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https://www.readbyqxmd.com/read/28549670/cilastatin-attenuates-vancomycin-induced-nephrotoxicity-via-p-glycoprotein
#1
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
#2
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...
May 25, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28533362/cgas-is-essential-for-cellular-senescence
#3
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...
May 22, 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
#4
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
#5
Pedro Caetano-Pinto, Amer Jamalpoor, Janneke Ham, Anastasia Goumenou, Monique Mommersteeg, Dirk Pijnenburg, Rob Ruijtenbeek, Natalia Sánchez-Romero, Bertrand van Zelst, Sandra 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 over-expressing 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 and/or cetuximab treatment...
May 11, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28489572/ck2-and-pi3k-are-direct-molecular-targets-of-quercetin-in-chronic-lymphocytic-leukaemia
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28379424/combination-therapy-with-potent-pi3k-and-mapk-inhibitors-overcomes-adaptive-kinome-resistance-to-single-agents-in-preclinical-models-of-glioblastoma
#13
Robert S McNeill, Demitra A Canoutas, Timothy J Stuhlmiller, Harshil D Dhruv, David M Irvin, Ryan E Bash, Steven P Angus, Laura E Herring, Jeremy M Simon, Kasey R Skinner, Juanita C Limas, Xin Chen, Ralf S Schmid, Marni B Siegel, Amanda E D Van Swearingen, Michael J Hadler, Erik P Sulman, Jann N Sarkaria, Carey K Anders, Lee M Graves, Michael E Berens, Gary L Johnson, C Ryan Miller
Background.: Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Prognosis remains poor despite multimodal therapy. Developing alternative treatments is essential. Drugs targeting kinases within the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) effectors of receptor tyrosine kinase (RTK) signaling represent promising candidates. Methods.: We previously developed a non-germline genetically engineered mouse model of GBM in which PI3K and MAPK are activated via Pten deletion and KrasG12D in immortalized astrocytes...
March 30, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28356007/fluorescent-immortalized-human-adipose-derived-stromal-cells-hascs-ts-gfp-for-studying-cell-drug-delivery-mediated-by-microvesicles
#14
Valentina Coccè, Luigi Balducci, Maria Laura Falchetti, Luisa Pascucci, Emilio Ciusani, Anna Teresa Brini, Francesca Sisto, Giovanna Piovani, Giulio Alessandri, Eugenio Parati, Laura Cabeza, Augusto Pessina
BACKGROUND: A new tool for the drug delivery is based on the use of Mesenchymal Stromal Cells (MSCs) loaded in vitro with anti-cancer drugs. Unfortunately, the restricted lifespan of MSCs represents a significant limitation to produce them in high amounts and for long time studies. Immortalized MSCs from adipose tissue (hASC) have been generated as good source of cells with stable features. These cells could improve the development of standardized procedures for both in vitro and preclinical studies...
March 27, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28346106/isolation-and-characterization-of-a-distinct-subpopulation-from-the-wm115-cell-line-that-resembles-in-vitro-properties-of-melanoma-cancer-stem-cells
#15
Sonia G Escobar, Mark H Chin, Mark L Sandberg, Han Xu
Despite key advances in cancer therapies, malignant tumors, such as melanoma, continue to be one of the leading causes of mortality. Recent debate on whether cancer can originate from a tumor-initiating subpopulation has permeated oncology and stem cell research. It has been well established that primary and immortalized tumor cells consist of heterogeneous cell populations. The profound effect of tumor heterogeneity on tumor growth and drug resistance remains elusive, but it is highly likely that subpopulations of cancer cells have different capabilities of self-renewal and drug resistance...
June 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28339479/mouse-newborn-cells-allow-highly-productive-mouse-cytomegalovirus-replication-constituting-a-novel-convenient-primary-cell-culture-system
#16
Vu Thuy Khanh Le-Trilling, Mirko Trilling
Mammalian cell culture is indispensable for most aspects of current biomedical research. Immortalized cell lines are very convenient, but transforming principles (e.g. oncogenic viruses or their oncogenes) can heavily influence the experimental outcome. Primary cells do not share this apparent disadvantage but are more laborious to generate. Certain viruses (e.g. mouse cytomegalovirus) do not replicate efficiently in most transformed cell lines. In the past, such viruses have been routinely propagated on primary mouse embryonic fibroblasts (MEF) established around day 17 (d17) of gestation...
