Quantitative evaluation of the intratumoral distribution of platinum in oxaliplatin-treated rectal cancer

In situ visualization of platinum via synchrotron radiation X-ray fluorescence spectrometry

Ryo Koba, Hayato Fujita, Maiko Nishibori, Kiyoshi Saeki, Kinuko Nagayoshi, Yoshihiko Sadakari, Shuntaro Nagai, Oki Sekizawa, Kiyofumi Nitta, Tatsuya Manabe, Takashi Ueki, Tatsuhiro Ishida, Yoshinao Oda, Masafumi Nakamura

研究成果: ジャーナルへの寄稿記事

抄録

Oxaliplatin (l-OHP), a platinum-based drug, is a key chemotherapeutic agent for colorectal cancer (CRC), but drug resistance and toxic effects have been major limitations of its use. Synchrotron radiation X-ray fluorescence spectrometry (SR-XRF) is a rapid, nondestructive technique for monitoring the distribution of metals and trace elements in cells or tissue samples. We applied SR-XRF to visualize the distribution of platinum and other elements in 30 rectal cancer specimens resected from patients who received l-OHP-based preoperative chemotherapy and quantified platinum concentration in the tumor epithelium and stroma, respectively, using calibration curves. The platinum concentration in rectal cancer tissue ranged 2.85–11.44 ppm, and the detection limit of platinum was 1.848 ppm. In the tumor epithelium, the platinum concentration was significantly higher in areas of degeneration caused by chemotherapy than in nondegenerated area (p < 0.001). Conversely, in the tumor stroma, the platinum concentration was significantly higher in patients with limited therapeutic responses than in those with strong therapeutic responses (p < 0.001). Furthermore, multivariate analysis illustrated that higher platinum concentration in the tumor stroma was an independent predictive factor of limited histologic response (odds ratio; 19.99, 95% confidence interval; 2.04–196.37, p = 0.013). This is the first study to visualize and quantify the distribution of platinum in human cancer tissues using SR-XRF. These results suggest that SR-XRF analysis may contribute to predicting the therapeutic effect of l-OHP-based chemotherapy by quantifying the distribution of platinum.

元の言語英語
ジャーナルInternational Journal of Cancer
DOI
出版物ステータス受理済み/印刷中 - 1 1 2019

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oxaliplatin
X-Ray Emission Spectrometry
Synchrotrons
Rectal Neoplasms
Platinum
Radiation
Neoplasms
Drug Therapy
Epithelium

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Quantitative evaluation of the intratumoral distribution of platinum in oxaliplatin-treated rectal cancer : In situ visualization of platinum via synchrotron radiation X-ray fluorescence spectrometry. / Koba, Ryo; Fujita, Hayato; Nishibori, Maiko; Saeki, Kiyoshi; Nagayoshi, Kinuko; Sadakari, Yoshihiko; Nagai, Shuntaro; Sekizawa, Oki; Nitta, Kiyofumi; Manabe, Tatsuya; Ueki, Takashi; Ishida, Tatsuhiro; Oda, Yoshinao; Nakamura, Masafumi.

:: International Journal of Cancer, 01.01.2019.

研究成果: ジャーナルへの寄稿記事

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title = "Quantitative evaluation of the intratumoral distribution of platinum in oxaliplatin-treated rectal cancer: In situ visualization of platinum via synchrotron radiation X-ray fluorescence spectrometry",
abstract = "Oxaliplatin (l-OHP), a platinum-based drug, is a key chemotherapeutic agent for colorectal cancer (CRC), but drug resistance and toxic effects have been major limitations of its use. Synchrotron radiation X-ray fluorescence spectrometry (SR-XRF) is a rapid, nondestructive technique for monitoring the distribution of metals and trace elements in cells or tissue samples. We applied SR-XRF to visualize the distribution of platinum and other elements in 30 rectal cancer specimens resected from patients who received l-OHP-based preoperative chemotherapy and quantified platinum concentration in the tumor epithelium and stroma, respectively, using calibration curves. The platinum concentration in rectal cancer tissue ranged 2.85–11.44 ppm, and the detection limit of platinum was 1.848 ppm. In the tumor epithelium, the platinum concentration was significantly higher in areas of degeneration caused by chemotherapy than in nondegenerated area (p < 0.001). Conversely, in the tumor stroma, the platinum concentration was significantly higher in patients with limited therapeutic responses than in those with strong therapeutic responses (p < 0.001). Furthermore, multivariate analysis illustrated that higher platinum concentration in the tumor stroma was an independent predictive factor of limited histologic response (odds ratio; 19.99, 95{\%} confidence interval; 2.04–196.37, p = 0.013). This is the first study to visualize and quantify the distribution of platinum in human cancer tissues using SR-XRF. These results suggest that SR-XRF analysis may contribute to predicting the therapeutic effect of l-OHP-based chemotherapy by quantifying the distribution of platinum.",
author = "Ryo Koba and Hayato Fujita and Maiko Nishibori and Kiyoshi Saeki and Kinuko Nagayoshi and Yoshihiko Sadakari and Shuntaro Nagai and Oki Sekizawa and Kiyofumi Nitta and Tatsuya Manabe and Takashi Ueki and Tatsuhiro Ishida and Yoshinao Oda and Masafumi Nakamura",
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T1 - Quantitative evaluation of the intratumoral distribution of platinum in oxaliplatin-treated rectal cancer

