Kazunobu Sugimura

Antitumor effects of Scutellariae radix and its components baicalein, baicalin, and wogonin on bladder cancer cell lines

OBJECTIVES To investigate the antitumor effects of Scutellariae radix and its components baicalein, baicalin, and wogonin on human bladder cancer cell lines (KU-1 and EJ-1) and a murine bladder cancer cell line (MBT-2). METHODS Bladder cancer cells were incubated with various concentrations of the agents. Antiproliferative activity against the bladder cancer cell lines was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diplenyl tetrazolium bromide assay. In an in vivo experiment, the mice were subcutaneously injected with MBT-2 cells, and Scutellariae radix was orally administered at a dose of 2 or 10 mg per mouse one time daily for 10 days from day 11 to day 20. RESULTS All the drugs inhibited cell proliferation in a dose-dependent manner, but baicalin exhibited the greatest antiproliferative activity. The concentration of baicalin necessary to obtain 50% inhibition was 3.4 microg/mL for KU-1, 4.4 microg/mL for EJ-1, and 0.93 microg/mL for MBT-2. For KU-1 and MBT-2, the percentage of cell survival significantly decreased (P <0.05) at a baicalin concentration of 1 microg/mL. In an in vivo experiment, antitumor effects of Scutellariae radix on C3H/HeN mice implanted with MBT-2 were investigated. All the control mice showed a progressive increase in tumor volume, reaching 2.81 +/- 0.18 cm(3) on day 20 and 5.36 +/- 0.44 cm(3) on day 25. However, when Scutellariae radix was orally administered at a dose of 10 mg per mouse one time daily for 10 days from day 11 to day 20, the tumor volume was 1.99 +/- 0.19 cm(3) on day 20 and 3.86 +/- 0.26 cm(3) on day 25, a significant inhibition of tumor growth (P <0.05). Conclusions. These results suggest that Chinese herbal medicines may become an attractive and promising treatment for bladder cancer.

The Prognostic Role of Brain Natriuretic Peptides in Hemodialysis Patients

Background: Although plasma concentrations of brain natriuretic peptides (BNP) increase in hemodialysis (HD) patients as well as patients with cardiovascular diseases (CD), the clinical significance of BNP in HD patients has yet to be elucidated. In this study, we investigated the pathophysiological significance of BNP in HD patients. Methods: Plasma BNP concentrations were measured in 164 HD patients after HD and 14 healthy volunteers. In 12 patients without CD, BNP was also measured before HD. Multiple regression analysis was performed to determine the important factors causing increased plasma BNP concentrations. Cardiac mortality was monitored for 36 months after baseline analysis, and the prognostic role of BNP was examined by Cox proportional hazards regression analysis. Results: Plasma BNP concentrations of HD patients without CD decreased significantly during HD session (124.5 ± 90.7 vs. 91.4 ± 67.6 pg/ml, mean ± SD, p = 0.004), but were still significantly higher than those of the healthy subjects (9.7 ± 9.2 pg/ml, p = 0.0002). Plasma BNP concentrations of patients with CD were significantly higher than of those without CD (579.6 ± 564.3 vs. 204.0 ± 241.5 pg/ml, p < 0.0001). Plasma BNP concentrations were also significantly higher in diabetes mellitus (DM) patients than in non-DM patients (514.1 ± 585.4 vs. 296.0 ± 347.0 pg/ml, p = 0.0031). Multiple regression analysis showed that left ventricular mass index (LVMI), CD and DM were independent factors for the elevated BNP (R2 = 0.303, p < 0.0001). During a 36-month follow-up period, cardiac death occurred in 13 patients. Kaplan-Meier survival estimates of patients from varying plasma BNP quartiles (<200, 200–450, 450–700 and >700 pg/ml) differed between the four groups (p < 0.0001). The group with the highest BNP level (>700 pg/ml) had the lowest survival. When compared with patients with BNP <200, the hazard ratios for cardiac death of patients with BNP of 200–450, 450–700 and >700 pg/ml were 2.3 [95% confidence interval (CI) 0.14–36.7], 18.7 (1.9–183.4) and 51.9 (6.5–416.3), respectively. The univariate Cox proportional hazards model showed that BNP, left ventricular ejection fraction, LVMI, age, DM, serum albumin and C-reactive protein (CRP) were significantly associated with the risk of cardiac mortality. By stepwise multivariate Cox proportional hazards analysis, only BNP, LVMI and CRP remained powerful independent predictors of cardiac death. The relative risk ratios were 1.002 (95% CI 1.001–1.002) for BNP, 2.192 (1.532–3.135) for CRP and 1.027 (1.013–1.042) for LVMI. Conclusion: High plasma BNP concentrations in HD patients were associated with volume overload, left ventricular hypertrophy, CD and DM. Plasma BNP concentration may be a useful parameter for assessing the risk of cardiac death in HD patients by providing prognostic information independently of other variables previously reported.

