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Biomedical subjects

Y Kakehi

Publications and source records attributed to Y Kakehi.

At least 109 records · Page 6Linked to original sources
PubMed1994

[Intraarterial chemotherapy for metastatic renal cell carcinomas: combination with MDR-overcoming agents].

We analyzed the sensitizing activity of five agents, which have been assumed to be MDR-overcoming drugs, in two human renal cell carcinoma cell lines expressing the MDR1 gene at high levels. In addition, we studied the sensitizing activity of cepharanthin, an MDR-overcoming agents, to vinblastine, adriamycin, epirubicin, cisplatin, mitomycin C and etoposide. Based on the results, we treated 6 patients with metastatic renal cell carcinomas (4: bones, 2: contralateral kidneys) by intraarterial injection of vinblastine and adriamycin (or epirubicin) in combination with cepharanthin. Two of the 4 bone metastasis cases responded markedly to the treatment. Renal tubular impairment was observed in one patient who was treated for the contralateral kidney metastasis.

Alkaloids↗
PubMed1993

Metachronous multifocal development of urothelial cancers by intraluminal seeding.

To investigate the clonal origin of multifocal urothelial tumours, we analysed the p53 tumour-suppressor gene in 3 cases with bladder tumours developing after treatment for a renal pelvic or ureteral tumour and in 1 case with a ureteral tumour after treatment for a bladder tumour. For each case, identical p53 gene mutations were detected in all primary and recurrent tumours. The results suggest that heterotopic recurrence by intraluminal seeding from the original tumour is common in urothelial cancer. The data also support the view that multifocal urothelial tumours are derived from a single progenitor cell.

Female↗
PubMed1993

Influence of cigarette smoking and schistosomiasis on p53 gene mutation in urothelial cancer.

The mutation patterns of the p53 tumor suppressor gene have been shown to reflect the specific carcinogen(s) involved, or the epidemiological background in some cancers. To elucidate the impact of cigarette smoking or bilharzial infection on the p53 gene mutation pattern, 61 cases of urothelial cancer from Japan and 7 cases of bladder cancer with schistosomiasis from Egypt were examined for mutations of the p53 gene. In total, p53 gene mutations were detected in 20 Japanese cases (33%) and 6 Egyptian cases (86%). Although the incidence of p53 gene mutation was not significantly influenced by habitual smoking, a different mutation pattern was observed as follows: 4 of 10 mutations in smokers in Japan were A:T to G:C transitions, whereas such mutations were not detected in any of 10 mutations in nonsmokers, or in any of 6 mutations associated with schistosomiasis. Although no specific mutation pattern was detected for the squamous cell carcinomas with schistosomiasis, all 8 base substitutions observed in tumors with squamous cell carcinomas occurred at G:C sites, whereas base substitutions at A:T sites were observed in 33% (6 of 18) of mutations in transitional cell carcinomas. Our results suggest that cigarette smoking may have a significant impact on the mutations of the p53 gene in urothelial cancers. Furthermore, the distinct spectrum of the p53 gene mutation found in tumors with squamous cell carcinomas may reflect their unique etiological backgrounds.

Carcinoma, Squamous Cell↗
PubMed1993

Accumulated allelic losses in the development of invasive urothelial cancer.

To investigate the roles of allelic loss in the development of urothelial cancer, loss of heterozygosity was examined on 7 chromosomal arms in 49 cases of urothelial cancer of various grades and stages. Loss of heterozygosity was found in alleles in order of frequency as follows: 9q (21/38, 55%), 11p (20/44, 45%), 17p (18/42, 43%), 13q (10/39, 26%), 3p (8/41, 20%), 10q (2/29, 7%), and 1p (1/36, 3%). Invasive (high-grade or > or = pT2) tumors showed the loss of 17p (13/16, 81%) and the loss of 13q (7/16, 44%) with significantly higher frequencies than non-invasive (grade 1-2 < or = pT1) tumors. Although the loss of 3p and the loss of 11p were also more frequently associated with the invasive phenotypes, the loss of 11p was detected in a considerable number (9 of 26, 35%) of non-invasive tumors. Our results indicate that the loss of 11p might generally occur at an earlier stage before the loss of 3p, 13q or 17p in tumor progression. Since no correlation was found between the loss of 9q and the tumor grade or stage, this genetic alteration appears to be unrelated to invasiveness, and could be one of the initial events in tumorigenesis. Although accumulated allelic losses of 3p, 11p, 13q and 17p are considered to be involved in the development of the invasive type of urothelial cancers, these multiple genetic alterations may have already occurred in some pathologically non-invasive urothelial cancers. Furthermore, there appears to be some variation in the pattern of cumulative allelic loss.

