Takanori Ito - Academia.edu (original) (raw)

Papers by Takanori Ito

Journal of gastroenterology and hepatology, Jan 13, 2015

Hepatocellular carcinoma (HCC) can develop in patients with chronic hepatitis C after they have a... more Hepatocellular carcinoma (HCC) can develop in patients with chronic hepatitis C after they have achieved a sustained virologic response (SVR) to antiviral therapy, i.e., eradication of hepatitis C virus (HCV). Thus, surveillance for HCC remains necessary after SVR. We investigated factors that are predictive of HCC in HCV-infected patients who achieved SVR. The incidence and risk factors for HCC were evaluated in 522 patients who achieved SVR with interferon-based antiviral therapy for HCV. Patients maintained regular follow-up every 6 months for HCC surveillance. The FIB-4 index and aspartate aminotransferase to platelet count ratio index calculated based on laboratory data at the time that SVR was documented (SVR24). Patients continued follow-up visits for 1.0 to 22.9 years (median, 7.2 years) after SVR. HCC developed in 18 patients. The incidence of HCC was 1.2% at five years and 4.3% at ten years. Use of peginterferon or ribavirin for treatment and a history of antiviral therapy...

Nucleic acids research, Jan 15, 2003

The synthesis of oligonucleotides (ODNs) containing 5-(N-aminohexyl)carbamoyl-2'-O-methylurid... more The synthesis of oligonucleotides (ODNs) containing 5-(N-aminohexyl)carbamoyl-2'-O-methyluridine (D) is described, and thermal stability and resistance to enzymatic hydrolysis of the ODNs are compared with ODNs containing 5-(N-aminohexyl)carbamoyl-2'-deoxyuridine (H). The ODNs containing D and the complementary RNA demonstrated a duplex thermal stabilization of 0.4-3.9 degrees C per modification depending on the position and the number, while the ODNs containing H with the RNA showed slightly less effective thermal stabilization. Further more, the ODNs containing D were found to be more resistant to nucleolytic hydrolysis, not only by snake venom phosphodiesterase (SVPD; a 3'-exonuclease) but also by DNase I (an endonuclease). The half-life of the 17mer containing five molecules of D against nucleolytic hydrolysis by SVPD was 240 times greater than the unmodified 17mer ODN, which is 1.8 times greater than the ODN containing 5Hs in the same sequence. Against DNase I, the ...

Nucleic Acids Research, 2007

containing 5-(N-aminohexyl) carbamoyl-modified uracils have promising features for applications a... more containing 5-(N-aminohexyl) carbamoyl-modified uracils have promising features for applications as antigene and antisense therapies. Relative to unmodified DNA, oligonucleotides containing 5-(N-aminohexyl)carbamoyl-2 0 -deoxyuridine ( N U) or 5-(N-aminohexyl)carbamoyl-2 0 -O-methyluridine ( N U m ), respectively exhibit increased binding affinity for DNA and RNA, and enhanced nuclease resistance. To understand the structural implications of N U and N U m substitutions, we have determined the X-ray crystal structures of DNA:DNA duplexes containing either N U or N U m and of DNA:RNA hybrid duplexes containing N U m . The aminohexyl chains are fixed in the major groove through hydrogen bonds between the carbamoyl amino groups and the uracil O4 atoms. The terminal ammonium cations on these chains could interact with the phosphate oxygen anions of the residues in the target strands. These interactions partly account for the increased target binding affinity and nuclease resistance. In contrast to N U, N U m decreases DNA binding affinity. This could be explained by the drastic changes in sugar puckering and in the minor groove widths and hydration structures seen in the N U m containing DNA:DNA duplex structure. The conformation of N U m , however, is compatible with the preferred conformation in DNA:RNA hybrid duplexes. Furthermore, the ability of N U m to render the duplexes with altered minor grooves may increase nuclease resistance and elicit RNase H activity.

Journal of Hepatology, 2013

The gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic r... more The gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) often depicts non-hypervascular hypointense hepatic nodules during the hepatobiliary phase in patients with hepatocellular carcinoma (HCC). It is unclear whether the presence of these nodules is associated with HCC recurrence after hepatectomy. We conducted a prospective observational study to investigate the impact of the presence of non-hypervascular hypointense hepatic nodules on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI on the recurrence of HCC after hepatectomy. A total of 77 patients who underwent hepatectomy for primary, non-recurrent, hypervascular HCC were prospectively followed up after hepatectomy. Post-operative recurrence rates were compared according to the presence of non-hypervascular hypointense nodules on preoperative Gd-EOB-DTPA-enhanced MRI. Recurrence rates after hepatectomy were higher in patients with non-hypervascular hypointense nodules (risk ratio 1.9396 [1.3615-2.7222]) and the presence of non-hypervascular hypointense nodules was an independent factor associated with postoperative recurrence (risk ratio 2.1767 [1.5089-3.1105]) along with HCC differentiation and portal vein invasion. While no differences were found in the rate of intrahepatic metastasis recurrence based on the preoperative presence of non-hypervascular hypointense hepatic nodules, the rate of multicentric recurrence was significantly higher in patients with preoperative non-hypervascular hypointense hepatic nodules. Patients with preoperative non-hypervascular hypointense hepatic nodules detected during the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI are at higher risk of HCC recurrence after hepatectomy, mainly due to multicentric recurrence.

Journal of Gastroenterology, 2014

The macroscopic type of hepatocellular carcinoma (HCC) is a predictor of prognosis. We clarified ... more The macroscopic type of hepatocellular carcinoma (HCC) is a predictor of prognosis. We clarified the diagnostic value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in the macroscopic classification of nodular hepatocellular carcinoma (HCC) as compared to angiography-assisted computed tomography (CT). A total of 71 surgically resected nodular HCCs with a maximum diameter of ≤5 cm were investigated. HCCs were evaluated preoperatively using Gd-EOB-DTPA-enhanced MRI and angiography-assisted CT. HCCs were pathologically classified as simple nodular (SN), SN with extranodular growth (SN-EG), or confluent multinodular (CMN). SN-EG and CMN were grouped as non-SN. Five readers independently reviewed the images using a five-point scale. We examined the accuracy of both imaging modalities in differentiating between SN and non-SN HCC. Overall, the area under the receiver operating characteristic curve (A z ) for the diagnosis of non-SN did not differ between Gd-EOB-DTPA-enhanced MRI and angiography-assisted CT [0.879 (95% confidence interval (CI), 0.779-0.937) and 0.845 (95% CI, 0.723-0.919), respectively]. For HCCs &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;2 cm, the A z for Gd-EOB-DTPA-enhanced MRI was greater than 0.9. The sensitivity, specificity, and accuracy of Gd-EOB-DTPA-enhanced MRI for identifying non-SN were equal to or higher than values with angiography-assisted CT in all three categories (all tumors, ≤2 cm, and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;2 cm), but the differences were not statistically significant. Using Gd-EOB-DTPA-enhanced MRI to assess the macroscopic findings in nodular HCC was equal or superior to using angiography-assisted CT.