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Biomedical subjects

K Gohji

Publications and source records attributed to K Gohji.

At least 55 records · Page 3Linked to original sources
PubMed1998

Molecular cloning and analysis of the 5'-flanking region of the human bone morphogenetic protein-6 (BMP-6).

We cloned a genomic fragment of the 5'-flanking region of the gene encoding bone morphogenetic protein-6 (BMP-6) and assessed its promoter activity. Primer extension revealed the presence of one major transcription start site 178 bp upstream of the translation start site. The promoter region lacked a canonical TATA box but did contain a GC-rich region. A putative tramtrack responsive element, a Drosophila transcriptional factor regulating the segment polarity, was found in the promoter region. Known steroid hormonal responsive elements, however, were not found. Although BMP-6 is classified as a member of the vgr-1 family, the structure of the promoter was similar to that of BMP-2 and 4.

Base Sequence↗
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

Imbalance between serum matrix metalloproteinase-2 and its inhibitor as a predictor of recurrence of urothelial cancer.

Serum levels of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinases-2 (TIMP-2) were evaluated as prognostic indicators of the recurrence of urothelial cancer. Sera were obtained from 127 healthy control subjects and 97 urothelial cancer patients who underwent complete resection and were measured for MMP-2 and TIMP-2 using a one-step enzyme immunoassay. The relationship between the serum MMP-2/TIMP-2 ratio and the recurrence of urothelial cancer was examined. The mean serum MMP-2/TIMP-2 ratio in the 31 advanced urothelial cancer patients with recurrence was significantly higher than that in the 22 patients without recurrence (P = 0.0029) and in the 44 superficial bladder cancer patients (P < 0.0001). The 1- and 3-year disease-free survival rates in the patients with high MMP-2/TIMP-2 ratios (50% and 12%) were significantly poorer than those of the patients with normal ratios (82% and 56%) (P = 0.0152). Univariate and multivariate analyses of recurrence demonstrated that the serum MMP-2/TIMP-2 ratio is a significant independent indicator of advanced urothelial cancer. Our results indicate that an imbalance between the serum levels of MMP-2 and TIMP-2 could be a new predictor of recurrence in advanced urothelial cancer patients.

Adult↗
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

Results of transurethral resection plus adjuvant intravesical chemotherapy for superficial bladder cancer.

BACKGROUND: We analyzed the results of conservative therapy for superficial bladder cancer to determine the risk factors for recurrence and progression. METHODS: Between May 1984 and February 1997, 111 patients with primary superficial bladder cancer were treated by a transurethral resection with or without intravesical instillation of chemotherapy, or for patients with concomitant carcinoma in situ (CIS), bacillus Calmette-Guérin. We examined the relationship between tumor stage, grade, incidence of concomitant CIS and recurrence-free survival according to pathologic findings and the drugs instilled. RESULTS: The incidence of concomitant CIS in pT1, grade 3 tumors was significantly higher than that in pTa, grade 1 tumors (42% vs. 3%, P= 0.006). The 5-year recurrence-free survival rate of all patients was 73%. There was no significant difference in recurrence-free survival and pathologic stage, tumor grade, presence of concomitant CIS, or drugs used for instillation. However, the recurrence-free survival in patients with > or = 5 tumors was significantly lower than in patients with less than 5 tumors. Of the 111 patients, only 3 patients demonstrated disease progression and underwent a radical cystectomy, while 1 patient with a pT1b, grade 3 tumor developed a tumor in the ureter. No patient died of bladder cancer. CONCLUSION: Our results indicate that the prognosis of superficial bladder cancer patients with a high-stage, high-grade (pT1, grade 3) tumor is favorable when treated by a transurethral resection and intravesical instillation. Bacillus Calmette-Guérin therapy is useful to prevent the recurrence of tumors with concomitant CIS.

Administration, Intravesical↗
PubMed1998

Squamous cell carcinoma in an ileal conduit.

We report a patient with squamous cell carcinoma that developed at the ureteroileal anastomosis and extended into the ileal conduit 11 years after a radical cystectomy for transitional cell carcinoma of the bladder. To our knowledge, this is the first report to document the development of a squamous cell carcinoma in an ileal conduit after a radical procedure for bladder cancer.

Aged↗
PubMed1998

Assessment of proliferating cell nuclear antigen expression and prognosis in patients with renal cell carcinoma with pulmonary metastases.

BACKGROUND: The presence of proliferating cell nuclear antigen (PCNA) has been suggested as a more important prognostic marker than either grade or mitotic index in the prognosis of patients with renal cell carcinoma. We assessed the immunoreactivity of PCNA in primary lesions and pulmonary metastases from patients with renal cell carcinoma and correlated the results with various histopathologic features and prognostic factors. METHODS: We studied the relationship between PCNA expression and clinical prognostic factors from resected primary lesions and pulmonary metastases from 10 patients and primary lesions from 32 patients with renal cell carcinoma without metastases. The cells were immunohistochemically stained with PCNA monoclonal antibody (PC-10) and 1000 nuclei were counted. The results were expressed as a ratio of stained to total cells (PCNA labeling index, LI %). RESULTS: The PCNA LI of pulmonary metastatic nuclei was significantly higher than the PCNA LI of renal lesions either from patients with (P < 0.05) or without (P < 0.01) metastases. Also, the mean PCNA LI of the pulmonary lesions in patients dying within 3 years of diagnosis was higher than the mean PCNA LI of patients surviving greater than 3 years. CONCLUSION: Our findings suggest that the PCNA LI, which was determined by immunohistochemical analysis, is an important marker reflecting the biologic behavior of renal cell carcinomas. The degree of PCNA expression in this study was of prognostic significance.

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↗