Alleles↗
PubMed1993

Primary signet ring cell adenocarcinoma of the prostate: a case report and literature review.

We report a rare case of primary signet ring cell adenocarcinoma of the prostate in a 61-year-old male, who died of systemic lymphatic spread. Autopsy ruled out another primary signet ring cell adenocarcinoma outside the prostate. However, immunohistochemically, the tumor stained negatively for prostate-specific antigen. A review of the literature revealed only 15 case reports, including our case.

Adenocarcinoma, Mucinous↗
PubMed1993

[Circumvention of the multidrug-resistance in renal cancer by bisbenzylisoquinoline].

A bisbenzylisoquinoline alkaloid, cepharanthine, significantly enhanced vinblastine, adriamycin and etoposide sensitivities in P-glycoprotein positive renal cancer cells. However, it did not show any enhancing effect on cisplatin sensitivity. Four patients with metastatic renal cell carcinomas were treated with intraarterial chemotherapy using vinblastine and/or adriamycin in combination with cepharanthine for their metastatic lesions (3 bone and 1 contralateral kidney metastases). A partial response was observed in 1 patient with femoral bone metastasis and a minor response in 1 patient with lumbar bone metastasis, although they were also treated with interferons. No adverse effects associated with cepharanthine were seen except in one patient complaining of redness and burning sense of the skin probably due to its vaso-dilatation effect.

Alkaloids↗
PubMed1993

[Multiple calcium oxalate stone formation in a patient with glycogen storage disease type I (von Gierke's disease) and renal tubular acidosis type I: a case report].

A case of multiple urinary stones in a patient with glycogen storage disease type 1 (GSD-1) is reported. In spite of the presence of hyperuricemia, these stones did not consist of uric acid, but mainly of calcium oxalate. Laboratory studies revealed distal renal tubular acidosis and hypocitraturia, but no significant abnormality in calcium metabolism. We discussed the mechanism of calcium stone formation in our case, and its prophylactic treatment by oral administration of citrate compound.

Acidosis, Renal Tubular↗
PubMed1992

Allelic losses at chromosome 17p in human renal cell carcinoma are inversely related to allelic losses at chromosome 3p.

Recent studies have demonstrated that allelic losses at chromosome 17p are associated with the genesis of a wide variety of human cancers. In order to assess whether the rearrangement of chromosome 17p was responsible for the genesis of renal cell carcinoma (RCC), we used restriction fragment length polymorphism analysis of chromosome 17p. We studied 48 RCCs, including 6 metastatic RCCs, from 43 patients with 5 polymorphic probes to loci within or near the p53 gene. Allelic losses at chromosome 17p were detected in only 6 of the 36 informative cases (17%), and no definitive correlation was demonstrated between allelic losses at 17p and the tumor stages. The 6 RCCs with allelic losses at 17p were histopathologically classified as a clear cell type in one, a mixed cell type in one, and granular cell types in the other four cases. Allelic losses at 17p in the clear cell type of RCC were infrequent (6%, 1 of 18), and were not detected even in the metastatic tumor from a highly advanced case. This finding suggests that allelic losses at 17p could be random genetic rearrangements in the case of the clear cell type of RCC. On the other hand, allelic losses at 17p in the granular cell type of RCC were demonstrated with a significantly higher frequency (44%, 4 of 9). We previously reported that allelic losses at 3p were specific to the clear cell type of RCC (Ogawa et al., Cancer Res., 51:949-953, 1991). Examination of the association of allelic losses at 17p with those at 3p revealed that none of 5 informative RCCs with allelic losses at 17p showed allelic losses at 3p. Conversely, 17 of 25 informative RCCs with retention of 17p alleles lost alleles at 3p. Thus, an inverse relationship was demonstrated with statistical significance (P less than 0.01). These data suggest that the types of rearrangement on chromosome 17p and/or chromosome 3p can differentiate between the histopathological subtypes of RCC.

Alleles↗
PubMed1992

Allelic loss of chromosome 17p in urothelial cancer: strong association with invasive phenotype.

