Biomedical subjects

Norio Nonomura

Publications and source records attributed to Norio Nonomura.

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

Isolation of germ cells from leukemia and lymphoma cells in a human in vitro model: potential clinical application for restoring human fertility after anticancer therapy.

More than 70% of patients survive childhood cancer, but chemotherapy and radiation therapy may cause irreversible impairment of spermatogenesis. To treat infertility secondary to anticancer treatment for childhood cancer, we have developed a procedure to isolate germ cells from leukemic mice by fluorescence-activated cell sorting with two surface markers, and transplantation of isolated germ cells successfully restored fertility without inducing leukemia. In the present study, we analyzed human germ cells and human malignant cells, including five leukemia cell lines and three lymphoma cell lines, by fluorescence-activated cell sorting with antibodies against MHC class I and CD45. Testicular specimens were obtained from a patient who underwent surgery for testicular rupture. In the high forward scatter and low side scatter region, no malignant cells were found in the MHC class I-negative and CD45-negative fraction (the germ cell fraction), with the exception of K562 cells. A total of 39.2% of the germ cells were found in the germ cell fraction. A total of 1.45% of K562 cells were found in the germ cell fraction. Treatment with IFNgamma induced the expression of MHC class I on K562 cells but not on germ cells and made it possible to isolate germ cells from K562 cells. In conclusion, we isolated human germ cells from malignant cells with two surface markers after treatment with IFNgamma. Immunophenotyping for each patient will be necessary before isolation and induction of surface marker will be clinically applicable.

Cell Line, Tumor↗

PubMed2006

High-dose-rate brachytherapy without external beam irradiation for locally advanced prostate cancer.

BACKGROUND AND PURPOSE: High-dose-rate brachytherapy (HDR-BT) had been used only in combination with external beam irradiation (EBI) until our previously reported first trial of HDR-BT alone without EBI. The purpose of the current report is to evaluate the feasibility, toxicity and efficacy of this regimen, with more patient accrual and longer follow-up. MATERIAL AND METHODS: From 1995 through 2004, 111 patients with localized prostate cancer were treated with HDR-BT without EBI. Fifteen patients were considered as low-risk, 28 as intermediate-risk, and 68 as high-risk. The prescribed dose was 48 Gy/8 fractions/5 days or 54 Gy/9 fractions/5 days. Median follow-up time was 27 months (range 5-119). RESULTS: All the patients completed the treatment regimen. The 3- and 5-year PSA failure-free rates were 83% and 70%, and the local control rates 100% and 97%. The maximum toxicities observed were Grade 3 by CTCAE v3.0 (6 acute, 1 chronic). CONCLUSIONS: HDR-BT without EBI was feasible and its toxicity acceptable. Short-term tumor control was promising, even for locally advanced cases. More patient accrual and longer follow-up are needed to confirm the efficacy of this novel approach.

Aged↗

PubMed2006

Hepatocyte growth factor has protective effects on crystal-cell interaction and crystal deposits.

OBJECTIVES: To investigate whether hepatocyte growth factor (HGF) has a protective role against crystal-cell interaction and crystal deposits in a stone-forming rat model kidney. Crystal-cell interaction is an important step during the early stages of stone formation. High oxalate levels induce cell injuries and increase adhesion of calcium oxalate monohydrate (COM) crystals to renal tubular cells. HGF was initially identified as the most potent growth factor for hepatocytes and is well known as a mesenchyme-derived pleiotropic factor for various types of cells. HGF has mitogenic, morphogenic, and anti-apoptotic effects on renal tubular cells. METHODS: Madin-Darby canine kidney cells were exposed to potassium oxalate or COM crystals in the presence or absence of HGF. We measured lactate dehydrogenase activity in the medium and analyzed apoptosis by FACScan. COM crystal formation was induced by administration of 0.5% ethylene glycol in the drinking water and forced feeding of 0.5 microg of 1alpha-OH-D3 every other day to male Sprague-Dawley rats. Plasmid vector encoding HGF was transferred to stone-forming rats on day 1, and the kidneys were excised on day 8. RESULTS: Exposure of Madin-Darby canine kidney cells to both potassium oxalate (KOX) and COM crystals resulted in an increase in lactate dehydrogenase release and the proportion of apoptotic cells, but these effects were reduced by HGF. HGF had inhibitory activity against the adhesion of COM crystals to Madin-Darby canine kidney cells. HGF gene transfer significantly reduced crystal deposits on the renal tubules in stone-forming rats. CONCLUSIONS: These findings suggest that HGF might play an important role in stone formation.

