Biomedical subjects

Yukihiro Kondo

Publications and source records attributed to Yukihiro Kondo.

At least 19 recordsLinked to original sources

PubMed2006

Significance of noninvasive diagnosis of prostate cancer with cytologic examination of prostatic fluid.

OBJECTIVES: While reassessing the value of exfoliative cytologic examination of prostatic fluid (PF) for the diagnosis of prostate cancer, we found that PF is easily obtained with transrectal ultrasonography during prostate biopsy and that cytologic examination of PF is useful for the diagnosis of prostate cancer. METHODS: The cohort included 53 consecutive patients who underwent transrectal prostate biopsy from May through September 2005. Patient age was 66.7 +/- 7.24 years, and the mean concentration of prostate-specific antigen (PSA) was 15.1 +/- 25.8 ng/ml. The PF for cytologic examination was obtained before biopsy, and Papanicolaou's staining was performed. The results of cytologic examination are expressed as class 1 to 5. Results of cytologic examination and prostate tissue pathologic examination were analyzed. Patient age, PSA levels, total prostate volume (TPV), and PF volume were compared with cytologic class by means of analysis of variance. RESULTS: The mean PF volume was 378.4 +/- 245.3 microl, and the mean TPV was 38.0 +/- 18.8 ml. The numbers of patient in classes 1 to 5 were 1 (1.9%), 37 (69.8%), 11 (20.7%), 1 (1.9%), and 3 (5.7%), respectively. Pathologic examination showed 23 (43.4%) cases of cancer, 27 (50.9%) cases of benign prostatic hyperplasia, and 3 (5.7%) cases of high-grade prostatic intraepithelial neoplasia. All three patients with class 5 results had prostate cancer (Gleason score, 7 to 10). All 9 patients with a PSA level greater than 16 ng/ml had biopsy-proven cancer, and 3 of these 9 patients (33.3%) were in cytology class 5. Therefore, PF cytologic examination showed a specificity of 100% and a sensitivity of 33.3% in patients with PSA levels higher than 16 ng/ml. The cytologic classes differed in PSA levels (F=8.271, P=0.000) but not in patient age, TPV, or PF volume. CONCLUSIONS: Exfoliative cytologic examination of PF is a valuable, noninvasive method for detecting prostate cancer, especially in patients with high PSA levels.

Aged↗

PubMed2006

Study of prostatic fluid from patients with elevated levels of prostate-specific antigen.

INTRODUCTION: Characteristics of prostatic fluid (PF), which can be obtained in large amounts during screening transrectal ultrasound just before prostate biopsy to detect prostate cancer, were investigated. These characteristics include the amount of PF obtained and the number of leukocytes in PF, which would be useful for planning cell-biological or immunological studies of leukocytes in PF and for increasing the understanding of prostatitis in elderly men. PATIENTS AND METHODS: The volume of PF and the number of leukocytes in PF were measured in 50 patients suspected of having prostate cancer because of elevated levels of serum prostate-specific antigen (PSA). Correlations of the volume of PF, the number of leukocytes per milliliter, the total leukocyte number with age and prostate volume and correlation of PSA levels with the number of leukocytes per milliliter and total leukocyte number were also investigated. RESULTS: The average patient age was 67.2 years, and PF specimens were obtained from 43 of the 50 patients (86%). The mean +/- SD of PF volume, number of leukocytes in PF, and total leukocyte number were 347.65 +/- 305.76 microl, 4.84 +/- 6.07 x 10(6) /ml, and 1.47 +/- 2.10 x 10(6), respectively. A correlation was observed only between the total leukocyte number and the volume of the transitional zone (P=0.039). CONCLUSIONS: These data provide information for investigators to plan cell-biological or immunological studies of leukocytes in PF and for understanding prostatitis in elderly men.

Aged↗

PubMed2005

Reduction of drug leakage by negative-balance isolated pelvic perfusion: correlation between leakage and in-out flow rate in a pig model.

