Refractory fistula of bladder repaired with transurethral cystoscopic injection of N-butyl-2-cyanoacrylate.

INTRODUCTION: Refractory fistulas of the bladder are not rare, but they can rarely be closed naturally. Bladder fistulas can be treated in various ways. We report the case of an old woman who had a refractory fistula of the bladder that was able to be repaired with transurethral cystoscopic injection of N-butyl-2-cyanoacrylate. CASE PRESENTATION: For decades after being treated for cervical cancer in 1970s, the woman frequently suffered from fevers. A computed tomography scan showed pelvic abscess at the left side of her bladder, and cystography showed urine leakage at the wall. Thus, we diagnosed her with a pelvic abscess due to a bladder fistula after radiation. Then, we treated her with drainage, antibiotic agents, and N-butyl-2-cyanoacrylate. After that, she no longer had fevers, and cystography showed no leakage of urine. CONCLUSION: This result indicates transurethral cystoscopic injection of N-butyl-2-cyanoacrylate may treat bladder fistulas safely, minimally invasively, and quickly.

Case of renal mucinous tubular and spindle cell carcinoma with high nuclear grade.

INTRODUCTION: Renal mucinous tubular and spindle cell carcinoma is a rare subtype of renal cell carcinoma newly added to the World Health Organization classification in 2004. Although it has been considered as a tumor with good prognosis, aggressive cases have recently been reported. CASE PRESENTATION: A 52-year-old man was diagnosed as having left renal cell carcinoma. Open radical left nephrectomy and left-sided pelvic lymph nodes dissection were performed. Pathological diagnosis revealed a renal mucinous tubular and spindle cell carcinoma with high nuclear grade and extra-regional lymph nodes metastasis classified as pT3aN0M1. After nephrectomy, metastasis at second lumbar vertebra and lymph nodes recurrence were occurred. CONCLUSION: This tumor with high nuclear grade may be potentially aggressive and carries a poor prognosis.

Pneumatosis cystoides intestinalis linked to sunitinib treatment for renal cell carcinoma.

INTRODUCTION: Pneumatosis cystoides intestinalis is a rare condition characterized by air-filled cysts within intestinal walls. It can be caused by various factors. We report a case of pneumatosis cystoides intestinalis linked to sunitinib treatment for renal cell carcinoma. CASE PRESENTATION: A 67-year-old female with advanced renal cell carcinoma who had been treated with sunitinib visited our hospital complaining of abdominal pain. Computed tomography scans showed diffuse air-filled cystic formation of intestine. We treated with conservative therapy, and she recovered. However, although air-filled cysts disappeared in the images, intraoperative findings in the resection of a recurrent paracaval lymph node showed a thinning of the intestine. CONCLUSION: It is necessary to consider pneumatosis cystoides intestinalis when a patient using a tyrosine kinase inhibitor complains of abdominal symptoms. It should also be noted that the effect of pneumatosis cystoides intestinalis may remain even if pneumatosis disappears from the image on tomography scans.

[LAPAROSCOPIC RADICAL PROSTATECTOMY OF 926 PATIENTS AT THE HIROSHIMA ENDOUROLOGICAL ASSOCIATION].

