BackgroundTo assess the outcome of neoadjuvant chemohormonal therapy comprising complete androgen blockade followed by treatment with docetaxel and estramustine phosphate before radical prostatectomy in Japanese patients with a high risk of localized prostate cancer (PCa).MethodsComplete androgen blockade followed by 6 cycles of docetaxel (30 mg/m2) with estramustine phosphate (560 mg) were given to 18 PCa patients before radical prostatectomy. Subsequently, the clinical and pathological outcomes were analyzed.ResultsNo patients had severe adverse events during chemohormonal therapy, and hence they were treated with radical prostatectomy. Two patients (11.1%) achieved pathological complete response. Surgical margins were negative in all patients. At a median follow-up of 18 months, 14 patients (77.8%) were disease-free without PSA recurrence. All 4 patients with PSA recurrence had pathologic T3b or T4 disease and 3 of these 4 patients had pathologic N1 disease.ConclusionWe found that neoadjuvant chemohormonal therapy with complete androgen blockade followed by treatment with docetaxel and estramustine phosphate before radical prostatectomy was safe, feasible, and associated with favorable pathological outcomes in patients with a high risk of localized PCa.

The incidence of hyperuricemia in our cohort was 38%. Male gender and long-term pretransplantation dialysis were predictors for the development of hyperuricemia. The eGFR was lower in patients with hyperuricemia, but graft survival did not differ between the patients with hyperuricemia treated with alloprinol and those without hyperuricemia. We could not define the significance of the pharmacokinetics of immunosuppressants and genetic risk factors for hyperuricemia.

Abnormal survivin expression has been reported to be involved in many types of cancer. A single-nucleotide polymorphism (SNP), C-31G, located in the promoter region of survivin reportedly may alter the mRNA level, while the significance of the nonsynonymous SNP A9194G in exon 4 has not yet been clarified. Here, the association between the two survivin SNPs and bladder cancer susceptibility and progression was investigated in 235 patients with bladder cancer and 346 healthy controls. Regarding the C-31G SNP, subjects with the CC genotype had a significantly higher risk of bladder cancer compared to those with the GG 1 CG genotype [odds ratio (OR) 5 1.85, p 5 0.001]. Regarding the A9194G SNP, the presence of the G allele was associated with a significantly reduced risk with a gene dosage effect (OR 5 0.69, p 5 0.002). Using the C-A haplotype as a reference, the G-G haplotype was associated with a significantly lower risk (OR 5 0.11, p 5 0.00006), indicating the cooperative effect of the two SNPs. Immunohistological evaluation of surgical specimens showed that cancer cells of the C-31G CC genotype had significantly higher nuclear survivin expression than those of the C-31G GG 1 CG genotype. With reverse transcriptase-polymerase chain reaction analysis, a significantly higher survivin mRNA expression level was observed in surgical specimens with an increase in the number of the C-31G C allele (p 5 0.016). These results indicate that the two SNPs have a significant and cooperative influence on bladder cancer susceptibility.Bladder cancer is the fourth most common cancer in men and the ninth most common cancer in women in the United States, 1 and it is the sixth most common cancer in men and the 11th most common cancer in women in Japan. 2 The most common type of bladder cancer is transitional cell carcinoma (TCC, also called urothelial carcinoma), and 55-60% of all newly diagnosed bladder cancers are well differentiated or moderately differentiated, superficial (confined to the urothelium or lamina propria) papillary TCCs. Tumor recurrences are observed in majority of these patients after endoscopic resection, with 16-25% of patients developing high-grade tumors. Muscle-invasive or metastatic cancer subsequently develops in 10-20% of patients with superficial papillary TCCs. 1 The 5-year survival rate of this variant is approximately 90%. However, nonpapillary muscle-invasive TCC, which accounts for 20-30% of urothelial malignancies, is invasive at diagnosis and carries a high risk for further invasion and metastasis. At least 50% patients with muscleinvasive cancers generally die within 2 years of diagnosis. 3 Concerning the heterogeneous behavior of bladder TCC, several studies have attempted to identify molecular markers that help clinicians in prognosis of patients with TCC. However, successful applications of molecular markers are limited because of the heterogeneity of molecular genetic alterations in bladder cancer. [4][5][6] Survivin is a protein involved in the inhibition of apoptosis and the control of mito...

We investigated the inhibitory effect of sunitinib, a newly approved multitargeted tyrosine kinase inhibitor, against the progression of renal cell cancer (RCC) bone metastases in vivo. In vitro cell proliferation was determined using the MTS assay. To investigate the inhibitory effects of sunitinib in vivo, we established luciferase-labeled ACHN Luc cells derived from papillary RCC. Mice in which ACHN Luc cells had been transplanted into the left ventricle to establish bone metastases were treated orally with 40 mg/kg/day sunitinib or vehicle control for 3 weeks. Growth of the cancer cells was monitored using an in vivo imaging system. In addition, 16 patients with metastatic RCC were treated with sunitinib, and serum and urine levels of amino-terminal telopeptide (NTx) were measured as markers of bone resorption. Sunitinib did not inhibit the growth of RCC cells in vitro at clinically or experimentally achievable serum levels (100 nM-1 lM). To investigate the inhibitory effect of sunitinib in vivo, we established luciferase-labeled human RCC cells (ACHN Luc ). Sunitinib prevented the growth of ACHN Luc RCC cells in the bone metastatic mouse model. The number of osteoclasts in sunitinib-treated mice was significantly less than that in control mice. Serum and urine levels of NTx in patients with metastatic RCC declined significantly during the first 4 weeks of sunitinib treatment (p 5 0.027). Sunitinib is a potent anticancer agent for RCC bone metastases, at least for papillary RCC.Bone is a common site of metastasis, with the frequency of solitary or multiple metastases to bone ranging from 24 to 51% in patients with metastatic renal cell cancer (RCC). 1-3 Although bone metastasis is not an independent prognostic factor associated with poor survival, the prognosis of patients with bone metastasis is not favorable when they are treated with cytokines, with an average life expectancy of 8-16 months. [2][3][4] Moreover, bone metastases are associated with poor performance status due to intractable pain and pathological fractures. 5 Because treatment options for RCC patients with bone metastasis are limited, appropriate treatment strategies are desired.Sunitinib is a newly approved, multitarget, small-molecule tyrosine kinase inhibitor for the treatment of metastatic RCC. It inhibits various receptor tyrosine kinases, including vascular endothelial growth factor (VEGF) receptors 1, 2 and 3; stem cell factor receptor (KIT) and PDGF receptors a and b. 6-8 Moreover, sunitinib has been known to inhibit the phosphorylation of colony-stimulating factor (CSF)-1R, resulting in the prevention of osteoclast function and CSF-1R-dependent osteolysis in an experimental breast cancer bone metastasis model. 9,10 These findings led us to propose the hypothesis that sunitinib may inhibit tumor growth and osteolysis in bone metastatic lesions in RCC patients.Although establishing a treatment strategy for bone metastases from RCC is important for urologists, the assessment of inhibitory effects on the growth of bone metastases is oft...

The present murine model provides a potentially interesting option to develop immunotherapy using gammadelta T cells for bladder cancer in human.