Biomedical subjects

Hideaki Miyake

Publications and source records attributed to Hideaki Miyake.

At least 37 records · Page 2Linked to original sources

PubMed2006

Clinical utility of serum macrophage migration inhibitory factor in men with prostate cancer as a novel biomarker of detection and disease progression.

Macrophage migration inhibitory factor (MIF) has been shown to play an important role in the growth and metastasis of prostate cancer. The objective of this study was to determine whether the serum level of MIF could be used as a diagnostic biomarker for prostate cancer as well as a predictor of disease progression. A total of 369 men who underwent systematic prostate biopsy from January 2000 to April 2004 and 30 healthy controls were included in this study. The serum MIF level was measured using an enzyme linked immunosorbent assay. Associations between the serum MIF level and several clinicopathological factors were analyzed. Among 359 patients, 137 were diagnosed as having prostate cancer. The mean values of serum MIF in the control, benign and cancer-groups were 2.1, 3.5 and 10.8 ng/ml, respectively. The MIF levels of patients with prostate cancer were significantly higher than those of the other two groups. A comparison of MIF and PSA values in all patients showed a positive correlation (correlation coefficient r(2)=0.56, p<0.0001). The MIF value in patients with prostate cancer was significantly associated with clinical T stage, Gleason score and percentage of positive biopsy core (PPBC). MIF levels in patients with metastasis were significantly elevated compared with those in patients without metastasis. Among patients undergoing radical prostatectomy, the level of MIF in those with pathologically confirmed extraprostatic disease was significantly higher than that in patients with organ-confined disease. Moreover, multivariate analysis showed that MIF values, PSA values and PPBC were independent predictors for extraprostatic disease. These findings suggest that an increased serum MIF level is closely associated with the progression of prostate cancer, and thus the serum MIF level could be useful as a novel biomarker for the detection of prostate cancer as well as a predictor of disease progression.

Adult↗

PubMed2005

Synthesis of phosphorus ylides bearing a P-H bond from a kinetically stabilized 1,3,6-triphosphafulvene.

In mixing 2,4,6-tris(2,4,6-tri-tert-butylphenyl)-1,3,6-triphosphafulvene with alkyllithium compounds and acetic acid, both of nucleophilic alkylation and electrophilic protonation occurred at the exo sp2-phosphorus atoms to afford [2,4-bis(2,4,6-tri-tert-butylphenyl)-1,3-diphosphacyclopentadienylidene](alkyl)(2,4,6-tri-tert-butylphenyl)phosphoranes which are phosphorus ylides that bear a P-H bond. A phosphorus ylide bearing both P-H and P-F bonds was obtained by reaction of 2,4,6-tris(2,4,6-tri-tert-butylphenyl)-1,3,6-triphosphafulvene with hydrogen tetrafluoroborate, and the structure was determined by X-ray crystallography. Both P=C double bond and P(+)-C(-) zwitterionic character was indicated by the metric parameters. The isolated phosphorus ylide bearing a P-H bond, [2,4-bis(2,4,6-tri-tert-butylphenyl)-1,3-diphosphacyclopentadienylidene](2,4,6-tri-tert-butylphenyl)phosphorane, showed no isomerization by H-migration to the corresponding phosphinodiphospholes, probably due to the pi-accepting ability of the unsaturated PC bonds and aromaticity of the C3P2 ring. The ylide structure and aromaticity of 2,4-diphosphacyclopenta-2,4-dienylidenephosphorane was characterized by theoretical calculations. In addition, the regioselective protonation of the lithiated phosphinodiphospholes generated from the 1,3,6-triphosphafulvene is discussed.

Journal Article↗

PubMed2005

Detection of micrometastases in pelvic lymph nodes in patients undergoing radical cystectomy for locally invasive bladder cancer by real-time reverse transcriptase-PCR for cytokeratin 19 and uroplakin II.

