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Int. J. Mol. Sci., Volume 12, Issue 2 (February 2011) – 36 articles , Pages 865-1430

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1580 KiB  
Article
Anchoring Intrinsically Disordered Proteins to Multiple Targets: Lessons from N-Terminus of the p53 Protein
by Yongqi Huang and Zhirong Liu
Int. J. Mol. Sci. 2011, 12(2), 1410-1430; https://doi.org/10.3390/ijms12021410 - 23 Feb 2011
Cited by 19 | Viewed by 9358
Abstract
Anchor residues, which are deeply buried upon binding, play an important role in protein–protein interactions by providing recognition specificity and facilitating the binding kinetics. Up to now, studies on anchor residues have been focused mainly on ordered proteins. In this study, we investigated [...] Read more.
Anchor residues, which are deeply buried upon binding, play an important role in protein–protein interactions by providing recognition specificity and facilitating the binding kinetics. Up to now, studies on anchor residues have been focused mainly on ordered proteins. In this study, we investigated anchor residues in intrinsically disordered proteins (IDPs) which are flexible in the free state. We identified the anchor residues of the N-terminus of the p53 protein (Glu17–Asn29, abbreviated as p53N) which are involved in binding with two different targets (MDM2 and Taz2), and analyzed their side chain conformations in the unbound states. The anchor residues in the unbound p53N were found to frequently sample conformations similar to those observed in the bound complexes (i.e., Phe19, Trp23, and Leu26 in the p53N-MDM2 complex, and Leu22 in the p53N-Taz2 complex). We argue that the bound-like conformations of the anchor residues in the unbound state are important for controlling the specific interactions between IDPs and their targets. Further, we propose a mechanism to account for the binding promiscuity of IDPs in terms of anchor residues and molecular recognition features (MoRFs). Full article
(This article belongs to the Special Issue Advances in Molecular Recognition)
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3537 KiB  
Article
Comparison of Free Energy Surfaces Calculations from Ab Initio Molecular Dynamic Simulations at the Example of Two Transition Metal Catalyzed Reactions
by Marc Brüssel, Philipp J. Di Dio, Kilian Muñiz and Barbara Kirchner
Int. J. Mol. Sci. 2011, 12(2), 1389-1409; https://doi.org/10.3390/ijms12021389 - 23 Feb 2011
Cited by 12 | Viewed by 10959
Abstract
We carried out ab initio molecular dynamic simulations in order to determine the free energy surfaces of two selected reactions including solvents, namely a rearrangement of a ruthenium oxoester in water and a carbon dioxide addition to a palladium complex in carbon dioxide. [...] Read more.
We carried out ab initio molecular dynamic simulations in order to determine the free energy surfaces of two selected reactions including solvents, namely a rearrangement of a ruthenium oxoester in water and a carbon dioxide addition to a palladium complex in carbon dioxide. For the latter reaction we also investigated the gas phase reaction in order to take solvent effects into account. We used two techniques to reconstruct the free energy surfaces: thermodynamic integration and metadynamics. Furthermore, we gave a reasonable error estimation of the computed free energy surface. We calculated a reaction barrier of ΔF = 59:5 ± 8:5 kJ mol-1 for the rearrangement of a ruthenium oxoester in water from thermodynamic integration. For the carbon dioxide addition to the palladium complex in carbon dioxide we found a ΔF = 44:9 ± 3:3 kJ mol-1 from metadynamics simulations with one collective variable. The investigation of the same reactions in the gas phase resulted in ΔF = 24:9 ± 6:7 kJ mol-1 from thermodynamic integration, in ΔF = 26:7 ± 2:3 kJ mol-1 from metadynamics simulations with one collective variable, and in ΔF = 27:1 ± 5:9 kJ mol-1 from metadynamics simulations with two collective variables. Full article
(This article belongs to the Special Issue Applications of Molecular Dynamics)
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548 KiB  
Article
Biodegradable Tri-Block Copolymer Poly(lactic acid)-poly(ethylene glycol)-poly(L-lysine)(PLA-PEG-PLL) as a Non-Viral Vector to Enhance Gene Transfection
by Chunhua Fu, Xiaoli Sun, Donghua Liu, Zhijing Chen, Zaijun Lu and Na Zhang
Int. J. Mol. Sci. 2011, 12(2), 1371-1388; https://doi.org/10.3390/ijms12021371 - 23 Feb 2011
Cited by 44 | Viewed by 12868
Abstract
Low cytotoxicity and high gene transfection efficiency are critical issues in designing current non-viral gene delivery vectors. The purpose of the present work was to synthesize the novel biodegradable poly (lactic acid)-poly(ethylene glycol)-poly(L-lysine) (PLA-PEG-PLL) copolymer, and explore its applicability and feasibility as a [...] Read more.
Low cytotoxicity and high gene transfection efficiency are critical issues in designing current non-viral gene delivery vectors. The purpose of the present work was to synthesize the novel biodegradable poly (lactic acid)-poly(ethylene glycol)-poly(L-lysine) (PLA-PEG-PLL) copolymer, and explore its applicability and feasibility as a non-viral vector for gene transport. PLA-PEG-PLL was obtained by the ring-opening polymerization of Lys(Z)-NCA onto amine-terminated NH2-PEG-PLA, then acidolysis to remove benzyloxycarbonyl. The tri-block copolymer PLA-PEG-PLL combined the characters of cationic polymer PLL, PLA and PEG: the self-assembled nanoparticles (NPs) possessed a PEG loop structure to increase the stability, hydrophobic PLA segments as the core, and the primary ε-amine groups of lysine in PLL to electrostatically interact with negatively charged phosphate groups of DNA to deposit with the PLA core. The physicochemical properties (morphology, particle size and surface charge) and the biological properties (protection from nuclease degradation, plasma stability, in vitro cytotoxicity, and in vitro transfection ability in HeLa and HepG2 cells) of the gene-loaded PLA-PEG-PLL nanoparticles (PLA-PEG-PLL NPs) were evaluated, respectively. Agarose gel electrophoresis assay confirmed that the PLA-PEG-PLL NPs could condense DNA thoroughly and protect DNA from nuclease degradation. Initial experiments showed that PLA-PEG-PLL NPs/DNA complexes exhibited almost no toxicity and higher gene expression (up to 21.64% in HepG2 cells and 31.63% in HeLa cells) than PEI/DNA complexes (14.01% and 24.22%). These results revealed that the biodegradable tri-block copolymer PLA-PEG-PLL might be a very attractive candidate as a non-viral vector and might alleviate the drawbacks of the conventional cationic vectors/DNA complexes for gene delivery in vivo. Full article
(This article belongs to the Section Materials Science)
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173 KiB  
Article
In Vitro and in Vivo Anti-Hyperglycemic Effects of Omija (Schizandra chinensis) Fruit
by Sung-Hoon Jo, Kyoung-Soo Ha, Kyoung-Sik Moon, Ok-Hwan Lee, Hae-Dong Jang and Young-In Kwon
Int. J. Mol. Sci. 2011, 12(2), 1359-1370; https://doi.org/10.3390/ijms12021359 - 23 Feb 2011
Cited by 48 | Viewed by 10401
Abstract
The entrocytes of the small intestine can only absorb monosaccharides such as glucose and fructose from our diet. The intestinal absorption of dietary carbohydrates such as maltose and sucrose is carried out by a group of a-glucosidases. Inhibition of these enzymes can significantly [...] Read more.
