Insight into the mechanisms underlying tumor response to boron neutron capture therapy in the hamster cheek pouch oral cancer model

Aromando, Romina F.; Heber, Elisa M.; Trivillin, Verónica A.; Nigg, David W.; Schwint, Amanda E.; Itoiz, M. E.

doi:10.1111/j.1600-0714.2008.00720.x

Cited by 11 publications

(16 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fujita et al stated that apoptosis was a form of cell death induced by BNCT [25]. While Aromando et al reported that apoptosis did not have a significant role in BNCT-induced hamster cheek pouch tumor control [26], and Kamida et al described that differences in apoptotic cells pre- and post-BNCT in human oral squamous cell carcinoma xenografts were minimal [27]. Whether BNCT can induce significant apoptosis rate in glioma cells in vivo and whether the pro-apoptotic effect is cell-type-dependant deserved further study.…”

Section: Discussionmentioning

confidence: 99%

Boron neutron capture therapy induces apoptosis of glioma cells through Bcl-2/Bax

et al. 2010

View full text Add to dashboard Cite

BackgroundBoron neutron capture therapy (BNCT) is an alternative treatment modality for patients with glioma. The aim of this study was to determine whether induction of apoptosis contributes to the main therapeutic efficacy of BNCT and to compare the relative biological effect (RBE) of BNCT, γ-ray and reactor neutron irradiation.MethodsThe neutron beam was obtained from the Xi'an Pulsed Reactor (XAPR) and γ-rays were obtained from [60Co] γ source of the Fourth Military Medical University (FMMU) in China. Human glioma cells (the U87, U251, and SHG44 cell lines) were irradiated by neutron beams at the XAPR or [60Co] γ-rays at the FMMU with different protocols: Group A included control nonirradiated cells; Group B included cells treated with 4 Gy of [60Co] γ-rays; Group C included cells treated with 8 Gy of [60Co] γ-rays; Group D included cells treated with 4 Gy BPA (p-borono-phenylalanine)-BNCT; Group E included cells treated with 8 Gy BPA-BNCT; Group F included cells irradiated in the reactor for the same treatment period as used for Group D; Group G included cells irradiated in the reactor for the same treatment period as used for Group E; Group H included cells irradiated with 4 Gy in the reactor; and Group I included cells irradiated with 8 Gy in the reactor. Cell survival was determined using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium (MTT) cytotoxicity assay. The morphology of cells was detected by Hoechst33342 staining and transmission electron microscope (TEM). The apoptosis rate was detected by flow cytometer (FCM). The level of Bcl-2 and Bax protein was measured by western blot analysis.ResultsProliferation of U87, U251, and SHG44 cells was much more strongly inhibited by BPA-BNCT than by irradiation with [60Co] γ-rays (P < 0.01). Nuclear condensation was determined using both a fluorescence technique and electron microscopy in all cell lines treated with BPA-BNCT. Furthermore, the cellular apoptotic rates in Group D and Group E treated with BPA-BNCT were significantly higher than those in Group B and Group C irradiated by [60Co] γ-rays (P < 0.01). The clonogenicity of glioma cells was reduced by BPA-BNCT compared with cells treated in the reactor (Group F, G, H, I), and with the control cells (P < 0.01). Upon BPA-BNCT treatment, the Bax level increased in glioma cells, whereas Bcl-2 expression decreased.ConclusionsCompared with γ-ray and reactor neutron irradiation, a higher RBE can be achieved upon treatment of glioma cells with BNCT. Glioma cell apoptosis induced by BNCT may be related to activation of Bax and downregulation of Bcl-2.

show abstract

Section: Discussionmentioning

confidence: 99%

Boron neutron capture therapy induces apoptosis of glioma cells through Bcl-2/Bax

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Studies on the correlation between the cytotoxic effect of BNCT and the p53 status are limited [31,32], but more studies are employing high LET carbon-ion beams. Indeed, Iwadate et al[13] reported that high LET carbon-ion beams were more cytotoxic than low LET X-rays for glioma cells, and the effects of the carbon-ion beams were not dependent on the p53 gene status.…”

