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hepatocellular carcinoma recent advances

Sunyoung Lee, Matthew Loecher, Renuka Iyer
Hepatocellular carcinoma (HCC) is the fastest growing malignancy in the United States in relation to mortality. HCC relies on a complex immunosuppressive network to modify the host immune system and evade destruction. Intrinsic to the liver's function and anatomy, native hepatic and immune cells produce many inhibitory cytokines that promote tolerogenicity and limit immune response. Since the introduction of sorafenib in 2008, no treatment has been able to demonstrate improved survival in patients with advanced HCC post disease progression treated with sorafenib...
February 2018: Journal of Gastrointestinal Oncology
Julian A Gingold, Dandan Zhu, Dung-Fang Lee, Ahmed Kaseb, Jian Chen
Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), the two most common primary liver cancers, represent the second most common cancer-related cause of death worldwide, with most cases being diagnosed at an advanced stage. Recent genome-wide studies have helped to elucidate the molecular pathogenesis and genetic heterogeneity of liver cancers. This review of the genetic landscape of HCC and iCCA discusses the most recent findings from genomic profiling and the current understanding of the pathways involved in the initiation and progression of liver cancer...
March 9, 2018: Trends in Molecular Medicine
Jean-Charles Nault, Peter R Galle, Jens U Marquardt
Hepatocellular carcinomas (HCC) are characterized by considerable phenotypic and molecular heterogeneity. Treatment and design of clinical trials are particularly challenging due a co-existing liver disease present in the majority of patients which limits aggressive therapeutic options. Despite positive results in recent phase III clinical trials, that confirmed the high value of antiangiogenic therapies for HCC in both first (sorafenib and lenvatinib) and second line (regorafenib and cabozantinib) treatment modalities, failure of several large randomized controlled clinical trials over the last 10 years underlines the necessity for innovative treatment strategies and implementation of findings from translational studies to overcome this unmet clinical need...
March 2, 2018: Journal of Hepatology
Akiyoshi Ogino, Tatsuo Hirai, Toru Serizawa, Atsuo Yoshino
BACKGROUND: Brain metastases from hepatocellular carcinoma (HCC) are rare, but their incidence is increasing because of developments in recent therapeutic advances. The purpose of this study was to investigate the characteristics of brain metastases from HCC, to evaluate the predictive factors, and to assess the efficacy of gamma knife surgery (GKS). METHOD: A retrospective study was performed on patients with brain metastases from HCC who were treated at Tokyo Gamma Unit Center from 2005 to 2014...
March 2, 2018: Acta Neurochirurgica
Zhuo Yu, Hai Feng, Xuehua Sun, Yunhui Zhuo, Man Li, Zhenhua Zhou, Lingying Huang, Yun Jiang, Xiaojun Zhu, Xin Zhang, Fan Le, Chao Zheng, Alfred Szelok Cheng, Yueqiu Gao
Hepatocellular carcinoma (HCC) is one of the most aggressive malignant tumors, of which treatment options are limited especially in advanced stage. Bufalin, the major digoxin-like component of the traditional Chinese medicine Chansu, exhibits significant antitumor activities in hepatoma cells, but the potential mechanism is obscure. Cell cycle-related kinase (CCRK) is recently identified to be a crucial oncogenic master regulator to drive hepatocarcinogenesis. Here we investigated the molecular function of bufalin on CCRK-regulated signaling pathway, and expounded the underlying mechanism in HCC suppression...
March 1, 2018: Scientific Reports
Jingcheng Wang, Tian Yang, Hui Chen, Hui Li, Shusen Zheng
As the sixth most prevalent cancer, hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Human replication protein A (RPA), a three-subunit protein, plays a central role in eukaryotic DNA replication, homologous recombination, and excision repair, including RPA1, RPA2 and RPA3. Recently, some studies focusing on the relation between RPA1 and carcinogenesis have demonstrated that RPA1 is a candidate oncogene and influences tumor biological behaviors in many cancers such as esophageal carcinoma, colon cancer, urothelial carcinomas, etc...
February 22, 2018: Biochemical and Biophysical Research Communications
Eiichiro Suzuki, Shuichi Kaneko, Takuji Okusaka, Masafumi Ikeda, Kensei Yamaguchi, Rie Sugimoto, Takeshi Aramaki, Akinori Asagi, Kohichiroh Yasui, Keiji Sano, Ayumu Hosokawa, Naoya Kato, Hiroshi Ishii, Tosiya Sato, Junji Furuse
Objective: To evaluate prospectively the efficacy and safety of sorafenib, which has been the first-line treatment for advanced hepatocellular carcinoma (HCC), in Japanese HCC patients (pts) with not only Child-Pugh (C-P) A class but also C-P B class. Methods: Sorafenib was administered orally at the dose of 400 mg twice daily for pts with HCC and liver function of C-P score of 5-8. Administration was continued until the detection of disease progression or appearance of unacceptable toxicity...
