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1.
Biochem Biophys Res Commun ; 640: 173-182, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36512849

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a cancerous tumor that ranks as the third leading cause of cancer death across the globe. Protein kinase membrane-associated tyrosine/threonine kinase 1 (PKMYT1) is overexpressed in many cancer types, including HCC, but the potential mechanism and biological function of PKMYT1 are not fully understood. MATERIALS AND METHODS: The expression level of PKMYT1 was detected in human HCC tissues and adjacent tissues. We then established HCC cell lines with PKMYT1 knockdown and observed proliferation, migration, autophagy, apoptosis in cell lines and tumor growth in a nude mouse model. To investigate the underlying mechanism by which PKMYT1 regulates autophagy and apoptosis, RNA sequencing was performed in HCC-LM3 cells with and without PKMYT1 knockdown. RESULTS: Here, we observed that human HCC tissues had higher expression of PKMYT1 than adjacent tissues. Overexpression of PKMYT1 was closely associated with poor prognosis in HCC patients. PKMYT1 knockdown inhibited the proliferative potential and migration of HCC cell lines. We also found that downregulation of PKMYT1 inhibited autophagy and induced apoptosis. RNA sequencing analysis showed that the MAPK and PI3K-AKT pathways, which have been reported to affect autophagy and apoptosis, may be regulated after PKMYT1 knockdown by KEGG pathway enrichment analysis. Furthermore, we identified that knockdown of PKMYT1 attenuated the phosphorylation levels of p38 MAPK, ERK and PI3K/Akt/mTOR, which might mediate autophagy inhibition and apoptosis induction via these signaling pathways to inhibit the development of HCC. CONCLUSION: Our study suggests that PKMYT1 functions as an oncogene and may be a new target for HCC treatment.


Assuntos
Apoptose , Autofagia , Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteínas de Membrana , Proteínas Tirosina Quinases , Animais , Humanos , Camundongos , Apoptose/genética , Autofagia/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Hepáticas/patologia , Proteínas de Membrana/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Serina-Treonina Quinases , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo
2.
Ann Hepatol ; 23: 100345, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33812045

RESUMO

INTRODUCTION AND OBJECTIVES: This study aimed to explore the functional mechanism of the miRNA-20b-5p/cytoplasmic polyadenylation element binding protein 3 (miR-20b-5p/CPEB3) axis in hepatocellular carcinoma (HCC) so as to provide a new idea for targeted therapy of HCC. MATERIALS AND METHODS: Bioinformatics analysis was employed to obtain markedly differentially expressed miRNAs and mRNAs in The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset, so as to find target miRNA and its target mRNA. Real-time quantitative PCR was conducted to detect miR-20b-5p and CPEB3 mRNA expression. Western blot was performed to determine CPEB3 protein expression. Dual-luciferase reporter assay was carried out to verify the targeting relationship between miR-20b-5p and CPEB3. Cell counting kit-8 assay, wound healing assay, Transwell invasion assay and flow cytometry were conducted to evaluate the proliferation, migration, invasion and apoptosis of HCC cells. RESULTS: Bioinformatics analysis suggested that miR-20b-5p and CPEB3 were markedly highly and lowly expressed, respectively, in HCC tissue in TCGA-LIHC dataset. Over-expressing miR-20b-5p facilitated the proliferation, migration and invasion, and suppressed the apoptosis of HCC cells. Dual-luciferase reporter assay validated that there was a targeting relationship between miR-20b-5p and CPEB3. The inhibitory effect of CPEB3 over-expression on HCC cell proliferation, migration and invasion was reversed by over-expressing miR-20b-5p. CONCLUSIONS: The present study proved that miR-20b-5p promotes HCC cell proliferation, migration and invasion by inhibiting CPEB3 expression, which may provide a theoretical basis for the prognosis and treatment of HCC patients.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Proteínas de Ligação a RNA/genética , Carcinoma Hepatocelular/metabolismo , Estudos de Casos e Controles , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Bases de Dados Factuais , Humanos , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , Invasividade Neoplásica , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo
3.
BMC Surg ; 21(1): 178, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794850