Silent Cerebral Infarction in Hemodialysis Patients

Background: Cerebrovascular diseases are very common in hemodialysis (HD) patients. Silent cerebral infarction (SCI) has not been investigated in HD patients although it may be a significant risk factor for cerebrovascular diseases. Hypothesis: Chronic renal failure may be an independent risk factor for SCI and cerebrovascular diseases. Methods: Cranial magnetic resonance imaging (MRI) was performed on 123 HD patients without symptomatic cerebrovascular disease and on 52 control subjects. We investigated the prevalence of SCI and performed cross-sectional study using multiple logistic analysis to assess the relationship between SCI and the risk factors. Results: The prevalence of SCI was significantly higher in HD patients than in the healthy control group (60 patients (48.8%) vs. 5 patients (9.6%), χ2 = 22.4, p < 0.0001). Multiple logistic regression analysis with all subjects showed that independent risk factors of SCI were chronic renal failure, hypertension, smoking and age (R2 = 0.468, p < 0.0001). In only the HD patient group, age and smoking were shown to be independent risk factors of SCI (R2 = 0.378, p < 0.0001) while HD duration and hypertension were not. Conclusions: The findings of the present study indicate that chronic renal failure maintained by hemodialysis increases the prevalence of SCI and that age and smoking habits are also significantly associated with SCI in HD patients.

Interleukin-6, tumour necrosis factor α and interleukin-1β in patients with renal cell carcinoma

As regulators of malignant cell behaviour and communication with stroma, cytokines have proved useful in understanding cancer biology and developing novel therapies. In renal cell carcinoma, patients with inflammatory reactions are known to have poor prognosis. In order to elucidate the relation between renal cell carcinoma and the host, serum levels of inflammatory cytokines, interleukin-6, tumour necrosis factor α, interleukin-1β, were measured. One hundred and twenty-two patients with renal cell carcinoma and 21 healthy control subjects were studied, and serum cytokine levels were measured using a highly sensitive ELISA kit. As a result, in the control group, interleukin-6, tumour necrosis factor α and interleukin-1β levels were 1.79±2.03, 2.74±0.94 and 0.16±0.17 pg ml−1, respectively. In the renal cell carcinoma patients, they were 8.91±13.12, 8.44±4.15 and 0.53±0.57 pg ml−1, respectively, and significantly higher. In the comparison of stage, interleukin-6 level was significantly higher in the stage IV group compared to the other stage groups including the control group, while tumour necrosis factor α level was significantly higher in each stage group compared to the control group. As for grade, interleukin-6 level was significantly higher in the grade 3 group compared to the control, grade 1 and grade 2 groups, while tumour necrosis factor α level was significantly higher in each grade group compared to the control group. All cytokines had a positive correlation with tumour size. In regard to the correlation with CRP, all cytokines had a positive correlation with CRP, while interleukin-6 had a particularly strong correlation. In conclusion, interleukin-6 may be one of the factors for the poor prognosis of patients with renal cell carcinoma. In addition, tumour necrosis factor α may be useful in the early diagnosis of renal cell carcinoma and post-operative follow-up.

Interleukin-6, tumour necrosis factor alpha and interleukin-1beta in patients with renal cell carcinoma.

