[Outcome of Low-Dose-Rate Brachytherapy in Patients with Prostate Cancer and the Characteristics of Patients with Recurrence].

In our hospital, 553 patients with clinically localized prostate cancer underwent low-dose-rate (LDR) brachytherapy between March 2007 and December 2019. The patients were stratified based on the following prognosis according to the D'Amico risk classification criteria: low-risk and intermediate-risk groups (PSA ＜10, ≦T2a, GS : 3＋4 (≦30%)) were treated with LDR brachytherapy without supplemental extra beam radiotherapy (EBRT), while some patients in the high- and intermediate-risk groups were treated with LDR and supplemental EBRT. The 5- and 10-year overall survival rates were 94.8 and 85.5%, disease-specific survival rates were 99.8 and 97.7%, and biochemical recurrence-free survival rates were 95.7 and 90.7%. By risk stratification, the 5- and 10-year biochemical recurrence-free survival rates were 98.0 and 98.0% (low risk), 96.1 and 89.6% (intermediate risk), and 90.6 and 77.3% (high risk). The LDR outcome was generally good, but, 32 recurrence cases were observed. In the recurrent group, 9 patients did not undergo the recommended therapeutic strategy and 26 patients did not undergo preoperative magnetic resonance imaging.

Successful Treatment of a Large Superficial Bladder Cancer with Neoadjuvant Arterial Infusion Chemotherapy: A Case Report.

We present a case in which neoadjuvant arterial infusion chemotherapy was effective in treating a large superficial bladder cancer. A 50-year-old male was admitted to the Kanazawa Medical Center with the complaint of dizziness. The patient exhibited severe anemia, and his computer tomography showed a large bladder tumor. Cystoscopy revealed a large papillary tumor. Magnetic resonance imaging showed no muscle invasion and no metastasis. To avoid a prolonged operation time and excessive blood loss, we performed neoadjuvant arterial infusion chemotherapy for tumor volume reduction before transurethral resection of the bladder tumor (TUR-BT). The arterial infusion chemotherapy was performed twice, and the tumor size gradually reduced from 275 to 28 cm3. After neoadjuvant chemotherapy, TUR-BT was safely performed without blood transfusion. The tumor was staged as T1 with G1. This is the first report demonstrating that neoadjuvant arterial infusion chemotherapy is effective in treating large superficial bladder cancer and is a possible strategy for bladder preservation.

Impact of Gleason Pattern 5 on outcomes of patients with prostate cancer and iodine-125 prostate brachytherapy.

BACKGROUND: The Gleason grading system is a powerful predictor of prostate cancer (PCa) prognosis. Gleason scores (GS) of 8-10 are considered as a single high-risk grade category, and Gleason Pattern 5 (GP5) predicts biochemical recurrence. We report the clinical outcomes of patients treated with 125I prostate brachytherapy for clinically localized PCa and prognosis in the presence or absence of GP5. METHODS: We enrolled 316 patients with T1c-T2N0M0 PCa and undergoing prostate brachytherapy treatment. All patients were followed up for ≥ 1 year. The primary endpoint was biochemical recurrence-free survival. Biochemical recurrence was defined by the Phoenix criteria. Survival curves were calculated by the Kaplan-Meier method, and the prognostic impact of biochemical recurrence was analyzed using a Cox proportional hazards model. RESULTS: The 5-year biochemical recurrence-free survival rate for all patients was 95.2%, and according to the D'Amico risk classification criteria, the rates were 98.7% for patients in low-risk, 96.9% in intermediate-risk, and 81.1% in high-risk groups (P < 0.0001). The 5-year biochemical recurrence-free survival rates for patients with GS8 or GS9-10 were 87.7% and 61.5%, respectively (P = 0.0057). Multivariate analysis found that GS and clinical T stage were independent predictors of biochemical recurrence. CONCLUSIONS: The presence of GP5 in GS9-10 prostate cancer has a worse prognosis than GS8 prostate cancer in the absence of GP5 for patients undergoing prostate brachytherapy.

Mucosa-associated lymphoid tissue lymphoma involving the kidney: a case report and review of the literature.

Mucosa-associated lymphoid tissue (MALT) lymphomas arise from various anatomic sites, mostly observed in the gastrointestinal tract; however, involvement of the kidney is extremely rare. We report a case of MALT lymphoma involving the kidney in a 70-year-old man. Radical nephrectomy was performed under the diagnosis of renal cell carcinoma preoperatively. However, the renal specimen showed that the diffuse small- to medium-sized lymphocytes were scattered and formed colonies, and the neoplastic lymphoid cells were positive for CD20, CD79α, and Bcl-2, but negative for CD10 and Cyclin D1; therefore, the final histological diagnosis was MALT lymphoma involving the renal pelvis. Although he was referred to the department of hematology, no additional treatment was given postoperatively, and he has survived for 4 months without evidence of a recurrence of lymphoma at the last follow-up. To the best of our knowledge, to date 37 reports of MALT lymphoma involving the kidney have been published in the literature. We report a case of MALT lymphoma involving the kidney, and review the existing literature.

