Search results for "CISPLATIN"
showing 10 items of 267 documents
Targeting Cancer Chemotherapy Resistance by Precision Medicine-Driven Nanoparticle-Formulated Cisplatin.
2021
Therapy resistance is the major cause of cancer death. As patients respond heterogeneously, precision/personalized medicine needs to be considered, including the application of nanoparticles (NPs). The success of therapeutic NPs requires to first identify clinically relevant resistance mechanisms and to define key players, followed by a rational design of biocompatible NPs capable to target resistance. Consequently, we employed a tiered experimental pipeline fromiin silico/ito analytical andiin vitro/ito overcome cisplatin resistance. First, we generated cisplatin-resistant cancer cells and used next-generation sequencing together with CRISPR/Cas9 knockout technology to identify the ion cha…
Humans and chimpanzees differ in their cellular response to DNA damage and non-coding sequence elements of DNA repair-associated genes.
2008
Compared to humans, chimpanzees appear to be less susceptible to many types of cancer. Because DNA repair defects lead to accumulation of gene and chromosomal mutations, species differences in DNA repair are one plausible explanation. Here we analyzed the repair kinetics of human and chimpanzee cells after cisplatin treatment and irradiation. Dot blots for the quantification of single-stranded (ss) DNA repair intermediates revealed a biphasic response of human and chimpanzee lymphoblasts to cisplatin-induced damage. The early phase of DNA repair was identical in both species with a peak of ssDNA intermediates at 1 h after DNA damage induction. However, the late phase differed between specie…
Final results of OV16, a phase III randomized study of sequential cisplatin-topotecan and carboplatin-paclitaxel (CP) versus CP in first-line chemoth…
2013
5502 Background: Topotecan was evaluated in a novel combination regimen in comparison to standard therapy in front-line EOC. Methods: Women with newly diagnosed advanced EOC stages IIB-IV, ECOG performance status (PS) 0-1, age < 75, were randomized to either Arm 1: cycles 1 - 4: cisplatin 50 mg/m2 d1 plus topotecan 0.75 mg/m2 d1-5 IV; cycles 5 - 8: paclitaxel 175 mg/m2over 3 hrs d1 followed by carboplatin AUC5 day 1 or Arm 2: paclitaxel plus carboplatin as in Arm 1 for 8 cycles. The primary endpoint was progression free survival (PFS) and secondary endpoints included objective response, overall survival (OS), adverse event (AE) and Quality of Life (QoL). The sample size required 800 pts…
Killing of p53-deficient hepatoma cells by parvovirus H-1 and chemotherapeutics requires promyelocytic leukemia protein
2008
To evaluate the synergistic targeting and killing of human hepatocellular carcinoma (HCC) cells lacking p53 by the oncolytic autonomous parvovirus (PV) H-1 and chemotherapeutic agents and its dependence on functional promyelocytic leukemia protein (PML).The role of p53 and PML in regulating cytotoxicity and gene transfer mediated by wild-type (wt) PV H-1 were explored in two pairs of isogenic human hepatoma cell lines with different p53 status. Furthermore, H-1 PV infection was combined with cytostatic drug treatment.While the HCC cells with different p53 status studied were all susceptible to H-1 PV-induced apoptosis, the cytotoxicity of H-1 PV was more pronounced in p53-negative than in p…
Multifunctional Poly(ethylene glycol)s
2011
In the rapidly evolving multidisciplinary field of polymer therapeutics, tailored polymer structures represent the key constituent to explore and harvest the potential of bioactive macromolecular hybrid structures. In light of the recent developments for anticancer drug conjugates, multifunctional polymers are becoming ever more relevant as drug carriers. However, the potentially best suited polymer, poly(ethylene glycol) (PEG), is unfavorable owing to its limited functionality. Therefore, multifunctional linear copolymers (mf-PEGs) based on ethylene oxide (EO) and appropriate epoxide comonomers are attracting increased attention. Precisely engineered via living anionic polymerization and d…
Neuroprotection elicited by P2Y13 receptors against genotoxic stress by inducing DUSP2 expression and MAPK signaling recovery.
