Biomedical subjects

Y Kakehi

Publications and source records attributed to Y Kakehi.

At least 91 records · Page 5Linked to original sources

PubMed1996

Urinary calculi as a late complication of the Indiana continent urinary diversion: comparison with the Kock pouch procedure.

PURPOSE: Although urinary calculi have been frequent late complications of the Kock continent urinary diversion, they have not been regarded as significant problems in patients with the Indiana pouch because of the lack of foreign material present. However, stones developed in a significant percentage of our patients with an Indiana pouch. We investigated the characteristics of stone formation in patients with the Indiana pouch and compared them to those with a Kock pouch. MATERIALS AND METHODS: Detailed clinical courses regarding stone formation were reviewed in 72 patients with a Kock pouch and 54 with an Indiana pouch who had a minimum followup of 12 months. RESULTS: Stones developed in 7 of 54 patients (12.9%) with an Indiana pouch compared to 31 of 72 (43.1%) with a Kock pouch. The incidence gradually increased with longer followup but it was lower in the Indiana than in the Kock pouch group (5-year stone-free rate 84% versus 66%, respectively). Although the stones consisted principally of a mixture of struvite, carbonate apatite and ammonium hydrogen urate, variable amounts of calcium oxalate were identified in 50% of the Indiana pouch calculi. CONCLUSIONS: Not only urinary infections but also metabolic factors were considered to be involved in stone formation within the Indiana pouch. However, the substantially higher rate of stone formation in our Kock and Indiana pouch groups than has been reported in the United States suggested that no or infrequent pouch irrigations in our patients were important risk factors for urinary calculi.

Case-Control Studies↗

PubMed1996

[Asynchronous metastases solely to the bilateral adrenal glands from bladder cancer: a case report].

We report a case of transitional cell carcinoma of the bladder metastasizing to bilateral adrenal glands without other metastasis. A 47-year-old male underwent total cystectomy due to bladder cancer (TCC, G2, pT2) in 1992. One year later, CT scan showed a large tumor in the right adrenal gland. Right adrenalectomy revealed metastatic transitional cell carcinoma. He underwent 3 courses of M-VAC postoperatively. However, one year after the second operation, left adrenal tumor was detected by CT. Because there was no apparent metastasis other than the adrenal gland, left adrenalectomy was performed and the tumor was transitional cell carcinoma of grade 3. He was discharged from the hospital after 2 courses of CISCA chemotherapy, and has been doing well without evidence of recurrence for two years, being supported by the adrenocortical steroids.

Adrenal Gland Neoplasms↗

PubMed1996

[A case of localized amyloidosis of the ureter].

A case of localized amyloidosis of the ureter is reported. The patient was a 49-year-old female whose chief complaint was macrohematuria. Roentogenographic examination showed left hydronephrosis due to stenosis of left middle ureter. Left nephrouretectomy with cuff was performed with a diagnosis of the left ureteral tumor, and pathological examination revealed localized amyloidosis of the left ureter. Localized amyloidosis of the ureter is a rare lesion, and this is the twenty-first case reported in the Japanese literature. Review of the literature revealed that it is difficult to differentiate this lesion from other ureteral tumors by roentgenographic examination, and it is important to perform preoperative or intraoperative biopsy of ureteral tumors if benign diseases cannot be ruled out.

Amyloidosis↗

PubMed1996

Mainz pouch with appendix-umbilical stoma using catheterizable conduit elongated with continuous cecal segment: a case report.

The Mainz pouch with appendix-umbilical stoma is a very stable method for continent, self-catheterizable urinary reservoir in the presence of a healthy appendix. If the appendix is too short or an unexpected stenosis is seen at its distal portion, the elongation of the conduit using a part of the cecum and the implantation of the conduit to the pouch by the Mitrofanoff method can be a good alternative procedure. We herein report our experience in a 53-year-old male with high grade, invasive bladder tumor, who underwent cystourethrectomy and appendix Mainz pouch operation using the above technique.

