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Katsusuke Naito

Publications and source records attributed to Katsusuke Naito.

At least 19 recordsLinked to original sources
PubMed2007

Long-term results of first-line sequential high-dose carboplatin, etoposide and ifosfamide chemotherapy with peripheral blood stem cell support for patients with advanced testicular germ cell tumor.

OBJECTIVE: Standard chemotherapy shows relatively low long-term survival in patients with poor-risk testicular germ cell tumor (GCT). First-line high-dose chemotherapy (HD-CT) may improve the result. High-dose carboplatin, etoposide, ifosfamide chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) was investigated as first-line chemotherapy in patients with advanced testicular GCT. METHODS: Fifty-five previously untreated testicular GCT patients with Indiana 'advanced disease' criteria received three cycles of bleomycin, etoposide and cisplatin (BEP) followed by one cycle of HD-CT plus PBSCT, if elevated serum tumor markers were observed after three cycles of the BEP regimen. RESULTS: Thirty patients were treated with BEP alone, because the tumor marker(s) declined to normal range. Twenty-five patients received BEP and HD-CT. One patient died of rhabdomyolysis due to HD-CT. Three and six (13% and 25%) out of 24 patients treated with BEP and HD-CT achieved marker-negative and marker-positive partial responses, respectively. The other patients achieved no change. Fifteen (63%) are alive and 14 (58%) are free of disease at a median follow-up time of 54 months. Severe toxicity included treatment-related death (4%). CONCLUSIONS: HD-CT with peripheral stem cell support can be successfully applied in a multicenter setting. HD-CT demonstrated modest anticancer activity for Japanese patients with advanced testicular GCT and was well tolerated. This regimen might be examined for further investigation in randomized trials in first-line chemotherapy for patients with poor-risk testicular GCT.

Adolescent↗
PubMed2006

Mass spectrometry analysis of the native protein complex containing actinin-4 in prostate cancer cells.

Actinin-4 was originally identified as an actin-binding protein associated with cell motility and cancer invasion and metastasis. However, actinin-4 forms complexes with a large number of different partner proteins and is speculated to have several distinct functions depending on its partner. The level of actinin-4 expression was found to be significantly lower in prostate cancer cells than in non-cancerous basal cells, and restoration of actinin-4 expression inhibited cell proliferation by prostate cancer cell line 22RV1. Immunoprecipitation and mass spectrometry analysis revealed that actinin-4 forms native complexes with several partner proteins in 22RV1 cells, including with beta/gamma-actin, calmodulin, the clathrin heavy chain, non-muscular myosin heavy chain, heterogeneous nuclear ribonucleoprotein A1, and Ras-GTPase-activating protein SH3 domain-binding protein. Clathrin is a coat protein that covers the internalized membrane pit that forms during early endocytosis. We found that other clathrin-related and unrelated cargo proteins, including dynamin, adaptin-delta, beta subunit of neuronal adaptin-like protein, and p47A, also interact with actinin-4. Immunofluorescence microscopy revealed that dynamin and clathrin co-localized with actinin-4 at the sites of membrane ruffling, and transfection of actinin-4 cDNA facilitated the transport of transferrin into perinuclear endosomes. Endocytosis terminates signaling evoked by cell surface receptors and regulates the recycling of receptors and ligands. We identified a panel of proteins whose expression and/or subcellular localization was regulated by actinin-4 by performing organelle fractionation and ICAT-LC-MS/MS. The decreased expression of actinin-4 protein in prostate cancer cells may cause aberrations in the intracellular trafficking of various cell surface molecules and contribute to carcinogenesis.

Actinin↗
PubMed2006

Chromosome 20q13.2 gain may predict intravesical recurrence after nephroureterectomy in upper urinary tract urothelial tumors.

