Author Huang, P| Kaku, H| Chen, J| Kashiwakura, Y| Saika, T| Nasu, Y| Urata, Y| Fujiwara, T| Watanabe, M| Kumon, H|
Published Date 2010-07
Publication Title Cancer Gene Therapy
Volume volume17
Issue issue7
Content Type Journal Article
JaLCDOI 10.18926/AMO/48076
FullText URL 66_1_7.pdf
Author Kawauchi, Keiichiro| Watanabe, Masami| Kaku, Haruki| Huang, Peng| Sasaki, Kasumi| Sakaguchi, Masakiyo| Ochiai, Kazuhiko| Huh, Nam-ho| Nasu, Yasutomo| Kumon, Hiromi|
Abstract The preclinical safety and therapeutic efficacy of adenoviral vectors that express the REIC/Dkk-3 tumor suppressor gene (Ad-REIC) was examined for use in prostate cancer gene therapy. The Ad-human (h) and mouse (m) REIC were previously demonstrated to induce strong anti-cancer effects in vitro and in vivo, and we herein report the results of two in vivo studies. First, intra-tumor Ad-hREIC administration was examined for toxicity and therapeutic effects in a subcutaneous tumor model using the PC3 prostate cancer cell line. Second, intra-prostatic Ad-mREIC administration was tested for toxicity in normal mice. The whole-body and spleen weights, hematological and serum chemistry parameters, and histological evaluation of tissues from throughout the body were analyzed. Both experiments indicated that there was no significant difference in the examined parameters between the Ad-REIC-treated group and the control (PBS- or Ad-LacZ-treated) group. In the in vitro analysis using PC3 cells, a significant apoptotic effect was observed after Ad-hREIC treatment. Confirming this observation, the robust anti-tumor efficacy of Ad-hREIC was demonstrated in the in vivo subcutaneous prostate cancer model. Based on the results of these preclinical experiments, we consider the adenovirus-mediated REIC/Dkk-3 in situ gene therapy to be safe and useful for the clinical treatment of prostate cancer.
Keywords REIC Dickkopf-3 gene therapy prostate cancer preclinical study
Amo Type Original Article
Published Date 2012-02
Publication Title Acta Medica Okayama
Volume volume66
Issue issue1
Publisher Okayama University Medical School
Start Page 7
End Page 16
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders CopyrightⒸ 2012 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 22358134
Web of Sience KeyUT 000300800700002
JaLCDOI 10.18926/AMO/47013
FullText URL 65_5_315.pdf
Author Wang, Lei| Kaku, Haruki| Huang, Peng| Xu, Kexin| Yang, Kai| Zhang, Jiheng| Li, Ming| Xie, Liping| Wang, Xiaofeng| Sakai, Akiko| Watanabe, Masami| Nasu, Yasutomo| Shimizu, Kenji| Kumon, Hiromi| Na, Yanqun|
Abstract Deficiencies in the human DNA repair gene WRN are the cause of Werner syndrome, a rare autosomal recessive disorder characterized by premature aging and a predisposition to cancer. This study evaluated the association of WRN Leu1074Phe (rs1801195), a common missense single nucleotide polymorphism in WRN, with prostate cancer susceptibility in Chinese subjects. One hundred and forty-seven prostate cancer patients and 111 male cancer-free control subjects from 3 university hospitals in China were included. Blood samples were obtained from each subject, and the single nucleotide polymorphism WRN Leu1074Phe was genotyped by using a Snapshot assay. The results showed that WRN Leu1074Phe was associated with the risk of prostate cancer in Chinese men and that the TG/GG genotype displayed a decreased prevalence of prostate cancer compared with the TT genotype (OR=0.58, 95%CI:0.35-0.97, p=0.039). Through stratified analysis, more significant associations were revealed for the TG/GG genotype in the subgroup with diagnosis age <_ 72 yr (OR=0.27, 95%CI:0.12-0.61, p=0.002) and in patients with localized diseases (OR=0.36, 95%CI:0.19-0.70, p=0.003). However, no statistically significant difference was found in the subgroup with age >72 yr or in patients with advanced diseases. We concluded that the genetic variant Leu1074Phe in the DNA repair gene WRN might play a role in the risk of prostate cancer in Chinese subjects.
