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ABSTRACT: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: It is known that a prostate cancer gene 3 (PCA3) urine assay is superior to serum PSA level or PSA-related indices for predicting a positive biopsy result in European and US men. This is the first report on PCA3 in a large cohort of Japanese men. The diagnostic value of the PCA3 score in Japanese men was similar to those reported in European and US men. The study concludes that a combination of PSA density and PCA3 score may be useful for selecting patients who could avoid an unnecessary biopsy. OBJECTIVE: To examine the diagnostic performance of the prostate cancer gene 3 (PCA3) score for prostate cancer in Japanese men undergoing prostate biopsy. PATIENTS AND METHODS: This Japanese, multicentre study included 647 Asian men who underwent extended prostate biopsy with elevated prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE). Urine samples were collected after DRE. The PCA3 score was determined using a PROGENSA PCA3 assay and correlated with biopsy outcome. Its diagnostic accuracy was compared with that of serum PSA level, prostate volume (PV), PSA density (PSAD), and free/total PSA ratio (f/t PSA). RESULTS: A total of 633 urine samples were successfully analysed (the informative rate was 98%). Median PSA was 7.6 ng/mL. Biopsy revealed cancer in 264 men (41.7%). The PCA3 score for men with prostate cancer was significantly higher than that for men with negative biopsies (median PCA3 score: 49 vs. 18; P < 0.001). The rate of positive biopsy was 16.0% in men with a PCA3 score of <20 and 60.6% in those with a PCA3 score of ≥50. Using a PCA3 score threshold of 35, sensitivity and specificity were 66.5 and 71.6%, respectively. The area under the curve of the PCA3 score was significantly higher than that of the f/t PSA in men with PSA 4-10 ng/mL (0.742 vs 0.647; P < 0.05). In men with PSAD < 0.15 and PCA3 < 20, only three (4.2%) out of 72 men had prostate cancer. CONCLUSIONS: The PCA3 score was significantly superior to f/t PSA in predicting a positive biopsy result for prostate cancer in Japanese men with PSA 4-10 ng/mL. The combination of PSAD and PCA3 score may be useful for selecting patients who could avoid an unnecessary biopsy.
BJU International 01/2013; · 2.84 Impact Factor
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ABSTRACT: p16INK4a (p16), a key molecule in bladder tumor development, inhibits the activities of cyclin-dependent kinases (CDKs) and maintains the retinoblastoma protein (pRb) in its active hypophosphorylated state. Following the finding that the p16 antitumor peptide dramatically inhibits the growth of aggressive leukemia̸lymphoma through the restoration of p16 function using the Wr-T peptide transporter system, in this study, we developed a systemic therapy using mouse‑p16 peptide (m‑p16) in subcutaneous p16‑null mouse bladder tumors. In vitro analysis showed that the growth of p16‑null bladder tumor cells and the hyperphosphorylation of their pRbs were inhibited by p16 transduction in a concentration‑dependent manner. In an animal model, p16‑null MBT‑2 cells were injected subcutaneously into KSN/SKC nude mice. The systemic delivery of the m‑p16 peptide using Wr‑T by cardiac injection significantly inhibited the growth of solid MBT‑2 tumors compared with the control phosphate‑buffered saline (PBS) injection. Histological examination by TUNEL staining revealed that apoptosis was increased and pRb phosphorylation was inhibited. Thus, the systemic peptide delivery of p16 restores the hypophosphorylation of pRb and may be a useful tool for the treatment of bladder tumors.
International Journal of Oncology 12/2012; · 2.40 Impact Factor
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Mizuki Onozawa,
Naoto Miyanaga,
Shiro Hinotsu,
Jun Miyazaki,
Takehiro Oikawa,
Tomokazu Kimura,
Ei-Ichiro Takaoka,
Koji Kawai, Toru Shimazui,
Hideyuki Sakurai,
Hiroyuki Nishiyama,
Hideyuki Akaza
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ABSTRACT: The aim of the present study was to analyze the pattern of recurrences after bladder-preserving therapy for muscle-invasive bladder cancer.
