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Tsuneharu Miki

Publications and source records attributed to Tsuneharu Miki.

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

Long-term results of first-line sequential high-dose carboplatin, etoposide and ifosfamide chemotherapy with peripheral blood stem cell support for patients with advanced testicular germ cell tumor.

OBJECTIVE: Standard chemotherapy shows relatively low long-term survival in patients with poor-risk testicular germ cell tumor (GCT). First-line high-dose chemotherapy (HD-CT) may improve the result. High-dose carboplatin, etoposide, ifosfamide chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) was investigated as first-line chemotherapy in patients with advanced testicular GCT. METHODS: Fifty-five previously untreated testicular GCT patients with Indiana 'advanced disease' criteria received three cycles of bleomycin, etoposide and cisplatin (BEP) followed by one cycle of HD-CT plus PBSCT, if elevated serum tumor markers were observed after three cycles of the BEP regimen. RESULTS: Thirty patients were treated with BEP alone, because the tumor marker(s) declined to normal range. Twenty-five patients received BEP and HD-CT. One patient died of rhabdomyolysis due to HD-CT. Three and six (13% and 25%) out of 24 patients treated with BEP and HD-CT achieved marker-negative and marker-positive partial responses, respectively. The other patients achieved no change. Fifteen (63%) are alive and 14 (58%) are free of disease at a median follow-up time of 54 months. Severe toxicity included treatment-related death (4%). CONCLUSIONS: HD-CT with peripheral stem cell support can be successfully applied in a multicenter setting. HD-CT demonstrated modest anticancer activity for Japanese patients with advanced testicular GCT and was well tolerated. This regimen might be examined for further investigation in randomized trials in first-line chemotherapy for patients with poor-risk testicular GCT.

Adolescent↗
PubMed2006

A low-dose combination therapy of interleukin-2 and interferon-alpha is effective for lung metastasis of renal cell carcinoma: a multicenter open study.

BACKGROUND: To confirm the usefulness of a combination therapy of interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) against metastatic renal cell carcinoma, the recommended dose of IFN-alpha to use in combination with low-dose IL-2 was determined (phase 1). Efficacy and safety at this dose was evaluated (phase 2). METHODS: In phase 1, the dose of IL-2 was fixed at 0.7 x 10(6) Japan reference unit (JRU)/person for 5 days a week. The dose of IFN-alpha was increased from 3 x 10(6) IU for 3 days a week (level I) to 6 x 10(6) IU for 3 days a week (level II) and to 6 x 10(6) IU for 5 days a week (level III). RESULTS: In phase 1, 10 patients were registered, with 9 (3 at each level) able to be evaluated. Because grade 3 and grade 4 neutropenia were observed at level III in 1 patient each, level II was found to be the recommended regimen. The response rate in phase 1 was 44.4% (4/9). In phase 2, 46 patients were registered, with a response rate in 37 patients, classified as per protocol set (PPS), of 21.6% (8/37). Toxicities observed were primarily flu-like symptoms due to cytokines, and gastrointestinal symptoms. Leukocyte abnormalities were observed, but they were milder and tolerable. CONCLUSION: In the 46 patients evaluated in phase 1 and phase 2, the response rate was 26.1% (12/46), being highest in 38.7% (12/31) of those who were nephrectomized, and with only lung metastases.

Adenocarcinoma↗
PubMed2006

The significance of the expression of dihydropyrimidine dehydrogenase in prostate cancer.

OBJECTIVE: To measure dihydropyrimidine dehydrogenase (DPD), an enzyme involved in the metabolism of 5-fluorouracil (5-FU), expression in prostate cancer and determine whether 5-chloro-2,4-dihydroxypyridine (CDHP), a potent inhibitor of DPD, enhances the antitumoral activity of 5-FU against prostate cancer. PATIENTS, MATERIALS AND METHODS: In all, 44 prostate tissue specimens were obtained from men who had a radical prostatectomy alone for prostate cancer, and 38 specimens from men who had had neoadjuvant hormonal therapy. We analysed the cancerous tissue and normal prostate tissue for DPD expression using immunohistochemistry, and determined its prognostic significance. In cultured human prostate cancer lines (DU145 and LNCaP), we compared the cytotoxicity of 5-FU/CDHP with that of 5-FU alone. Finally, in experiments on immunodeficient mice, we studied the effect of oral administration of tegafur, a pro-drug for 5-FU, with or without CDHP on the growth of tumours introduced by injection of DU145 cells. RESULTS: The expression of DPD was significantly higher in cancerous than normal prostate tissue; 36 of 44 (82%) specimens of prostate cancer expressed DPD, whereas only 25 of 44 (57%) specimens of normal prostate tissue expressed DPD. For men with prostate cancer who had radical prostatectomy alone, men with negative DPD expression tended to have a longer recurrence-free survival than those with positive expression; there were no recurrences in men with prostate cancer and negative DPD expression in the 5-year follow-up. DPD expression was significantly lower in men with prostate cancer who received neoadjuvant hormonal therapy. In vitro treatment of human prostate cancer cell lines with 5-FU/CDHP showed more cytotoxicity than with 5-FU treatment alone. Finally, DU145 tumours in mice treated with tegafur and CDHP were significantly smaller than in mice given tegafur alone. CONCLUSION: The present study showed that DPD expression is elevated in prostate cancer, and indicate that DPD inhibitors might enhance the antitumour activity of 5-FU against prostate cancer.

