Track topics on Twitter Track topics that are important to you
This study demonstrated a pronounced synergistic growth-inhibitory effect of an MDM2 inhibitor Nutlin-3 and a proteasome inhibitor bortezomib in mantle cell lymphoma (MCL) cells regardless of TP53 mutant status and innate bortezomib sensitivity. In the mutant TP53 MCL cells which are intrinsically resistant to bortezomib, the combination of Nutlin-3/bortezomib synergistically induced cytotoxicity through the mitochondrial apoptotic pathway mediated by transcription-independent upregulation of NOXA, sequestration of MCL-1, activation of BAX, BAK, caspase-9 and -3. In the bortezomib sensitive wild-type TP53 MCL cells, the Nutlin-3/bortezomib combination caused G0/G1 cell cycle arrest followed by the increase in apoptosis induction. These findings indicate potential therapeutic efficacy of Nutlin-3/bortezomib combination for the treatment of chemorefractory MCL.
Department of Clinical Pathology, Juntendo University School of Medicine, Tokyo, Japan.
This article was published in the following journal.
Name: Cancer letters
p53 deletion prevents the embryonic lethality of normal tissues lacking Mdm2, suggesting that cells can survive without Mdm2 if p53 is also absent. Here we report evidence challenging this view, with ...
Melanoma tumors usually retain wild-type p53; however, its tumor-suppressor activity is functionally disabled, most commonly through an inactivating interaction with mouse double-minute 2 homolog (Mdm...
Malignant Pleural Mesothelioma (MPM) is a chemoresistant tumor characterized by low rate of p53 mutation and upregulation of Murine Double Minute 2 (MDM2), suggesting that it may be effectively target...
Neuroblastoma (NB), which accounts for about 15% of cancer-related mortality in children, is the most common childhood extracranial malignant tumor. In NB, somatic mutations of the tumor suppressor, p...
Multiple myeloma (MM) is an incurable hematological malignancy, although bortezomib has markedly improved its outcomes. Growing clinical evidence indicates that enhancing induced natural killer (NK) o...
This phase 0/I trial studies the side effects and best dose of MDM2 inhibitor AMG-232 in treating patients with glioblastoma that is newly diagnosed or has come back. MDM2 inhibitor AMG-23...
Study of the efficacy and safety of bortezomib administered in combination with vorinostat in patients with relapsed or refractory multiple myeloma. Histone deacetylases (HDAC) facilitate ...
Study of vorinostat in combination with bortezomib in patients with relapsed or refractory multiple myeloma after at least 2 prior treatment regimens. Histone deacetylases (HDAC) facilita...
An association between insulin resistance and mitochondrial dysfunction has been observed in aging, T2D, and in offspring of patients with T2D. It remains to be determined whether pharmac...
Our central hypothesis is that oral CoQ10 is a safe and effective treatment for children with inborn errors of mitochondrial energy metabolism due to defects in specific respiratory chain ...
A multi-domain mitochondrial membrane protein and member of the bcl-2 Protein family. Bak protein interacts with TUMOR SUPPRESSOR PROTEIN P53 and promotes APOPTOSIS.
An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)
An inhibitor of apoptosis protein that is translated by a rare cap-independent mechanism. It blocks caspase-mediated cellular destruction by inhibiting CASPASE 3; CASPASE 7; and CASPASE 9.
A 33-amino acid peptide derived from the C-terminal of PROGLUCAGON and mainly produced by the INTESTINAL L CELLS. It stimulates intestinal mucosal growth and decreased apoptosis of ENTEROCYTES. GLP-2 enhances gastrointestinal function and plays an important role in nutrient homeostasis.
In vitro fertilization technique that uses mitochondrial DNA from a healthy donor in order to prevent the transmission of MITOCHONDRIAL DISEASE.