Prostatic Neoplasms: Egawa S

Kamidono S, Ohshima S, Hirao Y, Suzuki K, Arai Y, Fujimoto H, Egawa S, Akaza H, Hara I, Hinotsu S, Kakehi Y, Hasegawa T, Anonymous00384. · No affiliation provided · Int J Urol. · Pubmed #18184166 No free full text.

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Satoh T, Irie A, Egawa S, Baba S. · Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. · Curr Gene Ther. · Pubmed #15638715 No free full text.

Abstract: The incidence of prostate cancer has dramatically increased worldwide in the past decade, with mortality rates also increasing in many countries. Once prostate cancer is diagnosed, it is important to rapidly begin a treatment regimen that is either potentially curative or impedes disease progression. When the disease is confined to the prostate, it can be cured by radical prostatectomy or irradiation therapy. However, there are no curative therapies for locally advanced, recurrent, or metastatic diseases. Clearly, new therapies are needed for these patients. Gene therapy may provide additional therapeutic options with the potential to affect both localized and metastatic disease. Virus-mediated transduction of the herpes simplex virus thymidine kinase (HSV-tk) gene transfer, followed by a course of the prodrug ganciclovir (GCV), so-called suicide gene therapy, has been demonstrated by several investigators. The present in situ gene therapy clinical trial for human prostate cancer demonstrated safety, clinical efficacy, and biological effects of antitumor activity. HSV-tk clinical trials for prostate cancer are also ongoing in Japan, the Netherlands, and Mexico. Currently, numerous preclinical studies have reported immunomodulatory cytokine gene therapy, such as interleukin-2, interleukin-12, B7-1 (CD80), B7-2 (CD86) and granulocyte-macrophage colony-stimulating factor. Several clinical studies have been approved that potentially will show that these immunomodulatory gene therapies may generate an effective local and systemic antitumor activity and that should provide options for patients with prostate cancer. We review the multiple issues involved in current in situ gene therapy (gene/immunotherapy), its outcome, and future directions for patients with prostate cancer.

Kuruma H, Egawa S, Oh-Ishi M, Kodera Y, Maeda T. · Department of Urology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan. · Prostate Cancer Prostatic Dis. · Pubmed #15477873 No free full text.

Abstract: In this paper, we briefly review cancer proteomics in general, with particular attention to our proteome analyses of prostate cancer. Our efforts include development of new tools and novel approaches to discovering proteins potentially useful as cancer diagnostic and/or prognostic biomarkers or as therapeutic targets. To this end, we analyzed prostate cancer proteomes using two-dimensional gel electrophoresis employing agarose gels for the initial isoelectric focusing step (agarose 2-DE), with mass spectrometry used for protein identification. Agarose 2-DE offers advantages over the more widely used immobilized pH gradient 2-DE for separating high molecular mass proteins (15-500 kDa), thereby increasing its power to detect changes in the cancer's high-molecular mass proteomes.

Egawa S, Baba S. · Department of Urology, Kitasato University School of Medicine. · Nippon Rinsho. · Pubmed #12599586 No free full text.

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Egawa S. · Department of Urology, Kitasato University School of Medicine. · Nippon Rinsho. · Pubmed #12599553 No free full text.

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Egawa S. · Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. · Biomed Pharmacother. · Pubmed #11325209 No free full text.

Abstract: The use of prostate-specific antigen (PSA) for early detection of prostate cancer has dramatically increased the reported incidence of this malignancy but its net benefit is unclear and remains controversial at present. Although several countries have adopted prostate cancer screening as a health policy, a reduction of cancer mortality would be an ultimate indication of the effectiveness of early detection. Since screening upon patient request cannot be refused, appropriate information should be provided until further support is available.

Egawa S. · Department of Urology, Kitasato University School of Medicine. · Nippon Rinsho. · Pubmed #11022723 No free full text.

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Tabata K, Satoh T, Matsumoto K, Fujita T, Irie A, Iwamura M, Yanagisawa N, Matsuda D, Muramoto M, Kadowaki K, Suyama K, Shoji K, Koh H, Kawakami T, Okayasu I, Egawa S, Baba S. · Department of Urology, Kitasato University, School of Medicine. · Nippon Hinyokika Gakkai Zasshi. · Pubmed #16898594 No free full text.

