Koichi Shoji

FGF19 promotes progression of prostate cancer.

Fibroblast growth factor (FGF) signaling pathways have been reported to play important roles in prostate cancer (PCa) progression. FGF19 is one of a subfamily of FGFs that circulate in serum and act in an endocrine manner. Our objective was to investigate its role in the progression of PCa.

Prognostic significance of C-reactive protein in patients with intermediate-risk metastatic renal cell carcinoma treated with molecular targeted therapy

The present study aimed to investigate the impact of pre-treatment C-reactive protein (CRP) levels on the prediction of prognosis in patients with metastatic renal cell carcinoma (mRCC), who were classified as intermediate-risk patients using the Memorial Sloan Kettering Cancer Center (MSKCC) risk classification and who received molecular targeted therapy. The oncological outcome of 140 patients with mRCC who underwent molecular targeted therapy was analyzed. Patients were divided into favorable-, intermediate- and poor-risk groups (groups F, I and P, respectively) based on the MSKCC risk classification. The patients in group I were then further classified into two groups based on pre-treatment serum CRP levels. The overall survival (OS) rates of the patients in these groups were then assessed. The OS rate of the patients in group I with normal pre-treatment CRP levels was found to be significantly increased compared with that of patients with high pre-treatment CRP levels (P<0.0001), while there was no significant difference in the OS rate in the patients with normal pre-treatment CRP levels in group I compared with those in group F. Multivariate analyses revealed that high pre-treatment CRP levels were an independent prognostic factor for OS in the patients in group I (P<0.0001; hazard ratio, 3.898). Thus, pre-treatment CRP levels may be a candidate predictor for OS in patients with intermediate-risk mRCC.

Relationship between the localization of fibroblast growth factor 9 in prostate cancer cells and postoperative recurrence

Background:Fibroblast growth factor 9 (FGF9) enhances cell proliferation and invasiveness in several malignant diseases. The aim of the present study is to investigate the role of FGF9 in postoperative recurrence after radical prostatectomy.Methods:Cell viability and invasion of LNCaP cells were assessed using MTT assay and Matrigel invasion assay, respectively, in the presence or absence of treatment with recombinant FGF9. Tissues obtained during a radical prostatectomy in 133 male patients were immunohistochemically stained using anti-FGF9 antibody.Results:Cell viability and invasion of LNCaP was significantly enhanced by treatment with recombinant FGF9. Immunohistochemical staining detected FGF9-positive cells in 20 samples. The prevalence of FGF9-positive cells in cases with a Gleason score of 8 or higher was 34.2%, which was significantly higher than that in those with Gleason scores of 7 or lower (7.3%, P=0.0003), respectively. The 3-year biochemical relapse-free survival rate was 17.5% in cases with FGF9-positive cells, which was significantly lower than that in cases in which FGF9-positive cells were not detectable (75.5%, P<0.0001).Conclusions:These results indicate that FGF9 can stimulate proliferation and invasion in prostate cancer cells, thus FGF9 could be a candidate of a predictive factor for recurrence after radical prostatectomy.

The impact of change in serum C-reactive protein level on the prediction of effects of molecular targeted therapy in patients with metastatic renal cell carcinoma

To investigate the impact of pretreatment serum C‐reactive protein (CRP) level and its change after targeted therapy on the anti‐tumour effect of targeted agents in patients with metastatic renal cell carcinoma (mRCC).

Impact of laparoscopic experience on the proficiency gain of urologic surgeons in robot-assisted surgery.

