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Mikio Namiki

Publications and source records attributed to Mikio Namiki.

At least 19 recordsLinked to original sources
PubMed2007

Validation study of the prediction system for clinical response of M-VAC neoadjuvant chemotherapy.

To predict the efficacy of the M-VAC neoadjuvant chemotherapy for invasive bladder cancers, we previously established the method to calculate the prediction score on the basis of expression profiles of 14 predictive genes. This scoring system had clearly distinguished the responder group from the non-responder group. To further validate the clinical significance of the system, we applied it to 22 additional cases of bladder cancer patients and found that the scoring system correctly predicted clinical response for 19 of the 22 test cases. The group of patients with positive predictive scores had significantly longer survival than that with negative scores. When we compared our results with a previous report describing the prognosis of the patients with cystectomy alone, the results imply that patients with positive scores are likely to benefit from M-VAC neoadjuvant chemotherapy, but that the chemotherapy would shorten the lives of patients with negative scores. We are confident that our prediction system to M-VAC therapy should provide opportunities for achieving better prognosis and improving the quality of life of patients. Taken together, our data suggest that the goal of 'personalized medicine', prescribing the appropriate treatment regimen for each patient, may be achievable by selecting specific sets of genes for their predictive values according to the approach shown here.

Aged↗
PubMed2007

Global update on defining and treating high-risk localized prostate cancer with leuprorelin: an Asian perspective.

Data from the Japanese Urological Society showed that, in Japan, almost half of patients with localized prostate cancer are treated with hormone therapy (HT), regardless of disease stage, and that radiation therapy (RT) is also widely used to treat high-risk patients. A retrospective study was undertaken in Japan to evaluate the potential benefits of using primary HT in locally advanced prostate cancer. Of 628 patients in the study, 63.5% were treated with combined androgen blockade (CAB; luteinizing hormone-releasing hormone agonists plus an antiandrogen) and 36.5% with medical or surgical castration. CAB treatment was significantly better than hormone monotherapy for disease-specific survival. The results also showed that, even if a patient is classified as 'high-risk', a good prognosis could normally be predicted based on certain variables: if their initial prostate-specific antigen (PSA) level was < or = 20 ng/mL, their Gleason score was < or = 6, and their nadir PSA decreased to < or = 0.2 ng/mL within 6 months of HT. In this subgroup of 'good responders', any treatment, be it prostatectomy, RT or CAB, is likely to be effective. However, in 'poor responders', combined therapies with CAB and high-dose rate brachytherapy are likely to be needed for a clinical response. While HT is effective, it might be associated with a reduction in the patient's quality of life (QoL) due to adverse effects, e.g. a reduction in sexual function. Results from the analysis of QoL questionnaires completed by men of different ages with prostate cancer found that only sexual function, and not other QoL variables, in men aged 50-59 years appeared to be reduced in men who had HT, compared to age-matched controls.

Antineoplastic Agents, Hormonal↗
PubMed2006

Liquid chromatography-mass spectrometric assay of androstenediol in prostatic tissue: influence of androgen deprivation therapy on its level.

Androstenediol (Adiol, androst-5-ene-3beta,17beta-diol) is suspected of being an endogenous proliferation agent of prostate cancer (PCa) even after androgen deprivation therapy (ADT). A liquid chromatography-electron capture atmospheric pressure chemical ionization-mass spectrometric (LC-ECAPCI-MS) method for the determination of Adiol in prostatic tissue was developed and validated for evaluating the influence of ADT on the prostatic Adiol level. After derivatization of Adiol with 4-nitrobenzoyl chloride, the detection response of the derivative was increased 150 times more than that of intact Adiol. The LC-MS method was specific and reliable for the measurement of a trace amount of Adiol in 30 mg of tissue. The clinical study using the developed method showed that the prostatic Adiol level was not changed by ADT. That is, the prostatic Adiol levels of PCa patients with ADT (n = 12), benign prostate hypertrophy patients without ADT (n = 8) and bladder cancer patients (without prostatic disease) (n = 6) were 0.83 +/- 0.28, 0.62 +/- 0.31 and 0.71 +/- 0.28 ng g(-1)tissue, respectively, and there was no significant difference between these groups.

Androstenediol↗
PubMed2006

Is a genetic defect in Fkbp6 a common cause of azoospermia in humans?

