Antibodies against cisplatin-modified DNA and cisplatin-modified (di) nucleotides

Terheggen, P. M. A. B.; Floot, Ben; Lempers, E. L. M.; Tellingen, Olaf van; Begg, Adrian C.; Engelse, L. Den

doi:10.1007/bf00685507

Cited by 25 publications

(16 citation statements)

References 28 publications

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“…The following antibodies were used for IHC staining of tumors: the in-house-produced NKI-A59 antibody for the detection of cisplatin DNA adducts (as described previously; ref. 18), anti-Ki67 from Abcam (ab15580, 1:3,000), anti-gH2AX from Cell Signaling Technology (#2577, 1:50), and also anti-cleaved caspase-3 from Cell Signaling Technology (#9661, 1:400). The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed using the ApopTag Peroxidase In Situ Apoptosis Detection Kit (Chemicon International, S7100).…”

Section: Ihcmentioning

confidence: 99%

Selected Alkylating Agents Can Overcome Drug Tolerance of G0-like Tumor Cells and Eradicate BRCA1-Deficient Mammary Tumors in Mice

Pajic

Blatter

Guyader

et al. 2017

Clinical Cancer Research

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We aimed to characterize and target drug-tolerant BRCA1-deficient tumor cells that cause residual disease and subsequent tumor relapse. We studied responses to various mono- and bifunctional alkylating agents in a genetically engineered mouse model for -mutant breast cancer. Because of the large intragenic deletion of the gene, no restoration of BRCA1 function is possible, and therefore, no BRCA1-dependent acquired resistance occurs. To characterize the cell-cycle stage from which mammary tumors arise after cisplatin treatment, we introduced the fluorescent ubiquitination-based cell-cycle indicator (FUCCI) construct into the tumor cells. Despite repeated sensitivity to the MTD of platinum drugs, the -mutated mammary tumors are not eradicated, not even by a frequent dosing schedule. We show that relapse comes from single-nucleated cells delaying entry into the S-phase. Such slowly cycling cells, which are present within the drug-naïve tumors, are enriched in tumor remnants. Using the FUCCI construct, we identified nonfluorescent G-like cells as the population most tolerant to platinum drugs. Intriguingly, these cells are more sensitive to the DNA-crosslinking agent nimustine, resulting in an increased number of multinucleated cells that lack clonogenicity. This is consistent with our finding that the nimustine MTD, among several alkylating agents, is the most effective in eradicating-mutated mouse mammary tumors. Our data show that targeting G-like cells is crucial for the eradication of BRCA1/p53-deficient tumor cells. This can be achieved with selected alkylating agents such as nimustine. .

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Section: Ihcmentioning

confidence: 99%

Selected Alkylating Agents Can Overcome Drug Tolerance of G0-like Tumor Cells and Eradicate BRCA1-Deficient Mammary Tumors in Mice

Pajic

Blatter

Guyader

et al. 2017

Clinical Cancer Research

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“…NKI-A59 antiserum is a polyclonal rabbit antiserum containing antibodies that recognize cisplatin-DNA adducts (Terheggen et al, 1987(Terheggen et al, , 1991. The NKI-A59 antiserum was a kind gift of Drs.…”

Section: Nki-a59 Antiserummentioning

confidence: 99%

Immunohistochemical detection of platinated DNA in the cochlea of cisplatin-treated guinea pigs

et al. 2005

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“…This means that NKI-A59, which was originally raised against cisplatin-modified calf thymus DNA, is not only able to recognize cisplatin-and carboplatin-induced DNA modifications (Terheggen et al 1991;Blommaert et al 1993), but also DNA modifications induced by other platinum derivatives. Previous investigations with the antiserum NKI-A59 showed that there was a good correlation in vitro between the surviving fraction and the nuclear density induced by cisplatin (Terheggen et al 1990).…”

Section: Discussionmentioning

confidence: 99%

“…Cytospin slides were treated with phosphate-buffered saline H202 (to inactivate endogenous peroxidases), 1 M KC1, proteinase K, ethanol/NaOH (the last three steps served to denature the DNA and to increase the accessibility of the platinum-DNA adducts), 1% bovine serum albumin (to reduce nonspecific antibody binding) and rabbit antiserum NKI-A59 raised against cisplatin-modified calf thymus DNA (Terheggen et al 1991). To visualize the cisplatin-DNA adducts we used a biotinylated F(ab'); fragment of swine anti-(rabbit immunoglobulin) (Dako, Denmark), an avidin/horseradish-peroxidase vector for amplification and 3,3-diaminobenzidine-hydrochloride/nickel as peroxidase substrate.…”

Section: Immunocytochemical Analysis Of Platinum-dna Modificationmentioning

confidence: 99%

Hyperthermia enhances the cytotoxicity and platinum-DNA adduct formation of lobaplatin and oxaliplatin in cultured SW 1573 cells

Rietbroek

Vaart

Haveman

et al. 1997

J Cancer Res Clin Oncol

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Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Abstract The cytotoxicity of cisplatin and cisplatin-DNA adduct formation in vitro and in vivo is clearly enhanced by hyperthermia. We investigated whether cytotoxicity and platinum-DNA adduct formation of two promising new third-generation platinum derivatives, lobaplatin [1,2-diamminomethylcyclobutane platinum(II) lactate] and oxaliplatin [oxalato-l,2-diaminocyclohexane platinum(II)], are also enhanced by hyperthermia. Cisplatin was used for comparison. SW 1573 cells were incubated with cisplatin, lobaplatin or oxaliplatin at different concentrations for 1 h at 37 ~ 41 ~ and 43~ The reproductive capacity of cells was determined by cloning experiments. Immunocytochemical detection of platinum-DNA adducts was performed with the rabbit antiserum NKI-A59. At 37~ cisplatin was the most cytotoxic, followed by oxaliplatin and lobaplatin. Hyperthermia clearly enhanced the cytotoxicity of cisplatin, lobaplatin and oxaliplatin. There was no further increase in cytotoxicity at 43~ compared to 41~ for cisplatin and oxaliplatin. A further increase in cytotoxicity at 43~ was observed for lobaplatin. At 43~ thermal enhancement was higher for lobaplatin than for oxaliplatin, with the reverse pattern at 41~ For both drugs, thermal enhancement of cytotoxicity was lower than observed for cisplatin. Immunocytochemical detection of platinum-DNA adducts was feasible for all the drugs. Adduct formation was enhanced at 43~ for cisplatin, lobaplatin and oxaliplatin with a relative increase of 410%, 170% and 180%. These results seem to confirm that an increase in platinum-DNA adduct formation is involved in the in vitro thermal enhancement of cytotoxicity. The observed thermal enhancement of cytotoxicity of lobaplatin and oxaliplatin in vitro warrants further in vivo investigations.

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Antibodies against cisplatin-modified DNA and cisplatin-modified (di) nucleotides

Cited by 25 publications

References 28 publications

Selected Alkylating Agents Can Overcome Drug Tolerance of G0-like Tumor Cells and Eradicate BRCA1-Deficient Mammary Tumors in Mice

Selected Alkylating Agents Can Overcome Drug Tolerance of G0-like Tumor Cells and Eradicate BRCA1-Deficient Mammary Tumors in Mice

Immunohistochemical detection of platinated DNA in the cochlea of cisplatin-treated guinea pigs

Hyperthermia enhances the cytotoxicity and platinum-DNA adduct formation of lobaplatin and oxaliplatin in cultured SW 1573 cells

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