Abstract: PURPOSE: To evaluate the clinicopathological outcomes of 8 months of neoadjuvant hormonal therapy (NHT) prior to radical prostatectomy for high-risk prostate cancer. PATIENTS AND METHODS: A multi-institutional prospective trial was performed between July 2000 and May 2003 involving high-risk prostate cancer patients without metastasis, including 21 who received 8 months of NHT before radical prostatectomy. High-risk group was defined as clinical stage > or =T2c and/or prostate-specific antigen (PSA) >20 ng/ml and/or Gleason score > or =8. PSA values were considered elevated (biochemical failure) if values of 0.1 ng/ml or greater were obtained. RESULTS: Median of initial PSA levels before prostate biopsy was 27.6 ng/ml (8.5-80.7 ng/ml), and median of pre-operative PSA levels after NHT was 0.28 ng/ml (0.02-4.2 ng/ml). There were 5 patients (23.8%) with lower limit of PSA detection (less than 0.02 ng/ml) in 8 months after NHT. The clinical T stage was T1c in 9 patients (42.9%), T2a-b in 8 patients (38.1%), T2c in 3 patients (14.3%), and T3a in 1 patient (4.8%). The median follow-up was 25 months (range 4 to 37). There were 2 patients (9.5%) in pT0, 5 patients (23.8%) with positive surgical margin, 5 patients (23.8%) with extracapsular extension (ECE) and 3 patients (14.3%) with seminal vesicle involvement (SVI). Biochemical failure was occurred in 9 of 21 (42.9%) including of one pT0. Range of time to postoperative biochemical failure was 2 to 25 months (median 6 months) and most of biochemical failure was found within 12 months after surgery. Biochemical failure rate was significantly higher in patient with positive SVI (p = 0.0308) and higher in patients with pre-operative PSA levels of more than 0.1 ng/ml (p = 0.0836), positive ECE (p = 0.0545) and positive surgical margin (p = 0.0545). CONCLUSION: Biochemical failure was frequent after this combined treatment, even in a pT0 case. Long-term follow-up of patients is needed to assess the impact of this therapy on mortality.

Egawa S, Okusa H, Matsumoto K, Suyama K, Baba S. · Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. · Prostate Cancer Prostatic Dis. · Pubmed #12970730 No free full text.

Abstract: We conducted a study in order to characterize changes after withdrawal of androgen ablation (AA) for prostate cancer. AA was withdrawn in 38 Japanese patients with prostate cancer who had undergone this therapy for various periods. Patients were stratified into those who had undergone AA for less than 24 months (Group 1, n=12) and those with longer periods of AA (Group 2, n=26). Serial changes in hormones and prostate-specific antigen (PSA) were prospectively monitored following cessation of AA. The median durations of AA in the two groups were 8.5 and 54.5 months, respectively. Levels of total testosterone (T), luteinizing hormone and PSA increased significantly with time. At the end of 2 y, 30/38 patients (78.9%) had T levels above 50 ng/dl and 19/38 (50%) had levels above 320 ng/dl. Patients in Group 2 required significantly longer duration for T recovery. Complete T recovery is not always accompanied by rising PSA. Recovery of T levels is often slow following cessation of prolonged AA. Expression of PSA after AA is often variable and unpredictable. Thus, interpretation of outcomes in clinical trials incorporating AA needs caution and careful consideration.

Kuruma H, Fujita T, Shitara T, Egawa S, Yokoyama E, Baba S. · Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. · Int J Urol. · Pubmed #12941125 No free full text.

Abstract: BACKGROUND: Paclitaxel used in combination with estramustine has been shown to exert synergistic cytotoxicity in patients with hormone-refractory prostate cancer (HRPC). There have been few reports of this therapy in an Asian male population. METHODS: Nine patients with progressive metastatic HRPC completed at least one cycle of combination therapy employing weekly paclitaxel plus estramustine. Paclitaxel was given weekly for 3 weeks as a 2-h intravenous infusion at a dose of 100 mg/infusion. The cycle was repeated every 4 weeks. A dose of 280 mg of oral estramustine was administrated twice daily for 21 days from the first day of each cycle. Both efficacy and toxicity were recorded. RESULTS: Grade 1 sensory neuropathy was seen in three patients (33%) and grade 4 thrombopenia/anemia was seen in one patient (11%). Performance status improved in three of seven patients (43%), while six patients (67%) showed a 50% or greater decline in prostate-specific antigen levels. Two of these patients experienced significant improvement in bone pain. One patient died of cardiac infarction during this trial and another died of disseminated intravascular coagulopathy subsequent to gastrointestinal bleeding. An additional patient suffered non-fatal pulmonary infarction. The one-year median survival rate was 22.2% and the overall survival period was 36 weeks. CONCLUSION: Although weekly paclitaxel plus estramustine may pose a significant risk, this combination may have a beneficial effect on the quality of life HRPC patients. A well-designed phase I-II trial in an Asian male population is highly recommended.

