Abstract:
:The poor prognosis of pancreatic cancer patients using currently available therapies mandates novel therapeutics that combine anti-neoplastic potency with toxicity-minimizing cancer specificity. Employing an overlapping pathway screen to identify genes exhibiting coordinated expression as a consequence of terminal cell differentiation and replicative senescence, we identified human polynucleotide phosphorylase (hPNPase(old-35)), a 3',5'-exoribonuclease that exhibits robust growth-suppressing effects in a wide spectrum of human cancers. A limitation to the anti-neoplastic efficacy of hPNPase(old-35) relates to its lack of cancer specificity. The promoter of Progression Elevated Gene-3 (PEG-Prom), discovered in our laboratory via subtraction hybridization in a transformation progression rodent tumor model functions selectively in a diverse array of human cancer cells, with limited activity in normal cells. An adenovirus constructed with the PEG-Prom driving expression of hPNPase(old-35) containing a C-terminal Hemaglutinin (HA)-tag (Ad.PEG.hPNPase(old-35)) was shown to induce robust transgene expression, growth suppression, apoptosis, and cell-cycle arrest in a broad panel of pancreatic cancer cells, with minimal effects in normal immortalized pancreatic cells. hPNPase(old-35) expression correlated with arrest in the G(2)/M phase of the cell cycle and up-regulation of the cyclin-dependent kinase inhibitors (CDKI) p21(CIP1/WAF-1/MDA-6) and p27(KIP1). In a nude mouse xenograft model, Ad.PEG.hPNPase(old-35) injections effectively inhibited growth of human pancreatic cancer cells in vivo. These findings support the potential efficacy of combining a cancer-specific promoter, such as the PEG-Prom, with a novel anti-neoplastic agent, such as hPNPase(old-35), to create a potent, targeted cancer therapeutic, especially for a devastating disease like pancreatic cancer.
journal_name
J Cell Physioljournal_title
Journal of cellular physiologyauthors
Chan I,Lebedeva IV,Su ZZ,Sarkar D,Valerie K,Fisher PBdoi
10.1002/jcp.21320subject
Has Abstractpub_date
2008-05-01 00:00:00pages
401-9issue
2eissn
0021-9541issn
1097-4652journal_volume
215pub_type
杂志文章abstract::Apelin is an endogenous ligand of seven-transmembrane G protein-coupled receptor APJ. Apelin and APJ are distributed in various tissues, including the heart, lung, kidney, and even in tumor tissues. Studies show that apelin mRNA is highly expressed in the inner stripe of kidney outer medulla, which plays an important ...
journal_title:Journal of cellular physiology
pub_type: 杂志文章,评审
doi:10.1002/jcp.26144
更新日期:2018-05-01 00:00:00
abstract::Many critical factors such as hypoxia, nutrient deficiency, activation of glycolytic pathway/Warburg effect contribute to the observed low pH in tumors compared to normal tissue. Studies suggest that such tumor specific acidic environment can be exploited for the development of therapeutic strategies against cancer. I...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.22865
更新日期:2012-04-01 00:00:00
abstract::Diabetic nephropathy (DN) is an important factor leading to end-stage kidney disease that affects diabetes mellitus patients globally. Our previous transcriptome sequencing has identified a large group of differentially expressed long noncoding RNA (lncRNA) in early development of DN. On basis of this, we aimed to inv...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.28485
更新日期:2019-08-01 00:00:00
abstract::Over the past decade, a wide range of scientific investigations have been performed to reveal neuropathological aspects of cognitive disorders; however, only limited therapeutic approaches currently exist. The failures of conventional therapeutic options as well as the predicted dramatic rise in the prevalence of cogn...
journal_title:Journal of cellular physiology
pub_type: 杂志文章,评审
doi:10.1002/jcp.27289
更新日期:2019-03-01 00:00:00
abstract:BACKGROUND:Pulmonary arterial hypertension (PAH) is characterized by the apoptosis resistance and hyperproliferation of pulmonary artery smooth muscle cells (PASMCs). Its pathogenesis has not been revealed. Here, we carried out experiments to investigate the functions of miR-140-5p and tumor necrosis factor-α (TNF-α). ...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.27642
更新日期:2019-06-01 00:00:00
abstract::Proteinuria in diabetic nephropathy has been correlated with reduction in heparan sulfate proteoglycan (HSPG) content of the glomerular basement membrane. We have previously shown that the underlying mechanism probably involves reduction in the synthesis by glomerular epithelial cells. In this study we explored whethe...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/(SICI)1097-4652(199604)167:1<131::AID-JCP1
更新日期:1996-04-01 00:00:00
abstract::A successful aging could be gained by life satisfaction, social functioning, or psychological resources and, definitely, by increasing resistance to diverse age-related pathologies. Nowadays, cancer can be considered an age-related disease since the incidence of most cancers increases with age, rising more rapidly beg...