As regulators of malignant cell behaviour and communication with stroma, cytokines have proved useful in understanding cancer biology and developing novel therapies. In renal cell carcinoma, patients with inflammatory reactions are known to have poor prognosis. In order to elucidate the relation between renal cell carcinoma and the host, serum levels of inflammatory cytokines, interleukin-6, tumour necrosis factor α, interleukin-1β, were measured. One hundred and twenty-two patients with renal cell carcinoma and 21 healthy control subjects were studied, and serum cytokine levels were measured using a highly sensitive ELISA kit. As a result, in the control group, interleukin-6, tumour necrosis factor α and interleukin-1β levels were 1.79±2.03, 2.74±0.94 and 0.16±0.17 pg ml−1, respectively. In the renal cell carcinoma patients, they were 8.91±13.12, 8.44±4.15 and 0.53±0.57 pg ml−1, respectively, and significantly higher. In the comparison of stage, interleukin-6 level was significantly higher in the stage IV group compared to the other stage groups including the control group, while tumour necrosis factor α level was significantly higher in each stage group compared to the control group. As for grade, interleukin-6 level was significantly higher in the grade 3 group compared to the control, grade 1 and grade 2 groups, while tumour necrosis factor α level was significantly higher in each grade group compared to the control group. All cytokines had a positive correlation with tumour size. In regard to the correlation with CRP, all cytokines had a positive correlation with CRP, while interleukin-6 had a particularly strong correlation. In conclusion, interleukin-6 may be one of the factors for the poor prognosis of patients with renal cell carcinoma. In addition, tumour necrosis factor α may be useful in the early diagnosis of renal cell carcinoma and post-operative follow-up.

Serum hepatocyte growth factor levels in patients with chronic renal failure.

The serum levels of hepatocyte growth factor (HGF) were determined in chronic renal failure (CRF) patients. Nondialysis patients with renal insufficiency had significantly higher serum HGF than normal subjects (0.34 +/- 0.10 ng/ml, n = 21 vs. 0.19 +/- 0.05 ng/ml, n = 15; p < 0.001), and the elevated serum HGF correlated with their serum creatinine levels. Hemodialysis (HD) patients treated for 5-10 years showed higher serum HGF than those receiving HD for 1 year or less (0.45 +/- 0.14 ng/ml, n = 8 vs. 0.33 +/- 0.11 ng/ml, n = 9; p < 0.05). Continuous ambulatory peritoneal dialysis patients also showed elevated serum HGF levels comparable to those of HD patients. There was no difference in serum HGF levels in HD patients with or without acquired cystic disease of kidney. Consequently, serum HGF is elevated in CRF, which may be attributed to the increased production of HGF in response to the chronic renal injury, the effect of heparin, or reduced removal of serum HGF in CRF patients.

“Decoy” of androgen‐responsive element induces apoptosis in LNCaP cells

In an androgen‐dependent manner, the androgen receptor (AR) binds to the androgen‐responsive element (ARE) in the regulatory region of target genes. We hypothesize that an “ARE decoy,” a double‐stranded oligonucleotide containing the same DNA sequence as ARE, can inhibit prostatic proliferation by competitive inhibition of AR transcriptional activity.

The prevalence of metabolic syndrome in Japanese renal transplant recipients.

Background:  The prevalence of metabolic syndrome (MS) after renal transplantation has yet to be elucidated. In the present study, we investigated the prevalence of MS in Japanese renal transplant recipients.

Renal allograft arteriovenous fistula and large pseudoaneurysm

Abstract:  The patient was a 51‐year‐old female. Post‐biopsy arteriovenous fistula (AVF) and pseudoaneurysm in a renal allograft were diagnosed 5 yr and 4 months after she received a renal transplantation. Four years after the diagnosis, interventional treatment for the AVF and pseudoaneurysm was performed because of a high risk of pseudoaneurysm rupture. Although the longitudinal diameter of the pseudoaneurysm was more than 5 cm, this AVF and pseudoaneurysm were treated successfully by a percutaneous transluminal embolization, and renal function has remained stable after embolization. A selective interventional procedure proved effective for the large pseudoaneurysm in the renal allograft. Therefore, when a transcutaneous needle biopsy of the renal allograft is performed, although there are no apparent symptoms or signs of vascular complications during the clinical course, periodical examinations such as echo‐Doppler imaging should be made on the allograft.

Hepatocyte Growth Factor in Glycerol-induced Acute Renal Failure

Hepatocyte growth factor (HGF) facilitates the regeneration of injured kidney in acute renal failure (ARF). Here we investigated the HGF production in glycerol-induced ARF rats. HGF mRNA expression levels were elevated in liver, spleen, and lung 6-24 h after glycerol injection. Tissue HGF protein levels determined by an enzyme-linked immunosorbent assay also increased in liver and spleen, whereas they decreased in the injured kidney 24 h after injection. Immunohistochemical studies showed that the number of HGF-producing cells did not increase in the liver. HGF receptor/c-Met mRNA levels were elevated only in the kidney. These results indicate that HGF supplied in an endocrine manner may play an important role in the regenerating process following ARF.