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Biomedical subjects

Hiroyuki Fujimoto

Publications and source records attributed to Hiroyuki Fujimoto.

At least 19 recordsLinked to original sources

A randomized trial comparing radical prostatectomy plus endocrine therapy versus external beam radiotherapy plus endocrine therapy for locally advanced prostate cancer: results at median follow-up of 102 months.

BACKGROUND: To investigate the optimal treatment of locally advanced prostate cancer, a prospective randomized trial was conducted to compare radical prostatectomy plus endocrine therapy versus external beam radiotherapy plus endocrine therapy. METHODS: One hundred patients with T2b-3N0M0 prostate cancer were enrolled and 95 were evaluated. Of 95 cases, 46 underwent radical prostatectomy with pelvic lymph node dissection and 49 were treated with external beam radiation by linear accelerator with 40-50 Gy to the whole pelvis and 20-Gy boost to the prostatic area. For all patients, endocrine therapy was initiated 8 weeks before surgery or radiotherapy and continued thereafter. The long-term outcome and morbidity were examined. RESULTS: Median follow-up period was 102 months. At 10 years overall survival rates in the surgery group were better than the radiation group (76.2% versus 71.1% for biochemical progression-free rates; P=0.25, 83.5% versus 66.1% for clinical progression-free rates; P=0.14, 85.7% versus 77.1% for cause-specific survival rates; P=0.06, and 67.9% versus 60.9% for overall survival rates; P=0.30), although none of them reached statistical significance. Erectile dysfunction was recognized in almost all patients as a result of continuous endocrine therapy. Incontinence requiring more than one pad per day was observed more frequently in the surgery group than the radiation group (P<0.01). CONCLUSIONS: For the treatment of patients with locally advanced prostate cancer, when combined with endocrine therapy, either radical prostatectomy or external beam radiotherapy demonstrated favorable long-term outcomes. The radiation dose of 60-70 Gy might not be enough for the local treatment of locally advanced prostate cancer.

Adenocarcinoma↗

Regional DNA hypermethylation and DNA methyltransferase (DNMT) 1 protein overexpression in both renal tumors and corresponding nontumorous renal tissues.

To evaluate the significance of altered DNA methylation during renal tumorigenesis, tumorous tissues (T) and corresponding nontumorous renal tissues (N) from 94 patients with renal tumors, and normal renal tissues (C) from 16 patients without renal tumors were investigated. DNA methylation status on CpG islands of the p16, human MutL homologue 1 (hMLH1), von-Hippel Lindau (VHL) and thrombospondin-1 (THBS-1) genes and the methylated in tumor (MINT) -1, -2, -12, -25 and -31 clones and DNA methyltransferase (DNMT) 1 expression were examined by bisulfite modification and immunohistochemistry, respectively. The average number of methylated CpG islands was significantly higher in N than in C, and was even higher in T. The average number of methylated CpG islands in N was significantly correlated with a higher histological grade of corresponding conventional renal cell carcinomas (RCCs). The average number of methylated CpG islands in RCCs was significantly correlated with macroscopic configuration with extranodular or multinodular growth, higher histological grade, infiltrating growth pattern and vascular involvement. The recurrence-free survival rate of patients with RCCs showing accumulation of DNA methylation was significantly lower than that of patients not showing this feature. The incidence of nuclear immunoreactivity for DNMT1 tended to be higher in proximal tubules from N than in those from C, and was significantly higher in RCCs. From the viewpoint of altered DNA methylation, N is at the precancerous stage, and N showing accumulation of DNA methylation may generate more malignant RCCs. Regional DNA hypermethylation may be associated with renal tumorigenesis from a precancerous condition to malignant progression and become a predictor of patient prognosis.

Adaptor Proteins, Signal Transducing↗

Distant metastasis of prostate cancer: early detection of recurrent tumor with dual-phase carbon-11 choline positron emission tomography/computed tomography in two cases.

