RESUMO
Drug resistance occurs commonly in cancers, especially in hepatocellular carcinoma (HCC). Accumulating evidence has demonstrated that microRNAs (miRNAs) play a vital role in tumour chemoresistance. However, little is known about the role of miR-383 in HCC chemoresistance. In the present study, RT-PCR and western blotting were used to identify the expression profile of miR-383 and eukaryotic translation initiation factor 5A2 (EIF5A2). The bioinformatics website Targetscan was used to predict the target genes of miR-383. In vitro and in vivo loss- and gain-of-function studies were performed to reveal the effects and potential mechanism of the miR-383/EIF5A2 axis in chemoresistance of HCC cells. The expression level of miR-383 correlated negatively with doxorubicin (Dox) sensitivity. Overexpression of miR-383 promoted HCC cells to undergo Dox-induced cytotoxicity and apoptosis, whereas miR-383 knockdown had the opposite effects. EIF5A2 was predicted as a target gene of miR-383. EIF5A2 knockdown sensitized HCC cells to Dox. Moreover, miR-383 inhibition-mediated HCC Dox resistance could be reversed by silencing EIF5A2. Finally, we demonstrated that miR-383 inhibition could enhance Dox sensitivity by targeting EIF5A2 in vivo. The results indicated that miR-383 inhibited Dox resistance in HCC cells by targeting EIF5A2. Targeting the miR-383/EIF5A2 axis might help to alleviate the chemoresistance of HCC cells.
Assuntos
Carcinoma Hepatocelular/patologia , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Fatores de Iniciação de Peptídeos/metabolismo , Proteínas de Ligação a RNA/metabolismo , Animais , Antibióticos Antineoplásicos/farmacologia , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proliferação de Células , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fatores de Iniciação de Peptídeos/genética , Prognóstico , Proteínas de Ligação a RNA/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Fator de Iniciação de Tradução Eucariótico 5ARESUMO
OBJECTIVES: We aimed to examine the significance of ephrin receptor A2 (EphA2) expression in pancreatic adenocarcinoma (PAAD) and its associated mechanism. METHODS: EphA2 mRNA expression patterns were compared in pancreatic cancer and normal tissues using GEPIA. Kaplan-Meier analysis was used to examine the correlation between EphA2 expression and PAAD patient prognosis. EphA2 gene methylation and associations with tumor immune cell infiltration were analyzed with UALCAN and TIMER, respectively. EphA2-interacting proteins were investigated with GeneMANIA, while STRING helped predict potentially relevant signaling pathways. EphA2 protein expression was examined with immunohistochemistry (IHC) in PAAD patient tissues. RESULTS: EphA2 was highly expressed in pancreatic cancer tissues and associated with pathological stage. PAAD patients with high EphA2 expression had shorter overall survival and disease-free survival times. EphA2 expression levels were significantly and positively associated with CD4+ T cell infiltration. EphA2 can interact with ENFNA1, ACP1, and CDC42. High EphA2 mRNA expression was enriched for regulation of cell size and cell proliferation. IHC assays suggested that pancreatic cancer tissues had higher EphA2 protein levels than normal pancreatic tissues. CONCLUSIONS: EphA2 is highly expressed in PAAD and closely related to poor patient prognosis, and is therefore a potential biomarker and target for PAAD diagnosis and treatment.
Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Receptor EphA2 , Humanos , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Receptor EphA2/genética , Prognóstico , RNA Mensageiro/genética , EfrinasRESUMO
BACKGROUND: Hepatic epithelioid angiomyolipoma (HEA) has a low incidence and both clinical manifestations and imaging lack specificity. Thus, it is easy to misdiagnose HEA as other tumors of the liver, especially in the presence of liver diseases such as hepatitis cirrhosis. This article reviewed the diagnosis and treatment of a patient with HEA and alcoholic cirrhosis, and analyzed the literature, in order to improve the understanding of this disease. CASE SUMMARY: A 67-year-old male patient with a history of alcoholic cirrhosis was admitted due to the discovery of a space-occupying lesion in the liver. Based on the patient's history, laboratory examinations, and imaging examinations, a malignant liver tumor was considered and laparoscopic partial hepatectomy was performed. Postoperative pathology showed HEA. During outpatient follow-up, the patient showed no sign of recurrence. CONCLUSION: HEA is difficult to make a definite diagnosis before surgery. HEA has the potential for malignant degeneration. If conditions permit, surgical treatment is recommended.
RESUMO
BACKGROUND: Myopericytoma is a benign tumor that typically occurs within subcutaneous tissue and most often involves the distal extremities, followed by the proximal extremities, neck, thoracic vertebrae and oral cavity. Complete resection is often curative. Malignant myopericytoma is extremely rare and has a poor prognosis. Here, we report for the first time a case of malignant myopericytoma originating from the colon. CASE SUMMARY: A 69-year-old male was admitted to our hospital with right upper quadrant pain for five days. Imaging suggested a liver mass with hemorrhage. A malignant hepatic tumor was the initial diagnosis. Surgical resection was performed after a complete preoperative work up. Initial postoperative pathology suggested that the mass was a malignant myoblastoma unrelated to the liver. Four months after the first surgery, an enhanced computed tomography (CT) scan revealed a recurrence of the tumor. The diagnosis of malignant myopericytoma derived from the colon was confirmed on histopathological examination of the specimen from the second surgery. The patient did not return to the hospital regularly for surveillance. The first postoperative abdominal CT examination six months after the second surgery demonstrated multiple liver metastases. Survival time between the diagnosis of the tumor to death was approximately one year. CONCLUSION: Malignant myopericytoma is a rare cancer. Preoperative diagnosis may be difficult. Due to a lack of treatment options, prognosis is poor.
