Biomedical subjects

I Hara

Publications and source records attributed to I Hara.

At least 73 records · Page 4Linked to original sources

PubMed1999

Elevation of serum level of vascular endothelial growth factor as a new predictor of recurrence and disease progression in patients with superficial urothelial cancer.

OBJECTIVES: To determine whether the serum vascular endothelial growth factor (VEGF) level in patients with urothelial cancer could be used as a predictor of recurrence and disease progression. METHODS: Serum levels of VEGF in 51 healthy controls and 135 patients with urothelial cancer (81 superficial and 54 invasive cancers) were measured using a sandwich enzyme immunoassay, and the results were analyzed with respect to several clinicopathologic factors. RESULTS: Significant differences in the serum VEGF level were observed between healthy controls and patients with superficial urothelial cancer (34+/-12 pg/mL versus 49+/-27 pg/mL, P<0.001) and between healthy controls and patients with invasive cancer (34+/-12 pg/mL versus 51+/-35 pg/mL, P<0.001), whereas there was no significant difference in the serum VEGF level between superficial and invasive cancers (49+/-27 pg/mL versus 51+/-35 pg/mL, P = 0.31). Among patients with superficial cancer, the disease-free survival rate of patients with elevated serum levels of VEGF was significantly lower than that of patients with normal levels (P<0.05). The progression-free survival rate of superficial cancer patients with elevated serum levels of VEGF was also significantly lower than that of patients with normal levels (P<0.01). In addition, Cox's multivariate analysis revealed that the elevation of serum VEGF level was strongly associated with disease-free survival and progression-free survival in patients with superficial cancer (P<0.05). CONCLUSIONS: The results of this study suggest that the elevation of serum VEGF level could be used as a new independent predictor of recurrence and disease progression in patients with superficial urothelial cancer.

Adult↗

PubMed1999

Expression of MAGE genes in testicular germ cell tumors.

OBJECTIVES: Some of the MAGE gene family that encode tumor-rejection antigens recognized by cytotoxic T lymphocytes are expressed at the mRNA level in various malignant tumors. However, these genes are silent in normal tissues, except in the testis and placenta. It is therefore important to understand how MAGE gene expression changes with malignant transformation of the testis. We investigated the expression of MAGE-1, -2, -3, and -4 genes at the mRNA level in testicular germ cell tumors. METHODS: Reverse transcriptase-polymerase chain reaction for MAGE genes was performed using 32 testicular germ cell tumor specimens. RESULTS: MAGE-1, -2, -3, and -4 mRNA was detected in 16 (72%), 15 (68%), 18 (82%), and 17 (77%) of 22 patients with pure seminoma or mixed type with seminomatous elements. MAGE-1 , -2, -3, and -4 mRNA was found in 2 (20%), 5 (50%), 4 (40%), and 4 (40%) of 10 patients with nonseminomatous germ cell tumor (NSGCT). The expression rate of MAGE-1, -3, and -4 mRNA was significantly higher in patients with seminomatous elements than that in those with NSGCT. MAGE expression did not correlate with disease progression. CONCLUSIONS: MAGE genes are more preserved in seminoma than in NSGCT. This suggests that seminoma has traits more similar to normal testis than does NSGCT.

Adolescent↗

PubMed1999

Expression of CD44 adhesion molecules in nonpapillary renal cell carcinoma and normal kidneys.

OBJECTIVES: To analyze the relationship between the alterations in the expression of the CD44 gene in nonpapillary renal cell carcinoma (RCC) and several clinicopathologic factors. METHODS: The expression of the CD44 gene in 10 human RCC cell lines, 60 nonpapillary RCC tumor samples, and 15 normal kidney samples was investigated by reverse-transcription polymerase chain reaction (RT-PCR) using a set of primers capable of amplifying all CD44 variant isoforms. The results were analyzed with respect to several clinicopathologic factors. RESULTS: Nine of the 10 human RCC cell lines predominantly expressed the standard CD44 isoform (CD44s); CD44v10 was the major isoform in the 10th RCC cell line. The 15 normal kidney samples revealed the identical CD44 gene expression pattern; that is, CD44s, CD44v8-10, and CD44v10 were detectable in normal kidneys, and among them, CD44s was expressed most dominantly. In the 60 nonpapillary RCC samples, CD44s, CD44v8-10, and CD44v10 were the major isoforms in 46 (77%), 11 (18%), and 3 (5%) cases, respectively. Furthermore, the incidence of the predominant expression of CD44v8-10 in high-stage RCC was significantly higher than that in low-stage RCC. CD44s was more frequently expressed as a major isoform in clear cell RCC than in other histologic types of RCC. CONCLUSIONS: The results of this study show that the alternative splicing pattern of CD44 gene in RCC is different in each histologic type of RCC and suggest that CD44v8-10 upregulation in the progression of nonpapillary RCC is important.