PURPOSE The aim of our study is to assess the impact of skill in laparoscopic surgery on the learning of robot-assisted surgery by urologic surgeons using the Mimic dV-trainer (MdVT). MATERIALS AND METHODS Twenty-three urologic surgeons using the MdVT were assessed. Ten of them were laparoscopic surgeons certified by the Japanese Society of Endourology. Each of the subjects completed four trials of a program consisting of four EndoWrist modules and two needle-driving modules. The performances of all subjects were recorded using a built-in scoring algorithm. RESULTS In only one of the needle-driving tasks, Suture Sponge (that all subjects felt was the most difficult task), the scores of the certified laparoscopic surgeons became significantly better than those of the other subjects at the 2nd and the 3rd trials (p=0.0236 and p=0.0043 at the 2nd and 3rd trials, respectively). At the 4th trial there was no significant difference between the two groups with regard to the overall scores of any tasks. CONCLUSIONS Our data indicate that familiarity with laparoscopic surgery is not associated with any advantage in learning the most fundamental techniques of robot-assisted surgery.

Prostate cancer detection by prostate-specific antigen-based screening in Japanese Hiroshima area shows early stage, low-grade, and low rate of cancer-specific death compared with clinical detection

INTRODUCTION We investigate the effectiveness of prostate-specific antigen (PSA) screening for prostate cancer. We compare the characteristics of 2 sets of patients: (1) those in whom prostate cancer was detected via PSA screening (the PS group) and (2) those in whom prostate cancer was detected at the outpatient office (the non-PS group). METHODS Between 2002 and 2010, prostate cancer was detected in 315 patients by PSA screening. Their age, initial PSA level, pathological findings in biopsy specimens, clinical stage, and prognosis were compared with those of 497 prostate cancer patients diagnosed at the outpatient office of the Department of Urology, Hiroshima University, in the same period. RESULTS The rates of patients with initial PSA higher than 50 ng/mL, with a Gleason score of 8 or higher, and with clinical stage D were significantly lower in the PS group than those in the non-PS group. The 5-year overall survival and cancer-specific survival in the PS group was 91.3% and 98.2%, respectively; these results were significantly better than those in the non-PS group (86.4%, p = 0.0178, and 94.9%, p = 0.0112, respectively). A Cox hazard analysis showed that PSA screening was an independent predictive factor for cancer-specific survival. CONCLUSIONS Although our study is limited by its retrospective nature and small size, the present data indicate that prostate cancer detected in the PS group showed earlier stage, lower grade, and better prognosis than in the non-PS group.

Impact of pre-implant lower urinary tract symptoms on postoperative urinary morbidity after permanent prostate brachytherapy

Objectives:  To assess the impact of baseline lower urinary tract symptoms on postoperative urinary morbidity in patients being treated for prostate cancer with 125‐I permanent prostate brachytherapy.

Restoration of fibroblast growth factor receptor 2IIIb enhances the chemosensitivity of human prostate cancer cells.

Fibroblast growth factor receptor 2 (FGFR2) is thought to mediate an important signaling pathway between prostate epithelial cells and stromal cells for maintenance of homeostasis in normal prostate tissue. Abnormalities of FGFR2 have been shown in advanced prostate cancer or prostate cancer cell lines, and we previously demonstrated the tumor-suppressive effects of the restoration of FGFR2IIIb in prostate cancer cells. The aim of the present study was to determine whether FGFR2IIIb plays a role in the chemosensitivity of castration-resistant prostate cancer cells. A clonal line of PC-3 cells expressing FGFR2IIIb (PC-3R2IIIb) was established by transfection with an IRESneo2-expressing vector bearing FGFR2IIIb cDNA. The effects of chemotherapeutic agents (docetaxel, cisplatin, 5-fluorouracil and zoledronic acid) on cell viability and apoptosis were examined by MTT assay and western blot analysis, respectively. Expression levels of molecules that were markers of epithelial-to-mesenchymal transition and chemosensitivity-related proteins were assessed by western blot analysis. Viability of the PC-3R2IIIb cells was significantly lower than that of the control PC-3 cells transfected with the vector alone (PC-3neo), and viability was further suppressed by treatment with chemotherapeutic agents, particularly docetaxel. Induced expression of caspase-3 was evident in the PC-3R2IIIb cells and was further enhanced by treatment with docetaxel. Expression of N-cadherin, vimentin, survivin and XIAP was lower in the PC-3R2IIIb cells than that in the PC-3neo cells. In contrast, expression of p21 was higher in the PC-3R2IIIb cells than that in the control PC-3neo cells. These data indicate that restoration of FGFR2IIIb in castration-resistant prostate cancer cells may reverse some of the epithelial-to-mesenchymal cell properties characteristic of tumor cells and induce in part mesenchymal-to-epithelial transition properties. This together with enhancement of apoptotic pathways involving caspase-3 may enhance chemosensitivity particularly to docetaxel which is widely used in the treatment of castration-resistant prostate cancer.

