• This is a heavy metal coordination complex that exerts its cytotoxic effect by platination of DNA, a mechanism analogous to alkylation, leading to interstrand and intrastrand DNA crosslinks and inhibition of DNA replication. (medscape.com)
  • Cisplatin can cause intrastrand and interstrand crosslinks between purine bases and is a chemotherapeutic drug widely used to treat cancer. (oncotarget.com)
  • Cisplatin mainly induces intrastrand crosslinks and to a lesser extent also interstrand crosslinks. (biomedcentral.com)
  • The achievement of alkylating realtors has prompted the introduction of pseudo-alkylating realtors such as for example cisplatin (cis-diamminedichloroplatinum(II)) and related derivatives which stimulate 1,2-intrastrand crosslinks with purine bases, but haven't any alkyl groups designed for an alkylation response [3, 4]. (buyresearchchemicalss.net)
  • Pemetrexed is a folic acid antagonist that inhibits the synthesis of precursor nucleotides, whereas cisplatin directly induces DNA adducts, the repair of which is dependent on sufficiently high nucleotide levels. (biomedcentral.com)
  • To explore novel platinum-based anticancer agents that are distinct from the structure and interaction mode of the traditional cisplatin by forming the bifunctional intrastrand 1,2 GpG adduct, the monofunctional platinum + DNA adducts with extensive non-covalent interactions had been studied. (biomedcentral.com)
  • Cisplatin acts to destroy the template function of the DNA double helix by forming intra-chain and inter-chain adducts, leading to DNA damage [ 3 ]. (biomedcentral.com)
  • Their participation in the molecular mechanisms of resistance to cisplatin, a drug commonly used in chemotherapy, is also revised. (hindawi.com)
  • We show that loss of the DNA repair protein XPA markedly augments the synthetic lethality between MK2 and p53, enhancing anti-tumor responses alone and in combination with cisplatin chemotherapy. (nature.com)
  • Non-small cell lung cancer (NSCLC) accounts for approximately 85 % of all lung cancers, with the current standard regimen of care for NSCLC including chemotherapy with pemetrexed as a single agent or in combination with platinum-based agents, e.g. cisplatin. (biomedcentral.com)
  • Since the discovery of cisplatin [ cis -(NH 3 ) 2 PtCl 2 ], as an anticancer agent, a series of platinum anticancer drugs were used in treatment of various cancers in clinical chemotherapy [ 1 - 6 ]. (biomedcentral.com)
  • There is an urgent need to identify strategies that increase cisplatin sensitivity and improve the outcomes of chemotherapy. (biomedcentral.com)
  • SETD8 was a promising therapeutic target to ameliorate cisplatin resistance and improve the efficacy of chemotherapy. (biomedcentral.com)
  • Platinum-based mixture regimen such as for example cisplatin/oxaliplatin plus 5-FU and taxotere may be the current first-line neoadjuvant chemotherapy for locally advanced HNSCC [22]. (healthdisparitiesks.org)
  • Cisplatin is a chemotherapy drug used to treat several cancer types such as bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, brain tumors, and neuroblastoma. (springeropen.com)
  • Chronic treatment with cisplatin induces replication-dependent sister chromatid recombination to confer cisplatin-resistant phenotype in nasopharyngeal. (oncotarget.com)
  • Here, we report that chronic treatment with cisplatin induces HR to confer cisplatin resistance in nasopharyngeal carcinoma (NPC) cells. (oncotarget.com)
  • Adaptation of the standard treatment schedule to include pretreatment with pemetrexed optimizes the anticancer efficiency of pemetrexed-cisplatin combination therapy, which correlates with a persistence of treatment-induced DNA damage. (biomedcentral.com)
  • This is compared with the NMR structure of the same duplex intrastrand cross-linked at the d(G*pG*) site by cis-(Pt(NH3)2¿2+, derived from the anticancer drug cisplatin. (ox.ac.uk)
  • 2016 ). This study was conducted to analyze the anticancer effects of green-synthesized AgNPs using Juniperus polycarpos on A549 (adenocarcinomic human alveolar basal epithelial cells) cell lines, as well as comparing it with Cisplatin commercial drug. (springeropen.com)
  • Intrastrand cross-linking of DNA and inhibition of DNA precursors are among the proposed mechanisms of action for cisplatin. (medscape.com)
  • Ifosfamide forms DNA interstrand and intrastrand bonds that interfere with protein synthesis. (medscape.com)
  • The results obtained with pol η are compared with translesion synthesis past other intrastrand cross-linked lesions with previously published results of others that include the isomeric G[8-5m]T lesions generated by ionizing radiation, the cis-syn cyclobutane pyrimidine dimer and the 6-4 photoproduct generated by UV irradiation, and the Pt-G∗G∗ lesions derived from the reactions of the chemotherapeutic agent cisplatin with DNA. (nyu.edu)