Adult↗

PubMed1999

Overexpression of Bcl-2 enhances metastatic potential of human bladder cancer cells.

We investigated the effect of Bcl-2 expression on the metastatic process of bladder cancer cells by using the Bcl-2-transfected human bladder cancer cell lines (KoTCC-1/BH) and the control vector only-transfected cell line (KoTCC-1/C), which were generated in our previous study (Miyake et al (1998) Oncogene 16: 933-934). When they were injected intravenously into athymic nude mice, KoTCC-1/BH formed more than three times as many tumour nodules in the lungs as did KoTCC-1/C. In addition, tumour progression, including lymph node metastasis and haemorrhagic ascites, was observed to be more advanced after the implantation of KoTCC-1/BH cells into the bladder wall of nude mice than after implantation of KoTCC-1/C cells. These enhanced malignant progression of KoTCC-1/BH cells were well correlated with anti-apoptotic activity under anchorage-independent conditions in in vitro experimental models. In contrast, there were no significant differences among these cell lines in their growth rates both in vitro and in vivo, invasive ability and cell motility. These findings suggest that, if it is overexpressed, Bcl-2 prolongs cell survival under unfavourable conditions encountered in the metastatic process, resulting in the enhanced metastatic potential of bladder cancer.

Animals↗

PubMed1999

Outcome of precise vesicourethral anastomosis following retropubic radical prostatectomy using a Foley catheter.

PURPOSE: In order to evaluate precise anastomosis using a Foley catheter, complications following radical retropubic prostatectomy were examined. METHODS: Twenty-one patients underwent radical retropubic prostatectomy. Precise vesicourethral anastomosis was performed, visualizing the urethral stump by raising up the urogenital diaphragm using a Foley catheter. Complications, such as prolonged urinary extravasation and temporary urinary retention, were checked when the catheter was removed. Incontinence was evaluated both within 6 weeks and more than 6 weeks after operation. Anastomotic and urethral strictures were also checked during follow up. RESULTS: The follow-up period ranged from 4 to 47 months (mean (+/- SD) 22.0 +/- 12.1 months). Eighteen of 21 patients (85.7%) achieved continence after the operation. However, two patients still had stress incontinence and one patient had mild incontinence. Neither prolonged urinary extravasation nor temporally urinary retention were observed. Anastomotic and urethral stricture were not experienced during follow up. CONCLUSIONS: Precise anastomosis using a Foley catheter is technically easy and useful, even for relatively inexperienced urologists, to perform. Patients can often achieve continence following this procedure.

Adult↗

PubMed1999

Pharmacokinetics of natural human IFN-alpha in hemodialysis patients.

A pharmacokinetic study of natural human interferon-alpha (IFN-alpha) was conducted in hemodialysis patients. Natural human IFN-alpha was intramuscularly (i.m.) administered to 8 hemodialysis patients at a single dose of 5 million IU and to 7 patients undergoing hemodialysis at the same dose once daily for 5 successive days. The serum antiviral activity was determined by a cytopathic effect bioassay. In the single dose study, the serum antiviral activity reached a maximum (Cmax) of 56.4 +/- 33.3 IU/ml at 8.3 +/- 2.7 h after dosing, and the area under the serum concentration-time curve (AUC0-24h) was 957.2 +/- 601.8 IU h/ml. The Cmax and AUC0-24h values at day 5 following the repeated dosing were both 2.6-fold higher than those of day 1, and the serum antiviral activity reached a steady state within 3 days after initiation of repeated administration. The serum antiviral activity in hemodialysis patients showed a tendency to increase compared with that in the subjects with normal renal function, but the magnitude of the differences was not great. In one nonhemodialysis patient with poor renal function (creatinine clearance < 30 ml/min), no increases in serum antiviral activity owing to repeated dosing were observed. The main adverse events seen were fever (4 of 13, 30.8%), leukopenia (3 of 13, 23.1%), and fatigue (2 of 13, 15.4%). These results suggest that dosage modifications of natural human IFN-alpha are unnecessary for patients with low renal function, even those undergoing hemodialysis.

