M V Blagosklonny

Summary

Affiliation: New York Medical College
Country: USA

Publications

  1. ncbi request reprint How cancer could be cured by 2015
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, New York Medical College, Hawthorne, New York 10532, USA
    Cell Cycle 4:269-78. 2005
  2. ncbi request reprint Depletion of mutant p53 and cytotoxicity of histone deacetylase inhibitors
    Mikhail V Blagosklonny
    New York Medical College, Valhalla, New York 12208, USA
    Cancer Res 65:7386-92. 2005
  3. doi request reprint Aging, stem cells, and mammalian target of rapamycin: a prospect of pharmacologic rejuvenation of aging stem cells
    Mikhail V Blagosklonny
    Cancer Center, Ordway Research Institute, 150 New Scotland Avenue, Albany, NY 12208, USA
    Rejuvenation Res 11:801-8. 2008
  4. ncbi request reprint Oncogenic resistance to growth-limiting conditions
    Mikhail V Blagosklonny
    Department of Medicine, New York Medical College, Brander Cancer Research Institute, Hawthorne 10532, USA
    Nat Rev Cancer 2:221-5. 2002
  5. ncbi request reprint A new science-business paradigm in anticancer drug development
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, Dept of Medicine, New York Medical College, 19 Bradhurst Ave, Hawthorne, NY 10532, USA
    Trends Biotechnol 21:103-6. 2003
  6. ncbi request reprint Cyclotherapy: protection of normal cells and unshielding of cancer cells
    Mikhail V Blagosklonny
    Laboratory of Translational Oncology, New York Medical College, Hawthorne, New York 10532, USA
    Cell Cycle 1:375-82. 2002
  7. ncbi request reprint Histone deacetylase inhibitors all induce p21 but differentially cause tubulin acetylation, mitotic arrest, and cytotoxicity
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, New York Medical College, Valhalla, New York 10595, USA
    Mol Cancer Ther 1:937-41. 2002
  8. ncbi request reprint Flavopiridol inversely affects p21(WAF1/CIP1) and p53 and protects p21-sensitive cells from paclitaxel
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, Hawthorne, New York 10532, USA
    Cancer Biol Ther 1:420-5. 2002
  9. ncbi request reprint Four birds with one stone: RAPA as potential anticancer therapy
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, New York Medical College, Hawthorne, New York 10532, USA
    Cancer Biol Ther 1:359-61. 2002
  10. ncbi request reprint Analysis of FDA approved anticancer drugs reveals the future of cancer therapy
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, New York Medical College, Hawthorne 10532, USA
    Cell Cycle 3:1035-42. 2004

Collaborators

Detail Information

Publications97

  1. ncbi request reprint How cancer could be cured by 2015
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, New York Medical College, Hawthorne, New York 10532, USA
    Cell Cycle 4:269-78. 2005
    ..And finally, these strategies will benefit from molecular diagnostics and can be used for chemoprevention...
  2. ncbi request reprint Depletion of mutant p53 and cytotoxicity of histone deacetylase inhibitors
    Mikhail V Blagosklonny
    New York Medical College, Valhalla, New York 12208, USA
    Cancer Res 65:7386-92. 2005
    ..In a broader perspective, this shows how selectivity may be achieved by targeting a non-cancer-specific target, such as histone deacetylases, in the presence of a cancer-specific alteration, such as mutant p53...
  3. doi request reprint Aging, stem cells, and mammalian target of rapamycin: a prospect of pharmacologic rejuvenation of aging stem cells
    Mikhail V Blagosklonny
    Cancer Center, Ordway Research Institute, 150 New Scotland Avenue, Albany, NY 12208, USA
    Rejuvenation Res 11:801-8. 2008
    ..On the basis of the hypothesis that insensitivity to stimuli is in part due to hyperactivation of the target of rapamycin (TOR), this article suggests a means of pharmacologic rejuvenation of stem cells and wound-healing cells...
  4. ncbi request reprint Oncogenic resistance to growth-limiting conditions
    Mikhail V Blagosklonny
    Department of Medicine, New York Medical College, Brander Cancer Research Institute, Hawthorne 10532, USA
    Nat Rev Cancer 2:221-5. 2002
    ..But why aren't all cytotoxins carcinogenic?..
  5. ncbi request reprint A new science-business paradigm in anticancer drug development
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, Dept of Medicine, New York Medical College, 19 Bradhurst Ave, Hawthorne, NY 10532, USA
    Trends Biotechnol 21:103-6. 2003
    ..The pharmacological industry could develop low cost, effective therapeutic modalities, by "re-using" already marketed and late-stage products in cancer-selective therapeutic kits...
  6. ncbi request reprint Cyclotherapy: protection of normal cells and unshielding of cancer cells
    Mikhail V Blagosklonny
    Laboratory of Translational Oncology, New York Medical College, Hawthorne, New York 10532, USA
    Cell Cycle 1:375-82. 2002
    ..Following pretreatment with low doses of kinase inhibitors, the chemotherapy that predominantly induces apoptosis in cycling cells (cyclotherapy) will kill cancer cells while sparing normal cells...
