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Y Nasu

Publications and source records attributed to Y Nasu.

At least 37 records · Page 2Linked to original sources
PubMed2000

Epidermal growth factor in urine from patients with bladder cancer.

Epidermal growth factor (EGF), a mitogenic polypeptide with a molecular weight of 6000, is excreted in human urine in nanomolar quantities. Recently, some reports showed that urothelial neoplasm was related to the concentration of EGF in urine. In this study, EGF concentration in urine was measured by enzyme-linked immunosorbent assay (ELISA) in 207 samples from 112 male patients (30-90 years old, median 66.2) who had previously been treated for bladder cancer. Then, we tried to clarify the significance of urinary EGF as a marker for recurrence of bladder cancer in comparison with urine cytology. The samples were collected on occasional follow up cystoscopy. Urine from nine age-adjusted males without urological disease was also measured to obtain normal control values. In 123 samples from patients without tumors, EGF concentrations in urine decreased with age. In 84 samples obtained from patients with recurrent tumor, EGF concentrations were significantly lower than those in 123 samples from patients without tumors (P < 0.001) Furthermore, EGF concentrations in longitudinal samples collected the same patients during tumor recurrence and at the times when no tumor was detected were measured in 56 patients. EGF concentrations in the samples collected during tumor recurrence was significantly lower than that in specimens collected when there was no tumor (P < 0.01). There were no significant differences between the same samples collected during tumor recurrence with regard to tumor grade, stage shape and number of tumors. However, EGF concentration in urine from patients with carcinoma in situ (CIS) was lower than that in specimens from patients without CIS. These results indicate the usefulness of determining the EGF concentration as a marker for detecting bladder cancer recurrence. Urine cytology was also examined in the same series and findings were compared with those of urinary EGF. On cytology, class IV and V were considered positive, and on urinary EGF, less than 10 ng/mgCr were considered positive. Sensitivity was 25% for cytology and 57% for urinary EGF, while specificity was 98% and 66%, respectively. The predictive positive value was 0.88 and 0.53, respectively. With the combined use of urinary EGF and cytology, the sensitivity, specificity and predictive positive value were 68%, 64% and 0.92, respectively. In conclusion, urinary EGF seems to be a useful marker for detecting bladder cancer recurrence if performed in addition to cytology. cancer recurrence if performed in addition to cytology.

Adult↗
PubMed2000

Chromosomal numerical aberrations of exfoliated cells in the urine detected by fluorescence in situ hybridization: clinical implication for the detection of bladder cancer.

Numerical aberrations of chromosomes 7 and 9 of exfoliated cells from the urinary tract were examined using fluorescence in situ hybridization (FISH). To minimize contamination with inflammatory, squamous and normal transitional cells all samples were stained using Giemsa's solution and clusters of transitional cells were selected for FISH analysis. Samples collected from 21 patients who had cystoscopic monitoring for bladder cancer were used in this study. Cystoscopy was positive in seven patients and five biopsy-proven transitional cell carcinomas were identified. Among the patients with cancer recurrence, numerical chromosomal aberrations were detected in four cases (sensitivity: 80%) and positive cytology in two cases. This preliminary pilot study shows FISH can be a useful tool for the detection of recurrence during a follow up of bladder cancer.

Adult↗
PubMed2000

The absorption of pirarubicin instilled intravesically immediately after transurethral resection of superficial bladder cancer.

OBJECTIVES: To assess the validity of the prophylactic use of pirarubicin ([2'R]-4-O-tetrahydropyranyl-doxorubicin) immediately after transurethral resection of bladder tumour (TURBT), using pharmacodynamic studies. PATIENTS AND METHODS: The study included 20 consecutive patients with superficial bladder cancer. Pirarubicin (30 mg/50 mL or 30 mg/100 mL, 10 patients each) was instilled immediately after TURBT and retained in the bladder for 1 h. Blood samples were obtained before and at 15, 30, 60 and 120 min after the instillation. After retaining the drug for 1 h all the intravesical fluid was collected and assayed for pirarubicin. RESULTS: The plasma pirarubicin concentration in those receiving either dose was below detectable levels at any time after instillation. The mean recovery rate of pirarubicin in the drained fluid was 73%. CONCLUSION: The intravesical instillation of pirarubicin immediately after TURBT caused no detectable plasma concentration and few systemic side-effects.

