NEDD9 crucially regulates TGF-ß-triggered epithelial-mesenchymal transition and cell invasion in prostate cancer cells: involvement in cancer progressiveness.

BACKGROUND: NEDD9 is one of the Crk-associated substrate (Cas) family proteins that mediate downstream signaling processes including cytoskeletal organization, cell-cycle and tumorigenesis. While NEDD9 plays a crucial role in epithelial-mesenchymal transition (EMT), the functional mechanism underlying NEDD9-mediated EMT in prostate cancer (PCa) remains uncertain. METHODS: The expression levels of NEDD9 and its downstream molecules in PC-3, LNCaP, and VCaP cells exposed to transforming growth factor-ß (TGF-ß) were determined by western blotting. The invasion of these cells with ectopic overexpression of NEDD9 or silencing of NEDD9 expression was measured by transwell invasion assay. Human tissue samples comprising 45 PCa specimens and ten specimens of normal prostatic tissue were used for immunohistochemical (IHC) analysis of NEDD9 expression. RESULTS: Both NEDD9 and its downstream signaling molecules associated with EMT were strongly induced by TGF-ß in PCa cells. PC-3 cells with stable overexpression of NEDD9 had a mesenchymal phenotype and significantly enhanced cell invasion, despite their decreased cell proliferation. Knockdown of endogenous NEDD9 expression completely diminished TGF-ß-triggered tumor invasion in several PCa cell lines. The IHC data revealed a significant positive correlation between the NEDD9 staining score and tumor aggressiveness (e.g., Gleason grade, serum PSA level). The NEDD9 staining score in primary PCa with bone metastasis was significantly higher than that in PCa without metastasis. CONCLUSIONS: NEDD9 may be a key mediator involved in TGF-ß-mediated EMT and cell motility in PCa cells and a novel target in the treatment of metastatic PCa and prevention of spread of localized PCa cells to other organs.

A Case of Pulmonary Pleomorphic Carcinoma With Renal Metastasis.

A 62-year-old man was referred to our hospital for an axillary mass. Computed tomography (CT) revealed a right axillary tumor and a left renal tumor. Needle biopsies of lung tumor and renal tumor were performed, but a definite diagnosis was impossible. Because his performance status worsened and the lung tumor grew day by day, chemotherapy with gemcitabine and cisplatin was started without definite diagnosis. However, the chemotherapy could not be continued because of interstitial pneumonia and the patient died because of the progression of disease. The final histopathologic diagnosis was pulmonary pleomorphic carcinoma based on immunohistochemical staining.

Urinary levels of hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein as a diagnostic biomarker in patients with bladder cancer.

BACKGROUND: To assess the possibility of hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP) as a biological marker for detecting Bladder cancer (BCa), we examined the expression of HIP/PAP in both BCa specimens and BCa cell lines and measured HIP/PAP levels in urine from patients with BCa. METHODS: HIP/PAP expression in BCa samples was evaluated by western blot analysis, and urinary levels of HIP/PAP in patients with BCa were measured by enzyme-linked immunosorbent assay. Urine samples were collected from 10 healthy volunteers and 109 with benign urological disorders as controls, and from 101 patients who were diagnosed with BCa. RESULTS: HIP/PAP was highly expressed in BCa samples as compared with control bladder. Urinary HIP/PAP concentrations were significantly higher in BCa patients than in controls (median value; 3.184 pg/mL vs. 55.200 pg/mL, P <0.0001, by Mann-Whitney U test). Urinary HIP/PAP levels in BCa patients correlated positively with pathological T stages and progression-risk groups among non-muscle invasive BCa (P = 0.0008, by Kruskal-Wallis test). Regarding the recurrence-risk classifications of non-muscle invasive BCa, the urinary levels of HIP/PAP were significantly higher in the intermediate than in the low risk group (P = 0.0002, by Mann-Whitney U test). Based on a cut-off of 8.5 pg/mL, the ability of urinary HIP/PAP levels to detect BCa had a sensitivity of 80.2%, specificity of 78.2%, positive predictive value (PPV) of 75.7%, and negative predictive value (NPV) of 82.3%. CONCLUSIONS: HIP/PAP was abundantly expressed in BCa, and the urinary levels of HIP/PAP could be a novel and potent biomarker for detection of BCa, and also for predicting the risks of recurrence- and progression-risk of non-muscle invasive BCa. A large scale study will be needed to establish the usefulness of this biomarker.

Intermediate oncological outcomes of percutaneous radiofrequency ablation for small renal tumors: initial experience.

BACKGROUND: For T1 stage incidental renal cell carcinoma (RCC), partial nephrectomy with or without laparoscopy is widely used on the basis of its nephron- sparing and minimally invasive nature. However, high-risk patients of advanced age, or with cardiovascular events are not often suitable candidates for surgery under general anesthesia. Percutaneous radiofrequency ablation (RFA) for mainly the treatment of these patients reportedly achieves satisfactory outcomes. We evaluated the clinical usefulness of this procedure in our initial cases. PATIENTS AND METHODS: In total, 24 renal tumors in 22 patients who had been diagnosed with T1 stage RCC were treated by percutaneous RFA. A LeVeen Needle (Radiotherapeutics) was used with an RF3000 generator. The overlapping ablation method was applied to these tumors, which were larger than 3 cm or located close to the renal hilus. Dynamic contrast-enhanced computed tomography or magnetic resonance imaging was routinely carried out to evaluate the post-treatment state. RESULTS: Maximum tumor diameters ranged from 1.0 to 4.5 cm (mean=2.4 cm). The follow-up period was 1-61 months (mean=18 months) after RFA treatment. Contrast enhancement completely disappeared immediately after this procedure in 23 tumors, the one exception being a 4.5-cm tumor. The tumor recurrence-free and overall survival rates were 85% and 79%, respectively, at two years after RFA. CONCLUSION: Percutaneous RFA is a feasible option for the treatment of RCCs, particularly for those less than 3 cm in diameter.

Hyperbaric oxygen therapy for painful bladder syndrome/interstitial cystitis resistant to conventional treatments: long-term results of a case series in Japan.

BACKGROUND: There is no confirmed strategy for treating painful bladder syndrome/interstitial cystitis (PBS/IC) with unclear etiology. Therefore, a pilot study was carried out to evaluate the efficacy and safety of hyperbaric oxygen (HBO) therapy in treatment-resistant PBS/IC patients. METHODS: HBO treatment (2.0 ATA for 60 minutes/day × 5 days/week for 2 or 4 weeks) was performed on 11 patients with severe symptoms that had not been improved by previous therapy regimens between December 2004 and July 2009. RESULTS: Seven of the 11 patients demonstrated persistent improvement in symptoms during the 12 months after HBO treatment. These responders demonstrated a decrease in the pelvic pain scale and urgency scale from 7.7 ± 1.0 and, 6.6 ± 0.9 to 3.4 ± 2.5 and 4.3 ± 2.4 after 12 months, respectively (p < 0.05). The total score of the interstitial cystitis symptom index and 24-hour urinary frequency demonstrated a significant sustained decrease from the baseline. Two responders, who received an additional course of HBO 12 and 13 months after initial treatment, respectively, did not suffer impairment for more than two years. There was one case of transient eustachian tube dysfunction and three cases of reversible exudative otitis media as a consequence of HBO treatment. CONCLUSIONS: HBO is a potent treatment for PBS/IC patients resistant to conventional therapy. It was well tolerated and provided maintained amelioration of pain, urgency and urinary frequency for at least 12 months.