Keywords polymorphism prostatic neoplasms single nucleotide susceptibility WRN
Amo Type Original Article
Published Date 2011-10
Publication Title Acta Medica Okayama
Volume volume65
Issue issue5
Publisher Okayama University Medical School
Start Page 315
End Page 323
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders CopyrightⒸ 2011 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 22037267
Web of Sience KeyUT 000296116400005
Author Ochiai, Kazuhiko| Watanabe, Masami| Ueki, Hideo| Huang, Peng| Fujii, Yasuyuki| Nasu, Yasutomo| Noguchi, Hirofumi| Hirata, Takeshi| Sakaguchi, Masakiyo| Huh, Nam-ho| Kashiwakura, Yuji| Kaku, Haruki| Kumon, Hiromi|
Published Date 2011-08-26
Publication Title Biochemical and Biophysical Research Communications
Volume volume412
Issue issue2
Content Type Journal Article
JaLCDOI 10.18926/AMO/32881
FullText URL fulltext.pdf
Author Murakami, Takanori| Ebara, Shin| Saika, Takashi| Irie, Shin| Takeda, Katsuji| Maki, Yoshio| Miyaji, Sadayuki| Manabe, Daisuke| Kaku, Haruki| Nasu, Yasutomo| Tsushima, Tomoyasu| Kumon, Hiromi|
Abstract <p>We evaluated the need for transurethral biopsy at first follow-up after intravesical bacillus Calmette-Guerin (BCG) therapy for superficial bladder cancer. The records of 84 patients with superficial bladder cancer who received a 6- or 8-week course of BCG were reviewed. Pathological results before BCG, cystoscopic findings, urinary cytology, and biopsy results for evaluation of BCG therapy were reviewed. All 19 patients with positive urinary cytology had evidence of positive bladder biopsy results. Fifty-three of 54 patients (98.1%) with no visible recurrent tumor and negative urinary cytology demonstrated negative pathological results on bladder biopsy. When not found in conjunction with positive urinary cytology, erythematous mucosa on cystoscopy was not an indicator of tumor recurrence or residual cancer. In conclusion, routine transurethral biopsy of the bladder for evaluating the response to BCG intravesical therapy is not necessary in patients who have no visible tumor on cystoscopy and negative urinary cytology./</p>
Keywords bladder cancer BCG therapy transurethral biopsy cystoscopy urinary cytology
Amo Type Original Article
Published Date 2007-12
Publication Title Acta Medica Okayama
Volume volume61
Issue issue6
Publisher Okayama University Medical School
Start Page 341
End Page 344
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 18183079
JaLCDOI 10.18926/AMO/32815
FullText URL fulltext.pdf
Author Saika, Takashi| Tsushima, Tomoyasu| Nasu, Yasutomo| Arata, Ryoji| Kaku, Haruki| Akebi, Naoki| Kusaka, Nobuyuki| Kumon, Hiromi|
Abstract <p>The aim of this study was to reveal the clinical features of anterior urethral recurrence in patients with superficial bladder cancer, and to determine the appropriate treatment. Three hundred and three patients with superficial bladder cancer, who were newly diagnosed and initially treated conservatively in our hospital between 1965 and 1990, were followed for at least 5 years and their clinical outcomes were analyzed. Clinical factors, including anterior urethral recurrence, were evaluated statistically regarding tumor progression. Eight patients (2.6%) had anterior urethral recurrence following superficial bladder cancer. Twenty-four patients (7.9%) had tumor progression and 149 (49.2%) had tumor recurrence. In a multivariate analysis using a logistic model, anterior urethral recurrence was the most important factor, followed by histological grade. Four of 5 patients who were treated for anterior urethral recurrent tumors by transurethral resection showed progression and died of the cancer within one year. Two of the remaining three patients who underwent radical cysto-urethrectomy at the time of anterior urethral recurrence survived. Anterior urethral recurrence following superficial bladder cancer is a predictor for rapid subsequent malignant progression. Once there is anterior urethral recurrence, radical intensive therapy, including radical cysto-urethrectomy, should be carried out immediately.</p>
Keywords superficial bladder cancer anterior urehral recurrence prognosis predictor
Amo Type Article
Published Date 2003-12
Publication Title Acta Medica Okayama
Volume volume57
Issue issue6
Publisher Okayama University Medical School
Start Page 293
End Page 297
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 14726966
Web of Sience KeyUT 000187556500004
JaLCDOI 10.18926/AMO/31973
FullText URL fulltext.pdf
Author Edamura, Kohei| Saika, Takashi| Senoh, Takashi| Koizumi, Fumihito| Manabe, Daisuke| Ebara, Shin| Kaku, Haruki| Yokoyama, Teruhiko| Abarzua, Fernando| Nagai, Atsushi| Nasu, Yasutomo| Tsushima, Tomoyasu| Kumon, Hiromi|