Allelic loss of chromosome 17p with a mutated p53 gene on the remaining allele has been observed in various kinds of human cancers. To examine the significance of allelic loss of chromosome 17p in human urothelial cancer with special attention to the clinicopathological features, 49 tumors with various stages and grades from 43 cases (35 bladder cancers and 8 renal pelvic or ureteral cancers) were examined for loss of heterozygosity using 5 polymorphic probes on chromosome 17p. Thirty-seven cases were informative, and allelic loss of chromosome 17p was observed in 15 (41%) of them. In bladder cancers, the loss of 17p was observed with significantly higher frequency (p < 0.01) in cases with invasive (> or = pT2) tumors (7/10, 70%) than in cases with superficial (pTa or pT1) tumors (4/21, 19%). In renal pelvic or ureteral cancers, none of 2 superficial tumors and all of 4 invasive tumors showed the allelic loss. As to tumor grade, the allelic loss was observed in 1/9 (11%) for grade 1 cases, 6/18 (33%) for grade 2 cases, and 8/10 (80%) grade 3 cases (grade 1 versus 3, p < 0.01; grade 2 versus 3, p < 0.05). On the other hand, examination of clinical features, such as primary tumor site, tumor multiplicity or previous history of urothelial cancer did not significantly influence the frequency of the allelic loss. Our results suggest that the allelic loss of chromosome 17p is strongly associated with invasive phenotype in urothelial cancer. The results further indicate that the 17p deletion may represent a new genetic marker of malignant potentials in urothelial cancers.

Adult↗
PubMed1992

[Prophylactic effect of UFT in combination with intravesical chemotherapy on the recurrence of superficial bladder tumor].

The influence of N1-(2-tetrahydrofuryl)-5-fluorouracil plus uracil (UFT) on the recurrence of superficial bladder tumors was evaluated in a randomized clinical study. Group A (n = 196) underwent transurethral resection (TUR) and the intravesical chemoprophylaxis, while group B (n = 193) received 400 mg per a day of UFT orally for 6 months in addition to the instillation therapy. These adjuvant therapy was started one week after TUR. Consequently, 30 patients in group B showed UFT-related toxicity and administration of UFT was discontinued in 10 of them. In addition, 87 patients in group B did not complete the 6-month course of UFT administration. Comparison of 2-year actuarial non-recurrence curves revealed no significant difference between groups A and B. However, UFT seemed to have a favorable prophylactic effect when recurrence rates were compared among those patients with recurrent tumors (generalized Wilcoxon: p = 0.1277), and those with recurrent multiple tumors (p = 0.0847).

Administration, Intravesical↗
PubMed1992

[Circumvention of the intrinsic multidrug-resistance in renal cell carcinoma].

Most of renal cell carcinomas (RCCs) are refractory at the start of chemotherapy. We have demonstrated that the frequently elevated expression of the multidrug resistance gene (MDR) in RCCs is associated with the intrinsic vinca alkaloids and anthracyclines resistance. The preliminary clinical trials using verapamil or amiodarone in combination with vinblastine or doxorubicin to overcome multidrug-resistant (MDR) tumors could not achieve satisfactory results owing to severe cardiovascular toxicities of such reversing agents. In the present study, we studied the sensitizing ability of bis-benzyl-isoquinoline (cepharanthine) and SDB-ethylenediamine (N-1379) in natural MDR kidney cancer cells. Cepharanthine remarkably sensitized vinblastine and doxorubicin sensitivities in those cells with high MDR RNA levels. From a clinical point of view, cepharanthine seems to be a potent and less toxic agent to treat natural MDR kidney cancers.

Alkaloids↗
PubMed1992

[Clinicopathological analysis on invasion and metastasis in superficial bladder cancer].

We analyzed the clinico-pathological features of the initial tumors in 205 patients with superficial bladder cancer, admitted to Kyoto University Hospital between 1974 and 1988, to investigate the prognostic factors for progression to the muscle invasive disease or metastasis. Of 205 patients, 35 (17%) exhibited muscular invasion alone (12 patients) and/or metastasis (23 patients). Tumor multiplicity, higher grade and positive urinary cytology were the significant risk factors for later malignant progression. Expression of A, B, H-blood group isoantigens in the bladder tumor were significantly decreased from the onset in the patients with initially T1 tumor but not in those with Ta tumor. Significant loss of expression was also found at the time of progression in the initially Ta cases. Thus, loss of A, B, H-blood group antigen expression seems to be correlated with the malignant potential of superficial bladder cancer. However, more feasible and reliable diagnostic markers such as molecular genetical and biochemical markers remain to be developed to predict the malignant potential of the superficial bladder cancer.

ABO Blood-Group System↗
PubMed1991

Allelic loss at chromosome 3p characterizes clear cell phenotype of renal cell carcinoma.

Incidence of the loss of heterozygosity on chromosome 3p was evaluated using 7 polymorphic probes in 35 Japanese patients with sporadic renal cell carcinoma (RCC). Overall frequency of the loss of heterozygosity on 3p was 53%, representing 16 of 30 informative cases. Examination of the relationship between histopathological phenotypes of RCC and incidence of the 3p loss revealed that the loss of heterozygosity in clear cell type tumors (75%, 12 of 16) was significantly (P less than 0.01) more frequent than that in granular cell type tumors (14%, 1 of 7). In addition, three mixed cell type tumors, consisting predominantly of granular cell components, showed no loss of chromosome 3p loci. These findings may support the notion that the loss of heterozygosity on chromosome 3p is a nonrandom event in the tumorigenesis of sporadic RCC, and suggest that this type of chromosomal rearrangement is specific to the clear cell phenotype of RCC.

