Sotaro Miwa

The bisphosphonate YM529 inhibits osteolytic and osteoblastic changes and CXCR-4-induced invasion in prostate cancer

Bisphosphonates are useful for the treatment of prostate cancer bone metastasis. However, the role of bisphosphonate on the development of the osteoblastic component of prostate cancer bone metastases is not defined. In the present study, the third-generation bisphosphonate, YM529 (minodoronate), was tested for its effects on the osteolytic PC-3 and novel osteoblastic LNCaP-SF cell lines. YM529 inhibited both osteolytic and osteoblastic changes in an intratibial tumor injection murine model. In vitro, YM529 inhibited both the proliferation and the invasion of both prostate cancer cell lines. The stromal cell-derived factor-1 (or CXCL12)/CXCR-4 pathway is believed to play an important role in the development of prostate cancer bone metastases. Thus, we determined if YM529 affected this pathway. YM529 suppressed CXCR-4 expression in PC-3 and LNCaP-SF in vitro and in vivo and this was associated with decreased in vitro invasion. These results suggest that YM529 may inhibit cancer cell invasion into the bone matrix by repressing the expression of CXCR-4 in bone metastasis lesions.

Risedronate Recovers Bone Loss in Patients With Prostate Cancer Undergoing Androgen-deprivation Therapy

OBJECTIVES To perform a prospective observational study between risedronate and no risedronate (control) groups to determine the effectiveness of risedronate against bone loss in patients with prostate cancer (PCa) receiving androgen-deprivation therapy (ADT). ADT for PCa has iatrogenic complications (eg, bone loss and fracture). METHODS We enrolled 60 Japanese patients with PCa who were receiving ADT or were newly scheduled for ADT. The lumbar spine bone mineral density (BMD) was determined by dual-energy x-ray absorptiometry. Patients with a BMD <90% of the young adult mean received risedronate. We analyzed 29 and 27 patients in the risedronate and control groups, respectively. The BMD, urinary deoxypyridinoline, and serum bone alkaline phosphatase were measured as bone turnover markers at 6 and 12 months. RESULTS The BMD/young adult mean ratio correlated inversely with the duration of ADT. The initial mean BMD was significantly lower in the risedronate group than in the control group (1.02 +/- 0.19 vs 1.19 +/- 0.16 g/cm(2)). We focused on patients treated with ADT for >6 months. The mean percentage of changes in the BMD/young adult mean ratio of the risedronate and control groups was +2.6 +/- 4.5% and -2.8 +/- 2.6% after 1 year, respectively (P = .0001). The urinary deoxypyridinoline and bone alkaline phosphatase in the risedronate group decreased significantly after 12 months compared with the levels in the controls. CONCLUSIONS The results of our study have shown that oral administration of risedronate is effective for the recovery of ADT-induced bone loss in patients with PCa.

Increases in bone turnover marker levels at an early phase after starting zoledronic acid predicts skeletal-related events in patients with prostate cancer with bone metastasis.

Study Type – Prognosis (case series)

A Case of Bone, Lung, Pleural and Liver Metastases from Renal Cell Carcinoma Which Responded Remarkably Well to Zoledronic Acid Monotherapy

Herein, we report a rare case in which bisphosphonate zoledronic acid (ZA) effectively treated not only multiple bone metastases but also lung, pleural and liver metastases from renal cell carcinoma (RCC). Recently, ZA is used to treat skeletal-related events (SREs) such as bone pain caused by bone metastasis from many kinds of cancer. The patient in the present report had multiple bone metastases from RCC. Remarkable improvement of the bone metastasis was observed following treatment with ZA at a dosage of 4 mg administered once every 4 weeks. Moreover, lung, pleural and liver metastases also diminished markedly in size in response to the treatment. The metastases have shown no progression for 20 months since starting the ZA treatment. We believe that the present report is the first of its kind announcing that ZA monotherapy has been effective for lung, pleural and liver metastases from RCC.

Bisphosphonate induces apoptosis and inhibits pro-osteoclastic gene expression in prostate cancer cells.

Aim:  Bisphosphonates are well established for the management of cancer‐induced skeletal complications. Recent studies suggest that bisphosphonates promote apoptosis of cancer cells as well as osteoclasts in bone metastatic sites. To determine the direct effects of bisphosphonate on prostate cancer, we examined the effects of minodronate on prostatic cancer cell growth and the expression of apoptosis‐related proteins and osteoclastogenic factors.

