Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 931
Filtrar
1.
BMC Gastroenterol ; 21(1): 195, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33931011

RESUMO

BACKGROUND: Donor age is an important predictor for liver transplant recipients. Studies have not fully explored its impact on transplant outcomes in hepatocellular carcinoma (HCC) patients as well as its involvement in tumor recurrence. METHODS: HCC patients who received liver transplants during 2010-2017 from the Scientific Registry of Transplant Recipients database were included. The recipients were divided into four groups based on donor age: I (≤ 34 years), II (35-49 years), III (50-64 years), and IV (≥ 65 years). Transplant outcomes, including the overall survival (OS), tumor recurrence, and risks, were evaluated. RESULTS: A total of 13,276 HCC recipients were included in this study. Statistical significant differences were observed in OS among the four groups. The best 5-year survival was 76.0% in group I, followed by 73.5% in group II, 72.8% in group III, and 69.2% in group IV (P < 0.001). However, the liver-specific survival did not differ among these groups (P = 0.260). Donor age was found to be the independent predictor of OS after adjusting for other variables (P < 0.001, ref. group I; 1.087 (0.979-1.208) for group II, P = 0.119; 1.124 (1.015-1.246) for group III, P = 0.025; 1.395 (1.215-1.602) for group IV, P < 0.001). In subgroup analysis, OS was significantly different in recipients with hepatitis C virus (HCV), but there was no significant difference for recipients with hepatitis B virus (HBV), alcoholic liver diseases and nonalcoholic steatohepatitis (NASH). The post-transplant cumulative tumor recurrence rates were similar among the four groups (P = 0.382). CONCLUSIONS: Older donor age was associated with decreased OS but not liver-specific survival as well as post-transplant tumor recurrence in HCC recipients. Donor age also had different effects in patients with different underlying liver diseases.

2.
Signal Transduct Target Ther ; 6(1): 153, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33888679

RESUMO

The extracellular matrix (ECM) is one of the major components of tumors that plays multiple crucial roles, including mechanical support, modulation of the microenvironment, and a source of signaling molecules. The quantity and cross-linking status of ECM components are major factors determining tissue stiffness. During tumorigenesis, the interplay between cancer cells and the tumor microenvironment (TME) often results in the stiffness of the ECM, leading to aberrant mechanotransduction and further malignant transformation. Therefore, a comprehensive understanding of ECM dysregulation in the TME would contribute to the discovery of promising therapeutic targets for cancer treatment. Herein, we summarized the knowledge concerning the following: (1) major ECM constituents and their functions in both normal and malignant conditions; (2) the interplay between cancer cells and the ECM in the TME; (3) key receptors for mechanotransduction and their alteration during carcinogenesis; and (4) the current therapeutic strategies targeting aberrant ECM for cancer treatment.

3.
Eur J Surg Oncol ; 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33902956

RESUMO

BACKGROUND: The use of the immunosuppressive agent sirolimus (SRL) following liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) is controversial. Sirolimus is a typical mammalian target of rapamycin (mTOR) inhibitor, and tuberous sclerosis 1-tuberous sclerosis 2 complex (TSC1/TSC2) is an important negative effector in the mTOR pathway. In this study, we investigated the effect of SRL-based immunosuppression on the prognosis of LT recipients with HCC beyond the Milan criteria based on TSC1/2 expression and explored the effect of TSC1 on HCC in vitro and in vivo. METHODS: We retrospectively analyzed 120 HCC patients who underwent LT in our hospital between January 1, 2015 and December 30, 2018. All patients had HCC beyond the Milan criteria and were divided into the SRL group (n = 50) and non-SRL group (n = 70). TSC1/2 expression levels in paraffin-embedded tissues were determined by immunohistochemistry (IHC) and then analyzed as subgroups. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method. TSC1 expression was silenced in Huh-7 and Bel-7402 cell lines for further cell function experiments. RESULTS: 88.3% of patients were HBV LT recipients. The SRL group exhibited better DFS and OS compared to the non-SRL group (P = 0.02, P = 0.003). Subgroup (TSC1-based or TSC2-based) analyses revealed that patients with low TSC1 or TSC2 expression benefited from sirolimus (DFS: P = 0.046, OS: P = 0.006 for TSC1; DFS: P = 0.05, OS: P = 0.003 for TSC2) compared with patients with high expression. TSC1 knockdown in Huh-7 and Bel-7402 HCC cell lines activated the mTORC1 pathway and enhanced cell proliferation, migration and sensitivity to SRL in vitro and in vivo. CONCLUSION: TSC1/2 expression could be used to predict the prognosis of patients with HCC beyond the Milan criteria who underwent SRL-based immunosuppression following LT. TSC1 knockdown promoted HCC malignancy and enhanced sensitivity to SRL.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33726966