(Objective) The aim of this study is to investigate the treatment outcome of laparoscopic radical prostatectomy (LRP). (Patients and methods) The study cohort consisted of 926 hormone-naïve patients with localized prostate cancer who underwent LRP at the Hiroshima Endourological Association from January 2007 to December 2016. (Results) The mean age was 69.4 years, the mean initial PSA was 9.1 ng/ml, and the mean follow-up period was 40.3 months. The D'Amico Risk Classification was Low: 232 cases, Intermediate: 344 cases, and High: 350 cases. Nerve preservation was performed bilaterally for 138 patients and unilaterally for 181 patients. The mean operative time was 181.0 minutes and the mean estimated blood loss was 360.7 ml. As the number of experienced cases increased, the operative time was significantly shorter and the estimated blood loss was significantly decreased. According to Clavien-Dindo classification, the ratio of perioperative complication degree IIIa or above was 4.0% (37 cases). The pathological results were Gleason score (GS) ≤6: 174 cases, GS7: 514 cases, GS ≥8: 232 cases, pT2≥: 704 cases, pT3a: 172 cases, pT3b: 47 cases, pT4: 3 cases, pN0: 917 cases, and pN1: 9 cases. Positive surgical margins were found in 278 cases (30.0%). The biochemical recurrence-free survival rate at 5 years was 78.1%. In multivariate analysis, age (≥70 yrs), initial PSA (≥10 ng/ml), biopsy GS (GS ≥8), cancer positive core ratio at biopsy (≥30%), pT (pT≥3), pathological GS (GS≥8), positive surgical margin and total number of patients in the facility were predictive factors of postoperative biochemical PSA recurrence. Younger age and nerve preservation were found to be predictive factors for the early recovery of urinary continence after surgery, with 88% regaining urinary continence at 12 months after surgery. (Conclusion) This study revealed the clinical outcome and appropriate candidates for LRP in Japanese patients.

Clinicopathological significance of RCAN2 production in gastric carcinoma.

AIMS: Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. Genes expressed only in cancer tissue may be useful biomarkers for cancer diagnosis and therapeutics. The aims of the present study were to analyse regulator of calcineurin 2 (RCAN2) in a large number of GCs, and to investigate how these expression patterns correlate with clinicopathological parameters and various markers. METHODS AND RESULTS: An immunohistochemical analysis of RCAN2 in 207 GC tissue samples showed that 110 (53%) GCs were positive for RCAN2. RCAN2-positive GCs were more advanced in terms of TNM classification and tumour stage than RCAN2-negative GCs. Furthermore, RCAN2 was an independent prognostic classifier for GC patients. The cell growth and invasiveness of RCAN2 small interfering RNA (siRNA)-transfected GC cell lines were less than those of the negative control siRNA-transfected cell lines, whereas those of RCAN2-transfected cells were significantly increased as compared with those of empty vector-transfected cells. RCAN2 siRNA inhibits the phosphorylation of AKT and p44/p42 (ERK1/2). RCAN2 was colocalised with EGFR, nuclear ß-catenin, MMP7, laminin-γ2, VEGF-A, and VEGF-C. CONCLUSION: These results suggest that RCAN2 is involved in tumour progression and is an independent prognostic classifier in patients with GC.

Longitudinal analysis of laparoendoscopic single-site adrenalectomy and conventional laparoscopic adrenalectomy regarding patient-reported satisfaction and cosmesis outcomes.

BACKGROUND/OBJECTIVE: To compare longitudinal patient-reported cosmesis of laparoendoscopic single-site adrenalectomy (LESS-A) to that of conventional laparoscopic adrenalectomy (CLA). METHODS: A total of 23, 15, and 9 patients underwent transumbilical LESS-A (TU-LESS), subcostal LESS-A (SC-LESS), and CLA, respectively. A questionnaire was administered asking the patient to assess wound pain (0: not painful to 10: very painful), satisfaction (0: not satisfied to 10: very satisfied), and cosmesis (0: very ugly to 10: very beautiful) on the basis of a visual analogue scale. We mailed questionnaires to all patients who received LESS-A and CLA at postoperative 1, 3, 6, 9, and 12 months. RESULTS: No significant differences were observed in the pain scores between TU-LESS, SC-LESS, and CLA at every time point. In the CLA group, the cosmesis and satisfaction scores were significantly lower at postoperative 3 months (p = 0.0033, 0.0130). There were no significant inter-group differences in the cosmesis score between the three groups after postoperative 6 months. However, the satisfaction score of SC-LESS decreased after postoperative 3 months and was significantly lower at postoperative 9 and 12 months (p = 0.0333, 0.0160). The difference between the satisfaction scores of each procedure gradually increased after postoperative 6 months. CONCLUSION: This study is the first comprehensive longitudinal analysis of patient-reported satisfaction and cosmesis outcomes between LESS-A and CLA. The resulting data provide important insights into the improvement in satisfaction in patients who underwent TU-LESS. These findings can facilitate the treatment decision-making process for patients who are considering laparoscopic adrenalectomy.

