Hideki Sakai

Publications of Hideki Sakai

• Angiogenesis and Lymphangiogenesis in Bladder Cancer

  Authors: Yasuyoshi Miyata, Hideki Sakai, Shigeru Kanda

  02/2012;

  ISBN: 978-953-307-839-7

• High density of tryptase-positive mast cells in patients with renal cell carcinoma on hemodialysis: correlation with expression of stem cell factor and protease activated receptor-2.

  Authors: Shin-Ichi Watanabe, Yasuyoshi Miyata, Tomohiro Matsuo, Yasushi Mochizuki, Masaharu Nishikido, Tomayoshi Hayashi, Hideki Sakai

  Human pathology. 12/2011;

  Patients on hemodialysis are at higher risk of renal cell carcinoma probably because of inflammatory and immune system disorders. The aim of this study was to clarify the pathologic roles of 2Patients on hemodialysis are at higher risk of renal cell carcinoma probably because of inflammatory and immune system disorders. The aim of this study was to clarify the pathologic roles of 2 phenotypes of mast cells, mast cell tryptase and mast cell chymase, and their correlation with stem cell factor and protease-activated receptor 2 in patients with renal cell carcinoma on hemodialysis. The densities of mast cell tryptase and mast cell chymase and expressions of stem cell factor and protease-activated receptor 2 were examined in 35 patients with hemodialysis-renal cell carcinoma and 39 with non-hemodialysis-renal cell carcinoma who were diagnosed and treated in our hospital. Protein expression was examined by immunohistochemistry. The proliferation index represented the number of Ki-67-positive cells. There were no significant differences in clinicopathologic features between the 2 groups. Mast cell tryptase densities in intratumoral (8.3 per high-power field) and peritumoral areas (8.7 per high-power field) were higher in hemodialysis-renal cell carcinoma than non-hemodialysis-renal cell carcinoma (2.7 and 5.3 per high-power field). No such significant correlations were detected in mast cell chymase. In hemodialysis-renal cell carcinoma, intratumoral mast cell tryptase density correlated with the proliferation index (P = .039 and P = .008, respectively) and also with stem cell factor and protease-activated receptor 2 expression. Our results emphasize the important roles of mast cell tryptase in cancer cell proliferation and recurrence in hemodialysis-renal cell carcinoma. Stem cell factor and protease-activated receptor 2 seem to up-regulate mast cell tryptase functions in these patients. The results suggest collaborative effects of stem cell factor, mast cell tryptase, and protease-activated receptor 2 on the malignant potential of hemodialysis-renal cell carcinoma.

• Emphysematous pyelonephritis with complete duplication of the left urinary tract.

  Authors: Yasuto Yamasaki, Shigehiko Koga, Yuzo Minami, Hideki Sakai

  Canadian Urological Association journal = Journal de l'Association des urologues du Canada. 12/2011; 5(6):E101-3.

  Emphysematous pyelonephritis (EPN) is a life-threatening bacterial infection and should be treated rapidly and carefully. We report a case of EPN with complete duplication of the left urinary tract.Emphysematous pyelonephritis (EPN) is a life-threatening bacterial infection and should be treated rapidly and carefully. We report a case of EPN with complete duplication of the left urinary tract. A 68-year-old woman was admitted to our hospital complaining of high-grade fever and left flank pain. An abdominal computed tomography scan showed gas was presented in the renal parenchyma, not only the pelvis and ureter. Based on these findings, a diagnosis of left EPN was made. A partial nephrectomy of the affected left upper pole moiety was performed and the patient underwent additional medical management. Other 83 cases of EPN from the Japanese literature were reviewed.

• Effect of maintenance chemotherapy with gemcitabine and paclitaxel on recurrent squamous cell carcinoma of the bladder: a case report.

  Authors: Yasuyoshi Miyata, Shin-Ichi Watanabe, Hajime Takahashi, Yuji Sagara, Tomohiro Matsuo, Kojiro Ohba, Hideki Sakai

  Anticancer research. 12/2011; 31(12):4465-8.