RESUMO

BACKGROUND: Acute kidney injury (AKI) is a common complication after liver transplantation (LT) and is an indicator of poor prognosis. The establishment of a more accurate preoperative prediction model of AKI could help to improve the prognosis of LT. Machine learning algorithms provide a potentially effective approach. METHODS: A total of 493 patients with donation after cardiac death LT (DCDLT) were enrolled. AKI was defined according to the clinical practice guidelines of kidney disease: improving global outcomes (KDIGO). The clinical data of patients with AKI (AKI group) and without AKI (non-AKI group) were compared. With logistic regression analysis as a conventional model, four predictive machine learning models were developed using the following algorithms: random forest, support vector machine, classical decision tree, and conditional inference tree. The predictive power of these models was then evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: The incidence of AKI was 35.7% (176/493) during the follow-up period. Compared with the non-AKI group, the AKI group showed a remarkably lower survival rate (P < 0.001). The random forest model demonstrated the highest prediction accuracy of 0.79 with AUC of 0.850 [95% confidence interval (CI): 0.794-0.905], which was significantly higher than the AUCs of the other machine learning algorithms and logistic regression models (P < 0.001). CONCLUSIONS: The random forest model based on machine learning algorithms for predicting AKI occurring after DCDLT demonstrated stronger predictive power than other models in our study. This suggests that machine learning methods may provide feasible tools for forecasting AKI after DCDLT.

5.
J Cell Mol Med ; 25(7): 3511-3523, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33713546

RESUMO

Hepatocellular carcinoma (HCC) is one of the most aggressive tumours with marked fibrosis. Mycophenolate mofetil (MMF) was well-established to have antitumour and anti-fibrotic properties. To overcome the poor bioavailability of MMF, this study constructed two MMF nanosystems, MMF-LA@DSPE-PEG and MMF-LA@PEG-PLA, by covalently conjugating linoleic acid (LA) to MMF and then loading the conjugate into polymer materials, PEG5k -PLA8k and DSPE- PEG2k , respectively. Hepatocellular carcinoma cell lines and C57BL/6 xenograft model were used to examine the anti-HCC efficacy of nanoparticles (NPs), whereas NIH-3T3 fibroblasts and highly-fibrotic HCC models were used to explore the anti-fibrotic efficacy. Administration of NPs dramatically inhibited the proliferation of HCC cells and fibroblasts in vitro. Animal experiments revealed that MMF-LA@DSPE-PEG achieved significantly higher anti-HCC efficacy than free MMF and MMF-LA@PEG-PLA both in C57BL/6 HCC model and highly-fibrotic HCC models. Immunohistochemistry further confirmed that MMF-LA@DSPE-PEG dramatically reduced cancer-associated fibroblast (CAF) density in tumours, as the expression levels of alpha-smooth muscle actin (α-SMA), fibroblast activation protein (FAP) and collagen IV were significantly downregulated. In addition, we found the presence of CAF strongly correlated with increased HCC recurrence risk after liver transplantation. MMF-LA@DSPE-PEG might act as a rational therapeutic strategy in treating HCC and preventing post-transplant HCC recurrence.

6.
Transplant Proc ; 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33775417

RESUMO

Liver transplantation (LT) for acute-on-chronic liver failure (ACLF) accompanied by acute necrotizing pancreatitis is still unclear. We have a reported case of LT for ACLF associated with acute necrotizing pancreatitis. The postoperative multiorgan dysfunction and secondary infection were successfully managed under close supervision. The patient was a 47-year-old man with chronic hepatitis B virus infection presented with ACLF and acute necrotizing pancreatitis. After receiving LT from a deceased donor, the patient's liver functioning rapidly reverted to a normal level, and the acute pancreatitis was simultaneously stabilized. However, the patient later developed multiorgan dysfunction secondary to multidrug resistant bacteria infection, which was treated successfully with repeated percutaneous drainage, sensitive antibiotics, continuous renal replacement therapy, microbial balance, and best supportive care. LT can be considered for ACLF associated with acute necrotic pancreatitis without absolute contraindication. Moreover, we recommend a close observation of possible postoperative severe infection, and cautious multidisciplinary management was needed for the prevention of organ dysfunction.