Anastomosing haemangioma with fatty changes in the perirenal space: a lesion mimicking liposarcoma.

Anastomosing haemangioma is a rare subtype of capillary haemangioma. Pathologically, anastomosing haemangioma presents with anastomosing sinusoidal capillary-sized vessels in an architecture reminiscent of the splenic parenchyma. Its anastomosing architecture pathologically can lead to concern for angiosarcoma. Many cases of anastomosing haemangioma, which often occurred in the retroperitoneum, were well circumscribed, hyperdense on plain CT, revealed avid contrast enhancement and some of them exhibited fatty changes. In cases of tumours with fat of retroperitoneal occurrence, images frequently do not allow for easy differentiation from liposarcoma. Although anastomosing haemangioma with fatty changes and liposarcoma can be difficult to differentiate, no previous report has addressed this diagnostic difficulty. We have encountered a case of anastomosing haemangioma with fatty changes occurring in the perirenal space that was difficult to differentiate from liposarcoma. With retroperitoneal tumours accompanied by fatty changes and including a strongly enhanced area, the possibility of anastomosing haemangioma-which is a benign tumour-may also be considered. In such cases, biopsy is an effective means of diagnosis.

Usefulness of personalized three-dimensional printed model on the satisfaction of preoperative education for patients undergoing robot-assisted partial nephrectomy and their families.

OBJECTIVE: To clarify the usefulness of a personalized three-dimensional (3D) printed model of the kidney for preoperative education among patients who underwent robot-assisted partial nephrectomy (RAPN). METHODS: Twenty-nine cases of patients who planned to undergo RAPN and 19 of their families participated in this study. A three-dimensional model consisting of the kidney, tumors, ureter, inferior vena cava, and abdominal aorta in each case was generated using a Z Printer 450 based on the findings of preoperative enhanced CT. After preoperative education using enhanced CT and a 3D-printed model, two anatomy-related issues, three tumor-related issues, and two surgical procedure-related issues were evaluated using a visual analogue scale. RESULTS: The median age of all participants was 64 years old. The rate in male patients was significantly higher than that in families. In all three issues in patients and in two of three issues in families, scores in the 3D model were significantly higher than those in CT. In all issues in CT, scores of patients 64 years old or younger were higher than those of patients 65 years old or higher. On the other hand, no significant difference was found in the 3D model for scores on two of three issues regardless of the age of participants. CONCLUSION: Our data indicate that the personalized 3D printed model of the kidney is useful for preoperative education among patients and their families who underwent RAPN, especially in elderly people.

Normalization of C-reactive protein levels following cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors is associated with improved overall survival.

INTRODUCTION AND OBJECTIVES: Pretreated C-reactive protein (CRP) has been suggested as one of the most important prognostic factors for metastatic renal cell carcinoma (mRCC). The aim of this study was to investigate the prognostic impact of the change in CRP level before and after cytoreductive nephrectomy (CN) in patients with mRCC treated with tyrosine kinase inhibitor. MATERIALS AND METHODS: The CRP in 60 patients undergoing molecular targeted therapy for mRCC was measured before and after CN. The cutoff value of CRP was determined to be 0.5mg/dl.; thus, all patients were classified into lower CRP groups and higher ones according to their CRP before CN. The higher CRP group was further classified into 2 groups based on the kinetics after CN, "normalized CRP group" and "nonnormalized CRP group," respectively. The overall survival (OS) of these groups was compared. RESULTS: The median of the observation period was 21.6 months. The OS of patients in the lower CRP, normalized CRP, and nonnormalized CRP groups were 28.6, 23.1, and 12.3 months, respectively (nonnormalized CRP group vs. others, P<0.0001). Multivariate analysis revealed that the postoperative CRP level (≥0.5mg/dl) (hazard ratio = 0.218; 95% CI: 0.091-0.522; P = 0.0006) was an independent predictive factor of OS. CONCLUSION: The CRP level after CN can be a predictive factor for OS in patients with mRCC treated with tyrosine kinase inhibitor.

