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Background & Aims: The steatotic grafts have been applied in liver transplantation frequently owing to the high incidence of non-alcoholic fatty liver disease. However, fatty livers are vulnerable to graft injury. Myeloid-derived suppressor cell (MDSC) recruitment during liver graft injury promotes tumour recurrence. Lipid metabolism exerts the immunological influence on MDSCs in tumour progression. Here, we aimed to explore the role and mechanism of inflammasome activation in MDSCs induced by lipid metabolism during fatty liver graft injury and the subsequent effects on tumour recurrence. Methods: MDSC populations and nucleotide-binding oligomerisation domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome levels were investigated in a clinical cohort and a rat liver transplantation model. The mechanism of NLRP3 activation by specific fatty acids was explored in mouse hepatic ischaemia/reperfusion injury (IRI) with tumour recurrence model and in vitro studies. Results: MDSC populations and NLRP3 levels were increased with higher tumour recurrent rate in patients using steatotic grafts. NLRP3 was upregulated in MDSCs with lipid accumulation post mouse fatty liver IRI. Mechanistically, arachidonic acid was discovered to activate NLRP3 inflammasome in MDSCs through fatty acid transport protein 2 (FATP2), which was identified by screening lipid uptake receptors. The mitochondrial dysfunction with enhanced reactive oxygen species bridged arachidonic acid uptake and NLRP3 activation in MDSCs, which subsequently stimulated CD4+ T cells producing more IL-17 in fatty liver IRI. Blockade of FATP2 inhibited NLRP3 activation in MDSCs, IL-17 production in CD4+ T cells, and the tumour recurrence post fatty liver IRI. Conclusions: During fatty liver graft injury, arachidonic acid activated NLRP3 inflammasome in MDSCs through FATP2, which subsequently stimulated CD4+ T cells producing IL-17 to promote tumour recurrence post transplantation. Impact and implications: The high incidence of non-alcoholic fatty liver disease resulted in the frequent application of steatotic donors in liver transplantation. Our data showed that the patients who underwent liver transplantation using fatty grafts experienced higher tumour recurrence. We found that arachidonic acid activated NLRP3 inflammasome in MDSCs through FATP2 during fatty liver graft injury, which led to more IL-17 secretion of CD4+ T cells and promoted tumour recurrence post transplantation. The inflammasome activation by aberrant fatty acid metabolism in MDSCs bridged the acute-phase fatty liver graft injury and liver tumour recurrence.
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The robotic liver resection (RLR) has been increasingly applied in recent years and its benefits shown in some aspects owing to the technical advancement of robotic surgical system, however, controversies still exist. Based on the foundation of the previous consensus statement, this new consensus document aimed to update clinical recommendations and provide guidance to improve the outcomes of RLR clinical practice. The guideline steering group and guideline expert group were formed by 29 international experts of liver surgery and evidence-based medicine (EBM). Relevant literature was reviewed and analyzed by the evidence evaluation group. According to the WHO Handbook for Guideline Development, the Guidance Principles of Development and Amendment of the Guidelines for Clinical Diagnosis and Treatment in China 2022, a total of 14 recommendations were generated. Among them were 8 recommendations formulated by the GRADE method, and the remaining 6 recommendations were formulated based on literature review and experts' opinion due to insufficient EBM results. This international experts consensus guideline offered guidance for the safe and effective clinical practice and the research direction of RLR in future.
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Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Hepatectomia/efeitos adversos , China , Consenso , Fígado/cirurgiaRESUMO
Numerous studies reported a small subpopulation of TCRαß+CD4-CD8- (double-negative) T cells that exert regulatory functions in the peripheral lymphocyte population. However, the origin of these double-negative T (DNT) cells is controversial. Some researchers reported that DNT cells originated from the thymus, and others argued that these cells are derived from peripheral immune induction. We report a possible mechanism for the induction of nonregulatory CD4+ T cells to become regulatory double-negative T (iDNT) cells in vitro. We found that immature bone marrow dendritic cells (CD86+MHC-II- DCs), rather than mature DCs (CD86+MHC-II+), induced high levels of iDNT cells. The addition of an anti-MHC-II antibody to the CD86+MHC-II+ DC group significantly increased induction. These iDNT cells promoted B cell apoptosis and inhibited B cell proliferation and plasma cell formation. A subgroup of iDNT cells expressed NKG2D. Compared to NKG2D- iDNT cells, NKG2D+ iDNT cells released more granzyme B to enhance B cell regulation. This enhancement may function via NKG2D ligands expressed on B cells following lipopolysaccharide stimulation. These results demonstrate that MHC-II impedes induction, and iDNT cells may be MHC independent. NKG2D expression on iDNT cells enhanced the regulatory function of these cells. Our findings elucidate one possible mechanism of the induction of peripheral immune tolerance and provide a potential treatment for chronic allograft rejection in the future.