journal_title:Journal of cellular physiology
pub_type: 杂志文章,评审
doi:10.1002/jcp.26825
更新日期:2018-11-01 00:00:00
abstract::Sevoflurane has been commonly utilized in nonobstetric surgeries in pregnant women, and its impacts on fetal brain are still not completely known. Ectopic NR4A2 expression has been reported to be related with familial Parkinson disease, and through dual luciferase we found that NR4A2 is a target gene of microRNA-183 (...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.27158
更新日期:2019-04-01 00:00:00
abstract::Breast cancer, as the most common cancer in women which affects patients both mentally and physically, requires great attention in many areas and many levels as this cancer is known to be multifactorial. Single-stranded molecules called microRNAs with near 22 nucleotides are seen to act in central dogma of molecular b...
journal_title:Journal of cellular physiology
pub_type: 杂志文章,评审
doi:10.1002/jcp.29966
更新日期:2021-03-01 00:00:00
abstract::Epithelial Cell Adhesion Molecule (EpCAM), or CD326, is a trans-membrane glycoprotein expressed by multiple normal epithelia as well as carcinoma. Human hepatic stem cells and bile duct epithelium of the liver are EpCAM positive. In tumor cell lines, its intracellular domain can be released after cleavage of the extra...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.26286
更新日期:2018-06-01 00:00:00
abstract::Suppression of PKC activity can selectively induce apoptosis in cells expressing a constitutively activated p21Ras protein. We demonstrate that continued expression of p21Ras activity is required in PKC-mediated apoptosis because farnesyltransferase inhibitors abrogated the loss of viability in p21Ras-transformed cell...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.10409
更新日期:2004-02-01 00:00:00
abstract::Over-production and activation of osteoclasts is a common feature of osteolytic conditions such as osteoporosis, tumor-associated osteolysis, and inflammatory bone erosion. Cyanidin Chloride, a subclass of anthocyanin, displays antioxidant and anti-carcinogenesis properties, but its role in osteoclastic bone resorptio...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.26126
更新日期:2018-03-01 00:00:00
abstract::Surface membrane expression and conformational activation of CD18 integrins into an open molecular configuration play critical roles in neutrophil ligand binding, membrane attachment, spreading on the endothelium, and cell migration to sites of inflammation. Previously, we observed pseudopod retraction and concomitant...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.21235
更新日期:2008-02-01 00:00:00
abstract::Optical tweezers were used to scan individual Chronic Myelogenous Leukemia cells to determine if the cell death depends on the scanning conditions. Although increasing the scanning frequency or amplitude means greater force applied to the cells, their effects on cell death are not a simple increasing trend, as observe...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.24369
更新日期:2013-10-01 00:00:00
abstract::Exosomes extracted from mesenchymal stem cells (MSCs) was reported to reduce myocardial ischemia/reperfusion damage. Besides, stromal-derived factor 1 (SDF1a) functions as cardiac repair after myocardial infarction (MI). Therefore, the present study aims to identify whether exosomes (Exo) released from SDF1-overexpres...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.28070
更新日期:2019-08-01 00:00:00
abstract::Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the etiopathogenesis of lung cancer and is a promising tool for cancer detection. In the present study, promoter hypermethylation of p16INK4A and CDH13 genes was investigated in tumor tissue and in matched s...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.20503
更新日期:2006-03-01 00:00:00
abstract::Hair follicle stem cells (HFSCs) are able to differentiate into neurons and glial cells. Distinct microRNAs (miRNAs) regulate the proliferation and differentiation of HFSCs. However, the exact role of miR-124 in the neural differentiation of HFSCs has not been elucidated. HFSCs were isolated from mouse whisker follicl...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.27563
更新日期:2019-06-01 00:00:00
abstract::Norepinephrine (NE) produced a dose-dependent inhibition of 125I-epidermal growth factor (EGF) binding to adult rat hepatocytes in primary culture. This effect was maximal after 1 hr of incubation with NE and could be blocked by the presence of an alpha 1-specific adrenergic receptor antagonist. The inhibition of bind...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041270106
更新日期:1986-04-01 00:00:00