Absorption↗
PubMed2000

Suicide gene therapy for urogenital cancer: current outcome and prospects.

Viral-mediated transfer of the herpes simplex virus thymidine kinase (HSV-tk) gene has been demonstrated by several investigators to confer sensitivity to nucleoside analogs such as ganciclovir (GCV) in a variety of tumor cells including brain, prostate, bladder, kidney, ovary, head and neck, lung, pancreas, and liver cancers. Fourteen suicide gene clinical protocols using adenovirus vectors have been conducted, including four in prostate cancer. Two additional protocols for prostate cancer are in preparation in Japan and the Netherlands. A study conducted at Baylor College of Medicine was the first to demonstrate the safety of HSV-tk plus GCV therapy for human prostate cancer and the anticancer activity of gene therapy in this disease. However, it is still in the early stage of its development, with a number of problems to be overcome. Systemic delivery, specific introduction, and specific expression of the target gene are the major issues to be managed in order to establish a clinically relevant treatment strategy.

Clinical Protocols↗
PubMed2000

Circulating adhesion molecules in patients with vibration-induced white finger.

We investigated whether a relationship existed between soluble adhesion molecules and vascular damage from vibration-induced white finger. Thirty-five men exposed to vibration and 40 healthy control subjects were examined. Concentrations of soluble E-selectin intercellular adhesion molecules, and vascular cell adhesion molecules in serum were measured with sandwich enzyme-linked adhesion immunosorbent assay. Neither E-selectin nor intercellular adhesion molecule levels are elevated in men exposed to vibration with white finger compared to levels in men exposed to vibration without white finger and control subjects. The serum level of soluble vascular cell adhesion molecules is significantly increased in patients with vibration-induced white finger.

Aged↗
PubMed2000

[Gene therapy].

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Genetic Therapy↗
PubMed2000

Prostate cancer gene therapy: comparison of adenovirus-mediated expression of interleukin 12 with interleukin 12 plus B7-1 for in situ gene therapy and gene-modified, cell-based vaccines.

We have documented previously that adenovirus-mediated interleukin 12 (IL-12) gene therapy is effective for orthotopic tumor control and suppression of pre-established metastases in a preclinical prostate cancer model (Y. Nasu et al., Gene Ther., 6: 338-349, 1999). In this report, we directly compare the effectiveness of an adenovirus that expresses both IL-12 and the costimulatory molecule B7-1 (AdmIL12/B7) with one that expresses IL-12 alone (AdmIL-12) using the poorly immunogenic RM-9 orthotopic murine model of prostate cancer. We document AdmIL-12/B7-mediated secretion of IL-12 and increased surface expression of B7-1 in infected RM-9 tumor cells. A significant reduction in orthotopic tumor size and increased survival was demonstrated in mice treated with a single orthotopic injection of AdmIL-12/B7 compared with AdmIL-12 or controls. Six of 19 animals treated with AdmIL-12/B7 survived long term with apparent eradication of the primary tumor in contrast to one of 38 animals in the AdmIL-12-treated group. Orthotopic treatment of tumors with both vectors led to an infiltration of both CD4+ and CD8+ immunoreactive cells, with AdmIL-12/B7 treatment having a more prolonged infiltration of CD8+ cells. AdmIL-12/B7 was also more effective than AdmIL-12 or controls at suppression of pre-established metastases. We further developed a vaccine model based on s.c. injection of infected, irradiated RM-9 cells and found that both AdmIL-12 and AdmIL-12/B7 are effective at suppressing the development and growth of challenge orthotopic tumors using this protocol.

