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https://www.readbyqxmd.com/read/28640863/induced-pluripotent-stem-cell-derived-limbal-epithelial-cells-lipsc-as-a-cellular-alternative-for-in-vitro-ocular-toxicity-testing
#1
Edith Aberdam, Isabelle Petit, Linda Sangari, Daniel Aberdam
Induced pluripotent stem cells hold great potential to produce unlimited amount of differentiated cells as cellular source for regenerative medicine but also for in vitro drug screening and cytotoxicity tests. Ocular toxicity testing is mandatory to evaluate the risks of drugs and cosmetic products before their application to human patients by preventing eye irritation or insult. Since the global ban to use animals, many human-derived alternatives have been proposed, from ex-vivo enucleated postmortem cornea, primary corneal cell culture and immortalized corneal epithelial cell lines...
2017: PloS One
https://www.readbyqxmd.com/read/28628795/knockout-of-the-nogo-b-gene-attenuates-tumor-growth-and-metastasis-in-hepatocellular-carcinoma
#2
Bo Zhu, Shaobo Chen, Xiaoding Hu, Xiaofeng Jin, Yichen Le, Lihuan Cao, Zhonghua Yuan, Zhen Lin, Songmin Jiang, Lichun Sun, Long Yu
Human hepatocellular carcinoma (HCC) is a malignant cancer. It is a challenge to develop anti-HCC drugs due to HCC's extreme aggressiveness and with the sensitivity of the liver to show severe adverse effects. More importantly, the precise mechanisms causing HCC pathogenicity are not known. Our previous study disclosed Nogo-B as a reticulon 4 (Rtn4) family member. In the present study, we first identified that Nogo-B played a critical role in HCC progression. We found, via in vitro and in vivo assays, that Nogo-B was expressed aberrantly in primary HCC tumor tissues and immortal HCC cells but was relatively scarce in the normal liver tissues or cells...
June 16, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28615694/selective-serotonin-reuptake-inhibitor-fluoxetine-impairs-e-cadherin-mediated-cell-adhesion-and-alters-calcium-homeostasis-in-pancreatic-beta-cells
#3
Huang-Yu Chang, Shu-Ling Chen, Meng-Ru Shen, Mei-Lang Kung, Lee-Ming Chuang, Yun-Wen Chen
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed drugs for mood disorders. Long term use of SSRIs is associated with an increased risk of diabetes, but the underlying mechanism(s) remains elusive. E-cadherin-mediated cell-cell adhesion and elevated [Ca(2+)]i are important for insulin release and pancreatic β cell functions. This study aims to investigate whether a SSRI, fluoxetine (Prozac), induces pancreatic β cell dysfunction through affecting E-cadherin and/or [Ca(2+)]i...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28607007/synergistic-activity-with-notch-inhibition-and-androgen-ablation-in-erg-positive-prostate-cancer-cells
#4
Ahmed A Mohamed, Shyh-Han Tan, Charles P Xavier, Shilpa Katta, Wei Huang, Lakshmi Ravindranath, Muhammad Jamal, Hua Li, Meera Srivastava, Eri S Srivatsan, Taduru L Sreenath, David G McLeod, Alagarsamy Srinivasan, Gyorgy Petrovics, Albert Dobi, Shiv Srivastava
The oncogenic activation of the ETS related gene (ERG) due to gene fusions is present in over half of prostate cancer (CaP) in Western countries. Due to its high incidence and oncogenic role, ERG and components of ERG network have emerged as potential drug targets for CaP. Utilizing gene expression datasets, from matched normal and prostate tumor epithelial cells, an association of NOTCH transcription factors with ERG expression status was identified; confirming that NOTCH factors are direct transcriptional targets of ERG...
June 12, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28586195/ex-vivo-cell-based-screening-platform-for-modulators-of-hepatosteatosis
#5
Shan Yu, Emily Chen, Lance Sherwood, Mitchell Hull, Ashley K Woods, Matthew S Tremblay
Nonalcoholic fatty liver disease (NAFLD) is the result of the ectopic accumulation of lipids in hepatic cells and is the early stage of liver diseases including fibrosis, cirrhosis, and hepatocellular carcinoma. While some mechanisms of aberrant lipid storage are understood, unbiased phenotypic drug screening holds the potential to identify new therapeutic small molecule mechanisms that reverse lipid accumulation in hepatic cells and prevent disease progression. Immortalized hepatocyte cell lines are often used as in vitro models of hepatocyte function, including in the study of lipid accumulation...