Several types of recurrence may be detected by radiologic assessment after treatment in patients with prostate cancer. However, early detection of distant metastasis using positron emission tomography has so far never been published. We report two patients who underwent hormone therapy or surgical resection for prostate cancer. They developed distant metastases which were detected on whole body [C-11] choline positron emission tomography/computed tomography with significant elevation of serum PSA level. In one patient, recurrent tumor of the supraclavicular node (6 mm) diminished in size after subsequent hormone therapy. Surgical resection of recurrent tumor of the lung (12 mm) was performed in the other patient, the pathology of which confirmed the metastatic adenocarcinoma derived from the prostate. The recurrent tumor can be correctly detected by dual-phase whole body [C-11] choline positron emission tomography/computed tomography.

Adenocarcinoma↗

Whole-cell arsenite biosensor using photosynthetic bacterium Rhodovulum sulfidophilum. Rhodovulum sulfidophilum as an arsenite biosensor.

An arsenite biosensor plasmid was constructed in Escherichia coli by inserting the operator/promoter region of the ars operon and the arsR gene from E. coli and the crtA gene, which is responsible for carotenoid synthesis in the photosynthetic bacterium, Rhodovulum sulfidophilum, into the broad-host-range plasmid vector, pRK415. The biosensor plasmid, pSENSE-As, was introduced into a crtA-deleted mutant strain of R. sulfidophilum (CDM2), which is yellow in culture due to its content of spheroiden (SE) and demethylspheroidene (DMSE). CDM2 containing pSENSE-As changed from yellow to red by the addition of arsenite, which caused enzymatic transformation of SE and DMSE to spheroidenone (SO) and demethylspheroidenone (DMSO). Reverse transcriptase PCR analysis showed that the color change depended on transcription of the crtA gene in pSENSE-As. The color change could be clearly recognized with the naked eye at 5 microg/l arsenite. The biosensor strain did not respond to other metals except for bismuth and antimony, which caused significant accumulation of SO and DMSO in the cells at 60 and 600 microg/l, respectively. This biosensor indicates the presence of arsenite with a bacterial color change without the need to add a special reagent or substrate for color development, enabling this pollutant to be monitored in samples by the naked eye in sunlight, even where electricity is not available.

Antimony↗

Lewis acid-catalyzed tri- and difluoromethylation reactions of aldehydes.

The first Lewis acid-catalyzed trifluoromethylation reactions of aldehydes with Me3SiCF3 under TiF4/DMF, Ti(O iPr)4/DMF and Cu(OAc)2/dppp/toluene conditions are described. We have successfully applied this methodology to the difluoromethylation of aldehydes using Me3SiCF2SePh, Me3SiCF2P(O)OEt2 and Me3SiCF2SPh.

Journal Article↗

Leiomyosarcoma of the renal vein: arterial encasement on contrast-enhanced dynamic computed tomography.

We report a case of leiomyosarcoma of the renal vein, which is a rare tumor with no more than 30 cases found in the published English language literature. This case demonstrates encasement of the renal artery by the tumor mass, a previously unreported manifestation. The present study could be useful in considering this rare tumor in the differential diagnosis of renal hilar tumors.

Aged↗

Effectiveness of adjuvant intermittent endocrine therapy following neoadjuvant endocrine therapy and external beam radiation therapy in men with locally advanced prostate cancer.

PURPOSE: To clarify the optimal duration and methods for adjuvant endocrine therapy after external beam radiation therapy (EBRT) in patients with locally advanced prostate cancer. MATERIALS AND METHODS: Between 2001 and 2003, 215 patients with locally advanced prostate cancer were enrolled in the study. Patients were registered as primary candidates of the study and were treated with 6 months of LHRH agonist, with short-term of antiandrogen treatment for flare-up prevention. Patients with PSA levels below 10 ng/ml after the 6-month endocrine treatment were randomly divided into two arms. Then, a total dose of 72 Gy was given to the prostate. After 14 months of the protocol treatment, patients were treated with continuous androgen ablation (arm 1) or intermittent androgen ablation (arm 2). RESULTS: A total of 188 cases (87%) remained in the protocol. The median PSA level at entry was 25.3 ng/ml. The Gleason score was 2-6 in 32 cases (16%), 7 in 94 cases (48%), and 8-10 in 68 cases (35%). The median PSA level showed a remarkable decrease to 1.1, 0.2, and 0.1 ng/ml, after 6, 8, and 14 months of the protocol treatment, respectively. Of the 157 cases treated with EBRT, 153 cases (97.5%) had no biochemical failure in the mean follow-up of 17.3 months. CONCLUSIONS: The present study may reveal the possibilities of intermittent endocrine therapy after EBRT. However, the follow-up interval is short and little can be said about the results observed so far, exception of acute tolerance and patient acceptance of the protocol.