  7. ncbi request reprint Histone deacetylase inhibitors all induce p21 but differentially cause tubulin acetylation, mitotic arrest, and cytotoxicity
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, New York Medical College, Valhalla, New York 10595, USA
    Mol Cancer Ther 1:937-41. 2002
    ..We conclude that HDIs have differential effects on non-histone deacetylases and that rapid acetylation of tubulin caused by TSA is a marker of nontranscriptional effects of TSA...
  8. ncbi request reprint Flavopiridol inversely affects p21(WAF1/CIP1) and p53 and protects p21-sensitive cells from paclitaxel
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, Hawthorne, New York 10532, USA
    Cancer Biol Ther 1:420-5. 2002
    ..As predicted, low concentrations of FL antagonized PTX-mediated cytotoxicity in HL60 and SKBr3 cell lines. In summary, only low concentrations of FL can induce p21, and, in turn, only p21-sensitive cells are protected from PTX...
  9. ncbi request reprint Four birds with one stone: RAPA as potential anticancer therapy
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, New York Medical College, Hawthorne, New York 10532, USA
    Cancer Biol Ther 1:359-61. 2002
  10. ncbi request reprint Analysis of FDA approved anticancer drugs reveals the future of cancer therapy
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, New York Medical College, Hawthorne 10532, USA
    Cell Cycle 3:1035-42. 2004
    ....
  11. ncbi request reprint Combining phorbol ester (PMA) with UCN-01: fueling fire with water
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, Department of Medicine, New York Medical College, Hawthorne, NY 10532, USA
    Cell Cycle 1:258-9. 2002
  12. ncbi request reprint Gefitinib (iressa) in oncogene-addictive cancers and therapy for common cancers
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, New York Medical College, Hawthorne, New York 10532, USA
    Cancer Biol Ther 3:436-40. 2004
    ..But in order to be cancer-selective, these chemotherapeutic agents need to be combined with selective agents. Such combinations can be effective and selective in common cancers...
  13. ncbi request reprint Flavopiridol, an inhibitor of transcription: implications, problems and solutions
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, New York Medical College, New York 10532, USA
    Cell Cycle 3:1537-42. 2004
    ..This article reviews the molecular and cellular effects of flavopiridol as well as mechanisms of therapeutic and side effects, suggesting its novel clinical applications as a single agent and in drug combinations...
  14. ncbi request reprint Sequential activation and inactivation of G2 checkpoints for selective killing of p53-deficient cells by microtubule-active drugs
    Mikhail V Blagosklonny
    Department of Medicine, New York Medical College, Brander Cancer Research Institute, Hawthorne, New York, NY 10532, USA
    Oncogene 21:6249-54. 2002
    ..This rational sequence of agents that induces p53-dependent and abrogates p53-independent arrest represents a cancer-selective strategy for treatment of p53-deficient tumors...
  15. ncbi request reprint Paclitaxel-induced FasL-independent apoptosis and slow (non-apoptotic) cell death
    Mikhail V Blagosklonny
    Medicine Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Cancer Biol Ther 1:113-7. 2002
    ..Following PTX-induced mitotic arrest Jurkat cells undergo apoptosis, whereas MDA-MB-231 cells exit mitosis and form multinucleated cells which then die in a slower non-apoptotic manner...
  16. ncbi request reprint Are p27 and p21 cytoplasmic oncoproteins?
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, 19 Bradhurst Ave, Suite 2400, Hawthorne, New York 10532, USA
    Cell Cycle 1:391-3. 2002
    ....
  17. ncbi request reprint From the war on cancer to translational oncology
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, New York Medical College, Hawthorne, NY 10532, USA
    Cancer Biol Ther 1:711-4. 2002
  18. ncbi request reprint Matching targets for selective cancer therapy
    Mikhail V Blagosklonny
    New York Medical College, 19 Bradhurst Avenue, Suite 2400, Hawthorne, NY 10532, USA
    Drug Discov Today 8:1104-7. 2003
  19. ncbi request reprint Targeting cancer cells by exploiting their resistance
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, New York Medical College, 19 Bradhurst Ave, Hawthorne, NY 10532, USA
    Trends Mol Med 9:307-12. 2003
    ..By abolishing several dose-limiting side effects of chemotherapy, this strategy provides a means to treat selectively most deranged, aggressive and resistant cancers...
  20. ncbi request reprint Cell immortality and hallmarks of cancer
    Mikhail V Blagosklonny
    Brander Cancer Research Institute New York Medical College 19 Bradhurst Ave, Suite 2400 Hawthorne, New York 10532, USA
    Cell Cycle 2:296-9. 2003
    ..In growth-limiting conditions, cells that express telomerase and inactivate tumor suppressors have a selective advantage due to resistance to growth arrest. Accidentally such cells become immortal...
  21. ncbi request reprint Do cells need CDK2 and ... Bcr-Abl?
