Abstract:
:To evaluate the growth-inhibitory properties of the potent multi-kinase antagonist Regorafenib (Fluoro-Sorafenib), which was synthesized as a more potent Sorafenib, a Raf inhibitor and to determine whether similar mechanisms were involved, human hepatoma cell lines were grown in the presence or absence of Regorafanib and examined for growth inhibition. Western blots were performed for Raf targets, apoptosis, and autophagy. Regorafenib inhibited growth of human Hep3B, PLC/PRF/5, and HepG2 cells in a concentration- and time-dependent manner. Multiple signaling pathways were altered, including MAP kinases phospho-ERK and phospho-JNK and its target phospho-c-Jun. There was evidence for apoptosis by FACS, cleavage of caspases and increased Bax levels; as well as induction of autophagy, as judged by increased Beclin-1 and LC3 (II) levels. Prolonged drug exposure resulted in cell quiescence. Full growth recovery occurred after drug removal, unlike with doxorubicin chemotherapy. Regorafenib is a potent inhibitor of cell growth. Cells surviving Regorafenib treatment remain viable, but quiescent and capable of regrowth following drug removal. The reversibility of tumor cell growth suppression after drug removal may have clinical implications.
journal_name
J Cell Physioljournal_title
Journal of cellular physiologyauthors
Carr BI,Cavallini A,Lippolis C,D'Alessandro R,Messa C,Refolo MG,Tafaro Adoi
10.1002/jcp.24148subject
Has Abstractpub_date
2013-02-01 00:00:00pages
292-7issue
2eissn
0021-9541issn
1097-4652journal_volume
228pub_type
杂志文章abstract::The present study was performed to clarify second messenger signaling in parathyroid hormone (PTH)-induced c-fos gene expression, to characterize the participation of the c-fos gene in the regulation of osteoblast proliferation and function as well as osteoclast-like cell formation by PTH and to compare these effects ...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041610221
更新日期:1994-11-01 00:00:00
abstract::The biological actions of retinoids are mediated by nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs). We have recently reported that decreased expression of RARα and RXRα has an important role in high glucose (HG)-induced cardiomyocyte apoptosis. However, the regulatory mechanisms of HG effects o...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.23005
更新日期:2012-06-01 00:00:00
abstract::Chronic hyperglycemia and activation of receptor for advanced glycation end products (RAGE) are known risk factors for microvascular disease development in diabetic retinopathy. Thioredoxin-interacting protein (TXNIP), an endogenous inhibitor of antioxidant thioredoxin (TRX), plays a causative role in diabetes and its...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.21852
更新日期:2009-10-01 00:00:00
abstract::Entry of certain free amino acids (alpha aminoisobutyric acid (AIB), alanine and proline), but not of leucine into rat thymic lymphocytes increased progressively when the cells were incubated in amino acid deficient medium. Actinomycin D, cycloheximide, or a high concentration of AIB abolished the time-related increas...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1040890307
更新日期:1976-11-01 00:00:00
abstract::Nidogen/entactin is a Mr = 150,000 glycoprotein which is present within basement membranes in a noncovalent stable complex with laminin. We have studied the effects of nidogen/entactin complexed or not with laminin on attachment, spreading, and functions of adult rat hepatocytes in primary culture. Freshly isolated he...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041610210
更新日期:1994-11-01 00:00:00
abstract::The predominant cyclooxygenase products of keratinocytes are prostaglandin (PG)E2 and PGF2 alpha with only trace amounts of PGI2 synthesis detected. When normal or immortal (NM1) keratinocytes were co-cultured with mitomycin C-treated 3T3 cells, increased synthesis of PGI2 was noted compared to mitomycin C-treated 3T3...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041500208
更新日期:1992-02-01 00:00:00
abstract::Our main objective is probing the effect of methylation of CLEC14A on its expression and lung adenocarcinoma (LUAD) progression. Microarray analysis was utilized to screen out differentially downregulated genes with hypermethylation in LUAD tissues. The CLEC14A expression level was measured by western blot analysis an...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.27112
更新日期:2019-03-01 00:00:00
abstract::Nowadays, epigenetics covers a crucial role in different fields of science. The enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2), is a big proponent of how epigenetic changes can affect the initiation and progression of several diseases. Through its catalytic activi...
