[The 90th Annual Meeting of Japanese Urological Association].
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Biomedical subjects
Publications and source records attributed to Masaru Murai.
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PURPOSE: Signal transducer and activator of transcription 3 (STAT3) is known to have an important role in cytokine and growth factor signaling pathways. In various types of human malignant tumors STAT3 has been shown to be constitutively activated due to aberrant production of cytokines and growth factors. We examined the presence of STAT3 activation and its association with pathological features and clinical outcome in renal cell carcinoma cases. MATERIALS AND METHODS: We examined 48 paraffin embedded renal cell carcinoma specimens and corresponding nonneoplastic kidney tissues for the activation status of STAT3 on immunohistochemistry using anti-phospho-specific (p)-STAT3 antibody, which recognizes only activated STAT3. Based on the percent of cells with positive nuclear staining the activation status of STAT3 was determined and categorized into 2 groups, including low-less than 10% and high-90% or more tumor cells positive. The associations of the activation status of STAT3 with pathological features and clinical outcome were analyzed. RESULTS: Of 48 tumors 24 (50%) demonstrated high levels of nuclear immunostaining for p-STAT3, while the other 24 (50%) showed low levels. Adjacent nonneoplastic kidney tissues showed only little immunostaining for p-STAT3. A significant association of high levels of p-STAT3 with metastasis was observed (p = 0.0094). No significant associations of p-STAT3 immunostaining with pathological stage or grade were observed. A high level of p-STAT3 was a significant indicator of a poor prognosis on univariate and multivariate analysis (p = 0.0117 and 0.0439, respectively) CONCLUSIONS: Our results indicate a high frequency of STAT3 activation in renal cell carcinoma, especially in metastatic disease. STAT3 activation was an independent prognostic variable in renal cell carcinoma cases. Our results strongly suggest that the activation of STAT3 contributes to the development and progression of renal cell carcinoma.
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The bacterial strains isolated from patients diagnosed as having urinary tract infections (UTIs) in 10 institutions in Japan were supplied between the period of August 2000 and July 2001. Then, the susceptibilities of them to many kinds of antimicrobial agents were investigated. The number of them were 511 strains. The breakdown of these strains was Gram-positive bacteria as 29.0% and Gram-negative bacteria as 71.0%. Susceptibilities of these bacteria to antimicrobial agents were as follows; vancomycin (VCM), ampicillin (ABPC) and imipenem (IPM) showed strong activities against Enterococcus faecalis. No increase in low-susceptible strains of E. faecalis observed against these antimicrobial agents. VCM showed a strong activity against MRSA preventing growth of all strains with 1 microgram/ml. In addition, the activity of arbekacin (ABK) was strong with the MIC90 of 2 micrograms/ml against MRSA and prevented growth of all strains with 4 micrograms/ml. ABK showed a strong activity against Staphylococcus epidermidis preventing growth of all strains with 0.5 microgram/ml. ABPC, cefotiam (CTM) and cefozopran (CZOP) also showed a relatively strong activity against S. epidermidis (MIC90: 4 to 8 micrograms/ml). Against Escherichia coli, carbapenems showed high activities: meropenem (MEPM) prevented growth of all strains within 0.125 microgram/ml; IPM prevented growth of all strains with 0.25 microgram/ml. CZOP and CTM also showed strong activities against E. coli: MIC90 of CZOP was within 0.125 microgram/ml; MIC80 and MIC90 of CTM were 0.25 and 0.5 microgram/ml, respectively. Quinolone resistant E. coli was detected at frequency of 14.0%, which was significantly higher than that in the last year. Almost all drugs showed strong activities against Klebsiella pneumoniae and Proteus mirabilis, and MEPM prevented growth of all strains within 0.125 microgram/ml. Against Pseudomonas aeruginosa, almost drugs were not so active. The MIC90 of carbapenems and gentamicin (GM) were 16 micrograms/ml and those of all other drugs were more than 32 micrograms/ml. Against Serratia marcescens, the MIC90 of IPM and GM were the lowest value being 2 micrograms/ml, and that of MEPM was 4 micrograms/ml.