  Squamous cell carcinoma (SCC) of the bladder is a relatively rare malignancy and the standard treatment is surgical resection. Prognosis of unresectable and recurrent SCC of the bladder is poorSquamous cell carcinoma (SCC) of the bladder is a relatively rare malignancy and the standard treatment is surgical resection. Prognosis of unresectable and recurrent SCC of the bladder is poor because no effective treatment is available at present. Here, we describe the response of one patient with this cancer to combination chemotherapy of gemcitabine and paclitaxel. A 47-year-old man with recurrent bladder SCC underwent radical cystectomy, but initially refused any adjuvant therapy. The pathological diagnosis was pT3. The patient was treated with three cycles of methotrexate, vinblastin, epirubicin, and cisplatin but with no response (no decrease in tumor volume). Subsequently, he received the combination chemotherapy of gemcitabine (GEM, 700 mg/m(2) on days 1 and 8) and paclitaxel (PTX, 700 mg/m(2) on days 1 and 8) per each 28-day cycle. After five cycles, the tumor volume had decreased from 562 to 101 cm(3) (18.0%). The combination therapy was reduced to GEM monotherapy, but the tumor volume increased to 573 cm(3). GEM+PTX administration was re-instituted; however, the patient died 21 months after recurrence. The combination GEM+PTX chemotherapy was applied at the outpatient treatment and caused no severe side-effects. Although the maintenance chemotherapy of GEM+PTX did not induce complete remission, it improved quality of life and had no serious side-effects, making it a promising combination chemotherapy for recurrent SCC of the bladder. Although further studies are necessary to determine its therapeutic efficacy, we suggest that this combined therapy is a useful option in the treatment of this disease including recurrent cases.

• [A case report of bilateral spermatocytic seminoma].

  Authors: Sugure Maruta, Yohei Shida, Kousuke Takehara, Toru Onita, Tsukasa Igawa, Hideki Sakai

  Hinyokika kiyo. Acta urologica Japonica. 09/2011; 57(9):525-8.

  Spermatocytic seminoma is a rare germ cell tumor which was first described by Masson in 1946. We experienced a case of bilateral spermatocytic seminoma. A 56-year-old man presented with painlessSpermatocytic seminoma is a rare germ cell tumor which was first described by Masson in 1946. We experienced a case of bilateral spermatocytic seminoma. A 56-year-old man presented with painless swelling of left scrotal contents. This patient was diagnosed with bilateral testicular tumor after various image examinations (ultrasonography/computerized tomography/magnetic resonance imaging) and bilateral high orchidectomy was performed. Histological diagnosis was bilateral spermatocytic seminoma, pT1. After the operation, this patient was followed closely without adjuvant therapy. There has been no sign of recurrence at five months after the operation.

• [Intravesical therapy of heparin and lidocaine for interstitial cystitis : a case report].

  Authors: Tomohiro Matsuo, Yohei Shida, Yasushi Hayashida, Hideki Sakai

  Hinyokika kiyo. Acta urologica Japonica. 09/2011; 57(9):513-6.

  Interstitial cystitis (IC) is a chronic inflammatory condition of the urinary bladder, and its treatment has many uncertainties. We report a case of IC treated with intravesical instillation ofInterstitial cystitis (IC) is a chronic inflammatory condition of the urinary bladder, and its treatment has many uncertainties. We report a case of IC treated with intravesical instillation of heparin and alkalized lidocaine. A 64-year-old woman presented with urinary frequency and urgency with suprapubic pain. She underwent intravesical treatment with combined heparin and alkalinized lidocaine for IC, since prior medical treatments (imipramine, solifenacin, suplatast tosilate, and kampo extracts) and hydrodistention of bladder had little or no effect on her symptoms. A 50 ml solution containing 20,000 units of heparin, 200 mg of lidocaine and 7% sodium bicarbonate was administered intravesically twice a week for 12 months. The O'Leary-Sant IC symptom index score and IC problem index score improved from 20 to 8 and from 16 to 8, respectively, and her bladder capacity increased from 90 ml to 300 ml. Intravesical instillation of combined heparin and lidocaine was useful in the treatment of IC.

• Pathologic significance and prognostic value of phosphorylated cortactin expression in patients with sarcomatoid renal cell carcinoma.

  Authors: Tomohiro Matsuo, Yasuyoshi Miyata, Shin-ichi Watanabe, Kojiro Ohba, Tomayoshi Hayashi, Shigeru Kanda, Hideki Sakai

  Urology. 06/2011; 78(2):476.e9-15.

