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Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the abnormal accumulation of surfactant-derived substances in the lungs. To the best of our knowledge, the successful treatment of metastatic renal cell carcinoma in patients with PAP has not been reported. Here, we describe such treatment of a patient via avelumab plus axitinib therapy. After four courses of treatment, computed tomography showed size reduction of the pulmonary metastatic nodule and improvement of PAP. This study highlights that avelumab plus axitinib therapy is a safe and effective treatment option for metastatic renal cell carcinoma, even in patients with PAP.

(Objective) We retrospectively evaluated the clinical efficacy and safety of abiraterone acetate (AA) in patients with castration-resistant prostate cancer (CRPC). (Methods) We analyzed the clinical records of 50 patients who had received AA in Gunma Cancer Center between October 2014 and June 2017. We assessed the response of prostate-specific antigen (PSA) to AA, and analyzed the association between overall survival and various parameters, including the types of primary hormonal therapy, PSA level, Gleason score, time to CRPC, prior treatment with enzalutamide (Enz) and docetaxel, and sites of metastases. (Results) The median patient age was 74.5 years and median PSA level at baseline was 15.9 ng/ml; 39 (78%) patients had Gleason score ≥8. Eleven (45.8%) of the 24 docetaxel-naïve patients achieved50% reduction in PSA level from baseline as opposed to one (4.5%) of the 22 patients previously treated with docetaxel.Eleven (55%) of the 20 Enz-naïve patients achieved50% reduction in PSA level from baseline compared to one (3.8%) of the 26 patients previously treated with Enz. The overall survival of the group with time to CRPC12 months was significantly longer than that of the group with time to CRPC12 months (p=0.035). In general, AA was tolerated; the most frequently reported adverse events included liver dysfunction (22%) and fatigue (6%). (Conclusion) Our results suggest that AA is tolerated and may be suitable for patients with time to CRPC12 months.

Introduction Primitive neuroectodermal tumors are small round-cell tumors - Ewing sarcoma family, frequently occurring in the extremities, but rarely in the kidney. Case presentation A 58-year-old woman presented with whole-body edema and weakness of lower limb muscles. Computed tomography revealed a left renal tumor, and the plasma adrenocorticotropic hormone level was elevated. The tumor was surgically removed without complications, her plasma adrenocorticotropic hormone reverted to normal levels, and symptoms disappeared after surgery. Histopathological examination revealed a primitive neuroectodermal tumor arising in her kidney. The patient was alive without metastasis 3 years after the surgery. Conclusion We report the first case of renal primitive neuroectodermal tumor accompanying elevated plasma adrenocorticotropic hormone levels which are thought to be produced and secreted in an ectopic fashion.

(Purpose) We created an image reconstructing multiparametric MRI system called VIVID (Visualization of Various Integration with Diffusion) and examined the efficacy of VIVID in detecting prostate cancer. (Methods and materials) The subjects were 80 patients who underwent one target biopsy with reference to MRI images in addition to 8-20 biopsies. (Results) The significant cancer detection rate was 61%, the significant cancer detection rate of PI-RADS 4 or 5 was 55%, and the significant cancer detection rate of VIVID score 4 or 5 was 55%. Three cases with PI-RADS 4 at TZ lesion with positive T2WI only were evaluated as having VIVID scores 1 or 2. Cancer was not detected with target biopsy from the site. (Conclusion) Our finding suggest that VIVID correctly excludes TZ lesions with only T2WI positively in multiparametric MRI.