Animals↗

PubMed2006

The expression of thymidine phosphorylase is a prognostic predictor for the intravesical recurrence of superficial bladder cancer.

BACKGROUND: Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor, has been implicated in the angiogenesis of bladder cancer. The aim of this study is to investigate the association between TP expression and the clinicopathologic findings, and the prognostic value. METHODS: TP immunohistochemical staining was performed in specimens from 71 patients (50 men and 21 women) with superficial bladder cancer (pTa or pT1). Thirty-nine patients had received intravesical instillation of tetrahydropyranyladriamycin (THP) after transurethral resection (TUR) and the other 32 had not. For immunohistochemistry, paraffin-embedded specimens were stained with mouse monoclonal antibody against TP. When more than 10% of tumor cells were positively stained, staining was defined as positive. The correlations between TP immunostaining and clinicopathological features were analyzed. Multivariate analysis, using the Cox proportional hazard model, was performed to determine the risk factors for intravesical recurrence. RESULTS: Specimens from 29 of the 71 patients (19 men and 10 women) were positive for TP. The expression of TP was not correlated with age, sex, histological grade, multiplicity, or morphology. Also, TP expression was not associated with whether the cases were primary or recurrent. Multivariate analysis demonstrated that the decreased expression of TP and the use of THP instillation could be independent predictors of a higher rate of intravesical recurrence-free bladder cancer. CONCLUSION: The present study suggests that immunohistochemical TP staining is useful for predicting the intravesical recurrence of superficial bladder cancer after Transurethral resection of bladder tumor (TUR-Bt).

Administration, Intravesical↗

PubMed2006

Laparoscopic adrenalectomy for primary hyperaldosteronism: clinical experience with 60 cases.

PURPOSE: To assess the long-term outcome of patients with primary hyperaldosteronism who underwent laparoscopic adrenalectomy and to study hormone dynamics and differences between postoperative and preoperative blood pressure. PATIENTS AND METHODS: From December 1992 to February 2005, 60 patients with primary hyperaldosteronism underwent laparoscopic adrenalectomy at our institution. Their clinical and biochemical parameters were reviewed retrospectively. In 45 patients, it was possible to follow the hormone dynamics and blood pressure to compare the preoperative values with those >or=2 months after the operation. RESULTS: The average operating time was 261.7 minutes (range 95-835 minutes), and the average blood loss was 204.2 mL (range 10-3740 mL). The average time to ambulation was 1.7 days (range 1-7 days). Five patients (8.3%) had intraoperative hemorrhage that necessitated blood transfusion. Serum aldosterone in all 45 patients who were followed up was normalized postoperatively. At >or=2 months postoperatively, only 12 of the 45 patients (26.7%) needed antihypertensive drug(s). CONCLUSIONS: Laparoscopic adrenalectomy is a safe and effective way to treat primary hyperaldosteronism. Many of the patients in whom hypertension persisted postoperatively were men or elderly.

Adenoma↗

PubMed2006

A case of renal cell carcinoma with multiple lung metastases refractory to interferon-alpha showing complete remission by interleukin-2 monotherapy.

We report a case in which a regimen of interleukin-2 (IL-2) achieved pathologically complete remission against renal cell carcinoma with multiple lung metastases. A 63-year-old man was admitted to the Osaka University Hospital with a right renal tumor and multiple lung metastases. Right radical nephrectomy was performed and the histological diagnosis was clear cell carcinoma, G3 > G2, INFbeta, pT3a, pN0. Postoperatively, despite treatment with interferon-alpha, the lung metastases progressed. Consequently, intravenous administration of IL-2 was started at a dose of 70 x 10(4) JRU/day five times per week. After 16 weeks of IL-2 therapy, most of the multiple lung metastases completely vanished and the largest metastatic lung mass was reduced in size. Resection of this residual lung mass was performed and pathological examination revealed no viable cancer cells.

Adenocarcinoma, Clear Cell↗

PubMed2006

Significance of electrostimulation in detecting neurovascular bundle during radical prostatectomy.