RESUMO
BACKGROUND: Simple hepatic cysts are commonly occurring lesions that are usually asymptomatic and require no treatment. Hepatic cyst infection, however, is considered a severe complication. We report a case of hepatic cyst infection following pancreatoduodenectomy with repeated fever lasting for almost 3 years, and two cysts were infected successively. CASE SUMMARY: A 72-year-old woman diagnosed with adenocarcinoma of duodenal papilla underwent pancreatoduodenectomy with Child reconstruction. She then suffered repeated occurrences of bacteremia and hepatic cyst infection for 3 years. Blood cultures were positive for Klebsiella pneumoniae and Escherichia coli a total of 7 times and 4 times, respectively. During the early stage, we suspected that postoperative reflux cholangitis was the cause of fever and bacteremia. Multiple cysts were observed, so it was difficult to determine which cyst was infected. Through repeat examination, we found the focus of infection, and we treated the patient with antimicrobials and performed percutaneous cyst drainage. The patient did not experience another cyst infection for more than 4 years. CONCLUSION: Biliary reconstruction inducing hepatic cyst infection is easily misdiagnosed as biliary reflux infection, Repeated imaging examination is a method for identifying the infected focus.
RESUMO
Method of molecularly imprinted solid phase extraction (MISPE) of (-)-ephedrine from Chinese Ephedra has been developed in the research. The molecularly imprinted polymer (MIP) with good selectivity and affinity for (-)-ephedrine was synthesized with (-)-ephedrine as the template, methacrylic acid as the functional monomer. The washing and elution conditions in MISPE were selected and optimized for efficient analyte extraction and sample clean-up. A clean analytical HPLC base line of ephedra extract was obtained after MISPE, which indicated that the sample pre-treatment was efficient. Good recovery and precision were obtained in the assessment for the MISPE-HPLC procedure, which demonstrated it is a reliable method and can be used for the determination of (-)-ephedrine in herbal ephedra.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ephedra/química , Efedrina/isolamento & purificação , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Solventes/químicaRESUMO
Emodin is a traditional Chinese medicine, which has been demonstrated to inhibit the growth of pancreatic cancer cells. However, the underlying molecular mechanisms remain to be elucidated. The present study investigated whether emodin suppresses angiogenesis in pancreatic cancer. A nude mouse pancreatic cancer xenograft model was established using SW1990 human pancreatic cancer cells by surgical orthotopic implantation. Different doses of emodin were injected into the abdominal cavities of the tumorbearing mouse models and controls three times each week for 2 weeks. The tumors were measured and weighed, the expression of cluster of differentiation 34 was detected using immunochemistry, and microvessel densities were calculated. Reverse transcriptionquantitative polymerase chain reaction (RTqPCR) and western blotting were performed to determine the mRNA and protein expression levels of transforming growth factor (TGF)ß and drosophila mothers against decapentaplegic (Smad) homologs. The angiogenesisassociated microRNAs (miR), miR20, miR155 and miR210 were assessed by RTqPCR. A negative dosedependent association was revealed between treatment with emodin and the volume and weight of tumors and microvessel density. Emodin was associated with lower mRNA and protein expression levels of TGFß1 and its downstream target, angiopoietinlike 4, and higher mRNA and protein expression levels of TGFß receptor (TßR)I, TßRII and Smad4. Notably, treatment with emodin was associated with lower expression levels of miR155 and miR210 and higher expression levels of miR20b. The present study suggested that treatment with emodin may repress angiogenesis in pancreatic cancer by altering the activities of the TGF-ß/Smad pathway and angiogenesis-associated miR-20b, miR-155, and miR-210.
Assuntos
Emodina/farmacologia , MicroRNAs/genética , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/farmacologia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Biomarcadores , Linhagem Celular Tumoral , Modelos Animais de Doenças , Emodina/administração & dosagem , Feminino , Expressão Gênica , Xenoenxertos , Humanos , Camundongos , Neovascularização Patológica/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , RNA Mensageiro/genética , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptor do Fator de Crescimento Transformador beta Tipo II , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Proteína Smad4/genética , Proteína Smad4/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Carga Tumoral/efeitos dos fármacosAssuntos
Adenocarcinoma/complicações , Colangiocarcinoma/complicações , Neoplasias Hepáticas/complicações , Neoplasias Retais/complicações , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Fluordesoxiglucose F18/química , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Neoplasias Retais/cirurgiaRESUMO
Ginsenoside Rg3 (Rg3), a trace tetracyclic triterpenoid saponin, is extracted from ginseng and shown to have anticancer activity against several types of cancers. This study explored the effect of Rg3 on pancreatic cancer vasculogenic mimicry. Altered vasculogenic mimicry formation was assessed using immunohistochemistry and PAS staining and associated with the expression of vascular endothelial-cadherin (VE-cadherin), epithelial cell kinase (EphA2), matrix metalloproteinase (MMP)-2 and MMP-9. The effect of Rg3 on the regulation of pancreatic cancer vasculogenic mimicry was evaluated in vitro and in vivo. The data showed vasculogenic mimicry in pancreatic cancer tissues. In addition, the expression of VE-cadherin, EphA2, MMP-2 and MMP-9 proteins associated with formation of pancreatic cancer vasculogenic mimicry. Rg3 treatment reduced the levels of vasculogenic mimicry in nude mouse xenografts in vitro and in vivo, while the expression of VE-cadherin, EphA2, MMP-2 and MMP-9 mRNA and proteins was downregulated by Rg3 treatment in vitro and in tumor xenografts. In conclusion, ginsenoside Rg3 effectively inhibited the formation of pancreatic cancer vasculogenic mimicry by downregulating the expression of VE-cadherin, EphA2, MMP9 and MMP2. Further studies are required to evaluate ginsenoside Rg3 as an agent to control pancreatic cancer.