PURPOSE: Amplification or gain of copy number of chromosome 20q13.2 has been implicated as a causal factor for chromosome instability. We investigated the impact of chromosomal instability and its causative molecular markers, 20q13.2 gain and centrosome amplification, on patient outcome in upper urinary tract transitional cell carcinoma (UUT-TCC). EXPERIMENTAL DESIGN: The number of centrosomes was assessed by immunohistochemistry. Numerical aberrations of chromosomes 7, 9, and 17 that allowed the estimation of chromosomal instability and 20q13.2 gain were evaluated by fluorescence in situ hybridization in 96 frozen specimens from UUT-TCC and compared with clinicopathologic background and patient outcome. RESULTS: Chromosomal instability, 20q13.2 gain, and centrosome amplification were detected in 62 of 96 (64.6%), 61 of 96 (63.5%), and 45 of 90 (50.0%) tumors, respectively. 20q13.2 Gain was significantly associated with tumor stage (P = 0.042), chromosomal instability (P < 0.0001), and centrosome amplification (P < 0.0001). Kaplan-Meier analysis showed that 20q13.2 gain was strongly associated with intravesical recurrence-free survival in all patients (P = 0.0050), as well as in patients with grade 2 tumors (P = 0.0011, log-rank test). On multivariate analysis, 20q13.2 gain was found to be the sole independent prognostic factor predicting subsequent intravesical recurrence (hazard ratio, 1.65; 95% confidence interval, 1.03-2.90; P = 0.036). CONCLUSIONS: 20q13.2 gain was strongly associated with a reduced time to intravesical recurrence in all patients. Our data suggest that 20q13.2 gain may be a predictive marker of intravesical recurrence in patients with UUT-TCC.

Aged↗
PubMed2006

Overexpression of polo-like kinase 1 (PLK1) and chromosomal instability in bladder cancer.

Polo-like kinase 1 (PLK1) participates in bipolar spindle formation and entry into mitosis. Chromosomal instability (CIN) is caused by abnormalities in spindle formation and chromosome segregation. In this study, we investigated the relationship of PLK1 overexpression to CIN, and compared the PLK1 status with clinicopathological parameters in 101 human urothelial carcinomas of the urinary bladder. Expression of PLK1 and the number of centrosomes were assessed by immunohistochemistry. Numerical aberrations of chromosomes 7, 9 and 17 spots that allowed estimation of CIN were evaluated by fluorescence in situ hybridization, and DNA ploidy was assessed by laser scanning cytometry. Cancers with a large intercellular variation in centromere copy number were defined as CIN cancers. Tumors with PLK1 overexpression were associated more frequently with CIN (p < 0.0001), DNA aneuploidy (p = 0.0007) and centrosome amplification (p = 0.0013) than those without. Overexpression of PLK1 was significantly related to higher pathological grade (p = 0.0024), multiple tumors (p = 0.0241) and positive urine cytology (p = 0.0192). These data suggest that a high level expression of PLK1 confers tumor progression advantages to urothelial cancer cells, although other factors are also involved.

Adult↗
PubMed2006

Generation of 4-hydroxy-2-nonenal modified proteins in testes predicts improvement in spermatogenesis after varicocelectomy.

Increasing evidence suggests that testes with varicocele are exposed to oxidative stress (OS) with deterioration in spermatogenesis; however, the relationship between testicular OS and outcome after varicocelectomy is poorly understood. Levels of testicular 4-hydroxy-2-nonenal modified proteins, an OS marker, were significantly higher in responders than in nonresponders, suggesting that varicocelectomy reduces OS in testis.

Adult↗
PubMed2006

Biological characteristics in bladder cancer depend on the type of genetic instability.

PURPOSE: Malignant tumors show an inherent genetic instability that can be classified as microsatellite instability (MSI) or chromosomal instability (CIN). To elucidate the differences in biological characteristics of bladder cancer between the two types of genetic instability, the expression of the mismatch repair (MMR) proteins, Aurora-A and p53 proteins, the number of centrosomes, numerical aberrations of chromosomes and 20q13, and DNA ploidy were examined in 100 human urothelial carcinomas of the bladder. EXPERIMENTAL DESIGN: Expressions of the MLH1, MSH2, Aurora-A, and p53 proteins and the numbers of centrosomes were immunohistochemically assessed. Numerical aberrations of chromosomes 7, 9, 17, and 20q13 spots were evaluated by fluorescence in situ hybridization, and DNA ploidy was assessed by laser scanning cytometry. RESULTS: The expression levels of the MMR related-proteins decreased in 9 of 100 tumors. Tumors with low MLH1 or MSH2 expression (designated as MSI cancers) were not linked with centrosome amplification, Aurora-A overexpression, increased p53 immunoreactivity, 20q13 gain, DNA aneuploidy, and disease progression. MSI cancers showed a favorable prognosis. CIN cancers (49 cases), defined as tumors with a large intercellular variation in centromere copy numbers, were associated more frequently with centrosome amplification, Aurora-A overexpression, increased p53 immunoreactivity, and 20q13 gain than the others (51 cases). Tumors with disease progression were included in the CIN cancer group. CONCLUSIONS: The present observations suggest that there are differences in the biological characteristics of the two types of genetic instability.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Evidence that FTY720 induces rat thymocyte apoptosis.

