Biomedical subjects

I Hara

Publications and source records attributed to I Hara.

At least 91 records · Page 5Linked to original sources

PubMed1998

Serum matrix metalloproteinase-2 and its density in men with prostate cancer as a new predictor of disease extension.

We examined whether the serum matrix metalloproteinase-2 (MMP-2) level and MMP-2 density could be predictors of the development and extension of prostate cancer. Serum samples were collected before any clinical treatment from 98 patients with prostate cancer and from 76 patients with benign prostatic hyperplasia (BPH). Control sera were obtained from 70 healthy men. The serum level of MMP-2 was determined by 1-step enzyme immunoassay. A newly defined MMP-2 density parameter was determined by dividing the serum level of MMP-2 by the prostate volume, which was measured by ultrasonography. The mean serum level of MMP-2 in prostate cancer patients was significantly higher than in the control and BPH groups. Furthermore, the serum MMP-2 levels in prostate cancer patients with metastasis were highly elevated compared with those without metastases. The MMP-2 density in pathologically organ-confined prostate cancer was significantly higher than that in BPH. There was a statistically significant difference in the MMP-2 density between pT2N0M0 and pT1N0M0 prostate cancers. Moreover, the serum MMP-2 level correlated well with the clinical course of prostate cancer with bone metastasis. Our results suggest that MMP-2 plays an important role in the development and extension of prostate cancer and that the serum level of MMP-2 and the MMP-2 density indicate prostate cancer extension and are, therefore, useful for the followup of prostate cancer patients.

Aged↗

PubMed1998

Overexpression of Bcl-2 in bladder cancer cells inhibits apoptosis induced by cisplatin and adenoviral-mediated p53 gene transfer.

To investigate the effects of the expression of Bcl-2 protein in bladder cancer on the apoptosis induced by cisplatin or adenoviral-mediated p53 gene (Ad5CMV-p53) transfer, we transfected the bcl-2 gene into KoTCC-1, a human bladder cancer cell line that does not express the Bcl-2 protein. The Bcl-2-transfected KoTCC-1 (KoTCC-1/B) exhibited significantly higher resistance to both cisplatin and Ad5CMV-p53 transfer than did either the parental KoTCC-1 (KoTCC-1/P) or the vector-only transfected cell line (KoTCC-1/C). The flow cytometric analysis of the propidium iodide-stained nuclei and DNA fragmentation analysis after cisplatin or Ad5CMV-p53 treatment revealed DNA degradation in both KoTCC-1/P and KoTCC-1/C, whereas KoTCC1/B showed a marked inhibition of DNA degradation. Following the treatment with cisplatin or Ad5CMV-p53, the accumulation of p53 protein was highly detectable for a long period in KoTCC-1/B compared to that in KoTTC-1/P and KoTCC-1/C. Furthermore, the cisplatin and Ad5CMV-p53 treatments each reduced the volume of the subcutaneous tumors established in nude mice formed by KoTCC-1/P or KoTCC-1/C; in contrast, their reductive effects on the tumors formed by KoTCC-1/B were significantly suppressed. The intraperitoneal tumor cell implantation model revealed that the prognoses of mice injected with KoTCC-1/B were significantly inferior to those of the mice injected with either KoTCC-1/P or KoTCC-1/C after treatment with cisplatin or Ad5CMV-p53. These findings suggest that the expression of Bcl-2 in bladder cancer cells interferes with the therapeutic effects of cisplatin and Ad5CMV-p53 through the inhibition of the apoptotic pathway.

Adenoviruses, Human↗

PubMed1998

Expression of basic fibroblast growth factor is associated with resistance to cisplatin in a human bladder cancer cell line.