PURPOSE: Isolated pelvic perfusion (IPP) therapy exposes target tissues to high doses of anticancer drugs with low systemic concentrations, but the major drawback is drug leakage into the systemic circulation, which often thwarts the increased drug concentration. In this study, the efficacy of altering the in-out flow rate during IPP in order to decrease the leakage was assessed in adult pigs. METHODS: The abdominal aorta and the infrarenal vena cava were occluded with two balloon catheters, blood in the extracorporeal circuit was circulated with twin rotary pumps, and the IPP was performed with platinum. Three sets of in-out flow rates were used, and the degree of drug leakage into the systemic circulation was evaluated. The volume of blood withdrawn was equal to the volume returned (300 ml/min; group A), 5% higher (group B), or 10% higher (group C). The platinum concentrations in the pelvic circulation, systemic circulation, and urine were measured and compared. RESULTS: The average and maximum plasma platinum concentrations in the pelvic circulation did not significantly differ among the three groups. The plasma platinum concentrations in the systemic venous circulation of the three groups significantly (P<0.01) decreased as the volume withdrawn during IPP increased. The percentage of platinum eliminated in the urine during IPP was significantly (P<0.01) lower in group B and C than in group A. CONCLUSIONS: Setting the volume withdrawn higher than the volume returned decreased leakage into the systemic circulation under isolated pelvic perfusion.

Angiography↗

PubMed2005

Over expression of hypoxia-inducible factor-1alpha in renal and bladder cancer cells increases tumorigenic potency.

PURPOSE: Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcriptional factor that regulates genes involved in the response to hypoxia. We evaluated the effects of HIF-1alpha over expression on the tumorigenic potency of renal cell carcinoma VMRC cells and bladder cancer EJ cells in vitro and in vivo. MATERIALS AND METHODS: We introduced HIF-1alpha expression vectors into VMRC and EJ cells, and generated the HIF-1alpha over expressing cell lines VMRC-HIF1alpha and EJ-HIF1alpha, and the vector only transfected cell lines VMRC-neo and EJ-neo. We then evaluated in vitro cell proliferation and in vivo tumor growth of these cell lines after subcutaneous injection into athymic nude mice. RESULTS: In vitro studies showed that HIF-1alpha over expression in VMRC and EJ cells accelerated cell proliferation during the confluent growth phase and rendered these cells resistant to hypoxic stress. Furthermore, in vivo studies revealed that all 4 types of cancer cells (VMRC-neo, VMRC-HIF1alpha, EJ-neo and EJ-HIF1alpha) formed tumors in nude mice and the size of VMRC-HIF1alpha cell derived xenografts was much larger than that of VMRC-neo cell derived xenografts. Although HIF-1alpha over expression did not affect the size of EJ cell derived xenografts, histological examination showed that there was only a small area of necrosis in EJ-HIF1alpha cell derived xenografts, whereas a large area of central necrosis was observed in EJ-neo cell derived xenografts. It was also found that HIF-1alpha over expression increased intratumor microvessel density in the xenografts. CONCLUSIONS: These results suggest that HIF-1alpha may have important roles in bladder and renal cancer angiogenesis and proliferation.

DNA-Binding Proteins↗

PubMed2005

Utility of extracorporeal traction with nylon thread for easier vesicourethral anastomosis in laparoscopic prostatectomy.

PURPOSE: Vesicourethral anastomosis in laparoscopic prostatectomy is a very difficult procedure. Our purpose in this study was to evaluate a new method using extracorporeal bladder neck traction with nylon thread for vesicourethral anastomosis during laparoscopic radical prostatectomy. MATERIALS AND METHODS: A total of 10 patients underwent laparoscopic radical prostatectomy by this technique, and we evaluated anastomosis time, operative time, and postoperative status of vesicourethral anastomosis. RESULTS: It was possible to shorten both anastomosis time and operative time by this procedure, and to obtain a hermetic anastomosis without higher risk of incontinence, stricture, or leakage. CONCLUSIONS: Extracorporeal bladder neck traction with nylon thread is a very useful procedure to carry out easier vesicourethral anastomosis, especially for a surgeon's initial experience in laparoscopic radical prostatectomy.

