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Screening and clinical evaluation of dominant peptides of centromere protein F antigen for early diagnosis of hepatocellular carcinoma.
Li, S, Li, X, Xu, A, Zhang, B, He, X, Chen, H, Huang, J
Molecular medicine reports. 2018;(3):4720-4728
Abstract
Tumor-associated antigens, such as centromere protein F (CENP‑F), have been recognized as potential serological biomarkers for early diagnosis of hepatocellular carcinoma (HCC); however, the exact regions corresponding to the dominant peptides of CENP‑F antigen remain to be explored. We aimed to screen and evaluate potential dominant peptides of CENP‑F for early diagnosis of HCC. Dominant peptides of CENP‑F were predicted by BioSun version 3.0, and the corresponding recombinant proteins were prepared. Enzyme‑linked immunosorbent assays were conducted for initial screening of dominant peptides, and selected dominant peptides were subjected to further clinical evaluation. Eight dominant peptides of CENP‑F antigens were predicted at amino acids (a.a) 121‑220, 335‑416, 1100‑1265, 1670‑1791, 1759‑2093, 2075‑2210, 2485‑2592, and 2808‑2960. Initial screening of the predicted peptides in samples of 47 HCC cases showed the highest diagnostic value for 121‑220 a.a and 1670‑1791 a.a peptides with area under the curve (AUC) values of 0.795 [95% confidence interval (CI), 0.706‑0.884] and 0.809 (95% CI, 0.721‑0.896), sensitivity of 58.3 and 85.4%, and specificity of 93.9 and 65.3%, respectively. Further evaluation of the two peptides in 405 samples comprised of 153 HCC, 126 liver cirrhosis and 126 healthy controls, presenting an AUC of 0.743 (95% CI, 0.674‑0.812) for 121‑220 a.a peptide in detecting early‑stage HCCs. Specifically, the 121‑220 a.a peptide showed a complementary effect in combination with α‑fetoprotein (AFP) for the detection of early‑stage HCC with increased AUC value of 0.840 (95% CI, 0.781‑0.899), and sensitivity of 81.4% and specificity of 72.2%. In conclusion, our study identified the 121‑220 a.a dominant peptide as the region of CENP‑F antigen with the highest immunogenicity and demonstrated its value in combination with AFP for diagnosis of early-stage HCC.
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Which is the best combination of TACE and Sorafenib for advanced hepatocellular carcinoma treatment? A systematic review and network meta-analysis.
Feng, F, Jiang, Q, Jia, H, Sun, H, Chai, Y, Li, X, Rong, G, Zhang, Y, Li, Z
Pharmacological research. 2018;:89-101
Abstract
The aim of this study was to assess the comparative efficacy and safety of combination therapy with transarterial chemoembolization (TACE) and Sorafenib for patients with advanced hepatocellular carcinoma (HCC) through a systematic review and network meta-analysis and identify the best combination of TACE and Sorafenib. We searched databases for publications prior to May 2018. The prespecified efficacy outcomes were the objective response rate, overall survival rate, and time to progression. adverse effects included dermatologic, gastrointestinal, and general disorders. Subgroup analyses, meta-regression, and a network meta-analysis regarding two types of outcomes by different chemotherapy agents in TACE (5-fluorouracil, Adriamycin, Platinum, mitomycin C, hydroxycamptothecin) were included. The study is registered with PROSPERO (CRD42018098541). For efficacy outcomes, subgroups which included 5-fluorouracil and hydroxycamptothecin ranked higher than other chemotherapy agents, while mitomycin C ranked the lowest. For advanced effects, the use of mitomycin C or 5-fluorouracil as the chemotherapy agent ranked higher, while hydroxycamptothecin ranked the lowest. Therefore, we excluded 5-Fu and Mitomycin C in subsequent studies. Additionally, in the evaluation of primary adverse effects by the network meta-analysis, Platinum ranked the highest while hydroxycamptothecin ranked the lowest. Therefore, we excluded Platinum this time. Furthermore, all types of Adriamycin are not same, and some studies included two types of Adriamycin. The network meta-analysis results showed that the TACE (hydroxycamptothecin + pirarubicin) +Sorafenib arm and TACE (hydroxycamptothecin + epirubicin) +Sorafenib arm had significant efficacy differences. In conclusion, for patients with advanced HCC, combination therapy with HCPT plus THP/EPI in TACE and Sorfenib may be used as a first-line treatment.