OBJECTIVE: The reported rate of erectile dysfunction after nerve-sparing prostatectomy varies according to physicians. Because exact preservation of the neurovascular bundle (NVB) solely depends on the judgment of the physician, he or she should try to correctly identify the NVB and also avoid neurophysiologic injury of the NVB during the procedure. The purpose of the present study is to assess the status of the NVB preservation by physician's judgment at the operation, the changes in intracavernous pressure related to intraoperative electrical stimulation and postoperative histopathological examination. PATIENTS AND METHODS: Thirty-eight patients who underwent nerve-sparing radical prostatectomy judged by intraoperative electrical stimulation of the NVB were included in this study. Bilateral, unilateral and non-nerve-sparing procedures were performed in 18, 17, and 3 cases, respectively. The NVB preservation evaluated by intraoperative physician's judgment was compared to that evaluated by postoperative histopathological examination. Furthermore, the NVB preservation evaluated by intraoperative electrical stimulation was compared to that by physician's judgment and postoperative histopathological examination. RESULTS: For 68 of 76 NVB (89.5%), intraoperative subjective judgment and histopathological assessment were identical. For 66 of 76 NVB (86.8%), electrical stimulation findings and the physician's judgments were identical, and for 70 of 76 NVB (92.1%), electrical stimulation findings and histopathological findings were identical. CONCLUSION: Even if physicians are convinced of a successful nerve-sparing procedure, there are some cases in which the NVB is not preserved accurately or neurophysiological damage is suffered. Therefore, intraoperative electrical stimulation of the NVB as well as the cavernosal nerve is very useful in evaluation of NVB preservation.

Aged↗

PubMed2006

Possible correlation between polymorphism in the tumor necrosis factor-beta gene and the clinicopathological features of bladder cancer in Japanese patients.

OBJECTIVES: In a variety of cancers, several polymorphisms of the tumor necrosis factor (TNF) genes have been reported to result in different clinical outcomes. We investigated whether a polymorphism of the TNF gene is associated with a susceptibility to bladder cancer and its disease status. METHODS: Polymorphisms in the TNF-alpha gene promoter (-308 bp) and the NcoI site in the first intron of the TNF-beta gene were analyzed in 141 Japanese patients with bladder cancer and 173 Japanese controls by polymerase chain reaction-restriction fragment length polymorphism. The correlations between the polymorphisms of the TNF genes and the clinicopathological features were analyzed. RESULTS: The number of cases and controls with TNF-alpha2 was too small to be assessable. In contrast, the TNF-beta1/2 genotype at the NcoI site in the first intron conferred a 1.71-fold increased risk of bladder cancer compared to the TNF-beta2/2 genotype. In the bladder cancer group, patients with the TNF-beta1 allele had a significantly higher risk for a high-grade tumor (grade 3) or carcinoma in situ (CIS) than those without the TNF-beta1 allele. Moreover, in the superficial bladder cancers, patients with the TNF-beta1 allele showed a significantly higher intravesical recurrence rate than those without the TNF-beta1 allele. CONCLUSION: This polymorphism in the TNF-beta gene appears to be associated with tumor occurrence and disease status, such as the tumor grade and the presence of CIS. Further study with an increased sample size is warranted.

Adult↗

PubMed2006

Rare case of aggressive angiomyxoma presenting as a retrovesical tumor.

Aggressive angiomyxoma (AAM) is a rare mesenchymal benign tumor that preferentially involves the pelvic and perineal regions in relatively young females. We report here a rare case of AAM presenting as a retrovesical tumor in a male patient. A 59-year-old man undergoing abdominal ultrasound examination because of benign prostatic hyperplasia was found to have a retrovesical mass. Computed tomography and magnetic resonance imaging of the pelvis showed the retrovesical tumor to be 7.4 x 6.7 cm. The tumor was resected, and diagnosed histopathologically as AAM. The patient showed no recurrence 26 months after resection. Although the majority of retrovesical tumors are considered to be sarcoma or neurogenic tumor, AAM should also be recognized as a differential diagnosis.

Biopsy, Needle↗

PubMed2006

Renal cell carcinoma in dialysis patients: a single center experience.