The effect of kinetics of C-reactive protein in the prediction of overall survival in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitor.

INTRODUCTION AND OBJECTIVES: The aim of this study was to investigate the effect of kinetics of C-reactive protein (CRP) in the prediction of overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) treated with a tyrosine kinase inhibitor. MATERIALS AND METHODS: The CRP in 118 cases of molecular-targeted therapy for mRCC was measured before starting the prescription of the first-line targeted agents and at the first time a CT scan was conducted during treatments. All cases were classified into higher-CRP groups and lower ones according to their data at the time of starting treatments. A higher-CRP group was further classified into 2 subgroups based on the kinetics after first-line targeted therapy: "decreased-CRP subgroup" and "nondecreased CRP subgroup." RESULTS: The median of the observation period was 23.4 months. The OS in cases with CRP higher than 0.5mg/dl was significantly worse than those in other cases (P<0.0001). Multivariate analysis revealed that the pretreated CRP (hazard ratio = 2.093; 95% CI: 1.176-3.858; P = 0.0179) was an independent predictive factor of OS. In the higher-CRP group, the OS for the decreased-CRP subgroup (1 year, 85.0%) was significantly better than those for the nondecreased CRP subgroup (1 year, 37.2%, P<0.0001). Multivariate analyses in the higher-CRP group revealed that the decrease in the CRP was an independent predictive factor for OS (hazard ratio = 0.176; 95% CI: 0.064-0.488; P = 0.0008). CONCLUSION: A decrease in CRP as well as pretreatment CRP can be a predictive factor for OS in patients with mRCC treated with a tyrosine kinase inhibitor. Cases with mRCC could be stratified into 3 groups with different prognoses using the pretreated CRP and its changes.

Combination therapy using molecular-targeted drugs modulates tumor microenvironment and impairs tumor growth in renal cell carcinoma.

Tumor growth and metastasis are determined not by cancer cells alone but also by a variety of stromal cells, various populations of which overexpress platelet-derived growth factor receptors (PDGF-Rs). In addition, activation of PI3K-AKT-mammalian target of rapamycin (mTOR) signaling is frequently observed in many cancer types as well. mTOR comprises a serine/threonine kinase that increases the production of proteins that stimulate key cellular processes such as cell growth and proliferation, cell metabolism, and angiogenesis. In this study, we investigated the impact of molecular-targeting agents including PDGF-R and mTOR inhibitors on the tumor stroma of human kidney cancer and examined the efficacy of combination therapy with these agents against this disease. Treatment with sunitinib did not suppress tumor growth, but significantly decreased stromal reactivity, microvessel density, and pericyte coverage of tumor microvessels in an orthotopic mouse model. In contrast, treatment with everolimus decreased tumor growth and microvessel density but not stromal reactivity. However, sunitinib and everolimus in combination reduced both the growth rate and stromal reaction. These findings suggest that target molecule-based inhibition of the cancer-stromal cell interaction appears promising as an effective antitumor therapy.

A comparison of clinicopathological features and prognosis in prostate cancer between atomic bomb survivors and control patients.

An atomic bomb (A-bomb) was dropped on Hiroshima on 6th August 1945. Although numerous studies have investigated cancer incidence and mortality among A-bomb survivors, only a small number have addressed urological cancer in these survivors. The aim of the present study was to investigate the clinicopathological features of prostate cancer (PCa) in A-bomb survivors. The clinicopathological features and prognosis of PCa were retrospectively reviewed in 212 survivors and 595 control patients between November 1996 and December 2010. The histopathological and clinical outcomes of surgical treatment of PCa were also evaluated in 69 survivors and 162 control patients. Despite the higher age at diagnosis compared with the control group (P=0.0031), survivors were more likely to have been diagnosed with PCa from a health check compared with the control group (P<0.0001). As a consequence, the survivors were found to exhibit metastasis significantly less frequently (199/212, 93.9%) compared with the control patients (521/595, 87.6%; P=0.0076). Prognosis in the two groups was examined, subsequent to a mean length of follow-up of 44 months. Overall survival (OS) and PCa-specific survival (CS) were similar between the two groups (OS, P=0.2196; CS, P=0.1017). A-bomb exposure was not found to be an independent predictor for prognosis by multivariate analysis (OS, P=0.7800; CS, P=0.8688). The clinicopathological features of patients who underwent a prostatectomy were similar except for the diagnosis opportunity between the two groups. Progression-free survival rates were similar between the two groups (P=0.5630). A-bomb exposure was not a significant and independent predictor for worsening of progression-free prognosis by multivariate analysis (P=0.3763). A-bomb exposure does not appear to exert deleterious effects on the biological aggressiveness of PCa and the prognosis of patients with PCa.