FK506-binding protein 6 (Fkbp6) is a member of a gene family containing a prolyl isomerase/FK506-binding domain and tetratricopeptide protein-protein interaction domains. Recently, the targeted inactivation of Fkbp6 in mice has been observed to result in aspermic males and the absence of normal pachytene spermatocytes. The loss of Fkbp6 results in abnormal pairing and a misalignment of the homologous chromosomes, and in non-homologous partner switches and autosynapsis of the X chromosome cores in meiotic spermatocytes. In this study, we analyzed whether human FKBP6 gene defects might be associated with human azoospermia. We performed a mutation analysis in all the coding regions of the human FKBP6 gene in 19 patients with azoospermia resulting from meiotic arrest. The expression of the human FKBP6 gene was specific to the testis, and a novel polymorphism site, 245C --> G (Y60X) could be found in exon 3. Our findings suggest that the human FKBP6 gene might be imprinted in the testis based on an analysis using two polymorphism sites.

Amino Acid Sequence↗
PubMed2006

[Disorder of AZF].

Explore the source record for details and available documents.

Base Sequence↗
PubMed2006

Polymorphic alleles of the human MEI1 gene are associated with human azoospermia by meiotic arrest.

Genetic mechanisms are implicated as a cause of some male infertility, yet are poorly understood. Mouse meiotic mutant mei1 (meiosis defective 1) was isolated by a screening of infertile mice. Male mei1 mice have azoospermia due to meiotic arrest, and the mouse Mei1 gene is responsible for the mei1 phenotype. To investigate whether human MEI1 gene defects are associated with azoospermia by meiotic arrest, we isolated the human MEI1 cDNA based on the mouse Mei1 amino acid sequence. MEI1 is expressed specifically in the testis. Mutational analysis by direct sequencing of all MEI1 coding regions was performed in 27 men (13 European Americans, 13 Israeli and 1 Japanese) having azoospermia due to complete early meiotic arrest. This identified four novel, coding single-nucleotide-polymorphisms (cSNPs), i.e., SNP1 (T909G), SNP2 (A1582G), SNP3 (C1791A) and SNP4 (C2397T) in exons 4, 8, 9 and 14, respectively. Using these cSNPs, an association study was carried out between 26 non-Japanese patients with azoospermia and two sets of normal control men (61 normal European Americans and 60 Israelis). Consequently, SNP3 and SNP4 were shown to be associated with azoospermia among European Americans (P =0.0289 and P =0.0299 for genotype and allele frequencies at both the polymorphic sites, respectively), although no such association was observed among Israelis (P >0.05). Haplotype estimation revealed that the frequencies of SNP3-SNP4 (C-T), SNP3-SNP4 (A-C) and SNP3-SNP4 (A-T) were higher in the European American patients, and the frequency of SNP3-SNP4 (A-T) was also higher than in both control groups. These results suggest that MEI1 may play a role in meiosis during spermatogenesis, especially in European Americans.

Alleles↗
PubMed2006

Resin-based micropipette tip for immunochromatographic assays in urine samples.

A novel bioanalysis system based on immunochromatography was developed in connection with a nitrocellulose resin modified micropipette tip, such as ZipTip. The sandwich-type immunoassay was applied to our bioanalysis system. The simple handling of the micropipette enabled us to increase the sample volume and detect low concentrations of target antigens in urine samples. In addition, the washing procedure could also be performed easily to reduce the background signal levels. For analytical evaluations, the color intensity was captured by a flatbed scanner, and processed by a software. We have achieved the detection of human chorionic gonadotropin (hCG) and prostate-specific antigen (PSA). The detection limit of hCG was 0.5 ng/ml (0.05 ng/tip), which is comparable to that of other conventional immunochromatographic systems. Moreover, the detection of PSA was greatly improved over the existing systems with the application of different sample volumes, such as 1 ng/ml (0.2 ng/tip) in a 200 microl sample volume, and 1 ng/ml (0.3 ng/tip) in 300 microl sample volume. Our bioanalysis system is a promising candidate for application to point-of-care tests with its simple handling and high sensitivity.

Antibodies, Monoclonal↗
PubMed2006

Reevaluation of azoospermic factor c microdeletions using sequence-tagged site markers with confirmed physical positions from the GenBank database.