  To clarify the clinical and prognostic significance of cortactin and phosphorylated cortactin in patients with sarcomatoid renal cell carcinoma (SRCC). We retrospectively reviewed the data from 31To clarify the clinical and prognostic significance of cortactin and phosphorylated cortactin in patients with sarcomatoid renal cell carcinoma (SRCC). We retrospectively reviewed the data from 31 patients with SRCC and 33 with conventional renal cell carcinoma matched for clinicopathologic features. The immunoreactive score for cortactin, pY421 cortactin, and pY466 cortactin were measured using immunohistochemistry. The relationships between each immunoreactive score and the clinicopathologic features and survival were investigated. The immunoreactive score of p421 cortactin, but not that of cortactin and pY466 cortactin, was significantly greater in SRCC than in conventional renal cell carcinoma (P < .001). The expression of pY421 cortactin in SRCC correlated with the pT stage and metastasis (P < .001). The expression of pY466 cortactin showed a similar trend with pT stage (P = .043) but not with metastasis. Although both of pY421 cortactin and pY466 cortactin were identified as useful predictors for survival in univariate analyses, only pY421 cortactin expression was considered an independent predictor in patients with SRCC (odds ratio 4.53, 95% confidence interval 1.07-19.12, P = .040) in the multivariate analysis model, including pT stage and metastasis. Our results have demonstrated that phosphorylation of cortactin is a key process in malignant aggressiveness, and its expression is a useful predictor of cause-specific survival and could be a useful potential therapeutic target in patients with SRCC.

• Response of recurrent urachal cancer to gemcitabine and cisplatin therapy: a case report and literature review.

  Authors: Yasuyoshi Miyata, Yuji Sagara, Tomohiro Matsuo, Kojiro Ohba, Hajime Takahashi, Hideki Sakai, Hiroshi Kanetake

  Anticancer research. 06/2011; 31(6):2335-8.

  Urachal cancer is a rare malignancy and the standard treatment is surgical resection. The prognosis of recurrent and metastatic urachal cancer is extremely poor because there is no establishedUrachal cancer is a rare malignancy and the standard treatment is surgical resection. The prognosis of recurrent and metastatic urachal cancer is extremely poor because there is no established chemotherapy regimen. Here, the response of one patient with recurrent urachal cancer to combination chemotherapy of gemcitabine (GEM) and cisplatin (CDDP) (GC) is described. And the chemo- and radiotherapeutic regimens available for such patients are reviewed. A 67-year-old man diagnosed with stage IIIA urachal cancer underwent complete surgical resection. However, pelvic recurrence was detected on computed tomography (CT) 5 months after surgery. GC therapy was started immediately and resulted in a pronounced reduction in pelvic mass after three cycles. However, a follow-up CT scan taken 5 months later showed growth of the pelvic mass and new liver metastasis. He received GC therapy again, which resulted in reduction of the pelvic and liver metastatic masses after two cycles. However, the patient refused another course of GC therapy due to severe side-effects. Subsequent progression of the disease included spread in both regions, followed by death 16 months after recurrence. Various treatment strategies offer relatively long survival of patients with urachal cancer including those with recurrence and metastasis. Although further studies are necessary to determine its therapeutic efficacy, GC therapy may be a useful option in the treatment of urachal tumors, including recurrent tumours.

• Pathological significance and predictive value for biochemical recurrence of c-Fes expression in prostate cancer.

  Authors: Yasuyoshi Miyata, Shin-ichi Watanabe, Tomohiro Matsuo, Tomayoshi Hayashi, Hideki Sakai, Jim W Xuan, Peter A Greer, Shigeru Kanda

  The Prostate. 05/2011; 72(2):201-8.

  c-Fes is a proto-oncogene encoded non-receptor protein-tyrosine kinase (PTK). However, genetic studies have indicated that it has anti-tumorigenic effects in certain cancers. The pathological andc-Fes is a proto-oncogene encoded non-receptor protein-tyrosine kinase (PTK). However, genetic studies have indicated that it has anti-tumorigenic effects in certain cancers. The pathological and clinical significance of c-Fes in prostate cancer are unknown. Expression of c-Fes was evaluated in normal glands, prostatic intraepithelial neoplasia (PIN), cancer cells in tissues of knock-in mouse adenocarcinoma prostate (KIMAP) model, and prostate cancer patients free of metastasis. Expression of c-Fes was analyzed by immunohistochemistry, and quantified by using the immunoreactivity score (IRS) (staining intensity × percentage of positive cells). Relationships between c-Fes expression and pT stage, Gleason's score (GS), and biochemical recurrence in patients who underwent radical surgery were also investigated. In KIMAP, the percentage in normal glands, PIN and cancer cells positive for c-Fes expression were 0 (0/7), 25.0 (2/8), and 100% (7/7), respectively. In human tissues, c-Fes expression was also significantly higher in cancer cells than in normal cells and PIN, and it correlated with pT stage (P < 0.001) and GS (P = 0.047). Multivariate analysis showed that c-Fes expression was an independent predictor of poor outcome poor prognosis (hazard ratio = 3.21, 95% confidence interval = 1.11-9.37, P = 0.032). The results suggested that c-Fes expression is a useful predictor of biochemical recurrence after radical surgery. The results also suggested that c-Fes is a potentially useful therapeutic target in prostate cancer and a predictor of biochemical recurrence after radical prostatectomy.

