The DNA methyltransferase Dnmt1 directly interacts with the SET and RING finger-associated (SRA) domain of the multifunctional protein Uhrf1 to facilitate accession of the catalytic center to hemi-methylated DNA

This research was originally published in Journal of Biological Chemistry. Ahmet Can Berkyurek, Isao Suetake, Kyohei Arita, Kohei Takeshita, Atsushi Nakagawa, Masahiro Shirakawa and Shoji Tajima. The DNA methyltransferase Dnmt1 directly interacts with the SET and RING finger-associated (SRA) domain of the multifunctional protein Uhrf1 to facilitate accession of the catalytic center to hemi-methylated DNA. Journal of Biological Chemistry. 2014; 289, 379-386. © the American Society for Biochemistry and Molecular Biology

Case report: Rehabilitation course in thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly syndrome complicated by cerebral infarction in the left parabolic coronary region

Although thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly (TAFRO) syndrome was first reported in 2010, its pathogenesis and prognosis are still unknown. Moreover, reports on rehabilitation in patients with TAFRO are limited. In severe cases, dyspnea and muscle weakness could impede improvements in activities of daily living (ADL). However, reports on exercise intensity showed no worsening of TAFRO within the load of 11–13 on the Borg scale. Herein, we describe the rehabilitation and progress in a 61-year-old woman with TAFRO syndrome complicated by cerebral infarction from early onset to discharge. After cerebral infarction onset in the perforating artery, she was admitted to the intensive care unit due to decreased blood pressure and underwent continuous hemodiafiltration. Two weeks following transfer to a general ward, the patient started gait training using a brace due to low blood pressure, respiration, and tachycardia. After initiating gait training, increasing the amount of training was difficult due to a high Borg scale of 15–19, elevated respiratory rate, and worsening tachycardia. Furthermore, there was little improvement in muscle strength on the healthy side after continuous training, owing to long-term steroid administration. On day 100 after transfer, the patient was discharged home with a T-cane gait at a monitored level. The patient had severe hemiplegia due to complications with severe TAFRO syndrome delaying early bed release and gait training; tachycardia; and respiratory distress. Additionally, delayed recovery from muscle weakness on the non-paralyzed side made it difficult for the patient to walk and perform ADLs. Despite these issues, low-frequency rehabilitation was useful. However, low-frequency rehabilitation with gait training, using a Borg scale 15–19 orthosis, did not adversely affect the course of TAFRO syndrome

Association between an 8q24 locus and the risk of colorectal cancer in Japanese

<p>Abstract</p> <p>Background</p> <p>A genome-wide association study (GWAS), which assessed multiple ethnicities, reported an association between single nucleotide polymorphisms in the 8q24 region and colorectal cancer risk. Although the association with the identified loci was strong, information on its impact in combination with lifestyle factors is limited.</p> <p>Methods</p> <p>We conducted a case-control study in 481 patients with colorectal cancer (CRC) and 962 sex-age matched non-cancer controls. Data on lifestyle factors, including diet, were obtained by self-administered questionnaire. Two 8q24 loci, rs6983267 and rs10090154, were assessed by the TaqMan method. Associations were then assessed by multivariate logistic regression models that considered potential confounders.</p> <p>Results</p> <p>We found an increased risk of CRC with rs6983267 but not with rs10090154. An allelic OR was 1.22 (1.04-1.44, p for trend = 0.014), which remained significant after adjustment for confounders (OR = 1.25). No statistically significant interaction with potential confounding factors was observed.</p> <p>Conclusion</p> <p>The polymorphism rs6983267 showed a significant association with CRC in a Japanese population. Further investigation of the biological mechanism of this association is warranted.</p

Turicibacter and Acidaminococcus predict immune-related adverse events and efficacy of immune checkpoint inhibitor