Aged↗

PubMed1999

Clinical outcome of high-dose chemotherapy combined with peripheral blood stem cell transplantation for male germ cell tumors.

Peripheral blood stem cell transplantation (PBSCT) is widely performed currently instead of bone marrow transplantation (BMT) because bone marrow reconstruction is better and the procedure is less invasive. We applied 26 courses of high-dose chemotherapy (1250 mg/m2 of carboplatin, 1500 mg/m2 of etoposide and 7.5 g/m2 of ifosfamide) to 14 male patients with germ cell tumors. Eleven patients underwent high-dose chemotherapy as induction after two to three courses of conventional BEP therapy. The remaining three patients had recurrent disease after conventional chemotherapies. Peripheral blood stem cells were harvested during previous chemotherapy and sufficient CD34+ cells were harvested for transplantation. Although all patients had grade 4 hematotoxicity, the white blood cell count recovered to more than 1000/microl within 8-11 days after PBSCT. No treatment-related death was found. Nine of 14 patients (64.3%) remain disease free at 18 months of median follow up time (range 12-60). We conclude that high-dose chemotherapy is a safe and effective means of treating advanced or refractory germ cell tumors in male patients.

Adult↗

PubMed1999

Calcium ionophore, ionomycin inhibits growth of human bladder cancer cells both in vitro and in vivo with alteration of Bcl-2 and Bax expression levels.

PURPOSE: The objective of this study was to characterize the antiproliferative effects of the calcium ionophore, ionomycin on the human bladder cancer cell line HT1376 both in vitro and in vivo. MATERIALS AND METHODS: The in vitro growth rate of HT1376 after treatment with ionomycin was measured by using the MTT assay. The apoptotic features in HT1376 after ionomycin treatment were evaluated by flow cytometric analysis and DNA degradation assay. Bcl-2 and Bax expression levels in HT1376 after ionomycin treatment were examined by Northern and Western blot analyses. The effects of intratumoral injection of ionomycin on the growth of subcutaneous HT1376 tumors established in athymic nude mice were then tested. The efficacy of combined treatment with ionomycin and cisplatin against HT1376 growth was also examined. RESULTS: The in vitro growth rate of HT1376 was suppressed by ionomycin in a dose- and time-dependent manner, and characteristic apoptotic DNA degradation was observed in HT1376. Ionomycin treatment caused a marked decrease in the ratios of Bcl-2 to Bax mRNA and protein in HT1376 cells. Intratumoral injection of ionomycin into subcutaneous HT1376 tumors reduced the tumorigenicity in nude mice. Furthermore, these in vivo growth-inhibitory effects of ionomycin were significantly enhanced by pretreatment with cisplatin. CONCLUSIONS: These findings suggest that ionomycin-based therapy could be used as a novel therapeutic strategy for advanced bladder cancer through the effective induction of apoptosis by decreasing the ratio of Bcl-2 to Bax.

Animals↗

PubMed1999

Elevation of urokinase-type plasminogen activator and its receptor densities as new predictors of disease progression and prognosis in men with prostate cancer.

We examined whether two newly defined parameters, the density of urokinase-type plasminogen activator (uPAD) and the density of its receptor (uPARD), which were determined by dividing the serum levels of uPA and uPAR by the prostate volume, respectively, could be used as predictors of the progression and prognosis of prostate cancer (PC). Serum levels of uPA and uPAR in 40 healthy controls, 70 patients with benign prostatic hypertrophy (BPH) and 80 patients with PC were measured by a sandwich enzyme immunoassay, and prostate volume was measured by ultrasonography. The mean levels of uPAD and uPARD in patients with PC were significantly higher than those in healthy controls and patients with BPH. Furthermore, the uPAD and uPARD levels in PC patients with metastasis were significantly elevated compared with those in patients without metastasis. Among patients who underwent radical prostatectomy, the levels of uPAD and uPARD in patients with pathologically organ-confined disease were significantly lower than in those with advanced disease. The overall survival rate of PC cancer patients with elevated levels of either uPAD or uPARD, or of both, was significantly lower than that of patients with normal levels of uPAD and uPARD. In addition, Cox's multivariate analysis revealed that the elevation of uPAD or uPARD level, or of both, was strongly associated with overall survival in PC patients. These findings suggest that the elevation of uPAD or uPARD, or of both, could be used as new predictors of progression and prognosis in patients with PC.