Adenocarcinoma↗

Harmony seeking and the risk of prostate cancer: a prebioptic study.

OBJECTIVE: This semiprospective case-control study was performed to investigate the relationship between harmony-seeking personality and the occurrence of prostate cancer. METHODS: Out of 217 consecutive participants admitted to hospital for biopsy, 86 and 81 were classified into the case and control groups, respectively, based on their initial diagnosis and eligibility criteria. The participants answered several questionnaires after admission. The logistic regression model was used for multivariate analyses to assess the association. RESULTS: "Harmony-seeking personality" was selected as the only psychological variable significantly contributing to the model, while "family history of prostate cancer" as the only somatic variable. "Harmony-seeking" maintained a significant contribution to the model, also including "family history" and even to the model adjusted by "patient prediction of cancer diagnosis" and "prostate-specific antigen" (PSA), probably related to the consequences of the disease. CONCLUSION: The harmony-seeking personality could differentiate between groups of men with and without prostate cancer.

Affect↗

Loss of blood group A antigen expression in bladder cancer caused by allelic loss and/or methylation of the ABO gene.

Loss of ABO blood group antigen expression has been reported in transitional cell carcinoma (TCC) of the bladder. Synthesis of the ABO blood group antigen was genetically determined by allelic variants of the ABO gene assigned on 9q34.1. We analyzed loss of heterozygosity (LOH) and promoter hypermethylation of the ABO gene in TCC and compared them with alterations of A antigen expression in TCC, dysplasia and normal urothelium. A total of 81 samples of TCC of the bladder obtained from transurethral resection (TUR) (n=44) and radical cystectomy (n=37) were examined. Expression of the A antigen was evaluated by immunohistochemical staining (IHC) using anti-A antigen monoclonal antibody. LOH of the ABO gene locus was examined by blunt-end single-strand DNA conformational polymorphism (SSCP) analysis using flouresence-based auto sequencer. Promoter hypermethylation of the ABO gene were examined by bisulfite PCR-SSCP (BiPS) analysis and/or methylation-specific PCR (MSP). Loss of A allele and/or hypermethylation were significantly associated with abnormal expression of the A antigen in cases undergoing TUR (P=0.02) and radical cystectomy (P=0.0005). For the analysis of the concomitant dysplasia in 23 cases with TCC of the bladder, the expression of the A antigen was maintained, regardless of the A allelic loss or methylation status in the tumor. In conclusion, A allelic loss and hypermethylation in the promoter region of the ABO gene showed significant correlation with reduction of A antigen expression in TCC, while the expression of the A antigen is maintained in concomitant dysplasia or normal urothelium, suggesting that loss of the ABO gene and/or its promoter hypermethylation is a specific marker for TCC.

ABO Blood-Group System↗

[Radical prostatectomy with neoadjuvant hormone therapy for cT3 prostate cancer].

The efficacy of neoadjuvant hormone therapy and radical prostatectomy for cT1-2 prostate cancer have been reported to be negative from some randomized prospective studies. On the other hand, radical prostatectomy alone for cT3 prostate cancer is understood as out of indication because of high rate of positive surgical margin and PSA failure. Several investigators have examined the role of neoadjuvant hormone therapy before radical prostatectomy for cT3 prostate cancer to improve outcome. This document was reviewed the literature whether neoadjuvant hormone therapy is beneficial or not, for organ confined prostate cancer and for locally advanced prostate cancer, and presented our extended resection of prostate with neoadjuvant hormone therapy is improved the results in cT3 prostate cancer.

Antineoplastic Agents, Hormonal↗

Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study.

