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Biomedical subjects

Katsusuke Naito

Publications and source records attributed to Katsusuke Naito.

At least 37 records · Page 2Linked to original sources
PubMed2005

Smoking may cause genetic alterations at 5q22.2 approximately q23.1 in clear-cell renal cell carcinoma.

The aim of this study was to examine the relationship between allelic imbalance (AI) on chromosome 5q and clinico-pathologic parameters, including cigarette smoking. We examined the AI on chromosome 5q in 119 clear-cell renal cell carcinomas (CRCC) by a fluorescent polymerase chain reaction technique using nine microsatellite markers. AI of one or more loci was found in 43 cases (36.1%). The most frequent AI was observed at chromosome 5q23.1 (D5S467), where the LOX gene is located. The minimally involved region ranged from 5q22.1 to 5q23.2, with a possible breakpoint between 5q22 and 5q22.1. Regarding the relationships between the frequency of AI and the clinico-pathologic and environmental backgrounds, smokers had a significantly higher frequency of AI of 5q22.2 approximately q22.3 (D5S471) than nonsmokers (P = 0.013). No other significant associations were found between AI of specific loci and other parameters. Our results suggest that AI at 5q plays an important role in the genesis of CRCC. In addition, smoking may cause genetic alterations at 5q22.2 approximately q23.1, where the LOX gene is located.

Adenocarcinoma, Clear Cell↗
PubMed2005

Clinical significance of lymph node dissection in renal cell carcinoma.

OBJECTIVE: To identify the role of lymph node dissection in renal cell carcinoma (RCC). MATERIAL AND METHODS: A total of 100 patients (66 males, 34 females) were enrolled in the study. The mean age and tumor size were 61.4 years and 5.8 cm, respectively. A total of 41 patients (41%) had tumors <4 cm in diameter. The pathological status was pT1, pT2 and pT3 in 60, 11 and 29 patients, respectively. RESULTS: In total, lymph node metastases were found in seven cases (7%). Of 40 patients with pT1a tumors (tumor size <4 cm), one (2.5%) had lymph node metastasis. Patients with lymph node metastases had significantly larger tumors than those without (8.9 vs 5.5 cm; p<0.05). Regarding patient outcome, 33 (33%) had tumor progression (alive with disease, n=14; disease-specific death, n=19) after a median follow-up period of 54.0 months. In univariate analysis, 15/18 prognostic markers [tumor size, tumor grade, pT, pN and M categories, stage, microscopic venous invasion (V category), microscopic lymphatic invasion (Ly category), pathological tumor infiltration pattern (INF category), plasma fibrinogen, C-reactive protein, immunosuppressive acidic protein, alpha-2 globulin and erythrocyte sedimentation rates at 1 and 2 h] were common significant predictors of tumor progression. A Cox hazard model revealed tumor size, tumor grade and pathological stage to be independent prognostic factors. CONCLUSIONS: Tumor size is a crucial prognostic factor for tumor progression, and lymph node dissection may be omitted in T1a tumors.

Carcinoma, Renal Cell↗
PubMed2005

Identification of 2 serum biomarkers of renal cell carcinoma by surface enhanced laser desorption/ionization mass spectrometry.

PURPOSE: Surface enhanced laser desorption/ionization mass spectrometry can generate robust information from a small amount of clinical samples such as serum and plasma. In this study we identified novel diagnostic biomarkers of renal cell carcinoma (RCC) by large-scale serum protein profiling using surface enhanced laser desorption/ionization mass spectrometry. MATERIALS AND METHODS: Proteomic spectra were generated by a time of flight mass spectrometer from a set of training samples (21 patients with RCC and 24 healthy volunteers) and another set of validation samples (19 patients with RCC, 20 healthy volunteers and 5 patients with pyelonephritis). Information on the peaks (intensity and m/z) was extracted from the mass spectra using newly developed algorithms, and the Mann-Whitney's U test and linear support vector machine were used to identify the peaks distinguishing RCC samples from the controls. RESULTS: Two peaks with molecular masses of 4,151 and 8,968 m/z were selected as significantly more prominent in RCC samples (p <0.01) among the 3,539 peaks in the range of 3,000 to 30,000 m/z obtained from the training samples. Simultaneous recognition of these 2 biomarkers was shown to have a sensitivity of 89.5% for the diagnosis of RCC and an overall specificity of 80.0% (95% [19 of 20] of healthy volunteers and 20% [1 of 5] of patients with pyelonephritis) in the blinded validation samples, and to allow detection of RCC in stage I (UICC) in 88.9% (16 of 18) of the cases. CONCLUSIONS: We identified 2 serum biomarkers potentially useful for the early diagnosis of RCC. This finding warrants a further large-scale multi-institutional analysis for clinical evaluation of the diagnostic significance of these biomarkers.

