Morusin exerts anti-cancer activity in renal cell carcinoma by disturbing MAPK signaling pathways.

BACKGROUND: Renal cell carcinoma (RCC) has gradually become a severe type of kidney malignant tumor, which warrants an urgent need for highly efficacious therapeutic agents. Morusin, a typical prenylated flavonoid, has been revealed to possess anticarcinogenic effects against several cancers by inhibiting cell proliferation and tumorigenesis. METHODS: Cells proliferation was examined by CCK-8. Migration assays were performed using a 24-well transwell chamber. Apoptotic cells were detected using the Annexin V PE/7-AAD apoptosis detection kit. Cell cycle analysis was carried out by flow cytometry. Western blotting and quantitative real time (qRT) PCR were used to exam the change of target gene in mRNA and protein level. Nude mouse xenograft experiments were performed to identify vivo function of morusin. RESULTS: Here, we evaluated the effect of morusin against RCC. We treated three RCC cell lines, 769-P, 786-O, and OSRC-2, with morusin to study its effects on cell growth, migration, apoptosis, cell cycle and cancer-related pathways. Additionally, we assessed the effects of morusin on tumor growth using a nude mouse model. Morusin could inhibit cell growth and migration, induce cell apoptosis and downregulate apoptosis-related proteins, and disturb the cell cycle arrest in the G1 phase. Additionally, morusin could suppress RCC tumorigenesis in vivo. Moreover, mitogen-activated protein kinase (MAPK) signal pathways were found to be involved in morusin-induced anti-cancer activity. P-p38 and P-JNK levels were up-regulated by morusin, while the ERK phosphorylation level was down-regulated. CONCLUSIONS: Our results show that morusin could inhibit the growth of RCC cells in vitro and in vivo through MAPK signal pathways. Thus, morusin could be a potential anti-cancer agent for RCC.

Collagen scaffolds tethered with bFGF promote corpus spongiosum regeneration in a beagle model.

Regeneration of the corpus spongiosum helps prevent complications following urethral reconstruction, but currently there is a lack of effective therapeutic methods in clinic. In previous studies, we fabricated a fusion protein collagen-binding domain (CBD)-basic fibroblast growth factor (bFGF) that specifically binds to and releases from collagen biomaterials. We demonstrated that CBD-bFGF could promote angiogenesis and tissue regeneration in vivo. In this study, we established a beagle model with extensive urethral defects, and reconstructed the defects with collagen biomaterials that were unmodified or modified with CBD-bFGF. The results demonstrate that CBD-bFGF promotes corpus spongiosum regeneration resulting in improved outcomes following urethral reconstruction. Modifying collagen biomaterials with CBD-bFGF may represent an effective strategy for urethral substitution in urethral reconstruction.

Bladder regeneration in a canine model using a bladder acellular matrix loaded with a collagen-binding bFGF.

Bladder reconstruction remains challenging for urological surgery due to lack of suitable regenerative scaffolds. In a previous study, we had used a collagen-binding basic fibroblast growth factor (CBD-bFGF) to bind bFGF to the collagen scaffold, which could promote bladder regeneration in rats. However, the limited graft size in rodent models cannot provide enough evidence to demonstrate the repair capabilities of this method for severely damaged bladders in humans or large animals. In this study, the CBD-bFGF was used to activate a bladder acellular matrix (BAM) scaffold, and the CBD-bFGF/BAM functional scaffold was assessed in a canine model with a large segment defect (half of the entire bladder was resected). The results demonstrated that the functional biomaterials could promote bladder smooth muscle, vascular, and nerve regeneration and improve the function of neobladders. Thus, the CBD-bFGF/BAM functional scaffold may be a promising biomaterial for bladder reconstruction.

The Efficacy of Percutaneous Nephrolithotomy Using Pneumatic Lithotripsy vs. the Holmium Laser: a Randomized Study.