Appendix↗

PubMed1995

Constitutive activation of mitogen-activated protein (MAP) kinases in human renal cell carcinoma.

Mitogen-activated protein kinases (MAPKs) play a pivotal role in the mitogenic signal transduction pathway and are essential components of the MAPK cascade, which includes MEK (also known as MAP kinase kinase), Raf-1, and Ras. In this study, we examined whether constitutive activation of the MAPK cascade was associated with the carcinogenesis of human renal cell carcinomas in a series of 25 tumors and in corresponding normal kidneys. Constitutive activation of MAPKs in tumor tissue, as determined by the appearance of phosphorylated forms, was found in 12 cases (48%), and this activation was confirmed by a direct in vitro kinase assay of immunoprecipitate using myelin basic protein as the substrate. The phosphorylation of MEK and of Raf-1, as monitored by a mobility shift in SDS-PAGE, which is reportedly associated with the activation of these kinases, occurred in 9 of 18 cases (50%) and in 6 of 11 cases (55%) respectively. The activation of MAPKs was correlated with MEK activation (P = 0.0045) and with Raf-1 activation (P = 0.067). Furthermore, overexpression of MEK was found in 13 of 25 cases (52%) by Western blot analysis, and this overexpression was associated significantly with MAPK activation (P = 0.034). No mutations were noted in H-,K-, or N-ras genes by PCR direct sequencing in any of the 25 tumor samples. Of the patients studied, 8 of 18 (44%) stage pT2 patients and four of six (67%) stage pT3 patients showed MAPK activation. The single stage pT1 patient did not evidence MAPK activation. Furthermore, one of seven (14%) grade 1 patients, 9 of 13 (69%) grade 2 patients, and two of five (40%) grade 3 patients showed MAPK activation (grade 1 versus grades 2 and 3, P = 0.046). Our results suggest that constitutive activation of MAPKs may be associated with the carcinogenesis of human RCCs.

Amino Acid Sequence↗

PubMed1995

Allelic frequency of p53 gene codon 72 polymorphism in urologic cancers.

Alterations in the p53 tumor suppressor gene appear to be important in the development of many human tumors. The wild-type p53 gene has a polymorphism at codon 72 that presents the arginine (CGC) or proline (CCC) genotype, which recently has been reported to be associated with genetically determined susceptibility to smoking-related lung cancers. To determine whether this p53 genotype influences individual risk of urologic cancer and/or its progression, we used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis to assay the allelic frequencies of this polymorphism in 85 renal cell carcinoma patients, 151 urothelial cancer patients, 33 testicular cancer patients, 28 prostatic cancer patients and 56 patients without neoplastic disease. The allelic distributions of the three genotypes (Arg/Arg, Arg/Pro, Pro/Pro) in patients with renal cell carcinoma (29.4%, 55.3%, 15.3%), urothelial cancers (45.7%, 39.7%, 14.6%), testicular cancer (45.4%, 48.5%, 6.1%) or prostate cancer (42.9%, 50.0%, 7.1%) did not differ significantly from those in the normal controls. However, Pro/Pro genotype in renal cell carcinoma and urothelial cancer (smoking-related cancers) was more frequent than that in prostate cancer and testicular cancer (smoking-unrelated cancers) with borderline significance (P = 0.0881). There was no particular correlation between frequency of the three genotypes and grade or stage of each type of tumor. The association of genetic predisposition to urologic cancers with p53 gene codon 72 polymorphism is not so clear as the previous study of Japanese lung cancer patients, but this polymorphism may play some role in urothelial cancers and renal cell carcinoma, in which smoking is an epidemiological risk factor.

Adult↗

PubMed1995

Multidrug resistance-associated protein-mediated multidrug resistance modulated by cyclosporin A in a human bladder cancer cell line.

