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| cisplatin |
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| CHEBI:27899 |
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| A diamminedichloroplatinum compound in which the two ammine ligands and two chloro ligands are oriented in a cis planar configuration around the central platinum ion. An anticancer drug that interacts with, and forms cross-links between, DNA and proteins, it is used as a neoplasm inhibitor to treat solid tumours, primarily of the testis and ovary. Commonly but incorrectly described as an alkylating agent due to its mechanism of action (but it lacks alkyl groups). |
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This entity has been manually annotated by the ChEBI Team.
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CHEBI:3722, CHEBI:23314
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| ChemicalBook:CB6236182, eMolecules:14089862, eMolecules:10182026, eMolecules:498535 |
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more structures >>
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call loadScript javascripts\jsmol\core\package.js call loadScript javascripts\jsmol\core\core.z.js -- required by ClazzNode call loadScript javascripts\jsmol\J\awtjs2d\WebOutputChannel.js
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| Cisplatin is a chemical compound with formula cis-[Pt(NH3)2Cl2]. It is a coordination complex of platinum that is used as a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, brain tumors and neuroblastoma. It is given by injection into a vein.
Common side effects include bone marrow suppression, hearing problems including severe hearing loss, kidney damage, and vomiting. Other serious side effects include numbness, trouble walking, allergic reactions, electrolyte problems, and heart disease. Use during pregnancy can cause harm to the developing fetus. Cisplatin is in the platinum-based antineoplastic family of medications. It works in part by binding to DNA and inhibiting its replication.
Cisplatin was first reported in 1845 and licensed for medical use in 1978 and 1979. It is on the World Health Organization's List of Essential Medicines. |
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Read full article at Wikipedia
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| InChI=1S/2ClH.2H3N.Pt/h2*1H;2*1H3;/q;;;;+2/p-2 |
| LXZZYRPGZAFOLE-UHFFFAOYSA-L |
| [H][N]([H])([H])[Pt](Cl)(Cl)[N]([H])([H])[H] |
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genotoxin
A role played by a chemical compound to induce direct or indirect DNA damage. Such damage can potentially lead to the formation of a malignant tumour, but DNA damage does not lead inevitably to the creation of cancerous cells.
nephrotoxic agent
A role played by any chemical compound (natural or synthetic) exhibiting itself through the ability to induce damage to the kidneys.
ferroptosis inducer
Any substance that induces or promotes ferroptosis (a type of programmed cell death dependent on iron and characterized by the accumulation of lipid peroxides) in organisms.
apoptosis inducer
Any substance that induces the process of apoptosis (programmed cell death) in multi-celled organisms.
mutagen
An agent that increases the frequency of mutations above the normal background level, usually by interacting directly with DNA and causing it damage, including base substitution.
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cross-linking reagent
A reagent with two reactive groups, usually at opposite ends of the molecule, that are capable of reacting with and thereby forming bridges between macromolecules, principally side chains of amino acids in proteins, allowing the locations of naturally reactive areas within the proteins to be identified.
photosensitizing agent
A chemical compound that can be excited by light of a specific wavelength and subsequently transfer energy to a chosen reactant. This is commonly molecular oxygen within a cancer tissue, which is converted to (highly rective) singlet state oxygen. This rapidly reacts with any nearby biomolecules, ultimately killing the cancer cells.
antineoplastic agent
A substance that inhibits or prevents the proliferation of neoplasms.
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View more via ChEBI Ontology
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(SP-4-2)-diamminedichloridoplatinum
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(SP-4-2)-diamminedichloroplatinum
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cis-diamminedichloridoplatinum(II)
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cis-diamminedichloroplatinum(II)
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cisplatin
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ChemIDplus
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cisplatine
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ChemIDplus
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cisplatino
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ChemIDplus
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cisplatinum
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ChemIDplus
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[PtCl2(NH3)2]
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KEGG COMPOUND
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CDDP
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KEGG COMPOUND
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cis- [PtCl2(NH3)2]
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MolBase
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cis-DDP
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ChemIDplus
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cis-diamminedichloroplatinum
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ChemIDplus
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cis-Diamminedichloroplatinum(II)
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KEGG COMPOUND
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cis-diammineplatinum(II) dichloride
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ChemIDplus
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cis-dichlorodiammineplatinum(II)
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ChemIDplus
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cis-platin
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ChEBI
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Cisplatin
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KEGG COMPOUND
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Peyrone's chloride
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ChemIDplus
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Peyrone's salt
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ChEBI
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Platamine
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DrugBank
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Briplatin
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ChemIDplus
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Cismaplat
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DrugBank
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Lederplatin
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DrugBank
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Neoplatin
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DrugBank
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Platinex
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DrugBank
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Platinol
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KEGG DRUG
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Randa
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DrugBank
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11324567
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Reaxys Registry Number
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Reaxys
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15663-27-1
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CAS Registry Number
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KEGG COMPOUND
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15663-27-1
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CAS Registry Number
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ChemIDplus
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2519
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Gmelin Registry Number
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Gmelin
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Guo J, Xu B, Han Q, Zhou H, Xia Y, Gong C, Dai X, Li Z, Wu G (2018)
Ferroptosis: A Novel Anti-tumor Action for Cisplatin.
