Browsing by Subject "hepatocellular carcinoma"
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Item Open Access Observation of different tumor motion magnitude within liver and estimate of internal motion margins in postoperative patients with hepatocellular carcinoma.(Cancer management and research, 2017-01) Zhao, Yu-Ting; Liu, Zhi-Kai; Wu, Qiu-Wen; Dai, Jian-Rong; Zhang, Tao; Jia, Angela Y; Jin, Jing; Wang, Shu-Lian; Li, Ye-Xiong; Wang, Wei-HuTo assess motion magnitude in different parts of the liver through surgical clips in postoperative patients with hepatocellular carcinoma and to examine the correlation between the clip and diaphragm motion.Four-dimensional computed tomography images from 30 liver cancer patients under thermoplastic mask immobilization were selected for this study. Three to seven surgical clips were placed in the resection cavity of each patient. The liver volume on computed tomography image was divided into the right upper (RU), right middle (RM), right lower (RL), hilar, and left lobes. Agreement between the clip and diaphragm motion was assessed by calculating intraclass correlation coefficient, and Bland-Altman analysis (Diff). Furthermore, population-based and patient-specific margins for internal motion were evaluated.The clips located in the RU lobe showed the largest motion, (7.5±1.6) mm, which was significantly more than in the RM lobe (5.7±2.8 mm, p=0.019), RL lobe (4.8±3.3 mm, p=0.017), and hilar lobe (4.7±2.7 mm, p<0.001) in the cranial-caudal direction. The mean intraclass correlation coefficient values between the clip and diaphragm motion were 0.915, 0.735, 0.678, 0.670, and the mean Diff values between them were 0.1±0.8 mm, 2.3±1.4 mm, 3.1±2.0 mm, 2.4±1.5 mm, when clips were located in the RU lobe, RM lobe, RL lobe, and hilar lobe, respectively. The clip and diaphragm motions had high concordance when clips were located in the RU lobe. Internal margin can be reduced from 5 mm in the cranial-caudal direction based on patient population average and to 3 mm based on patient-specific margins.The motion magnitude of clips varied significantly depending on their location within the liver. The diaphragm was a more appropriate surrogate for tumor located in the RU lobe than for other lobes.Item Open Access Pathogenesis of Hepatic Tumors following Gene Therapy in Murine and Canine Models of Glycogen Storage Disease.(Molecular therapy. Methods & clinical development, 2019-12) Kang, Hye-Ri; Gjorgjieva, Monika; Smith, Stephanie N; Brooks, Elizabeth D; Chen, Zelin; Burgess, Shawn M; Chandler, Randy J; Waskowicz, Lauren R; Grady, Kylie M; Li, Songtao; Mithieux, Gilles; Venditti, Charles P; Rajas, Fabienne; Koeberl, Dwight DGlycogen storage disease type Ia (GSD Ia) is caused by mutations in the glucose-6-phosphatase (G6Pase) catalytic subunit gene (G6PC). GSD Ia complications include hepatocellular adenomas (HCA) with a risk for hepatocellular carcinoma (HCC) formation. Genome editing with adeno-associated virus (AAV) vectors containing a zinc-finger nuclease (ZFN) and a G6PC donor transgene was evaluated in adult mice with GSD Ia. Although mouse livers expressed G6Pase, HCA and HCC occurred following AAV vector administration. Interestingly, vector genomes were almost undetectable in the tumors but remained relatively high in adjacent liver (p < 0.01). G6Pase activity was decreased in tumors, in comparison with adjacent liver (p < 0.01). Furthermore, AAV-G6Pase vector-treated dogs with GSD Ia developed HCC with lower G6Pase activity (p < 0.01) in comparison with adjacent liver. AAV integration and tumor marker analysis in mice revealed that tumors arose from the underlying disorder, not from vector administration. Similarly to human GSD Ia-related HCA and HCC, mouse and dog tumors did not express elevated α-fetoprotein. Taken together, these results suggest that AAV-mediated gene therapy not only corrects hepatic G6Pase deficiency, but also has potential to suppress HCA and HCC in the GSD Ia liver.Item Open Access Plasma miRNAs as early biomarkers for detecting hepatocellular carcinoma.