A doxorubicin-resistant subline (5637/DR5.5) from human bladder cancer cells (5637) was induced by stepwise increase in the doxorubicin concentration. 5637/DR5.5 cells were cross-resistant to vinblastine and etoposide but not to mitomycin C and cisplatin. We analyzed the mdr1, MRP (multidrug resistance-associated protein), and DNA topoisomerase II gene expression using the reverse transcription polymerase chain reaction assay (RT-PCR) and investigated possible differences in the accumulation and efflux of radiolabeled daunorubicin. 5637/DR5.5 cells do not express the mdr1 gene, but the expression levels of MRP are markedly higher than in drug-sensitive 5637 cells. The intracellular accumulation of radiolabeled daunorubicin was markedly decreased in the 5637/DR5.5 cells in comparison with the parent cells. This reduced drug accumulation was associated with an enhanced drug efflux, but was reversed when cells were incubated with cyclosporin A. Cyclosporin A at the concentration of 5 microM caused 3.4-fold enhancement of daunorubicin-sensitivity in the 5637/DR5.5 cells. On the other hand, there was no difference in DNA-topoisomerase II activity between the parent and resistant cells. The resistance of the 5637/DR5.5 cells is therefore associated with an enhanced drug efflux mediated by the MRP gene overexpression, as distinct from P-glycoprotein, and is modulated by cyclosporin A.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1995

Contribution of chromosome 9p21-22 deletion to the progression of human renal cell carcinoma.

To investigate the possible role of genomic aberrations of chromosome 9p21-22 in the tumorigenesis of human renal cell carcinoma (RCC), 10 RCC cell lines, 55 primary RCCs and 5 metastatic lesions were studied by Southern blotting and polymerase chain reaction-based analysis. Nine of 10 RCC cell lines showed a homozygous deletion of MTSI/CDKN2/(p16), while only 1 in 55 primary tumors had this deletion. Loss of heterozygosity on 9p21-22 was observed in 5 of 10 informative primary RCCs from patients with metastasis, but in only 4 of 31 informative tumors (13%) without metastasis (P = 0.025). Futhermore, 3 of 5 metastatic tumors (60%) showed hemi- or homozygous deletion of MTSI/CDKN2. These results indicate that the 9p21-22 deletion may be a relatively late event in RCC tumorigenesis and could be associated with RCC metastasis.

Alleles↗

PubMed1995

Basic research.

Basic research is currently investigating the molecular cascade associated with bladder cancer development. Many new findings are potential leads towards the improvement of the diagnosis and prognosis of this disease. Special care, however, should be taken in the design of protocols for clinical evaluation of the value of these markers. Some initial guidelines have been put forward in this report.

Alleles↗

PubMed1995

Serum granulocyte colony-stimulating factor levels in patients with urinary bladder tumour and various urological malignancies.

OBJECTIVES: To measure the serum levels of granulocyte colony-stimulating factor (G-CSF) in patients with urinary bladder tumour (UBT) or various urological malignant tumours, and to assess G-CSF production by tumour cells. PATIENTS AND METHODS: Peripheral blood was obtained, before operation or anti-cancer therapy, from 141 patients with UBT, 37 patients with other urological malignant tumours (21 with renal cell carcinoma, nine with renal pelvic or ureteric tumours, five with prostatic cancer, and two with testicular cancer), 38 patients with benign urological diseases (21 with benign prostatic hypertrophy, 11 with urolithiasis and six with a varicocele), and from 15 healthy donors. The serum G-CSF levels were quantified using an enzyme immunoassay. RESULTS: Of 141 patients with UBT, 13 showed elevated serum G-CSF levels above the sensitivity of the assay (30 pg/mL) with a mean value of 328 pg/mL. The serum levels in normal healthy donors and in patients with prostatic cancer, testicular cancer or varicocele were < 30 pg/mL, while the levels were > 30 pg/mL in two of nine patients with renal pelvic or ureteric tumour (mean 754 pg/mL) and in one of 21 patients with renal cell carcinoma (40 pg/mL). The levels of serum G-CSF in several patients with benign prostatic hypertrophy or urolithiasis were also elevated, but the mean levels were low. The serum G-CSF levels in patients with UBT correlated with the increase of grade and the progression of the stage of UBT. Furthermore, patients with UBT and an undetectable level of serum G-CSF had higher disease-specific survival rates at the 5-year follow-up when compared with those with an elevated level of serum G-CSF. There was a positive correlation between serum G-CSF levels and white blood cell counts. T24 and J82 UBT cell lines and freshly separated tumour cells derived from the patient whose serum G-CSF level was high produced G-CSF. CONCLUSION: These results suggest that elevated serum G-CSF level might be associated with a poor prognosis in patients with UBT and be due to the production of G-CSF by UBT cells.