RESUMO

BACKGROUND: The inflammation indexes in blood routine play an essential role in evaluating the prognosis of patients with hepatocellular carcinoma, but the effect on early recurrence has not been clarified. The study aimed to investigate the risk factors of early recurrence (within 2 years) and recurrence-free survival after curative hepatectomy and explore the role of inflammatory indexes in predicting early recurrence. METHODS: The baseline data of 161 patients with hepatocellular carcinoma were analyzed retrospectively. The optimal cut-off value of the inflammatory index was determined according to the Youden index. Its predictive performance was compared by the area under the receiver operating characteristic curve. Logistic and Cox regression analyses were used to determine the risk factors of early recurrence and recurrence-free survival. RESULTS: The area under the curve of monocyte to lymphocyte ratio (MLR) for predicting early recurrence was 0.700, which was better than systemic inflammatory response index (SIRI), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and systemic immune-inflammatory index (SII). MLR, tumour size, tumour differentiation and BCLC stage are all risk factors for early recurrence and recurrence-free survival of HCC. Combining the above four risk factors to construct a joint index, the area under the curve for predicting early recurrence was 0.829, which was better than single MLR, tumour size, tumour differentiation and BCLC stage. Furthermore, with the increase of risk factors, the recurrence-free survival of patients is worse. CONCLUSION: The combination of MLR and clinical risk factors is helpful for clinicians to identify high-risk patients with early recurrence and carry out active postoperative adjuvant therapy to improve the prognosis of patients.


Assuntos
Carcinoma Hepatocelular , Hepatectomia , Inflamação , Neoplasias Hepáticas , Recidiva Local de Neoplasia , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/cirurgia , Humanos , Inflamação/sangue , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/cirurgia , Contagem de Linfócitos , Monócitos , Recidiva Local de Neoplasia/sangue , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco
4.
J Cell Mol Med ; 23(11): 7190-7199, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30801960

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 5A
5.
J Int Med Res ; 52(1): 3000605231218559, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38180878

RESUMO

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 , Efrinas
6.
World J Clin Cases ; 12(14): 2382-2388, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38765741

RESUMO

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.

7.
J Hepatocell Carcinoma ; 11: 1445-1457, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39050810

RESUMO

Background: A limited number of studies have examined the use of radiomics to predict 3-year overall survival (OS) after hepatectomy in patients with hepatocellular carcinoma (HCC). This study develops 3-year OS prediction models for HCC patients after liver resection using MRI radiomics and clinicopathological factors. Materials and Methods: A retrospective analysis of 141 patients who underwent surgical resection of HCC was performed. Patients were randomized into two set: the training set (n=98) and the validation set (n=43) including the survival groups (n=111) and non-survival groups (n=30) based on 3-year survival after hepatectomy. Furthermore, x2 or Fisher's exact test, univariate and multivariate logistic regression analyses were conducted to determine independent clinicopathological risk factors associated with 3-year OS. 1688 quantitative imaging features were extracted from preoperative T2-weighted imaging (T2WI) and contrast-enhanced magnetic resonance imaging (CE-MRI) of arterial phase (AP), portal venous phases (PVP)and delay period (DP). The features were selected using the variance threshold method, the select K best method and the least absolute shrinkage and selection operator (LASSO) algorithm. By using Bernoulli Naive Bayes (BernoulliNB) and Multinomial Naive Bayes (MultinomialNB) classifiers, we constructed models based on the independent clinicopathological factors and Rad-scores. To determine the best model, receiver operating characteristics (ROC) and Delong's test were used. Moreover, calibration curves were used to determine the calibration ability of the model, while decision curve analysis (DCA) was implemented to evaluate its clinical benefit. Results: The fusion model showed excellent prediction precision with AUC of 0.910 and 0.846 in training and validation set and revealed significant diagnostic accuracy and value in the calibration curve and DCA analysis. Conclusion: Nomograms based on MRI radiomics and clinicopathological factors have significant predictive value for 3-year OS after hepatectomy and can be used for risk classification.

