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1.  Nadir PSA level and time to nadir PSA are prognostic factors in patients with metastatic prostate cancer 
BMC Urology  2014;14:33.
Background
Primary androgen deprivation therapy (PADT) is the most effective systemic therapy for patients with metastatic prostate cancer. Nevertheless, once PSA progression develops, the prognosis is serious and mortal. We sought to identify factors that predicted the prognosis in a series of patients with metastatic prostate cancer.
Methods
Two-hundred eighty-six metastatic prostate cancer patients who received PADT from 1998 to 2005 in Nara Uro-Oncology Research Group were enrolled. The log-rank test and Cox’s proportional hazards model were used to determine the predictive factors for prognosis; rate of castration-resistant prostate cancer (CRPC) and overall survival.
Results
The median age, follow-up period and PSA level at diagnosis were 73 years, 47 months and 174 ng/mL, respectively. The 5-year overall survival rate was 63.0%. The multivariable analysis showed that Gleason score (Hazard ratio [HR]:1.362; 95% confidence interval [C.I.], 1.023-1.813), nadir PSA (HR:6.332; 95% C.I., 4.006-9.861) and time from PADT to nadir (HR:4.408; 95% C.I., 3.099-6.271) were independent prognostic factors of the incidence of CRPC. The independent parameters in the multivariate analysis that predicted overall survival were nadir PSA (HR:5.221; 95% C.I., 2.757-9.889) and time from PADT to nadir (HR:4.008; 95% C.I., 2.137-7.517).
Conclusions
Nadir PSA and time from PADT to nadir were factors that affect both CRPC and overall survival in a cohort of patients with metastatic prostate cancer. Lower nadir PSA level and longer time from PADT to nadir were good for survival and progression.
doi:10.1186/1471-2490-14-33
PMCID: PMC4018264  PMID: 24773608
Prostate cancer; Metastasis; Risk factors
2.  Novel missense mutation in the FH gene in familial renal cell cancer patients lacking cutaneous leiomyomas 
BMC Research Notes  2014;7:203.
Background
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare tumor predisposition syndrome characterized by cutaneous and uterine leiomyomas and papillary type 2 renal cell cancer. Germline mutation of the fumarate hydratase (FH) gene is known to be associated with HLRCC.
Case presentation
We describe a 64-year-old father and his 39-year-old son with HLRCC who developed papillary type 2 RCCs lacking cutaneous leiomyomas at any site. A common missense mutation in the FH gene, (c.1021G > A, p.D341N) in exon 7, was detected in the 2 cases. Functional prediction with the bioinformatics programs, SIFT and Polyphen-2, reported “damaging (SIFT score 0.00)” and “probably damaging (PSIC score 1.621)” values, respectively. In 162 healthy individuals, there were no cases of a G transition to any base. Finally, (c.1021G > A) in exon 7, was identified as a point mutation.
Conclusion
We report a family with HLRCC in which a novel missense mutation was detected. A familial papillary type 2 renal cancer should be considered HLRCC unless typical cutaneous leiomyomas do not occur.
doi:10.1186/1756-0500-7-203
PMCID: PMC3978052  PMID: 24684806
Familial renal cell cancer; Papillary renal cell cancer; Fumarate hydratase; Missense mutation
3.  Diagnostic markers of urothelial cancer based on DNA methylation analysis 
BMC Cancer  2013;13:275.
Background
Early detection and risk assessment are crucial for treating urothelial cancer (UC), which is characterized by a high recurrence rate, and necessitates frequent and invasive monitoring. We aimed to establish diagnostic markers for UC based on DNA methylation.
Methods
In this multi-center study, three independent sample sets were prepared. First, DNA methylation levels at CpG loci were measured in the training sets (tumor samples from 91 UC patients, corresponding normal-appearing tissue from these patients, and 12 normal tissues from age-matched bladder cancer-free patients) using the Illumina Golden Gate methylation assay to identify differentially methylated loci. Next, these methylated loci were validated by quantitative DNA methylation by pyrosequencing, using another cohort of tissue samples (Tissue validation set). Lastly, methylation of these markers was analyzed in the independent urine samples (Urine validation set). ROC analysis was performed to evaluate the diagnostic accuracy of these 12 selected markers.