PURPOSE: The objective of this study was to clarify the significance of micrometastases in pelvic lymph nodes in patients who underwent radical cystectomy for bladder cancer. EXPERIMENTAL DESIGN: We included 40 patients with locally invasive bladder cancer who underwent radical cystectomy and pelvic lymphadenectomy. Expression of cytokeratin 19 (CK19), uroplakin II (UP II), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in 760 lymph nodes were assessed by a fully quantitative real-time reverse transcription-PCR (RT-PCR) assay. The quantification value of CK19 or UP II mRNA was described as each value relative to GAPDH mRNA. In this study, we regarded specimen in which either CK19 or UP II mRNA was positive as "presence of micrometastasis." RESULTS: Routine pathologic examinations detected tumor cells in 29 lymph nodes from six patients. Real-time RT-PCR identified positive expression of CK19 and UP II mRNAs in 49 lymph nodes from 10 patients and 98 lymph nodes from 16 patients, respectively. Of 633 lymph nodes from 34 patients with no pathologic evidence of nodal involvement, 13 nodes from five patients and 58 nodes from 10 patients were diagnosed as positive for CK19 and UP II mRNAs expression, respectively, by real-time RT-PCR. Presence of micrometastases was significantly associated with other conventional prognostic variables, including pathologic stage and microvascular invasion. Disease recurrence was occurred in eight patients, among whom four patients were negative for lymph node metastasis by routine pathologic examination and diagnosed as having micrometastasis by real-time RT-PCR assay. Furthermore, cause-specific survival rate in patients without micrometastasis was significantly higher than that in those with micrometastasis, irrespective of the presence of pathologic-positive nodes. CONCLUSIONS: Approximately 30% of locally invasive bladder cancer shed cancer cells to pelvic lymph nodes, and disease recurrence after radical cystectomy could be explained, at least in part, by micrometastases in pelvic lymph nodes.

Cystectomy↗

PubMed2005

Use of antisense oligonucleotides targeting the cytoprotective gene, clusterin, to enhance androgen- and chemo-sensitivity in prostate cancer.

The discovery and targeting of genes mediating androgen-independence may lead to the development of novel therapies that delay progression of hormone refractory prostate cancer (HRPC). Clusterin is a stress-associated cell survival gene that increases after androgen ablation. Here, we review clusterin's functional role in apoptosis and the use of antisense oligonucleotides (ASOs) against clusterin to enhance apoptosis in prostate cancer models. Immunostaining of tissue microarrays constructed from untreated and post-hormone treated radical prostatectomy specimens confirm that clusterin is highly expressed in virtually all HRPC cells, 80% of prostate cancer cells after neoadjuvant hormone therapy, but is low or absent (<20%) in untreated specimens. Overexpression of clusterin in LNCaP cells confers resistance to both androgen ablation and chemotherapy. Clusterin ASOs reduced clusterin levels in a dose-dependent and sequence-specific manner. Adjuvant treatment with murine clusterin ASOs after castration of mice bearing Shionogi tumors decreased clusterin levels, accelerated apoptotic tumor regression, and significantly delayed the recurrence of androgen-independent tumors. A human clusterin ASO targeting the translation initiation site and incorporating MOE-gapmer backbone (OGX-011) synergistically enhanced the cytotoxic effects of paclitaxel in human xenografts of prostate, renal cell, bladder, and lung cancer. Clusterin, is an anti-apoptosis protein upregulated in an adaptive cell survival manner by androgen ablation and chemotherapy that confers resistance to various cell death triggers. Suppression of clusterin levels using ASOs enhances cell death following treatment with androgen ablation, radiation, and chemotherapy.

Androgens↗

PubMed2005

Beyond simple castration: targeting the molecular basis of treatment resistance in advanced prostate cancer.

Over the past 20 years, research on hormonal treatments for prostate cancer focused on maximizing androgen ablation through combination therapy. Unfortunately, maximal androgen ablation increases treatment-related side effects and expense and has not significantly prolonged time to androgen-independent (AI) progression. Intermittent androgen suppression (IAS) is based on the hypothesis that if tumor cells surviving androgen withdrawal can be forced along a normal pathway of differentiation by androgen replacement, then apoptotic potential might be restored, androgen dependence may be prolonged and progression to androgen independence may be delayed. Observations from animal model studies suggest that progression to androgen independence is delayed by IAS and this strategy is now being evaluated in phase III trials. Another strategy for improving therapies in advanced prostate cancer involves targeting genes that are activated by either androgen withdrawal or chemotherapy to delay or prevent the emergence of the resistant AI phenotype. Targeted inhibition of stress-associated increases in gene expression precipitated by androgen withdrawal or chemotherapy may enhance treatment-induced apoptosis and delay progression to AI disease. Proteins fulfilling these criteria include antiapoptotic members of the Bcl-2 protein family, clusterin, Hsp27, and IGFBP-2 and IGFBP-5. The purpose of this paper is to review the rationale and progress in using targeted gene therapies to enhance tumor cell death after androgen withdrawal or taxane chemotherapy. Antisense oligonucleotides offer one approach to target genes involved in cancer progression, especially those not amenable to small molecule or antibody inhibition. The current status and future direction of several antisense oligonucleotides that have potential clinical use in cancer are also reviewed.