The entrocytes of the small intestine can only absorb monosaccharides such as glucose and fructose from our diet. The intestinal absorption of dietary carbohydrates such as maltose and sucrose is carried out by a group of a-glucosidases. Inhibition of these enzymes can significantly decrease the postprandial increase of blood glucose level after a mixed carbohydrate diet. Therefore, the inhibitory activity of Omija (Schizandra chinensis) extract against rat intestinal a-glucosidase and porcine pancreatic a-amylase were investigated in vitro and in vivo. The in vitro inhibitory activities of water extract of Omija pulp/skin (OPE) on a-glucosidase and a-amylase were potent when compared to Omija seeds extract (OSE). The postprandial blood glucose lowering effect of Omija extracts was compared to a known type 2 diabetes drug (Acarbose), a strong a-glucosidase inhibitor in the Sprague-Dawley (SD) rat model. In rats fed on sucrose, OPE significantly reduced the blood glucose increase after sucrose loading. Furthermore, the oxygen radical absorbance capacity (ORAC) of OSE and OPE was evaluated. OPE had higher peroxyl radical absorbing activity than OSE. These results suggest that Omija, which has high ORAC value with a-glucosidase inhibitory activity and blood glucose lowering effect, could be physiologically useful for treatment of diabetes, although clinical trials are needed. Full article
(This article belongs to the Special Issue Advances in Nutraceutical Research)
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1197 KiB  
Article
Claudin 4 Is Differentially Expressed between Ovarian Cancer Subtypes and Plays a Role in Spheroid Formation
by Kristin L. M. Boylan, Benjamin Misemer, Melissa S. DeRycke, John D. Andersen, Katherine M. Harrington, Steve E. Kalloger, C. Blake Gilks, Stefan E. Pambuccian and Amy P. N. Skubitz
Int. J. Mol. Sci. 2011, 12(2), 1334-1358; https://doi.org/10.3390/ijms12021334 - 22 Feb 2011
Cited by 33 | Viewed by 9787
Abstract
Claudin 4 is a cellular adhesion molecule that is frequently overexpressed in ovarian cancer and other epithelial cancers. In this study, we sought to determine whether the expression of claudin 4 is associated with outcome in ovarian cancer patients and may be involved [...] Read more.
Claudin 4 is a cellular adhesion molecule that is frequently overexpressed in ovarian cancer and other epithelial cancers. In this study, we sought to determine whether the expression of claudin 4 is associated with outcome in ovarian cancer patients and may be involved in tumor progression. We examined claudin 4 expression in ovarian cancer tissues and cell lines, as well as by immunohistochemical staining of tissue microarrays (TMAs; n = 500), spheroids present in patients’ ascites, and spheroids formed in vitro. Claudin 4 was expressed in nearly 70% of the ovarian cancer tissues examined and was differentially expressed across ovarian cancer subtypes, with the lowest expression in clear cell subtype. No association was found between claudin 4 expression and disease-specific survival in any subtype. Claudin 4 expression was also observed in multicellular spheroids obtained from patients’ ascites. Using an in vitro spheroid formation assay, we found that NIH:OVCAR5 cells treated with shRNA against claudin 4 required a longer time to form compact spheroids compared to control NIH:OVCAR5 cells that expressed high levels of claudin 4. The inability of the NIH:OVCAR5 cells treated with claudin 4 shRNA to form compact spheroids was verified by FITC-dextran exclusion. These results demonstrate a role for claudin 4 and tight junctions in spheroid formation and integrity. Full article
(This article belongs to the Special Issue Cancer Molecules in Ovarian Cancer)
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1538 KiB  
Review
Accounting for Large Amplitude Protein Deformation during in Silico Macromolecular Docking
by Karine Bastard, Adrien Saladin and Chantal Prévost
Int. J. Mol. Sci. 2011, 12(2), 1316-1333; https://doi.org/10.3390/ijms12021316 - 22 Feb 2011
Cited by 6 | Viewed by 8441
Abstract
Rapid progress of theoretical methods and computer calculation resources has turned in silico methods into a conceivable tool to predict the 3D structure of macromolecular assemblages, starting from the structure of their separate elements. Still, some classes of complexes represent a real challenge [...] Read more.
Rapid progress of theoretical methods and computer calculation resources has turned in silico methods into a conceivable tool to predict the 3D structure of macromolecular assemblages, starting from the structure of their separate elements. Still, some classes of complexes represent a real challenge for macromolecular docking methods. In these complexes, protein parts like loops or domains undergo large amplitude deformations upon association, thus remodeling the surface accessible to the partner protein or DNA.We discuss the problems linked with managing such rearrangements in docking methods and we review strategies that are presently being explored, as well as their limitations and success. Full article
(This article belongs to the Special Issue Advances in Molecular Recognition)
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207 KiB  
Article
The Effects of G-CSF on Proliferation of Mouse Myocardial Microvascular Endothelial Cells
by Jiming Li, Yunzeng Zou, Junbo Ge, Daifu Zhang, Aili Guan, Jian Wu and Lei Li
Int. J. Mol. Sci. 2011, 12(2), 1306-1315; https://doi.org/10.3390/ijms12021306 - 22 Feb 2011
Cited by 4 | Viewed by 7184
Abstract
This paper explores the effect of granulocyte colony-stimulating factor (G-CSF) on mouse myocardial microvascular endothelial cell (CMECs) proliferation. CMECs were harvested from C57/BL6 mice. CMECs were cultured in medium containing G-CSF (0 ng/mL, 20 ng/mL, 40 ng/mL, 60 ng/mL) for five days. Proliferative [...] Read more.
This paper explores the effect of granulocyte colony-stimulating factor (G-CSF) on mouse myocardial microvascular endothelial cell (CMECs) proliferation. CMECs were harvested from C57/BL6 mice. CMECs were cultured in medium containing G-CSF (0 ng/mL, 20 ng/mL, 40 ng/mL, 60 ng/mL) for five days. Proliferative activity of CMECs was examined by CCK-8 method. Hypoxia inducible factor-1 (HIF-1) and p53 expression levels was determined from the mRNA obtained by reverse transcription polymerase chain reaction (RT-PCR). Results showed that the purity quotient of the CMECs, which were cultured by the method of modified myocardial tissue explant culture, was higher than 95%. Compared with control untreated cells, the proliferative activity of CMECs and the expression level of HIF-1 mRNA in these cells were enhanced by G-CSF treatment, whereas the expression level of p53 mRNA was markedly reduced. It may be concluded that G-CSF could promote the proliferative activity of CMECs, which might be mediated by upregulation of HIF-1 and downregulation of p53. Full article
(This article belongs to the Section Biochemistry)
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682 KiB  
Article
Effect of Annealing Temperature on the Optical Spectra of CdS Thin Films Deposited at Low Solution Concentrations by Chemical Bath Deposition (CBD) Technique
by Zahid Rizwan, Azmi Zakaria, Mohd Sabri Mohd Ghazali, Atefeh Jafari, Fasih Ud Din and Reza Zamiri
Int. J. Mol. Sci. 2011, 12(2), 1293-1305; https://doi.org/10.3390/ijms12021293 - 22 Feb 2011
Cited by 15 | Viewed by 8907
Abstract
Two different concentrations of CdCl2 and (NH2)2CS were used to prepare CdS thin films, to be deposited on glass substrate by chemical bath deposition (CBD) technique. CdCl2 (0.000312 M and 0.000625 M) was employed as a source [...] Read more.
