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  1. AU="Duesberg, Max S"
  2. AU="Sunzi, Kejimu"
  3. AU="Agosti, Valter"
  4. AU="Dupé, Bertrand"
  5. AU="Morello, Rémy"
  6. AU="Payrastre, Laurence"
  7. AU="Pereira, Duane G"
  8. AU="Cristofaro, Rosa Carmela"
  9. AU="Wan, Xiaolin"
  10. AU="Renfu, Chen"
  11. AU="Pisani, Antonio Rosario"
  12. AU=Zhang Yue-Miao AU=Zhang Yue-Miao
  13. AU="Chen, Z P"
  14. AU="Pinzón-Navarro, Beatriz Adriana"
  15. AU="Dong, Chuan-Ding"
  16. AU="Gomes, Rafael"
  17. AU="Goncin, Una"
  18. AU="Chen, Yan-Nan"
  19. AU="Revuelta, Belen"
  20. AU="Parmar, Dharati"
  21. AU="Herrera-Mateo, Sergio"
  22. AU="Fejes, I"
  23. AU="Zhang, Zhuhua"
  24. AU="Taillé, C"
  25. AU="San Martín, Juan Víctor"
  26. AU=Sun Yi AU=Sun Yi
  27. AU="Wu, Changping"
  28. AU="Polette, Myriam"
  29. AU="Ian D. Hickson"
  30. AU="Raasch, Siegfried"
  31. AU="Liu, Miao-Miao"
  32. AU="Beschastnov, V V"
  33. AU="Mehdi Benamar"
  34. AU="Manzoor, Jaida"

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  1. Artikel ; Online: Therapeutic Targeting of P53: A Comparative Analysis of APR-246 and COTI-2 in Human Tumor Primary Culture 3-D Explants.

    Nagourney, Adam J / Gipoor, Joshua B / Evans, Steven S / D'Amora, Paulo / Duesberg, Max S / Bernard, Paula J / Francisco, Federico / Nagourney, Robert A

    Genes

    2023  Band 14, Heft 3

    Abstract: Background: ...

    Abstract Background:
    Mesh-Begriff(e) Female ; Humans ; Cisplatin ; Tumor Suppressor Protein p53/metabolism ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Doxorubicin/pharmacology ; Doxorubicin/therapeutic use ; Ovarian Neoplasms/drug therapy
    Chemische Substanzen Cisplatin (Q20Q21Q62J) ; Tumor Suppressor Protein p53 ; Antineoplastic Agents ; Doxorubicin (80168379AG)
    Sprache Englisch
    Erscheinungsdatum 2023-03-19
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2527218-4
    ISSN 2073-4425 ; 2073-4425
    ISSN (online) 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes14030747
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Therapeutic Targeting of P53: A Comparative Analysis of APR-246 and COTI-2 in Human Tumor Primary Culture 3-D Explants

    Nagourney, Adam J. / Gipoor, Joshua B. / Evans, Steven S. / D’Amora, Paulo / Duesberg, Max S. / Bernard, Paula J. / Francisco, Federico / Nagourney, Robert A.

    Genes (Basel). 2023 Mar. 19, v. 14, no. 3

    2023  

    Abstract: Background: TP53 is the most commonly mutated gene in human cancer with loss of function mutations largely concentrated in “hotspots” affecting DNA binding. APR-246 and COTI-2 are small molecules under investigation in P53 mutated cancers. APR binds to ... ...

    Abstract Background: TP53 is the most commonly mutated gene in human cancer with loss of function mutations largely concentrated in “hotspots” affecting DNA binding. APR-246 and COTI-2 are small molecules under investigation in P53 mutated cancers. APR binds to P53 cysteine residues, altering conformation, while COTI-2 showed activity in P53 mutant tumors by a computational platform. We compared APR-246 and COTI-2 activity in human tumor explants from 247 surgical specimens. Methods: Ex vivo analyses of programmed cell death measured drug-induced cell death by delayed-loss-of-membrane integrity and ATP content. The LC50s were compared by Z-Score. Synergy was conducted by the method of Chou and Talalay, and correlations were performed by Pearson moment. Results: APR-246 and COTI-2 activity favored hematologic neoplasms, but solid tumor activity varied by diagnosis. COTI-2 and APR-246 activity did not correlate (R = 0.1028) (NS). COTI-2 activity correlated with nitrogen mustard, cisplatin and gemcitabine, doxorubicin and selumetinib, with a trend for APR-246 with doxorubicin. For ovarian cancer, COTI-2 showed synergy with cisplatin at 25%. Conclusions: COTI-2 and APR-246 activity differ by diagnosis. A lack of correlation supports distinct modes of action. Cisplatin synergy is consistent with P53’s role in DNA damage. Different mechanisms of action may underlie disease specificity and offer better disease targeting.
    Schlagwörter DNA ; DNA damage ; cisplatin ; cysteine ; doxorubicin ; genes ; humans ; mutants ; nitrogen ; ovarian neoplasms ; programmed cell death ; therapeutics
    Sprache Englisch
    Erscheinungsverlauf 2023-0319
    Erscheinungsort Multidisciplinary Digital Publishing Institute
    Dokumenttyp Artikel ; Online
    ZDB-ID 2527218-4
    ISSN 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes14030747
    Datenquelle NAL Katalog (AGRICOLA)

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