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3.
Effectiveness and safety of robotic-assisted versus laparoscopic hepatectomy for liver neoplasms: A meta-analysis of retrospective studies.
Hu, L, Yao, L, Li, X, Jin, P, Yang, K, Guo, T
Asian journal of surgery. 2018;(5):401-416
Abstract
This meta-analysis aimed to investigate the effectiveness and safety of RAH and LLR for liver neoplasms. A systematic search was performed in PubMed, EMbase, the Cochrane Library, Web of science, and China Biology Medicine disc up to July 2016 for studies that provided comparisons between the surgical outcomes of RAH and LLR for liver neoplasms. WMD, OR and 95% CI were calculated and data combined using the random-effect model. The quality of the evidence was assessed using GRADE methods. A total of 17 studies were included in the meta-analysis, in which 487 patients were in the RAH group and 902 patients were in the LLR group. The meta-analysis results indicated: compared to LLR, RAH was associated with more estimated blood loss, longer operative time, and longer time to first nutritional intake (p < 0.05). There was no significant difference in length of hospital stay, conversion rate during operation, R0 resection rate, complications and mortality (p > 0.05). Three studies reported the total cost, and the result showed a higher cost in the RAH group when compared with the LLR group (p < 0.05). This meta-analysis indicated that RAH and LLR display similar effectiveness and safety in hepatectomy. Considering the lack of high quality original studies, prospective clinical trials should be conducted to provide strong evidence for clinical guidelines formation, and the insurance coverage policies should be established to promote the application of robotic surgery in the future.
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4.
Fatal adverse events with molecular targeted agents in the treatment of advanced hepatocellular carcinoma: a meta-analysis of randomized controlled trials.
Li, X, Wan, J, Wu, Z, Tu, J, Hu, Y, Wu, S, Lou, L
Drug design, development and therapy. 2018;:3043-3049
Abstract
AIMS: Concerns have increased about the risk of fatal adverse events (FAEs) associated with molecular targeted agents (MTAs) in the treatment of advanced hepatocellular carcinoma (HCC). The purpose of this study is to investigate the overall incidence and risk of FAEs in advanced HCC with administration of MTAs by using a meta-analysis of available clinical trials. MATERIALS AND METHODS Electronic databases were searched for relevant articles before March 2017. Eligible studies were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Pooled incidence, Peto ORs and 95% CIs were calculated according to the heterogeneity of selected studies. RESULTS A total of 4,716 HCC participants from 10 randomized controlled trials (RCTs) were finally considered for this meta-analysis. The pooled incidence of death due to MTAs was 2.1% (95% CI 1.6%-2.8%) with a Peto OR of 1.79 (95% CI 1.07-3.01; p=0.027) in comparison with controlled groups. Subgroup analysis according to biological agents showed that brivanib treatment in HCC patients significantly increased the risk of developing FAEs (Peto OR 3.97; 95% CI 1.17-13.51; p=0.028) but not for sorafenib (Peto OR 1.78; 95% CI 0.54-5.89; p=0.34) and other MTAs (Peto OR 1.43; 95% CI 0.75-2.76; p=0.28). Sensitive analysis showed that the pooled results were influenced by removing each single trial. The most common causes of FAEs were hepatic failure (22.2%) and hemorrhage (13.3%), respectively. CONCLUSION Clinicians should be aware of the risks of FAEs during the administration of MTAs in advanced HCC patients, especially for patients with abnormal liver function. However, the use of sorafenib remains justified in its approved indications due to their potential survival benefits and limited toxicities.
