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Tomonori Habuchi

Publications and source records attributed to Tomonori Habuchi.

At least 91 records · Page 5Linked to original sources

Increased risk of prostate cancer and benign prostatic hyperplasia associated with transforming growth factor-beta 1 gene polymorphism at codon10.

Transforming growth factor-beta 1 (TGF-beta1) plays a significant role in regulating the proliferation and apoptosis of prostate epithelial and stromal cells. We explored the association between the T (Leu) to C (Pro) polymorphism at codon10 of the TGF-beta1 gene (TGFB1) and the risk of prostate cancer (PCa) or benign prostatic hyperplasia (BPH) in 351 PCa patients, 221 BPH patients and 303 male controls in Japan. There were significant differences in the CC versus TC + TT genotype distribution between PCa patients and male controls (P=0.008), and between BPH patients and male controls (P=0.041). Males with the TC or TT genotype had a 1.62-fold increased risk of PCa [95% confidence interval (95% CI)=1.14-2.30, P=0.007] and a 1.51-fold increased risk of BPH (95% CI=1.02-2.24, P=0.041) compared with those with the CC genotype, therefore suggesting the dominant effect of the TGFB1 T allele on development of PCa and BPH. There were no significant differences in the TGFB1 genotype distribution between different groups of tumor grades and stages in the PCa patients and no significant differences when PCa patients were stratified by the age of onset. The results suggest that the codon10 polymorphism in TGFB1 may have a significant influence on the development of PCa and BPH, therefore underscoring the importance of the TGF pathway in the development of these prostatic diseases. However, it appeared to have no impact on the disease status or age of onset of PCa.

Aged↗

Factors that influence the results of salvage surgery in patients with chemorefractory germ cell carcinomas with elevated tumor markers.

BACKGROUND: A standard concept for the integration of surgery into the chemotherapy-based treatment of patients with advanced germ cell carcinoma has been that surgery should be avoided in patients with serum tumor markers (alpha-fetoprotein [AFP] and human chorionic gonadotropin [HCG]) that remain elevated. However, some patients may benefit from resection under such chemorefractory conditions. The objective of this retrospective study was to clarify the outcome and clinical prognostic variables of salvage surgery in patients with disseminated (AJCC Stage II or III) testicular germ cell carcinoma or extragonadal germ cell carcinoma who had elevated serum markers. METHODS: The authors reviewed the clinical records of 24 patients who underwent salvage surgery with elevated serum AFP and/or HCG levels after at least 3 courses of cisplatin-based, systemic chemotherapy between January, 1985 and December, 2000. The survival rates were compared between the subgroups with regard to preoperative and postoperative clinical parameters using the Kaplan-Meier method and a Cox proportional hazards model. RESULTS: Ten of 24 patients (41.7%) were rendered free of disease and alive without disease after the surgery with or without adjuvant therapy at a median follow-up of 74 months (range, 24-207 months). Among the preoperative parameters, high HCG levels were associated with significantly poorer survival (hazard ratio [HR], 8.321; 95% confidence interval [95% CI], 1.0753-64.553; P = 0.043 and P = 0.016, respectively; log-rank test). In addition, patients who had visceral lesions at resection had a significantly poorer prognosis compared with patients who had retroperitoneal and/or mediastinal lymph node lesions (P = 0.038; log-rank test). Among postoperative parameters, incomplete resection and persistently high HCG levels were associated significantly with poor survival, with a risk of death from disease of 12.516-fold (95% CI, 1.786-87.781) and 9.311-fold (95% CI, 1.796-48.256), respectively. CONCLUSIONS: Salvage surgery in patients with high serum tumors markers resulted in long-term disease free status in approximately 40% of patients in a small subset with advanced germ cell carcinoma. Patients with elevated AFP levels alone (i.e., normal HCG levels) or with lymph node lesions alone seem to be good candidates for such surgery. Complete resection of target lesions and normalization of HCG levels after surgery are mandatory to achieve long-term disease free status.

Adolescent↗

Insulin-like growth factor-binding protein-3 gene -202 A/C polymorphism is correlated with advanced disease status in prostate cancer.