A comparison of clinicopathological features and prognosis in prostate cancer between atomic bomb survivors and control patients

An atomic bomb (A-bomb) was dropped on Hiroshima on 6th August 1945. Although numerous studies have investigated cancer incidence and mortality among A-bomb survivors, only a small number have addressed urological cancer in these survivors. The aim of the present study was to investigate the clinicopathological features of prostate cancer (PCa) in A-bomb survivors. The clinicopathological features and prognosis of PCa were retrospectively reviewed in 212 survivors and 595 control patients between November 1996 and December 2010. The histopathological and clinical outcomes of surgical treatment of PCa were also evaluated in 69 survivors and 162 control patients. Despite the higher age at diagnosis compared with the control group (P=0.0031), survivors were more likely to have been diagnosed with PCa from a health check compared with the control group (P<0.0001). As a consequence, the survivors were found to exhibit metastasis significantly less frequently (199/212, 93.9%) compared with the control patients (521/595, 87.6%; P=0.0076). Prognosis in the two groups was examined, subsequent to a mean length of follow-up of 44 months. Overall survival (OS) and PCa-specific survival (CS) were similar between the two groups (OS, P=0.2196; CS, P=0.1017). A-bomb exposure was not found to be an independent predictor for prognosis by multivariate analysis (OS, P=0.7800; CS, P=0.8688). The clinicopathological features of patients who underwent a prostatectomy were similar except for the diagnosis opportunity between the two groups. Progression-free survival rates were similar between the two groups (P=0.5630). A-bomb exposure was not a significant and independent predictor for worsening of progression-free prognosis by multivariate analysis (P=0.3763). A-bomb exposure does not appear to exert deleterious effects on the biological aggressiveness of PCa and the prognosis of patients with PCa.

Regeneration of rat corpora cavernosa tissue by transplantation of CD133 (+) cells derived from human bone marrow and placement of biodegradable gel sponge sheet.

The objective is to develop an easier technique for regenerating corpora cavernosa tissue through transplantation of human bone marrow-derived CD133 + cells into a rat corpora cavernosa defect model. We excised 2 mm × 2 mm squares of the right corpora cavernosa of twenty-three 8-week-old male nude rats. Alginate gel sponge sheets supplemented with 1 × 10 4 CD133 + cells were then placed over the excised area of nine rats. Functional and histological evaluations were carried out 8 weeks later. The mean intracavernous pressure/mean arterial pressure ratio for the nine rats (0.34258 ± 0.0831) was significantly higher than that for eight rats with only the excision (0.0580 ± 0.0831, P = 0.0238) and similar to that for five rats for which the penis was exposed, and there was no excision (0.37228 ± 0.1051, P = 0.8266). Immunohistochemical analysis revealed that the nine fully treated rats had venous sinus-like structures and quantitative reverse transcription polymerase chain reaction analysis of extracts from their alginate gel sponge sheets revealed that the amounts of mRNA encoding the nerve growth factor (NGF), and vascular endothelial growth factor (VEGF) were significantly higher than those for rats treated with alginate gel sheets without cell supplementation (NGF: P = 0.0309; VEGF: P < 0.0001). These findings show that transplantation of CD133 + cells accelerates functional and histological recovery in the corpora cavernosa defect model.