Abstract:
:Control of VEGF signaling is an intense objective of pre-clinical and clinical studies in HCC disease with steadily increasing clinical application. Despite its emerging role, several aspects of anti-VEGF based treatments are poorly investigated, like the impact on tumor cells themselves, such as the effect on intracellular signaling and apoptosis induction in hepatoma cells. Effects of siRNA-VEGF on VEGF, VEGF-receptor expression and VEGF-A signaling such as AKT and JNK phosphorylation were determined under normoxic or hypoxic conditions in murine hepatoma cells. Apoptosis induction was analyzed by SubG1-fraction, JC1-staining and caspase-8 activation. VEGF receptor expression was analysed by semiquantitative real time PCR. Independent of oxygen status, siRNA-VEGF reduced VEGF levels resulting in decreased AKT and increased JNK phosphorylation in Hepa129 cells. The VEGF-receptors neuropilin-1 (Nrp1) and neuropilin-2 (Nrp2) were downregulated following siRNA-VEGF treatment or hypoxia induction respectively. Functionally, hypoxia significantly increased the apoptosis rate (as analyzed by SubG1-fraction, JC1-staining and JNKphosphorylation) which was further stimulated by siRNA-VEGF treatment. Our data indicate that antitumoral efficacy of an anti-VEGF based treatment with siRNA is partly based on negative autocrine feedback mechanisms which are even enhanced under hypoxic conditions. This observation helps to understand why antitumoral efficacy can be maintained despite of counteracting stimulation of tumoral VEGF secretion due to hypoxia. The direct impact on tumor cells further underscores the attractiveness of an anti-VEGF based siRNA treatment.
journal_name
Curr Pharm Biotechnoljournal_title
Current pharmaceutical biotechnologyauthors
Raskopf E,Vogt A,Decker G,Hirt S,Daskalow K,Cramer T,Standop J,Gonzalez-Carmona MA,Sauerbruch T,Schmitz Vdoi
10.2174/138920112802502088subject
Has Abstractpub_date
2012-09-01 00:00:00pages
2290-8issue
11eissn
1389-2010issn
1873-4316pii
BSP/CPB/E-Pub/000226-12-16journal_volume
13pub_type
杂志文章abstract:BACKGROUND:Biologic drugs, introduced in clinical practice almost twenty years ago, represent nowadays a prominent treatment option in patients with chronic inflammatory arthritis, such as Rheumatoid Arthritis, Psoriatic Arthritis and Spondyloarthritis, that include ankylosing spondylitis and non-radiographic axial spo...
journal_title:Current pharmaceutical biotechnology
pub_type: 杂志文章,评审
doi:10.2174/1389201019666171226151852
更新日期:2017-01-01 00:00:00
abstract::Interstitial lung disease (ILD) is one of the most common complications of polymyositis (PM) and dermatomyositis (DM). It is always progressive and does not respond to conventional immunosuppressive agent treatment. Biologics are commonly used in treatment of rheumatic diseases. They are also used in polymyositis and ...
journal_title:Current pharmaceutical biotechnology
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abstract::Momordica balsamina, African pumpkin (Cucurbitaceae), is a tendril-bearing, wild climber containing wide spectrum of medicinal and nutritional values and has been used as a traditional folk medicine in many countries. The leaves, fruits, seeds, and bark of the plant contains resins, alkaloids, flavonoids, glycosides, ...
journal_title:Current pharmaceutical biotechnology
pub_type: 杂志文章,评审
doi:10.2174/138920109789542066
更新日期:2009-11-01 00:00:00
abstract:BACKGROUND & OBJECTIVE:Nutritional culturomics (NCs) is a specific focus area of culturomics epistemology developing digital humanities and computational linguistics approaches to search for macro-patterns of public interest in food, nutrition and diet choice as a major component of cultural evolution. Cultural evoluti...
journal_title:Current pharmaceutical biotechnology
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更新日期:2019-01-01 00:00:00
abstract::The idea of cancer stem cell (CSC) has recently moved to the forefront of cancer research. There is still a lack of a widespread consensus on their description and definition. ,The increasing literature on CSCs has compelled researchers worldwide to rewrite the natural history of cancer including those cells as princi...
journal_title:Current pharmaceutical biotechnology
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更新日期:2011-02-01 00:00:00
abstract::Most cancer patients will experience moderate to severe pain and/or neuropathy during the course of their disease. Recent improvements in the primary treatment of cancer have increased the life span of cancer patients, but not necessarily their quality of life (QoL). The pain and suffering cancer patients experience m...
journal_title:Current pharmaceutical biotechnology
pub_type: 杂志文章,评审
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abstract::Staphylococcus aureus is a leading causative agent in sepsis, endocarditis, and pneumonia. An emerging concept is that prognosis worsens when the infecting S. aureus strain has the capacity to not only colonize tissue as an extracellular pathogen, but to invade host cells and establish intracellular bacterial populati...