The circulating level of insulin-like growth factor-binding protein-3 (IGFBP-3) is inversely associated with the risk of prostate cancer (PCa) and its progression and may be modulated by the A/C polymorphism at position -202 in the promoter region of IGFBP-3. This study was conducted to evaluate the role of the A/C polymorphism as a genetic modifier in the etiology of PCa and its disease status. The polymorphism was analyzed by a PCR restriction fragment-length polymorphism technique in 307 PCa patients, 221 benign prostatic hyperplasia (BPH) patients, and 227 male controls. No significant difference in the genotype frequency was found between the PCa or BPH patients and controls (PCa versus control, P = 0.316; BPH versus control, P = 0.964). Regarding the tumor stage, the C allele was more frequently observed in patients having tumors with higher stage (P for trend = 0.002). When the PCa patients with localized disease (stage A + B + C) were considered as reference, those with CC and AC genotype had a significantly increased risk of metastatic disease (stage D) compared with those with AA genotype [age-adjusted odds ratio (aOR) = 3.89, 95% confidence interval (CI) = 1.42-10.64, P = 0.008, and aOR = 1.68, 95% CI = 1.01-2.79, P = 0.044, respectively]. The presence of the C allele appeared to be associated with an increased risk of metastatic PCa with a gene dosage effect (aOR = 1.82, 95% CI = 1.23-2.68, P = 0.002). Similarly, significant findings were also observed when PCa patients were compared between those with organ-confined disease (stage A + B) and those with extra-prostatic extension (stage C + D). Furthermore, the C allele was present more frequently in patients with higher tumor grade. In conclusion, the IGFBP-3 -202 A/C polymorphism was not associated with susceptibility to PCa and BPH in Japanese men, but the presence of the C allele may cumulatively increase the risk for tumor metastasis and for having tumors with a biologically more aggressive phenotype. Because of the significant differences in incidence of clinically evident PCa according to racial backgrounds, the conjecture should be further examined in different racial populations.

Aged↗

Increased risk of prostate cancer associated with AA genotype of cyclin D1 gene A870G polymorphism.

CCND1 mRNA is alternatively spliced to produce 2 transcripts, and the splicing pattern may be modulated by a frequent A870G single-nucleotide polymorphism within the conserved splice donor site of exon 4. Several studies have suggested a significant association between the CCND1 genotype and onset or progression of various cancers. To investigate the correlation of the polymorphism with genetic susceptibility to PCa and its disease status, we examined the polymorphism in 214 cases of PCa, 234 cases of BPH and 254 male controls. The CCND1 A allele was more frequently observed in the PCa group (p = 0.015) and the BPH group (p = 0.018) than the control group. Men with the AA genotype had an increased risk of PCa (aOR = 1.93, 95% CI 1.13-3.30, p = 0.016) and BPH (aOR = 1.84, 95% CI 1.09-3.09, p = 0.023) compared to those with the GG genotype. No significant association was observed when men with the AG genotype were compared to those with the GG genotype (PCa: aOR = 1.00, 95% CI 0.65-1.54, BPH: aOR = 0.91, 95% CI 0.60-1.39). The risk of PCa associated with the AA genotype appeared to be stronger in men aged 73 years or younger (aOR = 2.89, 95% CI 1.38-6.01, p = 0.005), whereas no association was found in men older than 73 years (aOR = 1.02, 95% CI 0.44-2.34). No significant difference in genotype frequency was found among patients with low-, intermediate- and high-grade tumors (p = 0.730) or between patients with localized and metastatic PCa (p = 0.679). However, in patients with high-grade or metastatic PCa, a significantly increased risk associated with the AA genotype compared to controls was observed, while no significant results were found in those with low/intermediate or localized PCa. The A allele of the CCND1 A870G polymorphism was recessively associated with susceptibility to PCa and BPH in a Japanese population, giving a 2-fold increased risk of PCa and BPH in men with the AA genotype compared to those with the GG genotype. Although the risk of PCa associated with the AA genotype appeared to contribute especially to men aged 73 years or younger and the A allele may be associated with disease status of PCa, these conjectures require validation in future studies on a larger number of subjects.

Adenocarcinoma↗

High incidence of urinary bladder involvement in carcinomas of the sigmoid and rectum: a retrospective review of 580 patients with colorectal carcinoma.