8.
World J Gastrointest Surg ; 16(6): 1918-1925, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38983349

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.

9.
World J Clin Cases ; 10(25): 9156-9161, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36157635

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.

10.
Braz J Med Biol Res ; 54(4): e10273, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33656054

RESUMO

Vascular invasion and systemic immune-inflammation index (SII) are risk factors for the prognosis of patients with hepatocellular carcinoma. At present, the correlation between the two is not clear. This meta-analysis explored the relationship between preoperative SII and vascular invasion in patients with hepatocellular carcinoma. According to the search formula, the Pubmed, Embase, Cochrane, Web of Science, and CNKI databases were searched for the relevant research until March 2020. After the quality evaluation of the included literature, the odds ratio (OR) and its corresponding 95% confidence interval (CI) were used as the effect measure. Stata 15. 0 software was used for statistical analysis. The meta-analysis eventually included seven retrospective cohort studies of 3583 patients with hepatocellular carcinoma. The results showed that the choice of SII cut-off value affects SII's efficiency in predicting the risk of vascular invasion. In the cohort of studies with appropriate SII cut-off value, the high SII preoperative group had a higher risk of vascular invasion (OR=2.62; 95%CI: 2.07-3.32; P=0.000) and microvascular invasion (OR=1.82; 95%CI: 1.01-3.25; P=0.045) than the low SII group. The tumor diameter (OR=2.88; 95%CI: 1.73-4. 80; P=0.000) of the high SII group was larger than that of the low SII group. There was no publication bias in this study (Begg's test, P=0.368). As a routine, cheap, and easily available index, SII can provide a certain reference value for clinicians to evaluate vascular invasion before operation.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/cirurgia , Humanos , Inflamação , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos , Fatores de Risco
11.
Mitochondrial DNA B Resour ; 6(3): 1071-1072, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33796742

RESUMO

Ottelia acuminate var. crispa is an endangered aquatic herb with extremely narrow distribution. In this study, we assembled the chloroplast genome of this species based on the second-generation high-throughput sequencing. The genome is 157,783 bp in length with a typical quadripartite structure including a large single-copy region (LSC) of 88,294 bp, a small single-copy region (SSC) of 49,379 bp, and a pair of inverted repeats (IRs) of 10,055 bp each. A total of 128 genes were annotated, including 83 protein-coding genes (PCG), 37 tRNA genes, and 8 rRNA genes. The phylogenetic tree shows that O. acuminate var. crispa has a close relationship with the genus Elodea. The chloroplast genome presented here provides a valuable resource to conserve this endangered species.

12.
Biosci Rep ; 40(7)2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32463473

RESUMO

Hepatocellular carcinoma (HCC) is a frequently seen malignant tumor globally. The occurrence of cisplatin (DDP) resistance is one of the main reasons for the high mortality of HCC patients. Therefore, it is of great theoretical significance and application value to explore the mechanism of chemotherapy resistance. Drug resistance can be modulated by exosomes containing mRNAs, micro RNAs (miRNAs) and other non-coding RNA (ncRNAs). Exosomal miR-199a-3p (Exo-miR-199a-3p) was subjected to extraction and verification. Whether exo-miR-199a-3p could make HCC cells sensitive to DDP in vitro was verified via flow cytometry, Cell Counting Kit-8 (CCK-8) assay, immunofluorescence assay and Transwell assay. Intravenous injection of exo-miR-199a-3p and intraperitoneal injection of DDP were carried out in vivo. Moreover, the possible targets of miR-199a-3p were screened through bioinformatics analysis, which were ascertained by Western blotting (WB). Then, miR-199a-3p levels in human normal liver epithelial cell line HL-7702 and HCC cell lines HuH7 and HuH7/DDP were elevated in a concentration-dependent manner. Exo-miR-199a-3p has abilities to adjust underlying targets and conjugate cells, to repress cells to invade, stimulate their apoptosis and abate their ability. Additionally, the caudal injection of exo-miR-199a-3p reversed the chemoresistance of tumors and slowed down their growth in the body owing to the up-regulation of miR-199a-3p and down-regulation of underlying target proteins in tumors. Finally, exo-miR-199a-3p was found to overturn the HCC's resistance to DDP, and it may function in DDP-refractory HCC therapy as an underlying option in the future.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Hepáticas/tratamento farmacológico , MicroRNAs/administração & dosagem , Animais , Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Cisplatino/uso terapêutico , Portadores de Fármacos/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Exossomos/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos , MicroRNAs/agonistas , MicroRNAs/isolamento & purificação , MicroRNAs/metabolismo , Nanopartículas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Braz J Med Biol Res ; 52(5): e8265, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31116313