Anastomosis, Surgical↗

PubMed2005

Luteinizing hormone-releasing hormone agonist monotherapy for prostate cancer: outcome and prognostic factors.

BACKGROUND: We assessed the outcome and prognostic factors in men with prostate cancer after luteinizing hormone-releasing hormone agonist monotherapy. METHODS: Between April 1998 and August 2002, 62 men with prostate cancer who were treated with monotherapy at our institution were included in this analysis. Prostate-specific antigen (PSA) failure-free (bNED) survival was calculated using Kaplan-Meier methods. Prognostic factors were evaluated using Cox proportional hazards regression model. RESULTS: We reviewed the data of patients, with a median follow-up from the commencement of monotherapy of 26 months. The overall survival rate at 3 years was 89.9%. The bNED survival rate was 63.7% at 3 years. Of the 20 patients with clinical stage B, 2 progressed to PSA failure, whereas PSA failure was seen in 8 of 30 patients with stage C and 8 of 12 patients with stage D. The significant factors for bNED status were an initial PSA level of <30 ng/ml (p=0.0044), achievement of PSA nadir level of <2.0 ng/ml (p<0.001), and Gleason score of or=30 ng/ml, and high Gleason score of >or=7 are at increased risk for PSA failure. Failure to achieve PSA nadir level of <2.0 ng/ml is an important predictor of the progression. The use of PSA nadir can provide useful guidelines for the reconsideration of treatment in patients who have received monotherapy.

Aged↗

PubMed2004

Subcellular localization and regulation of hypoxia-inducible factor-2alpha in vascular endothelial cells.

The hypoxia-inducible factors 1alpha (HIF-1alpha) and 2alpha (HIF-2alpha) have extensive structural homology and have been identified as transcription factors that mediate hypoxia-inducible gene expression through hypoxia-responsive element (HRE). They play critical roles not only in normal development, but also in tumor progression. Endothelial cells (EC) express both HIF-1alpha and -2alpha. In this study, we examined the subcellular localization of HIF-1alpha and -2alpha in bovine arterial EC (BAEC) by immunoblotting and immunocytostaining analysis and found that even under normoxic conditions, as with its heterodimeric partner ARNT, HIF-2alpha was stable, and was localized in the nucleus of BAEC differently than HIF-1alpha. HIF-2alpha might be regulated by a different mechanism than HIF-1alpha and might mediate the expression of some EC-specific genes under normoxic conditions. We further found that cardiovascular helix-loop-helix factor (CHF) 2, which had been identified as an ARNT-interacting protein, was expressed in BAEC and suppressed HRE-dependent gene expression both under normoxia and hypoxia. CHF2 might be one of the key regulators of HIF-2alpha-mediated gene expression in normoxic EC.

Amino Acid Sequence↗

PubMed2004

Intracranial metastatic prostate carcinoma presenting as intermittent double vision.

We describe a prostate cancer patient whose initial symptom was intermittent double vision. Intracranial magnetic resonance imaging demonstrated a pituitary mass extending to the cavernous sinus, which caused the double vision. After hormonal therapy for prostate cancer, the pituitary mass disappeared, and double vision was completely resolved without local therapy for the brain. In the 19 months of follow-up after hormone treatment, the prostate cancer remained stable, and the patient remained neurologically intact.

Adenocarcinoma↗

PubMed2004

Effect of adjuvant transarterial infusion of anticancer agents after transurethral resection in patients with pT2a muscle invasive transitional cell carcinoma of the bladder: five and ten-year outcome.

