Search

A 25-year-old man with a left testicular tumor underwent a high inguinal orchiectomy. Histopathological examination of the resected specimen revealed tumors of more than one histological type, mixed forms (seminoma, immature teratoma). Further evaluation revealed no metastasis (pT1N0M0S1 Stage IS).Four months after orchiectomy, alpha-fetoprotein (AFP) was elevated.CT scan revealed retroperitoneal masses of recurrent tumor. Although the AFP returned to normal level after four courses of BEP (bleomycin, etoposide and cisplatin), the retroperitoneal lymph nodes continued to grow. He underwent excision of the retroperitoneal lymph node dissection. Histopathological examination of the resected specimen revealed mature teratoma.Few reports examined about the development mechanism of growing teratoma syndrome (GTS). We considered that the development mechanism of GTS in this case is induction of differentiation. In this case report, we discuss the development mechanism of GTS based on bibliographical consideration.

To assess the effect of survivin gene expression on the proliferation of prostate cancer (PCa) cells and study the association of suvivin and its spliced isoforms gene expression levels with the pathologic grade of PCa.Gene expression of survivin and its spliced isoforms in the LNCaP and PC-3 PCa cell lines was determined using reverse transcriptase-polymerase chain reaction. We knocked down the gene expression of survivin using small interfering RNA and assessed the cell proliferation using the MTS assay. Next, we quantified the gene expression levels of survivin and its isoforms in prostate biopsy samples (PCa, n = 37; benign prostatic hyperplasia, n = 13; PCa after androgen deprivation therapy, n = 12) using the quantitative real-time polymerase chain reaction method.In PCa cells, survivin and survivin-2alpha and survivin-2B were expressed more than survivin-DeltaEx3. The decrease in survivin gene expression by transfection of siRNA was accompanied by the inhibition of cell proliferation of PCa cells (31% and 25% decreased in LNCaP and PC-3 cells, P0.01). In the prostate biopsy samples, the survivin expression in PCa was significantly greater than that in BPH or PCa after androgen deprivation therapy (PCa, 1; BPH, 0.16; PCa after androgen deprivation therapy, 0.27; P0.01). In the PCa samples, the survivin expression level was associated significantly with high-grade cancer (Gleason score 8 or 9; Gleason score 7 versus 8 or 9, 1 versus 2.00, respectively; P0.05). The survivin-2B/survivin ratio in high-grade cancer was lower than that in low-grade (Gleason score 7) cancer (Gleason score 7 versus 8 or 9, 1 versus 0.69; P0.10).These findings suggest that survivin and its spliced isoforms have associations with PCa cell proliferation and aggressive phenotypes.

Sulfation is a key pathway in xenobiotic metabolism and chemical defense, and phenol sulfotransferase SULT1A1 plays a central role in this reaction. Genetic polymorphism of the SULT1A1 gene, SULT1A1, was reported to be associated with risks of several cancers; however, one study showed no significant relation between SULT1A1 genotype with prostate cancer risk. The present study was conducted to confirm the association of a G638A polymorphism, Arg213His, in SULT1A1 with familial prostate cancer risk in a Japanese population. A case-control study consisting of 126 cases and 119 controls was performed. In controls, GG, GA, and AA genotypes were observed in 85 (71.4%), 32 (26.9%), and 2 (1.7%), respectively; whereas, GG, GA, and AA genotypes were observed in 94 (74.6%), 32 (25.4%), and 0 cases, respectively. No significant differences were found in genotypic frequencies among cases and controls. Furthermore, stratification of cases according to clinical stages (localized or metastatic), pathological grades (Gleason score7, or7), age at diagnosis (70 years or70) and the number of affected relatives (2 or2) did not show any significant differences among categories. These findings suggested that genetic polymorphism of SULT1A1 might not be involved in genetic susceptibility to prostate cancer.

1987年から慢性腎不全の臨床治療として腎移植治療を継続的に施行している. 2006年12月までの20年間で62回 (59名) の生体腎移植を施行した. 移植腎生着率は, 1年92％, 5年81％, 10年62％であり, 患者生存率は1年95％, 5年91％, 10年91％であった. 生体腎提供者は親が49名と最も多く, 姻族は4名であった. ABO血液型不適合移植を8名, 2次移植を3名に施行した. 急性拒絶反応出現率は後半の10年で激減した. 腎移植後の妊娠出産を3名に認め, 合計5名の挙児を得た. 移植腎機能喪失原因は, 慢性移植腎症が7例と最も多く, 次いで死亡が4例であった. 腎移植後に甲状腺癌1名, 精巣腫瘍1名を認めたが, 現在再発なく移植腎機能も良好である.