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Linfócitos B/imunologia , Antígenos CD4/imunologia , Antígenos CD8/imunologia , Subfamília K de Receptores Semelhantes a Lectina de Células NK/imunologia , Linfócitos T/imunologia , Animais , Antígeno B7-2/genética , Antígeno B7-2/imunologia , Antígeno B7-2/metabolismo , Antígenos CD4/genética , Antígenos CD4/metabolismo , Antígenos CD8/genética , Antígenos CD8/metabolismo , Células Cultivadas , Citocinas/genética , Citocinas/imunologia , Citocinas/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Expressão Gênica/imunologia , Granzimas/genética , Granzimas/imunologia , Granzimas/metabolismo , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Antígenos de Histocompatibilidade Classe II/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Imunológicos , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Linfócitos T/metabolismoRESUMO
OBJECTIVE: To observe the effects of dendritic cells (DC) in donor C57BL/6 (H-2b) micetransfected with recombinant adenovirus vector Ad-PD-L1 on proliferation and activation of lymphocytes in recipient DBA/2 (H-2d) mice. METHODS: The pSport 1-mSD274 plasmid containing the full-length PD-L1 cDNA of the mouse was digested and subcloned to the shuttle plasmid pShuttle-GFP-CMV(-), and then the adenovirus skeleton plasmid pAdxsi-GFP-CMV-PD-L1 was constructed by enzymolysis and ligation, transformed into DH5α sensitive bacteria, and screened for positive clones. After enzyme digestion, sequencing, and identification, 293 cells were transfected with liposome after linearization for packaging and amplification, and the virus was purified by cesium chloride density gradient centrifugation. DC of donor C57BL/6 mice were isolated, cultured, and divided into the following 3 groups: group A, adenovirus vector Ad-PD-L1 transfection group; group B, empty vector transfection group; and group C, control group. Western blot was used to detect the expression of PD-L1 in each group of cells after transfection. Isolate lymphocytes from recipient DBA/2 mice were labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE) and mixed with DC of donor C57BL/6 mice with lymphocytes of recipient DBA/2 mice. Flow cytometry was performed to observe the proliferation of lymphocytes. RESULTS: Digestion and sequencing confirmed that the recombinant adenovirus vector Ad-PD-L1 containing PD-L1 was successfully constructed. After transfection with DC of donor C57BL/6 mice, the expression of PD-L1 increased by 37% (P < .05), and the PD-L1 transfected DC and recipient DBA/2. Mouse lymphocytes were cocultured. Compared with the control group, the increased expression of PD-L1 significantly inhibited the proliferation and activation of lymphocytes. The lymphocyte proliferation of DBA/2 mice decreased by 41% (P < .01). CONCLUSION: The recombinant adenovirus vector Ad-PD-L1 containing the mouse PD-L1 gene was successfully constructed. After transfection with dendritic cells of donor C57BL/6 mice, PD-1/PD-L1 inhibited lymphocytes proliferation and activation of recipient DBA/2 mice through costimulatory pathway.