Aged↗
PubMed2006

Effectiveness of cervical cancer screening over cervical cancer mortality among Japanese women.

BACKGROUND: Various studies have revealed that cervical cancer (CC) screening significantly reduces both CC incidence and mortality in developed countries. Although Japan introduced a nationwide government funded annual CC screening for the women aged 30+ in 1982, the effectiveness of CC screening on CC mortality has not yet been evaluated by any prospective cohort study. Therefore, the present study evaluated the association of CC mortality with self-reported CC screening and some other factors by a nationwide cohort study. METHODS: Baseline survey of the Japan Collaborative Cohort Study for the enrollment of subjects was completed during 1988-90 and followed until 2003. This study only analyzed 63,541 women, aged 30-79 years, who were free from any cancer history at enrollment. RESULTS: During the follow-up period, 38 CC deaths were identified. The mean age at mortality was 67.0 years, with a mortality rate of 4.2 per 100,000 person-years. Participation rate in CC screening was 46.9%. Age-adjusted Cox model indicated significantly lower CC mortality [hazard ratio (HR) = 0.30, 95% confidence interval (CI) = 0.12-0.74] due to CC screening. Protectiveness remained almost the same (HR = 0.30, 95% CI = 0.12-0.76) when adjusted for age, body mass index and number of deliveries. The results also revealed that CC screening could reduce at least 50% of CC deaths even after excluding the effect of possible self-selection bias. CONCLUSIONS: CC screening in Japan may reduce CC mortality significantly for women aged 30-79 years. However, further studies with more CC deaths and increased statistical power are needed to validate the findings.

Adult↗
PubMed2006

Prospective cohort study of the risk of prostate cancer among rotating-shift workers: findings from the Japan collaborative cohort study.

Shift workers have been reported to have an increased risk of some cancers. However, the risk of prostate cancer in shift workers is not known to have been examined previously. This study prospectively examined the association between shift work and risk of prostate cancer incidence among 14,052 working men in Japan enrolled in a large-scale prospective cohort. A baseline survey was conducted between 1988 and 1990. Subjects were asked to indicate the most regular work schedule they had undertaken previously: day work, rotating-shift work, or fixed-night work. During 111,974 person-years, 31 cases of prostate cancer were recorded. The Cox proportional hazards model was used to estimate the risk, with adjustments for age, family history of prostate cancer, study area surveyed, body mass index, smoking, alcohol drinking, job type, physical activity at work, workplace, perceived stress, educational level, and marriage status. Compared with day workers, rotating-shift workers were significantly at risk for prostate cancer (relative risk = 3.0, 95% confidence interval: 1.2, 7.7), whereas fixed-night work was associated with a small and nonsignificant increase in risk. This report is the first known to reveal a significant relation between rotating-shift work and prostate cancer.

Adult↗
PubMed2006

[Sexual precocity].

Explore the source record for details and available documents.

Androgen Antagonists↗
PubMed2006

Expression of novel molecules, MICAL2-PV (MICAL2 prostate cancer variants), increases with high Gleason score and prostate cancer progression.