Matsui Y, Egawa S, Tsukayama C, Terai A, Kuwao S, Baba S, Arai Y. · Department of Urology, Kurashiki Central Hospital, Okayama, Japan. · Jpn J Clin Oncol. · Pubmed #12578902 links to  free full text

Abstract: BACKGROUND: Although prostate cancer has been prevalent in Japan, there has been no particular model for predicting the pathological stage in the Japanese population. We examined whether artificial neural network analysis (ANNA), which is a relatively new diagnostic tool in prostate cancer, can be one of the predictive methods for predicting organ confinement, compared with the traditional logistic regression model, in the Japanese population for the first time. METHODS: The study population comprised 178 men who underwent radical prostatectomy at our institutions between October 1992 and May 1999. As additional pretreatment parameters to the preoperative serum PSA level, clinical TNM classification and biopsy Gleason score, the percentage of number of cores exhibiting traces of tumor, maximum tumor length in biopsy cores, PSA density and patient age were used. The predictive ability of ANNA with several parameters for a set of 36 randomly selected test data was compared with those of logistic regression analysis and 'Partin Tables' by area under the receiver operating characteristics (ROC) curve analysis. RESULTS: Of 178 patients, 97 (54.5%) had organ-confined disease but 81 (45.5%) had locally advanced disease. With three parameters, the area under the ROC curve of ANNA (0.825 +/- 0.071) was larger than those for logistic regression (0.782 +/- 0.079) and Partin Tables (0.756 +/- 0.087), but not to a significant extent (P = 0.690 and 0.541). Although the expansion of the parameters did not increase the difference in area under the ROC curve between the best ANNA and logistic regression (0.899 +/- 0.053 and 0.873 +/- 0.065, respectively), the difference between the best ANNA and Partin Tables did not reach but approached statistical significance (P = 0.157). CONCLUSION: Although more modeling optimization is necessary to improve the predictive accuracy and generalizability of ANNA, we suggest that there is the possibility for this new predictive method to evolve in the analysis of clinical staging of prostate cancer.

Egawa S, Suyama K, Arai Y, Tsukayama C, Matsumoto K, Kuwao S, Baba S. · Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. · Int J Urol. · Pubmed #11389745 No free full text.

Abstract: BACKGROUND: North American investigators have suggested the usefulness of risk-group stratification based on prostate-specific antigen (PSA), clinical stage and biopsy Gleason score for predicting the biochemical outcome of prostate cancer after radical prostatectomy. There have been no reports of the application of this stratification to early biochemical outcome after radical surgery in Japanese men. METHODS: The study population consisted of 178 men treated with radical retropubic prostatectomy and bilateral pelvic lymph node dissection at Kitasato University Hospital (n = 110) and Kurashiki Central Hospital (n = 68) between October 1992 and May 1999. Pathologic and biochemical outcomes after radical prostatectomy were analyzed based on risk-group stratification. Risk groups were further analyzed according to detailed pathologic findings at biopsy. RESULTS: The median follow-up period for the 178 patients after radical surgery was 41.5 months (range, 2.0--82.0 months; mean, 40.9 months). Fifty-eight patients experienced PSA failure at a median of 8.0 months following surgery (range, 0.0--58.0). Risk-group stratification distinctly defined groups of pathologic findings in the radical prostatectomy specimens. The proportion of patients with PSA failure for low, intermediate and high-risk groups were 9.5%, 23.9% and 56.9%, respectively (P < 0.0001). Use of the number of cores with cancer and maximum cancer length in biopsy cores failed to improve risk stratification for PSA outcome in all risk groups. CONCLUSIONS: Risk-group stratification based on preoperative variables may significantly improve a physician's ability to counsel patients about PSA outcome after radical prostatectomy. Further improvement in risk stratification may call for use of variables other than the pathologic information in biopsy cores.

Egawa S, Suyama K, Takashima R, Mizoguchi H, Kuwao S, Baba S. · Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. · Int J Urol. · Pubmed #10533900 No free full text.