Clusterin↗

PubMed2005

Clinicopathological features of prostate cancer in Japanese men diagnosed on repeat transrectal ultrasound-guided biopsy.

BACKGROUND: The objective of this study was to analyze the clinicopathological features of prostate cancer detected on repeat transrectal ultrasound-guided random biopsy in comparison with those detected on initial biopsy. METHODS: Between January 1999 and March 2004, 132 Japanese men underwent radical retropubic prostatectomy without neoadjuvant therapy at our institution. In 109 patients (group A) prostate cancer was detected on initial biopsy, while in the remaining 23 (group B), it was diagnosed on repeat biopsy. We retrospectively characterized differences in clinicopathological features between these two groups. RESULTS: There were no significant differences in age, serum prostate specific antigen (PSA) value, or biopsy Gleason score between groups A and B. However, prostate volume in group A was significantly smaller than that in group B, while PSA density, the percentage of positive biopsy cores, and the percentage of cancers in the biopsy set in group A were significantly higher than those in group B. Pathological examination of the radical prostatectomy specimens showed that there were no significant differences in the distribution of pathological T stage or in the Gleason score; or in the incidences of lymphatic invasion, vascular invasion, and perineural invasion between groups A and B. Despite there being a significantly larger tumor volume in the radical prostatectomy specimens in group A compared to that in group B, there was no significant difference in the incidence of insignificant disease between these two groups. CONCLUSION: These findings suggest that missing the cancer on the initial needle biopsy may be due to a small cancer focus in a large prostate; however, there were no significant differences in the final pathological features of prostate cancers detected on the initial and repeat biopsies, suggesting similar biological behaviors. Thus performance of a repeat biopsy in cases negative for malignancy on the initial biopsy is advocated. Missing prostate cancer on the initial biopsy may be due to a small cancer focus in a large prostate; however prostate cancers detected on initial and repeat biopsies may have similar biological behavior.

Aged↗

PubMed2005

Clinical outcome of combined immunotherapy with low-dose interleukin-2 and interferon-alpha for Japanese patients with metastatic renal cell carcinoma who had undergone radical nephrectomy: a preliminary report.

BACKGROUND: The objective of this study was to evaluate the clinical outcome of combined immunotherapy with interferon-alpha (IFN-alpha) and low-dose interleukin-2 (IL-2) for Japanese patients with metastatic renal cell carcinoma (RCC) who had undergone radical nephrectomy. METHODS: This study included 13 patients who were diagnosed as having metastatic RCC following radical nephrectomy. These patients received a subcutaneous injection of IFN-alpha (6 x 10(6) IU per day) three times per week and an intravenous injection of IL-2 (1.4 x 10(6) IU per day) twice per week. Tumor response was evaluated every 16 weeks, and as a rule, this weekly regimen was repeated 50 times in patients with evidence of objective response or stable disease. RESULTS: One of the 13 patients dropped out because of severe toxicity; hence, 12 patients were evaluable, with a median follow-up period of 18 months after the start of this combined therapy. Six patients (50.0%) achieved objective responses, with 1 complete response (CR), while only 2 (16.7%) demonstrated progressive disease. The median duration of response in the 6 responders was 13.5 months. Toxicity associated with this combined immunotherapy was limited to WHO grade 1 or 2 in these 12 patients. All patients were alive at last follow-up, and 2 remain disease-free after 1 additional patient showed a CR following surgical resection of the remaining metastatic disease. CONCLUSION: Our preliminary experience suggests that long-term, repeated treatment with IFN-alpha and low-dose IL-2 is feasible in Japanese patients with metastatic RCC who have undergone radical nephrectomy. Although it will be necessary to accumulate data from a larger number of patients with a longer follow-up period, the combined immunotherapy tested in this study may become the preferred therapy for Japanese patients with metastatic RCC.

Aged↗

PubMed2005

Significance of the percentage of prostate needle biopsy cores with cancer as a predictor of disease extension in radical prostatectomy specimens in Japanese men.

