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| 1.
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Konaka, Hiroyuki ; Egawa, Shin ; Saito, Shiro ; Yorozu, Atsunori ; Takahashi, Hiroyuki ; Miyakoda, Keiko ; Fukushima, Masanori ; Dokiya, Takushi ; Yamanaka, Hidetoshi ; Stone, Nelson N. ; Namiki, Mikio ; 小中, 弘之 ; 並木, 幹夫
概要:
金沢大学医薬保健研究域医学系<br />Background: Patients with high Gleason score, elevated prostate specific antigen (PSA) level, and ad
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vanced clinical stage are at increased risk for both local and systemic relapse. Recent data suggests higher radiation doses decrease local recurrence and may ultimately benefit biochemical, metastasis-free and disease-specific survival. No randomized data is available on the benefits of long-term hormonal therapy (HT) in these patients. A prospective study on the efficacy and safety of trimodality treatment consisting of HT, external beam radiation therapy (EBRT), and brachytherapy (BT) for high-risk prostate cancer (PCa) is strongly required.Methods/Design: This is a phase III, multicenter, randomized controlled trial (RCT) of trimodality with BT, EBRT, and HT for high-risk PCa (TRIP) that will investigate the impact of adjuvant HT following BT using iodine-125 ( 125I-BT) and supplemental EBRT with neoadjuvant and concurrent HT. Prior to the end of September 2012, a total of 340 patients with high-risk PCa will be enrolled and randomized to one of two treatment arms. These patients will be recruited from more than 41 institutions, all of which have broad experience with 125I-BT. Pathological slides will be centrally reviewed to confirm patient eligibility. The patients will commonly undergo 6-month HT with combined androgen blockade (CAB) before and during 125I-BT and supplemental EBRT. Those randomly assigned to the long-term HT group will subsequently undergo 2 years of adjuvant HT with luteinizing hormone-releasing hormone agonist. All participants will be assessed at baseline and every 3 months for the first 30 months, then every 6 months until 84 months from the beginning of CAB.The primary endpoint is biochemical progression-free survival. Secondary endpoints are overall survival, clinical progression-free survival, disease-specific survival, salvage therapy non-adaptive interval, and adverse events.Discussion: To our knowledge, there have been no prospective studies documenting the efficacy and safety of trimodality therapy for high-risk PCa. The present RCT is expected to provide additional insight regarding the potency and limitations of the addition of 2 years of adjuvant HT to this trimodality approach, and to establish an appropriate treatment strategy for high-risk PCa.Trial registration: UMIN000003992. © 2012 Konaka et al; licensee BioMed Central Ltd.
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| 2.
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Kitagawa, Yasuhide ; Machioka, Kazuaki ; Yaegashi, Hiroshi ; Nakashima, Kazufumi ; Ofude, Mitsuo ; Izumi, Kouji ; Ueno, Satoru ; Kadono, Yoshifum ; Konaka, Hiroyuki ; Mizokami, Atsushi ; Namiki, Mikio ; 北川, 育秀 ; 泉, 浩二 ; 上野, 悟 ; 小中, 弘之 ; 溝上, 敦 ; 並木, 幹夫
概要:
金沢大学医薬保健研究域医学系<br />To clarify the recent trends in prostate-specific antigen (PSA) distribution in men in Japan, we ana
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lyzed the PSA distributions of men undergoing PSA-based population screening. We summarized the annual individual data of PSA-based population screening in Kanazawa, Japan, from 2000 to 2011, and analyzed baseline serum PSA values of the participants at the first population screening. Serum PSA distributions were estimated in all participants and those excluding prostate cancer patients according to age. From 2000 to 2011, 19 620 men participated aged 54-69 years old in this screening program. Mean baseline serum PSA level of all participants at the first screening was 2.64 ng ml⁻¹ in 2000, and gradually decreased to approximately 1.30 ng ml⁻¹ in 2006. That of participants excluding prostate cancer patients was 1.46 ng ml⁻¹ in 2000, and there was no remarkable change during the study period. The 95 th percentiles in the participants excluding prostate cancer patients detected at the first population screening of men aged 54-59, 60-64, and 65-69 years old were 2.90, 3.60, and 4.50 ng ml⁻¹, respectively. After the commencement of population screening, the proportion of prostate cancer patients with high serum PSA levels decreased. However, there were no changes in serum PSA levels in men without prostate cancer. Age-specific PSA reference level of men without prostate cancer in Japan was similar to that in China and Korea.
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| 3.