Adult↗

PubMed1999

[A case of true carcinosarcoma in bladder diverticulum].

We report a case of carcinosarcoma arising from a bladder diverticulum. A 71-year-old male was referred to our hospital for macroscopic hematuria. Two diverticula were identified in the left wall of the urinary bladder, one of which showed a broad-based tumor. The bladder tumor was resected using a transuretheral approach and the tumor was histologically diagnosed as leiomyosarcoma. The patient underwent partial resection of the bladder including the two diverticula and the tumor. Pathological examination revealed that the resected specimen was composed of three elements, transitional cell carcinoma (G3), squamous cell carcinoma, and leiomyosarcoma. Thus, the patient was diagnosed with carcinosarcoma. He died 5 months after surgery to remove the panperitonitis carcinomatosa. This case is the 38th reported case of bladder carcinosarcoma in Japan.

Aged↗

PubMed1999

[Expression of CD44 variant isoform in urine samples of urothelial cancer patient].

CD44v8-10 variant isoform is frequently expressed in many kinds of cancers. We have already reported that 77% of bladder cancer specimens expressed CD44v8-10 and using CD44v8-10/CD44v10 competitive reverse transcription-polymerase chain reaction (CC-RT-PCR), we detected exfoliated urothelial cancer cells in urine samples of urothelial cancer patients (Int J Cancer 79: 560, 1998, J Urol 160: 2004). In this paper, we review the expressing of CD44 variant isoform in various kinds of cancers, and the principle of CC-RT-PCR which can be a novel screening method for urothelial cancer.

Carcinoma, Transitional Cell↗

PubMed1999

Relative expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in mouse renal cell carcinoma cells regulates their metastatic potential.

To clarify the significance of the balance between matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in the progression of renal cell carcinoma, we transfected both the MMP-2 and TIMP-2 genes simultaneously into RenCa, a mouse renal cell carcinoma cell line that does not express detectable levels of either MMP-2 or TIMP-2 mRNAs, and established several clones with various MMP-2:TIMP-2 expression ratios. On the basis of the quantitative evaluation of the MMP-2: TIMP-2 mRNA expression ratio by Northern blot analysis, we selected a clone overexpressing MMP-2 alone (RenCa/M), a clone overexpressing TIMP-2 alone (RenCa/T), and two kinds of clones overexpressing both, i.e., one with a high (RenCa/MTh) and one with a low (RenCa/MTl) MMP-2: TIMP-2 ratio, to compare the tumor cell phenotypes. In an in vitro tumor cell invasion assay, the MMP-2:TIMP-2 ratios of the RenCa sublines were directly correlated with their invasive potential. The invasive abilities of the parental RenCa cells induced by conditioned media from RenCa sublines were also correlated with the MMP-2:TIMP-2 ratios of the sublines. The cell adhesion assay showed the inverse correlation between the MMP-2 expression levels in the sublines and their cell adhesion to several extracellular matrix components. Furthermore, when injected i.v. or into the renal subcapsule in syngeneic mice, RenCa sublines formed metastatic nodules in the lungs, and the number of nodules was correlated with the MMP-2:TIMP-2 ratio of each clone. In contrast, despite the growth-inhibitory effects of TIMP-2 overexpression, MMP-2 overexpression had no effect on either proliferation in vitro of RenCa sublines or on their growth as tumors in vivo. These results suggest that the MMP-2:TIMP-2 expression ratio is a critical factor in the invasion and metastasis of renal cell carcinoma.

Animals↗

PubMed1999

[Laparoscopic resection of retroperitoneal tumors: report of two cases].