The subjects were 77 patients with T2-3N0M0 bladder cancer whose bladder was preserved by intra-arterial chemotherapy and radiation. The patterns of the first recurrences were retrospectively analyzed.
With a median follow-up of 38.5 months, 17 patients (22.1%) experienced intravesical recurrence without metastasis, 14 (82.4%) of which were cases of non-muscle-invasive bladder cancer recurrence and 3 (17.6%) of which were muscle-invasive bladder cancer recurrences. Muscle-invasive bladder cancer recurred at the same site as the initial tumor site in all three cases, whereas non-muscle-invasive bladder cancer recurred at different sites in 64% of the patients in that group. The peak hazard of the non-muscle-invasive bladder cancer recurrence was observed at around a year after treatment. Recurrent non-muscle-invasive bladder cancer was of a significantly lower histological grade with lower Ki-67-labeling indices than the initial muscle-invasive bladder cancer. Twelve (85.7%) of 14 patients with non-muscle-invasive bladder cancer recurrence achieved disease-free status. The multivariate analysis revealed that multiplicity, grade and tumor size were significantly correlated with the recurrence (P= 0.0001, 0.0442 and 0.0412, respectively).
Most of the recurrences after bladder-preserving therapy were cases of non-muscle-invasive bladder cancer. The recurrence pattern and characteristics of the tumors did not differ from those of primary non-muscle-invasive bladder cancer. Patients with high-risk factors would be candidates for prophylactic intravesical therapy for non-muscle-invasive bladder cancer recurrence.
Japanese Journal of Clinical Oncology 07/2012; 42(9):825-30. · 1.78 Impact Factor
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Tomokazu Kimura,
Takehiro Oikawa,
Atsushi Ikeda,
Takayuki Yoshino,
Takahiro Suetomi,
Jun Miyazaki, Toru Shimazui,
Takayuki Hashimoto,
Shintaro Sugita,
Masayuki Noguchi,
Hiroyuki Nishiyama
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ABSTRACT: A 75-year-old man, with a past history of radiation therapy for prostatic carcinoma ten years ago, was referred to our hospital with complaints of penile tumor. After pathological examination by core biopsy, the patient was treated by radical penectomy for a penile tumor. Pathological examinations demonstrated that the tumor was composed of pleomorphic spindle cells without any differentiation tendency and diagnosed as spindle cell sarcoma. Although the patient had a past history of radiation therapy for the prostate, the causal relation of development of penile sarcoma with the radiation therapy was uncertain because the main tumor was very near but outside of the irradiation field. The sarcoma rarely occurs in the penis, and this is the first report of penile spindle cell sarcoma, to our knowledge.
Hinyokika kiyo. Acta urologica Japonica 06/2012; 58(6):299-305.
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Kenji Zennami,
Kazuhiro Yoshikawa,
Eisaku Kondo,
Kogenta Nakamura,
Yoshiaki Upsilonamada,
Marco A De Velasco,
Motoyoshi Tanaka,
Hirotsugu Uemura, Toru Shimazui,
Hideyuki Akaza,
Shinsuke Saga,
Ryuzo Ueda,
Nobuaki Honda
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ABSTRACT: Molecular targeting agents have become formidable anticancer weapons showing much promise against refractory tumors and functional peptides and are among the more desirable of these nanobio-tools. Intracellular delivery of multiple functional peptides forms the basis for a potent, non-invasive mode of delivery, providing distinctive therapeutic advantages. We examine the growth suppression efficiency of human renal cell carcinoma (RCC) by single-peptide targeting. We simultaneously introduced p16INK4a tumor suppressor peptides by Wr-T-mediated peptide delivery. Wr-T-mediated transport of p16INK4a functional peptide into 10 RCC lines, lacking expression of the p16INK4a molecule, reversed the specific loss of p16 function, thereby drastically inhibiting tumor growth in all but 3 lines by >95% within the first 96 h. In vivo analysis using SK-RC-7 RCC xenografts in nude mice demonstrated tumor growth inhibition by the p16INK4a peptide alone, however, inoculation of Wr-T and the p16INK4a functional peptide mixture, via the heart resulted in complete tumor regression. Thus, restoration of tumor suppressor function with Wr-T peptide delivery represents a powerful approach, with mechanistic implications for the development of efficacious molecular targeting therapeutics against intractable RCC.