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Miyamoto, Toshinobu ; Tsujimura, Akira ; Miyagawa, Yasushi ; Koh, Eitetsu ; Sakugawa, Naoko ; Miyakawa, Hiroe ; Sato, Hisashi ; Namiki, Mikio ; Okuyama, Akihiko ; Sengoku, Kazuo ; 高, 栄哲 ; 並木, 幹夫
概要:
金沢大学医薬保健研究域医学系<br />Genetic mechanisms have been implicated as a cause of some cases of male infertility. Recently, 10 n
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ovel genes involved in human spermatogenesis were identified by microarray analysis of human testicular tissue. One of these is spermatogenesis-associated 17 (SPATA17). To investigate whether defects in the SPATA17 gene are associated with azoospermia due to meiotic arrest, a mutational analysis was conducted, in which the SPATA17 coding regions of 18 Japanese patients with this condition were sequenced. A statistical analysis was carried out that included 18 patients with meiotic arrest, 20 patients with Sertoli-cell-only syndrome (SCOS) and 96 healthy control men. No mutations were found in SPATA17. However, three coding single nucleotide polymorphisms (cSNPs: SNP1-SNP3) were detected in the patients with meiotic arrest. No significant differences in the genotype or allele frequencies of SNP1 and SNP2 were found between patients with meiotic arrest and the others. However, the frequency of the SNP3 allele was significantly elevated in the meiotic arrest group (P < 0.05). This study suggests that SPATA17 may play a critical role in human spermatogenesis, especially in meiosis.
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Miyamoto, Toshinobu ; Tsujimura, Akira ; Miyagawa, Yasushi ; Koh, Eitetsu ; Namiki, Mikio ; Horikawa, Michiharu ; Saijo, Yasuaki ; Sengoku, Kazuo ; 高, 栄哲 ; 並木, 幹夫
概要:
金沢大学医薬保健研究域医学系<br />Genetic mechanisms are implicated as a cause of some male infertility, yet are poorly understood. Me
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iosis is unique to germ cells and essential for reproduction. The synaptonemal complex is a critical component for chromosome pairing, segregation and recombination. Hormad1 is essential for mammalian gametogenesis as knockout male mice are infertile. Hormad1-deficient testes exhibit meiotic arrest in the early pachytene stage and synaptonemal complexes cannot be visualized. To analyze the hypothesis that the human HORMAD1 gene defects are associated with human azoospermia caused by meiotic arrest, mutational analysis was performed in all coding regions by direct sequence analysis of 30 Japanese men diagnosed with azoospermia resulting from meiotic arrest. By the sequence analysis, three polymorphism sites, Single Nucleotide Polymorphism 1 (c. 163A>G), SNP2 (c. 501T>G) and SNP3 (c. 918C>T), were found in exons 3, 8 and 10. The 30 patients with azoospermia and 80 normal pregnancy-proven, fertile men were analyzed for HORMAD1 polymorphisms. Both SNP1 and SNP2 were associated with human azoospermia caused by complete early meiotic arrest (P<0.05). We suggest that the HORMAD1 has an essential meiotic function in human spermatogenesis. © 2012 AJA, SIMM & SJTU. All rights reserved.
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Kawaguchi, Shohei ; Shigehara, Kazuyoshi ; Sasagawa, Toshiyuki ; Shimamura, Masayoshi ; Nakashima, Takao ; Sugimoto, Kazuhiro ; Nakashima, Kazufumi ; Furubayashi, Keiichi ; Namiki, Mikio ; 川口, 昌平 ; 重原, 一慶 ; 笹川, 寿之 ; 島村, 正喜 ; 中嶋, 孝夫 ; 杉本, 和宏 ; 中嶋, 一史 ; 古林, 敬一 ; 並木, 幹夫
概要:
金沢大学医薬保健研究域医学系<br />Liquid-based urine cytology (LB-URC) was evaluated for cytological diagnosis and detection of human
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papillomavirus (HPV), Mycoplasma, and Ureaplasma. Midstream urine samples were collected from 141 male patients with urethritis and 154 controls without urethritis, and sediment cells were preserved in liquid-based cytology solution. Urethral swabs from urethritis patients were tested for the presence of Neisseria gonorrhoeae and Chlamydia trachomatis. Papanicolaou tests were performed for cytological evaluation. HPV, Mycoplasma, and Ureaplasma genomes were determined by PCR-based methods, and localization of HPV DNA in urothelial cells was examined by in situ hybridization (ISH). The β-globin gene was positive in 97.9% of LB-URC samples from urethritis patients and in 97.4% of control samples, suggesting that high-quality cellular DNA was obtained from the LB-URC samples. HPV DNA was detected in 29 (21.0%) urethritis cases and in five (3.3%) controls (P<0.05). HPV type 16 (HPV 16) was most commonly found in urethritis patients. Cytological evaluations could be performed for 92.1% of urethritis patients and 64.3% of controls. Morphological changes suggestive of HPV infection were seen in 20.7% of the HPV-positive samples, and ISH demonstrated the presence of HPV DNA in both squamous and urothelial cells in HPV-positive samples. Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma urealyticum were detected in 14.5%, 10.9%, 6.5%, and 12.3% of urethritis patients, respectively. The prevalence rates of these microorganisms (except Ureaplasma parvum) were significantly higher in urethritis cases than controls (P<0.05). LB-URC is applicable for detection of HPV, Mycoplasma, and Ureaplasma. HP infection occurs in urothelial cells, especially in gonococcal urethritis. Copyright © 2012, American Society for Microbiology. All Rights Reserved.