Five-hundred eighty eight bacterial strains isolated from 435 patients diagnosed as having urinary tract infections (UTIs) in 10 institutions in Japan were supplied between August 2000 and July 2001. Then, the clinical background of patients were investigated such as sex, age, and type of infections, infections and kind of bacteria, frequency of bacteria isolation by age and infections, bacteria and infections by timing of antibiotics administration, and bacteria and infections by surgical procedures. About the relationship between age and sex of patients and type of infections, the number of male patients aged less than 50 years was few, and complicated UTIs without indwelling catheter was the most frequent. In females, the number of patients aged less than 20 years was few. The majority of female patients aged 40 years and over had complicated UTIs while uncomplicated UTIs was most frequent in the patients being twenties. As for type of infections and kind of bacteria, Escherichia coli decreased when the infections became complicated, and pseudomonas aeruginosa increased when the infection became complicated. Enterococcus faecalis was isolated more frequently in complicated UTIs than in uncomplicated UTIs. Considering this result by age of patients, isolated frequency of E. coli was gradually decreased with aging in patients aged 20 years and over with uncomplicated UTIs or complicated UTIs without indwelling catheter. The isolated frequencies of Klebsiella spp., P. aeruginosa, and E. faecalis were high in the patients with complicated UTIs without indwelling catheter. In the patients aged 70 years and over with complicated UTIs with indwelling catheter, P. aeruginosa and E. faecalis were frequently isolated. As for type of causative organisms in UTIs before and after the administration of antibiotics, the isolation of bacteria was remarkably decreased after administration in the patients with uncomplicated UTIs and complicated UTIs without indwelling catheter. E. coli decreased after administration of antibiotics, and P. aeruginosa increased after administration in the patients with all types of infections. As for type of causative organisms in UTIs and surgical procedures, E. coli was frequently isolated in the patients without surgery in all types of infections, while P. aeruginosa was frequently isolated in the patients who underwent surgery. In uncomplicated UTIs, Proteus spp. and E. faecalis were frequently isolated in the patients with surgery. In complicated UTIs without indwelling catheter, Klebsiella spp. was frequently isolated in the patients without surgery and E. faecalis was frequently isolated in the patients with surgery. In complicated UTIs with indwelling catheter, most of organisms except P. aeruginosa and S. aureus were frequently isolated in the patients without surgery.
The impact of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma (RCC) is discussed herein with consideration of prolonged survival and quality of life. A nephrectomy can be indicated in a patient with good performance status and pulmonary metastases when adjuvant immunotherapy is an option. In contrast, in a patient with poor performance status and/or metastases including multiple organs, a nephrectomy is not indicated. To relieve symptoms, options other than nephrectomy should be considered.
The first Conference on Asian Trends in Prostate Cancer Hormone Therapy was held in September 2001 to serve as a forum for Asian urologists to compare data on prostate cancer and discuss issues regarding the use of hormone therapy. The conference revealed that due to various cultural and philosophical factors, differences exist in prostate cancer management among the Asian countries. In addition, a lack of databases on hormone therapy was exposed in some countries. It was noted that many decisions in the treatment of prostate cancer are influenced by the strategies adopted in Western countries, and that attempts to formulate uniform guidelines for the Asian region have hitherto been unsuccessful. The main findings of the conference are reported in this review.