Adult↗
PubMed2005

Expression of thymidine phosphorylase in human superficial bladder cancer.

BACKGROUND: The purpose of the present paper was to investigate the expression level of thymidine phosphorylase (TPase) in superficial bladder cancer tissues obtained by transurethral resection, and determine whether its expression correlates with tumor recurrence. METHODS: From March 1998 to December 2001, 99 patients with superficial bladder cancer were diagnosed and treated at eight affiliated hospitals. Tissue specimens obtained by transurethral resection of superficial bladder cancer (TURBT) were applied to immunohistochemical study using anti-TPase antibody as well as pathological diagnosis. The data were subjected to statistical analysis. RESULTS: Using MoAb 654-1 as the primary antibody, TPase was clearly stained in human bladder cancer tissues. The maximum TPase level measured by enzyme-linked immunosorbent assay (ELISA) method in normal bladder tissues was 18.7 U/mg protein. The TPase activity was 2.8-fold higher in tumors than in normal bladder samples (P = 0.037). The TPase positivity rates determined by immunohistochemical and ELISA methods were distinctly correlated (P = 0.046). For the recurrence-free rates in pT1 tumors treated by TURBT alone (n = 46), there were no statistically significant differences between Tpase-positive or -negative cases. CONCLUSIONS: The TPase expression determined by ELISA and immunohistochemistry is significantly up-regulated in superficial bladder tumors compared with normal bladder samples. However, TPase expression by immunohistochemistry is not a predictive index of recurrence-free rate for superficial bladder cancer treated with TURBT alone.

Aged↗
PubMed2005

Usefulness and limitation of punched-out orchidometer in testicular volume measurement.

AIM: To determine the limitations of a punched-out orchidometer in practical use, we compared with a scrotal ultrasound (USG). METHODS: A total of 281 testes from 142 males were examined using both a punched-out orchidometer and a USG. The volume differential between both methods was calculated and expressed as orchidometer/USG volume (O/U ratio). Distribution of the O/U ratio was determined and subdivided by clinical or pathological diagnosis. The correlations between the O/U ratio and patient age or orchidometer results were assessed. RESULTS: There was a significant linear relationship between the results of orchidometer and USG (r=0.94, P <0.0001). The relationship between the O/U ratio and age or testicular volumes showed significant inverse correlations (r=0.22, P=0.0002, r=0.45, P <0.0001, respectively). Klinefelter's syndrome, ipsilateral detorted testes and hypogonadotropic hypogonadism comparatively showed a high O/U ratio. No incidental lesion was detected by USG necessitating treatment. CONCLUSION: The punched-out orchidometer gives estimates that correlated well with the USG measurements and provides enough information for routine andrological evaluation. We should be aware that the orchidometer often overestimates the testicular volume, especially for the patients with small testis or adolescents.

Adolescent↗
PubMed2005

Inherited antithrombin deficiency and end stage renal disease.

Antithrombin is a potent inhibitor of the coagulant effect of thrombin. In the latter half of 20th century, many families have been described in which an autosomaly dominant inherited antithrombin deficiency has caused severe venous thromboembolic disease in successive generations. The important complication is severe venoocclusive disease by deep venous thrombus. Some inherited antithrombin deficient patients developed renal failure because of fibrin deposition in the kidney glomeruli or renal vein thrombus, and therefore the need for replacement therapy for end stage renal disease (ESRD). Although an inherited antithrombin deficiency with renal failure is rare, prevention against renal failure in such patients, and their renal replacement therapy for ESRD are important. Proteinuria decreases plasma antithrombin level leading to more severe hyper-coagulation state. Therefore early in renal disease, it may be prudent for adaptation of anti-coagulation therapy even if recurrent thrombosis has not occurred. All replacement therapy (hemodialysis, transplantation or peritoneal dialysis) for ESRD are available for such thrombophilic disorders. Anticoagulation agents working without aggravation of antithrombin effects (Argatroban, Nafamostat mesilate etc.) are useful for hemodialysis. The renal allograft recipients with thrombophilia seem to be at risk of developing an acute rejection or other vascular event. Peritoneal dialysis is potentially a good adaptation for such thrombophilic disorders. However which therapy has the best mortality and morbidity outcomes is not clear. Physicians and Surgeons must pay attention to the coagulation state and thrombophilia in ESRD patients, give strong consideration for adequate anti-coagulation therapy and review the best renal replacement modality for each patient.

