Masaru Hasumi

Genistein, a soy isoflavone, induces glutathione peroxidase in the human prostate cancer cell lines LNCaP and PC-3.

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.

Regulation of metallothionein and zinc transporter expression in human prostate cancer cells and tissues.

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.

NK cell-mediated anti-tumor immune response to human prostate cancer cell, PC-3: immunogene therapy using a highly secretable form of interleukin-15 gene transfer

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.

Vitamin D receptor gene polymorphism in familial prostate cancer in a Japanese population

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.

Association of the genetic polymorphism in cytochrome P450 (CYP) 1A1 with risk of familial prostate cancer in a Japanese population: a case-control study

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.

Seminoma associated with bilateral cryptorchidism in Down's syndrome:A case report

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.

Psychological distress in men with prostate cancer and their partners before and after cancer diagnosis: a longitudinal study

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.

Examination of Cadaveric Renal Transplantation at Gunma University Hospital during 20-year Period

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.

Clinical study on poor PSA response to initial endocrine therapy with MAB or estrogenic drugs for treatment of prostate cancer

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.

HER‐2 gene polymorphism at codon 655 in familial prostate cancer in a Japanese population

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.