June 16, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28584711/quercetin-reduces-hydroxyurea-induced-cytotoxicity-in-immortalized-mouse-aortic-endothelial-cells
#6
Zachary M Kiser, Monica D M McGee, Racquel J Wright, Alexander Quarshie, Gale W Newman, Karen R Randall, Jonathan K Stiles, Adel Driss, Jacqueline M Hibbert
BACKGROUND: Chronic inflammation is a characteristic of sickle cell disease (SCD), and is invariably associated with vascular endothelial injury. Hydroxyurea (HU), a naturally cytotoxic chemotherapeutic agent, is the only FDA drug approved for SCD, and is therefore naturally cytotoxic. Quercetin (QCT) is a dietary flavonoid found ubiquitously in plants and foods that have anti-oxidative and anti-inflammatory characteristics. Our hypothesis is that dietary QCT will decrease cytotoxic effects of lipopolysaccharide (LPS) and HU induced vascular cell damage...
2017: PeerJ
https://www.readbyqxmd.com/read/28582447/action-of-ym155-on-clear-cell-renal-cell-carcinoma-does-not-depend-on-survivin-expression-levels
#7
Mei Yi Sim, Hung Huynh, Mei Lin Go, John Shyi Peng Yuen
The dioxonapthoimidazolium YM155 is a survivin suppressant which has been investigated as an anticancer agent in clinical trials. Here, we investigated its growth inhibitory properties on a panel of immortalized and patient derived renal cell carcinoma (RCC) cell lines which were either deficient in the tumour suppressor von Hippel-Lindau (VHL) protein or possessed a functional copy. Neither the VHL status nor the survivin expression levels of these cell lines influenced their susceptibility to growth inhibition by YM155...
2017: PloS One
https://www.readbyqxmd.com/read/28566574/quantitative-targeted-absolute-proteomics-qtap-based-pharmacoproteomics-the-importance-of-international-collaboration
#8
Tetsuya Terasaki
 Proteins such as membrane transporters, enzymes, receptors and channels play key roles in drug absorption, distribution, metabolism, and elimination, and also influence efficacy and the likelihood of adverse reactions. Therefore, if we can quantify the activities of these molecules, it may be possible to predict the behavior of candidate drugs in humans in disease states; such methodology would be extremely helpful for efficient drug development. We have developed an in silico method to select appropriate peptides within amino acid sequences in order to quantify targeted proteins by LC-MS/MS in selected reaction monitoring (SRM) mode...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28549670/cilastatin-attenuates-vancomycin-induced-nephrotoxicity-via-p-glycoprotein
#9
Dai Sig Im, Hye Jin Shin, Keum Jin Yang, So Young Jung, Ho Yeon Song, Hyeon Seok Hwang, Hyo-Wook Gil
BACKGROUND: Oxidative stress is one of the main pathogenic mechanisms in vancomycin-induced nephrotoxicity (VIN). Some studies suggest proximal renal tubular cell necrosis by vancomycin accumulation as a mechanism of nephrotoxicity, and other studies demonstrate that cilastatin has protective effects against drug-induced nephrotoxicity. We investigated whether cilastatin regulates p-gp expression and whether cilastation prevents VIN. MATERIALS AND METHODS: We conducted an in vitro study using an immortalized proximal tubule epithelial cell line from a normal adult human kidney (HK-2) and an in vivo study using male C57BL/6J mice...
May 23, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28541801/enemies-or-weapons-in-hands-investigational-anti-diabetic-drug-glibenclamide-and-cancer-risk
#10
Rui Gao, Tao Yang, Wei Xu
Epidemiological evidence suggests that diabetes is associated with elevated cancer risk through the actions of hyperglycemia, hyperinsulinemia and chronic inflammation. Metformin, a first-line medication for type 2 diabetes mellitus, arouses growing concerns on its anti-cancer effect. However, data regarding the effect of glibenclamide on tumor growth and cancer risk are less consistent, which may be a potential anti-cancer drug. Areas covered: In this review, we clarified probable underlying mechanisms in preclinical studies and reviewed epidemiological evidence on glibenclamide's cancer risk in clinical studies...