February 21, 2018: Japanese Journal of Clinical Oncology
Gadi Lalazar, Sanford M Simon
Fibrolamellar hepatocellular carcinoma (FLC) is a rare form of primary liver cancer that affects adolescents and young adults without underlying liver disease. Surgery remains the mainstay of therapy; however, most patients are either not surgical candidates or suffer from recurrence. There is no approved systemic therapy and the overall survival remains poor. Historically classified as a subtype of hepatocellular carcinoma (HCC), FLC has a unique clinical, histological, and molecular presentation. At the genomic level, FLC contains a single 400kB deletion in chromosome 19, leading to a functional DNAJB1-PRKACA fusion protein...
February 2018: Seminars in Liver Disease
Zhangang Xiao, Jing Shen, Lin Zhang, Mingxing Li, Wei Hu, Chihin Cho
Due to the high mortality rate and unsatisfactory treatment options available, hepatocellular carcinoma (HCC) remains one of the most common malignancies and a leading cause of cancer-associated mortality. Novel therapeutic targets for HCC are urgently required. Advanced RNA sequencing technology enables the identification of considerable amounts of noncoding RNAs (ncRNAs), including small noncoding RNAs and long noncoding RNAs, which exhibit no protein-coding activities. In this respect, ncRNAs and their regulatory processes are important factors in liver tumorigenesis...
March 2018: Oncology Letters
Thomas T DeLeon, Daniel H Ahn, James M Bogenberger, Panos Z Anastasiadis, Mansi Arora, Ramesh K Ramanathan, Bashar A Aqel, George Vasmatzis, Mark J Truty, Rahmi Oklu, Tanios S Bekaii-Saab, Mitesh J Borad
Worldwide hepatobiliary cancers are the second leading cause of cancer related death. Despite their relevance, hepatobiliary cancers have a paucity of approved systemic therapy options. However, there are a number of emerging therapeutic biomarkers and therapeutic concepts that show promise. In hepatocellular carcinoma, nivolumab appears particularly promising and recently received US FDA approval. In intrahepatic cholangiocarcinoma, therapies targeting FGFR2 and IDH1 and immune checkpoint inhibitors are the furthest along and generating the most excitement...
February 20, 2018: Future Oncology
Weijing Sun, Roniel Cabrera
To date, sorafenib, a multiple tyrosine kinase inhibitor, is the only systemic agent approved by the FDA in the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). Several other tyrosine kinase-inhibiting agents have been investigated in the first-line setting, either alone (sunitinib, brivanib, linifanib, and lenvatinib) or in combination with sorafenib (erlotinib and doxorubicin) in phase 3 trials. However, none of these studies demonstrated an improvement in survival over sorafenib...
February 17, 2018: Journal of Gastrointestinal Cancer
Bruno Roche, Audrey Coilly, Jean Charles Duclos-Vallee, Didier Samuel
Hepatitis C virus infection is a major cause of chronic hepatitis resulting in cirrhosis and hepatocellular carcinoma (HCC). The recent introduction of direct acting antivirals (DAA), results in sustained virological response (SVR) rates of >90% in treated patients whatever the stage of liver fibrosis with an excellent safety profile. This major advancement has allowed treatment of a larger number of patients, some with more advanced liver dysfunction and a higher risk of HCC. An SVR is associated with a reduced risk of hepatic decompensation, the need for liver transplantation and both liver-related and overall mortality...
February 2018: Liver International: Official Journal of the International Association for the Study of the Liver
Peter Dietrich, Kim Freese, Abdo Mahli, Wolfgang Erwin Thasler, Claus Hellerbrand, Anja Katrin Bosserhoff
Inhibition of RAS-RAF-ERK-signaling is a major mechanism mediated by the multi-kinase inhibitors sorafenib and regorafenib, the only effective therapeutic approaches for advanced hepatocellular carcinoma (HCC). This underlines the importance of RAS-RAF-ERK-signaling in HCC. Most RAS isoforms were not yet described to play crucial roles in HCC. However, several studies indicate that the HRAS isoform can function as potent oncogene in HCC, but pharmacologic RAS inhibition has not yet been investigated. Moreover, the cell cycle promoting polo-like kinase 1 (PLK1) is an increasingly recognized therapeutic target in HCC that can be activated by RAS-RAF-signaling...
