Read by QxMD icon Read

immortality drugs

John K Fallon, Nicole Houvig, Catherine L Booth-Genthe, Philip C Smith
Information is needed on the expression of transporters in lung to inform drug development and therapeutic decisions. Much of the information currently available is from semiquantitative gene expression or immunometric densitometry studies reported in the literature. NanoLC-MS/MS (MRM mode) isotope dilution targeted quantitative proteomics was used here to quantify twelve selected transporters in fresh human lung membrane fraction samples and in the membrane fraction of selected immortalized human lung epithelial cell line samples...
February 22, 2018: Journal of Pharmaceutical and Biomedical Analysis
Amer Jamalpoor, Rolf W Sparidans, Carla Pou Casellas, Johannes J M Rood, Mansi Joshi, Rosalinde Masereeuw, Manoe J Janssen
Nephropathic cystinosis is characterized by abnormal intralysosomal accumulation of cystine throughout the body causing irreversible damage to various organs, particularly the kidneys. Cysteamine, the currently available treatment, can reduce lysosomal cystine and postpone disease progression. However, cysteamine poses serious side effects and does not address all symptoms of cystinosis. To screen for new treatment options, a rapid and reliable high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed to quantify cystine in conditionally immortalized human proximal tubular epithelial cells (ciPTEC)...
March 8, 2018: Biomedical Chromatography: BMC
Meiyan Zhu, Akira Koibuchi, Hideyuki Ide, Hanae Morio, Minaka Shibuya, Atsuko Kamiichi, Akihito Tsubota, Naohiko Anzai, Hidetaka Akita, Kan Chiba, Tomomi Furihata
Liver sinusoidal endothelial cells (LSECs), which are specialized endothelial cells that line liver sinusoids, have been reported to participate in a variety of liver functions, such as blood macromolecule clearance and factor VIII production. In addition, LSECs play crucial roles in liver regeneration following acute liver injury, as well as the development and progression of liver diseases or drug-induced hepatotoxicity. However, the molecular mechanisms underlying their roles remain mostly unknown. Therefore, in order to contribute to the clarification of those mechanisms, herein we report on the development of a new immortalized human LSEC (HLSEC) line...
2018: Biological & Pharmaceutical Bulletin
Takemasa Senoo, Ryu Sasaki, Yuko Akazawa, Tatsuki Ichikawa, Satoshi Miuma, Hisamitsu Miyaaki, Naota Taura, Kazuhiko Nakao
BACKGROUND: Geranylgeranylacetone (GGA), an anti-ulcer drug widely used in Japan, has attracted interest because of its various therapeutic effects. Therefore, we investigated the effects of GGA on human hepatic stellate cells (HSCs) in vitro and in a mouse model of liver fibrosis. METHODS: LX2, an immortalized human HSC line, was cultured and treated with GGA at concentrations up to 0.5 mM. After GGA treatment, changes in cellular morphology, apoptosis, and fibrosis-related gene expression were assessed...
February 27, 2018: BMC Gastroenterology
Michele Patrizii, Monica Bartucci, Sharon R Pine, Hatem E Sabaawy
Despite substantial effort and resources dedicated to drug discovery and development, new anticancer agents often fail in clinical trials. Among many reasons, the lack of reliable predictive preclinical cancer models is a fundamental one. For decades, immortalized cancer cell cultures have been used to lay the groundwork for cancer biology and the quest for therapeutic responses. However, cell lines do not usually recapitulate cancer heterogeneity or reveal therapeutic resistance cues. With the rapidly evolving exploration of cancer "omics," the scientific community is increasingly investigating whether the employment of short-term patient-derived tumor cell cultures (two- and three-dimensional) and/or patient-derived xenograft models might provide a more representative delineation of the cancer core and its therapeutic response...
2018: Frontiers in Oncology
Tracey Hurrell, Andrea Antonio Ellero, Zelie Flavienne Masso, Allan Duncan Cromarty
Hepatotoxicity remains a major challenge in drug development despite preclinical toxicity screening using hepatocytes of human origin. To overcome some limitations of reproducing the hepatic phenotype, more structurally and functionally authentic cultures in vitro can be introduced by growing cells in 3D spheroid cultures. Characterisation and reproducibility of HepG2 spheroid cultures using a high-throughput hanging drop technique was performed and features contributing to potential phenotypic variation highlighted...
February 21, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Aline Steinmetz, Luiza Steffens, Ana Moira Morás, Flávia Prezzi, Elizandra Braganhol, Jenifer Saffi, Rafael Scorsatto Ortiz, Helena M T Barros, Dinara Jaqueline Moura
Cocaine is one of the most popular illicit drug worldwide. Due its great addictive potential, which leads to euphoria and hyperactivity, it is considered a public health concern. At the central nervous system, the drug acts inhibiting catecholamine re-uptake. It is now known that in addition to the toxicity of the drug itself, the contaminants present in the street drug have raised concern about the harmful effects on health. Toxicological in vivo and in vitro studies have demonstrated the toxic effects of cocaine correlated with the generation of reactive oxygen species (ROS), which in turn lead to oxidative damage to the cells...