Oncology Reports 08/2011; 26(2):327-33. · 1.84 Impact Factor
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Jun Miyazaki,
Koji Kawai,
Takahiro Kojima,
Takehiro Oikawa,
Akira Joraku, Toru Shimazui,
Akihiro Nakaya,
Ikuya Yano,
Takashi Nakamura,
Hideyoshi Harashima,
Hideyuki Akaza
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ABSTRACT: • To conduct a preclinical evaluation of the ability of natural killer cells to cytolyze bladder cancer cells that were modified to show enhanced expression of natural-killer group 2, member D (NKG2D) ligands by R8-liposome-bacillus Calmette-Guéin (BCG)-cell wall skeleton (CWS) treatment.
• The T24 cells and RT-112 cells were co-cultured with R8-liposome-BCG-CWS and BCG for 2, 4, or 6 h, and then the surface expression of NKG2D ligands was analyzed using TaqMan real-time quantitative RT-PCR. • Peripheral blood mononuclear cells were obtained with a conventional preparation kit, and then lymphokine-activated killer (LAK) cells were generated from these purified peripheral blood mononuclear cells via interleukin-2 stimulation. • The anti-tumour effect of LAK cells against untreated and R8-liposome-BCG-CWS co-cultured with cells of the human bladder cancer cell lines T24 and RT-112 was analyzed using the cytotoxic WST-8 assay method at 4 h of culture at various effector/target (E : T) ratios.
• Major histocompatibility complex class I-related chain B (MICB) expression was increased ≈1.5-fold on T24 cells and RT-112 cells with BCG. • UL-16-binding protein (ULBP) 1 expression was also increased ≈1.5-fold on T24 cells and RT-112 cells with BCG. R8-liposome-BCG-CWS increased the surface expression of MICB 2.2-fold on T24 cells but did not increase it significantly on RT-112 cells. • ULBP1 expression was increased ≈2.2-fold on RT-112 cells, although no differences were observed between the expression of ULBP2 and 3 with R8-liposome-BCG-CWS. • T24 cells that were co-cultured with R8-liposome-BCG-CWS showed an ≈1.3-fold increase in sensitivity to cytolysis by LAK cells at an E : T ratio of 4 and RT-112 cells showed an ≈1.4-fold increase at an E : T ratio of 2.
• In the present study, the induction of surface NKG2D ligands by R8-liposome-BCG-CWS rendered cancer cells more susceptible to cytolysis by LAK cells. • T24 cells and RT-112 cells, even when cultured singly in the absence of immune cells, can directly respond to R8-liposome-BCG-CWS. • The results obtained in the present study may therefore indicate a novel adoptive immunotherapy against bladder cancers.
BJU International 02/2011; 108(9):1520-6. · 2.84 Impact Factor
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ABSTRACT: A 40-year-old man was referred to our hospital for treatment of metastatic testicular cancer. Computerized tomography revealed multiple lung, liver, and retroperitoneal lymph node metastases. In addition, magnetic resonance imaging revealed multiple brain metastases. Induction chemotherapy with bleomycin, etoposide, and cisplatin was started the day after a high orchiectomy. The pathological diagnosis of the surgical specimen was yolk sac carcinoma. The serum human chorionic gonadotropin (hCG) was markedly increased to 630,000 mIU/ml, which suggested the presence of a choriocarcinoma element at metastatic sites. The patient subsequently suffered respiratory failure due to pulmonary hemorrhage. Intensive supportive care prevented a fatal outcome. Physicians who treat advanced testicular tumors should be aware of the potential complication of acute pulmonary hemorrhage, called choriocarcinoma syndrome, in cases with a high hCG level, which indicates a rapidly progressive and high-volume choriocarcinoma.