Adenoviridae↗
PubMed1999

Adenovirus-mediated interleukin-12 gene therapy for prostate cancer: suppression of orthotopic tumor growth and pre-established lung metastases in an orthotopic model.

Interleukin-12 (IL-12) can elicit potent antitumoral effects that involve the recruitment of specific immune effector cells. We investigated the efficacy of a single injection of a recombinant adenovirus expressing murine IL-12 (AdmIL-12) directly into orthotopic mouse prostate carcinomas generated from a poorly immunogenic cell line (RM-9) derived from the mouse prostate reconstitution system. Significant growth suppression (> 50% reduction of tumor weight) and increased mean survival time (23.4 to 28.9 days) were observed compared with controls. Suppression of pre-established lung metastases was also observed following the injection of AdmIL-12 into the orthotopic tumor. Cytolytic natural killer cell activity was markedly enhanced 1-2 days after virus injection. Immunohistochemical analysis showed significantly elevated intratumoral infiltration of CD4+ and CD8+ T cells 7 days after virus injection. However, splenocyte-derived cytotoxic T lymphocytes were not detected during the 14 days following treatment. Increased numbers of nitric oxide synthase-positive macrophages were seen in the AdmIL-12 treated group 7 days following injection. Systemic inhibition of natural killer cells with antiasialo-GM1 serum led to increased numbers of lung metastases in AdmIL-12-treated orthotopic tumors but did not affect local tumor growth. In this model system the antitumor effects of a single injection of adenovirus-mediated IL-12 appears to be based to a large extent on the activation of nitric oxide synthase in macrophages and possibly T cell activities, whereas the relatively early cytolytic activity of natural killer cells are largely but not exclusively responsible for the antimetastatic effects.

Adenoviridae↗
PubMed1999

Pulmonary embolectomy for acute massive pulmonary embolism under percutaneous cardiopulmonary support.

Portable percutaneous cardiopulmonary support (PCPS) with heparin-coated circuits and a biopump was employed in a patient who had a massive pulmonary embolism with circulatory collapse after stripping of varicosities of the leg. Emergency pulmonary embolectomy was successfully performed. The main pulmonary incision was facilitated by cross-clamping of the main pulmonary arterial root. The bypass circuit was kept closed, and used with the normothermic beating heart without converting to conventional total cardiopulmonary bypass. Blood flow from the lung was removed by pump suction, stored in the reservoir, and intermittently returned to the venous circulation. Heparin was added to the circuits to keep the activated clotting time greater than 300 sec. In massive pulmonary embolism, PCPS is useful for preoperative, intraoperative, and postoperative support.

Acute Disease↗
PubMed1999

[The removal of renal carcinoma thrombus extending to the right atrium by means of extracorporeal circulation: report of a case].

A case of renal cell carcinoma with a tumor thrombus extending to the right atrium was reported. A 70-year-old woman was admitted with a diagnosis of right renal tumor which had been detected on a routine abdominal ultrasonography. MRI revealed a tumor thrombus extending into the right atrium through the inferior vena cava. A transesophageal echocardiogram confirmed that the tumor extended into the right atrium, and was not adherent to the inferior vena cava and the atrium. Right nephrectomy and removal of the tumor thrombus were performed using extracorporeal circulation. Temporary occlusion of portal venous and hepatic arterial inflow was effective in reducing blood loss. She has been doing well, and there has been no evidence of recurrence during 18 month postoperatively.

Aged↗
PubMed1999

[A comparative study of a thick and standard loop in transurethral resection of the prostate].