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Antígeno B7-H1/imunologia , Células Dendríticas/imunologia , Rejeição de Enxerto/imunologia , Tolerância Imunológica/imunologia , Ativação Linfocitária/imunologia , Adenoviridae , Animais , Antígeno B7-H1/genética , Técnicas de Cocultura , Vetores Genéticos , Rejeição de Enxerto/prevenção & controle , Linfócitos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Transfecção/métodos , Regulação para CimaRESUMO
BACKGROUND: Anillin (ANLN) is required for tumor growth. It has been proven that knockdown of ANLN effectively reduces the occurrence of hepatocellular carcinoma (HCC) in transgenic mice. However, the functional role of ANLN in HCC patients remains to be elucidated. METHODS: Both microarray and TCGA project were used for the analyses of ANLN expression and regulation in HCC. The effect of ANLN on proliferation and cell cycle was detected by CCK-8, colony formation assay and flow cytometry. ANLN expression was measured by immunohistochemistry. Correlation between ANLN expression and clinicopathological features was assessed by Pearson Chi-square test and 5-year overall survival after liver resection was evaluated by Kaplan-Meier method. RESULTS: Increased copy number, decreased methylation levels in the CpG island and upregulated histone hypermethylation of ANLN were found in HCC. Knockdown of ANLN inhibited proliferation and induced G2/M phase arrest in SMMC-7721 cells. ANLN was mainly expressed in the nucleus and showed significantly higher expression levels in cancerous tissues than those in paired adjacent tissues. Moreover, nuclear ANLN expression levels in HCC metastases were significantly higher than those in primary HCC. The results of Cox proportional hazards regression model suggested that ANLN nuclear expression in HCC was an independent risk factor for poor 5-year overall survival of patients after liver resection. CONCLUSIONS: ANLN is a potential therapeutic target for HCC. Patients with nuclear ANLN overexpression in HCC tissue may need adjuvant therapy after liver resection.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/cirurgia , Linhagem Celular Tumoral , Proliferação de Células , Proteínas Contráteis , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirurgia , Camundongos , PrognósticoRESUMO
Objective Hilar cholangiocarcinoma (HC) is invariably fatal without surgical resection. The primary aim of the current study was to determine the safety of variable surgical resections for patient with HC and their survival after surgical resection. In addition, prognostic factor for the overall survival was also evaluated. Methods The study included 59 consecutive patients who were newly diagnosed with HC and underwent surgical resections with curative intend between February 2009 and February 2017. Patients were followed up at 3-6 months intervals after hospital discharge. Postoperative complications and overall survival were determined. Associations of clinicopathologic and surgeon-related factors with overall survival were evaluated through univariate analysis and Cox regression analysis. Results Of patients with Bismuth and Corlette (B & C) type â ¢ (n=19) and â £ (n=25) HC lesions, 33 (55.9%) were treated with hilar resection combined with major liver resection (MLR), while the other 11 patients with type â ¢ and â £, and those with type â (n=8) and â ¡ (n=7) HC lesions were treated with hilar resection. The overall surgical mortality was 5.1% and surgical morbidity was 35.6%. There was no statistical difference in the mortality between MLR group and hilar resection group (6.1% vs. 3.8%; X2=0.703, P=0.145). The median follow-up period was 18 months (range, 1-94 months). The 1-, 3-, 5-year survival rate was 59.3%, 36.5%, and 17.7%, respectively. The overall survival after resections was 18 months. In HC patients with B & C type â ¢ and â £ lesions, the median survival was 23 months for hilar resection with MLR and 8 months for hilar resection alone; the 1-, 3-, 5-year cumulative survival rate was 63.9%, 23.3%, and 15.5%, respectively for hilar resection with MLR, and 11.1%, 0, and 0, respectively for hilar resection alone, with significant differene observed (HR, 9.902; 95% CI, 2.636-19.571, P=0.001). Four factors were independently associated with overall survival: preoperative serum Ca19-9 (HR, 7.039; 95% CI, 2.803-17.678, P<0.001), histopathologic grade (HR, 4.964; 95% CI, 1.046-23.552, P=0.044), surgical margins (P=0.031), and AJCC staging (P=0.015). Conclusions R0 resection is efficacious in surgical treatment of HC. MLR in combination with caudate lobe resection may increase the chance of R0 resection and improve survival of HC patients with B & C type â ¢ and â £ lesions. Preoperatively prepared for biliary drainage may ensure the safety of MLR in most HC patients. Novel adjuvant therapies are needed to improve the survival of HC patients with poor prognostic factors.