T2 - In situ visualization of platinum via synchrotron radiation X-ray fluorescence spectrometry

AU - Koba, Ryo

AU - Fujita, Hayato

AU - Nishibori, Maiko

AU - Saeki, Kiyoshi

AU - Nagayoshi, Kinuko

AU - Sadakari, Yoshihiko

AU - Nagai, Shuntaro

AU - Sekizawa, Oki

AU - Nitta, Kiyofumi

AU - Manabe, Tatsuya

AU - Ueki, Takashi

AU - Ishida, Tatsuhiro

AU - Oda, Yoshinao

AU - Nakamura, Masafumi

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Oxaliplatin (l-OHP), a platinum-based drug, is a key chemotherapeutic agent for colorectal cancer (CRC), but drug resistance and toxic effects have been major limitations of its use. Synchrotron radiation X-ray fluorescence spectrometry (SR-XRF) is a rapid, nondestructive technique for monitoring the distribution of metals and trace elements in cells or tissue samples. We applied SR-XRF to visualize the distribution of platinum and other elements in 30 rectal cancer specimens resected from patients who received l-OHP-based preoperative chemotherapy and quantified platinum concentration in the tumor epithelium and stroma, respectively, using calibration curves. The platinum concentration in rectal cancer tissue ranged 2.85–11.44 ppm, and the detection limit of platinum was 1.848 ppm. In the tumor epithelium, the platinum concentration was significantly higher in areas of degeneration caused by chemotherapy than in nondegenerated area (p < 0.001). Conversely, in the tumor stroma, the platinum concentration was significantly higher in patients with limited therapeutic responses than in those with strong therapeutic responses (p < 0.001). Furthermore, multivariate analysis illustrated that higher platinum concentration in the tumor stroma was an independent predictive factor of limited histologic response (odds ratio; 19.99, 95% confidence interval; 2.04–196.37, p = 0.013). This is the first study to visualize and quantify the distribution of platinum in human cancer tissues using SR-XRF. These results suggest that SR-XRF analysis may contribute to predicting the therapeutic effect of l-OHP-based chemotherapy by quantifying the distribution of platinum.

AB - Oxaliplatin (l-OHP), a platinum-based drug, is a key chemotherapeutic agent for colorectal cancer (CRC), but drug resistance and toxic effects have been major limitations of its use. Synchrotron radiation X-ray fluorescence spectrometry (SR-XRF) is a rapid, nondestructive technique for monitoring the distribution of metals and trace elements in cells or tissue samples. We applied SR-XRF to visualize the distribution of platinum and other elements in 30 rectal cancer specimens resected from patients who received l-OHP-based preoperative chemotherapy and quantified platinum concentration in the tumor epithelium and stroma, respectively, using calibration curves. The platinum concentration in rectal cancer tissue ranged 2.85–11.44 ppm, and the detection limit of platinum was 1.848 ppm. In the tumor epithelium, the platinum concentration was significantly higher in areas of degeneration caused by chemotherapy than in nondegenerated area (p < 0.001). Conversely, in the tumor stroma, the platinum concentration was significantly higher in patients with limited therapeutic responses than in those with strong therapeutic responses (p < 0.001). Furthermore, multivariate analysis illustrated that higher platinum concentration in the tumor stroma was an independent predictive factor of limited histologic response (odds ratio; 19.99, 95% confidence interval; 2.04–196.37, p = 0.013). This is the first study to visualize and quantify the distribution of platinum in human cancer tissues using SR-XRF. These results suggest that SR-XRF analysis may contribute to predicting the therapeutic effect of l-OHP-based chemotherapy by quantifying the distribution of platinum.

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