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Sorafenib in HCC

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https://www.readbyqxmd.com/read/30334999/complete-response-of-hepatocellular-carcinoma-with-right-atrium-and-pulmonary-metastases-treated-by-combined-treatments-a-possible-treatment-effect-of-natural-killer-cell-a-case-report-and-literature-review
#1
Dong Hyun Kim, Eunae Cho, Sung Bum Cho, Sung Kyu Choi, Sunmin Kim, Jieun Yu, Young-Il Koh, Da Woon Sim, Chung Hwan Jun
RATIONALE: Hepatocellular carcinomas (HCCs) with metastases to the right atrium (RA) and lungs are rare, with a poor prognosis. Furthermore, the treatment outcomes in patients with advanced HCCs remain unsatisfactory. PATIENT CONCERNS: A 46-year-old man presented to our hospital for dyspnea on exertion and abdominal pain. DIAGNOSES: HCC and extra-hepatic metastases to the lung and RA. INTERVENTIONS: Multidisciplinary treatment including radiotherapy (RT), transarterial chemoembolization (TACE), and sorafenib...
October 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/30324097/update-on-hepatocellular-carcinoma-from-the-2018-gastrointestinal-cancer-symposium-asco-gi
#2
REVIEW
Victor Hugo Fonseca de Jesus, Aldo Lourenço Abbade Dettino
At the 2018 Gastrointestinal Cancer Symposium, sponsored by the American Society of Clinical Oncology, significant advances in the management of hepatocellular carcinoma (HCC) were announced. In intermediate-stage disease (Barcelona Clinic Liver Cancer stage B), interest in combining transarterial chemoembolization and sorafenib has been reignited as a consequence of the TACTICS trial. In advanced-stage disease (BCLC C), external-beam radiotherapy combined with transarterial chemoembolization proved to be superior to sorafenib in patients with portal vein thrombosis according to the START trial...
2018: Journal of Hepatocellular Carcinoma
https://www.readbyqxmd.com/read/30321984/emodin-sensitizes-hepatocellular-carcinoma-cells-to-the-anti-cancer-effect-of-sorafenib-through-suppression-of-cholesterol-metabolism
#3
Young-Seon Kim, Yoon-Mi Lee, Taek-In Oh, Dong Hoon Shin, Geon-Hee Kim, Sang-Yeon Kan, Hyeji Kang, Ji Hyung Kim, Byeong Mo Kim, Woo Jong Yim, Ji-Hong Lim
Reduced therapeutic efficacy of sorafenib, a first-generation multikinase inhibitor, is often observed during the treatment of advanced hepatocellular carcinoma (HCC). Emodin is an active component of Chinese herbs, and is effective against leukemia, lung cancer, colon cancer, pancreatic cancer, and HCC; however, the sensitizing effect of emodin on sorafenib-based HCC therapy has not been evaluated. Here, we demonstrate that emodin significantly improved the anti-cancer effect of sorafenib in HCC cells, such as HepG2, Hep3B, Huh7, SK-HEP-1, and PLC/PRF5...
October 12, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30315182/sorafenib-resistance-in-hepatocarcinoma-role-of-hypoxia-inducible-factors
#4
REVIEW
Carolina Méndez-Blanco, Flavia Fondevila, Andrés García-Palomo, Javier González-Gallego, José L Mauriz
Sorafenib, a multikinase inhibitor with antiproliferative, antiangiogenic, and proapoptotic properties, constitutes the only effective first-line drug approved for the treatment of advanced hepatocellular carcinoma (HCC). Despite its capacity to increase survival in HCC patients, its success is quite low in the long term owing to the development of resistant cells through several mechanisms. Among these mechanisms, the antiangiogenic effects of sustained sorafenib treatment induce a reduction of microvessel density, promoting intratumoral hypoxia and hypoxia-inducible factors (HIFs)-mediated cellular responses that favor the selection of resistant cells adapted to the hypoxic microenvironment...
October 12, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/30311444/sestrin-2-confers-primary-resistance-to-sorafenib-by-simultaneously-activating-akt-and-ampk-in-hepatocellular-carcinoma
#5
Jimin Dai, Qichao Huang, Kunwei Niu, Bo Wang, Yijie Li, Chen Dai, Zhinan Chen, Kaishan Tao, Jingyao Dai
Hepatocellular carcinoma (HCC) is the malignancy derived from normal hepatocytes with increasing incidence and extremely poor prognosis worldwide. The only approved first-line systematic treatment agent for HCC, sorafenib, is capable to effectively improve advanced HCC patients' survival. However, it is gradually recognized that the therapeutic response to sorafenib could be drastically diminished after short-term treatment, defined as primary resistance. The present study is aimed to explore the role of stress-inducible protein Sestrin2 (SESN2), one of the most important sestrins family members, in sorafenib primary resistance...
