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Takaaki Higashi, Hiromitsu Hayashi, Yuki Kitano, Kensuke Yamamura, Takayoshi Kaida, Kota Arima, Katsunobu Taki, Shigeki Nakagawa, Hirohisa Okabe, Hidetoshi Nitta, Katsunori Imai, Daisuke Hashimoto, Akira Chikamoto, Toru Beppu, Hideo Baba
Diabetes and obesity are associated with non-alcoholic steatohepatitis and an increased incidence of hepatocellular carcinoma (HCC). TAZ and YAP are equivalently placed downstream effectors of the Hippo pathway with oncogenic roles in human cancers. Statins are commonly used to patients with metabolic problems as hypercholesterolemia. Statins also have anti-cancer properties, and the cross-talk between mevalonate pathway and Hippo pathway was known. The aim of this study is to confirm the statin's anti-cancer effects on HCC cells and its survival benefits in HCC patients with curative surgery...
November 2016: Medical Oncology
Doan Duy Hai Tran, Alexandra Koch, Aldrige Allister, Shashank Saran, Florian Ewald, Martina Koch, Björn Nashan, Teruko Tamura
Over 100 putative driver genes that are associated with multiple recurrently altered pathways were detected in hepatocellular carcinoma (HCC), suggesting that multiple pathways will need to be inhibited for any therapeutic method to be effective. In this context, functional modification of the RNA regulating protein, tristetraprolin (TTP) that regulates approximately 2500 genes represents a promising strategy in HCC therapy. Since overexpression of TTP induces cell death in all cell types, it would be useful to target the regulator of TTP...
December 2016: Cellular Signalling
Shannon H Lacy, Collynn F Woeller, Thomas H Thatcher, Krishna Rao Maddipati, Kenneth V Honn, Patricia J Sime, Richard P Phipps
Human lung fibroblasts (HLFs) act as innate immune sentinel cells that amplify the inflammatory response to injurious stimuli. Here, we use targeted lipidomics to explore the hypothesis that HLFs also play an active role in the resolution of inflammation. We detected cyclooxygenase-2 (COX-2)-dependent production of both pro-inflammatory and pro-resolving prostaglandins (PGs) in conditioned culture medium from HLFs treated with a pro-inflammatory stimulus, IL-1β. Among the pro-resolving PGs in the HLF lipidome were several known ligands for peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor whose activation in the lung yields potent anti-inflammatory, anti-fibrotic and pro-resolving effects...
September 9, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Hui Zhang, Alvin T Kho, Qing Wu, Andrew J Halayko, Karen Limbert Rempel, Robert P Chase, Neil B Sweezey, Scott T Weiss, Feige Kaplan
Chronic lung disease of prematurity/bronchopulmonary dysplasia (BPD) is the leading cause of perinatal morbidity in developed countries. Inflammation is a prominent finding. Currently available interventions have associated toxicities and limited efficacy. While BPD often resolves in childhood, survivors of preterm birth are at risk for acquired respiratory disease in early life and are more likely to develop chronic obstructive pulmonary disease (COPD) in adulthood. We previously cloned Crispld2 (Lgl1), a glucocorticoid-regulated mesenchymal secretory protein that modulates lung branching and alveogenesis through mesenchymal-epithelial interactions...
September 2016: Physiological Reports
Asahiro Morishita, Hisakazu Iwama, Shintaro Fujihara, Teppei Sakamoto, Koji Fujita, Joji Tani, Hisaaki Miyoshi, Hirohito Yoneyama, Takashi Himoto, Tsutomu Masaki
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-associated mortality worldwide. Although surgery is considered the most effective treatment for patients with HCC, its indication is restricted by limited criteria and a high relapse rate following surgery; therefore, systemic chemotherapy is required for patients with advanced-stage HCC to prolong their survival. MicroRNAs (miRNAs) are endogenous non-coding RNAs of 18-22 nucleotides in length. It has been reported that aberrant expression of miRNAs is a feature shared by various types of human cancer...