We compared the safety and efficacy of transurethral resection of the prostate (TURP) with a thick loop and with a standard loop. We compared 36 consecutive men (median age, 70 years) with symptomatic benign prostatic hyperlasia (BPH) treated by TURP with a thick loop to a cohort of 36 men (median age, 72 years) treated by TURP with a standard loop. The safety parameters of evaluation included the operative time, blood loss, chronological changes in serum sodium, and complications. The efficacy parameters of evaluation included International Prostate Symptom Score, quality of life assessment, peak urinary flow rate, and post-void residual urine volume. The operative time (median, 49.5 versus 43.5 minutes), blood loss (median, 179 versus 127 ml), and change in serum sodium (median, -4.0 versus -6.0 mEq/L) were not significantly greater in the thick loop group than in the standard loop group, respectively. There were no major complications in either group. Clinically significant improvement was observed in all efficacy parameters in both groups, with no difference between the two groups. These results suggest that TURP with a thick loop is not necessarily superior to TURP with a standard loop in terms of decreasing the blood loss and decreasing the operative time.

Aged↗
PubMed1999

Metastasis-related genes in prostate cancer.

The identification of genes specifically related to the development of metastatic disease in prostate cancer is complicated by tumor cell heterogeneity and the presence of expressed sequences that are not related to metastasis. A system was designed to minimize these complications using differential display-polymerase chain reaction (DD-PCR) together with genetically paired cell lines derived from primary mouse prostate cancer and their associated metastases generated in vivo by the metastatic mouse prostate cancer reconstitution model. Using this system, a number of metastasis-related sequences were identified, including a cDNA that encodes caveolin-1.

Animals↗
PubMed1999

Prostate cancer gene therapy: outcome of basic research and clinical trials.

With the advances in genetic engineering, tumor biology, and immunology, gene therapy has been recognized as a promising new treatment option for cancer, including prostate cancer. Several clinical trials of prostate cancer gene therapy currently underway are using therapeutic genes, including suicide genes, immunomodulatory genes, tumor suppressor genes, and antioncogenes. Although gene therapy for prostate cancer as a clinical alternative is still at an early stage that requires several technological breakthroughs, information obtained from clinical trials indicates the full potential of prostate cancer gene therapy. Concordant progress in basic research and gene therapy technology will ready prostate cancer gene therapy for widescale use in the future. In this report, the general concept and current progress in prostate cancer gene therapy are summarized.

Animals↗
PubMed1998

Suppression of caveolin expression induces androgen sensitivity in metastatic androgen-insensitive mouse prostate cancer cells.

Although prostate cancer cells are often initially sensitive to androgen ablation, they eventually lose this response and continue to survive, grow and spread in the absence of androgenic steroids. The mechanism(s) that underlie resistance to androgen ablation therapy remain mostly unknown. We have demonstrated that elevated caveolin protein levels are associated with human prostate cancer progression in pathological specimens. Here we show that suppression of caveolin expression by a stably transfected antisense caveolin-1 cDNA vector converted androgen-insensitive metastatic mouse prostate cancer cells to an androgen-sensitive phenotype. Orthotopically grown tumors and low-density cell cultures derived from antisense caveolin clones had increased apoptosis in the absence of androgenic steroids, whereas similarly grown tumors and cells from vector (control) clones and parental cells were not sensitive to androgens. Studies using a representative antisense caveolin clone showed that selection for androgen resistance in vivo correlated with increased caveolin levels, and that adenovirus-mediated caveolin expression blocked androgen sensitivity. Our results identify a new candidate gene for hormone-resistant prostate cancer in man and indicate that androgen insensitivity can be an inherent property of metastatic prostate cancer.

Androgens↗
PubMed1998

Clinical evaluation of serum prostate-specific antigen-alpha1-antichymotrypsin complex values in diagnosis of prostate cancer: a cooperative study.