• Clinical significance and predictive value of prostaglandin E2 receptors (EPR) 1 - 4 in patients with renal cell carcinoma.

  Authors: Kojiro Ohba, Yasuyoshi Miyata, Shin-Ichi Watanabe, Tomayoshi Hayashi, Hiroshi Kanetake, Shigeru Kanda, Hideki Sakai

  Anticancer research. 02/2011; 31(2):597-605.

  The clinical significance of prostaglandin E2 receptor (EPR) expression in renal cell carcinoma (RCC) tissues remains unclear. Patients and Μethods: Four subtypes of EPRs were examined in 112 humanThe clinical significance of prostaglandin E2 receptor (EPR) expression in renal cell carcinoma (RCC) tissues remains unclear. Patients and Μethods: Four subtypes of EPRs were examined in 112 human RCC tissues by immunohistochemical and Western blot analysis. The relationships between EPR immunoreactivity score (IS) and various pathological features and survival were then analyzed. The IS of EP4R was significantly higher (p < 0.001) in cancer cells (mean = 2.7 and SD = 2.1) than in normal kidney tissues (1.8 and 1.2). EP4R expression correlated with pT stage, metastasis, and grade. EP2R expression was also associated with metastasis. Expressions of both EP2R and EP4R were found to be significant predictors for cause-specific survival on Kaplan-Meier survival analysis (p = 0.006 and 0.023, respectively). EP2R and EP4R may play important roles in malignant behavior. EP4R in particular was closely associated with pathological features, implicating this receptor as a potential therapeutic target in patients with RCC.

• [Efficacy of naftopidil in patients with overactive bladder associated with benign prostatic hyperplasia: prospective randomized controlled study to compare differences in efficacy between morning and evening medication].

  Authors: Hideki Sakai, Tsukasa Igawa, Toru Onita, Masataka Furukawa, Tomoaki Hakariya, Mikio Hayashi, Fukuzo Matsuya, Yohei Shida, Naoki Nishimura, Yasuo Yogi, Toshifumi Tsurusaki, Kousuke Takehara, Koichiro Nomata, Kazutaka Shiraishi, Takefumi Shono, Daiyu Aoki, Hiroshi Kanetake

  Hinyokika kiyo. Acta urologica Japonica. 01/2011; 57(1):7-13.

  A total of 100 patients with benign prostatic hyperplasia (BPH) and overactive bladder (OAB) symptoms (BPH/OAB), enrolled between June 2006 to March 2008, were randomly divided into 2 groups ofA total of 100 patients with benign prostatic hyperplasia (BPH) and overactive bladder (OAB) symptoms (BPH/OAB), enrolled between June 2006 to March 2008, were randomly divided into 2 groups of morning medication (M) and evening medication (E) groups, then 50 mg of naftopidil was given once a day after breakfast or supper for 8 weeks. Data were available for efficacy analysis on 80 patients (M group ; 43, E group ; 37). Naftopidil significantly improved the overall international prostatic symptom score ; from 19.2±7.9 to 11.7±5.8 in the M group and from 19.4±6.4 to 12.3±6.8 in the E group (p<0.0001), QOL score from 4.9±0.8 to 3.2±1.4 in the M group and from 5.0±0.8 to 3.6±1.3 in the E group (p<0.0001), and OAB symptom score from 7.8±2.6 to 5.0±2.5 in the M group (p<0.0001) and from 8.6±2.9 to 5.8± 3.3 in the E group (p<0.0001). There was no significant difference in the incidence of adverse effects between the M group (6.1%) and E group (2.2%). These results suggest that naftopidil improves storage symptoms as well as voiding symptoms regardless of timing of administration.