    M V Blagosklonny
    Brander Cancer Research Institute, New York Medical College, Valhalla, NY 10532, USA
    Cell Death Differ 11:249-51. 2004
  22. ncbi request reprint Conceptual research and phenomenology--harmonizing slices
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, New York Medical College, 19 Bradhurst Avenue, Hawthorne, NY 10532, USA
    Cell Cycle 2:3-4. 2003
  23. ncbi request reprint Why Iressa failed: toward novel use of kinase inhibitors (outlook)
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, New York Medical College, Hawthorne, New York 10532 USA
    Cancer Biol Ther 2:137-40. 2003
    ..This approach may be most beneficial to patients who do not respond to monotherapy with kinase inhibitors. Development of molecular diagnostics will further diversify these strategies...
  24. pmc Cell senescence and hypermitogenic arrest
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, New York Medical College, Hawthorne, New York 10532, USA
    EMBO Rep 4:358-62. 2003
    ..The concept of hypermitogenic arrest defines cell senescence as a functionally active, stable and conditionally reversible state...
  25. ncbi request reprint Antiangiogenic therapy and tumor progression
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, New York Medical College, 19 Bradhurst Avenue, Hawthorne, NY 10532, USA
    Cancer Cell 5:13-7. 2004
    ..Second, only successful antiangiogenic therapy, which is capable of controlling cancer, will select for resistance and progression. After all, in order to occur, therapy-induced tumor progression must be preceded by tumor regression...
  26. ncbi request reprint Apoptosis, proliferation, differentiation: in search of the order
    Mikhail V Blagosklonny
    Department of Medicine, Brander Cancer Research Institute, New York Medical College, 19 Bradhurst Avenue, Hawthorne, NY 10532, USA
    Semin Cancer Biol 13:97-105. 2003
    ..When depicted in multidimensional axis, this universal model may also include invasiveness, senescence, metastatic and angiogenic responses and even such integral characteristics as malignant transformation...
  27. ncbi request reprint Loss of cell cycle control allows selective microtubule-active drug-induced Bcl-2 phosphorylation and cytotoxicity in autonomous cancer cells
    M V Blagosklonny
    Medicine Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Cancer Res 60:3425-8. 2000
    ..Exploitation of growth factor dependency may allow the protection of normal cells from microtubule-active drugs...
  28. ncbi request reprint Resistance to growth inhibitory and apoptotic effects of phorbol ester and UCN-01 in aggressive cancer cell lines
    M V Blagosklonny
    Medicine Branch, Division of Clinical Sciences, National Cancer Institute, NIH, Bldg 10, 12N226, Bethesda, MD 20892, USA
    Int J Oncol 18:697-704. 2001
    ..2 nM) and UCN-01. In PrEC, UCN-01 downregulated cyclin D1 and arrest growth with an IC50 less than 100 nM. We conclude that loss of sensitivity to either UCN-01 or PMA accompanies progression of prostate cancer...
  29. pmc Destabilization of Raf-1 by geldanamycin leads to disruption of the Raf-1-MEK-mitogen-activated protein kinase signalling pathway
    T W Schulte
    Clinical Pharmacology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA
    Mol Cell Biol 16:5839-45. 1996
    ..Thus, we demonstrate that interaction between HSP90 and Raf-1 is a sine qua non for Raf stability and function as a signal transducer and that the effects observed cannot be attributed to a general impairment of protein kinase function...
  30. ncbi request reprint Treatment with inhibitors of caspases, that are substrates of drug transporters, selectively permits chemotherapy-induced apoptosis in multidrug-resistant cells but protects normal cells
    M V Blagosklonny
    Medicine Branch, National Cancer Institute, Building 10, R 12N226 NIH, Bethesda, MD 20892, USA
    Leukemia 15:936-41. 2001
    ..Clinical application of this approach may diminish the toxic side-effects of chemotherapy in patients with multidrug-resistant tumors...
  31. ncbi request reprint Like p53, the proliferation-associated protein p120 accumulates in human cancer cells following exposure to anticancer drugs
    M V Blagosklonny
    Medicine Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Biochem Biophys Res Commun 244:368-73. 1998
    ..p120 protein stabilization represents an expedient means for accumulation of key response proteins following exposure to cytotoxic agents...
  32. pmc Pretreatment with DNA-damaging agents permits selective killing of checkpoint-deficient cells by microtubule-active drugs
    M V Blagosklonny
    Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Clin Invest 105:533-9. 2000
    ....
  33. ncbi request reprint Inhibition of HIF-1- and wild-type p53-stimulated transcription by codon Arg175 p53 mutants with selective loss of functions
    M V Blagosklonny
    Medicine Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA
    Carcinogenesis 22:861-7. 2001
    ..Therefore, endogenous mutant p53s are unable to display a dominant negative effect. This explains why loss of the second p53 allele is required to eliminate p53 functions in cancer cells...
  34. ncbi request reprint The Hsp90 inhibitor geldanamycin selectively sensitizes Bcr-Abl-expressing leukemia cells to cytotoxic chemotherapy
    M V Blagosklonny
    Department of Developmental Therapeutics, Medicine Branch, National Cancer Institute, NIH, Bethesda and Rockville, MD 20892, USA
    Leukemia 15:1537-43. 2001
    ..Thus, GA differentially affects leukemia cells depending on their Bcr-Abl expression and selectively increases apoptosis in Bcr-Abl-expressing cells...
