This study demonstrated that URSL achieved excellent results for upper ureteral calculi greater than 1 cm. Thus, this procedure should be considered first line therapy for large proximal ureteral stones.
Biological activities of peanut stilbenoids, mainly resveratrol and its derivatives, have attracted increased attention and interest because of peanut being a potent producer and a dietary channel to convey these polyphenols to the human body. As arachidin-1 and piceatannol are structurally close to resveratrol, it is worthy to investigate their immunological activities on inhibition of lipopolysaccharide (LPS)-induced production of PGE2 and NO and mediation of the related transcription factors (NF-kappaB and C/EBP) of RAW 264.7 macrophage cells. Productions of PGE2 and NO were inhibited by all the test stilbenoids in a dose-dependent manner while gene and protein expressions of COX-2 and iNOS were not inhibited. As shown by NF-kappaB-driven luciferase assay, LPS-induced NF-kappaB activities were also reduced by the stilbenoids. In further, when these stilbenoids were subjected to monitoring their inhibitory effectiveness on LPS-induced transcription factor expressions of C/EBPdelta and C/EBPbeta, only C/EBPdelta expressions were reduced. Thus, these stilbenoids were effective in inhibition of PGE2- or NO-mediated inflammation and NF-kappaB- or C/EBPdelta-mediated inflammatory gene expression. In comparison, the highest inhibitory activity on LPS-induced PGE2/NO production, C/EBPdelta gene expression, and NF-kappaB activation was piceatannol which was followed in order by arachidin-1 and resveratrol. The observed anti-inflammatory activities of these peanut stilbenoids are of merit in further consideration for nutraceutical applications.
BACKGROUND AND PURPOSE
Bladder cancer is a highly recurrent cancer after intravesical therapy, so new drugs are needed to treat this cancer. Hence, we investigated the anti‐cancer activity of combretastatin A‐4 (CA‐4), an anti‐tubulin agent, in human bladder cancer cells and in a murine orthotopic bladder tumour model.
EXPERIMENTAL APPROACH
Cytotoxicity of CA‐4 was measured by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, propidium iodide (PI) staining assay and clonogenic survival assay. In vivo microtubule assembly assay, cell cycle analyses, Western blot and cell migration assay were used to study the mechanism of CA‐4. The effect of intravesical CA‐4 therapy on the development of tumours was studied in the murine orthotopic bladder tumour model.
KEY RESULTS
CA‐4 inhibited microtubule polymerization in vivo. Cytotoxic IC50 values of CA‐4 in human bladder cancer cells were below 4 nM. Analyses of cell‐cycle distribution showed CA‐4 obviously induced G2‐M phase arrest with sub‐G1 formation. The analyses of apoptosis showed that CA‐4 induced caspase‐3 activation and decreased BubR1 and Bub3 in cancer cells. In addition to apoptosis, CA‐4 was also found to induce the formation of multinucleated cells. CA‐4 had a significantly reduced cell migration in vitro. Importantly, the in vivo study revealed that intravesical CA‐4 therapy retarded the development of murine bladder tumours.
CONCLUSIONS AND IMPLICATIONS
These data demonstrate that CA‐4 kills bladder cancer cells by inducing apoptosis and mitotic catastrophe. It inhibited cell migration in vitro and tumour growth in vivo. Hence, CA‐4 intravesical therapy could provide another strategy for treating superficial bladder cancers.
Patients with transitional cell carcinoma on dialysis had a higher recurrence rate in the upper urinary tract than patients not on dialysis. Most cases were at an early stage but with high grade tumor behavior. In 11 patients (36.7%) total exenteration of the urinary tract except the urethra was eventually done. The final bilateral nephroureterectomy rate was 56.7%. Since the rate of total exenteration and bilateral nephrectomy was abnormally high at such a short followup, 1-step bilateral nephroureterectomy and radical cystectomy are a recommended treatment for patients with transitional cell carcinoma on dialysis.
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