Editorial Comment from Dr Kadono to Postoperative urinary incontinence exacerbates nocturia-specific quality of life after robot-assisted radical prostatectomy

Embargo Period 12 month

MDCK腎上皮細胞のv-srcによる膜型マトリックスメタロプロテアーゼ1の発現と浸潤性の誘導

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1351号，学位授与年月日：平成11年3月25日,学位授与年：199

v-src導入腎上皮細胞の肺転移モデルを利用した転移性腎癌に対する治療戦略

金沢大学医薬保健研究域医学系腎上皮細胞のMDCK細胞にv-srcを導入することでMDCK細胞はトランスフォームし、浸潤転移能を獲得し、浸潤に重要とされる膜型マトリックスメタロプロテアーゼであるMT1-MMPが発現誘導されることを示した。また、この細胞が高率に転移を起こし、転移浸潤にMT1-MMPが重要と考えられた。MT1-MMPをMDCK細胞に遺伝子導入した場合、細胞の形態変化は認められなかった。MDCK細胞はコラーゲンゲル内での三次元培養を行った場合、HGFの存在下で管腔構造を形成することが知られている。この管腔形成はMMPの阻害剤であるBB94で阻害され、MMPのinhibitorであるTIMP-2では阻害されるが、TIMP-1では阻害されないことが分かった(MDCK細胞へのそれぞれの遺伝子導入細胞とリコンビナントタンパクで確認した)。また、コラーゲンゲル内にMDCK細胞を三次元培養することでMT1-MMPが発現誘導されたが、HGFの有無にはよらなかった。MT1-MMPを導入したMDCK細胞をコラーゲンゲル内で三次元培養した場合、もとの細胞に比べて、内腔が非常に大きい嚢胞状の形態を示し、ここにHGFを加えると嚢胞から突起を出したような形態をとった。この嚢胞形成は、TIMP-1では阻害されなかったが、TIMP-2では阻害された。MT1-MMPは当初はgelatinase Aを活性化するタンパクとして同定されたが、geratinase AはTIMP-1、TIMP-2いずれでも阻害されるため、今回の現象はMT1-MMP自身がコラーゲンを分解して起こったと考えられた。MT1-MMPは細胞がコラーゲンと接触することで発現が誘導され、HGFの存在下でその局在が規定されているようであった。細胞が浸潤転移を起こす場合、また、器官形成を行う場合、周囲の間質を分解し空間を作る必要があり、MT1-MMPがそのプロセスに重要な役割を果たすと考えられた。研究課題/領域番号:17791068, 研究期間(年度):2005 – 2006出典：「v-src導入腎上皮細胞の肺転移モデルを利用した転移性腎癌に対する治療戦略」研究成果報告書　課題番号17791068（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-17791068/)を加工して作

Therapies for castration-resistant prostate cancer in a new era: The indication of vintage hormonal therapy, chemotherapy and the new medicines

When advanced prostate cancer recurred during hormonal therapy and became the castration-resistant prostate cancer, "vintage hormonal therapy," such as antiandrogen alternating therapy or estrogen-related hormonal therapy, was widely carried out in Japan until 2013. This vintage hormonal therapy controlled the progression of castration-resistant prostate cancer. When castration-resistant prostate cancer relapses during these therapies, chemotherapy using docetaxel has been carried out subsequently. Since new hormonal therapies using abiraterone acetate and enzalutamide, which improve the prognosis of castration-resistant prostate cancer, became available in Japan from 2014, therapeutic options for castration-resistant prostate cancer have increased. Furthermore, the improvement of the further prognosis is promising by using cabazitaxel for docetaxel-resistant castration-resistant prostate cancer and radium-223 for castration-resistant prostate cancer with bone metastasis. An increase in therapeutic options gives rise to many questions, including best timing to use them and the indication. Furthermore, physicians have to consider the treatment for the recurrence after having carried out chemotherapy. We want to argue the difference in hormonal therapy between Japan and Western countries, and problems when carrying out new treatments, and the importance of imaging in the present review article. © 2017 The Japanese Urological Association.Embargo Period 12 month

Differential diagnosis between bacterial infection and neoplastic fever in patients with advanced urological cancer: The role of procalcitonin