Cancer research and treatment 50, 445-460 [PubMed:28494534]
[show Abstract]
PurposeFerroptosis is a new mode of regulated cell death, which is completely distinct from other cell death modes based on morphological, biochemical, and genetic criteria. This study evaluated the therapeutic role of ferroptosis in classic chemotherapy drugs, including the underlying mechanism.Materials and methodsCell viabilitywas detected by using the methylthiazoltetrazlium dye uptake method. RNAiwas used to knockout iron-responsive element binding protein 2, and polymerase chain reaction, western blot was used to evaluate the efficiency. Intracellular reduced glutathione level and glutathione peroxidases activitywere determined by related assay kit. Intracellularreactive oxygen species levelswere determined by flowcytometry. Electron microscopywas used to observe ultrastructure changes in cell.ResultsAmong five chemotherapeutic drugs screened in this study, cisplatin was found to be an inducer for both ferroptosis and apoptosis in A549 and HCT116 cells. The depletion of reduced glutathione caused by cisplatin and the inactivation of glutathione peroxidase played the vital role in the underlying mechanism. Besides, combination therapy of cisplatin and erastin showed significant synergistic effect on their anti-tumor activity.ConclusionFerroptosis had great potential to become a new approach in anti-tumor therapies and make up for some classic drugs, which open up a new way for their utility in clinic. | Michels J, Vitale I, Galluzzi L, Adam J, Olaussen KA, Kepp O, Senovilla L, Talhaoui I, Guegan J, Enot DP, Talbot M, Robin A, Girard P, Oréar C, Lissa D, Sukkurwala AQ, Garcia P, Behnam-Motlagh P, Kohno K, Wu GS, Brenner C, Dessen P, Saparbaev M, Soria JC, Castedo M, Kroemer G (2013)
Cisplatin resistance associated with PARP hyperactivation.
Cancer research 73, 2271-2280 [PubMed:23554447]
[show Abstract]
Non-small cell lung carcinoma patients are frequently treated with cisplatin (CDDP), most often yielding temporary clinical responses. Here, we show that PARP1 is highly expressed and constitutively hyperactivated in a majority of human CDDP-resistant cancer cells of distinct histologic origin. Cells manifesting elevated intracellular levels of poly(ADP-ribosyl)ated proteins (PAR(high)) responded to pharmacologic PARP inhibitors as well as to PARP1-targeting siRNAs by initiating a DNA damage response that translated into cell death following the activation of the intrinsic pathway of apoptosis. Moreover, PARP1-overexpressing tumor cells and xenografts displayed elevated levels of PAR, which predicted the response to PARP inhibitors in vitro and in vivo more accurately than PARP1 expression itself. Thus, a majority of CDDP-resistant cancer cells appear to develop a dependency to PARP1, becoming susceptible to PARP inhibitor-induced apoptosis. | Chen W, Xiao Y, Liu X, Chen Y, Zhang J, Xu X, Tang R (2013)
Overcoming cisplatin resistance in chemotherapy by biomineralization.
Chemical communications (Cambridge, England) 49, 4932-4934 [PubMed:23604226]
[show Abstract]
Nano-solidified intermedias (NSI) of cisplatin were prepared via biomineralization and applied to reverse the drug resistance of cancers in vitro and in vivo by an alternative internalization pathway. | Gonçalves MS, Silveira AF, Teixeira AR, Hyppolito MA (2013)
Mechanisms of cisplatin ototoxicity: theoretical review.