Abstract: BACKGROUND: The diagnostic value of prostate-specific antigen (PSA) for differentiating prostate cancer from benign prostatic conditions is limited by its lack of specificity. Several PSA-related parameters have been suggested as enhancing the discriminatory power of total PSA values, but their clinical utility should be considered preliminary until established in a prospectively evaluated cohort. METHODS: In a prospective cohort study, results of ultrasound-guided biopsy and/or transurethral resection of the prostate gland were assessed in 706 consecutive Japanese men. The clinical usefulness of total PSA, free PSA, percentage of free PSA, PSA density (PSAD), PSA density for transition zone (PSADT) and gland volume for predicting prostate cancer was investigated using receiver operating characteristic (ROC) curve analysis in 16 different patient subgroups. RESULTS: Overall, 150 of the 706 patients (21.2%) had prostate carcinoma. The ROC curve analysis showed that PSAD and PSADT were more powerful predictors of prostate cancer than total PSA in most of the 16 patient subgroups tested. The improvement in performance was modest, however. No substantial difference was noted between PSAD and PSADT. Total gland volume did not significantly affect the performance of these parameters. The use of a PSAD threshold value of 0.11-10.15 ng/mL per cm3 (or a PSADT value of 0.23-0.27 ng/mL per cm3) would have avoided 24-48% (or, for PSADT, 34-40%) of unnecessary biopsies at the cost of missing 5-10% of detectable cancers in a patient subgroup with intermediate total PSA levels. The performance of free PSA and percentage of free PSA was worse than that of any other test in this study. This may be due to inappropriate handling of sera prior to measurement. CONCLUSIONS: The discriminatory potential of total PSA for predicting prostate cancer was modestly improved by the use of PSAD and PSADT. No substantial advantage of PSADT over PSAD could be demonstrated. Stringent and standardized storage conditions should always be maintained when applying free PSA-related parameters.

Matsumoto K, Egawa S, Suyama K, Satou T, Iwamura M, Kuwao S, Koshiba K. · Department of Urology, Kitasato University School of Medicine. · Nippon Hinyokika Gakkai Zasshi. · Pubmed #10067306 No free full text.

Abstract: BACKGROUND: Many men with clinically suspicious findings would not be diagnosed to have prostate cancer. Establishing criteria for indicating repeat biopsy is imperative for early detection of prostate cancer. METHODS: Eighty-one patients underwent repeat prostatic biopsies under sonographic guidance at Kitasato University Hospital between March 1992 and October 1996. Clinicopathological parameters such as age, prostate specific antigen (PSA), PSA adjusted for transition zone volume (PSAT), PSA density (PSAD), PSA velocity, transition zone volume, prostatic volume, rectal findings, ultrasound findings and initial biopsy histology were compared with the results of repeat biopsy for searching for possible predictors of positive biopsy. RESULTS: Cancer was confirmed in 14 patients (17.3%), 10 patients by the second biopsy (15.4%, 10/65) and 4 patients by the third biopsy (28.6%, 4/14). No cancer was found at the 4th or more biopsies. Twelve (85.7%) of these patients had prostatic volume less than 40 cm3. Univariate analysis indicated PSAT, PSAD, transition zone volume and prostatic volume to be more frequent in men with positive biopsies (p < 0.05). But multivariate logistic regression analysis failed to identify any significant predictors of positive results in repeat biopsies. CONCLUSIONS: No clinicopathological parameters could reliably predict repeat biopsy findings. One or 2 additional sets of biopsies is recommended based on clinical judgement (symptoms, life expectancy, small glands < or = 40 cm3 etc.) for the purpose of early detection of prostate cancer in patients with previously negative biopsy but still with suspicious findings in consideration of approximately 20% false negative rates by the initial biopsy.

Kuruma H, Kamata Y, Takahashi H, Igarashi K, Kimura T, Miki K, Miki J, Sasaki H, Hayashi N, Egawa S. · Department of Urology, Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, Japan. · Am J Pathol. · Pubmed #19435788 No free full text.

Abstract: Using high molecular-weight proteomic analysis, we previously showed that Staphylococcal nuclease domain-containing protein 1 (SND1) is highly expressed in recurrent androgen-insensitive prostate cancer tissues. SND1 is a component of the RNA-induced splicing complex that mediates RNA interference, leading to degradation of specific mRNAs. The objective of this study was to further characterize SND1 expression and to investigate its biological potential in prostate cancer. Radical prostatectomy specimens were obtained from 62 prostate cancer patients. SND1 immunohistochemical staining patterns were evaluated using an in-house polyclonal antibody. We confirmed SND1 mRNA expression in prostate cancer cells using an in situ hybridization technique. To determine the importance of SND1 mRNA, we knocked down SND1 in vitro with small interfering RNA and observed a significant decrease in cell growth. SND1 was expressed in 60 of 62 prostate cancers (97%), appearing in the cytoplasm as small, granular structures; it was also present at high levels in prostate cancer specimens, while in hyperplasia specimens and normal epithelium, it was weakly or negatively expressed. SND1 expression intensity increased with increasing grade and aggressiveness of the cancer. As SND1 mRNA was overexpressed in cancer cells, the growth of these cells was suppressed following SND1 knockdown in vitro, thus representing a promising prostate cancer biomarker and therapeutic target.