  35. pmc P21-dependent g(1)arrest with downregulation of cyclin D1 and upregulation of cyclin E by the histone deacetylase inhibitor FR901228
    V Sandor
    Medicine Branch, DSC, NCI, NIH, Bethesda, MD 20892, USA
    Br J Cancer 83:817-25. 2000
    ..In contrast to the G1 arrest, the G2/M arrest is p21-independent, but is associated with significant cytotoxicity...
  36. ncbi request reprint Low concentrations of paclitaxel induce cell type-dependent p53, p21 and G1/G2 arrest instead of mitotic arrest: molecular determinants of paclitaxel-induced cytotoxicity
    P Giannakakou
    Medicine Branch, National Cancer Institute, NIH, Bethesda, Maryland, MD 20892, USA
    Oncogene 20:3806-13. 2001
    ..High levels of p53 and Bax/Bcl-2 ratio can also explain why loss of p21 is rarely found in human cancer...
  37. ncbi request reprint Pharmacological induction of Hsp70 protects apoptosis-prone cells from doxorubicin: comparison with caspase-inhibitor- and cycle-arrest-mediated cytoprotection
    Z N Demidenko
    Brander Cancer Research Institute, New York Medical College, Valhalla, NY, USA
    Cell Death Differ 13:1434-41. 2006
    ..Since GA does not protect apoptosis-reluctant cancer cells, we envision a therapeutic strategy to decrease side effects of chemotherapy without affecting its therapeutic efficacy...
  38. ncbi request reprint p53 inhibits hypoxia-inducible factor-stimulated transcription
    M V Blagosklonny
    Department of Experimental Therapeutics, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 273:11995-8. 1998
    ..These data support a model in which stoichiometric binding of p53 to a HIF/p300 transcriptional complex mediates inhibition of HIF activity...
  39. ncbi request reprint The mitogen-activated protein kinase pathway mediates growth arrest or E1A-dependent apoptosis in SKBR3 human breast cancer cells
    M V Blagosklonny
    Medicine Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA
    Int J Cancer 78:511-7. 1998
    ..E1A-driven proliferation of PMA-treated SKBr3 cells was accompanied by apoptosis. New therapeutic approaches can be envisioned that would utilize stimulation of the Raf-1/MEK/MAPK pathway to inhibit growth of PMA-sensitive cancer cells...
  40. ncbi request reprint The histone deacetylase inhibitor FR901228 (desipeptide) restores expression and function of pseudo-null p53
    Masaki Kitazono
    Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Cancer Biol Ther 1:665-8. 2002
    ..This study validates the concept of pseudo-null p53, as a mechanism of p53 inactivation, and demonstrates that pseudo-null p53 can be rescued pharmacologically...
  41. ncbi request reprint Differential sensitivity of cancer cells to inhibitors of the epidermal growth factor receptor family
    Philippe C Bishop
    Medicine Branch, NCI, NIH, Bethesda, Maryland, MD 20892, USA, and FDA CBER OTRR DCTDA Oncology Branch, HFM 573, Rockville, Maryland, MD 20852, USA
    Oncogene 21:119-27. 2002
    ..We infer that independence from mitogen-mediated signaling confers insensitivity to HER1 inhibitors in a large subset of cancer cell lines...
  42. ncbi request reprint Molecular effects of paclitaxel: myths and reality (a critical review)
    M V Blagosklonny
    Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
    Int J Cancer 83:151-6. 1999
    ....
  43. ncbi request reprint The P-glycoprotein antagonist PSC 833 increases the plasma concentrations of 6alpha-hydroxypaclitaxel, a major metabolite of paclitaxel
    M H Kang
    Medicine Branch, Division of Clinical Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Clin Cancer Res 7:1610-7. 2001
    ..CONCLUSIONS: PSC 833 increases the plasma concentration of 6alpha-hydroxypaclitaxel during paclitaxel therapy. Inhibition of cytochrome P-450 3A4 by PSC 833 may explain this in part, although other mechanisms cannot be excluded...
  44. pmc Mutant conformation of p53 translated in vitro or in vivo requires functional HSP90
    M V Blagosklonny
    Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 93:8379-83. 1996
    ..Furthermore, we show that the mutated conformation of p53 can be pharmacologically antagonized by drugs targeting HSP90...
  45. ncbi request reprint Acute overexpression of wt p53 facilitates anticancer drug-induced death of cancer and normal cells
    M V Blagosklonny
    Medicine Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA
    Int J Cancer 75:933-40. 1998
    ..We conclude that exogenous wt p53 accelerates cell death induced by DNA damaging agents in both normal and cancer cells and offers no protection from anticancer drugs...
  46. ncbi request reprint Hypoxia-inducible factor: Achilles' heel of antiangiogenic cancer therapy (review)
    M V Blagosklonny
    Medicine Branch, National Institutes of Health, Bethesda, MD 20892, USA
    Int J Oncol 19:257-62. 2001
    ..Furthermore, inhibition of HIF-1 is a mechanism-based antiangiogenic strategy because it is the HIF-mediated response that drives tumor angiogenesis. Pharmacological approaches to HIF-1 inhibition are discussed...