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Colangiocarcinoma/terapia , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de SobrevidaAssuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Anilidas/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Compostos de Fenilureia/uso terapêutico , Prognóstico , Piridinas/uso terapêutico , Quinolinas/uso terapêutico , Medição de Risco , Sorafenibe/uso terapêutico , Análise de Sobrevida , Resultado do TratamentoRESUMO
AIMS: To investigate molecular alteration and expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in hepatocellular carcinoma (HCC), and to evaluate the correlation between PTEN and cancer stem cell (CSC) markers and the prognostic value of these markers. METHODS: We evaluated changes of PTEN and CSC markers (CD133, epithelial cell adhesion molecule (EpCAM) and CK19) in 183 resection specimens by immunohistochemistry (IHC) and detected PTEN and phosphoinositide-3-kinase catalytic-alpha (PIK3CA) gene by fluorescence in situ hybridisation (FISH) in some specimens. RESULTS: PTEN and CD133, EpCAM and CK19 in 183 resection specimens were studied by IHC, and PTEN and PIK3CA genes were detected by FISH. PTEN expression was reduced in 92 HCC tissues (50.3%). There were 16 HCCs with PTEN deletion (51.6%). Comparison between PTEN IHC and FISH showed that the analysis was highly concordant (54/59, 91.5%). There were 19 HCCs with PIK3CA amplification. Deletion of PTEN was positively correlated with amplification of PIK3CA. Positive expression of CD133, EpCAM and CK19 was correlated with steatosis, moderate to poor differentiation, and so on. Reduction of PTEN expression was negatively correlated with positive expression of CD133, EpCAM and CK19. Reduced expression of PTEN (p=0.028) was an independent predictor for HCC recurrence and overall survival in HCC. PTEN-/CD133+ group had shorter OS and RFS time. CONCLUSIONS: PTEN plays a key role in hepatocarcinogenesis and reduction of PTEN expression is related to increased expression of CD133, EpCAM and CK19, which is a useful tool to evaluate HCC prognosis and recurrence.
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Biomarcadores Tumorais , Carcinoma Hepatocelular , Amplificação de Genes , Neoplasias Hepáticas , Células-Tronco Neoplásicas , PTEN Fosfo-Hidrolase , Antígeno AC133/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Classe I de Fosfatidilinositol 3-Quinases/genética , Regulação para Baixo , Molécula de Adesão da Célula Epitelial/análise , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Queratina-19/análise , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Células-Tronco Neoplásicas/enzimologia , Células-Tronco Neoplásicas/patologia , PTEN Fosfo-Hidrolase/análise , PTEN Fosfo-Hidrolase/genética , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
The robotic surgical system has been applied in liver surgery. However, controversies concerns exist regarding a variety of factors including the safety, feasibility, efficacy, and cost-effectiveness of robotic surgery. To promote the development of robotic hepatectomy, this study aimed to evaluate the current status of robotic hepatectomy and provide sixty experts' consensus and recommendations to promote its development. Based on the World Health Organization Handbook for Guideline Development, a Consensus Steering Group and a Consensus Development Group were established to determine the topics, prepare evidence-based documents, and generate recommendations. The GRADE Grid method and Delphi vote were used to formulate the recommendations. A total of 22 topics were prepared analyzed and widely discussed during the 4 meetings. Based on the published articles and expert panel opinion, 7 recommendations were generated by the GRADE method using an evidence-based method, which focused on the safety, feasibility, indication, techniques and cost-effectiveness of hepatectomy. Given that the current evidences were low to very low as evaluated by the GRADE method, further randomized-controlled trials are needed in the future to validate these recommendations.