1987年から慢性腎不全の臨床治療として腎移植治療を継続的に施行している. 2006年までの20年間で19例の献腎移植を施行した. 移植腎生着率は, 1年95％, 5年76％, 10年44％であり, 患者生存率は1年100％, 5年87％, 10年73％であった. 移植腎機能喪失原因は, 死亡が4例と最も多く次いで慢性移植腎症が3例であった. 現在当科外来通院中の11名の血清クレアチニンは1mg/dl前後であり移植腎機能は非常に良好である. また, 合併症は腎移植後13年経過する1症例に循環器系の合併症を認め薬物療法中であるが, その他の症例には合併症をほとんど認めず, 外来通院の11名は非常に高いQOLを保持している.

Background: Androgen plays a central role in the normal and malignant development of prostate glands. Genetic polymorphisms of genes involved in androgen metabolism and signaling might be associated with the risk of prostate cancer. Methods: One hundred and two patients with prostate cancer with a family history and 117 healthy age- and residence-matched male controls were enrolled. Genotypes of the CAG repeat length of androgen receptor (AR), CYP17, 5α-reductase type II (SRD5A2), UDG-glucuronosyltransferase (UGT) 2B15, PSA promoter genes were analyzed. Results: For single polymorphisms, the presence of Y alleles showed a significantly lower risk of prostate cancer in comparison with the D/D genotype in UGT2B15 (odds ratio [OR]=0.41, 95% confidence interval [CI]=1.40–4.28, p =0.0015), and the presence of A2 alleles showed a weak tendency to decrease prostate cancer risk in comparison with the A1/A1 genotype in CYP17 (OR=0.69, 95% CI=0.39–1.23, p =0.21). The stratification of cases according to clinical stage and pathological grade showed that the A2/A2 genotype was significantly associated with localized stage cancer in comparison with metastatic stage cancer (OR=5.18, 95% CI=1.49–17.95, p =0.007). The combination of UGT2B15 and CYP17 genotypes could identify higher risk subjects even in subjects with low-risk UGT2B15 genotypes, i.e., Y/Y+D/Y genotypes (OR=1.97, 95% CI=0.92–4.22, p =0.079). Conclusion: Genetic polymorphisms of the genes involved in androgen metabolism and signaling were significantly associated with familial prostate cancer risk. Single nucleotide polymorphisms of low-penetrance genes could be targets to understand genetic susceptibility to familial prostate cancer.

Background: The Ile to Val polymorphism at codon 655 of HER-2 was reported to be associated with a risk of sporadic prostate cancer and breast cancer. In this study, we examined the association of the HER-2 polymorphism with familial prostate cancer in a Japanese population. Materials and methods: We performed a case-control study consisting of 144 familial prostate cancer cases and 119 normal control subjects. The genetic polymorphism was analyzed by the restriction fragment length polymorphism method. Results: There was no significant difference between the case group and the control group for the allele or genotype distribution. Conclusion: In the present study, we could not confirm any significant association between the HER-2 polymorphism with familial prostate cancer risk in a Japanese population. Further large-scale studies are warranted to confirm the association of the HER-2 polymorphism with the risk of development of prostate cancer.

The RNASEL gene on chromosome 1q25 has been identified as a prostate cancer susceptibility gene. We screened for RNASEL germline mutations in familial prostate cancer patients, and performed a case-control study to examine the association of specific variants with prostate cancer risk in the Japanese. Three variants within the RNASEL gene, G282A, G1385A and T1623G were identified. G1385 and T1623G variants result in previously reported Arg462Gln and Asp541Glu variants, respectively. The novel G282A variant does not cause amino-acid substitution. A case-control study consisting of 101 familial prostate cancer cases and 105 noncancer controls showed that the Gln/Gln genotype of codon462 was observed in 7.6% of controls. However, the Gln/Gln genotype was not observed in cases, and reduced prostate cancer risk (odds ratio (OR)=0.061, P=0.014). The Asp/Asp genotype of codon541 increased the familial prostate cancer risk (OR=7.37, P=0.0004). In subset analysis, a significant association was observed in patients with more than two affected members (OR=3.15, P=0.028), and weak associations were found in patients with metastatic disease (OR=2.40, P=0.11) and high-grade disease (Gleason score >or=7) (OR=3.07, P=0.14). These findings suggested that the polymorphic changes within the RNASEL gene may be associated with familial prostate cancer risk in a Japanese population.