June 1, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28533362/cgas-is-essential-for-cellular-senescence
#11
Hui Yang, Hanze Wang, Junyao Ren, Qi Chen, Zhijian J Chen
Cellular senescence is a natural barrier to tumorigenesis and it contributes to the antitumor effects of several therapies, including radiation and chemotherapeutic drugs. Senescence also plays an important role in aging, fibrosis, and tissue repair. The DNA damage response is a key event leading to senescence, which is characterized by the senescence-associated secretory phenotype (SASP) that includes expression of inflammatory cytokines. Here we show that cGMP-AMP (cGAMP) synthase (cGAS), a cytosolic DNA sensor that activates innate immunity, is essential for senescence...
June 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28528134/enhancing-tumor-cell-response-to-multidrug-resistance-with-ph-sensitive-quercetin-and-doxorubicin-conjugated-multifunctional-nanoparticles
#12
Cenk Daglioglu
Classical chemotherapy uses chemotherapeutic agents as a mainstay of anticancer treatment. However, the development of multidrug resistance to chemotherapy limits the effectiveness of current cancer treatment. Nanosized bioconjugates combining a chemotherapeutic agent with a pharmacological approach may improve the curative effect of chemotherapeutic agents. Herein I addressed this issue by describing the synthesis, and testing of, pH-responsive Fe3O4@SiO2(FITC)-BTN/QUR/DOX multifunctional nanoparticles. The particles were designed to modulate resistance-mediating factors and to potentiate the efficacy of DOX against chemoresistance...
May 10, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28493713/cetuximab-prevents-methotrexate-induced-cytotoxicity-in-vitro-through-epidermal-growth-factor-dependent-regulation-of-renal-drug-transporters
#13
Pedro Caetano-Pinto, Amer Jamalpoor, Janneke Ham, Anastasia Goumenou, Monique Mommersteeg, Dirk Pijnenburg, Rob Ruijtenbeek, Natalia Sanchez-Romero, Bertrand van Zelst, Sandra G Heil, Jitske Jansen, Martijn J Wilmer, Carla M L van Herpen, Rosalinde Masereeuw
The combination of methotrexate with epidermal growth factor receptor (EGFR) recombinant antibody, cetuximab, is currently being investigated in treatment of head and neck carcinoma. As methotrexate is cleared by renal excretion, we studied the effect of cetuximab on renal methotrexate handling. We used human conditionally immortalized proximal tubule epithelial cells overexpressing either organic anion transporter 1 or 3 (ciPTEC-OAT1/ciPTEC-OAT3) to examine OAT1 and OAT3, and the efflux pumps breast cancer resistance protein (BCRP), multidrug resistance protein 4 (MRP4), and P-glycoprotein (P-gp) in methotrexate handling upon EGF or cetuximab treatment...
June 5, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28489572/ck2-and-pi3k-are-direct-molecular-targets-of-quercetin-in-chronic-lymphocytic-leukaemia
#14
Maria Russo, Alfonsina Milito, Carmela Spagnuolo, Virginia Carbone, Anders Rosén, Paola Minasi, Fabio Lauria, Gian Luigi Russo
Despite the encouraging results of the innovative therapeutic treatments, complete remission is uncommon in patients affected by chronic lymphocytic leukaemia, which remains an essentially incurable disease. Recently, clinical trials based on BH3-mimetic drugs showed positive outcomes in subjects with poor prognostic features. However, resistance to treatments occurs in a significant number of patients. We previously reported that the multi-kinase inhibitor quercetin, a natural flavonol, restores sensitivity to ABT-737, a BH3-mimetic compound, in both leukemic cell lines and B-cells isolated from patients...