Establishment and characterization of androgen‐independent human prostate cancer cell lines, LN‐REC4 and LNCaP‐SF, from LNCaP

Aim:  To investigate the mechanisms of androgen‐independent growth in prostate cancer (PCa), we established two PCa cell lines, LN‐REC4 and LNCaP‐SF, from the androgen‐dependent PCa cell line, LNCaP.

Cardiovascular and respiratory effects of the degree of head-down angle during robot-assisted laparoscopic radical prostatectomy

Robot‐assisted laparoscopic radical prostatectomy (RALP) requires a steep Trendelenburg position and CO2 pneumoperitoneum for several hours to secure the surgical visual field. The present study was performed to investigate the influence of each angle of Trendelenburg position during RALP on cardiovascular and respiratory homeostasis.

Exogenous SPARC Suppresses Proliferation and Migration of Prostate Cancer by Interacting With Integrin β1

The matricellular protein secreted protein acidic and rich in cysteine (SPARC) plays an important role on tumor metastasis and progression in several cancers. However, the roles of SPARC in prostate cancer (PCa) remain unclear.

Urodynamic Evaluation Before and Immediately After Robot-assisted Radical Prostatectomy

OBJECTIVE To evaluate continence status and mechanism of urinary incontinence immediately after robot-assisted radical prostatectomy (RARP) by performing urodynamic evaluation. METHODS A total of 87 patients with localized prostate cancer who underwent RARP were included. Filling cystometry, urethral pressure profilometry, and abdominal leak point pressure (ALPP) tests were performed before and immediately after RARP. RESULTS The mean urine loss ratio (ULR), calculated by dividing the total urine volume by the weight of urine loss after RARP, was 17.8%. Nerve-sparing (NS) surgery significantly affected ULR compared with non-NS surgery. In the comparison between preoperative and postoperative results, the mean maximal cystometric capacity (MCC) and maximal closure urethral pressure (MUCP) decreased from 341 mL and 84.6 cm H2O to 250 mL and 35.6 cm H2O, respectively. No urine leakage was observed in ALPP test preoperatively; however, urine leakage was observed postoperatively in 75 patients (86%), with a mean ALPP of 47.7 cm H2O. Multivariate analysis revealed that MCC, MUCP, and ALPP after RARP were predictive factors for ULR. Linear correlations were found between ULR and MUCP and between ULR and ALPP after RARP. NS status and MUCP after RARP (r=0.247; P=.021) and the ALPP (r=0.254; P=.018) were significantly correlated. CONCLUSION In urodynamic evaluation immediately after RARP, MCC, MUCP, and ALPP were found to predictive factors for urinary incontinence. The NS procedure contributed to continence status after RARP.

Prospective longitudinal comparative study of health-related quality of life and treatment satisfaction in patients treated with hormone therapy, radical retropubic prostatectomy, and high or low dose rate brachytherapy for prostate cancer

Purpose: To evaluate the effects of four different prostate cancer treatments on quality of life (QoL) and patient satisfaction. Methods: Ninety-six prostate cancer patients were treated with hormone therapy, radical retropubic prostatectomy, high dose rate brachytherapy, or low dose rate brachytherapy. We assessed general, cancer-specific, and prostate disease-specific QoL. More than one year since commencement of treatment, the patients were asked the following questions: 1) How do you feel about your treatment? 2) Would you undergo the same treatment again? Results: The comparison of baseline and 12-month results showed that general and cancer-specific QoL had changed little in all groups. At baseline, the general and cancer-specific QoL tended to be lower in the hormone therapy patients. In the radical the retropubic prostatectomy patients, all scores on the Medical Outcomes Study 36-Item Short Form were worse than the baseline scores at three months. Scores for the International Index of Erectile Function-5 had also worsened, with no recovery. In the low-dose rate brachytherapy patients, the prostate disease-specific QoL at baseline tended to improve. However, the satisfaction levels for each treatment were reasonably good, and most patients would choose the same treatment again. Conclusions: The results of each of the four treatments differed in assessments of QoL. In the radical retropubic prostatectomy patients, the decrease in the International Index of Erectile Function-5 scores was especially remarkable and did not show recovery. In contrast, both brachy therapy groups had attained superior sexual function. However, regardless of the quality of life evaluations, most patients surveyed were satisfied with their treatments and would choose the same treatment again.