Kenya Yamaguchi

Mature, Adipocyte Derived, Dedifferentiated Fat Cells Can Differentiate Into Smooth Muscle-Like Cells and Contribute to Bladder Tissue Regeneration

PURPOSE We recently reported that mature, adipocyte derived, dedifferentiated fat cells show high proliferative activity and multilineage differentiation potential. In the current study we investigated whether such cells could differentiate into a smooth muscle cell lineage and contribute to bladder tissue regeneration in a mouse bladder injury model. MATERIALS AND METHODS Human adipocyte derived dedifferentiated fat cells were cultured for 1 week under conditions favorable for smooth muscle cell differentiation and immunostained for alpha-smooth muscle actin. The expression of smooth muscle cell marker genes for differentiating dedifferentiated fat cells was measured by real-time reverse transcription-polymerase chain reaction. Green fluorescence protein labeled dedifferentiated fat cells were injected into cryo-injured bladder walls in mice. The ability of the fat cells to regenerate smooth muscle tissue was examined immunohistochemically 14 and 30 days after transplantation. RESULTS Immunohistochemical analysis revealed that more than 50% of the fat cells were successfully differentiated into alpha-smooth muscle actin positive cells under the optimum culture condition of a medium containing 5% fetal bovine serum and 5 ng/ml transforming growth factor-beta1. Real-time reverse transcription-polymerase chain reaction revealed increased expression of SM22alpha, alpha-smooth muscle actin and smooth muscle-myosin heavy chain in dedifferentiated fat cells during week 1 of differentiation culture. Cells expressing alpha-smooth muscle actin plus green fluorescence protein were observed at the bladder wall injection sites in mice 14 and 30 days after transplantation. Alpha-smooth muscle actin positive areas in injured bladder tissue in mice with fat cell injection were significantly larger than those in saline injected control mice. CONCLUSIONS These findings suggest that dedifferentiated fat cells can differentiate into smooth muscle cell lineages and contribute to the regeneration of bladder smooth muscle tissue.

Methylseleninic acid sensitizes prostate cancer cells to TRAIL-mediated apoptosis

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytotoxic agent that preferentially induces apoptosis in a variety of human cancer cells. Unfortunately, some tumor cells remain resistant to TRAIL. Therefore, agents that sensitize malignant cells to TRAIL-mediated cell death might be of particular importance for the development of novel antitumor therapeutic regimens. Recent studies establish a critical role of selenium in prostate cancer prevention in vitro and in vivo. Here, we demonstrate that concomitant administration of TRAIL and methylseleninic acid (MSA) produces synergistic effects on the induction of apoptosis in androgen-dependent LNCaP and androgen-independent DU-145 prostate cancer cells. MSA rapidly and specifically downregulates expression of the cellular FLICE inhibitory protein, a negative regulator of death receptor signaling. In addition, we demonstrate that the synergistic effects of MSA and TRAIL result from the activation of the mitochondrial pathway-mediated amplification loop. Addition of MSA effectively blocked TRAIL-mediated BAD phosphorylation at Ser112 and Ser136 in DU-145 cells and was accompanied by induction of the mitochondrial permeability transition and release of apoptogenic cytochrome c and Smac/DIABLO proteins from the mitochondria and into the cytosol. These results suggest that selenium-based dietary compounds may help to overcome resistance to TRAIL-mediated apoptosis in prostate cancer cells.

Tension‐free vaginal mesh procedure for pelvic organ prolapse: A single‐center experience of 310 cases with 1‐year follow up

Objective:  To prospectively evaluate the efficacy of a tension‐free vaginal mesh (TVM) procedure for pelvic organ prolapse (POP).

Transplantation of mature adipocyte-derived dedifferentiated fat (DFAT) cells improves urethral sphincter contractility in a rat model.

Objectives:  To examine the effects of mature adipocyte‐derived dedifferentiated fat (DFAT) cell transplantation on urethral tissue regeneration and sphincter function.

Characterization of ureteral lesions associated with impacted stones.

Background: Few studies have addressed the various types of ureteral lesions apparent in patients treated for ureteral stones, especially in those with impacted stones. Macroscopic and microscopic analyses of ureteral lesions associated with impacted stones were therefore undertaken.

Prospective Study of Estramustine Phosphate for Hormone Refractory Prostate Cancer Patients following Androgen Deprivation Therapy

Introduction: Estramustine phosphate (EMP) in combination with other cytotoxic agents has been widely used in clinical trials as an anti-tumor agent for the treatment of hormone-refractory prostate cancer (HRPC). However, few prospective studies have considered the efficacy of EMP monotherapy for HRPC patients following androgen-deprivation therapy (ADT), given the availability of methods to measure prostate-specific antigen (PSA) levels in the serum. We therefore initiated a prospective study to determine whether EMP is efficient for HRPC following ADT using changes in PSA levels as the major endpoint. Methods: After a diagnosis of anti-androgen withdrawal syndrome had been excluded, 34 patients with HRPC who showed an elevated serum PSA level in 3 or more sequential tests following ADT were treated orally with 560 mg/day of EMP. The clinical stage and the median PSA value for inclusion in the study were D2 and 25.9 (range 6.5–540.8) ng/ml, respectively. Treatment was continued until evidence of disease progression reappeared or until severe adverse effects appeared. Results: Of the 34 patients enrolled, 29 were evaluated, while the other 5 (15%) patients were discontinued due to severe gastrointestinal side effects. Seven of the 29 patients (24%) showed a decrease of 50% or greater in serum PSA levels from the initially elevated values, with the median duration of PSA response being 8.0 (range 2.2–18.8) months. Baseline PSA, hemoglobin, alkaline phosphatase, lactate dehydrogenase, performance status, and length of time of initial hormonal treatment did not correlate with the PSA response. With a median follow-up time of 20.0 (range 3.2–45.6) months, the cancer-specific survival rate at 2 years was 83% in the PSA responders and 44% in the non-responders. The PSA response was correlated with cancer-specific survival (p = 0.029). Conclusions: Following ADT one quarter of HRPC patients responded to EMP, with more than 50% of patients showing a decrease in PSA levels and an enhanced survival rate.