Two different concentrations of CdCl2 and (NH2)2CS were used to prepare CdS thin films, to be deposited on glass substrate by chemical bath deposition (CBD) technique. CdCl2 (0.000312 M and 0.000625 M) was employed as a source of Cd2+ while (NH2)2CS (0.00125 M and 0.000625 M) for S2− at a constant bath temperature of 70 °C. Adhesion of the deposited films was found to be very good for all the solution concentrations of both reagents. The films were air-annealed at a temperature between 200 °C to 360 °C for one hour. The minimum thickness was observed to be 33.6 nm for film annealed at 320 °C. XRD analyses reveal that the films were cubic along with peaks of hexagonal phase for all film samples. The crystallite size of the films decreased from 41.4 nm to 7.4 nm with the increase of annealing temperature for the CdCl2 (0.000312 M). Optical energy band gap (Eg), Urbach energy (Eu) and absorption coefficient (α) have been calculated from the transmission spectral data. These parameters have been discussed as a function of annealing temperature and solution concentration. The best transmission (about 97%) was obtained for the air-annealed films at higher temperature at CdCl2 (0.000312 M). Full article
(This article belongs to the Section Materials Science)
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383 KiB  
Article
Application of Molecular Topology for the Prediction of Reaction Yields and Anti-Inflammatory Activity of Heterocyclic Amidine Derivatives
by Jordi Pla-Franco, María Gálvez-Llompart, Jorge Gálvez and Ramón García-Domenech
Int. J. Mol. Sci. 2011, 12(2), 1281-1292; https://doi.org/10.3390/ijms12021281 - 22 Feb 2011
Cited by 11 | Viewed by 8677
Abstract
Topological-mathematical models based on multiple linear regression analyses have been built to predict the reaction yields and the anti-inflammatory activity of a set of heterocylic amidine derivatives, synthesized under environmental friendly conditions, using microwave irradiation. Two models with three variables each were selected. [...] Read more.
Topological-mathematical models based on multiple linear regression analyses have been built to predict the reaction yields and the anti-inflammatory activity of a set of heterocylic amidine derivatives, synthesized under environmental friendly conditions, using microwave irradiation. Two models with three variables each were selected. The models were validated by cross-validation and randomization tests. The final outcome demonstrates a good agreement between the predicted and experimental results, confirming the robustness of the method. These models also enabled the screening of virtual libraries for new amidine derivatives predicted to show higher values of reaction yields and anti-inflammatory activity. Full article
(This article belongs to the Special Issue A Systematic Development Method for Rational Drug Design)
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392 KiB  
Article
A Classification Study of Respiratory Syncytial Virus (RSV) Inhibitors by Variable Selection with Random Forest
by Ming Hao, Yan Li, Yonghua Wang and Shuwei Zhang
Int. J. Mol. Sci. 2011, 12(2), 1259-1280; https://doi.org/10.3390/ijms12021259 - 21 Feb 2011
Cited by 12 | Viewed by 9328
Abstract
Experimental pEC50s for 216 selective respiratory syncytial virus (RSV) inhibitors are used to develop classification models as a potential screening tool for a large library of target compounds. Variable selection algorithm coupled with random forests (VS-RF) is used to extract the [...] Read more.
Experimental pEC50s for 216 selective respiratory syncytial virus (RSV) inhibitors are used to develop classification models as a potential screening tool for a large library of target compounds. Variable selection algorithm coupled with random forests (VS-RF) is used to extract the physicochemical features most relevant to the RSV inhibition. Based on the selected small set of descriptors, four other widely used approaches, i.e., support vector machine (SVM), Gaussian process (GP), linear discriminant analysis (LDA) and k nearest neighbors (kNN) routines are also employed and compared with the VS-RF method in terms of several of rigorous evaluation criteria. The obtained results indicate that the VS-RF model is a powerful tool for classification of RSV inhibitors, producing the highest overall accuracy of 94.34% for the external prediction set, which significantly outperforms the other four methods with the average accuracy of 80.66%. The proposed model with excellent prediction capacity from internal to external quality should be important for screening and optimization of potential RSV inhibitors prior to chemical synthesis in drug development. Full article
(This article belongs to the Section Biochemistry)
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341 KiB  
Article
Molecular Arrangement in Self-Assembled Azobenzene-Containing Thiol Monolayers at the Individual Domain Level Studied through Polarized Near-Field Raman Spectroscopy
by Marc Chaigneau, Gennaro Picardi and Razvigor Ossikovski
Int. J. Mol. Sci. 2011, 12(2), 1245-1258; https://doi.org/10.3390/ijms12021245 - 21 Feb 2011
Cited by 17 | Viewed by 9128
Abstract
6-[4-(phenylazo)phenoxy]hexane-1-thiol self-assembled monolayers deposited on a gold surface form domain-like structures possessing a high degree of order with virtually all the molecules being identically oriented with respect to the surface plane. We show that, by using polarized near-field Raman spectroscopy, it is possible [...] Read more.
6-[4-(phenylazo)phenoxy]hexane-1-thiol self-assembled monolayers deposited on a gold surface form domain-like structures possessing a high degree of order with virtually all the molecules being identically oriented with respect to the surface plane. We show that, by using polarized near-field Raman spectroscopy, it is possible to derive the Raman scattering tensor of the ordered layer and consequently, the in-plane molecular orientation at the individual domain level. More generally, this study extends the application domain of the near-field Raman scattering selection rules from crystals to ordered organic structures. Full article
(This article belongs to the Special Issue Molecular Symmetry)
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510 KiB  
Review
Characterization and Emulsification Properties of Rhamnolipid and Sophorolipid Biosurfactants and Their Applications
by Thu T. Nguyen and David A. Sabatini
Int. J. Mol. Sci. 2011, 12(2), 1232-1244; https://doi.org/10.3390/ijms12021232 - 18 Feb 2011
Cited by 96 | Viewed by 14752
Abstract
Due to their non-toxic nature, biodegradability and production from renewable resources, research has shown an increasing interest in the use of biosurfactants in a wide variety of applications. This paper reviews the characterization of rhamnolipid and sophorolipid biosurfactants based on their hydrophilicity/hydrophobicity and [...] Read more.
