Thymol inhibits bladder cancer cell proliferation via inducing cell cycle arrest and apoptosis.

Thymol is a phenolic compound with various pharmacological activities such as anti-inflammatory, anti-bacterial and anti-tumor effects. However, the effect of thymol on bladder cancer cell growth is still elusive. The purpose of this study is to investigate the efficacy of thymol in bladder cancer cells and its underlying mechanism. Thymol inhibited bladder cancer cell proliferation in a dose and time-dependent manner. We also observed cell cycle arrest at the G2/M phase after the treatment of thymol. Moreover, thymol could induce apoptosis in bladder cancer cells via the intrinsic pathway along with caspase-3/9 activation, release of cytochrome c and down-regulation of anti-apoptotic Bcl-2 family proteins. The activation of JNK and p38 was also critical for thymol-induced apoptosis since it was abrogated by the treatment of JNK inhibitor (SP600125), and p38 inhibitor (SB203580) but not ERK inhibitor (SCH772984). Furthermore, the generation of ROS (reactive oxygen species) was detected after the treatment of thymol. ROS scavenger NAC (N-acetyl cysteine) could block the thymol-triggered apoptosis and activation of MAPKs. These findings offer a novel therapeutic approach for bladder cancer.

[Transurethral resection of the prostate versus transurethral holmium laser enucleation of the prostate for benign prostatic hyperplasia with bladder detrusor overactivity].

OBJECTIVE: To compare and analyze the effects of transurethral resection of the prostate (TURP) and transurethral holmium laser enucleation of the prostate (HoLEP) in the treatment of benign prostatic hyperplasia (BPH) with bladder detrusor overactivity. METHODS: his study included 51 cases of BPH with bladder detrusor overactivity treated by TURP and another 58 treated by HoLEP. We evaluated the urination of the two groups of patients during the recovery period and at 3 and 6 months postoperatively. RESULTS: There were no statistically significant differences in such baseline data as the blood PSA level, prostate volume, International Prostate Symptom Score (IPSS), and quality of life (QOL) between the two groups of patients, except in effective bladder capacity, which was higher in the TURP than in the HoLEP group (ï¼»315±59ï¼½ vs ï¼»287±76ï¼½ ml, P<0.05). Urine storage symptoms were obviously improved in both of the groups postoperatively, with the storage symptoms score significantly decreased from 12.6±4.9 preoperatively to 7.5±3.9 at 3 months and 6.1±4.2 at 6 months after surgery in the TURP group (P<0.01) and from 13.7±5.7 to 7.9±4.2 and 7.0±5.1 in the HoLEP group (P<0.01). HoLEP manifested significant advantages over TURP in the postoperative urethral catheterization time (ï¼»2.7±0.8ï¼½ vs ï¼»5.1±1.2ï¼½ d, P<0.05), postoperative bladder contracture time (ï¼»4.1±1.9ï¼½ vs ï¼»5.8±2.4ï¼½ d, P<0.05), postoperative hospital stay (ï¼»4.4±1.8ï¼½ vs ï¼»5.9±2.5ï¼½ d, P<0.05), and improvement of the maximum urinary flow rate, which was increased from (7.9±3.7) ml/s preoperatively to (16.8±4.3) ml/s at 3 months after surgery in the HoLEP group and from (8.6±3.2) ml/s to (14.6±4.3) ml/s in the TURP group (P<0.05). CONCLUSIONS: Both TURP and HoLEP can improve bladder function and detrusor overactivity in BPH patients, with similar effects in improving urination at 3 to 6 months after surgery. However, HoLEP has more advantages over TURP during the period of postoperative recovery.

siRNA targeting survivin inhibits growth and induces apoptosis in human renal clear cell carcinoma 786-O cells.