Kanoh Y, Egawa S, Baba S, Akahoshi T. · Department of Laboratory Medicine, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa, Japan. · J Clin Lab Anal. · Pubmed #19288446 No free full text.

Abstract: We previously reported on a number of cases of metastatic prostate cancer (PCa) in which serum alpha2-macroglobulin (alpha2M) levels were markedly decreased to less than 20 mg/dl (alpha2M deficiency). All PCa patients with alpha2M deficiency had multiple bone metastases. Proteases in ten PCa patients with and without alpha2M deficiency were studied and compared against ten healthy controls in order to elucidate the relationships between changes in sugar chain structure and neoplasia. We assessed the relationship between ratios of Fr4 to Fr1 and Fr2 (Fr4/Fr1+Fr2 ratios) of oligosaccharide chains, and ratios of free prostate-specific antigen (PSA) to total PSA (F/T ratios), and serum levels of matrix-metalloproteinase-2 (MMP-2) in PCa progression. Measurement of serum alpha2M concentration was performed by laser nephelometry. Serum PSA and MMP-2 levels were determined by enzyme immunoassay and free PSA by radioimmunoassay. N-linked oligosaccharides of human serum immunoglobulin G were analyzed using fluorophore-associated carbohydrate electrophoresis. In those PCa patients with alpha2M deficiency: (a) serum alpha2M and F/T ratios were lower (P<0.05) and (b) Fr4/Fr1+Fr2 ratios and serum MMP-2 levels were higher when compared with those PCa patients without alpha2M deficiency. There was a significant correlation between Fr4/Fr1+Fr2 ratios and F/T ratios or serum MMP-2 levels in PCa with alpha2M deficiency (P<0.05). Therefore, these markers may serve as an auxiliary serum tumor marker for monitoring of the bone metastases or progression of disease in PCa.

Satoh T, Ishiyama H, Matsumoto K, Tsumura H, Kitano M, Hayakawa K, Ebara S, Nasu Y, Kumon H, Kanazawa S, Miki K, Egawa S, Aoki M, Toya K, Yorozu A, Nagata H, Saito S, Baba S. · Department of Urology, Kitasato University School of Medicine, Kangawa, Japan. · BJU Int. · Pubmed #19040526 No free full text.

Abstract: OBJECTIVE: To examine the incidence, timing, and magnitude of the prostate-specific antigen (PSA) level 'bounce' after permanent prostate brachytherapy (BT) and correlate the PSA bounce with clinical and dosimetric factors in Japanese patients with prostate cancer. PATIENTS AND METHODS: A multi-institutional pooled analysis was carried out in 388 consecutive patients with T1-T2N0M0 prostate cancer treated with (125)I-seed implant BT with no hormonal therapy or external beam radiotherapy. All patients had >or=1 year of follow-up and at least three follow-up PSA level measurements. Three definitions of PSA bounce were used: definition A, a PSA level rise of 0.1 ng/mL; definition B, a PSA level rise of 0.4 ng/mL; and definition C, a PSA level rise of 35% over the previous value, followed by a subsequent fall. RESULTS: The actuarial likelihood of having PSA bounce at 24 months was 50.8% for definition A, 23.5% for definition B, and 19.4% for definition C. The median time to develop PSA bounce was 12 months for definition A, 18 months for definition B, and 18 months for definition C. There was a PSA bounce magnitude of 2 ng/mL in 5.3% of patients, and 95.3% of PSA bounce occurred within 24 months after (125)I-BT. Among the before and after (125)I-BT factors, clinical stage, initial PSA level, and Gleason score did not predict for PSA bounce using any definition; only being younger predicted for PSA bounce on multivariate analysis (P < 0.001). CONCLUSIONS: PSA bounce is a common phenomenon after (125)I-BT and occurred at a rate of 19-51% in the Japanese men who underwent (125)I-BT, depending on the definition used. It is more common in younger patients, and early PSA bounce should be considered when assessing a patient with a rising PSA level after (125)I-BT, before implementing salvage interventions. Furthermore, PSA bounce magnitude might be lower in Japanese than in Caucasian patients.