Background To date, research has not determined the optimal procedure for adjuvant androgen deprivation therapy (ADT) in patients with locally advanced prostate cancer (PCa) treated for 6 months with neoadjuvant ADT and external-beam radiation therapy (EBRT). Methods A multicenter, randomized, phase 3 trial enrolled 303 patients with locally advanced PCa between 2001 and 2006. Participants were treated with neoadjuvant ADT for 6 months. Then, 280 patients whose prostate-specific antigen levels were less than pretreatment levels and less than 10 ng/mL were randomized. All 280 participants were treated with 72 Gy of EBRT in combination with adjuvant ADT for 8 months. Thereafter, participants were assigned to long-term ADT (5 years in all; arm 1) or intermittent ADT (arm 2). The primary endpoint was modified biochemical relapse-free survival (bRFS) with respect to nonmetastatic castration-resistant prostate cancer (nmCRPC) progression, clinical relapse, or any cause of death. Results The median follow-up time after randomization was 8.2 years. Among the 136 and 144 men assigned to trial arms 1 and 2, respectively, 24 and 30 progressed to nmCRPC or clinical relapse, and 5 and 6 died of PCa. The 5-year modified bRFS rates were 84.8% and 82.8% in trial arms 1 and 2, respectively (hazard ratio, 1.132; 95% confidence interval, 0.744-1.722). Conclusions Although modified bRFS data did not demonstrate noninferiority for arm 2, intermittent adjuvant ADT after EBRT with 14 months of neoadjuvant and short-term adjuvant ADT is a promising treatment strategy, especially in a population of responders after 6 months of ADT for locally advanced PCa.

Objective To examine the relative risk of psychological distress of men with prostate cancer and their partners during the period before and after prostate cancer diagnosis compared with men without prostate cancer and their partners. Methods The participants reported questionnaires on psychological distress at four time points: before prostate cancer biopsy, and at 1, 3 and 6 months following prostate cancer diagnosis. We performed multiple logistic regression analyses to examine the relative risk of psychological distress. Results A total of 115 couples answered the questionnaires at all four time points. Men with prostate cancer showed a significantly higher risk of psychological distress compared to men without prostate cancer at 1 (odds ratio [OR] = 4.8, 95% confidence interval [CI] = 1.9-13.1), 3 (OR = 3.2, 95% CI = 1.1-10.2) and 6 months following prostate cancer diagnosis (OR = 6.9, 95% CI = 2.3-25.7). Their partners showed a significantly higher risk of psychological distress compared to the partners of men without prostate cancer at 1 month following prostate cancer diagnosis (OR = 2.6, 95% CI = 1.1-6.6). Conclusions Men with prostate cancer showed psychological distress during the 6 months following the cancer diagnosis. Their partners also showed psychological distress at 1 month following the cancer diagnosis. Inviting both men with prostate cancer and their partners to speak to their concerns, empathizing with them, finding the solutions together and monitoring of their psychological status regularly should be regarded as important following prostate cancer diagnosis.

Objective: Partners of prostate cancer patients have been reported to suffer from high levels of psychological distress, although there are few reports of the changes in their distress levels observed before and after the diagnosis and the factors influencing them. This study constructed a longitudinal psychosocial database of prostate cancer biopsy subjects and their partners. This paper describes a summary of the database and the nature and severity of the psychological distress and cancer-related worry. Methods: We distributed self-administered questionnaires to subjects scheduled for a prostate cancer biopsy and their partners on four occasions: prior to the biopsy, and 1, 3 and 6 months after being informed whether the diagnosis was cancer or not. The questionnaires included questions pertaining to the psychological distress, cancer-related worry and correlational factors. Results: Of the 240 couples who agreed to participate in the database project, 184 couples completed the fi rst and second surveys; thus, the database consists of them. While no signif icant differences in the levels of psychological distress were found among the participants before the biopsy, the prostate cancer patients and their partners had significantly higher levels of psychological distress as compared with the non-prostate cancer patients at 1 month after being informed whether the diagnosis was cancer or not. Conclusions: This study constructed a longitudinal psychosocial database of prostate cancer biopsy subjects and their partners. Our findings suggest that partners of prostate cancer patients might experience a similar psychological impact to the prostate cancer patients before and after the diagnosis.

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.

PURPOSE The prostate specific antigen (PSA) level usually is lowered in response to initial endocrine therapy even in advanced cases of prostate cancer, but in some cases, it is not. We examined the cases in which the PSA level was not sufficiently lowered by initial endocrine therapy with maximal androgen blockade (MAB) or estrogenic drugs. MATERIALS AND METHODS The subjects were 20 patients with prostate cancer diagnosed between January 1992 and December 2005 whose PSA level was not lowered below 10 ng/ml after initial endocrine therapy with MAB or estrogenic drugs. We investigated the frequency of cases, pretreatment PSA levels, PSA nadir levels after initial endocrine therapy and throughout the therapy, PSA response to second line therapy, and the prognosis. RESULTS The PSA level was not lowered below 10 ng/ml after initial endocrine therapy with MAB or estrogenic drugs in 4.9% of the cases. Cancer-specific survival rates in all cases were extremely poor, 75.0% at 1 year and 14.7% at 3 years. Prognosis tended to be worse in patients with a higher PSA nadir level throughout the therapy and on whom second therapy was not effective, although the difference was not statistically significant. CONCLUSION The patients whose PSA levels were not lowered sufficiently by MAB or estrogenic drugs had an extremely poor prognosis. These results are useful in planning the therapy, and in explaining the status or future prospective of the disease to patients and their families.