October 11, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/30310535/treatment-strategies-for-advanced-hepatocellular-carcinoma-sorafenib-vs-hepatic-arterial-infusion-chemotherapy
#6
REVIEW
Issei Saeki, Takahiro Yamasaki, Masaki Maeda, Takuro Hisanaga, Takuya Iwamoto, Koichi Fujisawa, Toshihiko Matsumoto, Isao Hidaka, Yoshio Marumoto, Tsuyoshi Ishikawa, Naoki Yamamoto, Yutaka Suehiro, Taro Takami, Isao Sakaida
Sorafenib is used worldwide as a first-line standard systemic agent for advanced hepatocellular carcinoma (HCC) on the basis of the results of two large-scale Phase III trials. Conversely, hepatic arterial infusion chemotherapy (HAIC) is one of the most recommended treatments in Japan. Although there have been no randomized controlled trials comparing sorafenib with HAIC, several retrospective analyses have shown no significant differences in survival between the two therapies. Outcomes are favorable for HCC patients exhibiting macroscopic vascular invasion when treated with HAIC rather than sorafenib, whereas in HCC patients exhibiting extrahepatic spread or resistance to transcatheter arterial chemoembolization, good outcomes are achieved by treatment with sorafenib rather than HAIC...
September 27, 2018: World Journal of Hepatology
https://www.readbyqxmd.com/read/30309643/evolving-systemic-therapy-in-hepatocellular-carcinoma-current-management-and-opportunities-for-integration-with-radiotherapy
#7
REVIEW
Florence K Keane, Theodore S Hong, Andrew X Zhu
The majority of patients with hepatocellular carcinoma (HCC) present with advanced disease. While first-line therapy with sorafenib is considered standard of care for patients with advancedHCC, outcomes remain poor. Despite early evidence of antitumor activity from Phase II trials of multiple other tyrosine kinase inhibitors, Phase III trials have largely failed to show an improvement insurvival outcomes over sorafenib. Given the encouraging early results with liver-directed radiotherapy for patients with advanced HCC, there is an increased interest in combination of these therapies tooptimize patient outcomes and improve survival by maximizing both local and distant disease control...
October 2018: Seminars in Radiation Oncology
https://www.readbyqxmd.com/read/30302192/systemic-treatments-for-hepatocellular-carcinoma-challenges-and-future-perspectives
#8
REVIEW
Francesco Tovoli, Giulia Negrini, Francesca Benevento, Chiara Faggiano, Elisabetta Goio, Alessandro Granito
Sorafenib has been the only approved systemic treatment of hepatocellular carcinoma (HCC) for almost a decade. Recently, two new drugs showed positive results in two Phase III studies. The RESORCE trial identified regorafenib as a valid second-line treatment for patients progressing to sorafenib, the REFLECT trial showed that lenvatinib is noninferior to sorafenib as front-line treatment. Following these trials, the therapeutic scenario will be dominated by anti-VEGFR drugs, with three different molecules showing a proven anticancer activity...
January 2018: Hepatic Oncology
https://www.readbyqxmd.com/read/30292139/a-novel-aurora-a-inhibitor-mln8237-synergistically-enhances-the-antitumor-activity-of-sorafenib-in-hepatocellular-carcinoma
#9
Kai Zhang, Ting Wang, Hao Zhou, Bing Feng, Ying Chen, Yingru Zhi, Rui Wang
Currently, sorafenib-based therapy is the standard treatment for advanced hepatocellular carcinoma (HCC), and there is a strong rationale for investigating its use in combination with other agents to achieve better therapeutic effects. Aurora-A, a member of a family of mitotic serine/threonine kinases, is frequently overexpressed in human cancers and therefore represents a target for therapy. Here, we investigated a novel Aurora-A inhibitor, MLN8237, together with sorafenib in HCC cells in vitro and in vivo, and elucidated the possible molecular mechanism...
September 12, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/30287340/ketoconazole-exacerbates-mitophagy-to-induce-apoptosis-by-downregulating-cyclooxygenase-2-in-hepatocellular-carcinoma
#10
Yan Chen, Hai-Ning Chen, Kui Wang, Lu Zhang, Zhao Huang, Jiayang Liu, Zhe Zhang, Maochao Luo, Yunlong Lei, Yong Peng, Zong-Guang Zhou, Yuquan Wei, Canhua Huang
BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a common cancer worldwide and remains a major clinical challenge. Ketoconazole, a traditional antifungal agent, has attracted considerable attention as a therapeutic option for cancer treatment. However, the involved mechanism of action is still not clearly defined. We aimed to evaluate the effect of ketoconazole on HCC and investigate the underlying mechanisms. METHODS: We examined the antitumor effect of ketoconazole on HCC cells, cell line-derived xenografts, and patient-derived xenograft (PDX) model...