Adult↗

PubMed1995

[E-cadherin expression and histopathological features in renal cell carcinomas].

E-cadherin, a member of the cadherin family, plays a major role in cell-cell adhesion of normal epithelium. Recent studies have demonstrated that heterogeneous expression, reduction or loss of E-cadherin is involved in invasion and metastasis of cancer cells. In this study, the localization of E-cadherin in the normal human kidney and the relationship between E-cadherin expression and histopathological features in renal cell carcinomas was examined immunohistochemically. Renal cell carcinoma tissues and normal kidney counterparts were obtained from 20 patients. E-cadherin in the normal kidney was detected in the cell-cell border of the distal tubules, collecting duct and Bowman's capsule but not in the proximal tubules. E-cadherin expression was reduced in all the clear cell type renal cell carcinomas with compact or cystic configuration (n = 15), while it was well preserved in all the papillary type (n = 3) and chromophobe cell type (n = 1) renal cell carcinomas. Different expression patterns between primary site and metastasis, i.e., homogeneously weak in primary tumor and heterogeneously positive in metastatis, was observed in a case of clear cell type renal cell carcinoma. Different patterns of expression between clear and non-clear cell type, or between papillary and non-papillary type, together with strong expression in chromophobe type might reflect the origin of each type of renal cell carcinoma. Further studies will clarify whether the change in expression of E-cadherin is associated with the prognosis of renal cell carcinoma.

Adult↗

PubMed1995

Cepharanthin, a multidrug resistant modifier, is a substrate for P-glycoprotein.

P-glycoprotein modulators are respected to be multidrug resistance reversing agents in cancer chemotherapy. Some calcium channel blockers, calmodulin inhibitors or immunosuppressive agents have been used in clinical studies, although the dose of these drugs required to test in vitro experimental data might cause potent pharmacological effects which are not desirable in patients. By using LLC-GA5-COL150 cells that express P-glycoprotein specifically on the apical membranes, we examined the transport of anticancer drugs mediated by P-glycoprotein. Cepharanthin, a biscoclaurine alkaloid, potently inhibits the transport of vinblastine and daunorubicin, both commonly used anticancer agents. The 50% inhibitory concentration of cepharanthin on daunorubicin transport was 2.06 microM. Combined inhibitory effects on daunorubicin transport were observed when cepharanthin was used together with cyclosporin A, a potent immunosuppressive agent and P-glycoprotein modulator. Cepharanthin itself was transported by P-glycoprotein. Transcellular transport of cepharanthin across LLC-GA5-COL150 cell monolayers was saturable when its concentration was under 5 microM, and the transport was inhibited by P-glycoprotein modulators. These results indicate that cepharanthin can reverse multidrug resistance, and proper combination with other P-glycoprotein modulators could potentiate its inhibitory effect on expelling the anticancer drugs out of the cell via P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1995

Comparison of multidrug resistance gene expression levels with malignant potentials and influence of chemotherapy in urothelial cancers.

