Supergravity Analysis of Hybrid Inflation Model from D3--D7 System

The slow-roll inflation is a beautiful paradigm, yet the inflaton potential can hardly be sufficiently flat when unknown gravitational effects are taken into account. However, the hybrid inflation models constructed in D = 4 N = 1 supergravity can be consistent with N = 2 supersymmetry, and can be naturally embedded into string theory. This article discusses the gravitational effects carefully in the string model, using D = 4 supergravity description. We adopt the D3--D7 system of Type IIB string theory compactified on K3 x T^2/Z_2 orientifold for definiteness. It turns out that the slow-roll parameter can be sufficiently small despite the non-minimal Kahler potential of the model. The conditions for this to happen are clarified in terms of string vacua. We also find that the geometry obtained by blowing up singularity, which is necessary for the positive vacuum energy, is stabilized by introducing certain 3-form fluxes.Comment: 21 pages; v3. a typo corrected, and some changes made in sections 4.1 and 4.2, accordingl

Quantum Moduli Space of the Cascading Sp(p+M) x Sp(p) Gauge Theory

We extend the detailed analysis of the quantum moduli space of the cascading SU(p+M) x SU(p) gauge theory in the recent paper of Dymarsky, Klebanov, and Seiberg for the Sp(p+M) x Sp(p) cascading gauge theory, which lives on the world volume of p D3-branes and M fractional D3-branes at the tip of the orientifolded conifold. As in their paper, we also find in this case that the ratio of the deformation parameters of the quantum constraint on the different branches in the gauge theory can be reproduced by the ratio of the deformation parameters of the conifold with different numbers of mobile D3-branes.Comment: 15 page

ヒト大腸癌肝転移におけるHVEM発現の重要性について

Background: Herpesvirus entry mediator (HVEM) has been suggested to play various roles in cancer biology. The authors report that HVEM expression in tumor cells is associated with a reduction in the number of tumor-infiltrating lymphocytes and a poor prognosis after surgical resection in various human gastrointestinal cancers. This study aimed to clarify the clinical significance of HVEM expression in human colorectal liver metastasis (CRLM). Methods: This study examined the cases of 104 patients with CRLM who underwent curative liver resection at Nara Medical University between 2000 and 2014. The median follow-up period was 50.2 months. Immunohistochemical staining was performed using antibodies against HVEM, CD4, CD8, and CD45RO. Results: High HVEM expression was observed in 49 patients (47.1%) with CRLM. Expression of HVEM was not associated with age, gender, administration of preoperative chemotherapy, tumor size, number of tumors, or histologic differentiation. The high-HVEM group exhibited significantly worse overall survival (OS) than the low-HVEM group (P = 0.002). Multivariate analysis showed that high HVEM expression in CRLM, age of 70 years or older, and having five or more tumors are independent poor prognostic factors for OS (hazard ratio [HR], 3.35; 95% confidence interval [CI], 1.41-7.93; P = 0.006). The number of tumor-infiltrating CD8+ and CD45RO+ T cells was significantly lower in the high-HVEM group than in the low-HVEM group. High HVEM expression in primary colorectal cancer was significantly associated with synchronous CRLM, but not with metachronous CRLM. Conclusions: Tumor HVEM expression might play a critical role in CRLM.博士（医学）・乙第1447号・令和元年12月5日© Society of Surgical Oncology 2019This is a post-peer-review, pre-copyedit version of an article published in Annals of surgical oncology. The final authenticated version is available online at: http://dx.doi.org/10.1245/s10434-019-07625-

下部直腸癌におけるMRIを用いた歯状線浸潤の診断精度

Purpose: To retrospectively assess the accuracy of magnetic resonance imaging (MRI) in predicting dentate line invasion in low rectal cancer. Materials and methods: Eighty-one patients with primary rectal cancer were assessed by dynamic contrast-enhanced MRI. The location of the dentate line was assessed on MRI in 27 patients with upper-mid rectal cancer. Two observers independently evaluated the distance between the distal tumor edge and the MRI-defined dentate line in 54 patients with low rectal cancer, and the imaging and histological findings were compared. Results: The MRI-defined dentate line was 24.0 ± 3.8 mm above the anal verge in patients with upper-mid rectal cancer. The dentate line invasion status agreed with the histological findings in 49/54 (91%) patients (κ = 0.72 [95% CI 0.50-0.95]) for observer 1, and in 51/54 (94%) patients (κ = 0.83 [0.65-1.00]) for observer 2 in patients with low rectal cancer. Interobserver agreement was good (κ = 0.83 [0.65-1.00]). The MRI-derived distance between the distal tumor edge and the dentate line had significant correlation with the histological distance (r = 0.86 for reader 1 and 0.75 for observer 2). Conclusion: MRI demonstrates high accuracy in predicting dentate line invasion in low rectal cancer.博士（医学）・甲第748号・令和2年6月30日© Japan Radiological Society 2020© 2020 Springer Nature Switzerland AG. Part of Springer Nature.This is a post-peer-review, pre-copyedit version of an article published in Japanese journal of radiology. The final authenticated version is available online at: http://dx.doi.org/10.1007/s11604-020-00933-5