Animals↗
PubMed2004

Centrosome hyperamplification predicts progression and tumor recurrence in bladder cancer.

PURPOSE: Recent studies have reported that centrosome hyperamplification (CH) is closely related to chromosomal instability in bladder cancer. In this study, we investigated whether CH could be used as a prognostic biomarker for patients with bladder cancer. EXPERIMENTAL DESIGN: CH was evaluated by immunohistochemistry in 50 bladder cancers (< or =pT1: 43; > or =pT2: 7). In addition, numerical aberrations of chromosomes 7, 9, and 17 and gain of 20q13, on which the Aurora-A gene is located, were evaluated by fluorescence in situ hybridization, and DNA ploidy was assessed. Preliminary experiments on eight bladder cancer cell lines found that six had over 5% of CH cells associated with a gain of 20q13 and overexpression of Aurora-A; therefore, CH-positive cases (CH+) were defined as those having over 5% of cells with > or =3 centrosomes per cell. RESULTS: CH+, 20q13 gain, chromosomal instability, and DNA aneuploidy were detected in 30 (60%), 18 (36%), 22 (44%), and 19 (38%) patients, respectively. There were significant differences in tumor number, grade, recurrence, and progression between the CH+ and CH- groups. The later had significantly higher recurrence-free and progression-free survivals than the former (P = 0.0028 and P = 0.0070, respectively, log-rank test). Multivariate analysis revealed that CH+ was the strongest predictor for tumor recurrence in nonmuscle invasive (pTa and pT1) bladder cancer (hazard ratio, 1.882; 95% confidence interval, 1.161-3.325; P = 0.0094). CONCLUSIONS: Detection of CH may provide crucial prognostic information about tumor recurrence in bladder cancer.

Adult↗
PubMed2004

Association of a haplotype of matrix metalloproteinase (MMP)-1 and MMP-3 polymorphisms with renal cell carcinoma.

It has been shown that the matrix metalloproteinase (MMP)-1 promoter polymorphism 1G/2G is associated with an increased risk of developing various cancers including renal cell carcinoma (RCC), and is in linkage disequilibrium (LD) with the MMP-3 promoter polymorphism 5A/6A. These two genes are localized in 11q22 adjacent to each other. However, the relationship between the MMP-3 5A/6A polymorphism and susceptibility to cancer remains ambiguous. In this study, we genotyped eight polymorphisms in the region containing the MMP-1 and MMP-3 genes in 177 healthy subjects, and explored the relationships between RCC and these polymorphisms or haplotypes in 156 RCC cases and 230 age- and gender-matched controls. All the subjects studied were of Japanese descent. There were three polymorphisms that showed stronger LD with the MMP-1 1G/2G promoter variant than with the MMP-3 5A/6A promoter variant. One of these three polymorphisms was present in exon 2 of the MMP-3 gene and caused an amino acid change, Glu45Lys (G/A). When the genotype distribution of Glu45Lys was compared between RCC patients and controls, the frequency of the G/G genotype was significantly higher in the patients [age- and gender-adjusted odds ratio (OR) = 1.81, 95% confidence interval (CI) = 1.20-2.74]. A significant increase in the frequency of the 2G/2G genotype of the MMP-1 1G/2G polymorphism was also observed in the patients (age- and gender-adjusted OR = 1.86, CI = 1.23-2.82), whereas there was no significant difference for the MMP-3 5A/6A polymorphism. As expected based on these genotype-level results, the frequency of the 2G-G haplotype of MMP-1 1G/2G and MMP-3 Glu45Lys (G/A) polymorphisms was significantly higher in the patients than in the controls (crude OR = 1.95, CI = 1.31-2.91). These findings suggest that this haplotype of MMP-1 and MMP-3 variants may be associated with the risk of developing RCC.