To clarify the role of basic fibroblast growth factor (FGF-2) in the drug resistance of bladder cancer, we transfected the FGF-2 gene into HT1376, an FGF-2 negative human bladder cancer cell line. The FGF-2-transfected cell lines exhibited three- to four-fold higher resistant potential to cisplatin than the vector-only transfected control cell lines in vitro. When cisplatin was injected intraperitoneally after s.c. implantation of HT1376 sublines into nude mice, FGF-2 transfectants formed tumors about twice as large as did controls. In contrast, there was no significant difference in either cell proliferation in vitro or tumor growth in vivo among these cell lines without cisplatin treatment. Furthermore, DNA degradation following cisplatin treatment was markedly suppressed in FGF-2 transfectants compared to control cells. These results suggest that the expression of the FGF-2 gene plays an important role in the acquisition of the cisplatin-resistant phenotype of bladder cancer, probably through the protection against cisplatin-induced apoptosis.

Animals↗

PubMed1998

Influence of cytokines and growth factors on matrix metalloproteinase-2 production and invasion of human renal cancer.

This study evaluated the influence of cytokines and growth factors on the production of matrix metalloproteinase-2 (MMP-2, 72-kDa type IV collagenase, gelatinase A) and invasion of the human renal cell carcinoma (HRCC) cell line KG-2. The cells were treated with cytokines and growth factors, and the gelatiolytic activity and in vitro invasion were examined. Basic fibroblast growth factor (bFGF) stimulated MMP-2 production by KG-2 cells to 2.0-, 4.84- and 4.53-fold that of the untreated group at 0.1, 1.0 and 10 ng/ml, respectively. Transforming growth factor-beta1 (TGF-beta1) at very low concentrations of 10 pg/ml and 100 pg/ml stimulated enzyme production in KG-2 cells by 1.74- and 2.83-fold, respectively. In contrast, interferon-gamma (IFN-gamma) decreased MMP-2 production by KG-2 cells at 10 and 100 U/ml to 69% and 41% of the level in the untreated group, respectively. At those concentrations, IFN-gamma did not cause cytostasis in KG-2 cells. Moreover, bFGF and TGF-beta1 (low concentrations) stimulated in vitro invasion of KG-2 cells, but IFN-gamma decreased the invasive activity, which was well correlated with the levels of MMP-2. However, the expression of MMP-2 mRNA of KG-2 cells treated with 10 ng/ml bFGF, 100 pg/ml TGF-beta1 and 100 U/ml IFN-gamma was shown to be 3.8-, 3.4- and 0.7-fold, respectively, those in untreated groups. Thus the production of MMP-2 in HRCC was influenced by cytokines and growth factors, and MMP-2 plays an important role in the invasion and metastasis of certain types of HRCC.

Cytokines↗

PubMed1998

Isolation and characterization of vanadium bromoperoxidase from a marine macroalga, Ecklonia stolonifera.

The bromoperoxidase has been isolated from the marine brown alga, Ecklonia stolonifera (83 kDa) and has been characterized. Bromoperoxidase requires vanadium for enzyme activity as has been evidenced by EPR spectroscopy. The enzyme activity increased ca. 250% with the action of V5+ on the isolated enzyme, since more than 2/3 of the protein molecules were in the apo form. The increase in the enzyme activity was specific to V5+, while Fe2+, Fe3+, and Cu2+ inhibited the enzyme activity. This effect of V5+ addition was inhibited in phosphate buffer, probably because phosphate and vanadate compete for the active site. The bromoperoxidase exhibited a high thermostability (Tm = 68 degrees C) and a high stability in organic solvents (completely intact even in the presence of 50% methanol, ethanol and 1-propanol).

Chromatography, Gel↗

PubMed1998

Determination of progesterone and 17-hydroxyprogesterone by high performance liquid chromatography after pre-column derivatization with 4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionohydra zide.

Progesterone, 17-hydroxyprogesterone and four other 3-keto steroids were determined by high performance liquid chromatography with fluorescence detection. Each steroid was derivatized with 4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene++ +-3- propionohydrazide (BODIPY FL hydrazide) and separated on a Wakosil 5C4 column with acetonitrile-water (7 + 3) as mobile phase. The limits of detection of progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone and 17-methyltestosterone were 550-3700 fmol per 10 microliters injection (signal-to-noise ratio = 5) serum. The calibration curves were linear up to 1000 ng/ml serum. The proposed method was most sensitive among the available high performance liquid chromatographic methods after fluorescence and chemiluminescence pre-labeling with dansylhydrazine.