Here we report two rare cases of retroperitoneal tumors which were found incidentally and resected laparoscopically. Case 1; A 43-year-old woman presented with general fatigue and revealed liver dysfunction. Although the initial diagnosis with computed tomography (CT) was left non-functioning adrenal tumor, it was proven as a retroperitoneal tumor adjacent to the left adrenal gland by laparoscopic examination. The tumor was resected laparoscopically and diagnosed histopathologically as a solitary retroperitoneal neurofibroma. Case 2; A 68-year-old man was being followed for a renal stone and a perirenal tumor was found by CT. It was resected laparoscopically and diagnosed as a mature retroperitoneal teratoma by histopathological examination. We conclude that laparoscopic resection is useful for the retroperitoneal tumors as well as for adrenal tumors.

Adult↗

PubMed1999

[Clinical results of super high-dose chemotherapy with peripheral blood stem cell transplantation for patients with advanced germ cell tumor].

We examined the clinical results of super high-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) in 14 patients with poor-risk advanced germ cell tumors. The mean number of nadir white blood cells was 205 +/- 126/microliter; the mean period of number of white blood cells fewer than 1,000/microliter was at 8-10 days (mean +/- SD; 9.2 +/- 0.92). The nadir number of blood platelet cells was 1.7 +/- 0.70 x 10(4)/microliter; the mean period of number of platelet cells fewer than 5 x 10(4)/microliter was at 12.6 +/- 2.17 days. Of 10 patients treated with super high-dose chemotherapy with PBSCT as induction therapy, 8 patients (80%) showed that the serum tumor marker returned within the normal range after super high-dose chemotherapy. Of 8 patients, 7 underwent resection of the residual tumor. Surgical or pathological CR was obtained in 5 of these 7 patients, 4 patients of whom were alive with no evidence of disease 29 to 49 months after initial consultation: the other patient died with recurrence 20 months after initial visit. On the other hand, super high-dose chemotherapy with PBSCT was performed for one patient as consolidation, and for 3 patients with recurrence. Of these 4 patients, one died from disease 6 months after detection of recurrence. The other 3 patients were alive with no evidence of disease at 7-37 months after initial visit. The 1- and 3-year disease-free survival rates were 88% and 72%, respectively. In conclusion, super high-dose chemotherapy with PBSCT can be done safely and could be useful for patients with poor-risk germ cell tumor.

Adult↗

PubMed1999

[High-dose chemotherapy with peripheral blood stem cell autotransplantation for patients with poor-risk testicular germ cell tumors--pilot study of the Japan Blood Cell Transplantation Study Group].

The efficacy and toxicity of a single cycle of high-dose chemotherapy with peripheral blood stem cell autotransplantation (PBSCT) in patients with poor-risk testicular germ cell tumors (GCT) enrolled in the Japan Blood Cell Transplantation Study Group was investigated. Previously untreated poor-risk testicular GCT patients were treated with BEP therapy (cisplatin, etoposide and bleomycin) with or without high-dose chemotherapy (carboplatin, etoposide and ifosphamide) followed by PBSCT. Patients were qualified for a change to high-dose chemotherapy if elevated serum tumor markers (human chorionic gonadotropin-beta, alpha-fetoprotein and lactate dehydrogenase) was observed after 3 cycles of BEP therapy. Eighteen patients were treated with BEP therapy alone and 16 with BEP and high-dose chemotherapy. At the completion of high-dose chemotherapy, all tumor markers had returned to normal in 6 patients. Among them, 1 had only teratoma found at resection and 5 had carcinoma resected. Nine patients who had persistent elevation of any tumor marker were treated with high-dose chemotherapy or another anticancer drug. Thirteen are alive (81%) and 9 (56%) are continuously disease-free at a median follow up of 11 months. The median time from PBSCT to a granulocyte count > 500/microL was 9.5 days and to a platelet count > 50,000/microL was 13 days.

Adolescent↗

PubMed1999

Appearance of highly sensitive cells to L-type Ca antagonist in cultured cerebellar granule cells.