Association between genetic polymorphisms of CYP1A1 and familial prostate cancer risk was examined by a case-control study of 185 individuals. Although the individual analysis of m1 or m2 genotype of CYP1A1 showed no significant association with prostate cancer risk, the presence of any mutated alleles significantly increased prostate cancer risk in comparison with wild-type genotypes by combination analysis (odds ratio [OR]=2.38; 95% confidence interval [CI]=1.72-3.29; P=0.0069). Furthermore, metastatic cancer had a significant association with mutated alleles of m1 and m2. These finding suggested that CYP1A1 polymorphisms has an association with prostate cancer risk, especially with progression of prostate cancer.

Aim: Vitamin D acts as an antiproliferative agent against prostate cells. Epidemiological study has shown that a low level of serum vitamin D concentration is a risk factor for prostate cancer. Vitamin D acts via vitamin D receptor (VDR), and an association of genetic polymorphisms of the VDR gene has been reported. In the current study, we examined the association of VDR gene polymorphisms with familial prostate cancer in a Japanese population. Methods: We performed a case–control study consisting of 81 familial prostate cancer cases and 105 normal control subjects. Three genetic polymorphisms (BsmI, ApaI and TaqI) in the VDR gene were examined by the restriction fragment restriction length polymorphism method. Results: Overall, there was no significant association of the VDR gene polymorphisms with familial prostate cancer risk in the cases and control subjects. However, a weak association between BsmI or TaqI genotypes and cancer risk was observed in subjects under 70 years of age. Stratification of cases by clinical stage or pathological grade did not show significant association between the VDR gene polymorphisms and prostate cancer risk. Conclusion: In the present study, we could not confirm any significant association between VDR gene polymorphisms with familial prostate cancer risk in a Japanese population. Further large-scale case–control studies are warranted to confirm the importance of VDR gene polymorphisms in familial prostate cancer.

症例は32歳, 男性.腹痛の精査で, 後腹膜に巨大な腫瘍を認めた.病理組織学的所見, 画像所見より, 左腎転移, 多発性肺転移, 縦隔リンパ節転移を有する性腺外胚細胞腫瘍と診断された.PEB(CDDP+etoposide+bleomycin)療法4コースを施行し, 腫瘍マーカーの正常化, 腫瘍の著明縮小が得られた.画像上, 腎門部に残存腫瘍を認め, 残存腫瘍摘出術を行った.摘出標本より, 少量のviable cellを認め, 末梢血幹細胞移植を併用したVIP(CDDP+etoposide+ifosfamide)療法を3コース施行した.現在, 外来経過観察中であるが, 画像上の再発, 及び, 腫瘍マーカーの上昇を認めていない.

The patient was a 47-year-old male, who visited Hidaka Hospital with a chief complaint of swelling in the right inguinal region and the scrotum. With a diagnosis of a right spermatic cord tumor, right high orchiectomy was performed. Since an inflammatory type of malignant fibrous histiocytoma (MFH) was diagnosed from histopathological findings, chemotherapy and radiation therapy were performed as postoperative treatment. Malignant fibrous histiocytoma with the primary focus of the spermatic cords is a rare disease. To our knowledge, this is the 20th case of MFH of the spermatic cord in Japan (the 42nd in the world) and it is the second case of inflammatory type of MFH in Japan.

Androgen insensitivity syndrome (AIS) is an X-linked recessive disorder. The molecular mechanism of AIS is reduction or absence of androgen signalling caused by androgen receptor (AR) malfunction or absence. The phenotype of AIS varies from a complete female phenotype (complete AIS, CAIS) to male genitalia with mild hypospadias (partial AIS, PAIS). In the current study, we characterize a novel point mutation in the ligand binding domain of the AR gene in a 50-year-old Japanese CAIS patient. Sequence analysis showed a single point mutation at nucleotide 3359 (Genbank, NM 000044), T to C, in exon E in the AR gene. This mutation led to the conversion of codon 739 tyrosine into aspartic acid in the ligand binding domain. No specific androgen binding was detected in genital fibroblasts isolated from the patient. Transcriptional activating activity of the mutant AR was examined by transient DNA transfection into COS-1 cells. Wild-type AR successfully activated androgen inducible MMTV promoter dose-dependently. In contrast, the mutant AR did not activate MMTV promoter. Thus, we demonstrated the molecular characteristics of the novel point mutation in the ligand binding domain of the AR gene associated with CAIS. This information will provide a further understanding of the structure and function of the AR gene.