  • Platinum compounds type DNA intrastrand or interstrand cross-links that significantly stop DNA synthesis and bring about mutations and apoptosis [5]. (healthdisparitiesks.org)
  • These findings establish a mechanism for co-targeting DNA damage-induced cell cycle checkpoints in combination with repair of cisplatin-DNA lesions in vivo using RNAi nanocarriers, and motivate further exploration of ASL as a generalized strategy to improve cancer treatment. (nature.com)
  • Cisplatin is an extremely effective chemotherapeutic agent used for the treatment of testicular and other solid tumours. (icr.ac.uk)
  • Further, this study elucidated the cellular and molecular mechanisms of nanoparticles for anti-proliferative and apoptotic effects on human lung cancer cells (A549) and compared them with commercial drug cisplatin. (springeropen.com)
  • Delivery of siRNA-peptide nanoplexes co-targeting MK2 and XPA to pre-existing p53-deficient tumors in a highly aggressive, immunocompetent mouse model of lung adenocarcinoma improves long-term survival and cisplatin response beyond those of the synthetic lethal p53 mutant/MK2 combination alone. (nature.com)
  • The combination of topotecan and cisplatin improves overall survival. (medscape.com)
  • Cisplatin is a platinum-containing compound that exerts an antineoplastic effect by covalently binding to DNA, with preferential binding to N-7 position of guanine and adenosine. (medscape.com)
  • In the case of 1, 2-intrastrand d(GpG)-cisplatin cross-link, inserts dCTP opposite the 3' guanine (PubMed:24449906). (icr.ac.uk)
  • The platinum(II) center of traditional cisplatin reacts with DNA forming two covalent bonds to N7 atoms of two adjacent guanine (G) bases with the bifunctional intrastrand 1,2 GpG adduct, to prevent the replication and transcription of cancer genes, and ultimately to induce tumor cell apoptosis [ 6 - 9 ]. (biomedcentral.com)
  • Cisplatin is the agent used most commonly, although 5-fluorouracil also is used frequently. (medscape.com)
  • A high frequency of sister chromatid exchanges (SCE) occurs in the cisplatin-resistant NPC cells. (oncotarget.com)
  • Consistent with this result, depletion of several genes in the HR, TS, or FA pathway sensitizes the cisplatin-resistant NPC cells to cisplatin. (oncotarget.com)
  • Targeting the HR, TS, or FA pathways could be a potential therapeutic strategy for treating cisplatin-resistant cancer. (oncotarget.com)
  • This population was highly resistant to concomitant pemetrexed-cisplatin treatment but was sensitized by pemetrexed pretreatment. (biomedcentral.com)
  • In addition, a subpopulation of therapy resistant cells with EMT and cancer stem cell features was identified that was resistant to the standard treatment regimen but sensitive to pemetrexed pretreatment combined with cisplatin. (biomedcentral.com)
  • Further, UNC0379 as a small molecule inhibitor of SETD8 was found to enhance cisplatin sensitivity both in vitro and in vivo. (biomedcentral.com)
  • In addition, MTA-cisplatin combination therapy is also the recommended treatment regimen for malignant pleural mesothelioma (MPM) (reviewed in [ 3 ]. (biomedcentral.com)
  • Overall, the results revealed that the green-synthetized AgNPs had anti-metastasis and anti-proliferation effects on lung cancer cells in comparison to cisplatin with lower side effects on the normal cell line. (springeropen.com)
  • Tirapazamine (3-amino-1,2,4-benzotriazine-1,4-dioxide) is a promising hypoxia-selective cytotoxin that has shown significant activity in advanced clinical trials in combination with radiotherapy and cisplatin. (aacrjournals.org)
  • In the clinical setting, the pemetrexed-cisplatin combination therapy is administered concomitantly. (biomedcentral.com)
  • However, identical experiments conducted in a two-buffer system, 24 mM HEPES plus 24 mM carbonate, showed no DNA mobility changes, indicating that carbonate blocks formation of the 1,2 intrastrand cross-link on DNA. (syr.edu)
  • Significantly, depletion of HR gene BRCA1, TS gene UBC13, or FA gene FANCD2 suppresses SCE and causes cells to accumulate in the S phase, concomitantly with high γH2AX foci formation in the presence of low-dose cisplatin. (oncotarget.com)
  • We hypothesized that prolonged pretreatment with pemetrexed could be beneficial, as prior depletion of nucleotide pools could sensitize cancer cells to subsequent treatment with cisplatin. (biomedcentral.com)
  • Prolonged pemetrexed pretreatment for 48 h prior to cisplatin treatment maximally delayed long-term cell growth and significantly reduced the number of recovering clones. (biomedcentral.com)
  • In addition, 24 h of cisplatin treatment was initiated at day 1, 2 or 3 resulting in either simultaneous pemetrexed application or pemetrexed pretreatment for 24 or 48 h, respectively. (biomedcentral.com)