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Find video protocols related to scientific articles indexed in Pubmed.
Postoperative peritoneal infection enhances migration and invasion capacities of tumor cells in vitro: an insight into the association between anastomotic leak and recurrence after surgery for colorectal cancer.
Ann. Surg.
PUBLISHED: 09-23-2014
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The aim of this study was to investigate the effect of postoperative peritoneal infection on proliferation, migration, and invasion capacities of cancer cells lines in vitro after surgery for colorectal cancer.
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Cyclopalladated primary amines: a preliminary study of antiproliferative activity through apoptosis induction.
Eur J Med Chem
PUBLISHED: 07-14-2014
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Twelve cyclometallated palladium(II) complexes containing primary aromatic amines [benzylamine (a), (R)-1-(1-naphthyl)ethylamine (b) and 2-phenylaniline (c)] as anionic bidentate (C,N)(-) ligands have been evaluated against a panel of human adenocarcinoma cell lines (A549 lung, MDA-MB231 and MCF7 breast, and the cisplatin resistant HCT116 colon). The results revealed a remarkable antiproliferative activity of the triphenylphosphane mononuclear compounds 3-4 (series a, b, c) and the best inhibition was provided for 3c and 4c with the 2-phenylaniline ligand and a six membered chelate ring. Interestingly, 3c and 4c were 14 and 19 times more potent than cisplatin for the inhibition of the cisplatin resistant HCT116 human adenocarcinoma cell line, respectively. Cyclopalladated complexes 3c and 4c exercise their antiproliferative activity over A549 cells mainly through the induction of apoptosis (38 and 31-fold increase in early apoptotic cells, respectively).
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Cyclopalladated and cycloplatinated benzophenone imines: antitumor, antibacterial and antioxidant activities, DNA interaction and cathepsin B inhibition.
J. Inorg. Biochem.
PUBLISHED: 03-18-2014
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The antitumor, antibacterial and antioxidant activity, DNA interaction and cathepsin B inhibition of cyclo-ortho-palladated and -platinated compounds [Pd(C,N)]2(?-X)2 [X=OAc (1), X=Cl (2)] and trans-N,P-[M(C,N)X(PPh3)] [M=Pd, X=OAc (3), M=Pd, X=Cl (4), M=Pt, X=Cl (5)] are discussed [(C,N)=cyclo-ortho-metallated benzophenone imine]. The cytotoxicity of compound 5 has been evaluated towards human breast (MDA-MB-231 and MCF-7) and colon (HCT-116) cancer cell lines and that of compounds 1-4 towards the HCT-116 human colon cancer cell line. These cytotoxicities have been compared with those previously reported for compounds 1-4 towards MDA-MB-231 and MCF-7 cancer cell lines. Compound 3 and 4 were approximately four times more active than cisplatin against the MDA-MB-231 and MCF-7 cancer cell lines, and compound 5, was approximately four times more potent than cisplatin against the HCT-116 cancer cell line. The antibacterial activity of compounds 1-5 was in between the ranges of activity of the commercial antibiotic compounds cefixime and roxithromycin. Complexes 1-2 and 4-5 presented also antioxidant activity. Compounds 1-5 alter the DNA tertiary structure in a similar way to cisplatin, but at higher concentration, and do not present a high efficiency as cathepsin B inhibitors. Compound 5 has not been previously described, and its preparation, characterization, and X-ray crystal structure are reported.
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Pt(II) complexes with (N,N) or (C,N,E)(-) (E=N,S) ligands: cytotoxic studies, effect on DNA tertiary structure and structure-activity relationships.
Bioorg. Med. Chem.
PUBLISHED: 03-01-2013
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The cytotoxic activity of two series of platinum(II) complexes containing the polyfunctional imines R(1)-CHN-R(2) [R(1)=phenyl or ferrocenyl unit and R(2)=(CH2)n-CH2-NMe2 where n=1 or 2) (1 and 2) or C6H4-2-SMe (3)] acting as a bidentate (N,N) (4-7) or terdentate [C(phenyl or ferrocenyl),N,N](-) (8-10) or [C(ferrocenyl),N,S](-) ligand (11) in front of A549 lung, MDA-MB231 breast and HCT116 colon human adenocarcinoma cell lines is reported. The results reveal that most of the platinum(II) complexes are active against the three assayed lines and compounds 6, 7 and the platinacycles 10 and 11 exhibit a remarkable antiproliferative activity, even greater than cisplatin itself, in the cisplatin resistant HCT116 human cancer cell line. Electrophoretic DNA migration studies showed that most of them modify the DNA tertiary structure in a similar way as the reference cisplatin. Solution studies of a selection of the most relevant complexes have also been performed in order to test: (a) their stability in the aqueous biological medium and/or the formation of biologically active species and (b) their proclivity to react with 9-methylguanine (9-MeG), as a model nucleobase. Computational studies at DFT level have also been performed in order to explain the different solution behaviour of the complexes and their proclivity to react with the nucleobase.
