Impact of daily lifestyle on coronary heart disease.

Limited data are available with regard to the impact of daily lifestyle choices in patients with coronary heart disease (CHD) who have undergone stent placement. Thus, the aim of the present study was to investigate the impact of daily lifestyle factors in patients with CHD following stent implantation. Between March 2005 and March 2006, 129 consecutive patients with CHD were admitted to Cangzhou Central Hospital at Hebei Medical University (Cangzhou, China). The patients underwent coronary stenting and participated in a 7-year clinical follow-up that analyzed the impact of their daily lifestyle choices on CHD following the stent placement. Rates of dinner satiety [95% confidence interval (CI), 1.121-10.97, P=0.005], smoking (95% CI, 4.05-34.90, P=2.01×10-7) and heavy alcohol use (95% CI, 1.32-11.05, P=0.006) were significantly higher in the repeated (re)-revascularization group when compared with the non-revascularization group. In addition, the exercise rate was significantly lower in the re-revascularization group when compared with the non-revascularization group (95% CI, 0.02-0.65, P=0.005). However, no statistically significant differences were observed between the groups with regard to sleeping patterns (95% CI, 0.03-0.71, P=0.270) or anxiety rates (P=0.289). A coronary angiography performed during re-revascularization revealed in-stent restenosis in 26% of the patients, stenoses at the entrance to or exit from the stent in 29% of the patients and new lesions in 19% of the patients. Furthermore, original lesions exhibited deterioration in 26% of the patients. The clinical endpoint was reached in 55% of the patients between 3 and 5 years of the follow-up period. In conclusion, poor daily lifestyle habits can increase the in-stent restenosis rate, accelerate the progression of the original lesion and promote the emergence of new lesions in patients with CHD following stent placement.

Inhibition of KIF22 suppresses cancer cell proliferation by delaying mitotic exit through upregulating CDC25C expression.

KIF22 is a microtubule-dependent molecular motor protein with DNA-binding capacity. It is well known that KIF22 plays a critical role in cell mitosis as a motor protein; however, the role of altered KIF22 expression and its transcriptional regulatory function in cancer development have not yet been defined. This study showed that KIF22 was overexpressed in human cancer tissues, and inhibition of KIF22 significantly led to accumulation of cells in the G2/M phases, resulting in suppression of cancer cell proliferation. The investigation of the molecular mechanisms demonstrated that cell division cycle 25C (CDC25C) is a direct transcriptional target of KIF22, and inhibition of KIF22 increased CDC25C expression and cyclin-dependent kinase 1 (CDK1) activity, resulting in delayed mitotic exit. Phosphorylation of KIF22 was required for its transcriptional regulatory function and the reduction of CDK1 activity. Thus, we conclude that inhibition of KIF22 suppresses cancer cell proliferation by delaying mitotic exit through the transcriptional upregulation of CDC25C.

Cell-free circulating mitochondrial DNA in the serum: a potential non-invasive biomarker for Ewing's sarcoma.

BACKGROUND AND AIMS: Altered levels of circulating cell-free mitochondrial DNA (ccf mtDNA) have been recently detected in several cancer types and have been proposed as a promising noninvasive diagnostic or prognostic biomarker. There has been no report regarding quantification of ccf mtDNA in patients with Ewing's sarcoma (EWS). METHODS: Ccf mtDNA copy number in serum samples obtained from 25 patients with EWS as well as 20 age-matched individuals were detected by quantitative real-time PCR assays. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic applicability of serum ccf mtDNA as a noninvasive biomarker for discriminating between patients and healthy cohorts. The potential connection between ccf mtDNA levels and various clinicopathological factors of EWS was also determined. RESULTS: We found that levels of ccf mtDNA in the serum of EWS patients were significantly lower than in healthy controls. The receiver operating curve analysis demonstrated that using serum ccf mtDNA content as a molecular marker allowed distinguishing between EWS patients and healthy subjects with a sensitivity of 76.1 and a specificity of 68.4%. In addition, serum levels of ccf mtDNA were associated with the status of tumor metastasis. CONCLUSIONS: These results suggest that serum ccf mtDNA has the potential capacity as a novel and convenient noninvasive biomarker for molecular diagnosis of EWS. Scrutinizing quantitative changes of serum ccf mtDNA may provide valuable clues for better management of EWS patients.

Establishment of a reperfusion model in rabbits with acute myocardial infarction.

