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Cell Biology and Toxicology

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https://www.readbyqxmd.com/read/28589243/rnai-targeting-stmn-alleviates-the-resistance-to-taxol-and-collectively-contributes-to-down-regulate-the-malignancy-of-nsclc-cells-in-vitro-and-in-vivo
#1
Dan Long, Ting Yu, Xian Chen, Ying Liao, Xuechi Lin
Stathmin (STMN) plays a vital role in maintaining the malignant behavior of cancer through directly regulating microtubule dynamics equilibrium. Taxol, an effective chemotherapeutics mainly acting to promote microtubule polymerization, has been commercially applied in treating solid tumors, which results in serious drug resistance. Our study demonstrated that STMN RNA interference (RNAi) enlarged taxol-induced inhibitions in cellular proliferation, colony formation, and multidimensional spaces of cell immigration and decreased half maximal inhibitory concentration (IC50) of taxol in nonsmall cell lung cancer (NSCLC) NCI-H1299 cells; STMN RNAi and taxol jointly attenuated the expressions of extracellular regulated kinase (ERK), nuclear factor kappa B (NF-κB) and B cell lymphoma-2 (Bcl-2), but up regulated Bax expression and initiated intrinsic cell death pathway by activating caspase-3 and caspase-9, while inhibited interleukin 10 (IL-10) autocrine from cell culture supernatant and xenografted mouse serum, as well as intracellular expressions of IL-10 protein and mRNA in vitro; additionally, neutralizing IL-10 alone would incur cell apoptosis to some degree; the further study confirmed that RNAi targeting STMN promoted the sensitivity of taxol in different NSCLC cells...
June 7, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28540451/exogenous-cgrp-upregulates-profibrogenic-growth-factors-through-pkc-jnk-signaling-pathway-in-kidney-proximal-tubular-cells
#2
Sang Pil Yoon, Jinu Kim
Kidney denervation prevents the development of tubulointerstitial fibrosis, but the neuropeptide calcitonin gene-related peptide (CGRP) in the denervated kidneys restores the fibrotic feature through the upregulation of profibrogenic growth factors. CGRP is involved in aggravation of inflammation by increasing the number of circulating cells and chemotactic factors. However, it is not clear how CGRP contributes to the upregulation of profibrogenic factors during fibrogenesis. In both human and pig kidney proximal tubular cell lines, administration of 1 nM CGRP significantly increased the levels of transforming growth factor-β1 (TGF-β1) production and connective tissue growth factor (CTGF) expression at 6 and 24 h after the administration...
May 24, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28474249/t-cell-modulation-in-immunotherapy-for-hematological-malignancies
#3
EDITORIAL
Chen Lin, Shaohua Chen, Yangqiu Li
No abstract text is available yet for this article.
May 4, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28470556/critical-roles-of-mucin-1-in-sensitivity-of-lung-cancer-cells-to-tumor-necrosis-factor-alpha-and-dexamethasone
#4
Menglin Xu, Xiangdong Wang
Lung cancer is the leading cause of death from cancer. Mucins are glycoproteins with high molecular weight, responsible for cell growth, differentiation, and signaling, and were proposed to be correlated with gene heterogeneity of lung cancer. Here, we report aberrant expression of mucin genes and tumor necrosis factor receptors in lung adenocarcinoma tissues compared with normal tissues in GEO datasets. Mucin-1 (MUC1) gene was selected and considered as the target gene; furthermore, the expression pattern of adenocarcinomic cells (A549, H1650, or H1299 cells) was validated under the stimulation with tumor necrosis factor-alpha (TNFα) or dexamethasone (DEX), separately...
May 3, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28466226/analysis-of-dna-damage-response-to-ionizing-radiation-in-serum-shock-synchronized-human-fibroblasts
#5
Samantha Corrà, Riccardo Salvadori, Leonardo Bee, Vito Barbieri, Maddalena Mognato
Many aspects of cellular physiology, including cellular response to genotoxic stress, are related to the circadian rhythmicity induced by the molecular clock. The current study investigated if the cellular response to DNA damage is in relation to endogenous expression levels of the PER2 protein, a key component of the molecular regulatory system that confers rhythmicity in mammalian cells. Human normal fibroblasts (CCD-34Lu) were subjected to serum shock to induce circadian oscillations of the PER2 protein and then irradiated with γ- rays at times corresponding to the trough and peak expression of the PER2 protein...