FTY720, a novel immunomodulator with the potential to improve immunosuppressive therapy after organ transplantation, is currently under clinical investigation. FTY720 drastically decreases blood lymphocytes, especially T cells, accelerating lymphocyte homing to secondary lymphoid organs. However, its immunosuppressive effects remain unknown. We investigated these effects in rat thymocytes. Rats were intramuscularly injected with 10mg/kg/day FTY720 or saline for 7days. Thymuses were removed on days 0, 1, 3, 5, 7 and 14 after treatment. Three-color analysis was performed with a flow cytofluorometer. Apoptotic nuclei in the tissue sections were identified by TUNEL. Genomic DNA was then extracted and samples were electrophoresed on 2.0% agarose gel. FTY720 reduced the total number of thymocytes and, with time, significantly reduced the percentage of CD4+8+ TCRalphabeta(negative/low) thymocytes. Light microscopy of thymuses of FTY720-treated rats revealed obvious reductions in the size of the cortical region. TUNEL analysis showed that FTY720 induced thymocyte apoptosis in the cortical region. Furthermore, DNA fragmentation was observed in thymocytes treated with FTY720, indicating thymocyte apoptosis. FTY720 reduced the number of CD4+8+ thymocytes before TCRalphabeta expression resulting in impaired thymocyte differentiation and maturation. This might be an immunosuppressive effect of FTY720.

Animals↗
PubMed2006

Polymorphisms of DNA repair genes are associated with renal cell carcinoma.

DNA repair gene alterations have been shown to cause a reduction in DNA repair capacity and may influence an individual's susceptibility to carcinogenesis. Single nucleotide polymorphisms (SNPs) of DNA repair genes have been shown to cause a reduction in repair activity. We hypothesized that SNPs of DNA repair genes may be a risk factor for renal cell carcinoma (RCC). To test this hypothesis, DNA samples from 112 cases of renal cell cancer and healthy controls (n=180) were analyzed by PCR-RFLP to determine the genotypic frequency of six different polymorphic loci on five DNA repair genes (XRCC1, XPC, ERCC1, XRCC3, and XRCC7). The chi(2) test was applied to compare the genotype frequency between patients and controls. We found that the frequency of 399Gln variant at XRCC1 Arg399Gln was significantly higher in RCC cases than in controls (OR=2.83, 95%CI=1.24-6.49, P=0.01). The frequency of T-A haplotype of XRCC1 194 Trp and XRCC1 399Gln was significantly higher in RCC than controls. No differences in genotypes were observed at the other sites. This is the first report on SNPs of DNA repair genes in renal cell carcinoma that suggests XRCC1 399Gln polymorphism may be a risk factor for RCC. Our present data suggest that the XRCC1 399Gln allele may be linked to susceptibility for RCC.

Adult↗
PubMed2006

Salvage chemotherapy with paclitaxel, ifosfamide, and nedaplatin in patients with urothelial cancer who had received prior cisplatin-based therapy.

