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Yawei Li, Tiantian Zhang, Shukui Qin, Rui Wang, Yumei Li, Zhengguang Zhou, Yufo Chen, Qiong Wu, Fang Su
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. It has been reported that HCC has a poor prognosis. In the majority of cases, once metastatic, HCC is incurable. To identify an effective treatment for HCC, it is important to understand the underlying molecular mechanisms of HCC‑associated occurrence, proliferation, metastasis and carcinogenesis. In the present study, the role of Up‑frameshift 1 (UPF1), a potential tumor suppressor, was investigated in the HCC cell lines...
January 10, 2019: Molecular Medicine Reports
Yen-Tze Liu, Ming-Ju Hsieh, Jen-Tsun Lin, Gene Chen, Chia-Chieh Lin, Yu-Sheng Lo, Yi-Ching Chuang, Yi-Ting Hsi, Mu-Kuan Chen, Ming-Chih Chou
The incidence of oral cancer is increasing all over the world, with rates particularly high in Southeast Asian countries, such as Taiwan. Coronarin D (CD) has been confirmed to have anti-inflammatory, anti-bacterial effects, and anti-apoptotic effects in human hepatocellular carcinoma and nasopharyngeal carcinoma. The purpose of this study is to explore whether CD has a suppression effect on oral cancer cells and the mechanisms involved. The results of our study revealed the significantly decreased cancer cell viability and increased activation of apoptosis via increased loss of mitochondrial membrane potential, increased death receptors, leading to the activation of caspase-8, -9, -3...
January 9, 2019: Environmental Toxicology
Fabia de Oliveira Andrade, Kelly Silva Furtado, Renato Heidor, Silvana Sandri, Cristina Bichels Hebeda, Mayara Lilian Paulino Miranda, Laura Helena Gasparini Fernandes, Roberto Carvalho Yamamoto, Maria Aderuza Horst, Sandra Helena Poliselli Farsky, Fernando Salvador Moreno
Agents that inhibit angiogenic factors may prevent the development of hepatocellular carcinoma. Thus, the objective of this study was to kinetically evaluate the anti-angiogenic activity of tributyrin (TB), a butyric acid prodrug, in the promotion stage of hepatocarcinogenesis. For this purpose, the resistant hepatocyte model was used for induction of preneoplastic lesions in Wistar rats. During the promotion phase, the animals received TB or maltodextrin (MD) as control daily. The rats were euthanized at three different time-points (P1, P2, P3)...
December 24, 2018: Carcinogenesis
Yuying Liu, Hui Zhu, Zhenxue Zhang, Changchun Tu, Dongyuan Yao, Bin Wen, Ru Jiang, Xing Li, Pengfei Yi, Jiejie Zhan, Jiaping Hu, Jianwu Ding, Liping Jiang, Fanglin Zhang
Tumor suppressor genes (TSGs), including Ten-eleven translocation 1 (TET1), are hypermethylated in hepatocellular carcinoma (HCC). TET1 catalytic domain (TET1-CD) induces genome-wide DNA demethylation to activate TSGs, but so far, anticancer effects of TET1-CD are unclear. Here we showed that after HCC cells were transiently transfected with TET1-CD, the methylation levels of TSGs, namely APC, p16, RASSF1A, SOCS1 and TET1, were distinctly reduced, and their mRNA levels were significantly increased and HCC cells proliferation, migration and invasion were suppressed, but the methylation and mRNA levels of oncogenes, namely C-myc, Bmi1, EMS1, Kpna2 and c-fos, were not significantly change...
2018: PloS One
Bijay Dhungel, Charmaine A Ramlogan-Steel, Jason C Steel
In hepatocellular carcinoma (HCC), which usually develops in a cirrhotic liver, treatments preserving normal liver function and viability are vitally important. Here, we utilise the differential expression of miRNAs 122a and 199a between normal hepatocytes and HCC to generate vectors harbouring their binding sites for hepatocyte detargeting. Using a reporter gene, we observed a synergistic detargeting of cells expressing both miRNAs as well as cells expressing either of the miRNAs; while expression was retained in HCC cells negative for both miRNA122a and miRNA199a...
