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Jinhua Piao, Shiori Takai, Takahiro Kamiya, Takeshi Inukai, Kanji Sugita, Kazuma Ohyashiki, Domenico Delia, Mitsuko Masutani, Shuki Mizutani, Masatoshi Takagi
Poly (ADP-ribose) polymerase (PARP) is an indispensable component of the DNA repair machinery. PARP inhibitors are used as cutting-edge treatments for patients with homologous recombination repair (HRR)-defective breast cancers harboring mutations in BRCA1 or BRCA2. Other tumors defective in HRR, including some hematological malignancies, are predicted to be good candidates for treatment with PARP inhibitors. Screening of leukemia-derived cell lines revealed that lymphoid lineage-derived leukemia cell lines, except for those derived from mature B cells and KMT2A (MLL)-rearranged B-cell precursors, were relatively sensitive to PARP inhibitors...
November 25, 2016: Cancer Letters
Afrah Sattikar, Mark R Dowling, Elizabeth M Rosethorne
BACKGROUND AND PURPOSE: Human lung fibroblasts (HLF) express high levels of the LPA1 receptor, a G protein-coupled receptor (GPCR) that responds to the endogenous lipid mediator lysophosphatidic acid (1-acyl-2-hydroxy-sn-glycero-3-phosphate; LPA). Several molecular species or analogues of LPA exist and have been detected in biological fluids such as serum and plasma. The most widely expressed of the LPA receptor family is the LPA1 receptor, which predominantly couples to Gq/11 , Gi/o and G12/13 proteins...
November 16, 2016: British Journal of Pharmacology
Jun Xie, Jia-Hui Liu, Heng Liu, Xiao-Zhong Liao, Yuling Chen, Mei-Gui Lin, Yue-Yu Gu, Tao-Li Liu, Dong-Mei Wang, Hui Ge, Sui-Lin Mo
BACKGROUND: The study was designed to develop a platform to verify whether the extract of herbs combined with chemotherapy drugs play a synergistic role in anti-tumor effects, and to provide experimental evidence and theoretical reference for finding new effective sensitizers. METHODS: Inhibition of tanshinone IIA and adriamycin on the proliferation of A549, PC9 and HLF cells were assessed by CCK8 assays. The combination index (CI) was calculated with the Chou-Talalay method, based on the median-effect principle...
November 18, 2016: BMC Cancer
Irene Vacca, Elena Del Tordello, Gianmarco Gasperini, Alfredo Pezzicoli, Martina Di Fede, Silvia Rossi Paccani, Sara Marchi, Tsisti D Mubaiwa, Lauren E Hartley-Tassell, Michael P Jennings, Kate L Seib, Vega Masignani, Mariagrazia Pizza, Davide Serruto, Beatrice Aricò, Isabel Delany
Neisserial Heparin Binding Antigen (NHBA) is a surface-exposed lipoprotein ubiquitously expressed by Neisseria meningitidis strains and an antigen of the Bexsero® vaccine. NHBA binds heparin through a conserved Arg-rich region that is the target of two proteases, the meningococcal NalP and human lactoferrin (hLf). In this work, in vitro studies showed that recombinant NHBA protein was able to bind epithelial cells and mutations of the Arg-rich tract abrogated this binding. All N-terminal and C-terminal fragments generated by NalP or hLf cleavage, regardless of the presence or absence of the Arg-rich region, did not bind to cells, indicating that a correct positioning of the Arg-rich region within the full length protein is crucial...
2016: PloS One
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 proinflammatory and proresolving prostaglandins (PGs) in conditioned culture medium from HLFs treated with a proinflammatory stimulus, IL-1β. Among the proresolving PGs in the HLF lipidome were several known ligands for peroxisome proliferator-activated receptor-γ (PPARγ), a transcription factor whose activation in the lung yields potent anti-inflammatory, antifibrotic, and proresolving effects...
November 1, 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
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