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.

Retrospective analysis of the efficacy of two cycles of M-VAC neoadjuvant chemotherapy followed by radical cystectomy for muscle-invasive bladder cancer.

BACKGROUND: Neoadjuvant chemotherapy before radical cystectomy for muscle-invasive bladder cancer is a commonly used treatment modality. However, in terms of chemotherapeutic regimens and the number of cycles of neoadjuvant chemotherapy, there is yet no international consensus, as various studies indicate the efficacy of several platinum-based combination chemotherapeutic regimens. We determined the efficacy of two cycles of neoadjuvant chemotherapy with methotrexate, vinblastine, adriamycin, and cisplatin followed by radical cystectomy. PATIENTS AND METHODS: The study population included patients with clinical stage T2 - T4a, N0, M0 bladder cancer who underwent radical cystectomy. Clinical courses were compared between 27 patients treated with two cycles of M-VAC neoadjuvant chemotherapy and 25 treated with cystectomy alone. RESULTS: The incidence of pT0 was 25.9% in the group treated with neoadjuvant chemotherapy. The probabilities of disease-free and cause-specific survival were significantly higher in patients treated with, than without neoadjuvant chemotherapy. On univariate Cox proportional hazards regression analysis for the patients treated with neoadjuvant chemotherapy, pathological stage and the pathological findings of venous involvement were significant prognostic factors. CONCLUSION: The results of this retrospective study demonstrated the clinical effectiveness of two cycles of neoadjuvant M-VAC chemotherapy for muscle-invasive bladder cancer.

Exogenous SPARC suppresses proliferation and migration of prostate cancer by interacting with integrin ß1.

BACKGROUND: 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. METHODS: To identify SPARC protein in prostate tissue, immunohistochemical analysis of SPARC was conducted using human prostate tissue microarray. To detect SPARC expression in prostate cancer (LNCaP, DU145, and PC-3) and stromal cells, RT-PCR, western blot analysis, and ELISA was conducted. To reveal the function of exogenous SPARC in PCa cells, AKT phosphorylation was confirmed by western blot analysis after coculture with stromal cells. Proliferation and migration of PCa cells were examined by addition of SPARC. The interaction between SPARC and integrin ß1 was confirmed by western blot analysis after immunoprecipitation. RESULTS: SPARC protein was expressed well in normal tissue compared with PCa tissue. ELISA showed high secreted SPARC protein in normal prostate-derived stromal cell (PrSC) compared with PCa-derived stromal cell (PCaSC) and PCa. PCa cells cocultured with PrSC showed reduced AKT phosphorylation more than with PCaSC. PCa cells cocultured with PrSC whose SPARC was knocked-down restored AKT phosphorylation. Moreover, PCa cells treated with SPARC led to reduced AKT phosphorylation. Immunoprecipitation with SPARC revealed interaction of SPARC and integrin ß1 in PCa cells. Inhibited proliferation and migration of PCa cells by SPARC was restored by integrin ß1 neutralizing antibody. CONCLUSIONS: Reduced SPARC secretion from stromal cells might affect PCa progression mediating through limiting AKT phosphorylation after interaction with integrin ß1.

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

BACKGROUND: 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. METHODS: Forty-seven ASA physical status 1 and 2 patients underwent open retropubic radical prostatectomy (RRP) or RALP. Patients receiving RALP were randomized to undergo the operation in the 20°, 25° or 30° Trendelenburg position. Heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), end-tidal CO2 pressure (PetCO2 ), tidal volume (Vt), peak inspiratory pressure (PIP) and dynamic compliance (Cdyn) were recorded during the operation. RESULTS: Angle of head-down tilt was significantly correlated with MAP, PIP and Cdyn, but not with HR, RR or PetCO2 . MAP decreased gradually over time in each group in the Trendelenburg position with pneumoperitoneum. As the angle of head-down tilt became stronger, MAP, RR, PetCO2 and PIP tended to increase and Cdyn tended to decrease. CONCLUSIONS: This study demonstrated that the degree of the head-down angle at RALP affected the cardiovascular and respiratory parameters. Pneumoperitoneum with head-down position in RALP influenced the cardiovascular and respiratory system to a greater extent than RRP, and these effects were stronger with deeper head-down angle.

The effectiveness of interferon-alpha subtypes alternation for metastasis from renal cell carcinoma.