It is difficult to determine the cause of high fever in patients with advanced cancer, because they tend to have both neoplastic fever and concomitant bacterial infections with elevated white blood cells and C-reactive protein levels. Procalcitonin has been reported to be a valuable marker for bacterial infections in a wide range of clinical scenarios. However, there have been no studies regarding the usefulness of procalcitonin to differentiate between febrile episodes caused by bacterial infections and neoplastic fever in patients with advanced urological cancer. In the present study, 37 febrile episodes were retrospectively analyzed. Although there were no differences in white blood cell number, C-reactive protein level or body temperature between bacterial infections and non-bacterial infections, procalcitonin levels were significantly higher in the former than the latter. Our findings suggest that measurement of procalcitonin might be valuable to determine the cause of febrile episodes in patients with advanced urological cancer, and can help clinicians to make appropriate decisions for treatment. © 2013 The Japanese Urological Association

Chronological urodynamic evaluation of changing bladder and urethral functions after robot-assisted radical prostatectomy

Objective To examine chronological changes in urethral and bladder functions before, immediately after, and 1 year after robot-assisted radical prostatectomy (RARP), urodynamic studies were prospectively performed. Methods Sixty-three consecutive patients underwent pressure-flow studies, urethral pressure profiles, and abdominal leak point pressure (ALPP) tests 1-2 days before, immediately after, and 1 year after RARP. Results The mean bladder compliance was 28.3 mL/cm H2O before RARP; it worsened to 16.3 mL/cm H2O immediately after RARP and recovered to 27.1 mL/cm H2O at 1 year. The mean detrusor pressure at maximum flow rate was 61.9 cm H2O before RARP; it decreased to 34.3 cm H2O immediately after RARP and remained at 35.6 cm H2O at 1 year. The mean maximum urethral closure pressure was 84.2 cm H2O before RARP; it decreased to 33.4 cm H2O immediately after RARP and recovered to 63.0 cm H2O at 1 year. Intrinsic sphincter deficiency (ISD) evaluated by the ALPP test was observed in 53 patients immediately after RARP, although no patient showed ISD before RARP. ISD remained in 7 patients at 1 year. Both ALPP and maximum urethral closure pressure at 1 year were significant factors for continence in multivariate analysis. Conclusion Urethral sphincter and bladder function worsen immediately after RARP and recover over time. The bladder storage function after RARP returns to almost the same level before RARP, and the voiding function improves compared with the condition before RARP; however, the urethral sphincter function does not return to its preoperative level. Urethral sphincter dysfunction is considered the main factor for urinary incontinence after RARP. © 2015 Elsevier Inc.Embargo Period 12 month

Role of surgical resection in adult urological soft tissue sarcoma: 25-Year experience

金沢大学附属病院泌尿器科The effect of chelating ligands on iron (Fe) uptake and growth of radish (Raphanus sativus L.) was investigated. The ethylenediaminetetraacetic acid (EDTA) increased 55Fe uptake in roots of radish though its subsequent translocation from roots to shoots and leaves did not increase. About 70%-80% of the total 55Fe was distributed in the roots while about 5%-15% and 11%-17% were in shoots and leaves, respectively. The EDTA increased iron uptake into the roots of radish, but not in the above ground parts of the plant. The growth of radish (Raphanus sativus L.) decreased drastically in alkaline condition (pH > 9), even though the concentration of iron was sufficient in the growth medium. The growth of radish was enhanced successfully by the addition of hydroxyiminodisuccinic acid (HIDS) and EDTA. This might be because HIDS and EDTA solubilize iron from its precipitation with hydroxides at higher pH, and increase iron bioavailability. The influence of EDTA and HIDS on radish growth was comparable. Increase of radish growth by ethylenediaminedisuccinic acid (EDDS) and methylglicinediacetic acid (MGDA) was less than those by EDTA and HIDS. Considering the reproducibility of the radish growth (biomass production) at pH 10, HIDS is supposed to be more effective compared to EDTA. © Taylor & Francis Group, LLC

Androgen replacement therapy for cancer-related symptoms in male advanced cancer patients : study protocol for a randomised prospective trial (ARTFORM study)

Recent studies reveal that hypogonadism with low serum androgen levels is associated with advanced cancer and induction of most cancer-related symptoms.We designed an ARTFORM study to evaluate the efficacy of androgen replacement therapy in male advanced cancer patients. The ARTFORM study is an investigatorinitiated, randomised controlled trial comparing intramuscle injection of testosterone enanthate with non-administration in male advanced cancer patients with non-curative locally advanced or metastatic lesions. Serum total and free testosterone levels are measured and patients with low testosterone level are randomised. The primary endpoint is the difference in validated health-related quality of life questionnaires at week 12. Trial registration of the ARTFORM study is assigned to University hospital Medical Information Network, Center identifier UMIN 000010939