Monitoring trifluridine incorporation in the peripheral blood mononuclear cells of colorectal cancer patients under trifluridine/tipiracil medication

Ryota Nakanishi, Hiroyuki Kitao, Mamoru Kiniwa, Yosuke Morodomi, Makoto Iimori, Junji Kurashige, Masahiko Sugiyama, Yuichiro Nakashima, Hiroshi Saeki, Eiji Oki, Yoshihiko Maehara

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Trifluridine/tipiracil (TFTD, TAS-102) is an orally administrated anti-cancer drug with efficacy validated for patients with metastatic colorectal cancer (mCRC). Trifluridine (FTD) is an active cytotoxic component of TFTD and mediates the anticancer effect via its incorporation into DNA. However, it has not been examined whether FTD is incorporated into the tissues of patients who received TFTD medication. By detecting FTD incorporation into DNA by a specific antibody, we successfully detected FTD in the bone marrow and spleen cells isolated from FTD-challenged mice as well as human peripheral blood mononuclear cells (PBMCs) activated with phytohemagglutinin-P and exposed to FTD in vitro. FTD was also detected in PBMCs isolated from mCRC patients who had administrated TFTD medication. Intriguingly, weekly evaluation of PBMCs from mCRC patients revealed the percentage of FTD-positive PBMCs increased and decreased in parallel with the administration and cessation of TFTD medication, respectively. To our knowledge, this is the first report to detect an active cytotoxic component of a chemotherapeutic drug in clinical specimens using a specific antibody. This technique may enable us to predict the clinical benefits or the adverse effects of TFTD in mCRC patients.

Original languageEnglish
Article number16969
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

Fingerprint

Trifluridine
Colorectal Neoplasms
Blood Cells
Antibodies
DNA
Bone Marrow Cells
Pharmaceutical Preparations
Spleen
Neoplasms

All Science Journal Classification (ASJC) codes

  • General

Cite this

Monitoring trifluridine incorporation in the peripheral blood mononuclear cells of colorectal cancer patients under trifluridine/tipiracil medication. / Nakanishi, Ryota; Kitao, Hiroyuki; Kiniwa, Mamoru; Morodomi, Yosuke; Iimori, Makoto; Kurashige, Junji; Sugiyama, Masahiko; Nakashima, Yuichiro; Saeki, Hiroshi; Oki, Eiji; Maehara, Yoshihiko.

In: Scientific reports, Vol. 7, No. 1, 16969, 01.12.2017.

Research output: Contribution to journalArticle

Nakanishi, Ryota ; Kitao, Hiroyuki ; Kiniwa, Mamoru ; Morodomi, Yosuke ; Iimori, Makoto ; Kurashige, Junji ; Sugiyama, Masahiko ; Nakashima, Yuichiro ; Saeki, Hiroshi ; Oki, Eiji ; Maehara, Yoshihiko. / Monitoring trifluridine incorporation in the peripheral blood mononuclear cells of colorectal cancer patients under trifluridine/tipiracil medication. In: Scientific reports. 2017 ; Vol. 7, No. 1.
@article{676fa14a3dc34d2fb6b4125d2d817e69,
title = "Monitoring trifluridine incorporation in the peripheral blood mononuclear cells of colorectal cancer patients under trifluridine/tipiracil medication",
abstract = "Trifluridine/tipiracil (TFTD, TAS-102) is an orally administrated anti-cancer drug with efficacy validated for patients with metastatic colorectal cancer (mCRC). Trifluridine (FTD) is an active cytotoxic component of TFTD and mediates the anticancer effect via its incorporation into DNA. However, it has not been examined whether FTD is incorporated into the tissues of patients who received TFTD medication. By detecting FTD incorporation into DNA by a specific antibody, we successfully detected FTD in the bone marrow and spleen cells isolated from FTD-challenged mice as well as human peripheral blood mononuclear cells (PBMCs) activated with phytohemagglutinin-P and exposed to FTD in vitro. FTD was also detected in PBMCs isolated from mCRC patients who had administrated TFTD medication. Intriguingly, weekly evaluation of PBMCs from mCRC patients revealed the percentage of FTD-positive PBMCs increased and decreased in parallel with the administration and cessation of TFTD medication, respectively. To our knowledge, this is the first report to detect an active cytotoxic component of a chemotherapeutic drug in clinical specimens using a specific antibody. This technique may enable us to predict the clinical benefits or the adverse effects of TFTD in mCRC patients.",
author = "Ryota Nakanishi and Hiroyuki Kitao and Mamoru Kiniwa and Yosuke Morodomi and Makoto Iimori and Junji Kurashige and Masahiko Sugiyama and Yuichiro Nakashima and Hiroshi Saeki and Eiji Oki and Yoshihiko Maehara",
year = "2017",
month = "12",
day = "1",
doi = "10.1038/s41598-017-17282-5",
language = "English",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Monitoring trifluridine incorporation in the peripheral blood mononuclear cells of colorectal cancer patients under trifluridine/tipiracil medication

