Current status of hepatocellular carcinoma treatment in Japan: Hepatic arterial infusion chemotherapy

Hepatic arterial infusion chemotherapy (HAIC) allows the long-term administration of cytotoxic drugs to the liver. In Japan, HAIC has traditionally been used to treat patients with advanced hepatocellular carcinoma (HCC) with vascular invasion or multiple intrahepatic lesions, or both. The most common chemotherapy drugs used for HAIC in Japan are 5-fluorouracil and cisplatin. Although HAIC is associated with a high rate of response in some studies, it is not associated with a survival benefit. Furthermore, HAIC is associated with complications that are not observed with systemic chemotherapy, including peptic ulcer, arterial occlusion and port infection. A molecular targeted agent, sorafenib, recently became the standard therapy for advanced HCC on the basis of data from two randomized controlled trials. For this reason, the position of HAIC in the treatment of advanced HCC in Japan is under discussion. Clinical trials must be undertaken to establish standardized protocols and regimens for HAIC, and to determine the efficacy of HAIC in comparison with other therapies for HCC. Without evidence from such trials, HAIC may not find an established role in the treatment of HCC, and may even fall out of use. Recent evidence suggests that HAIC may be useful in combination with molecular targeted therapy; this is currently being investigated in a number of clinical trials. © 2012 Adis Data Information BV. All rights reserved

Reforestation following harvesting of conifer plantations in Japan: Current issues from silvicultural and ecological perspectives

Following the Second World War, the number of Cupressaceae plantations in Japan increased, in accordance with government policy for the restoration of timber resources and conservation of soil and water. Currently, these even-aged plantations occupy approximately 44% of the forested area and 24% of the national land area of Japan. Although many of these plantations have become available as timber resources, there are several silviculture-related problems associated with reforestation following clear-cutting of these plantations. The abundant annual precipitation in Japan allows for dominance by competitive vegetation, which makes natural regeneration difficult and increases the cost of silvicultural operations during and after the planting of seedlings. Because the number of seedling producers has decreased, there has been little incentive to keep seedling production techniques up to date. Additionally, damage to planted seedlings by the overabundant sika deer (Cervus nippon) population has increased dramatically in the last dozen years or so. To determine how to overcome these difficulties, various studies are underway in Japan. For example, seedling studies have examined the relationship between seedling size and competitive ability with other species in reforested areas, and have led to the development of lower-cost systems to produce customized Cupressaceae seedlings, as well as measures to minimize transplanting damage to seedlings. Previous studies have shown that no-weeding operations might lower the risk of sika deer browsing seedlings, although this silvicultural countermeasure may potentially reduce seedling growth. Studies have also examined the types of physical protection against sika deer browsing that are most efficient. We must combine these findings into a unified silvicultural system for successful restoration via lower-cost plantations

Gravitational Kaluza-Klein Modes in Warped Superstring Compactification

The Kaluza-Klein (KK) modes of graviton are studied in the IIB superstring compactification where the warped geometry is realized at the Klebanov-Strassler (KS) throat. Knowledge of the metric of the KS throat enables us to determine their wave functions with good accuracy, without any further specification of the rest of Calabi-Yau space, owing to the localization of the KK modes. Mass spectrum and couplings to the four dimensional fields are computed for some type of the KK modes, and compared to those of the well-known Randall-Sundrum model. We find that the properties of the KK modes of the two models are very different in both the masses and the couplings, and thus they are distinguishable from each other experimentally.Comment: 13 pages, Table 2 replaced, the related discussion modifie

Peretinoin, an acyclic retinoid, improves the hepatic gene signature of chronic hepatitis C following curative therapy of hepatocellular carcinoma

BACKGROUND: The acyclic retinoid, peretinoin, has been shown to be effective for suppressing hepatocellular carcinoma (HCC) recurrence after definitive treatment in a small-scale randomized clinical trial. However, little has been documented about the mechanism by which peretinoin exerts its inhibitory effects against recurrent HCC in humans in vivo. METHODS: Twelve hepatitis C virus-positive patients whose HCC had been eradicated through curative resection or ablation underwent liver biopsy at baseline and week 8 of treatment with either a daily dose of 300 or 600 mg peretinoin. RNA isolated from biopsy samples was subjected to gene expression profile analysis. RESULTS: Peretinoin treatment elevated the expression levels of IGFBP6, RBP1, PRB4, CEBPA, G0S2, TGM2, GPRC5A, CYP26B1, and many other retinoid target genes. Elevated expression was also observed for interferon-, Wnt-, and tumor suppressor-related genes. By contrast, decreased expression levels were found for mTOR- and tumor progression-related genes. Interestingly, gene expression profiles for week 8 of peretinoin treatment could be classified into two groups of recurrence and non-recurrence with a prediction accuracy rate of 79.6% (P<0.05). In the liver of patients with non-recurrence, expression of PDGFC and other angiogenesis genes, cancer stem cell marker genes, and genes related to tumor progression was down-regulated, while expression of genes related to hepatocyte differentiation, tumor suppression genes, and other genes related to apoptosis induction was up-regulated. CONCLUSIONS: Gene expression profiling at week 8 of peretinoin treatment could successfully predict HCC recurrence within 2 years. This study is the first to show the effect of peretinoin in suppressing HCC recurrence in vivo based on gene expression profiles and provides a molecular basis for understanding the efficacy of peretinoin