International Journal of Clinical Oncology 12/2010; 15(6):611-4. · 1.41 Impact Factor
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ABSTRACT: To estimate the risk of intravesical recurrence in patients with primary urothelial cancer of the upper urinary tract.
Ninety patients who underwent radical nephroureterectomy for clinically localized urothelial cancer of the upper urinary tract were initially considered. Those with a previous and/or concomitant history of bladder cancer, and those who had previously received systemic chemotherapy were excluded. Overall, data from 60 patients with no evidence of bladder cancer and distant or lymph node metastasis were retrospectively reviewed. The clinical course and the risk pattern of intravesical recurrence were estimated by using a smoothing technique on estimated hazard function plots. Multivariate analysis was carried out using a Cox proportional hazards regression model.
Mean patient age was 64.7 years. Median follow up was 51.3 months. Thirty patients (50%) had intravesical recurrence during the follow-up period. The peak of intravesical recurrence was detected in the early period (less than 2.5 years) after surgery. The intravesical recurrence hazard became lower afterwards. Nevertheless, it persisted over a long period of time. On univariate and multivariate analyses, none of the clinical or pathological parameters had a statistically significant impact on intravesical recurrence.
Even if an intravesical recurrence in patients with upper urinary tract urothelial cancer is more likely in the early period, it persists over a long period of time. This might reflect different mechanisms of recurrence, having a significant impact on the definition of the optimal treatment and follow-up schedules.
International Journal of Urology 04/2010; 17(7):623-8. · 1.75 Impact Factor
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ABSTRACT: The goal of this study was to identify genes related to the metastasis of clear cell renal cell carcinoma (CRCC). We analyzed copy number alterations in renal tissue specimens of patients with CRCC patients with or without metastasis by using high-resolution single-nucleotide polymorphism (SNP) arrays and then integrated these data with gene expression profiling data obtained using oligonucleotide microarrays. The expression levels of target genes were determined by quantitative real-time RT-PCR (qRT-PCR) with an independent tumor set. An analysis of specimens from 23 CRCC cases with SNP arrays revealed that hemizygous deletions at 10q and 13q were found only in cases of metastatic disease. We found the homozygous deletion of TCF7L2 at 10q25.2 in an aggressive case that had hemizygous deletions at 10q. In addition, a qRT-PCR analysis of TCF7L2 mRNA levels in tumor samples revealed significantly lower levels in patients with metastasis when compared with those without metastasis. FOXO1 was identified as a down-regulated gene in the minimal overlapping region of the 13q hemizygous deletion in CRCC. Decreased FOXO1 expression was significantly correlated with metastasis and poor survival outcome. Knockdown of FOXO1 inhibited apoptosis after doxorubicin treatment in CRCC cells and reduced the expression of downstream genes involved in cell proliferation (CDKN1B) and survival (BCL2L11). Lower levels of FOXO1 expression were associated with decreased expression of CDKN1B and BCL2L11 in CRCC specimens. We conclude that FOXO1 and TCF7L2 are involved in metastasis and that molecules in these signaling pathways may be targets for diagnostic procedures and therapies for CRCC.
Genes Chromosomes and Cancer 04/2010; 49(4):379-89. · 3.31 Impact Factor
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ABSTRACT: We present the clinical course of a ureteroiliac arterial fistula in a patient who had been managed by ureteral stenting for 8 years for severe ureteral stricture after abdominoperineal resection with pelvic irradiation for advanced rectal cancer. A multidisciplinary team approach including provocative angiography and an endovascular stent saved the life of the patient. Ureteroarterial fistula is a rare complication of a long-term indwelling ureteral stent that is potentially fatal unless a prompt diagnosis and adequate therapy are provided. Heightened awareness and a high index of suspicion for this condition are required to make an early diagnosis.