PURPOSE: Prostate-specific membrane antigen (PSMA), which is a transmembrane glycoprotein predominantly expressed in prostate cancer, is an attractive target for tumor-specific immunotherapy. To identify human leukocyte antigen (HLA)-A24-restricted epitope peptides from PSMA for further application of the dendritic cell (DC)-based immunotherapy targeting prostate cancer, we have screened several PSMA-encoded HLA-A24-binding peptides for their capabilities to elicit specific antitumor CTL response in vitro. EXPERIMENTAL DESIGN: The amino acid sequence of PSMA was screened for peptides consisting of 9 or 10 amino acids, which possess the known HLA-A24-binding motif. Nine candidate peptides were screened for binding to HLA-A24 molecules. Then, each of these nine peptides was studied to determine whether CTL responses could be induced by primary in vitro immunization of CD8(+) T cells using peptide-pulsed autologous DCs derived from peripheral blood mononuclear cells of HLA-A24(+) healthy donor as antigen-presenting cells. The antigen specificity of the CTL lines was confirmed using several tumor cell lines as target cells, which were genetically modified to express both HLA-A24 and PSMA. RESULTS: Two peptides, LYSDPADYF and NYARTEDFF, were demonstrated to elicit CTL lines that lyse peptide-pulsed, HLA-A24(+) B-lymphoblastoid cells. Each of the CTL lines recognized their specific PSMA-expressing target cells in a HLA-A24-restricted manner. The capability to release IFN-gamma by the CTL lines was specifically inhibited by anti-MHC class I and anti-CD8 monoclonal antibodies but not by anti-MHC class II and anti-CD4 monoclonal antibodies. CONCLUSION: Two novel HLA-A24-restricted PSMA-derived epitopes were identified in this study. These epitopes can be used to further evaluate the clinical utility of DC-based immunotherapeutic strategies for treatment of hormone-refractory prostate cancers.
The bacteria (Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa) isolated from patients diagnosed as having urinary tract infections (UTIs) in 10 institutions in Japan were supplied between August 2000 and July 2001. Then, the susceptibilities of these bacteria to various antimicrobial agents were examined, and the results were compared with those obtained between 1992 and 1999. Comparison was made by classifying strains isolated from patients into those in uncomplicated UTIs and those in complicated UTIs (including with or without indwelling catheter). E. faecalis showed good susceptibility to ampicillin (ABPC) and imipenem (IPM), and the MIC90s were 2 micrograms/ml. Also, E. faecalis showed good susceptibility to vancomycin (VCM). However, the MIC90, which was 2 micrograms/ml between 1992 and 1999, rose to 4 micrograms/ml in patients with complicated UTIs because the strains inhibited at 4 micrograms/ml increased more than before. The low susceptibility of S. aureus to arbekacin (ABK) in complicated UTIs, as shown in 1998 and 1999, recovered in 2000, and no strains inhibited at > or = 4 micrograms/ml were detected. E. coli showed good susceptibility to CTM (MIC90: 0.25-0.5 microgram/ml) and CZOP (MIC90: < or = 0.125 microgram/ml) and was not resistant to those. E. coli also showed good susceptibility to the other drugs except to penicillins. Decreases in susceptibility of E. coli to quinolones, ciprofloxacin (CPFX), and sparfloxacin (SPFX) were observed in the patients with complicated UTIs. The susceptibility of Klebsiella spp. to all drugs did not significantly change in 2000 and was generally good except to penicillins. Although the susceptibility of P. aeruginosa to carbapenems was notable, the MIC90 went up from 4 micrograms/ml to 16 micrograms/ml in complicated UTIs compared with those observed in the previous year.
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We conducted a randomized controlled trial to compare local recurrence rate after transurethral resection of superficial bladder cancer treated by either intravesical instillation of an anticancer drug alone (method A) and the intravesical instillation plus oral chemotherapy (doxifluridine, 5'-DFUR, an intermediate metabolite of capecitabine) (method B). Results between groups showed no difference in recurrence-free survival curves in 196 patients subjected to primary analysis. However, patients subjected to secondary analysis (method B, over 3 months administration of 5'-DFUR) showed a significantly better prognosis than method A (p=0.0244, Wilcoxon). Regarding correlation between thymidine phosphorylase (TP, an enzyme to convert 5'-DFUR to 5-fluorouracil) level and prognosis, method A patients showed poorer prognosis in higher TP level cases than in lower TP levels. However, there was no significant difference in prognosis between those with higher and lower TP levels. In method B patients, there was no difference in prognosis between those with higher and lower TP levels. Method A patients tended to show a slightly better prognosis than those with lower TP levels, while method B patients tended to have a slightly better prognosis with higher TP levels, but no significant difference was observed. These findings suggested 5'-DFUR showed a mild efficacy in patients with higher TP levels and that patients with higher TP levels resulted in poorer prognosis.