Due to their non-toxic nature, biodegradability and production from renewable resources, research has shown an increasing interest in the use of biosurfactants in a wide variety of applications. This paper reviews the characterization of rhamnolipid and sophorolipid biosurfactants based on their hydrophilicity/hydrophobicity and their ability to form microemulsions with a range of oils without additives. The use of the biosurfactants in applications such as detergency and vegetable oil extraction for biodiesel application is also discussed. Rhamnolipid was found to be a hydrophilic surfactant while sophorolipid was found to be very hydrophobic. Therefore, rhamnolipid and sophorolipid biosurfactants in mixtures showed robust performance in these applications. Full article
(This article belongs to the Special Issue Biosurfactants)
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229 KiB  
Article
Role of Rho Kinase in Microvascular Damage Following Cerebral Ischemia Reperfusion in Rats
by Kang Liu, Zhen Li, Tao Wu and Suju Ding
Int. J. Mol. Sci. 2011, 12(2), 1222-1231; https://doi.org/10.3390/ijms12021222 - 18 Feb 2011
Cited by 34 | Viewed by 7694
Abstract
Rho kinase (ROCK) is a well-known downstream effector of Rho and plays an important role in various physiopathological processes. In this study, we aim to investigate the correlation between ROCK and microvascular damage in rat brain subjected to middle cerebral artery occlusion (MCAO) [...] Read more.
Rho kinase (ROCK) is a well-known downstream effector of Rho and plays an important role in various physiopathological processes. In this study, we aim to investigate the correlation between ROCK and microvascular damage in rat brain subjected to middle cerebral artery occlusion (MCAO) and reperfusion, and to elucidate the mechanisms underlying the microvascular damage. ROCK and matrix metalloproteinase 9 (MMP9) mRNA levels were determined by real time quantitative PCR, Laminin was detected by immunofluorescence and Blood Brain Barrier (BBB) permeability was examined by Evans Blue (EB) in rat MCAO models. We observed similar patterns of changes in ROCK expression, brain EB content, and Laminin expression at different time points after brain ischemia. Statistical analysis further confirmed a significant linear correlation of ROCK expression with the onset of microvascular damage in brain. Furthermore, the ROCK inhibitor fasudil decreased brain EB content but increased Laminin expression. These results provide strong evidence that ROCK mediates microvascular damage. In addition, we found that fasudil could significantly inhibit MMP9 expression induced by ischemia. Thus, our findings suggest that ROCK promotes microvascular damage by upregulating MMP9 and reveal ROCK as a promising therapeutic target for stroke. Full article
(This article belongs to the Section Biochemistry)
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3585 KiB  
Article
Studies of New Fused Benzazepine as Selective Dopamine D3 Receptor Antagonists Using 3D-QSAR, Molecular Docking and Molecular Dynamics
by Jing Liu, Yan Li, Shuwei Zhang, Zhengtao Xiao and Chunzhi Ai
Int. J. Mol. Sci. 2011, 12(2), 1196-1221; https://doi.org/10.3390/ijms12021196 - 18 Feb 2011
Cited by 9 | Viewed by 9616
Abstract
In recent years, great interest has been paid to the development of compounds with high selectivity for central dopamine (DA) D3 receptors, an interesting therapeutic target in the treatment of different neurological disorders. In the present work, based on a dataset of 110 [...] Read more.
In recent years, great interest has been paid to the development of compounds with high selectivity for central dopamine (DA) D3 receptors, an interesting therapeutic target in the treatment of different neurological disorders. In the present work, based on a dataset of 110 collected benzazepine (BAZ) DA D3 antagonists with diverse kinds of structures, a variety of in silico modeling approaches, including comparative molecular field analysis (CoMFA), comparative similarity indices analysis (CoMSIA), homology modeling, molecular docking and molecular dynamics (MD) were carried out to reveal the requisite 3D structural features for activity. Our results show that both the receptor-based (Q2 = 0.603, R2ncv = 0.829, R2pre = 0.690, SEE = 0.316, SEP = 0.406) and ligand-based 3D-QSAR models (Q2 = 0.506, R2ncv =0.838, R2pre = 0.794, SEE = 0.316, SEP = 0.296) are reliable with proper predictive capacity. In addition, a combined analysis between the CoMFA, CoMSIA contour maps and MD results with a homology DA receptor model shows that: (1) ring-A, position-2 and R3 substituent in ring-D are crucial in the design of antagonists with higher activity; (2) more bulky R1 substituents (at position-2 of ring-A) of antagonists may well fit in the binding pocket; (3) hydrophobicity represented by MlogP is important for building satisfactory QSAR models; (4) key amino acids of the binding pocket are CYS101, ILE105, LEU106, VAL151, PHE175, PHE184, PRO254 and ALA251. To our best knowledge, this work is the first report on 3D-QSAR modeling of the new fused BAZs as DA D3 antagonists. These results might provide information for a better understanding of the mechanism of antagonism and thus be helpful in designing new potent DA D3 antagonists. Full article
(This article belongs to the Section Biochemistry)
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148 KiB  
Article
N-Acetyl Glucosamine Obtained from Chitin by Chitin Degrading Factors in Chitinbacter tainanesis
by Jeen-Kuan Chen, Chia-Rui Shen, Chao-Hsien Yeh, Bing-Shiun Fang, Tung-Li Huang and Chao-Lin Liu
Int. J. Mol. Sci. 2011, 12(2), 1187-1195; https://doi.org/10.3390/ijms12021187 - 17 Feb 2011
Cited by 37 | Viewed by 9813
Abstract
A novel chitin-degrading aerobe, Chitinibacter tainanensis, was isolated from a soil sample from southern Taiwan, and was proved to produce N-acetyl glucosamine (NAG). Chitin degrading factors (CDFs) were proposed to be the critical factors to degrade chitin in this work. When [...] Read more.
A novel chitin-degrading aerobe, Chitinibacter tainanensis, was isolated from a soil sample from southern Taiwan, and was proved to produce N-acetyl glucosamine (NAG). Chitin degrading factors (CDFs) were proposed to be the critical factors to degrade chitin in this work. When C. tainanensis was incubated with chitin, CDFs were induced and chitin was converted to NAG. CDFs were found to be located on the surface of C. tainanensis. N-Acetylglucosaminidase (NAGase) and endochitinase activities were found in the debris, and the activity of NAGase was much higher than that of endochitinase. The optimum pH of the enzymatic activity was about 7.0, while that of NAG production by the debris was 5.3. These results suggested that some factors in the debris, in addition to NAGase and endochitinase, were crucial for chitin degradation. Full article
(This article belongs to the Special Issue Chitins)
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430 KiB  
Article
Development of a Chitosan-Based Biofoam: Application to the Processing of a Porous Ceramic Material
by Jean-Denis Mathias, Nicolas Tessier-Doyen and Philippe Michaud
Int. J. Mol. Sci. 2011, 12(2), 1175-1186; https://doi.org/10.3390/ijms12021175 - 16 Feb 2011
Cited by 16 | Viewed by 11909
Abstract
Developing biofoams constitutes a challenging issue for several applications. The present study focuses on the development of a chitosan-based biofoam. Solutions of chitosan in acetic acid were dried under vacuum to generate foams with high-order structures. Chitosan concentration influenced significantly the morphology of [...] Read more.
