Biomedical subjects

Masaru Murai

Publications and source records attributed to Masaru Murai.

At least 37 records · Page 2Linked to original sources

PubMed2005

Clinical and pathologic significance of activation of signal transducer and activator of transcription 3 in prostate cancer.

OBJECTIVES: To evaluate the association of signal transducer and activator of transcription 3 (STAT3) with the invasiveness and aggressiveness of localized prostate cancer. METHODS: Paraffin-embedded specimens from 92 patients with clinically localized prostate cancer who underwent radical prostatectomy without neoadjuvant treatment were analyzed by immunohistochemistry using two antibodies: anti-phospho-specific STAT3 (p-STAT3) antibody, which recognized only activated STAT3, and anti-total STAT3 antibody, which recognized both activated and inactivated STAT3. The patients were separated into one of four groups according to the percentage of the cells with positive nuclear staining using a 0 to 3+ scoring system. The associations between the immunostaining and invasiveness and aggressiveness of clinically localized prostate cancer were analyzed. RESULTS: Pathologically, 66 patients (71.7%) had organ-confined disease. Of the 92 tumors examined, 8, 20, 23, and 41 showed staining patterns for p-STAT3 of 0, 1+, 2+, and 3+, respectively. In addition, 0, 3, 2, and 87 tumors showed staining patterns for STAT3 of 0, 1+, 2+, and 3+, respectively. The staining patterns for p-STAT3 correlated significantly with pathologic stage, Gleason score, and extracapsular extension. No significant correlation was found between p-STAT3 immunostaining and microvascular invasion, perineural invasion, or seminal vesicle invasion. Patients with 3+ immunostaining of p-STAT3 had a significantly greater biochemical prostate-specific antigen failure rate than those with 2+ or less immunostaining. CONCLUSIONS: Increased p-STAT3 immunoreactivity showed a highly invasive and aggressive potential in patients with localized prostate cancer treated with radical prostatectomy. This suggests that STAT3 signaling contributes to the invasiveness and aggressiveness of prostate cancer.

Aged↗

PubMed2005

Prostate specific antigen adjusted for transition zone epithelial volume: the powerful predictor for the detection of prostate cancer on repeat biopsy.

PURPOSE: The indications for repeat prostate biopsy for persistently increased prostate specific antigen (PSA) in men with prostate cancer never detected on previous biopsy are not clear. In this study we determined that PSA adjusted for transition zone (TZ) epithelial volume is the most powerful predictor for detecting prostate cancer on repeat biopsy. MATERIALS AND METHODS: Repeat prostate biopsies including additional TZ cores were performed in 75 men with PSA between 4.0 and 10.0 ng/ml. TZ epithelial volume was calculated by multiplying TZ volume by the percent of epithelium, which was measured by morphometric analysis using image analysis computer software. RESULTS: Prostate cancer was detected on repeat biopsy in 19 of the 75 patients. Patients with prostate cancer had a significant smaller percent area of epithelium or glandular lumen than those without cancer. In patients without prostate cancer TZ epithelial volume significantly correlated with total PSA. According to ROC analysis PSA adjusted for TZ epithelial volume had the greatest AUC for cancer detection (0.879). This parameter was able to avoid more than 90% of unnecessary repeat biopsies with 90% sensitivity. Multiple logistic regression analysis showed that PSA complex adjusted for TZ epithelial volume was the significant independent predictor of cancer. CONCLUSIONS: PSA adjusted for TZ epithelial volume is the most powerful predictor of cancer in men who have undergone previous negative prostate biopsies and in whom PSA remains between 4.0 and 10.0 ng/ml.

Aged↗

PubMed2005

C-jun activation in acquired cystic kidney disease and renal cell carcinoma.