The Journal of laryngology and otology 127, 536-541 [PubMed:23651576]
[show Abstract]
IntroductionCisplatin is an effective chemotherapeutic agent commonly used in the treatment of malignant tumours, but ototoxicity is a significant side effect.ObjectivesTo discuss the mechanisms of cisplatin ototoxicity and subsequent cell death, and to present the results of experimental studies.Material and methodsWe conducted a systematic search for data published in national and international journals and books, using the Medline, SciELO, Bireme, LILACS and PubMed databases.ResultsThe nicotinamide adenine dinucleotide phosphate oxidase 3 isoform (also termed NOX3) seems to be the main source of reactive oxygen species in the cochlea. These reactive oxygen species react with other molecules and trigger processes such as lipid peroxidation of the plasma membrane and increases in expression of the transient vanilloid receptor potential 1 ion channel.ConclusionCisplatin ototoxicity proceeds via the formation of reactive oxygen species in cochlear tissue, with apoptotic cell death as a consequence. | Mirandola P, Sponzilli I, Gobbi G, Marmiroli S, Rinaldi L, Binazzi R, Piccari GG, Ramazzotti G, Gaboardi GC, Cocco L, Vitale M (2006)
Anticancer agents sensitize osteosarcoma cells to TNF-related apoptosis-inducing ligand downmodulating IAP family proteins.
International journal of oncology 28, 127-133 [PubMed:16327988]
[show Abstract]
Although TNF-related apoptosis-inducing ligand (TRAIL) usually induces cell death in tumor cells, there are some tumor cell types that are resistant to its apoptogenic effects. Some chemotherapeutic drugs, however, can sensitize resistant cancer cells to TRAIL by either upregulating surface TRAIL death receptor expression or by modulating intracellular signalling pathways emanating from TRAIL receptors. U2OS human osteosarcoma cells express TRAIL-R2 but are resistant to TRAIL-induced apoptosis. however, the genotoxic drugs, Doxorubicin and Cisplatin, are able to sensitize U2OS cells to TRAIL, without affecting their surface expression of either death or decoy TRAIL receptors. We demonstrate that Doxorubicin and Cisplatin downmodulate X-IAP, while not affecting FLIP levels in U2OS cells. Selective downmodulation of X-IAP protein synthesis by specific small interference RNA transfection induced a sensitization of U2OS cells to TRAIL comparable to that induced by pharmacological treatment with genotoxic drugs. TRAIL-R2 downmodulation by siRNAs completely abolished the TRAIL-induced apoptosis of genotoxin-treated U2OS cells. Our findings demonstrate that Doxorubicin and Cisplatin do not sensitize U2OS osteosarcoma cells to TRAIL by surface receptor modulation but rather by the removal of the intracellular signalling inhibition generated by X-IAP, suggesting a foreseeable relevant advantage to the therapy of these tumors by the combined regimen of genotoxin-based chemotherapy and TRAIL. | Chen Z, Zhang J, Mohr G (2003)
Enhancing alkylating agent resistance through ERCC2 gene transfection in human glioma cell line.
Chinese medical journal 116, 1171-1174 [PubMed:12935404]
[show Abstract]
ObjectiveTo confirm the enhancing effect of excision repair cross complementing rodent repair deficiency gene 2 (ERCC2) on alkylating agents resistance.MethodsThe authors constructed a pcDNA3-ERCC2 plasmid. The pcDNA3-ERCC2 was transfected into a selected ERCC2 negative human glioma cell line, SKMG-4, using liposome-mediated transfection. After G418 selection, a stable transfected cell line was obtained and tested for cytotoxicity of several alkylating agents.ResultsThe stable transfectant was obtained and confirmed by RT-PCR as well as Western blot analysis to be strongly expressing ERCC2 at both mRNA and protein levels. The IC(90) ( micro mol/L) of two alkylating agents, cisplatin and melphalan, increased from 1.0 to 1.75 (75%) and 5.6 to 9.0 (61%), respectively, compared with control cell line.ConclusionThe present data provided evidences and confirmed the authors' previous results that ERCC2 contributes, at least partially, to alkylating agent resistance in human glioma cell line. | Cojocel C, Thomson MS (2003)
Impairment of the renal p-aminohippurate transport induced by 6-hydroxydopamine.
