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A 60-year-old man presented with postoperative recurrence of intrahepatic cholangiocarcinoma with right portal vein tumor thrombosis (PVTT). After failure of standard chemotherapy, a liver biopsy showed that his microsatellite instability (MSI) status was high. Treatment with the immune checkpoint inhibitor (ICI) pembrolizumab was commenced, which resulted in a partial response and resolution of the PVTT. There were no significant immune-related adverse events. According to recently published reports, the frequency of MSI-high biliary tract cancer (BTC) is about 0%-2.1%, which is extremely rare. However, ICIs may be effective in patients with MSI-high BTC, such as the present patient.

Unnatural nucleosides are attracting interest as potential diagnostic tools, medicines, and functional molecules. However, it is difficult to couple unnatural nucleobases to the 1′-position of ribose in high yield and with β-regioselectivity. Purine nucleoside phosphorylase (PNP, EC2.4.2.1) is a metabolic enzyme that catalyses the conversion of inosine to ribose-1α-phosphate and free hypoxanthine in phosphate buffer with 100% α-selectivity. We explored whether PNP can be used to synthesize unnatural nucleosides. PNP catalysed the reaction of thymidine as a ribose donor with purine to produce 2′-deoxynebularine (3, β form) in high conversion (80%). It also catalysed the phosphorolysis of thymidine and introduced a pyrimidine base with a halogen atom substituted at the 5-position into the 1′-position of ribose in moderate yield (52–73%), suggesting that it exhibits loose selectivity. For a bulky purine substrate [e.g., 6-(N,N-di-propylamino)], the yield was lower, but addition of a polar solvent such as dimethyl sulfoxide (DMSO) increased the yield to 74%. PNP also catalysed the reaction between thymidine and uracil possessing a large functional fluorescent group, 5-(coumarin-7-oxyhex-5-yn) uracil (C4U). Conversion to 2′-deoxy-[5-(coumarin-7-oxyhex-5-yn)] uridine (dRC4U) was drastically enhanced by DMSO addition. Docking simulations between dRC4U and E. coli PNP (PDB 3UT6) showed the uracil moiety in the active-site pocket of PNP with the fluorescent moiety at the entrance of the pocket. Thus, the bulky fluorescent moiety has little influence on the coupling reaction. In summary, we have developed an efficient method for producing unnatural nucleosides, including purine derivatives and modified uracil, using PNP.

A 72‒year‒old man with hepatocellular carcinoma(HCC)was treated with transarterial chemoembolization(TACE)and radiofrequency ablation(RFA). Six months after RFA, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd‒ EOB‒DTPA)‒enhanced magnetic resonance imaging(MRI)revealed multiple metastatic recurrences in the liver. TACE was performed for the recurrent HCC. However, the treatment response on the Gd‒EOB‒DTPA‒enhanced MRI showed that the lesions had advanced and that the liver metastatic nodules had ring‒shaped contrast effects. We suspected metastatic liver cancer based on the MRI findings and performed colonoscopy. Finally, we diagnosed the patient with multiple hepatic metastases of sigmoid colon cancer based on the results of the endoscopic colon biopsy and percutaneous liver tumor biopsy. In conclusion, we had a teachable case of the treatment of HCC.

It is very difficult to treat patients with liver metastasis presenting with jaundice or cachexia. We herein report a successfully treated case of huge liver metastasis of gastrointestinal stromal tumor (GIST) that initially showed jaundice and cachexia. The patient was a woman in her early 40 s. She had a history of duodenal GIST 4 years before this admission. She was admitted to our hospital for abdominal fullness and anorexia. Abdominal computed tomography revealed huge liver metastasis of GIST. She showed jaundice and cancer cachexia with a modified Glasgow Prognostic Score of 2. After applying nutritional support, 400 mg of imatinib was administered. Although leg edema transiently worsened, the withdrawal of imatinib and administration of diuretics improved it. Imatinib was re-administered, and nutritional support was continued. The total bilirubin level decreased, and the serum albumin level increased. The tumor gradually decreased in size. Finally, she received surgical resection after 16 months of treatment with imatinib. Although adjuvant imatinib administration was continued after surgery, and no recurrence was observed as of 18 months after surgery.