  47. ncbi request reprint Unwinding the loop of Bcl-2 phosphorylation
    M V Blagosklonny
    Medicine Branch, Building 10, R 12N226, National Cancer Institute, NIH, Bethesda, MD 20892, USA
    Leukemia 15:869-74. 2001
    ..The role of BcI-2 phosphorylation in cell death is discussed...
  48. ncbi request reprint Flavopiridol induces p53 via initial inhibition of Mdm2 and p21 and, independently of p53, sensitizes apoptosis-reluctant cells to tumor necrosis factor
    Zoya N Demidenko
    Brander Cancer Research Institute and Department of Medicine, New York Medical College, Valhalla, New York, USA
    Cancer Res 64:3653-60. 2004
    ..We discuss that, as a reversible inhibitor of transcription, FP can be used clinically in novel rational drug combinations...
  49. ncbi request reprint Do VHL and HIF-1 mirror p53 and Mdm-2? Degradation-transactivation loops of oncoproteins and tumor suppressors
    M V Blagosklonny
    Medicine Branch, National Cancer Institute, NIH, Bethesda, Maryland, MD 20892, USA
    Oncogene 20:395-8. 2001
    ....
  50. ncbi request reprint Wild-type p53 marginally induces endogenous MDR-1 mRNA without causing a measurable drug resistance in human cancer cells
    M I Nicoletti
    Medicine Branch and Developmental Therapeutics Program, National Cancer Institute, NIH, Bethesda, MD 20892, USA
    Int J Oncol 18:375-81. 2001
    ..Thus, partial promoter constructs may not accurately represent endogenous MDR-1...
  51. ncbi request reprint Selective killing of adriamycin-resistant (G2 checkpoint-deficient and MRP1-expressing) cancer cells by docetaxel
    Zoya N Demidenko
    Brander Cancer Research Institute, New York Medical College, Valhalla, New York, USA
    Cancer Res 65:4401-7. 2005
    ..We propose a therapeutic strategy to prevent normal cells from entering mitosis while increasing apoptosis selectively in mitotic cancer cells...
  52. ncbi request reprint Kinase-addiction and bi-phasic sensitivity-resistance of Bcr-Abl- and Raf-1-expressing cells to imatinib and geldanamycin
    Zoya N Demidenko
    Brander Cancer Research Institute, New York Medical College, Valhalla, New York, USA
    Cancer Biol Ther 4:484-90. 2005
    ..Although Bcr-Abl renders cells hyper-sensitive, an excess of Bcr-Abl results in resistance (due to the remaining activity). We discuss therapeutic approaches to overcome bi-phasic resistance to mechanisms-based agents...
  53. ncbi request reprint Accumulation of hypoxia-inducible factor-1alpha is limited by transcription-dependent depletion
    Zoya N Demidenko
    Brander Cancer Research Institute, New York Medical College, Valhalla, NY, USA
    Oncogene 24:4829-38. 2005
    ..But under hypoxia, HIF-1alpha accumulates and transcriptionally activates its own degradation that is independent from the PHD/VHL pathway...
  54. ncbi request reprint How Avastin potentiates chemotherapeutic drugs: action and reaction in antiangiogenic therapy
    Mikhail V Blagosklonny
    Cancer Center, Ordway Research Institute, Albany, New York, NY 12208, USA
    Cancer Biol Ther 4:1307-10. 2005
    ..And this is exactly what Avastin does (by blocking VEGF). While chemotherapy inhibits angiogenesis, Avastin abrogates the reactive resistance, sensitizing both endothelial and cancer cells to therapy...
  55. ncbi request reprint A node between proliferation, apoptosis, and growth arrest
    M V Blagosklonny
    Medicine Branch, National Cancer Institute, Bldg 10, R 12N226, NIH, Bethesda, Maryland 20892, USA
    Bioessays 21:704-9. 1999
    ....
  56. ncbi request reprint STI-571 must select for drug-resistant cells but 'no cell breathes fire out of its nostrils like a dragon'
    M V Blagosklonny
    Medicine Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA
    Leukemia 16:570-2. 2002
    ..In addition to mutation rate and number of tumor cells, one additional factor determines relapse vs. 'extinction' of the leukemia cell population...
  57. ncbi request reprint Regulation of actin cytoskeleton in lymphocytes: PKC-delta disrupts IL-3-induced membrane ruffles downstream of Rac1
    L Y Romanova
    Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 4255, USA
    J Cell Physiol 179:157-69. 1999
    ..Experiments with overexpression in Baf3 of individual PKC isoforms and a dominant negative PKC-delta indicate that activation of PKC-delta but not other PKC isoforms is responsible for disruption of membrane ruffles...
  58. ncbi request reprint Exploiting cancer cell cycling for selective protection of normal cells
    M V Blagosklonny
    Medicine Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA
    Cancer Res 61:4301-5. 2001
    ..g., p53, Rb, and p16) may not arrest cycling of cancer cells. But growth arrest of normal cells will then permit selective killing of cancer cells by cycle-dependent chemotherapy...