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Therapeutic targeting of tumor growth and angiogenesis with a novel anti-S100A4 monoclonal antibody.
PLoS ONE
PUBLISHED: 01-01-2013
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S100A4, a member of the S100 calcium-binding protein family secreted by tumor and stromal cells, supports tumorigenesis by stimulating angiogenesis. We demonstrated that S100A4 synergizes with vascular endothelial growth factor (VEGF), via the RAGE receptor, in promoting endothelial cell migration by increasing KDR expression and MMP-9 activity. In vivo overexpression of S100A4 led to a significant increase in tumor growth and vascularization in a human melanoma xenograft M21 model. Conversely, when silencing S100A4 by shRNA technology, a dramatic decrease in tumor development of the pancreatic MiaPACA-2 cell line was observed. Based on these results we developed 5C3, a neutralizing monoclonal antibody against S100A4. This antibody abolished endothelial cell migration, tumor growth and angiogenesis in immunodeficient mouse xenograft models of MiaPACA-2 and M21-S100A4 cells. It is concluded that extracellular S100A4 inhibition is an attractive approach for the treatment of human cancer.
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Platinum(II) and palladium(II) complexes with (N,N) and (C,N,N)- ligands derived from pyrazole as anticancer and antimalarial agents: synthesis, characterization and in vitro activities.
J. Inorg. Biochem.
PUBLISHED: 05-31-2011
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The study of the reactivity of three 1-(2-dimethylaminoethyl)-1H-pyrazole derivatives of general formula [1-(CH(2))(2)NMe(2)}-3,5-R(2)-pzol] {where pzol represents pyrazole and R=H (1a), Me (1b) or Ph (1c)} with [MCl(2)(DMSO)(2)] (M=Pt or Pd) under different experimental conditions allowed us to isolate and characterize cis-[M{?(2)-N,N-{[1-(CH(2))(2)NMe(2)}-3,5-R(2)-pzol])}Cl(2)] {MM=PtPt (2a-2c) or Pd (3a-3c)} and two cyclometallated complexes [M{?(3)-C,N,N-{[1-(CH(2))(2)NMe(2)}-3-(C(5)H(4))-5-Ph-pzol])}Cl] {M=Pt(II) (4c) or Pd(II) (5c)}. Compounds 4c and 5c arise from the orthometallation of the 3-phenyl ring of ligand 1c. Complex 2a has been further characterized by X-ray crystallography. Ligands and complexes were evaluated for their in vitro antimalarial against Plasmodium falciparum and cytotoxic activities against lung (A549) and breast (MDA MB231 and MCF7) cancer cellular lines. Complexes 2a-2c and 5c exhibited only moderate antimalarial activities against two P. falciparum strains (3D7 and W2). Interestingly, cytotoxicity assays revealed that the platinacycle 4c exhibits a higher toxicity than cisplatin in the three human cell lines and that the complex 2a presents a remarkable cytotoxicity and selectivity in lung (IC(50)=3 ?M) versus breast cancer cell lines (IC(50)>20 ?M). Thus, complexes 2c and 4c appear to be promising leads, creating a novel family of anticancer agents. Electrophoretic DNA migration studies in presence of the synthesized compounds have been performed, in order to get further insights into their mechanism of action.
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Characterization of the metabolic changes underlying growth factor angiogenic activation: identification of new potential therapeutic targets.
Carcinogenesis
PUBLISHED: 04-15-2009
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Angiogenesis is a fundamental process to normal and abnormal tissue growth and repair, which consists of recruiting endothelial cells toward an angiogenic stimulus. The cells subsequently proliferate and differentiate to form endothelial tubes and capillary-like structures. Little is known about the metabolic adaptation of endothelial cells through such a transformation. We studied the metabolic changes of endothelial cell activation by growth factors using human umbilical vein endothelial cells (HUVECs), [1,2-(13)C(2)]-glucose and mass isotopomer distribution analysis. The metabolism of [1,2-(13)C(2)]-glucose by HUVEC allows us to trace many of the main glucose metabolic pathways, including glycogen synthesis, the pentose cycle and the glycolytic pathways. So we established that these pathways were crucial to endothelial cell proliferation under vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) stimulation. A specific VEGF receptor-2 inhibitor demonstrated the importance of glycogen metabolism and pentose cycle pathway. Furthermore, we showed that glycogen was depleted in a low glucose medium, but conserved under hypoxic conditions. Finally, we demonstrated that direct inhibition of key enzymes to glycogen metabolism and pentose phosphate pathways reduced HUVEC viability and migration. In this regard, inhibitors of these pathways have been shown to be effective antitumoral agents. To sum up, our data suggest that the inhibition of metabolic pathways offers a novel and powerful therapeutic approach, which simultaneously inhibits tumor cell proliferation and tumor-induced angiogenesis.
