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To examine the expression of the KAI1 metastasis suppressor gene and to evaluate its relationship with tumor recurrence in primary pTa and pT1 urothelial bladder carcinoma. Samples were obtained from 87 patients after transurethral resection (TUR). Tumor stage and grade were reviewed in 33 patients with pTa and in 54 patients with pT1, with a mean follow-up time of 47.4 ± 30.1 months. The KAI1 protein immunohistochemical assay was performed. Prognosis was analyzed using the Kaplan–Meier method and Cox's proportional hazards model. Correlation between KAI1 expression and recurrence according to each clinicopathological factor was comparatively evaluated using the chi-squared test. Decreased expression of KAI1 protein failed to reach statistical significance for stage ( P = 0.25) or morphology of tumor stem ( P = 0.19), but it was significantly related to tumor size ( P = 0.016). The recurrence-free 5-year survival rates of the group with decreased KAI1 expression was 69.7%, which was significantly higher than the 22.2% for the KAI1-positive group ( P < 0.0001). In univariate and multivariate analyses, decreased expression of KAI1 protein, stage pT1, tumor size >3 cm and sessile tumors were independent prognosis factors of recurrence. Despite the lower recurrence rate expected by considering only the clinicopathological factors, decreased KAI1 expression was able to identify the group with a high risk of recurrence. Downregulated KAI1 expression in bladder tumors tends to relate to stage and morphology of the tumor stem and was significantly correlated to tumor size. Decreased expression of KAI1 was associated with the degree of invasiveness and progression of the cancer and was an independent prognostic factor of recurrence in primary pTa and pT1 urothelial bladder carcinoma. [ABSTRACT FROM AUTHOR]

Procarbazine [N-isopropyl-α-(2-methylhydrazino)-p-toluamide], a hydrazine derivative, which has been shown to have effective antineoplastic activity, induces cancer in some experimental animals and humans. To clarify a new mechanism for its carcinogenic effect, we examined DNA damage induced by procarbazine in the presence of metal ion, using 32P-5′-end-labeled DNA fragments obtained from the human p53 tumor suppressor gene and the c-Ha-ras-1 protooncogene. Procarbazine plus Cu(II) induced piperidine-labile and formamidopyrimidine-DNA glycosylase-sensitive lesions at the 5′-ACG-3′ sequence, complementary to a hotspot of the p53 gene, and the 5′-TG-3′ sequence. Catalase partially inhibited DNA damage, suggesting that not only H2O2 but also other reactive species are involved. Procarbazine plus Cu(II) significantly increased the formation of 8-oxo-7,8-dihydro-2′-deoxyguanosine, which was completely inhibited by calatase. Electron spin resonance spin-trapping experiments revealed that methyl radicals were generated from procarbazine and Cu(II). On the basis of these findings, it is considered that procarbazine causes DNA damage through non-enzymatic formation of the Cu(I)–hydroperoxo complex and methyl radicals. In conclusion, in addition to alkylation, oxidative DNA damage may play important roles in not only antitumor effects but also mutagenesis and carcinogenesis induced by procarbazine. [Copyright &y& Elsevier]

One of the main objectives of cancer immunotherapy is the activation and increase in number of antitumor effector cells. Recently, genetically modified tumor cell vaccines have been proposed for elicitation of antitumor effector cells. Native α antigen (α Ag) (also known as MPT59 and antigen 85B) of mycobacteria, which cross-reacts among mycobacteria species, may play an important biological role in host-pathogen interaction because it elicits various helper T-cell type 1 immune responses. To assess the induction of antitumor immune responses by α Ag, mouse tumor cell lines transfected with cDNA of α Ag from Mycobacterium kansasii were established, and the possibility of producing a tumor cell vaccine for induction of antitumor effects was explored. Transfection of tumor cell lines with an α Ag gene lead to primary tumor rejection and the establishment of protective immunity to nontransfected original tumor cell lines in Mycobacterium bovis bacillus Calmette-Guérin (BCG)-primed and unprimed mice. Mice immunized with tumor cell lines transfected with the α Ag gene showed delayed-type hypersensitivity responses in vivo and proliferative responses together with induction of interferon-γ of spleen cells against nontransfected wild-type tumor cell lines in in vitro experiments. Moreover, immunization of mice with α Ag-expressing tumor cells elicited tumor-specific and cytotoxic T lymphocyte (CTL) epitope peptide-specific CD8[sup +] CTLs. The results of this study provided evidence of the potential usefulness of α Ag in tumor cell vaccines. [ABSTRACT FROM AUTHOR]