September 2016: Oncology Letters
Shaper Mirza, William H Benjamin, Patricia A Coan, Shen-An Hwang, Anne-Kathryn Winslett, Janet Yother, Susan K Hollingshead, Kohtaro Fujihashi, David E Briles
Pneumococcal surface protein A (PspA) is the only pneumococcal surface protein known to strongly bind lactoferrin on the bacterial surface. In the absence of PspA Streptococcus pneumoniae becomes more susceptible to killing by human apolactoferrin (apo-hLf), the iron-free form of lactoferrin. In the present study we examined diverse strains of S. pneumoniae that differed by 2 logs in their susceptibility to apo-hLf. Among these strains, the amount of apo-hLf that bound to cell surface PspA correlated directly with the resistance of the strain to killing by apo-hLf...
October 2016: Microbial Pathogenesis
Jian Ping Zhou, Wei Tang, Yun Feng, Ning Li, Chen Juan Gu, Qing Yun Li, Huan Ying Wan
Previous studies have shown that the RAS (renin-angiotensin system) might participate in airway remodelling in asthma. As a main component of the RAS, Ang-(1-7) [angiotensin-(1-7)] has been reported in few studies regarding its protective effect on asthma. However, the functional roles and relevant signalling pathways of Ang-(1-7) have not been well illustrated. In the present study, we analysed the effect of Ang-(1-7) on AngII (angiotensin II)-induced HLF (human lung fibroblast)-MF (myofibroblast) transition by detecting Col-I (collagen type I), TGF-β1 (transforming growth factor-β1) and α-SMA (α-smooth muscle actin) expression...
November 1, 2016: Clinical Science (1979-)
Shu Chen, Yang Wang, Chunxia Ni, Ge Meng, Xiaofang Sheng
Glioma is a malignant cancer with high mortality. A key prognostic factor of glioma is radiosensitivity. It has also been known that microRNAs (miR) significantly contribute to the development of glioma. miR-132 has been previously reported to inhibit tumor growth in some cancers, but not well studied in glioma. It is necessary to understand the association between miR-132 and glioma, including miR-132 expression in glioma, effects of miR-132 on cancer metastasis and radiosensitivity, and the involved molecular mechanism...
August 10, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Anna R O'Callaghan, Louise Morgan, Julie T Daniels, Mark P Lewis
AIM: To investigate human oral mucosal fibroblasts (HOMF) and human limbal fibroblasts (HLF) as alternatives to murine 3T3 feeder fibroblasts currently used to support epithelial cell expansion for the treatment of limbal epithelial stem cell deficiency. METHODS: HLF and HOMF were compared with 3T3s for their ability to support the culture of human limbal epithelial cells and human oral mucosal epithelial cells. RESULTS: HOMF, but not HLF, were equivalent to 3T3s in terms of the number of epithelial population doublings achieved...
September 2016: Regenerative Medicine
Chiaki Yamamoto, Kazutaka Takamatsu, Koji Hirano, Masahiro Miura
A copper-catalyzed intramolecular amination occurs at the benzylic C-H of 2-methylbenzamides to deliver the corresponding isoindolinones of great interest in medicinal chemistry. The mild and abundant MnO2 works well as a terminal oxidant, and the reaction proceeds smoothly under potentially explosive organic peroxide-free conditions. Additionally, the directing-group-dependent divergent mechanisms are proposed: 8-aminoquinoline-containing benzamides include a Cu-mediated organometallic pathway whereas an aminyl radical-promoted Hofmann-Loffler-Freytag (HLF)-type mechanism can be operative in the case of N-naphthyl-substituted substrates...
September 2, 2016: Journal of Organic Chemistry
Linya You, Lin Li, Jinfeng Zou, Kezhi Yan, Jad Belle, Anastasia Nijnik, Edwin Wang, Xiang-Jiao Yang
Hematopoietic stem cells (HSCs) serve as a life-long reservoir for all blood cell types and are clinically useful for a variety of HSC transplantation-based therapies. Understanding the role of chromatin organization and regulation in HSC homeostasis may provide important insights into HSC development. Bromodomain- and PHD finger-containing protein 1 (BRPF1) is a multivalent chromatin regulator that possesses 4 nucleosome-binding domains and activates 3 lysine acetyltransferases (KAT6A, KAT6B, and KAT7), suggesting that this protein has the potential to stimulate crosstalk between different chromatin modifications...
