[show abstract][hide abstract] ABSTRACT: Hormone-resistant (HR) prostate cancers are highly aggressive and respond poorly to treatment. A better understanding of the molecular mechanisms involved in HR should lead to more rational approaches to therapy. The role of IL-6/STAT3 signaling in the transition of HR with aggressive tumor behavior and its possible link with myeloid-derived suppressor cells (MDSCs) were identified. In the present study, murine prostate cancer cell line (TRAMP-C1) and a hormone-resistant cell sub-line (TRAMP-HR) were used. Changes in tumor growth, invasion ability, and the responsible pathway were investigated in vitro and in vivo. We also examined the role of IL-6 in HR tumor progression and the recruitment of MDSCs. As seen in both in vitro and in vivo experiments, HR had aggressive tumor growth compared to TRAMP-C1. From mRNA and protein analysis, a higher expression of IL-6 associated with a more activated STAT3 was noted in HR tumor. When IL-6 signaling in prostate cancer was blocked, aggressive tumor behavior could be overcome. The underlying changes included decreased cell proliferation, less epithelial-mesenchymal transition, and decreased STAT3 activation. In addition to tumor progression, circulating IL-6 levels were significantly correlated with MDSC recruitment in vivo. Inhibition of IL-6 abrogated the recruitment of MDSCs in tumor- bearing mice, associated with slower tumor growth and attenuated angiogenesis. In conclusion, altered IL-6/STAT3 signaling is crucial in HR transition, aggressive behavior, and MDSC recruitment. These findings provide evidence for therapeutically targeting IL-6 signaling in prostate cancer.
Journal of Molecular Medicine 06/2012; 90(11):1343-55. · 4.77 Impact Factor
[show abstract][hide abstract] ABSTRACT: The identification of potential tumor markers will help improve therapeutic planning and patient management. Therefore, the aim of this study was to highlight the role of DNA methyltransferase 1 (DNMT1) in bladder cancer.
A total of 50 samples of nonmalignant urothelium, 65 of muscle-invasive bladder cancers, 15 of distant metastasis, and 50 of nonmuscle-invasive bladder cancers were selected for immunohistochemical staining analysis. Furthermore, human bladder cancer cell lines HT1376 and HT1197 were selected for cell and animal experiments investigating changes in tumor behavior, treatment response, and related signaling in bladder cancer.
The incidence of nuclear DNMT1 immunoreactivity in the bladder cancer specimens (45%) was significantly higher than in nonmalignant urothelium (15%, P = .0005), and the incidence in cancer was positively linked to clinical stage (24% in ≤T1 vs 55% in T2-T4, P = .0007). The staining of DNMT1 was also significantly linked to lower complete response rates (P = .0014) and reduced survival rates (P = .000). By in vitro and in vivo experiments, DNMT1 silencing vector reduced tumor growth and attenuated treatment resistance in bladder cancer cells. Less epithelial-mesenchymal transition, less invasion, and slower tumor growth were noted in cancer cells with inhibited DNMT1. Furthermore, the epidermal growth factor receptor-mediated phosphatidylinositol 3'-kinase-protein kinase B pathway might be the mechanism underlying the effects of DNMT1 on bladder cancer.
DNMT1 could be a significant clinical predictor for stage and treatment response of bladder cancer. Moreover, targeting this enzyme could be a promising strategy for treating bladder cancer, as evidenced by inhibited tumor growth and enhanced radiosensitivity.
Cancer 04/2011; 117(22):5221-33. · 5.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: Diabetic nephropathy is the leading cause of end-stage renal disease in the world. The cause of diabetic nephropathy seems to be multifactorial, and about one-third of patients with diabetes eventually develop this complication. The gene encoding ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is a candidate susceptibility gene for obesity and type 2 diabetes. We assessed rs1044498 (K173Q) located in the ENPP1 gene for association with diabetes nephropathy among 201 diabetic subjects without nephropathy and 215 diabetic subjects with nephropathy in the Taiwanese population. The single-nucleotide polymorphism (SNP) rs1044S498 in ENPP1 was associated with diabetes nephropathy in our study subjects. The AC+CC genotype of the rs1044498 SNP was a risk factor for the development of nephropathy in diabetic patients. Further, the AC+CC genotype of rs1044498 was a genetic risk factor in obese (defined by waist circumference) diabetic patients, but not in nonobese diabetic patients. We confirmed the association between the rs1044498 SNP in ENPP1 and diabetic nephropathy, especially among obese diabetic patients, in the Taiwanese population.
[show abstract][hide abstract] ABSTRACT: Objective
Single nucleotide polymorphisms (SNPs) in the coding region of interleukin 7 receptor (IL7R) are associated with severe combined immunodeficiency and multiple sclerosis. Based on the known mechanisms involved, IL7R has a high potential for being a candidate gene conferring allergy and asthma susceptibility. The purpose of this study was to investigate the possible genetic association between SNPs in the IL7R coding region and mite-sensitized asthma in Taiwanese children.
[show abstract][hide abstract] ABSTRACT: We report a rare case of right primary testicular actinomycosis presenting as multiple testicular lesions mimicking a metastatic tumor in a 71-year-old patient with gastric adenocarcinoma. Preoperative diagnosis is difficult. The enlarged and inflamed testis was removed by orchiectomy and testicular actinomycosis was diagnosed after pathological examination. The patient had not received any further antibiotic prescription and there was no recurrent or other site involvement after orchiectomy. We illustrate this case, though it is rare, to alert pathologists and clinicians to the possible occurrence of primary testicular actinomycosis mimicking metastatic lesions in a cancer patient. To diagnose, extensive sampling of the tissue specimens may be needed. We also reviewed the published literature and found that the treatment of choice for testicular actinomycosis was orchiectomy. The usage of penicillin after orchiectomy does not seem to affect the outcomes of the disease.
International Journal of Urology 06/2005; 12(5):519-21. · 1.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: This randomized trial was conducted to compare the efficacy and side effects of intravesical mitoxantrone instillation with those of doxorubicin in superficial bladder cancer following transurethral resection.
Sixty-three patients were randomized into mitoxantrone and doxorubicin groups. Most of the patients enrolled were elderly people (mean age, 71 years). The instilled doses of doxorubicin and mitoxantrone were 30 and 14 mg, respectively. Disease recurrence and side effects were compared using Fisher's exact test. The interval to recurrence was shown by Kaplan-Meier survivorship curves, and the log-rank test was used to compare the time to recurrence.
The median follow-up period was 36 months. Thirty-three patients received mitoxantrone, whereas 30 patients used doxorubicin. The recurrence rate in the doxorubicin group was 30% (95% CI: 19.8%-38.8%), while it was 27.3% (95% CI: 17.5%-36.8%) in the mitoxantrone group. The median recurrence-free survival in the mitoxantrone group and in the doxorubicin group was 22 and 20 months, respectively (p=0.580). Higher recurrence rates were found for Grade III and multiple primary tumors. There was no significant difference in response rates (p=0.784). The incidence of side effects was 20% in the doxorubicin group and 21.2% in the mitoxantrone group. However, the difference was not significant (p>0.99).
The results revealed that the efficacy and side effects of mitoxantrone were similar to those of doxorubicin. Especially for patients with pulmonary tuberculosis or aged patients with primary bladder tumors, mitoxantrone and doxorubicin may be the tolerable and effective intravesical agents.