We studied intracellular Ca2+ ([Ca2+]i) kinetics within single cells using and image-analyzing system. We prepared a culture dish with a bottom made of quartz (non-fluorescent glass) for reducing the background fluorescence during [Ca2+]i measurement. Furthermore, we changed the concentration of the poly-L-lysine solution which had been used to make cells adhere to the dish bottom from the conventional 5 micrograms/ml to 15 micrograms/ml. This modification improved cell viability, prevented colony formation, and therefore, provided favorable cell samples for detection within single cells. Then, we investigated 25 mM KCl-evoked changes in the [Ca2+]i level of rat cerebellar granule cells. We found that sensitivity to KCl was high in some cells but low in others. In a study using the highly sensitive cells, nicardipine, nimodipine and nifedipine were active even at nanomolar or picomolar levels, although their affinities to the L-type Ca ion channel have been reported to act only at micromolar levels.

Animals↗

PubMed1999

Utility of Competitive Reverse Transcription-Polymerase Chain Reaction Analysis of Specific CD44 Variant RNA for Detecting Upper Urinary Tract Transitional-Cell Carcinoma.

Recently, we developed a novel molecular approach, CD44 v8-10/CD44 v10 competitive reverse transcription-polymerase chain reaction (CC-RT-PCR), to detect a sparse population of cancer cells overexpressing CD44v8-10 among a much larger population of nonneoplastic cells in body fluids by the measurement of the transcriptional level of CD44v8-10 relative to that of CD44v10. We have shown the utility of CC-RT-PCR in diagnosing disease using urine samples from patients with bladder cancer. In this study, we initially examined the expression of CD44 splice variants in human upper urinary tract transitional-cell carcinomas (UUT-TCCs) and their adjacent normal urinary tissues by RT-PCR. Any CD44 variant isoforms were barely detectable in normal urinary tissues, whereas CD44v8-10 was predominantly expressed in 21 of the 25 UUT-TCC specimens (84%). We then applied CC-RT-PCR to spontaneously voided urine samples from 40 patients with UUT-TCC and 40 patients with benign urologic diseases. The CC-RT-PCR analysis revealed that all of the samples from patients with benign diseases presented a predominant expression of the CD44v10 transcript, whereas 26 of the 40 samples from patients with UUT-TCC dominantly expressed the CD44v8-10 transcript. In addition, the positive rate obtained by the CC-RT-PCR analysis was significantly higher than that obtained by cytologic examination, especially in patients with low-grade UUT-TCC. These findings strongly suggest that CC-RT-PCR is a useful noninvasive tool for the diagnosis of UUT-TCC.

Journal Article↗

PubMed1998

Highly specific and sensitive detection of malignancy in urine samples from patients with urothelial cancer by CD44v8-10/CD44v10 competitive RT-PCR.

CD44 is a widely expressed cell surface adhesion molecule in which various isoforms arise from alternative RNA splicing mechanism. Overexpression of specific CD44 splice variant, i.e., CD44v8-10, has been found in several human malignancies and is considered to be associated with tumor progression and metastasis. We have demonstrated a novel molecular approach, CD44v8-10/CD44v10 competitive reverse transcription-polymerase chain reaction (CC-RT-PCR) for the detection of cancer cells overexpressing CD44v8-10 by the measurement of the transcriptional level of CD44v8-10 relative to that of CD44v10 (v8-10/v10 ratio). In this study, we initially examined the expression of CD44 splice variants in human urothelial cancers and their adjacent normal urinary tissues by RT-PCR. Any CD44 variant isoforms were barely detectable in normal urinary tissues, whereas CD44v8-10 was predominantly expressed in 23 of the 30 (77%) urothelial cancer specimens. We then applied CC-RT-PCR to spontaneously voided urine samples from patients with 80 urothelial cancer and 50 various benign urologic diseases. The CC-RT-PCR analysis revealed that all of the samples associated with benign diseases presented a predominant expression of the CD44v10 transcript (the v8-10/v10 ratios = 0.00-0.87), whereas 62 of the 80 samples associated with urothelial cancers mostly expressed the CD44v8-10 transcript (the v8-10/v10 ratios > 1.00). In addition, the positivity rate obtained by the CC-RT-PCR analysis was high regardless of the pathological grade of the urothelial cancers, although the sensitivity of the cytological examination declined with decreasing tumor grade. Our findings suggest strongly that CC-RT-PCR is a non-invasive useful tool for the diagnosis of urine samples from patients with urothelial cancer.

Adolescent↗