January 9, 2018: Oncotarget
Jihyun Kwon, Youngil Koh, Su Jong Yu, Jung-Hwan Yoon
INTRODUCTION: Portal vein thrombosis (PVT) is a well-known complication in patients with liver cirrhosis (LC). The aim of this study is to investigate the outcomes of cirrhotic patients with PVT treated with low-molecular-weight heparin (LMWH). METHOD: Ninety-one LC patients with PVT were treated with dalteparin or enoxaparin for six months. Patients with major bleeding during the last three months, severe thrombocytopenia, or impaired renal function were excluded...
February 1, 2018: Thrombosis Research
Marc Najjar, Surbhi Agrawal, Jean C Emond, Karim J Halazun
Hepatocellular carcinoma (HCC) is the most common liver malignancy and the third most common cause of cancer-related deaths. Liver resection (LR) and liver transplantation (LT) are the only curative modalities for HCC. Despite recent advances and the adoption of the Milan and University of California, San Francisco, criteria, HCC recurrence after LR and LT remains a challenge. Several markers and prognostic scores have been proposed to predict tumor aggressiveness and supplement radiological data; among them, neutrophil-lymphocyte ratio (NLR) has recently gained significant interest...
2018: Journal of Hepatocellular Carcinoma
Lohit Khera, Catherine Paul, Rajeev Kaul
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer associated deaths. The prognosis is relatively poor in cases where Hepatitis C Virus (HCV) is associated as its causative agent mainly due to increased risk of metastasis. Tumor metastasis can be defined as the transfer of cancer from one organ to another which is not directly connected to it. Metastasis is the major cause of all cancer related deaths. HCV infection is associated with expression of multiple pro-metastatic factors in HCC patients...
January 28, 2018: Current Drug Metabolism
Kimberley D Bruce, Karen R Jonscher
Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide and is present in a third of the general population and the majority of individuals with obesity and type 2 diabetes. Importantly, NAFLD can progress to severe nonalcoholic steatohepatitis (NASH), associated with liver failure and hepatocellular carcinoma. Recent research efforts have extensively focused on identifying factors contributing to the additional "hit" required to promote NALFD disease progression...
2018: Methods in Molecular Biology
Song Feng, Lu Gao, Xinchun Han, Taishan Hu, Yimin Hu, Haixia Liu, Andrew William Thomas, Zhipeng Yan, Song Yang, John A T Young, Hongying Yun, Wei Zhu, Hong C Shen
The chronic infection of hepatitis B virus (HBV) inflicts 250 million people worldwide representing a major public health threat. A significant sub-population of chronically infected HBV patients eventually develop cirrhosis and hepatocellular carcinoma (HCC) which aggravate the issues caused by hepatitis alone. Unfortunately, none of the current standard therapies for chronic Hepatitis B (CHB) result in a satisfactory clinical cure rate. Driven by a highly unmet medical need for novel and more effective treatments of HBV infection, multiple pharmaceutical companies and research institutions have been engaged in drug discovery and development to improve the CHB functional cure rate, which is defined by sustainable viral suppression and HBsAg clearance after a finite treatment...
January 25, 2018: ACS Infectious Diseases
Lu Gan, Zhenjiang Liu, Chao Sun
Hepatocellular carcinoma (HCC) is the commonest primary liver cancer and the second leading cause of cancer death worldwide. Obesity is rapidly becoming pandemic and associated with increased carcinogenesis. In this review, we describe the obesity-related factors that influence the development of HCC. We provide evidence of strong links between neural regulation, endocrine and HCC in obesity. We discuss recent advances in our understanding of how adipose tissue alters hepatic metabolism and immune response in HCC development through inter-organ communication...
January 20, 2018: Biochimica et Biophysica Acta
Felix Krenzien, Moritz Schmelzle, Benjamin Struecker, Nathanael Raschzok, Christian Benzing, Maximilian Jara, Marcus Bahra, Robert Öllinger, Igor M Sauer, Andreas Pascher, Johann Pratschke, Andreas Andreou
BACKGROUND: Both liver transplantation (LT) and liver resection (LR) represent curative treatment options for hepatocellular carcinoma (HCC) in patients with liver cirrhosis. In this study, we have compared outcomes between historical and more recent patient cohorts scheduled either for LT or LR, respectively. METHODS: Clinicopathological data of all patients with HCC and cirrhosis who underwent LT or LR between 1989 and 2011 were evaluated. Overall survival of patients with HCC within the Milan criteria (MC) was analyzed focusing on changes between different time periods...
January 23, 2018: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
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