2014
AbstractNucleotides activating P2Y13 receptors display neuroprotective actions against different apoptotic stimuli in cerebellar granule neurons. In the present study, P2Y13 neuroprotection was analyzed in conditions of genotoxic stress. Exposure to cisplatin and UV radiation induced caspase-3-dependent apoptotic cell death, and p38 MAPK signaling de-regulation. Pre-treatment with P2Y13 nucleotide agonist, 2methyl-thio-ADP (2MeSADP), restored granule neuron survival and prevented p38 long-lasting activation induced by cytotoxic treatments. Microarray gene expression analysis in 2MeSADP-stimulated cells revealed over-representation of genes related to protein phosphatase activity. Among them…
Mevalonate pathway inhibitors affect anticancer drug-induced cell death and DNA damage response of human sarcoma cells
2011
Lovastatin (Lov), bisphosphonates (BP) and metformin (Met) are widely used drugs, having in common that they interfere with the mevalonate pathway (MP). The MP generates isoprene moieties required for the function of regulatory GTPases controlling cell proliferation and survival. Here, we addressed the question whether MP inhibitors interfere with the anti-tumor efficacy of anticancer drugs. We comparatively analyzed the effect of equitoxic doses of Lov, BP and Met on cell viability, cell cycle progression, apoptosis and DNA damage response (DDR) of human osteo- and fibrosarcoma cells exposed to doxorubicin or cisplatin. We found that Lov, BP and Met modulated the anticancer drug sensitivit…
Pt(II) complex @mesoporous silica: preparation, characterization and study of release
2016
Cisplatin analogs, having cytotoxic activity higher than that exerted by cisplatin, have recently triggered considerable interest by the community. The cis-[PtCl2(DMSO)HL]·2DMSO, where HL = 7-amino-2-(methylthio)[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxylic acid, has shown a potent cytotoxic activity on HepG2 hepatocarcinoma cells, while under identical conditions, it did not affect normal immortalized human liver cells (Chang). In this work, the above complex has been incorporated into MCM41 mesoporous silica, pure and functionalized with amino group, which is considered one of the best host for a drug delivery system for carrying high dosages of a variety of drugs in their mesopores. Sinc…
Mono- and polynuclear complexes of Pt(II) with polypyridyl ligands. Synthesis, spectroscopic and structural characterization and cytotoxic activity.
2007
Abstract An array of poly- and mononuclear complexes of Pt(II) with polypyridyl ligands is reported. The framework complexes [(PtCl 2 ) 2 (bpp) 2 (μ-PtCl 2 )](H 2 O) 2 [bpp = 2,3-bis(2-pyridyl)pyrazine], [PtCl 2 (μ-tptz)PtClNCPh]Cl [tptz = 2,4,6-tris(2-pyridyl)-1,3,5-triazine], and mononuclear PtCl 2 (NH 2 dpt) [NH 2 dpt = 4-amino-3,5-bis(2-pyridyl)-1,2,4-triazole] have been prepared and structurally characterized. Both neutral and ionic complexes are present, with bifunctional and monofunctional Pt(II) moieties, whose size and shape enable them to behave as novel scaffolds for DNA binding. Pt(II) complexes were tested for their biological activity. Cell viability assay and flow cytometric …
The nucleotide excision repair protein XPC is essential for bulky DNA adducts to promote interleukin-6 expression via the activation of p38-SAPK
2016
Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants, and many are potent carcinogens. Benzo[a]pyrene (B[a]P), one of the best-studied PAHs, is metabolized ultimately to the genotoxin anti-B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE). BPDE triggers stress responses linked to gene expression, cell death and survival. So far, the underlying mechanisms that initiate these signal transduction cascades are unknown. Here we show that BPDE-induced DNA damage is recognized by DNA damage sensor proteins to induce activation of the stress-activated protein kinase (SAPK) p38. Surprisingly, the classical DNA damage response, which involves the kinases ATM and ATR, is not involved in p38-SA…