Intravesical Recurrence after Surgical Management of Urothelial Carcinoma of the Upper Urinary Tract

Objectives: To elucidate clinicopathological risk factors for intravesical recurrence (IVR) in patients undergoing nephroureterectomy for upper urinary tract urothelial carcinoma (UUT-UC). Methods: We identified a study population of 151 consecutive patients without previous or concurrent bladder cancer who underwent nephroureterectomy for UUT-UC. IVR was assessed in relation to tumor location, size, and multifocality, operation modality and time, stage, grade, lymphovascular invasion, regional lymph node metastasis, preoperative urinary cytology, and perioperative chemotherapy. The median follow-up time was 24 months. Results: Of 151 patients, 51 (34%) developed IVR after nephroureterectomy, and 50 (98%) of the patients presented with IVR within 2 years. Tumor multifocality and site (located in ureter) were determined as risk factors for IVR by univariate analysis. In a multivariate analysis, only tumor multifocality (relative risk: 4.024, p = 0.001) was an independent predictor of IVR. Ten-year cancer-specific survival rates for the patients with and without IVR were 68 and 52%, respectively (p = 0.06). Conclusions: Tumor multifocality is a significant risk factor in developing IVR after surgery for UUT-UC. These results indicate that despite most IVR occurring within 2 years of treatment, it is necessary to follow such patients more closely using cystoscopy. However, IVR is unlikely to indicate a poorer prognosis.

Silodosin versus naftopidil for the treatment of benign prostatic hyperplasia: A multicenter randomized trial

This was a multicenter randomized trial to investigate the clinical efficacy and the impact on sexual function of alpha‐1A selective silodosin and alpha‐1D selective naftopidil for treatment of benign prostatic hyperplasia. A total of 97 patients with lower urinary tract symptoms/benign prostatic hyperplasia who had an International Prostate Symptom Score of 8 or more were randomly assigned to receive silodosin (8 mg/day, n = 53) or naftopidil (75 mg/day, n = 44). Before and 4, 8 and 12 weeks after treatment, International Prostate Symptom Score and its quality of life score were used to assess lower urinary tract symptoms. Also, International Index of Erectile Function‐5, and an original questionnaire were used to evaluate erectile function and ejaculation for sexually active patients, respectively. The silodosin group showed advantages in terms of voiding symptoms and quality of life of International Prostate Symptom Score when compared with the naftopidil group. Both silodosin and naftopidil showed no significant effect on International Index of Erectile Function‐5. A total of 23 sexually active patients in the silodosin group experienced more ejaculatory impairment than 21 patients in the naftopidil group, with a decrease of ejaculation volume (87% vs 40%, P = 0.003), prolonged time to ejaculation (56% vs 33%, P = 0.027) and decrease of orgasm (50% vs 39%, P = 0.027). These results suggest that alpha‐1A selective blockers are more effective for voiding symptoms, whereas alpha‐1D selective blockers offer a minor degree of ejaculatory dysfunction.

How do symptoms have an impact on the prognosis of renal cell carcinoma

Aim:  Symptomatic renal cell carcinoma (RCC) is well known to have a characteristic behavior. We therefore evaluated the impact of systemic symptoms on the prognosis of RCC.

Immunohistochemical and Ultrastructural Features of Neuroendocrine Differentiated Carcinomas of the Prostate: An Immunoelectron Microscopic Study

The purpose of this study was to further define the immunohistochemical and ultrastructural characteristics of neuroendocrine (NE) differentiated prostatic carcinomas. Seventy-seven specimens were obtained from prostatic carcinoma tumors during prostatectomy, transurethral resection of prostate or biopsy in 77 prostate cancer patients, and analyzed by immunohistochemical staining for chromogranin A (CgA). Nine of these tumors were also studied by elctron microscopy and 4 were examined by pre-embedding immunoelectron microscopy. CgA-stained cells were detected in 36 tumors (47%). Clinically advanced tumors or tumors with higher histological grades were associated with increased NE differentiation. Three of the tumors studied by electron microscopy contained cells showing unequivocal NE differentiation revealed by the presence of neurosecretory granules, while the poorly NE-differentiated malignant cells contained pleomorphic granules, which were lysosomal-like rather than NE-type granules. Immunoelectron microscopy demonstrated the presence of CgA immunoreactivity on the pleomorphic granules in the poorly differentiated malignant glands. This study suggests that NE-differentiated malignant cells in prostate cancer tissues may induce aggressive behavior in adjacent proliferating neoplastic cells via a paracrine mechanism.