7.
Free Radic Biol Med ; 167: 1-11, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33705959

RESUMO

Rapamycin is a crucial immunosuppressive regimen for patients that have undergone liver transplantation (LT). However, one of the major side effects of rapamycin include metabolic disorders such as dyslipidemia, and the mechanism remains unknown. This study aims to explore the biomolecules that are responsible for rapamycin-induced dyslipidemia and the control strategies that can reverse the lipid metabolism disorder. In this study, data collected from LT patients, cell and mouse models treated with rapamycin were analyzed. Results showed an increase of triglycerides (TGs) induced by rapamycin. MicroRNAs (miRNAs) play important roles in many vital biological processes including TG metabolism. hsa-miR-372-3p was filtered using RNA sequencing and identified as a key regulator in rapamycin-induced TGs accumulation. Using bioinformatics and experimental analyses, target genes of hsa-miR-372-3p were predicted. These genes were alkylglycerone phosphate synthase (AGPS) and apolipoprotein C4 (APOC4), which are reported to be involved in TG metabolism. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was also identified as an upstream regulatory factor of hsa-miR-372-3p. From the results of this study, NEAT1/hsa-miR-372-3p/AGPS/APOC4 axis plays a vital role in rapamycin-disruption of lipid homeostasis. Therefore, targeting this axis is a potential therapeutic target combating rapamycin-induced dyslipidemia after LT.

8.
Biochem Pharmacol ; 188: 114494, 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33684390

RESUMO

Targeting the cell cycle checkpoints and DNA damage response are promising therapeutic strategies for cancer. Adavosertib is a potent inhibitor of WEE1 kinase, which plays a critical role in regulating cell cycle checkpoints. However, the effect of adavosertib on hepatocellular carcinoma (HCC) treatment, including sorafenib-resistant HCC, has not been thoroughly studied. In this study, we comprehensively investigated the efficacy and pharmacology of adavosertib in HCC therapy. Adavosertib effectively inhibited the proliferation of HCC cells in vitro and suppressed tumor growth in HCC xenografts and patient-derived xenograft (PDX) models in vivo. Additionally, adavosertib treatment effectively inhibited the motility of HCC cells by impairing pseudopodia formation. Further, we revealed that adavosertib induced DNA damage and premature mitosis entrance by disturbing the cell cycle. Thus, HCC cells accumulating DNA damage underwent mitosis without G2/M checkpoint arrest, thereby leading to mitotic catastrophe and apoptosis under adavosertib administration. Given that sorafenib resistance is common in HCC in clinical practice, we also explored the efficacy of adavosertib in sorafenib-resistant HCC. Notably, adavosertib still showed a desirable inhibitory effect on the growth of sorafenib-resistant HCC cells. Adavosertib markedly induced G2/M checkpoint arrest and cell apoptosis in a dose-dependent manner, confirming the similar efficacy of adavosertib in sorafenib-resistant HCC. Collectively, our results highlight the treatment efficacy of adavosertib in HCC regardless of sorafenib resistance, providing insights into exploring novel strategies for HCC therapy.

9.
J Int Med Res ; 49(2): 300060520987059, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33626941

RESUMO

OBJECTIVE: Length of hospital stay is a sensitive indicator of short-term prognosis. In this retrospective study, we investigated how pancreas preservation time affects length of hospital stay after pancreas transplantation. METHODS: Patients receiving pancreas transplantation (1998.7-2018.6) were identified from the Scientific Registry of Transplant Recipients database and grouped according to pancreas preservation time. We analyzed the relationship of pancreas preservation time with graft and patient survival and prolonged length of stay (PLOS; i.e., hospital stay ≥20 days). RESULTS: We included 18,099 pancreas transplants in the survival analysis. Pancreas preservation time >20 hours had a significantly higher risk of graft failure than 8 to 12 hours. Pancreas preservation time was not significantly associated with patient survival. We included 17,567 pancreas transplants in the analysis for PLOS. Compared with 8 to 12 hours, pancreas preservation time >12 hours had a significantly higher PLOS risk, which increased with increased pancreas preservation time. In simultaneous pancreas-kidney transplantation, we also found that pancreas preservation time was positively associated with PLOS risk with pancreas preservation time >12 hours. CONCLUSION: Pancreas preservation time is a sensitive predictor of PLOS. Transplant centers should minimize pancreas preservation time to optimize patient outcomes.