Adult↗
PubMed2004

DNA sequence copy number aberrations in prostate cancers: a comparison of comparative genomic hybridization data between Japan and European countries.

Incidence of prostate cancer in Japan and resultant mortality rates are lower than in Western countries. To elucidate the reasons behind this, the genetic characteristics of prostate cancer in Japanese patients were investigated. Comparative genomic hybridization was applied in 27 cases of prostate cancers in Japanese patients. Frequent gains were found at Xq, 8q, Xp, and 7q and frequent losses at 8p, 6q, 2q, 16q, and 17p (in decreasing order of frequency). Loss of 6q was frequently detected in both early and advanced tumors. Gains of 7q and 8q and loss of 8p were more frequent in advanced than early tumors. The frequency of 13q loss in primary tumors was significantly lower in patients in Japan than in European countries. These data suggest that a loss of 6q is associated with the development of prostate cancer, and that gains of 7q and 8q and a loss of 8p are linked with cancer progression. The frequency of 13q loss may imply differences in biological behavior of prostate cancer between Japan and Western countries.

Aged↗
PubMed2004

Accuracy of an array comparative genomic hybridization (CGH) technique in detecting DNA copy number aberrations: comparison with conventional CGH and loss of heterozygosity analysis in prostate cancer.

Although genomic DNA microarray (array comparative genomic hybridization [CGH]) technique is a rapid and powerful diagnostic tool for the comprehensive analysis of detailed chromosomal alterations of DNA copy numbers, its accuracy has not been well demonstrated. To clarify the accuracy of this technique, we applied array CGH spotted with 283 specific genes to 11 clinical prostate cancers, and the results were compared with comparative genomic hybridization (conventional CGH) and loss of heterozygosity (LOH) analysis using microsatellite DNA markers. The overall rate of correspondence between array CGH and conventional CGH with respect to the loss of DNA sequences was 94.5%. When the results of both CGH techniques were compared with those of LOH analysis, the correspondence rate of array CGH was significantly higher than that of conventional CGH (93.4% vs. 72.2%, P<0.05). In conclusion, the accuracy of array CGH was higher than that of conventional CGH in detecting losses of the DNA sequences. Array CGH is shown to be a promising tool for screening to identify unknown genes involved in tumorigenesis in prostate cancer.

Aged↗
PubMed2004

Does surgical repair of pelvic prolapse improve patients' quality of life?

OBJECTIVES: The aims of this study were to evaluate the efficacy of surgical repair in patients with pelvic prolapse, and to assess the postoperative quality of life (QOL). METHODS: A total of 70 patients (mean age: 66.7 years) underwent transvaginal two-corner bladder neck suspension in combination with transvaginal hysterectomy (63 cases), and anterior with (49) or without (21) posterior colporrhaphy. The status of recurrence and complications were followed in all patients at a mean follow-up period of 32.0 months. Postoperative patients' quality of life (QOL) consisting of four items (sensation of vaginal bulging, urinary incontinence, difficulty to urinate, and health-related QOL) was assessed in 52 cases whose were followed at least two years (mean: 41.6 months, range: 24.3-69.1). RESULTS: Sixty-eight patients (97%) were recurrence-free. Nine of the 39 (23%) patients with difficulty to urinate before surgery had persistent symptoms postoperatively. Multivariate analysis revealed that cystometric abnormalities, voiding symptoms at seventh days after surgery, and weak detrusor contraction were independent prognostic factors for persistent voiding symptoms. As for the QOL, all items had significant improvement at 13 months after surgery as compared to baseline condition. A longitudinal study showed improvement of these symptoms sustained at least up to four years. CONCLUSIONS: This study suggests that surgical repair can achieve results with long-term durability as well as improving the QOL. In addition, assessment of the detrusor function may be needed for patients who complain difficulty to urinate in avoiding persistent such symptoms.

Adult↗
PubMed2004

Novel prophylactic effect of doxifluridine in superficial bladder cancer.

