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Sorafenib in HCC

Zheng Liu, Jing Yang, Chao Ge, Fangyu Zhao, Hong Li, Ming Yao, Jinjun Li, Hua Tian
Inhibitor of DNA binding/differentiation (Id2) is an important regulator involved in the initiation and progression of cancer. However, the function and mechanism of the regulation of Id2 in hepatocellular carcinoma (HCC) was unclear. In the present study, we found that the overexpression of Id2 increased HCC cell proliferation in vitro and in vivo . Knockdown of Id2 inhibited HCC cell proliferation in vitro and in vivo . Furthermore, knockdown of Id2 enhanced sorafenib-induced apoptosis in HCC. Conversely, overexpression of Id2 weakened sorafenib-induced apoptosis in HCC...
2018: American Journal of Cancer Research
Toshifumi Tada, Takashi Kumada, Hidenori Toyoda, Kunihiko Tsuji, Atsushi Hiraoka, Kojiro Michitaka, Akihiro Deguchi, Toru Ishikawa, Michitaka Imai, Hironori Ochi, Koji Joko, Noritomo Shimada, Kazuto Tajiri, Masashi Hirooka, Yohei Koizumi, Yoichi Hiasa, Junko Tanaka
BACKGROUND AND AIMS: Albumin-bilirubin (ALBI) grade was developed as a new method to assess hepatic function. Sorafenib has been confirmed to be effective in improving survival in patients with advanced hepatocellular carcinoma (HCC). In this study, we investigated the impact of ALBI grade versus Child-Pugh classification on survival in HCC patients who received sorafenib. METHODS: A total of 567 patients with advanced HCC who received sorafenib were included. We analyzed survival based on Child-Pugh classification or score and ALBI grade or score...
December 14, 2018: Journal of Gastroenterology and Hepatology
Zhi Dong, Kun Huang, Bing Liao, Huasong Cai, Yu Dong, Mengqi Huang, Xiaoqi Zhou, Yingmei Jia, Ling Xu, Yanji Luo, Zi-Ping Li, Shi-Ting Feng
PURPOSE: To investigate the feasibility of prediction for targeted therapy-related gene expression in hepatocellular carcinoma (HCC) using preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI). MATERIALS AND METHODS: Ninety-one patients (81 men, mean age 53.9 ± 12 years) with solitary HCC who underwent preoperative enhanced MRI were retrospectively analyzed. Features including tumor size, signal homogeneity, tumor capsule, tumor margin, intratumoral vessels, peritumor enhancement, peritumor hypointensity, signal intensity ratio on DWI, T1 relaxation times, and the reduction rate between pre- and post-contrast enhancement images were assessed...
December 13, 2018: European Radiology
Leonardo Gomes da Fonseca, Guilherme Nader Marta, Maria Ignez Freitas Melro Braghiroli, Aline Lopes Chagas, Flair Jose Carrilho, Paulo Marcelo Hoff, Jorge Sabbaga
BACKGROUND: Before the targeted therapies era, cytotoxic chemotherapy (CCT) was an option for advanced hepatocellular carcinoma (HCC), even with the lack of supporting evidence. Since the last decade, sorafenib has been established as the first-line therapy. Although new agents are being incorporated, CCT is still considered in regions where new drugs are not available or for patients who progressed through the approved therapies and remain in good clinical condition. We aimed to describe our experience regarding the use of CCT as second-line treatment after sorafenib...
December 13, 2018: BMC Cancer
Zonghong Han, Zhongming He, Caoye Wang, Qi Wang
RATIONALE: Most patients with hepatocellular carcinoma (HCC) have lost the chance of radical treatment at the time of their visit, and the prognosis of metastatic HCC is even worse. Sorafenib is currently regarded as a first-line systemic therapy in patients with advanced and metastatic HCC. Apatinib is a new inhibitor of vascular endothelial growth factor receptor 2 tyrosine kinase, which has been reported to be effective in some solid tumors. We herein report a case of apatinib in the treatment of the patient with metastatic HCC who was resistant to sorafenib...
