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The Klotho (KL) gene was first identified as a potent aging suppressor. The KL family currently comprises of three proteins: α-Klotho (KLA), β-Klotho (KLB), and γ-Klotho (KLG). Many studies have shown that KLA and KLB participate in tumor progression or suppression, depending on the type of cancer; however, the relationship between KLG and prostate cancer has not yet been studied. Some studies have claimed that KL is correlated to sensitivity to chemotherapy. Here, we investigated the oncogenic potential of KLG in castration-resistant prostate cancer (CRPC). Immunohistochemical analysis using prostate biopsy specimens revealed that patients with high KLG expression in primary prostate cancer tissue had a significantly poor prognosis for overall survival. In addition, the prostate-specific antigen response rate after docetaxel (DTX) therapy in patients with high KLG expression was lower than that in patients with low KLG expression. To evaluate the potential of KLG as a therapeutic target in human prostate cancer, we generated a xenograft model of human CRPC cell line (PC-3) in male athymic mice. The animals were randomly divided into four groups as follows: i) control group (vehicle only); ii) DTX group (intraperitoneal administration); iii) small interfering RNA targeting KLG (KLG siRNA) group (intratumoral administration); and iv) a combination group (DTX plus KLG siRNA). After 3 weeks of treatment, the tumor weight and tumor Ki-67 labeling index were significantly lower in the KLG siRNA group and the combination group than in the control group. Sensitivity to DTX was increased upon treatment with KLG siRNA. These findings suggest that KLG expression in primary prostate cancer lesions is associated with resistance to DTX in CRPC and has potential as a diagnostic and therapeutic target for patients with CRPC., 博士（医学）・甲第740号・令和2年3月16日, Copyright: © Onishiet al. This is an open access article distributed under theterms of CreativeCommons Attribution License(https://creativecommons.org/licenses/by-nc-nd/4.0/).

We present comprehensive spectroscopic and photometric analyses of the intermediate luminosity type lax supernova (SN lax) 2019muj based on multi-band datasets observed through the framework of the OISTER target-of-opportunity program. SN 2019muj exhibits almost identical characteristics to the subluminous SNe lax 2008ha and 2010ae in terms of the observed spectral features and the light curve evolution at the early phase, except for the peak luminosity. The long-term observations unveil late-time flattening light curves as seen in luminous SN lax 2014dt. This can be explained by the existence of an inner dense and optically thick component possibly associated with a bound white dwarf remnant left behind after the explosion. We demonstrate that the weak deflagration model with a wide range of explosion parameters can reproduce the late-phase light curves of other SNe lax. Therefore, we conclude that a common explosion mechanism operates for different subclass SNe lax., DST-JSPS grant [DST/INT/JSPS/P-281/2018]; Optical and Near-infrared Astronomy Inter-University Cooperation Program; JSPS KAKENHI [JP19K23461, 21K13959, JP20H00174, JP20H04737, JP18H04585, JP18H05223, JP17H02864, JP17K14253]; Turkish Scientific and Technical Research Council (TUBITAK-2211C); Turkish Scientific and Technical Research Council (TUBITAK-2214A); [19B-N-CN02]; [19B-N-CT01], We are grateful to the staff at the Seimei and Subaru telescopes for their support. The spectral data using the Seimei telescope were taken under the programs 19B-N-CN02, 19B-N-CT01. The latephase observation was performed with the Subaru telescope under S19B-055. We are honored and grateful for the opportunity of observing the Universe from Maunakea, which has cultural, historical, and natural significance in Hawaii. We thank the support staff at IAO and CREST who enabled the 2m HCT observations. The IAO is operated by the Indian Institute of Astrophysics, Bangalore, India. D.K.S. and G.C.A. acknowledge partial support through DSTJSPS grant DST/INT/JSPS/P-281/2018. The authors also thank T. J. Moriya and M. Tanaka for insightful comments. This research has made use of the NASA/IPAC Extragalactic Database (NED), which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with theNational Aeronautics and Space Administration. The spectral data of comparison SNe were downloaded from the SUSPECT7 (Richardson et al. 2001) and WISeREP8 (Yaron & Gal-Yam 2012) databases. This research has made use of data obtained from the High Energy Astrophysics Science Archive Research Center (HEASARC), a service of the Astrophysics Science Division at NASA/GSFC and of the Smithsonian Astrophysical Observatory's High Energy Astrophysics Division. This work is supported by the Optical and Near-infrared Astronomy Inter-University Cooperation Program. The authors declare that there is no conflict of interests. M.K. acknowledges support by JSPS KAKENHI Grants (JP19K23461, 21K13959). K.M. acknowledges support by JSPS KAKENHI Grants (JP20H00174, JP20H04737, JP18H04585, JP18H05223, JP17H02864). M.Y. is partly supported by JSPS KAKENHI Grant (JP17K14253). U.B. acknowledges the support provided by the Turkish Scientific and Technical Research Council (TUBITAK-2211C and 2214A).