Five- and ten-year survival rates in patients who had transurethral resection for pT2aN0M0 muscle invasive transitional cell carcinoma of the bladder was studied with emphasis on the effect of adjuvant transarterial infusions of anticancer agents (TAI). A total of 17 patients out of 290 patients with bladder cancer who had initial treatment in our department between January 1991 and May 2001 were found to be pT2aN0M0 and were included in the present study. Fifteen patients received intravesical instillations of BCG after transurethral resection of the bladder tumor and 8 patients received TAI which was given two weeks after bacillus Calmette-Guerin therapy, with the exception of 1 patient. Five- and ten-year overall survival rates were 76.0% and 52.1%, respectively, and both five- and ten-year cancer-specific survival rates were 76.0% with an average follow up of 71 months. Significant prognostic factor associated with survival rates was only the infiltration pattern of the tumor cells between the alpha and beta group and gamma group (P = 0.0420) in cancer-specific survival rates. The data support conservative management of transurethral resection followed by intravesical instillation of BCG and TAI in patients with pT2a bladder cancer.

Aged↗

PubMed2004

Detection of urine survivin in 40 patients with bladder cancer.

PURPOSE: We investigated whether urine survivin, an inhibitor of the apoptosis protein, is useful for diagnosing bladder tumor. METHOD: We measured urine survivin levels in 40 patients with bladder tumors and 9 healthy volunteers. RESULTS: The average urine survivin levels in the 40 patients and 9 healthy controls were not significantly different (3.802+/-8.669 and 1.127+/-1.529, respectively (p=0.3646) ). However, significantly high urine survivin levels were observed in 3 of the 40 patients, but not in healthy volunteers. Urine Cyfra 21-1 was not elevated (1.3 ng/ml) in one patient with a significantly elevated urine survivin level (33.54 ng/ml), while in two patients with elevated Cyfra (320 ng/ml and 240 ng/ml), the urine survivin level was not detectable. CONCLUSION: With improvements in the sensitivity of our Elisa system for urine survivin and combined use of urine Cyfra 21-1, it is possible that urine survivin will be a useful tumor marker in detecting both new-onset and recurrent bladder tumors.

Adult↗

PubMed2004

Laparoscopic partial nephrectomy using a microwave tissue coagulator for treating small peripheral renal tumors.

BACKGROUND: Laparoscopic partial nephrectomy has been recently applied as a minimally invasive procedure. Several non-ischemic operation devices in partial nephrectomy have been developed. However, the problem related to maintenance of renal homeostasis remains. We investigated the efficacy and safety of a microwave tissue coagulator in laparoscopic partial nephrectomy. METHODS: Between April 2001 and February 2003, eleven patients with small renal tumors underwent laparoscopic partial nephrectomy using a microwave tissue coagulator. Seven patients underwent hand-assisted laparoscopic procedure and 4 pure laparoscopic procedure. RESULTS: The mean tumor size on preoperative CT scan was 2.5 cm (range: 2.0 to 4.0 cm), the mean operative time was 307 minutes (range: 160 to 580 minutes), and the mean estimated blood loss was 154.4 ml (range: 50 to 1,140 ml). The microwave tissue coagulator well controlled the renal bleeding and maintained renal function. All patients safely underwent partial nephrectomy without inducing renal ischemia. A complication of urine leakage was recognized in only one patient with hypoproteinemia caused by nephrotic syndrome. CONCLUSIONS: Laparoscopic partial nephrectomy using a microwave tissue coagulator was a useful method for achieving homeostasis, and was less invasive for treating small renal tumors.

Aged↗

PubMed2004

Transitional cell carcinoma of the bladder in four patients on maintenance hemodialysis.

We report four patients on maintenance hemodialysis (HD) with transitional cell carcinoma (TCC) of the bladder. Three patients underwent transurethral resection (TUR) of their tumors, which were grade 2 or 3, stage pT1 TCC. Among them, one patient underwent repeat TUR for recurrent superficial TCC. The remaining one patient underwent total cystectomy for grade 3, stage pT4 TCC and squamous cell carcinoma of the bladder. Subsequently, he died suddenly without evidence of local recurrence or systemic metastasis. We discuss the relationship between the duration of HD and the tumor grade and stage of primary bladder TCC in maintenance HD patients.

Aged↗

PubMed2004

[Indication and limitation of endoscopic surgery against urological cancer].