Japanese Journal of Clinical Oncology 12/2009; 40(3):267-70. · 1.78 Impact Factor
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ABSTRACT: Down-regulation of carcinogen detoxifying enzymes might be a critical factor in tumour formation by increasing the carcinogen concentration in the target organ. Previous reports revealed that the expression of UGT1A mRNA is either lost or decreased in certain human cancer tissues, including urinary bladder cancer. To elucidate this down-regulation mechanism, we used an N-nitrosobutyl (4-hydroxybutyl) amine (BBN)-induced mouse urinary bladder carcinogenesis model. Similar to human cancer, the expressions of Ugt1a6, Ugt1a9 and total Ugt1a mRNA in the BBN-induced bladder cancer were markedly decreased compared with those of normal mice. BBN down-regulated the basal Ugt1a mRNA expression in a time-dependent manner and this was reversible in the first 2 weeks of BBN treatment. However, after 4 weeks of BBN treatment the repression became persistent after the cessation of BBN treatment. Aryl hydrocarbon receptor (AhR) regulates the constitutive and inducible expression of Ugt1a mRNA. We found that the constitutive Ugt1a mRNA expression is decreased in the bladder of AhR knockout (KO) mice. Furthermore, BBN-induced Ugt1a down-regulation was lost in AhR KO mice, and the canonical AhR target gene Cyp1a1 was similarly down-regulated by BBN in the bladder. These results demonstrate that BBN repressed Ugt1a mRNA expression via suppression of AhR signaling pathway during BBN-induced carcinogenesis.
Journal of biochemistry 10/2009; 147(3):353-60. · 1.95 Impact Factor
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ABSTRACT: We previously reported that microarray expression profiling identified several candidate genes in association with interferon-alpha (IFN-alpha) response in renal cell carcinoma (RCC) cell lines (Cancer Sci 2007; 98: 529). Among them, we focused on microphthalmia-associated transcription factor (MITF), because its expression profile correlated well with IFN-alpha-response status. In addition, we investigated the clinical significance of the expression level of MITF using surgical specimens. RNA was extracted from 14 RCC cell lines and 65 RCC samples and was used in this study. Transfection of MITF cDNA into IFN-alpha-resistant RCC cell lines resulted in elevation of MITF expression and acquisition of IFN-alpha-sensitivity by quantitative PCR and WST-8 assay, respectively. Statistical analysis revealed that low MITF mRNA expression in RCC samples was significantly correlated with the presence of metastasis and poor survival of the patient. However, the correlation between MITF expression and IFN-alpha response was not obvious in the clinical cases. MITF gene transfection elevated IFN-alpha-sensitivity in RCC cell lines, suggesting that this gene is a target molecule for modulation of the IFN-alpha response. Quantification of MITF mRNA expression might be clinically useful to predict metastasis and survival of patients with RCC.
Cancer Science 06/2009; 100(9):1714-8. · 3.33 Impact Factor
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ABSTRACT: We report the case of a 62-year-old Japanese man who presented with right renal cell carcinoma and multiple metastases. The patient had a past medical history of idiopathic interstitial pneumonia 6 years previously. He had received pulse corticosteroid therapy and oral prednisolone, which resulted in marked clinical improvement. He had been followed up for the interstitial pneumonia, without medication, for 5 years and the idiopathic interstitial pneumonia was inactive when the metastatic renal cell carcinoma was diagnosed. However, the patient presented with extremely acute exacerbation of the interstitial pneumonia that occurred after only three intramuscular injections of standard-dose interferon-alpha. Urologists should be aware of this complication in the treatment of renal cell carcinoma patients who have a prior history of interstitial pneumonia.
International Journal of Clinical Oncology 05/2009; 14(2):171-3. · 1.41 Impact Factor
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ABSTRACT: Several recent studies suggested that the prevalence of erectile dysfunction (ED) was higher in men with metabolic syndrome (MS).