May 3, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28455626/influences-of-flavones-on-cell-viability-and-camp-dependent-steroidogenic-gene-regulation-in-ma-10-leydig-cells
#6
Michelle Cormier, Firas Ghouili, Pauline Roumaud, William Bauer, Mohamed Touaibia, Luc J Martin
Testicular Leydig cells are major contributors of androgen synthesis and secretion, which play an important role in testis development, normal masculinization, maintenance of spermatogenesis, and general male fertility. The rate-limiting step in testosterone biosynthesis involves the transfer of cholesterol to the mitochondrial inner membrane by the steroidogenic acute regulatory (Star) protein, a critical factor in steroid hormone biosynthesis. Once inside the mitochondria, cholesterol is metabolized by the steroidogenic enzyme Cyp11a1 to pregnenolone, which is further converted to testosterone by the action of other steroidogenic enzymes...
April 28, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28382404/prediction-of-hepatotoxicity-for-drugs-using-human-pluripotent-stem-cell-derived-hepatocytes
#7
Jong Hyun Kim, Min Wang, Jaehun Lee, Han-Jin Park, Chungseong Han, Hee Su Hong, Jeong Seong Kim, Geun Ho An, Kijung Park, Hee-Kyung Park, Shi Feng Zhu, Xiao-Bo Sun, Jong-Hoon Kim, Dong-Hun Woo
Drug-induced liver toxicity is a main reason for withdrawals of new drugs in late clinical phases and post-launch of the drugs. Thus, hepatotoxicity screening of drug candidates in pre-clinical stage is important for reducing drug attrition rates during the clinical development process. Here, we show commercially available hepatocytes that could be used for early toxicity evaluation of drug candidates. From our hepatic differentiation technology, we obtained highly pure (≥98%) hepatocytes from human embryonic stem cells (hESCs) having mature phenotypes and similar gene expression profiles with those of primary human tissues...
April 5, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28474250/single-cell-crispr-screening-in-drug-resistance
#8
EDITORIAL
William Wang, Xiangdong Wang
No abstract text is available yet for this article.
June 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28064403/knockdown-of-clusterin-alters-mitochondrial-dynamics-facilitates-necrosis-in-camptothecin-induced-cancer-stem-cells
#9
Parthasarathy Arumugam, Annie Samson, Jieun Ki, Joon Myong Song
The existence of a well-established drug resistance mechanism in cancer stem cells (CSC) complicates the cancer treatment. Clusterin (CLU) plays a key role in maintaining the integrity of endoplasmic reticulum (ER) during drug-induced stress. Hence, silencing the CLU could significantly reduce the inherent drug resistance mechanism of CSC. The combination of drug-induced cytotoxicity, as well as the suppression of drug resistance in CSC, could circumvent the recurrence capability of the tumor. In the present study, camptothecin (CPT)-induced apoptosis and necrosis in CSC with and without siCLU treatment were simultaneously measured using Qdot-based total internal reflection fluorescence microscope (TIRF)...
June 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28039590/ten-years-of-ipsc-clinical-potential-and-advances-in-vitro-hematopoietic-differentiation
#10
REVIEW
Bárbara Cristina Martins Fernandes Paes, Pablo Diego Moço, Cristiano Gonçalves Pereira, Geciane Silveira Porto, Elisa Maria de Sousa Russo, Luiza Cunha Junqueira Reis, Dimas Tadeu Covas, Virginia Picanço-Castro
Ten years have passed since the first publication announcing the generation of induced pluripotent stem cells (iPSCs). Issues related to ethics, immune rejection, and cell availability seemed to be solved following this breakthrough. The development of iPSC technology allows advances in in vitro cell differentiation for cell therapy purpose and other clinical applications. This review provides a perspective on the iPSC potential for cell therapies, particularly for hematological applications. We discuss the advances in in vitro hematopoietic differentiation, the possibilities to employ iPSC in hematology studies, and their potential clinical application in hematologic diseases...