PURPOSE: The aim of this study is to identify novel molecular targets for development of novel treatment or diagnostic markers of prostate cancer through genome-wide cDNA microarray analysis of prostate cancer cells purified by laser microdissection. EXPERIMENTAL DESIGN AND RESULTS: Here, we identified molecule interacting with CasL-2 prostate cancer variants (MICAL2-PV), novel splicing variants of MICAL2, showing overexpression in prostate cancer cells. Immunohistochemical analysis using an antibody generated specific to MICAL2-PV revealed that MICAL2-PV was expressed in the cytoplasm of cancer cells with various staining patterns and intensities, whereas it was not or hardly detectable in adjacent normal prostate epithelium or prostatic intraepithelial neoplasia. Interestingly, immunohistochemical analysis of 105 prostate cancer specimens on the tissue microarray indicated that MICAL2-PV expression status was strongly correlated with Gleason scores (P < 0.0001) or tumor classification (P < 0.0001). Furthermore, the expression levels of MICAL2-PVs were also concordant to those of c-Met, a marker of tumor progression, with statistical significance (P = 0.0018). To investigate its potential of molecular therapeutic target for prostate cancers, we knocked down endogenous MICAL2-PVs in prostate cancer cells by small interfering RNA, which resulted in the significant reduction of prostate cancer cell viability. CONCLUSIONS: Our findings suggest that MICAL2-PV is likely to be involved in cancer progression of prostate cancer and could be a candidate as a novel molecular marker and/or target for treatment of prostate cancers with high Gleason score.

Adaptor Proteins, Signal Transducing↗
PubMed2006

The expression of thymidine phosphorylase is a prognostic predictor for the intravesical recurrence of superficial bladder cancer.

BACKGROUND: Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor, has been implicated in the angiogenesis of bladder cancer. The aim of this study is to investigate the association between TP expression and the clinicopathologic findings, and the prognostic value. METHODS: TP immunohistochemical staining was performed in specimens from 71 patients (50 men and 21 women) with superficial bladder cancer (pTa or pT1). Thirty-nine patients had received intravesical instillation of tetrahydropyranyladriamycin (THP) after transurethral resection (TUR) and the other 32 had not. For immunohistochemistry, paraffin-embedded specimens were stained with mouse monoclonal antibody against TP. When more than 10% of tumor cells were positively stained, staining was defined as positive. The correlations between TP immunostaining and clinicopathological features were analyzed. Multivariate analysis, using the Cox proportional hazard model, was performed to determine the risk factors for intravesical recurrence. RESULTS: Specimens from 29 of the 71 patients (19 men and 10 women) were positive for TP. The expression of TP was not correlated with age, sex, histological grade, multiplicity, or morphology. Also, TP expression was not associated with whether the cases were primary or recurrent. Multivariate analysis demonstrated that the decreased expression of TP and the use of THP instillation could be independent predictors of a higher rate of intravesical recurrence-free bladder cancer. CONCLUSION: The present study suggests that immunohistochemical TP staining is useful for predicting the intravesical recurrence of superficial bladder cancer after Transurethral resection of bladder tumor (TUR-Bt).

Administration, Intravesical↗
PubMed2006

Visual analog scale questionnaire to assess quality of life specific to each symptom of the International Prostate Symptom Score.

PURPOSE: We assessed patient quality of life specific to each of the 7 items on the International Prostate Symptom Score, as evaluated with a novel visual analog scale questionnaire. MATERIALS AND METHODS: A total of 246 male patients with a chief complaint of lower urinary tract symptom were asked to complete the International Prostate Symptom Score and visual analog scale questionnaires to assess bother or satisfaction regarding patient quality of life specific to each of the 7 items on the International Prostate Symptom Score. RESULTS: An item with the maximum visual analog scale measure matched the chief complaint in 169 patients (69%). In contrast, the chief complaint failed to match to an item with the most severe International Prostate Symptom Score in 104 patients (42%) (p = 0.012). Multiple regression analysis to define the best predictor of International Prostate Symptom Score quality of life score of the 14 items, including International Prostate Symptom Score and visual analog scale, revealed that the best predictor was the visual analog scale measure for nocturia (p = 0.0003), followed by visual analog scale measures for frequency (p = 0.0004) and incomplete emptying (p = 0.01). After alpha-blocker treatment improvement in the visual analog scale measure for the chief complaint correlated better with improvement in the International Prostate Symptom Score quality of life score than the change in International Prostate Symptom Score. The overall test-retest correlation for the visual analog scale questionnaire in 55 healthy elderly men and 44 patients with lower urinary tract symptoms was 0.772 and 0.742, respectively (p <0.00001). CONCLUSIONS: The novel visual analog scale measure of quality of life specific to each of the 7 items on the International Prostate Symptom Score has a significant impact on identifying the patient chief complaint as well as on patient specific quality of life. Our study supports the concomitant use of the International Prostate Symptom Score and visual analog scale questionnaires.

