Spectrum of cellular responses to pyriplatin, a monofunctional cationic antineoplastic platinum(II) compound, in human cancer cells

Pyriplatin, cis-diammine(pyridine)chloroplatinum(II), a platinum-based antitumor drug candidate, is a cationic compound with anticancer properties in mice and is a substrate for organic cation transporters that facilitate oxaliplatin uptake. Unlike cisplatin and oxaliplatin, which form DNA cross-links, pyriplatin binds DNA in a monofunctional manner. The antiproliferative effects of pyriplatin, alone and in combination with known anticancer drugs (paclitaxel, gemcitabine, SN38, cisplatin, and 5-fluorouracil), were evaluated in a panel of epithelial cancer cell lines, with direct comparison to cisplatin and oxaliplatin. The effects of pyriplatin on gene expression and platinum–DNA adduct formation were also investigated. Pyriplatin exhibited cytotoxic effects against human cell lines after 24 hours (IC[subscript 50] = 171–443 μmol/L), with maximum cytotoxicity in HOP-62 non–small cell lung cancer cells after 72 hours (IC[subscript 50] = 24 μmol/L). Pyriplatin caused a G[subscript 2]-M cell cycle block similar to that induced by cisplatin and oxaliplatin. Induction of apoptotsis and DNA damage response was supported by Annexin-V analysis and detection of phosphorylated Chk2 and H2AX. Treatment with pyriplatin increased CDKN1/p21 and decreased ERCC1 mRNA expression. On a platinum-per-nucleotide basis, pyriplatin–DNA adducts are less cytotoxic than those of cisplatin and oxaliplatin. The mRNA levels of genes implicated in drug transport and DNA damage repair, including GSTP1 and MSH2, correlate with pyriplatin cellular activity in the panel of cell lines. Synergy occurred for combinations of pyriplatin with paclitaxel. Because its spectrum of activity differs significantly from those of cisplatin or oxaliplatin, pyriplatin is a lead compound for developing novel drug candidates with cytotoxicity profiles unlike those of drugs currently in use

Angstrom-Scale Distance Dependence of Antenna-Enhanced Vibrational Signals

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Characterisation and clinical management of CPT-11 (irinotecan)-induced adverse events: The European perspective

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Cytotoxic agents with activity in breast cancer patients previously exposed to anthracyclines: current status and future prospects.

Journal ArticleReviewinfo:eu-repo/semantics/publishe

Oxaliplatin clinical activity: A review

Oxaliplatin (Eloxatin(TM)), a recently developed third-generation cisplatin analogue with a 1,2-diaminocyclohexane (DACH) carrier ligand, has displayed preclinical and clinical activity in a wide variety of tumour types. Synergistic with 5-FU in colorectal cancer (CRC), the combination has proven efficacy in 5-FU-resistant advanced disease and in previously untreated CRC, as demonstrated in controlled phase III trials, while evaluation in the adjuvant setting is ongoing. Due to its excellent safety profile, its unique mechanism of action and lack of cross-resistance with other active agents in CRC, oxaliplatin has also been combined with CPT-11 and Raltitrexed with promising results. Trials in pretreated and untreated advanced ovarian cancer (AOC), as a single agent or in combination with cisplatin, cyclophosphamide or paclitaxel, indicate a yet to be defined role in AOC and confirm its lack of cross-resistance with cis/carboplatin. Clinical investigations of single agent and combination therapies in breast, lung, prostate and germ-cell carcinomas, non-Hodgkin's lymphoma and malignant mesothelioma are being pursued. While the role of oxaliplatin in medical oncology is yet to be fully defined, it appears to be an important new anticancer agent. Copyright (C) 2000 Elsevier Science Ireland Ltd.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Apertureless SNOM study on gold nanoparticles: Experiments and simulations

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Gemcitabine combined with oxaliplatin in advanced pancreatic adenocarcinoma: final results of a GERCOR multicenter phase II study.

Based on preclinical in vitro synergy data, this study evaluated the activity and toxicity of a gemcitabine/oxaliplatin combination in patients with metastatic and locally advanced pancreatic adenocarcinoma.Clinical TrialClinical Trial, Phase IIJournal ArticleMulticenter StudyResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Effects of protein kinase C modulation by PEP005, a novel ingenol angelate, on mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling in cancer cells

PEP005 (ingenol-3-angelate) is a novel anticancer agent extracted from Euphorbia peplus that was previously shown to modulate protein kinase C (PKC), resulting in antiproliferative and proapoptotic effects in several human cancer cell lines. In Colo205 colon cancer cells, exposure to PEP005 induced a time- and concentration-dependent decrease of cells in S phase of cell cycle and apoptosis. In Colo205 cells exposed to PEP005, a variety of signaling pathways were activated as shown by increased phosphorylation of PKCδ, Raf1, extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase (MAPK), c-Jun NH2-terminal kinase, p38 MAPK, and PTEN. PEP005-induced activation of PKCδ was associated with its translocation from the cytosol to the nucleus and other cellular membranes. Interestingly, PEP005 treatment also resulted in reduced expression of PKCα and reduced levels of phosphorylated active form of AKT/protein kinase B. These data suggest that PEP005-induced activation of PKCδ and reduced expression of PKCα resulted in apoptosis by mechanisms mediated by activation of Ras/Raf/MAPK and inhibition of the phosphatidylinositol 3-kinase/AKT signaling pathways. This study supports ongoing efforts targeting PKC isoforms in cancer therapy with PEP005 alone and in combination with other cytotoxic agents