Disease relevance of Platidiam

• Virilizing hepatoblastoma: precocious sexual development and partial response of pulmonary metastases to cis-platinum [1].
• Depletion of intracellular levels of polyamines, which are believed to have a role in the intranuclear stabilization of DNA, alters the cytotoxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea and cis-diamminedichloroplatinum II in 9L rat brain tumor cells [2].
• BACKGROUND: Cisplatin (cis-diamminedichloroplatinum) is one of the most active agents against a broad range of malignancies, including ovarian cancer [3].
• Hyperthermia prior to cis-platinum administration increased cis-platinum inhibition of leukemia colony formation as much as 2 logs; however, antileukemia synergism ws greatest when cis-platinum administration immediately preceded hyperthermia and no evidence existd of synergism against normal bone marrow colonies [4].
• Letter: Allergic reactions to cis platinum [5].

Psychiatry related information on Platidiam

• The SHP complexes were the most reactive toward DNA and produced a greater reduction in the transforming activity of Bacillus subtilis DNA after 3-hr reaction times than did the DDP or DDCP complexes [6].
• Lorazepam (Ativan) appears to be a safe medication to induce amnesia for cis-platinum chemotherapy and deserves further study to determine its effect on anticipatory vomiting, nausea and vomiting, and patient compliance with continued chemotherapy [7].
• Evaluation of auditory thresholds in 33 children receiving cis-platinum shows that a threshold shift at 6 and 8 kHz is first measurable after a cumulative dose of 201 to 300 mg/m2 [8].
• Each drug caused a different pattern of effects, but they all altered body weight, rectal temperature, peripheral nerve conduction velocity, the somatosensory evoked potential and undifferentiated motor activity. cis-Platinum was the most toxic, and maytansine was the least toxic [9].
• 56 inoperable patients with HCC were divided into IFN-alpha plus cis-platinum treated group (n = 30) and no antitumor therapy group (n = 26) [10].

High impact information on Platidiam

• The pharmacokinetics of CDDP and CTX were altered in animals bearing the respective resistant tumors [11].
• EMT-6 murine mammary tumors were made resistant to cis-diamminedichloroplatinum (II) (CDDP), carboplatin, cyclophosphamide (CTX), or thiotepa in vivo by treatment of tumor-bearing animals with the drug during a 6-month period [11].
• Tumor cell lines with acquired resistance to the antineoplastic agent cis-diamminedichloroplatinum(II) overexpressed metallothionein and demonstrated cross-resistance to alkylating agents such as chlorambucil and melphalan [12].
• Crystals of the adduct of the anticancer drug cis-diamminedichloroplatinum(II), cis-DDP, with d(pGpG), its putative target on DNA in the cancer cell, have been obtained and used in an x-ray crystallographic study to elucidate the molecular structure to atomic resolution [13].
• Using the Xenopus egg extract system, we show that lesions induced by UV irradiation and cis-platinum cause the functional uncoupling of MCM helicase and DNA polymerase activities, an event previously shown for aphidicolin [14].

Chemical compound and disease context of Platidiam

• Comparative activity and toxicity of cis-diamminedichloroplatinum (DDP) and a combination of doxorubicin, cyclophosphamide, and DDP in disseminated transitional cell carcinomas of the urinary tract [15].
• Fifty-three patients with recurrent and advanced stage (III and IV) non-small-cell lung cancer (NSCLC) were treated with a combination of bleomycin, etoposide (VP-16-213), and cis-diamminedichloroplatinum (BEP) [16].
• It was active against P388 leukemia sublines resistant to cyclophosphamide, L-phenylalanine mustard, and cis-diamminedichloroplatinum(II) [17].
• Here we demonstrate that a variety of chemotherapeutic agents, including cis-platinum, 5-fluorouracil (5-FU), and taxol, induce the switch from the latent to lytic form of EBV infection in tumor cells [18].
• Comparison of intra-arterial cis-diamminedichloroplatinum II with high-dose methotrexate and citrovorum factor rescue in the treatment of primary osteosarcoma [19].

Biological context of Platidiam

• Binding kinetics of tetrachloro-1,2-diaminocyclohexaneplatinum (IV) (tetraplatin) and cis-diamminedichloroplatinum (II) at 37 degrees C with human plasma proteins and with bovine serum albumin. Does aquation precede protein binding [20]?
• Phospholipase C-mediated hydrolysis of phosphatidylcholine is activated by cis-diamminedichloroplatinum(II) [21].
• We have investigated the effect of cis-diamminedichloroplatinum(II) (CDDP) on signal transduction pathways [21].
• It has been postulated that the selective action of cis-DDP occurs through specific binding of nuclear proteins to cis-DDP-damaged DNA sites and that binding blocks DNA repair [22].
• Preferred bleomycin cleavage sites adjacent to oligo(dG) regions on two restriction fragments of plasmid pBR322 DNA were masked by pretreatment with cis-diamminedichloroplatinum(II). trans-Diamminedichloroplatinum(II), which is inactive as an antitumor drug, showed similar but not identical behavior [23].