The objective of the study is to compare the efficacy of percutaneous nephrolithotomy using holmium laser vs pneumatic lithotripsy. From August 2010 to March 2014, 200 patients with double kidney and single kidney stones without previous operations or other diseases were randomized into two groups according to the type of lithotripter used: pneumatic (n = 100) and laser (n = 100). The preoperative, intraoperative, and post-operative follow-up findings were analyzed and compared. The average stone size was similar in both the pneumatic and holmium laser lithotripsy groups (202.8 ± 52.6 mm2 vs. 200.3 ± 50.8 mm2). No significant difference was found between the operation time for the two groups (55.9 ± 16.5 min vs. 62.4 ± 17.6 min). The concentrations of creatinine in both groups increased 2-24 h after the operation and decreased to a normal level 1-4 days after the operation in both groups. Renal diuretic scan revealed that the peak and the renal index were both abnormal after the operation but became normal 4 days after the operation in both groups. No significant difference of creatinine concentration or the diuresis renogram was observed between the two groups. However, two cases in the holmium laser group had almost lost the renal function of the operated kidney 1 year later. Both pneumatic and holmium laser lithotripsy can be associated with acute renal injury in some patients after the operation without any significant difference. However, some infrequent severe renal function damage in laser lithotripsy should be noted.

Transplantation of human adipose-derived mesenchymal stem cells on a bladder acellular matrix for bladder regeneration in a canine model.

Tissue engineering brings new hope for the reconstruction of injured bladders. The aim of the present study was to evaluate human adipose-derived mesenchymal stem cells (hADSCs) combined with a bladder acellular matrix (BAM) for bladder regeneration. A BAM or BAM loaded with hADSCs (BAM/hADSCs) was used to repair partial cystectomy of the bladder in a canine model. 6 months after implantation, calculi and urine leakage were not found in either the BAM or BAM/hADSCs group by cystography. And compared to the BAM group, a significant increase of maximum bladder volume and bladder compliance was observed in the BAM/hADSCs group by urodynamics evaluation. Moreover, histological analysis showed that the BAM/hADSCs group could more effectively promote the regeneration of bladder smooth muscle and vascularization than the BAM group. These results demonstrated that a BAM/hADSCs could be an effective approach to promote bladder reconstruction with potential clinical applications.

Urethral tissue regeneration using collagen scaffold modified with collagen binding VEGF in a beagle model.

Extensive urethral defects have a serious impact on quality of life, and treatment is challenging. A shortage of material for reconstruction is a key limitation. Improving the properties of biomaterials and making them suitable for urethral reconstruction will be helpful. Previously, we constructed a fusion protein, collagen-binding VEGF (CBD-VEGF), which can bind to collagen scaffold, stimulate cell proliferation, and promote angiogenesis and tissue regeneration. We proposed that CBD-VEGF could improve the performance of collagen in reconstruction of extensive urethral defects. Our results showed that collagen scaffolds modified with CBD-VEGF could promote urethral tissue regeneration and improve the function of the neo-urethra in a beagle extensive urethral defect model. Thus, modifying biomaterials with bioactive factors provides an alternative strategy for the production of suitable biomaterials for urethral reconstruction.

Total retroperitoneal laparoscopic nephroureterectomy with bladder-cuff resection for upper urinary tract transitional cell carcinoma.

BACKGROUND: Open nephroureterectomy (ONU) and bladder cuff resection (ONU-BCR) has been the gold standard of surgical treatment for upper urinary tract transitional cell carcinoma (UUT-TCC). The aim of this study is to introduce a modified total retroperitoneal laparoscopic nephroureterectomy (LNU) with bladder-cuff resection (LNU-BCR) method for treating UUT-TCC and compare its clinical efficacy with ONU-BCR. METHODS: Sixty-five patients with UUT-TCC, who underwent ONU-BCR (n = 36) or LNU-BCR (n = 29) between January 2008 and June 2012, were analyzed in this retrospective study. Perioperative data as well as incidence of disease recurrence at the primary site or distant metastasis was compared in patients with at least 6 months follow-up. RESULTS: As compared with patients with ONU-BCR, the patients with LNU-BCR had significantly shorter operative time, lower estimated blood loss, shorter time to oral intake, lower analgesic dose, shorter duration of analgesic use, shorter duration of incision drainage tube, shorter time to ambulation out of bed and reduced postoperative hospital stay (all, p < .05). No significant difference in postoperative complications or incidence of bladder carcinoma recurrence and distant metastasis during the follow-up period was observed. CONCLUSIONS: The modified LNU-BCR represents an effective and safe alternative technique to ONU-BCR with the advantages of reduced invasiveness, bleeding and hospitalization.