Abstract Background: The present study was conducted to investigate the incidence of renal cell carcinoma by sex, age group and different regions in Japan. Methods: The survey was conducted from the beginning of January 1997 to the end of December 1997. A total of 1306 Institutions in all 47 prefectures throughout Japan were requested to register cases. Results: There were 6358 persons with renal cell carcinoma, consisting of 4372 men and 1986 women. The age-specific incidence rates showed a peak in the age group of 65–70 years in both men and women. The crude incidence rates per 100 000 population for men and women were 7.1 and 3.1, respectively, and age-standardized incidence rates per 100 000 population for men and women were 4.9 and 1.8, respectively. The incidence rates in the Hokkaido region were significantly higher than in other regions (P < 0.05), among which there was no significant difference in incidence rates. Conclusions: The present study showed that the incidence rates of renal cell carcinoma in Japan were approximately the same as among Japanese in Los Angeles. The rates were, however, lower than North American and European countries, but higher than China, Central or South American countries and African countries. The reasons for the high incidence of renal cancer in the Hokkaido region are not entirely clear. Further epidemiologic research is required. [ABSTRACT FROM AUTHOR]

To assess upper urinary tract function and determine an ideal continent reservoir capacity, we investigated the relationship between intrareservoir pressure and functional parameters using radioisotope renography. Forty-three patients for whom ileal reservoir construction was performed by Kock pouch (n = 33) or Hautmann’s ileal neobladder (n = 14) approaches between November 1984 and September 1996 were studied. After the reservoir contents were catheterized, [sup 99m] Tc-MAG 3 renoscintigraphy was carried out and time activity curves in the kidney (renogram) and reservoir (reservoirgram) were recorded, while saline solution was poured into the reservoir for monitoring of intrareservoir pressure. Three basic abnormal curves were noted in the excretory phase on renograms: a normal downward curve followed by an upward curve, a continuous upward curve associated with or without a sharp decline after the catheterization of the reservoir contents, and episodes of spike waves. Based on these curves, renograms were classified into five types: normal, high pressure, retention, obstruction, and reflux. Abnormal types were noted with 51 of 65 renal units (78.5%) in the Kock pouch group and 15 of 25 renal units (60.0%) in the neobladder group. This examination method may be useful for evaluating urodynamics in the upper urinary tract of patients with a continent ileal reservoir and provide data on adequate voiding volumes for the individual patient.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Various types of tumors, including benign tumors, arise from the renal parenchyma or renal capsule, but it is difficult to predict the histological type preoperatively. Here, we report a case of perirenal non-specific lymphadenitis resected laparoscopically. A 79-year-old man with a history of diabetic mellitus and noninvasive bladder cancer had an incidentally-detected enhanced mass in contact with the surface of the left kidney. Given the possibility that the tumor was malignant, we resected the mass laparoscopically. Intraoperative findings revealed that the tumor did not invade the renal parenchyma, and it could be easily resected. Microscopic findings showed that the tumor consisted of inflammation of a lymph node, lymphoid follicles with hyperplasia of germ center and granulomatous inflammation with giant cells, and there was no malignant finding. Despite various additional examinations, the specific cause of the lymphadenitis was not clarified, leading to a final diagnosis of non-specific lymphadenitis. To our knowledge this is the first report about perirenal non-specific lymphadenitis difficult to distinguish from perirenal malignant tumor in preoperative computed tomography imaging.