Impact of neutrophil-to-lymphocyte ratio on effects of targeted therapy for metastatic renal cell carcinoma patients with extrapulmonary metastasis.

INTRODUCTION: The aim of our present study was to investigate the impact of the pretreatment neutrophil-to-lymphocyte ratio (NLR) on the antitumour effects of targeted agents in patients with metastatic renal cell carcinoma (mRCC). METHODS: The NLRs in 283 cases of molecular targeted therapy for mRCC were measured before starting the prescription of the molecular targeted agent. The significance of pretreatment NLR on the site of metastatic organs and on progression-free survival (PFS) in each case was analyzed. RESULTS: Metastases other than lung, which is defined as "extrapulmonary metastasis," were observed in 190 cases (67.1%). The median of pretreated NLR was 2.39 (0.49-68.7). In 97 of the 283 cases, pretreated NLR was 3.0 or higher. These cases were categorized as the high NLR group and the rest as the low NLR group. When the cases with extrapulmonary metastasis were investigated and classified based on their pretreated NLR, 50% PFS in the high NLR and low NLR groups was 6.7 months and 12 months (p=0.0001), respectively. Multivariate analysis revealed that high NLR (>3.0) was an independent predictive factor for PFS in the cases with extrapulmonary metastasis (hazard ratio 2.762; p<0.0001), while there was no significant difference between PFS in the high and low NLR groups in cases with no extrapulmonary metastasis (p=0.3457). CONCLUSIONS: Our data indicate that the predictive significance of the NLR in mRCC cases involving targeted therapy depends on the metastatic organs. NLR is an independent predictive factor of PFS in cases of mRCC with extrapulmonary metastasis treated with targeted therapy.

Serous adenocarcinoma of retroperitoneum: a case report.

Primary retroperitoneal serous adenocarcinoma (PRSA) is an extremely rare malignancy, with only seven cases having been previously reported. We report a case of PRSA in a 42-year-old woman treated with surgical resection and adjuvant chemotherapy. The histopathological findings of PRSA resemble those of ovarian serous carcinoma, which indicates that a combination of complete surgical resection with adjuvant chemotherapy may be the best treatment option for PRSA.

Regeneration of rat corpora cavernosa tissue by transplantation of CD133+ cells derived from human bone marrow and placement of biodegradable gel sponge sheet.

The objective is to develop an easier technique for regenerating corpora cavernosa tissue through transplantation of human bone marrow-derived CD133 + cells into a rat corpora cavernosa defect model. We excised 2 mm × 2 mm squares of the right corpora cavernosa of twenty-three 8-week-old male nude rats. Alginate gel sponge sheets supplemented with 1 × 10 4 CD133 + cells were then placed over the excised area of nine rats. Functional and histological evaluations were carried out 8 weeks later. The mean intracavernous pressure/mean arterial pressure ratio for the nine rats (0.34258 ± 0.0831) was significantly higher than that for eight rats with only the excision (0.0580 ± 0.0831, P = 0.0238) and similar to that for five rats for which the penis was exposed, and there was no excision (0.37228 ± 0.1051, P = 0.8266). Immunohistochemical analysis revealed that the nine fully treated rats had venous sinus-like structures and quantitative reverse transcription polymerase chain reaction analysis of extracts from their alginate gel sponge sheets revealed that the amounts of mRNA encoding the nerve growth factor (NGF), and vascular endothelial growth factor (VEGF) were significantly higher than those for rats treated with alginate gel sheets without cell supplementation (NGF: P = 0.0309; VEGF: P < 0.0001). These findings show that transplantation of CD133 + cells accelerates functional and histological recovery in the corpora cavernosa defect model.