We analyzed the impact of MS on the responsiveness to sildenafil.
A total of 133 ED patients were evaluated for the prevalence of MS and graded on severity of ED. MS was diagnosed according to the International Diabetes Federation (IDF) definition. The severity of ED was evaluated by the International Index of Erectile Function (IIEF) questionnaire. Hormonal parameters were measured for all patients, and the IIEF questionnaire was conducted after administration of eight tablets of 50-mg doses of sildenafil. If the scores to questions 3 and 4 of the IIEF were 4 or higher after administration, the patients were defined as responders to sildenafil.
To clarify the negative impact of MS on the responsiveness to sildenafil.
The mean age of the patients was 56.9 years, and 25 patients were diagnosed with MS. The IIEF-erectile function score and the response rate for sildenafil decreased as the number of MS components increased. Logistic regression analysis showed that the presence of MS along with severity of ED and history of pelvic surgery were significant independent risk factors of nonresponse for sildenafil. The hazard ratio for the presence of MS was 3.30 (95% confidence interval [CI]: 1.17-9.73). No meaningful association was observed between total testosterone or free testosterone levels and MS in this population.
We demonstrated the negative impact of MS on the responsiveness to sildenafil. Erectile function and response rate for sildenafil decreased as the number of MS components increased.
Journal of Sexual Medicine 07/2008; 5(6):1443-50. · 3.55 Impact Factor
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ABSTRACT: A 69-year-old man was hospitalized for treatment of a left renal tumor. The tumor had originally been demonstrated as a simple renal cyst 4 years before. However, the size of the tumor decreased, and at the time of hospitalization, the tumor showed a solid, papillary component that was enhanced by contrast medium on computed tomography (CT) and had high signal intensity on T2-weighted magnetic resonance imaging (MRI). We diagnosed this tumor as a cystic renal cell carcinoma of the left kidney, cT1aN0M0, arising from the epithelium of a renal cyst, and performed a left partial nephrectomy. The pathological diagnosis was cavernous hemangioma of the left kidney. Generally, it is difficult to diagnose a cavernous hemangioma of the kidney preoperatively. This case is unusual because the configuration of this tumor changed within a few years. When we find a renal cyst with a solid component, renal cavernous hemangioma arising from the cyst wall should be considered in the differential diagnosis, and a conservative surgical approach should be considered.
International Journal of Clinical Oncology 05/2008; 13(2):166-8. · 1.41 Impact Factor
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ABSTRACT: Nuclear factor-erythroid 2 (NF-E2)-related factor 2 (Nrf2), a transcription factor that regulates inducible expression of detoxifying enzymes, is critical in preventing N-nitrosobutyl(4-hydroxybutyl)amine (BBN)-induced urinary bladder carcinogenesis. To explore whether Nrf2 and the tumor suppressor p53 cooperatively act in tumor prevention, we investigated the susceptibility of Nrf2-/-::p53+/- mice to BBN-induced urinary bladder carcinogenesis. The incidence of BBN-induced urinary bladder carcinoma was 63.0% in Nrf2-/- mice (P = 0.115), 75.8% in p53+/- mice (P < 0.01) and 89.6% in Nrf2-/-::p53+/- mice (P < 0.01) compared with 37.9% in wild-type. Higher incidence of carcinoma was observed in Nrf2-/-::p53+/- mice when compared with either Nrf2-/- (P < 0.01) or p53+/- mice (P = 0.382). Similarly, muscular invasive carcinoma incidence was higher in Nrf2-/-::p53+/- mice (62.0%) than either wild-type (6.9%, P < 0.01), p53+/- (38.0%, P = 0.110) or Nrf2-/- mice (3.7%, P < 0.01). Furthermore, urinary concentrations of N-nitrosobutyl(3-carboxypropyl)amine, a proximate carcinogen of BBN, were only increased when Nrf2 but not p53 was disrupted. These results demonstrate that tumor susceptibility is synergistically exacerbated in Nrf2-/-::p53+/- mice due to poor detoxification and accelerated proliferation in comparison with either single mutant alone. BBN administration increased p53-mediated expression of p21, Mdm2 and Bax, and the inducible expression of p21 was significantly enhanced in Nrf2-/- mice. Conversely, modest increases in NAD(P)H dehydrogenase, quinone 1 (NQO1) and uridine diphosphate (UDP) glucuronosyltransferase 1A6 (UGT1A6) expression were observed in p53+/- compared with those of wild-type mice after BBN exposure. These results thus reveal potential interactions between p53 and Nrf2 and their gene batteries, and indicate that both factors cooperatively contribute to tumor prevention.