BACKGROUND AND OBJECTIVES: It is not uncommon for colorectal carcinomas to invade the urinary bladder. However, the actual incidence of urinary bladder invasion of colorectal carcinomas and the common sites of the original tumors are still unclear. METHODS: The clinical records of 580 patients diagnosed with colorectal carcinoma were retrospectively reviewed. A further review of patients with urinary bladder invasion was performed. RESULTS: Of the 580 patients, 17 (2.9%) had a diagnosis of urinary bladder invasion intraoperatively. The incidence of bladder involvement was significantly higher in carcinomas of the sigmoid and rectum than in carcinomas of other colon segments (4.1 vs. 0.5%, P = 0.017). Although a combination of computed tomography (CT) and cystoscopy predicted 80% of the bladder involvement, preoperative diagnostic modalities could not provide information for the differentiation between macroscopic and pathological invasion or the necessity for total cystectomy. CONCLUSIONS: The sigmoid colon and rectum were common sites of the original tumors invading the urinary bladder compared with other colon segments. CT and cystoscopy are recommended for preoperative screening of the bladder involvement of sigmoid colon and rectal cancer. However, it appeared to be difficult to predict the pathological invasion of malignant cells and the necessity for total cystectomy preoperatively.

Adult↗

Ratio of prostate specific antigen minor molecular forms-to-total prostate specific antigen is constant regardless of the pathological condition of the prostate.

PURPOSE: We assessed 3 molecular forms of prostate specific antigen (PSA) prospectively to determine the real proportion of the nonfree, nonalpha1-antichymotrypsin complex form of PSA-to-total PSA and evaluated the clinical significance of its various forms. MATERIALS AND METHODS: We prospectively assessed 1,878 serum samples from 994 subjects for total PSA, free PSA and PSA-alpha1-antichymotrypsin complex (ACT). Nonfree, nonPSA-ACT PSA (minor form PSA) was calculated as the difference between total PSA and the sum of free PSA plus PSA-ACT complex. RESULTS: The proportion of the minor form PSA was approximately 20% to 25% of total PSA at any range of total PSA, whereas that of free PSA and PSA-ACT decreased and increased, respectively, in correlation with the increment of total PSA. There was no significant difference in the percent of minor form PSA in patients with prostatic carcinoma and those with benign prostatic status. The proportion of minor form PSA was constant, while the percent of free PSA and PSA-ACT increased and decreased, respectively, in accordance with total PSA regression after hormonal therapy for prostatic carcinoma. PSA-ACT was judged to be superior to total PSA for distinguishing prostatic carcinoma in men with PSA 2 to 10 ng./ml. by ROC analysis. CONCLUSIONS: Approximately a fourth of total PSA consists of minor forms of complexed PSA. The average proportion of minor form-to-total PSA was constant at various levels of total PSA and at any prostatic status of patients. PSA-ACT was superior to total PSA for the early detection of prostatic carcinoma.

Adult↗

Transitional cell carcinoma in an ectopic ureter.

We experienced an 82-year-old man with transitional cell carcinoma in an ectopic ureter draining into the prostatic urethra. Carcinoma arising from an ectopic ureter is very rare and a differential diagnosis is difficult. To our knowledge, our case is the third male case reported in the literature.

Aged↗

Hypermethylation of an E-cadherin (CDH1) promoter region in high grade transitional cell carcinoma of the bladder comprising carcinoma in situ.

PURPOSE: We elucidated the role of methylation in the promoter region of the 1 gene in bladder carcinogenesis, particularly in those comprising carcinoma in situ. MATERIALS AND METHODS: A total of 49 cases of transitional cell carcinoma of the bladder obtained from transurethral resection were examined. Methylation status of the 1 promoter region was analyzed by methylation specific polymerase chain reaction from chemically modified DNA after Na-bisulfite treatment. Loss of heterozygosity on 16q was examined by blunt end single strand DNA conformation polymorphism using 4 tetranucleotide repeat microsatellite markers assigned on 16q13 to 22.1. E-cadherin expression was evaluated by immunostaining on formalin fixed, paraffin embedded tissue sections using anti E-cadherin murine monoclonal antibody, HECD1 and standard avidin-biotin immunoperoxidase complex technique. RESULTS: Analysis of the 49 bladder transitional cell carcinoma samples showed 1 promoter methylation in 23 (47%). Methylation of the 1 gene did not correlate with tumor stage (p = 0.2097) but with high grade transitional cell carcinoma (p = 0.0416). 1 promoter methylation was observed at a significantly higher frequency in the carcinoma in situ positive group than in the carcinoma in situ negative group (16 of 18 cases or 89% versus 7 of 31 or 23%, p <0.0001) and it strongly correlated with abnormal E-cadherin expression (p <0.0001). We found 16q loss of heterozygosity in 16 of 47 cases (34%), which correlated with higher histological grade (p = 0.0069) but not with the presence of the carcinoma in situ component (p = 0.1235). CONCLUSIONS: This study showed that 1 gene promoter methylation is strongly associated with bladder transitional cell carcinoma comprising carcinoma in situ.