17-alpha-Hydroxyprogesterone↗

PubMed1998

The significance of lymphadenectomy in transitional cell carcinoma of the upper urinary tract.

OBJECTIVE: To determine the efficacy of lymphadenectomy after nephroureterectomy in patients with transitional cell carcinoma (TCC) of the upper urinary tract. PATIENTS AND METHODS: Between January 1986 and December 1995, 72 patients (mean age 67 years, range 45-82) underwent nephroureterectomy for primary TCC of the upper urinary tract. In 35 patients, a lymphadenectomy was also performed. The clinicopathological data were analysed retrospectively, focusing on the significance of lymphadenectomy. RESULTS: Lymph vessel invasion was found in 28 patients and its incidence was closely correlated with both tumour grade and pathological stage. Of the 35 patients who underwent lymphadenectomy, lymph node metastases were found in 13 patients, all of whom had lymph vessel invasion. There was no significant difference in the survival rate between patients with and without lymphadenectomy; however, among the 44 patients with no lymph vessel invasion, the survival rate of those with lymphadenectomy was significantly higher than in those without (P<0.05). CONCLUSION: Lymphadenectomy may provide a therapeutic advantage in patients with upper urinary tract TCC and no lymph vessel invasion. However, patients with lymph vessel invasion seem to have systemic disease; therefore, aggressive systemic adjuvant therapies rather than regional lymphadenectomy should be applied in these patients.

Aged↗

PubMed1998

Urinary cytology and competitive reverse transcriptase-polymerase chain reaction analysis of a specific CD44 variant to detect and monitor bladder cancer.

PURPOSE: Recently a novel molecular approach, CD44 variant exon (v)8-10/CD44 v10 competitive reverse transcription-polymerase chain reaction (RT-PCR), was developed. CD44 competitive RT-PCR can detect a sparse population of cancer cells over expressing CD44 v8-10 among a much larger population of nonneoplastic cells in body fluids, that is pleural effusion and urine, by the measurement of transcriptional CD44 v8-10 relative to CD44 v10. The use of the CD44 competitive RT-PCR assay to diagnose and monitor bladder cancer was compared to urinary cytology. MATERIALS AND METHODS: Spontaneously voided urine samples from 71 patients with bladder cancer and 50 with benign urological diseases were analyzed by CD44 competitive RT-PCR and conventional urinary cytology. Urine samples from 24 patients with completely resected bladder tumors also were analyzed. RESULTS: The CD44 competitive RT-PCR assay and urinary cytology revealed a sensitivity of 77 and 58%, and a specificity of 100 and 98%, respectively. Furthermore, combining the results of the 2 methods increased sensitivity to 90%. Urine samples from patients with bladder cancer following curative surgery were correctly diagnosed in 96% with the CD44 competitive RT-PCR assay compared to 83% with urinary cytology. CONCLUSIONS: The CD44 competitive RT-PCR assay is a useful, noninvasive method to diagnose and monitor bladder cancer. The assay could be an important adjunct to urinary cytology to detect exfoliated bladder cancer cells in urine.

Adolescent↗

PubMed1998

Construction and voiding functions of three types of orthotopic neobladders using colonic segments: the Kobe University experience.