Developing biofoams constitutes a challenging issue for several applications. The present study focuses on the development of a chitosan-based biofoam. Solutions of chitosan in acetic acid were dried under vacuum to generate foams with high-order structures. Chitosan concentration influenced significantly the morphology of developed porosity and the organization of pores in the material. Physico-chemical characterizations were performed to investigate the effects of chitosan concentration on density and thermal conductivity of foams. Even if chitosan-based biofoams exhibit interesting insulating properties (typically around 0.06 W·m−1·K−1), it has been shown that their durabilities are limited when submitted to a wet media. So, a way of application consists to elaborate a ceramic material with open porosity from a slurry prepared with an organic solvent infiltrating the porous network of the foam. Full article
(This article belongs to the Special Issue Chitins)
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377 KiB  
Article
Correlation of the Rates of Solvolysis of Neopentyl Chloroformate—A Recommended Protecting Agent
by Malcolm J. D’Souza, Shannon E. Carter and Dennis N. Kevill
Int. J. Mol. Sci. 2011, 12(2), 1161-1174; https://doi.org/10.3390/ijms12021161 - 15 Feb 2011
Cited by 13 | Viewed by 8901
Abstract
The specific rates of solvolysis of neopentyl chloroformate (1) have been determined in 21 pure and binary solvents at 45.0 °C. In most solvents the values are essentially identical to those for ethyl and n-propyl chloroformates. However, in aqueous-1,1,1,3,3,3-hexafluoro-2-propanol mixtures [...] Read more.
The specific rates of solvolysis of neopentyl chloroformate (1) have been determined in 21 pure and binary solvents at 45.0 °C. In most solvents the values are essentially identical to those for ethyl and n-propyl chloroformates. However, in aqueous-1,1,1,3,3,3-hexafluoro-2-propanol mixtures (HFIP) rich in fluoroalcohol, 1 solvolyses appreciably faster than the other two substrates. Linear free energy relationship (LFER) comparison of the specific rates of solvolysis of 1 with those for phenyl chloroformate and those for n-propyl chloroformate are helpful in the mechanistic considerations, as is also the treatment in terms of the Extended Grunwald-Winstein equation. It is proposed that the faster reaction for 1 in HFIP rich solvents is due to the influence of a 1,2-methyl shift, leading to a tertiary alkyl cation, outweighing the only weak nucleophilic solvation of the cation possible in these low nucleophilicity solvents. Full article
(This article belongs to the Special Issue Correlation Analysis Applied to Solvolysis Reactions)
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253 KiB  
Article
Antioxidant Activities of Fractions of Polymeric Procyanidins from Stem Bark of Acacia confusa
by Shu-Dong Wei, Hai-Chao Zhou and Yi-Ming Lin
Int. J. Mol. Sci. 2011, 12(2), 1146-1160; https://doi.org/10.3390/ijms12021146 - 15 Feb 2011
Cited by 23 | Viewed by 9497
Abstract
The polymeric procyanidins extracted from Acacia confusa stem bark were fractionated with a step gradient of water, methanol and acetone on a Sephadex LH-20 column. The antioxidant activity of the collected fractions was investigated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and ferric [...] Read more.
The polymeric procyanidins extracted from Acacia confusa stem bark were fractionated with a step gradient of water, methanol and acetone on a Sephadex LH-20 column. The antioxidant activity of the collected fractions was investigated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and ferric reducing/antioxidant power (FRAP) assays. All fractions possessed potent antioxidant activity with the highest activity observed for fraction F9. The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and reversed-phase high performance liquid chromatography (RP-HPLC) analyses suggested that the collected fractions consisted primarily of oligomeric and polymeric procyanidins, with different polymer ranges and most abundant polymer size. For each fraction, catechin and epicatechin were present as both terminal and extension units, and epicatechin was the major component in the extended chain. The mean degree of polymerization (mDP) of each fraction differed, ranging from 1.68 (fraction F2) to 17.31 (fraction F11). There was a relationship between antioxidant activity (IC50/DPPH and FRAP) and mDP (R2DPPH = 0.861, P = 0.006 and R2FRAP = 0.608, P = 0.038), respectively. However, the highest antioxidant activity of fraction (F9) was not coincident with the maximum mDP of fraction (F11). Full article
(This article belongs to the Section Biochemistry)
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462 KiB  
Article
Expression and Clinical Role of Protein of Regenerating Liver (PRL) Phosphatases in Ovarian Carcinoma
by Reuven Reich, Shany Hadar and Ben Davidson
Int. J. Mol. Sci. 2011, 12(2), 1133-1145; https://doi.org/10.3390/ijms12021133 - 11 Feb 2011
Cited by 20 | Viewed by 7047
Abstract
The present study analyzed the expression and clinical role of the protein of regenerating liver (PRL) phosphatase family in ovarian carcinoma. PRL1-3 mRNA expression was studied in 184 tumors (100 effusions, 57 primary carcinomas, 27 solid metastases) using RT-PCR. PRL-3 protein expression was [...] Read more.
The present study analyzed the expression and clinical role of the protein of regenerating liver (PRL) phosphatase family in ovarian carcinoma. PRL1-3 mRNA expression was studied in 184 tumors (100 effusions, 57 primary carcinomas, 27 solid metastases) using RT-PCR. PRL-3 protein expression was analyzed in 157 tumors by Western blotting. PRL-1 mRNA levels were significantly higher in effusions compared to solid tumors (p Full article
(This article belongs to the Special Issue Cancer Molecules in Ovarian Cancer)
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338 KiB  
Article
Effects of Intermediates between Vitamins K2 and K3 on Mammalian DNA Polymerase Inhibition and Anti-Inflammatory Activity
by Yoshiyuki Mizushina, Jun Maeda, Yasuhiro Irino, Masayuki Nishida, Shin Nishiumi, Yasuyuki Kondo, Kazuyuki Nishio, Kouji Kuramochi, Kazunori Tsubaki, Isoko Kuriyama, Takeshi Azuma, Hiromi Yoshida and Masaru Yoshida
Int. J. Mol. Sci. 2011, 12(2), 1115-1132; https://doi.org/10.3390/ijms12021115 - 10 Feb 2011
Cited by 9 | Viewed by 9477
Abstract
Previously, we reported that vitamin K3 (VK3), but not VK1 or VK2 (=MK-4), inhibits the activity of human DNA polymerase γ (pol γ). In this study, we chemically synthesized three intermediate compounds between VK2 and VK3 [...] Read more.
