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Full-Text Articles in Medicine and Health Sciences
Inhibition Of The Mdm2 E3 Ligase Induces Apoptosis And Autophagy In Wild-Type And Mutant P53 Models Of Multiple Myeloma, And Acts Synergistically With Abt-737, Dongmin Gu, Shuhong Wang, Isere Kuiatse, Hua Wang, Jin He, Yun Dai, Richard J. Jones, Chad C. Bjorklund, Jing Yang, Steven Grant, Robert Z. Orlowski
Inhibition Of The Mdm2 E3 Ligase Induces Apoptosis And Autophagy In Wild-Type And Mutant P53 Models Of Multiple Myeloma, And Acts Synergistically With Abt-737, Dongmin Gu, Shuhong Wang, Isere Kuiatse, Hua Wang, Jin He, Yun Dai, Richard J. Jones, Chad C. Bjorklund, Jing Yang, Steven Grant, Robert Z. Orlowski
Massey Comprehensive Cancer Center Publications
Intracellular proteolytic pathways have been validated as rational targets in multiple myeloma with the approval of two proteasome inhibitors in this disease, and with the finding that immunomodulatory agents work through an E3 ubiquitin ligase containing Cereblon. Another E3 ligase that could be a rational target is the murine double minute (MDM) 2 protein, which plays a role in p53 turnover. A novel inhibitor of this complex, MI-63, was found to induce apoptosis in p53 wild-type myeloma models in association with activation of a p53-mediated cell death program. MI-63 overcame adhesion-mediated drug resistance, showed anti-tumor activity in vivo, enhanced …
Live Cell Interferometry Quantifies Dynamics Of Biomass Partitioning During Cytokinesis, Thomas A. Zangle, Michael A. Teitell, Jason Reed
Live Cell Interferometry Quantifies Dynamics Of Biomass Partitioning During Cytokinesis, Thomas A. Zangle, Michael A. Teitell, Jason Reed
Massey Comprehensive Cancer Center Publications
The equal partitioning of cell mass between daughters is the usual and expected outcome of cytokinesis for self-renewing cells. However, most studies of partitioning during cell division have focused on daughter cell shape symmetry or segregation of chromosomes. Here, we use live cell interferometry (LCI) to quantify the partitioning of daughter cell mass during and following cytokinesis. We use adherent and non-adherent mouse fibroblast and mouse and human lymphocyte cell lines as models and show that, on average, mass asymmetries present at the time of cleavage furrow formation persist through cytokinesis. The addition of multiple cytoskeleton-disrupting agents leads to increased …
Circumvention Of Mcl-1-Dependent Drug Resistance By Simultaneous Chk1 And Mek1/2 Inhibition In Human Multiple Myeloma Cells, Xin-Yan Pei, Yun Dai, Jessica Felthousen, Shuang Shen, Yukie Takabatake, Liang Zhou, Leena E. Youssefian, Michael W. Sanderson, Wesley W. Bodie, Lora B. Kramer, Robert Z. Orlowski, Steven Grant
Circumvention Of Mcl-1-Dependent Drug Resistance By Simultaneous Chk1 And Mek1/2 Inhibition In Human Multiple Myeloma Cells, Xin-Yan Pei, Yun Dai, Jessica Felthousen, Shuang Shen, Yukie Takabatake, Liang Zhou, Leena E. Youssefian, Michael W. Sanderson, Wesley W. Bodie, Lora B. Kramer, Robert Z. Orlowski, Steven Grant
Massey Comprehensive Cancer Center Publications
The anti-apoptotic protein Mcl-1 plays a major role in multiple myeloma (MM) cell survival as well as bortezomib- and microenvironmental forms of drug resistance in this disease. Consequently, there is a critical need for strategies capable of targeting Mcl-1-dependent drug resistance in MM. The present results indicate that a regimen combining Chk1 with MEK1/2 inhibitors effectively kills cells displaying multiple forms of drug resistance stemming from Mcl-1 up-regulation in association with direct transcriptional Mcl-1 down-regulation and indirect disabling of Mcl-1 anti-apoptotic function through Bim up-regulation and increased Bim/Mcl-1 binding. These actions release Bak from Mcl-1, accompanied by Bak/Bax activation. Analogous …
Adjuvant Exemestane With Ovarian Suppression In Premenopausal Breast Cancer, Olivia Pagani, Meredith M. Regan, Barbara A. Walley, Gini F. Fleming, Marco Colleoni, István Láng, Henry L. Gomez, Carlo Tondini, Harold J. Burstein, Edith A. Perez, Eva Ciruelos, Vered Stearns, Hervé R. Bonnefoi, Silvana Martino, Charles E. Geyer Jr., Graziella Pinotti, Fabio Puglisi, Diana Crivellari, Thomas Ruhstaller, Eric P. Winer, Manuela Rabaglio-Poretti, Rudolf Maibach, Barbara Ruepp, Anita Giobbie-Hurder, Karen N. Price, Jürg Bernhard, Weixiu Luo, Karin Ribi, Giuseppe Viale, Alan S. Coates, Richard D. Gelber, Aron Goldhirsch, Prudence A. Francis
Adjuvant Exemestane With Ovarian Suppression In Premenopausal Breast Cancer, Olivia Pagani, Meredith M. Regan, Barbara A. Walley, Gini F. Fleming, Marco Colleoni, István Láng, Henry L. Gomez, Carlo Tondini, Harold J. Burstein, Edith A. Perez, Eva Ciruelos, Vered Stearns, Hervé R. Bonnefoi, Silvana Martino, Charles E. Geyer Jr., Graziella Pinotti, Fabio Puglisi, Diana Crivellari, Thomas Ruhstaller, Eric P. Winer, Manuela Rabaglio-Poretti, Rudolf Maibach, Barbara Ruepp, Anita Giobbie-Hurder, Karen N. Price, Jürg Bernhard, Weixiu Luo, Karin Ribi, Giuseppe Viale, Alan S. Coates, Richard D. Gelber, Aron Goldhirsch, Prudence A. Francis
Massey Comprehensive Cancer Center Publications
BACKGROUND Adjuvant therapy with an aromatase inhibitor improves outcomes, as compared with tamoxifen, in postmenopausal women with hormone-receptor-positive breast cancer. METHODS In two phase 3 trials, we randomly assigned premenopausal women with hormone-receptor-positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years. Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin, oophorectomy, or ovarian irradiation. The primary analysis combined data from 4690 patients in the two trials. RESULTS After a median follow-up of 68 months, disease-free survival at 5 years was …