June 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/27987184/look-who-s-talking-the-crosstalk-between-oxidative-stress-and-autophagy-supports-exosomal-dependent-release-of-hcv-particles
#11
REVIEW
Regina Medvedev, Eberhard Hildt, Daniela Ploen
Autophagy is a highly conserved and regulated intracellular lysosomal degradation pathway that is essential for cell survival. Dysregulation has been linked to the development of various human diseases, including neurodegeneration and tumorigenesis, infection, and aging. Besides, many viruses hijack the autophagosomal pathway to support their life cycle. The hepatitis C virus (HCV), a major cause of chronic liver diseases worldwide, has been described to induce autophagy. The autophagosomal pathway can be further activated in response to elevated levels of reactive oxygen species (ROS)...
June 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/27981389/pro-differentiating-effects-of-a-synthetic-flavagline-on-human-teratocarcinomal-cancer-stem-like-cells
#12
Fathi Emhemmed, Sarah Ali Azouaou, Qian Zhao, Aline Appert-Collin, Amar Bennasroune, Valérie B Schini-Kerth, Christian D Muller, Laurent Désaubry, Guy Fuhrmann
As initiators of the carcinogenic process, cancer stem cells (CSCs) are considered as new targets for anti-cancer therapies. However, these cells are hidden in the cancer bulk and remain relatively insensitive to chemotherapy, which targets their proliferative capacities. Alternatively, growing evidences have pointed out that a differentiation therapy could adversely affect these cells, which consequently should lose their self-renewal properties and become less aggressive. In order to evaluate the differentiation potential of an emerging class of anti-cancer drugs, we used the poorly differentiated teratocarcinomal cell as a model of Oct4-expressing CSC and determined the molecular mechanisms induced by the highly active flavagline FL3...
June 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/27942899/screening-of-molecular-cell-targets-for-carcinogenic-heterocyclic-aromatic-amines-by-using-calux%C3%A2-reporter-gene-assays
#13
Pablo Steinberg, Peter A Behnisch, Harrie Besselink, Abraham A Brouwer
Heterocyclic aromatic amines (HCAs) are compounds formed when meat or fish are cooked at high temperatures for a long time or over an open fire. To determine which pathways of toxicity are activated by HCAs, nine out of the ten HCAs known to be carcinogenic in rodents (2-amino-9H-pyrido[2,3-b]indole (AαC), 2-aminodipyrido[1,2-a:3',2-d]imidazole (Glu-P-2), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAαC), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2)) were tested in the estrogen receptor α (ERα), androgen receptor (AR), glucocorticoid receptor (GR), peroxisome proliferator-activated receptor γ2 (PPARγ2), polycyclic aromatic hydrocarbons (PAH), Nrf2, and p53 CALUX® reporter gene assays...
June 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/27822587/disruption-of-endolysosomal-trafficking-pathways-in-glioma-cells-by-methuosis-inducing-indole-based-chalcones
#14
Nneka E Mbah, Jean H Overmeyer, William A Maltese
Methuosis is a form of non-apoptotic cell death involving massive vacuolization of macropinosome-derived endocytic compartments, followed by a decline in metabolic activity and loss of membrane integrity. To explore the induction of methuosis as a potential therapeutic strategy for killing cancer cells, we have developed small molecules (indole-based chalcones) that trigger this form of cell death in glioblastoma and other cancer cell lines. Here, we report that in addition to causing fusion and expansion of macropinosome compartments, the lead compound, 3-(5-methoxy-2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (MOMIPP), disrupts vesicular trafficking at the lysosomal nexus, manifested by impaired degradation of EGF and LDL receptors, defective processing of procathepsins, and accumulation of autophagosomes...
June 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/27796700/benzophenone-3-increases-metastasis-potential-in-lung-cancer-cells-via-epithelial-to-mesenchymal-transition
#15
Preeyaporn Plaimee Phiboonchaiyanan, Kesarin Busaranon, Chuanpit Ninsontia, Pithi Chanvorachote
Exposure to compounds with cancer-potentiating effects can contribute to the progression of cancer. Herein we have discovered for the first time that benzophenone-3 (BP-3), a chemical used as sunscreen in various cosmetic products, enhances the ability of lung cancer cells to undergo metastasis. The exposure of the lung cancer cells to BP-3 at non-toxic concentrations significantly increased the number of anoikis resistant cells in a dose-dependent manner. Also, BP-3 increased the growth rate as well as the number of colonies accessed by anchorage-independent growth assay...