December 2018: Medicine (Baltimore)
Xiaofeng Tang, Weigang Yang, Zheyue Shu, Xiaodong Shen, Weichen Zhang, Chao Cen, Linping Cao, Min Zhang, Shusen Zheng, Jun Yu
Hepatocellular carcinoma (HCC) is a globally prevalent malignancy associated with a poor patient prognosis. We investigated the relationship between microRNA‑223 (miR‑223) expression and the sensitivity of HCC cells to sorafenib treatment. miR‑223 expression was determined in HCC cell lines with differential sorafenib sensitivity using reverse transcription‑quantitative PCR. miR‑223 inhibitor, miR‑223 mimic, and F‑box and WD repeat domain‑containing 7 (FBW7) short interfering RNAs (siRNAs) were transfected into the HCC cells to regulate the expression levels of miR‑223 and FBW7...
December 6, 2018: Oncology Reports
Joong-Won Park, Yoon Jun Kim, Do Young Kim, Si-Hyun Bae, Seung Woon Paik, Youn-Jae Lee, Hwi Young Kim, Han Chu Lee, Sang Young Han, Jae Youn Cheong, Oh Sang Kwon, Jong Eun Yeon, Bo Hyun Kim, Jaeseok Hwang
BACKGROUND/AIMS: To compare clinical outcomes of sorafenib combined with concurrent conventional transarterial chemoembolization (cTACE) (SOR+T) with those of sorafenib alone in patients with advanced hepatocellular carcinoma (HCC) in an investigator-initiated, multicenter, randomized, phase III trial. METHODS: After randomization, all eligible patients received sorafenib with (Arm C, n=170) or without (Arm S, n=169) cTACE within 3 days and cTACE within 7-21 days, with repeated cTACE on demand (Arm C)...
December 5, 2018: Journal of Hepatology
Tongwang Yang, Yuxue Gao, Daojie Liu, Yang Wang, Jing Wu, Xiaoni Liu, Ying Shi, Dexi Chen
Apoptosis stimulated protein of p53-2 (ASPP2) induces the transcription of p53-targeted genes to stimulates its pro-apoptosis function. The poor chemotherapeutic sensitivity is associated with the decreased ASPP2 expression in many human cancers. Here, multiple genes real-time RT-PCR array and western blotting analysis show that ASPP2 suppress the expression of X-linked inhibitor of apoptosis protein (XIAP), determinant of chemoresistance in cancer, in hepatocellular carcinoma (HCC) in a p53-independent manner...
December 6, 2018: Biochemical and Biophysical Research Communications
Changhoon Yoo, Joong-Won Park, Yoon Jun Kim, Do Young Kim, Su Jong Yu, Tae Seop Lim, Su Jin Lee, Baek-Yeol Ryoo, Ho Yeong Lim
Background The pivotal RESORCE trial showed that regorafenib was effective as second-line therapy for patients with advanced HCC who progressed on first-line sorafenib. Real-world data are needed to assess clinical outcomes and adverse events in the setting of daily practice. Methods Between April 2017 and August 2017, the Named Patient Program (NPP) was activated to provide controlled, pre-approval access of regorafenib in Korea. This analysis is a multicenter retrospective study of patients who received regorafenib under the NPP...
December 7, 2018: Investigational New Drugs
Hamdy A Azim, Ashraf Omar, Hesham Atef, Heba Zawahry, Mohamed K Shaker, Ah Kamel Abdelmaksoud, Mohamed EzzElarab, Omar Abdel-Rahman, Mohamed Ismail, Loay Kassem, Imam Waked
Background: Phase II trials found that tegafur-uracil (UFT) is an effective drug in hepatocellular carcinoma (HCC), while preclinical data suggested that its combination with sorafenib may have a promising activity. Our Phase II randomized trial aimed to evaluate efficacy and tolerability of sorafenib plus UFT vs sorafenib in advanced HCC. Methods: Patients with advanced HCC, with no prior systemic therapy, were randomized to receive either UFT at 125 mg/m2 twice daily for 4 out of 5 weeks plus sorafenib at 400 mg twice daily (arm 1) or single agent sorafenib at 400 mg twice daily (arm 2)...