(Int J Cancer, 2015-10-01) Wen, Yang; Han, Jing; Chen, Jianguo; Dong, Jing; Xia, Yongxiang; Liu, Jibin; Jiang, Yue; Dai, Juncheng; Lu, Jianhua; Jin, Guangfu; Han, Jiali; Wei, Qingyi; Shen, Hongbing; Sun, Beicheng; Hu, ZhibinThe early detection of hepatocellular carcinoma (HCC) presents a challenge because of the lack of specific biomarkers. Serum/plasma microRNAs (miRNAs) can discriminate HCC patients from controls. We aimed to identify and evaluate HCC-associated plasma miRNAs originating from the liver as early biomarkers for detecting HCC. In this multicenter three-phase study, we first performed screening using both plasma (HCC before and after liver transplantation or liver hepatectomy) and tissue samples (HCC, para-carcinoma and cirrhotic tissues). Then, we evaluated the diagnostic potential of the miRNAs in two case-control studies (training and validation sets). Finally, we used two prospective cohorts to test the potential of the identified miRNAs for the early detection of HCC. During the screening phase, we identified ten miRNAs, eight of which (miR-20a-5p, miR-25-3p, miR-30a-5p, miR-92a-3p, miR-132-3p, miR-185-5p, miR-320a and miR-324-3p) were significantly overexpressed in the HBV-positive HCC patients compared with the HBV-positive cancer-free controls in both the training and validation sets, with a sensitivity of 0.866 and specificity of 0.646. Furthermore, we assessed the potential for early HCC detection of these eight newly identified miRNAs and three previously reported miRNAs (miR-192-5p, miR-21-5p and miR-375) in two prospective cohorts. Our meta-analysis revealed that four miRNAs (miR-20a-5p, miR-320a, miR-324-3p and miR-375) could be used as preclinical biomarkers (pmeta < 0.05) for HCC. The expression profile of the eight-miRNA panel can be used to discriminate HCC patients from cancer-free controls, and the four-miRNA panel (alone or combined with AFP) could be a blood-based early detection biomarker for HCC screening.Item Open Access Targeting Tumor-Associated Antigens in Hepatocellular Carcinoma for Immunotherapy: Past Pitfalls and Future Strategies.(Hepatology (Baltimore, Md.), 2020-08-07) Lu, Ligong; Jiang, Jun; Zhan, Meixiao; Zhang, Hui; Wang, Qian-Ting; Sun, Sheng-Nan; Guo, Xiao-Kai; Yin, Hua; Wei, Yadong; Li, Shi-You; Liu, Jun O; Li, Yong; He, You-WenThere are few treatment options for advanced-stage hepatocellular carcinoma (HCC). Targeting tumor-associated antigens (TAAs) for HCC immunotherapy has been tested clinically for many years with limited success. Recent advances in applying mutated tumor-specific neoantigens as immunotherapeutic targets raise hope that this class of antigens may be used in HCC treatment. Accordingly, multiple clinical trials have been initiated to test this concept. However, recent findings demonstrate that mutated neoantigens are rarely detected while unmutated antigens derived from TAAs are represented in the HLA ligandomes of HCC patients, suggesting a requirement to target TAAs for HCC immunotherapy. Herein, we review the potential pitfalls of previous clinical applications of targeting TAAs in HCC immunotherapy. Based on further understanding of the roles of different arms of adaptive immunity in antitumor immunity, we provide a perspective on how to address the unsatisfactory previous immunotherapy attempts in HCC. We propose a new vaccine platform that enhances all three arms of the adaptive immune system to improve TAA-based cancer vaccination in HCC patients. As many solid tumors with low and intermediate mutation burdens have similar TAA and neoantigen expression and presentation patterns, the new vaccine platform is broadly applicable. In conclusion, targeting TAA in HCC for immunotherapy is necessary and new strategies are needed to improve clinical efficacy.