Abstract:
:Hypoxia is a major hallmark of the tumor microenvironment that is strictly associated with rapid cancer progression and induction of metastasis. Hypoxia inhibits disulfide bond formation and impairs protein folding in the Endoplasmic Reticulum (ER). The stress in the ER induces the activation of Unfolded Protein Response (UPR) pathways via the induction of protein kinase RNA-like endoplasmic reticulum kinase (PERK). As a result, the level of phosphorylated Eukaryotic Initiation Factor 2 alpha (eIF2α) is markedly elevated, resulting in the promotion of a pro-adaptive signaling pathway by the inhibition of global protein synthesis and selective translation of Activating Transcription Factor 4 (ATF4). On the contrary, during conditions of prolonged ER stress, pro-adaptive responses fail and apoptotic cell death ensues. Interestingly, similar to the activity of the mitochondria, the ER may also directly activate the apoptotic pathway through ER stress-mediated leakage of calcium into the cytoplasm that leads to the activation of death effectors. Apoptotic cell death also ensues by ATF4-CHOP- mediated induction of several pro-apoptotic genes and suppression of the synthesis of anti-apoptotic Bcl-2 proteins. Advancing molecular insight into the transition of tumor cells from adaptation to apoptosis under hypoxia-induced ER stress may provide answers on how to overcome the limitations of current anti-tumor therapies. Targeting components of the UPR pathways may provide more effective elimination of tumor cells and as a result, contribute to the development of more promising anti-tumor therapeutic agents.
journal_name
Curr Mol Medjournal_title
Current molecular medicineauthors
Rozpedek W,Pytel D,Mucha B,Leszczynska H,Diehl JA,Majsterek Idoi
10.2174/1566524016666160523143937subject
Has Abstractpub_date
2016-01-01 00:00:00pages
533-44issue
6eissn
1566-5240issn
1875-5666pii
CMM-EPUB-75880journal_volume
16pub_type
杂志文章,评审abstract::Interleukin-25 (IL-25) plays a key role in the initiation and expansion of T helper (Th) 2 cell-mediated immune responses, thereby contributing to allergic diseases and host defense against helminthic parasites. More recent studies have however shown that IL-25 can also control the function of non-T cells, such as ant...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652411794474365
更新日期:2011-02-01 00:00:00
abstract:BACKGROUND:The phenotypic severity of β-thalassemia is highly modulated by three genetic modifiers: β-globin (HBB) mutations, co-inheritance of α-thalassemia and polymorphisms in the genes associated with fetal haemoglobin (HbF) production. This study was aimed to evaluate the effect of HbF related polymorphisms mainly...
journal_title:Current molecular medicine
pub_type: 临床试验,杂志文章
doi:10.2174/1566524018666181004121604
更新日期:2018-01-01 00:00:00
abstract::Chondroitin sulfate (CS)-glycosaminoglycans (GAGs) are linear, negatively charged polysaccharides attached to CS proteoglycans that make up a major component of biological matrices throughout both central and peripheral tissues. The position of their attached sulfate groups to the CS disaccharide is predicted to influ...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524020666200915110707
更新日期:2020-09-15 00:00:00
abstract::p66Shc is the only known proapoptotic member of the Shc protein family of molecular adaptors. Through its redox activity, p66Shc oxidates cytochrome-c, leading to increased ROS production and, eventually, to apoptosis. p66Shc has been implicated in the control of oxidative stress and life span in mammals. In this revi...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652409787847254
更新日期:2009-04-01 00:00:00
abstract::The purpose of this review is to provide a concise overview of developments over the last 15 years in the field of laboratory tests in human medicine that are based on the detection of alterations in the glycan part of glycoconjugates. We show how glycosylation-based diagnostic testing is widespread in the current cli...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652407780831629
更新日期:2007-06-01 00:00:00
abstract::In sum, the FTIs are signal transduction inhibitors that display promising clinical activity against a broad spectrum of malignancies. We are just beginning to explore and elucidate the mechanisms by which transformed cells respond to FTIs and the optimal settings in which they do so. The clinical trials that are curr...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652405774641052
更新日期:2005-11-01 00:00:00
abstract::Human genetic data on psychiatric disorders repeatedly demonstrate the involvement of various genes that are associated with neural development and neurogenesis. Neurogenesis is a biological process that is critical in brain development and continues throughout life. Neurogenesis is a multi-step process starting from ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524015666150303002834
