Biomedical subjects

Sadao Kamidono

Publications and source records attributed to Sadao Kamidono.

At least 55 records · Page 3Linked to original sources

PubMed2004

Synergistic inhibition of tumor growth and metastasis by combined treatment with TNP-470 and gemcitabine in a human bladder cancer KoTCC-1 model.

PURPOSE: TNP-470 (O-(chloroacetylcarbamoyl)fumagillol) is a potent inhibitor of angiogenesis that was reported to enhance synergistically the antitumor effects of cytotoxic agents. We evaluated the effectiveness of combined treatment with TNP-470 and gemcitabine in vitro and in vivo using highly metastatic human bladder cancer KoTCC-1 cells. MATERIALS AND METHODS: The in vitro growth inhibitory and apoptotic effects of gemcitabine and/or TNP-470 on KoTCC-1 cells were assessed using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and TUNEL staining, respectively. We then evaluated the combined effect of gemcitabine and TNP-470 therapy after subcutaneous and orthotopic injection of KoTCC-1 cells into athymic nude mice. Established tumors were analyzed by TUNEL staining and immunohistochemical staining of CD31 to quantify microvessel density. RESULTS: In vitro TNP-470 enhanced the cytotoxic effect of gemcitabine on KoTCC-1 cells, decreasing its IC50 by more than 50%. This combined treatment significantly induced apoptosis compared with treatment with either agent alone. In vivo combined treatment with TNP-470 and gemcitabine significantly decreased tumor growth after subcutaneous and orthotopic injection into athymic nude mice and significantly decreased the incidence of lymph node metastasis after arthotopic injection compared with either agent alone. Immunohistochemical analysis of the subcutaneous tumor after each treatment demonstrated that gemcitabine administration significantly induced apoptotic cell death. In contrast, a significant decrease in microvessel density was observed after TNP-470 treatment. CONCLUSIONS: These findings demonstrate that TNP-470 and gemcitabine act synergistically to inhibit tumor growth and metastasis by enhancing apoptosis and suppressing angiogenesis.

Angiogenesis Inhibitors↗

PubMed2004

Mutations in the gyrA and parC genes and in vitro activities of fluoroquinolones in 91 clinical isolates of Neisseria gonorrhoeae in Japan.

BACKGROUND AND OBJECTIVES: Fluoroquinolone resistance in Neisseria gonorrhoeae has been associated with alternations in the quinolone-resistance determining regions in the gyrA and parC genes. GOAL: The goal of this study was to investigate the correlation between fluoroquinolone minimum inhibitory concentrations (MICs) and mutations in the gyrA and parC genes of 91 N. gonorrhoeae clinical isolates from Japan. STUDY DESIGN: The MICs of fluoroquinolones ciprofloxacin, levofloxacin, and gatifloxacin for 91 clinical isolates from male gonococcal urethritis in Hyogo or Osaka, Japan, were measured, and the gyrA and parC genes of these isolates were sequenced. RESULTS: Among 91 isolates tested, over 70% isolates were resistant to ciprofloxacin. We found that 4 mutations (Ser-91-Phe, Ser-91-Ile, Asp-95-Gly in gyrA, and Ser-88-Pro in parC) had significant correlation to MICs of fluoroquinolone (ciprofloxacin, levofloxacin, and gatifloxacin). CONCLUSION: Some mutations in QRDR had a significant relationship to the fluoroquinolone resistance of N. gonorrhoeae clinical isolates from Japan.

Anti-Infective Agents↗

PubMed2004

Introduction of 65 kDa antigen of Mycobacterium tuberculosis to cancer cells enhances anti-tumor effect of BCG therapy.

