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1.  The best objective response of target lesions and the incidence of treatment-related hypertension are associated with the survival of patients with metastatic renal cell carcinoma treated with sunitinib: a Japanese retrospective study 
BMC Research Notes  2016;9:79.
Background
The aim of this study is to investigate the prognostic relevance of the best objective response of metastatic target lesions during sunitinib treatment in patients with metastatic renal cell carcinoma.
Methods
Radiographic analysis of the best objective response according to the Response Evaluation Criteria in Solid Tumors was assessed in 50 patients. Clinicopathological characteristics including the Heng risk classification and sunitinib-related adverse reactions were compared among four patient subgroups [complete response or partial response (CR/PR), stable disease (SD), progressive disease (PD), and those without treatment evaluation (NE)]. Kaplan–Meier and Cox proportional regression analyses of progression-free survival and overall survival were performed to identify prognostic variables.
Results
The best objective response was CR/PR in 12 (24 %) patients, SD in 22 (44 %), PD in 6 (12 %), and NE in 10 (20 %). The incidence of hypertension and hypothyroidism was associated with a better objective response. Progression-free survival was 15.0, 9.2, 6.8, and 2.2 months in the CR/PR, SD, PD, and NE groups, respectively (P = 0.0004, log-rank test), while the corresponding median overall survival was 59.7, 24.2, 17.1, and 18.1 months, respectively (P = 0.007). Multivariate analysis revealed that hazard ratios for risk of death of the SD, PD, and NE groups were 4.51 (P = 0.06), 7.93 (P = 0.02), and 4.88 (P = 0.04), respectively, as compared to the CR/PR group.
Conclusions
Our findings suggested that the best objective response of target lesions was a prognostic marker for both progression-free survival and overall survival in sunitinib treatment. Furthermore, the incidence of sunitinib-induced hypertension was associated with a longer progression-free survival.
doi:10.1186/s13104-016-1895-8
PMCID: PMC4748467  PMID: 26861149
Renal cell carcinoma; Sunitinib; Survival; RECIST
2.  Risk factors of PSA progression and overall survival in patients with localized and locally advanced prostate cancer treated with primary androgen deprivation therapy 
BMC Cancer  2015;15:420.
Background
Primary androgen deprivation therapy (PADT) has played an important role in the treatment of prostate cancer. We sought to identify factors of PSA progression in our series of patients with localized and locally advanced prostate cancer treated with PADT.
Methods
Six-hundred forty-nine patients with localized and locally advanced prostate cancer who received PADT from 1998 to 2005 by Nara Uro-Oncology Research Group were enrolled. Age, T classification, stage, PSA level at diagnosis, Gleason score, laterality of cancer detected by biopsy and seminal vesicle involvement (SVI) were adopted as parameters of PSA progression. Cox’s proportional hazards model was used to determine the predictive factors for PSA progression.
Results
The median follow-up period and the median PSA level at diagnosis were 49 months and 15 ng/mL. The 5-year disease specific survival rate, overall survival rate and PSA progression-free survival (PFS) rate were 97.9 %, 91.9 % and 71.2 %, respectively. The univariate analysis showed that the PSA level at diagnosis, Gleason score, laterality of cancer detected by biopsy and SVI were independent predictive parameters of PSA-PFS. However, by multivariate analysis, only laterality of cancer detected by biopsy (unilateral vs. bilateral) was an independent predictive parameter of PSA-PFS (p = 0.034). The patients were classified into new risk groups base on three factors: PSA level at diagnosis, Gleason score, and laterality of cancer detected by biopsy. The PSA-PFS rates at 5-years in the low- (none or one factor), intermediate- (two factors) and high-risk (three factors) groups were 78.2 %, 62.5 % and 46.9 % (p < 0.001), respectively.
Conclusion
In localized or locally advanced prostate cancer patients who received PADT, laterality of cancer detected by biopsy was a significant predictor associated with a longer PSA-PFS. Our new risk grouping indicates the usefulness of PSA-PFS.
doi:10.1186/s12885-015-1429-0
PMCID: PMC4446859  PMID: 25990314
Localized and locally advanced prostate cancer; Primary androgen deprivation therapy; Risk factors
3.  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
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.  5-fluorouracil enhances the antitumor effect of sorafenib and sunitinib in a xenograft model of human renal cell carcinoma 
Oncology Letters  2012;3(6):1195-1202.