AU - Nakanishi, Ryota

AU - Kitao, Hiroyuki

AU - Kiniwa, Mamoru

AU - Morodomi, Yosuke

AU - Iimori, Makoto

AU - Kurashige, Junji

AU - Sugiyama, Masahiko

AU - Nakashima, Yuichiro

AU - Saeki, Hiroshi

AU - Oki, Eiji

AU - Maehara, Yoshihiko

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Trifluridine/tipiracil (TFTD, TAS-102) is an orally administrated anti-cancer drug with efficacy validated for patients with metastatic colorectal cancer (mCRC). Trifluridine (FTD) is an active cytotoxic component of TFTD and mediates the anticancer effect via its incorporation into DNA. However, it has not been examined whether FTD is incorporated into the tissues of patients who received TFTD medication. By detecting FTD incorporation into DNA by a specific antibody, we successfully detected FTD in the bone marrow and spleen cells isolated from FTD-challenged mice as well as human peripheral blood mononuclear cells (PBMCs) activated with phytohemagglutinin-P and exposed to FTD in vitro. FTD was also detected in PBMCs isolated from mCRC patients who had administrated TFTD medication. Intriguingly, weekly evaluation of PBMCs from mCRC patients revealed the percentage of FTD-positive PBMCs increased and decreased in parallel with the administration and cessation of TFTD medication, respectively. To our knowledge, this is the first report to detect an active cytotoxic component of a chemotherapeutic drug in clinical specimens using a specific antibody. This technique may enable us to predict the clinical benefits or the adverse effects of TFTD in mCRC patients.

AB - Trifluridine/tipiracil (TFTD, TAS-102) is an orally administrated anti-cancer drug with efficacy validated for patients with metastatic colorectal cancer (mCRC). Trifluridine (FTD) is an active cytotoxic component of TFTD and mediates the anticancer effect via its incorporation into DNA. However, it has not been examined whether FTD is incorporated into the tissues of patients who received TFTD medication. By detecting FTD incorporation into DNA by a specific antibody, we successfully detected FTD in the bone marrow and spleen cells isolated from FTD-challenged mice as well as human peripheral blood mononuclear cells (PBMCs) activated with phytohemagglutinin-P and exposed to FTD in vitro. FTD was also detected in PBMCs isolated from mCRC patients who had administrated TFTD medication. Intriguingly, weekly evaluation of PBMCs from mCRC patients revealed the percentage of FTD-positive PBMCs increased and decreased in parallel with the administration and cessation of TFTD medication, respectively. To our knowledge, this is the first report to detect an active cytotoxic component of a chemotherapeutic drug in clinical specimens using a specific antibody. This technique may enable us to predict the clinical benefits or the adverse effects of TFTD in mCRC patients.

UR - http://www.scopus.com/inward/record.url?scp=85037146747&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85037146747&partnerID=8YFLogxK

U2 - 10.1038/s41598-017-17282-5

DO - 10.1038/s41598-017-17282-5

M3 - Article

VL - 7

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 16969

ER -