PURPOSE: Activator protein-1 has a central role in transducing cytokine signals. Activator protein-1 is composed of 2 proto-oncogene families, namely Jun and Fos. Of them c-Jun has been suggested to have a role in cell cycle progression and neoplastic transformation. We examined the impact of c-Jun protein activation on pathological parameters in renal cell carcinoma (RCC). MATERIALS AND METHODS: The expression of total c-Jun protein and phosphorylated c-Jun protein was determined by immunohistochemistry in 72 patients with RCC, including 10 with tumor arising from acquired cystic kidney disease (ACKD) of end stage kidneys. RESULTS: c-Jun expression was observed in the distal but not the proximal tubules. Atypical hyperplastic cells in ACKD were positive for phosphorylated c-Jun. RCC arising in end stage kidneys was pT1 and 5 of these cases showed increased c-Jun activation. Of 62 cases arising from normally functioning kidneys 21 showed an increased degree of c-Jun activation. In localized small cell cases (pT1a) 55.5% (10 of 18) showed enhanced activation, whereas such enhanced activation was only observed in 25% (11 of 44) of more advanced cases (pT1b or greater). Therefore, c-Jun activation was considered to be related to the early carcinogenesis of RCC. CONCLUSIONS: This study emphasizes the role that c-Jun activation has in early RCC carcinogenesis. Thus, chronic stimulation of cytokines inducing c-Jun activation may have a role in the aberrant proliferation of hyperplastic atypical cells in ACKD and RCC.

Adult↗

PubMed2005

Photodynamic therapy with PAD-S31, a new hydrophilic chlorin photosensitizer, in an orthotopic rat bladder tumor model.

PURPOSE: PAD-S31 (13,17-bis (1-carboxypropion) carbamoylethyl-3-ethenyl-8-ethoxyiminoethylidene-7-hydroxy-2,7,12,18-tetramethyl-porphyrin sodium) (Photochemical Co., Ltd., Okayama, Japan), 1 of the latest second-generation photosensitizers, has hydrophilic characteristics and excitation wavelengths of around 670 nm. Using an orthotopic rat bladder tumor model we investigated the biodistribution of PAD-S31 and assessed the antitumor effects of photodynamic therapy (PDT) with PAD-S31. MATERIALS AND METHODS: An orthotopic rat bladder tumor was established by implanting AY-27 cells in the bladder wall. After intravenous PAD-S31 administration the accumulation of PAD-S31 in the tumor and normal bladder wall was investigated by a fluorometric technique. One or 3 hours after intravenous administration of PAD-S31 (5 mg/kg) bladder tumors in rats were transurethrally irradiated at 100 mW/cm with a light dose of 50 to 200 J/cm. The efficacy of PDT was evaluated 7 days later by observation with an ultrathin cystoscope and histopathological examination. RESULTS: The ratio of PAD-S31 concentration in tumor tissue to that in normal bladder wall was more than 1 at all time points and it achieved a maximum (more than 10) 150 to 240 minutes after PAD-S31 administration. All rats that were irradiated at 100 J/cm 3 hours after PAD-S31 administration showed more than 50% tumor destruction. When the light dose was more than 150 J/cm, more than half of the rats showed complete tumor eradication, of which the average size was 6 mm. CONCLUSIONS: We report that PDT using PAD-S31 is effective for destroying bladder tumors in an orthotopic rat model. These experimental results suggest that this therapy could be a clinically promising method for the treatment of patients with bladder cancer.

Animals↗

PubMed2005

Lymphovascular invasion independently predicts increased disease specific survival in patients with transitional cell carcinoma of the upper urinary tract.

PURPOSE: We investigated the prognostic impact of lymphovascular invasion (LVI) and traditional prognostic factors for survival in a large series of patients treated surgically for upper tract transitional cell carcinoma (TCC). We also developed a prognostic factors-based model for risk stratification of upper tract TCC. MATERIALS AND METHODS: We identified a study population of 173 consecutive patients treated surgically for upper tract TCC at our institution between 1980 and 2002. We compared LVI with other pathological features and determined the disease specific survival rate. RESULTS: LVI was found in 52 patients (30.1%). As tumor grade and pathological stage increased, the incidence of LVI increased significantly. LVI was found in 12 of 133 patients (9.0%) without lymph node metastasis compared with 40 of 40 patients (100%) with lymph node metastasis. Five and 10-year disease specific survival rates were 84.9% and 80.4% in the absence of LVI, and 40.2% and 21.1% in the presence of LVI, respectively (p <0.001). In multivariate analysis LVI, pathological T stage and tumor grade were independent predictors for disease specific survival. The relative risk of death could be expressed with the formula, exp(0.729 x tumor grade + 1.659 x pathological T stage + 1.160 x LVI). Using this equation the patients were stratified into low risk (grade 1 or 2, LVI negative, stage pT2 or lower), high risk (any tumor grade, LVI positive, stage pT3 or greater) and intermediate risk (all others) groups with significant differences in survival. Five and 10-year disease specific survival rates were 93.0% and 89.4% in the low risk group (82 patients), 66.8% and 62.9% in the intermediate risk group (53 patients), and 25.6% and 0% in the high risk group (38 patients), respectively. CONCLUSIONS: In addition to pathological stage and tumor grade, LVI is an independent prognostic factor for disease specific survival in upper tract TCC. Patients in the high and/or intermediate risk groups may benefit from integrated therapies with surgery and postoperative systemic chemotherapy.