OBJECTIVES: The prophylactic effect of 5'-deoxy-5-fluorouridine (5'-DFUR) has not been fully studied in superficial bladder cancer. The aims of this work were to investigate the prophylactic effects of 5'-DFUR in terms of tumor recurrence after transurethral resection of bladder tumor (TURBT) and to study whether thymidine phosphorylase (TdRPase) immunostaining predicts tumor recurrence. MATERIAL AND METHODS: A total of 112 patients with pTa or pT1 bladder cancer were eligible for the analysis and were allocated to either an adjuvant group (TURBT+5'-DFUR; n = 47; initial 23 months) or a control group (TURBT alone; n = 65, final 23 months). Tumor specimens were studied immunohistochemically using anti-TdRPase antibody. RESULTS: Tumor recurrence was observed in 54 of the patients (48%) after a median follow-up period of 26.8 months. No significant clinico-pathologic bias was observed between the two groups. Although patients in the adjuvant group had a significantly higher recurrence-free survival rate than those in the control group when considering 78 patients with pathological T1 tumors (p = 0.0272) and 65 patients who did not recur within 12 months (p = 0.001), overall there was no significant difference between the two groups. Multivariate analysis revealed that 5'-DFUR administration was the strongest predictor of late tumor recurrence, which was defined as development of recurrence 12 months after TURBT (hazard ratio 5.744; 95% CI 1.495-30.45; p = 0.0094). Immunostaining did not predict prophylactic effects of 5'-DFUR. Mild, reversible toxicity was found in 9/58 (15.5%) of the cases evaluated. CONCLUSIONS: Oral administration of 5'-DFUR after TURBT did not prevent tumor recurrence in the overall cohort, although this novel drug may have a prophylactic effect in patients belonging to several subgroups.

Administration, Oral↗
PubMed2004

Bax to Bcl-2 ratio and Ki-67 index are useful predictors of neoadjuvant chemoradiation therapy in bladder cancer.

OBJECTIVE: In this study, locally advanced bladder cancer was treated by radiation combined with cisplatin therapy and a retrospective analysis was conducted to predict the clinical response to chemoradiotherapy (CRT) based on the immunohistochemistry of apoptosis-related proteins. METHODS: Sixty-two patients (median age, 68 years; range, 45-89 years) with transitional cell carcinoma of the bladder (pT1G3-pT4M0) treated with CRT (median dose: 40.5 Gy of radiation and 230 mg of cisplatin) were studied. Mucosal biopsy was performed before and after CRT. Paraffin-embedded tumor specimens were examined with TUNEL and were immunostained for Ki-67, p53, Bcl-2 and Bax; the Bax/Bcl-2 ratio and apoptosis index (AI) were calculated. Clinical features of the patients and response to CRT were compared with data obtained from examination of the tumors. RESULTS: The 62 patients had a median follow-up period of 34 months (range, 3-84 months). Responses to CRT were as follows: CR, 34%; PR, 45%; NC, 21%. The survival rate of patients with Ki-67-positive tumors was significantly lower than those of patients with Ki-67-negative tumors (P < 0.05). No significant correlation was observed between the expression of any protein, the AI and the clinical response. However, the Bax/Bcl-2 ratio showed a significant association with the CR rate (P = 0.0289). CONCLUSIONS: The results of this study suggest that the combined assessment of Bcl-2 and Bax protein expression may be used to predict a clinical response to CRT based on the Bax/Bcl-2 ratio determined before therapy. The Ki-67 index may be a useful predictor of prognosis in patients treated by CRT.

Aged↗
PubMed2004

[True hermaphroditism].

True hermaphroditism in humans is defined as the simultaneous presence of both testicular and ovarian tissue in a single individual. I reviewed clinical findings, karyotype, findings of recent molecular analysis, diagnostic tools and treatment of true hermaphroditism. Recent molecular analysis in true hermaphroditism revealed that duplication of 22q was recognized in a 46,XX SRY-negative case. A 46,XX true hermaphrodite in which SRY was negative in blood leukocytes and epithelial oral cells but present and partially deleted in DNA obtained from the testicular portion of the ovotestes was reported. And also, the study using PCR and FISH analyses revealed the presence of hidden mosaicism for SRY or other Y sequences in some patients with XX true hermaphroditism and mosaicism for SRY limited to the gonads is an alternative mechanism for testicular development in 46,XX true hermaphrodites.

