- 著者
- Yuto Amano Hiroshi Honda Ryusuke Sawada Yuko Nukada Masayuki Yamane Naohiro Ikeda Osamu Morita Yoshihiro Yamanishi
- 出版者
- The Japanese Society of Toxicology
- 雑誌
- The Journal of Toxicological Sciences (ISSN:03881350)
- 巻号頁・発行日
- vol.45, no.3, pp.137-149, 2020 (Released:2020-03-06)
- 参考文献数
- 47
- 被引用文献数
- 5
In silico models for predicting chemical-induced side effects have become increasingly important for the development of pharmaceuticals and functional food products. However, existing predictive models have difficulty in estimating the mechanisms of side effects in terms of molecular targets or they do not cover the wide range of pharmacological targets. In the present study, we constructed novel in silico models to predict chemical-induced side effects and estimate the underlying mechanisms with high general versatility by integrating the comprehensive prediction of potential chemical-protein interactions (CPIs) with machine learning. First, the potential CPIs were comprehensively estimated by chemometrics based on the known CPI data (1,179,848 interactions involving 3,905 proteins and 824,143 chemicals). Second, the predictive models for 61 side effects in the cardiovascular system (CVS), gastrointestinal system (GIS), and central nervous system (CNS) were constructed by sparsity-induced classifiers based on the known and potential CPI data. The cross validation experiments showed that the proposed CPI-based models had a higher or comparable performance than the traditional chemical structure-based models. Moreover, our enrichment analysis indicated that the highly weighted proteins derived from predictive models could be involved in the corresponding functions of the side effects. For example, in CVS, the carcinogenesis-related pathways (e.g., prostate cancer, PI3K-Akt signal pathway), which were recently reported to be involved in cardiovascular side effects, were enriched. Therefore, our predictive models are biologically valid and would be useful for predicting side effects and novel potential underlying mechanisms of chemical-induced side effects.
- 著者
- Tomoyuki NOGUCHI Takashi YOSHIURA Akio HIWATASHI Osamu TOGAO Koji YAMASHITA Kouji KOBAYASHI Futoshi MIHARA Hiroshi HONDA
- 出版者
- Japanese Society for Magnetic Resonance in Medicine
- 雑誌
- Magnetic Resonance in Medical Sciences (ISSN:13473182)
- 巻号頁・発行日
- vol.6, no.2, pp.91-97, 2007 (Released:2007-08-07)
- 参考文献数
- 19
- 被引用文献数
- 17 22
Purpose: Pulsed arterial spin labeling (PASL) is a magnetic resonance (MR) method for measuring cerebral blood flow. Although several validation studies for PASL in animals and humans have been reported, no reports have detailed the fundamental study of PASL using a flow phantom. We compared the true and theoretical flow rates in a flow phantom to confirm the analytical validity of quantitative perfusion imaging with Q2TIPS sequence. Methods: We built a flow phantom consisting of a 40-mm diameter plastic syringe filled with plastic beads and small plastic tubes 4 mm in diameter. Gd-DTPA-doped 8L water solution (0.1 mM) was circulated between the syringe and a tank through a plastic tube by a constant flow pump while the flow rate was adjusted between 0 and 2.61 cm/s. Q2TIPS sequence parameters were TI1=50 ms and TI2=1400 ms. Five imaging slices of 50 subtraction images were acquired sequentially in a distal-to-proximal direction using a single-shot echo planar imaging (EPI) technique. The theoretical flow rate calculated based upon the previously reported kinetic model for Q2TIPS was compared with the true flow rate. Results: A good linear relationship was observed between the theoretical, F′, and true flow rates, F, in a flow rate range of 1.43 to 1.95 cm/s (F′=1.024•F−1.915, R2=0.902). The ratio of theoretical to true flow rate was 92 (+/−) 4%. Conclusion: Flow rate was quantified with reasonable accuracy when the entire amount of labeled bolus within the phantom could be recovered. Our experiment confirmed the analytical validity of Q2TIPS and suggested that blood flow measurement may be feasible using the Q2TIPS pulse sequence and kinetic model of the PASL equation.
- 著者
- Nobuhiro FUJITA Akihiro NISHIE Yoshiki ASAYAMA Kousei ISHIGAMI Yasuhiro USHIJIMA Yukihisa TAKAYAMA Daisuke OKAMOTO Koichiro MORITA Ken SHIRABE Kazuhiro KOTO Yuichiro KUBO Yoshinao ODA Hiroshi HONDA
- 出版者
- Japanese Society for Magnetic Resonance in Medicine
- 雑誌
- Magnetic Resonance in Medical Sciences (ISSN:13473182)
- 巻号頁・発行日
- vol.15, no.1, pp.111-120, 2016-01-01 (Released:2016-01-12)
- 参考文献数
- 28
- 被引用文献数
- 7 9
Purpose: We attempted to clarify the relationship between the signal intensity (SI) in the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance (MR) imaging and the efficacy of hepatic arterial infusion chemotherapy (HAIC) in hepatocellular carcinomas (HCCs).Methods: We enrolled 14 patients with HCCs who underwent gadoxetic acid-enhanced MR imaging prior to HAIC using cisplatin and 5-fluorouracil. In the hepatobiliary phase, we calculated the SI of the HCCs and the background liver. In cases with multiple HCCs, we calculated the SI of the largest lesion. Patients were classified into high (n = 7) and low intensity (n = 7) groups based on the median value of the SI ratio (SI of the tumor/SI of the background liver). We analyzed progression-free survival using the Kaplan-Meier method and the log-rank test. In the 5 patients with a history of HCC surgery, we compared the expression of immunohistochemical organic anion-transporting polypeptide (OATP) 8 between the high and low intensity groups by chi-square test.Results: The SI ratios were 0.568 ± 0.093 (mean ± standard deviation) in the high intensity group and 0.251 ± 0.086 in the low intensity group. Compared to the group with low signal intensity, the group with high signal intensity demonstrated significantly lower serum levels of alpha fetoprotein (AFP) (P = 0.0350), significantly higher progression-free survival (P = 0.0108), better differentiation of tumor grade at histologic examination (P = 0.0253), and significantly higher OATP8 expression (P = 0.0253).Conclusion: Patients with HCCs of high SI ratio in the hepatobiliary phase of gadoxetic acid-enhanced MR imaging can respond better to HAIC.