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Guozhen Cui, Robert C Martin, Hang Jin, Xingkai Liu, Harshul Pandit, Hengjun Zhao, Lu Cai, Ping Zhang, Wei Li, Yan Li
BACKGROUND: Upregulated fibroblast growth factor 19 (FGF19) expression in human hepatocellular carcinoma (HCC) specimens is associated with tumor progression and poor prognosis. Nonalcoholic steatohepatitis (NASH) patients are at high risk for malignant transformation into HCC. METHODS: A steatohepatitis-HCC model was established in male C57L/J mice treated with N-nitrosodiethylamine (DEN) and high-fat diet (HFD). A mouse HCC cell line (Hepa1-6) and a mouse hepatocyte line (FL83B) were used to elucidate the mechanism by free fatty acids (FFA) treatment...
July 4, 2018: Journal of Experimental & Clinical Cancer Research: CR
Heba A Metwaly, Amal M El-Gayar, Mamdouh M El-Shishtawy
AIM OF WORK: The study was conducted for evaluation of the antitumor activity of SSTN92-119 against HCC induced by thioacetamide in rats. METHODS: Sixty male Sprague-Dawley rats were randomized into four equal groups: Control, SSTN92-119 , HCC, and HCC + SSTN92-119 . Liver function tests were measured in serum. Liver homogenate was used for determination of: i) integrinαѴβ3 (ITGαѴβ3), insulin like growth factor-1 receptor (IGF-1R), vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2) and alpha-fetoprotein (AFP) levels by ELISA, ii) syndecan-1 (CD-138), IGF-1R and VEGF genes expressions by qRT-PCR, iii) MDA, NO, GSH concentrations and SOD activity...
August 15, 2018: Archives of Biochemistry and Biophysics
Bijay Dhungel, Charmaine A Ramlogan-Steel, Christopher J Layton, Jason C Steel
In this study, we report a miRNA122a based targeted gene therapy for hepatocellular cancer stem cells (CSCs). First, we assessed the levels of miRNA122a in normal human hepatocytes, a panel of hepatocellular carcinoma (HCC) cell lines and hepatocellular CSCs observing its significant downregulation in HCC and CSCs. The miRNA122a binding site was then incorporated at the 3'-UTR of reporter genes gaussia luciferase (GLuc) and eGFP which resulted in significant hepatocyte detargeting. Using this strategy for the delivery of gene directed enzyme prodrug therapy (GDEPT) utilizing the cytosine deaminase/5-fluorocytosine (CD/5-FC) system, we showed significant killing in cells with low or no miRNA122a while those cells, such as hepatocytes with high miRNA122a were largely spared...
May 4, 2018: Oncotarget
Jong Bin Kim, Seulki Lee, Hye Ri Kim, Seo-Young Park, Minjong Lee, Jung-Hwan Yoon, Yoon Jun Kim
Hepatocellular carcinoma (HCC) can result from hepatitis B or C infection, fibrosis or cirrhosis. Transforming growth factor-β (TGF-β) is one of the main growth factors associated with fibrosis or cirrhosis progression in the liver, but its role is controversial in hepatocarcinogenesis. In the present study, the effect of TGF-β on the HCC Huh-7 and Huh-Bat cell lines was evaluated. To study the effect of TGF-β, Huh-7 and Huh-Bat cells were treated with TGF-β and a TGF-β receptor inhibitor (SB431542). Cell survival, cell cycle, numbers of side population (SP) cells and expression of the cancer stem cell marker cluster of differentiation (CD)133, epithelial-mesenchymal transition markers (E-cadherin, α-smooth muscle actin and vimentin) and TGF-β-regulated proteins [phospho-c-Jun N-terminal kinase (p-JNK), p-c-Jun and p-smad2] were investigated...