• Infection of XC cells by MLVs and Ebola virus is endosome-dependent but acidification-independent.

  Authors: Haruka Kamiyama, Katsura Kakoki, Hiroaki Yoshii, Masatomo Iwao, Tsukasa Igawa, Hideki Sakai, Hideki Hayashi, Toshifumi Matsuyama, Naoki Yamamoto, Yoshinao Kubo

  PloS one. 01/2011; 6(10):e26180.

  Inhibitors of endosome acidification or cathepsin proteases attenuated infections mediated by envelope proteins of xenotropic murine leukemia virus-related virus (XMRV) and Ebola virus, as well asInhibitors of endosome acidification or cathepsin proteases attenuated infections mediated by envelope proteins of xenotropic murine leukemia virus-related virus (XMRV) and Ebola virus, as well as ecotropic, amphotropic, polytropic, and xenotropic murine leukemia viruses (MLVs), indicating that infections by these viruses occur through acidic endosomes and require cathepsin proteases in the susceptible cells such as TE671 cells. However, as previously shown, the endosome acidification inhibitors did not inhibit these viral infections in XC cells. It is generally accepted that the ecotropic MLV infection in XC cells occurs at the plasma membrane. Because cathepsin proteases are activated by low pH in acidic endosomes, the acidification inhibitors may inhibit the viral infections by suppressing cathepsin protease activation. The acidification inhibitors attenuated the activities of cathepsin proteases B and L in TE671 cells, but not in XC cells. Processing of cathepsin protease L was suppressed by the acidification inhibitor in NIH3T3 cells, but again not in XC cells. These results indicate that cathepsin proteases are activated without endosome acidification in XC cells. Treatment with an endocytosis inhibitor or knockdown of dynamin 2 expression by siRNAs suppressed MLV infections in all examined cells including XC cells. Furthermore, endosomal cathepsin proteases were required for these viral infections in XC cells as other susceptible cells. These results suggest that infections of XC cells by the MLVs and Ebola virus occur through endosomes and pH-independent cathepsin activation induces pH-independent infection in XC cells.

• Efficacy and safety of dutasteride on prostate cancer risk reduction in Asian men: the results from the REDUCE study.

  Authors: Hideyuki Akaza, Hiroshi Kanetake, Taiji Tsukamoto, Naoto Miyanaga, Hideki Sakai, Naoya Masumori, Hiroomi Nakatsu, Kazuyuki Sagiyama, Sadaaki Sakamoto, Yukihiro Endo, Takayoshi Yamanouchi

  Japanese journal of clinical oncology. 12/2010; 41(3):417-23.

  A post hoc analysis of Asian men in the REDUCE study was conducted to investigate whether the outcomes were in line with those of the overall population. REDUCE was a 4-year international,A post hoc analysis of Asian men in the REDUCE study was conducted to investigate whether the outcomes were in line with those of the overall population. REDUCE was a 4-year international, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Inclusion criteria were men between 50 and 75 years of age, a serum prostate-specific antigen level of 2.5-10.0 ng/ml (50-60 years) or 3.0-10.0 ng/ml (>60 years), and a single, negative prostate biopsy (6-12 cores) within 6 months before enrollment. The primary endpoint was biopsy-detectable prostate cancer. This post hoc analysis included subjects who were recorded as Asian. A total of 134 Asians, including 57 Japanese, were randomized to the study treatment. During the study period, the incidence of prostate cancer in the placebo and dutasteride groups was 19.6% (11/56) and 9.3% (5/54), respectively (relative risk reduction, 54%; 95% confidence intervals, -27 to 83%, P = 0.12), in the Asian subpopulation. Fewer tumors with the Gleason scores of 7-10 and 8-10 were detected among dutasteride-treated men. Although the incidences of drug-related sexual adverse events were higher in the dutasteride group, only in rare occasions did they lead to drug discontinuation. The incidence of prostate cancer in the dutasteride group was lower than that in the placebo group, although the difference was not significant. These results paralleled those for the overall population and support the value of dutasteride for prostate cancer risk reduction in Asian men with an increased risk of prostate cancer.

• Expression of X-linked inhibitor of apoptosis protein in human prostate cancer specimens with and without neo-adjuvant hormonal therapy.