肝癌免疫遺伝子治療ウイルスベクターの基礎的研究

金沢大学附属病院本年度はレンチウイルスに関する研究を中心に研究を進めた。HBVの表面蛋白を発現するベクターとしてS蛋白のS, M, Lに対応するベクターを作製した。HBVウイルスではこれらの蛋白が一定の比率で表面蛋白を構成していることが知られているため、これらの蛋白の比率を変えて検討した。またHCVに関してはE12, E1p7, E2, E2p7のそれぞれの組み合わせの共感染とE12,E1p7の単独感染にてウイルスを作製して検討した.またこれらの蛋白の発現についてはHBVに関しては市販のHBs抗体を用いたWestern blotを用い,HCVに関してはT7を用いたin vitro transcription and translationにて確認したところ良好な蛋白発現がみられた.これらの系を用いレンチウイルスベクターを作製したがこれらのベクターでのレポーター遺伝子の発現は認められなかった.今回検討したHBV, HCVいずれも培養細胞感染系が一般的ではなく,その検出感度も低いため培養細胞系への感染実験システムが確立されているダックB型肝炎ウイルス(DHBV)を用い検討した.HBVと同様にpreSとS蛋白を発現するベクターを作成して,その蛋白発現をウエスタンブロットにて確認した.その後ダック肝細胞の初代培養細胞を作製し,これらの細胞に作製したウイルス感染させluciferase assayにて検討した.コントロールのVSV-Gの表面蛋白を有するウイルスでは良好な発現を確認できたが,DHBV S蛋白を表面に発現するウイルスとその組み合わせでは発現は確認できなかった.これらの検討でレンチウイルスのパッケージを含めた更なる検討が必要であると考えられた.研究課題/領域番号:15790343, 研究期間(年度):2003 – 2004出典：「肝癌免疫遺伝子治療ウイルスベクターの基礎的研究」研究成果報告書　課題番号15790343（KAKEN：科学研究費助成事業データベース（国立情報学研究所））（https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-15790343/)を加工して作

C末端欠損可溶性組み換え型C型肝炎ウイルスNS5B蛋白質のRNA依存型RNAポリメラーゼ活性

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1325号，学位授与年月日：平成10年6月30日,学位授与年：199

Curved-Tip Disposable Injector (OUReP Injector) to Insert Photoelectric Dye-Coupled Polyethylene Film (OUReP) as Retinal Prosthesis into Subretinal Space of Rabbit Eyes

The photoelectric dye-coupled thin polyethylene film functions as a novel type of retinal prosthesis in subretinal space of the eye. We previously reported a novel disposable injector to insert the thin film into subretinal space of the rabbit eye by vitreous surgery. The injection system composed of two separate parts, injector and loader. A circular film in 5 mm to 10 mm diameter was pulled into a transparent tube of the loader with a commercial 25-gauge forceps. The loader tube was joined with a sleeve to tube tip of the injector. The film in the loader was pushed with a plunger for the loader into the injector tube tip. The loader with the sleeve was removed from the injector tip, and the tube tip with the film was filled with solution. This study reported a small-bore curved-tip disposable injector with outer diameter of 1.6 mm. A curved-tip polypropylene tube was formed by the process of heating and cooling of the tube inserted with a curved guide wire. The plunger for the curved-tip tube was made of a polyphenylsulfone tip connected with a press-fitting inner polypropylene tube to a nylon rod. Bleb retinal detachment in 4 surgically aphakic eyes of rabbits were induced by infusing solution into subretinal space with a 38-gauge polyimide tip, and a retinal tear was made at the edge of retinal detachment with 25-gauge diathermy. The injector tip with the rolled film in 6 mm diameter was inserted from 2 mm wide scleral incision into vitreous and then into subretinal space. The rolled films were released into subretinal space with the tip end inserted into the retinal tear, and the released films were confirmed to stay under the retina with no additional aid. Dissection one month after surgeries confirmed successful implantation of 4 films into subretinal space of each rabbit eye. The curved-tip injector could release the rolled film into the subretinal space without additional effort, compared with the straight-tip injector, and would help surgeons implant photoelectric dye-coupled thin film retinal prosthesis easily at vitreous surgery