RESUMO

We determined the effects of enhanced recovery after surgery (ERAS) in patients undergoing radical surgery for gastric carcinoma. Sixty patients undergoing radical gastrectomy for gastric carcinoma in Lishui Hospital between March and October 2016 were randomized to receive either ERAS (30 patients) or conventional care (30 patients, controls). Clinical, economic, and laboratory indices were analyzed. ERAS patients showed faster recovery and shorter postoperative hospital stays than the controls (P<0.05). Some clinical indices (i.e., time to first flatus and defecation, time to removal of drainage tubes, time to resumption of oral feeding, time to postoperative mobilization, and postoperative complications) were significantly better in ERAS patients than in controls. Duration of postoperative infusion was lower in ERAS patients than in controls (P<0.05). In ERAS patients, serum albumin and prealbumin were higher on postoperative day 7, C-reactive protein was lower on postoperative days 3 and 7, and neutrophil count was lower on postoperative day 3 compared to the values in controls (P<0.05 for all). IgM levels were higher in ERAS patients on postoperative days 3 and 7 (P<0.05), while IgG levels were higher on postoperative day 3 (P<0.05). Total T lymphocytes were higher in ERAS patients on postoperative day 3, while helper T cells and CD4+/CD8+ ratio were higher on postoperative days 3 and 7 (P<0.05 for all). In gastric carcinoma patients, ERAS may reduce perioperative inflammation, improve immunity and postoperative nutrition, shorten hospitalization, and enhance rehabilitation.


Assuntos
Gastrectomia/reabilitação , Neoplasias Gástricas/cirurgia , Estudos de Casos e Controles , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento
14.
Int J Biol Sci ; 15(5): 1020-1029, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31182922

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) has unique microenvironment with extensive infiltration of fibroblasts, which are mainly derived from the resident pancreatic stellate cells (PaSCs). As activated PaSCs constitute a major contributor to pancreatic cancer progression, the mechanisms underlying their activation have been being intensively studied. Previous studies showed that Sequestosome-1 (sqstm1) can modulate the functional status of fibroblasts in cancer. Here, we further delineated the role of sqstm1 in PaSCs. The analysis of PDAC patient samples revealed reduction of sqstm1 expression in activated PaSCs in both mRNA and protein level. Downregulated sqstm1 via shRNA in PaSCs led to an inflammatory and senescent phenotype with increased IL8, CXCL1, and CXCL2 expression. Further analysis demonstrated that increased intracellular reactive oxygen species level contributed to the senescence in sqstm1-downregulated PaSCs. This was mediated via impaired NRF2 activity since reduced sqstm1 resulted in accumulation of KEAP1. Meanwhile, we found that sqstm1 degradation caused by enhanced autophagy was not associated with transformation of senescent phenotype. At last, the data revealed that sqstm1-downregulated PaSCs promoted pancreatic tumor cell growth, invasion, and macrophage phenotype transformation. Collectively, the current study indicated that sqstm1 controlled transformation of senescent phenotype of PaSCs, which in turn is pro-tumorigenic.