journal_title:Journal of cellular physiology
pub_type: 杂志文章,评审
doi:10.1002/jcp.26545
更新日期:2018-09-01 00:00:00
abstract::Generation of reactive oxygen species (ROS) is a common event in the pathogenesis of acute lung injury. Endothelial cells may be both a target and a source of the ROS. Exposure of bovine pulmonary endothelial cells (BPAEC) to lipopolysaccharide (LPS) has been shown to result in intracellular generation of both ROS and...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/(SICI)1097-4652(199611)169:2<333::AID-JCP1
更新日期:1996-11-01 00:00:00
abstract::Expression of plasminogen activator inhibitor type-1 (PAI-1), a member of the SERPIN gene family that functions to regulate the plasmin-based pericellular proteolytic cascade, is growth state-regulated in normal rat kidney (NRK) cells (Ryan and Higgins, 1990, J. Cell. Physiol., 155:376-384; Ryan et al., 1996, Biochem....
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/(SICI)1097-4652(199701)170:1<8::AID-JCP2>3
更新日期:1997-01-01 00:00:00
abstract::The specific activity of a peroxisomal enzyme, lactate oxidase, and of pyruvate kinase and lactate dehydrogenase, which are not peroxisomal, increased rapidly when shaken cultures of Tetrahymena were transferred to conditions of oxygen restriction and supplemented with glucose. Two other peroxisomal enzymes, catalase ...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1040850106
更新日期:1975-02-01 00:00:00
abstract::The phenotype of a ouabain-resistant Aedes albopictus cell line has been partially characterized. Treatment of ouabain-sensitive cells with 0.005-1.0 mM ouabain resulted in an 80% reduction in the uptake of 86rubidium (86Rb+), an ion with an affinity for the K+ pump binding site; ouabain-resistant cells showed only a ...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041010317
更新日期:1979-12-01 00:00:00
abstract::Clear cell renal cell carcinoma (ccRCC) is a common urinary neoplasm, looking for useful candidates to establish scientific foundation for the therapy of ccRCC is urgent. We downloaded genomic profiles of GSE781, GSE6244, GSE53757, and GSE66271 from the Gene Expression Omnibus (GEO) database. GEO2R was used to analyze...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.28597
更新日期:2019-11-01 00:00:00
abstract::Mitogen-activated protein (MAP) kinases are serine/threonine kinases that are rapidly activated in response to mitogenic stimuli. Here we examined the enzymatic activity and phosphorylation state of the individual p44mapk and p42mapk isoforms during early G1 and late G1 phase of the mammalian cell cycle. Release of fi...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041630319
更新日期:1995-06-01 00:00:00
abstract::Grb10 is a member of a superfamily of adapter proteins that includes Grb10, 7, 14, and a protein of Caenorhabditis elegans called Mig10. Grb10 proteins are binding partners for several trans-membrane tyrosine-kinase receptors, including the insulin-like growth factor receptor (IGF-IR) and the insulin receptor (IR). Ma...
journal_title:Journal of cellular physiology
pub_type: 杂志文章,评审
doi:10.1002/jcp.10363
更新日期:2003-12-01 00:00:00
abstract::Cardiac hypertrophy (CH) has become a huge threat to human health. Recent years, long noncoding RNAs (lncRNAs) have been studied in human diseases, including CH. According to bioinformatics analysis, 10 lncRNAs possibly involved in the progression of CH were screened out. Among which, lncRNA SYNE1 antisense RNA 1 (SYN...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.28131
更新日期:2019-08-01 00:00:00
abstract::Lung cancer is the leading cause of cancer death worldwide. Although diagnostic methods and targeted drugs have been rapidly developed in recent years, the underlying molecular mechanisms in the pathogenesis of lung cancer remain enigmatic. The N6-methyladenosine (m6 A) modification is the most common modification of ...
journal_title:Journal of cellular physiology
pub_type: 杂志文章,评审
doi:10.1002/jcp.30136
更新日期:2020-11-01 00:00:00
abstract::Two transport systems for neutral amino acids have been characterised in LLC-PK, cells. The first, which transports alanine in a sodium-dependent manner, also mediates alanine exchange and is perferentially inhibited by serine, cysteine, and alpha-amino-n-butyric acid. This system resembles the ASC system in Ehrlich a...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041120205
更新日期:1982-08-01 00:00:00
abstract::MCF-10A human mammary epithelial cells cultured inside reconstituted basement membrane form acini that resemble the acinar structures of mammary lobules. This three-dimensional culture system has been used for identifying and characterizing the signal transduction pathways controlling cell proliferation and death, and...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.20639
更新日期:2006-07-01 00:00:00
abstract::Calcium ions (Ca2+ ) is the main element of dental pulp capping materials. Ca 2+ signaling plays a crucial role in a myriad of cell activities. An overwhelming array of studies have already reported the experimental and clinical benefits of Ca2+ -enriched materials in the treatment of teeth with accidental vital pulp ...