OBJECTIVE: To investigate microdeletions and palindrome complexes in the azoospermic factor (AZF) c regions of the Y chromosome, by polymerase chain reaction (PCR) with sequence-tagged site (STS) markers with known physical positions, after verification of the exact physical locations of candidate STSs and exclusion of those that would give ambiguous results on PCR. DESIGN: Retrospective STS deletion study in infertile Japanese men. SETTING: University hospital and reproductive clinic. PATIENT(S): A total of 410 men with nonobstructive azoospermia and severe oligospermia (sperm concentrations of <5 x 10(6)/mL). INTERVENTION(S): Polymerase chain reaction was performed for all STS markers confirmed to be physically located in the partial AZFb and AZFc regions of the Y chromosome. All STSs were retrieved from the University of California at Santa Cruz database, and their location and specificity were verified. MAIN OUTCOME MEASURE(S): Presence or absence of appropriately sized PCR products. RESULT(S): Sixty-nine markers were retrieved, 32 of which were not specific to the long arm of the Y chromosome (Yq). The markers retained for test use were contiguous deletions classified as P1+P2 (AZFc) or P3 proximal/P1 (AZFb+c). The prevalence of accurately mapped microdeletions was 5.1% (21 of 410) in this patient population. CONCLUSION(S): Although noncontiguous deletions were observed, considerable confusion remained until the genome sequence was finally determined because many of the STSs were either repetitive sequences or polymorphic between individuals or races.

Animals↗
PubMed2006

The case for androgen deprivation as primary therapy for early stage disease: results from J-CaP and CaPSURE.

PURPOSE: We analyzed the outcome of primary androgen depletion therapy, which has gained more attention as a potential therapeutic option in patients with localized or locally advanced prostate cancer as it has been increasingly implemented despite limited data on its therapeutic impact in Japan and the United States. MATERIALS AND METHODS: We analyzed data from CaPSURE and the Japanese Prostate Cancer study. RESULTS: In Japan primary androgen depletion therapy has long been the treatment of choice for localized and locally advanced prostate cancer. Based on CaPSURE data the frequency of primary androgen depletion therapy being chosen to treat localized and locally advanced disease is also increasing in clinical practice in the United States. A study of the outcomes of endocrine therapy is currently being performed in Japan by the Japanese Prostate Cancer Study Group. CONCLUSIONS: It is important to obtain such information about the role of primary androgen depletion therapy for localized and locally advanced prostate cancer from studies of natural history and clinical trials. It is also important to update practical treatment guidelines.

Androgen Antagonists↗
PubMed2006

Central muscarinic receptor subtypes regulating voiding in rats.

PURPOSE: Muscarinic receptors are distributed widely in the brain. A recent study revealed that central muscarinic receptors are involved in voiding regulation. However, to our knowledge the role of each muscarinic receptor subtype has not been resolved. Therefore, we evaluated the effect of intracerebroventricular administration of selective muscarinic M1 to M4 receptor antagonists on voiding function in rats. MATERIALS AND METHODS: Female Sprague-Dawley rats were cannulated for intracerebroventricular infusion under halothane anesthesia. In experiment 1 cystometry was performed in conscious rats, and BC and maximal voiding pressure were measured. In experiment 2 a catheter was inserted via the bladder dome to the bladder neck and UPP was measured by saline infusion. Repeat cystostomy was performed, and saline infusion and discharge saline, BC, maximal IVP and minimal UPP were measured in conscious rats. Pirenzepine, methoctramine, pFHHSiD and MT-3 were used as selective M1, M2, M3 and M4 muscarinic receptor antagonists, respectively, which were injected intracerebroventricularly. RESULTS: In experiment 1 pirenzepine and pFHHSiD increased BC and decreased maximal voiding pressure. Methoctramine and MT-3 decreased BC. In experiment 2 pirenzepine and pFHHSiD increased BC and minimal UPP, and decreased maximal IVP. Methoctramine and MT-3 decreased BC and maximal IVP. Minimal UPP remained unchanged. CONCLUSIONS: Intracerebroventricular administration of muscarinic M1 and M3 receptor antagonists inhibited urination in conscious rats, while M2 and M4 receptor antagonists induced excitatory changes.

Animals↗
PubMed2006

Durability of working channel in flexible ureteroscopes when inserting ureteroscopic devices.

PURPOSE: We studied the physical damage to the working channel of flexible ureteroscopes caused by insertion of various accessories. A procedure was developed to avoid channel damage. MATERIALS AND METHODS: An experimental model representing a flexible ureteroscope was prepared, and damage to its working channel was evaluated by inserting instruments through it. Deflection angles of the channel were changed from 0 degrees to 120 degrees, and each device was inserted and removed 100 times for each selected angle of the channel. Any induced pinholes were identified by an air-leak test. Also, the inside of the channel was inspected with an extremely fine fiberscope. RESULTS: Insertions of 3F biopsy forceps or a 2.4F Nitinol stone-retrieval device caused only slight damage to the model channel, even when the deflection angle was 120 degrees. However, the tips of 200- or 250-microm holmium laser fibers shaved the inner surface of the channel at 60 degrees of deflection, and at 120 degrees, the laser fiber either penetrated the channel or could not be advanced because of resistance by the channel wall. When the laser fiber was inserted within a protective tube, the channel was never damaged, even when the deflection angle was 120 degrees. CONCLUSIONS: When devices are inserted into the working channel of a flexible ureteroscope, damage to the wall depends on the kind of device and deflection angle. Harm could be avoided by inserting the devices, especially laser probes, within a protective tube.