IntroductionImmune checkpoint inhibitors have had a major impact on cancer treatment. Gut microbiota plays a major role in the cancer microenvironment, affecting treatment response. The gut microbiota is highly individual, and varies with factors, such as age and race. Gut microbiota composition in Japanese cancer patients and the efficacy of immunotherapy remain unknown. MethodsWe investigated the gut microbiota of 26 patients with solid tumors prior to immune checkpoint inhibitor monotherapy to identify bacteria involved in the efficacy of these drugs and immune-related adverse events (irAEs).ResultsThe genera Prevotella and Parabacteroides were relatively common in the group showing efficacy towards the anti-PD-1 antibody treatment (effective group). The proportions of Catenibacterium (P = 0.022) and Turicibacter (P = 0.049) were significantly higher in the effective group than in the ineffective group. In addition, the proportion of Desulfovibrion (P = 0.033) was significantly higher in the ineffective group. Next, they were divided into irAE and non-irAE groups. The proportions of Turicibacter (P = 0.001) and Acidaminococcus (P = 0.001) were significantly higher in the group with irAEs than in those without, while the proportions of Blautia (P = 0.013) and the unclassified Clostridiales (P = 0.027) were significantly higher in the group without irAEs than those with. Furthermore, within the Effective group, Acidaminococcus and Turicibacter (both P = 0.001) were more abundant in the subgroup with irAEs than in those without them. In contrast, Blautia (P = 0.021) and Bilophila (P= 0.033) were statistically significantly more common in those without irAEs.DiscussionOur Study suggests that the analysis of the gut microbiota may provide future predictive markers for the efficacy of cancer immunotherapy or the selection of candidates for fecal transplantation for cancer immunotherapy

修士論文要旨 : F. 臨床心理学研究領域

departmental bulletin pape

A versatile synthetic strategy for macromolecular cages: intramolecular consecutive cyclization of star-shaped polymers

Cage-shaped polymers, or macromolecular cages, are of great interest as the macromolecular analogues of molecular cages because of their various potential applications in supramolecular chemistry and materials science. However, the systematic synthesis of macromolecular cages remains a great challenge. Herein, we describe a robust and versatile synthetic strategy for macromolecular cages with defined arm numbers and sizes based on the intramolecular consecutive cyclization of highly reactive norbornene groups attached to each end of the arms of a star-shaped polymer precursor. The cyclizations of three-, four-, six-, and eight-armed star-shaped poly(epsilon-caprolactone)s (PCLs) bearing a norbornenyl group at each arm terminus were effected with Grubbs' third generation catalyst at high dilution. H-1 NMR, SEC, and MALDI-TOF MS analyses revealed that the reaction proceeded to produce the desired macromolecular cages with sufficient purity. The molecular sizes of the macromolecular cages were controlled by simply changing the molecular weight of the star-shaped polymer precursors. Systematic investigation of the structure-property relationships confirmed that the macromolecular cages adopt a much more compact conformation, in both the solution and bulk states, as compared to their linear and star-shaped counterparts. This synthetic approach marks a significant advance in the synthesis of complex macromolecular architectures and provides a platform for novel applications using cage-shaped molecules with polymer frameworks

Progress in Multimodal Treatment for Advanced Esophageal Squamous Cell Carcinoma: Results of Multi-Institutional Trials Conducted in Japan

In Japan, the therapeutic strategies adopted for esophageal carcinoma are based on the results of multi-institutional trials conducted by the Japan Esophageal Oncology Group (JEOG), a subgroup of the Japan Clinical Oncology Group (JCOG). Owing to the differences in the proportion of patients with squamous cell carcinoma among all patients with esophageal carcinoma, chemotherapeutic drugs available, and surgical procedures employed, the therapeutic strategies adopted in Asian countries, especially Japan, are often different from those in Western countries. The emphasis in respect of postoperative adjuvant therapy for patients with advanced esophageal squamous cell carcinoma (ESCC) shifted from postoperative radiotherapy in the 1980s to postoperative chemotherapy in the 1990s. In the 2000s, the optimal timing of administration of perioperative adjuvant chemotherapy returned from the postoperative adjuvant setting to the preoperative neoadjuvant setting. Recently, the JEOG commenced a three-arm randomized controlled trial of neoadjuvant therapies (cisplatin + 5-fluorouracil (CF) vs. CF + docetaxel (DCF) vs. CF + radiation therapy (41.4 Gy) (CRT)) for localized advanced ESCC, and patient recruitment has been completed. Salvage and conversion surgeries for ESCC have been developed in Japan, and the JEOG has conducted phase I/II trials to confirm the feasibility and safety of such aggressive surgeries. At present, the JEOG is conducting several trials for patients with resectable and unresectable ESCC, according to the tumor stage. Herein, we present a review of the JEOG trials conducted for advanced ESCC