Adult↗

PubMed2005

Repeated regression of pulmonary metastases from renal cell carcinoma after treatment using different interferon-alpha preparations.

A 49-year-old man with pulmonary metastasis from renal cell carcinoma (RCC) was treated with recombinant IFN-alpha2b (Intron A). A complete response was achieved within 4 months and thereafter persisted for 5 years until he developed another lung lesion. Interleukin-2 (Imunace) was administered without any response. Finally, he was treated by natural IFN-alpha (OIF). The pulmonary lesion achieved a partial response after 11 months of treatment. Because IFN-alpha preparations include different subtypes, changing the use of IFN-alpha preparations may thus be a potentially useful option for the successful immunotherapy of RCC.

Antineoplastic Agents↗

PubMed2005

New genetic causes of pheochromocytoma: current concepts and the clinical relevance.

Pheochromocytoma and paraganglioma are tumors of the autonomous nervous system mainly occurring in the adrenal medulla, but also in the extraadrenal paraganglias of the abdomen, thorax, neck and skull basis. The etiology comprises germline mutations of now 6 genes. About 10 years known are the RET gene susceptible for multiple endocrine neoplasia type 2, the VHL gene for von Hippel-Lindau Disease, and the NF 1 gene for neurofibromatosis Recklinghausen (neuro- fibromatosis type 1). Since 2000 the genes for succinatedehydrogenase subunits SDHB, SDHC, and SDHD have been identified for paraganglioma syndromes type 4, type 3, and type 1 respectively. Investigations of series of pheochromocytoma patients identified germline mutations in one of the genes SDHB, SDHD, VHL and RET in 24% to 50% of the patients. Multifocal tumors, young age and positive family history, known features associated with inheritence, have not been present in all patients. Therefore, analyses of blood DNA for mutations in these genes are recommended. Positive tests provide the patients and their relatives with essential platforms for clinical care. Experiences in this field of medicine have shown that optimal management of patients with pheochromocytoma-associated syndromes is a high challenge. National registries may be instrumental in order to provide with adequate facilities.

Adrenal Gland Neoplasms↗

PubMed2005

Modulation of bcl-2 family proteins in MAPK independent apoptosis induced by a cdc25 phosphatase inhibitor Cpd 5 in renal cancer cells.

Protein phosphatases have been classified into two basic types, namely protein serine/threonine phosphatase (PP), and protein tyrosine phosphatase (PTP). Cpd 5 is a selective inhibitor of cdc25 phosphatases, which belong to members of PTPs and regulate cell proliferation by controlling cyclin-dependent kinases (cdks). The present study was undertaken to investigate the potential utility of Cpd 5 as an anti-neoplastic agent for renal cell carcinomas (RCCs). Three renal cancer cell lines, 769P, Sw839, and A498 were used. The effects of Cpd 5 on the viability of renal cancer cell lines was analyzed using an Alamar Blue assay. Apoptosis was determined by flow cytometric TUNEL analysis. Changes in the expression of cdc25 phosphatases, mitogen-activated protein kinases (MAPKs), and bcl-2 family proteins were detected using Western blot analysis. The apoptosis-inducing effect of Cpd 5 on human RCC tissue was analyzed through TUNEL staining of organ cultures from RCCs. Cpd 5 showed a strong cytotoxicity against all renal cancer cell lines with an apoptosis-inducing effect. All cell lines treated with Cpd 5 resulted in a down-regulation of cdc25A, cdc25B, and cdc25C, however, the MAPK pathways were not affected. In addition, the up-regulation of bax, and the down-regulation of bcl-2 and bcl-xL, was observed. In organ cultures from RCCs, TUNEL-positive apoptotic nuclei were observed when treated with Cpd 5. Cpd 5 was thus found to effectively inhibit the proliferation of human renal cancer cells while also inducing apoptosis by inhibiting cdc25 phosphatases and modulating bcl-2 family proteins. The administration of Cpd 5 may thus be an effective therapeutic approach for RCCs.