Equipment Design↗
PubMed2006

Four year clinical statistics of iridium-192 high dose rate brachytherapy.

BACKGROUND: We evaluated the efficacy and complications of high dose rate (HDR) brachytherapy using iridium-192 (192Ir) combined with external beam radiotherapy (EBRT) in patients with prostate cancer. METHODS: Ninety-seven patients underwent 192Ir HDR brachytherapy combined with EBRT at our institution between February 1999 and December 2003. Of these, 84 patients were analysed in the present study. 192Ir was delivered three times over a period of 2 days, 6 Gy per time, for a total dose of 18 Gy. Interstitial application was followed by EBRT at a dose of 44 Gy. Progression was defined as three consecutive prostate-specific antigen (PSA) rises after a nadir according to the American Society for Therapeutic Radiology and Oncology criteria. The results were classified into those for all patients and for patients who did not undergo adjuvant hormone therapy. RESULTS: The 4-year overall survival of all patients, the nonadjuvant hormone therapy group (NAHT) and the adjuvant hormone therapy group (AHT) was 87.2%, 100%, and 70.1%, respectively. The PSA progression-free survival rate of all patients, NAHT, and AHT was 82.6%, 92.0%, and 66.6%, respectively. Of all patients, the 4-year PSA progression-free survival rates of PSA<20 and PSA>or=20 groups were 100%, and 46.8%, respectively. According to the T stage classification, PSA progression-free survival rates of T1c, T2, T3, and T4 were 100%, 82.8%, 100%, and 12.1%, respectively. Prostate-specific antigen progression-free survival rates of groups with Gleason scores (GS)<7 and GS>or=7 were 92.8% and 60.1%, respectively. Of NAHT, PSA progression-free survival of PSA<20 was 100% vs 46.8% for PSA>or=20, that of T1c was 100% vs 75% for T2, and that of GS<7 was 100% vs 75% for GS>or=7. No significant intraoperative or postoperative complications requiring urgent treatment occurred except cerebellum infarction. CONCLUSIONS: 192Ir HDR brachytherapy combined with EBRT was as effective as radical prostatectomy and had few associated complications.

Aged↗
PubMed2006

Novel HER2 selective tyrosine kinase inhibitor, TAK-165, inhibits bladder, kidney and androgen-independent prostate cancer in vitro and in vivo.

PURPOSE: TAK-165 is a new potent inhibitor of human epidermal growth factor receptor 2 (HER2) tyrosine kinase. Several reports suggest HER2 expression in bladder cancer, renal cell carcinoma (RCC) and androgen-independent prostate cancer. We therefore investigated the antitumor effect of TAK-165 on these urological cancer cells. MATERIALS AND METHODS: Western blot analysis was performed to confirm HER2 expression in cell lines. To study in vitro efficacy, cells were treated with TAK-165 at various concentrations for 72 h and then counted using a hemocytometer. Then the IC50 value was calculated. In the xenograft model, after the tumor reached 200-300 mm3 in volume, mice were orally administered TAK-165 10 mg/kg per day or 20 mg/kg per day or saline for 14 consecutive days (n=6-8). RESULTS: HER2 expression was observed in HT1376, UMUC3, T24 (bladder), ACHN (kidney), DU145, LNCaP, LN-REC4 (prostate), although the expression level in these cells was weak compared with BT474 (a breast cancer cell line which expresses HER2 strongly). IC50 was varied from 0.09 to greater than 25 micromol/L in the bladder cancer cell line. ACHN cells were less sensitive in vitro. The prostate cancer cell lines studied were all sensitive (IC50 0.053-4.62 micromol/L). In the xenograft model, treatment with TAK-165 significantly inhibited growth of UMUC-3, ACHN, and LN-REC4. The antitumor effect (T/C [%]=growth of TAK-165 treated tumor/average growth of control tumorx100) after 14 days treatment were 22.9%, 26.0%, and 26.5% in UMUC3, ACHN and LN-REC4, respectively. CONCLUSIONS: TAK-165 may be a hopeful new agent for bladder, kidney and androgen-independent prostate cancer.