PURPOSE Screening by only prostate specific antigen (PSA) for prostate cancer was started since PSA had been added to mass screening as one of check lists in 1997 in Isesaki city, Gunma pref. We expected PSA screening to be introduced into other areas. We therefore studied how to perform a screening procedure for prostate cancer as well as discussed our result of the screening conducted lately. MATERIALS AND METHODS 1,382 out of 1,423 Isesaki citizens who took mass screening aged 40 to 64 were chosen. Regardless of age, men with a serum PSA level equal or larger than 4.1 ng/ml (Tandem R) were selected for second screening since we determined it was a cut-off level for further check-up. Of those men, 38 were requested for second screening and actually only 24 took it. All these men took PSA check-up again, furthermore 23 took transrectal examination (TRE) and/or transrectal ultra sonography (TRUS) except for one of them. The next screening was requested for sixteen of them. Prostate biopsy was conducted for all of them. RESULTS More old men took screening and were diagnosed prostate cancer. The findings derived from such diagnosis showed one of them aged 50 to 59 and six of them aged 60 to 64 had the cancer. Moreover, four out of twenty with PSA level ranging 4.1 to 10.0 ng/ml and all of three with PSA level over 20.0 ng/ml had the cancer. Five out of sixteen with a positive sign for further PSA check-ups had the cancer. All the three suspect of the cancer by TURS and DRE had prostate cancer. Two of seven with PSA negative showed suspicion of prostate cancer and had the cancer. No neo-adjuvant and total prostatectomy was conducted for four with 4.0 to 10.0ng/ml diagnosed T2N0 M0. One of them with PSA equal or over 20.0 ng/ml was diagnosed T3N0M0. After hormone therapy its PSA decreased to that equal or under 0.5 ng/ml. Total prostatectomy was conducted for it. CONCLUSION It is not proved that only PSA mass screening for prostatic cancer contributes to detect early cancer and better prognosis cure case. For the proof, it will be nessary that PSA mass screening is examined more people in the wide area. We conclude men aged 65 to 69 also should take PSA check-up based on epidemiological feature of prostatic cancer.

1993年1月から1999年4月までの約6年間に群馬大学医学部附属病院泌尿器科において加療を行った精巣腫瘍77例に対して臨床的検討を行った.胚細胞性腫瘍が71例を占め, セミノーマが34例, 非セミノーマが37例であった.非胚細胞性腫瘍は悪性リンパ腫5例, Leydig cell tumorが1例であった.年齢は0歳から75歳に分布し, 30歳代が最も多かった.病理組織型別, 臨床病期別の生存率の比較を行ったが, それぞれセミノーマ, 早期症例で良好であったが有意差を認めなかった.再発症例は4例あり, そのうち2例が癌死した, また, 初回化学療法が奏功せずに進行症例2例が治療開始後1年以内に癌死した.治療上の課題として, 進行症例における化学療法の選択基準早期症例におけるsurveillance policy導入の是非などがあげられ, 今後なお検討を要すると考えられた.

群馬大学医学部附属病院泌尿器科における1996年の外来初診患者の臨床統計を報告した.総数878名であり, 男性629名, 女性249名で男女比は2.52 : 1であった.年齢は, 男女ともピークは60～69歳に認めた.紹介患者は68.2% (599名) で, 他医よりの紹介が43.1% (378名) を占めていた.悪性新生物は149例あり, 前立腺癌51例, 腎癌41例, 精巣腫瘍25例および膀胱腫瘍19例であった.良性新生物では前立腺肥大症が100例と大部分を占めていた.その他多い疾患として, 尿路結石が60例, 以下, 移植・透析関係54例, 膀胱炎35例であった.他報告に比し, 前立腺癌, 腎癌, 移植・透析関係, 精巣腫瘍が多く, 膀胱炎, 膀胱癌STD, 包茎, 亀頭包皮炎, 外傷などは少ない傾向だった.