Kanoh Y, Ohara T, Egawa S, Baba S, Akahoshi T. · Department of Laboratory Medicine, School of Medicine, Kitasato University, Kanagawa, Japan. · J Clin Lab Anal. · Pubmed #18623104 No free full text.

Abstract: We previously reported on a number of cases of metastatic prostate cancer (PCa) in which serum alpha2-macroglobulin (alpha2M) levels were markedly decreased to less than 20 mg/dl (alpha2M deficiency). In order to elucidate the relative proportions of free and a prostate-specific antigen (PSA) complex in PCa patients with alpha2M deficiency, we have assessed serum alpha2M and total PSA levels, and ratios of free PSA to total PSA (F/T ratios) at each stage of PCa. Moreover, the PSA reactivity profile was determined on fractionated serum specimens of PCa patients using high-performance liquid chromatography (HPLC) using a TSKG-3000 SWXL column. Measurement of alpha2M concentration was performed by laser-nephelometry. PSA levels were determined by enzyme immunoassay, free PSA by radioimmunoassay. In those PCa patients with alpha2M deficiency, serum alpha2M and F/T ratios were lower, whereas PSA levels were higher when compared with those PCa patients without alpha2M deficiency (P<0.05). PSA elution profiles on HPLC columns revealed two major peaks. The proportion of PSA-antichymotrypsin (PSA-ACT) increased, whereas the proportion of free PSA decreased in PCa patients with alpha2M deficiency as compared with those PCa patients without alpha2M deficiency. F/T ratios were significantly lower in PCa patients with alpha2M deficiency than in those PCa patients without alpha2M deficiency. PSA-ACT and F/T ratio may be useful for monitoring bone metastasis in PCa.

Saito S, Murayama Y, Pan Y, Taima T, Fujimura T, Murayama K, Sadilek M, Egawa S, Ueno S, Ito A, Ishidoya S, Nakagawa H, Kato M, Satoh M, Endoh M, Arai Y. · Department of Urology, Tohoku University, Graduate School of Medicine, Aoba-ku, Sendai, Japan. · Int J Cancer. · Pubmed #18464263 No free full text.

Abstract: In our previous study, monoclonal antibody RM2, established toward the glycosyl epitope, reflected grade of malignancy of prostate cancer cells whereas RM2 reactivity to benign glands was negative or weak. RM2 reactivity was also detected in stroma, suggesting the glycoprotein RM2 recognizes could be released into the bloodstream. Then, we explored RM2 reactivity to sera of early prostate cancer. We compared RM2 reactivity to sera between 62 patients with early prostate cancer and 43 subjects with benign prostatic disease, and examined RM2 reactivity before and after radical prostatectomy in 15 patients by Western blotting. We also examined RM2 reactivity to sera of the other urogenital cancers. RM2 reactivity was significantly enhanced on a serum glycoprotein with molecular mass approximately 40 kDa, hereby termed GPX, in the patients with early prostate cancer when compared with those with benign prostatic disease (p < 0.0001). Setting an appropriate cutoff level, RM2 reactivity to GPX for detection of prostate cancer had sensitivity of 87% and specificity of 84%, respectively. Furthermore, the level of RM2 reactivity significantly decreased after radical prostatectomy (p = 0.006). However, increased RM2 reactivity to GPX was also observed in the other urogenital cancers. The proteomics approach identified GPX as haptoglobin-beta chain and RM2 showed preferential reactivity toward haptoglobin-beta chain derived from prostate cancer when compared with polyclonal anti-haptoglobin antibody. Haptoglobin-beta chain defined by RM2 is a novel serum marker that may be useful for detection of early prostate cancer when coupled with prostate-specific antigen because it is not specific to prostate cancer.

Kakehi Y, Kamoto T, Shiraishi T, Ogawa O, Suzukamo Y, Fukuhara S, Saito Y, Tobisu K, Kakizoe T, Shibata T, Fukuda H, Akakura K, Suzuki H, Shinohara N, Egawa S, Irie A, Sato T, Maeda O, Meguro N, Sumiyoshi Y, Suzuki T, Shimizu N, Arai Y, Terai A, Kato T, Habuchi T, Fujimoto H, Niwakawa M. · Department of Urology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. · Jpn J Clin Oncol. · Pubmed #18272471 links to  free full text