OBJECTIVES: To evaluate the significance of the percent of positive biopsy cores (PPBC) with cancer, which has been shown to be one of the most useful predictors of prostate cancer extension in patients undergoing radical prostatectomy. MATERIALS AND METHODS: This study included 120 patients who underwent radical prostatectomy for prostate cancer without any neoadjuvant therapies. All of these patients were diagnosed by random prostate biopsy targeting 8 cores; that is, standard sextant cores and 2 additional cores from the bilateral anterior lateral horns. We evaluated the appropriate cut-off points of PPBC for predicting disease extension according to the number of biopsy cores. Based on these criteria, multivariate analysis was then performed to determine whether PPBC could be an independent factor differentiating organ-confined disease from extraprostatic disease. RESULTS: The most suitable PPBC cut-off value using findings targeting 8 cores for predicting disease extension was 37.5%. If PPBC was calculated based on the outcome of standard sextant cores alone, it is most appropriate to use 33.3% as the cut-off point. Multivariate analysis showed that PPBC calculated based on the standard sextant cores and percent of cancer in the biopsy set could be used as independent factors predicting disease extension irrespective of other biopsy-associated factors. CONCLUSIONS: For predicting disease extension, it may be useful to calculate PPBC based on the outcomes of standard sextant biopsy cores alone even if additional cores were taken, and that PPBC calculated in such a way may be the strongest preoperative predictor of prostate cancer extension in Japanese men scheduled for radical prostatectomy.

Aged↗

PubMed2005

Preoperative prediction of final pathological features is not improved by the free-to-total prostate-specific antigen ratio in Japanese men with clinically localized prostate cancer.

BACKGROUND: The objective of the present study was to determine whether the percentage of free/total prostate-specific antigen (f/tPSA) in patients scheduled to undergo radical prostatectomy for clinically localized prostate cancer can preoperatively predict organ-confined versus extraprostatic disease. METHODS: Serum levels of fPSA and tPSA were measured in 97 patients with clinically organ-confined disease before they underwent radical prostatectomy. The relationships of tPSA, f/tPSA and the pathological stage of the prostatectomy specimens were analyzed. Furthermore, the ability of f/tPSA to predict the pathological features was compared with those of tPSA and systematic biopsy findings. RESULTS: Organ-confined and extraprostatic extension diseases were present in 51 and 46 men, respectively. tPSA in patients with extraprostatic diseases was significantly higher than that in those with organ-confined diseases; however, there was no significant difference in f/tPSA between these two groups. There was also a significant difference in tPSA levels at each pathological stage, while f/tPSA did not parallel the pathological stage. Furthermore, there was no additional information concerning the extent of prostate cancer obtained when f/tPSA was combined with tPSA or with the percent of positive biopsy cores, which is the most significant predictor of the extent of prostate cancer among factors associated with systematic biopsy. CONCLUSION: f/tPSA could not predict the final pathological features in patients with clinically localized prostate cancer before radical prostatectomy. Moreover, the predictive value provided by tPSA or systematic biopsy findings was not improved by combined analysis with f/tPSA.

Aged↗

PubMed2005

Prognostic significance of vascular invasion in patients with bladder cancer who underwent radical cystectomy.

BACKGROUND: The objective of this study was to determine whether vascular invasion (i.e. lymphatic and blood vessel invasion) could be a useful prognostic predictor in patients with locally invasive transitional cell carcinoma (TCC) of the bladder who underwent radical cystectomy. METHODS: This series included 114 consecutive patients undergoing radical cystectomy for primary TCC of the bladder between November 1989 and July 2003. Several clinicopathological characteristics of these patients were analyzed, focusing on the association between vascular invasion and disease recurrence after radical cystectomy. RESULTS: Lymphatic and blood vessel invasions were detected in 55 (48.2%) and 33 (29.8%) specimens, respectively. Lymphatic invasion was significantly associated with pathological stage, tumor grade, lymph node metastasis, blood vessel invasion and disease recurrence, whereas blood vessel invasion was significantly related to pathological stage, lymph node metastasis, lymphatic invasion and disease recurrence. Recurrence-free survival in patients with lymphatic invasion was significantly lower than that in those without lymphatic invasion, and a similar significant difference in recurrence-free survival was observed between patients with and without blood vessel invasion. However, multivariate analysis using the Cox proportional hazards model showed that only pathological stage and lymph node metastasis could be used as independent predictors for disease recurrence after radical cystectomy. CONCLUSIONS: Despite a significant association between several prognostic parameters, vascular invasion was not an independent predictor of disease recurrence; therefore, if there are other conventional parameters available, there might not be any additional advantage to considering the presence of vascular invasion when predicting the prognosis of patients undergoing radical cystectomy for TCC of the bladder.