10.
J Int Med Res ; 49(2): 300060520987771, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33557655

RESUMO

OBJECTIVE: False positive and negative results are associated with biliary tract cell brushing cytology during endoscopic retrograde cholangiopancreatography (ERCP). The causes are uncertain. The purpose of this study was to evaluate the accuracy of diagnoses made via cell brushing in our center, and to explore the factors influencing diagnosis. METHODS: The clinical data of patients who underwent cell brushing at our center from January 2016 to August 2019 were retrospectively analyzed. These included age, gender, stricture location, thickness of the bile duct wall in the narrow segment, maximum diameter of the biliary duct above the stricture, number of cell brush smears, carbohydrate antigen 19-9, and carcinoembryonic antigen. Positive brush cytology results were compared with results of surgical histology or tumor biopsy as well as with the patient's clinical course. RESULTS: Of the 48 patients who underwent cell brushing cytology, 27 (56.3%) had positive results. The sensitivity and specificity of biliary duct cell brushing was 79.4%, and 85.7%, respectively. None of the above-mentioned factors were associated with positive cytology brushing results. CONCLUSIONS: Cell brushing cytology remains a reliable method for diagnosis of pancreaticobiliary malignancies.

11.
Theranostics ; 11(5): 2318-2333, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33500727

RESUMO

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide, and its specific mechanism has not been fully elucidated. Inactivation of tumor suppressors may contribute to the occurrence, progression, and recurrence of HCC. DNA methylation is a crucial mechanism involved in regulating the occurrence of HCC. Herein, we aimed to identify the key methylation-related tumor suppressors as well as potential biomarkers and therapeutic targets in HCC. Methods: Combined analysis of TCGA and GEO databases was performed to obtain potential methylation-related tumor suppressors in HCC. Methyl-target sequencing was performed to analyze the methylation level of the GNA14 promoter. The diagnostic value of GNA14 as a predictor of HCC was evaluated in HCC tumor samples and compared with normal tissues. The functional role of GNA14 and its upstream and downstream regulatory factors were investigated by gain-of-function and loss-of-function assays in vitro. Subcutaneous tumorigenesis, lung colonization, and orthotopic liver tumor model were performed to analyze the role of GNA14 in vivo. Results: The expression of GNA14 was found to be downregulated in HCC and it was negatively correlated with hepatitis B virus (HBV) infection, vascular invasion, and prognosis of HCC. DNA methylation was demonstrated to be responsible for the altered expression of GNA14 and was regulated by HBV-encoded X protein (HBx). GNA14 regulated the RB pathway by promoting Notch1 cleavage to inhibit tumor proliferation, and might inhibit tumor metastasis by inhibiting the expression of JMJD6. Conclusion: GNA14 could be regulated by HBx by modulating the methylation status of its promoter. We identified GNA14 as a potential biomarker and therapeutic target for HCC.

12.
BMC Surg ; 21(1): 4, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397346

RESUMO

BACKGROUND: Mesentericoportal vein (MPV) resection in pancreatic ductal adenocarcinoma (PDAC) surgery has become a common procedure. A few studies had described the use of falciform ligament (FL) for MPV reconstruction and received encouraging preliminary effects. AIMS: This study was designed to explore the feasibility and efficacy of this technique compared with others. METHODS: Patients who underwent pancreaticoduodenectomy (PD) with MPV resection for PDAC from 2009 to 2018 were enrolled. Medical records were retrospectively reviewed, MPV reconstructions using FL were distinguished and compared with other techniques. RESULTS: 146 patients underwent MPV reconstruction, and 13 received FL venoplasty. Other reconstruction techniques included primary end-to-end anastomosis (primary, n = 30), lateral venorrhaphy (LV, n = 19), polytetrafluoroethylene conduit interposition (PTFE, n = 24), iliac artery (IA) allografts interposition (n = 47), and portal vein (PV) allografts interposition (n = 13). FL group holds the advantages of shortest operation time (p = 0.023), lowest blood loss (p = 0.109), and shortest postoperative hospital stay (p = 0.125). The grouped patency rates of FL, primary, LV, PTFE, IA, and PV were 100%, 90%, 68%, 54%, 68%, and 85% respectively. Comparison displayed that FL had the highest patency rate (p = 0.008) and lowest antiplatelet/anticoagulation proportion (p = 0.000). Complications and long-term survival were similar among different techniques. The median survival time of patent group (24.0 months, 95% CI: 22.0-26.0) was much longer than that of the thrombosed (17.0 months, 95% CI: 13.7-20.3), though without significant difference (P = 0.148). CONCLUSIONS: PD with MPV resection and reconstruction by FL is safe, feasible, and efficacious, it might provide a potential benefit for patients.