February 20, 2018: Chemico-biological Interactions
Tianqi Yu, Suthakar Ganapathy, Ling Shen, Bo Peng, Sung-Hoon Kim, Alexandros Makriyannis, Changyan Chen
Side effects of anti-cancer drugs are always challenging for effective cancer treatments. The polysaccharides extracted from Phellinus linteus (PLGL) have been widely used in treating cancers. However, the mechanism by which PLGL antagonizes cancerous growth has not been fully investigated. The current study demonstrated that human colon cancer HCT116 and HT29 cells became highly susceptible to cell death when being co-treated with PLGL and low dose of camptothecin11 (CPT11, a topoisomerase inhibitor-based drug), the efficacy of which was comparable as that generated by the high dose of CPT11...
January 19, 2018: Oncotarget
Xinyi Wang, Haiyang Zhang, Ming Bai, Tao Ning, Shaohua Ge, Ting Deng, Rui Liu, Le Zhang, Guoguang Ying, Yi Ba
Chemoresistance is one of the causes of adverse effects in gastric cancer, including a poor response to cisplatin (DDP). Exosomes loaded with microRNA (miRNA), mRNA, and other non-coding RNAs could regulate drug resistance. Exo-anti-214 was extracted and verified. A Cell Counting Kit-8 (CCK-8) cell viability assay, flow cytometry, and transwell and immunofluorescence assays were performed to determine whether exo-anti-214 could sensitize cells to DDP in vitro. A combination of intravenously injected exo-anti-214 and intraperitoneal DDP was utilized in vivo...
January 8, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Xi Han, Yang Liu, Wendy R Kam, David A Sullivan
We recently discovered that the anti-glaucoma pharmaceuticals timolol, a β adrenergic antagonist, and pilocarpine, a cholinergic compound, negatively influence the morphology, proliferative capacity and survival of human meibomian gland epithelial cells (HMGECs). We hypothesize that another class of anti-glaucoma drugs, the α2 adrenergic agonists, also acts directly on HMGECs to affect their structure and function. We tested this hypothesis. Immortalized (i) HMGECs were cultured with brimonidine, as well as clonidine (α2 agonist), phenylephrine (α1 agonist), RX821002 (inverse α2 agonist) and MK912 (neutral α2 agonist) for up to 7 days...
February 13, 2018: Experimental Eye Research
Chelsea Snyder, Lanlan Yu, Tin Ngo, Daniel Sheinson, Yuda Zhu, Min Tseng, Dinah Misner, Karin Staflin
Neurotoxicity is a major concern during drug development, and together with liver and cardio-toxicity, it is one of the main causes of clinical drug attrition. Current pre-clinical models may not sufficiently identify and predict the risk for central or peripheral nervous system toxicity. One such example is clinically dose-limiting neuropathic effects after the administration of chemotherapeutic agents. Thus, the need to establish novel in vitro tools to evaluate the risk of neurotoxicities, such as neuropathy, remains unmet in drug discovery...
February 7, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Jieyu Xu, Shingo Oda, Tsuyoshi Yokoi
Immortalized liver cells have been used for evaluating the toxicity of compounds; however, excessive glutathione is considered to lessen cytotoxicity. In this study, we compared the effects of glutathione depletion on cytotoxicities of drugs using HepaRG and HepG2 cells, which express and lack drug-metabolizing enzymes, respectively, for predicting drug-induced liver injury (DILI) risks. These cells were pre-incubated with L-buthionine-S,R-sulfoximine (BSO) and then exposed to 34 test compounds with various DILI risks for 24 h...
January 30, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Mehdi Jorfi, Carla D'Avanzo, Rudolph E Tanzi, Doo Yeon Kim, Daniel Irimia
Neurospheroids are commonly used for in vitro disease modeling and drug screening. However, the heterogeneity in size of the neurospheroids mixtures available through current methods limits their utility when employed for basic mechanistic studies of neurodegenerative diseases or screening for new interventions. Here, we generate neurospheroids from immortalized neural progenitor cells and human induced pluripotent stem cells that are uniform in size, into large-scale arrays. In proof of concept experiments, we validate the neurospheroids array as a sensitive and robust tool for screening compounds over extended time...
February 5, 2018: Scientific Reports
Xifeng Fei, Anqi Wang, Delin Wang, Xan Meng, Jiawei Ma, Lei Hong, Ruwei Qin, Aidong Wang, Jun Dong, Qiang Huang, Zhimin Wang
BACKGROUND: As a factor contributing to the tumor cell drug resistance, tumor microenvironment (TME) is being paid increasingly attention. However, the drug resistance of malignantly transformed cells in TME has rarely been revealed. This paper is designed to investigate the sensitivity of malignantly transformed cell line (ihDCTC) induced by glioma stem cells (GSCs) in TME to chemotherapeutic drugs. METHODS: (1) Establishment of ihDCTC cell line,The bone marrow cells from enhanced green fluorescent protein (EGFP) transgenic nude mice were employed to culture the dendritic cells (DCs) in vitro, which were then co-cultured with red fluorescence protein (RFP) transgenic GSCs (SU3) to obtain ihDCTC (2) Res and Cis were used to intervene in the growth of abovemetioned cell lines in vitro and Res treated in bearing ihDCTC tumor mice, followed by evaluating their drug sensitivity and changes in key signaling proteins via half maximal inhibitory concentration (IC50), tumor mass and immunostaining method...