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Consenso , Hepatectomia/normas , Laparoscopia/normas , Hepatopatias/cirurgia , Procedimentos Cirúrgicos Robóticos/normas , Técnica Delphi , Gastroenterologia/métodos , Gastroenterologia/normas , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Cellular senescence-inhibited gene (CSIG) strongly prolongs the progression of replicative senescence. However, roles and mechanisms of CSIG in tumor progression have not been studied widely. METHODS: Roles of CSIG in migration and proliferation of SMMC7721 and Huh7 cells were analyzed by transwell or cell viability assays, respectively. Tumorigenicity assays were used to study whether CSIG knockdown could affect SMMC7721 proliferation in vivo. Next, Western blotting and RT-PCR were preformed to evaluate the effects of CSIG on P-ERK cascade and epithelial mesenchymal transformation markers. Then, the location and expression of CSIG protein was detected by immunofluorescence and Western blotting, respectively. Finally, the Cancer Genome Atlas dataset was used to analyze CSIG mRNA levels in hepatocellular carcinoma (HCC) and adjacent non-tumor tissues. RESULTS: In this study, we found that CSIG overexpression promoted SMMC7721 cell migration, and CSIG knockdown suppressed tumorigenicity of SMMC7721 cells. In contrast to expectation, CSIG up-regulation could significantly inhibit Huh7 cell growth and migration. CSIG could promote P-ERK activation and levels of mesenchymal-like markers in SMMC7721 cells, whereas CSIG suppressed P-ERK activation and levels of mesenchymal-like markers in Huh7 cells. CSIG protein was located in nucleoli as well as nucleoplasm of SMMC7721 cells, whereas CSIG protein was mainly expressed in the nucleoli rather than nucleoplasm of Huh7 cells. Finally, due to individual differences, raised or down-regulated trends of CSIG in HCC as compared with adjacent non-tumor tissues are different among various patient populations. CONCLUSION: In summary, these results indicate that CSIG might play different roles in SMMC7721 and Huh7 cells through regulating P-ERK pathway and mesenchymal-like markers. The differential distribution of CSIG might be an important factor that causes its different functions in SMMC7721 and Huh7 cells. CSIG might play different roles in various patient populations.
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BACKGROUND: This study aims to compare the efficacy and safety of treatment after transarterial chemoembolization(TACE) with best supportive care (BSC) in patients with hepatocellular carcinoma (HCC) with PVTT. METHODS: This retrospective study was conducted on 1,040 patients with HCC with PVTT who were treated either with TACE (nâ¯=â¯675) or BSC (nâ¯=â¯365). BSC did not include sorafenib. The two groups of patients were compared with or without propensity score matching. A subgroup analysis was subsequently performed by stratifying patients according to the stages of PVTT in the Cheng's PVTT classification. RESULTS: In PVTTtypes I-III, TACE was associated with significantly better overall survival (OS) thanBSC (Pâ¯<â¯0.05). Within each type of PVTT for patients who received TACE or BSC, OS was significantly worse in patients with type IVPVTT than in any of the other three types of PVTT (all Pâ¯<â¯0.05). TACE was associated with better long-termOS than BSC after propensity score matching or on stratification by the PVTT types. CONCLUSION: TACE was associated with better OS than BSC in HCC patients with PVTT types I-III but not type IV. Patients with type IV PVTT showed the worst prognosis, regardless of whether TACE or BSC was used.
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Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Células Neoplásicas Circulantes/patologia , Veia Porta/patologia , Conduta Expectante/métodos , Adulto , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Quimioterapia do Câncer por Perfusão Regional/métodos , China , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Metástase Neoplásica/patologia , Estadiamento de Neoplasias , Veia Porta/efeitos dos fármacos , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
AIMS: To evaluate stromal histopathological features and immunostaining expression for differential diagnosis of low- and high-grade dysplastic nodules (HGDN) to early and progressed hepatocellular carcinomas (eHCC, pHCC). MATERIALS: We evaluated sinusoid capillarisation (SC), solitary artery (SA), ductular reaction (DR), stromal invasion and expression of six biomarkers (GPC3, HSP70, GS, CD34, CK19, EpCAM) in a series of 97 cases. RESULTS: Stromal morphological changes, including SC, DR and SA, exhibited significant differences in differential diagnosis. In one indicator, SC had the best sensitivity (90.00%) and accuracy (85.42%), and SA had the best specificity at 88.89 %. In combinations, SC +and SA +were favourable and optimal. The immunoreactivity of GPC3, HSP70 and GS increased significantly in line with the stepwise progression of hepatocarcinogenesis. CONCLUSIONS: Stromal histopathology features are useful for diagnosing HGDN, eHCC and small HCC. The immunostaining panel of GPC3, HSP70 and GS can also be supplementary.
