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ABSTRACT: Memory T cells are well known to have a critical role for host defense in humans. However, their role in actual human cancer remains largely unknown. In this study, we tried to reveal the clinical importance of tumour-infiltrating CD45RO+ memory T cells in renal cell carcinoma (RCC).
We analysed 105 patients with RCC, who received radical or partial nephrectomy. Those were 65 in TNM stage I, 7 in stage II, 15 in stage III, and 18 in stage IV, respectively. CD45RO expression was evaluated by immunohistochemistry. CD4 and CD8 expressions were also systematically assessed in the same manner.
Patients with higher TNM stage or high nuclear grade were found to have higher densities of CD45RO. Furthermore, CD45RO status was positively correlated with preoperative C-reactive protein level. In prognostic analysis, CD45RO+lo patients had a significantly better prognosis than CD45RO+hi patients. There was also a significant difference between CD4+lo and CD4+hi groups, whereas no significant difference was observed in CD8 T-cell status. Finally, multivariate analysis revealed that CD45RO+ status was the independent prognostic factor for patient overall survival.
CD45RO+ memory T-cell status has a significant independent prognostic value, indicating that the adaptive immune response is functionally critical in human RCC.
British Journal of Cancer 09/2011; 105(8):1191-6. · 5.04 Impact Factor
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ABSTRACT: The aim of this study was to evaluate the effect of supplementing healthy men with soy isoflavones on the serum levels of sex hormones implicated in prostate cancer development. A total of 28 Japanese healthy volunteers (18 equol producers and 10 equol non-producers) between 30 and 59 years of age were given soy isoflavones (60 mg daily) supplements for 3 months, and the changes in their sex hormone levels were investigated at the baseline and after administration. The serum and urine concentrations of daidzein, genistein, and the levels of equol in the fasting blood samples and 24-h stored urine samples were also measured. All 28 volunteers completed the 3-month supplementation with isoflavone. No changes in the serum levels of estradiol and total testosterone were detected after 3-month supplementation. The serum levels of sex hormone-binding globulin significantly increased, and the serum levels of free testosterone and dihydrotestosterone (DHT) decreased significantly after 3-month supplementation. Among the 10 equol non-producers, equol became detectable in the serum of two healthy volunteers after 3-month supplementation. This study revealed that short-term administration of soy isoflavones stimulated the production of serum equol and decreased the serum DHT level in Japanese healthy volunteers. These results suggest the possibility of converting equol non-producers to producers by prolonged and consistent soy isoflavones consumption.
Prostate cancer and prostatic diseases 08/2009; 12(3):247-52. · 2.10 Impact Factor
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ABSTRACT: Racial differences in the incidence of prostate cancer are manifest worldwide, possibly due to the different dietary habits. To elucidate the relationship between the recent trend of phytoestrogenic isoflavone intake and the increased incidence of prostate cancer in Japan, we conducted an age-stratified dietary survey of soybean foods in 102 Japanese healthy men (age range: 10-59 years) and measured the serum isoflavones and equol levels in them and 100 Korean healthy men. The intergroup comparison among the age-stratified groups showed significant differences in the daily intake of genistein and daidzein between the teenager group and the other groups of age >or=30 years (P<0.05). In the Japanese study, the proportion of equol producers in the teenager group was 10%, being significantly the lowest among the age-stratified groups. The proportions of equol producers in the age-stratified groups from 10 to 49 years were also significantly lower than those in the fifties. The equol non-producers consumed significantly less amounts of isoflavones than the equol producers. In the Korean study, the proportions of equol producers were 45% in the teenager and 40% in the twenties and thirties, being significantly lower than in the forties (80%) and fifties (65%). The decreased intake of isoflavones, low serum level of equol and low incidence of equol production in the young generation may become potential risk factors for prostate cancer not only in Japan but also in Korea in the near future. Elucidating the mechanism of equol production may be promising in developing strategies for chemoprevention against prostate cancer.
