Yu Ren

Superiority of Minimally Invasive Oesophagectomy in Reducing In-Hospital Mortality of Patients with Resectable Oesophageal Cancer: A Meta-Analysis

Background Compared with open oesophagectomy (OE), minimally invasive oesophagectomy (MIO) proves to have benefits in reducing the risk of pulmonary complications for patients with resectable oesophageal cancer. However, it is unknown whether MIO has superiority in reducing the occurrence of in-hospital mortality (IHM). Objective The objective of this meta-analysis was to explore the effect of MIO vs. OE on the occurrence of in-hospital mortality (IHM). Data Sources Sources such as Medline (through December 31, 2014), Embase (through December 31, 2014), Wiley Online Library (through December 31, 2014), and the Cochrane Library (through December 31, 2014) were searched. Study Selection Data of randomized and non-randomized clinical trials related to MIO versus OE were included. Interventions Eligible studies were those that reported patients who underwent MIO procedure. The control group included patients undergoing conventional OE. Study Appraisal and Synthesis Methods Fixed or random -effects models were used to calculate summary odds ratios (ORs) or relative risks (RRs) for quantification of associations. Heterogeneity among studies was evaluated by using Cochran’s Q and I2 statistics. Results A total of 48 studies involving 14,311 cases of resectable oesophageal cancer were included in the meta-analysis. Compared to patients undergoing OE, patients undergoing MIO had statistically reduced occurrence of IHM (OR=0.69, 95%CI =0.55 -0.86). Patients undergoing MIO also had significantly reduced incidence of pulmonary complications (PCs) (RR=0.73, 95%CI = 0.63-0.86), pulmonary embolism (PE) (OR=0.71, 95%CI= 0.51-0.99) and arrhythmia (OR=0.79, 95%CI = 0.68-0.92). Non-significant reductions were observed among the included studies in the occurrence of anastomotic leak (AL) (OR=0.93, 95%CI =0.78-1.11), or Gastric Tip Necrosis (GTN) (OR=0.89, 95%CI =0.54-1.49). Limitation Most of the included studies were non-randomized case-control studies, with a diversity of study designs, demographics of participants and surgical intervention. Conclusions Minimally invasive oesophagectomy (MIO) has superiority over open oesophagectomy (OE) in terms of the occurrence of in-hospital mortality (IHM) and should be the first-choice surgical procedure in esophageal surgery.

Common Chromosomal Fragile Site Gene WWOX in Metabolic Disorders and Tumors

WWOX, a gene that spans the second most common chromosomal fragile site (FRA16D), often exhibits homozygous deletions and translocation breakpoints under multiple cellular stresses induced by extrinsic or intrinsic factors, such as hypoxia, UV, and DNA damage regents. Loss of WWOX is closely related to genomic instability, tumorigenesis, cancer progression and therapy resistance. WWOX heterozygous knockout mice show an increased incidence of spontaneous or induced tumors. WWOX can interact via the WW domain with proteins that possess proline PPxY motifs and is involved in a variety of cellular processes. Accumulating evidence has shown that WWOX that contains a short-chain dehydrogenase/reductase (SDR) domain is involved in steroid metabolism and bone development. Reduced or lost expression of WWOX will lead to development of metabolic disease. In this review, we focus on the roles of WWOX in metabolic disorders and tumors.

Enhanced SLC34A2 in breast cancer stem cell-like cells induces chemotherapeutic resistance to doxorubicin via SLC34A2-Bmi1-ABCC5 signaling

AbstractsEven though early detection methods and treatment options are greatly improved, chemoresistance is still a tremendous challenge for breast cancer therapy. Breast cancer stem cells (BCSCs) represent a subpopulation that is central to chemoresistance. We aim to investigate the relationship between SLC34A2 and chemoresistance in BCSCs and identify the underlying mechanisms by which SLC34A2 regulates chemoresistance in BCSCs. Fluorescence Activated Cell Sorting (FACS) analysis showed the presence of a variable fraction of CD44+CD24− cells in 25 out of 25 breast cancer samples. We cultured primary breast cancer sample cells and breast cancer cell line cells to induce sphere formation in serum-free medium. Following sorting of CD44+CD24− cells from spheres, we showed that CD44+CD24− cells displayed stem cell-like features and were resistant to chemotherapy drug doxorubicin. Significantly, enhanced SLC34A2 expression correlated with chemoresponse and survival of breast cancer patients. We subsequently indicated that increased SLC34A2 expression in BCSCs directly contributed to their chemoresistance by a series of in vitro and in vivo experiments. Furthermore, we demonstrated that SLC34A2 induced chemoresistance in BCSCs via SLC34A2-Bmi1-ABCC5 signaling. Finally, we showed that ABCC5 was a direct transcriptional target of Bmi1 by chromatin immunoprecipitation (ChIP). In conclusion, our work indicated that decreased SLC34A2 expression sensitized BCSCs to doxorubicin via SLC34A2-Bmi1-ABCC5 signaling and shed new light on understanding the mechanism of chemoresistance in BCSCs. This study not only bridges the missing link between stem cell-related transcription factor (Bmi1) and ABC transporter (ABCC5) but also contributes to development of potential therapeutics against breast cancer.