To assess the limitation of standard cisplatin-based combination chemotherapy for metastatic germ cell tumor, clinical records of 37 patients with metastatic testicular cancer and extragonadal germ cell tumor treated with primary chemotherapy were reviewed. Thirteen patients of 37 had limitation of the treatment. We categorized the mode of treatment limitation into 5 criteria according to the response of tumor marker levels and radiographic findings, and recurrence. Tumor volume was strongly associated with the limitation of the treatment. Indiana University Staging System, not Royal Marsden Hospital's classification clearly discriminated the patient with limitation of standard cisplatin-based combination chemotherapy. High dose chemotherapy was effective for patients to whom the initial chemotherapy with standard cisplatin-based regimen was effective. It did not offer any benefit to patients with refractory tumor. We conclude that it is important to introduce more aggressive chemotherapy regimens as an initial chemotherapy to patients with large volume tumor.

Intra–arterial infusion therapy following alteration of pelvic blood flow and concurrent radiation therapy was performed in 13 patients with muscle invading bladder cancer (T2, 2; T3, 6; T4, 5). The internal iliac artery of the opposite side was embolized and the ipsilateral gluteal and obturator arteries were embolized by metallic coils. A catheter was placed in the ipsilateral internal iliac artery. CDDP was administered daily at a dose of 7–9 mg/body over 1 minute. Radiation was done by Microtron using 10 MV x–ray. Total dose was 4500–7060 cGy. Evaluation was done by cystoscopy, radiography and biopsy. Eight patients achieved complete response (CR) histologically. Others had partial response (PR). All CR patients had no recurrence. The observation period was between 3 and 29 months, with a mean of 11 months. This treatment modality is effective for locally advanced bladder cancer.

Twenty-three dogs received prostatectomy by transurethral balloon laserthermia, and the in vivo effects and morbidity were evaluated. The prostate was heated transurethrally, and tissue temperature at a depth of 5 mm. from the urethral mucosa was maintained at 60C for 20 minutes. Immediately after the treatment, coagulative necrosis was observed around the urethra to an average depth of 5 mm., and the tissue started to slough off within 1 week. Cavity formation and reepithelialization were complete after 4 weeks. Histologically, no tissue damage was found in the bladder neck or the urethral sphincter. The cavity formation threshold was 46.1C for 20 minutes. There was no incontinence or macroscopic hematuria in any case. No abnormality was found in hematological or biological examinations after treatment. From these data, the clinical use of transurethral balloon laserthermia for prostatectomy is considered both safe and effective.

Background: Many studies have shown the relationship between pretreatment serum testosterone levels and the clinical stage or histological grade, but the clinical significance of pretreatment testosterone levels is controversial. We studied the association of pretreatment total testosterone levels with the clinical stage and histological grade of prostate cancer. Methods: We evaluated 2914 patients whose pretreatment testosterone levels were recorded from 1982 to 2002. Serum testosterone levels were measured by radioimmunoassay. Results: There was a trend toward decreasing testosterone values with worsening clinical staging. There was a trend toward decreasing testosterone values with worsening histological grading, too. Patients with poorly differentiated adenocarcinoma had significantly lower testosterone levels than those with the others (versus well; p p Conclusions: Newly diagnosed patients with poorly differentiated adenocarcinoma of prostate have lower testosterone levels than the others.

Estrogen is crucial for development of benign prostate hyperplasia and prostate cancer. Aromatase (CYP19) is a key enzyme for estrogen synthesis in males. The genetic polymorphism of the CYP19 intron 4 [TTTA]n tetranucleotide has been studied in relation to breast cancer susceptibility.We examined the association of the tetranucleotide repeat polymorphism of the CYP19 gene with familial prostate cancer risk in a Japanese population by performing a case-control study consisting of 99 familial prostate cancer cases and 116 normal controls.[TTTA] repeats ranged from 7 to 13 and were designated as A1 to A7 according to the repeat number. We did not observe any A3 allele among cases and controls, nor A7 among cases. Short repeat alleles, A1 and A2, had a tendency to be frequently observed in cases (odds ratio [OR] = 1.43, 95% confidence interval [CI] = 0.96-2.14, p = 0.080). Analysis of polymorphic genotypes showed that short genotypes, i.e., A1A1, A1A2 and A2A2, significantly increased prostate cancer risk in comparison with other longer genotypes (OR = 1.80, 95% CI = 1.04-3.11, p = 0.035). Stratification of cases according to the pathological grade or the clinical stage showed no significant differences among categories.In the present study, we found that short polymorphic genotypes of [TTTA]n repeats of the CYP19 gene were associated with familial prostate cancer risk.