Section: Discussionmentioning

confidence: 99%

“…Aromando et al [32] reported that BNCT-induced control of hamster cheek pouch tumors would be an inhibitory effect on DNA synthesis and apoptosis does not have a significant role in tumor control. Masunaga et al [31] examined the effect of BNCT on SAS xenografts in nude mice.…”

Section: Discussionmentioning

confidence: 99%

Role of p53 mutation in the effect of boron neutron capture therapy on oral squamous cell carcinoma

et al. 2009

View full text Add to dashboard Cite

BackgroundBoron neutron capture therapy (BNCT) is a selective radiotherapy, being effective for the treatment of even advanced malignancies in head and neck regions as well as brain tumors and skin melanomas. To clarify the role of p53 gene, the effect of BNCT on oral squamous cell carcinoma (SCC) cells showing either wild- (SAS/neo) or mutant-type (SAS/mp53) p53 was examined.MethodsCells were exposed to neutron beams in the presence of boronophenylalanine (BPA) at Kyoto University Research Reactor. Treated cells were monitored for modulations in colony formation, proliferation, cell cycle, and expression of cell cycle-associated proteins.ResultsWhen SAS/neo and SAS/mp53 cells were subjected to BNCT, more suppressive effects on colony formation and cell viability were observed in SAS/neo compared with SAS/mp53 cells. Cell cycle arrest at the G1 checkpoint was observed in SAS/neo, but not in SAS/mp53. Apoptotic cells increased from 6 h after BNCT in SAS/neo and 48 h in SAS/mp53 cells. The expression of p21 was induced in SAS/neo only, but G2 arrest-associated proteins including Wee1, cdc2, and cyclin B1 were altered in both cell lines.ConclusionThese results indicate that oral SCC cells with mutant-type are more resistant to BNCT than those with wild-type p53, and that the lack of G1 arrest and related apoptosis may contribute to the resistance. At a physical dose affecting the cell cycle, BNCT inhibits oral SCC cells in p53-dependent and -independent manners.

show abstract

“…Kreimann et al (2001) identified vacuolation as one of the morphological changes after BPAmediated BNCT in hamster buccal pouch tumours. Aromando et al (2009) indicated that BNCT had a marked inhibitory effect on DNA synthesis in hamster cheek pouch tumours and that apoptosis did not have a significant role in BNCT-induced tumour control. We found morphological changes such as chromosomal condensation, micronucleation, nuclear segmentation and vacuolation throughout the BNCT-treated SAS/neo and SAS/mp53 tumours.…”

Section: Discussionmentioning

confidence: 95%

“…Gamma ray irradiation, carbon-ion beams, iodine-131 and chemotherapeutic agents such as doxorubicin, cisplatin and paclitaxel have been shown to induce mitotic catastrophe (Ianzini et al 2006, Vakifahmetoglu et al 2008, Maalouf et al 2009). With regard to BNCT, apoptosis has been detected in a small proportion of treated SCC cells (Masunaga et al 2002, Kamida et al 2006, Aromando et al 2009), but other type of cell death such as mitotic catastrophe in response to BNCT has not. In the present study, we produced nude mouse tumours using oral SCC cells expressing wild-or mutant-type p53 with the same background and examined whether morphological alterations representing mitotic catastrophe can be induced by BNCT in a p53independent manner.…”

Section: Introductionmentioning

confidence: 98%

Induction of multinucleation in oral squamous cell carcinoma tissue with mutated p53 surviving boron neutron capture therapy

Fujita

Yamamoto

Kato

et al. 2010

International Journal of Radiation Biology

View full text Add to dashboard Cite

show abstract

Insight into the mechanisms underlying tumor response to boron neutron capture therapy in the hamster cheek pouch oral cancer model

Abstract: One of the mechanisms involved in BNCT-induced tumor control in our model would be an inhibitory effect on DNA synthesis. Apoptosis does not seem to have a significant role in BNCT-induced tumor control in our model.

Cited by 11 publications

References 39 publications

Boron neutron capture therapy induces apoptosis of glioma cells through Bcl-2/Bax

Boron neutron capture therapy induces apoptosis of glioma cells through Bcl-2/Bax

Role of p53 mutation in the effect of boron neutron capture therapy on oral squamous cell carcinoma

Induction of multinucleation in oral squamous cell carcinoma tissue with mutated p53 surviving boron neutron capture therapy

Contact Info

Product

Resources

About