  Authors: Shin-Ichi Watanabe, Yasuyoshi Miyata, Shigeru Kanda, Takahisa Iwata, Tomayoshi Hayashi, Hiroshi Kanetake, Hideki Sakai

  Journal of cancer research and clinical oncology. 11/2009;

  PURPOSE: X-linked inhibitor of apoptosis (XIAP) has high affinity and strong inhibitory activity on apoptosis-related caspase-3. The relationships between expression of XIAP and cleaved caspase-3,PURPOSE: X-linked inhibitor of apoptosis (XIAP) has high affinity and strong inhibitory activity on apoptosis-related caspase-3. The relationships between expression of XIAP and cleaved caspase-3, and response to neo-adjuvant hormonal therapy (NHT) remain elusive. The aim was to investigate whether NHT influences with XIAP expression in prostate cancer patients. In addition, the relationship between XIAP expression and apoptosis in patients who did or did not receive NHT was also investigated. METHODS: Eighty-three patients who had undergone radical prostatectomy were examined retrospectively and divided into NHT group (n = 40) and non-NHT group (n = 43). Immunohistochemistry was used to analyze the expressions of XIAP and cleaved caspase-3. The apoptotic cells reconfirmed the number of terminal deoxynucleotidyl transferase-mediated nick and labeling (TUNEL)-positive cells. RESULTS: In the non-NHT group, the proportion of TUNEL-positive cells correlated with expression of cleaved caspase-3 (r = 0.592, P < 0.001), and the expression of XIAP correlated negatively with that of cleaved caspase-3 and TUNEL-positive cells (r = -0.464, P < 0.001 and r = 0.431, P = 0.002, respectively). The expression of cleaved caspase-3, but not that of XIAP, was higher in NHT group than non-NHT group (P = 0.017). In the NHT group, there was no significant correlation between XIAP expression and cleaved caspase-3 expression or the proportion of TUNEL-positive cells. CONCLUSIONS: NHT did not influence XIAP expression. We speculate that the inhibition of XIAP expression may reinforce the apoptotic effect of NHT and improve the prognosis in patients with prostate cancer.

• E1AF expression is associated with extra-prostatic growth and matrix metalloproteinase-7 expression in prostate cancer.

  Authors: Sugure Maruta, Hideki Sakai, Shigeru Kanda, Tomayoshi Hayashi, Hiroshi Kanetake, Yasuyoshi Miyata

  APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. 11/2009; 117(11):791-6.

  E1AF is associated with malignant aggressiveness via regulation of matrix metalloproteinases (MMPs), which play pivotal roles in invasion through the degradation of extracellular matrix of tissuesE1AF is associated with malignant aggressiveness via regulation of matrix metalloproteinases (MMPs), which play pivotal roles in invasion through the degradation of extracellular matrix of tissues surrounding tumors. However, the clinical significance of E1AF and MMPs in patients with prostate cancer is not fully understood. We reviewed 50 tissue samples from patients with T2-3N0M0 prostate cancer who had undergone radical operation. Expression levels of E1AF, MMP-1, -3, -7, -9 and -14 were determined semiquantitatively by immunohistochemistry. The mean +/- SD percentage of E1AF-stained cancer cells was 8.56 +/- 5.22, and it was significantly higher (p < 0.001) than the E1AF-immunostaining index of normal cells (1.17 +/- 0.61). E1AF immunostaining index in pT3 (12.74 +/- 4.80) was significantly higher (p < 0.001) than that in pT2 (5.78 +/- 3.31). Although E1AF expression correlated with that of MMP-7 and MMP-9 (r = 0.47, p < 0.001 and r = 0.41, p = 0.004, respectively), multivariate analysis showed that E1AF correlated with only MMP-7 expression (OR = 5.81, 95% CI = 1.27-26.59, p = 0.023). Our results demonstrated that increased expression of E1AF is involved in tumor aggression of prostate cancer. This finding may be influenced by regulation of MMP-7. We speculate that E1AF is a possible target in treatment and prevention of tumor growth in prostate cancer.

• [Secondary endocrine therapy with oral estrogen for relapsed prostate cancer.]

  Authors: Toru Onita, Tsukasa Igawa, Hiroshi Hisamatsu, Hideki Sakai, Hiroshi Kanetake

  Hinyokika kiyo. Acta urologica Japonica. 10/2009; 55(10):595-598.

