Yuta Yamada

Expression of androgen and estrogen signaling components and stem cell markers to predict cancer progression and cancer-specific survival in patients with metastatic prostate cancer

Purpose: Genes of androgen and estrogen signaling cells and stem cell–like cells play crucial roles in prostate cancer. This study aimed to predict clinical failure by identifying these prostate cancer-related genes. Experimental Design: We developed models to predict clinical failure using biopsy samples from a training set of 46 and an independent validation set of 30 patients with treatment-naïve prostate cancer with bone metastasis. Cancerous and stromal tissues were separately collected by laser-captured microdissection. We analyzed the association between clinical failure and mRNA expression of the following genes androgen receptor (AR) and its related genes (APP, FOX family, TRIM 36, Oct1, and ACSL 3), stem cell–like molecules (Klf4, c-Myc, Oct 3/4, and Sox2), estrogen receptor (ER), Her2, PSA, and CRP. Results: Logistic analyses to predict prostate-specific antigen (PSA) recurrence showed an area under the curve (AUC) of 1.0 in both sets for Sox2, Her2, and CRP expression in cancer cells, AR and ERα expression in stromal cells, and clinical parameters. We identified 10 prognostic factors for cancer-specific survival (CSS): Oct1, TRIM36, Sox2, and c-Myc expression in cancer cells; AR, Klf4, and ERα expression in stromal cells; and PSA, Gleason score, and extent of disease. On the basis of these factors, patients were divided into favorable-, intermediate-, and poor-risk groups according to the number of factors present. Five-year CSS rates for the 3 groups were 90%, 32%, and 12% in the training set and 75%, 48%, and 0% in the validation set, respectively. Conclusions: Expression levels of androgen- and estrogen signaling components and stem cell markers are powerful prognostic tools. Clin Cancer Res; 20(17); 4625–35. ©2014 AACR.

Tubulovillous adenoma developing after urinary reconstruction using ileal segments

Abstract  A case of tubulovillous adenoma arising in an augmented bladder is described. Ureteroileal substitution and ileocystoplasty was performed when the patient was 18 years old. She noticed gross hematuria 44 years after the surgery. Cystoscopy revealed a non‐papillary multiple tumor at the site of ileovesical anastomosis and transurethral resection biopsy was performed. Histopathological examination revealed a tubulovillous adenoma. A tubulovillous adenoma developing at the augmented bladder is rare. To our knowledge, this is the second case in which a tubulovillous adenoma developed in an augmented bladder.

The effect of combined androgen blockade on bone turnover and bone mineral density in men with prostate cancer.

SummaryOur study and previous reports suggest that castration results in increased bone turnover and lowered BMD and that these changes might be attenuated by anti-androgens, such as BL and EMP.IntroductionRecent studies have shown that castration for PC decreases bone mineral density (BMD), while estrogen therapy or bicalutamide (BL) monotherapy maintains BMD. However, the effect of combined androgen blockade (CAB) on bone turnover is not well studied.MethodsA total of 204 men were evaluated in the study (control group: n = 56, castration group: n = 102, ‘CAB with BL’ group: n = 22, ‘CAB with estramustine phosphate (EMP)’ group: n = 24). We measured steroid hormone levels, BMD (measured at one-third distal radius), bone turnover markers (levels of urinary N-telopeptide cross links of type 1 collagen (u-NTx) and deoxypyridinoline (u-DPD), serum concentrations of osteocalcin (OC)) in order to assess differences between groups.ResultsThe BMD % Z score of the castration group was significantly lower than that of the control group or the ‘CAB with EMP’ group (90.6% vs. 95.5%, 98.6%; p < 0.042, p < 0.044, respectively). Levels of u-NTx, u-DPD, OC of the castration group were the highest followed by the control group, then the ‘CAB with BL’ group and the ‘CAB with EMP’ group.ConclusionsOur study and previous reports suggests that castration results in increased bone turnover and lowered BMD and that these changes might be attenuated by anti-androgens, such as BL and EMP.

A novel prognostic factor TRIM44 promotes cell proliferation and migration, and inhibits apoptosis in testicular germ cell tumor

Tripartite motif 44 (TRIM44) is one of the TRIM family proteins that are involved in ubiquitination and degradation of target proteins by modulating E3 ubiquitin ligases. TRIM44 overexpression has been observed in various cancers. However, its association with testicular germ cell tumor (TGCT) is unknown. We aimed to investigate the clinical significance of TRIM44 and its function in TGCT. High expression of TRIM44 was significantly associated with α feto‐protein levels, clinical stage, nonseminomatous germ cell tumor (NSGCT), and cancer‐specific survival (P = 0.0009, P = 0.0035, P = 0.0004, and P = 0.0140, respectively). Multivariate analysis showed that positive TRIM44 IR was an independent predictor of cancer‐specific mortality (P = 0.046). Gain‐of‐function study revealed that overexpression of TRIM44 promoted cell proliferation and migration of NTERA2 and NEC8 cells. Knockdown of TRIM44 using siRNA promoted apoptosis and repressed cell proliferation and migration in these cells. Microarray analysis of NTERA2 cells revealed that tumor suppressor genes such as CADM1, CDK19, and PRKACB were upregulated in TRIM44‐knockdown cells compared to control cells. In contrast, oncogenic genes including C3AR1, ST3GAL5, and NT5E were downregulated in those cells. These results suggest that high expression of TRIM44 is associated with poor prognosis and that TRIM44 plays significant role in cell proliferation, migration, and anti‐apoptosis in TGCT.