This paper analyses early 20th-century Japanese translations of Hardy's Tess of the d'Urbervilles and demonstrates the significant impact of censorship and the emergence of mass publication on the image of Hardy and his fiction among contemporary Japanese readers, scholars, critics and translators. It argues that the effects of the Japanese censorship law were complex: the translated text of Tess of the d'Urbervilles contained word games, evoking a strange kind of erotic pleasure while pretending to de-eroticise Tess's story. The paper also discusses the ideas that the image of ‘pure Tess’ was nonetheless shaped by a series of translators and that publishers' marketing strategies contributed to the crystallisation and wide dissemination of this image in Japan.

A study of the significant compositional changes in Hardy's manuscript revisions and their impact upon characterization, notably upon the characters of Newson and Susan.

【背景と目的】 放射線治療を受けている乳がん患者の気持ちを明らかにした研究が少ない. そこで乳がん患者の放射線治療経過に伴う気持ちの変化を明らかにし, 看護支援を検討する. 【対象と方法】 研究参加に同意の得られた放射線治療を受けた乳がん患者6名で, 半構成的面接法及び看護記録, 診療記録からデータを収集した. 質的帰納的手法により患者の気持ちに関する言語をコード化し, 類似性に沿ってサブカテゴリー・カテゴリー化へと抽象化した. 【結果】 放射線治療開始時の気持ちは「がんと放射線治療の受容」「がんと放射線治療の苦悩」「家族や仲間に求める癒し」「病気回復と医療への期待」, 放射線治療中間時は「放射線治療を生活の一部として受容」「放射線治療を受けている苦悩」「他者との関係における心強さ」「将来への不安と希望」, 放射線治療終了時は「放射線治療が終了した安堵感と将来への希望」「症状・副作用・再発に対する苦悩」「他者から受けたサポートへの感謝」「医療・医療従事者への要望」というカテゴリーが明らかになった. 【結語】 放射線治療を受ける乳がん患者への看護支援は, 気持ちの葛藤に合わせた情報の提供と適切な技術の提供が重要であることが示唆された.

Sixty year-old male positive for both HCV-RNA and HBsAg was treated by triple therapy of peginterferon alpha2b, ribavirin and telaprevir. Eight weeks after the beginning of the therapy, the patient developed drug induced hypersensitivity syndrome (DIHS) with general erythema multiforme and 64 times anti-HHV6 antibody elevation. Sixty milligram of prednisolone was administered with gradual dose reduction and the skin lesion was improved. HBV-DNA and transaminase elevated one week after the steroid induction and entecavir improved them. DIHS itself and the aggravation of hepatitis B by corticosteroid should be kept in mind in cases with dual infection of HBV and HCV treated by antivirals including telaprevir.

Herein, we describe β-selective coupling between a modified uracil and a deoxyribose to produce functionalized nucleosides catalyzed by thymidine phosphorylase derived from Escherichia coli. This enzyme mediates nucleobase-exchange reactions to convert unnatural nucleosides possessing a large functional group such as a fluorescent molecule, coumarin or pyrene, linked via an alkyl chain at the C5 position of uracil. 5-(Coumarin-7-oxyhex-5-yn)uracil (C4U) displayed 57.2% conversion at 40% DMSO concentration in 1.0 mM phosphate buffer pH 6.8 to transfer thymidine to an unnatural nucleoside with C4U as the base. In the case of using 5-(pyren-1-methyloxyhex-5-yn)uracil (P4U) as the substrate, TP also could catalyse the reaction to generate a product with a very large functional group at 50% DMSO concentration (21.6% conversion). We carried out docking simulations using MF myPrest for the modified uracil bound to the active site of TP. The uracil moiety of the substrate binds to the active site of TP, with the fluorescent moiety linked to the C5 position of the nucleobase located outside the surface of the enzyme. As a consequence, the bulky fluorescent moiety binding to uracil has little influence on the coupling reaction.