Androgens↗
PubMed2006

Bisphosphonate induces apoptosis and inhibits pro-osteoclastic gene expression in prostate cancer cells.

AIM: Bisphosphonates are well established for the management of cancer-induced skeletal complications. Recent studies suggest that bisphosphonates promote apoptosis of cancer cells as well as osteoclasts in bone metastatic sites. To determine the direct effects of bisphosphonate on prostate cancer, we examined the effects of minodronate on prostatic cancer cell growth and the expression of apoptosis-related proteins and osteoclastogenic factors. METHODS: PC-3, DU145 and LNCaP cells were treated with amino-bisphosphonate minodronate. Then proliferation, apoptosis and expression of bcl-2, bax, poly (ADP)-ribose polymerase (PARP), caspase-3, receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), matrix metalloproteinases-2 (MMP-2), and parathyroid hormone related protein (PTHrP) were assessed. RESULTS: The proliferation of prostatic cancer cells was inhibited by minodronate. DNA fragmentation and TUNEL-positive nuclei were observed in minodronate-treated PC-3 cells. Minodronate decreased bcl-2 expression and induced bax expression, caspase-3 activity and degradation of PARP in DU145 and PC-3 cells. Minodronate decreased expression of RANKL, PTHrP and MMP-2 in PC-3 cells. CONCLUSIONS: Our results suggest that bisphosphonate not only promotes apoptosis directly but also decreases pro-osteoclastic gene expression in prostate cancer cells.

Apoptosis↗
PubMed2006

Efficacy of primary hormonal therapy for patients with localized and locally advanced prostate cancer: a retrospective multicenter study.

AIM: A retrospective review of patients with localized and locally advanced prostate cancer was performed to evaluate the efficacy of primary hormonal therapy and predict long-term prognosis in these patients. METHODS: A total of 628 patients who were diagnosed with stage T1c to T3 prostate cancer were treated with primary hormonal therapy at participating institutions. The patients were classified based on pretreatment prostate-specific antigen (PSA) level, Gleason score, and time to nadir PSA level. Disease-specific and progression-free survival rates were investigated, and compared among the subgroups. RESULTS: The mean age of patients was 74.5 years, and median pretreatment PSA level was 14.0 ng/mL. A total of 399 patients (63.5%) were treated with combined androgen blockade (CAB), and 229 patients (36.5%) were treated with castration monotherapy. The disease-specific survival rate of all 628 patients was 89.1% at 8 years. The group that showed a good response to primary hormonal therapy (Group G, pretreatment PSA level < or =20 ng/mL, Gleason score < or =7, and time to nadir PSA < or =6 months) accounted for approximately one-third of the total number of T1c-T3 patients. Disease-specific and progression-free survival rates at 8 years in Group G were 98.9% and 82.0%, respectively. These rates increased to 100% and 87.3%, respectively, in patients receiving CAB treatment in Group G. CONCLUSIONS: The results indicate the usefulness of primary hormonal therapy, especially CAB treatment, for patients showing a good response to hormonal therapy in long-term control of localized and locally advanced prostate cancer.

Aged↗
PubMed2006

Comparison of the clinical outcome after hormonal therapy for prostate cancer between Japanese and Caucasian men.

OBJECTIVE: To investigate the impact of race on the effectiveness of hormonal therapy in patients with prostate cancer, by comparing the outcomes of Caucasian men (CM) and Japanese-American men (JAM) treated with hormonal therapy at one institution. PATIENTS AND METHODS: Fifty-nine CM and 105 JAM with prostate cancer were treated with hormonal therapy at The Queen's Medical Center in Honolulu. Age, stage, Gleason score, race, and pretreatment PSA levels were abstracted. The Kaplan-Meier method was used to construct overall and cause-specific survival curves, which were compared using log-rank statistics. These factors were assessed as to their interdependence and correlation with the clinical course using a Cox proportional hazards regression model. RESULTS: Although there were no statistical differences in patient background, JAM who had received hormonal treatment had a better outcome than CM for overall and cause-specific survival rate (P = 0.001 and 0.036, respectively). Race was one of the significant prognostic factors in the multivariate analysis (P = 0.03). The findings suggest a difference in the effectiveness of hormonal therapy for prostate cancer in JAM living in Hawaii compared to CM. CONCLUSIONS: There were marked racial differences in clinical outcome after hormonal therapy between JAM and CM. A prospective study with more patients might be necessary to elucidate the differential effectiveness of hormonal therapy for prostate cancer in different races, especially between Japanese and Caucasians.

Aged↗