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The natural sulfoglycolipid derivative SQAP improves the therapeutic efficacy of tissue factor-targeted radioimmunotherapy in the stroma-rich pancreatic cancer model BxPC-3
α-Sulfoquinovosylacyl-1,3-propanediol (SQAP) is a semi-synthetic derivative of natural sulfoglycolipid that sensitizes tumors to external-beam radiotherapy. How SQAP affects internal radiotherapy, however, is not known. Here, we investigated the effects of SQAP for radioimmunotherapy (RIT) targeting...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8628266/ https://www.ncbi.nlm.nih.gov/pubmed/34839108 http://dx.doi.org/10.1016/j.tranon.2021.101285 |
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author | Takakusagi, Yoichi Sugyo, Aya Tsuji, Atsushi B. Sudo, Hitomi Yasunaga, Masahiro Matsumura, Yasuhiro Sugawara, Fumio Sakaguchi, Kengo Higashi, Tatsuya |
author_facet | Takakusagi, Yoichi Sugyo, Aya Tsuji, Atsushi B. Sudo, Hitomi Yasunaga, Masahiro Matsumura, Yasuhiro Sugawara, Fumio Sakaguchi, Kengo Higashi, Tatsuya |
author_sort | Takakusagi, Yoichi |
collection | PubMed |
description | α-Sulfoquinovosylacyl-1,3-propanediol (SQAP) is a semi-synthetic derivative of natural sulfoglycolipid that sensitizes tumors to external-beam radiotherapy. How SQAP affects internal radiotherapy, however, is not known. Here, we investigated the effects of SQAP for radioimmunotherapy (RIT) targeting tissue factor (TF) in a stroma-rich refractory pancreatic cancer mouse model, BxPC-3. A low dose of SQAP (2 mg/kg) increased tumor uptake of the (111)In-labeled anti-TF antibody 1849, indicating increased tumor perfusion. The addition of SQAP enhanced the growth-inhibitory effect of (90)Y-labeled 1849 without leading to severe body weight changes, allowing for the dose of (90)Y-labeled 1849 to be reduced to half that when used alone. Histologic analysis revealed few necrotic and apoptotic cells, but Ki-67–positive proliferating cells and increased vascular formation were detected. These results suggest that the addition of a low dose of SQAP may improve the therapeutic efficacy of TF-targeted RIT by increasing tumor perfusion, even for stroma-rich refractory pancreatic cancer. |
format | Online Article Text |
id | pubmed-8628266 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-86282662021-12-16 The natural sulfoglycolipid derivative SQAP improves the therapeutic efficacy of tissue factor-targeted radioimmunotherapy in the stroma-rich pancreatic cancer model BxPC-3 Takakusagi, Yoichi Sugyo, Aya Tsuji, Atsushi B. Sudo, Hitomi Yasunaga, Masahiro Matsumura, Yasuhiro Sugawara, Fumio Sakaguchi, Kengo Higashi, Tatsuya Transl Oncol Original Research α-Sulfoquinovosylacyl-1,3-propanediol (SQAP) is a semi-synthetic derivative of natural sulfoglycolipid that sensitizes tumors to external-beam radiotherapy. How SQAP affects internal radiotherapy, however, is not known. Here, we investigated the effects of SQAP for radioimmunotherapy (RIT) targeting tissue factor (TF) in a stroma-rich refractory pancreatic cancer mouse model, BxPC-3. A low dose of SQAP (2 mg/kg) increased tumor uptake of the (111)In-labeled anti-TF antibody 1849, indicating increased tumor perfusion. The addition of SQAP enhanced the growth-inhibitory effect of (90)Y-labeled 1849 without leading to severe body weight changes, allowing for the dose of (90)Y-labeled 1849 to be reduced to half that when used alone. Histologic analysis revealed few necrotic and apoptotic cells, but Ki-67–positive proliferating cells and increased vascular formation were detected. These results suggest that the addition of a low dose of SQAP may improve the therapeutic efficacy of TF-targeted RIT by increasing tumor perfusion, even for stroma-rich refractory pancreatic cancer. Neoplasia Press 2021-11-25 /pmc/articles/PMC8628266/ /pubmed/34839108 http://dx.doi.org/10.1016/j.tranon.2021.101285 Text en © 2021 The Authors. Published by Elsevier Inc. https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Original Research Takakusagi, Yoichi Sugyo, Aya Tsuji, Atsushi B. Sudo, Hitomi Yasunaga, Masahiro Matsumura, Yasuhiro Sugawara, Fumio Sakaguchi, Kengo Higashi, Tatsuya The natural sulfoglycolipid derivative SQAP improves the therapeutic efficacy of tissue factor-targeted radioimmunotherapy in the stroma-rich pancreatic cancer model BxPC-3 |
title | The natural sulfoglycolipid derivative SQAP improves the therapeutic efficacy of tissue factor-targeted radioimmunotherapy in the stroma-rich pancreatic cancer model BxPC-3 |
title_full | The natural sulfoglycolipid derivative SQAP improves the therapeutic efficacy of tissue factor-targeted radioimmunotherapy in the stroma-rich pancreatic cancer model BxPC-3 |
title_fullStr | The natural sulfoglycolipid derivative SQAP improves the therapeutic efficacy of tissue factor-targeted radioimmunotherapy in the stroma-rich pancreatic cancer model BxPC-3 |
title_full_unstemmed | The natural sulfoglycolipid derivative SQAP improves the therapeutic efficacy of tissue factor-targeted radioimmunotherapy in the stroma-rich pancreatic cancer model BxPC-3 |
title_short | The natural sulfoglycolipid derivative SQAP improves the therapeutic efficacy of tissue factor-targeted radioimmunotherapy in the stroma-rich pancreatic cancer model BxPC-3 |
title_sort | natural sulfoglycolipid derivative sqap improves the therapeutic efficacy of tissue factor-targeted radioimmunotherapy in the stroma-rich pancreatic cancer model bxpc-3 |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8628266/ https://www.ncbi.nlm.nih.gov/pubmed/34839108 http://dx.doi.org/10.1016/j.tranon.2021.101285 |
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