Alleles↗

Association of V89L SRD5A2 polymorphism with prostate cancer development in a Japanese population.

PURPOSE: The SRD5A2 gene codes the steroid 5-reductase type II, a critical mediator of androgen action, and the V89L and A49T polymorphisms of this gene may be associated with a distinct enzyme activity. We explored the association among these polymorphisms and the risk of prostate cancer or benign prostatic hyperplasia (BPH) in a Japanese population. MATERIALS AND METHODS: This study included 302 patients with prostate cancer, 228 with BPH and 243 male controls. V89L and A49T polymorphisms were analyzed by the polymerase chain reaction restriction fragment length polymorphism method. Genotypes were evaluated by electrophoresis on agarose gel. RESULTS: For the V89L polymorphism there were no significant differences in genotype frequencies in patients with prostate cancer and controls (p = 0.071) or in patients with BPH and male controls (p = 0.219). However, males with the VV or VL genotype were at significantly increased risk for prostate cancer compared with those with the LL genotype (adjusted OR 1.69, 95% CI 1.07 to 2.65, p = 0.024). The risk of BPH in males with the VV or VL genotype was not significantly elevated in comparison with those with the LL genotype (adjusted OR 1.37, 95% CI 0.85 to 2.20, p = 0.194). The V89L variant was not associated with the grade or stage of prostate cancer, or with patient age. For the A49T polymorphism all subjects had the AA genotype. CONCLUSIONS: The V allele of the V89L polymorphism in the SRD5A2 gene may dominantly increase the risk of prostate cancer.

Aged↗

Distribution and genetic association of putative uropathogenic virulence factors iroN, iha, kpsMT, ompT and usp in Escherichia coli isolated from urinary tract infections in Japan.

PURPOSE: Many virulence factors (VFs) have been reported in uropathogenic Escherichia coli. Recently we found a putative uropathogenic island including a gene encoding uropathogenic specific protein (USP). We have described the association between usp and other VFs reported previously. In the current study we examined epidemiological associations among 5 putative uropathogenic VFs. MATERIALS AND METHODS: In 427 E. coli strains, including 194, 76 and 107 isolates from patients with cystitis, pyelonephritis and prostatitis, respectively, and 50 isolates from the stool of healthy adults, we detected catecholate siderophore receptor (iroN), iron regulated gene A homologue adhesin (iha), group II capsule (kpsMT) and outer membrane protease T (ompT) by polymerase chain reaction assays. We analyzed their distribution and genetic association. RESULTS: Relative prevalence ratios of iroN, iha, kpsMT, ompT and usp were 2.0 to 4.3 times more frequently in urinary tract infection isolates than in fecal isolates. Isolates from prostatitis were frequently associated with iroN, ompT and usp, whereas isolates from pyelonephritis frequently harbored usp. Together with iroN and iha we noted S-/F-fimbriae and iucD aerobactin (OR 95.9 and 187.2), while usp showed a close association with kpsMT and ompT (OR 38.3 and 38.4, respectively). CONCLUSIONS: Of the putative uropathogenic VFs examined iroN, iha, kpsMT, ompT and usp were frequently associated with urinary tract infection. Especially iroN and usp were most frequently associated with prostatitis. Some VFs were closely associated with a specific anatomical site of infection. Strong associations among several VFs might indicate not only well-known genetic linkages, but also unknown functional linkages among these VFs.

Adult↗

[Therapeutic strategy for prostate specific antigen (PSA) failure after radical prostatectomy].