(Objectives) Nephron sparing surgery (NSS) is strongly recommended for patients with T1a renal cell carcinoma (RCC) whenever surgically feasible. However, partial nephrectomy, particularly laparoscopic approach, remains underutilized in Japan compared to laparoscopic radical nephrectomy (LRN). In this study, we examined the safety and efficacy of laparoscopic partial nephrectomy (LPN) for T1a RCC compared to LRN. We also assessed the factors that affect the decision to perform LPN or LRN. (Patients and methods) From March 2001 to September 2014, 112 patients with T1a renal tumors received renal surgery at our institution. Of these, 100 patients (LPN: 36 patients, LRN: 64 patients) underwent laparoscopic surgery. Treatment outcomes including surgical and oncological outcomes among each approach were compared. In addition, multivariate analysis was performed to reveal the factors that affect the decision on surgical approach. (Results) The ratio of patients more than 75 years old and the RENAL nephrometry score were higher in LRN group than those in LPN group. Operating time was longer but renal function was well preserved in LPN group. Importantly, blood loss, intraoperative and postoperative complication rate, and oncological outcome (recurrence-free survival and overall survival) were similar in both groups. Multivariate analysis revealed that age (≥75 years old), high RENAL nephrometry score, operation period (before 2011), and the absence of Endoscopic Surgical Skill Qualification (ESSQ) in surgeon were independent predictive factors that select LRN. (Conclusions) Our data suggests that LPN for T1a renal tumor could be performed safely and the decision whether LPN or LRN were performed were associated with technical factors such as the presence of ESSQ or operation period, as well as patient's factor such as age and tumor factor such as tumor complexity.

We report a case of renal arteriovenous fistula, which was found during treatment for pyelonephritis. A 61-year-old woman was referred to our hospital because of lumbar backache and infectious fever. The computed tomographic scan showed right hydronephrosis and perinephritis. We treated her conservatively for pyelonephritis, but 5 days later, the contrast-enhanced computed tomographic scan showed retroperitoneal hemorrhage. Renal angiography demonstrated an arteriovenous fistula in the central portion of the right kidney. Superselective transcatheter arterial embolization of the AVF was performed. Hemostasis was possible by embolization. She has not had any recurrence of renal arteriovenous fistula. To our knowledge, this is the 5th report of a rupture in the retroperitoneum of an arteriovenous fistula, and renal arteriovenous fistula with the pyelonephritis is very rare.

A retrospective analysis was done on the outcomes of 278 patients who underwent radical prostatectomies at our institutions from November, 1994 to April, 2006. The treatment outcomes measured were disease-specific survival and prostate specific antigen (PSA) biochemical failure-free survival rates. Univariate and multivariate analyses were performed on patient age, clinical T-stage, Gleason sum at the time of prostate biopsy, PSA value before treatment, and any patient history of neoadjuvant hormone therapy. For all patients, the overall survival and the disease-specific survival rates at 10 years were 96.3 and 99.3%, respectively, with PSA biochemical failure-free survival rates at 5 and 10 years of 67.9 and 55.1%, respectively. On multivariate analysis, both the PSA values (> 20 ng/ml) and Gleason sums (> or = 7) were statistically significant independent risk factors for PSA biochemical failure after radical prostatectomy. Neoadjuvant hormone therapy was found to have no effect on PSA biochemical failure.

We performed a clinical trial on patients with upper urinary tract stone disease (renal stone disease) to prove the clinical equivalence as the target for removal of renal stones between the new formulation (miniaturized tablet) and the conventional formulation (capsule) of UROCALUN. The clinically effective rate of both formulations was the same at 70% (28 of 40 cases), and it was suggested that these two formulations possess the same clinical efficacy. Adverse drug reactions were observed in 10.0% (4 of 40 cases) with the tablet and 5.0% (2 of 40 cases) with the capsule. There were no significant differences between the two formulations in the incidence of adverse drug reactions, and there were no clinically significant safety problems. In the questionnaire survey for patients about medication compliance, we found that the patients felt the miniaturized tablets were much easier to swallow than the conventional formulation. In conclusion, it is suggested that the miniaturized tablet contributes to improve the medication compliance for patients and thus it is expected to improve the clinical efficacy.