BACKGROUND: At Kobe University Hospital we have created orthotopic neobladders since 1988 by using several colonic segments. Various types of neobladders were compared and a detailed description of these procedures and the voiding function outcome is presented. METHODS: Thirty-two men with invasive bladder carcinoma or recurrent carcinoma in situ underwent a radical cystectomy followed by orthotopic neobladder replacement using a right colonic, ileocolic or sigmoid colonic segment. The functional capacity, percentage of residual urine volume, configuration of the neobladder, and location in the pelvis were evaluated 1 year after surgery. Voiding function was evaluated using a questionnaire which included questions on diurnal and nocturnal continence, and by uroflowmetric analysis. RESULTS: Operative time, blood loss, and functional neobladder capacity did not differ for the 3 types of neobladders. The configuration of the right colonic and ileocolic neobladders resembled the shape of a rugby ball. The configuration of the sigmoid neobladder was oval. The right colonic and ileocolic neobladders tended to be located along the right side wall of the pelvis. The sigmoid neobladder was located in the center of the pelvis. Daytime and nocturnal continence was not affected by either the type of neobladder or its configuration or position. Neobladders located in the center of the pelvis exhibited a better maximum flow rate than those located along the right wall of the pelvis. CONCLUSION: The technical difficulty in constructing the 3 types of neobladders was approximately the same. For better voiding a neobladder should be located in the center of the pelvis.

Aged↗

PubMed1998

Clinical evaluation of random biopsy of urinary bladder in patients with superficial bladder cancer.

BACKGROUND: Superficial bladder cancer has a tendency to recur in the urinary bladder. One reason for recurrence is the presence of concomitant carcinoma in situ (CIS) or dysplasia. However, the usefulness of random biopsy of the urinary bladder has been unclear. METHODS: Between September 1990 and March 1996, 83 patients with superficial bladder cancer underwent mucosal biopsy of 6 different sites in the urinary bladder with macroscopically normal findings (random biopsy). The relationship between a positive biopsy (CIS or dysplasia) and the tumor characteristics was examined. The disease-free survival of the patients according to the biopsy results was determined. RESULTS: The positive biopsy rate was 24.1% (CIS, 14.5%; dysplasia, 9.6%). The incidence of positive biopsy in patients with high-grade (G3), pT1 tumors, 3 or more and non-papillary wide-based tumors was significantly higher than that in patients with 1 or 2 tumors, low-grade (G1, G2), pTa tumors and papillary tumors (P < 0.05). In patients with a single papillary tumor, positive biopsy was found in 9.5%. The disease-free survival in patients with a positive biopsy did not differ from that in patients with a negative biopsy, because intravesical bacillus Calmette-Guérin was instilled in patients with a positive biopsy. CONCLUSION: Our results indicate that random biopsy is useful for detecting concomitant CIS or dysplasia and in the choice of drugs for intravesical instillation.

Adult↗

PubMed1998

Preliminary report of a modified continent appendix stoma in a sigmoid urinary reservoir pouch.

BACKGROUND: The application of an appendix stoma in a Mainz urinary reservoir pouch is an established procedure and assures good continence. We modified this method for use with a sigmoid pouch. METHODS: In each of 3 men with bladder carcinoma, an appendix with a blood supply was prepared and anastomosed to the detubularized sigmoid pouch with a 3-cm submucosal tunnel. RESULTS: In all 3 patients, this procedure was performed successfully, and the pouch was completely continent. Self-catheterization could be performed without difficulty by 2 patients, and with slight resistance in the remaining patient. The patients are satisfied with their quality of life. CONCLUSIONS: We conclude, based on our findings and these preliminary observations, that this procedure is a potentially good alternative for the placement of continent stoma in continent urinary reservoir surgery.

Aged↗

PubMed1998

Clinical study of renal cell carcinoma with brain metastasis.