Sorafenib and sunitinib are multi-kinase inhibitors with antitumor activity in patients with advanced renal cell carcinoma (RCC). Several studies have evaluated the effect of sorafenib/sunitinib in combination with chemotherapeutic agents in different types of tumor. However, few studies have addressed the activity of fluorinated pyrimidine in combination with sorafenib/sunitinib. In this study, we examined the potential of combination therapy with 5FU and sorafenib/sunitinib in human RCC cell lines. Three human RCC cell lines, ACHN, Caki-1 and Caki-2, were used to assess sensitivity to 5-fluorouracil (5FU), sorafenib and sunitinib alone or in combination using an in vitro cell survival assay. Caki-2 cells demonstrated significantly higher resistance to 5FU and sorafenib as compared to ACHN and Caki-1. Additive antitumor effects of the combination therapy were observed in the in vitro study. There was a tendency for a positive correlation between the sensitivity to sunitinib and platelet-derived growth factor β (PDGFR-β) expression levels, which were examined by reverse transcription polymerase chain reaction. Caki-1 xenograft models were prepared by inoculating cells subcutaneously into nude mice, which were divided randomly into six groups: control, 5FU (8 mg/kg/day, intraperitoneally), sorafenib (15 mg/kg/day, orally), sunitinib (20 mg/kg/day, orally), and 5FU with sorafenib or sunitinib. The treatments were administered on 5 days each week, and tumor growth was monitored for 42 days following inoculation of cells. Synergistic antitumor effects of the combination therapy were observed in an in vivo study. The resected tumors were evaluated using the Ki-67 labeling index and microvessel density. Both the Ki-67 labeling index and microvessel density were decreased in tumors treated with the combination therapy compared to those treated with sorafenib/sunitinib alone. These findings suggest that the combination therapy of 5FU with sorafenib/sunitinib may be an effective therapeutic modality for advanced RCC patients.
doi:10.3892/ol.2012.662
PMCID: PMC3392575  PMID: 22783417
renal cell carcinoma; 5-fluorouracil; sorafenib; sunitinib; angiogenesis
6.  PTEN Knockout Prostate Cancer as a Model for Experimental Immunotherapy 
The Journal of urology  2008;181(1):354-362.
Purpose
Testing immunotherapeutic strategies for prostate cancer has been impeded by the lack of relevant tumor models in immunocompetent animals. This opportunity is now provided by the recent development of prostate specific PTEN knockout mice, which show spontaneous development of true adenocarcinoma arising from prostate epithelium and more faithfully recapitulate the human disease than any previous model. We investigated the feasibility of using tumor cells derived from this model to test tumor vaccination and adoptive immunotherapeutic strategies for prostate cancer.
Materials and Methods
PTEN-CaP8 adenocarcinoma cells derived from the biallelic PTEN knockout prostate cancer model were used to vaccinate nontumor bearing litter mates. Tumor specific effector cells were generated from splenocytes of vaccinated mice by mixed lymphocyte-tumor reactions, and antiproliferative effects and cytokine generation were examined in vitro. The effect of vaccination or adoptive immunotherapy on luciferase marked PTEN-CaP8 subcutaneous tumors was monitored by tumor volumetric measurements and noninvasive bioluminescence imaging.
Results
Vaccination of litter mate mice with irradiated PTEN-CaP8 cells showed a significant prophylactic effect against the subsequent tumor challenge. Effector cells harvested from vaccinated litter mates showed significant interferon-γ secretion upon co-incubation with PTEN-CaP8 target cells and they were capable of efficient target cell growth inhibition in vitro. Intratumor adoptive transfer of effector cells resulted in significant growth inhibition of preestablished prostate tumors in vivo.
Conclusions
The PTEN knockout model serves as a highly useful model in which to investigate tumor cell vaccination and adoptive immunotherapeutic strategies in the context of true adenocarcinoma of the prostate. This model should accelerate efforts to develop effective immunotherapies for human prostate cancer.
doi:10.1016/j.juro.2008.08.124
PMCID: PMC2838731  PMID: 19010487
prostate; prostatic neoplasms; PLIP protein; mouse; cancer vaccines; immunotherapy; adoptive

Results 1-6 (6)