BACKGROUND: We sought to determine how often P-glycoprotein is involved in the drug-resistance of urothelial cancer, and whether MDR1 gene expression is correlated with tumor grade, invasiveness, or metastasis. METHODS: Forty-two tumor specimens and two normal bladder mucosal samples obtained from 34 urothelial cancer patients were analyzed. Reverse-transcription and polymerase chain reaction were conducted. MDR1 mRNA levels were determined by measuring the relative ratio of the MDR1 to beta-2-microglobulin (b2 m) mRNA specific PCR products. RESULTS: The MDR1/b2 m in two normal urothelial samples were 0.044 and 0.045. For untreated primary tumors, levels of MDR1 gene expression in 46% tumor samples were less than that of normal urothelium, while 27% showed expression levels with a MDR1/b2 m ratio more than 0.1. There was no statistical correlation between MDR1 mRNA level and tumor grade, stage, or metastatic status. There was higher MDR1 gene expression in two lymph node metastasis specimens and almost equal expressions in two more. There was no significant difference in the mean MDR1/b2 m ratio between postchemotherapy and untreated tumors. A remarkable elevation of the MDR1 mRNA level (15 times greater than prechemotherapy) was found in one tumor; mRNA levels of the multidrug resistance-associated protein (MRP) gene, glutathione S-transferase pi (GST-pi) gene or DNA topoisomerase II (topo II) gene did not increase. CONCLUSIONS: It is still unclear whether the MDR1 gene expression in urothelial tumor cells is inducible by the current combination chemotherapy regimens. RT-PCR quantitation is useful for determining the expression level of MDR1 gene in urothelial cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1995

Shorter interval between cycles of cyclophosphamide, doxorubicin, cisplatin using recombinant human granulocyte colony-stimulating factor for urothelial cancer--phase I/II study.

BACKGROUND: Despite improvement in the response rate and protraction of the progression-free period of urothelial cancer produced by chemotherapy, severe bone marrow suppression often results in delays in the initiation of treatment cycles and/or decreases in drug dosages. Reduction of leukopenia during chemotherapy has been demonstrated by the combined administration of granulocyte colony-stimulating factor (G-CSF) in various malignancies. METHODS: A phase I/II study was conducted to assess whether the interval between cycles of CISCA (cyclophosphamide, doxorubicin, cisplatin) chemotherapy could be shortened under support of recombinant human granulocyte colony-stimulating factor (rhG-CSF) for urothelial cancer. Three or more patients with transitional cell carcinoma of the urinary tract were allocated to each of four different treatment intervals (step 1: 28 days, step 2: 21 days, step 3: 17 days, and step 4: 14 days) by reducing the interval in a step-wise manner. Two mg/kg/day of a rhG-CSF, lenograstim, was injected subcutaneously on days 3 to 16 (until day 14 for the 14-day interval group). RESULTS: Sixteen patients were enrolled, four patients were treated with the step 1 protocol, five with step 2, four with step 3, and three with step 4. Leukopenia/neutropenia was the most severe toxic reaction, but none of the patients at any step manifested neutropenia of WHO grade 4 for more than four days. There were no significant differences in the hematological and nonhematological toxicities among the 4 steps. Seven of eight patients with measurable diseases were treated with CISCA on shortened schedules (steps 2-4), and one complete remission (CR) and four partial responses (PR) were demonstrated. CONCLUSIONS: CISCA chemotherapy supported by rhG-CSF was safely shortened to a 14-day interval in the pilot study. The potential role of rhG-CSF in shortening the interval of CISCA, as well as the benefit of the intensified schedule, remains to be clarified.

Adolescent↗

PubMed1994

Formation of 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal-modified proteins in human renal-cell carcinoma.

To study the possible involvement of reactive oxygen species (ROS) in the tumor biology of human renal-cell carcinoma (RCC), we analyzed 35 cases of RCC for 2 parameters of oxidative damage: 8-hydroxy-2'-deoxyguanosine (8-OHdG), a mutation-prone DNA-base-modified product, was measured by means of high-performance liquid chromatography (HPLC) with an electrochemical (EC) detector, and 4-hydroxy-2-nonenal (HNE)-modified proteins were measured with a polyclonal antibody against HNE-modified proteins. A 54% higher content of 8-OHdG was found in RCC than in the corresponding non-tumorous kidney, suggesting that the DNA of RCC is more exposed to ROS than is the DNA of non-tumorous kidneys. Immunohistochemistry for HNE-modified proteins showed a distinct staining pattern of fine to coarse granularity in the cytoplasm of RCC (n = 15), implying that lipid peroxidation products are located in cytoplasmic organelles. These results suggest that RCC constitutionally elaborates more ROS than is produced by the non-tumorous parts of kidneys. No correlation was found between clinical stage, histology, age or sex and the 2 parameters examined.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1994

Oncogene amplification in urothelial cancers with p53 gene mutation or MDM2 amplification.