Assuntos
Carcinoma Ductal Pancreático/cirurgia , Ligamentos/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Veia Porta/cirurgia , Anastomose Cirúrgica , Estudos de Coortes , Estudos de Viabilidade , Humanos , Masculino , Veias Mesentéricas/cirurgia , Neoplasias Pancreáticas/patologia , Pancreaticoduodenectomia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/métodos
13.
J Med Internet Res ; 23(1): e17680, 2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-33459597

RESUMO

BACKGROUND: The internet has changed the way of people acquiring health information. Previous studies have shown that Wikipedia is a reasonably reliable medical resource, and it has been ranked higher than other general websites in various search engines. Baidu Encyclopedia is one of the most popular encyclopedia websites in China. However, no studies have shown the quality of the content provided in the Baidu Encyclopedia. OBJECTIVE: This study aimed to evaluate the quality of liver disease information provided by Wikipedia (in English) and Baidu Encyclopedia (in Chinese) and to perform a comparison of the quality and timeliness of the articles published in these two encyclopedias. Moreover, a 3-year follow-up study was conducted to compare if the information in both these websites was updated regularly over this period. METHODS: We searched for information on liver diseases by using the International Statistical Classification of Diseases and Related Health Problems 10th Revision Version 2016 codes on Wikipedia (in English) and Baidu Encyclopedia (in Chinese). The quality of the articles was assessed using the DISCERN instrument, which consists of 3 sections. We recorded the latest editing date of the webpages and calculated the date interval to evaluate the update timeliness of these websites. RESULTS: We found 22 entries on liver diseases in Baidu Encyclopedia and 15 articles in Wikipedia between September 15, 2016, and September 30, 2016, and we found 25 entries in Baidu Encyclopedia and 16 articles in Wikipedia between September 15, 2019, and September 30, 2019. In section 1 of the DISCERN instrument, the mean (SE) scores of Baidu Encyclopedia entries were significantly lower than those of Wikipedia articles. In section 2 and section 3 of the DISCERN instrument, the DISCERN scores of Baidu Encyclopedia entries were lower than those of Wikipedia articles, but the differences were not statistically significant. The total DISCERN scores of Baidu Encyclopedia entries were significantly lower than those of Wikipedia articles. The update interval of the entries in Baidu Encyclopedia was found to be significantly longer than that of the articles in Wikipedia. CONCLUSIONS: This study shows that the quality of articles and the reliability of the research content on liver diseases in Wikipedia are better than those of the entries in Baidu Encyclopedia. However, the quality of the treatment choices provided in both Wikipedia and Baidu Encyclopedia is not satisfactory. Wikipedia is updated more frequently than Baidu Encyclopedia, thereby ensuring that the information presented has the most recent research findings. The findings of our study suggest that in order to find accurate health information, it is important to seek the help of medical professionals instead of looking for a prescription amid the confusing information provided on the internet.


Assuntos
Hepatopatias/epidemiologia , Humanos , Internet , Estudos Longitudinais , Ferramenta de Busca
14.
Cancer Lett ; 502: 154-165, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33340617

RESUMO

Lipid metabolic reprogramming plays a pivotal role in hepatocellular carcinoma (HCC) development, but the underlying mechanisms are incompletely characterized. Long chain acyl CoA synthetase 4 (ACSL4), a member of acyl-CoA synthetases (ACS) family, has been identified as a novel marker of alpha-fetoprotein-high subtype HCC and as an oncogene. Here, we identified a new function of ACSL4 in HCC lipid metabolism. ACSL4 can modulate de novo lipogenesis by accumulating intracellular triglycerides, cholesterols, and lipid droplets in HCC. Mechanistically, ACSL4 upregulates the master lipogenesis regulator sterol regulatory element binding protein 1 (SREBP1) and its downstream lipogenic enzymes in HCC cells via c-Myc. Moreover, SREBP1 is crucial for ACSL4-mediated regulation of lipogenesis as well as HCC cell proliferation and metastasis, as SREBP1 overexpression rescues lipogenic deficiency and decreased oncogenic capabilities associated with ACSL4 suppression in vitro and in vivo. Clinically, our data showed that the expression of ACSL4 was positively correlated with that of SREBP1 in HCC patients, and the combinational biomarkers showed strong predictive value for HCC. Together, our findings uncover a new mechanism by which ACSL4 modulates aberrant lipid metabolism and promotes the progression of HCC.

