Noriyasu Kawai

Effect of heat therapy using magnetic nanoparticles conjugated with cationic liposomes on prostate tumor in bone

We have developed magnetite nanoparticles conjugated with cationic liposomes (MCLs) to induce intracellular hyperthermia with exposure to an alternating magnetic field (AMF). We have previously demonstrated the hyperthermic effect of MCLs against certain types of malignant tumor cells in vivo. Here, we examine the effects of MCL + AMF heat therapy on prostate cancer tissue in a bone microenvironment and on bone destruction in a rat model.

Osteopontin Expression in Prostate Cancer and Benign Prostatic Hyperplasia

Objectives: Osteopontin (OPN), a secreted adhesive glycoprotein, has been shown to be produced in excessive amounts in a variety of experimental models of malignancy. Increased levels of OPN exist in blood from the lungs, breasts, and gastrointestinal tracts of cancer patients with metastases. However, there have been no reports on the expression of OPN in human urological malignancies. The present study investigates the presence of OPN in adenocarcinoma of the human prostate and in benign prostatic hyperplasia (BPH). Patients and Methods: Using prostate tissue from 34 patients with primary prostate cancer, 13 patients with prostate cancer after having undergone hormonal therapy, and 12 patients with BPH, formalin-fixed paraffin sections were prepared. Specimens were obtained by needle biopsy or radical prostatectomy. Immunohistochemical staining (ABC method) was then performed. Staining was divided into either negative or positive categories. Results: Positive staining of OPN was observed on cancer cells and macrophages in 52.9% of the primary prostate cancers and 14.5% of the prostate cancers after hormonal therapy. In BPH specimens, 66.7% of the cases displayed positive staining of OPN. The staining level of OPN showed no correlation with serum prostate-specific antigen, but did correlate with stage, differentiation, and Gleason’s score. Conclusions: The result postulates that the expression of OPN is an indicator of cell differentiation; however, it cannot be used as a marker of malignance in prostate cancer.

Long‐term outcome of upper urinary tract carcinoma in situ: Effectiveness of nephroureterectomy versus bacillus Calmette‐Guérin therapy

Background:  We examined the long‐term outcome and compared the usefulness of nephroureterectomy with that of bacillus Calmette‐Guérin (BCG) therapy for the management of upper urinary tract carcinoma in situ (CIS).

Efficacy of Endoscopic Combined Intrarenal Surgery in the Prone Split-Leg Position for Staghorn Calculi

UNLABELLED Abstract Purpose: To evaluate the efficacy of endoscopic combined intrarenal surgery (ECIRS) using retrograde flexible ureteroscopy and miniature percutaneous nephrolithotomy (PNL) for the treatment of patients with staghorn calculi in the prone split-leg position. PATIENTS AND METHODS We retrospectively reviewed the records of 42 patients with staghorn calculi (45.8±3.2 mm) who underwent ECIRS using retrograde flexible ureteroscopy and miniature PNL in the prone split-leg position for the treatment of staghorn calculi in our center between December 2010 and August 2013. A flexible ureteroscope with a laser fiber was inserted through a ureteral access sheath, and lithoclast lithotripsy was performed through a mini-percutaneous tract. Both procedures were performed simultaneously by two urologists. Surgical parameters, including surgical time, stone-free (SF) rates, modified Clavien complication grades, and risk factors for residual stones, were analyzed. RESULTS Fifteen patients (35.7%) had complete staghorn calculi. Among the 42 staghorn calculi treated, 23 had 0 to 5 stone branches, 14 had 6 to 10 stone branches, and 5 had ≥11 stone branches. All procedures were performed successfully using a single lithotripsy tract with the patient in the prone split-leg position. The mean surgical time was 143.2±9.2 minutes. The initial SF rate was 71.4%, and the final SF rate was 83.3% after further treatment. One patient required a blood transfusion (2.4%), but no patient experienced a ≥3 Clavien grade complication. Risk factors for residual stones were stone size, stone surface area, complete staghorn calculi, and the number of stone branches. CONCLUSIONS ECIRS for staghorn calculi in the prone split-leg position is a safe, efficient, and versatile method for the effective management of staghorn calculi without the creation of multiple percutaneous tracts.