Aged↗
PubMed2006

The endoscopic surgical skill qualification system in urological laparoscopy: a novel system in Japan.

PURPOSE: The Japanese Urological Association, and Japanese Society of Endourology and ESWL have established the Endoscopic Surgical Skill Qualification System in urological laparoscopy. The system consists of a urological section as well as gynecology and general surgery sections. We present details of the Endoscopic Surgical Skill Qualification System and year 1 results. MATERIALS AND METHODS: Endoscopic Surgical Skill Qualification System requirements test the ability to complete common laparoscopic surgeries in each field. In urology applicants are required to complete adrenalectomies or nephrectomies appropriately and safely. Applicants should have 2 years of experience with laparoscopic practice, in addition to having completed a 6-year formal urological training program. Also, each surgeon must have performed more than 20 laparoscopic surgeries. According to assessment guidelines applicant skills are assessed by 2 referees who view unedited videotapes showing the entire laparoscopic procedure. To establish these referees 6 expert referees were first selected and 23 were then chosen from 36 referee applicants. Each referee had completed more than 100 laparoscopic surgeries and was chosen after video assessments by the 6 initial expert referees. RESULTS: Of 5,600 certified urologists in Japan 205 applied to this system in its first year, including 6 expert referees and 36 referee applicants. After video assessments by the referees 136 applicants were certified as having appropriate skills, resulting in a 66% pass rate. CONCLUSIONS: The Endoscopic Surgical Skill Qualification System has just started but it has drawn a lot of attention from the public. We hope that this qualification system will help prevent complications of urological laparoscopic surgeries and promote safer surgical procedures.

Clinical Competence↗
PubMed2006

Running suture for vesicourethral anastomosis in minilaparotomy radical retropubic prostatectomy.

INTRODUCTION: We used a running suture method for vesicourethral anastomosis in patients undergoing minilaparotomy radical retropubic prostatectomy. TECHNICAL CONSIDERATIONS: The vesicourethral anastomosis using a single knot at the 6:30-o'clock position is created with two steps of semicircular running suture. A total of 21 consecutive patients underwent this running suture method using the Endostitch in the hands of a single surgeon (T.M.) between March and November 2004. The running suture procedure was completed in 15 minutes on average. After surgery, no urinary leakage at the anastomotic site was found. Satisfactory continence was achieved in the short term in 100% (0 to 1 pad per day) of cases. However, dilation at the anastomosis using a metal dilator was required in 2 patients immediately after surgery. CONCLUSIONS: The running suture method is considered a feasible alternative in minilaparotomy radical retropubic prostatectomy.

Anastomosis, Surgical↗
PubMed2006

Complexed PSA improves prostate cancer detection: results from a multicenter Japanese clinical trial.

OBJECTIVES: To compare the distribution of total and complexed prostate-specific antigen (cPSA) in men with and without prostate cancer with another studied population and to ascertain whether cPSA could enhance the detection of prostate cancer in Japanese men. METHODS: A total of 760 men whose serum total PSA (tPSA) values ranged from 1.0 to 100 ng/mL were enrolled. Serum samples for tPSA and cPSA (ADVIA Centaur) were obtained in all cases. The area under the curve was calculated for comparison of the tPSA and cPSA values. We calculated the number of cancers missed and false-positive results at various cutoff values of cPSA compared with the conventional tPSA threshold of 4.0 ng/mL. RESULTS: Prostate cancer was detected in 268 (35.3%) of 760 patients. cPSA was greater than 8.3 ng/mL (equivalent to 10.0 ng/mL tPSA) in 46.6% of the men with cancer. The area under the curve for cPSA (0.741) was significantly better than that for tPSA (0.721, P <0.001). At a sensitivity of 85% to 95%, significant differences were found in the corresponding specificity between tPSA and cPSA. cPSA at a 3.0-ng/mL threshold detected an identical number of cancers as a tPSA cutoff of 4.0 ng/mL; however, it decreased the false-positive results by 28 cases. CONCLUSIONS: To our knowledge, this is the first report of the distribution of cPSA in Japanese men using a urologic referral population. cPSA can be an alternative to tPSA as the first screening test. A substantial number of men in Japan with prostate cancer are currently diagnosed with a tPSA value greater than 10.0 ng/mL.

Aged↗
PubMed2006

Partial androgen insensitivity syndrome with thermolability in the androgen receptor.