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Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/química , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/química , Neoplasias Hepáticas/patologia , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Células Estromais/química , Células Estromais/patologia , Adulto , Idoso , Carcinoma Hepatocelular/cirurgia , Feminino , Glutamato-Amônia Ligase/análise , Glipicanas/análise , Proteínas de Choque Térmico HSP70/análise , Humanos , Imuno-Histoquímica , Imunofenotipagem/métodos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Fenótipo , Lesões Pré-Cancerosas/cirurgia , Valor Preditivo dos Testes , Estudos RetrospectivosRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) (about 85-90% of primary liver cancer) is particularly prevalent in China because of the high prevalence of chronic hepatitis B infection. HCC is the fourth most common malignancy and the third leading cause of tumor-related deaths in China. It poses a significant threat to the life and health of Chinese people. SUMMARY: This guideline presents official recommendations of the National Health and Family Planning Commission of the People's Republic of China on the surveillance, diagnosis, staging, and treatment of HCC occurring in China. The guideline was written by more than 50 experts in the field of HCC in China (including liver surgeons, medical oncologists, hepatologists, interventional radiologists, and diagnostic radiologists) on the basis of recent evidence and expert opinions, balance of benefits and harms, cost-benefit strategies, and other clinical considerations. KEY MESSAGES: The guideline presents the Chinese staging system, and recommendations regarding patients with HCC in China to ensure optimum patient outcomes.
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OBJECTIVE: The aim of the study was to investigate the biochemical and functional properties of a rat acellular pancreatic bioscaffolds (APBs). METHODS: Fresh pancreata from 10 rats were soaked and perfused through portal veins using Easy-Load Digital Drive peristaltic pumps. The histological structure, extracellular matrix composition, and the DNA content of the APBs were evaluated. Biocompatibility studies had also been performed. The proliferation and differentiation of AR42J pancreatic acinar cells were assessed. RESULTS: The pancreatic tissue became translucent after decellularization. There were no visible vascular endothelial cells, cellular components, or cracked cellular debris. The extracellular matrix components were not decreased after decellularization (P > 0.05); however, the DNA content was decreased significantly (P < 0.05). The subcutaneous implantation sites showed low immunological response and low cytotoxicity around the APB. The proliferation rate was higher and the apoptosis rate was lower when AR42J cells were cultured on APB (P < 0.05). The gene expression and the protein expression were higher for the APB group (P < 0.001). CONCLUSIONS: Our findings support the biological utility of whole pancreas APBs as biomaterial scaffolds, which provides an improved approach for regenerative medicine.
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Materiais Biocompatíveis/metabolismo , Matriz Extracelular/metabolismo , Pâncreas/metabolismo , Alicerces Teciduais , Animais , Apoptose/efeitos dos fármacos , Materiais Biocompatíveis/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Expressão Gênica , Masculino , Pâncreas/citologia , Proteoma/genética , Proteoma/metabolismo , Ratos Sprague-Dawley , Engenharia Tecidual/métodosRESUMO
BACKGROUND: The negative effects of hepatic inflow occlusion (HIO) on postoperative liver function of patients with hepatocellular carcinoma (HCC) after liver resection have been reported. Nevertheless, whether or not HIO could influence the long-term outcomes remains unclear. METHODS: A total of 396 patients were included in this study and divided into without occlusion (WO) group (N.=112) and HIO group (N.=284). Aiming to minimize influence of selection bias and confounding variables, we used propensity score matching (PSM) of a 0.2 caliper to balance baseline variables. Overall survival (OS) and disease-free survival (DFS) were compared by the Kaplan-Meier method. Independent prognostic factors for OS and DFS were identified by Cox proportional hazards regression model. RESULTS: PSM were used to generate 101 pairs of patients. After PSM, OS was not significantly different between WO and HIO group (1-year: 86.1% vs. 83.2%; 3-year: 61.4% vs. 61.4%; 5-year: 45.5% vs. 39.6%; P = 0.626). Similar results of DFS were obtained between WO and HIO group (1-year: 54.5% vs. 53.5%; 3-year: 30.5% vs. 28.7%; 5-year: 14.2% vs. 14.9%; P=0.873). WO and HIO groups did not differ in 30-day, 90-day mortality and rate of postoperative complications (all P>0.05). CONCLUSIONS: Our data indicates that HIO might not negatively affect the OS and DFS of HCC patients undergoing liver resection and is likely to be a safe and viable option for intraoperative blood loss control.