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| 6.
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並木, 幹夫 ; 奥山, 明彦 ; Namiki, Mikio ; Okuyama, Akihiko
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金沢大学医薬保健研究域医学系<br />出版者照会後に全文公開
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並木, 幹夫 ; Namiki, Mikio
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金沢大学医薬保健研究域医学系<br />出版者照会後に全文公開
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| 8.
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Kadono, Yoshifumi ; Miwa, Sotaro ; Shima, Takashi ; Konaka, Hiroyuki ; Mizokami, Atsushi ; Yotsuyanagi, Satoshi ; Hirata, Akio ; Takase, Yasukazu ; Sugata, Toshiaki ; Shimamura, Masayoshi ; Namiki, Mikio ; 角野, 佳史 ; 三輪, 聰太郎 ; 小中, 弘之 ; 溝上, 敦 ; 並木, 幹夫
概要:
金沢大学医薬保健研究域医学系<br />Interferon-alpha (IFN-α) has been used in systemic treatment for metastatic renal cell carcinoma (mR
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CC). IFN-α has at least 14 subtypes, each of which has different biological activity. There have been reports that mRCC resistant to an IFN-α treatment responded to another IFN-α subtype. This study was performed to evaluate the effectiveness of alternation of different IFN-α subtypes for mRCC that did not respond to initial IFN-α treatment. In our department and associated institutions, alternating therapy of IFN-α was provided for 15 initial IFN-α refractory mRCC cases from June 2005 to September 2008. Among the 15 patients, the effects of alternating IFN-α therapy were as follows: complete response (CR), 0 cases; partial response (PR), 1 case; stable disease (SD), 3 cases; progressive disease (PD), 11 cases. The response rate (CR+PR) was 7% and disease control rate (CR+PR+SD) was 27%. No severe side effects were observed in any of these cases. The PR case is still in PR 21 months after alternating IFN-α therapy. Among the three SD cases, one has continued SD for 14 months and the other for 12 months. Alternating IFN-α therapy for mRCC can be attempted even if other cytokines are not effective. © 2012 Biomedical Research Press.
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| 9.
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Takami, Akiyoshi ; Asakura, Hidesaku ; Koshida, Kiyoshi ; Namiki, Mikio ; Nakao, Shinji ; 高見, 昭良 ; 朝倉, 英策 ; 越田, 潔 ; 並木, 幹夫 ; 中尾, 眞二
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金沢大学医薬保健研究域医学系<br />We report the cases of 3 patients with advanced renal cell carcinoma who underwent reduced-intensity
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allogeneic stem cell transplantation. In 2 partial responders, histologic analyses of metastases revealed prominent accumulation of CD8+ T cells and degenerative changes of clear cell carcinoma, suggestive of induction of tumor-specific cytotoxic T lymphocytes.
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| 10.
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Iwamoto, Hiroaki ; Shigehara, Kazuyoshi ; Miyagi, Tohru ; Nakashima, Takao ; Shimamura, Masayoshi ; Namiki, Mikio ; 岩本, 大旭 ; 重原, 一慶 ; 並木, 幹夫
概要:
金沢大学大学院医学系研究科泌尿器集学的治療学 / Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Me
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dical Sciences<br />Background Prevalence of fluoroquinolone (FQ)-resistant Escherichia coli has been recently increasing worldwide. We analyzed the incidence and characteristics of acute bacterial prostatitis after transrectal ultrasound-guided needle prostate biopsy (TRUSP-Bx) with prophylactic tazobactam/piperacillin (TAZ/PIPC) treatment as an alternative regimen. Methods A total of 391 patients who underwent TRUSP-Bx were included in the study. All patients received intravenous TAZ/PIPC (4.5 g) 30 minutes before and 6 hours after TRUSP-Bx. Results Acute bacterial prostatitis developed in six patients (1.5%); the frequency of its occurrence was significantly higher in patients in whom rectal disinfection was not performed (P < 0.05). These six patients developed clinical symptoms of acute bacterial prostatitis a median of 24 hours after the biopsy. Escherichia coli was isolated in urine or blood bacterial cultures in four cases, and Klebsiella pneumoniae in two cases. All of the isolated organisms showed excellent sensitivity to TAZ/PIPC. Conclusions The incidence rate of acute prostatitis with prophylactic TAZ/PIPC was consistent with those reported previously with FQ-based regimens, despite the favorable sensitivity of isolated organisms. Two-time regimen of TAZ/PIPC may not always prevent the post-TRUSP-Bx infection, possibly due to the pharmacokinetic characteristics of TAZ/PIPC. However, if each case was considered individually to select the best setting and frequency of dosage of TAZ/PIPC, this can be an optimal prophylaxis in the era of widespread FQ-resistant microorganisms. Copyright © 2015 Asian Pacific Prostate Society, Published by Elsevier. All rights reserved.
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