Abstract: OBJECTIVE: Selection criteria for active surveillance (AS) program of localized prostate cancer remain to be standardized. The purpose was to evaluate the validity of selection criteria and investigate the feasibility of this AS program. METHODS: Patients meeting the criteria (i) stage T1cN0M0, (ii) age 50-80, (iii) serum prostate-specific antigen (PSA) </=20 ng/ml, (iv) one or two positive cores per 6-12 systematic biopsy cores, (v) Gleason score </=6, and (vi) cancer involvement in positive core </=50% were enrolled and encouraged to start AS for at least 6 months during the period between January 2002 and December 2003. PSA was measured bimonthly for 6 months and every 3 months thereafter. Trigger of treatment recommendation was PSA-doubling time (PSADT) of </=2 years or pathological progression at re-biopsy. Primary endpoint was '%PSADT > 2y', which was defined as the proportion of patients who showed PSADT assessed at 6 months >2 years out of all the patients who chose AS. Point estimate of '%PSADT > 2y' was expected to be >80%. RESULTS: One hundred and eighteen patients opted for AS and 16 chose immediate treatment at enrollment. PSADT for the initial 6 months based on four measurements could be assessed in 106 patients. Intent-to-treat analysis of '%PSADT > 2y' was 71.2% (84/118, 95% CI: 62.1-79.2). Pathological progression rate at 1-year re-biopsy was 33%. Fifty-four (46%) patients remained on AS for maximal observation of 54 months. General health-related QOL in patients undergoing AS was not impaired. CONCLUSIONS: The primary endpoint, '%PSADT > 2y', did not meet the pre-specified decision criteria. Further prospective study with revised program and endpoint is needed.

Hayashi N, Urashima M, Kuruma H, Arai Y, Kuwao S, Iwamura M, Egawa S. · Department of Urology, Jikei University School of Medicine, Minato-ku, Tokyo, Japan. · BJU Int. · Pubmed #17850362 No free full text.

Abstract: OBJECTIVES: To evaluate maximum tumour length (MTL) in biopsy cores as a predictor of prostate-specific antigen (PSA)-failure, systemic failure, and death from prostate cancer after radical prostatectomy (RP). PATIENTS AND METHODS: We assessed 209 men with clinically localized prostate cancer treated with RP; preoperative variables were correlated with unfavourable pathological characteristics in the RP specimens and with outcome after surgery, using univariate and multivariate analysis. RESULTS: The median (range) MTL was 4 (0.2-19) mm and correlated with adverse pathological findings, including specimen Gleason score (P = 0.003), pT3 (P < 0.001), seminal vesicle invasion (P < 0.001) and lymph node involvement (P = 0.019) in multivariate analysis. Preoperative PSA (P < 0.001), biopsy Gleason score (P = 0.002), and MTL (P = 0.045) were independent predictors of PSA failure, whereas only MTL remained a predictor of systemic-failure (P < 0.001) and death from prostate cancer (P = 0.004). The median (range) follow-up after surgery was 90 (17-152) months, during which 83 patients had PSA failure, 20 developed systemic failure and 15 died from prostate cancer. CONCLUSIONS: The MTL correlates well with adverse pathological findings and appears to be an independent predictor of outcome after RP. Patients with a greater MTL might have cancer with an aggressive phenotype and therefore be candidates for more aggressive therapies.

Miki J, Furusato B, Li H, Gu Y, Takahashi H, Egawa S, Sesterhenn IA, McLeod DG, Srivastava S, Rhim JS. · Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA. · Cancer Res. · Pubmed #17409422 links to  free full text

Abstract: Understanding normal and cancer stem cells may provide insight into the origin of and new therapeutics for prostate cancer. Normal and cancer stem cells in prostate have recently been identified with a CD44(+)/alpha(2)beta(1)(high)/CD133(+) phenotype. Stromal cell-derived factor-1 (SDF-1) and its receptor, CXCR4, have multiple essential functions, including homing of stem cells and metastasis of cancer cells. We show here that human telomerase reverse transcriptase (hTERT)-immortalized primary nonmalignant (RC-165N/hTERT) and malignant (RC-92a/hTERT) tumor-derived human prostate epithelial cell lines retain stem cell properties with a CD133(+)/CD44(+)/alpha(2)beta(1)(+)/34betaE12(+)/CK18(+)/p63(-)/androgen receptor (AR)(-)/PSA(-) phenotype. Higher CD133 expression was detected in the hTERT-immortalized cells than in primary prostate cells. These immortalized cells exhibited "prostaspheres" in nonadherent culture systems and also maintained higher CD133 expression. The CD133(+) cells from these immortalized cell lines had high proliferative potential and were able to differentiate into AR(+) phenotype. In three-dimensional culture, the CD133(+) cells from RC-165N/hTERT cells produced branched structures, whereas the CD133(+) cells from RC-92a/hTERT cells produced large irregular spheroids with less branched structures. SDF-1 induced, but anti-CXCR4 antibody inhibited, migration of CD133(+) cells from RC-92a/hTERT cells, which coexpressed CXCR4. CXCR4/SDF-1 may sustain tumor chemotaxis in cancer stem cells. Furthermore, immunostaining of clinical prostate specimens showed that CD133 expression was detected in a subpopulation of prostate cancer cells and corresponded to the loss of AR. Expression of CXCR4 was also detected in CD133(+) cancer cells. These novel in vitro models may offer useful tools for the study of the biological features and functional integration of normal and cancer stem cells in prostate.