Prostate cancer and prostatic diseases 01/2008; 11(3):252-7. · 2.10 Impact Factor
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ABSTRACT: Hormonal responses were assessed in men with prostate cancer (T2-4, Nx, Mx) who were randomized to receive either a single injection of goserelin 3.6 mg or leuprolide 3.75 mg. Testosterone increased over the first week, with a significantly higher mean rate of change of total testosterone (day 3) and free testosterone (days 3 and 7) with leuprolide. Following the initial rise in luteinizing hormone (LH), the rate of decrease in LH levels was significantly greater with goserelin by day 28. There are significant differences in endocrine response to goserelin and leuprolide in the 4 weeks following administration.
Read More: http://informahealthcare.com/doi/abs/10.1080/01485010701601222
Systems Biology in Reproductive Medicine 05/2007; 53(5):289-293. · 1.52 Impact Factor
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ABSTRACT: The object of the study was to examine the usefulness of volume-adjusted prostate-specific antigen (PSA) parameters for prediction of prostate cancer in the patients with intermediate PSA levels. The subjects were 235 patients with intermediate PSA levels (range: 4.1-10.0 ng/ml) whose prostate volume (PV) and prostate transition zone volume (TZV) were evaluated between August 1996 and April 2004. PSA, PV, TZV, PSA density (PSAD) (PSA/PV) and PSA transition zone density (PSATZD) (PSA/TZV) were assessed with the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Simple and multivariate logistic regression analyses were used to analyze the odds ratios of age, PSA, PSAD, PSATZD, PV, TZV, digital rectal examination (DRE) and transrectal ultrasonography (TRUS) findings. Fifty-five patients (23.4%) of 235 patients had biopsy-proven prostate cancer. The univariate analysis revealed significant differences in the mean values of age, PSAD, PSATZD, PV, TZV and DRE between the patients with cancer and the non-cancer patients. The ROC curve analysis revealed that PV, TZV, PSAD and PSATZD had significant predictive values as compared with that of PSA. However, there was no difference in AUC between them. The stepwise logistic regression analysis showed that the age, PV, PSATZD and DRE had significant predictive values, and that PSATZD had the most predictive power. In conclusion, both PSAD and PSATZD had significant predictive values in discriminating prostate cancer. Furthermore, the stepwise logistic regression analysis showed that PSATZD had the strongest predictive value.
Prostate Cancer and Prostatic Diseases 02/2007; 10(3):274-8. · 2.42 Impact Factor
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ABSTRACT: Advanced glycation end products (AGEs) accumulate in lesions of arteriosclerosis, Alzheimer's disease, rheumatoid arthritis, diabetic retinopathy, and diabetic nephropathy. Among AGEs, chemical quantification and immunohistologic methods for pentosidine have been established. Free pentosidine-eliminated by renal excretion- is mainly affected by renal function. In this study, we measured concentrations of plasma free and total pentosidine and immunohistologically investigated kidney graft biopsy specimens in patients after renal transplantation to investigate the renal function, plasma free and total pentosidine, and its relationship with deposition in the renal tissue.
In 28 patients who underwent renal transplantation from 1996 to 2003, we measured the time course of plasma concentrations of free pentosidine, total pentosidine, and serum creatinine starting right after renal transplantation. Thirty-four graft biopsy specimens were immunohistologically investigated using anti-pentosidine antibody. Plasma free and total pentosidine, and serum creatinine were measured at the same time.
Plasma free and total pentosidine were positively correlated with serum creatinine. Plasma free pentosidine and serum creatinine reached nadir values on day 34.2 +/- 14.2, when the blood concentrations were 5.1 +/- 1.6 pmol/mL and 1.7 +/- 0.7 mg/dL, respectively. Plasma total pentosidine reached a nadir on day 116.5 +/- 39.7 when the plasma concentration was 4.0 +/- 1.5 pmol/mg. We correlated the time required to reach the nadir of plasma free and total pentosidine concentrations. However, neither the concentration of plasma free nor plasma total pentosidine at nadir correlated with serum creatinine. The intensity of immunostaining with anti-pentosidine antibody in proximal tubular cells was graded as weakly positive, positive, or strongly positive. Significant differences were obtained among plasma free pentosidine values between the weakly positive and strongly positive groups.
