Effect of Boron Neutron Capture Therapy (BNCT) on normal liver regeneration: Towards a novel therapy for liver metastases

Cardoso, Jorge; Trivillin, Verónica A.; Heber, Elisa M.; Nigg, David W.; Calzetta, Osvaldo; Longhino, Juan; Itoiz, M. E.; Bumaschny, Eduardo; Pozzi, Enrique J. Sánchez; Schwint, Amanda E.

doi:10.1080/09553000701570212

Cited by 20 publications

(8 citation statements)

References 17 publications

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“…Extensive international efforts have been made by physicists, chemists, clinicians, and biologists for over 50 years focused on the development and testing of BNCT in the treatment of cancer (Barth et al, 2005; Coderre and Morris, 1999; Hatanaka, 1991; Kabalka et al, 2003; Kabalka and Yao, 2006; Li et al, 2006; Pellettieri et al, 2008). Clinical interest in BNCT has focused primarily on the treatment of high-grade gliomas, either cutaneous primaries or cerebral metastases of melanoma, and, more recently, head and neck and liver cancer (Barth et al, 2005; Pellettieri et al, 2008; Cordoso et al, 2007; Dagrosa et al, 2007; Kankaaranta et al, 2007; Wittig et al, 2008). …”

Section: Introductionmentioning

confidence: 99%

Biological evaluation of boronated unnatural amino acids as new boron carriers

Kabalka

Yao

Marepally

et al. 2009

Applied Radiation and Isotopes

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There is a pressing need for new and more efficient boron delivery agents to tumor cells for use in boron neutron capture therapy (BNCT). A class of boronated unnatural cyclic amino acids has demonstrated a remarkable selectivity toward tumors in animal and cell culture models, far superior to currently used agents in clinical BNCT. One of these amino acids, 1-amino-3-boronocyclopentanecarboxylic acid (ABCPC), has shown a tumor to blood ratio of 8 and a tumor to normal brain ratio of nearly 21 in a melanoma bearing mouse model. This work represents further biological characterization of this compound for tumor targeting in an EMT6 murine mammary carcinoma mouse model and a T98G human glioblastoma cell line. Female BALB/c mice bearing EMT6 tumors were injected with the fructose complex form of racemic mixtures of cis-and trans isomers of ABCPC in identical concentrations. Boron concentrations were measured in the tumor, blood, brain, skin, and liver tissues at 1, 3, and 5 hr post injection. These observations revealed a remarkable difference in racemic mixtures of cis and trans isomers in tumor targeting by boron. This implies that further separation of the L and D forms of this compound may enhance tumor targeting to an even higher degree than that provided by the racemic mixtures. Since the uptake measurements were made in homogenized tumor and normal tissues, little is known about the subcellular location of the boron arising from the various isomeric forms of the amino acid. To study subcellular delivery of boron from ABCPC in T98G human glioblastoma cells, we employed secondary ion mass spectrometry (SIMS) based technique of ion microscopy, which is capable of quantitatively imaging isotopic (elemental) gradients in cells and tissues at 500 nm spatial resolution. The T98G cells were exposed to the nutrient medium containing 100 ppm boron equivalent of a mixture of both L and D isomers of ABCPC in the form of a fructose complex for 1 hr. Following this treatment, the cells were fast frozen, freeze-fractured, and freeze-dried for SIMS analysis. Within an hour of exposure, ABCPC provided partitioning of intracellular to extracellular boron of 3/1. SIMS imaging revealed that boron from ABCPC was distributed throughout the cell, including the nucleus. This level of boron delivery within an hour of exposure is superior to p-boronophenylalanine (BPA) and sodium borocaptate (BSH), which have been previously studied by SIMS in the same cell line. These encouraging observations provide compelling support for further isomeric separations of ABCPC into the D and L forms for enhanced tumor targeting and continued testing of these compounds as new boron carriers in BNCT.

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Section: Introductionmentioning

confidence: 99%

Biological evaluation of boronated unnatural amino acids as new boron carriers

Kabalka

Yao

Marepally

et al. 2009

Applied Radiation and Isotopes

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“…In contrast, Cardoso et al reported,based on their animal experiment, that post-hepatectomy liver regeneration at 9 days was not impaired by the preceding boron neutron capture therapy (24). The only noticeable difference between these reports was the sequence of operation and radiotherapy.…”

Section: Discussionmentioning

confidence: 89%

Does Adjuvant Radiotherapy Suppress Liver Regeneration After Partial Hepatectomy?

Choi

Kim

Chie

et al. 2009

International Journal of Radiation Oncology*Biology*Physics

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“…Besides, authors also reported that pro-apoptotic effect and the inhibition in cell growth following the treatment were intensively observed. In their study, Cardoso et al (18) analyzed the effects of boron compounds on liver metastasis and liver regeneration induced with PH suggested that boron in high densities triggered apoptosis. Garabalino et al (19) noted that boron compounds could be used in the treatment of cancer in a concentration-dependent manner in liver metastasis.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis induced by boric anhydrite (B2O3) after partial hepatectomy in rat liver

Özen¹,

Canbek²

2016

BLL

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Boron is one of the important elements that have a cell-growth suppressing effect. The apoptotic effects of B 2 O 3 that were investigated in rats on liver regeneration following 70 % partial hepatectomy (PH). Wistar albino male rats were used and divided into 4 groups (n = 7). The Saline control groups were given only a single dose of saline; the B 2 O 3 -treated groups that were only given a single dose of 1800 mg.kg -1 B 2 O 3 by means of intraperitoneal injections following hepatectomy. Three and 6 hours after surgical procedures, all the groups were dissected and liver tissue samples were taken from the groups for NF-κB for caspase-3 gene and protein levels investigation by RT-PCR and TaqMan Protein Assay and histological analyses by TUNEL assay. B 2 O 3 -treated animals were examined and it was observed that NF-κB levels were decreased; however, caspase-3 gene expression and protein levels were increased signifi cantly. This study demonstrated that B 2 O 3 induces caspase-3 and inhibits NF-κB at the early stage of liver regeneration (Fig. 4, Ref. 26). Text in PDF www.elis.sk.

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Effect of Boron Neutron Capture Therapy (BNCT) on normal liver regeneration: Towards a novel therapy for liver metastases

Abstract: The BNCT protocols, at the physical doses selected, did not impair the capacity of normal liver hepatocytes to regenerate.

Cited by 20 publications

References 17 publications

Biological evaluation of boronated unnatural amino acids as new boron carriers

Biological evaluation of boronated unnatural amino acids as new boron carriers

Does Adjuvant Radiotherapy Suppress Liver Regeneration After Partial Hepatectomy?

Apoptosis induced by boric anhydrite (B2O3) after partial hepatectomy in rat liver

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