September 1, 2016: Journal of Clinical Investigation
Shuang Guo, Bai-Ling Qiu, Chen-Qi Zhu, Ya-Ya Gao Yang, Di Wu, Qi-Hui Liang, Nan-Yin Han
Gravitational field-flow fractionation (GrFFF) is a useful technique for separation and characterization for micrometer-sized particles. Elution behavior of micrometer-sized particles in GrFFF was researched in this study. Particles in GrFFF channel are subject to hydrodynamic lift forces (HLF), fluid inertial forces and gravity, which drive them to different velocities by carrier flow, resulting in a size-based separation. Effects of ionic strength, flow rate and viscosity as well as methanol were investigated using polystyrene latex beads as model particles...
September 15, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Shilei Zhao, Yan Wang, Tao Guo, Wendan Yu, Jinxiu Li, Zhipeng Tang, Zhenlong Yu, Lei Zhao, Yixiang Zhang, Ziyi Wang, Peng Wang, Yechi Li, Fengzhou Li, Zhe Sun, Yang Xuan, Ranran Tang, Wu-Guo Deng, Wei Guo, Chundong Gu
Y-box binding protein 1 (YBX1) is involved in the multi-tumor occurrence and development. However, the regulation of YBX1 in lung tumorigenesis and the underlying mechanisms, especially its relationship with CDC25a, was remains unclear. In this study, we analyzed the expression and clinical significance of YBX1 and CDC25a in lung adenocarcinoma and identified their roles in the regulation of lung cancer growth. The retrospective analysis of 116 patients with lung adenocarcinoma indicated that YBX1 was positively correlated with CDC25a expression...
June 15, 2016: Oncotarget
Nurul-Syakima Ab Mutalib, Sri Noraima Othman, Azliana Mohamad Yusof, Shahrun Niza Abdullah Suhaimi, Rohaizak Muhammad, Rahman Jamal
Background. Papillary thyroid carcinoma (PTC) is the commonest thyroid malignancy originating from the follicle cells in the thyroid. Despite a good overall prognosis, certain high-risk cases as in those with lymph node metastasis (LNM) have progressive disease and poorer prognosis. MicroRNAs are a class of non-protein-coding, 19-24 nucleotides single-stranded RNAs which regulate gene expression and these molecules have been shown to play a role in LNM. The integrated analysis of miRNAs and gene expression profiles together with transcription factors (TFs) has been shown to improve the identification of functional miRNA-target gene-TF relationships, providing a more complete view of molecular events underlying metastasis process...
2016: PeerJ
Shaozheng Song, Mengmin Zhu, Yuguo Yuan, Yao Rong, Sheng Xu, Si Chen, Junyan Mei, Yong Cheng
To knock out β-lactoglobulin (BLG) gene and insert human lactoferrin (hLF) coding sequence at BLG locus of goat, the transcription activator-like effector nucleases (TALEN) mediated recombination was used to edit the BLG gene of goat fetal fibroblast, then as donor cells for somatic cell nuclear transfer. We designed a pair of specific plasmid TALEN-3-L/R for goat BLG exon III recognition sites, and BLC14-TK vector containing a negative selection gene HSV-TK, was used for the knock in of hLF gene. TALENs plasmids were transfected into the goat fetal fibroblast cells, and the cells were screened three days by 2 μg/mL puromycin...
March 2016: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
Reena Buurman, Maria Sandbothe, Brigitte Schlegelberger, Britta Skawran
BACKGROUND: Histone deacetylation, a common hallmark in malignant tumors, strongly alters the transcription of genes involved in the control of proliferation, cell survival, differentiation and genetic stability. We have previously shown that HDAC1, HDAC2, and HDAC3 (HDAC1-3) genes encoding histone deacetylases 1-3 are upregulated in primary human hepatocellular carcinoma (HCC). The aim of this study was to characterize the functional effects of HDAC1-3 downregulation and to identify functionally important target genes of histone deacetylation in HCC...