BACKGROUND AND AIMS: The aim of the present phase II study was to evaluate the efficacy of combination chemotherapy of paclitaxel, ifosfamide, and nedaplatin (PIN regimen) in patients with recurrent urothelial cancer who had been treated with cisplatin-based chemotherapy. PATIENTS/METHODS: Eligible patients were those with histologically confirmed urothelial cancer who had progressed or relapsed after cisplatin-based chemotherapy. The PIN regimen consisted of paclitaxel 175 mg/m(2) on day 1; ifosfamide 4.5 g/m2 divided over days 1, 2, and 3; and nedaplatin 70 mg/m(2) on day 1; PIN was given every 28 days. RESULTS: Among the 32 patients enrolled in the study (median age, 66 years), complete and partial responses were obtained in 5 patients and 19 patients, respectively, with an overall response rate of 75% (95% confidence interval [CI], 59-91%). The median time to progression was 8 months (range, 0-50+ months) and the median survival was 22 months (range, 4-52+ months). The 1- and 2-year overall survival rates were 53.7 and 42.9%, respectively. All patients experienced Grade 3 or 4 neutropenia, while Grade 3 or 4 thrombocytopenia was seen in 8 patients; Grade 3 or 4 anemia was seen in 6 patients; Grade 3 neuropathy was observed in 1 patient, for whom the PIN therapy was discontinued. There were no treatment-related deaths. CONCLUSION: The PIN combination was highly active and tolerable in previously treated patients with urothelial cancer as a second-line treatment.

Adult↗
PubMed2006

Follow up of surgical repair of female pelvic floor disorders by a mailed questionnaire.

BACKGROUND: This study was conducted to determine whether surgical repair of pelvic prolapse enhances patients' quality of life (QOL) in the long term. METHODS: A total of 91 patients (median age, 68.0 years) with pelvic prolapse including cystoceles underwent bladder neck suspension with anterior/posterior colporrhaphy between 1997 and 2003. Postoperative QOL was longitudinally assessed by three disease-specific items (sensation of vaginal bulging, obstructive symptoms, urinary incontinence), and one overall health-related QOL (HR-QOL) item. RESULTS: A longitudinal study demonstrated that a significant improvement in these symptoms was sustained at a median follow up of 65.5 months, although poor HR-QOL was significantly higher in patients whose age was more than 70 years at surgery (P = 0.0234, Fisher's test). Multivariate analysis revealed update urinary incontinence, update obstructive symptoms, and basic comorbidity to be independent prognostic factors for predicting postoperative moderate-to-poor HR-QOL. CONCLUSIONS: Longer follow up with adequate assessment of patients' QOL may be crucial for the management of postoperative patients, in particular those having basic comorbidity and aged 70 years or more at surgery.

Adult↗
PubMed2006

Angiotensin-II combined intra-arterial chemotherapy for locally advanced bladder cancer: a case series study at a single institution.

Patients with locally advanced bladder cancer are at significant risk for metastases. We aimed to evaluate the usefulness of intra-arterial chemotherapy (IAC) combined with angiotensin-II (AT-II) in such patients. The possibility of bladder preservation is also discussed. Patients were enrolled if they had muscle-invasive bladder cancer (stage T2 to T4NxM0). Cisplatin, pirarubicin, and AT-II were infused through the tumor-feeding arteries. Cause-specific survival was the end point. We enrolled 37 patients who were treated with neoadjuvant IAC and 5 patients with adjuvant IAC. There were 7 patients (16.7%) with pathological complete remission. Overall 5-year and 10-year survival rates of the patients were 61.3% and 47.7%, respectively. The 5-year cause-specific survival rate was 100% for the clinical T2 group and 63% for the T3-4 group, and the 8-year survival rate was 33% and 63%, respectively. There was no statistically significant difference between these two groups (P=0.445). Multivariable analysis using tumor number, pattern of growth, and tumor size seemed to independently correlate with cause-specific survival, but there were no significant differences. Our results suggest that intra-arterial chemotherapy combined with AT-II is a useful treatment for patients with locally advanced bladder cancer, since this modality achieves a favorable response rate without severe toxicity or mortality.

Aged↗
PubMed2006

Lower urinary tract symptoms in 1,912 apparently healthy persons of both sexes.