更新日期:2015-01-01 00:00:00
abstract::Salmonella infections are a serious public health problem in developing countries and represent a constant concern for the food industry. The severity and the outcome of a systemic Salmonella infection depends on the "virulence" of the bacteria, on the infectious dose as well as on the genetic makeup and immunological...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524023362492
更新日期:2002-06-01 00:00:00
abstract::Most lysosomal storage diseases (LSD) exhibit neurological symptoms and there has been limited success in their treatment. Innovative treatments employing novel therapy or gene therapy may offer the prospect of improvement. Recent attempts to treat the neurological forms of LSD include neural stem cell therapy, mesenc...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524023363112
更新日期:2002-02-01 00:00:00
abstract::WHIM syndrome is a dominantly inherited primary immunodeficiency disorder representing the first identified example of human disease caused by mutations in the gene encoding for the chemokine receptor CXCR4. Pathogenesis is mediated by CXCR4 hyperfunction, leading to increased responsiveness to its unique ligand CXCL1...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652411795677963
更新日期:2011-06-01 00:00:00
abstract::As tumors progress to increased malignancy, cells within them develop the ability to invade into surrounding normal tissues and through tissue boundaries to form new growths (metastases) at sites distinct from the primary tumor. The molecular mechanisms involved in this process are incompletely understood but those as...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524033479447
更新日期:2003-11-01 00:00:00
abstract::Bitter gourd (Momordica charantia, BG) is both a nutritious and healthy food with a distinctive bitter flavor, and it is also widely exploited in folklore medicine. This review focuses on the efficacies and molecular mechanisms of BG-induced anti-diabetic, anti-HIV, and antitumor activities contributed by over twenty ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652411795976583
更新日期:2011-07-01 00:00:00
abstract:OBJECTIVES:Celastrol, a quinone methide triterpenoid, could induce apoptosis in pancreatic cancer cells. The purpose of this study is to determine whether there is protective autophagy after celastrol treatment in pancreatic cancer cells and the synergistic effects of celastrol and 3-MA in vitro and in vivo. METHODS:T...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524014666140414211223
更新日期:2014-05-01 00:00:00
abstract::Classical Hodgkin lymphoma (cHL) is now recognized as a B-cell-derived lymphoma which is characterized by only about 1% malignant pathognomonic Hodgkin and Reed-Sternberg (HRS) cells and an abundant infiltrate of reactive bystander cells. HRS cells are unique with respect to their lost B-cell-specific gene expression ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652411795243423
更新日期:2011-04-01 00:00:00
abstract:PURPOSE:Accumulated evidence have well established that protein sumoylation plays multiple roles in various cellular processes. In the vertebrate eye, we and others have demonstrated that sumoylation displays indispensable roles in regulating eye development. Various ocular cell lines including human embryonic cell lin...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666190107153440
更新日期:2018-01-01 00:00:00
abstract::Our current understanding of the mechanisms of information processing and storage in the brain, based on the concept proposed more than fifty years ago by D. Hebb, is that a key role is played by changes in synaptic efficacy induced by coincident pre- and postsynaptic activity. Decades of studies of the properties of ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524023362041
更新日期:2002-11-01 00:00:00
abstract::Nanotechnology has witnessed tremendous advancement over the last several decades. Zinc oxide (ZnO), which can exhibit a wide variety of nanostructures, possesses unique semiconducting, optical, and piezoelectric properties hence has been investigated for a wide variety of applications. The most important features of ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524013666131111130058
更新日期:2013-12-01 00:00:00
abstract::After several years of controversy, antibodies (Abs) are now believed to play an important role in the protection against fungal infections. Among them, recent data are strongly supporting the relevance of protective yeast killer toxin-like Abs ("antibiobodies", KT-Abs), which are able to exert a direct microbicidal a...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524054022558
更新日期:2005-06-01 00:00:00
abstract::Since the discovery almost fifteen years ago that E2F transcription factors are key targets of the retinoblastoma protein (RB), studies of the E2F family have uncovered critical roles in the control of transcription, cell cycle and apoptosis. E2F proteins are encoded by at least eight genes, E2F1 through E2F8. While s...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524010606070739
