Search results for "PLATINUM"
showing 10 items of 629 documents
Phase I/II trial of capecitabine and oxaliplatin in combination with bevacizumab and imatinib in patients with metastatic colorectal cancer: AIO KRK …
2013
Background: Combined inhibition of platelet-derived growth factor receptor beta signalling and vascular endothelial growth factor promotes vascular normalisation in preclinical models and may lead to increased delivery of chemotherapy to tumour tissue. This phase I/II trial assessed the safety and efficacy of capecitabine plus oxaliplatin (XELOX) plus bevacizumab and imatinib in the first-line treatment of patients with metastatic colorectal cancer. Methods: Two dose levels (I/II) were defined: capecitabine 850/1000 mg m−2 twice daily on days 1–14; oxaliplatin 100/130 mg m−2 on day 1; bevacizumab 7.5 mg kg−1 on day 1; imatinib 300 mg day−1 on days 1–21 every 21 days. The primary study endpo…
Optically Active Hyperbranched Polyglycerol as Scaffold for Covalent and Noncovalent Immobilization of Platinum(II) NCN-Pincer Complexes. Catalytic A…
2004
New optically active hyperbranched polymers have been used as microenvironments as well as scaffolds for noncovalent and covalent immobilization of pincer platinum(II) complexes, respectively. The catalytic activity/selectivity of the incorporated platinum(II) complexes in these polymeric chiral supports was investigated. Chiral amphiphilic hyperbranched polyglycerols with core−shell “nanocapsules” structure, namely (−)-P(G40C160.5) (1) and (+)-P(G73C160.5) (2), have been prepared in two straightforward steps by ring-opening multibranching polymerization (ROMBP) of either (−)- or (+)-glycidol, resulting in (−)-PG40 (Mn = 3000, Mw/Mn = 1.3) or (+)-PG73 (Mn = 5500, Mw/Mn = 1.6), respectively.…
New light on an old debate: Does the RCN-PtCl2 bond include any back-donation? RCN←PtCl2 backbonding: Vs. the IR ν CN blue-shift dichotomy in organon…
2019
For a series of organonitrile [RCN (R = Me, CF3, Ph, CH3Ph, CF3Ph)] ligands, the nature of the N-Pt bond in the related cis-/trans-(RCN)2PtCl2 complexes has been computationally investigated by Density Functional Theory. A fragment based bond analysis has been performed in the canonical Kohn-Sham molecular orbitals framework, and it has been ultimately assessed that this bond is characterized both by N→Pt σ and by N←Pt π contributions. Voronoi Deformation Density charges further confirms the occurrence of N←Pt π interactions. Moreover, the Energy Decomposition Analysis-Natural Orbital for Chemical Valence (EDA-NOCV) method shows that the strength of the N←Pt π interaction is not negligible …
Bcl-xL and Myeloid cell leukaemia-1 contribute to apoptosis resistance of colorectal cancer cells
2008
AIM: To explore the role of Bcl-x(L) and Myeloid cell leukaemia (Mcl)-1 for the apoptosis resistance of colorectal carcinoma (CRC) cells towards current treatment modalities. METHODS: Bcl-x(L) and Mcl-1 mRNA and protein expression were analyzed in CRC cell lines as well as human CRC tissue by Western blot, quantitative PCR and immunohistochemistry. Bcl-x(L) and Mcl-1 protein expression was knocked down or increased in CRC cell lines by applying specific siRNAs or expression plasmids, respectively. After modulation of protein expression, CRC cells were treated with chemotherapeutic agents, an antagonistic epidermal growth factor receptor (EGFR1) antibody, an EGFR1 tyrosine kinase inhibitor, …
DNA Binding Studies and Cytotoxicity of a Dinuclear PtII Diazapyrenium- Based Metallo-supramolecular Rectangular Box
2012
The interaction with native DNA of a 2,7-diazapyrenium-based ligand 1 and its Pt II rectangular metal- lacycle 2 is explored through circular and linear dichroism and fluorescence spectroscopies. The metal-free ligand 1 binds through intercalation, with a binding constant of approximately 5 � 10 5 m � 1 , whereas the metallacycle 2 binds and bends the DNA with a bind- ing constant of 7 � 10 6 m � 1 . PCR assays show that metallo-supramolecular box 2 interferes with DNA transactions in vitro whereas the intercalator 1 does not. The metallacycle is active against four human cancer cell lines, with IC50 values ranging between 3.1 and 19.2 mm and shows similar levels of efficacy, but a differen…