  59. ncbi request reprint From cytometry to cell cycle: a portrait of Zbigniew Darzynkiewicz
    Zoya N Demidenko
    Department of Medicine, New York Medical College, Valhalla, USA
    Cell Cycle 3:525-8. 2004
  60. ncbi request reprint Paclitaxel induces primary and postmitotic G1 arrest in human arterial smooth muscle cells
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, New York Medical College, Hawthorne, New York, USA
    Cell Cycle 3:1050-6. 2004
    ..These post-mitotic cells were subsequently arrested in G(1) but maintained normal elongated morphology and were viable for at least 21 days. We conclude that in SMC PTX causes post-mitotic cell cycle arrest rather than cell death...
  61. ncbi request reprint Hormonal and differentiation agents in cancer growth suppression
    Mikhail V Blagosklonny
    Medicine Branch, National Institutes of Health, Bethesda, MD, USA
    Methods Mol Biol 223:505-22. 2003
  62. ncbi request reprint Hsp-90-associated oncoproteins: multiple targets of geldanamycin and its analogs
    M V Blagosklonny
    National Cancer Institute, NIH, Bethesda, MD 20892, USA
    Leukemia 16:455-62. 2002
    ..By attacking a nonspecific target, HSP-90-active compounds still may preferentially kill certain tumor cells. How can this be achieved? How can therapeutic potentials be exploited? This article starts the discussion...
  63. ncbi request reprint Carcinogenesis, cancer therapy and chemoprevention
    M V Blagosklonny
    Brander Cancer Research Institute, New York Medical College, 19 Bradhurst Ave, Hawthorne, NY 10532, USA
    Cell Death Differ 12:592-602. 2005
    ....
  64. ncbi request reprint Prospective strategies to enforce selectively cell death in cancer cells
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, New York Medical College, 19 Bradhurst Ave, Hawthorne, Valhalla, NY 10532, USA
    Oncogene 23:2967-75. 2004
    ..In theory, consecutive use of these drug combinations may control cancer...
  65. ncbi request reprint Cytostatic activity of paclitaxel in coronary artery smooth muscle cells is mediated through transient mitotic arrest followed by permanent post-mitotic arrest: comparison with cancer cells
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, New York Medical College, Valhalla, New York, USA
    Cell Cycle 5:1574-9. 2006
    ..These in vitro findings suggest a mechanism for the cytostatic activity of PTX in CASMC for the inhibition of restenosis...
  66. pmc The regulation of hypoxic genes by calcium involves c-Jun/AP-1, which cooperates with hypoxia-inducible factor 1 in response to hypoxia
    Konstantin Salnikow
    Department of Environmental Medicine, NIEHS and Kaplan Comprehensive Cancer Center, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
    Mol Cell Biol 22:1734-41. 2002
    ..Cooperation between the HIF-1 and AP-1 pathways allows fine regulation of gene expression during hypoxia...
  67. ncbi request reprint Growth stimulation leads to cellular senescence when the cell cycle is blocked
    Zoya N Demidenko
    Oncotarget, Albany, New York, USA
    Cell Cycle 7:3355-61. 2008
    ..Inhibition of TOR partially prevented senescent phenotype caused by DOX. Thus growth stimulation coupled with cell cycle arrest leads to senescence, whereas quiescence (a condition with inactive TOR) prevents senescence...
  68. ncbi request reprint Inhibition of transcription results in accumulation of Wt p53 followed by delayed outburst of p53-inducible proteins: p53 as a sensor of transcriptional integrity
    Mikhail V Blagosklonny
    Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Cell Cycle 1:67-74. 2002
    ..Transient inhibition of p53- stimulated transcription by numerous stimuli including nucleotide depletion, hypoxia, UV light may be an prevalent mechanism of activation of wt p53 and its downstream pathways...
  69. pmc Tissue-selective therapy of cancer
    M V Blagosklonny
    Department of Medicine, New York Medical College, Valhalla, NY 10595, USA
    Br J Cancer 89:1147-51. 2003
    ..Despite inherent limitations, such as fostering resistance and dedifferentiation, tissue-selective therapy have enormous potentials to control cancer...
  70. ncbi request reprint Stabilization of wild-type p53 by hypoxia-inducible factor 1alpha
    W G An
    Department of Cell and Cancer Biology, Medicine Branch, NCI, NIH, Bethesda, Maryland 20892, USA
    Nature 392:405-8. 1998
    ..Our results suggest that hypoxic induction of transcriptionally active wild-type p53 is achieved as a result of the stabilization of p53 by its association with HIF-1alpha...
  71. ncbi request reprint P53: an ubiquitous target of anticancer drugs
    Mikhail V Blagosklonny
    Medicine Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA
    Int J Cancer 98:161-6. 2002
    ....
  72. ncbi request reprint Basic cell cycle and cancer research: is harmony impossible?