journal_title:Journal of cellular physiology
pub_type: 杂志文章,评审
doi:10.1002/jcp.27068
更新日期:2019-03-01 00:00:00
abstract::New compounds with promising antidiabetic activity were synthesized. For the first time, a portion of the glibenclamide molecule was bound to a part of the core structure of thiazolidinedione to evaluate insulin secretagogue activity. Following studies in our laboratory, 4-{2-[2-(3,4-dichlorophenyl)-4-oxo-1,3-thiazoli...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.26746
更新日期:2018-01-01 00:00:00
abstract::We have previously identified two stimulatory activities affecting blood cell maturation in PHA-stimulated human lymphocytes conditioned medium (PHA-LyCM). One was granulocyte-macrophage colony stimulatory activity (GM-CSA), and the other was T lymphocyte growth stimulatory activity (TL-GSA) in suspension culture. In ...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041010206
更新日期:1979-11-01 00:00:00
abstract::The development of atherosclerotic plaque is associated with neovascularization in the thickened intima and media of vascular walls. Neovascularization may have a role in the progression of atherosclerotic plaque as well as in the development of intraplaque hemorrhage. However, the mechanism and stimulus for neovascul...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041640324
更新日期:1995-09-01 00:00:00
abstract::The actions of prostaglandins (PG) on cAMP in dispersed chief cells from guinea pig stomach were examined and compared to the actions of these agents on pepsinogen secretion. Maximal concentrations of A, B, or E prostaglandins caused a 2-5-fold increase in pepsinogen secretion and cellular cAMP. The relative order of ...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041320119
更新日期:1987-07-01 00:00:00
abstract::The advent of high throughput gene expression profiling, from microarrays to sequence based assays has yielded vast insight into the biology of tumors. New technologies are constantly being unveiled which promise to generate more accurate maps of tumor gene deregulation, and demand the development of new strategies in...
journal_title:Journal of cellular physiology
pub_type: 杂志文章,评审
doi:10.1002/jcp.21554
更新日期:2008-12-01 00:00:00
abstract::We studied the influence of hydrocortisone (HC) on hyaluronan (HA) metabolism in explants of human skin, a model retaining normal three-dimensional architecture of dermal connective tissue and dynamic growth and stratification of epidermal keratinocytes. The synthesis of hyaluronan and proteoglycans (PGs), and DNA, we...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041640204
更新日期:1995-08-01 00:00:00
abstract::Established RAW264.7 cell lines for osteoclastic differentiation has been widely engaged in bone homeostasis research, however, the efficacy of RANKL independently stimulating has rarely been defined, because protocols were usually developed and modified by various laboratories. Otherwise, problematic issues are also ...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.27852
更新日期:2019-07-01 00:00:00
abstract::Osteoblasts are terminally differentiated cells with mesenchymal origins, known to possess pivotal roles in sustaining bone microstructure and homeostasis. These cells are implicated in the pathophysiology of various bone disorders, especially osteoporosis. Over the last few decades, strategies to impede bone resorpti...
journal_title:Journal of cellular physiology
pub_type: 杂志文章,评审
doi:10.1002/jcp.27582
更新日期:2019-06-01 00:00:00
abstract::Tenascin-C, a six-armed extracellular matrix glycoprotein, is expressed in a temporally and spatially restricted pattern during carcinogenesis and invasion or metastasis of carcinoma cells in association with stromal-epithelial interactions. The human epidermoid carcinoma-derived cell lines, A431 and HEp-2, which do n...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041650104
更新日期:1995-10-01 00:00:00
abstract::Conditions have been established under which the antizyme of ornithine decarboxylase (E.C. 4.1.1.17, L-ornithine carboxy-lyase, ODC) a non-competitive protein inhibitor of ODC, can be detected in cells in response to as little as 10(-7) M putrescine. The maintenance of intracellular antizyme activity depends upon the ...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041070206
更新日期:1981-05-01 00:00:00