MR imaging of urinary bladder cancer for T‐staging: A review and a pictorial essay of diffusion‐weighted imaging

Treatment decisions for bladder cancer patients are mainly based on the depth of bladder wall invasion by the tumor. In this article, we review the conventional MRI and exhibit a recently emerged diffusion‐weighted imaging (DWI) of urinary bladder cancer for T‐staging. We discuss limitations of conventional MRI, scanning protocols of DWI, normal pelvic findings on DWI, determination of T‐stage using DWI, and pitfalls of DWI. DWI provides high contrast between bladder cancer and background tissue because the cancer shows markedly high SI. DWI has high sensitivity for detecting the stalk seen in stage Ta or T1. An inflammatory change or fibrosis surrounding the tumor mimics the invasion of bladder cancer on T2‐weighted imaging or enhanced MRI and could lead to over‐staging, but DWI could differentiate them clearly because these benign changes do not show high SI on DWI. DWI is also useful for detecting ureteral, urethral, and prostatic extension by means of the urethra. DWI provides more accurate information on the extent of bladder cancer and contributes to determination of the treatment strategy. J. Magn. Reson. Imaging 2013;38:1299–1309.

Solitary Fibrous Tumor of the Peritoneum Found in the Prevesical Space

Solitary fibrous tumors (SFT) are well recognized in the pleura, but their rare occurrence at other sites has become appreciated only in recent years. We experienced a 68-year-old male patient who presented with frequency of urination and difficulty in voiding. Computed tomographic scan revealed a solid and cystic mass which measured 12 × 10 cm in the prevesical space. This tumor showed typical histopathologic features of SFT, and was immunostained positive for vimentin, CD34 and CD99. This is an extremely rare case of SFT arising from the parietal peritoneum found in the prevesical space.

GPX2 overexpression is involved in cell proliferation and prognosis of castration-resistant prostate cancer

There is a need for exploration of new therapeutic strategies that target distinct molecular mechanisms of castration-resistant prostate cancer (CRPC) because its emergence following androgen deprivation therapy is a major clinical problem. In this report, we investigated the role of glutathione peroxidase 2 (GPX2) in CRPC. GPX2 expression was analyzed in rat and human CRPC cells. Next, we determined the proliferation rate and level of reactive oxygen species (ROS) in GPX2-small interfering RNA (siRNA)-transfected CRPC cells. For in vivo analysis, siRNA-transfected cells were subcutaneously implanted into normal and castrated nude mice. Further, immunohistochemical and prognostic analyses of GPX2 were performed using human specimens. Silencing of GPX2 caused significant growth inhibition and increased intracellular ROS in both rat (PCai1) and human (PC3) CRPC cells. Flow cytometry and western blot analyses revealed that the decrease in proliferation rate of the GPX2-silenced cells was due to cyclin B1-dependent G2/M arrest. Furthermore, knockdown of Gpx2 inhibited tumor growth of PCai1 cells in castrated mice. Immunohistochemical analyses indicated that expression of GPX2 was significantly higher in residual cancer foci after neoadjuvant hormonal therapy than in hormone naive cancer foci. Moreover, patients with high GPX2 expression in biopsy specimen had significantly lower prostate-specific antigen recurrence-free survival and overall survival than those with no GPX2 expression. These findings suggest that GPX2 is a prognostic marker in CRPC and affects proliferation of prostate cancer under androgen depletion partially through protection against ROS signaling.