We report case of partial androgen insensitivity syndrome in a 12-year-old boy referred to our clinic complaining of bilateral gynecomastia and left undescended testicle. Laparoscopy for undescended testicle and bilateral mastectomy were performed, and the left testicle was absent. When skin fibroblasts of the scrotum obtained during surgery were cultured to analyse the androgen receptors, a slight thermolability was observed. Genomic examination of the androgen receptor gene could not detect any mutations.

Androgen-Insensitivity Syndrome↗
PubMed2006

Significant relationship of time-dependent uroflowmetric parameters to lower urinary tract symptoms as measured by the International Prostate Symptom Score.

AIMS: The aim of the present paper is to elucidate the possible involvement of time-dependent parameters as obtained by uroflowmetry in the manifestation of lower urinary tract symptoms (LUTS) in elderly patients. METHODS: Using simple and multiple regression analyses, the correlation of the International Prostate Symptom Score (IPSS) with objective parameters including age, postvoid residual, uroflowmetry and transrectal ultrasonic measurements of the prostate was analyzed in 206 male patients (average age of 68.0 +/- 7.4 years) who visited our outpatient clinic complaining of LUTS. RESULTS: In the 206 patients, the mean maximum flow rate was 12.2 mL/s (13.7 mL/s in mild, 11.9 mL/s in moderate, and 11.2 mL/s in severe IPSS total score) and average flow rate was 4.4 mL/s (5.4 mL/s in mild, 4.3 mL/s in moderate, and 3.5 mL/s in severe IPSS total score). Simple regression analyses demonstrated that age, voiding time, and average and maximum flow rates correlate significantly with symptom scores. In particular, relatively strong relationships were found between average flow rate and scores of intermittency, weak stream and total and voiding symptoms scores. Serum prostate specific antigen level, postvoid residual and prostatic ultrasonic measurements did not show a significant correlation with symptom scores. Multiple regression analyses revealed age and average flow rate to be independent determinants for symptom scores. These results suggest that the time-dependent function in micturition interferes in the manifestation of LUTS in elderly men who have borderline or pathologic maximum flow rate. When evaluating uro flowmetry in elderly male patients with LUTS, attention should be paid to time-dependent parameters such as voiding time and average flow rate.

Aged↗
PubMed2006

Gene therapy with TRAIL against renal cell carcinoma.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells. However, TRAIL is not toxic against most normal cells. We have accordingly examined by in vivo electroporation whether TRAIL induces apoptosis in renal cell carcinoma. In addition, combination treatment with TRAIL and 5-fluorouracil (5-FU) against renal cell carcinoma was also investigated. The NC65 renal cell carcinoma line was used as a target. pCAGGS TRAIL was injected into the NC65 tumors in the right flanks of severe combined immunodeficient mice. Tumors were pulsed with the CUY21 electroporator. Electroporation was done once on day 0 or thrice on days 0, 2, and 4. Apoptosis was determined by terminal deoxyribonucleotide transferase-mediated nick-end labeling assay. When TRAIL gene therapy using in vivo i.t. electroporation was done once only, the growth of NC65 tumors was not inhibited. However, when TRAIL gene therapy was done thrice, growth suppression of the NC65 tumors was observed. Transfection of the TRAIL gene by in vivo electroporation induced apoptosis in NC65 tumors. When NC65 cells were treated with TRAIL gene therapy in combination with 5-FU, stronger growth suppression was obtained. TRAIL gene therapy did not induce liver dysfunction in severe combined immunodeficient mice. This study shows that TRAIL gene therapy induced growth suppression and apoptosis in NC65 tumors without severe side effects, and that combination treatment of NC65 cells with TRAIL gene therapy and 5-FU resulted in higher antitumor activity. These findings suggest that TRAIL gene therapy and/or 5-FU may be effective against renal cell carcinoma without harmful toxic effects.

Animals↗
PubMed2006

[Progress in therapy for testicular tumors].

Approximately 80% of patients with metastatic testicular tumors are cured by cisplatin-containing chemotherapy and surgery. However, the remaining 20% of patients with advanced testicular tumors can not be cured at present. Thus, therapy for these testicular tumors infractory to treatment is the most important issue. Recently, chemotherapy for such tumors is developing, especially salvage chemotherapy using novel anticancer agents(paclitaxel, gemcitabine,irinotecan, docetaxel, oxaliplatin, etc) and high-dose anticancer drugs. Some of the new modalities are very attractive. In this article, we reviewed mainly these new forms of chemotherapy for testicular tumors.

Antineoplastic Agents↗