June 2018: Oncology Letters
Koji Minami, Kiyokazu Hiwatashi, Shinichi Ueno, Masahiko Sakoda, Satoshi Iino, Hiroshi Okumura, Motoyuki Hashiguchi, Yota Kawasaki, Hiroshi Kurahara, Yuko Mataki, Kosei Maemura, Hiroyuki Shinchi, Shoji Natsugoe
Cluster of differentiation (CD)68 may be used as a pan-macrophage or M1 marker, whereas CD163 may be used as an M2 marker. Furthermore, folate receptor (FR)β exhibits an M2-like functional profile. In the present study, CD68 and CD163 were used to evaluate and classify tumor-associated macrophages (TAMs). The expression of CD68, CD163 and FRβ by TAMs in hepatocellular carcinoma (HCC) Tissues was investigated. Samples from 105 patients with HCC were evaluated using immunohistochemistry. The results revealed that CD68 and CD163 overexpression was associated with a worse prognosis...
May 2018: Experimental and Therapeutic Medicine
Bijay Dhungel, Slawomir Andrzejewski, Aparna Jayachandran, Ritu Shrestha, Charmaine A Ramlogan-Steel, Christopher J Layton, Jason C Steel
Hepatocellular carcinoma (HCC) is a major health problem as evidenced by its increasing incidence and high morbidity and mortality rates. Most patients with HCC have underlying liver disease and dysfunction which limits the current therapeutic options. Treatments that spare the liver and destroy the HCC are needed. Targeting transcriptional differences between HCC and liver cells may provide this therapeutic window. In this study, we examine the potential of the Glypican 3 (GPC3) promoter as a targeting strategy...
April 2018: Gene Therapy
Zhengxi Wei, Zhongguo Shan, Zahir A Shaikh
Epidemiological and experimental studies have implicated cadmium (Cd) with breast cancer. In breast epithelial MCF10A and MDA-MB-231 cells, Cd has been shown to promote cell growth. The present study examined whether Cd also promotes epithelial-mesenchymal transition (EMT), a hallmark of cancer progression. Human breast epithelial cells consisting of non-cancerous MCF10A, non-metastatic HCC 1937 and HCC 38, and metastatic MDA-MB-231 were treated with 1 or 3 μM Cd for 4 weeks. The MCF10A epithelial cells switched to a more mesenchymal-like morphology, which was accompanied by a decrease in the epithelial marker E-cadherin and an increase in the mesenchymal markers N-cadherin and vimentin...
April 1, 2018: Toxicology and Applied Pharmacology
Qingqing Xiong, Mangmang Cui, Ge Yu, Jian Wang, Tianqiang Song
Combination of doxorubicin with sorafenib (SF) was reported to be a promising strategy for treating hepatocellular carcinoma (HCC). In this study, we designed a reduction-responsive supramolecular nanosystem based on poly (ethylene glycol)-β-cyclodextrin (PEG-CD) and a disulfide-containing adamantine-terminated doxorubicin prodrug (AD) for efficient co-delivery of doxorubicin and sorafenib. PEG-CD/AD supramolecular amphiphiles were formed through host-guest interaction between cyclodextrin and adamantine moieties, and then self-assembled into regular spherical nanoparticles with a uniform size of 166...
2018: Frontiers in Pharmacology
Qingyu Xu, Junfei Gu, You Lv, Jiarui Yuan, Nan Yang, Juan Chen, Chunfei Wang, Xuefeng Hou, Xiaobin Jia, Liang Feng, Guowen Yin
Tumor vascular normalization involved in immune response is beneficial to the chemotherapy of tumors. Recombinant human endostatin (Endostar), an angiogenesis inhibitor, has been demonstrated to be effective in hepatocellular cancer (HCC). However, its vascular normalization in HCC and the role of the immune response in angiogenesis were unclear. In the present study, effects of Endostar on tumor vascular normalization were evaluated in hepatoma 22 (H22) tumor-bearing mice. Endostar was able to inhibit the proliferation and infiltration of tumor cells and improve α-fetoprotein, tumor necrosis factor-α and cyclic adenosine 5'-phosphate levels in the serum of H22-bearing mice, as well as the protein expression levels of the immune factors interferon-γ and cluster of differentiation (CD)86 in liver tissue...