BACKGROUND: The clinical outcome of patients with renal cell carcinoma with brain metastasis was analyzed. METHODS: Nine patients (median age, 60 years) with primary renal cell carcinoma and distant metastasis, including brain metastasis, were treated. The median time to the development of brain metastasis was 15 months after the initial visit. Patients with poor performance status or progressive disease were treated with interferon or conservative therapy alone. Patients with good performance status and other well-controlled metastatic foci were treated either with radiotherapy, or by tumorectomy of brain metastasis, or both. The median follow-up was 26 months after the initial visit. RESULTS: The 1-year, cause-specific survival rate was 17%. Of the 5 patients treated with alpha-interferon alone, all died of disease after the treatments, without improvement of performance status, 1 to 4 months after the diagnosis of brain metastasis. Two of 4 patients who underwent radiotherapy were treated with a combination of gamma-knife and tumorectomy of brain metastasis. They remained alive 10 and 22 months after diagnosis of brain metastasis. The 2 patients who underwent the combination treatment of gamma-knife and tumorectomy showed improvement of their performance status after these treatments for brain metastasis. CONCLUSION: Brain metastasis is an unfavorable prognostic factor in renal cell carcinoma. Although a larger number of patients would be necessary to demonstrate the definitive effects of gamma-knife treatment, our results suggest that the combination of gamma-knife and tumorectomy of brain metastases may be recommended for selected patients with good performance status and other well-controlled metastatic foci.

Aged↗

PubMed1998

Long-term follow-up study of penile cancer.

BACKGROUND: We reviewed the outcomes for patients with penile cancer to determine factors predictive of their survival. METHODS: Between 1966 and 1996, 59 patients with penile cancer were treated at Kobe University Hospital. The median follow-up period was 109 months (range, 4 to 240 months). The prognostic factors were determined by multivariate analysis. Disease progression rates, according to stage and the type of surgery, were studied. RESULTS: The 5- and 10-year, cause-specific survival rates were 75.9% and 73.8%, respectively. Lymph node involvement, tumor stage, and tumor differentiation were the independent risk factors identified by multivariate analysis. Among the patients at stage 1 and 2, none of the 29 patients treated with early lymphadenectomy showed recurrence in the inguinal region, while 4 (27%) of 15 patients without lymphadenectomy showed such recurrence. CONCLUSION: Our results suggest that tumor stage, lymph node involvement, and tumor differentiation are significant prognostic factors for survival, and that early inguinal lymphadenectomy would improve the prognosis of patients with stage 1 or 2 penile cancer.

Aged↗

PubMed1998

Expression of MAGE genes in renal cell carcinoma.

We investigated the expression of MAGE genes in 10 renal cell carcinoma (RCC) cell lines, 50 RCC tumor samples and 5 normal kidney samples using reverse transcription-polymerase chain reaction (RT-PCR). MAGE-1, -2, -3 and -4 genes were expressed in 4, 1, 10 and 3 of 10 RCC cell lines, respectively, and 11, 8, 38 and 15 of 50 RCC samples. In contrast, there was no expression of MAGE genes detected in any of the normal kidneys. The incidence of the expression of plural MAGE genes in high stage RCC was significantly higher than that in low stage RCC. An analysis based on clinicopathological factors revealed that MAGE-4 gene was more frequently expressed in clear cell subtype than in granular cell subtype RCCs. Our results suggest that owing to the high incidence of MAGE gene expression in RCC, a large proportion of patients could be suitable candidates for novel immune therapies involving tumor-specific antigens encoded by MAGE genes.

Antigens, Neoplasm↗

PubMed1998

p53 modulation of Fas/Apo-1 mediated apoptosis in a human renal cell carcinoma cell line.

The mutant p53 gene was transfected into ACHN, a wild-type p53-containing human renal cell carcinoma (RCC) cell line. The colony forming efficiency in soft agar in the mutant-type p53-transfected cell line (ACHN/MP) was significantly higher than that in the vector-only transfected control cell line (ACHN/C). The anti-Fas monoclonal antibody (CH11) induced apoptosis in the ACHN/C cells in a dose-dependent manner, whereas the effect of CH11 on the ACHN/ MP cells was markedly suppressed. In addition, the cytotoxic effect of CH11 on the ACHN/MP cells was augmented by the pretreatment with interferon- , but the corresponding effect on ACHN/C cells was not. These findings suggest that Fas-mediated therapy could be a novel approach to RCC, if interferon- treatment is added according to the p53 gene status.

