scholarly journals Impact of the p53 Status of the Tumor Cells on the Effect of Reactor Neutron Beam Irradiation, with Emphasis on the Response of Intratumor Quiescent Cells

2002 ◽  
Vol 93 (12) ◽  
pp. 1366-1377 ◽  
Author(s):  
Shin-ichiro Masunaga ◽  
Koji Ono ◽  
Akihisa Takahashi ◽  
Yoshinori Sakurai ◽  
Ken Ohnishi ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Neutron Beam ◽  
Reactor Neutron ◽  
Beam Irradiation ◽  
Quiescent Cells ◽  
P53 Status

scholarly journals The Effect of p53 Status of Tumor Cells on Radiosensitivity of Irradiated Tumors With Carbon-Ion Beams Compared With γ-Rays or Reactor Neutron Beams

2015 ◽  
Vol 6 (4) ◽  
pp. 398-409 ◽  
Author(s):  
Shin-ichiro Masunaga ◽  
Akiko Uzawa ◽  
Ryoichi Hirayama ◽  
Yoshitaka Matsumoto ◽  
Yoshinori Sakurai ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Ion Beams ◽  
Reactor Neutron ◽  
Carbon Ion ◽  
Neutron Beams ◽  
P53 Status ◽  
Γ Rays

Abstract C218: Relevance of p53 status for the response of tumor cells to MET inhibitors combined with irradiation.

2013 ◽  
Author(s):  
Kei Mikami ◽  
Michaela Medová ◽  
Bruno Streit ◽  
Mario P. Tschan ◽  
Andree Blaukat ◽  
...  
Keyword(s):  
Tumor Cells ◽  
P53 Status

Activity of Bendamustine (TREANDA™) in Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma Cells with Alterations in DNA Damage Response Pathway.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2510-2510
Author(s):  
Gaël Roué ◽  
Mónica López-Guerra ◽  
Pierre Milpied ◽  
Patricia Pérez-Galán ◽  
Neus Villamor ◽  
...  
Keyword(s):  
Cell Death ◽  
Chronic Lymphocytic Leukemia ◽  
Mantle Cell Lymphoma ◽  
Tumor Cells ◽  
Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Low Grade ◽  
Mantle Cell ◽  
P53 Status

Abstract Mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) are two different types of mature B-cell non-Hodgkin’s lymphoma (NHL). CLL has an indolent natural history and patients are very responsive to frontline chemotherapy. Unfortunately, multiple relapses are inevitable, and ultimately, no regimen or treatment strategy offers a distinct survival benefit over another. In contrast, patients with MCL generally experience a more aggressive course, with rapid disease progression and also without specific therapeutic options. Bendamustine hydrochloride (Treanda™) is a multifunctional, alkylating agent that exhibits single-agent activity in multiple hematologic and solid tumors. Recently, the combination of bendamustine with rituximab has demonstrated to be a highly active regimen in the treatment of low-grade lymphomas and MCL. However, very little is known about its mode of action. The ability of bendamustine to induce apoptosis in vitro in MCL and CLL cells and the mechanisms implicated in bendamustine-evoked cell death signaling were investigated. Bendamustine exerted cytostatic and cytotoxic effects in 11 MCL cell lines and primary tumor cells from 7 MCL patients and 10 CLL patients independent of their p53 status, and other gene alterations. In vitro treatment of cells with bendamustine induced activation of both p53-dependent and -independent signaling pathways that converged in all cases to the activation of the pro-apoptotic protein Noxa, conformational changes of Bax and Bak, and mitochondrial depolarization. These events led to cytosolic release of the mitochondrial apoptogenic factors cytochrome c, Smac/DIABLO and AIF, and activation of both caspase -dependent and -independent cell death. Genotoxic stress and caspase-independent cell death are often associated with the generation of reactive oxygen species (ROS). We observed that ROS production was a key step in the induction of apoptosis by bendamustine, since pre-incubation of tumor cells with ROS scavengers reverted all the typical hallmarks of apoptosis. Furthermore, bendamustine exerted a cytotoxic effect in p53 deleted CLL cases that were resistant to fludarabine treatment. These findings support the use of bendamustine as a therapeutic agent in MCL and CLL cells and also establish the basis for the use of bendamustine in lymphoid malignancies that show resistance to classic genotoxic agents that depend on cellular p53 status.

scholarly journals DNA replication stress induced by trifluridine determines tumor cell fate according to p53 status

2019 ◽  
Author(s):  
Yuki Kataoka ◽  
Makoto Iimori ◽  
Ryo Fujisawa ◽  
Tomomi Morikawa-Ichinose ◽  
Shinichiro Niimi ◽  
...  
Keyword(s):  
Dna Replication ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Fate ◽  
Replication Fork ◽  
Apoptotic Cell ◽  
Replication Stress ◽  
Dna Replication Stress ◽  
P53 Status ◽  
Fork Stalling

ABSTRACTDNA replication stress is a predominant cause of genome instability, a driver of tumorigenesis and malignant progression. Nucleoside analog-type chemotherapeutic drugs introduce DNA damage and exacerbate DNA replication stress in tumor cells. However, the mechanisms underlying tumor cytotoxicity triggered by the drugs are not fully understood. Here, we show that the fluorinated thymidine analog trifluridine (FTD), an active component of the chemotherapeutic drug trifluridine/tipiracil, delayed DNA synthesis by human replicative DNA polymerases. FTD acted as an inefficient deoxyribonucleotide triphosphate source (FTD triphosphate) and as an obstacle base (trifluorothymine) in the template DNA strand. At the cellular level, FTD decreased thymidine triphosphate in the dNTP pool and induced FTD triphosphate accumulation, resulting in replication fork stalling caused by FTD incorporation into DNA. DNA lesions involving single-stranded DNA were generated as a result of replication fork stalling, and the p53-p21 pathway was activated. Although FTD suppressed tumor cell growth irrespective of p53 status, tumor cell fate diverged at the G2/M phase transition according to p53 status; tumor cells with wild-type p53 underwent cellular senescence via mitosis skip, whereas tumor cells that lost wild-type p53 underwent apoptotic cell death via aberrant late mitosis with severely impaired separation of sister chromatids. These results suggest that DNA replication stress induced by a nucleoside analog-type chemotherapeutic drug triggers tumor cytotoxicity by determining tumor cell fate according to p53 status.SignificanceThis study identified a unique type of DNA replication stress induced by trifluridine, which directs tumor cell fate either toward cellular senescence or apoptotic cell death according to p53 status.

In vitro sensitivity of colon tumor cells to 5 fluoro-uracile (5 FU), oxaliplatin and irinotecan: Role of microsatellite instability and p53 status

2003 ◽  
Vol 124 (4) ◽  
pp. A238
Author(s):  
Beatrice Parmentier ◽  
Jacques Abello ◽  
Catherine Bohas ◽  
Jean-Alain Chayvialle ◽  
Jean-Christophe Saurin
Keyword(s):  
Microsatellite Instability ◽  
Tumor Cells ◽  
Colon Tumor ◽  
In Vitro Sensitivity ◽  
P53 Status
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