journal_title:Current pharmaceutical biotechnology
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abstract::Pathophysiological changes are common in critically ill patients, and can alter the time course of drug concentrations following dosing. The latter is termed pharmacokinetics (PK), and describes the relationship between dose administered and drug concentrations in plasma. Thus, modifications in PK necessitate dose adj...
journal_title:Current pharmaceutical biotechnology
pub_type: 杂志文章,评审
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更新日期:2011-12-01 00:00:00
abstract:BACKGROUND:Many health hazardous diseases are caused by clinical pathogens. Drugresistant microbes are one of the major health problems in the world. To overcome the effect of infectious diseases new antimicrobial agent from nature has been explored which is environmentally friendly, less costly and more effective for ...
journal_title:Current pharmaceutical biotechnology
pub_type: 信件
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abstract::Proliposomes are phospholipid based drug delivery systems that are finding important applications in the field of pharmaceutics. Proliposomes have been extensively studied as a potential carrier for oral delivery of drugs with poor bioavailability, but the mechanism of absorption and cellular uptake pathways has not y...
journal_title:Current pharmaceutical biotechnology
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更新日期:2015-01-01 00:00:00
abstract::Spirulina, a filamentous cyanobacterium, possesses diverse biological activities and nutritional significance due to high concentration of natural nutrients, having bio-modulatory and immuno-modulatory functions. Different Spirulina preparations influence immune system viz. increase phagocytic activity of macrophages,...
journal_title:Current pharmaceutical biotechnology
pub_type: 杂志文章,评审
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更新日期:2005-10-01 00:00:00
abstract::The blood-brain barrier (BBB), which impedes drug penetration into the central nervous system, is composed of specific structures formed by brain capillary endothelial cells and sheathed by astrocytic end-feet through basement membrane. Many brain drug delivery strategies have focused on adsorptive-mediated transcytos...
journal_title:Current pharmaceutical biotechnology
pub_type: 杂志文章,评审
doi:10.2174/138920112803341851
更新日期:2012-09-01 00:00:00
abstract::The triterpenes α- and β-amyrins display important pharmacological activities. As a result of their high hydrophobia, they present low water solubility and reflect poor oral bioavailability. Different techniques can be used for the improvement of amyrins solubility, one of them is the use of nanoemulsions. Therefore, ...
journal_title:Current pharmaceutical biotechnology
pub_type: 杂志文章
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更新日期:2013-01-01 00:00:00
abstract::Malignant glioma is a primary tumor of the central nervous system, representing a major cause of mortality in a young, productive subset of population. The management of this neoplasm requires aggressive treatments, including radiotherapy. Accurate imaging plays a central role in treatment planning process with curati...
journal_title:Current pharmaceutical biotechnology
pub_type: 杂志文章,评审
doi:10.2174/1389201015666140408122318
更新日期:2014-01-01 00:00:00
abstract::Mammalian cell lines are important host cells for the industrial production of pharmaceutical proteins owing to their capacity for correct folding, assembly and post-translational modification. In particular, Chinese hamster ovary (CHO) cells are the most dependable host cells for the industrial production of therapeu...
journal_title:Current pharmaceutical biotechnology
pub_type: 杂志文章,评审
doi:10.2174/138920110791111960
更新日期:2010-04-01 00:00:00
abstract::CNS disorders are the third major problem of health in developed countries, with approximately 10% of direct costs associated with a pharmacological treatment of doubtful cost-effectiveness. There is an alarming abuse of psychotropic drugs worldwide and only 20-30% of patients with CNS disorders appropriately respond ...
journal_title:Current pharmaceutical biotechnology
pub_type: 杂志文章,评审
doi:10.2174/138920112799857576
更新日期:2012-04-01 00:00:00
abstract::The ubiquitin-proteasome pathway (UPP) is the major non-lysosomal proteolytic system in the cytosol and nucleus of all eukaryotic cells. Bortezomib (also known as PS-341 and Velcade) is a proteasome inhibitor, a novel class of cancer therapies. Bortezomib blocks multi-ubiquitinated protein degradation by inhibiting 26...
journal_title:Current pharmaceutical biotechnology
pub_type: 杂志文章,评审
doi:10.2174/138920106779116865
更新日期:2006-12-01 00:00:00
abstract::Several of the 28 mammalian transient receptor potential (TRP) channel subunits are expressed throughout the alimentary canal where they play important roles in taste, chemo- and mechanosensation, thermoregulation, pain and hyperalgesia, mucosal function and homeostasis, control of motility by neurons, interstitial ce...
journal_title:Current pharmaceutical biotechnology
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doi:10.2174/138920111793937862
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Fractalkine (FKN) in its free and membrane bound-forms and its receptor CX3CR1are reported to have an atherosclerotic effect. The relationship of Single Nucleotide Polymorphisms (SNPs) in FKN and CX3CR1genes with the Coronary Artery Disease (CAD) risk showed conflicting results in different populations. The ...
