Science (American Association for the Advancement of Science), 2011-11, Vol.334 (6059), p.1129-1133
- Chonghaile, Triona Ni
- Sarosiek, Kristopher A.
- Vo, Thanh-Trang
- Ryan, Jeremy A.
- Tammareddi, Anupama
- Del Gaizo Moore, Victoria
- Deng, Jing
- Anderson, Kenneth C.
- Richardson, Paul
- Tai, Yu-Tzu
- Mitsiades, Constantine S.
- Matulonis, Ursula A.
- Drapkin, Ronny
- Stone, Richard
- DeAngelo, Daniel J.
- McConkey, David J.
- Sallan, Stephen E.
- Silverman, Lewis
- Hirsch, Michelle S.
- Carrasco, Daniel Ruben
- Letai, Anthony
2011
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- Autor(en) / Beteiligte
- Chonghaile, Triona Ni
- Sarosiek, Kristopher A.
- Vo, Thanh-Trang
- Ryan, Jeremy A.
- Tammareddi, Anupama
- Del Gaizo Moore, Victoria
- Deng, Jing
- Anderson, Kenneth C.
- Richardson, Paul
- Tai, Yu-Tzu
- Mitsiades, Constantine S.
- Matulonis, Ursula A.
- Drapkin, Ronny
- Stone, Richard
- DeAngelo, Daniel J.
- McConkey, David J.
- Sallan, Stephen E.
- Silverman, Lewis
- Hirsch, Michelle S.
- Carrasco, Daniel Ruben
- Letai, Anthony
- Titel
- Pretreatment Mitochondrial Priming Correlates with Clinical Response to Cytotoxic Chemotherapy
- Ist Teil von
- Science (American Association for the Advancement of Science), 2011-11, Vol.334 (6059), p.1129-1133
- Ort / Verlag
- Washington, DC: American Association for the Advancement of Science
- Erscheinungsjahr
- 2011
- Quelle
- Science Online_科学在线
- Beschreibungen/Notizen
- Cytotoxic chemotherapy targets elements common to all nucleated human cells, such as DNA and microtubules, yet it selectively kills tumor cells. Here we show that clinical response to these drugs correlates with, and may be partially governed by, the pretreatment proximity of tumor cell mitochondria to the apoptotic threshold, a property called mitochondrial priming. We used BH3 profiling to measure priming in tumor cells from patients with multiple myeloma, acute myelogenous and lymphoblastic leukemia, and ovarian cancer. This assay measures mitochondrial response to peptides derived from proapoptotic BH3 domains of proteins critical for death signaling to mitochondria. Patients with highly primed cancers exhibited superior clinical response to chemotherapy. In contrast, chemoresistant cancers and normal tissues were poorly primed. Manipulation of mitochondrial priming might enhance the efficacy of cytotoxic agents.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0036-8075eISSN: 1095-9203DOI: 10.1126/science.1206727Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3280949
- Format
- –
- Schlagworte
- Adult, Aged, Animals, Antineoplastic agents, Antineoplastic Agents - therapeutic use, Apoptosis, Biological and medical sciences, Bone marrow, Cancer, Cell Line, Tumor, Cell Proliferation, Chemotherapy, Child, Depolarization, Disease-Free Survival, Drug Resistance, Neoplasm, Female, Hematologic and hematopoietic diseases, Humans, Leukemia, Myeloid, Acute - drug therapy, Leukemia, Myeloid, Acute - physiopathology, Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis, Male, Medical sciences, Membrane Potential, Mitochondrial, Mice, Mice, Inbred C57BL, Middle Aged, Mitochondria, Mitochondria - physiology, Multiple myeloma, Multiple Myeloma - drug therapy, Multiple Myeloma - physiopathology, Myeloid leukemia, Narcotics, Neoplasms - drug therapy, Neoplasms - physiopathology, Ovarian cancer, Ovarian Neoplasms - drug therapy, Ovarian Neoplasms - physiopathology, Patients, Peptide Fragments - metabolism, Permeability, Pharmacology. Drug treatments, Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma - physiopathology, Pretreatment, Proto-Oncogene Proteins c-bcl-2 - chemistry, Proto-Oncogene Proteins c-bcl-2 - metabolism, Remission Induction, Signal Transduction, Tumors