2018: Journal of Hepatocellular Carcinoma
Jian-Hong Fang, Li Xu, Li-Ru Shang, Chu-Zhi Pan, Jin Ding, Yun-Qiang Tang, Hui Liu, Chu-Xing Liu, Jia-Lin Zheng, Yao-Jun Zhang, Zhong-Guo Zhou, Jing Xu, Limin Zheng, Min-Shan Chen, Shi-Mei Zhuang
Sorafenib is the most recommended first-line systemic therapy for advanced hepatocellular carcinoma (HCC). Yet there is no clinically applied biomarker for predicting sorafenib response. We have demonstrated that a vascular pattern, named VETC (vessels that encapsulate tumor clusters), facilitates the release of whole tumor clusters into the bloodstream; VETC-mediated metastasis relies on vascular pattern but not on the migration and invasion of cancer cells. In this study, we aimed to explore whether the vascular pattern could predict sorafenib benefit...
December 1, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Timothy A Lin, Jessica S Lin, Timothy Wagner, Ngoc Pham
Stereotactic body radiation therapy (SBRT) is a form of radiation therapy that has been used in the treatment of primary hepatocellular carcinoma (HCC) over the past decade. To evaluate the clinical efficacy of SBRT in primary HCC, a literature search was conducted to identify original research articles published from January 2000 through January 2018 in PubMed on SBRT in HCC. All relevant studies published from 2004 to 2018 were included. Prospective studies demonstrated 2-year local control (LC) rates ranging from 64-95% and overall survival (OS) rates ranging from 34% (2-year) to 65% (3-year)...
October 2018: Journal of Gastrointestinal Oncology
V V Pavan Kedar Mukthinuthalapati, Yuchen Wang, Yazan Abu Omar, Moin Syed, Bashar Attar
Background: Sorafenib is first line chemotherapy for advanced hepatocellular carcinoma (HCC). There are little real-world experiences with sorafenib done on US population except for the US arm of the GIDEON study, a phase IV multi-national study. In this context, we present a single institution experience with sorafenib for HCC in a tertiary inner-city safety-net hospital of Chicago. Methods: We retrospectively analyzed electronic medical records of patients with HCC (confirmed with radiographic criteria and/or biopsy) who received sorafenib from 2009 to 2016...
October 2018: Journal of Gastrointestinal Oncology
Ruiqi Liu, Yuejin Li, Lantian Tian, Huawen Shi, Jiabei Wang, Yingjian Liang, Boshi Sun, Shuangjia Wang, Meng Zhou, Li Wu, Jianhua Nie, Binlin Lin, Shuli Tang, Yanqiao Zhang, Guangyu Wang, Chunhui Zhang, Jiguang Han, Benjie Xu, Lianxin Liu, Kunmei Gong, Tongsen Zheng
Gankyrin plays important roles in tumorigenicity and metastasis of hepatocellular carcinoma (HCC). We have for the first time investigated the effects of Gankyrin on glycolysis and glutaminolysis both in vitro and in vivo, including in patient-derived xenografts. We reported Gankyrin increases glucose consumption, lactate production, glutamine consumption and glutamate production in HCC through upregulating the expression of the transporters and enzymes involved in glycolysis and glutaminolysis, including HK2, GLUT1, LDHA, PKM2, ASCT2 and GLS1...
November 29, 2018: Cancer Letters
Issei Saeki, Takahiro Yamasaki, Masaki Maeda, Reo Kawano, Takuro Hisanaga, Takuya Iwamoto, Toshihiko Matsumoto, Isao Hidaka, Tsuyoshi Ishikawa, Taro Takami, Isao Sakaida
Background: Sorafenib is a standard therapy for patients with advanced hepatocellular carcinoma (HCC). However, no predictive biomarkers of sorafenib efficacy have been discovered. Herein, we investigated the impact of body composition, such as skeletal muscle and visceral fat, on the prognosis of advanced HCC patients treated with sorafenib. Methods: We enrolled 100 patients with advanced HCC treated with sorafenib. Prior to receiving sorafenib therapy, skeletal muscle index (SMI) and visceral fat area (VFA) were measured using computed tomography at the third lumbar vertebra and umbilical level, respectively...