Diagnosis, Differential↗
PubMed2003

Heat shock transcription factor 1 is involved in quality-control mechanisms in male germ cells.

Quality-control mechanisms in spermatogenesis are important to eliminate injured or abnormal cells, thereby protecting the organism from abnormal development in the next generation. The processes of spermatogenesis are highly sensitive to high temperatures; however, the mechanisms by which injured germ cells are eliminated remain unclear. Here, we found that heat shock proteins are not induced in male germ cells in response to thermal stress, although heat shock transcription factor 1 (HSF1) is activated. Using HSF1-null mice, we showed that apoptosis of pachytene spermatocytes was markedly inhibited in testes with a single exposure to heat and in the cryptorchid testes, indicating that HSF1 promotes apoptotic cell death of pachytene spermatocytes exposed to thermal stress. In marked contrast, HSF1 acts as a cell-survival factor of more immature germ cells, probably including spermatogonia, in testes exposed to high temperatures. These results demonstrate that HSF1 has two opposite roles in male germ cells independent of the activation of heat shock genes.

Animals↗
PubMed2003

A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter is associated with conventional renal cell carcinoma.

Matrix metalloproteinase (MMP)-1 is associated with tumor cell invasion and metastasis, and its promoter polymorphism has been shown to influence the transcriptional level. Our study explored the association between this polymorphism and renal cell carcinoma in a Japanese population. DNA was extracted from peripheral blood and normal tissue of 119 patients with conventional renal cell carcinoma (RCC) and from 210 age- and sex-matched healthy volunteers. Genotyping was carried out using direct sequencing. In the MMP-1 gene promoter polymorphism, it was demonstrated that the frequency of the 2G/2G genotype, which is associated with higher enzyme activity, was significantly higher in patients with RCC than in controls (p = 0.0015; OR = 2.082; 95% CI 1.317-3.293). When stratified for gender, only men showed a significant association of the polymorphism with RCC (p = 0.0028; OR = 2.307; 95% CI 1.333-3.990). However, no significant association was observed between the 2G/2G genotype and clinicopathologic parameters including age, gender, tumor grade and pathologic stage. Our present data suggest that the MMP-1 promoter polymorphism may be linked to susceptibility for conventional RCC.

Adult↗
PubMed2003

Urinary interleukin-2 may predict clinical outcome of intravesical bacillus Calmette-Guérin immunotherapy for carcinoma in situ of the bladder.

PURPOSE: The mechanism by which bacillus Calmette-Guérin (BCG) mediates antitumor activity has not been clearly established. Specific cytokines in the urine after BCG intravesical instillation therapy may serve as a prognostic factor of treatment response. In this study, various urinary cytokines such as interleukin-1beta (IL-1beta), IL-2, IL-6, IL-8. IL-10, IL-12, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) were measured. MATERIALS AND METHODS: In total 20 patients were treated with BCG intravesical instillation therapy for carcinoma in situ of the bladder. At the completion of the first and eighth instillations, spontaneously voided urine specimens were collected before BCG instillation, every 2 h until 12 h, and thereafter until 24 h. All specimens were ultrafiltrated using an ADVANTEC UK-10 membrane. The cytokines were measured using ELISA and RIA techniques. RESULTS: Significantly higher levels of IL-2, IL-6, IL-8, IL-10, IFN-gamma, and TNF-alpha were detected in the eighth instillation as compared to the first instillation ( p<0.001). After BCG intravesical instillation therapy, treatment failure occurred in 6 of the 20 patients (30%), including primary failure (persistence of CIS) in 3, and de novo failure (tumor recurrence) in 3 with a median follow-up of 46.9 months. Significantly higher production of IL-2, IL-6, IL-8, IL-10, and TNF-alpha was observed in the responder group than in the non-responder group ( p<0.05). Multivariate analysis revealed IL-2 as an independent prognostic cytokine of responder status. CONCLUSIONS: This study indicates that urinary IL-2 at the eighth instillation of BCG may serve as a valuable prognostic factor of treatment efficacy as well as tumor recurrence after treatment.

Administration, Intravesical↗