Colony-Stimulating Factor-1 Signaling Suppresses Renal Crystal Formation

We recently reported evidence suggesting that migrating macrophages (Mϕs) eliminate renal crystals in hyperoxaluric mice. Mϕs can be inflammatory (M1) or anti-inflammatory (M2), and colony-stimulating factor-1 (CSF-1) mediates polarization to the M2Mϕ phenotype. M2Mϕs promote renal tissue repair and regeneration, but it is not clear whether these cells are involved in suppressing renal crystal formation. We investigated the role of M2Mϕs in renal crystal formation during hyperoxaluria using CSF-1-deficient mice, which lack M2Mϕs. Compared with wild-type mice, CSF-1-deficient mice had significantly higher amounts of renal calcium oxalate crystal deposition. Treatment with recombinant human CSF-1 increased the expression of M2-related genes and markedly decreased the number of renal crystals in both CSF-1-deficient and wild-type mice. Flow cytometry of sorted renal Mϕs showed that CSF-1 deficiency resulted in a smaller population of CD11b(+)F4/80(+)CD163(+)CD206(hi) cells, which represent M2-like Mϕs. Additionally, transfusion of M2Mϕs into CSF-1-deficient mice suppressed renal crystal deposition. In vitro phagocytosis assays with calcium oxalate monohydrate crystals showed a higher rate of crystal phagocytosis by M2-polarized Mϕs than M1-polarized Mϕs or renal tubular cells. Gene array profiling showed that CSF-1 deficiency resulted in disordered M2- and stone-related gene expressions. Collectively, our results provide compelling evidence for a suppressive role of CSF-1 signaling in renal crystal formation.

Clinicopathologic significance of high signal intensity on diffusion-weighted MR imaging in the ureter, urethra, prostate and bone of patients with bladder cancer.

RATIONALE AND OBJECTIVES The aim of this study was to determine the clinicopathologic significance of high-intensity areas in the ureter, urethra, prostate, and bone incidentally found on diffusion-weighted magnetic resonance imaging (DWI) for the staging of bladder cancer. MATERIALS AND METHODS Axial and sagittal DWI and T2-weighted imaging of the pelvis were evaluated in 157 patients with bladder cancer. Two observers assessed T2-weighted imaging with DWI independently. The observers pointed out 67 areas showing abnormal high signal intensity on DWI in the ureter (n = 17), urethra (n = 8), prostate (n = 20), and bone (n = 22). Of the 67 high-intensity areas, 33 lesions were confirmed histopathologically (ureter, n = 10; urethra, n = 7; prostate, n = 16), and 22 bone lesions were diagnosed using T1-weighted imaging and follow-up computed tomography. Thus, 55 lesions were evaluable for correlation with DWI findings. RESULTS Of the 55 high-intensity areas, 28 (53%) were synchronous or metastatic urothelial cancer or invasion of urothelial cancer. The remaining 27 (47%) were a ureteral clot in one, a ureteral stone granuloma in one, prostatic cancer in six, granulomatous prostatitis in three, and normal red bone marrow in 16. CONCLUSIONS DWI is useful to comprehend the extent of bladder cancer and to detect incidentally coexisting diseases. Other imaging, endoscopic, and clinical findings would be useful to reduce false positivity.

N-acetyl-L-cysteine enhances chemotherapeutic effect on prostate cancer cells.

Abstract. Transcription factor nuclear factor κB (NF-κB) controls gene expression of a number of genes, including cytokines such as interleukin-6 (IL-6), granulocyte-macrophage (GM)-CSF, and interleukin-8 (IL-8). IL-6 is known to play important roles in the growth of prostate cancer cells, activation of androgen receptor, and prostate-specific protein expression. NF-κB is activated by extracellular signals such as proinflammatory cytokines, chemotherapeutic reagents, and radiation. Here we demonstrate that cisplatin (CDDP) and etoposide (VP-16) induce nuclear translocation of NF-κB in prostate cancer cell lines, followed by secretion of IL-6. We also demonstrated that the growth of hormone-independent prostate cancer cell lines can be inhibited by the anti-NF-κB reagent N-acetyl-L-cysteine (NAC). These observations indicate that NF-κB can be a target of new adjuvant therapy against hormone refractory prostate cancer.