Renal cell carcinoma (RCC) is an immunogenic tumor and pathological specimen generally contain large quantities of tumor-infiltrating lymphocytes (TILs). Numerous cell types and cytokines could affect the immune escape mechanism of tumor cells. The aim of the present study was to investigate the prognostic impact of TILs and the associated circulating cytokines on localized clear cell RCC following radical nephrectomy. A total of 87 patients who had undergone radical nephrectomy and were pathologically diagnosed with localized clear cell RCC were included. The present study evaluated the profile of TILs with immunohistochemical analysis of tumor specimens using a panel of antibodies [cluster of differentiation (CD)-4, CD8, CD80, CD86, CD276, and Forkhead box p3 (Foxp3)]. Counts of each TIL were compared with clinicopathological variables. Based on the results of immunohistochemical analyses, putative cytokines, including interleukin (IL)-6, IL-10, IL-17, interferon-γ, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β, were selected, and their levels in preoperative serum were measured by ELISA. The levels were compared with TIL counts in tumor specimens. High counts of the CD276+ and Foxp3+ TILs were identified as independent factors for poor prognosis for metastasis and local recurrence following radical nephrectomy (P=0.033 and 0.006, respectively). A high CD276+ TIL count was associated with preoperative serum levels of TNF-α and IFN-γ (P=0.027 and P=0.035, respectively), whereas a high count of Foxp3+ TILs was associated with preoperative serum levels of TGF-β (P=0.021). High levels of TNF-α and TGF-β were associated with recurrence-free survival (P=0.035 and P=0.031, respectively). Topical intra-tumoral immunoreaction and systemic immune status may be associated with patients with localized RCC. The topical induction of the CD276+ and Foxp3+ TILs was suggested to be associated with high levels of serum TNF-α and IFN-γ. Preoperative serum levels of TNF-α and TGF-β could be simple and non-invasive biomarkers for risk stratification before radical surgery., 博士（医学）・甲第741号・令和2年3月16日, Copyright © Spandidos Publications 2019. All rights reserved., Articles from Oncology Letters are provided here courtesy of Spandidos Publications.

Additional file 3: Table S2. Comparison of variables according to patterns of intravesical BCG treatment: before propensity score matching.

Additional file 5: Fig. S2. Landmark analysis of recurrence among patients treated with non-maintenance induction BCG (iBCG) or iBCG plus maintenance BCG (mBCG) at 24 months. Landmark RFS at 6, 12, and 18 months among patients treated with non-maintenance iBCG or iBCG plus mBCG are plotted and compared between matched groups A and B (left panel) and between matched groups B and C (right panel). The P values, hazard ratios (HRs), and 95% confidence intervals (CIs) are shown in the figures.