Bacillus Calmette Guerin (BCG) immunotherapy has anti-tumorigenic effects against bladder cancer. To improve the efficacy of BCG therapy, we introduced the gene encoding the 65 kDa heat shock protein (hsp) of Mycobacterium tuberculosis into a mouse malignant melanoma cell line (B16). An expression vector harboring the 65 kDa antigen gene was transfected into B16 using Lipofectamine, then expression of the antigen was confirmed by RT-PCR and Western blotting. Several cell lines expressing 65 kDa antigen were established (B16/65 kDa). We also established a control cell line transfected with the vector alone (B16/con). All cell lines (B16, B16/con, B16/65 kDa) were injected intraperitoneally into syngeneic mice with or without BCG prior immunization and the development of tumor ascites was examined. To analyze the mechanism of the anti-tumor effect, CD4 T cells or CD8 T cells were depleted in vivo by administering the corresponding monoclonal antibody. B16/65k Da expressed the 65 kDa hsp of M. tuberculosis. The tumor growth of B16/65 kDa was slightly retarded in naive mice, but significantly inhibited by BCG. The anti-tumor effect was totally abrogated in mice deficient in CD4 T cells, suggesting that CD4 T cells are involved in this process. The 65 kDa hsp of M. tuberculosis was expressed after gene transduction in a malignant melanoma cell line and significantly enhanced the anti-tumor effect of BCG immunotherapy. CD4 T cells play an important role in this anti-tumor effect.

Animals↗

PubMed2004

Stromal invasion of the prostate following a complete response to bacillus Calmette-Guerin instillation therapy for carcinoma in situ of the ureter and the bladder.

Bacillus Calmette-Guerin (BCG) instillation therapy is now a standard therapy for high-risk superficial bladder cancer patients. Although the complete response rate is approximately 70%, extra-vesical progression is sometimes observed. In particular, those patients who present a positive urinary cytology even after complete response from bladder lesion should be thoroughly examined. We present two cases of stromal invasion of the prostate after complete remission by BCG therapy of carcinoma in situ of the ureter and bladder found by transrectal prostate biopsy.

Adjuvants, Immunologic↗

PubMed2004

Long-term outcome of postoperative interferon-alpha adjuvant therapy for non-metastatic renal cell carcinoma.

AIM: To investigate the long-term efficacy of postoperative interferon-alpha (IFN-alpha) adjuvant therapy in preventing recurrence in non-metastatic renal cell carcinoma treated with radical nephrectomy and to identify related prognostic markers. METHODS: Long-term follow-up was conducted to study rates of survival and non-recurrence in 88 subjects following radical nephrectomy for non-metastatic disease. RESULTS: The overall survival rate was 90% at 5 years and 88% at 10, with corresponding non-recurrence rates of 81% and 74%. Survival rates reviewed by preadministration pT stage showed a falling tendency from T1 through to T3 in line with pathological progression; when cases at stage pT1b or below were compared with those at stage pT2 or above, the latter showed a tendency to lower survival rates (P = 0.0966, Breslow-Gehan-Wilcoxon). Similarly, non-recurrence rates tended to fall in line with pathological progression, with a significant difference found in the comparison of cases at stage pT1b or below with those at stage pT2 or above (P = 0.0265, log-rank, Mantel-Cox). Duration of IFN-alpha administration showed a tendency to positive correlation with long-term survival (P = 0.3765, Breslow-Gehan-Wilcoxon). Non-recurrence rate was not found to differ according to duration of administration. Comparison of groups with normal and abnormal preadministration immunosuppressive acidic protein values showed that the normal group tended to have higher rates of survival and non-recurrence (P = 0.3371, Breslow-Gehan-Wilcoxon). CONCLUSIONS: Immunosuppressive acidic protein values appear to be a useful predictive marker for recurrence. A randomized trial, examining long-term outcome according to tumor stage and variables such as duration of administration, dose, administration time, and dosing schedule is required.

Adult↗

PubMed2004

Cut-to-the-light technique and potassium titanyl phosphate laser ureterotomy for complete ureteral obstruction.

We describe a case of complete ureteral obstruction managed by endoscopic recanalization using a 'cut-to-the-light' technique followed by potassium titanyl phosphate (KTP) laser ureterotomy. A 53-year-old man developed a ureteral obstruction following the transurethral resection of a bladder tumor (TUR-Bt) at the left ureteral orifice. The length of the obstructed segment was estimated at 1 cm based on combined antegrade and retrograde contrast studies. Histopathological analysis indicated that the obstruction was caused by fibrosis. The 'cut-to-the-light' technique was used for recanalization, and KTP laser ureterotomy was performed to obtain an adequate ureteral lumen. A 14 F/7 F endoureterotomy stent was removed 6 weeks after the operation. No significant complications and no signs of stenosis were observed 24 months after endoscopic repair. Endoscopic recanalization is a safe, effective technique for the management of a completely obliterated ureteral segment, especially in combination with subsequent KTP laser ureterotomy.