  We report clinical outcomes of secondary endocrine therapy with oral estrogen for relapsed prostate cancer. A total of 18 patients were treated with oral estrogen as a secondary endocrine therapy forWe report clinical outcomes of secondary endocrine therapy with oral estrogen for relapsed prostate cancer. A total of 18 patients were treated with oral estrogen as a secondary endocrine therapy for relapsed prostate cancer between February 2002 and December 2007. One mg/day of ethinylestradiol was administered orally and the dose was increased to 3 mg/day if necessary. A decrease of serum prostate specific antigenn (PSA) level was seen in all of the 15 patients who were able to take ethinylestradiol without severe side effects. The PSA level was decreased more than 50% in 11 out of 15 (73.3%) patients. Median re-relapse-free survival was 15 (3-32) months. This effectiveness was as good as intravenous high-dose diethylstilbestrol diphosphate (DES-DP) treatment which was used as a secondary endocrine therapy for relapsed prostate cancer at our institute previously. Oral administration of ethinylestradiol is effective and outpatients can be treated at a low cost, so it should be considered as one of the treatment options for relapsed prostate cancer after initial endocrine therapy.

• Synaptophysin immunoreactivity in adrenocortical adenomas: a correlation between synaptophysin and CYP17A1 expression.

  Authors: Kazuto Shigematsu, Noriyuki Nishida, Hideki Sakai, Tsukasa Igawa, Kan Toriyama, Akira Nakatani, Osamu Takahara, Kioko Kawai

  European journal of endocrinology / European Federation of Endocrine Societies. 09/2009;

  Design and methods: The adrenal cortex is not considered to be an intrinsic part of the diffuse neuroendocrine system, but adrenocortical neoplasms possess neuroendocrine properties. In this study,Design and methods: The adrenal cortex is not considered to be an intrinsic part of the diffuse neuroendocrine system, but adrenocortical neoplasms possess neuroendocrine properties. In this study, we examined synaptophysin (SYP) and neural cell adhesion molecule (NCAM) expression in adrenocortical adenomas in relation to adrenal function. Results: Immunohistochemical analysis showed that 50.7 % and 98.6 % of the cortical adenomas showed SYP and NCAM immunoreactivities, respectively. There was no apparent difference in NCAM immunoreactivity among the adenomas. However, the immunostaining for SYP was significantly stronger in cortisol-producing adenomas (CPA) than in aldosterone-producing adenomas (APA), non-functioning adenomas (NFA), showing no clinical or endocrinological abnormality, or adenomas associated with preclinical Cushing's syndrome (preCS). Western blotting and real-time PCR demonstrated that the expression level of SYP protein and mRNA was significantly higher in CPA than in APA or NFA. Additionally, the SYP mRNA level showed a positive correlation with CYP17A1 mRNA. In addition to the plasma membrane, mitochondria and smooth endoplasmic reticulum, SYP immunoreactivity was detected in the Golgi area, which is known to be involved in the regulation of mitochondrial cholesterol and the transport of steroid intermediates. It was unexpected that the ratio of positive cells for SYP in preCS was less than that in APA and NFA. However, further examination is required, because the number of preCS cases we investigated was very small. Conclusions: We propose that SYP expression in adrenocortical cells may be involved in some aspect of adrenal function such as transport or secretion of glucocorticoids.

• Primary Aldosteronism with Aldosterone-Producing Adenoma Consisting of Pure Zona Glomerulosa-Type Cells in a Pregnant Woman.

  Authors: Kazuto Shigematsu, Noriyuki Nishida, Hideki Sakai, Tsukasa Igawa, Shin Suzuki, Kioko Kawai, Osamu Takahara

  Endocrine pathology. 03/2009;

  Aldosterone-producing adenoma (APA) consisting of pure zona glomerulosa (ZG)-type cells is extremely rare, and primary aldosteronism complicated by pregnancy is also rare. We report a case of APAAldosterone-producing adenoma (APA) consisting of pure zona glomerulosa (ZG)-type cells is extremely rare, and primary aldosteronism complicated by pregnancy is also rare. We report a case of APA discovered in a 32-year-old pregnant woman who visited our hospital for hypertension and hypokalemia at 26 weeks gestation. Elevated plasma aldosterone concentration and hypokalemia were observed, and an magnetic resonance imaging scan demonstrated a right adrenal mass. A laparoscopic adrenalectomy was performed because of refractory hypokalemia. Pathologically, the adrenal mass was diagnosed as APA, and in addition to the cytological features, in situ hybridization and real-time polymerase chain reaction proved that all the component cells were ZG-type cells. The cells also showed estrogen receptor beta immunoreactivity and melanocortin 2 receptor mRNA expression, suggesting that estrogen and/or ACTH might be related to the proliferation of APA cells during pregnancy. Our case is the first report of APA consisting of ZG-type cells discovered during pregnancy.

