Results of Hepatectomy for Hepatocellular Carcinoma at the National Cancer Center Hospital

The number of hepatectomies has increased greatly in recent years. Surgery for hepatocellular carcinoma (HCC) in the normal liver has not increased. However, the increase in numbers of hepatectomies for HCC associated with liver cirrhosis is remarkable. More than 80% of our hepatectomy cases were cirrhotic and about 80% of these cirrhotic cases had HCCs 5cm or less in diameter. The operative mortality rate has improved in the latter half of this series, from 10.1% (9/89) to 1.5% (5/338), in spite of an increase in cases with poor liver function. This corresponds to a decrease in the mean value of the annual operative blood loss. The survival rates after hepatectomy for all cases (n = 378) were 40.6% ± 6.6 (% ± SE) for 5 year and 22.7% ± 5.3 for 10 year at the end of 1988. A difference of the 5-year survival rate between the patients operated on before 1981 (n = 78, 25.6% ± 4.9) and after 1982 (n = 300, 46.1% ± 4.8) was observed (p<0.05). Because the cancer-free survival rates of the patients operated on in the two periods, before 1981 and after 1982, were almost the same, the recent improvement of the survival rates seems to be due to a prolongation of survival time after recurrence

Feasibility and Efficacy of Definitive Radiotherapy with 66 Gy and Concurrent Carboplatin-Paclitaxel Chemotherapy for Stage III Non-Small Cell Lung Cancer.

Purpose/Objectives : This study was conducted to assess the feasibility and efficacy of definitive radiotherapy (RT) with a total dose of 66 Gy and concurrent carboplatin-paclitaxel chemotherapy for patients (pts) with stage Ⅲ non-small celllung cancer. Materials/Methods : Between April 2007 and December 2013，99 pts with non-small cell lung cancer were treated using RT with concurrent carboplatin-paclitaxel chemotherapy in our hospital. Sixty-eight of them received RT with a total dose of 66 Gy. We analyzed 46 Stage Ⅲ pts who had been treated with RT using three-dimensional radiotherapy treatment planning. The prophylactic mediastinal lymph nodes were included in the clinical target volume for RT. The survival rate after the start of RT was estimated using the Kaplan-Meier method. We estimated the cumulative local failure and distant metastasis rates with the Fine-Gray method. Adverse events were evaluated according to the CTCAE (v.4.0). Results : The median age of the pts was 70.9 (52.8-78.7) years old (y.o.). The performance status (PS) of each pt was fairly good (ECOG PS 0: 25, PS 1: 20, PS 3:1), and their clinical stages (UICC 7th) were twenty-nine Ⅲ A and seventeen Ⅲ B. Diagnoses were pathologically confirmed in 32 pts. The median follow-up period was 35.7 (2.0-82.2) months among all pts, and 55.9 (40.1-82.2) months among survivors. The 3- and 5-year Kaplan-Meier overall survival rates were 52.2 and 34.0%，respectively, and the median survival time was 36.6 months. The 3- and 5-year Kaplan-Meier progression-free survival rates were 29.1 and 21.9%，respectively, and the median progression-free survival time was 9.9 months. The 5-year local failure rate was 37.6%, and the 5-year distant metastasis rate was 49.7%. Sixteen (34.8%) pts required steroid administration because of radiation pneumonitis (CTCAE Grade 2 or higher) and two of them died (Grade 5). No other severe non-hematologic toxicity (Grade 3 or higher) was observed. Conclusion : These results suggest that definitive RT with a total dose of 66 Gy and concurrent carboplatin-paclitaxel chemotherapy is feasible and may be promising for pts with Stage Ⅲ non-small cell lung cancer

DNA-PKcsのリジン3241と3260はゲノムの安定性と放射線抵抗性に重要である

DNA-dependent protein kinase (DNA-PK) is a serine/threonine kinase that plays an essential role in the repair of DNA double-strand breaks (DSBs) in the non-homologous end-joining (NHEJ) pathway. The DNA-PK holoenzyme consists of a catalytic subunit (DNA-PKcs) and DNA-binding subunit (Ku70/80, Ku). Ku is a molecular sensor for double-stranded DNA and once bound to DSB ends it recruits DNA-PKcs to the DSB site. Subsequently, DNA-PKcs is activated and heavily phosphorylated, with these phosphorylations modulating DNA-PKcs. Although phosphorylation of DNA-PKcs is well studied, other post-translational modifications of DNA-PKcs are not. In this study, we aimed to determine if acetylation of DNA-PKcs regulates DNA-PKcs-dependent DSB repair. We report that DNA-PKcs is acetylated in vivo and identified two putative acetylation sites, lysine residues 3241 and 3260. Mutating these sites to block potential acetylation results in increased radiosensitive, a slight decrease in DSB repair capacity as assessed by γH2AX resolution, and increased chromosomal aberrations, especially quadriradial chromosomes. Together, our results provide evidence that acetylation potentially regulates DNA-PKcs.博士（医学）・甲第670号・平成29年6月28日Copyright © 2016 Elsevier Inc. All rights reserved

DNA-PKcsのリジン3241と3260はゲノムの安定性と放射線抵抗性に重要である

DNA-dependent protein kinase (DNA-PK) is a serine/threonine kinase that plays an essential role in the repair of DNA double-strand breaks (DSBs) in the non-homologous end-joining (NHEJ) pathway. The DNA-PK holoenzyme consists of a catalytic subunit (DNA-PKcs) and DNA-binding subunit (Ku70/80, Ku). Ku is a molecular sensor for double-stranded DNA and once bound to DSB ends it recruits DNA-PKcs to the DSB site. Subsequently, DNA-PKcs is activated and heavily phosphorylated, with these phosphorylations modulating DNA-PKcs. Although phosphorylation of DNA-PKcs is well studied, other post-translational modifications of DNA-PKcs are not. In this study, we aimed to determine if acetylation of DNA-PKcs regulates DNA-PKcs-dependent DSB repair. We report that DNA-PKcs is acetylated in vivo and identified two putative acetylation sites, lysine residues 3241 and 3260. Mutating these sites to block potential acetylation results in increased radiosensitive, a slight decrease in DSB repair capacity as assessed by γH2AX resolution, and increased chromosomal aberrations, especially quadriradial chromosomes. Together, our results provide evidence that acetylation potentially regulates DNA-PKcs.博士（医学）・甲第670号・平成29年6月28日Copyright © 2016 Elsevier Inc. All rights reserved

(1R*,2S*,4S*,5R*)-Cyclo­hexane-1,2:4,5-tetra­carb­oxy­lic dianhydride

The title compound, C10H8O6, a promising raw material to obtain colorless polyimides which are applied to microelectronic and optoelectronic devices, adopts a folded conformation in which the dihedral angle between the two anhydro rings is 55.15 (8)°. The central six-membered ring assumes a conformation inter­mediate between boat and twist-boat. In the crystal, mol­ecules are linked by weak C—H⋯O inter­actions, forming a layer parallel to the bc plane