    Mikhail V Blagosklonny
    National Cancer Institute Medicine Branch, Building 10, Room 12N226, 10 Center Drive, MSC 1906, Bethesda, Maryland 20892, USA
    Cell Cycle 1:3-5. 2002
  73. ncbi request reprint Bcl-xL is phosphorylated in malignant cells following microtubule disruption
    M S Poruchynsky
    Division of Clinical Sciences, Medicine Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Cancer Res 58:3331-8. 1998
    ..By analogy with Bcl-2, this phosphorylation may play a critical role in modulating Bcl-xL function and may be an important determinant of microtubule-directed chemotherapeutic efficacy in human tumors...
  74. ncbi request reprint Proteasome-dependent regulation of p21WAF1/CIP1 expression
    M V Blagosklonny
    Howard Hughes Medical Institute, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA
    Biochem Biophys Res Commun 227:564-9. 1996
    ..p21 induction was correlated with the cytostatic effects of LC. The results suggest that p21 protein expression could be increased by transcriptional mechanisms as well as inhibition of proteolysis by LC...
  75. ncbi request reprint p53 from complexity to simplicity: mutant p53 stabilization, gain-of-function, and dominant-negative effect
    M V Blagosklonny
    Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    FASEB J 14:1901-7. 2000
    ..Applications to cancer therapy are discussed. -Blagosklonny, M. V. p53 from complexity to simplicity: mutant p53 stabilization, gain-of-function, and dominant-negative effect...
  76. ncbi request reprint Paradox of Bcl-2 (and p53): why may apoptosis-regulating proteins be irrelevant to cell death?
    M V Blagosklonny
    Medicine Branch, Bldg 10, Room 12 N 226, NIH, Bethesda, MD 20892, USA mikhailb2box m nih gov
    Bioessays 23:947-53. 2001
    ..This explains why Bcl-2 overexpression can be a marker of chemosensitivity and favorable prognosis in certain cancers and why retention of wild-type p53 may manifest inactivation of caspases in aggressive cancers...
  77. ncbi request reprint How carcinogens (or telomere dysfunction) induce genetic instability: associated-selection model
    M V Blagosklonny
    Medicine Branch, National Cancer Institute, NIH, Bldg 10, R 12 N 226, Bethesda, MD 20892, USA
    FEBS Lett 506:169-72. 2001
    ..As an example, a putative link between prior exposure to carcinogens and the ability to develop a telomerase-independent growth is discussed...
  78. ncbi request reprint Overcoming limitations of natural anticancer drugs by combining with artificial agents
    Mikhail V Blagosklonny
    Brander Cancer Research Institute, New York Medical College, 19 Bradhurst Avenue, Hawthorne, NY 10532, USA
    Trends Pharmacol Sci 26:77-81. 2005
    ..Using rational drug combinations, such selective agents can assist natural agents to eradicate cancer cells selectively...
  79. ncbi request reprint Complementation of two mutant p53: implications for loss of heterozygosity in cancer
    Zoya N Demidenko
    Brander Cancer Research Institute, New York Medical College, Valhalla, NY, USA
    FEBS Lett 579:2231-5. 2005
    ..We suggest that, due to complementation of two mutant p53, cancer cells need to delete the second p53 allele rather than mutate it...
  80. ncbi request reprint Phosphorylation of paxillin tyrosines 31 and 118 controls polarization and motility of lymphoid cells and is PMA-sensitive
    Larisa Y Romanova
    Molecular Genetics Section, Laboratory of Genetics, National Cancer Institute, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA
    J Cell Sci 117:3759-68. 2004
    ..They also suggest that inhibition of upstream signaling by PMA contributes to the decrease of paxillin phosphorylation and subsequent changes in cell morphology...
  81. ncbi request reprint p21 (CDKN1A) is a negative regulator of p53 stability
    Eugenia V Broude
    Cancer Center, Ordway Research Institute, Albany, New York 12208, USA
    Cell Cycle 6:1468-71. 2007
    ..These results indicate that p21 acts as a negative regulator of p53 stability in different cell types. p53 regulation by p21 may provide a negative regulatory loop that limits p53 induction...
  82. ncbi request reprint An anti-aging drug today: from senescence-promoting genes to anti-aging pill
    Mikhail V Blagosklonny
    Oncotarget Inc, Albany, NY 12203, USA
    Drug Discov Today 12:218-24. 2007
    ..I also discuss other potential anti-aging agents (calorie restriction, metformin, resveratrol and sirtuins) and their targets, interference with the TOR pathway and combination with antioxidants...
  83. ncbi request reprint Aging and immortality: quasi-programmed senescence and its pharmacologic inhibition
    Mikhail V Blagosklonny
    Cell Cycle 5:2087-102. 2006
    ..Finally, I discuss that extended life span will reveal new causes for aging (e.g., ROS, 'wear and tear', Hayflick limit, stem cell exhaustion) that play a limited role now, when quasi-programmed senescence kills us first...
  84. ncbi request reprint Cell senescence: hypertrophic arrest beyond the restriction point
    Mikhail V Blagosklonny
    Cancer Center, Ordway Research Institute, 150 New Scotland Avenue, Albany, NY 12208, USA
    J Cell Physiol 209:592-7. 2006
    ..Prolonged hypertrophic arrest culminates in cell senescence. This review discusses that quiescence and senescence are two opposite, mutually exclusive conditions and that cell senescence can be reversed and prevented...