Expression of a mutant HSP110 sensitizes colorectal cancer cells to chemotherapy and improves disease prognosis
2011
Heat shock proteins (HSPs) are necessary for cancer cell survival. We identified a mutant of HSP110 (HSP110ΔE9) in colorectal cancer showing microsatellite instability (MSI CRC), generated from an aberrantly spliced mRNA and lacking the HSP110 substrate-binding domain. This mutant was expressed at variable levels in almost all MSI CRC cell lines and primary tumors tested. HSP110ΔE9 impaired both the normal cellular localization of HSP110 and its interaction with other HSPs, thus abrogating the chaperone activity and antiapoptotic function of HSP110 in a dominant-negative manner. HSP110ΔE9 overexpression caused the sensitization of cells to anticancer agents such as oxaliplatin and 5-fluorou…
Survivin is regulated by interleukin-4 in colon cancer stem cells
2010
Colorectal cancer has provided an important model to test the stem cell hypothesis of cancer origin, which implies that cancer arises as a result of genetic aberrations in stem cells leading to deregulation of the proliferation/differentiation balance. We and others have demonstrated that, similarly to other solid tumors, colon carcinogenesis and progression are dictated by highly apoptosis-resistant stem-like cells. Our data have suggested that protection from apoptosis is achieved by autocrine production of interleukin-4 (IL-4) through up-regulation of anti-apoptotic mediators. In this study, we extend our analysis to another apoptosis inhibitor widely expressed in tumors, namely survivin…
New heteronuclear gold(I)-platinum(II) complexes with cytotoxic properties: are two metals better than one?
2014
A series of mono- and heterodinuclear gold(I) and platinum(II) complexes with a new bipyridylamine-phosphine ligand have been synthesized and characterized. The X-ray structures of the ligand precursor 4-iodo-N,N-di(pyridin-2-yl)benzamide, and of one gold derivative are reported. All the complexes display antiproliferative properties in vitro in human cancer cells in the range of cisplatin or higher, which appear to correlate with compounds' uptake. Interestingly, studies of the interactions of the compounds with models of DNA indicate different mechanisms of actions with respect to cisplatin. The biological activity study of these complexes provides useful information about the interest of…
cis-Dichloroplatinum(II) complexes tethered to dibenzo[c,h][1,6]naphthyridin-6-ones: Synthesis and cytotoxicity in human cancer cell lines in vitro
2013
A novel family of cisplatin-type complexes tethered to dibenzo[c,h][1,6]naphthyridin-6-one topoisomerase inhibitor via a polymethylene chain and their nonplatinated counterparts were prepared. Their potential cytotoxicity was assessed in three human colorectal cancer cell lines HCT 116, SW480 and HT-29 and compared to the reference molecules cisplatin and oxaliplatin. Platinated compounds were poorly active whilst nonplatinated dibenzo[c,h][1,6]naphthyridin-6-one moieties exhibited higher cytotoxic properties than cisplatin and oxaliplatin whatever the length of the polymethylene chain; molecules containing the tri- and hexamethylene chain length were the most cytotoxic.
A solution study of complex formation between iron(III) and oxalate in dimethylsulphoxide
1991
The complex formation between iron(III) and oxalic acid (ethanedioic acid, H2ox) has been studied by potentiometry in dimethylsulphoxide (dmso) solution. H2ox behaves as a weak diprotic acid in such a solvent, with overall association constants: log βj1=8.551(3) and log βj2=14.242(3) at 25°C and 0.1 Mn-Bu4NClO4. A reliable set of overall stability constants for the iron(III)-oxalato complexes, log β11=13.16(4), log β12=23.66(4) and log β13=30.75(4), have been obtained for the first time under identical conditions. The electrochemical behaviour of such complexes was studied in dmso at a platinum electrode. The coordination ability of oxalate towards iron(III) in dmso and water media is compa…