Apoptosis↗

PubMed2005

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2003). I. Susceptibility distribution].

The bacterial strains isolated from 565 patients diagnosed as having urinary tract infections (UTIs) in 14 institutions in Japan were collected between August 2003 and July 2004. The susceptibilities of them to many kinds of antimicrobial agents were investigated. Of them, 701 strains were estimated as prophlogistic bacteria and used for the investigation. The strains consisted of 258 Gram-positive bacterial strains (36.8%) and 443 Gram-negative bacterial strains (63.2%). Against Staphylococcus aureus, vancomycin (VCM) showed the strongest activity and prevented the growth of all strains with 2 microg/mL. Against Streptococcus agalactiae, ampicillin (ABPC), cefozopran (CZOP), imipenem (IPM), and clarithromycin (CAM) showed a strong activity and the MIC90 was 0.125 microg/mL or less. Against Enterococcus faecalis, VCM, ABPC, and IPM showed a strong antibacterial activity. The antibacterial activity of cephems to Escherichia coli was generally good, and especially CZOP and cefpirome (CPR) showed the strongest activity (MIC90: < or = 0.125 microg/mL). Quinolone resistant E. coli [MIC of ciprofloxacin (CPFX): > or =4 microg/mL] was detected at frequency of 15.7%, which was higher than that in the last year. Against Klebsiella pneumoniae, meropenem (MEPM) showed the strongest activity and next, the antibacterial activity of CRMN and CZOP was good. The antibacterial activity of the other cephems, however, significantly decreased, compared with that evaluated in last year. Against Serratia marcescens, MEPM had the strongest antibacterial activity. Against Proteus mirabilis, MEPM and CRMN showed the strongest activity and prevented the growth of all strains with 0.125 microg/mL or less. Nest, cefmenoxime (CMX), ceftazidime (CAZ), cefixime (CFIX), cefpodoxime (CPDX), CPR, CZOP, and cefditoren (CDTR) showed a strong activity. The antibacterial activity of the drugs to Pseudomonas aeruginosa was generally low, and MIC90 of all the drugs was ranged from 32 to < or = 256 microg/mL except IPM and amikacin (AMK) having 16 microg/mL. The antibacterial activity of CZOP was relatively good (MIC50: 2 microg/mL).

Drug Resistance, Microbial↗

PubMed2005

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2003). II. Background of patients].

Seven hundred and nineteen bacterial strains isolated from 565 patients diagnosed as having urinary tract infections (UTIs) in 14 institutions in Japan were collected between August 2002 and July 2003. The frequency of bacteria isolation divided with patient clinical background was compared. The clinical background investigated included sex, age, type of infections, timing of antibiotics administration, and presence or absence of surgery affecting a decrease in defense against infection. The bacterial strains were divided with the age and sex of the patients and the types of infections. In males, the number of patients aged less than 50 years was few and the complicated UTIs without indwelling catheter was observed most frequently. Number of patients aged 20-39 years was greater in female than male. In all of ages except 0-9 and 70-79 years, the ratio of the uncomplicated UTIs was high, accounting for 44.4-91.7% of all types of infections. In the present time, the bacteria most frequently isolated were Escherichia coli, Pseudomonas aeruginosa and Enterococcus faecalis also were relatively frequently isolated. E. coli was most frequently isolated from the uncomplicated UTIs, and P. aeruginosa and E. faecalis were frequently isolated from the complicated UTIs with indwelling catheter. With respect to the relation of these results to the age of the patients, in the uncomplicated UTIs, the isolation frequency of E. coli was the highest in all age groups, accounting for 40% or higher. In the complicated UTIs without indwelling catheter, the isolation frequency of E. coli decreased with aging of the patients but still was the highest in all age groups. In the complicated UTIs with indwelling catheter, the isolation frequency of E. coli was lower than in the uncomplicated UTIs in all age groups and P. aeruginosa and E. faecalis were more frequently isolated. In comparison of causative bacteria in UTIs between before and after the administration of antibiotics, P. aeruginosa increased after the administration in any types of UTIs. In comparison of causative bacteria in UTIs with or without surgery, E. coli was more frequently isolated in the patients without surgery, while P. aeruginosa and E. faecalis were more frequently isolated in the patients with surgery in any UTIs.