AIM: Renal cell carcinoma (RCC) is a life-threatening complication of end-stage renal disease with an unclear pathogenesis. We evaluated RCC developing in patients undergoing dialysis. METHODS: In 2624 patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis at our hospital between July 1993 and March 2004, we performed annual screening for RCC using abdominal computed tomography and ultrasonography. Patients diagnosed with RCC underwent radical nephrectomy as well as clinical and pathologic evaluation. RESULTS: RCC was detected in 44 patients (1.68%; 31 males and 13 females). The age of RCC patients was 55.5 +/- 11.1 years. Dialysis duration before RCC diagnosis was 11.2 +/- 7.2 years. Most RCC were early stage and low stage by TNM classification, 43 patients had N0M0 RCC, whereas one had N1M0. Tumor size was 2.9 +/- 1.9 cm. The predominant histological type of RCC was common or conventional cell-type carcinoma (clear cell carcinoma and granular cell carcinoma). Of patients, 5(11.4%) had bilateral RCC, and satellite tumor lesions in RCC were detected in 13 (29.5%). In 36 patients (81.8%) RCC was accompanied by acquired cystic disease of the kidney. These patients had longer dialysis durations (P = 0.01) and smaller tumors (P = 0.048). RCC metastasized postoperatively in 4 patients (9.1%), while one (2.3%) died of cancer. CONCLUSIONS: Our dialysis patients showed a higher incidence of RCC than the general population. Prognosis was favorable because tumors were detected by screening when they were small. Therefore, periodical screening for RCC seems very important in dialysis patients.

Adult↗

PubMed2006

[The growing teratoma syndrome report of a case].

A 26-year-old man presented with a swelling of the right scrotal content, lumbago and exertional dyspnea. He underwent high inguinal orchiectomy. Histopathological examination of the specimen revealed yolk sac tumor and mature teratoma. Further evaluation revealed mediastinal and retroperitoneal lymph node metastases (stage IIIA). A single course of BEP (bleomysin, etoposide and cisplatin), two courses of chemotherapy consisting of nedaplatin and irinotecan, and three courses of TIP (paclitaxel, ifosfamide and cisplatin) were delivered. The previous abnormally elevated serum biomarkers (AFP, beta-hCG and LDH) returned to normal levels, but the mediastinal and retroperitoneal masses continued to enlarge slowly. The CT-guided biopsy of the mediastinal mass was performed, and histologic study revealed no evidence of malignancy. He underwent excision of the mediastinal masses and retroperitoneal lymph node dissection. Histologic examination of the resected specimens revealed mature teratoma without malignant components. These results were compatible with growing teratoma syndrome. 30 months after the first excision of mediastinal mass, he underwent the second excision of recurrent mediastinal mass in the absence of biomarker elevation. The resected specimens revealed mature teratoma without malignant components. He is alive for 49 months after high inguinal orchiectomy and free of carcinoma.

Adult↗

PubMed2006

[Testicular cancer metastatic to multiple organs including the stomach, kidneys, and skin: a case report].

A 39-year-old man whose chief complaints were general fatigue and bloody phlegm was diagnosed with testicular cancer and underwent left high orchiectomy at an affiliated hospital. The histopathologic diagnosis was chorio carcinoma. Several imaging examinations revealed the metastases in the lung, liver, brain, stomach, kidneys and skin. In spite of various chemotherapies, he died 17 months after the operation. Skin metastasis of testicular cancer is very rare and this is the twelfth case reported in the world, to our knowledge. The significance of skin metastasis in testicular cancer is discussed.

Adult↗

PubMed2006

[Molecular-targeted therapy for hormone-refractory prostate cancer].

Molecular-targeted therapy is to treat pathologic pathways specifically in tumor cell or tumor microenvironment. Specific molecular-targeted therapeutic agents for hormone-refractory prostate cancer (HRPC) include endothelin-A receptor antagonist, EGF receptor (EGFR) inhibitor, platelet derived growth factor receptor (PDGFR) inhibitor, nuclear factor of kappaB (NF-kappaB) inhibitor, cyclooxygenase-2 (COX2) inhibitor, and active form of Vitamin D. These agents have been investigated in clinical trials. So far, none of the above-mentioned agent has shown a sufficient clinical efficacy alone. However, docetaxel-based combinations with thalidomide or calcitriol have promising clinical activities. Further investigations are needed to optimize the molecular-targeted agents in the combinations with chemotherapeutic agents for the treatment of HRPC.

Angiotensin Receptor Antagonists↗

PubMed2006

[Living unrelated renal transplantation in an eldery couple: a case report].

We present a 60-year-old female who underwent living unrelated renal transplantation from her 62-year-old husband. The primary immunosuppression consisted of tacrolimus, mycophenolate mofetil and steroid. We did not recognize any rejection in a histopathological study. The total ischemic time to carry out anastomosis of the two renal arteries was 121 minutes. After hemodialysis 5 times for acute tubular necrosis, her renal function improved. She was discharged on the 33rd postoperative day when her serum cretinine level was 1.0 mg/dl. The graft function was stable at 6 months after transplantation. We discussed living unrelated renal transplantation in the elderly population in Japan.