Systematic review and meta-analysis of rectal washout on risk of local recurrence for cancer

BACKGROUND It has been shown that intraluminal washout (WO) can prevent local recurrence (LR) of rectal cancer. This meta-analysis was to evaluate the association of rectal WO and the risk of LR after anterior resection in patients with rectal cancer. METHODS The relevant studies were identified by a search of the MEDLINE, Embase, Wiley Online Library, and Cochrane Oral Health Group Specialized Register with no restrictions on October 18, 2013, and these studies were included in a systematic review and meta-analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in fixed effects model. RESULTS A total of nine studies were included in our study, yielding a total of 5519 patients, and pooled ORs for overall LR in corresponding subgroups were calculated. Rectal WO was associated with a lower risk for LR (240/4176, 5.75% versus 9.75%, 131/1343, OR = 0.53, 95% CI = 0.42-0.68, and P < 0.00001) in patients with anterior resection, having total mesorectal excisions (234/3942, 5.93% versus 9.34%, 97/1039, OR = 0.59, 95% CI = 0.46-0.75, and P < 0.00001), and after radical resection (RR; 122/2665, 4.99% versus 8.90%, 74/831, OR = 0.56, 95% CI = 0.41-0.78, and P = 0.0005), with an overall LR rate of 6.72% (371/5519). But, the stability of RRs is not high in the total mesorectal excisions or RR subgroup by sensitivity analysis. CONCLUSIONS The use of rectal WO decreases risks of LR in patients after anterior resection of cancer.

Comparison of clinicopathologic features and survival in young American women aged 18–39 years in different ethnic groups with breast cancer

Background:Ethnic disparities in breast cancer diagnoses and disease-specific survival (DSS) rates in the United States are well known. However, few studies have assessed differences specifically between Asians American(s) and other ethnic groups, particularly among Asian American(s) subgroups, in women aged 18–39 years.Methods:The Surveillance, Epidemiology, and End Results database was used to identify women aged 18–39 years diagnosed with breast cancer from 1973 to 2009. Incidence rates, clinicopathologic features, and survival among broad ethnic groups and among Asian subgroups.Results:A total of 55 153 breast cancer women aged 18–39 years were identified: 63.6% non-Hispanic white (NHW), 14.9% black, 12.8% Hispanic-white (HW), and 8.7% Asian. The overall incidence rates were stable from 1992 to 2009. Asian patients had the least advanced disease at presentation and the lowest risk of death compared with the other groups. All the Asian subgroups except the Hawaiian/Pacific Islander subgroup had better DSS than NHW, black, and HW patients. Advanced tumour stage was associated with poorer DSS in all the ethnic groups. High tumour grade was associated with poorer DSS in the NHW, black, HW, and Chinese groups. Younger age at diagnosis was associated with poorer DSS in the NHW and black groups.Conclusion:The presenting clinical and pathologic features of breast cancer differ by ethnicity in the United States, and these differences impact survival in women younger than 40 years.

Comparative analysis of lifestyle factors, screening test use, and clinicopathologic features in association with survival among Asian Americans with colorectal cancer

Background:Colorectal cancer (CRC) diagnoses and disease-specific survival (DSS) vary between ethnic groups in the United States. However, few studies have assessed differences among Asian subgroups.Methods:The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients with invasive CRC between 1988 and 2008. Differences in clinicopathologic features, and DSS rates were compared among Asian subgroups. The California Health Interview Survey was used to examine risk factors and screening patterns for CRC.Results:The study included 359 374 patients with 8.4% Asian. Patients in all Asian subgroups were younger (median: 68 years) at diagnosis than non-Hispanic white (NHW) patients (median: 72 years). Most Asian subgroups, except Hawaiians, had better DSS than NHW patients although Asian subgroups had more advanced disease than NHW. Indian/Pakistani patients had a higher 5-year DSS than other Asian subgroups. Obesity proportions were lower in Asian subgroups (<50.2%) than in NHW (59.8%). Vietnamese men and Korean women had the lowest proportions of CRC screening. Advance tumour stages were highly associated with worse DSS in each ethnicity group. High tumour grades were associated with worse DSS in NHW, Filipino, and Chinese. Older age at diagnosis was associated with worse DSS in most ethnicity groups except Hawaiian and Vietnamese.Conclusion:Disparities exist between Asians and NHW with CRC, and among various Asian subgroups. Differences in cancer clinicopathologic features, patients’ behavioural habits, lifestyle, and screening patterns may explain some differences in CRC survival observed among ethnic groups.