Carcinogenesis 11/2007; 28(11):2398-403. · 5.70 Impact Factor
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ABSTRACT: The present study was undertaken to identify the patients suitable for bladder preservation by analysis of our data.
The subjects of this study were all 72 patients with T2-3N0M0 bladder cancer who underwent bladder-preserving therapy in our institute. The therapy involved intra-arterial chemotherapy with MTX and CDDP and concomitant radiotherapy.
Of the evaluable 70 cases, complete response (CR) was confirmed in 57 cases (81.4%). Among 56 bladder preserved cases, 47 (83.9%) preserved their functioning bladder, and 9 underwent salvage radical cystectomy at the following period. The median follow-up was 45.3 months. The 5-year cause-specific survival rate was 81% and the 5-year overall survival rate was 66%. On the basis of the results of univariate analysis, variables contributing to CR were selected. In T2, tumor size of </=3 cm was scored 0 and >3 cm was scored 1, whereas single tumor was scored 0 and multiple were scored 1. In T3, tumor size of </=3 cm was scored 0 and >3 cm was scored 1, whereas G2 was scored 0 and G3 scored 1. The CR rates were 93.8, 92.6, and 62.9% for total scores of 0, 1, and 2, respectively (P = 0.003; score 0 or 1 versus 2). The overall survival rate was significantly higher in the former group (P = 0.003).
Bladder-preserving therapy can be acceptable for cases of single T2N0M0 tumor with a size of </=3 cm and for T3N0M0 cases with a tumor size of </=3 cm.
Japanese Journal of Clinical Oncology 11/2007; 37(11):852-7. · 1.78 Impact Factor
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ABSTRACT: We previously reported that weekly treatment with docetaxel alone is useful for and well tolerated by patients with hormone-refractory prostate cancer (HRPC). Here, we compare it with the regimen of docetaxel once every 3 weeks (q3w) plus daily prednisone (PSL) based on a TAX 327 trial in order to clarify the efficacy and toxicity of docetaxel regimens in Japan.
Thirty-two patients with HRPC were treated with docetaxel weekly (regimen 1) or docetaxel q3w plus PSL daily (regimen 2) at Tsukuba University Hospital and the changes in serum prostate-specific antigen (PSA), tumor size and survival were evaluated. The dose of docetaxel in regimen 1 was based on our previous report and that of regimen 2 was modified from a TAX 327 trial.
A >50% decrease in PSA was observed in 53% of the patients with a median time to progression of 3.5 months and 69% with 8.5 months with regimens 1 and 2, respectively. Patients who received regimen 2 had a significantly better survival rate than those who received regimen 1. Myelosuppression and neuropathy were statistically more frequent in regimen 2 than in regimen 1.
A regimen of docetaxel q3w with PSL daily was associated with a high rate of PSA reduction and prolongation of patient survival. Although docetaxel has not been approved in Japan yet, this treatment is considered feasible for Japanese patients with HRPC.