October 2018: Liver Cancer
Yushi Sorin, Kenji Ikeda, Yusuke Kawamura, Shunichiro Fujiyama, Masahiro Kobayashi, Tetsuya Hosaka, Hitomi Sezaki, Norio Akuta, Satoshi Saitoh, Fumitaka Suzuki, Yoshiyuki Suzuki, Yasuji Arase, Hiromitsu Kumada
Aim: We analyzed the effectiveness of external particle radiotherapy (PRT) as an alternative therapy for various stages of hepatocellular carcinoma (HCC). Methods: Eighty-three patients with HCC underwent PRT in our hospital from 2007 to 2015 (proton beam radiation in 58 patients and carbon ion radiation in 25 patients), including patients with early-stage HCC (single HCC measuring ≤3 cm, Barcelona Clinic Liver Cancer [BCLC] stage 0 or A) (group A, n = 30), those with intermediate-stage HCC (HCCs measuring ≥3 cm but inoperable or multinodular and transcatheter arterial embolization [TACE]-refractory, BCLC stage B) (group B, n = 31), and those with advanced-stage HCC (HCC with portal invasion or extrahepatic metastasis) (group C, n = 22)...
October 2018: Liver Cancer
L W Guo, G L Shao, J Luo, W Y Hao, Z Yao, J P Zheng
Objective: To detect the expression level of YES-associated protein 1 (YAP) in hepatocellular carcinoma (HCC) cell lines and investigate its effects on the proliferation activity and the sensitivity to sorafenib in HCC cells. Methods: Western blot was used to detect the protein expression levels of YAP in SMMC-7721, SK-Hep-1, HepG-2, Huh7 and the normal liver cell line L-O2. YAP specific small interfering RNA (si-YAP) or YAP expression plasmid were transfected in SK-Hep-1 or Huh7 cells, respectively. Cell counting kit-8 (CCK-8) test was used to detect the cell proliferation activity and the cell cycle test was conducted by flow cytometry...
November 23, 2018: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
Gihan Hamdy Elsisi, Yousery Nada, Noha Rashad, João Carapinha
Background In light of constrained budgets and the need to fund efficient treatment options, this study set out to assess the cost-effectiveness of sorafenib as a first-line treatment of hepatocellular carcinoma (HCC) compared to best supportive care (BSC) from the military hospital perspective in Egypt. Methods A decision analytic Markov model simulated disease progression with clinical parameters and utility values derived from published data. Data on direct medical costs were collected from the local health care system or payer...
November 27, 2018: Journal of Medical Economics
Lijuan Zhang, Shuping Li, Rong Wang, Changyuan Chen, Wen Ma, Hongyi Cai
Sorafenib is a standard targeted drug used to treat hepatocellular carcinoma (HCC). Notably, cytokine has been found to further enhance the therapeutic effectiveness of the targeted drug. Thereby, the aim of this study is to verify whether cytokine IL-2 could increase the anti-cancer effects of sorafenib on liver cancer in vitro. Huh7 cells were used in the present study and the cell apoptosis and migration were determined in response to sorafenib treatment. Then, siRNA and pathway blocker were used to determine the molecular mechanisms by which IL-2 enhance the therapeutic effectiveness of Huh7 liver cancer cell in vitro...
November 23, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Lucas Tricoli, Suresh Niture, Uche Chimeh, Deepak Kumar
Hepatocellular Carcinoma (HCC) is a leading cause of cancer related death worldwide with a relatively poor survival rate. Aside from liver resection and subsequent transplant, the most effective and leading curative measure for HCC is the chemotherapeutic, sorafenib, a multi-kinase inhibitor used for treatment of late stage HCC. However, the effects of sorafenib are short lived due to the liver's rapid acquisition of Multi-Drug Resistance (MDR). MicroRNAs (miRNAs) have emerged as critical regulatory molecules for almost every biochemical pathway in an organism...
January 1, 2019: Frontiers in Bioscience (Landmark Edition)
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