The Journal of pharmacy and pharmacology 55, 669-674 [PubMed:12831510]
[show Abstract]
In this study, the effects of 6-hydroxydopamine (6-OHDA) on renal p-aminohippurate transport were investigated in-vitro using rat renal cortical slices. Cisplatin, a known nephrotoxin, was used as positive control. Renal cortical slices were incubated for 60 min in a cisplatin-containing medium (0.83-5.0 microM) at 37 degrees C under a 100% O(2) atmosphere. In another series of experiments, renal cortical slices were incubated in a 3.33 microM cisplatin-containing medium for 15-120 min or in a cisplatin-free medium. Subsequently, for each series of experiments, kidney slices were incubated at 25 degrees C for 90 min in a media containing p-aminohippurate. In a further series of experiments, renal cortical slices were incubated for 60 min in a 6-OHDA containing medium (3.125-100 microM) at 37 degrees C under a 100% O(2) atmosphere. In another series of experiments, renal cortical slices were incubated in a 50 microM 6-OHDA-containing medium for 15-120 min or in 6-OHDA-free medium. Subsequently, for each series of experiments, kidney slices were incubated at 25 degrees C for 90 min in a media containing p-aminohippurate. The results of this study where slices were incubated in 6-OHDA- or cisplatin-containing media indicate that both 6-OHDA and cisplatin induced a time- and concentration-dependent decrease in p-aminohippurate accumulation by renal cortical slices. Therefore, similarly to cisplatin, 6-OHDA causes functional injury of renal proximal tubule cells, leading to impairment of transport processes across the cell membrane. | Li W, Choy DF, Lam MS, Morgan T, Sullivan ME, Post JM (2003)
Use of cultured cells of kidney origin to assess specific cytotoxic effects of nephrotoxins.
Toxicology in vitro : an international journal published in association with BIBRA 17, 107-113 [PubMed:12537968]
[show Abstract]
During drug discovery, assessment of renal safety for a compound is important for further development of a candidate drug. In this study, we describe an in vitro cell-based assay capable of discerning nephrotoxicity. Three cell types, two of kidney origin and one of liver origin, were used to examine the effects of nephrotoxins. The cell types were the porcine normal kidney tubular epithelial cell line (LLC-PK1), the primary human renal proximal tubular epithelial cells (hRPTEC) and the human liver cell line (HepG2). Cytotoxicity was measured using a luciferin/luciferase assay that measures cellular ATP levels. Four known nephrotoxins, 4-aminophenol, cisplatin, cyclosporin A and paraquat, were tested in this cell-based assay to evaluate cytotoxicity on drug exposure. Kidney-derived LLC-PK1 cells and hRPTECs were found to be sensitive to selected nephrotoxins while liver-derived HepG2 cells were insensitive. Human RPTEC cells obtained from three individual donors demonstrated highly reproducible effects on drug exposure. With respect to drug discovery efforts, integration of the cell models described here are valuable for evaluation of nephrotoxic potentials during lead selection and optimization processes. | Pujol JL, Carestia L, Daurès JP (2000)
Is there a case for cisplatin in the treatment of small-cell lung cancer? A meta-analysis of randomized trials of a cisplatin-containing regimen versus a regimen without this alkylating agent.
British journal of cancer 83, 8-15 [PubMed:10883661]
[show Abstract]
Chemotherapy is the backbone of small-cell lung cancer therapy. However, optimal drug combinations and schedules remain to be defined and there is hitherto no world-wide accepted standard regimen. Cisplatin, an alkylating agent with high putative toxicity is currently widely used although its effectiveness in this disease has not been established firmly. We conducted a meta-analysis of published data reporting trials randomizing a cisplatin-containing regimen versus a regimen without this alkylating agent in order to determine possible differences in survival response and toxicity. Nineteen trials have been identified in medical literature (4054 evaluable patients). Ten trials randomized patients to receive a cisplatin-etoposide regimen versus a regimen without any of these two drugs. A subgroup analysis was, therefore, carried out in the nine remaining trials that randomly allocated patients between two regimens differing in the absence or presence of cisplatin, whereas etoposide was given (or not given) in both arms (1579 evaluable patients). The DerSimonian and Laird method was used to estimate the size effects and the Peto and Yusuf method was used in order to generate the odds ratios (OR) of reduction in risk of death and the increase in probability of being responders to chemotherapy. There was no significant difference between the cisplatin-containing regimen and the regimen without this drug when the risk of toxic-death was taken into account with respective probabilities of 3.1 and 2.7% (NS). Patients randomized in a cisplatin-containing regimen had an increase in probability of being responders with an OR of 1.35, 95% confidence interval (CI) of 1.18-1.55; P < 10(-5) corresponding to an increase of objective (partial plus complete) response rate from 0.62 to 0.69 (a result taking into account a significant heterogeneity). Patients treated with a cisplatin-containing regimen benefited from a significant reduction of risk of death at 6 months and 1 year with respective OR 0.87, 95% CI 0.75-0.98, P = 0.03, and or 0.80, 95% CI 0.69-0.93, P = 0.002 (no statistical heterogeneity). This corresponded to a significant increase in the probability of survival of 2.6% and 4.4% at 6 months and 1 year respectively. The meta-analysis restricted to the subset of nine trials without etoposide treatment imbalance reached similar conclusions. A cisplatin-containing regimen yields a higher response rate and probability of survival than does a chemotherapy containing others alkylating agents without a perceptible increase in risk of toxic-death. | Aletras V, Hadjiliadis D, Hadjiliadis N (1995)
On the Mechanism of Action of the Antitumor Drug cis-Platin (cis-DDP) and its Second Generation Derivatives.
