression of TP53 gene in patients with childhood cancer in northeastern of Santa Catarina, Brazil. Materials and Methods: Retrospectively, 282 patients diagnosed with cancer between 2005 and 2015 in Joinville were included. TP53 expression was evaluated by immunohistochemistry using a score based on the intensity and percentage of stained cells. Results The p53 protein was positive in 25.2% of cases, with no difference between sexes. Considering the five main groups of tumors in the sample, the expression was positive in 31.8%, 27.3%, 20%, 17.2% and 5.9% of lymphomas, nephroblastomas, neuroblastomas, tumors of the Central Nervous System and leukemias, respectively. Conclusion The prevalence of TP53 expression was evaluated in different childhood cancers in the northeastern of Santa Catarina. Positivity was higher among lymphomas and lower in leukemias, but with no significant difference among the five most frequent tumors. Further studies that allow correlation with aggressiveness and disease evolution are required.

J. Bras. Patol. Med. Lab. (Online) ; 58: e4452022, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1375699


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.

Acta Pharmaceutica Sinica B ; (6): 1225-1239, 2022.
Article in English | WPRIM | ID: wpr-929366


The dysregulation of transcription factors is widely associated with tumorigenesis. As the most well-defined transcription factor in multiple types of cancer, c-Myc can transform cells by transactivating various downstream genes. Given that there is no effective way to directly inhibit c-Myc, c-Myc targeting strategies hold great potential for cancer therapy. In this study, we found that WSB1, which has a highly positive correlation with c-Myc in 10 cancer cell lines and clinical samples, is a direct target gene of c-Myc, and can positively regulate c-Myc expression, which forms a feedforward circuit promoting cancer development. RNA sequencing results from Bel-7402 cells confirmed that WSB1 promoted c-Myc expression through the β-catenin pathway. Mechanistically, WSB1 affected β-catenin destruction complex-PPP2CA assembly and E3 ubiquitin ligase adaptor β-TRCP recruitment, which inhibited the ubiquitination of β-catenin and transactivated c-Myc. Of interest, the effect of WSB1 on c-Myc was independent of its E3 ligase activity. Moreover, overexpressing WSB1 in the Bel-7402 xenograft model could further strengthen the tumor-driven effect of c-Myc overexpression. Thus, our findings revealed a novel mechanism involved in tumorigenesis in which the WSB1/c-Myc feedforward circuit played an essential role, highlighting a potential c-Myc intervention strategy in cancer treatment.

Acta Pharmaceutica Sinica B ; (6): 821-837, 2022.
Article in English | WPRIM | ID: wpr-929309


Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-β2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-β2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-β2; the expressions of both miR-7-5p and TGF-β2 are correlated with patients' survival. We are the first to identify the role of the miR-7/TGF-β2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.

Acta Pharmaceutica Sinica B ; (6): 451-466, 2022.
Article in English | WPRIM | ID: wpr-929306


The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

Asian Journal of Andrology ; (6): 50-55, 2022.
Article in English | WPRIM | ID: wpr-928506


The purpose of our study is to investigate the prognostic value of phosphatase and tensin homolog on chromosome 10 (PTEN) expression in patients with de novo metastatic castration naïve prostate cancer (mCNPC). A total of 205 patients with mCNPC at Fudan University Shanghai Cancer Center (Shanghai, China) were retrospectively examined. Immunohistochemical staining of PTEN was performed on prostate biopsy samples of these patients. Associations among clinicopathological features, patient survival and PTEN protein expression were analyzed. PTEN loss occurred in 58 of 205 (28.3%) patients. Loss of PTEN was significantly correlated with high metastatic volume (P = 0.017). No association between PTEN expression and Gleason score was observed. Patients with PTEN loss had significantly shorter progression-free survival (PFS, P < 0.001) and overall survival (OS, P < 0.001) compared with patients with intact PTEN expression. Multivariate analysis showed that elevated alkaline phosphatase, high metastatic volume and PTEN loss were independent poor prognostic factors for PFS. The Eastern Cooperative Oncology Group performance status (ECOG PS)#8805; 2 and PTEN loss were independent poor prognostic factors for OS. The adjusted hazard ratio of PTEN loss for PFS and OS was 1.67 (95% confidence interval [CI]: 1.14-2.43, P = 0.008) and 1.95 (95% CI: 1.23-3.10, P = 0.005), respectively. PTEN loss was also significantly associated with shorter PFS (P = 0.025) and OS (P < 0.001) in patients with low-volume metastatic disease. Our data showed that PTEN loss is an independent predictor for shorter PFS and OS in patients with de novo mCNPC.