Renal transplantation improves renal function and decreases renal excretion of free pentosidine. Accordingly, total pentosidine also decreases. However, the concentrations of plasma free and total pentosidine at nadir varied among individuals; the blood concentrations were not determined by renal function alone. It was suggested that deposition of pentosidine in proximal tubular cells was more severe among patients with higher plasma free pentosidine and serum creatinine values.
Transplantation Proceedings 01/2006; 37(10):4266-72. · 1.00 Impact Factor
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ABSTRACT: A new modality is necessary to prevent recurrence of superficial bladder cancer after complete transurethral resection (TUR) because of the high recurrence rate even with current prophylaxis protocols. Prostaglandins (PGs) are known to be produced more in transitional cell carcinoma, and etiologically bladder cancer risk is negatively associated with the intake of non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit cyclooxygenase (COX), the rate-limiting enzyme of the PG production. We have shown the chemopreventive effect of piroxicam, an NSAID, on the N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced rat bladder cancer model. To avoid gastrointestinal side effects of regular NSAIDs, we also showed the chemopreventive effect of nimesulide, a selective inhibitor of the second isoform of COX, COX-2, which does not affect COX-l house-keeping activity in gastrointestinal mucosa on the same model. We also observed induction of COX-2 protein in the rat bladder tumor. In this study, we screened COX-2 protein expression in primary superficial bladder cancer tissues, to elucidate if COX-2 selective inhibitors can be a candidate chemopreventive agent for bladder cancer recurrence. Five and 6 samples of superficial bladder cancer cases with and without recurrence after complete TUR were examined by immunohistochemical analysis. We found more COX-2 protein positive samples in the cases with recurrence than in cases without recurrence. Even though the number of cases examined is small, this result supports our hypothesis that COX-2 contributes to superficial bladder cancer recurrence, thus, selective COX-2 inhibitors can be a candidate chemopreventive agent for the recurrence.
Aktuelle Urologie 08/2003; 34(4):256-8. · 0.27 Impact Factor
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ABSTRACT: Our previous study demonstrated the clear detection of MN/CA9 mRNA in peripheral blood samples from RCC patients. However, approximately 30 % of control blood samples from healthy volunteers showed MN/CA9 expression. We have developed a new primer set and optimized the PCR conditions, now resulting in a specificity of 100 %. In tissue samples, all clear cell type carcinomas but none of the spindle cell type and pleomorphic cell type tumors expressed the MN/CA9 message. Analysis of MN/CA9 messages in peripheral blood samples from RCC patients gave positive results for 0/2, 1/9, 0/4 and 4/12 of stage I, II, III and IV cases, respectively. RT-PCR analysis using preoperative renal venous blood samples resulted in clear detection of MN/CA9 positive cells in 2/4, 3/13, 2/6 and 1/1 of stage I, II, III and IV cases, respectively. Our results suggest that assessment of MN/CA9 expression by RT-PCR is a promising method for detecting cancer cells in the circulation of patients with RCC.
Aktuelle Urologie 08/2003; 34(4):270-2. · 0.27 Impact Factor
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ABSTRACT: To evaluate the effect of primary hormonal therapy for patients with localized and locally advanced prostate cancer.
Patients with stage T1b-T3 prostate cancer who were not scheduled for radical prostatectomy were allocated into two groups: group 1 (73 men) received luteinizing hormone-releasing hormone (LHRH) agonist monotherapy and group 2 (78 men) received LHRH agonist and chlormadinone acetate. Patients were followed using serum prostate specific antigen levels, prostate size and the detection of distant metastasis for 5 years.
The median (range) follow-up was 78 (63-87) months. The 5-year progression-free survival rate was significantly higher in group 2 (68%) than in group 1 (47%). However, the overall and cause-specific survival rate at 5 years were similar in both groups, at 72% and 93% in group 1, and 64% and 89% in group 2, respectively.