Anatomical context of Platidiam

• Results from pH 5.0 dissociation and receptor recycling experiments suggest that the mechanism of decreased internalization of cis-DDP-alpha 2M* involves poor dissociation from the receptor in endosomes and a decrease in available surface receptors over the time of exposure to the ligand [24].
• Human semaphorin E (H-sema E) was overexpressed in CDDP-resistant cell lines and was readily induced not only by diverse chemotherapeutic drugs but also by x-ray and UV irradiation [25].
• Thus in ovarian cancer patients, the formation of the intrastrand diammineplatinum adducts in leukocyte DNA is associated with favorable disease response to cis-diamminedichloroplatinum (II) or diamminecyclobutane-dicarboxylatoplatinum chemotherapy [26].
• Two recombinant phage have been isolated from a human B-cell lambda gt11 library by using a cis-DDP-modified DNA restriction fragment as a probe [27].
• To identify the molecules responsible for drug resistance that is unrelated to MDR1 or MRP gene products, a eukaryotic expression cDNA library of cis-diamminedichloroplatinum(II) (CDDP)-resistant ovarian cancer TYKnuR cells was introduced into Cos-7 cells [25].

Associations of Platidiam with other chemical compounds

• Cisplatin (CDDP; cis-diamminedichloroplatinum) and CPT-11 exhibit synergistic antitumor activity and have been used in combination-chemotherapy regimens [28].
• The results further emphasize the possibility that the synergism found when cis-diamminedichloroplatinum(II) and bleomycin are used in combination chemotherapy may be due to interactions at the level of DNA-drug binding [23].
• By contrast, DNA adducts of the clinically ineffective trans isomer of cisplatin, trans-diamminedichloroplatinum(II), are not recognized by hUBF [29].
• We show that the human mismatch recognition activity MutSalpha recognizes several types of DNA lesion including the 1,2-intrastrand d(GpG) crosslink produced by cis-diamminedichloroplatinum(II), as well as base pairs between O6-methylguanine and thymine or cytosine, or between O4-methylthymine and adenine [30].
• The nephrotoxic effects of cis-dichlorodiammineplatinum(II) (NSC-119875) administered to male F344 rats at the median lethal dose (LD50; 7.5 mg/kg) were inhibited by treatment with sodium diethyldithiocarbamate (500 or 750 mg/kg) between 1 and 4 hr after cis-platinum administration [31].

Gene context of Platidiam

• Cis-platinum, which activated SAPK2 but induced little ERK activity, also induced membrane blebbing that was dependent on the expression of HSP27 [32].
• BRCA1 up-regulation is associated with repair-mediated resistance to cis-diamminedichloroplatinum(II) [33].
• Treatment of both cells with cisplatin but not transplatin isomer activates JNK and ERK [34].
• MM cell lines with amplification of PDZK1 exhibited the resistance to melphalan-, cis-platin-, and vincristin-induced cell death compared with MM cell lines without its amplifications [35].
• Moreover, the wild type ATF2-expressing clones exhibited rapid DNA repair after treatment with the four DNA-damaging agents but not transplatin [36].

Analytical, diagnostic and therapeutic context of Platidiam

• Hence, by preventing EGFR-mediated survival signaling, the internalization route we uncovered enhances the cytotoxic effect of drugs like cis-platinum, which may underlie interactions between chemotherapy and EGFR-targeting drugs [37].
• A monoclonal antibody raised against trans-DDP-DNA was competitively inhibited in an ELISA by 40 nM trans-DDP bound to DNA, (D/N)b = 0.022 [38].
• The cells were treated with cis-dichlorodiammineplatinum and solubilized in NaDodSO4-containing buffer, and the DNA was pelleted by high-speed centrifugation [39].
• The interaction of cis-diamminedichloroplatinum(II) (c-DDP) with daily fractionated radiotherapy was studied in the SCCVII tumor, the duodenum, and the lungs of C3H/Km mice [40].
• After this period, as happened also with nodules treated with 5-FUra alone, vigorous regrowth occurred after treatment with cis-DDP plus 5-FUra, and all the nodules regained the size of the controls sooner or later [41].

References