BACKGROUND: We studied the clinical significance of serum prostate-specific antigen bound to alpha1-antichymotrypsin (PSA-ACT) values determined with a newly developed enzyme immunoassay. METHODS: Serum PSA-ACT values were determined in a total of 652 sera. Clinical utility for the diagnosis of prostate cancer was compared to that of Tandem-R PSA and gamma-seminoprotein (gamma-Sm). The new enzyme immunoassay is based on the use of the Stanford reference as an international standard for PSA assays. RESULTS: Serum PSA-ACT values ranged from less than 0.10 to 1.4 ng/mL in healthy males (n = 100) while values in patients with benign prostatic hyperplasia (n = 155) averaged 3.4 +/- 3.8 ng/mL (mean +/- SD). In patients with prostate cancer, serum PSA-ACT values increased significantly with progression of the clinical stage and there were statistically significant differences between benign prostatic hyperplasia and each stage of prostate cancer except for stage A. Using BPH levels as controls (4.8 ng/mL for PSA-ACT, 7.2 ng/mL for PSA, 3.8 ng/mL for gamma-Sm, and 2.4 ng/mL for the complexed/free PSA ratio of PSA-ACT/gamma-Sm), specificity was 80%. The sensitivity of prostate cancer detection was 79% for PSA-ACT, 77% for PSA, 57% for gamma-Sm, and 46% for the ratio between PSA-ACT/gamma-Sm. CONCLUSION: Although the determination of serum PSA-ACT showed essentially the same utility as that of PSA for the diagnosis of prostate cancer, PSA-ACT may allow prediction of the clinical stage. The PSA-ACT assay may therefore replace PSA in the detection of prostate cancer.

Disease Progression↗
PubMed1998

Prospective randomized comparative study of antibiotic prophylaxis in urethrocystoscopy and urethrocystography.

BACKGROUND: There has been a great deal of discussion regarding the necessity of the prophylactic use of antibiotics in transurethral procedures. In order to clarify this complicated issue, a randomized prospective study was performed for patients undergoing urethrocystoscopy or urethrocystography. PATIENTS AND METHODS: Patients who underwent urethrocystoscopy or urethrocystography and did not have pyuria and bacteriuria were included and divided randomly into 2 groups, either receiving a prophylactic antibiotic or no antibiotic. For antibiotic prophylaxis, 200 mg of sparfloxacin or fleroxacin were administered within a 1-hour period before the urethrocystoscopic or urethrocystographic examination, respectively. Analyses were performed on patients who were seen within 1 month after the examination, using the appearance of pyuria, bacteriuria, or a febrile infection as the endpoint. RESULTS: Of 47 patients undergoing urethrocystoscopy, 45 were eligible for analysis, and of these, sparfloxacin was administered to 21 patients. Thirty-three of 37 patients undergoing urethrocystography were eligible for analysis with fleroxacin administered to 16 patients. There were no significant differences in the background factors between the 2 groups undergoing either transurethral examination. None of the patients in either group developed pyuria, bacteriuria or a febrile infection after the examination. CONCLUSIONS: Prophylactic administration of antibiotics is not necessarily essential in urethrocystoscopy or urethrocystography in patients with sterile urine.

Adult↗
PubMed1998

Absorption of epirubicin instilled intravesically immediately after transurethral resection of superficial bladder cancer.

As postoperative adjuvant therapy for superficial bladder cancer, intravesical instillation therapy is commonly conducted. In this case, from the view point of prevention of intraoperative dissemination, commencement of instillation therapy at an early postoperative period is preferred. However, increased drug permeability is suspected because of damage to the bladder mucosa during operation. Therefore, this study was conducted to investigate the plasma level of epirubicin (EPI) instilled immediately after transurethral operation. EPI (20 mg/40 ml or 50 mg/100 ml) was instilled immediately after a transurethral operation, and retained in the bladder for 1 h. Blood samples were obtained before instillation, as well as 30, 60, 120 and 240 min after instillation, and EPI levels were assayed. The mean EPI concentrations (ng/ml) among the 20-mg/40 ml group (n = 5) were < 2.5 and < 2.0 at 30 and 60 min, respectively, after which they were undetectable. The 50-mg/100 ml group (n = 5) recorded 5.0, 4.4 and < 3.0 after 30, 60 and 120 min, respectively, and after 240 min it was undetectable. Intravesical instillation of EPI immediately after a transurethral operation causes a small increase in the plasma level and it is thought to cause small systemic side effects.

Absorption↗