Assuntos
Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Células Estreladas do Pâncreas/metabolismo , Células Estreladas do Pâncreas/patologia , Animais , Linhagem Celular Tumoral , Quimiocina CXCL1/metabolismo , Quimiocina CXCL2/metabolismo , Feminino , Imunofluorescência , Humanos , Immunoblotting , Imuno-Histoquímica , Interleucina-8/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Proteína Sequestossoma-1/metabolismo
15.
Oncotarget ; 8(67): 111623-111630, 2017 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-29340079

RESUMO

BACKGROUND: Angiogenesis plays a critical role in tumor growth and metastasis. Angiogenic factor with G patch and FHA domains 1 (AGGF1) has been recently identified as a novel initiator of angiogenesis. However, the function and the prognostic values of AGGF1 in hepatocellular carcinoma remain poorly understood. Our aim is to provide more information to assist design the angiogenesis therapy that targets AGGF1 in HCC. RESULTS: AGGF1-positive frequency in HCC tissues was significantly higher than in peritumor tissues. The high expression of AGGF1 expression in HCC tissue was well associated with the increased expression of VEGF and the high microvessel density (MVD). AGGF1 expression predicts a poor prognosis and AGGF1 was an independent prognostic factor for DFS. METHODS: The expression levels of AGGF1, vascular endothelial growth factor (VEGF) and microvessel density (MVD) were identified by immunohistochemistry in 79 HCC tumor tissues and 24 corresponding peritumor tissues. The expression level of AGGF1 and MVD were quantified by counting the positively stained endothelial cells in the HCC and the peritumor tissue on the immunohistochemically stained tissue slides. The prognostic value of AGGF1 was evaluated by survival analysis. CONCLUSIONS: Our study shows that AGGF1 is identified as the independent prognostic factor for the disease-free survival (DFS) of patients after the surgical resection. contribute to tumor angiogenesis in HCC, which indicates that AGGF1 may be a new potential therapeutic target for anti-angiogenesis treatment for patients with HCC.

16.
Am J Transl Res ; 9(5): 2608-2617, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28560008

RESUMO

Hypoxia is common in solid tumors and results in the activation of hypoxia-response genes. Hypoxia-inducible factor-1α (HIF-1α) is thought to reflect major cellular adaptation to hypoxia and contributes to chemoresistance in various tumors including hepatocellular carcinoma (HCC). N1-guanyl-1,7-diaminoheptane (GC7) is an inhibitor which suppresses the active eukaryotic translation initiation factor 5A-2 (eIF5A2), preventing epithelial-mesenchymal transition (EMT) in chemoresistance. In this study, we investigated the role of GC7 in the therapeutic effect of doxorubicin in hypoxia in HCC. We utilized four types of HCC cell line (Huh7, Hep3B, SNU387 and SNU449) in this study. Western blot and immunofluorescence were used to detect expression of epithelial/mesenchymal markers for EMT evaluation and HIF-1α was knocked down using HIF-1α-siRNA. Hypoxia-induced EMT contributed to doxorubicin chemoresistance in HCC cells. Low concentrations of GC7 sensitized Huh7 and Hep3B to doxorubicin by reversing EMT. Knockdown of HIF-1α attenuated hypoxia-induced EMT and abolished the unique feature of GC7. GC7 enhanced sensitivity to doxorubicin in HCC by reversing hypoxia-induced EMT via the HIF-1α-mediated signaling pathway. We suggest a new method of enhancing cytotoxicity of chemotherapy and improving the long-term survival rate in HCC.

17.
Braz. j. med. biol. res ; 54(4): e10273, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1153542

RESUMO

Vascular invasion and systemic immune-inflammation index (SII) are risk factors for the prognosis of patients with hepatocellular carcinoma. At present, the correlation between the two is not clear. This meta-analysis explored the relationship between preoperative SII and vascular invasion in patients with hepatocellular carcinoma. According to the search formula, the Pubmed, Embase, Cochrane, Web of Science, and CNKI databases were searched for the relevant research until March 2020. After the quality evaluation of the included literature, the odds ratio (OR) and its corresponding 95% confidence interval (CI) were used as the effect measure. Stata 15. 0 software was used for statistical analysis. The meta-analysis eventually included seven retrospective cohort studies of 3583 patients with hepatocellular carcinoma. The results showed that the choice of SII cut-off value affects SII's efficiency in predicting the risk of vascular invasion. In the cohort of studies with appropriate SII cut-off value, the high SII preoperative group had a higher risk of vascular invasion (OR=2.62; 95%CI: 2.07-3.32; P=0.000) and microvascular invasion (OR=1.82; 95%CI: 1.01-3.25; P=0.045) than the low SII group. The tumor diameter (OR=2.88; 95%CI: 1.73-4. 80; P=0.000) of the high SII group was larger than that of the low SII group. There was no publication bias in this study (Begg's test, P=0.368). As a routine, cheap, and easily available index, SII can provide a certain reference value for clinicians to evaluate vascular invasion before operation.