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Perda Sanguínea Cirúrgica/prevenção & controle , Carcinoma Hepatocelular/cirurgia , Hemostasia Cirúrgica/métodos , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Adulto , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Our recent study has shown that αA-crystallin appears to act as a tumor suppressor in pancreas. Here, we analyzed expression patterns of αA-crystallin in the pancreatic tumor tissue and the neighbor normal tissue from 74 pancreatic cancer patients and also pancreatic cancer cell lines. Immunocytochemistry revealed that αA-crystallin was highly expressed in the normal tissue from 56 patients, but barely detectable in the pancreatic tumor tissue. Moreover, a low level of αA-crystallin predicts poor prognosis for patients with pancreatic duct adenocarcinoma (PDAC). In the 12 pancreatic cell lines analyzed, except for Capan-1 and Miapaca-2 where the level of αA-crystallin was about 80% and 65% of that in the control cell line, HPNE, the remaining pancreatic cancer cells have much lower αA-crystallin levels. Overexpression of αA-crystallin in MiaPaca-1 cells lacking endogenous αA-crystallin significantly decreased its tumorigenicity ability as shown in the colony formation and wound healing assays. In contrast, knockdown of αA-crystallin in the Capan-1 cells significantly increased its tumorigenicity ability as demonstrated in the above assays. Together, our results further demonstrate that αA-crystallin negatively regulates pancreatic tumorigenesis and appears to be a prognosis biomarker for PDAC.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/patologia , Transformação Celular Neoplásica/patologia , Neoplasias Pancreáticas/patologia , Cadeia A de alfa-Cristalina/metabolismo , Idoso , Apoptose , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/cirurgia , Proliferação de Células , Transformação Celular Neoplásica/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/cirurgia , Prognóstico , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
In this study, we investigated the value of measurement of the chemokine CXCL1 in clinical management of hepatocellular carcinoma (HCC) and its possible role in the molecular pathogenesis of HCC. High CXCL1 expression predicted recurrence in HCC patients and promoted tumor progression in both in vivo and in vitro experimental systems. Overexpression of CXCL1 increased mitochondrial metabolism and activated the epithelial-to-mesenchymal transition (EMT). Using computational analysis we identified the microRNA miR-200a as a putative post-transcriptional regulator of CXCL1. We found that levels of miR-200a were inversely correlated with CXCL1 expression in HCC patient tissue samples by northern blot and qRT-PCR. Furthermore, CXCL1 was identified as a direct target which was bound and inhibited by miR- 200a. These findings provide new insights into the role of CXCL1 in HCC and its post-transcriptional regulation and suggest it may be a prognostic indicator for poor outcomes and a potential target for therapy.
Assuntos
Carcinoma Hepatocelular/patologia , Quimiocina CXCL1/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Carcinoma Hepatocelular/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , Neoplasias Hepáticas/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: Portal vein thrombosis (PVT) is a common complication in patients with liver cirrhosis. During liver transplantation (LT), PVT may complicate the procedure and lead to a poor prognosis. The aim of this study is to evaluate patients enrolled in the China Liver Transplant Registry, to understand the influence of PVT to the LT recipients. METHODS: We collected data from patients who underwent LT and were entered into the China Liver Transplant Registry. All data of medical records and follow-up were retrospectively reviewed. The preoperative condition, duration of surgery, intraoperative blood loss, postoperative early and late PVT, and survival rates were compared between patients with PVT and those without PVT. Multivariate Cox analysis and survival analysis were used to determine the influence of PVT. RESULTS: A total of 20,524 cases were recruited into the study. In all, 1810 (8.82%) patients were diagnosed with preoperative PVT of various severities. All patients were followed up for an average of 30.25±33.25months (up to a maximum of 171.68months). Patients with PVT had a significantly longer operating time, more intraoperative blood loss and a higher rate of post-LT PVT (P<0.001). Multivariate Cox analysis showed that PVT did not reduce the recipients' survival rate (HR=0.89, 95% CI: 0.774-1.024, P=0.103). There was no significant difference in cumulative survival rate (P=0.059) between patients without PVT, and patients with PVT. CONCLUSIONS: PVT increases the difficulty of LT, but doesn't reduce the survival rate. Therefore, PVT is not an absolute contraindication for LT in experienced transplantation centers.