The overall survival rates of the both groups were no different from that of the normal Japanese population of the same age group. Although this study did not include an untreated group, i.e. watchful waiting, these results might indicate the usefulness of primary hormonal therapy in controlling localized and locally advanced prostate cancer. The 5-year observation period is still short and the study is continuing to determine the 10-year survival.
BJU International 02/2003; 91(1):33-6. · 2.84 Impact Factor
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ABSTRACT: The caffeine test measures the activity of cytochrome p450 (CYP1A2) which is a major enzyme involved in the activation of flutamide. The usefulness of this test in predicting flutamide-induced hepatic injury in patients with prostate cancer was examined. The subjects were: (1). five patients whose aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level rose to 100 IU/l or higher following the start of flutamide (moderately injured group); (2). four patients whose AST and ALT levels were higher than normal but less than 100 IU/l (mildly injured group); and (3). two patients whose hepatic function remained normal (normal group). The subjects were each given canned coffee to drink. Urinary caffeine (137X), paraxanthine (17X) and 1, 7-dimethyluric acid (17U) levels were measured 4-5 h later. The metabolite ratio, (17U+17X)/137X, was calculated to serve as an indicator of CYP1A2 activity. The metabolite ratio for the moderately injured group (3.98+/-1.56) and the mildly injured group (5.55+/-1.42) were lower than that for the normal group (9.56). The results suggest that a decrease in CYP1A2 activity is involved in the onset of flutamide-induced hepatic injury, and that the caffeine test seems to provide a useful means of its prediction.
Prostate Cancer and Prostatic Diseases 02/2002; 5(2):128-31. · 2.42 Impact Factor
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ABSTRACT: The INK4a / ARF locus on chromosome 9p21, which encodes two distinct genes, p14(ARF) and p16(INK4a), is frequently altered in human neoplasms. To investigate the potential roles of p14(ARF) and p16(INK4a) genes in human renal cell carcinomas (RCCs), we analyzed 6 human RCC cell lines and 91 primary RCCs for homozygous deletion, promoter hypermethylation and expression of the p14(ARF) and p16(INK4a) gene products using differential PCR, methylation-specific PCR, and immunohistochemistry, respectively. Five cell lines showed homozygous co-deletion of both genes and one demonstrated promoter hypermethylation of the p16(INK4a) gene only. Eight of 91 RCCs showed aberrations of p14(ARF) or p16(INK4a) status and six of these featured gross extension into the renal vein. The results suggest that p14(ARF) and p16(INK4a) aberrations may play roles in the relatively late stage of renal tumorigenesis associated with tumor progression.
Japanese journal of cancer research: Gann 01/2002; 92(12):1293-9.
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ABSTRACT: We have reported the favorable therapeutic results of non-ischemic complete enucleation using a microwave tissue coagulator as a method of nephron-sparing surgery for small renal cell carcinoma (RCC). We experienced two elective cases that underwent translumbar nephrectomy subsequent to the tumor enucleation. The first case showed another RCC in a cyst, concomitant with the enucleated RCC. The second case was a pT3a spindle cell carcinoma with high-grade malignancy. We decided to nephrectomize these enucleated kidney after obtaining well-informed consent. Here we report these controversial cases and discuss about the indication and outcomes of complete tumor enucleation for small RCC.
Nippon Hinyōkika Gakkai zasshi. The japanese journal of urology 12/2001; 92(7):710-3.
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ABSTRACT: The present study was conducted to examine the natural history of superficial bladder cancer.
One hundred and forty-four patients with superficial bladder cancer who had been treated with transurethral resection of bladder tumor (TURBt) alone were analyzed.
The non-recurrence rate was 64.8% at 36 months and 61.2% at 60 months after TURBt. When the non-recurrence rate after TURBt was analyzed by background variables, the rate differed significantly between the solitary tumor group and the multiple tumor group. The tumor recurrence hazard curves for the entire population had one high peak before 500 days and another slight peak around 1500 days after TURBt.