Prostate specific antigen (PSA) failure occurs in 20% to 50% of patients who undergo radical prostatectomy. There is no consensus on how PSA failure should be managed. Recently, salvage radiotherapy is reported to be an effective treatment for PSA failure, and 20%-70% of cases are recurrence-free. The aim of salvage radiotherapy is a cure and this is quite different from other options, for example, endocrine therapy. Salvage radiotherapy is likely to become more important as a treatment for PSA failure after radical prostatectomy.

Biomarkers, Tumor↗

[A case report of a young patient with invasive bladder cancer].

A 29-year-old male with bladder cancer was referred to our hospital. Histological examination of transurethral biopsy showed transitional cell carcinoma with invasion into prostate (T4aN0M0, grade 3). Nerve-sparing radical cystectomy with ileal neobladder reconstruction was performed after 3 courses of neoadjuvant chemotherapy with Methotrexate, Epirubicin and Cisplatin. Continence and erectile function were preserved and no recurrence has been observed for 18 months after the operation. This is the sixth case of an invasive bladder cancer in Japanese patients under 30 years old.

Adult↗

Comparison of the effectiveness of ET-Kyoto with Euro-Collins and University of Wisconsin solutions in cold renal storage.

BACKGROUND: Previously, we developed a new organ preserving solution, ET-Kyoto solution (ETKS), and showed that it is effective for lung and skin cold storage. Our high sodium-low potassium solution containing trehalose and gluconate is chemically stable at room temperature. In this study, the efficacy of ETKS for renal cold storage compared with Euro-Collins solution (ECS) and University of Wisconsin solution (UWS) was investigated. METHODS: A preflush of Krebs-Henseleit buffer was used before cold storage because ECS and UWS, but not ETKS, failed to be distributed thoroughly into each renal segment when directly flushed, as determined by staining with trypan blue. The kidneys were stored at 4 degrees C in each solution after the preflush and were reperfused 24 hr later for 120 min with 37 degrees C Krebs-Henseleit buffer containing albumin. For physiological evaluation, perfusion flow rates, creatinine clearance, and fractional sodium reabsorption were evaluated. Histological examination also was performed to determine tubular, glomerular, and interstitial changes. Moreover, distribution of perfusate at the beginning of reperfusion was assessed by using trypan blue. RESULTS: The kidneys preserved in ETKS and UWS showed better physiological function and less histological damage than those preserved in ECS. Furthermore, at the beginning of reperfusion using trypan blue, almost all renal segments were stained in the ETKS and UWS groups, whereas they were partially stained in the ECS group. CONCLUSIONS: These results indicate that this simple and chemically stable solution, ETKS, could be a promising substitute for UWS.

Absorption↗

No association between HER-2 gene polymorphism at codon 655 and a risk of bladder cancer.

The amplification and overexpression of the human epidermal growth factor receptor 2 gene HER-2 (also known as c-erb-B2 or neu) have been shown to be associated with bladder cancer and its progression. Recent studies indicated an association between the Ile to Val polymorphism at codon 655 of HER-2 and susceptibility to breast cancer. To investigate the correlation between the Ile/Val polymorphism and the susceptibility and progression of bladder cancer, we analyzed the polymorphism in 232 patients with transitional cell carcinoma of the bladder and 408 normal controls. The frequencies of the Ile/Ile, Ile/Val and Val/Val genotype were 75.9%, 21.6% and 2.6%, respectively, in patients with bladder cancer and 75.7%, 23.0% and 1.2%, respectively, in controls. Statistical analyses of the genotype prevalence showed no significant difference between bladder cancer patients and normal controls (p = 0.419). Moreover, no significant differences in the genotype prevalence were observed when the patients were stratified according to the tumor grade, stage and smoking habits. When the Ile/Ile genotype was compared to the Ile/Val and Val/Val genotypes, a significant difference was found only between the patients with tumor stage Ta and those with T1-4 (age, gender and smoking habits-adjusted odds ratio = 2.13, 95% confidence interval = 1.09-4.15, p = 0.027). When the Ile/Ile + Ile/Val genotypes compared to the Val/Val genotype, no significant findings were observed. These results suggested that the HER-2 polymorphism at codon 655 is unlikely to be associated with the onset of bladder cancer. Furthermore, the findings suggest no association between this polymorphism and the disease progression in bladder cancer, although the possibility remains that the Ile/Ile genotype may be related to an increased risk of disease progression.