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: 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 1997 fourth Banff meeting revised the consensus for describing transplant biopsies. We have conducted a retrospective analysis of biopsies correlated between the Banff 97 classification and clinical outcome. The patients ( n=149), who had a total of 404 biopsy-proven rejections, were assessed and the biopsies taken from these patients were re-examined and classified according to the Banff 97 classification. Morphological changes in the glomeruli (g), interstitium (i), tubules(t), and arterial vessels (v) were scored. Severity of acute rejection was statistically associated with unresponsiveness to anti-rejection treatment ( P0.0001) and predicted an increased risk of graft failure ( P0.05). Each quantitative criterion (g, i, t, and v) was also statistically associated with unresponsiveness to anti-rejection treatment. Mean serum creatinine levels were significantly higher in the groups graded Banff 97 type I-III after 1 and 2 years of follow-up. The Banff 97 classification correlated with reversibility of rejection episodes and long-term graft survival.

症例は, 31歳, 女性. 腎血管筋脂肪腫破裂による, 右腎摘出の既往がある. 2002年2月上旬, 左腎血管筋脂肪腫破裂による出血性ショック状態で当科緊急入院となった. 保存的治療で軽快せず, 左腎摘出術を施行し血液透析 (HD) に導入した. 手術前後で輸血量は約6,000mLに及んだ. 術直後のHD時の抗凝固剤はメシル酸ナファモスタットを使用し, 術後4回目より低分子ヘパリン2,500単位one shotに変更した. しかし, 返血時回路内に残血を認めたため6回目より2,700単位に増量したところ, 残血なくHDを施行できた. 血小板数は7.2万から19.3万の間を変動していた. その後ヘパリン透析に変更したところ, 全身倦怠感, 網膜剥離, 脈絡膜循環障害による視力障害, 血小板減少の増悪, 貧血などが出現した. この時の抗ヘパリン抗体は陰性であったが, 眼底所見, 臨床所見よりheparin-induced thrombocytopenia (HIT) を疑い, 輸血を併用しながら抗凝固剤をアルガトロバン, メシル酸ナファモスタットに変更してHDを施行した. アルガトロバンを使用して早期に治療したことにより, 約2か月で血小板数は15万まで回復し, 血栓症による視力障害も重篤な障害を残すことなく回復した.

Prostate glands contain heavy metals such as zinc and cadmium, and epidemiological studies showed that both metals were associated with prostate cancer development. To understand the heavy metal metabolism in prostate glands, we investigated the regulation of metallothionein (MT), metal-responsive promoter element-binding transcription factor (MTF) and zinc transporter (ZnT) in human prostate cells and tissues. Growth of human prostate cancer cells, LNCaP and PC-3 cells, was suppressed by zinc or cadmium treatment in a dose-dependent manner. LNCaP cells expressed MT-1A, 1X and 2A mRNA, and PC-3 cells expressed MT-1X and 2A mRNA. Zinc or cadmium treatment up-regulated MTs, MTF-1 and ZnT-1 gene expression levels in both cell lines. In PC-3 cells, ZnT-1 protein was detected, and was up-regulated by the metal treatment. Human prostate cancer tissues expressed significantly lower levels of ZnT-1 gene in comparison with hyperplastic tissues. We demonstrated the ZnT-1 expression in human prostate for the first time. The present study showed that heavy metal-metabolizing proteins were involved in human prostate homeostasis, and that the metal metabolizing system might be different in malignant tissues.

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.