Endoscopy↗

PubMed2004

Safety and efficacy of vardenafil in patients with erectile dysfunction: result of a bridging study in Japan.

AIM: Vardenafil is a selective and highly potent phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction (ED), with improved selectivity for PDE5 and demonstrated efficacy for improving sexual function in men with ED. The current study investigated the safety and efficacy of this new PDE5 inhibitor in Japanese men with ED. METHODS: This was a prospective, double blind, randomized clinical trial designed to evaluate the efficacy and safety of vardenafil. Following a 4-week treatment-free observation period, 283 eligible patients were randomized to 12 weeks treatment with vardenafil 5 mg, 10 mg, 20 mg, or placebo. Primary efficacy responses were assessed using the scores of Q3 and Q4 of the international index of erectile function (IIEF). RESULTS: All three vardenafil doses showed significantly better improvement than the placebo group in Q3 and Q4 scores of the IIEF questionnaire, either at 12 weeks or at the 'last observation carried forward' (LOCF, P < 0.0001). Q3 scores were improved to 4.06 with vardenafil 5 mg, 4.53 with vardenafil 10 mg, and 4.64 with vardenafil 20 mg, versus 3.17 with placebo. Comparable scores for Q4 were 3.47, 4.15 and 4.31 versus 2.31 for placebo. Up to 86% of patients achieved improved erections as assessed by the global assessment question (GAQ). Reported adverse event rates were 35.3%, 45.3% and 54.5% with vardenafil 5 mg, 10 mg and 20 mg, respectively, versus 21.1% in the placebo group. No serious adverse drug reactions were reported. The most common treatment-emergent adverse events were transient headache, flushing and rhinitis, which were mostly mild. CONCLUSION: Vardenafil is an effective and well-tolerated treatment for ED and provides improvement in key indices of erectile function among Japanese men with ED. The results of our trial show that up to nearly 90% of patients achieve improved erections with the administration of vardenafil.

Adult↗

PubMed2004

Health-related quality of life after chemotherapy for advanced germ cell tumors: a comparison of standard-dose and high-dose chemotherapy.

BACKGROUND: The objective of this study was to evaluate the health-related quality of life (HRQoL) in patients with germ cell tumors who received standard-dose chemotherapy or high-dose chemotherapy combined with peripheral blood stem cell transplantation (PBSCT), and to compare the HRQoL of these patients with patients who had undergone surveillance therapy only. METHODS: Among the 102 patients included in this study, 38 underwent standard-dose cisplatin-based combination chemotherapy alone, 24 received high-dose chemotherapy with PBSCT following standard-dose chemotherapy, and 40 underwent surveillance monitoring. HRQoL was evaluated using the SF-36 survey, which contains 36 questions that assess eight quality-of-life aspects, including physical functioning, role-physical functioning, bodily pain, general health, vitality, social functioning, role-emotional functioning and mental health. RESULTS: The follow-up period of the surveillance group was significantly longer than that of the remaining two groups receiving chemotherapy; however, scale scores were not affected by the duration of follow up in either group. No significant difference was observed in any scale scores between the patients undergoing chemotherapy and those in the surveillance group. In comparison with the general population in the USA, social functioning in both the chemotherapy and surveillance groups was significantly lower, whereas vitality in these two groups was significantly higher. Patients undergoing standard-dose chemotherapy alone had a significantly higher score for mental health than those undergoing high-dose chemotherapy. However, there were no significant differences in the remaining seven scores, irrespective of the type of chemotherapy. CONCLUSIONS: Seven of the eight scale scores of HRQoL were favorable in patients who received chemotherapy or surveillance, and no significant difference was observed between these two groups. Moreover, with the exception of the mental health score, HRQoL was not significantly affected by the type of chemotherapy. Therefore, patients who received chemotherapy, including high-dose chemotherapy with PBSCT, seem to be generally satisfied with their overall HRQoL.