Adolescent↗

PubMed2005

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2003). III. Secular changes in susceptibility].

The bacteria (Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa) isolated from 565 patients diagnosed as urinary tract infections (UTIs) in 14 institutions in Japan were collected between August 2003 and July 2004. The susceptibilities of these bacteria to various antimicrobial agents were examined. The bacteria were divided into 2 groups consisting of uncomplicated UTIs and complicated UTIs (with and without indwelling catheter) based on their isolation origins. The results were compared with those obtained between 1994 and 2002. The drug sensitivity of S. aureus in this year was similar to those in up to the previous years and S. aureus showed the best susceptibility to vancomycin. The drug sensitivity of E. faecalis in this year also was similar to those in up to the previous years. The drug sensitivity of E. coli in this year was generally good except penicillins and was similar to those in up to the previous years. Among cephems, cefozopran (CZOP) and cefpirome (CPR) showed the highest potency activity (MIC90: < or = 0.125 microg/mL). An antibacterial activity of cefotiam (CTM) was stable for 10 years and was fine (MIC0: < or = 0.5 microg/mL). The sensitivity of E. coli to carbapenems and carumonam (CRMN) also was good like to CZOP. The sensitivity of the complicated UTIs group to quinolones, however, has decreased after 2000 and it was suggested that the resistance to the drug has developed. Kiebsiella spp. showed a decrease in the susceptibility to some of cephems. The drugs indicating a big decrease in the sensitivity were cefazolin, CTM, cefaclor, and cefpodoxime. Imipenem, carbapenems, also indicated a decrease in the sensitivity. The susceptibility of the strain to the other drugs was similar to that in up to the previous years. Among them, CZOP maintained good susceptibility (MIC90: > or = 0.125 microg/mL against uncomplicated UTIs, 0.25 microg/mL against complicated UTIs) like meropenem. The drug sensitivity of P. aeruginosa was generally low and was not much different from that in up to the previous years.

Anti-Infective Agents↗

PubMed2004

Identification of bladder cancer antigens recognized by IgG antibodies of a patient with metastatic bladder cancer.

To identify tumor antigens useful for the diagnosis and treatment of patients with bladder cancer, a lambda phage cDNA library constructed from a high-grade bladder cancer cell line was screened with autologous serum from a patient with metastatic bladder cancer. Forty-eight distinct antigens were isolated. By evaluating the immunogenicity and the tissue-specific expression, KU-BL-1 and KU-BL-2 were identified as immunogenic antigens with restricted tissue expression. KU-BL-1 was found to be a putative human lipoic acid synthetase with a metal-binding site, CXXXCXXC, that was expressed in bladder cancer cell lines and most bladder cancer tissues, as well as normal bladder mucosa and testis tissues. Immunoglobulin (Ig)G antibody to KU-BL-1 was detected in 2 of 28 patients with bladder cancer, but not in 30 healthy individuals. KU-BL-2 was found to be a putative human kelch-like protein that was homologous to Drosophila kelch, with a BTB/POZ domain and kelch repeats. KU-BL-2 was expressed in bladder cancer cell lines, most bladder cancer tissues, testis and heart, but not in normal bladder mucosa. IgG antibody to KU-BL-2 was detected in 8 of 28 patients with bladder cancer, but not in 16 healthy individuals. Tumor reactive T cells were induced from peripheral blood mononuclear cells (PBMC) by stimulation with one of the HLA-A24 binding KU-BL-2 peptides. Therefore, KU-BL-1 and KU-BL-2, which showed preferential expression in bladder cancer with restricted expression in normal tissues, as well as immunogenicity in multiple patients with bladder cancer, may be useful for the development of diagnostic and therapeutic methods for patients with bladder cancer.