2017: PloS One
https://www.readbyqxmd.com/read/28321651/effects-of-strontium-ranelate-treatment-on-osteoblasts-cultivated-onto-scaffolds-of-trabeculae-bovine-bone
#17
Gerluza Aparecida Borges Silva, Bruno Machado Bertassoli, Cristiane Aparecida Sousa, Juliano Douglas Albergaria, Rayan Silva de Paula, Erika Cristina Jorge
Blocks of Bovine bone have shown promising results as implantable scaffolds to promote bone regeneration. Strontium ranelate (SrR) is both an antiresorptive and an anabolic drug that has been indicated for oral administration to treat osteoporosis. Few studies, however, have investigated the local effects of SrR and its use in association with biomaterials thus far. In this work, we investigated SrR effects in cultures of primary osteoblasts (PO, from Wistar rats calvaria) and immortalized osteoblasts (IO, from MC3T3-E1 cell line) cultivated as a monolayer or in association with scaffolds of bovine bone in mineralized (MBB) and demineralized (DBB) forms...
March 20, 2017: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/28315467/hce-t-cell-based-permeability-model-a-well-maintained-or-a-highly-variable-barrier-phenotype
#18
Marina Juretić, Bisera Jurišić Dukovski, Iva Krtalić, Stephan Reichl, Biserka Cetina-Čižmek, Jelena Filipović-Grčić, Jasmina Lovrić, Ivan Pepić
The most extensively characterized human-derived cell line used in transcorneal permeability studies, in terms of passive transcellular and paracellular transport, transporter expression and metabolic enzymes, is the immortalized human corneal epithelial cell line (HCE-T). The purpose of this study is to describe the changes in the HCE-T barrier phenotype in vitro when valid cultivation conditions, in accordance with the standardized HCE-T cell-based model protocol, were employed. Evaluation of the structural and functional barrier properties revealed two different HCE-T barrier phenotypes, depending on the polycarbonate membrane pore size...
March 14, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28287250/changes-in-the-expression-of-cyclin-dependent-kinase-inhibitors-during-differentiation-of-immortalized-fibroblasts-into-adipocytes
#19
Ibon Alonso, Antonio Baroja, Blanca Fernández, Raquel Vielba, Jon Elorriaga, Jairo Pérez-Sanz, Juan Aréchaga, Juan J Goiriena de Gandarias, Carmen de la Hoz
The mechanisms implicated in the differentiation of fibroblastic precursors into adipocytes can be analyzed in vitro using cell models, such as the 3T3-L1 cell line. Since cell differentiation involves an exit from the cell cycle, it is likely that molecules that inhibit proliferation participate in the control of adipogenesis. This study was aimed at determining the role, if any, of several cyclin-dependent kinase (CDK)-inhibitors and the transcription factor C/EBPα in the process of adipocyte differentitation...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28285358/fluoroquinolones-and-propionic-acid-derivatives-induce-inflammatory-responses-in-vitro
#20
Akira Nakajima, Hiroki Sato, Shingo Oda, Tsuyoshi Yokoi
Fluoroquinolones and propionic acid derivatives are widely used antibacterials and non-steroidal anti-inflammatory drugs, respectively, which have been reported to frequently trigger drug hypersensitivity reactions. Such reactions are induced by inflammatory mediators such as cytokines and chemokines. The present study investigated whether levofloxacin, a fluoroquinolone, and loxoprofen, a propionic acid derivative, have the potential to induce immune-related gene expression in dendritic cell-like cell lines such as HL-60, K562, and THP-1, and immortalized keratinocytes such as HaCaT...
March 11, 2017: Cell Biology and Toxicology
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