[EXPERIMENTAL ASSESSMENT OF BLADDER REGENERATION BY COLLAGEN MEMBRANE SCAFFOLDS].

OBJECTIVE: To observe the bladder regeneration by collagen membrane scaffolds for bladder construction to find a new alternative scaffold material. METHODS: Twelve healthy adult male Sprague Dawley rats, weighing 300-350 g, were randomly divided into collagen membrane scaffold group (experimental group, n = 6), and sham operated group (control group, n = 6). Upper hemicystectomy was performed and collagen scaffold was used for reconstruction in experimental group, while the bladder was turned over without bladder resection in control group. At 30 days after operation, the animals were sacrificed and grafts were harvested; HE staining and Masson staining were used to evaluate the bladder regeneration, immunohistochemical staining was performed with α-smooth muscleactin (α-SMA) and von Willebrand factor (vWF) markers to evaluate the percentage of α-SMA positive area and capillary number. RESULTS: The rats of 2 groups survived to the end of the experiment, and no urine leakage or infection was observed in experimental group. Histologically, control group presented a pattern of normal bladder structure, experimental group presented a pattern of almost normal urothelium with a small amount of smooth muscle cells and a thin layer of undegraded collagen fibers. Immunohistochemically, experimental group showed ingrowth of smooth muscle fibers and new capillary formation along the collagen membrane scaffolds. The percentage of α-SMA positive area and capillary number in experimental group were significantly lower than those in control group (6.49% ± 2.14% vs. 52.42% ± 1.78% and 4.83 ± 0.75 vs. 14.83 ± 1.17, respectively) (t = 40.40, P = 0.00; t = 17.62, P = 0.00). CONCLUSION: The collagen membrane scaffolds could be an effective scaffold material for bladder reconstruction.

Effect of microbubble-enhanced ultrasound on prostate permeability: a potential therapeutic method for prostate disease.

OBJECTIVE: To explore the effect of microbubble-enhanced therapeutic ultrasound (MEUS) on prostate permeability and the blood-prostate barrier. METHODS: Experimental rabbits were assigned to 5 separate groups; the MEUS group, the MEUS 24-hour group, and the 3 control groups. A therapeutic ultrasound device was used to treat the rabbit prostates in vivo in combination with intravenous injection of microbubbles (MBs). Evans blue (EB) and lanthanum (La) nitrate were injected to assess the prostate permeability using laser scanning confocal microscopy (LSCM) and transmission electron microscopy (TEM). RESULTS: The MEUS group exhibited a significant increase in EB exudation and EB staining of the glandular parenchyma compared with the control groups. In the MEUS group, LSCM showed that a bright red fluorescence of EB was extensively distributed in the intercellular space of extravascular stroma and the glandular epithelium. In addition, TEM showed that the tight junction between vascular endothelial cells was opened, and the La particles used as tracers were seen in the stroma and glandular epithelium. The alterations in the MEUS group were significantly different from those in the groups exposed to MBs or ultrasound alone. These alterations were also not observed in the MEUS 24-hour group. CONCLUSION: MEUS enhanced the prostate permeability, and it effectively opened the blood-prostate barrier. Hence, MEUS may serve as a potential noninvasive therapy for targeted drug or gene delivery to the prostate. However, the relationship between the acoustic parameters of MEUS and prostate permeability or the bioeffects of MEUS needs to be evaluated in future studies.