March 2018: Oncology Letters
Zhen Kang, Enhua Xiao
Cluster of differentiation (CD)151, a member of tetraspanin family, is considered to be the first tetraspanin to be associated with tumor metastasis. Previous studies in vivo , in vitro and in the clinic have demonstrated that CD151 is involved in tumor progression at different levels through interaction with integrins, growth factor receptors and matrix metalloproteinases. Transcatheter arterial chemoembolization (TACE) is widely recommended for the treatment of patients with advanced hepatocellular carcinoma (HCC) worldwide...
January 2018: Oncology Letters
Chunying Shi, Yu Zhang, Haichao Yang, Tianxiu Dong, Yaodong Chen, Yutong Xu, Xiuhua Yang, Pengfei Liu
The aim of the present study was to investigate the effect of Forkhead family transcription factor P3 (Foxp3) knockdown on the function of cluster of differentiation (CD)4+ CD25+ regulatory T cell (Tregs) and the tumor growth of a hepatocellular carcinoma (HCC) mouse model. CD4+ CD25+ Tregs and CD4+ CD25- T cells were sorted from peripheral blood mononuclear cells (PBMCs) of patients with HCC. Then, ultrasound-targeted microbubble destruction (UTMD)-mediated Foxp3-microRNA (miRNA) was transfected into Tregs...
January 2018: Experimental and Therapeutic Medicine
Ketao Zhang, Siyao Che, Zheng Su, Shangyou Zheng, Huayao Zhang, Shanglin Yang, Wenda Li, Jianping Liu
Cluster of differentiation (CD)90 (Thy‑1) was proposed as a marker for the liver cancer stem cells that are responsible for tumorigenic activity, however its involvement in the progression of hepatocellular carcinoma (HCC) remains unknown. The aim of the present study was to determine the effect of CD90 on the biological functions of HCC and to investigate the associated circular RNA (circRNA) involved in this process. The analysis of the in vitro data demonstrated that CD90+ cells isolated from SK‑Hep‑1 cells exhibited increased viability, migration and invasive abilities compared with CD90‑ cells...
February 2018: International Journal of Molecular Medicine
Jun Hou, Zhixian Hong, Fan Feng, Yantao Chai, Yunkai Zhang, Qiyu Jiang, Yan Hu, Shunquan Wu, Yingsong Wu, Xunian Gao, Qiong Chen, Yong Wan, Jingfeng Bi, Zheng Zhang
BACKGROUND: Patients suffering from advanced stage hepatocellular carcinoma (HCC) often exhibit a poor prognosis or dismal clinical outcomes due to ineffective chemotherapy or a multi-drug resistance (MDR) process. Thus, it is urgent to develop a new chemotherapeutic sensitivity testing system for HCC treatment. The presence study investigated the potential application of a novel chemotherapeutic sensitivity-testing system based on a collagen gel droplet embedded 3D-culture system (CD-DST)...
November 8, 2017: BMC Cancer
Yunpeng Sun, Huanhuan Wu, Gang Chen, Xiaming Huang, Yunfeng Shan, Hongqi Shi, Qiyu Zhang, Yihu Zheng
Regulatory and effector T cells possess immunological cytotoxicity for tumor cells in the tumor microenvironment during tumor progression and are the primary suppressors inhuman cancer therapy. Interleukin‑2 (IL‑2) is an anticancer cytokine, which triggers human innate and adaptive immunity by stimulating T cell propagation and lymphocyte infiltration into tumor sites. IL‑2 has been used successfully for cancer therapy. Recombinant adenovirus expressing IL‑2 (rAd‑IL‑2) injection is a gene therapy agent that may improve prognosis of hepatocellular carcinoma (HCC) patients...
January 2018: Molecular Medicine Reports
Ya-Nan Yan, Ning Wang, Zhuo-Yu Wang, Yao Tian, Yu-Zhen Cheng, Hui-Fang Ma, Zhong-Wei Hou, Jia-Jia Ma, Han-Yu Guan
OBJECTIVE: To observe the effect of moxibustion stimulation of "Ganshu"(BL 18) region on contents of T cells in the peripheral blood in rats with Diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC), so as to explore its effective in improving immunoregulatory function. METHODS: Seventy male Wistar rats were randomly divided into control group ( n =10), model group( n =15), direct moxibustion-15 s group( n =15), direct moxibustion-30 s group ( n =15) and ginger-separated moxibustion group( n =15)...