Oxaliplatinによる肝類洞障害は肝臓内にvon Willebrand因子が血小板血栓を形成することにより発症する

Oxaliplatin-based chemotherapy is widely used to treat advanced colorectal cancer (CRC). Sinusoidal obstruction syndrome (SOS) due to oxaliplatin is a serious type of chemotherapy-associated liver injury (CALI) in CRC patients. SOS is thought to be caused by the sinusoidal endothelial cell damage, which results in the release of unusually-large von Willebrand factor multimers (UL-VWFMs) from endothelial cells. To investigate the pathophysiology of CALI after oxaliplatin-based chemotherapy, we analyzed plasma concentration of von Willebrand factor (VWF) and the distribution of VWFMs in CRC patients. Twenty-three patients with advanced CRC who received oxaliplatin-based chemotherapy with (n = 6) and without (n = 17) bevacizumab were analyzed. CALI (n = 6) and splenomegaly (n = 9) were found only in patients who did not treated with bevacizumab. Plasma VWF antigen (VWF:Ag) and serum aspartate aminotransferase (AST) levels increased after chemotherapy only in patients without bevacizumab. VWFM analysis in patients who did not receive bevacizumab showed the presence of UL-VWFMs and absence of high molecular weight VWFMs during chemotherapy, especially in those with CALI. In addition, plasma VWF:Ag and AST levels increased after chemotherapy in patients with splenomegaly (n = 9), but not in patients without splenomegaly (n = 14). Histological findings in the liver tissue of patients who did not receive bevacizumab included sinusoidal dilatation and microthrombi in the sinusoids. Many microthrombi were positive for both anti-IIb/IIIa and anti-VWF antibodies. Plasma UL-VWFM levels might be increased by damage to endothelial cells as a result of oxaliplatin-based chemotherapy. Bevacizumab could prevent CALI and splenomegaly through inhibition of VWF-rich platelet thrombus formation.博士（医学）・乙第1373号・平成28年3月15日Copyright: © 2015 Nishigori et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

皮下埋没縫合および皮下閉鎖式陰圧ドレーン挿入による、回腸人工肛門閉鎖術後創部感染の減少効果について

Purpose: The purpose of this study was to evaluate the effectiveness of a wound closure method using a combination of subcuticular sutures and subcutaneous closed-suction drainage (SS closure) for preventing incisional surgical site infection (SSI) in loop ileostomy closure. Methods: A total of 178 consecutive patients who underwent loop ileostomy closure at Nara Medical University Hospital between 2004 and 2018 were retrospectively assessed. The patients were divided into 2 groups: the conventional skin closure (CC) group from 2004 to 2009 (75 patients) and the SS closure (SS) group from 2010 to 2018 (103 patients). The incidence of incisional SSI was compared between the two groups, and the factors associated with incisional SSI were examined by univariate and multivariate analyses. Results: Incisional SSI occurred in 7 cases (9.3%) in the CC group but was significantly reduced to only 1 case (0.9%) in the SS group (p = 0.034). In the univariate analysis, the hemoglobin levels, serum creatinine levels, and SS closure were associated with incisional SSI. SS closure was the only independent preventive factor for incisional SSI according to the multivariate analysis (hazard ratio = 0.24, p = 0.011). Conclusion: The combination of subcuticular sutures and subcutaneous closed-suction drainage may be a promising way of preventing incisional SSI in loop ileostomy closure.博士（医学）・乙第1496号・令和3年3月15日© Springer Nature Singapore Pte Ltd. 2020This is a post-peer-review, pre-copyedit version of an article published in Surgery today. The final authenticated version is available online at: https://doi.org/10.1007/s00595-020-02128-x

エリスロポエチンによる腸管に対する抗炎症、組織再生効果

Background. The prevalence of inflammatory bowel disease (IBD) is increasing. Since patients usually need long-term treatment and suffer from reduced quality of life, there is a need to develop new therapeutic strategy. The aim of this study was to investigate the therapeutic potential of erythropoietin (EPO) for the treatment of IBD. Methods. Murine colitis was induced by 3.0% Dextran Sulfate Sodium (DSS). Recombinant human EPO (rhEPO) was given to evaluate the anti-inflammatory and regenerative effects on intestinal inflammation. The effect of rhEPO on human colon epithelial cells was also evaluated. Immunohistochemical analysis of EPO receptor was performed in human IBD tissues. Results. While about 62% of control mice with severe colitis induced by 5-day DSS died, 85% of mice treated with rhEPO survived. Histological analysis confirmed that EPO treatment reduced the colonic inflammation. Furthermore, EPO treatment significantly downregulated the local expressions of IFN-γ, TNF-α and E-selectin in the colon, suggesting that the effect was associated with inhibiting local immune activation. In a 4-day DSS-induced colitis model, rhEPO significantly improved the recovery of body weight loss compared to controls. Furthermore, proliferating cell nuclear antigen expression was significantly upregulated in the colon tissue from mice treated with rhEPO compared to controls. In addition, rhEPO increased the growth of cultured human colon epithelial cells in a dose-dependent manner. Furthermore, EPO-receptor expression was confirmed in human IBD colon tissues. Conclusion. Three major functions of EPO, hematopoiesis, anti-inflammation and regeneration, may produce significant effects on intestinal inflammation, therefore suggesting that rhEPO might be useful for IBD.博士（医学）・乙第1364号・平成27年7月31日© Informa UK Limited, an Informa Group CompanyThe definitive version is available at " http://dx.doi.org/10.3109/00365521.2015.1020861