April 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28487652/functional-gene-analysis-reveals-cell-cycle-changes-and-inflammation-in-endothelial-cells-irradiated-with-a-single-x-ray-dose
#15
Bjorn Baselet, Niels Belmans, Emma Coninx, Donna Lowe, Ann Janssen, Arlette Michaux, Kevin Tabury, Kenneth Raj, Roel Quintens, Mohammed A Benotmane, Sarah Baatout, Pierre Sonveaux, An Aerts
Background and Purpose: Epidemiological data suggests an excess risk of cardiovascular disease (CVD) at low doses (0.05 and 0.1 Gy) of ionizing radiation (IR). Furthermore, the underlying biological and molecular mechanisms of radiation-induced CVD are still unclear. Because damage to the endothelium could be critical in IR-related CVD, this study aimed to identify the effects of radiation on immortalized endothelial cells in the context of atherosclerosis. Material and Methods: Microarrays and RT-qPCR were used to compare the response of endothelial cells irradiated with a single X-ray dose (0...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28476050/influence-of-pilocarpine-and-timolol-on-human-meibomian-gland-epithelial-cells
#16
Yi Zhang, Wendy R Kam, Yang Liu, Xiaomin Chen, David A Sullivan
PURPOSE: Investigators have discovered that topical antiglaucoma drugs may induce meibomian gland dysfunction. This response may contribute to the dry eye disease commonly found in patients with glaucoma taking such medications. We hypothesize that drug action involves a direct effect on human meibomian gland epithelial cells (HMGECs). To test this hypothesis, we examined the influence of the antiglaucoma drugs, pilocarpine and timolol, on the morphology, survival, proliferation, and differentiation of HMGECs...
June 2017: Cornea
https://www.readbyqxmd.com/read/28433505/chemotherapy-induces-alternative-transcription-and-splicing-facts-and-hopes-for-cancer-treatment
#17
Charles A Lambert, Nancy Garbacki, Alain C Colige
Alternative promoter usage, alternative splicing and alternative cleavage/polyadenylation (referred here as to alternative transcription and splicing) are main instruments to diversify the transcriptome from a limited set of genes. There is a good deal of evidence that chemotherapeutic drugs affect these processes, but the therapeutic incidence of these effects is poorly documented. The scope of this study is to review the impact of chemotherapy on alternative transcription and splicing and to discuss potential implications in cancer therapy...
April 19, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28433067/chloroquine-and-hydroxychloroquine-inhibit-bladder-cancer-cell-growth-by-targeting-basal-autophagy-and-enhancing-apoptosis
#18
Yi-Chia Lin, Ji-Fan Lin, Sheng-I Wen, Shan-Che Yang, Te-Fu Tsai, Hung-En Chen, Kuang-Yu Chou, Thomas I-Sheng Hwang
Chloroquine (CQ) and hydroxychloroquine (HCQ), two antimalarial drugs, are suggested to have potential anticancer properties. in the present study, we investigated the effects of CQ and HCQ on cell growth of bladder cancer with emphasis on autophagy inhibition and apoptosis induction in vitro. The results showed that CQ and HCQ inhibited the proliferation of multiple human bladder cell lines (including RT4, 5637, and T24) in a time- and dose-dependent fashion, especially in advanced bladder cancer cell lines (5637 and T24) compared to immortalized uroepithelial cells (SV-Huc-1) or other reference cancer cell lines (PC3 and MCF-7)...
May 2017: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/28423575/activated-notch-signaling-augments-cell-growth-in-hepatocellular-carcinoma-via-up-regulating-the-nuclear-receptor-nr4a2
#19
Bo Zhu, Lichun Sun, Wei Luo, Min Li, David H Coy, Long Yu, Wenbo Yu
Hepatocellular carcinoma (HCC) is one of the most malignant cancers. Conventional therapies are limited due to the human liver being such a unique organ and easily showing side-effects. The unclear molecular mechanisms are tough challenges for scientists searching for new and effective anti-HCC targeting drugs. We identified that the nuclear receptor NR4A2 is a novel oncogene in HCC progression. In this study, we show that NR4A2 and the notch recceptor Notch1 were expressed highly in primary HCC tissues and immortal HCC cells by using qPCR, western blot and immuno-histochemistry assays...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401035/development-and-application-of-human-renal-proximal-tubule-epithelial-cells-for-assessment-of-compound-toxicity
#20
Shuaizhang Li, Jinghua Zhao, Ruili Huang, Toni Steiner, Maureen Bourner, Michael Mitchell, David C Thompson, Bin Zhao, Menghang Xia
Kidney toxicity is a major problem both in drug development and clinical settings. It is difficult to predict nephrotoxicity in part because of the lack of appropriate in vitro cell models, limited endpoints, and the observation that the activity of membrane transporters which plays important roles in nephrotoxicity by affecting the pharmacokinetic profile of drugs is often not taken into account. We developed a new cell model using pseudo-immortalized human primary renal proximal tubule epithelial cells. This cell line (SA7K) was characterized by the presence of proximal tubule cell markers as well as several functional properties, including transporter activity and response to a few well-characterized nephrotoxicants...
2017: Current Chemical Genomics and Translational Medicine
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