Interferon-alpha (IFN-α) has been used in systemic treatment for metastatic renal cell carcinoma (mRCC). IFN-α has at least 14 subtypes, each of which has different biological activity. There have been reports that mRCC resistant to an IFN-α treatment responded to another IFN-α subtype. This study was performed to evaluate the effectiveness of alternation of different IFN-α subtypes for mRCC that did not respond to initial IFN-α treatment. In our department and associated institutions, alternating therapy of IFN-α was provided for 15 initial IFN-α refractory mRCC cases from June 2005 to September 2008. Among the 15 patients, the effects of alternating IFN-α therapy were as follows: complete response (CR), 0 cases; partial response (PR), 1 case; stable disease (SD), 3 cases; progressive disease (PD), 11 cases. The response rate (CR+PR) was 7% and disease control rate (CR+PR+SD) was 27%. No severe side effects were observed in any of these cases. The PR case is still in PR 21 months after alternating IFN-α therapy. Among the three SD cases, one has continued SD for 14 months and the other for 12 months. Alternating IFN-α therapy for mRCC can be attempted even if other cytokines are not effective.

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.

OBJECTIVE: To examine whether bone turnover markers could be predictive markers of the probability of newly arising skeletal-related events (SRE) after the start of zoledronic acid treatment in patients with prostate cancer with bone metastasis. PATIENTS AND METHODS: In all, 30 patients with prostate cancer with bone metastasis were treated with zoledronic acid infusion every 4 weeks. Serum C-terminal crosslinking telopeptide of type 1 collagen (1CTP), bone alkaline phosphatase (BAP), and prostate-specific antigen (PSA) levels were measured at the start of zoledronic acid treatment to establish baseline values, and every 4 weeks thereafter. To judge in the early phase whether zoledronic acid is effective in these patients, we retrospectively compared 1CTP, BAP, and PSA levels at 1, 3, and 6 months after starting zoledronic acid treatment with those at baseline. RESULTS: SRE-free survival of patients with increases of 1CTP levels at 1 and 3 months and BAP levels at 3 months were significantly poorer than those of patients with decreases in 1CTP or BAP levels (P = 0.001, P = 0.042, and P = 0.004, respectively). Overall survival of patients with increases of 1CTP levels at 1 and 3 months and of BAP levels at 6 months were significantly poorer than those of patients with decreases of 1CTP or BAP levels (P = 0.013, P = 0.027, and P = 0.035, respectively). CONCLUSION: The measurement of 1CTP and BAP levels at an early phase after starting zoledronic acid treatment may be useful for physicians to inform patients of their prognosis and to determine the subsequent treatment plan.

Clinicopathological outcomes of clinical T1a renal cell carcinoma by tumor size.

OBJECTIVE: We performed a retrospective review of clinical T1a renal cell carcinoma patients treated in our institution. The clinicopathological findings and patients' prognoses were analyzed according to tumor size, and risk factors for tumor recurrence were elucidated. METHODS: A total of 140 cases of sporadic renal cell carcinoma with a diameter of 4 cm or less on computed tomography findings for preoperative evaluation were treated as clinical T1a. Patients underwent radical nephrectomy or nephron-sparing surgery, and were evaluated postoperatively every 3-6 months to screen for metastatic disease. Patients' medical records were reviewed retrospectively and the status of each patient was assessed. RESULTS: There were four cases of clinically metastatic disease at diagnosis. There were no correlations between tumor size and pathological stage, Fuhrman nuclear grade or histological type. The rate of cases with microvascular invasion on pathological findings increased according to tumor diameter. Disease recurrence occurred in six patients (5.7%) during a mean postoperative follow-up of 41.7 months. There was a significant difference in the recurrence-free rate between pT1a patients with a tumor diameter of 31 mm or more and other patient groups. In terms of microvascular invasion on histological findings, the probability of non-recurrence at 7 years was 0% for patients with and 92.9% for those without microvascular invasion. CONCLUSIONS: Among T1a renal cell carcinoma, tumors over 30 mm in diameter may have aggressive biological potential, possibly due to microvascular invasion. Long-term follow-up is needed for these tumors.

Antibiotics therapy was effective in preventing bilateral staghorn renal matrix stones.

Herein we report a case for which antibiotic therapy was effective in preventing bilateral staghorn renal matrix stones. A 34-year-old man was referred to our hospital for right lower abdominal pain and fever. Blood data and urinary analysis indicated a urinary tract infection and renal failure. The diagnosis was bilateral pyelonephritis for staghorn renal matrix stones. He had undergone percutaneous neprolithotripsy (PNL) for bilateral staghorn renal matrix stones. Almost all fragments were removed by the grasper. However, 3 months after the operation, bilateral staghorn renal matrix stones rapidly developed, so he underwent PNL again. After the operation, low-dose antibiotic therapy was continued to prevent pyelonephritis. As a result renal matrix stones did not reoccur. Until now, 1 year after the start of antibiotic therapy, no further sign of relapse has been noted.