Protein C inhibitor (PCI), a member of the serine protease inhibitor family, is produced in various human tissues, including the liver, kidney and testis. In addition to inhibiting the anticoagulant protein C pathway, PCI also inhibits urinary plasminogen activator (uPA), which is a well-known mediator of tumor cell invasion. In the present study, to clarify the biologic significance of PCI in the kidney, we compared the expression of PCI between human renal cell carcinoma (RCC) tissue and nontumor kidney tissue. The PCI antigen level in RCC tissue was found to be significantly lower than in nontumor kidney tissue, and expression of PCI mRNA was detected in normal renal proximal tubular epithelial cells (RPTEC), but not in RCC or in an RCC cell line (Caki-1 cells). No differences were detected between the nucleotide sequence of the major cis-elements in the promoter region of the PCI gene from nontumor kidney and RCC tissues, RPTEC and Caki-1 cells, an RPTEC-derived RCC cell line. The in vitro invasiveness of Caki-1 cells transfected with a PCI expression vector was significantly decreased compared to mock-transfected Caki-1 cells, and it was blocked in the presence of anti-PCI antibody. Since PCI itself did not affect the proliferation rate of Caki-1 cells or cell expression of uPA in vitro, the effect of uPA, PCI, heat-inactivated PCI and plasminogen activator inhibitor (PAI)-1 on the invasive potential of cultured RCC cells was evaluated. The in vitro invasiveness of Caki-1 cells, which express uPA, was significantly enhanced by the addition of uPA, and it was inhibited by anti-uPA antibody, PCI and PAI-1, but not by heat-inactivated PCI. In addition, uPA activity was significantly decreased and uPA-PCI complex level was significantly increased in the culture medium of PCI expression vector-transfected Caki-1 cells as compared to mock-transfected Caki-1 cells. These findings strongly suggest that PCI regulates the invasive potential of RCC cells by inhibiting uPA secreted by these cells. The results of our study suggest that PCI might be a potential therapeutic agent for inhibiting renal tumor invasion., (Copyright 2003 Wiley-Liss, Inc.)

Objective: This study was conducted to examine the natural history of renal cell carcinoma (RCC)., Methods: Inclusion criteria were the following: (1) patients who received diagnostic imaging of the kidney (CT, MRI) at two points in time before the diagnosis of RCC or patients who were followed, without treatment, after a diagnosis of RCC; and (2) patients in whom changes in tumor size were followed by the same modality of diagnostic imaging and who did not receive any treatment which could exert anti-tumor activity on the primary or metastatic lesions. The tumor doubling time (DT) and the growth rate of maximum tumor diameter (R) were determined. DT was calculated using the equation DT = (T - T(0)) x log2/logV - logV(0) (where T - T(0) indicates the length of time between two measurements and V(0) and V denote the tumor volume at two points of measurement). R was calculated using the equation R = (phi - f(0))/(T - T(0)) x 100 (where phi(0) and f indicate the maximum diameter at two points). Fifty-six cases registered with the Japanese Society of Renal Cancer were included in the evaluation., Results: DT was 603.1 +/- 510.1 days, which did not correlate with V(0). R was 0.263 +/- 0.346 cm/day x 100. In cases where the tumor diameter was >/=4 cm, a significant correlation was noted between f(0) and R., Conclusions: Elucidation of the natural history of RCC will contribute to facilitation of differential diagnosis and determination of optimum therapeutic strategy.