15.
Front Oncol ; 10: 595973, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33282744

RESUMO

Chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family (CMTMs) is a new gene family, consisting of CKLF and CMTM1 to CMTM8, which plays an important role in hematopoiesis system, autoimmune diseases, male reproduction etc. Abnormal expression of CMTMs is also associated with tumor genesis, development and metastasis. In this review, we briefly describe the characteristics of CMTM family, outline its functions in multiple kinds of carcinomas, and summarize the latest research on their roles in hepatocellular carcinoma which are mainly related to the expression, prognostic effect, potential functions, and mechanism of action. The CMTM family is expected to provide new ideas and targets for HCC diagnosis and treatment.

16.
Aging (Albany NY) ; 122020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33291080

RESUMO

Post-transplant liver fibrosis (PTLF) is a common and severe complication in liver recipients. In this study, we assessed the impact of donor liver genetics on the development of PTLF. A total of 232 patients undergoing liver transplantation were included. Twenty-two single nucleotide polymorphisms (SNPs) associated with liver fibrosis were analyzed. Univariate analysis revealed seven donor SNPs to be associated with PTLF. In a multivariate analysis, independent risk factors of PTLF were genetic variation of donor GRP78 rs430397 (OR = 8.99, p = 0.003), GSTP1 rs1695 (OR = 0.13, p = 0.021), miRNA-196a rs12304647 (OR = 16.01, p =0.001), and TNF-α rs1800630 (OR = 79.78, p = 0.001); blood tacrolimus levels at maintenance > 7 ng/ml (OR =7.48, p <0.001); and post-transplant diabetes mellitus (OR = 7.50, p = 0.001). A predictive model that included donor SNPs showed better prognostic ability for PTLF than a model with only clinical parameters (AUROC: 0.863 vs 0.707, P < 0.001). Given that donor gene SNPs are associated with an increased risk of PTLF, this model integrated with donor gene polymorphisms may help clinicians predict PTLF.

17.
Hepatobiliary Surg Nutr ; 9(6): 739-758, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33299829

RESUMO

Background: Liver transplantation (LT) is one of the most effective surgical treatment for patients with end-stage liver disease. Steatosis is a contributor for inferior graft quality. But its impact and safety on transplantation was less assessed in Chinese patients. Methods: Graft steatosis and related information involved in recipients, donors and surgical procedures were retrospectively collected from 239 patients. Results: Donor macrosteatosis (MaS) caused about 2.14 and 2.80 folds of increment on patient and graft mortality. Dose-response analysis revealed prominent risk of grafts on overall patient/organ mortality when MaS content exceeded 10% (P<0.05). Noteworthy, deaths were only observed in MaS group when concurrent with extremely higher post-transplant alanine aminotransferase (ALT, 64%). However, microsteatosis (MiS) grafts didn't affect outcomes after LT. In a cohort of Chinese patients, MaS had comprehensive effects on post-transplant outcomes with relatively lower safety threshold at 10%. Mortality gap caused by MaS grafts was observed in patients with severer ischemia reperfusion injury. Conclusions: Our study revealled the graft MaS affected the post-transplant outcomes in lower risk cutoff in Chinese patients. Further study is worthy to validate these results and investigate inner mechanism under the phenomenon.