[Asymptomatic pheochromocytoma of the urinary bladder : a case for which preoperative diagnosis was possible].

A 62-year-old man who was diagnosed as having a bladder tumor by computerized tomography in another hospital. On August 4,2006 he visited our hospital. Cystoscopic examination revealed a submucosal tumor posterior to the right orifice. Computer tomography and magnetic resonance imaging showed the same findings. Therefore, we considered the possibility of asymptomatic pheochromocytoma of the urinary bladder. 131I-metaiodoberzyl guanidine scanography showed an abnormal accumulation in the bladder. Endocrinologic examination disclosed an increased level of serum and urinary noradrenalin. Pheochromocytoma of the bladder was diagnosed, and on October 25, 2006 a partial cystectomy and right ureteroneostomy were performed. Histologically, the tumor was pheochromocytoma of the urinary bladder. He has been receiving follow-up clinical observation for 30 months following the operation, and there has not been any evidence of recurrence.

Successful treatment for metastases from renal cell carcinoma with alternation of interferon-alpha subtypes.

Here we present a case in which alternation of interferon-alpha (IFN-alpha) treatments was effective in treating pulmonary metastases and lymph node metastases from renal cell carcinoma (RCC). A 56-year-old man underwent left radical nephrectomy under the diagnosis of left RCC. The histological diagnosis was clear cell carcinoma G2, IFN-alpha, pT1b. He subsequently underwent two operations for right pulmonary metastasis and right hilar lymph node metastasis. Postoperatively he was treated with intramuscular administration of natural IFN-alpha (Sumiferon) which prevented definite recurrence for 1 year. However, multiple pulmonary metastases and left hilar lymph node metastasis occurred 11 months after discontinuation of Sumiferon. Therefore, treatment with another natural IFN-alpha (OIF) was started. Although OIF was continued for 7 months, pulmonary metastases and left hilar lymph node metastasis continued to progress. Therefore, treatment was changed to Sumiferon, after which the pulmonary metastases and left hilar lymph node metastasis decreased in size. The metastases showed no progression for 16 months after switching from OIF to Sumiferon.

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.

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.

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. MATERIALS AND METHODS: LN-Pre and LN-REC4 cells were generated from LNCaP tumors grown on intact and castrated severe combined immunodeficient (SCID) mouse, respectively. After we cultured LNCaP cells under a steroid-free conditions for 6 months in vitro, LNCaP-SF cells were established. To show the character of LN-REC4 and LNCaP-SF cells, androgen sensitivity was investigated through examination of growth rate, and prostate-specific antigen (PSA), androgen receptor (AR), p21, p27, and cyclin D1 expression were examined by reverse transcription-polymerase chain reaction (RT-PCR). Angiogenesis assay in vitro was carried out using conditioned medium. To examine the expression level of vascular endothelial growth factor (VEGF), RT-PCR and enzyme-linked immunosorbent assay were also done. RESULTS AND CONCLUSIONS: LN-REC4 cells proliferated better than LNCaP cells in castrated mice and did well irrespective of castration, although responsiveness for androgen of LN-REC4 cells attenuated less than that of LNCaP cells in vitro. LNCaP-SF cells in castrated mice proliferated more rapidly than in normal mice. The PSA expression in LNCaP-SF cells was still induced by androgen. Expression of AR, p21, p27 and cyclin D1 were not changed in LN-REC4 and LNCaP-SF cells. Angiogenesis assay showed that both cells stimulated angiogenesis. LN-REC4 induced VEGF more than LNCaP and LN-Pre cells. However, expression of VEGF per cell in LNCaP-SF was lower than LNCaP cells, suggesting that other factors might be involved in angiogenesis. These cell lines might be a useful tool for researching androgen-independent growth and treatments of recurred PCa.

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. METHODS: PC-3, DU145 and LNCaP cells were treated with amino-bisphosphonate minodronate. Then proliferation, apoptosis and expression of bcl-2, bax, poly (ADP)-ribose polymerase (PARP), caspase-3, receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), matrix metalloproteinases-2 (MMP-2), and parathyroid hormone related protein (PTHrP) were assessed. RESULTS: The proliferation of prostatic cancer cells was inhibited by minodronate. DNA fragmentation and TUNEL-positive nuclei were observed in minodronate-treated PC-3 cells. Minodronate decreased bcl-2 expression and induced bax expression, caspase-3 activity and degradation of PARP in DU145 and PC-3 cells. Minodronate decreased expression of RANKL, PTHrP and MMP-2 in PC-3 cells. CONCLUSIONS: Our results suggest that bisphosphonate not only promotes apoptosis directly but also decreases pro-osteoclastic gene expression in prostate cancer cells.