We aimed to evaluate lower urinary tract symptoms (LUTS) in apparently healthy persons of both sexes using the International Prostate Symptom Score (IPSS) and quality of life index (IPSS-QI) as related to aging. A total of 1,912 apparently healthy participants (1,052 women and 860 men) were enrolled in this study. They were informed as to the nature of the study and asked to fill out the IPSS questionnaires. The mean age of women was 46.8 years (range 18.0 to 83.0) and that of men was 48.5 years (range 19.0 to 76.0). The storage and voiding symptom scores gradually increased in parallel with increasing age in both sexes. The proportion of participants with moderate to severe symptoms (IPSS 8 or greater) increased from 5.6% in women younger than 30 years to 8.9, 15.7, 20.8, 21.0% and 28.6% for women 30 to 39, 40 to 49, 50 to 59, 60 to 69 and 70 years or older, respectively; the corresponding distribution for men was from 8.8 to 15.9, 18.7, 38.1, 48.6 and 68.8%, respectively. In both sexes, the majority of persons showed 1 or less nocturia. The distribution of IPSS-QI was very similar within each category of the IPSS severity in both sexes, showing that LUTS was equally bothersome to both sexes. These data should be taken into account to evaluate LUTS in both sexes.

Adult↗
PubMed2006

Identification of genes linked to gefitinib treatment in prostate cancer cell lines with or without resistance to androgen: a clue to application of gefitinib to hormone-resistant prostate cancer.

Understanding the molecular action of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, might allow us to perform more effective therapies for hormone-independent advanced prostate cancer. A DNA microarray study was undertaken to comprehensively analyze the alteration of levels of 1,081 genes after gefitinib treatment in androgen-independent PC3 and DU145 cells and androgen-dependent LNCaP cells. The proliferation of PC3, DU145 and LNCaP cells was significantly inhibited by 50.2%, 83.8% and 55.2%, respectively, 6 days after 10 microM gefitinib administration. Of the above 1,081 genes, we identified 23, 13 and 33 genes with significantly different expression in PC3, DU145 and LNCaP cells, respectively, 24 h after 10 microM-gefitinib exposure. Among the identified genes, only Quiescin Q6, a negative cell cycle regulator, was increased after gefitinib treatment in all three cell lines regardless of gefitinib sensitivity. Except for Quiescin Q6, there were no overlapping genes between PC3 and DU145 cells. However, levels of several oncogenes or proliferation-related genes were changed after gefitinib treatment in the 2 androgen-independent cell lines. We also identified 7 unique genes [glycyl-tRNA synthetase, interferon, alpha-inducible protein, stratifin, nuclear factor of kappa light polypeptide gene enhancer in B-cells 1, dual specificity phosphatase 9, guanine nucleotide binding protein (G protein) beta polypeptide 2, neural retina leucine zipper] whose levels were altered exclusively after gefitinib administration in gefitinib-resistant PC3 and LNCaP cells, but not in DU145 cells, suggesting that these 7 genes could be targets for overcoming gefitinib resistance. Collectively, our molecular profiling data will serve as a framework for understanding the molecular action of gefitinib for prostate cancer.

Androgens↗
PubMed2005

Association of the BCRP C421A polymorphism with nonpapillary renal cell carcinoma.

Breast cancer resistance protein (BCRP), the second member of the ATP-binding cassette membrane transporter family, has a single nucleotide polymorphism, C421A (resulting in Q141K), that is of functional importance. Our aim was to explore the relationship between this polymorphism of the BCRP gene and the risk of renal cell carcinoma (RCC) development. For a case-control study, DNA samples from 200 nonpapillary RCC patients and 200 healthy control subjects were analyzed using the TaqMan technique. The genotypic frequencies of the BCRP C421A polymorphism were compared between RCC patients and control subjects. The frequency of the C/C genotype was significantly higher in RCC patients than in control subjects (age- and gender-adjusted OR = 1.96, 95% CI 1.32-2.93). No associations were observed between the BCRP C421A polymorphism and clinicopathologic or epidemiologic factors, including age, gender, tumor grade, stage, cigarette smoking, family history of cancer and body mass index. Carriers with the C/C genotype of the BCRP C421A polymorphism are at risk of developing nonpapillary RCC. These data suggest that BCRP is a candidate RCC susceptibility gene.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2005

Impact of a genetic polymorphism of the interleukin-1 receptor antagonist on technique survival in peritoneal dialysis patients.

