Short hairpin RNA-mediated down-regulation of CENP-A attenuates the aggressive phenotype of lung adenocarcinoma cells.

BACKGROUND: Deregulation of centromere protein (CENP)-A, a centromere-specific histone variant, has in the past been linked to cancer initiation and progression. Additionally, our previous work has shown that CENP-A upregulation predicts a poor overall survival in patients with lung adenocarcinoma. The aim of this study was to uncover the biological role of CENP-A in lung adenocarcinoma growth and invasion, including its underlying molecular mechanisms. METHODS: CENP-A expression was knocked down in human lung adenocarcinoma A549 and PC-9 cells using a short hairpin RNA (shRNA) technology. Subsequently, the effects of this knock down on the proliferation, apoptosis, cell cycle progression, colony formation, migration, invasion and tumorigenicity were assessed. Additionally, Western blot analyses were performed to examine concomitant expression changes in key proteins involved in cell cycle regulation and apoptosis. RESULTS: We found that shRNA-mediated knock down of CENP-A significantly inhibited the in vitro proliferation and colony formation of A549 and PC-9 cells as compared to control shRNA-transfected cells. In addition, CENP-A down-regulation was found to induce G0/G1 cell cycle arrest and apoptosis, and to inhibit the in vitro migration and invasion of A549 and PC-9 cells. Down-regulation of CENP-A was also found to significantly suppress the in vivo growth of xenografted A549 cells. At the protein level, we found that the expression of p21, p27, CHK2 and Bax was markedly increased and that the expression of CCNG1, Skp2, Cks1 and Bcl-2 was markedly decreased in CENP-A down-regulated cells. CONCLUSION: Based on our results we conclude that down-regulation of CENP-A may attenuate the aggressive phenotype of lung adenocarcinoma cells. As such, CENP-A may serve as a promising therapeutic target for lung adenocarcinoma.

Clinical features and hypoxic marker expression of primary sinonasal and laryngeal small-cell neuroendocrine carcinoma: a small case series.

BACKGROUND: Small-cell neuroendocrine carcinoma (SCNEC) of the head and neck is rare. The prognosis of SCNEC in the nasal cavity and larynx is poor. The aim of this study was to investigate the clinicopathological features of nasal and laryngeal SCNEC and to determine the expression of HIF-1α, GLUT-1, PI3K, and p-Akt in SCNEC. METHODS: Between 2003 and 2012, 10 consecutive patients with histologically demonstrated nasal and laryngeal SCNEC were enrolled. Clinicopathological materials and follow-up data were analyzed retrospectively. Immunohistochemistry was used to detect GLUT-1, HIF-1α, PI3K, and p-Akt expression in paraffin wax-embedded tumor specimens. RESULTS: The subjects were eight males and two females with a mean age of 60.8 (range: 53 to 71) years. Tumors were located in the maxillary sinus (n = 3) and larynx (n = 7). At last follow-up, four patients (40.0%) had local recurrence and five patients (50.0%) had developed distant metastases. Six patients died. The mean overall survival was 19.3 ± 2.1 months. Expression of GLUT-1, HIF-1α, PI3K, and p-Akt was seen in sinonasal and laryngeal SCNEC in 80 (8 out of 10), 50 (5 out of 10), 40 (4 out of 10), and 40% (4 out of 10) of cases, respectively. Expression of GLUT-1, HIF-1α, PI3K, and p-Akt was higher in sinonasal and laryngeal SCNEC than in precancerous lesions. CONCLUSIONS: Primary sinonasal and laryngeal SCNEC is rare. This paper presents 10 cases of sinonasal and laryngeal SCNEC with more common local recurrence and distant metastasis. HIF-1α, GLUT-1, PI3K, and p-Akt expression was higher in sinonasal and laryngeal SCNEC than in precancerous lesions.

One-stage complete removal of intracardiac leiomyomatosis without cardiac arrest.

We present here a woman with an intracardiac leiomyoma originating from uterine leiomyomatosis. The tumor was completely removed in a one-stage procedure using cardiopulmonary bypass without cardiac arrest. Most one-stage operations were performed with total circulation arrest; however, using of on-pump beating-heart technique when removing the intracardiac mass has seldom been reported in detail. The patient was asymptomatic with no evidence of recurrence on 13-month follow-up.

Prostate-specific antigen velocity (PSAV) and PSAV per initial volume (PSAVD) for early detection of prostate cancer in Chinese men.

AIM: To investigate the utility of prostate-specific antigen velocity (PSAV) and PSAV per initial volume (PSAVD) for early detection of prostate cancer (PCa) in Chinese men. METHODS: Between January 2009 and June 2012, a total of 193 men (aged 49-84 years, median 67 years) with at least 2 transrectal ultrasonography (TRUS) procedures and concurrent serum PSA measurements underwent prostate biopsy because of suspicion of PCa. The total group were classified into PCa and non-PCa groups, and the variables of the two groups were compared. Univariate and multivariate analyses were used to investigate which variables were predictove. The diagnostic values of PSAV, PSAVD and prostate-specific antigen density (PSAD) were compared using receiver operating characteristic (ROC) analysis. RESULTS: Prostate cancer was diagnosed in 44 (22.8%) of the 193 men. There were significant differences between the groups in last and initial prostate volumes determined by TRUS, initial age, last serum PSA levels, PSAV, PSAD and PSAVD. After adjusting for confounding factors, the odds ratios of PCa across the quartile of PSAVD were 1, 4.06, 10.6, and 18.9 (P for trend <0.001).The area under the ROC curves (AUCs) of PSAD (0.779) and PSAVD (0.776) were similar and both significantly greater than that of PSA (AUC 0.667). PSAVD was a significantly better indicator of PCa than PSAV (AUC 0.736). There was no statistical significant difference between the AUC of PSAV and that of last serum PSA level. The sensitivity and specificity of PSAVD at a cutoff of 0.023ng in participants with last serum PSA levels of 4.0 ng/mL-10.0 ng was 73.7% and 70.7%, respectively. CONCLUSIONS: The results of this study demonstrated PSAVD may be a useful tool in PCa detection, especially in those undergoing previous TRUS examination.