February 2, 2018: BMC Immunology
Mathew Bloomfield, Peter Duesberg
Background: Foulds defined, "Tumor progression (as a) permanent, irreversible qualitative change in one or more of its characters" (Cancer Res. 1954). Accordingly progressions, such as metastases and acquired drug-resistance, were since found to be subspecies of cancers with conserved and numerous new chromosomes. Here we ask whether cancers acquire numerous new chromosomes gradually or simultaneously in progressions. The currently prevailing theory of Nowell (Science, 1976) holds that unexplained "genetic instability" generates "variant sublines (with) changes in chromosome number" and that "clonal" progressions arise by "stepwise selection of more aggressive sublines"...
2018: Molecular Cytogenetics
Yongyut Pewkliang, Siriwan Rungin, Kaewta Lerdpanyangam, Apisak Duangmanee, Phongthon Kanjanasirirat, Phichaya Suthivanich, Khanit Sa-Ngiamsuntorn, Suparerk Borwornpinyo, Jetsumon Sattabongkot, Rapatbhorn Patrapuvich, Suradej Hongeng
BACKGROUND: Eradication of malaria is difficult because of the ability of hypnozoite, the dormant liver-stage form of Plasmodium vivax, to cause relapse in patients. Research efforts to better understand the biology of P. vivax hypnozoite and design relapse prevention strategies have been hampered by the lack of a robust and reliable model for in vitro culture of liver-stage parasites. Although the HC-04 hepatoma cell line is used for culturing liver-stage forms of Plasmodium, these cells proliferate unrestrictedly and detach from the culture dish after several days, which limits their usefulness in a long-term hypnozoite assay...
January 25, 2018: Malaria Journal
Maolin Chu, Chunying Zhang
Angiogenesis plays an important role in bladder cancer (BCa). The immunosuppressive drug leflunomide has attracted worldwide attention. However, the effects of leflunomide on angiogenesis in cancer remain unclear. Here, we report the increased expression of soluble ephrin-A1 (sEphrin-A1) in supernatants of BCa cell lines (RT4, T24, and TCCSUP) co-cultured with human umbilical vein endothelial cells (HUVECs) compared with that in immortalized uroepithelial cells (SV-HUC-1) co-cultured with HUVECs. sEphrin-A1 is released from BCa cells as a monomeric protein that is a functional form of the ligand...
January 24, 2018: Scientific Reports
Elnaz Gozalpour, Katherine S Fenner
BACKGROUND: Renal proximal tubule (PT) epithelial cells, expressing uptake and efflux transporters at basolateral and apical membranes, are the location of active renal drug secretion and reabsorption. In addition to singly transfected cells, an in vitro renal cell-based model is a requirement to study the active renal secretion of drugs, drug-drug interactions (DDIs), drug-induced kidney injury, nephrotoxicity holistically, and potentially renal replacement therapies. OBJECTIVES: So far, two-dimensional (2D) cell culture of primary and immortalized PT cells has been the only tool to study drugs active secretion, interactions, and nephrotoxicity, however, a number of in vivo characteristics of cells such as drug transporter expression and function, along with morphological features are lost during in vitro cell culture...
January 18, 2018: Current Drug Metabolism
Takenori Shimo, Kana Hosoki, Yusuke Nakatsuji, Toshifumi Yokota, Satoshi Obika
Oligonucleotide-mediated splicing modulation is a promising therapeutic approach for Duchenne muscular dystrophy (DMD). Recently, eteplirsen, a phosphorodiamidate morpholino oligomer-based splice-switching oligonucleotide (SSO) targeting DMD exon 51, was approved by the U.S. Food and Drug Administration as the first antisense-based drug for DMD patients. For further exploring SSOs targeting other exons in the DMD gene, the efficacy of exon skipping and protein rescue with each SSO sequence needs evaluations in vitro...
January 16, 2018: Journal of Human Genetics
Yuyin Li, Guojun Pan, Yue Chen, Qian Yang, Tiantian Hao, Lianbo Zhao, Long Zhao, Yusheng Cong, Aipo Diao, Peng Yu
Telomerase is aberrantly expressed in many cancers and plays an important role in the development of cellular immortality and oncogenesis, which makes it a potential cancer therapeutic target for drug discovery. Here, we constructed a firefly luciferase reporter driven by the human telomerase reverse trancriptase (hTERT) gene promoter to screen for inhibitory compounds. Compound 5c was discovered and shown to significantly inhibit the promoter activity of hTERT gene. Furthermore, five analogs of compound 5c were synthesized, and compound 8b was shown to be a more potent inhibitor of hTERT gene promoter activity and subsequent expression of hTERT mRNA and protein...
December 27, 2017: European Journal of Medicinal Chemistry
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"