Effect of Spatial Cognitive Ability on Gain in Robot-Assisted Surgical Skills of Urological Surgeons.

BACKGROUND: Although previous studies have demonstrated the needs for a spatial cognitive ability that can give an accurate understanding of the position, orientation, and size and form of the objects in endoscopic surgery, there has been no study on the relationship between the skills of robot-assisted surgery and spatial cognitive ability. OBJECTIVE: To assess the effect of spatial cognitive ability on gain in robot-assisted surgical skills of urological surgeons. MATERIALS AND METHODS: The robot-assisted surgery skills of 24 urological surgeons who had no previous experience with the Mimic dV-Trainer (MdVT) and had not been the main surgeon in robot-assisted surgery and 20 volunteer medical students who had no previous experience of the MdVT were assessed by using a program consisting of 4 kinds of tasks. Their performances were recorded using a built-in scoring algorithm. Their spatial cognitive abilities were also assessed using a mental rotation test. RESULTS: Although there was a significant correlation between the spatial cognitive ability and a score of 2 for the more difficult tasks for student groups using the MdVT, there was no significant correlation between them for all tasks for groups of urological surgeons. CONCLUSION: The results of the present study indicate that differences in spatial cognitive ability in urological surgeons have no effect on the gain in fundamental robot-assisted surgery skills whereas there was a significant correlation between the spatial cognitive ability and fundamental robot-assisted surgical skills in the volunteers.

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.

OBJECTIVES: 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). PATIENTS AND METHODS: The serum CRP level in 190 cases of molecular targeted therapy for mRCC was measured before starting the prescription of molecular targeted agents and when computed tomography showed the maximum effect. Patients in which the pretreatment CRP level was ≥0.5 mg/dL were classified into a 'higher-CRP' group and others into a 'lower-CRP' group. The higher-CRP group was further classified into two subgroups, i.e. those whose serum CRP level decreased after molecular targeted therapy ('decreased-CRP' subgroup), and those whose level did not decrease after therapy ('non-decreased-CRP' subgroup). All patients were also classified according to their other clinical details and progression-free survival (PFS) rates of each subgroup were compared. RESULTS: Of the 190 patients, 97 were categorised as lower CRP and 93 as higher CRP, with 50 and 43 patients in the higher-CRP group further categorised as decreased- and non-decreased-CRP subgroups, respectively. For the maximum effects of the targeted therapy, determined based on the Response Evaluation Criteria In Solid Tumors (RECIST) criteria, in the lower-CRP group, significantly more patients had a complete response (CR) and partial response (PR) (P = 0.002) and significantly fewer had progressive disease (PD) (P < 0.001) vs the higher-CRP group. In the higher-CRP group, significantly fewer patients had PD in the decreased-CRP subgroup (P < 0.001) than those in the non-decreased-CRP subgroup. The 2-year PFS rate for the lower-CRP group (39.1%) was significantly better vs the decreased-CRP subgroup (21.2%; P = 0.013) and significantly better vs the non-decreased CRP subgroup (0%; P < 0.001). Multivariate analyses in the higher-CRP group revealed that decreased CRP was an independent predictive factor for PFS (P = 0.002, hazard ratio 2.454, 95% confidence interval 1.404-4.290). CONCLUSION: A decrease of CRP and pretreatment CRP levels show promise as a novel predictive factor for anti-tumour effects in patients treated with molecular targeted therapy.

Fukutin, identified by the Escherichia coli ampicillin secretion trap (CAST) method, participates in tumor progression in gastric cancer.