Aged↗

Molecular genetic analysis of chromosome 9 candidate tumor-suppressor loci in bladder cancer cell lines.

Underrepresentation of chromosome 9 is a common finding in bladder cancer. Frequent loss of the whole chromosome suggests the presence of at least one relevant tumor suppressor gene on each arm. Candidate regions identified by loss of heterozygosity (LOH) analysis include a region at 9p21 containing CDKN2A, which encodes p16 and p14(ARF), a large region at 9q12-31 including PTCH and many other genes, a small region at 9q32-33, which includes the DBCCR1 gene, and a region at 9q34 including the TSC1 gene. Experimental replacement of genes or chromosomes into tumor cells with appropriate deletions or mutations represents an important approach to test the functional significance of candidate tumor suppressor genes. Loss of an entire copy of chromosome 9 in many bladder tumor cell lines provides no indication of which gene or genes are affected, and selection of appropriate recipient cells for gene replacement is difficult. We have investigated three candidate tumor suppressor genes on chromosome 9 (CDKN2A, DBCCR1, and TSC1), at the DNA level and by expression analysis in a panel of bladder tumor cell lines, many of which have probable LOH along the length of the chromosome, as indicated by homozygosity for multiple polymorphic markers. Cytogenetically, we found no reduction in the numbers of chromosomes 9 relative to total chromosome count. Homozygous deletion of the CDKN2A locus was frequent but homozygous deletion of TSC1 was not found. A new cell line, DSH1, derived from a pT1G2 transitional cell carcinoma with known homozygous deletion of DBCCR1, is described. This study identifies suitable cell lines for future functional analysis of both CDKN2A and DBCCR1.

Carcinoma, Transitional Cell↗

Association of common missense changes in ELAC2 ( HPC2) with prostate cancer in a Japanese case-control series.

The recently identified prostate cancer susceptibility gene ELAC2 ( HPC2) harbors two common missense variants, a serine to leucine substitution at residue 217 (Leu217) and an alanine to threonine substitution at residue 541 (Thr541). We genotyped the two variants in a Japanese cohort consisting of 350 prostate cancer patients 242 male population controls, and 114 male low-risk controls. Both missense alleles, Leu217 and Thr541, were carried at higher frequency in Japanese patients than in the controls (Leu217, P= 0.0012; Thr541, P = 0.0145), and the odds ratios associated with carrying these sequence variants were higher in Japanese than in Caucasians. Although the Leu217 and Thr541 variants of ELAC2 are less common in Japanese than in Caucasians, both variants confer significantly increased risk of prostate cancer in Japanese. Carriage of these variants was not associated with age at diagnosis, tumor stage, or tumor grade in these Japanese prostate cancer patients. The allele-specific pattern of risk observed in Japanese and familial Caucasian patients was qualitatively similar; however, the magnitude of that risk was considerably greater in Japanese than in Caucasians.

Case-Control Studies↗

Health-related quality of life of ileocecal rectal bladder compared with ileal conduit diversion: a questionnaire survey.

BACKGROUND: The ileocecal rectal bladder (IRB) after cystectomy has been devised, in which continence is controlled by the anal sphincter. To assess how this procedure influences postoperative health-related quality of life (QOL), IRB patients were compared with ileal conduit (IC) patients using a questionnaire mail-out. METHODS: The questionnaire consisted of 35 questions. The questions were multiple choice and the answers were rated on a Linkert rank-type four-point scale. The IRB operation was performed on 29 patients between March 1990 and July 1998. The questionnaire was mailed to 21 of 29 IRB and 34 IRC patients, who underwent either operation during the same period abd had no persistent or recurrent tumor. Statistical analysis was performed by Mann-Whitney U-test. RESULTS: All 21 IRB patients (100%) and 24 IC patients (71%) responded to the questionnaire. The mean age and follow-up time of both groups were not significantly different. The IRB group had better scores in many items, especially, in those of self-care, turning over freely during sleep,and tension. However, 43% of IRB patients used pads for small amounts of incontinence (spotting) and worried about flatus. CONCLUSION: These findings show that many functional and symptomatic health related QOL scores are better after IRB and support the use of this procedure of urinary diversion for selected patients.

Adult↗