Carcinoma, Renal Cell↗
PubMed1991

Restriction fragment length polymorphism of the L-myc gene and susceptibility to metastasis in genitourinary cancers.

We examined Southern blot analysis of genomic DNAs from 70 patients with sporadic renal cell carcinoma, using the human L-myc oncogene fragment as a hybridization probe. Our purpose was to study the relationship between the restriction fragment length polymorphism (RFLP) of the L-myc and the frequencies of metastasis. The patients were classified into 3 genotypes according to the polymorphic patterns defined by two alleles (L-L:17, L-S:31, S-S:22). The relative ratios of the 3 genotypes in the renal cancer patients were similar to those seen in healthy Japanese. However, of 20 patients who exhibited distant metastases at diagnosis, only 2 belonged to the L-L type. The incidence of distant metastasis in L-L type patients was significantly lower than that in L-S and S-S patients (p = 0.068, by Fisher's exact probability test). These results basically correspond to the previous findings in the lung cancer patients [Kawashima et al.: Proc. natn. Acad. Sci. USA 85: 2353-2356, 1988]. On the other hand, L-myc RFLP analysis in 50 prostatic cancer patients revealed that the incidence of metastasis at diagnosis did not correlate with L-myc genotypes. L-myc RFLP seems to be less promising in prostatic cancer than in lung or kidney cancer.

Blotting, Southern↗
PubMed1991

Multidisciplinary treatment of invasive bladder cancer.

To improve cure rates of locally invasive bladder cancer patients, we have performed radiation therapy prior to radical cystectomy in 88 patients since 1980. Until 1984, a total dose of 40 Gy for 4 weeks had been irradiated to the pelvic cavity of 46 patients, while 24 Gy with or without hyperthermia for 2 weeks has been applied to 42 patients since 1985. The treatment efficacy was assessed histopathologically according to the evaluation system proposed by Shimosato et al. in 1971. Approximately 50% of the patients responded well to this preoperative therapy. Among these patients, those with pT3 lesion showed significantly favorable prognoses as compared with the same stage patients who did not respond to the radiation therapy. However, the survival rates of the other pT stage patients did not correlate with the responsiveness to radiation. These results suggest that pT3 stage patients are the best candidates for preoperative radiation therapy, while radical cystectomy alone is adequate for those with superficially invasive lesions. Systemic chemotherapy should be properly built into the treatment strategy for those with locally far-advanced bladder cancer.

Carcinoma, Transitional Cell↗
PubMed1991

Renal cell carcinoma extending into the vena cava: a multi-institute study.

The present paper reports the clinical results from cases of renal cell carcinoma with vena caval tumor thrombus. Fifty patients were entered into the study between 1980 and 1989. The primary tumor and vena caval tumor thrombus were completely removed in 39 (78%) patients, and 41 (82%) received postoperative treatment. The overall 12-, 36-, 60- and 90-month actuarial survival rates were 72, 41, 19 and 10%, respectively. Only tumor stage affected survival, however, other factors such as tumor grade, nodal status, metastatic status and level of vena caval involvement not affecting it. Postoperative interferon (IFN) treatment affected survival, whereas degree of curative surgery did not. The results of our study were, however, examined retrospectively in several institutes. Further investigation of the postoperative treatment for renal cell carcinoma with vena caval tumor thrombus will be necessary.

Actuarial Analysis↗
PubMed1991

[Transcatheter embolization of huge renal arteriovenous aneurysm: a case report--review of 270 cases of renal arteriovenous fistula reported in Japan].

We report a case of huge renal arteriovenous aneurysm, which was successfully treated with transcatheter arterial embolization (TAE). A 72-year-old woman was admitted with the clinical symptom of dyspnea on effort. She felt a tremor in the left abdomen. Computerized tomographic scan showed a large enhanced mass (8x7x7 cm) on the left kidney. Selective renal arteriography revealed a renal arteriovenous aneurysm. Transcatheter arterial embolization with a steel coil was performed with minimal loss of renal parenchyma. A total of 270 cases of arteriovenous fistula have been reported in Japan and were statistically analyzed. The number of reports on TAE has dramatically increased since 1978, TAE can be first indicated for treatment of renal arteriovenous fistula in view of less invasiveness and preservation of renal function.

Adolescent↗