Clinically effective cardioprotection under acute myocardial infarction (AMI) can only be achieved by establishing the mechanisms of reperfusion-induced cardiac cell death. In spite of the numerous earlier studies on the prevention of ischemia-reperfusion injury of myocardium, the problem of cardiac cell death upon reperfusion is not yet resolved. Even though animal models provide an immense opportunity in the understanding of the mechanisms of ischemia-reperfusion injury, clinically relevant animal models through which translation of this knowledge into clinic are lacking. In this work, we have established a reperfusion model in rabbits with induced AMI by obstructing and releasing the left anterior ventricular branch of left circumflex coronary artery, which is clinically more relevant. This was achieved by cutting the two left ribs of the rabbit followed by obstructing and releasing the artery unlike the traditional approach, which involves incision through sternum and blocking the anterior descending coronary artery. This animal model of ischemia-reperfusion more closely mimics the physiological condition and also the trauma the animal suffers is much smaller with higher survival rate and thus is a potentially better model for studying the pathology related to ischemia-reperfusion injury.

[Expression and clinical significance of KNSL4 in breast cancer].

BACKGROUND & OBJECTIVE: Previous screening of breast cancer metastasis-related genes found that the mRNA level of kinesin-like 4 (KNSL4) gene is down-regulated in metastatic lymph nodes as compared with the paired primary breast cancer. This study was to clarify the correlations of KNSL4 mRNA expression to metastasis and prognosis of breast cancer, and explore the correlation of KNSL4 expression to c-erbB-2 expression to explore potential mechanisms of promoting metastasis by KNSL4. METHODS: Real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify the mRNA level of KNSL4 in 108 specimens of primary breast cancer. The correlations of KNSL4 mRNA level to metastasis and prognosis of the 108 cases were analyzed. Immunohistochemistry was used to assess c-erbB-2 protien expression in 76 out of the 108 cases, and the correlation of KNSL4 expression to c-erbB-2 expression was analyzed. RESULTS: The mRNA level of KNSL4 was significantly lower in the cases at stages iii-iv than in the cases at stages iii-iv (P<0.001), significantly lower in the cases with more than 3 metastatic lymph nodes than in the cases with 0-3 metastatic positive lymph nodes (P<0.01), slightly lower in the cases with negative estrogen receptor or prognesterone receptor than in the cases with positive receptors (P>0.05), lower in the 6 cases with distant metastasis than in the rest cases without distant metastasis within 24 month follow up, lower in the 3 cases with bilateral breast cancer than in other cases with unilateral breast cancer, and significantly lower in c-erbB-2-positive group than in c-erB-2-negative group (P<0.01). CONCLUSIONS: The down-regulation of KNSL4 mRNA level is correlated to prognosis of primary breast cancer. It may enhance metastatic ability of breast cancer cells through promoting c-erbB-2 transcription and translation.

[Identification of the differentially expressed genes between primary breast cancer and paired lymph node metastasis through combining mRNA differential display and gene microarray].

OBJECTIVE: To identify and clone the genes related to breast cancer metastasis through comparing the mRNA expression profiling between primary breast cancer and paired lymph node metastasis. METHODS: First, primary breast cancer cells and paired lymph node metastasis tissues were used to identify their differentially expressed genes by using mRNA differential display, and fragments of differentially expressed genes were obtained by gel cutting and cloning to pGEM-T vector, then sequencing and blasting with the GenBank for their homologous genes. Then, the obtained genes were validated by using reverse dot blot hybridization and gene microarray. Finally, the mRNA expression levels in the 7 breast cancer cell lines with different metastasis behaviors were detected by real-time RT-PCR. RESULTS: The mRNA expression profiling of the metastatic breast cancers in lymph node was similar to that of their primary cancers. 16 differentially expressed gene fragments were obtained from mRNA differential display; four of them were found to be unknown genes, and had been accepted by the GenBank, with the accession numbers BG518428, BG518429, BM005520, and BM005521. Of the other 12 genes, 8 were known genes, and 4 were genes with known sequences but unknown functions. The kinesin-like DNA binding protein (KNSL4) and dihydropyrimidine dehydrogenase (DYPD) were down-regulated in the metastatic tissues in comparison with the paired primary tissues, which was identified by both radioactivity-labeled reverse dot blot hybridization and fluorescence-labeled gene microarray hybridization. KNSL4 mRNA expression had a down-regulation trend with increasing metastatic ability of breast cancer cell lines. CONCLUSIONS: The gene expression profiling of the lymph node metastasis is almost similar to that of their primary breast cancer, indicating that the metastatic cancer cells in lymph node are the subclone with higher metastasis ability of the primary cancer cells, and that some differentially expressed genes between them may be involved in the change of metastasis phenotype. KNSL4 and DYPD are potential metastasis-related genes, and KNSL4 mRNA expression is correlated with metastasis behaviors of the breast cancer cell lines, suggesting that KNSL4 may play an important role in the metastasis process of breast cancer.