2016: European Journal of Medical Research
Joseph Platz, Nicholas R Bonenfant, Franziska E Uhl, Amy L Coffey, Tristan McKnight, Charles Parsons, Dino Sokocevic, Zachary D Borg, Ying-Wai Lam, Bin Deng, Julia G Fields, Michael DeSarno, Roberto Loi, Andrew M Hoffman, John Bianchi, Brian Dacken, Thomas Petersen, Darcy E Wagner, Daniel J Weiss
BACKGROUND: A novel potential approach for lung transplantation could be to utilize xenogeneic decellularized pig lung scaffolds that are recellularized with human lung cells. However, pig tissues express several immunogenic proteins, notably galactosylated cell surface glycoproteins resulting from alpha 1,3 galactosyltransferase (α-gal) activity, that could conceivably prevent effective use. Use of lungs from α-gal knock out (α-gal KO) pigs presents a potential alternative and thus comparative de- and recellularization of wild-type and α-gal KO pig lungs was assessed...
August 2016: Tissue Engineering. Part C, Methods
Yasumichi Toki, Katsunori Sasaki, Hiroki Tanaka, Masayo Yamamoto, Mayumi Hatayama, Satoshi Ito, Katsuya Ikuta, Motohiro Shindo, Takumu Hasebe, Shunsuke Nakajima, Koji Sawada, Mikihiro Fujiya, Yoshihiro Torimoto, Takaaki Ohtake, Yutaka Kohgo
Hepcidin is a main regulator of iron metabolism, of which abnormal expression affects intestinal absorption and reticuloendothelial sequestration of iron by interacting with ferroportin. It is also noted that abnormal iron accumulation is one of the key factors to facilitate promotion and progression of cancer including hepatoma. By RT-PCR/agarose gel electrophoresis of hepcidin mRNA in a hepatocellular carcinoma cell line HLF, a smaller mRNA band was shown in addition to the wild-type hepcidin mRNA. From sequencing analysis, this additional band was a selective splicing variant of hepcidin mRNA lacking exon 2 of HAMP gene, producing the transcript that encodes truncated peptide lacking 20 amino acids at the middle of preprohepcidin...
August 5, 2016: Biochemical and Biophysical Research Communications
Shilei Zhao, Wei Guo, Jinxiu Li, Wendan Yu, Tao Guo, Wuguo Deng, Chundong Gu
BACKGROUND: Prognosis of small (≤2 cm) invasive lung adenocarcinoma remains poor, and identification of high-risk individuals from the patients after complete surgical resection of lung adenocarcinoma has become an urgent problem. YBX1 has been reported to be able to predict prognosis in many cancers (except lung adenocarcinoma) that are independent of TNM (tumor, nodes, metastases) staging, especially small invasive lung adenocarcinoma. Therefore, we examined the significance of YBX1 expression on prognosis and recurrence in patients with small invasive lung adenocarcinoma...
2016: OncoTargets and Therapy
R Chow, D Shabsovich, G Schiller, M Kallen, Carlos A Tirado
TCF3 (19p13.3) abnormalities are relatively common in B-cell acute lymphoblastic leukemia (B-ALL). The t(1;19)(q23;p13) involving PBX1 is the most common of these rearrangements. The t(17;19)(q22;p13.3), resulting in the TCF3-HLF fusion gene, is also seen in B-ALL and is associated with an extremely poor prognosis. Herein, we present the case of a 25-year-old male diagnosed with B-ALL whose initial karyotype showed a t(17;19)(q22p13.3). FISH confirmed TCF3 involvement and also revealed a 5' IGH deletion. After treatment, the patient relapsed, at which point conventional cytogenetic studies showed a t(17;19), loss of the 5' IGH region, and a t(3;10) not seen in initial studies...
2016: Journal of the Association of Genetic Technologists
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