We investigated the inhibitory effect of small interfering RNA (siRNA) targeting survivin gene on cell proliferation and apoptosis in human renal clear cell carcinoma 786-O cells. qRT-PCR, immunocytochemistry, and Western Blot were used to detect Survivin gene expression in 786-O cells. Cell proliferation was determined by BrdU assay and PCNA expression. Cell apoptosis was analyzed through detection of caspase-3 activity, and the effect of survivin-siRNA on Bcl-2 gene expression was also examined. Forty-eight hours after transfection, survivin expression was markedly inhibited at the mRNA and protein level. Downregulation of survivin resulted in a significant inhibition of tumor cell growth. Caspase-3 activity showed that siRNA targeting survivin gene induced cell apoptosis in 786-O cells. Moreover, Bcl-2 protein expression was markedly inhibited by transfection with siRNA against survivin. These results indicate that siRNA targeting survivin gene can downregulate survivin gene expression in 786-O cells, inhibit growth, and induce apoptosis of renal carcinoma cells.

[Diagnostic value of lesion-directed prostate biopsy under TRUS in early detection of prostate cancer].

OBJECTIVE: To evaluate lesion-directed biopsy in improving the detection rate of early prostate cancer (PCa) and in differentiating PCa from other prostate pathological changes. METHODS: We performed TRUS-guided prostate biopsy for 95 patients suspected of PCa, each subjected to extended random biopsy plus lesion-directed biopsy, and analyzed the sonographic characteristics and pathological findings. RESULTS: PCa was detected in 35 of the patients (36.8%), including 16 hypoechoic (45.7%), 4 hyperechoic (11.4%), 10 isoechoic (28.6%) and 5 mixed hetero-echoic lesions (14.3%). Of the 35 PCa cases, 17 (46.2%) were within T2b, 70.6% (12/17) of which were detected by lesion-directed biopsy and 29.4% (5/17) by sextant biopsy, the former obviously higher than the latter (P < 0.05). CONCLUSION: Lesion-directed prostate biopsy under TRUS can significantly improve the early diagnosis of prostate cancer, increase convenience and reduce patients' pain, but is not sufficient to replace traditional sextant biopsy.

Estrogen receptor expression in adrenocortical carcinoma.

OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare but highly malignant tumor, and its diagnosis is mostly delayed and prognosis is poor. We report estrogen receptor (ER) expression in this tumor and our clinical experiences with 17 ACC cases. METHODS: The data of the 17 patients (9 females and 8 males, age range from 16 to 69 years, mean age of 42.6 years) with ACC were reviewed, and symptoms, diagnostic procedures, treatment, and results of follow-up were evaluated. Immunohistochemistry was used to detect ER expression in tumor samples from the 17 patients. RESULTS: At the time of diagnosis, 4 tumors were classified as Stage I, 4 as Stage II, 3 as Stage III, and 6 as Stage IV. Eight patients demonstrated positive nuclear immunostaining of ER. The prognosis of patients with ER positive was significantly better (P<0.05) than that of patients with ER negative, with 1- and 5-year survival rates at 86% and 60% for ER-positive patients, and 38% and 0% for ER-negative patients, respectively. CONCLUSION: ER-positivity may be one of the factors associated with a worse prognosis of ACC.

[Inhibition on phenotypic transformation of detrusor smooth muscle cells after bladder outlet obstruction by E2F decoy strategy].