BACKGROUND/AIMS: There is a clear association between one allele of the interleukin-1 receptor-antagonist gene (IL-1RN) and inflammatory diseases in which IL-1 is implicated. We evaluated patient survival and technique survival of peritoneal dialysis (PD) patients, while analyzing independent risk factors, in a PD program. We also tested the association between IL-1RN polymorphism, patient survival and technique survival. METHODS: We retrospectively evaluated 129 Japanese CAPD patients undergoing initial treatment in eight centers in Japan. Using PCR, IL-1RN genotype and allele frequencies were determined, and clinical and biochemical variables were recorded at the start of PD. The relation of patient survival or technique survival with IL-1RN polymorphism and those variables was analyzed with a multivariate Cox's proportional-hazard model. RESULTS: The frequencies of IL-1RN*1/IL-1RN*1 and IL-1RN*1/IL-1RN*2 genotypes were 84.5 and 15.5%, respectively. Median patient survival was 37.0 months, and overall patient survival was 92.8 and 87.9% at 2 and 5 years, respectively. Age, cardiovascular disease and serum albumin were found to be independent predictors of patient survival. Median technique survival was 32 months. PD failure occurred in 37 patients, with technique survival rates of 92.0 and 72.7% at 2 and 5 years, respectively. Serum albumin, peritonitis and the presence of the IL-1RN*2 genotype were found to be independent predictors of technique survival. CONCLUSION: Serum albumin was the strongest predictive factor for mortality and technique failure in PD. Technique failure was also affected by IL-1RN polymorphism in this patient population.

Adult↗
PubMed2005

Allelic loss of 3p25 associated with alterations of 5q22.3 approximately q23.2 may affect the prognosis of conventional renal cell carcinoma.

Little is known about the clinical significance at the frequent association of 3p loss with 5q gain/loss in conventional renal cell carcinoma (RCC). We analyzed the clinical significance of copy number gain and loss at 5q21 approximately q23 combined with allelic loss of 3p25 (including the VHL gene). Fifty RCCs were examined by dual-color fluorescence in situ hybridization with DNA probes for D3Z1 (3cen), cCI3-865 (3p25.1 approximately p25.3), D5S23 (5p15.2), cCI5-243 (5q21.2 approximately q21.3), and cCI5-215 (5q22.3 approximately q23.2). In patients who had 3p loss, there was a significant association of loss at 5q22.3 approximately q23.2 with large tumors (>7 cm) and high-grade tumors (both P < 0.05), whereas gain at 5q22.3 approximately q23.2 was associated with low-grade tumors (P < 0.05). There was also a significant association loss at 5q21.2 approximately q21.3 high-grade tumors in patients with 3p loss (P < 0.05). Patients with 3p loss and gain at 5q22.3 approximately q23.2 had a significantly better disease-specific survival than those who had 3p loss without such gain (P < 0.05). Allelic loss of 3p25 including the VHL gene is thought to be an immediate event in the development of conventional RCC. Copy number gains or losses of 5q21 approximately q23 are thought to be events that lead to tumor progression although the clinical significance of either gains or losses is not well known.

Carcinoma, Renal Cell↗
PubMed2005

Deletion mapping of 18q in conventional renal cell carcinoma.

Loss of heterozygosity (LOH) is frequently associated with the inactivation of tumor suppressor genes. 18q LOH has been frequently reported in colorectal cancer and lung cancer; however, allelic loss on 18q has not been investigated in renal cell carcinoma (RCC). We evaluated LOH on 18q using nine microsatellite markers in 126 with conventional RCC (cRCC). LOH was observed in more than one 18q microsatellite locus in 24 cRCC (19%). We found the highest frequency of LOH (13.5%) at 18q21.3, where the DCC gene is located. We also assessed the relationship between LOH frequency and patient clinical parameters. Patients with a family history of cancer had a significantly higher frequency of 18q LOH than those without such a history (P=0.0017). No associations were found with other parameters, including gender, tumor grade, tumor stage, smoking status, and body mass index. The results suggest that inactivation of tumor suppressor genes at 18q21.3, including DCC and SMAD4 as candidates, may be involved in the tumorigenesis of some conventional RCCs.

Adult↗