Metal-based drugs 2, 153-185 [PubMed:18472761]
[show Abstract]
The present article attempts to summarise the elements of the mechanism of action of the antitumor drug cis -Platin presented the last few years. Highlights on the discovery, of the drug and the development of it's second generation derivatives are presented, as well as the ways that cis -DDP reacts with biomolecules as DNA and proteins and their models e.g. nucleosides, nucleotides. Also the hydrolysis data are presented for cis -DDP and its' inactive congener trans -DDP, as well as for the second generation drug carboplatin. Finally, usefull conclusions are given from this work, pointing out the unanswered questions about the action of cis -DDP as well as its differences in action, in comparison with trans -DDP. | Terheggen PM, Floot BG, Lempers EL, van Tellingen O, Begg AC, den Engelse L (1991)
Antibodies against cisplatin-modified DNA and cisplatin-modified (di)nucleotides.
Cancer chemotherapy and pharmacology 28, 185-191 [PubMed:1855275]
[show Abstract]
Cytotoxic effects of cis-diamminedichloroplatinum-(II) (cis-DDP) are thought to be mediated by binding to DNA. Studies on binding of cis-DDP to cellular DNA rely heavily on the availability of specific antibodies. We therefore raised and characterized four rabbit antisera: one against cis-DDP-modified DNA (antiserum NKI-A59) and three others against the cis-DDP-modified (di)nucleotides cis-Pt(NH3)2d(pApG) (NKI-A68), cis-Pt(NH3)2d(GMP)2 (NKI-A10), and Pt(NH3)3dGMP (NKI-A39). Reactivities to platinum compounds were determined in an enzyme-linked immunosorbent assay (ELISA) and in a quantitative immunocytochemical assay. In the ELISA, NKI-A59 showed a high affinity for DNA heavily substituted with either cis-DDP or CBDCA [cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II)]; amounts of platinum per well giving 50% inhibition (IA50) were as low as 15 and 76 fmol, respectively. NKI-A59 also showed affinity to cis-DDP-modified poly[d(G-C)].poly[d(G-C)], poly(dC), and poly(dG). No affinity was found for trans-DDP [trans-diamminedichloro-platinum(II)]-modified DNA, enzymatically digested cis-DDP-DNA, or cis-DDP-DNA, or cis-DDP-modified poly(dA).poly(dT), oligo(dA)15.oligo(dT)15, oligo(dG)21, oligo(dG)42, or oligo(dAAAG)10. The efficiency of binding to cis-DDP-DNA decreased with decreasing DNA modification levels. Although other cis-DDP-DNA- and cis-DDP-(di)nucleotide-specific antisera have been identified, NKI-A59 is the first antiserum described that is suitable for the in situ detection of cis-DDP-DNA adducts at clinically relevant platinum levels. Adduct-specific immunostaining signals in cultured RIF-1 cells or rat liver paralleled platinum-DNA binding as measured by atomic absorption spectroscopy. The antisera NKI-A68, NKI-A10, and NKI-A39 showed high affinity for their corresponding haptens and varying affinity for non-hapten cis-DDP-DNA adducts. Their affinity for digested cis-DDP-modified DNA was up to 30 times that for intact cis-DDP-DNA. Neither NKI-A68 nor NKI-A10 resulted in specific immunocytochemical staining of cis-DDP-DNA adducts. We conclude that NKI-A68, NKI-A10, and NKI-A39 are suitable for platinum-DNA adduct analysis of digested DNA in ELISA and that NKI-A59 is suitable for platinum-DNA adduct detection at the single-cell level using immunocytochemical methods. |
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