Previously, we reported that vitamin K3 (VK3), but not VK1 or VK2 (=MK-4), inhibits the activity of human DNA polymerase γ (pol γ). In this study, we chemically synthesized three intermediate compounds between VK2 and VK3, namely MK-3, MK-2 and MK-1, and investigated the inhibitory effects of all five compounds on the activity of mammalian pols. Among these compounds, MK-2 was the strongest inhibitor of mammalian pols α, κ and λ, which belong to the B, Y and X families of pols, respectively; whereas VK3 was the strongest inhibitor of human pol γ, an A-family pol. MK-2 potently inhibited the activity of all animal species of pol tested, and its inhibitory effect on pol λ activity was the strongest with an IC50 value of 24.6 μM. However, MK-2 did not affect the activity of plant or prokaryotic pols, or that of other DNA metabolic enzymes such as primase of pol α, RNA polymerase, polynucleotide kinase or deoxyribonuclease I. Because we previously found a positive relationship between pol λ inhibition and anti-inflammatory action, we examined whether these compounds could inhibit inflammatory responses. Among the five compounds tested, MK-2 caused the greatest reduction in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced acute inflammation in mouse ear. In addition, in a cell culture system using mouse macrophages, MK-2 displayed the strongest suppression of the production of tumor necrosis factor (TNF)-α induced by lipopolysaccharide (LPS). Moreover, MK-2 was found to inhibit the action of nuclear factor (NF)-κB. In an in vivo mouse model of LPS-evoked acute inflammation, intraperitoneal injection of MK-2 in mice led to suppression of TNF-α production in serum. In conclusion, this study has identified VK2 and VK3 intermediates, such as MK-2, that are promising anti-inflammatory candidates. Full article
(This article belongs to the Section Biochemistry)
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315 KiB  
Article
Effect of CO2 Enrichment on Synthesis of Some Primary and Secondary Metabolites in Ginger (Zingiber officinale Roscoe)
by Ali Ghasemzadeh and Hawa Z. E. Jaafar
Int. J. Mol. Sci. 2011, 12(2), 1101-1114; https://doi.org/10.3390/ijms12021101 - 10 Feb 2011
Cited by 77 | Viewed by 16707
Abstract
The effect of two different CO2 concentrations (400 and 800 µmol mol−1) on the photosynthesis rate, primary and secondary metabolite syntheses and the antioxidant activities of the leaves, stems and rhizomes of two Zingiber officinale varieties (Halia Bentong and Halia [...] Read more.
The effect of two different CO2 concentrations (400 and 800 µmol mol−1) on the photosynthesis rate, primary and secondary metabolite syntheses and the antioxidant activities of the leaves, stems and rhizomes of two Zingiber officinale varieties (Halia Bentong and Halia Bara) were assessed in an effort to compare and validate the medicinal potential of the subterranean part of the young ginger. High photosynthesis rate (10.05 µmol CO2 m−2s−1 in Halia Bara) and plant biomass (83.4 g in Halia Bentong) were observed at 800 µmol mol−1 CO2. Stomatal conductance decreased and water use efficiency increased with elevated CO2 concentration. Total flavonoids (TF), total phenolics (TP), total soluble carbohydrates (TSC), starch and plant biomass increased significantly (P ≤ 0.05) in all parts of the ginger varieties under elevated CO2 (800 µmol mol−1). The order of the TF and TP increment in the parts of the plant was rhizomes > stems > leaves. More specifically, Halia Bara had a greater increase of TF (2.05 mg/g dry weight) and TP (14.31 mg/g dry weight) compared to Halia Bentong (TF: 1.42 mg/g dry weight; TP: 9.11 mg/g dry weight) in average over the whole plant. Furthermore, plants with the highest rate of photosynthesis had the highest TSC and phenolics content. Significant differences between treatments and species were observed for TF and TP production. Correlation coefficient showed that TSC and TP content are positively correlated in both varieties. The antioxidant activity, as determined by the ferric reducing/antioxidant potential (FRAP) activity, increased in young ginger grown under elevated CO2. The FRAP values for the leaves, rhizomes and stems extracts of both varieties grown under two different CO2 concentrations (400 and 800 µmol mol−1) were significantly lower than those of vitamin C (3107.28 μmol Fe (II)/g) and α-tocopherol (953 μmol Fe (II)/g), but higher than that of BHT (74.31 μmol Fe (II)/g). These results indicate that the plant biomass, primary and secondary metabolite synthesis, and following that, antioxidant activities of Malaysian young ginger varieties can be enhanced through controlled environment (CE) and CO2 enrichment. Full article
(This article belongs to the Section Biochemistry)
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438 KiB  
Article
Design of New Competitive Dengue Ns2b/Ns3 Protease Inhibitors—A Computational Approach
by Neni Frimayanti, Chin Fei Chee, Sharifuddin M. Zain and Noorsaadah Abd. Rahman
Int. J. Mol. Sci. 2011, 12(2), 1089-1100; https://doi.org/10.3390/ijms12021089 - 9 Feb 2011
Cited by 43 | Viewed by 10280
Abstract
Dengue is a serious disease which has become a global health burden in the last decade. Currently, there are no approved vaccines or antiviral therapies to combat the disease. The increasing spread and severity of the dengue virus infection emphasizes the importance of [...] Read more.
Dengue is a serious disease which has become a global health burden in the last decade. Currently, there are no approved vaccines or antiviral therapies to combat the disease. The increasing spread and severity of the dengue virus infection emphasizes the importance of drug discovery strategies that could efficiently and cost-effectively identify antiviral drug leads for development into potent drugs. To this effect, several computational approaches were applied in this work. Initially molecular docking studies of reference ligands to the DEN2 NS2B/NS3 serine protease were carried out. These reference ligands consist of reported competitive inhibitors extracted from Boesenbergia rotunda (i.e., 4-hydroxypanduratin A and panduratin A) and three other synthesized panduratin A derivative compounds (i.e., 246DA, 2446DA and 20H46DA). The design of new lead inhibitors was carried out in two stages. In the first stage, the enzyme complexed to the reference ligands was minimized and their complexation energies (i.e., sum of interaction energy and binding energy) were computed. New compounds as potential dengue inhibitors were then designed by putting various substituents successively on the benzyl ring A of the reference molecule. These substituted benzyl compounds were then computed for their enzyme-ligand complexation energies. New enzyme-ligand complexes, exhibiting the lowest complexation energies and closest to the computed energy for the reference compounds, were then chosen for the next stage manipulation and design, which involved substituting positions 4 and 5 of the benzyl ring A (positions 3 and 4 for 2446DA) with various substituents. Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
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122 KiB  
Article
Lycium barbarum Polysaccharides Reduce Exercise-Induced Oxidative Stress
by Xiaozhong Shan, Junlai Zhou, Tao Ma and Qiongxia Chai
Int. J. Mol. Sci. 2011, 12(2), 1081-1088; https://doi.org/10.3390/ijms12021081 - 9 Feb 2011
Cited by 73 | Viewed by 10310
Abstract
The purpose of the present study was to investigate the effects of Lycium barbarum polysaccharides (LBP) on exercise-induced oxidative stress in rats. Rats were divided into four groups, i.e., one control group and three LBP treated groups. The animals received an oral [...] Read more.