These results will provide basic information useful when evaluating new regimens of intravesical instillation therapy for prophylaxis of superficial bladder cancer after our complete TURBt in the Nara Uro-Oncology Research Group.
Japanese Journal of Clinical Oncology 12/2001; 31(11):536-40. · 1.78 Impact Factor
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ABSTRACT: MN/CA IX is a carbonic anhydrase (CA) isoenzyme expressed in normal alimentary tract in a tissue-specific manner. This antigen is activated in the majority of renal cell carcinomas (RCC) but not in normal kidney tissues. Although the exact role of CA activity in carcinogenesis and metastasis has not been established, MN/CA9 has been suggested to be implicated in acidification of extracellular milieu surrounding the cancer cells and thus create a microenvironment conductive to tumor growth and spread. Mutations in the von Hippel-Lindau (VHL) gene cause the familial syndrome and are also found in the majority of sporadic RCC. Wild-type VHL was recently described to down-regulate MN/CA9 in RCC cell lines, and the molecular mechanism of MN/CA9 and VHL in renal carcinogenesis is of interest. To investigate the mechanism of MN/CA9 activation in RCC, we examined the methylation status of this gene in RCC cell lines and human tissue samples and found that hypomethylation in the promoter region may play an important role in the expression of MN/CA9. RT-PCR analysis of blood samples from RCC patients revealed the presence of circulating MN-positive cells in the blood. This antigen may be a potential therapeutic target as well as diagnostic marker for RCC. Therefore, we are currently investigating whether or not MN/CA IX peptide could be an appropriate molecule for use antigen specific immunotherapy on RCC patients.
Hinyokika kiyo. Acta urologica Japonica 12/2001; 47(11):809-14.
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ABSTRACT: The present study was conducted to compare the incidences of renal tumors in Wistar (W), Fischer (F) and F1 rats (WF: female Wistar rats x male Fischer rats; FW: female Fischer rats x male Wistar rats) induced by N-ethyl-N-hydroxyethylnitrosamine (EHEN). Levels of 8-OHdG in renal DNA were also investigated in Wistar and Fischer rats. After 2000 ppm of EHEN was administered orally for 2 weeks, the animals were fed basal diet until week 32. Wistar males and females demonstrated significantly higher sensitivity regarding induction of renal lesions, while both WF and FW rats had similar incidences, generally intermediate between those for the two parent strains. The formation of 8-OHdG was maximal 60-180 min after an intraperitoneal dose of 750 mg/kg to Wistar and Fischer rats, which correlates with the increase tending to the incidence of renal tumors in male and female Wistar and Fischer rats. The results suggest that EHEN induction of renal tumors is related to oxygen radical damage and that the genes in the Wistar strain responsible for the sensitivity are not inherited in a sex-dependent fashion, despite the male being more susceptible.
Cancer Letters 10/2001; 170(2):125-30. · 4.24 Impact Factor
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ABSTRACT: A 73-year-old man with the complaint of dysuria of 2 years' standing was admitted to our hospital for further examination of an intrapelvic cystic mass, 8.6 cm in diameter, detected incidentally by abdominal ultrasonography. The serum concentration of prostate specific antigen (PSA) was elevated to 44.9 ng/ml. Pelvic computed tomography (CT) and magnetic resonance imaging (MRI) revealed a cystic mass with an irregular thick cyst wall posterior to the urinary bladder originating from the prostate. Transrectal needle biopsy presented a moderately differentiated adenocarcinoma of the prostate. The bloody fluid of the cyst obtained by transperineal aspiration contained a significantly increased level of PSA, but no cancer cells were detected by cytological examination. Total prostatectomy was performed under the diagnosis of clinical stage C (cT3N0M0) prostate cancer. Pathological diagnosis was that cancer cells were present in the prostate tissue and had partly infiltrated the cyst wall. These results suggest that the present cyst was associated with the development of prostate cancer as a pseudocyst without an epithelial lining. The patient has remained free from the disease for over ten months. We review 56 cases of this rare condition that have been reported in Japan.
Hinyokika kiyo. Acta urologica Japonica 10/2001; 47(9):653-6.