October 19, 2018: Scientific Reports
Sanghoon Lee, Ping Zhou, Anita Gupta, Soona Shin
While reactive ductules (RDs) have been observed in viral hepatitis, biliary atresia, nonalcoholic fatty liver disease, and adult hepatocellular carcinoma (HCC), RDs in pediatric liver cancer remain uncharacterized. This study investigated the relationship of RDs with angiogenic paracrine factors, the extent of angiogenesis, and tumor cell proliferation in pediatric hepatoblastoma (HBL)/HCC livers. We quantified the extent of RDs and their expression of paracrine factors that include vascular endothelial growth factor (VEGF), vascular endothelial growth factor D (VEGFD), platelet-derived growth factor C, and angiopoietin 1 (ANGPT1)...
October 2018: Hepatology communications
Hao Cai, Bo-Gen Ye, Jian-Yang Ao, Xiao-Dong Zhu, Yuan-Yuan Zhang, Zong-Tao Chai, Cheng-Hao Wang, Hui-Chuan Sun
The S100 protein family is widely involved in the pathological process of various types of cancer. However, the prognostic value of the S100 protein family member S100A12 in hepatocellular carcinoma (HCC) remains unknown. A total of 139 patients undergoing curative surgical resection for HCC from December 2005 to June 2006 were investigated. Immunohistochemistry of S100A12 tissue was performed and expression was classified according to the total positive staining area. Co-expression of S100A12 with cluster of differentiation (CD)11B, CD15 and CD68 was evaluated using immunofluorescence...
October 2018: Oncology Letters
Bijay Dhungel, Charmaine A Ramlogan-Steel, Christopher J Layton, Jason C Steel
A gene therapeutic platform needs to be both efficient and safe. The criterion of safety is particularly important for diseases like hepatocellular carcinoma (HCC), which develop in a background of an already compromised liver. Gene vectors can be constructed either by targeting HCC or by detargeting liver and/or other major organs. miRNA-based negative detargeting has gained considerable attention in recent times due to its effectiveness and the ease with which it can be adapted into current gene delivery vectors...
August 24, 2018: Molecular Therapy. Nucleic Acids
Adianto Nugroho, Kwang-Woong Lee, Kyung-Bun Lee, Hyo-Shin Kim, Hyeyoung Kim, Nam-Joon Yi, Kyung-Suk Suh
The incidence of combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CC) in a single patient accounts for only 0.4 to 14% of all primary liver cancer. However, the prognosis of its intrahepatic cholangiocarcinoma (ICC) component is poor. We experienced a unique case of a sequentially developed cHCC-CC with adrenal metastasis as the primary presentation and a hidden primary hepatocellular carcinoma. A 65-year-old female with a history of jaundice and abdominal discomfort was diagnosed with S4 ICC measuring 5 cm in diameter, and characterized histologically as papillary adenocarcinoma with intraductal growth, but without any evidence of malignant hepatocyte...
August 2018: Annals of Hepato-Biliary-Pancreatic Surgery
Lin Zhou, Li-Chao Pan, Yong-Gen Zheng, Guo-Sheng Du, Xiao-Qian Fu, Zhi-Dong Zhu, Ji-Yong Song, Zhi-Jia Liu, Xiang-Zheng Su, Wen Chen, De-Hua Zheng, Long-Long Suo, Shao-Zhen Yang
Although liver transplantation (LT) lengthens the survival time of patients with hepatocellular carcinoma (HCC), LT patients exhibit a high recurrence rate; particularly those that had advanced HCC associated with the tumor biological characteristics and long-term application of immunosuppressants. A consensus on optimal prophylaxis and treatment for recurrent HCC following LT does not currently exist. The present study retrospectively analyzed data from 36 non-University of California at San Francisco criteria-eligible patients with advanced HCC who underwent LT, and then treated them with sirolimus (SRL)-based therapy with thymalfasin and huaier granules (SRL+, n=18), or with tacrolimus-based therapy (controls; n=18)...
October 2018: Oncology Letters
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
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