The purpose of the present study was to investigate the effects of Lycium barbarum polysaccharides (LBP) on exercise-induced oxidative stress in rats. Rats were divided into four groups, i.e., one control group and three LBP treated groups. The animals received an oral administration of physiological saline or LBP (100, 200 and 400 mg/kg body weight) for 28 days. On the day of the exercise test, rats were required to run to exhaustion on the treadmill. Body weight, endurance time, malondialdehyde (MDA), super oxide dismutase (SOD) and glutathione peroxidase (GPX) level of rats were measured. The results showed that the body weight of rats in LBP treated groups were not significantly different from that in the normal control group before and after the experiment (P > 0.05). After exhaustive exercise, the mean endurance time of treadmill running to exhaustion of rats in LBP treated groups were significantly prolonged compared with that in the normal control group. MDA levels of rats in LBP treated groups were significantly decreased compared with that in the normal control group (P < 0.05). SOD and GPX levels of rats in LBP treated groups were significantly increased compared with that in the normal control group (P < 0.05). Together, these results indicate that LBP was effective in preventing oxidative stress after exhaustive exercise. Full article
(This article belongs to the Section Biochemistry)
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219 KiB  
Article
In Vitro Binding Capacity of Bile Acids by Defatted Corn Protein Hydrolysate
by Jauricque Ursulla Kongo-Dia-Moukala, Hui Zhang and Pierre Claver Irakoze
Int. J. Mol. Sci. 2011, 12(2), 1066-1080; https://doi.org/10.3390/ijms12021066 - 8 Feb 2011
Cited by 45 | Viewed by 8960
Abstract
Defatted corn protein was digested using five different proteases, Alcalase, Trypsin, Neutrase, Protamex and Flavourzyme, in order to produce bile acid binding peptides. Bile acid binding capacity was analyzed in vitro using peptides from different proteases of defatted corn hydrolysate. Some crystalline bile [...] Read more.
Defatted corn protein was digested using five different proteases, Alcalase, Trypsin, Neutrase, Protamex and Flavourzyme, in order to produce bile acid binding peptides. Bile acid binding capacity was analyzed in vitro using peptides from different proteases of defatted corn hydrolysate. Some crystalline bile acids like sodium glycocholate, sodium cholate and sodium deoxycholate were individually tested using HPLC to see which enzymes can release more peptides with high bile acid binding capacity. Peptides from Flavourzyme defatted corn hydrolysate exhibited significantly (p Full article
(This article belongs to the Special Issue Advances in Nutraceutical Research)
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Graphical abstract

189 KiB  
Technical Note
FurinDB: A Database of 20-Residue Furin Cleavage Site Motifs, Substrates and Their Associated Drugs
by Sun Tian, Qingsheng Huang, Ying Fang and Jianhua Wu
Int. J. Mol. Sci. 2011, 12(2), 1060-1065; https://doi.org/10.3390/ijms12021060 - 8 Feb 2011
Cited by 72 | Viewed by 10588
Abstract
FurinDB (freely available online at http://www.nuolan.net/substrates.html) is a database of furin substrates. This database includes experimentally verified furin cleavage sites, substrates, species, experimental methods, original publications of experiments and associated drugs targeting furin substrates. The current database release contains 126 furin cleavage sites [...] Read more.
FurinDB (freely available online at http://www.nuolan.net/substrates.html) is a database of furin substrates. This database includes experimentally verified furin cleavage sites, substrates, species, experimental methods, original publications of experiments and associated drugs targeting furin substrates. The current database release contains 126 furin cleavage sites from three species: mammals, bacteria and viruses. A main feature of this database is that all furin cleavage sites are recorded as a 20-residue motif, including one core region (eight amino acids, P6–P2’) and two flanking solvent accessible regions (eight amino acids, P7–P14, and four amino acids, P3’–P6’), that represent our current understanding of the molecular biology of furin cleavage. This database is important for understanding the molecular evolution and relationships between sequence motifs, 3D structures, cellular functions and physical properties required by furin for cleavage, and for elucidating the molecular mechanisms and the progression of furin cleavage associated human diseases, including pathogenic infections, neurological disorders, tumorigenesis, tumor invasion, angiogenesis, and metastasis. FurinDB database will be a solid addition to the publicly available infrastructure for scientists in the field of molecular biology. Full article
(This article belongs to the Section Biochemistry)
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237 KiB  
Article
Photodynamic Treatment Induces an Apoptotic Pathway Involving Calcium, Nitric Oxide, p53, p21-Activated Kinase 2, and c-Jun N-Terminal Kinase and Inactivates Survival Signal in Human Umbilical Vein Endothelial Cells
by Wen-Hsiung Chan
Int. J. Mol. Sci. 2011, 12(2), 1041-1059; https://doi.org/10.3390/ijms12021041 - 7 Feb 2011
Cited by 30 | Viewed by 8520
Abstract
Photodynamic treatment (PDT) elicits a diverse range of cellular responses, including apoptosis. Previously, we showed that PDT stimulates caspase-3 activity, and subsequent cleavage and activation of p21-activated kinase 2 (PAK2) in human epidermal carcinoma A431 cells. In the current study, pretreatment with nitric [...] Read more.
Photodynamic treatment (PDT) elicits a diverse range of cellular responses, including apoptosis. Previously, we showed that PDT stimulates caspase-3 activity, and subsequent cleavage and activation of p21-activated kinase 2 (PAK2) in human epidermal carcinoma A431 cells. In the current study, pretreatment with nitric oxide (NO) scavengers inhibited PDT-induced mitochondrial membrane potential (MMP) changes, activation of caspase-9, caspase-3, p21-activated protein kinase 2 (PAK2) and c-Jun N-terminal kinase (JNK), and gene expression of p53 and p21 involved in apoptotic signaling. Moreover, PAK2 activity was required for PDT-induced JNK activation and apoptosis. Inhibition of p53 mRNA expression using small interfering RNA (siRNA) additionally blocked activation of PAK2 and apoptosis induced by PDT. Importantly, our data also show that PDT triggers cell death via inactivation of ERK-mediated anti-apoptotic pathway. PDT triggers cell death via inactivation of the HSP90/multi-chaperone complex and subsequent degradation of Ras, further inhibiting anti-apoptotic processes, such as the Ras→ERK signal transduction pathway. Furthermore, we did not observe two-stage JNK activation for regulation of PAK2 activity in the PDT-induced apoptotic pathway in HUVECs, which was reported earlier in A431 cells. Based on the collective results, we have proposed a model for the PDT-triggered inactivation of the survival signal and apoptotic signaling cascade with Rose Bengal (RB), which sequentially involves singlet oxygen, Ca2+, NO, p53, caspase-9, caspase-3, PAK2, and JNK. Full article
(This article belongs to the Section Biochemistry)
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364 KiB  
Article
Chemically Induced Breast Tumors in Rats Are Detectable in Early Stages by Contrast Enhanced Magnetic Resonance Imaging but Not by Changes in the Acute-Phase Reactants in Serum
by Shahram Golbabapour, Wei Wei Pang, John George, Thanikachalam Pasupati, Puteri Shafinaz Abdul-Rahman and Onn Haji Hashim
Int. J. Mol. Sci. 2011, 12(2), 1030-1040; https://doi.org/10.3390/ijms12021030 - 7 Feb 2011
Cited by 5 | Viewed by 8384
Abstract
The present study was undertaken to develop a rat model for monitoring the early development of breast cancer. Twelve female rats were divided into two groups of six rats that were either treated with N-methyl-N-nitrosourea to induce breast cancer or [...] Read more.
