Synthesis ofp-Boronophenylserine, a New Boron-containing Amino Acid for Boron Neutron Capture Therapy

1995 ◽  
Vol 59 (12) ◽  
pp. 2317-2318 ◽  
Author(s):  
Mitsunori Kirihata ◽  
Tsuguhiro Morimoto ◽  
Takanori Mizuta ◽  
Itsuo Ichimoto
Keyword(s):  
Amino Acid ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Neutron Capture Therapy ◽  
Boron Neutron Capture

scholarly journals In Vitro Studies to Define the Cell-Surface and Intracellular Targets of Polyarginine-Conjugated Sodium Borocaptate as a Potential Delivery Agent for Boron Neutron Capture Therapy

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2149
Author(s):  
Atsushi Fujimura ◽  
Seiji Yasui ◽  
Kazuyo Igawa ◽  
Ai Ueda ◽  
Kaori Watanabe ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cell Surface ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Cell Membrane Permeability ◽  
Neutron Capture Therapy ◽  
Translational Machinery ◽  
Boron Neutron Capture ◽  
The Future ◽  
Intracellular Targets

Boron neutron capture therapy (BNCT) requires pharmaceutical innovations and molecular-based evidence of effectiveness to become a standard cancer therapeutic in the future. Recently, in Japan, 4-borono-L-phenylalanine (BPA) was approved as a boron agent for BNCT against head and neck (H&N) cancers. H&N cancer appears to be a suitable target for BPA-BNCT, because the expression levels of L-type amino acid transporter 1 (LAT1), one of the amino acid transporters responsible for BPA uptake, are elevated in most cases of H&N cancer. However, in other types of cancer including malignant brain tumors, LAT1 is not always highly expressed. To expand the possibility of BNCT for these cases, we previously developed poly-arginine peptide (polyR)-conjugated mercaptoundecahydrododecaborate (BSH). PolyR confers the cell membrane permeability and tumor selectivity of BSH. However, the molecular determinants for the properties are not fully understood. In this present study, we have identified the cluster of differentiation 44 (CD44) protein and translational machinery proteins as a major cell surface target and intracellular targets of BSH-polyR, respectively. CD44, also known as a stem cell-associated maker in various types of cancer, is required for the cellular uptake of polyR-conjugated molecules. We showed that BSH-polyR was predominantly delivered to a CD44High cell population of cancer cells. Once delivered, BSH-polyR interacted with the translational machinery components, including the initiation factors, termination factors, and poly(A)-biding protein (PABP). As a proof of principle, we performed BSH-polyR-based BNCT against glioma stem-like cells and revealed that BSH-polyR successfully induced BNCT-dependent cell death specifically in CD44High cells. Bioinformatics analysis indicated that BSH-polyR would be suitable for certain types of malignant tumors. Our results shed light on the biochemical properties of BSH-polyR, which may further contribute to the therapeutic optimization of BSH-BNCT in the future.

Synthesis of 1-Amino-3-{2-[7-(6-deoxy-α/β-D-galactopyranos-6-yl)-1,7-dicarba-closo-dodecaboran(12)-1-yl]ethyl}cyclobutanecarboxylic Acid Hydrochloride

2002 ◽  
Vol 67 (6) ◽  
pp. 836-842 ◽  
Author(s):  
George W. Kabalka ◽  
Bhaskar C. Das ◽  
Sasmita Das ◽  
Guishing Li ◽  
Rajiv Srivastava ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cancer Cells ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Neutron Capture Therapy ◽  
Toxicity Data ◽  
Boron Neutron Capture ◽  
Cyclobutanecarboxylic Acid ◽  
Strecker Synthesis ◽  
Acid Hydrochloride

1-Amino-3-{2-[7-(6-deoxy-α/β-D-galactopyranos-6-yl)-1,7-dicarba-closo-dodecaboran(12)-1-yl]ethyl}cyclobutanecarboxylic acid was synthesized as a potential new agent for boron neutron capture therapy. The key step in the synthesis is the alkylation of 3-{2-[1,7-dicarba-closo-dodecaboran(12)-1-yl]ethyl}cyclobutanone ethylene monothioketal with 1,2:3,4-di-O-isopropylidene-6-O-triflyl-α-D-galactopyranose which gave the precursor ketone that was then converted to the title amino acid via a Bücherer-Strecker synthesis followed by removal of isopropylidene groups in HCl. Preliminary toxicity data in A 435 cancer cells were obtained.

scholarly journals HGG-05. REGRESSION OF RECURRENT GLIOBLASTOMA AFTER BORON NEUTRON CAPTURE THERAPY AND CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY IN A CHILD

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii345-iii345
Author(s):  
Hsin-Hung Chen ◽  
Yi-Wei Chen
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chimeric Antigen Receptor ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Antigen Receptor ◽  
Neutron Capture Therapy ◽  
T Cell Therapy ◽  
Boron Neutron Capture ◽  
Car T

Abstract A 6 y/o girl with recurrent multifocal glioblastoma received 3 times of boron neutron capture therapy (BNCT) and chimeric antigen receptor (CAR)–engineered T cells targeting the tumor-associated antigen HER2. Multiple infusions of CAR T cells were administered over 30 days through intraventricular delivery routes. It was not associated with any toxic effects of grade 3 or higher. After BNCT and CAR T-cell treatment, regression of all existing intracranial lesions were observed, along with corresponding increases in levels of cytokines and immune cells in the cerebrospinal fluid, but new lesions recurred soon after the treatment. This clinical response continued for 14 months after the initiation of first recurrence.

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