群馬大学医学部附属病院において1995年1月1日から2000年12月31日までの6年間にシャントと腹膜透析カテーテル関連手術以外の手術療法を受けた慢性維持透析患者延べ213名について, 手術内容, 基礎疾患などを検討し, 特に1999年と2000年の全身麻酔下手術症例に関しては手術前検査値, 手術後合併症なども検討した.各年ともに眼科系手術が約50%を占めていたが, 各科にわたりmajor surgeryが積極的に施行され, 心, 血管系手術は毎年施行されていた. 眼科系手術症例は糖尿病を基礎疾患として透析導入後比較的早い時期に手術が施行されていた.1999年 (16例) と2000年 (14例) の全身麻酔下手術症例の検討では, 2000年症例の方が手術時平均年齢の高齢化傾向や平均維持透析期間の長期化傾向を認めた. また, Hct, Hb, TP, BUN, 血清クレアチニン値などの手術前検査値が改善していた. 手術後合併症は感染症 (手術創移開, 肺炎) が最も多く, 次に出血 (消化管出血や脳出血) が続いた. 手術後合併症出現症例の基礎疾患は糖尿病と悪性腫瘍が多くを占めた.維持透析患者の周術期管理方法の改善により維持透析患者の手術適応は拡大し積極的に手術が施行されている. しかし, 基礎疾患に糖尿病と悪性腫瘍を持つ維持透析患者に関しては, 手術後合併症予防管理方法にまだ課題が残っている.

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.

群馬大学医学部附属病院における1999年の外来初診患者の臨床統計を報告した.総数729名であり, 男性529名, 女性200名で男女比は2.65:1であった.紹介患者は61.5%(448名)で院外の紹介が48.0%(350名)を占めていた.悪性新生物は96例で, 前立腺癌38例, 腎癌18例, 膀胱腫瘍17例, 精巣腫瘍10例であった.良性新生物では前立腺肥大症が205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59例, 血液透析51例, 膀胱炎46例と続いた.市中病院の報告に比し, 悪性腫瘍, 男性不妊, 透析関係は多く, 包茎, 外傷, STDは少ない傾向だった.

Some reports have indicated that bladder cancer is induced by radiation therapy for cervical cancer. We encountered 6 cases of urothelial cancer (5 cases of bladder cancer and 1 case of ureter cancer) following radiation therapy for cervical cancer. Age at the time of diagnosis of cervical cancer ranged from 38 to 66 years, and the average was 51.2 ± 11.0 (S.D.) years old. Age at the time of diagnosis of urothelial cancer ranged from 53 to 83 years, and the average was 67.5 ± 10.3 years old. The interval between the diagnosis of cervical cancer and urothelial cancer ranged from 3 to 25 years, averaging 16.3 years. It is impossible to evaluate the risk of development of urothelial cancer after radiation therapy based on our data. However, it is important to make an effort to diagnose urothelial cancer at an early stage by educating patients (e.g., advising regular urine tests) after the follow-up period to cervical cancer.

This case report describes a first case of granulomatous pneumonia occurring at the same site of the previous lung metastasectomy in a patient with high-grade non-muscle-invasive bladder cancer (NMIBC), which was treated with bladder preservation therapy despite multiple recurrences and failure of intravesical bacillus Calmette-Guẻrin (BCG) therapy. We report a 52-year-old woman who underwent transurethral surgery and BCG therapy for pT1, G3 bladder cancer. Although cystectomy was recommended after BCG failure, the operation was not performed because of the patient’s wish for bladder preservation. Eighteen months after the first surgery, computed tomography (CT) revealed solitary lung mass. Partial lobectomy which the patient underwent after chemotherapy revealed G3 metastatic urothelial carcinoma. Three years after lung metastasectomy, CT revealed lung mass at the same site of the previous lung metastasectomy. Dynamic contrast-enhanced magnetic resonance imaging showed the significantly enhanced lung mass, which indicated lung metastasis. However, lobectomy of the remnant lobe revealed that the lung mass was granulomatous pneumonia. Although no additional specific treatment was carried out, the patient remains free of disease for 53 months after surgery. Lung metastasis from NMIBC rarely occurs. Our case report confirms that lung metastasectomy in highly selected patients may contribute to long-term disease control. Moreover, our case report suggests that mycobacterial lung infections along the staple-suture line rarely occur, and percutaneous biopsy should be considered under these circumstances to avoid the unnecessary operation.

