Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Takakusagi, Yoichi, Sugyo, Aya, Tsuji, Atsushi B., Sudo, Hitomi, Yasunaga, Masahiro, Matsumura, Yasuhiro, Sugawara, Fumio, Sakaguchi, Kengo, Higashi, Tatsuya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2021
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
_version_ 1784606981131075584
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
work_keys_str_mv AT takakusagiyoichi thenaturalsulfoglycolipidderivativesqapimprovesthetherapeuticefficacyoftissuefactortargetedradioimmunotherapyinthestromarichpancreaticcancermodelbxpc3
AT sugyoaya thenaturalsulfoglycolipidderivativesqapimprovesthetherapeuticefficacyoftissuefactortargetedradioimmunotherapyinthestromarichpancreaticcancermodelbxpc3
AT tsujiatsushib thenaturalsulfoglycolipidderivativesqapimprovesthetherapeuticefficacyoftissuefactortargetedradioimmunotherapyinthestromarichpancreaticcancermodelbxpc3
AT sudohitomi thenaturalsulfoglycolipidderivativesqapimprovesthetherapeuticefficacyoftissuefactortargetedradioimmunotherapyinthestromarichpancreaticcancermodelbxpc3
AT yasunagamasahiro thenaturalsulfoglycolipidderivativesqapimprovesthetherapeuticefficacyoftissuefactortargetedradioimmunotherapyinthestromarichpancreaticcancermodelbxpc3
AT matsumurayasuhiro thenaturalsulfoglycolipidderivativesqapimprovesthetherapeuticefficacyoftissuefactortargetedradioimmunotherapyinthestromarichpancreaticcancermodelbxpc3
AT sugawarafumio thenaturalsulfoglycolipidderivativesqapimprovesthetherapeuticefficacyoftissuefactortargetedradioimmunotherapyinthestromarichpancreaticcancermodelbxpc3
AT sakaguchikengo thenaturalsulfoglycolipidderivativesqapimprovesthetherapeuticefficacyoftissuefactortargetedradioimmunotherapyinthestromarichpancreaticcancermodelbxpc3
AT higashitatsuya thenaturalsulfoglycolipidderivativesqapimprovesthetherapeuticefficacyoftissuefactortargetedradioimmunotherapyinthestromarichpancreaticcancermodelbxpc3
AT takakusagiyoichi naturalsulfoglycolipidderivativesqapimprovesthetherapeuticefficacyoftissuefactortargetedradioimmunotherapyinthestromarichpancreaticcancermodelbxpc3
AT sugyoaya naturalsulfoglycolipidderivativesqapimprovesthetherapeuticefficacyoftissuefactortargetedradioimmunotherapyinthestromarichpancreaticcancermodelbxpc3
AT tsujiatsushib naturalsulfoglycolipidderivativesqapimprovesthetherapeuticefficacyoftissuefactortargetedradioimmunotherapyinthestromarichpancreaticcancermodelbxpc3
AT sudohitomi naturalsulfoglycolipidderivativesqapimprovesthetherapeuticefficacyoftissuefactortargetedradioimmunotherapyinthestromarichpancreaticcancermodelbxpc3
AT yasunagamasahiro naturalsulfoglycolipidderivativesqapimprovesthetherapeuticefficacyoftissuefactortargetedradioimmunotherapyinthestromarichpancreaticcancermodelbxpc3
AT matsumurayasuhiro naturalsulfoglycolipidderivativesqapimprovesthetherapeuticefficacyoftissuefactortargetedradioimmunotherapyinthestromarichpancreaticcancermodelbxpc3
AT sugawarafumio naturalsulfoglycolipidderivativesqapimprovesthetherapeuticefficacyoftissuefactortargetedradioimmunotherapyinthestromarichpancreaticcancermodelbxpc3
AT sakaguchikengo naturalsulfoglycolipidderivativesqapimprovesthetherapeuticefficacyoftissuefactortargetedradioimmunotherapyinthestromarichpancreaticcancermodelbxpc3
AT higashitatsuya naturalsulfoglycolipidderivativesqapimprovesthetherapeuticefficacyoftissuefactortargetedradioimmunotherapyinthestromarichpancreaticcancermodelbxpc3