We report a multicenter trial with transrectal high-intensity focused ultrasound (HIFU) in the treatment of localized prostate cancer. A total of 72 consecutive patients with stage T1c-2NOM0 prostate cancer were treated using the Sonablate 500TM HIFU device (Focus Surgery, Indianapolis, USA). Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The median age and prostate specific antigen (PSA) level were 72 years and 8.10 ng/ml, respectively. The median follow-up period for all patients was 14.0 months. Biochemical disease-free survival rates in all patients at 1 and 2 years were 78% and 76%, respectively. Biochemical disease-free survival rates in patients with stage T1c, T2a and T2b groups at 2 years were 89, 67% and 40% (p = 0.0817). Biochemical disease-free survival rates in patients with Gleason scores of 2-4, 5-7 and 8-10 at 2 years were 88, 72% and 80% (p = 0.6539). Biochemical disease-free survival rates in patients with serum PSA of less than 10 ng/ml and 10-20 ng/ml were 75% and 78% (p = 0.6152). No viable tumor cells were noted in 68% of patients by postoperative prostate needle biopsy. Prostatic volume was decreased from 24.2 ml to 14.0 ml at 6 months after HIFU (p < 0.01). No statistically significant differences were noted in International Prostate Symptom Score, maximum urinary flow rate and quality of life analysis with Functional Assessment of Cancer Therapy. HIFU therapy appears to be minimally invasive, efficacious and safe for patients with localized prostate cancer with pretreatment PSA levels less than 20 ng/ml.

Adult↗

[A multicenter study to determine the efficacy and safety of strontium (89Sr) chloride for palliation of painful bony metastases in cancer patients].

PURPOSE: A multicenter study was conducted to evaluate the efficacy of strontium chloride (89SrCl2) for palliation of painful bony metastases using the Visual Analogue Scale (VAS), Brief Pain Inventory (BPI) and Functional Assessment for Cancer Therapy-General (FACT-G). METHODS: Ninety patients received a single injection of 2.0 MBq/kg and were classified as responders if VAS scores decreased without increased use of analgesics or if analgesic consumption decreased without an increase in the VAS. RESULTS: In the 69 subjects that could be evaluated, mean VAS values decreased significantly from 48.0 +/- 20.8 mm at baseline to 24.1 +/- 22.3 mm at last visit(Week 12) (p < 0.0001). VAS decreased more than 10 mm in 58.0% of these subjects, and analgesic consumption was reduced more than 10% in 39.1% of subjects. The response rates were 46.4% (95% confidence interval (CI) 34.3-58.8%) in the 69 subjects that could be evaluated and 43.3% (95% CI 32.9-54.2%) in all subjects. The scoring in BPI for interference in daily life improved together with improvement in its pain scores. Total FACT-G score showed significant improvement, as did its score in the subsection of physical well-being. Both platelets and leucocytes decreased by 22% at nadir (week 8), and such profiles of myelosuppression by 89SrCl2 were similar to those in the previous clinical studies. CONCLUSION: These results suggest the clinical utility of 89SrCl2 for pain palliation, which leads to QOL improvement in patients with painful generalized bone metastases.

Adult↗

Allogeneic hematopoietic stem cell transplantation with a reduced-intensity conditioning regimen for treatment of metastatic renal cell carcinoma: single institution experience with a minimum 1-year follow-up.

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of allogeneic hematopoietic stem cell transplantation with a reduced-intensity conditioning regimen (RIST) for interferon-alpha-refractory metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Of 26 patients referred to the National Cancer Center Hospital for possible RIST between June 2000 and April 2002, an HLA-identical relative was identified for 12 patients. Nine patients underwent RIST. The conditioning regimen consisted of fludarabine 180 mg/m2 or cladribine 0.66 mg/kg, plus busulfan 8 mg/kg and rabbit antithymocyte globulin 5 mg/kg. Graft-vs-host disease (GVHD) prophylaxis was cyclosporine alone. RESULTS: All patients achieved engraftment without grade III to IV nonhematologic regimen-related toxicity. All patients achieved complete donor-type chimerism without donor lymphocyte infusion by day 60. Four patients developed acute GVHD, and four developed chronic GVHD. One patient (11%) achieved partial response. As of July 2003, six patients were alive at median follow-up of 681 days. The actuarial overall survival rate was 89% at 1 year and 74% at 2 years. The overall survival rate tended to be higher in the 12 patients with a matched donor than in the other 14 patients without a matched donor (p = 0.088). CONCLUSION: Our RIST procedure is feasible without severe toxicity. The efficacy of RIST for RCC should be confirmed in phase II/III clinical trials.