今回我々は1972年から1995年までの24年間に精巣腫瘍を第1癌とする重複癌を3例経験した.3例の第2癌はそれぞれ腎癌, 肝癌, 膀胱癌であった.精巣腫瘍の患者では2次癌発生の危険性が約2倍になるとの報告もあり, 第1癌に対する治療がその要因のひとつとされている.今回我々が報告した3例中2例は, 術後予防的に放射線治療を行っているが, 2次癌発生を誘発した可能性は低いと思われた.

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.

Angiogenesis plays a crucial role in normal development and carcinogenesis of prostate glands. Placental growth factor (PlGF) belongs to the same family as the vascular endothelial growth factor. The presence of PlGF in human prostate has not been studied. In the current study, we investigated the gene expression profiles of PlGF in human prostate.Gene expression of PlGF-1 and PlGF-2 was assessed by RT-PCR and direct sequencing. Gene expression levels were quantified by real-time PCR, and we compared the transcript levels among benign prostate hyperplasia (BPH), prostate caner (CAP) and CAP after androgen deprivation therapy (CAP-Tx).Human prostate cancer cells, LNCaP, PC-3 and DU-145, expressed both PlGF-1 and -2 mRNAs. Human prostate tissues, BPH, CAP and CAP-Tx, also expressed both types of PlGF mRNA. BPH and CAP-Tx expressed similar levels of PlGF, however, CAP expressed significantly lower levels of PlGF than BPH or CAP-Tx (p0.01).PlGF mRNA was expressed in human prostate. Significantly lower levels of PlGF in CAP in comparison with those in BPH or CAP-Tx suggested that PlGF might have effects on vasculogenesis and angiogenesis in prostate disease.

We assessed the usefulness of combined multi-voxel magnetic resonance spectroscopy (MRS) and MR imaging (MRI) in the diagnosis of prostate cancer localization.MRS and MRI were performed in 21 patients with prostate cancer. On T2-weighted images, tumor localization was based on low signal intensity in the peripheral zone. At MRS, cancer patterns were diagnosed when the ratio of choline plus creatine to citrate was greater than 0.86. The results were analyzed with reference to pathological confirmation of prostate cancer at bilateral or unilateral lobe.Six out of 11 patients with unilateral positive biopsy specimens were diagnosed as unilateral cancer, and 9 of 10 patients with bilateral positive biopsy specimens were diagnosed as bilateral cancer on MRI. Two of 4 patients with unilateral cancer, who were not detected on MRI alone, were diagnosed as unilateral cancer on combined MRI and MRS. The accuracy of MRI alone was 71.4%, while that of combined MRI and MRS was 81.0%.Combined MRI and MRS improved the diagnostic accuracy for localization of prostate cancer.

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.

Magnetic resonance spectroscopy (MRS) is a new diagnostic tool which allows the detection of cellular metabolites. We assessed the usefulness of single- voxel MRS diagnosis for localization of prostate cancer.The study population consisted of 10 patients with prostate cancer. We set I or 2 voxels at the peripheral zone (PZ) of the prostate where biopsy had confirmed adenocarcinoma. MRS provided metabolic information about citrate, creatine and choline levels. We calculated the ratio of these metabolites ([choline + creatine]/citrate) and judged areas where the metabolic ratio was greater than 0.86 as positive.Thirteen out of 19 voxels showed a cancer pattern which indicated a high choline peak and low citrate peak The accuracy, sensitivity and specificity of MRS diagnosis of tumor localization were 84.2%, 81.3% and 100%, respectively.MRS is useful for the diagnosis of prostate cancer localization.

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.

Backgound: A case of testicular typical seminoma associated with bilateral undescended testes in Down’s syndrome is reported. A 42-year-old institutionalized male patient developed left testicular seminoma with retroperitoneal metastasis. Methods/Results: Neither adjuvant chemotherapy nor radiotherapy were performed due to his severe mental retardation. He died as a result of the cancer 2 years after a left radical orchiectomy and an autopsy was carried out. Discussion: Recently an increase in the incidence of the association of testicular tumors and Down’s syndrome has been repeatedly documented. Thirty-six cases of testicular tumors associated with Down’s syndrome have been reported and of these 17.1% had cryptorchidism. This is a much lower percentage considering the high risk of cryptorchidism in males with Down’s syndrome. The relationship between testicular germ cell tumors associated with cryptorchidism and Down’s syndrome is discussed.