Adult↗

PubMed2005

Prediction of potentially insignificant prostate cancer in men undergoing radical prostatectomy for clinically organ-confined disease.

BACKGROUND: The objectives of the present study were to characterize, according to tumor significance, the clinicopathological features of patients with prostate cancer who underwent radical prostatectomy, and to determine useful parameters for predicting insignificant disease before surgery. METHODS: In this series, we included 195 patients who underwent radical prostatectomy for clinically organ-confined prostate cancer at our institution between January 1999 and November 2003. Several clinicopathological factors were analyzed, focusing on whether the largest tumor volume in radical prostatectomy specimens was >/=0.5 cm(3) or <0.5 cm(3), which is the criterion defined to distinguish insignificant cancer from significant cancer. RESULTS: Potentially insignificant cancer was detected in 28 of 195 patients (14.4%). There were significant differences between patients with insignificant disease and those with significant disease in serum prostate specific antigen (PSA) as well as all biopsy parameters, with the exception of biopsy Gleason score. Furthermore, final pathological examination demonstrated that these two patient groups showed significant differences in Gleason score and the incidence of extraprostatic disease extension. Pearson's correlation analysis showed that tumor volume in the prostatectomy specimens was significantly associated with serum PSA and all biopsy parameters; however, each of the correlations was comparatively weak. There was no single parameter that could viewed as a useful predictor of tumor significance. The best model for predicting insignificant tumor was the combined use of biopsy Gleason score <7 and percent of positive biopsy core (PPBC) <15%; however, the further addition of serum PSA <10 ng/mL to these two parameters failed to enhance the predictive value of cancer significance. CONCLUSIONS: These findings indicate that clinicopathological findings suggesting favorable features are well observed in patients with potentially insignificant prostate cancer compared to those with significant prostate cancer, and the combination of a biopsy Gleason score <7 and PPBC <15% might be useful as a predictor of insignificant disease.

Adenocarcinoma↗

PubMed2005

Intussusception of the bladder neck does not promote early restoration to urinary continence after non-nerve-sparing radical retropubic prostatectomy.

BACKGROUND: The objectives of the present study were to investigate whether buttressing sutures, which prevent the bladder neck from pulling open as the bladder fills, can promote earlier recovery from urinary incontinence after radical retropubic prostatectomy (RRP) and to identify possible risk factors associated with urinary incontinence after RRP. METHODS: The present study included 72 patients who underwent non-nerve-sparing RRP without neoadjuvant therapy between January and December 2003. Among these 72 patients, intussusception of the bladder neck was performed in 24 who consented to this procedure. In the present series, continence was defined as the absence of any need to use sanitary pads or diapers. Continence was evaluated by a patient interview 1, 3 and 6 months after RRP. RESULTS: There were no significant differences in clinicopathological characteristics between patients with and without intussusception of the bladder neck. The percentage of continent patients 1, 3 and 6 months after RRP was 34.7%, 63.9% and 95.8%, respectively, and there were no significant differences in continence between the two groups at any time point. Among several factors examined, only bladder neck preservation was an independent predictor of recovery from urinary incontinence 1 and 3 months after RRP. CONCLUSIONS: These findings suggest that it would be important to preserve the bladder neck for early return to continence after non-nerve-sparing RRP; however, intussusception of the bladder neck may not offer significant improvement in earlier return of urinary control.

Aged↗

PubMed2005

Is a limited lymphadenectomy targeting obturator nodes alone an adequate procedure for Japanese men undergoing radical prostatectomy?