18.
Technol Cancer Res Treat ; 19: 1533033820979703, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33308041

RESUMO

BACKGROUND: Novel immunotherapy is one of the options for advanced biliary tract cancer (BTC) patients who are traditionally intolerant to chemotherapy. However, clinical evidence for single immunotherapy with pembrolizumab or nivolumab is limited. The present study assessed the safety and efficiency of the anti-PD-1 antibody, camrelizumab, as monotherapy in patients with unresectable or recurrent BTC. METHODS: A retrospective evaluation was conducted among 4 patients with BTC, including 2 with intrahepatic cholangiocellular carcinoma (ICC), one with extrahepatic bile duct cancer, and one with gallbladder cancer. The patients with unresectable or recurrent BTC were refractory or intolerant to gemcitabine plus cisplatin treatment regimens and received at least one intravenous dose (3 mg/kg) of camrelizumab monotherapy every 3 weeks. Gene sequencing analysis was also performed for biomarker screening. Patient reaction was evaluated according to modified response evaluation criteria in solid tumor (RECIST) version 1.1, progression-free survival (PFS), and toxicity. RESULTS: In this cohort, 1 patient with recurrent ICC had a positive response to treatment, with a substantial tumor size reduction in liver and lung metastases verified using a radiological test after receiving 3 cycles of camrelizumab. The PFS was 4.9 months. The remaining 3 patients showed no response to treatment and experienced disease progression. RNA sequence analysis didn't found high expression on genes that related to PD-L1, microsatellite instability, tumor mutation burden, and DNA mismatch repair in these patients. Grade 3 treatment-related adverse event was observed in 1 patient. CONCLUSIONS: Anti-PD-1 antibody camrelizumab had a manageable safety profile in patients with advanced BTC. This initial assessment of camrelizumab monotherapy provides effective evidence for patients with refractory BTC in biomarker-unselected patients.

19.
Bioengineered ; 11(1): 1313-1324, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33251971

RESUMO

Instantaneous blood coagulation after bioengineered liver transplantation is a major issue, and the key process in its prevention is the construction of the endothelial vascular bed on biomimetic scaffolds. However, the specific molecules involved in the regulation of the vascular bed formation remain unclear. Syndecan-4 is a type I transmembrane glycoprotein commonly expressed in the human body; its receptor has been reported as critical for optimal cell adhesion and initiation of intracellular signaling, indicating its promising application in vascular bed formation. In the current study, bioinformatics analysis and in vitro experiments were performed to evaluate whether syndecan-4 promoted endothelial cell migration and functional activation. Exogenous syndecan-4-overexpressing endothelial cells were perfused into the decellularized liver scaffold, which was assessed by Masson's trichrome staining. Western blotting and qRT-PCR were used to evaluate the effects of syndecan-4 on the thrombospondin 1 (THBS1) stability. We found that syndecan-4 promoted the adhesion of vascular endothelial cells and facilitated cell migration and angiogenesis. Furthermore, syndecan-4 overexpression resulted in a well-aligned endothelium on the decellularized liver scaffolds. Mechanistically, syndecan-4 destabilized THBS1 at the protein level. Therefore, our data revealed that syndecan-4 promoted the biological activity of endothelial cells on the bionic liver vascular bed through THBS1. These findings provide scientific evidences for solving transient blood coagulation after bionic liver transplantation.

20.
Genome Med ; 12(1): 102, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33225985

RESUMO

BACKGROUND: The gut-liver axis plays a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC). However, the correlations between the gut microbiome and the liver tumor transcriptome in patients with HCC and the impact of the gut microbiota on clinical outcome are less well-understood. METHODS: Fecal samples collected from HBV-related HCC patients (n = 113) and healthy volunteers (n = 100) were subjected to 16S rRNA sequencing of the microbiome. After a rigorous selection process, 32 paired tumor and adjacent non-tumor liver tissues from the HCC group were subjected to next-generation sequencing (NGS) RNA-seq. The datasets were analyzed individually and integrated with clinical characteristics for combined analysis using bioinformatics approaches. We further verified the potential of the gut microbiota to predict clinical outcome by a random forest model and a support vector machine model. RESULTS: We found that Bacteroides, Lachnospiracea incertae sedis, and Clostridium XIVa were enriched in HCC patients with a high tumor burden. By integrating the microbiome and transcriptome, we identified 31 robust associations between the above three genera and well-characterized genes, indicating possible mechanistic relationships in tumor immune microenvironment. Clinical characteristics and database analysis suggested that serum bile acids may be important communication mediators between these three genera and the host transcriptome. Finally, among these three genera, six important microbial markers associated with tumor immune microenvironment or bile acid metabolism showed the potential to predict clinical outcome (AUC = 81%). CONCLUSIONS: This study revealed that changes in tumor immune microenvironment caused by the gut microbiota via serum bile acids may be important factors associated with tumor burden and adverse clinical outcome. Gut microbes can be used as biomarkers of clinical features and outcomes, and the microbe-associated transcripts of host tumors can partly explain how gut microbiota promotes HCC pathogenesis.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...