無症候性腎機能障害が結腸癌術後の臨床経過に及ぼす影響

Purpose: To evaluate the effect of mild renal dysfunction on the clinical course after colectomy in patients with colon cancer. Methods: The subjects of this retrospective study were 263 patients who underwent surgical resection for colon cancer at our hospital between 2011 and 2015. Renal function was assessed based on preoperative estimated glomerular filtration rate (eGFR) values. Patients were divided into groups based on their eGFR value of 55 ml/min/1.73 m2. The Mann-Whitney U test, chi-square or Fisher exact test, and log-rank test were used in the data analysis. Results: There were 59 patients (22.4%) in the low eGFR group and 204 patients in the normal eGFR group. There were differences between the groups in age, comorbidities, and the levels of hemoglobin, albumin, and serum creatinine. The overall postoperative complication rate, frequency of severe complications, and length of stay were significantly higher in the low eGFR group than in the normal eGFR group. Multivariate analysis revealed that low eGFR was the only independent risk factor for severe complications (Clavien-Dindo classification III/IV). There were no differences in survival between the groups. Conclusion: Preoperative asymptomatic renal dysfunction may be correlated with the development of postoperative complications and a possible significant risk factor for severe complications after colon cancer surgery.博士（医学）・甲第804号・令和3年12月21日© 2021. Springer Nature Singapore Pte Ltd.The version of record of this article, first published in Surgery Today, is available online at Publisher’s website: http://dx.doi.org/10.1007/s00595-021-02363-w.発行元が定める登録猶予期間終了の後、本文を登録予定（2021.01

Local recurrence after rectal endoscopic submucosal dissection: a case of tumor cell implantation

We report a case of local recurrence of cancer after rectal endoscopic submucosal dissection (ESD). A 52-year-old male underwent a curative resection with ESD for rectal intramucosal cancer. Seventy-four months after ESD, surveillance colonoscopy showed an elevated lesion on the ESD scar, suspicious of a recurrence. The patient subsequently underwent a low anterior resection (intersphincteric) with lymph node dissection. Pathology revealed a well-differentiated adenocarcinoma, similar to the ESD specimen. We suspected that the local recurrence was caused by implantation of tumor cells during the ESD, due to surgical manipulation performed with the tumor in an exposed setting for a long period of time

下部直腸癌における側方リンパ節転移に関して、造影MRI で描出される中直腸動脈の転移予測因子に関する検討

Purpose: Lateral lymph node (LLN) metastasis is one of the leading causes of local recurrence in patients with lower rectal cancer. Unfortunately, no diagnostic biomarkers are currently available that can predict LLN metastasis preoperatively. Accordingly, we investigated the relationship between the middle rectal artery (MRA) identified by contrast-enhanced magnetic resonance imaging (ceMRI) and LLN metastases. Methods: Data from 102 patients with lower rectal cancer who underwent surgery, and were evaluated by preoperative ceMRI, between 2008 and 2016 were reviewed retrospectively. Two expert radiologists evaluated the MRA findings. The diagnostic performance of MRA for LLN metastasis was evaluated by a multivariate analysis with conventional clinicopathological factors. Results: The MRA was detected in 67 patients (65.7%), including 32 (31.4%) with bilateral MRA and 35 (34.3%) with unilateral MRA. The tumor size, presence of the MRA, and clinical LLN status were significantly correlated with LLN metastasis. A multivariate analysis demonstrated that the presence of MRA (P = 0.045) and clinical LLN status (P = 0.001) were independent predictive factors for LLN metastasis. Furthermore, the sensitivity and negative predictive value of MRA for LLN metastasis were 95% and 97.1%, respectively. Conclusion: We successfully demonstrated that MRAs could be clearly detected by ceMRI, and the presence of MRA robustly predicted LLN metastasis in patients with lower rectal cancer, highlighting its clinical significance in the selection of more appropriate treatment strategies. Trial registration: Trial registration number: retrospectively registered 2126 Trial registration date of registration: August 23, 2019.博士（医学）・乙第1512号・令和3年12月21日© 2021. The Author(s). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/