June 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/27957648/autophagy-from-molecular-mechanisms-to-clinical-relevance
#16
REVIEW
Mónika Lippai, Zsuzsanna Szatmári
Autophagy is a lysosomal degradation pathway of eukaryotic cells that is highly conserved from yeast to mammals. During this process, cooperating protein complexes are recruited in a hierarchic order to the phagophore assembly site (PAS) to mediate the elongation and closure of double-membrane vesicles called autophagosomes, which sequester cytosolic components and deliver their content to the endolysosomal system for degradation. As a major cytoprotective mechanism, autophagy plays a key role in the stress response against nutrient starvation, hypoxia, and infections...
April 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/27915387/the-translational-potential-of-human%C3%A2-induced-pluripotent-stem-cells-for-clinical-neurology-the-translational-potential-of-hipscs-in-neurology
#17
REVIEW
Helen Devine, Rickie Patani
The induced pluripotent state represents a decade-old Nobel prize-winning discovery. Human-induced pluripotent stem cells (hiPSCs) are generated by the nuclear reprogramming of any somatic cell using a variety of established but evolving methods. This approach offers medical science unparalleled experimental opportunity to model an individual patient's disease "in a dish." HiPSCs permit developmentally rationalized directed differentiation into any cell type, which express donor cell mutation(s) at pathophysiological levels and thus hold considerable potential for disease modeling, drug discovery, and potentially cell-based therapies...
April 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/27900567/clinical-potential-of-human-induced-pluripotent-stem-cells-perspectives-of-induced-pluripotent-stem-cells
#18
REVIEW
Dharmendra Kumar, Taruna Anand, Wilfried A Kues
The recent establishment of induced pluripotent stem (iPS) cells promises the development of autologous cell therapies for degenerative diseases, without the ethical concerns associated with human embryonic stem (ES) cells. Initially, iPS cells were generated by retroviral transduction of somatic cells with core reprogramming genes. To avoid potential genotoxic effects associated with retroviral transfection, more recently, alternative non-viral gene transfer approaches were developed. Before a potential clinical application of iPS cell-derived therapies can be planned, it must be ensured that the reprogramming to pluripotency is not associated with genome mutagenesis or epigenetic aberrations...
April 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/27900566/autophagy-regulates-death-of-retinal-pigment-epithelium-cells-in-age-related-macular-degeneration
#19
REVIEW
Kai Kaarniranta, Paulina Tokarz, Ali Koskela, Jussi Paterno, Janusz Blasiak
Age-related macular degeneration (AMD) is an eye disease underlined by the degradation of retinal pigment epithelium (RPE) cells, photoreceptors, and choriocapillares, but the exact mechanism of cell death in AMD is not completely clear. This mechanism is important for prevention of and therapeutic intervention in AMD, which is a hardly curable disease. Present reports suggest that both apoptosis and pyroptosis (cell death dependent on caspase-1) as well as necroptosis (regulated necrosis dependent on the proteins RIPK3 and MLKL, caspase-independent) can be involved in the AMD-related death of RPE cells...
April 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/27837347/tamoxifen-resistance-and-metastasis-of-human-breast-cancer-cells-were-mediated-by-the-membrane-associated-estrogen-receptor-er-%C3%AE-36-signaling-in-vitro
#20
Wenwen Gu, Nian Dong, Peng Wang, Changgen Shi, Jun Yang, Jian Wang
The drug resistance and tumor metastasis have been the main obstacles for the longer-term therapeutic effects of tamoxifen (TAM) on estrogen receptor-positive (ER(+)) breast cancer, but the mechanisms underlying the TAM resistance are still unclear. Here, we demonstrated that the membrane-associated estrogen receptor ER-α36 signaling, but not the G protein-coupled estrogen receptor 1 (GPER1) signaling, might be involved in the TAM resistance and metastasis of breast cancer cells. In this study, a model of ER(+) breast cancer cell MCF-7 that involves the up-regulated expression of ER-α36 and unchanged expression of ER-α66 and GPER1 was established via the removal of insulin from the cell culture medium...
April 2017: Cell Biology and Toxicology
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