China/epidemiology , Humans , Male , PTEN Phosphohydrolase/genetics , Prognosis , Prostatic Neoplasms , Retrospective Studies
Chinese Journal of Biotechnology ; (12): 1025-1038, 2022.
Article in Chinese | WPRIM | ID: wpr-927760


In order to explore the antitumor effect and mechanism of different extracts of cultivated Phellinus vaninii fruit body on H22 tumor bearing mice, 150 ICR mice were randomly divided into blank group, model group, CTX group, P. vaninii water extract group, ethanol extract group, petroleum ether extract group and crude polysaccharide group. H22 liver cancer cells were used to establish a solid tumor model and the mice were sacrificed on the 10th day after administration. The spleen and thymus organ index and tumor inhibition rate were calculated, the serum levels of TNF-α, INF-γ, VEGF, and hematoxylin-eosin were detected, and the immunohistochemical staining method was used to observe the pathological changes of tumor tissues, while Western blotting was used to detect the expression of tumor-related proteins. The high-dose petroleum ether extract group showed the best tumor inhibition rate (73.21%), increased serum levels of TNF-α, IFN-γ, and VEGF, as well as significantly promoted tumor necrosis and ablation. The immunohistochemistry of the water extract group showed negative regulation, indicating an insignificant tumor suppression. Western blotting showed the apoptosis genes Caspase-3, Caspase-9 and pathway genes NF-κB and JAK were all highly expressed in each administration group compared with the model group, and their expression levels gradually decreased with increasing doses. In summary, the petroleum ether extract of P. vaninii fruit body showed a significant anti-tumor effect which is presumably mediated through the mitochondrial pathway. The metabolism of drug in the body induces activation of Caspase-3 and Caspase-9 apoptotic proteins by Bax, Bcl-2, and TNF, which further caused nuclear chromatin or DNA to condense or degrade, and subsequently destroy the normal proliferation of tumor cells, thereby inducing their apoptosis and inhibiting tumor growth.

Animals , Apoptosis , Basidiomycota , Mice , Mice, Inbred ICR , Neoplasms/metabolism
Braz. oral res. (Online) ; 36: e072, 2022. tab, graf
Article in English | LILACS-Express | LILACS, BBO | ID: biblio-1374758


Abstract: The osteolytic activity of odontogenic cysts and tumors is directly associated with their growth and aggressiveness. The influence of proteins expressed by epithelial and mesenchymal cells on this biological event differs between indolent cystic lesions, aggressive cystic lesions, and odontogenic tumors. The objective of this study was to compare the immunohistochemical expression of factors that stimulate (receptor activator of nuclear factor kappa-Β ligand - RANKL, cathepsin K - CatK and matrix metallopeptidase 8 - MMP-8) and inhibit (osteoprotegerin - OPG) osteoclastogenesis between dentigerous cyst (DC), glandular odontogenic cyst (GOC), odontogenic keratocyst (OKC), and ameloblastoma (AB). Paraffin-embedded sections of nine DCs, nine GOCs, 20 OKCs, 21 ABs, and four dental follicles (DFs) were subjected to immunohistochemistry. Immunoreactivity was analyzed semiquantitatively and quantitatively in epithelium and connective tissue, respectively. The proteins were immunoexpressed in epithelial and mesenchymal cells of all lesions studied. The expression of RANKL and CatK was higher in OKC, AB, and GOC (p<0.005). Higher expression of OPG was found in DF and DC compared to the other markers (p<0.005). MMP-8 expression was high in GOC and OKC. This study demonstrated the differential expression of factors that inhibit and stimulate bone resorption during the development of DC, GOC, OKC, and AB. Higher expression of RANKL and CatK was observed in more aggressive lesions. OPG appears to be one of the molecules responsible for the slower growth of DC.