Antibodies, Monoclonal↗

PubMed1998

Synergistic anti-tumor effect of 13-cRA and IFN-alpha/beta in mouse renal cell carcinoma.

The synergistic anti-tumor effect of 13-cis retinoic acid (13-cRA) and interferon-alpha/beta (IFN-alpha/beta) was investigated using a highly metastatic mouse renal cell carcinoma cell subline (RenCa/F). Although 13-cRA inhibited tumor growth in vivo as well as in vitro, IFN-alpha/beta did not. Combined administration of 13-cRA and IFN-alpha/beta significantly enhanced the anti-tumor effect of 13-cRA. The retinoic acid receptor (RAR)-alpha and RAR-gamma were expressed in RenCa/F cells. Treatment with IFN-alpha/beta did not influence the expression level of these receptors at the mRNA level, which suggests that the synergism of 13-cRA and IFN-alpha/beta is not mediated through the RAR.

Animals↗

PubMed1998

Multifocal renal cell carcinoma in Japanese patients with tumors with maximal diameters of 50 mm. or less.

PURPOSE: We determined the risk of local recurrence in 64 Japanese patients a median of 69 years old with renal cell carcinoma who were possible candidates for nephron sparing surgery and who underwent radical nephrectomy. MATERIALS AND METHODS: A total of 64 kidneys in which tumors 50 mm. or less were resected were prospectively examined pathologically in 3 mm. sections. The incidence of satellite tumors and the relationship between the pathological findings of the primary and satellite tumors were evaluated. RESULTS: Satellite tumors were identified in 10 of the 64 kidneys (15.6%), a rate similar to that reported in the United States. The correlation of histological findings between primary and satellite tumors was 70% for tumor grade. Satellite tumor grade was less than that of the primary lesion in 3 cases. In 60% of the specimens with multifocal renal cancer satellite tumors were within 10 mm. of the margin of the primary tumor. At this distance, if partial nephrectomy had been performed, the satellite lesions would have been missed in 4 of these 10 patients (40%). Of the 10 kidneys with satellite renal tumors 8 (80%) had vascular invasion of the primary tumor. Multiple logistic regression analysis demonstrated that vascular invasion was a significant predictor of multifocality of renal cell carcinoma. CONCLUSIONS: Our results suggest that vascular invasion is a risk factor for multifocality in Japanese patients with renal cell carcinoma. Therefore, careful and long-term followup is necessary in patients with renal cell carcinoma who have undergone nephron sparing surgery, especially those with vascular invasion of the primary tumor.

Adult↗

PubMed1998

Expression patterns of CD44 adhesion molecule in testicular germ cell tumors and normal testes.

Despite recent extensive immunohistochemical studies, the expression patterns of CD44 in testicular germ cell tumors are still controversial. In the present study, we investigated the CD44 gene expression in 40 specimens including 18 seminomas, 16 nonseminomatous germ cell tumors (NSGCT), and 6 normal testes by reverse transcriptase-polymerase chain reaction and Western blotting. Reverse transcriptase-polymerase chain reaction analysis revealed that the standard CD44 isoform (CD44s) was expressed in all of the specimens, whereas the variant CD44 isoforms were highly expressed in NSGCTs but barely detectable in seminomas and normal testes. In addition, we confirmed by direct DNA sequence analysis that the predominantly expressed variant isoform in NSGCTs was CD44v8-10. In germ cell tumors, these results were paralleled in Western blot analysis; that is, CD44s protein was expressed in all of the tumor specimens, whereas high molecular weight variant isoforms were expressed only in NSGCTs. However, at the protein level, no detectable CD44 was expressed in normal testes. These findings show that the combined assessment of CD44 expression patterns at both the RNA and protein levels enables us to distinguish among seminoma, NSGCT, and normal testis specimens; hence, it could serve as a useful practical adjunct to conventional diagnostic methods for testicular germ cell tumors.

Adolescent↗