Endoscopic surgery in the urological field begins with cystoscopy and transurethral resection, and it develops into laparoscopic surgery. The indication of laparoscopic surgery for a malignant tumor also gradually expands. It is virtually impossible to search for urological cancer using laparoscopic procedures. In particular, out laparoscopic nephrectomy for renal cancer and transurethral resection for bladder cancer used widely in Japan. In the future, laparoscopic partial nephrectomy and the laparoscopic procedure for adrenal cancer and prostate cancer are considered to become widespread.

Adrenal Gland Neoplasms↗

PubMed2003

Citrate enhances the protective effect of orally administered bismuth subnitrate against the nephrotoxicity of cis-diamminedichloroplatinum.

Attenuation of the renal toxicity of cis-diamminedichloroplatinum (CDDP) is important in the use of this effective but cytotoxic anticancer agent. We have previously shown that the renal toxicity of CDDP can be efficiently reduced by the induction of metallothionein (MT) by preadministration of bismuth compounds in mice. Bismuth subnitrate (BSN) is used as an antigastric ulcer agent and as an antidiarrheic agent, and is suitable for inducing MT in the kidney in cancer patients. However, due to the low absorption rate of Bi from the gastrointestinal tract, the efficacy of BSN in inducing renal MT is low. In the present study, we examined the effects of citrate as a vehicle for oral administration of BSN on the tissue distribution of Bi and induction of MT in the kidneys and tumors in mice inoculated with Meth-A fibrosarcoma. Renal levels of MT and Bi were markedly increased in the mice given BSN dissolved in citrate solution compared with those given BSN suspended in saline. On the other hand, the use of citrate increased Bi accumulation in the tumor only slightly and did not increase tumor MT levels. Administration of BSN with citrate efficiently depressed the renal toxicity of CDDP, but did not affect its antitumor activity. Since both BSN and citrate are used clinically as pharmaceuticals, the combination regimen of BSN and citrate may be readily applicable as a countermeasure against the adverse side effects of CDDP without affecting its antitumor activity.

Administration, Oral↗

PubMed2003

Multiple splice variants of the human HIF-3 alpha locus are targets of the von Hippel-Lindau E3 ubiquitin ligase complex.

Functional inactivation of the von Hippel-Lindau (VHL) tumor suppressor protein is the cause of familial VHL disease and sporadic kidney cancer. The VHL gene product (pVHL) is a component of an E3 ubiquitin ligase complex that targets the hypoxia-inducible factor (HIF) 1 and 2 alpha subunits for polyubiquitylation. This process is dependent on the hydroxylation of conserved proline residues on the alpha subunits of HIF-1/2 in the presence of oxygen. In our effort to identify orphan HIF-like proteins in the data base that are potential targets of the pVHL complex, we report multiple splice variants of the human HIF-3 alpha locus as follows: hHIF-3 alpha 1, hHIF-3 alpha 2 (also referred to as hIPAS; human inhibitory PAS domain protein), hHIF-3 alpha 3, hHIF-3 alpha 4, hHIF-3 alpha 5, and hHIF-3 alpha 6. We demonstrate that the common oxygen-dependent degradation domain of hHIF-3 alpha 1-3 splice variants is targeted for ubiquitylation by the pVHL complex in vitro and in vivo. This activity is enhanced in the presence of prolyl hydroxylase and is dependent on a proline residue at position 490. Furthermore, the ubiquitin conjugation occurs on lysine residues at position 465 and 568 within the oxygen-dependent degradation domain. These results demonstrate additional targets of the pVHL complex and suggest a growing complexity in the regulation of hypoxia-inducible genes by the HIF family of transcription factors.

Alternative Splicing↗

PubMed2003

Laparoscopic radical prostatectomy: initial 30-case experience.