journal_title:Current pharmaceutical biotechnology
pub_type: 杂志文章
doi:10.2174/1389201019666181031163748
更新日期:2018-01-01 00:00:00
abstract:OBJECTIVE:We sought to evaluate the safety of imipenem and meropenem in the treatment of infections in neurosurgical patients. METHODS:An observational retrospective study was conducted of consecutive cases treated with imipenem from Sept. 2007 to Sept. 2009 and meropenem within 1 year from Sept. 2008 in Beijing Tiant...
journal_title:Current pharmaceutical biotechnology
pub_type: 杂志文章
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更新日期:2014-01-01 00:00:00
abstract::The interaction between reactive oxygen species (ROS) and inflammation plays an important role in the pathogenesis of endothelial dysfunction and cardiovascular disease, cancer and other diseases. Thus, antioxidant strategies may be important in immune regulation and in limiting inflammation. Surprisingly, large clini...
journal_title:Current pharmaceutical biotechnology
pub_type: 杂志文章,评审
doi:
更新日期:2012-10-01 00:00:00
abstract:BACKGROUND:In Saudi Arabia, the incidence and mortality rates of breast cancer are high. Although current treatments are effective, breast cancer cells develop resistance to these treatments. Numerous studies have demonstrated that active compounds in plant extracts, such as the phenolic compound Rosmarinic Acid (RA), ...
journal_title:Current pharmaceutical biotechnology
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doi:10.2174/1389201021666200318114817
更新日期:2020-01-01 00:00:00
abstract::It is now widely believed that tumors originate from normal cells as a result of accumulated genetic/epigenetic changes. These alterations affect the signaling pathways at transcriptional and post-transcriptional level that drive cells into uncontrolled cell division, growth, and migration. Recent advancement of molec...
journal_title:Current pharmaceutical biotechnology
pub_type: 杂志文章,评审
doi:10.2174/138920108785915102
更新日期:2008-10-01 00:00:00
abstract::Gene targeting can be loosely defined as a process through which a specific chromosomal sequence is recognized and bound by a reagent designed for the purpose. The endpoint may be modulation of events at the target, such as transcription, or a permanent change in sequence at the site. A facile strategy for mammalian c...
journal_title:Current pharmaceutical biotechnology
pub_type: 杂志文章,评审
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更新日期:2004-10-01 00:00:00
abstract::Diabetic retinopathy (DR) still represents one of the leading causes of vision loss worldwide. Since this condition affects the posterior segment of the eye, topical application of ophthalmic medicines is of limited benefit, considering that they seldom reach therapeutic levels in the affected tissues. Systemic medica...
journal_title:Current pharmaceutical biotechnology
pub_type: 杂志文章,评审
doi:10.2174/138920111794480598
更新日期:2011-03-01 00:00:00
abstract:BACKGROUND:Rheumatoid arthritis (RA) is a common connective tissue disease, characteristic of chronic and invasive synovitis in single or multiple joints and vasculitis. RA is a heterogeneous disease with unclear pathogenesis. Therefore, exploring the etiology and pathogenesis of the disease is essential for identifyin...
journal_title:Current pharmaceutical biotechnology
pub_type: 杂志文章
doi:10.2174/1389201021666201001142829
更新日期:2020-10-01 00:00:00
abstract::Toll-like receptor 9 (TLR9) can sense pathogen DNA and CpG ODN or even self-DNA by trafficking assisted by Unc93B1, an endoplasmic reticulum (ER) transmembrane protein, from ER to endolysosomes or cell surface. In previous study, we found that an oligodeoxynucleotide with CCT repeats (SAT05f) could selectively inhibit...
journal_title:Current pharmaceutical biotechnology
pub_type: 杂志文章
doi:10.2174/1389201015666141031114708
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Alfalfa and red clover are the most widespread and most important perennial legumes, primarily used as a high-quality feed for livestock. Both alfalfa and red clover, as well as some other plant species from Fabaceae family, are a rich natural source of phytoestrogens, nonsteroidal compounds with an estrogen...
journal_title:Current pharmaceutical biotechnology
pub_type: 杂志文章,评审
doi:10.2174/1389201019666180730165917
更新日期:2018-01-01 00:00:00
abstract::Increasing evidence shows that the interaction between neoplastic cells and the surrounding stroma is a critical factor in solid tumor growth. The tumor stroma is made up of diverse cellular populations including macrophages, lymphocytes, vascular cells, and carcinoma-associated fibroblasts. The complex interactions b...
journal_title:Current pharmaceutical biotechnology
pub_type: 杂志文章,评审
doi:10.2174/138920109787315088
更新日期:2009-02-01 00:00:00
abstract::Calcium-sensing receptor (CaSR), a member of family C of the G protein-coupled receptors, is expressed most abundantly in the parathyroid glands and kidney. It plays key role in these two organs because it senses changes in extracellular calcium and regulates PTH secretion and calcium reabsorption to suit the extracel...
journal_title:Current pharmaceutical biotechnology
pub_type: 杂志文章,评审
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更新日期:2009-04-01 00:00:00