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Diastereomerically pure platinum(II) complexes as antitumoral agents.: The influence of the mode of binding {(N), (N,O)- or (C,N)}- of (1S,2R)[(?5-C5H5)Fe{(?5-C5H4)CHNCH(Me)CH(OH)C6H5}] and the arrangement of the auxiliary ligands.
J. Inorg. Biochem.
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The study of the reactivity of (1S,2R) [(?(5)-C(5)H(5))Fe{[(?(5)-C(5)H(4)) CHNCH(Me)CH(OH)C(6)H(5)}] (1a) with cis-[PtCl(2)(DMSO)(2)] under different experimental conditions has allowed to isolate and characterize three pairs of isomeric and diastereomerically pure platinum(II) complexes. Two of the pairs are the trans- and cis- isomers of (1S,2R)[Pt{(?(5)-C(5)H(5))Fe[(?(5)-C(5)H(4))CHNCH(Me)CH(OH)C(6)H(5)]}Cl(2)(DMSO)] [trans-(2a) and cis-(3a), respectively], and of (1S,2R) [Pt{(?(2)-N,O)(?(5)-C(5)H(5))Fe[(?(5)-C(5)H(4))CHNCH(Me)CH(O)C(6)H(5)]}Cl(DMSO)], {trans-(Cl, N) in (4a)} or a cis-(Cl, N) {in (5a)}; while the third one is formed by platinacycles: [Pt{(?(2)-C,N[(?(5)-C(5)H(3))]CHN-CH(Me)CH(OH)C(6)H(5)]Fe(?(5)-C(5)H(5))}Cl(DMSO)] with different planar chirality [S(p) (in 6a) or R(p) (in 7a)]. The crystal structures of compounds 2a, 3a, 5a and 6a are also reported. The cytotoxic assessment of 1a-7a on lung (A549), breast (MDA-MB-231) and colon (HCT-116) cancer cell lines is also reported and reveals that the potency of the complexes is strongly dependent on the mode of binding of the iminoalcohol {(N) in 2a and 3a, (N,O)(-) in 4a and 5a or (C,N)(-) in 6a and 7a}, the relative arrangement of the monodentate ligands (in 2a-5a), and the planar chirality of the 1,2-ferrocenylunit in (6a and 7a). Among the new products (2a-7a), compounds 4a and 5a exhibit the highest potency with IC(50) values smaller than cisplatin in the three cancer cell lines assayed. Electrophoretic DNA migration studies in the presence of 2a-7a have been performed in order to get further insights into their mechanism of action. A comparative study of the solution behaviour of all the complexes in DMSO-d(6) or in DMSO-d(6):D(2)O (1:1) mixtures at 298 K is also reported.
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Seven-membered cycloplatinated complexes as a new family of anticancer agents. X-ray characterization and preliminary biological studies.
Eur J Med Chem
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A series of seven-membered cyclometallated Pt(II) complexes containing a terdentate [C,N,N] ligand (1a-1c and 2a-2c) have been developed as potential monofunctional DNA binding agents. By reactions of cis-[Pt(4-C(6)H(4)Me)(2)(?-SEt(2))](2) or cis-[Pt(C(6)H(5))(2)(SMe(2))(2)] with imines 2-ClC(6)H(4)CHNCH(2)CH(2)NMe(2) (b) or 2-F,6-ClC(6)H(3)CH=NCH(2)CH(2)NMe(2) (c) the new compounds 1b, 1c and 2c were synthesized and characterized. Complex 1b and 1c were further characterized by X-ray crystallography. The cytotoxicity assessment of the seven-membered platinacycles 1 (1a-1c) and 2 (2a-2c) against a panel of human cancer cell lines (A549 lung, HCT116 colon, and MDA MB231 breast adenocarcinomas) revealed that the six cycloplatinated complexes exhibit a remarkable antiproliferative activity, even greater than cisplatin in the three human cancer cell lines. From a pharmacological point of view, platinacycles 1 (1a-1c) and 2 (2a-2c) may represent compounds for a new class of antitumor drugs. Electrophoretic DNA migration studies showed that all of them modify the DNA tertiary structure. Induction of S-G2/M arrest and apoptosis were also observed for one of the representative compounds (1c) of the series.
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