Adult↗

PubMed2004

Antitumor effect of simultaneous transfer of interleukin-12 and interleukin-18 genes and its mechanism in a mouse bladder cancer model.

BACKGROUND: The objectives of this study were to evaluate the antitumor effects of the simultaneous introduction of interleukin 12 (IL-12) and IL-18 genes into a mouse bladder cancer cell line (MBT2). We intended to compare these with those of either gene alone and to investigate the mechanism of the effects induced by the transfer of IL-12 and/or IL-18 genes in this model system. METHODS: We transfected the IL-12 and/or IL-18 genes into MBT2 cells by the liposome-mediated gene transfer method. We confirmed the secretion of IL-12 and/or IL-18 by enzyme-linked immunosorbent assay. Parental (MBT2/P), IL-12-transfected (MBT2/IL-12), IL-18-transfected (MBT2/IL-18) or both IL-12- and IL-18-transfected (MBT2/Both) cells were subcutaneously or intravenously injected into syngeneic C3H mice. To analyze the mechanism of tumor rejection, these clones were subcutaneously injected into naive nude mice and those depleted with natural killer (NK) cells by antibody. RESULTS: MBT2/IL-12, MBT2/IL-18 and MBT2/Both were completely rejected when they were injected subcutaneously or intravenously into syngeneic mice. However, MBT2/IL-12, but not MBT2/IL-18, could grow in nude mice. Moreover, the antitumor effect of MBT2/IL-18 was partially abrogated when injected into nude mice of which NK cells were depleted by antibody treatment. MBT2/Both was completely rejected in both nude mice with and without NK cells. CONCLUSION: The results of the present study indicate that T cells and NK cells seem to play important roles in the antitumor effects by the secretion of IL-12 and IL-18, respectively, and MBT2/Both possesses both mechanisms.

Animals↗

PubMed2004

Successful treatment for squamous cell carcinoma of the female urethra with combined radio- and chemotherapy.

We report on two cases of women with locally advanced squamous cell carcinoma of the urethra. Patient 1 also displayed regional lymph node metastasis. Treatment comprised combined radiotherapy to 60 Gy and chemotherapy with 5-fluorouracil and cisplatin. Complete response was obtained in both patients, including the inguinal lymph nodes of Patient 1. Patient 1 experienced recurrent inguinal lymph node metastasis on the contralateral side at 42 months after initial treatment, and the same treatment was performed followed by surgical excision. Both patients remain alive with no evidence of disease, at 12 months after recurrence in Patient 1, and at 27 months after treatment in Patient 2.

Aged↗

PubMed2004

Detection of Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum (biovar 1) and Ureaplasma urealyticum (biovar 2) in patients with non-gonococcal urethritis using polymerase chain reaction-microtiter plate hybridization.

AIM: To use polymerase chain reaction (PCR)-microtiter plate hybridization assays to detect Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum (biovar 1) and Ureaplasma urealyticum (biovar 2) in first-voided urine specimens from patients with non-gonococcal urethritis (NGU). METHODS: A total of 153 male patients with NGU, who visited one of 24 clinics in Japan, were recruited for this study. All were examined using PCR-microtiter plate hybridization assays for the presence of M. genitalium, M. hominis, U. parvum (biovar 1) and U. urealyticum (biovar 2) in first-voided urine specimens. They were also examined for the presence of Chlamydia trachomatis. RESULTS: Of these 153 patients, 73 (47.7%) were positive for C. trachomatis. Overall, the prevalence was 17.0% for M. genitalium, 16.3% for U. urealyticum (biovar 2), 7.8% for U. parvum (biovar 1) and 2.6% for M. hominis. In the 80 patients with non-chlamydial NGU, the prevalence of M. genitalium, U. urealyticum (biovar 2), U. parvum (biovar 1) and M. hominis was 23.8%, 18.8%, 8.8% and 2.6%, respectively. CONCLUSIONS: This study shows the prevalence of mycoplasmas and ureaplasmas in NGU in Japan. M. genitalium and U. urealyticum (biovar 2) might be pathogens of NGU and could be associated with persistent and recurrent urethritis. When patients with NGU are treated, such pathogens should be taken into account. This PCR-microtiter plate hybridization assay provides a useful method for diagnosing NGU caused by M. genitalium and U. urealyticum (biovar 2).