abstract::We have previously reported that the proliferation of cloned MCF-7 and T47D human mammary tumor cells can be inhibited by increasing concentrations of charcoal-dextran stripped female human serum (CDFHS). The maximal proliferation rate was restored by the addition of 3 X 10(-11) M estradiol-17 beta to the culture medi...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041240305
更新日期:1985-09-01 00:00:00
abstract::Syndecans are constitutively shed from growing epithelial cells as the part of normal cell surface turnover. However, increased serum levels of the soluble syndecan ectodomain have been reported to occur during bacterial infections. The aim of this study was to evaluate the potential of lipopolysaccharide (LPS) from t...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.20287
更新日期:2005-07-01 00:00:00
abstract::Testicular germ cell tumors (TGCTs) are frequent solid malignant tumors and cause of death in men between 20-40 years of age. Genetic and environmental factors play an important role in the origin and development of TGCTs. Although the majority of TGCTs are responsive to chemotherapy, about 20% of patient presents inc...
journal_title:Journal of cellular physiology
pub_type: 杂志文章,评审
doi:10.1002/jcp.25482
更新日期:2017-02-01 00:00:00
abstract::The effects of ouabain on the growth of murine lymphoblasts in vitro have been studied. Exposure of cells to ouabain (0.1 mM) initially inhibited 86Rb+ uptake rate, reduced the intracellular potassium concentration, and decreased population growth rates. Continued exposure to the same ouabain concentration resulted in...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1040850208
更新日期:1975-04-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) is one of the most common malignancies and is a serious threat to people's health worldwide. The prognosis of advanced HCC is dim if left untreated. In the clinic, the treatment options for advanced HCC include surgery, radiotherapy, transcatheter arterial chemoembolization, and so forth...
journal_title:Journal of cellular physiology
pub_type: 杂志文章,评审
doi:10.1002/jcp.28048
更新日期:2019-08-01 00:00:00
abstract::Active oxygen species are generated in cells during pathophysiologic conditions such as inflammation and postischemic reperfusion. If oxygen radical scavengers are added before reperfusion, then the magnitude of injury is reduced. We investigated whether free radicals generated following exposure to hypoxia and reoxyg...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041560217
更新日期:1993-08-01 00:00:00
abstract::This study establishes a causal link between the limitation of myofibre transitions and modulation of calcineurin activity, during different exercise paradigms. We have designed a new swimming-based training protocol in order to draw a comparison between a high frequency and amplitude exercise (swimming) and low frequ...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.21168
更新日期:2008-01-01 00:00:00
abstract::The smooth muscle cell population in major arteries of humans and experimental animals is heterogeneous with regard to cellular DNA content. A proportion of cells has polyploid DNA content and this proportion increases with normal aging and with hypertension. We have isolated pure populations of rat aortic smooth musc...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041250322
更新日期:1985-12-01 00:00:00
abstract::Increased vascular resistance in the fetoplacental circulation is a characteristic of preeclampsia. However, the potential molecular mechanisms of this condition remain obscure. The current study aimed to determine the direct effect of the peptide antigen corresponding to the second extracellular loop of the angiotens...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.24113
更新日期:2013-01-01 00:00:00
abstract::Non-histone chromosomal proteins are phosphorylated and dephosphorylated within the intact nucleus by two independent sets of reactions, a protein kinase reaction which transfers the terminal phosphate group of a variety of nucleoside and deoxynucleoside triphosphates to serine and threonine residues in the proteins, ...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1040850412
更新日期:1975-04-01 00:00:00
abstract::Bone marrow mesenchymal stem cells (BMSC) can ameliorate ischemic injury of various tissues. However, the molecular mechanisms involved remain to be clarified. In this study, we intend to investigate the effects of BMSC-derived conditioned medium (BMSC-CM) on hypoxia/reoxygenation (H/R)-induced injury of H9c2 myocardi...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.28530
更新日期:2019-08-01 00:00:00
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