October 1, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/30277836/sorafenib-inhibits-caspase-1-expression-through-suppressing-tlr4-stat3-sumo1-pathway-in-hepatocellular-carcinoma
#11
Jun Li, Yuan Zhou, Yang Liu, Bo Dai, Yu-Hen Zhang, Peng-Fei Zhang, Xiao-Lei Shi
Sorafenib has been demonstrated to be a beneficial treatment for advanced hepatocellular carcinoma (HCC). Emerging evidence indicates that caspase-1 activation plays a crucial role in HCC progression. However, the relationship between caspase-1 and sorafenib has rarely been reported. In this study, we showed that caspase-1 was essential for lipopolysaccharide (LPS)-induced epithelial-mesenchymal transition (EMT). Moreover, sorafenib treatment could inhibit LPS-stimulated caspase-1 overexpression through restricting the nuclear transport of p65, which contributed to inactivation of NF-κB...
October 2, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/30272354/capsaicin-and-sorafenib-combination-treatment-exerts-synergistic-anti%C3%A2-hepatocellular-carcinoma-activity-by-suppressing-egfr-and-pi3k-akt-mtor-signaling
#12
Ninggao Dai, Ruifan Ye, Qikuan He, Pengyi Guo, Hao Chen, Qiyu Zhang
Capsaicin (8‑methyl N‑vanillyl‑6 nonenamide) is a natural plant extract that has antitumor properties and induces apoptosis and autophagy in various types of malignancies, including hepatocellular carcinoma (HCC). Sorafenib is a multi‑kinase inhibitor that improves the survival of patients with advanced HCC. In the present study, capsaicin and sorafenib were found to inhibit the growth of LM3, Hep3B and HuH7 cells. In addition, the combination of capsaicin and sorafenib exerted a synergistic inhibitory effect on HCC cell growth...
October 1, 2018: Oncology Reports
https://www.readbyqxmd.com/read/30271172/microrna-140-3p-enhances-the-sensitivity-of-hepatocellular-carcinoma-cells-to-sorafenib-by-targeting-pregnenolone-x-receptor
#13
Jiaqi Li, Jing Zhao, Huan Wang, Xiaohan Li, Aixia Liu, Qin Qin, Boan Li
Background: Pregnane X receptor (PXR), which is a member of the nuclear receptor protein family (nuclear receptor subfamily 1 group I member 2 [NR 1I2]), mediates the drug-resistance in the hepatocellular carcinoma (HCC) via enhancing the expression of drug-resistance-related genes which accelerate the clearance of antitumor drugs, eg, sorafenib. However, there are few reports on miRNA targeting PXR participating in the epigenetic regulation of PXR in HCC cells. Materials and methods: TargetScan 7...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/30271119/fatal-adverse-events-with-molecular-targeted-agents-in-the-treatment-of-advanced-hepatocellular-carcinoma-a-meta-analysis-of-randomized-controlled-trials
#14
Xiaofei Li, Jia Wan, Zhenping Wu, Juncai Tu, Yongtao Hu, Shuang Wu, Lianqing Lou
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...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/30271080/ten-years-of-sorafenib-in-hepatocellular-carcinoma-are-there-any-predictive-and-or-prognostic-markers
#15
REVIEW
Giorgia Marisi, Alessandro Cucchetti, Paola Ulivi, Matteo Canale, Giuseppe Cabibbo, Leonardo Solaini, Francesco G Foschi, Serena De Matteis, Giorgio Ercolani, Martina Valgiusti, Giovanni L Frassineti, Mario Scartozzi, Andrea Casadei Gardini
Sorafenib has been considered the standard of care for patients with advanced unresectable hepatocellular carcinoma (HCC) since 2007 and numerous studies have investigated the role of markers involved in the angiogenesis process at both the expression and genetic level and clinical aspect. What results have ten years of research produced? Several clinical and biological markers are associated with prognosis. The most interesting clinical parameters are adverse events, Barcelona Clinic Liver Cancer stage, and macroscopic vascular invasion, while several single nucleotide polymorphisms and plasma angiopoietin-2 levels represent the most promising biological biomarkers...
September 28, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/30267147/prognostic-factors-of-disease-free-and-overall-survival-in-patients-with-hepatocellular-carcinoma-undergoing-partial-hepatectomy-in-curative-intent
#16
Georg Lurje, Jan Bednarsch, Zoltan Czigany, Iakovos Amygdalos, Franziska Meister, Wenzel Schöning, Tom Florian Ulmer, Martin Foerster, Cornelis Dejong, Ulf Peter Neumann
PURPOSE: Tumor recurrence after liver resection continues to pose a major problem in hepatocellular carcinoma (HCC). Here we aimed to evaluate prognostic markers for disease-free (DFS) and overall survival (OS) in HCC-patients who underwent liver resection in curative intent. Additionally, we investigated the effects of HCC-recurrence in a subgroup of patients. METHODS: Between 2010 and 2016, 111 patients underwent surgical resection for HCC at our institution. A subgroup of 50 patients showed tumor recurrence (n = 50) during follow-up...