BACKGROUND: The objective of the present study was to investigate the significance of pelvic lymphadenectomy during radical prostatectomy in Japanese men with prostate cancer. METHODS: A total of 178 consecutive patients who underwent radical prostatectomy and standard pelvic lymphadenectomy targeting the external iliac nodes and obturator fossa for clinically localized prostate cancer were studied. The median observation period of this series was 18 months (range: 3-36 months). RESULTS: Lymph node metastases were detected in 13 patients; that is, positive nodes were located in the external iliac nodes alone in seven patients, the obturator fossa alone in four patients, and both external iliac nodes and obturator fossa in two patients. Of these 13 patients, all of the seven with more than one positive node demonstrated biochemical recurrence, whereas five of the six with single node involvement remained without signs of biochemical recurrence. Furthermore, a single positive node was located in the external iliac region in five of the six patients. When a group at high-risk for lymph node metastasis was defined as those meeting more than two of the following three criteria: (i) pretreatment serum prostate specific antigen value > or = 20 ng/mL; (ii) biopsy Gleason sum > or = 8; or (iii) percentage of positive biopsy core > or = 50%, the incidence of lymph node metastasis was 24.5% in the high-risk group and 0.8% in the low-risk group. CONCLUSIONS: These findings suggest that limited dissection of the obturator node alone may not be sufficient for Japanese men undergoing radical prostatectomy; therefore, we recommend performing standard pelvic lymphadenectomy targeting both the external iliac nodes and the obturator fossa for patients at high-risk of lymph node involvement.

Biopsy↗

PubMed2005

Clinical study of six cases showing late relapse of germ cell tumors.

Late relapse of germ cell tumors has been considered rare. We report six patients treated at our institution with relapses of germ cell tumors more than 2 years after first successful management. Median time to late relapse for pure seminomas and non-seminomatous germ cell tumors was 30.0 and 75.5 months, respectively. The sites of the late relapses in two cases of pure seminoma were located out of the fields of irradiation. After systematic chemotherapy, both these patients remain disease free. Two patients with non-seminomatous germ cell tumors received salvage chemotherapy at the time of late relapse, but tumor markers did not normalize in either case. A complete resection of relapsed masses was performed in three cases of non-seminomatous germ cell tumors. All three patients are without evidence of disease. The incidence of late relapse in patients with pure seminomas and non-seminomas was 2.4% and 3.3%, respectively, which suggests the necessity for long-term follow up.

Adult↗

PubMed2005

Antisense oligodeoxynucleotide therapy targeting clusterin gene for prostate cancer: Vancouver experience from discovery to clinic.

BACKGROUND: The objective of this study was to review our experience in the development of antisense (AS) oligodeoxynucleotide (ODN) therapy for prostate cancer targeting antiapoptotic gene, clusterin. METHODS: We initially summarized our data demonstrating that clusterin could be an optimal therapeutic target for prostate cancer, then presented the process of developing AS ODN therapy using several preclinical animal models. Finally, the preliminary data of the recently completed phase I clinical trial using AS clusterin ODN as well as the future prospects of this therapy are discussed. RESULTS: Expression of clusterin was highly up-regulated after androgen withdrawal and during progression to androgen-independence, but low or absent in untreated tissues in both prostate cancer animal model systems and human clinical specimens. Introduction of the clusterin gene into human prostate cancer cells confers resistance to several therapeutic stimuli, including androgen ablation, chemotherapy and radiation. AS ODN targeting the translation initiation site of the clusterin gene markedly inhibited clusterin expression in prostate cancer cells in a dose-dependent and sequence-specific manner. Systemic treatment with AS clusterin ODN enhanced the effects of several conventional therapies through the effective induction of apoptosis in prostate cancer xenograft models. Based on these findings, a phase I clinical trial was completed using AS clusterin ODN incorporating 2'-O-(2-methoxy)ethyl-gapmer backbone (OGX-011), showing up to 90% suppression of clusterin in prostate cancer. CONCLUSIONS: The data described above identified clusterin as an antiapoptotic gene up-regulated in an adaptive cell survival manner following various cell death triggers that helps confer a phenotype resistant to therapeutic stimuli. Inhibition of clusterin expression using AS ODN technology enhances apoptosis induced by several conventional treatments, resulting in the delay of AI progression and improved survival. Clinical trials using AS ODN confirm potent suppression of clusterin expression and phase II studies will begin in early 2005.

Clinical Trials as Topic↗

PubMed2005

Significance of routine transition zone biopsies in Japanese men undergoing transrectal ultrasound-guided prostate biopsies.