BACKGROUND Estrogen is one of the crucial hormones participating in the proliferation and carcinogenesis of the prostate glands. Genetic polymorphisms in the estrogen metabolism pathway might be involved in the risk of prostate carcinoma development. The authors evaluated the association between genetic polymorphisms in estrogen-related enzymes and receptors and the risk of developing familial prostate carcinoma. METHODS In the current study, 101 cases with prostate carcinoma whose first-degree relatives had prostate carcinoma and 114 healthy age and residence-matched male controls were enrolled. The genotypes of estrogen receptor (ER) alpha, aromatase (CYP19), and catechol-O-methyltransferase (COMT) genes were analyzed. RESULTS For single polymorphisms, a significant association of the T/T genotype of the PvuII site in the ER alpha gene (odds ratio [OR], 3.44; 95% confidence interval [CI], 1.97–5.99; P = 0.0028), and the C/T and T/T genotypes of the CYP19 gene (OR, 1.77; 95% CI, 1.02–3.09; P = 0.037) with prostate carcinoma risk, was observed. The G/A genotype of the COMT gene showed a weak tendency toward increased risk (OR, 1.48; 95% CI, 0.85–2.57; P = 0.18). Stratification of cases according to clinical stage and pathologic grade showed that the C/T and T/T genotypes of the CYP19 gene were associated significantly with high-grade carcinoma (OR, 2.59; 95% CI, 1.47–4.46; P = 0.048). The number of high-risk genotypes (the T/T in ER alpha, the C/T and T/T in CYP19, and the G/A in COMT) significantly increased the risk of developing prostate carcinoma (2 genotypes: OR, 3.00; 95% CI, 1.72–5.23; P = 0.008; 3 genotypes: OR, 6.30; 95% CI, 3.61–10.99; P = 0.002). CONCLUSIONS Genetic polymorphisms of genes in the estrogen metabolism pathway were associated significantly with familial prostate carcinoma risk. Single nucleotide polymorphisms of low-penetrance genes are targets for understanding the genetic susceptibility of familial prostate carcinoma. Cancer 2003;98:1411–6. © 2003 American Cancer Society. DOI 10.1002/cncr.11639

Glutathione-S-transferases (GSTs) are active in the detoxification of a wide variety of toxins and carcinogens. The genetic polymorphisms of GSTM1, GSTT1 and GSTP1 genes have been studied to estimate the relative risk of various cancers. In the current study, we examined the association of the GST gene polymorphisms with familial prostate cancer in a Japanese population by performing a case-control study consisting of 81 familial prostate cancer cases and 105 normal controls.No significant association of the GSTM1 and GSTT1 gene polymorphisms with familial prostate cancer risk was found; however, the Val/Val genotype of the GSTP1 gene significantly increased risk (OR = 9.31, 95% CI = 0.47-184, p = 0.030). The combination analysis of genotypes of the three genes showed that presence of two high-risk genotypes, i.e., null genotype of the GSTM1 or GSTT1 gene, or any Val genotypes of the GSP1 gene, significantly increased the risk of prostate cancer (OR = 2.67, 95% CI = 1.08-6.59, p = 0.03). Stratification of cases according to the pathological grade or the clinical stage showed no significant differences among categories.In the present study, we found that genotypes of GSTs, especially the Val-allele of the GSTP1 gene and the combination of three genotypes, were associated with familial prostate cancer risk.