BACKGROUND: Previously, p53 (also known as TP53) gene mutations have been shown to be frequently detected in highly malignant urothelial cancers. Evidence has been accumulating that the disruption of the normal function of p53 may lead to genomic instability, including predisposition to gene amplification. Furthermore, the normal function of p53 may be abrogated by MDM2 (murine double minute-2) gene amplification in some human tumors. PURPOSE: Our purpose was to investigate the relationship between protooncogene amplification and p53 alteration in urothelial cancers by examining the existence of amplification of MDM2 and 14 other protooncogenes in 50 urothelial tumors in which p53 gene status was known. METHODS: We analyzed gene amplification by Southern-blot analysis in 50 urothelial cancer specimens. These tumors were previously examined for p53 mutations by polymerase chain reaction-single-strand conformation analysis, and 17 tumors contained p53 mutations. RESULTS: Two high-grade advanced tumors (4%) without p53 mutation harbored MDM2 amplification with concurrent int-2 gene amplification. As for other genes, amplification was detected for int-2 (also known as WNT2) (seven [14%] of 50), erbB-2 (also known as ERBB2) (three [6%] of 50), N-ras (also known as NRAS) (one [2%] of 50), L-myc (also known as MYCL1) (one [2%] of 50), and raf-1 (also known as RAF1) (one [2%] of 50). The amplification of at least one gene examined was observed in 11 (22%) of 50 tumors. The presence of p53 mutations was not significantly associated with the occurrence of gene amplification, since the amplification was detected in six (35%) of 17 tumors with p53 mutations and in five (15%) of 33 tumors without p53 mutations. However, eight (73%) of 11 tumors with proto-oncogene amplification harbored p53 mutations or MDM2 amplification. CONCLUSIONS AND IMPLICATIONS: A subset of advanced urothelial cancers without p53 mutations may harbor MDM2 amplification. This finding should be taken into account when adopting p53 alteration as a marker of aggressiveness in urothelial cancers. Although the abrogation of normal p53 function may be one of the key steps to protooncogene amplification, the data further indicate that the predisposition to gene amplification in urothelial cancers was not determined by the presence of p53 alteration alone.

Blotting, Southern↗

PubMed1994

Intra-arterial infusion chemotherapy in combination with a biscoclaurine alkaloid, Cepharanthin, to treat bone metastasis arising from renal cell carcinoma.

A 64-year-old man with iliac bone metastasis from left renal cell carcinoma was treated by intra-arterial infusion chemotherapy using vinblastine and epirubicine in combination with a biscoclaurine alkaloid, Cepharanthin. A good response was confirmed by computed tomography scan and the symptoms related to the metastatic lesion were much improved. Partial resection of the left iliac bone was performed when no viable cancer cells were found in the metastatic lesion.

Alkaloids↗

PubMed1994

[Study on E-cadherin expression in relation to invasion and metastasis in urothelial cancer patients].

E-cadherin expression was investigated in 30 patients with urothelial cancer (bladder; 27, ureter; 2, urethra; 1) by an immunohistochemical method. Twelve out of 22 patients with strong and homogeneous expression of E-cadherin (preserved) had grade 1 tumors, while all 8 patients with heterogeneous, weak and homogeneous, or lost expression of E-cadherin (reduced) had grade 2 or grade 3 tumors. Only 2 out of 22 patients with preserved expression had invasive tumors (> or = pT2), whereas 6 out of 8 patients with reduced expression had invasive tumors (p = 0.002). Three out of 4 patients with metastasis had reduced expression and 2 of them died. These findings suggest that urothelial tumors with reduced expression of E-cadherin have high grade and high stage, and E-cadherin expression could be one of the prognostic factors.

Aged↗