The current clinicopathologic study for evaluation of superficial bladder cancer still has limitations in predicting the true behavior of recurrence. To determine the high-risk recurrence factors, we studied the influence of Ki-67, c-erbB-2, p53 and multidrug resistance-associated protein (MRP) expression. Samples were obtained from 33 pTa and 46pT1 diagnosed bladder cancer patients with a mean follow-up of 48.7 +/- 30.6 months. The contingency table method, Kaplan-Meier curve and multivariate analysis were used to evaluate the association among the immunohistochemical factors expression, clinicopathologic parameters with tumor recurrence. Stage pT1 tumors, sessile tumors and large tumors (> 3 cm) showed a significantly high recurrence rate (p = 0.0158, p = 0.0162, p = 0.0001 respectively). Tumors with overexpression of Ki-67, c-erbB-2 and p53 were more likely to recur (p = 0.0035, p = 0.0027, p = 0.0076 respectively), MRP expression was not associated with recurrence. Multivariate analysis showed that large tumors and high Ki-67 expression were independent indicators of recurrence. On the other hand, in tumors less than 1 cm, recurrence was significantly correlated with overexpression of Ki-67 and p53. High Ki-67 expression could discriminate higher recurrence cases in grade 2, pT1 and single tumors. The c-erbB-2 overexpression was more frequently associated with recurrence in sessile tumors, large tumors, multiple and grade 1 tumors. The p53 overexpression also predicted a higher risk of recurrence in pTa tumors. These data demonstrated that the use of proliferative related proteins yields significant prognostic information in addition to clinicopathological factors, high Ki-67 expression is a reliable indicator of recurrence. A combination rather than any factor alone could more accurately predict tumor recurrence.

Background: Prostate specific antigen (PSA) is regulated by growth factors and hormones through functional androgen responsive elements in the promoter region of the PSA gene. However, the molecular basis for androgen independent PSA elevation in hormone refractory prostate cancer is unknown. The purpose of this study was to investigate the role of MAP kinase activation in androgen independent regulation of PSA expression., Methods: LNCaP cells transfected with MEK1 expression vector with or without the MAP kinase inhibitor U0126 under low androgen conditions were analyzed by luciferase assay and electrophoretic mobility shift assay (EMSA)., Results: Transfection experiments of the proximal PSA promoter linked to Luc-reporter identified one region designated as "B" motif centered at -60 bp to be essential for basal activation. Co-transfection with the MEK1 activated vector enhanced PSA expression, while mutation of the "B" motif totally abrogated this induction. EMSA showed a specific DNA-protein complex, but Sp1 family members and AR do not interact with the "B" region by supershift analysis., Conclusions: Our data suggest that enhanced androgen-independent PSA gene expression in MAP kinase-induced LNCaP cells is mediated, at least in part, by the "B" motif of the PSA promoter., (Copyright 2003 Wiley-Liss, Inc.)

We report a case of cystic renal cell carcinoma (CRCC). In general, computed tomography (CT) and magnetic resonance imaging (MRI) are sufficient for diagnosing renal cell carcinoma (RCC). However, we often have difficulty in diagnosing CRCC based on these modalities alone. In the present case, to assess the contrast-enhancement of the cyst wall and the septum, we evaluated the usefulness of CT arteriography (CTA) by selective injection of contrast material into the renal artery. We believe that CTA could be a valid option for preoperative radiological differentiation of CRCC.

A 60-year-old male was admitted with bilateral renal masses with a diameter of 50 mm (right kidney), and 15 mm (left kidney) found incidentally by computed tomography. Renal angiography demonstrated neovascularization in the lower pole of the right kidney, but no remarkable findings in the left kidney. We could not deny the possibility of bilateral renal cell carcinoma. Right radical nephrectomy and left partial nephrectomy were performed. The histopathological finding revealed diagnosis of right papillary renal cell carcinoma and left oncocytoma. To our knowledge, this is the third case of renal oncocytoma with synchronous contralateral renal cell carcinoma reported in Japan.