September 28, 2018: Langenbeck's Archives of Surgery
https://www.readbyqxmd.com/read/30264594/optimal-management-of-patients-with-hepatocellular-carcinoma-treated-with-lenvatinib
#17
Masafumi Ikeda, Masahiro Kobayashi, Makoto Tahara, Shuichi Kaneko
Lenvatinib, a multi-kinase inhibitor, has demonstrated improved outcomes for patients with hepatocellular carcinoma (HCC) in clinical trials. The phase 3 REFLECT trial confirmed the non-inferiority of lenvatinib to sorafenib for overall survival of HCC patients and indicated clinical benefits in efficacy over sorafenib. Adverse events (AEs) included hypertension, diarrhea, decreased appetite, decreased weight, fatigue, palmar-plantar erythrodysesthesia, and proteinuria. Areas covered: AEs arising in HCC patients during lenvatinib treatment often lead to treatment interruption, dose reduction, or treatment discontinuation...
September 28, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/30256409/comprehensive-treatments-for-hepatocellular-carcinoma-with-portal-vein-tumor-thrombosis
#18
REVIEW
Jin-Cheng Wang, An-Liang Xia, Yong Xu, Xiao-Jie Lu
Portal vein tumor thrombosis (PVTT) is one of the most common complications in hepatocellular carcinoma (HCC). HCC with PVTT usually indicates poor prognosis, which has a number of characteristics including a rapidly progressive disease course, worse liver function, complications connected with portal hypertension, and poorer tolerance to treatment. The exact mechanisms of PVTT remain unknown, even though some concerned signal transduction or molecular pathways have been identified. In western countries, sorafenib is the only recommended therapeutic strategy regardless of PVTT types...
September 6, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/30255136/liver-allograft-failure-after-nivolumab-treatment-a-case-report-with-systematic-literature-research
#19
Dimitri Gassmann, Stefan Weiler, Joachim C Mertens, Cäcilia S Reiner, Bart Vrugt, Mirjam Nägeli, Joanna Mangana, Beat Müllhaupt, Fabienne Jenni, Benjamin Misselwitz
Background: Orthotopic liver transplantation (OLT) is a potential curative treatment in patients with hepatocellular carcinoma (HCC); however, treatment options for recurrent HCC after OLT are limited. Immune checkpoint inhibitors, such as nivolumab, an inhibitor of programmed cell death protein 1, have been successfully used for metastatic HCC but data on safety of nivolumab following solid organ transplantation are limited. Methods: We report a 53-year-old woman with HCC who was treated with OLT...
August 2018: Transplantation Direct
https://www.readbyqxmd.com/read/30244972/inhibition-of-acetyl-coa-carboxylase-by-phosphorylation-or-the-inhibitor-nd-654-suppresses-lipogenesis-and-hepatocellular-carcinoma
#20
James S V Lally, Sarani Ghoshal, Danielle K DePeralta, Omeed Moaven, Lan Wei, Ricard Masia, Derek J Erstad, Naoto Fujiwara, Vivian Leong, Vanessa P Houde, Alexander E Anagnostopoulos, Alice Wang, Lindsay A Broadfield, Rebecca J Ford, Robert A Foster, Jamie Bates, Hailing Sun, Ting Wang, Henry Liu, Adrian S Ray, Asish K Saha, Jeremy Greenwood, Sathesh Bhat, Geraldine Harriman, Wenyan Miao, Jennifer L Rocnik, William F Westlin, Paola Muti, Theodoros Tsakiridis, H James Harwood, Rosana Kapeller, Yujin Hoshida, Kenneth K Tanabe, Gregory R Steinberg, Bryan C Fuchs
The incidence of hepatocellular carcinoma (HCC) is rapidly increasing due to the prevalence of obesity and non-alcoholic fatty liver disease, but the molecular triggers that initiate disease development are not fully understood. We demonstrate that mice with targeted loss-of-function point mutations within the AMP-activated protein kinase (AMPK) phosphorylation sites on acetyl-CoA carboxylase 1 (ACC1 Ser79Ala) and ACC2 (ACC2 Ser212Ala) have increased liver de novo lipogenesis (DNL) and liver lesions. The same mutation in ACC1 also increases DNL and proliferation in human liver cancer cells...
September 19, 2018: Cell Metabolism
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