Results
Of the 1303 CpG sites, 158 were hyper ethylated and 356 were hypo ethylated in tumor tissues compared to normal tissues. In the panel analysis, 12 loci showed remarkable alterations between tumor and normal samples, with 94.3% sensitivity and 97.8% specificity. Similarly, corresponding normal tissue could be distinguished from normal tissues with 76.0% sensitivity and 100% specificity. Furthermore, the diagnostic accuracy for UC of these markers determined in urine samples was high, with 100% sensitivity and 100% specificity.
Conclusion
Based on these preliminary findings, diagnostic markers based on differential DNA methylation at specific loci can be useful for non-invasive and reliable detection of UC and epigenetic field defect.
doi:10.1186/1471-2407-13-275
PMCID: PMC3691617  PMID: 23735005
Urothelial cancer; DNA methylation; Pyrosequencing; ROC; Piagnostic accuracy
4.  Calculated Tumor Volume Is an Independent Predictor of Biochemical Recurrence in Patients Who Underwent Retropubic Radical Prostatectomy 
Advances in Urology  2012;2012:204215.
Purpose. The purpose of this study is to investigate whether the clinicopathological biopsy findings can predict the oncological outcome in patients who undergo radical prostatectomy. Materials and Methods. Between January 1997 and March 2006, 255 patients with clinically localized adenocarcinoma of the prostate (clinical T1-3N0M0) who had undergone retropubic radical prostatectomy were enrolled in this study. None of the patients received neoadjuvant or adjuvant therapy. Clinicopathological parameters were assessed to determine a predictive parameter of biochemical recurrence. Results. Of the total 255 patients, 77 showed biochemical recurrence during the follow-up period. The estimated 5-year overall survival, 5-year cause-specific survival, and 5-year biochemical recurrence-free survival rates were 97.7%, 99.5%, and 67.3%, respectively. Multivariate analysis using the Cox proportional hazards model showed that calculated cancer volume was an independent predictor among the preoperative clinicopathological parameters (P < 0.05). SVI and PSM were independent predictors among the postoperative parameters (SVI; P < 0.001, PSM; P = 0.049). Among the significant preoperative and postoperative parameters, calculated cancer volume remained an independent predictive parameter in multivariate analysis (P < 0.01). Conclusions. Tumor volume, as calculated by preoperative parameters, is an independent predictor of biochemical recurrence in patients who had undergone radical prostatectomy.
doi:10.1155/2012/204215
PMCID: PMC3359669  PMID: 22654901
5.  Unique DNA methylation patterns distinguish non-invasive and invasive urothelial cancers and establish an epigenetic field defect in premalignant tissue 
Cancer research  2010;70(20):8169-8178.
Urothelial cancer (UC) develops along two different genetic pathways, resulting in non-invasive or invasive tumors. However, it is unknown whether there are also different epigenetic pathways in UC. UC is also characterized by a high rate of recurrence and the presence of a field defect has been postulated. In this study, we compared the DNA methylation patterns between non-invasive and invasive UC, and the DNA methylation patterns in normal-appearing urothelium from bladders with cancer to urothelium from cancer-free bladders. We used the Illumina GoldenGate methylation assay at 1,370 loci in 49 non-invasive urothelial tumors, 38 invasive tumors with matched normal-appearing urothelium, and urothelium from 12 age-matched urothelial cancer-free patients. We found a distinct pattern of hypomethylation in the non-invasive tumors and widespread hypermethylation in the invasive tumors, confirming that the two pathways differ epigenetically in addition to genetically. We also found that 12% of the loci were hypermethylated in apparently normal urothelium from bladders with cancer, indicating an epigenetic field defect. X-chromosome inactivation analysis indicated that this field defect did not result in clonal expansion but occurred independently across the urothelium of bladders with cancer. The hypomethylation present in non-invasive tumors may counter-intuitively provide a biological explanation for the failure of these tumors to become invasive. In addition, an epithelium-wide epigenetic defect in bladders with cancer may contribute to a loss of epithelial integrity and create a permissible environment for tumors to arise.
doi:10.1158/0008-5472.CAN-10-1335
PMCID: PMC2955801  PMID: 20841482

Results 1-5 (5)