  85. ncbi request reprint "Targeting the absence" and therapeutic engineering for cancer therapy
    Mikhail V Blagosklonny
    Ordway Research Institute and Oncotarget Inc, Albany, NY, USA
    Cell Cycle 7:1307-12. 2008
    ..Here I discuss restrictive combinations of currently available drugs that could be tested in clinical trials. Could then these combinations cure cancer today? And what does 'cure' really mean? This article suggests the answer...
  86. ncbi request reprint Mitotic arrest and cell fate: why and how mitotic inhibition of transcription drives mutually exclusive events
    Mikhail V Blagosklonny
    Cancer Center, Ordway Research Institute, Albany, New York 12208, USA
    Cell Cycle 6:70-4. 2007
    ..Also, I discuss that mitotic depletion of short-lived proteins collaborates with mitotic phosphorylation of p53, Bcl-2 and BclxL. Finally this article clarifies notions of apoptosis-prone and -reluctant cells and mitotic catastrophe...
  87. ncbi request reprint Prolonged mitosis versus tetraploid checkpoint: how p53 measures the duration of mitosis
    Mikhail V Blagosklonny
    Cancer Center, Ordway Research Institute, Albany, New York 12208, USA
    Cell Cycle 5:971-5. 2006
    ..If a cell stays in mitosis too long, (e.g. mitotic arrest caused by Taxol or nocodazole), then p53 accumulates. This explains how p53 can measure mitotic time and perhaps represents the most fundamental function of p53...
  88. pmc Enhanced microtubule-dependent trafficking and p53 nuclear accumulation by suppression of microtubule dynamics
    Paraskevi Giannakakou
    Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA
    Proc Natl Acad Sci U S A 99:10855-60. 2002
    ..We propose that suppression of MT dynamics by low concentrations of MTCs enhances MT-dependent trafficking toward the minus ends of MTs and facilitates nuclear targeting...
  89. ncbi request reprint Raf-1 and Bcl-2 induce distinct and common pathways that contribute to breast cancer drug resistance
    Julianne M Davis
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
    Clin Cancer Res 9:1161-70. 2003
    ..These observations suggest both independent and overlapping roles for Raf-1 and Bcl-2 oncogenes in the resistance to growth inhibition by doxorubicin...
  90. ncbi request reprint Phase I trial of the histone deacetylase inhibitor, depsipeptide (FR901228, NSC 630176), in patients with refractory neoplasms
    Victor Sandor
    McGill University, Sir Mortimer B Davis Jewish General Hospital, Montreal, Quebec, Canada H3T 1E2
    Clin Cancer Res 8:718-28. 2002
    ..A secondary objective of the trial was to seek evidence of antineoplastic activity...
  91. ncbi request reprint No restriction points in life and science
    Mikhail V Blagosklonny
    Cell Cycle 1:100-2. 2002
  92. ncbi request reprint The restriction point of the cell cycle
    Mikhail V Blagosklonny
    National Cancer Institute National Institutes of Health Bethesda, Maryland 20892 USA
    Cell Cycle 1:103-10. 2002
    ..Finally, we discuss how loss of the restriction point in cancer leads to loss of checkpoint control and to insensitivity to antimitogens including some mechanism-based anticancer therapeutics...
  93. ncbi request reprint Cancer and aging: more puzzles, more promises?
    Mikhail V Blagosklonny
    Cell Cycle 7:2615-8. 2008
    ..Here, we discuss the relationship between aging and cancer, the mechanism of metformin action, and the prospects of using this compound for life span extension in humans...
  94. ncbi request reprint Cancer stem cell and cancer stemloids: from biology to therapy
    Mikhail V Blagosklonny
    Cancer Center, Ordway Research Institute, 150 New Scotland Ave, Albany, New York 12208, USA
    Cancer Biol Ther 6:1684-90. 2007
    ..In contrast, true CSCs are not only a difficult, but also an insufficient and perhaps even an unnecessary therapeutic target, especially in advanced malignancies...
  95. ncbi request reprint Program-like aging and mitochondria: instead of random damage by free radicals
    Mikhail V Blagosklonny
    Cancer Center, Ordway Research Institute, 150 New Scotland Ave, and Oncotarget, Albany, New York 12208, USA
    J Cell Biochem 102:1389-99. 2007
    ..In theory, pharmacologic inhibitors of the TOR pathway may reverse accumulation of defective mitochondria, while also inhibiting the aging process...
  96. ncbi request reprint Molecular theory of cancer
    Mikhail V Blagosklonny
    Cancer Center, Ordway Research Institute, Albany, New York 12208, USA
    Cancer Biol Ther 4:621-7. 2005
    ....
  97. ncbi request reprint Why therapeutic response may not prolong the life of a cancer patient: selection for oncogenic resistance
    Mikhail V Blagosklonny
    Cancer Center, Ordway Research Institute, Albany, New York 12208, USA
    Cell Cycle 4:1693-8. 2005
    ..Therapy will control cancer if it can selectively suppress proliferating cancer cells and will improve survival as long as acquired resistance can be exploited...