			Home About us Contact

Topoisomerase Inhibitor (topoisomerase + inhibitor)

Distribution by Scientific Domains

Life Sciences	60%
Medical Sciences	40%

Selected Abstracts

Topoisomerase inhibitor induced dephosphorylation of H1 and H3 histones as a consequence of cell cycle arrest

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2005
Nicole Happel
Abstract Posttranslational modifications of histones have an integral function in the structural and functional organization of chromatin. Several changes in the modification state of histones could be observed after induction of apoptosis with topoisomerase inhibitors and other inducers. Most of these studies include the analysis of the state of phosphorylation of histones, and the results are to some extent controversial, depending on cell lines and agents used. In the present study we compared the kinetics of the dephosphorylation of H1 and H3 histones with apoptosis markers after treatment of leukemic cell lines with topoisomerase inhibitors. In parallel, we determined cell cycle parameters in detail. Dephosphorylation of both histone classes started within 1 h of induction, and no direct correlation with timing and intensity of the investigated apoptotic features could be observed. In contrast, we show that the effect of topoisomerase inhibitors on the state of H1 and H3 phosphorylation is not directly related to apoptosis, but reflects the changes in the cell cycle distribution of cells treated with these inducers. © 2005 Wiley-Liss, Inc. [source]

Calpain-mediated androgen receptor breakdown in apoptotic prostate cancer cells

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2008
Huanjie Yang
Since androgen receptor (AR) plays an important role in prostate cancer development and progression, androgen-ablation has been the frontline therapy for treatment of advanced prostate cancer even though it is rarely curative. A curative strategy should involve functional and structural elimination of AR from prostate cancer cells. We have previously reported that apoptosis induced by medicinal proteasome-inhibitory compound celastrol is associated with a decrease in AR protein levels. However celastrol-stimulated events contributing to this AR decrease have not been elucidated. Here, we report that a variety of chemotherapeutic agents, including proteasome inhibitors, a topoisomerase inhibitor, DNA-damaging agents and docetaxel that cause cell death, decrease AR levels in LNCaP prostate cancer cells. This decrease in AR protein levels was not due to the suppression of AR mRNA expression in these cells. We observed that a proteolytic activity residing in cytosol of prostate cancer cells is responsible for AR breakdown and that this proteolytic activity was stimulated upon induction of apoptosis. Interestingly, proteasome inhibitor celastrol- and chemotherapeutic drug VP-16-stimulated AR breakdown was attenuated by calpain inhibitors calpastatin and N -acetyl- L -leucyl- L -leucyl- L -methioninal. Furthermore, AR proteolytic activity pulled down by calmodulin-agarose beads from celastrol-treated PC-3 cells showed immunoreactivity to a calpain antibody. Taken together, these results demonstrate calpain involvement in proteasome inhibitor-induced AR breakdown, and suggest that AR degradation is intrinsic to the induction of apoptosis in prostate cancer cells. J. Cell. Physiol. 217: 569,576, 2008. © 2008 Wiley-Liss, Inc. [source]

High-dose chemotherapy with autologous hematopoietic stem cell rescue for stage 4B retinoblastoma,

PEDIATRIC BLOOD & CANCER, Issue 1 2010
Ira J. Dunkel MD
Abstract Background Stage 4b retinoblastoma (central nervous system metastatic disease) has been lethal in virtually all cases reported. Here we describe a series of eight patients treated with intensive chemotherapy, defined as the intention to include high-dose chemotherapy with autologous hematopoietic stem cell rescue. Procedure Induction chemotherapy included cyclophosphamide and/or carboplatin with a topoisomerase inhibitor. High-dose chemotherapy regimens were carboplatin and thiotepa with or without etoposide (n,=,3) or carboplatin, etoposide, and cyclophosphamide (n,=,2). Results Seven patients had leptomeningeal disease and one patient had only direct extension to the CNS via the optic nerve. Three patients had stage 4b disease at the time of original diagnosis of the intra-ocular retinoblastoma; five had later onset at a median of 12 months (range 3,69 months). One patient died of toxicity (septicemia and multi-organ system failure) during induction and two had disease progression prior to high-dose chemotherapy. Five patients received high-dose chemotherapy at a median of 6 months (range 4,6) post-diagnosis of stage 4b disease. Two patients survive event-free at 40 and 101 months; one was irradiated following recovery from the high-dose chemotherapy. Conclusions Intensive multimodality therapy may be beneficial for some patients with stage 4b retinoblastoma. Longer follow-up will determine whether it has been curative. Pediatr Blood Cancer 2010;55:149,152. © 2010 Wiley-Liss, Inc. [source]

Survival is poorer in patients with secondary core-binding factor acute myelogenous leukemia compared with de novo core-binding factor leukemia

CANCER, Issue 14 2009
Gautam Borthakur MD
Abstract BACKGROUND: Therapy related secondary acute myelogenous leukemia (AML) was commonly associated with prior exposure to alkylating agents or topoisomerase inhibitor. The long-term outcome of such patients with secondary AML was found to be worse than that of patients with de novo AML. Earlier reports suggested similar outcomes for patients with de novo and secondary AML associated with core-binding factor (CBF) abnormalities. METHODS: A total of 188 patients with CBF AML were analyzed. The frequency of secondary CBF AML was 9%. RESULTS: Patients with secondary CBF AML were found to have significantly worse overall (OS) and event-free survival (EFS) compared with patients with de novo CBF AML. Secondary CBF AML status appeared to have only marginal significance in multivariate analysis. CONCLUSIONS: Matched analysis (by age, Eastern Cooperative Oncology Group performance status, and additional cytogenetic abnormality) indicated worse OS and EFS in patients with secondary CBF AML. Cancer 2009. © 2009 American Cancer Society. [source]