Additional file 1: Fig. S1. Distribution of doses of induction BCG (iBCG). A total of 2669 patients were stratified according to the number of BCG doses administered in iBCG. Most of the patients classified in the iBCG ≤5 group (n = 141) were BCG-intolerant patients who were unable to tolerate at least one full iBCG course. While six-dose iBCG is commonly used in the United States and Europe, eight-dose iBCG is frequently and traditionally used in Japan. In addition, maintenance BCG (mBCG) has not been recognized as a standard treatment option in Japan. The proportions of patients treated with mBCG were 31.7% (green bar, 405 of 1279) and 5.0% (purple bar, 60 of 1249) among patients undergoing six-dose iBCG and seven−/eight-dose iBCG, respectively.

We present optical observations of the Type Ia supernova (SN) 2019ein, starting two days after the estimated explosion date. The spectra and light curves show that SN 2019ein belongs to a high-velocity (HV) and broad-line group with a relatively rapid decline in the light curves (Delta m(15)(B) = 1.36 0.02 mag) and a short rise time (15.37 0.55 days). The Si ii lambda 6355 velocity, associated with a photospheric component but not with a detached high-velocity feature, reached similar to 20,000 km s(-1) 12 days before the B-band maximum. The line velocity, however, decreased very rapidly and smoothly toward maximum light, to similar to 13,000 km s(-1), which is relatively low among HV SNe. This indicates that the speed of the spectral evolution of HV SNe Ia is correlated with not only the velocity at maximum light, but also the light-curve decline rate, as is the case for normal-velocity (NV) SNe Ia. Spectral synthesis modeling shows that the outermost layer at >17,000 km s(-1) is well described by an O-Ne-C burning layer extending to at least 25,000 km s(-1), and there is no unburnt carbon below 30,000 km s(-1); these properties are largely consistent with the delayed detonation scenario and are shared with the prototypical HV SN 2002bo despite the large difference in Delta m(15)(B). This structure is strikingly different from that derived for the well-studied NV SN 2011fe. We suggest that the relation between the mass of Ni-56 (or Delta m(15)) and the extent of the O-Ne-C burning layer provides an important constraint on the explosion mechanism(s) of HV and NV SNe.

We report our experience with a case in which eroded mesh used for inguinal hernia repair migrated into the bladder. An 84-year-old man underwent surgery for colorectal cancer at the age of 40, and radical surgery for a right inguinal hernia at the age of 83. At his initial visit, he reported macroscopic hematuria. Cystoscopy revealed a yellowish-brown foreign body on the right bladder wall, and computed tomography showed the presence of emphysema in association with the foreign body. Based on a presumptive diagnosis of vesical calculi, transurethral lithotripsy was performed. However, the foreign body was strongly adherent to the bladder wall ; when lithotripsy was attempted, the calcified surface of the foreign body detached, and the exposed surface showed a mesh-like structure. Transurethral extraction was judged impossible ; therefore, laparotomy was performed at a later date to remove the foreign body, with en bloc resection including some of the bladder. The foreign body consisted of a surgical mesh that had been used for inguinal hernia repair. With the spread of surgery using surgical mesh, we should be careful about complications.

Systemic lupus erythematosus (SLE) is an autoimmune disease with various symptoms. We present a case of muscle invasive bladder cancer with lymph node swelling caused by SLE. A 60-year-old man was referred to our hospital with high fever and pollakisuria, micro hematuria, proteinuria. We detecteda papillary tumor located behind the left ureteral orifice. Magnetic resonance imaging showed invasion of the tumor to the fat aroundthe bladder. Computed tomography (CT) showed the swelling of left common iliac lymph node and bilateral inguinal lymph nodes. According to cystoscopy, imaging examination and transurethral resection of bladder tumor, we diagnosed it as a bladder cancer (cT3aN3M1). In addition, a close inspection of proteinuria was performed, and SLE was diagnosed. We started steroid therapy under the influence of neutropenia and thrombopenia caused by SLE. The swelling of lymph nodes disappeared on the CT three months later. After the therapy with gemcitabine andcisplatin, radical cystectomy and cutaneous ureterostomy were performed. Pathological examination showed invasive urothelial carcinoma and no lymph node metastasis. He now shows no evidence of disease 18 months after the operation.