Nocturia in men is a chaotic condition dominated by nocturnal polyuria.

To characterize nocturia in men based on frequency volume chart data and symptom profiles assessed using the Core Lower Urinary Tract Symptom Score and Athens Insomnia Scale questionnaires.

Lymphoepithelioma-like carcinoma of the renal pelvis

Abstract:  Lymphoepithelial‐like carcinoma of the renal pelvis is an extremely rare entity. Only four cases involving the renal pelvis have been previously reported. We report the fifth case of lymphoepithelioma‐like carcinoma of the renal pelvis.

Dysregulation of spliceosome gene expression in advanced prostate cancer by RNA-binding protein PSF

Significance Elevated downstream signals of androgen receptor (AR) and its variants are important for prostate cancer progression. We show that an RNA-binding transcriptional and splicing factor, splicing factor proline and glutamine-rich (PSF/SFPQ), predicts worse prognosis of prostate cancer patients. Inhibition of PSF expression repressed treatment-resistant prostate tumor growth in our animal model. Our global analysis of PSF-binding RNAs revealed that PSF enhances AR-regulated genes and noncoding RNAs associated with prostate cancer progression. Interestingly, various splicing factors, which are primary targets of PSF, are upregulated in metastatic prostate tumors. These enhanced factors form complexes with PSF to promote AR expression and splicing. Our findings suggest a role of RNA-binding protein for AR activation for prostate cancer progression. Developing therapeutic approaches are necessary for treating hormone-refractory prostate cancer. Activation of androgen receptor (AR) and its variants’ expression along with the downstream signals are mostly important for disease progression. However, the mechanism for marked increases of AR signals and its expression is still unclear. Here, we revealed that various spliceosome genes are aberrantly induced by RNA-binding protein PSF, leading to enhancement of the splicing activities for AR expression. Our high-speed sequence analyses identified global PSF-binding transcripts. PSF was shown to stabilize and activate key long noncoding RNAs and AR-regulated gene expressions in prostate cancer cells. Interestingly, mRNAs of spliceosome-related genes are putative primary targets of PSF. Their gene expressions are up-regulated by PSF in hormone-refractory prostate cancer. Moreover, PSF coordinated these spliceosome proteins to form a complex to promote AR splicing and expression. Thus, targeting PSF and its related pathways implicates the therapeutic possibility for hormone-refractory prostate cancer.

Validation of an educational program balancing surgeon training and surgical quality control during robot-assisted radical prostatectomy

To establish a mentoring program that allows novice surgeons to use robotics while maintaining surgical quality during robot‐assisted radical prostatectomy.

Metachronous testicular tumor developing eight years after retroperitoneal extragonadal germ cell tumor

Abstract:  A 30 year‐old man was admitted to our hospital with a chief complaint of left flank pain. Computed tomography revealed a retroperitoneal tumor. Levels of lactic dehydrogenase, human β‐chorionic gonadotropin, α‐fetoprotein, DUPAN‐2 and carbohydrate antigen 19–9 were elevated. No abnormal findings were present according to palpation and ultrasonography of the testes. The patient was diagnosed as having a retroperitoneal extragonadal germ cell tumor (EGCT) considering the elevated markers. Resection of the tumor, two cycles of neoadjuvant and one cycle of adjuvant chemotherapy (cisplatin and etoposide) were performed. The surgical specimen showed total necrotic tissue. Eight years later, the patient noticed an enlargement of his left testicle. The tumor felt elastic and firm on his left testis. Neither distant metastasis nor lymph node metastasis was present according to computed tomography. Left high orchiectomy was performed and histology revealed seminoma. Twenty‐three cases have been reported previously about metachronous testicular tumor developing after retroperitoneal EGCT. We report the 24th case.

Clinical significance of amyloid precursor protein in patients with testicular germ cell tumor.

Introduction. The biological role of amyloid precursor protein (APP) is not well understood, especially in testicular germ cell tumors (TGCTs). Therefore, we aimed to investigate the immunoreactivity (IR) and expression of APP in TGCTs and evaluated its clinical relevance. Materials and Methods. We performed an analysis of immunohistochemistry and mRNA expression of APP in 64 testicular specimens and 21 snap-frozen samples obtained from 1985 to 2004. We then evaluated the association between APP expression and clinicopathological status in TGCTs. Results. Positive APP IR was observed in 9.8% (4/41) of seminomatous germ cell tumors (SGCTs) and 39.1% (9/23) of nonseminomatous germ cell tumors (NGCTs). NGCTs showed significantly more cases of positive IR (P = 0.00870) and a higher mRNA expression level compared with those of SGCTs (P = 0.0140). Positive APP IR was also significantly associated with α-fetoprotein (αFP) elevation (P = 0.00870) and venous invasion (P = 0.0414). Conclusion. We observed an elevated APP expression in TGCTs, especially in NGCTs. APP may be associated with a more aggressive cancer in TGCTs.