更新日期:2006-11-01 00:00:00
abstract:OBJECTIVE:This study aims to investigate the effect of morphine with naloxone on intestinal peristalsis and the number of interstitial cells of Cajal (ICC) in colon tissues of rabbits. METHODS:Thirty rabbits were randomly divided into five groups (n=6, each group): saline control group (NS group), low concentration of...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666191023112837
更新日期:2020-01-01 00:00:00
abstract::Fibromyalgia (FM) is a prevalent disorder defined by the presence of chronic widespread pain in association with fatigue, sleep disturbances and cognitive dysfunction. Recent studies indicate that bipolar spectrum disorders frequently co-occur in individuals with FM. Furthermore, shared pathophysiological mechanisms a...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524016666160126144027
更新日期:2016-01-01 00:00:00
abstract::Plaque disruption and subsequent thrombus formation play a critical role in the clinical manifestations of atherothrombosis. Vulnerable lesions are characterized by the existence of core rich in lipid, macrophages and tissue factor (TF). Plaque disruption facilitates the interaction between flowing blood with the inne...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652406778018707
更新日期:2006-08-01 00:00:00
abstract::Osteopontin (OPN) is a matricellular protein that is produced by multiple tissues in our body and is most abundant in bone. It is also produced by cancer cells and plays a determinative role in the growth, progression and metastasis of cancer. Clinically, OPN has been reported to be upregulated in tumor cells per se; ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652410791065381
更新日期:2010-02-01 00:00:00
abstract::Spider venom is a large pharmacological repertoire containing many biologically active peptides, which may have a potent therapeutic implication. Here we investigated a peptide toxin, named lycosin-I, isolated from the venom of the spider Lycosa singoriensis. In contrast to most spider peptide toxins adopting inhibito...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/156652412803833643
更新日期:2012-12-01 00:00:00
abstract::p53 tumor suppressor plays a pivotal role in maintaining genomic integrity and preventing cancer development. The importance of p53 in tumor suppression is illustrated by the observation that about 50% human tumor cells have a dysfunctional p53 pathway. Although it has been well accepted that the activity of p53 is ma...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652408786733748
更新日期:2008-12-01 00:00:00
abstract::Abnormal and prolonged inflammatory reaction is seen in a wide variety of disorders, and high level of Tumor Necrosis Factor alpha (TNF-α) has been linked to these disorders. Therefore, modulation of TNF-α expression is important in the regulation of inflammatory disorders. In our previous study, we have shown that a ...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/156652411796268731
更新日期:2011-08-01 00:00:00
abstract::Asthma, chronic obstructive pulmonary disorder (COPD), and cystic fibrosis (CF), chronic diseases of the airways, are characterized by symptoms such as inflammation of the lung tissue, mucus hypersecretion, constriction of the airways, and excessive fibrosis of airway tissue. Transforming growth factor (TGF)-beta, a c...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652408785160943
更新日期:2008-08-01 00:00:00
abstract::The view that mitochondrial electron transport is the only site of aerobic respiration and the primary bioenergetic pathway in mammalian cells is well established in the literature. Although this paradigm is widely accepted for most tissues, the situation is less clear for proliferating cells. Increasing evidence indi...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652406779010777
更新日期:2006-12-01 00:00:00
abstract::Ca2+ ions are involved in the regulation of many diverse functions in animal and plant cells, e.g. muscle contraction, secretion of neurotransmitters, hormones and enzymes, fertilization of oocytes, and lymphocyte activation and proliferation. The intracellular Ca2+ concentration can be increased by different molecula...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524024605707
更新日期:2002-05-01 00:00:00
abstract::Immune tolerance can be induced by numerous methods. This review article aims to draw lines of similarity and contrast between two unique models of immune tolerance, namely Anterior Chamber Associated Immune Deviation (ACAID) and Nickel-induced oral tolerance. ACAID is an immune tolerance model that leads to the gener...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524015666150114114602
更新日期:2015-01-01 00:00:00