Acute Disease↗

Radical cystectomy for invasive bladder cancer: results of multi-institutional pooled analysis.

BACKGROUND: We report the outcome of radical cystectomy for patients with invasive bladder cancer, who did not have regional lymph node or distant metastases, at 21 hospitals. METHODS: Retrospective, non-randomized, multi-institutional pooled data were analyzed to evaluate outcomes of patients who received radical cystectomy. Between 1991 and 1995, 518 patients with invasive bladder cancer were treated with radical cystectomy at 21 hospitals. Of these, 250 patients (48.3%) received some type of neoadjuvant and/or adjuvant therapy depending on the treatment policy of each hospital. RESULTS: The median follow-up period was 4.4 years, ranging from 0.1 to 11.4 years. The 5-year overall survival rate was 58% for all 518 patients. The 5-year overall survival rates for patients with clinical T2N0M0, T3N0M0 and T4N0M0 were 67%, 52% and 38%, respectively. The patients with pT1 or lower stage, pT2, pT3 and pT4 disease without lymph node metastasis had 5-year overall survivals of 81%, 74%, 47% and 38%, respectively. The patients who were node positive had the worst prognosis, with a 30% overall survival rate at 5 years. Neoadjuvant or adjuvant chemotherapy did not provide a significant survival advantage, although adjuvant chemotherapy improved the 5-year overall survival in patients with pathologically proven lymph node metastasis. CONCLUSIONS: The current retrospective study showed that radical cystectomy provided an overall survival equivalent to studies reported previously, but surgery alone had no more potential to prolong survival of patients with invasive cancer. Therefore, a large-scale randomized study on adjuvant treatment as well as development of new strategies will be needed to improve the outcome for patients with invasive bladder cancer.

Adult↗

Dynamic computed tomography and color Doppler ultrasound of renal parenchymal neoplasms: correlations with histopathological findings.

BACKGROUND: We evaluated whether color Doppler ultrasound (US) had diagnostic accuracy equal to dynamic computed tomography (CT) and whether performing dynamic CT and Doppler US together would be more informative in preoperative diagnosis of renal solid tumors. METHODS: A total of 110 renal solid tumors smaller than 7 cm were evaluated with dynamic CT and Doppler US. We compared the enhancement and the color flow patterns with the histopathological subtypes. RESULTS: Eighty-seven (95.6%) of 91 clear cell carcinomas showed rich enhancement in the cortical nephrographic phase (CNP) and 82 (90.1%) of them had color flow in the Doppler US. Of the total of 110 tumors, nine (8.1%) did not show color flow in spite of rich enhancement in the CNP. Conversely, eight (7.2%) of the 110 tumors showed color flow in spite of poor enhancement, including two chromophobe cell carcinomas and two metastatic renal tumors. CONCLUSIONS: The enhancement pattern in dynamic CT and the color flow pattern in Doppler US were different among the subtypes of RCC. Color Doppler US had diagnostic accuracy equal to dynamic CT in most patients with renal solid tumors. Although Doppler US may play a unique role in the diagnosis of some renal parenchymal solid tumors, it is sufficient to perform dynamic CT alone for diagnosis of clear cell carcinoma.

Adenocarcinoma, Clear Cell↗

[Pyothorax associated lymphoma with increased neuron-specific enolase level in serum and pleural effusion: a case report].

A 72-year-old male with a past history of artificial pneumothorax for pulmonary tuberculosis at the age of 25 was referred to our hospital for the clinical signs of pain and swelling of the back. His neuron-specific enolase values were high in both serum and pleural effusion. The computed tomography image showed a tumor mass arising from the wall of chronic pyothorax. The tumor was resected including the wall of the chronic pyothrax and right chest wall with several ribs. The tumor was 7.2 x 7.0 x 3.0 cm in size and the pathological diagnosis was non-Hodgkin's lymphoma diffuse large cell, B-cell type. Postoperative chemotherapy and radiation therapy were performed but he died of recurrence and metastasis of the tumor 5 months later after the operation.

Aged↗