BACKGROUND: The objective of this study was to evaluate the clinical significance of additional routine transition zone (TZ) biopsies in Japanese men undergoing transrectal ultrasound (TRUS)-guided systematic 8-core peripheral zone (PZ) biopsies. METHODS: Between October 2002 and December 2004, a total of 788 consecutive patients underwent TRUS-guided systematic biopsy of the prostate for the fi rst time. As a rule, 10 cores were taken from each patient; that is, 8 cores from the PZ, including the standard sextant cores and 2 cores from the anterior lateral horns, and 2 additional cores from the bilateral TZ. The cancer detection rate was calculated according to several parameters. We also assessed the disease extent on radical prostatectomy specimens according to the cancer location within the biopsy specimens. RESULTS: Prostate cancer was detected by 10-core biopsies in 209 (26.5%) of the 788 patients, and 11 of these patients had positive cores only in the TZ; that is, the increase in cancer detection rate by sampling two additional cores from the TZ was 5.3%. Among 209 patients diagnosed as having prostate cancer, radical prostatectomy without any neoadjuvant therapy was performed in 59 patients with positive biopsy cores in the PZ, 7 in the TZ and 32 in both the PZ and TZ. Patients with positive cores in both zones showed significantly less favorable characteristics, indicating more advanced disease than that in those with positive cores in either zone. CONCLUSIONS: Routine TZ biopsy did not significantly increase the detection rate of prostate cancer; however, the anatomical location of positive biopsy cores could provide additional information concerning disease extension in patients undergoing radical prostatectomy.

Aged↗

PubMed2005

Prognostic significance of insulin-like growth factor (IGF) binding protein-2 to IGF-binding protein-3 ratio in patients undergoing radical cystectomy for invasive transitional cell carcinoma of the bladder.

OBJECTIVES: To analyse the prognostic significance of insulin-like growth factor binding protein-2 (IGFBP-2) and IGFBP-3 in patients having a radical cystectomy for invasive bladder cancer. PATIENTS AND METHODS: Tissue samples of invasive bladder cancer were obtained from 97 patients who had radical cystectomy. The expression of IGFBP-2 and IGFBP-3 mRNAs in these samples was measured by real-time reverse transcription-polymerase chain reaction (RT-PCR), and the findings analysed in relation to clinicopathological factors. RESULTS: During the observation period, 31 patients (group A) developed disease recurrence, while the remaining 66 (group B) had no evidence of recurrence. The expression level of IGFBP-2 mRNA was significantly higher in group A than in B, while IGFBP-3 mRNA expression was significantly lower in group A than in B, and there was a significant difference in the relative expression ratio of IGFBP-2 to IGFBP-3 (BP-2/BP-3 ratio) between the groups. Recurrence-free survival in patients with an elevated BP-2/BP-3 ratio was significantly lower than in those with a normal ratio. Multivariate analysis indicated that an elevated BP-2/BP-3 ratio, but not IGFBP-2 and IGFBP-3 mRNA levels, was an independent predictor of disease recurrence. CONCLUSIONS: These findings suggest that the BP-2/BP-3 ratio measured by real-time RT-PCR could be useful for predicting disease recurrence in patients who have had a radical cystectomy for invasive bladder cancer.

Aged↗

PubMed2005

A comparison of the biological features between prostate cancers arising in the transition and peripheral zones.

OBJECTIVES: To investigate differences in the biological features of prostate cancer according to the zonal origin. PATIENTS AND METHODS: Among 172 consecutive patients who had a radical prostatectomy (RP), the study included 124 diagnosed as having either transition zone (TZ) or peripheral zone (PZ) cancer, defined according to whether there was > 70% of the cancer area in the TZ or PZ, respectively. The clinicopathological features were then compared between these groups. In addition, the RP specimens were stained immunohistochemically with antibodies to Ki-67, Bcl-2, matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF). RESULTS: Twenty-four patients were diagnosed as having TZ cancer and the remaining 100 as having PZ cancer. Prostate specific antigen (PSA) values in patients with TZ cancer were significantly higher than in those with PZ cancer. Tumour volume in TZ cancer was significantly greater than that in PZ cancer, but there was no significant difference in biochemical recurrence-free survival between the groups. Immunohistochemistry showed that despite there being no differences in Bcl-2 and VEGF expression between TZ and PZ cancers, there was significantly greater expression of Ki-67, MMP-2 and MMP-9 in PZ than TZ cancers. CONCLUSIONS: Despite there being no significant difference in biochemical recurrence-free survival after RP between patients with TZ and PZ cancers, there was less cell proliferation and biomarker levels related to invasive potential in TZ than in PZ cancers.

Aged↗