• Hot Flashes During Androgen Deprivation Therapy With Luteinizing Hormone-Releasing Hormone Agonist Combined With Steroidal or Nonsteroidal Antiandrogen for Prostate Cancer.

  Authors: Hideki Sakai, Tsukasa Igawa, Toshifumi Tsurusaki, Morishi Yura, Yasuyuki Kusaba, Mikio Hayashi, Shotaro Iwasaki, Hironobu Hakariya, Tanetoshi Hara, Hiroshi Kanetake

  Urology. 12/2008;

  OBJECTIVES: To investigate hot flashes and quality of life during combined androgen blockade (CAB) therapy using steroidal or nonsteroidal antiandrogens. METHODS: A total of 151 patients withOBJECTIVES: To investigate hot flashes and quality of life during combined androgen blockade (CAB) therapy using steroidal or nonsteroidal antiandrogens. METHODS: A total of 151 patients with prostate cancer, who were enrolled into this study from May 2001 to June 2003, were randomized to receive CAB therapy using a luteinizing hormone-releasing hormone agonist (leuprorelin) combined with a steroidal antiandrogen (chlormadinone) or a nonsteroidal antiandrogen (bicalutamide). The incidence of, frequency of, and distress due to hot flashes were evaluated with a self-administered questionnaire during a 2-year period. The general and disease-specific quality-of-life outcomes were also measured using the Functional Assessment of Cancer Therapy-Prostate questionnaire. RESULTS: Data were available for analysis from 124 patients. Although the incidence of hot flashes largely tended to be greater in the bicalutamide group than in the chlormadinone group, no significant difference was noted in the cumulative incidence of hot flashes at 2 years. The median frequency of hot flashes daily was 1.3 and 2.2 for warmth/flushing (P = .16) and 1.0 and 3.6 for sweating (P = .021) in the chlormadinone and bicalutamide groups, respectively. Patients in the chlormadinone group were significantly less likely to be distressed by warmth/flushing (odds ratio 0.47, P < .001) and sweating (odds ratio 0.61, P = .01) than were those in the bicalutamide group. The Functional Assessment of Cancer Therapy-Prostate scores over time showed no intergroup differences. CONCLUSIONS: Our results suggest that CAB using a steroidal antiandrogen such as chlormadinone might induce fewer and less-distressing hot flashes than CAB with bicalutamide.

• TFE3-renal carcinoma in an adult patient: A case with strong expression of phosphorylated hepatocyte growth factor (HGFR)/Met.

  Authors: Yuji Sagara, Yasuyoshi Miyata, Koichiro Nomata, Kuniko Abe, Jiro Eguchi, Tomayoshi Hayashi, Hideki Sakai, Shigeru Kanda, Hiroshi Kanetake

  Pathology, research and practice. 11/2008;

  TFE3-renal carcinoma is rare in adults. Patients with this disease often have a poor prognosis, because it has reached an advanced stage at presentation, and there is lack of an effective therapy.TFE3-renal carcinoma is rare in adults. Patients with this disease often have a poor prognosis, because it has reached an advanced stage at presentation, and there is lack of an effective therapy. The exact mechanism of its malignant behavior is still unclear. In recent years, a significant relationship between TFE3 fusion protein and hepatocyte growth factor receptor (HGFR)/Met tyrosine kinase activity was reported in several malignancies. We previously reported that phosphorylation of HGFR/Met was associated with malignant aggressiveness and survival in patients with conventional RCC. Here, using immunohistochemical techniques, we examined two types of phosphorylated HGFR/Met (pY1234/1235 and pY1349) in a specimen of a 29-year-old man with TFE3-renal carcinoma. Strong expression of both proteins was detected in carcinoma cells, but not in normal kidney tissues. In addition, they were expressed more strongly in TFE3-renal carcinoma than in conventional RCC. Although tumor was diagnosed at T1N0M0 and the patient received radical nephrectomy, the tumor metastasized to multiple organs, and he died 2 years after surgery. We speculate that upregulated phosphorylation of HGFR/Met could be partly associated with the malignant aggressiveness and poor survival of this patient.