Koji Mita

Expression of the insulin-like growth factor system and cancer progression in hormone-treated prostate cancer patients

Abstract Background : The insulin‐like growth factor (IGF) system, which is composed of two ligands (IGF‐I and IGF‐II), two receptors (IGFR‐I and IGFR‐II) and six binding proteins (IGFBP‐1 to ‐6), plays an important role in cell biology. To identify the main components in the IGF system that contribute to human prostate cancer progression after hormone therapy, mRNA expression of the IGF system in human prostate cancer tissue was systematically examined.

Reg IV is an independent prognostic factor for relapse in patients with clinically localized prostate cancer

Regenerating islet‐derived family, member 4 (REG4, which encodes Reg IV) is a candidate marker for cancer and inflammatory bowel disease. We investigated the potential prognostic role of Reg IV immunostaining in clinically localized prostate cancer (PCa) after radical prostatectomy. Immunohistochemical staining of Reg IV was performed in 98 clinically localized PCa tumors obtained during curative radical prostatectomy. Intestinal and neuroendocrine differentiation was investigated by MUC2 and chromogranin A immunostaining, respectively. The prognostic significance of immunohistochemical staining for these factors on prostate‐specific antigen (PSA)‐associated recurrence was assessed by Kaplan–Meier analysis and a Cox regression model. Phosphorylation of the epidermal growth factor receptor (EGFR) by Reg IV was analyzed by Western blot. In total, 14 (14%) of the 98 PCa cases were positive for Reg IV staining. Reg IV positivity was observed frequently in association with MUC2 (P = 0.0182) and chromogranin A positivity (P = 0.0012). Univariate analysis revealed that Reg IV staining (P = 0.0004), chromogranin A staining (P = 0.0494), Gleason score (P < 0.0001) and preoperative PSA concentration (P = 0.0167) were significant prognostic factors for relapse‐free survival. Multivariate analysis indicated that Reg IV staining (P = 0.0312), Gleason score (P = 0.0014) and preoperative PSA concentration (P = 0.0357) were independent predictors of relapse‐free survival. In the LNCaP cell line, EGFR phosphorylation was induced by the addition of Reg IV‐conditioned medium. These results suggest that Reg IV expression is an independent prognostic indicator of relapse after radical prostatectomy. (Cancer Sci 2008; 99: 1570–1577)

DNA methylation of the RIZ1 gene is associated with nuclear accumulation of p53 in prostate cancer

The retinoblastoma protein‐interacting zinc finger gene, RIZ1, is thought to be a tumor suppressor gene. RIZ1 is inactivated by mutation, deletion and DNA methylation in several human cancers. In the present study, the relationship between DNA methylation of RIZ1 and mutation of p53 was investigated in prostate cancer (PCa). In total, 47 cases of node‐negative PCa (stages I–III) were analyzed. DNA methylation of the RIZ1 gene was detected in 20 (42.6%) of the 47 PCa tissues by methylation‐specific polymerase chain reaction. DNA methylation of the RIZ1 gene was not associated with clinicopathological features. DNA methylation of RIZ1 tended to be present more frequently in PCa specimens with a high Gleason score (16/30, 53.3%) than in those with a low Gleason score (4/17, 23.5%); however, this tendency was not statistically significant (P = 0.0675). Nuclear accumulation of p53 was observed in four (8.5%) of 47 PCa specimens by immunostaining. All four PCa specimens with nuclear accumulation of p53 were stage III disease and showed DNA methylation of RIZ1. However, of the remaining 43 cancers without nuclear accumulation of p53, DNA methylation of RIZ1 was observed in only 16 (37.2%) specimens (P = 0.0272). Of the three PCa cell lines, only the PC3 cell line showed loss of RIZ1 mRNA due to DNA methylation, and this loss was rectified by treatment with a demethylating agent, 5‐Aza‐2′‐deoxycytidine. These results suggest that transcriptional inactivation of RIZ1 by aberrant DNA methylation may contribute to prostate carcinogenesis. Genetic alterations are likely associated with epigenetic alterations in PCa. (Cancer Sci 2007; 98: 32–36)

Lower urinary tract symptoms and risk of prostate cancer in Japanese men

Aim: Our aim was to investigate whether or not men with lower urinary tract symptoms are at increased risk of prostate cancer.

Impact of radical perineal prostatectomy on urinary continence and quality of life: A longitudinal study of Japanese patients

Aim: We used self‐completed questionnaires to obtain a longitudinal assessment of urinary continence and urinary, bowel, and sexual domain‐related quality of life (QOL) in Japanese patients undergoing radical perineal prostatectomy (RPP).

Prevalence of painful bladder syndrome (PBS) symptoms in adult women in the general population in Japan

The aim of this study was to clarify the prevalence of painful bladder syndrome (PBS) symptoms in adult women in the general population in Japan.

Primary Mucosa-Associated Lymphoid Tissue Lymphoma in the Renal Pelvis

A primary low-grade lymphoma of mucosa-associated lymphoid tissue arising from the renal pelvis is extremely rare. We present a 77-year-old man with this disease which was difficult to diagnose preoperatively.

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).

Decrease of Renal Function due to Warm Ischemia after Laparoscopic Partial Nephrectomy: Evaluation Using 99mTc-DMSA Renal Scintigraphy

Introduction: The purpose of this study is, using technetium-99m-dimercaptosuccinic acid (99mTc-DMSA), to evaluate the decrease of renal function caused by warm ischemia. Patients and Methods: The 99mTc-DMSA scan was performed before and 1, 3 and 6 months after the operation for 19 consecutive patients. The patients were divided into three groups by warm ischemic time (group A: ≤40 min, B: >40 min ∩ ≤60 min, C: >60 min). Renal function of the unresected part was defined as the uptake to unresected part relative to the uptake to the contralateral kidney. The reduction of renal function was expressed as a ratio of the function after the surgery divided by function before the surgery and was compared between the three groups. Results: The reduction in group C after 1 and 3 months tended to be greater than that in group A or B, although not reaching statistical significance (one-way ANOVA test, 1 month: p = 0.15 and 3 months: p = 0.13). There was a significant difference in reduction of renal function between the three groups after 6 months (one-way ANOVA test, p = 0.02). The Scheffé test showed a statistical significance between groups A and C (p < 0.05). Conclusion: Renal function calculated by 99mTc-DMSA shows that prolonged ischemic time causes significant damage to the kidney.

Renal Artery Pseudoaneurysm Occurring after Laparoscopic Partial Nephrectomy

Renal artery pseudoaneurysm (RAP) is rare, and has been reported after renal biopsy and percutaneous renal surgery. We report a case of RAP after laparoscopic partial nephrectomy for renal cell carcinoma.