Japanese Journal of Clinical Oncology 08/2007; 37(8):603-8. · 1.78 Impact Factor
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Kenji Tamura,
Mutsuo Furihata,
Tatsuhiko Tsunoda,
Shingo Ashida,
Ryo Takata,
Wataru Obara,
Hiroki Yoshioka,
Yataro Daigo,
Yasutomo Nasu,
Hiromi Kumon, [......],
Nozomu Tanji,
Masayoshi Yokoyama, Toru Shimazui,
Hideyuki Akaza,
Yoichi Mizutani,
Tsuneharu Miki,
Tomoaki Fujioka,
Taro Shuin,
Yusuke Nakamura,
Hidewaki Nakagawa
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ABSTRACT: One of the most critical issues in prostate cancer clinic is emerging hormone-refractory prostate cancers (HRPCs) and their management. Prostate cancer is usually androgen dependent and responds well to androgen ablation therapy. However, at a certain stage, they eventually acquire androgen-independent and more aggressive phenotype and show poor response to any anticancer therapies. To characterize the molecular features of clinical HRPCs, we analyzed gene expression profiles of 25 clinical HRPCs and 10 hormone-sensitive prostate cancers (HSPCs) by genome-wide cDNA microarrays combining with laser microbeam microdissection. An unsupervised hierarchical clustering analysis clearly distinguished expression patterns of HRPC cells from those of HSPC cells. In addition, primary and metastatic HRPCs from three patients were closely clustered regardless of metastatic organs. A supervised analysis and permutation test identified 36 up-regulated genes and 70 down-regulated genes in HRPCs compared with HSPCs (average fold difference > 1.5; P < 0.0001). We observed overexpression of AR, ANLN, and SNRPE and down-regulation of NR4A1, CYP27A1, and HLA-A antigen in HRPC progression. AR overexpression is likely to play a central role of hormone-refractory phenotype, and other genes we identified were considered to be related to more aggressive phenotype of clinical HRPCs, and in fact, knockdown of these overexpressing genes by small interfering RNA resulted in drastic attenuation of prostate cancer cell viability. Our microarray analysis of HRPC cells should provide useful information to understand the molecular mechanism of HRPC progression and to identify molecular targets for development of HRPC treatment.
Cancer Research 07/2007; 67(11):5117-25. · 7.86 Impact Factor
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Toru Shimazui,
Yoshihiro Ami,
Kazuhiro Yoshikawa,
Kazuhiko Uchida,
Takahiro Kojima,
Takehiro Oikawa,
Kogenta Nakamura,
Nobuaki Honda,
Shiro Hinotsu,
Jun Miyazaki,
Noriko Kunita,
Hideyuki Akaza
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ABSTRACT: We analyzed the correlation between interferon-alpha (IFNalpha) response and gene expression profiles to predict IFNalpha sensitivity and identified key molecules regulating the IFNalpha response in renal cell carcinoma (RCC) cell lines. To classify eight RCC cell lines of the SKRC series into three subgroups according to IFNalpha sensitivity, that is, sensitive, resistant and intermediate group, responses to IFNalpha (300-3000 IU/mL) were quantified by WST-1 assay. Microarray, followed by supervised hierarchical clustering analysis, was applied to selected genes according to IFNalpha sensitivity. In order to find alteration of expression profiles induced by IFNalpha, sequential microarray analyses were performed at 3, 6, and 12 h after IFNalpha treatment of RCC cell lines and mRNA expression level was confirmed using quantitative real time polymerase chain reaction. According to the sequential microarray analysis between IFNalpha-sensitive and -resistant line, seven genes were selected as candidates for IFNalpha-sensitivity-related genes in RCC cell lines. Among these seven genes, we further developed a model to predict tumor inhibition with four genes, that is, adipose differentiation-related protein, microphthalmia associated transcription factor, mitochondrial tumor suppressor 1, and troponin T1 using multiple linear regression analysis (coefficient=0.948, P=0.0291) and validated the model using other RCC cell lines including six primary cultured RCC cells. The expression levels of the combined selected genes may provide predictive information on the IFNalpha response in RCC. Furthermore, the IFNalpha response to RCC might be modulated by regulation of the expression level of these molecules.
Cancer Science 05/2007; 98(4):529-34. · 3.33 Impact Factor