BACKGROUND: We carried out this study to clarify whether the operative methods of laparoscopic prostatectomy established in France could become standard therapy. The purpose was to evaluate the technical feasibility, oncological efficacy, and intraoperative and postoperative morbidity of laparoscopic prostatectomy performed by a general urologist. METHODS: Between June 2000 and August 2002, 30 patients with clinically localized prostate cancer underwent laparoscopic radical prostatectomy performed as previously reported by Guillonneau and colleagues. Oncological data were assessed by pathological examination and by postoperative prostate-specific antigen (PSA) levels. All prostatectomy specimens were processed according to the Stanford protocol. Prostate features, including tumor weight; Gleason score; and the tumor status of the capsule, seminal vesicles, and surgical margins were studied. RESULTS: Complete laparoscopic removal of the prostate and seminal vesicles was achieved in all 30 patients. Operating time averaged 325.5 min (range, 165 to 880 min). The transfusion rate for the patients in the series was 50%, using own-blood transfusion (800-1200 ml). No patient required an allogenic blood transfusion. Only 2 of the 30 patients had a positive surgical margin that involved the urethra. There were three complications: bladder injury, rectal injury, and ileus associated with a drainage tube. No vascular, nervous system, or urethral complications were found. CONCLUSION: These preliminary results demonstrated that radical prostatectomy can be performed laparoscopically by general urologists. Laparoscopy offered better luminosity and magnification than conventional procedures, permitting precise dissection. Thus, laparoscopic prostatectomy could be a standard operation for patients with clinically organ-confirmed prostate cancer.

Aged↗

PubMed2003

Optimal administration schedule of cisplatin for bladder tumor with minimal induction of metallothionein.

PURPOSE: The metal binding protein metallothionein (MT) confers drug resistance when MT is induced in tumor tissues. Cisplatin is known to induce MT synthesis in tumor tissues, which may lead to drug resistance. We examined whether a difference in the administration schedule of cisplatin affect the efficiency of MT induction. MATERIALS AND METHODS: Balb/c nude mice were inoculated with NMB-1 human bladder tumor tissues and injected with cisplatin (total dose of 64 micromol/kg) in a single injection or fractioned daily injections. Tumor MT concentration was determined 24 hours after the last injection of cisplatin by mercury binding assay. The effect of pretreatment with ZnCl2 on antitumor activity of cisplatin was examined in NMB-1 bearing mice. RESULTS: Tumor MT levels increased significantly with the increase in the number of cisplatin injections. Pretreatment of NMB-1 bearing mice with ZnCl2 (200 micromol/kg x 2) caused the same level of MT induction (1.6-fold) as that of fractioned injections of cisplatin (4 x 16 micromol/kg). Pretreatment of NMB-1 bearing mice with ZnCl2 (200 micromol/kg x 2) depressed cisplatin antitumor activity by about 50%. CONCLUSIONS: The induction of MT to a moderate extent (1.6-fold) in NMB-1 tumor inoculated in mice conferred cisplatin resistance. This level of MT induction can be achieved by fractioned daily injections of cisplatin but not by a single injection. Therefore, it is preferable to administer cisplatin as a single injection rather than as fractioned injections to achieve effective antitumor activity with minimum MT induction.

Animals↗

PubMed2002

Molecular cloning of one isotype of human lamina-associated polypeptide 1s and a topological analysis using its deletion mutants.

LAP1s (lamina-associated polypeptide 1s) are type 2 integral membrane proteins with a single membrane-spanning region of the inner nuclear membrane. We report here on the cloning of the full-length cDNA of human LAP1B (huLAP1B) that encodes 584 amino acids. The sequence homology between the predicted rat LAP1B and huLAP1B was found to be 73.6%. A topological analysis was carried out by transiently expressing N-terminal GFP fused deletion mutants of huLAP1B in cells. The transmembrane (TM) domain (aa 346-368) is required for the localization of the nuclear and endoplasmic reticulum membrane and that the TM domain and the C-terminal half of the nucleoplasmic domain (aa 190-331) are sufficient for the proper localization of LAP1B. In contrast, the well-conserved lumenal domain of the nuclear membrane is not required for its topological function. Biochemical analysis showed that huLAP1B is retained within the nucleus via interactions of the nucleoplasmic portion with nuclear components.

Amino Acid Sequence↗