Age Factors↗

PubMed2005

Laparoscopic nephroureterectomy for upper tract transitional cell carcinoma: comparison of laparoscopic and open surgery.

OBJECTIVES: We made a comparative study of laparoscopic nephroureterectomy (LNU) and standard open surgery (ONU) for upper urinary tract transitional cell carcinoma. METHODS AND METHODS: From July 2000 to February 2005, 49 patients underwent total nephroureterectomy for upper tract transitional cell carcinoma at Osaka University Medical Hospital. Of the 49 patients, twenty-five were treated with LNU, and twenty-four with ONU. Each group of cases was reviewed with respect to operative time, complications and postoperative convalescence. RESULTS: The average operative time of the LNU and ONU group was 305.9 min (range 190-480) and 271.2 min (range 135-480) respectively, and the average blood loss was 321.5 ml (80-1370) and 557.7 ml (range 100-1730), respectively. The average time until ambulation after LNU and ONU was 2.2 days (range 1-3) and 4.0 days (range 3-5), respectively. No major postoperative complications were observed in either group. CONCLUSION: ONU still represents the gold standard for the management of upper tract transitional cell carcinoma; however, for low stage cases, LNU offers the advantages of minimally invasive surgery.

Adult↗

PubMed2005

KIT (c-kit oncogene product) pathway is constitutively activated in human testicular germ cell tumors.

We investigated the expression of KIT (product of c-kit oncogene), gain-of-function mutations, and activation of its downstream signal transduction in human testicular cancers. KIT was expressed in 88% (22/25) of seminomas and in 44.4% (4/9) of non-seminomas compared to adjacent normal testicular tissue. Nine of the KIT-expressing seminomas had mutations (40.9%; 9/22) in the c-kit gene; two cases in exon 11 and 7 cases in exon 17. Two of these mutations in exon 17 were novel, and the other seven mutations were identical to the already known gain-of-function mutations which cause activation of KIT without ligand stem cell factor. All of the mutant KIT and 53.8% (7/13) of wild-type KIT were phosphorylated (activated) and associated with phosphorylated phosphatidylinositol 3-kinase (PI3K). Akt was also phosphorylated in these seminomas, suggesting that the KIT-PI3K-Akt pathway is activated in seminoma. These findings suggest that the KIT-PI3K-Akt pathway is constitutively activated in testicular germ cell tumors, due to overexpression of KIT protein and/or gain-of-function mutations in the c-kit gene.

Adult↗

PubMed2005

Cytochrome P450 1B1 is overexpressed and regulated by hypomethylation in prostate cancer.

PURPOSE: Cytochrome P450 1B1 (CYP1B1), a dioxin inducible member of the CYP supergene family, is overexpressed in various human malignancies including prostate cancer. We hypothesized that promoter/enhancer CpG methylation contributes to the regulation of CYP1B1 expression in human prostate tissue. EXPERIMENTAL DESIGN: Expression and induction of the CYP1B1 gene in clinical prostate tissues and prostate cancer cell lines were investigated. The methylation status of the CYP1B1 gene was analyzed in 175 prostate cancer and 96 benign prostatic hyperplasia samples using methylation-specific PCR (MSP) and bisulfite-modified DNA sequencing. MSP primers covered dioxin response elements (DRE) and Sp1 sites that are important for the expression of CYP1B1. RESULTS: Expressions of CYP1B1 mRNA and protein were increased in prostate cancer. The aryl hydrocarbon receptor (AhR)/AhR nuclear translocator (ARNT) heterodimer complex activates gene transcription by binding to the DREs of CYP1B1. In prostate cancer cells, CYP1B1 mRNA was induced by 2,3,7,8-tetrachlorodigenzo-p-dioxin (TCDD) and/or demethylation agent (5-aza-2-deoxycytidine). There was no change in the expressions of AhR and ARNT. Methylation of promoter/enhancer regions was significantly higher in benign prostatic hyperplasia compared with prostate cancer. MSP-positive patients had significantly lower risk for prostate cancer as compared with MSP-negative patients. There was no correlation between CYP1B1 methylation status and clinicopathologic features. CONCLUSIONS: CYP1B1 is overexpressed in prostate cancer and regulated by hypomethylation of its promoter/enhancer region. This is the first report about CYP1B1 regulation in human clinical prostate samples showing that hypomethylation of the CYP1B1 gene may play an important role in prostate cancer.

Aged↗