Assuntos
Humanos , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos , Fatores de Risco , Inflamação
18.
Exp Ther Med ; 11(5): 1809-1811, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27168808

RESUMO

Amyloidosis is a systemic disease caused by the accumulation of extracellular protein into amyloid deposits. Due to the involvement of a variety of organs and tissues, the disease has no specific clinical features and a high rate of misdiagnosis. The present study describes one case of primary amyloidosis, as confirmed by biopsies of rectal and renal tissues using Congo red staining, demonstrating that abdominal distension and diarrhea were the main symptoms of disease. The current case is also discussed within the context of a review of the associated literature.

19.
Exp Ther Med ; 11(6): 2379-2384, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27284324

RESUMO

Sarcoidosis is a multisystemic disease of unknown origin characterized by the formation of non-caseating granulomas. Thoracic involvement is the most common presentation; however, sarcoidosis can involve almost any other organ. To the best of our knowledge there have been only 10 cases of splenic sarcoidosis reported in the English literature, with no reports of sarcoidosis of an accessory spleen. The present study reports a case of isolated sarcoidosis of an accessory spleen in the greater omentum, which was identified postoperatively in a 44-year-old female. Chest X-ray results were normal. Gastric endoscopy demonstrated an ulcer in the antrum, which was confirmed to be a signet-ring cell carcinoma via biopsy. Computed tomography of the abdomen revealed mild thickening of the posterior antrum, and a mass in the inferior pole of the left kidney. Intraoperatively, no masses were detected in the liver and spleen. Moreover, no enlarged lymph nodes were detected in the abdominal cavity, pelvic cavity, mesenteric and para-aorta. Following a radical distal gastrectomy and left radical nephrectomy, postoperative pathology demonstrated signet-ring cell carcinoma in the antrum, left renal clear cell cancer and a red lesion measuring 0.5×0.5 cm in the greater omentum, which was similar to the spleen in the splenic cavity and was regarded as an accessory spleen. Following exclusion of fungi and acid-fast bacilli as causative agents, sarcoidosis of the accessory spleen in the greater omentum was confirmed. The patient recovered uneventfully and was discharged on day 8 postoperation. The patient remained alive after two-year follow-up without sarcoidosis and malignant tumor recurrence. The present case demonstrated that, intraoperatively, comprehensive exploration should be conducted to exclude the accessory spleen, which may also suffer from sarcoidosis.

20.
Exp Ther Med ; 11(4): 1265-1270, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27073434

RESUMO

Gastric bronchogenic cysts are rare lesions, first described in 1956, with only 34 cases reported in the literature to date. The present study described a case of bronchogenic cyst of the stomach in a 17-year-old female who presented with periodic epigastric pain. In addition, the study analyzed the existing literature on these lesions. Gastric bronchogenic cysts are more common in females (female:male ratio, 21:14) and the median age of their development is 43 years. In total, 48.57% of the 34 previously reported cases were identified incidentally, and the remainder presented mainly with epigastric pain. Cyst sizes varied between 1.7 and 15 cm. In 3 cases, preoperative diagnosis was performed using needle biopsy, whereas several studies were initially misdiagnosed as stromal tumors. In 85% of the cases (31/35), cyst resection was performed, with laparoscopy used in 4 of the cases. The findings of the present study and literature review suggested that bronchogenic cysts of the stomach are rare, and surgical resection is warranted to treat symptoms and prevent malignant transformation.

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