It is a known fact that the compressive strength and ductility of concrete can be considerably improved by lateral confinement. In this study, a ductility-type seismic retrofitting technique of RC columns by utilizing high-strength steel bars (PC bars) prestressing was applied, which is arranged on the four faces of the RC columns as external hoops. Hence, active confinement due to the tensile forces in the PC bars as well as passive confinement and transverse reinforcement can be expected. Recent axial compression tests showed that the active and passive confinement using PC bar prestressing can considerably improve the stress–strain characteristics of confined concrete. In this paper, the shear resistance mechanism and shear strength of RC columns retrofitted using PC bar prestressing was experimentally investigated under constant axial force and cyclic lateral forces.

We investigated the antimicrobial activities of twelve derivatives of benzyl phenyl sulfide by using Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values against 10 microbial strains. These derivatives of benzyl phenyl sulfides were synthesized by means of the nucleophilic coupling reaction at our laboratory. MIC testing revealed that all synthetic derivatives of benzyl and 4-methoxybenzyl phenyl sulfides had no effect against the tested microbial strains. However, the compounds of 4-nitrobenzyl phenyl sulfide showed antimicrobial activity against many of the tested strains. Above all, 4-nitrobenzyl 4-chlorophenyl sulfide 11 exhibited the strongest and widest ranging inhibitory effects among the twelve synthetic compounds. We researched the antimicrobial activities of the coupling materials of sulfide. As a result, it was considered important for the expression of antimicrobial activities that the sulfide had a 4-nitrobenzyl group and 4-chlorophenyl group in the same molecule as in the case of benzyl phenyl sulfide.

Background: Patients of gastric cancer with meningeal carcinomatosis may suddenly get worse and urgent medical treatment may be needed. Two didactic cases are presented. Case: Case 1 was a 48 years old woman was admitted with headache, neck pain, nausea, transient unconsciousness and liver dysfunction. Thickened gastric wall, lower bile duct stenosis was demonstrated by CT. Magnetic resonance imaging of brain showed dilated cerebral ventricle. Type 4 gastric cancer was found out by upper gastrointestinal endoscopy. Lumbar spinal puncture showed elevated cerebrospinal fluid pressure and malignant cells. Hydrocephalus and visual impairment got worse rapidly and she died on the 3rd hospital day by central respiratory failure. Case 2 was a 46 years old woman. After the surgical treatment for the gastric cancer, six courses of the combination chemotherapy of S-1 plus cisplatinum were performed as adjuvant chemotherapy. The chemotherapy could not withhold the progression and metastases to ovary and lymph nodes developed. Meningeal carcinomatosis developed and induced total blindness and hydrocephalus. To improve the cerebrospinal fluid pressure and meningeal carcinomatosis, intrathecal chemotherapy was initiated using Ommaya reservoir. She survived two months and finally died of respiratory failure. Discussion: Since the hydrocephalus accompanied by gastric cancer with meningeal carcinomatosis usually progress rapidly, prompt ventricular drainage is useful and mandatory to overcome oncology emergency such as progressive hydrocephalus with total blindness and respiratory failure.

MK615, a compound extracted from the Japanese apricot “Prunus mume” has been reported to have in vitro anti-tumor activities against several cancer cell lines, including hepatocellular carcinoma (HCC). However, the clinical effects and feasibility of administering MK615 for patients with HCC were unknown. We experienced a case with advanced HCC for which MK615 was effective against both lymph node and pulmonary metastases. A 60-year-old female underwent surgical resection of a 9 cm HCC in the right lobe. The pathological diagnosis was moderately differentiated HCC with vascular invasion. The HCC recurred in the liver 8 mo after the surgery. Radiofrequency ablation and transarterial infusion chemotherapy were performed, but the recurrence was not controlled. One year after the intrahepatic recurrence, pulmonary and lymph metastasis appeared. Sorafenib was administered, but was not effective. Then, MK615 was administered as a final alternative therapy after informed consent was obtained from the patient. Three months later, her alpha-fetoprotein level decrease and both the lymph node and pulmonary metastases decreased in size. The patient has survived for more than 17 mo after the MK615 administration, and was in good condition. Although further investigations are necessary to clarify its safety and efficacy in humans, MK615 may be useful for the treatment of HCC, without serious adverse effects.