Braz. oral res. (Online) ; 36: e071, 2022. tab, graf
Article in English | LILACS-Express | LILACS, BBO | ID: biblio-1374759


Abstract: The aim of this study was to analyze and compare the immunohistochemical expression of plasminogen activator system (PAS) proteins (uPA, uPAR, and PAI-1) in ameloblastomas (AMBs), odontogenic keratocysts (OKCs), and dental follicles (DFs) representing normal odontogenic tissue, as well as to investigate possible correlations between these proteins. Twenty AMBs, 20 OKCs, and 10 DFs were selected for immunohistochemical analysis. In each case, the immunoexpression of uPA, uPAR, and PAI-1 was evaluated semiquantitatively based on the percentage of positivity in odontogenic epithelial and connective tissue cells. The epithelial immunoexpression of uPA was significantly lower in AMBs when compared to OKCs (p = 0.001) and DFs (p = 0.029). Significantly higher epithelial immunostaining for uPAR was observed in AMBs when compared to OKCs (p < 0.001). There were no significant differences in the epithelial immunoexpression of PAI-1 between AMBs and OKCs (p = 1.000). The correlations found for the expression of the studied proteins were not statistically significant (p > 0.05). However, the epithelial and connective tissue expressions of uPAR have a strong positive and statistically significant correlation in AMBs. The present results suggest that uPA is involved in the pathogenesis of OKCs and that uPAR may participate in tumorigenesis in AMBs. The high percentage of PAI-1-positive cells suggests a possible role for this protein in the development of AMBs and OKCs. Furthermore, the studied proteins do not seem to act synergistically in AMBs, OKCs, and DFs.

Mastology (Online) ; 32: 1-5, 2022.
Article in English | LILACS-Express | LILACS | ID: biblio-1391029


Introduction: Because of its high incidence, breast cancer is the subject of numerous studies today. Despite being an uncommon disease in young women, when it affects this population, it tends to be more aggressive and has high mortality rates. Objective: The objective of this study was to evaluate the prognostic factors present in the immunohistochemical profile of young women with breast cancer, comparing the age groups of very young women (<35 years old ­ Group I) and young women (between 35 and 40 years old ­ Group II), to see if the data obtained match what is reported in the literature. Methods: A cross-sectional study was carried out, analyzing the immunohistochemical tests of 90 female patients with invasive breast carcinoma. The groups were classified on the basis of molecular subtype: luminal A, luminal B, hybrid luminal, human epidermal growth factor receptor 2 positive and triple-negative. Results: The histological type with the highest incidence was invasive breast carcinoma of no special type. The most frequent molecular subtypes were luminal B and triple-negative. With regard to estrogen and progesterone receptors, there was a slight predominance of positive receptors. Ki-67 levels showed that in the triple-negative and human epidermal growth factor receptor 2 positive subtypes, there was a predominance of high cell proliferation index. Conclusion: In the population of young women in this cohort of patients, there was agreement with literature data regarding the predominance of the invasive carcinoma of no special type histological type and the luminal B and triple-negative molecular subtypes, and the presence of high cell proliferation rates, attesting to the higher prevalence of more aggressive tumors in the younger population. There was also no statistically significant difference in all aspects analyzed when comparing Groups I and II. However, a higher frequency of negative hormone receptors or overexpressed human epidermal growth factor receptor 2 molecular subtypes was not detected, characteristics that are common to young women with breast cancer, which has been pointed out in several studies worldwide.

Mastology (Online) ; 32: 1-6, 2022.
Article in English | LILACS-Express | LILACS | ID: biblio-1363057


Introduction: The presence of brain metastases secondary to primary breast cancer implies a worse prognosis for those affected. Therefore, the aim of this study was to determine the median survival after the diagnosis of brain metastasis in patients with breast carcinoma in a center in northeastern Brazil. Methods: The medical records of 345 patients diagnosed with breast cancer, treated between 1998 and July 2018, were analyzed. Those with brain metastasis along with their treatment performed and survival were identified. Results: Nine (2.6%) patients had brain metastasis; the mean age was 56.8 years. The mean survival time determined by the Kaplan-Meier method was 23.8 months (95%CI 6.9­40.8). Seven patients (78%) died from the disease and two were lost to follow-up (22%); invasive carcinoma of no special type was the most frequent (78%). Molecular classification by immunohistochemistry was possible in seven patients: five luminal B subtype cases, one luminal A case and one triple-negative case; luminal B subtype was associated with longer survival: 23.3 months (95%CI 3.0­43.6). As for the initial clinical staging, according to the TNM Classification of Malignant Tumors, there was one IA case, one IIA case, three IIB cases and two IIIB cases. Three patients underwent modified radical mastectomy, and six underwent conservative treatment (quadrantectomy); there was no statistical difference in survival between the different forms of treatment (p=0.771). Conclusion: The median survival after diagnosis of brain metastasis from breast cancer was 23.80 months.