Aged↗

PubMed2004

Differential expression of activator protein-2 isoforms in renal cell carcinoma.

OBJECTIVES: To investigate the expression of activator protein-2 (AP-2) in renal cell carcinoma (RCC) by immunohistochemistry. Three AP-2 isoforms alpha (alpha), beta (beta), and gamma (gamma) are known to exhibit a highly homologous structure; however, their functions are considered to be different. AP-2 has been implicated to play a role in carcinogenesis, as well as in the development of the kidney. METHODS: The expression of the three AP-2 isoforms, alpha, beta, and gamma, was determined in 58 patients with RCC by immunohistochemistry. Epidermal growth factor receptor and erbB2 expression in 42 patients with RCC was also evaluated to investigate the correlation with AP-2 isoforms. RESULTS: AP-2 isoforms are differentially expressed in normal renal tubules. Of 58 RCC tissue specimens, 15 (25.9%) demonstrated nuclear and cytoplasmic expression of AP-2alpha. Clear cell RCC had a significantly greater rate of AP-2alpha expression than the nonclear subtypes (14 of 41 clear versus 1 of 17 nonclear subtypes). Of the 58 specimens, 8 (13.8%) showed nuclear staining for AP-2beta; notably, localized small cases had a significantly greater rate of nuclear staining for AP-2beta (5 of 13 in pT1a versus 3 of 45 in pT1b or greater). In addition, only 2 cases (3.5%) demonstrated nuclear staining for AP-2gamma. Epidermal growth factor receptor and erbB2 expression did not correlate with expression of the AP-2 isoforms. CONCLUSIONS: AP-2 isoforms were differentially expressed in RCC, as well as in the adult normal kidney. AP-2alpha was dominantly expressed in clear cell RCC. AP-2beta expression was observed in the low-stage subtypes of RCC, and this transcription factor may be related to early carcinogenesis.

Adenocarcinoma↗

PubMed2004

Endorectal MRI for prediction of tumor site, tumor size, and local extension of prostate cancer.

OBJECTIVES: To assess the value of endorectal magnetic resonance imaging (MRI) for detecting the tumor site, tumor size, and disease extent in patients with localized prostate cancer. METHODS: The MRI findings were compared with the histopathologic findings of radical prostatectomy specimens in 95 patients. RESULTS: The histologic examination revealed 186 cancer foci. Endorectal MRI detected 109 cancer foci. The accuracy, sensitivity, and positive predictive value of endorectal MRI for detecting tumor foci greater than 1.0 cm in diameter was 79.8%, 85.3%, and 92.6%, respectively; the corresponding value for detecting tumor foci smaller than 1.0 cm was 24.2%, 26.2%, and 75.9%, respectively. The maximal tumor diameter on endorectal MRI correlated with that shown by histologic examination for tumors larger than 1.0 cm in diameter. However, it did not correlate significantly with the histologic diameter of tumors smaller than 1.0 cm. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of endorectal MRI was 74.7%, 57.1%, 82.1%, 57.1%, and 82.1%, respectively, for the detection of extracapsular extension and was 75.8%, 62.1%, 81.8%, 60.0%, and 83.1%, respectively, for local staging. CONCLUSIONS: The results of the present study suggest that endorectal MRI is useful for predicting local extension, as well as tumor site and tumor size, of cancer foci greater than 1.0 cm in diameter.

Adenocarcinoma↗

PubMed2004

Tumor doubling time of renal cell carcinoma measured by CT: collaboration of Japanese Society of Renal Cancer.

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.

Adult↗

PubMed2004

Characteristics of patients with prostate cancer who have initially been treated by hormone therapy in Japan: J-CaP surveillance.