BACKGROUND: Gastric cancer (GC) is the fifth commonest malignancy worldwide and still one of the leading causes of cancer-related death. The aim of this study was to identify a novel prognostic marker or therapeutic target for GC. METHODS: We analyzed candidate genes from our previous Escherichia coli ampicillin secretion trap (CAST) libraries in detail, and focused on the FKTN gene because it was overexpressed in both GC cell line CAST libraries, MKN-1 and MKN-45. RESULTS: Quantitative reverse transcriptase PCR analysis of FKTN revealed that FKTN messenger RNA was overexpressed in nine of 28 (32.1 %) GC tissue samples compared with nonneoplastic gastric mucosa. Immunostaining of fukutin showed that 297 of 695 cases (42.7 %) were positive for fukutin. Fukutin-positive GC cases were significantly associated with differentiated histological features, and advanced T grade and N grade. In addition, fukutin expression was observed more frequently in the intestinal phenotype (51 %) of GC than in other phenotypes (37 %) when defined by the expression patterns of mucin 5AC, mucin 6, mucin 2, and CD10. FKTN small interfering RNA treatment decreased GC cell proliferation. CONCLUSIONS: These results indicate that the expression of fukutin may be a key regulator for progression of GC with the intestinal mucin phenotype.

Oligophrenin-1 is associated with cell adhesion and migration in prostate cancer.

OBJECTIVE: We performed Escherichia coli ampicillin secretion trap (CAST) analysis in prostate cancer (PCa) to identify novel biomarkers. We show here that OPHN1, which encodes oligophrenin-1 protein, is upregulated in PCa. OPHN1 was first determined to be one of the genes associated with X-linked mental retardation; however, neither the gene's function nor the link between its expression and survival of patients has been investigated. METHODS: We investigate the expression of oligophrenin-1 in 141 PCa tissue samples by immunohistochemistry and perform functional analysis using RNA interference. RESULTS: Immunohistochemical analysis of oligophrenin-1 demonstrated that 60 (43%) PCa cases were positive for oligophrenin-1. Positive oligophrenin-1 expression was significantly correlated with a high Gleason score (p = 0.0198). Furthermore, patients with oligophrenin-1-positive PCa had a worse biochemical recurrence-free survival rate than patients with oligophrenin-1-negative PCa (p = 0.0079). Cell adhesion to fibronectin was significantly reduced in OPHN1 small interfering (si)RNA-transfected LNCaP and PC3 cells in comparison to negative-control siRNA-transfected cells. Knockdown of OPHN1 reduced the expression of ITGA5 and stress fiber formation in LNCaP and PC3 cells. CONCLUSION: These results suggest that oligophrenin-1 is involved in tumor progression in PCa.

MicroRNA-145 is a potential prognostic factor of scirrhous type gastric cancer.

Gastric cancer (GC) is one of the most common malignancies worldwide. In particular, scirrhous type GC is highly metastatic and is characterized clinically by rapid disease progression and poor prognosis. MicroRNAs (miRNAs) play crucial roles in cancer development and progression. We previously demonstrated by microarray analysis that microRNA-145 (miR-145) is one of the more highly expressed miRNAs in scirrhous type GC vs. non-scirrhous types of GC. In the present study, we investigated the role of miR-145 in scirrhous type GC. The expression levels of miR-145 assessed by quantitative RT-PCR were higher in scirrhous type GC tissue samples than in non-scirrhous type GC and corresponding normal tissues. GC patients with high miR-145 expression were at a more advanced tumor stage (P=0.0156) and had more scirrhous type histology (P=0.0054) than those with low miR-145 expression. Furthermore, miR-145 expression was significantly associated with poor prognosis in GC patients (P=0.0438). miR-145 expression was localized in stromal fibroblasts of scirrhous type GC but not in cancer cells. miR-145 was induced by treatment by transforming growth factor-ß, and it enhanced the expression of α-smooth muscle actin, a marker of myofibroblasts, in both normal gastric fibroblasts and cancer-associated fibroblasts. These data suggest that miR-145 may contribute to the progression of scirrhous type GC by regulating activation of peri-tumoral fibroblasts.