August 25, 2016: Zhen Ci Yan Jiu, Acupuncture Research
Chun-Yu Huang, Ying Wang, Guang-Yu Luo, Feng Han, Yong-Qiang Li, Zhong-Guo Zhou, Guo-Liang Xu
As PD-1/PD-L1 immune checkpoint inhibitors exhibited promising clinical outcomes in various types of solid tumors, PD-1/PD-L1 blockades have been explored for the treatment of hepatocellular carcinoma (HCC). However, the association of PD-L1 with antitumor immunoregulation is not clearly defined in HCC. Here, we evaluated the characteristics of PD-L1 expression, CD8 T-cell infiltration and their relationship in HCC. A total of 411 resected tumor specimens from HCC patients were immunostained for PD-L1 and CD8...
October 13, 2017: Journal of Immunotherapy
Chun-Yu Huang, Ying Wang, Guang-Yu Luo, Feng Han, Yong-Qiang Li, Zhong-Guo Zhou, Guo-Liang Xu
As PD-1/PD-L1 immune checkpoint inhibitors exhibited promising clinical outcomes in various types of solid tumors, PD-1/PD-L1 blockades have been explored for the treatment of hepatocellular carcinoma (HCC). However, the association of PD-L1 with antitumor immunoregulation is not clearly defined in HCC. Here, we evaluated the characteristics of PD-L1 expression, CD8 T-cell infiltration and their relationship in HCC. A total of 411 resected tumor specimens from HCC patients were immunostained for PD-L1 and CD8...
November 2017: Journal of Immunotherapy
Kui Chen, Avrilynn Ding, Yu Ding, Anand Ghanekar
Hepatocellular carcinoma (HCC) remains a common and lethal cancer. Cancer stem cells, or tumor-initiating cells (TICs), are thought to contribute to the pathogenesis of HCC, but remain to be fully characterized. Unbiased screens of primary human HCC cells for the identification of novel HCC TIC markers have not been reported. We conducted high-throughput flow cytometry (HT-FC) profiling to characterize the expression of 375 CD antigens on tumor cells from 10 different human HCC samples. We selected 91 of these for further analysis based on HT-FC data that showed consistent expression in discrete, rare, sortable populations of HCC cells...
December 2016: Biochemistry and Biophysics Reports
Riccardo Pravisani, Umberto Baccarani, Miriam Isola, Gianluigi Adani, Dario Lorenzin, Giovanni Terrosu, Andrea Risaliti
Surgery-related morbidity has been identified as prognostic risk factor for tumor recurrence for several tumor types, but data regarding hepatocellular carcinoma (HCC) are limited and controversial. The aim of this study was to analyze the impact of surgical complications on the risk of HCC recurrence after hepatic resection (HR). A Retrospective study was conducted on a cohort of patients submitted to HR in a tertiary teaching hospital, between January 2006 and December 2015. 112 patients were submitted to HR during the study period...
March 2018: Updates in Surgery
Harumichi Itoh, Shimpei Nishikawa, Tomoya Haraguchi, Yu Arikawa, Masato Hiyama, Toshie Iseri, Yoshiki Itoh, Munekazu Nakaichi, Yasuho Taura, Kenji Tani, Kazuhito Itamoto
The majority of cases of chemotherapy for hepatocellular carcinoma (HCC) are not effective in human or veterinary medicine due to resistance against anticancer agents. In human medicine, hepatocellular carcinoma stem cells (HCSCs) were recently identified as cytokeratin 19 (CK19)-, cluster of differentiation (CD)-44-, and CD133-positive. However, there are few previous reports regarding canine HCSC (cHCSC). Additionally, to the best of our knowledge, the chemoresistance against anticancer agents of these cHCSCs has not been investigated...
July 2017: Biomedical Reports
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