Laser capture microdissection (LCM) enables the dissection of heterogeneous components of tissues, helping to investigate the molecular properties of these tissues. We have reported gene expression profiles in human benign prostatic hyperplasia (BPH) using LCM and quantitative real-time PCR. In the current work, we extended the previous observations. Firstly, we studied the relationship between the number of dissected acini and amplification by PCR, and found that androgen receptor (AR) and 18S rRNA transcripts were successfully amplified from total RNA obtained from one prostate acinus. Furthermore, LCM-dissected samples were applicable to methylation-specific PCR of E-cadherin promoter gene after bisulfite modification of genomic DNA. Next, we performed cDNA microarray analysis to screen gene expression profiles in the epithelium and stroma. RNA was amplified by T7-RNA polymerase and labeled with Cy3 and Cy5. Epithelium-related or stroma-related genes were identified through cDNA microarray. We confirmed true gene expression levels by quantitative real-time PCR. In epithelium, E-cadherin and serine protease 2, Kunitz-type gene expression levels were significantly elevated, while the connective tissue growth factor gene expression level was significantly elevated in stroma. Thus, LCM-dissected samples were applicable to various molecular examinations including methylation-specific PCR and cDNA microarray, and this will contribute to a precise understanding of the molecular profiles of prostate glands.

Genistein is a major component of soybean isoflavone and has multiple functions resulting in antitumor effects. Prostate cancer is 1 of the targets for the preventive role of genistein. We examined the effect of genistein on human prostate cancer (LNCaP and PC-3) cells. Proliferation of both cell lines was inhibited by genistein treatment in a dose-dependent manner. To obtain the gene expression profile of genistein in LNCaP cells, we performed cDNA microarray analysis. The expression of many genes, including apoptosis inhibitor (survivin), DNA topoisomerase II, cell division cycle 6 (CDC6) and mitogen-activated protein kinase 6 (MAPK 6), was downregulated. Expression levels were increased more than 2-fold in only 4 genes. The glutathione peroxidase (GPx)-1 gene expression level was the most upregulated. Quantitative real-time polymerase chain reaction revealed significant elevation of transcript levels of GPx-1 in both LNCaP and PC-3 cells. Upregulation of gene expression levels accompanied elevation of GPx enzyme activities. In contrast, no significant changes were observed in the gene expression levels and enzyme activities of the other antioxidant enzymes, superoxide dismutase and catalase. GPx activation might be one of the important characteristics of the effects of genistein on prostate cancer cells.

Interleukin (IL)-15 is a pleiotropic cytokine that is important forinnate and adaptive immune cell homeostasis. The expression of IL-15protein is controlled by posttranscriptional mechanisms. Here, weconstructed a human IL-15 expression vector consisting of the humanIL-2 signal peptide, the human IL-15 mature peptide-coding sequences,and an out-of-frame human growth hormone gene. Human prostate cancercells, PC-3, transfected with this highly secretable form of the IL-15gene, successfully secreted abundant bioactive IL-15 protein. In nudemice, the growth of PC-3 cells producing IL-15 was remarkably retarded.NK cell-depletion using anti-asialo GM1 antibody restoredtumorigenicity. Histologically, tumors derived from IL-15-producingPC-3 cells contained necrotic areas with high apoptotic index.Splenocytes incubated with supernatant of transfectants killed targetPC-3 cells and expressed a significantly high level of mIFN-γ mRNA.These observations suggest that NK cell-mediated, anti-tumor effects ofIL-15 could provide a potential rationale for gene therapy of prostatecancer.

PURPOSE AND METHODS: We investigated the influence of flutamide on plasma adrenal androgens in advanced prostate cancer patients treated with dietylstilbestrol diphosphate (DES-DP) followed by luteinizing hormone-releasing hormone agonist (LH-RH agonist). Nine patients were enrolled in this study and they were divided into the following two treatment groups; group A: LHRH agonist mono-therapy (n = 4) and group B: LHRH agonist with flutamide (n = 5). For prevention of flare up, all patients were treated with DES-DP. RESULTS: Two-week DES-DP administration led to reduction of plasma adrenal androgen levels. These levels were kept lower for 16 weeks in group B in contrast with group A in which the levels returned to the pretreatment levels. Basal ACTH levels in group B were significantly lower than those in group A. CONCLUSION: From our observations, we found that flutamide reduced adrenal androgen levels in prostate cancer patients treated with LH-RH agonist. ACTH suppression might be related to this phenomenon.

We report a case of transitional cell carcinoma arising in the fossa navicularis of the male urethra. The patient was 87-years-old and noticed intermittent urethral bleeding. We could see a tumor protruding from the urethral meatus, removed it successfully, and irradiated the base of the tumor with Nd:YAG laser. The histologic finding was grade 2 transitional cell carcinoma, pTa. There was no other tumor in the urinary bladder or upper urinary tract. The postoperative course was uneventful and the patient showed no evidence of disease for 4 months after treatment but died from other causes.