Asian People↗

PubMed2004

Advances in the management of non-seminomatous germ cell tumors during the cisplatin era: a single-institution experience.

BACKGROUND: The objectives of the present study were to review chronological changes in the long-term survival of patients with non-seminomatous germ cell tumor (NSGCT) who were treated at a single institution after the introduction of cisplatin-based combination chemotherapy. METHODS: One hundred and twenty patients with NSGCT who were treated between January 1978 and October 2001 were enrolled in this study. To evaluate chronological changes in treatment outcome between 1978 and 2001, data were analyzed according to the timing of initial treatment in two consecutive 12-year periods. The numbers of patients who were treated during 1978-1989 and 1990-2001 were 59 and 61, respectively. Patients were classified according to criteria of both the Japanese Urological Association (JUA classification) and the International Germ Cell Cancer Collaborative Group (IGCCCG classification). RESULTS: The mean follow up of surviving patients during the periods 1978-1989 and 1990-2001 was 84 months and 63 months, respectively. The overall 5-year survival rate of patients with NSGCT significantly increased from 72.8% during the period 1978-1989 to 83.6% during the period 1990-2001 (P = 0.02, log-rank test). A significant improvement in survival was found in the patients with stage III disease, according to the JUA classification, and in the patients with poor-risk disease, according to the IGCCCG classification (P = 0.004 and 0.05, respectively). CONCLUSIONS: The overall 5-year survival rate of patients with NSGCT increased significantly from 72.8% during 1978-1989 to 83.6% during 1990-2001. This improvement resulted mainly from an increased survival of patients with metastatic poor-risk NSGCT.

Adult↗

PubMed2004

Clinical outcome of retroperitoneal lymph node dissection after induction chemotherapy for metastatic non-seminomatous germ cell tumors.

BACKGROUND: Retroperitoneal lymph node dissection (RPLND) following induction chemotherapy has been considered a critical component in the comprehensive management of advanced non-seminomatous germ cell tumors (NSGCT). The objectives of the present study were to review the clinical outcome of patients who underwent RPLND and to evaluate the probability of necrosis alone, based on some readily available clinical data for these patients. METHODS: Forty-seven consecutive patients with NSGCT were treated with first-line chemotherapy at our institution between January 1993 and September 2002. Twenty-four of these patients, who underwent RPLND with normal values of tumor markers after induction chemotherapy, were included in the study. The cause-specific survival rate was calculated using the Kaplan-Meier method. Various predictive factors for the histology were analyzed using multivariate analysis. RESULTS: The pathological findings at resection were necrosis alone in 62.5% of cases, teratoma in 25.0%, and viable cancer in 12.5%. The cause-specific 3-year survival rate of patients who underwent complete and incomplete resection was 100% and 50.0%, respectively. Among several clinical factors, prechemotherapy tumor size less than 50 mm was found to be an independent predictor of necrosis alone (hazard ratio = 4.45, P= 0.04). CONCLUSION: Metastatic tumor size before chemotherapy appears to be one of the most important factors for the prediction of necrosis alone in the resected specimens of RPLND. The prognosis of patients might be influenced by the degree to which resection has been completed.

Adult↗

PubMed2004

Extraperitoneal laparoscopic retroperitoneal lymph node dissection in supine position after chemotherapy for advanced testicular carcinoma.

AIM: To evaluate the feasibility and usefulness of extraperitoneal laparoscopic retroperitoneal lymph node dissection (RPLND) in the supine position after chemotherapy for advanced testicular carcinoma. METHODS: Three patients with advanced testicular cancer underwent chemotherapy. Although serum markers were decreased compared with the normal range, residual masses requiring surgical resection were recognized by computed tomography scanning. We applied extraperitoneal laparoscopic RPLND. The patients were placed in the supine position and the first trocar was inserted two finger widths medial to the anterior iliac spine. The retroperitoneal space was dilated using a preperitoneal distention balloon. Two more ports were inserted into the retroperitoneal space and surgery proceeded thereafter. RESULTS: The residual tumors were completely resected by laparoscopy. The procedure required 250-310 min and the bleeding volume was below 50 mL. Although the histopathological findings consisted only of necrosis in all of the patients, one patient recurred at the same place. CONCLUSIONS: Extraperitoneal laparoscopic RPLND in the supine position for residual tumors after chemotherapy is technically feasible and useful in terms of postoperative recovery. With regard to cancer control, further evaluation should be necessary.