OBJECTIVE: Hormone therapy for prostate cancer has empirically prevailed in Japan. We planned to evaluate the trends and outcome of hormone therapy for establishing an adequate guideline. METHODS: Patients with prostate cancer who were initially treated by hormone therapy were registered through the J-CaP registration system. This report summarizes the background factors. RESULTS: From January 2001 to October 2003, 17,872 patients were registered from 395 institutes throughout Japan. The background factors of 17,312 patients were analyzed. The 17,872 patients were estimated as composing more than half of newly diagnosed prostate cancer patients in Japan. Of these, 22.9, 35.1, 32.9 and 8.6% belonged to T1, T2, T3 and T4, respectively. For the purposes of hormone therapy, 77.5% was primary hormone therapy. Neoadjuvant setting and adjuvant setting were 18.1 and 4.3%, respectively. About 60% of the hormone therapy was combined hormone therapy with LH-RHa plus anti-androgens. CONCLUSION: Irrespective of patients' age, TNM, stage of illness, or histological background, the majority of prostate cancer patients in Japan are receiving hormone therapy. It is necessary to evaluate whether this trend is merely a continuation of past experience of Japanese urologists or if there is a difference in the profile of effect and side-effect in the case of Japanese patients compared to therapy given in Westerners.

Aged↗

PubMed2004

The prediction of renal function 6 years after unilateral nephrectomy using preoperative risk factors.

PURPOSE: Since middle-aged and elderly patients seem to have risk factors affecting renal function, it is important to predict postoperative renal function prior to unilateral nephrectomy (UNx). We evaluated preoperative factors for predicting postoperative renal function in middle-aged and elderly patients with renal cell carcinoma (RCC) treated with radical nephrectomy (RNx). MATERIALS AND METHODS: In 201 patients who underwent RNx preoperative records and postoperative serum creatinine (SCR) 6 years after nephrectomy were available. Postoperative renal insufficiency was defined as serum creatinine 1.4 mg/dl or greater. The relationship of each preoperative and postoperative factor was analyzed. Logistic regression analysis was performed to evaluate preoperative factors for predicting postoperative SCR 1.4 mg/dl or greater after 6 years. RESULTS: There was a significant difference in postoperative SCR between female and male patients, and between those with and without hypertension, diabetes and proteinuria (p <0.05). Age, hemoglobin, preoperative SCR, blood urea nitrogen, uric acid and K significantly correlated with postoperative SCR (p <0.05). The increase in SCR during 6 years after UNx was significantly higher in patients with hypertension, diabetes and proteinuria than in their respective counterparts (p <0.05). Multivariate stepwise logistic regression analysis demonstrated that preoperative serum creatinine, hypertension and proteinuria were significant independent factors predicting postoperative renal function 6 years after UNx in patients with RCC (p <0.05). CONCLUSIONS: Preoperative SCR, hypertension and proteinuria are useful factors for predicting postoperative renal function after RNx in patients with RCC.

Carcinoma, Renal Cell↗

PubMed2004

Inhibition of MKP-1 expression potentiates JNK related apoptosis in renal cancer cells.

PURPOSE: Mitogen-activated protein kinases (MAPKs) comprise 3 subgroups, that is extracellular signal-regulated protein kinase, c-Jun N-terminal kinase (JNK) and p38 MAPK (p38). In this study we analyzed the role of JNK as well as the expression of MAPK phosphatase-1 (MKP-1) in renal cancers. MATERIALS AND METHODS: Four renal cell carcinoma (RCC) cell lines were used. The effects of anisomycin (JNK activator) and Ro-318220 (MKP-1 expression inhibitor) were analyzed by alamar blue assay. Apoptosis was determined by flow cytometric TUNEL analysis, nuclear morphological alternations and the detection of DNA fragmentation. Changes in MKP-1 expression as well as the activation of extracellular signal-regulated protein kinases and JNK were analyzed by Western blotting. RESULTS: All cell lines treated with anisomycin resulted in a transient activation of JNK without inducing apoptosis. Since we hypothesized that elevated MKP-1 expression could possibly prevent persistent JNK activation, Ro-318220 was used. When cells were treated with Ro-318220, MKP-1 expression decreased in Caki-1 and KU 20-01 cells but not in ACHN or 769P cells. Combined treatment of Caki-1 and KU 20-01 cells with anisomycin and Ro-318220 resulted in a decrease in MKP-1 expression concomitant with persistent JNK activation. Apoptosis was induced in each cell line. CONCLUSIONS: These results suggest that prevalent MKP-1 expression in RCC contributes to cancer cell survival by attenuating an apoptosis inducing signal cascade via JNK. Since Ro-318220 potentiated JNK related apoptosis, JNK activation by blocking MKP-1 expression may be an effective therapeutic approach to RCC.

Anisomycin↗