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ABSTRACT: MN/CA9 is a cancer-related gene, frequently activated in human renal cell carcinomas (RCCs). To reveal the activation mechanism, we investigated the relationship between methylation status of the MN/CA9 promoter region and gene expression using 13 human RCCs, and examined the effect of in vitro CpG methylation on the MN/CA9 promoter activity using a human RCC cell line (SK-RC-44), expressing MN/CA9. MN/CA9 expression was evaluated by RT-PCR and observed in 10 of 13 RCCs (77%). A total of 9 out of 10 MN/CA9 -positive RCCs (90%) contained clear cell components. Methylation status of 6 CpGs in the MN/CA9 promoter region was decided by using the bisulfite genomic sequencing protocol. Out of 13 RCCs 9 (69%) showed partial hypomethylation of the CpG at -74 bp, while the other 4 RCCs and 3 normal kidney tissue samples showed complete methylation. Hypomethylation of the CpG at -74 bp was strongly correlated with MN/CA9 expression. Luciferase assay revealed that the MN/CA9 promoter activity was strongly suppressed by methylation of the CpG at -74 bp. These findings suggest that hypomethylation of the CpG at -74 bp in the MN/CA9 promoter region might play an important role in this gene activation of human RCC.
British Journal of Cancer 09/2001; 85(4):563-7. · 5.04 Impact Factor
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ABSTRACT: Renal cell carcinoma (RCC) producing alpha-fetoprotein (AFP) is a rare condition with only 11 cases reported in Japan to our knowledge. A 69-year-old man was admitted to our hospital for further examination of an incidental right renal tumor. Laboratory tests showed markedly increased serum level of AFP whereas both HBs antigen and anti-HCV antibody were negative. Computed tomography and magnetic resonance imaging imagings showed a right renal tumor but no tumor in liver, testis or lymph node. We performed right radical nephrectomy. Serum level of AFP declined within the normal range 7 weeks after nephrectomy according to its half-life curve. The tumor specimen was composed mainly of granular cells. Immunohistochemical examination of the tumor cells proved the presence of AFP in the cytoplasm. The possibility of AFP as a tumor marker of renal cell carcinoma in this case was presented.
Hinyokika kiyo. Acta urologica Japonica 08/2001; 47(7):477-80.
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ABSTRACT: A 16-year-old boy with a painful tumor in the left scrotum was referred to our department. CT scans showed a low density area in the left testis, so we diagnosed a left testicular tumor and performed left inguinal orchiectomy. Histological examination revealed polyarteritis nodosa (PN) of the testis and epididymis. Systemic examination revealed no other evidence of PN. Although induration developed in the right epididymis after the operation, it resolved with steroid therapy. The patient is currently asymptomatic and is being followed at our clinic. The pathogenesis and management of this rare condition are discussed.
Hinyokika kiyo. Acta urologica Japonica 04/2001; 47(3):211-3.
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ABSTRACT: Background. It is well known that chronic renal failure shows an abnormal amino acid profile characterized by a decrease in branched
chain amino acid (BCAA).
Methods. To investigate the change in BCAA with uremia and the effect of recombinant human erythropoietin (rHuEPO) on BCAA level,
we measured the plasma and muscle levels of BCAA in adenine-induced renal anemia in Wistar rats.
Results. A significant correlation was found between plasma and muscle tissue levels of BCAA. Further, not only the plasma level but
the muscle level of each BCAA showed an inverse correlation with the serum creatinine value. Both plasma and muscle BCAA levels
showed, in addition, significant recovery after rHuEPO treatment.
Conclusions. Taking these results into account, we conclude that the decrease in BCAA is a clinicopathological feature essentially associated
with uremia (i.e., it is not an epiphenomenon), and that BCAA levels could be recovered by rHuEPO treatment. However, the
pathological mechanism by which BCAA level is decreased in the uremic state and is recovered after rHuEPO treatment remains
to be elucidated.
Clinical and Experimental Nephrology 03/2001; 5(1):28-32. · 1.37 Impact Factor