OBJECTIVE: To investigate the inhibitory effect of E2F decoy strategy on the phenotypic transformation of detrusor smooth muscle cells (DSMCs) so as to verify the effect of the E2F decoy strategy in improvement of the bladder function after bladder outlet obstruction (BOO). METHODS: Rat DSMCs were cultured, underwent cyclic mechanical stretch so as to establish BOO model, and then were divided into 3 groups: E2F-ODN decoy group [transfected with E2F-decoy ODN tagged with carboxy-fluorescein (FAM), a at its 3' end], Mis-decoy group (transfected with mismatch E2F-decoy ODN), and control group (without transfection). Inverted fluorescence microscopy was used to detect the green fluorescence of FAM in the successfully transfected cells. The proliferation of the cells was observed by MTT method. RT-PCR was used to examine the mRNA expression of proliferating cell nuclear antigen (PCNA). Western blotting was used to detect the protein expression of PCNA and cdk2 kinase. RESULTS: FAM-labeled E2F-ODN was detected stably in the DSMCs of the E2F-ODN decoy group 24 hours after transfection. The proliferation of the DSMCs of the E2F-ODN decoy group was decreased significantly compared with the mismatch E2F-ODN decoy and control groups (both P < 0.01). The mRNA expression of PCNA, protein expression of PCNA and cdk2 kinase of the E2F-ODN decoy group were all significantly lower than those of the other 2 groups (all P < 0.01). CONCLUSION: E2F-decoy ODN can be transfected and stably expressed in DSMCs. The phenotypic transformation of DSMCs can be successfully inhibited by E2F decoy strategy, which clarifies the potential role of structural stability-based method on improvement of bladder function recovery after BOO.

[Transurethral holmium laser enucleation for prostate adenoma greater than 100 g].

OBJECTIVE: To evaluate the effect of transurethral holmium laser enucleation of the prostate (HoLEP) for prostate adenoma greater than 100 g. METHODS: Sixty BPH patients with the prostate larger than 100 g were randomized to two treatment groups of HoLEP (n = 32) and open prostatectomy (n = 28). Comparisons were made between the two groups in operating time, blood loss, bladder irrigating time, catheterization time and hospital stay, as well as in the international prostate symptom score (IPSS), quality of life (QOL) score, maximum urinary flow rate (Qmax) and postvoid residual volume (PVR) before and 3 months after the surgery. RESULTS: Compared with the open prostatectomy group, the operating time was significantly longer (P < 0.01) but the blood loss, mean bladder irrigating time, catheterization time and hospital stay were significantly less in the HoLEP group (P < 0.01). Three-month follow-up revealed that HoLEP and open prostatectomy resulted in a similarly significant improvement in IPSS, QOL, Qmax and PVR (P < 0.01 ), with no statistical difference between the two groups (P > 0.05). CONCLUSION: HoLEP and open prostatectomy are equally effective procedures for removal of large prostate adenomas, but the former is a better surgical option for prostate adenomas larger than 100 g for its greater safety, less pain and faster recovery.

Do dietary lycopene and other carotenoids protect against prostate cancer?

To determine whether dietary intake of lycopene and other carotenoids has an etiological association with prostate cancer, a case-control study was conducted in Hangzhou, southeast China during 2001-2002. The cases were 130 incident patients with histologically confirmed adenocarcinoma of the prostate. The controls were 274 hospital inpatients without prostate cancer or any other malignant diseases. Information on usual food consumption, including vegetables and fruits, was collected by face-to-face interviews using a structured food frequency questionnaire. The risks of prostate cancer for the intake of carotenoids and selected vegetables and fruits rich in carotenoids were assessed using multivariate logistic regression, adjusting for age, locality, education, income, body mass index, marital status, number of children, family history of prostate cancer, tea drinking, total fat and caloric intake. The prostate cancer risk declined with increasing consumption of lycopene, alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein and zeaxanthin. Intake of tomatoes, pumpkin, spinach, watermelon and citrus fruits were also inversely associated with the prostate cancer risk. The adjusted odds ratios for the highest versus the lowest quartiles of intake were 0.18 (95% CI: 0.08-0.41) for lycopene, 0.43 (95% CI: 0.21-0.85) for alpha-carotene, 0.34 (95% CI: 0.17-0.69) for beta-carotene, 0.15 (95% CI: 0.06-0.34) for beta-cryptoxanthin and 0.02 (95% CI: 0.01-0.10) for lutein and zeaxanthin. The corresponding dose-response relationships were also significant, suggesting that vegetables and fruits rich in lycopene and other carotenoids may be protective against prostate cancer.