miR-215 functions as a tumor suppressor in epithelial ovarian cancer through regulation of the X-chromosome-linked inhibitor of apoptosis

Epithelial ovarian cancer (EOC) accounts for 90% of all ovarian cancer, which is the third most common gynaecological malignancy worldwide. Dysregulation of miRNAs is involved in the development of different types of EOC. The present study was designed to investigate the role of abnormal expression of miR-215 in the development of EOC and to elucidate the possible molecular mechanisms. mRNA expression of miR-215 was significantly decreased in EOC tissues and cell lines. Upregulation of miR-215 inhibited cell proliferation, promoted apoptosis and increased sensitivity to chemotherapy drugs in EOC cells. In contrast, downregulation of miR-215 increased cell proliferation, inhibited apoptosis and decreased sensitivity to chemotherapy drugs in EOC cells. In addition, the X-chromosome-linked inhibitor of apoptosis (XIAP) expression was significantly increased in EOC tissues and cell lines. Downregulation of XIAP inhibited cell proliferation, promoted apoptosis and increased sensitivity to chemotherapy drugs in EOC cells. Upregulation of miR-215 notably inhibited the expression of XIAP. Moreover, overexpression of XIAP significantly inhibited miR-215-exerted decrease of proliferation, increase of apoptosis and increase of sensitivity to chemotherapy drugs. In conclusion, we identified miR-215 as a potential tumor suppressor in patients with EOC downregulating expression of the oncogenic regulator XIAP. The data demonstrate that miR-215/XIAP pathway may serve as novel therapeutic targets and prognostic markers in patients with EOC.

A novel active gate drive for HV-IGBTs using feed-forward gate charge control strategy

Gate drives of todays high-voltage insulated gate bipolar transistors (HV-IGBTs) are in most cases voltage source based and with fixed gate resistors. Consequently, the contradiction between high-speed switching for minimized power loss and low-speed switching for low noise and low switching stress cannot be resolved simultaneously. This paper proposes a novel active gate drive (AGD) which operates basing on the feedforward gate charge control strategy. The proposed gate drive is composed of both digital and analog parts to achieve flexible control of the turn-on and turn-off operation of the IGBT. Thus, the conflicting requirements faced with the conventional gate drive (CGD) can be satisfied. The effectiveness of the feedforward gate charge control strategy has been verified by simulations, and promising results have been obtained. Besides, a chopper circuit is establishing to validate the operation of the active gate drive.

Cell polarity protein CRB3 is an independent favorable prognostic factor for clear cell renal cell carcinoma

Epithelial cells possess apical‑basal polarity and loss of epithelial cell polarity contributes to tumorigenesis and cancer progression. The Crumbs (CRB) polarity protein plays a crucial role in epithelial polarity maintenance, apical membrane formation, and tissue morphogenesis. Although evidence is increasing on involvement of deregulated polarity proteins in cancers, little is currently known about the roles of the CRB (Drosophila), especially the roles of CRB3, a homolog of the CRB, in clear cell renal cell carcinoma (ccRCC). Studies have shown that CRB3 may act as a tumor suppressor in non‑human mammalian cells; the study here was aimed to examine the expression status of CRB3 in ccRCC and the relationships between CRB3 expression and clinicopathologic parameters of ccRCC patients. Our results showed that CRB3 was weakly expressed in ccRCC tissues, but strongly expressed in adjacent normal kidney tissues. Patients with loss of CRB3 expression showed a significantly shorter overall survival (OS) than patients with positive CRB3 expression. Our results suggested that CRB3 may be an independent favorable prognostic factor for patients with ccRCC. We also found that overexpression of CRB3 restrained invasion and migration of 786‑O cells and loss of CRB3 expression promoted invasion and migration of human embryonic kidney 293T (HEK 293T) cells. This finding may explain why the negative CRB3 expression was associated with poor prognosis in human ccRCC. Altogether, our data demonstrated that CRB3 may be used as a new independent favorable prognostic factor for human ccRCC.

Epithelial Cell Polarity Determinant CRB3 in Cancer Development

Cell polarity, which is defined as asymmetry in cell shape, organelle distribution and cell function, is essential in numerous biological processes, including cell growth, cell migration and invasion, molecular transport, and cell fate. Epithelial cell polarity is mainly regulated by three conserved polarity protein complexes, the Crumbs (CRB) complex, partitioning defective (PAR) complex and Scribble (SCRIB) complex. Research evidence has indicated that dysregulation of cell polarity proteins may play an important role in cancer development. Crumbs homolog 3 (CRB3), a member of the CRB complex, may act as a cancer suppressor in mouse kidney epithelium and mouse mammary epithelium. In this review, we focus on the current data available on the roles of CRB3 in cancer development.