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A single-institute experience with sorafenib in untreated and previously treated patients with advanced hepatocellular carcinoma.
Balsom, SM, Li, X, Trolli, E, Rose, J, Bloomston, M, Patel, T, Bekaii-Saab, TS
Oncology. 2010;(3-4):210-2
Abstract
OBJECTIVES Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Sorafenib is considered the standard of care for patients with advanced HCC. METHODS We conducted a retrospective analysis of our cancer center's experience with sorafenib in patients with advanced HCC. Eligible patients were required to have measurable disease and were allowed to have been refractory (with documented progression) to prior systemic therapies before starting on sorafenib. RESULTS Twenty-six patients (median age = 56 years) who were treated at the Ohio State University with sorafenib were included in this study. Thirty-eight percent had exposure to prior systemic therapy. The median time to tumor progression was 5.4 months and the median overall survival 7 months. For the patients with exposure to prior systemic therapy, the median time to tumor progression was 9.1 months and is the median overall survival 9.83 months. There were no unexpected toxicities. CONCLUSION Sorafenib has interesting activity and acceptable tolerability in patients with advanced HCC, including those who failed prior therapies.
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6.
[Biological distribution of 131I-HAb18F(ab')2 in patients with hepatocellular carcinoma].
Lu, W, Li, X, Wang, C, Liu, W, Jiao, H, Mo, T, Chen, Z
Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi. 2003;(4):689-91
Abstract
Before 131I-HAb18F(ab')2 administration, 24 cases of mid-term or advanced hepatocellular carcinoma(HCC) were given Lugol's Liquid to block the thyroid gland, and submitted to hepatic colloid imaging. The cases were randomly divided into 3 groups. Then 131I-HAb18F(ab')2 was injected into the target hepatic artery with doses of 0.5, 0.75, 1.0 mCi/kg, respectively. At the followed 10, 48, 96 and 192 hours, 131I-HAb18F(ab')2 distribution in human body was acquired by whole body dynamic image with Single photon emission computed tomography(SPECT). The results showsed that 131I-HAb18F(ab')2 in tumor tissue was significantly higher than that in normal liver tissue and other organs. This difference became obvious as time passed. 131I-HAb18F(ab')2 is stable in human body and it can combine with HCC tissue specifically. So it is a new medicine deserving further research for the treatment of HCC.
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7.
[The prevention of primary liver cancer by selenium in high risk populations].
Li, W, Zhu, Y, Yan, X, Zhang, Q, Li, X, Ni, Z, Shen, Z, Yao, H, Zhu, J
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine]. 2000;(6):336-8
Abstract
OBJECTIVE To study the preventive effects of selenium on primary liver cancer. METHODS After screening of blood samples in 18,000 males from 20 to 65 years-old in Qidong, Jiangsu province (a high risk area for liver cancer), 2,065 cases of HBsAg positive, AFP negative and normal liver function (normal ALT values) were found. The subjects were randomly divided into two groups, based on their residence areas; 1,112 subjects (experimental group) received one tablet of sodium selenite (0.5 mg Se) every day and 953 subjects (control group) received one placebo tablet every day. RESULTS During three years of intervention and follow up, the blood selenium concentration and glutathione peroxidase activity of the subjects in the experimental group were increased and had significant difference as compared with those of the control group (P < 0.01). At the same time, the prevalence rate of micronucleus cells in peripheral blood lymphocytes in the experimental group was significantly lower than that of the control group (P < 0.01), and the incidence of new liver cancer in the experimental group (3 057.55/10(6), 34 cases out of 1,112 subjects) was significantly lower than the control group (5 981.11/10(6); 57 cases out of 953 subjects) (P < 0.01). CONCLUSION The results confirms that selenium supplementation in general populations lived in high risk is effective in the prevention of liver cancer and the using of selenium tablets is simple and feasible.