Matsumoto K, Egawa S, Satoh T, Kuruma H, Yanagisawa N, Baba S. · Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. · Int J Urol. · Pubmed #17010007 No free full text.

Abstract: OBJECTIVES: The objective of this study was to use computer simulation to investigate the optimal biopsy scheme for enhancing the detection of cancer in palpably benign prostate glands. METHODS: The predominant distribution of palpably benign prostate cancer is anterior apex to mid-prostate. We used computer simulation to optimize apical samplings and to simulate the biopsy procedure, including angle and length. A total of 254 consecutive patients with palpably benign prostate glands underwent sextant biopsy plus two additional deep apical biopsies. RESULTS: Based on the computer simulation, lateral sextant and two additional medially located deep apical cores with a sagittal penetration angle of 80 degrees had the maximum cancer detection. Of the 254 patients, 58 (22.8%) had prostate cancer: 28 (48.3%) were positive only at the standard sextant sites, 12 (20.7%) were positive exclusively at the deep apical sites, and the remaining 18 (31.0%) were positive at both sites. Patients with gray-zone prostate-specific antigen (PSA) ranges of 4.1-10.0 ng/mL had increased cancer detection rates of 24% compared to sextant biopsy. Enhanced cancer detection by the deep apical biopsy was also evident in patients with a prostatic volume >40 cm3 (by 36.4%) and PSA 2.1-4.0 ng/mL (by 13.3%). CONCLUSIONS: Using a computer simulation-based biopsy scheme with deep apical sampling cores enhanced the detection of prostate cancer in palpably benign glands, especially in men with PSA ranges of 4.1-10.0 ng/mL or a gland volume of >40 cm3. Our approach with fewer sampling cores may have been more cost-effective than other extensive biopsy schemes, but further studies with larger samples are warranted.

Hayashi N, Urashima M, Ikemoto I, Kuruma H, Arai Y, Kuwao S, Baba S, Egawa S. · Department of Urology, Jikei University School of Medicine, Minato-ku, Tokyo, Japan. · Prostate Cancer Prostatic Dis. · Pubmed #17003775 No free full text.

Abstract: The aim of this study was to investigate the potential prognostic value of preoperative serum prostate-specific antigen levels adjusted for total tumor volume (PSA-TTV density) for outcome following radical prostatectomy for prostate cancer by retrospective review in 268 patients. Lower PSA-TTV density was not only associated with a significantly higher risk for biological failure (bF), systemic failure and cancer death but also an independent predictor for bF (hazard ratio, 6.3). Therefore, these data suggest that there are subsets of prostate cancer with lower PSA secretion levels, and this phenotype is associated with a higher risk of failure after surgery.

Aoki M, Miki K, Takahashi H, Takagi S, Fukuda I, Honda C, Kobayashi M, Egawa S, Kanehira C. · Division of Radiation oncology, Department of Radiology, Jikei University School of Medicine. · Nippon Igaku Hoshasen Gakkai Zasshi. · Pubmed #16334395 No free full text.

Abstract: We have been performing TRUS-guided transperineal prostate brachytherapy with I-125 for prostate-confined adenocarcinoma since October 2003. We examined prostate volume using CT scanning on Day 1, Day 15, and Day 30 in the initial 15 patients, and investigated time-dependent changes of edema associated with I-125 prostate brachytherapy. Prostate volume had increased to 173% of the average on the first day after implantation. Improvements in the swelling of the prostate showed decreases in 30% in the first 2 weeks (Days 1-15) and 12% in the second 2 weeks (Days 15-30). V100 and D 90% showed statistically significant increases of 5.5% and 8.4% in the first 2 weeks after implantation and 2.3% and 5.2% in the second 2 weeks (Days 15-30). We considered one month a suitable time at which to calculate post-planning because V100 and D 90% changed little statistically.