The present study was undertaken to develop a rat model for monitoring the early development of breast cancer. Twelve female rats were divided into two groups of six rats that were either treated with N-methyl-N-nitrosourea to induce breast cancer or with bacterial lipopolysaccharide to induce inflammation. Serum samples taken from the rats prior to the treatment were used as controls. By the 14th week, presence of the tumor was detectable by contrast enhanced magnetic resonance imaging and confirmed by histopathology. When the serum proteins of the rats were examined by 2-dimensional electrophoresis (2-DE), no difference could be detected in the profiles of all proteins before and 18 weeks after administration of N-methyl-N-nitrosourea. However, higher expression of alpha-1B glycoprotein was detectable by 2-DE in serum samples of rats at the 18th week post-treatment with lipopolysaccharide. Full article
(This article belongs to the Section Biochemistry)
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780 KiB  
Review
Role of Versican, Hyaluronan and CD44 in Ovarian Cancer Metastasis
by Miranda P. Ween, Martin K. Oehler and Carmela Ricciardelli
Int. J. Mol. Sci. 2011, 12(2), 1009-1029; https://doi.org/10.3390/ijms12021009 - 31 Jan 2011
Cited by 106 | Viewed by 13686
Abstract
There is increasing evidence to suggest that extracellular matrix (ECM) components play an active role in tumor progression and are an important determinant for the growth and progression of solid tumors. Tumor cells interfere with the normal programming of ECM biosynthesis and can [...] Read more.
There is increasing evidence to suggest that extracellular matrix (ECM) components play an active role in tumor progression and are an important determinant for the growth and progression of solid tumors. Tumor cells interfere with the normal programming of ECM biosynthesis and can extensively modify the structure and composition of the matrix. In ovarian cancer alterations in the extracellular environment are critical for tumor initiation and progression and intra-peritoneal dissemination. ECM molecules including versican and hyaluronan (HA) which interacts with the HA receptor, CD44, have been shown to play critical roles in ovarian cancer metastasis. This review focuses on versican, HA, and CD44 and their potential as therapeutic targets for ovarian cancer. Full article
(This article belongs to the Special Issue Cancer Molecules in Ovarian Cancer)
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621 KiB  
Review
Epigenetic Regulation of Cancer-Associated Genes in Ovarian Cancer
by Mi Jeong Kwon and Young Kee Shin
Int. J. Mol. Sci. 2011, 12(2), 983-1008; https://doi.org/10.3390/ijms12020983 - 31 Jan 2011
Cited by 54 | Viewed by 17810
Abstract
The involvement of epigenetic aberrations in the development and progression of tumors is now well established. However, most studies have focused on the epigenetic inactivation of tumor suppressor genes during tumorigenesis and little is known about the epigenetic activation of cancer-associated genes, except [...] Read more.
The involvement of epigenetic aberrations in the development and progression of tumors is now well established. However, most studies have focused on the epigenetic inactivation of tumor suppressor genes during tumorigenesis and little is known about the epigenetic activation of cancer-associated genes, except for the DNA hypomethylation of some genes. Recently, we reported that the overexpression of cancer-promoting genes in ovarian cancer is associated with the loss of repressive histone modifications. This discovery suggested that epigenetic derepression may contribute to ovarian tumorigenesis by constituting a possible mechanism for the overexpression of oncogenes or cancer-promoting genes in tumors. The emerging importance of epigenetic aberrations in tumor initiation and in the regulation of cancer-initiating cells, suggests that epigenetically regulated genes may be promising therapeutic targets and biomarkers. Given that the current challenges in ovarian cancer include the identification of biomarkers for early cancer detection and the discovery of novel therapeutic targets for patients with recurrent malignancies undergoing chemotherapy, understanding the epigenetic changes that occur in ovarian cancer is crucial. This review looks at epigenetic mechanisms involved in the regulation of cancer-associated genes, including the contribution of epigenetic derepression to the activation of cancer-associated genes in ovarian cancer. In addition, possible epigenetic therapies targeting epigenetically dysregulated genes are discussed. A better understanding of the epigenetic changes in ovarian cancer will contribute to the improvement of patient outcomes. Full article
(This article belongs to the Special Issue Cancer Molecules in Ovarian Cancer)
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Graphical abstract

223 KiB  
Article
Identification of Receptor Tyrosine Kinase, Discoidin Domain Receptor 1 (DDR1), as a Potential Biomarker for Serous Ovarian Cancer
by Jinhua Quan, Tetsuro Yahata, Sosuke Adachi, Kosuke Yoshihara and Kenichi Tanaka
Int. J. Mol. Sci. 2011, 12(2), 971-982; https://doi.org/10.3390/ijms12020971 - 31 Jan 2011
Cited by 65 | Viewed by 9809
Abstract
Ovarian cancer, one of the most common gynecological malignancies, has an aggressive phenotype. It is necessary to develop novel and more effective treatment strategies against advanced disease. Protein tyrosine kinases (PTKs) play an important role in the signal transduction pathways involved in tumorigenesis, [...] Read more.
Ovarian cancer, one of the most common gynecological malignancies, has an aggressive phenotype. It is necessary to develop novel and more effective treatment strategies against advanced disease. Protein tyrosine kinases (PTKs) play an important role in the signal transduction pathways involved in tumorigenesis, and represent potential targets for anticancer therapies. In this study, we performed cDNA subtraction following polymerase chain reaction (PCR) using degenerate oligonucleotide primers to identify specifically overexpressed PTKs in ovarian cancer. Three PTKs, janus kinase 1, insulin-like growth factor 1 receptor, and discoidin domain receptor 1 (DDR1), were identified and only DDR1 was overexpressed in all ovarian cancer tissues examined for the validation by quantitative real-time PCR. The DDR1 protein was expressed in 63% (42/67) of serous ovarian cancer tissue, whereas it was undetectable in normal ovarian surface epithelium. DDR1 was expressed significantly more frequently in high-grade (79%) and advanced stage (77%) tumors compared to low-grade (50%) and early stage (43%) tumors. The expression of the DDR1 protein significantly correlated with poor disease-free survival. Although its functional role and clinical utility remain to be examined in future studies, our results suggest that the expression of DDR1 may serve as both a potential biomarker and a molecular target for advanced ovarian cancer. Full article
(This article belongs to the Special Issue Cancer Molecules in Ovarian Cancer)
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