Adult↗

PubMed2004

Global analysis of gene expression profiles in ileum in a rat bladder augmentation model using cDNA microarrays.

BACKGROUND: The objective of the present study was to globally characterize the changes in the gene expression profile in the ileum after long-term urine exposure in a rat ileal augmented bladder model using cDNA microarrays. METHODS: Bladder augmentation using the ileum was performed in female 8-week-old rats. The ileal epithelia used for bladder augmentation were harvested 1 and 3 months postoperatively and changes in the gene expression in these tissues were compared with that of intact ileal epithelia from sham-operated rats using cDNA microarrays consisting of 1176 rat genes. RESULTS: Marked changes in gene expression in the ileum used for bladder augmentation were observed for 30 genes (16 up-regulated and 14 down-regulated genes). The differentially expressed genes include those associated with signal transduction, cell adhesion and stress response. Subsequent evaluation of changes in two randomly selected genes from the 30 differentially expressed genes by semiquantitative reverse transcription-polymerase chain reaction demonstrated the reliability of the present cDNA microarray analyses. CONCLUSION: The present experiments identified an extensive list of genes differentially expressed in the ileum after bladder augmentation, providing valuable information for the pathophysiological assessment of patients who undergo urinary reconstruction and representing a source of novel targets for treating complications after urinary diversion.

Animals↗

PubMed2004

Long-term survival after bilateral adrenalectomy for metachronous adrenocortical cancer.

We report the case of a female patient with bilateral metachronous adrenocortical cancer who survived long-term after adrenalectomy. In 1991, the patient underwent left adrenalectomy to remove a huge adrenal mass (10 x 9 cm) displaying no hormonal abnormality. Histological diagnosis was adrenocortical cancer. A right adrenal mass (7 x 6 cm) was found 4 years after left adrenalectomy. Right adrenalectomy was performed, and histological diagnosis was again adrenocortical cancer. The patient remains alive with no evidence of disease 8 years after last surgery.

Adrenal Cortex Neoplasms↗

PubMed2004

Inhibition mechanism of Gosha-jinki-gan on the micturition reflex in rats.

We investigated the actions of Gosha-jinki-gan, a traditional Japanese medicine containing processed Aconiti tubers, on urinary bladder function in anesthetized rats. In cystometrical investigations, Gosha-jinki-gan (1.0 g/kg, i.d.) increased bladder capacity as well as micturition threshold pressure. In addition, it decreased the frequency of distension-induced rhythmic bladder contractions. However, it did not influence the amplitude of bladder contractions induced by electrical stimulation of the pontine micturition center. The inhibitory effect of Gosha-jinki-gan on bladder motility was abolished by pretreatment with nor-binaltorphimine (10 mg/kg, s.c.), and was diminished by the concomitant use of anti-dynorphin A antiserum (10 microg, i.t.), yohimbine (10 microg, i.t.), or methysergide (20 microg, i.t.). Processed Aconiti tuber extract (27 mg/kg, i.d.) also suppressed bladder motility, and the effect was abolished by nor-binaltorphimine. These results suggest that Gosha-jinki-gan attenuates bladder sensation via the kappa-opioid receptor-stimulating action of processed Aconiti tuber. Gosha-jinki-gan may be a useful anti-pollakiuria agent that does not influence bladder contractility at micturition.

Aconitum↗

PubMed2004

Benign cystic lesion of the tunica albuginea: a case report.

We describe a patient whose testicular parenchyma was displaced by a cyst. Histologic findings suggested that the cyst was a dilated efferent ductule passing through the tunica albuginea. Such a cyst is an important and benign consideration in the differential diagnosis of testicular masses. Although orchiectomy was performed in this case, early consideration and confirmation of benign lesions may permit testicular preservation.

Aged↗