Abstract <p>This study was undertaken to reveal the trends of prostate cancer and the outcome of treatment modalities for each disease stage in patients in a single institute over a 10-year period. From January 1994 through December 2003, 420 consecutive patients with previously untreated and histologically confirmed prostate cancer were analyzed for annual distributions of disease stages and treatment modalities and for long-term clinical progression-free survival, prostate cancer-specific survival, and prostate-specific antigen (PSA) failure-free survival rates for each stage and treatment modality. Annual trends showed that the number of patients, especially those with clinically localized cancer, increased dramatically. The 5-year disease-specific survival rates for patients with clinically localized disease were 100 percent for all treatment modalities, including hormonal therapy alone. Patients with PSA levels less than 10 ng/ml showed an 81 percent 5-year PSA failure-free survival rate with radical prostatectomy. Stage C patients treated by surgery or radiation-based therapy with concomitant hormonal therapy obtained 93 percent and 100 percent cause-specific survival rates, respectively, and those treated by hormonal therapy alone showed a 79 percent rate. The number of patients with localized prostate cancer was increasing in this decade. While long-term hormonal therapy alone was highly efficient in controlling localized prostate cancer, radical therapies in conjunction with neo-adjuvant hormonal therapy produced better survival rates in cases of locally advanced disease.</p>
Keywords prostate carcinoma long-term cohort retrospective outcome
Amo Type Article
Published Date 2005-10
Publication Title Acta Medica Okayama
Volume volume59
Issue issue5
Publisher Okayama University Medical School
Start Page 195
End Page 199
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 16286958
Web of Sience KeyUT 000232835600003
JaLCDOI 10.18926/AMO/30945
FullText URL fulltext.pdf
Author Kobayashi, Tomoko| Sakaguchi, Masakiyo| Tanimoto, Ryuta| Abarzua, Fernando| Takaishi, Mikiro| Kaku, Haruki| Kataoka, Ken| Saika, Takashi| Nasu, Yasutomo| Miyazaki, Masahiro| Kumon, Hiromi| Huh, Nam-ho|
Abstract <p>We have recently shown that a new therapeutic modality using the REIC/Dkk-3 gene (Ad-REIC) is effective against various human cancers, including those of prostate, testis and breast origins. The aim of the present study was to examine the sensitivity of bladder cancers to Ad-REIC and to clarify the molecular mechanisms that determine sensitivity/resistance. We found that 2 human bladder cancer cell lines, T24 and J82, are resistant to Ad-REIC. In T24 and J82 cells, the ER stress response and activation of JNK were observed in a manner similar to that in the sensitive PC3 cells. Translocation of Bax to mitochondria occurred in PC3 cells but not in T24 and J82 cells. Bcl-2 was remarkably overexpressed in T24 and J82 compared with the expression levels in sensitive cell lines. Treatment of T24 and J82 cells with a Bcl-2 inhibitor sensitized the cells to Ad-REIC-induced apoptosis. The results indicate that some human bladder cancers are resistant to apoptosis induced by overexpression of REIC/Dkk-3, which is at least in part due to up-regulation of Bcl-2. These results provide a basis for possible use of Bcl-2 as a marker of sensitive cancers and to try to sensitize resistant cancers to Ad-REIC by down-regulation of Bcl-2.</p>
Keywords REIC/Dkk-3 bladder cancer apoptosis Bcl-2
Amo Type Original Article
Published Date 2008-12
Publication Title Acta Medica Okayama
Volume volume62
Issue issue6
Publisher Okayama University Medical School
Start Page 393
End Page 401
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
Web of Sience KeyUT 000262025000006
JaLCDOI 10.18926/AMO/30759
FullText URL fulltext.pdf
Author Kaku, Haruki| Saika, Takashi| Tsushima, Tomoyasu| Nagai, Atsushi| Yokoyama, Teruhiko| Abarzua, Fernando| Ebara, Shin| Manabe, Daisuke| Nasu, Yasutomo| Kumon, Hiromi|
Abstract <p>We evaluated the efficiency and toxicity of estramustine phosphate (ECT), ifosfamide (IFM) and cisplatin (CDDP) combination chemotherapy in twenty-one patients with hormone-refractory prostate cancer (HRPC), for which there is currently no effective treatment. Patients received a daily dose of 560 mg ECT in combination with 1.2 g/m2 IFM on days 1 to 5 and 70 mg/m2 CDDP on day 1. This combination therapy was given every 3 to 4 weeks. An objective response of more than 50% reduction in prostate-specific antigen was observed in 9 of 18 patients (50%), and a more than 50% reduction in bi-dimensionally measurable soft-tissue lesions was observed in 2 of 7 patients (29%). The median duration of response among the cases showing partial response was 40 weeks, while the median duration of response of overall partial-response plus stable cases was 30 weeks. The median survival duration of all cases was 47 weeks. Toxicity was modest and acceptable. In conclusion, the ECT, IFM and CDDP combination chemotherapy regimen is a viable treatment option for HRPC. However, in comparison with our previous chemotherapy regimen of IFM and CDDP, no additional long-lasting effects resulting from the inclusion of ECT could be affirmed.</p>
Keywords hormone-refractory prostate cancer chemotherapy estramustine phosphate ifosfamide cisplatin
Amo Type Article
Published Date 2006-02
Publication Title Acta Medica Okayama
Volume volume60
Issue issue1
Publisher Okayama University Medical School
Start Page 43
End Page 49
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 16508688
Web of Sience KeyUT 000235538900005