Zhongyu Wang

New Insight into Ki67 Expression at the Invasive Front in Breast Cancer

Purpose To investigate the distribution of Ki67+ cells in breast cancer in relation to clinical-pathological parameters and prognosis. Materials and Methods Ki67 expression status was detected in 1,086 breast cancer specimens using immunohistochemistry staining and examining the relationship between the Ki67+ cells location. Subsequently, clinical-pathological parameters and prognosis were determined. Results In total, Ki67 protein expression was found in 781 (71.92%) of the 1,086 breast cancer specimens. Among the 781 Ki67+ cases, 461 were defined as diffuse type and 320 were defined as borderline type. After universal correlation analysis, significant differences were observed in age, histological grade, metastatic nodes, postoperative distant metastasis, and molecular subtype between Ki67+ and Ki67− cases (Pu200a=u200a0.01, 0.001, 0.001, 0.001, and 0.001, respectively). After subgroup analysis, the borderline cases were found to be characterized by a high distant metastasis rate compared to the diffuse cases as well as the Ki67− cases (Pu200a=u200a0.001). No differences were observed between diffuse type or Ki67− cases (Pu200a=u200a0.105). Multivariate analysis showed that age, tumor size, histological grade, lymph node metastasis, molecular subtype, and the Ki67 distribution pattern were observed to be related to postoperative distant metastasis (all P<0.05). Furthermore, borderline type was shown to attain a significantly more distant bone and liver metastasis and worse disease-specific survival than the other types (Pu200a=u200a0.001). In the Cox regression test, the Ki67 distribution pattern was detected as an independent prognostic factor (Pu200a=u200a0.001). Conclusion The distribution pattern of Ki67 may be a new independent prognostic factor for breast cancer.

Pancreaticogastrostomy versus pancreaticojejunostomy reconstruction after pancreaticoduodenectomy: a meta-analysis of randomized controlled trials

AbstractPurposeWe conducted this meta-analysis to establish whether pancreaticogastrostomy (PG) or pancreaticojejunostomy (PJ) is the better method of reconstruction for reducing the risk of postoperative pancreatic fistula (POPF).MethodsThis study involved a systematic article search and review of published randomized controlled trials (RCTs) comparing PG vs. PJ after pancreaticoduodenectomy (PD). Cochrane’s risk of bias-assessing tool was used to assess the quality of included studies. The fixed-effect model, random-effect model, and subgroup analysis were performed for the sensitivity analysis.nResultsSix RCTs reporting data on 998 patients were included. The incidence of POPF was lower in the PG group (risk ratio, RRxa0=xa00.65, 95xa0% CI 0.43–0.97, Pxa0=xa00.03), but there was no significant difference in delayed gastric emptying, intra-abdominal fluid collection, biliary fistula, wound infection, postpancreatectomy hemorrhage, overall postoperative complication, or postoperative mortality between the procedures.ConclusionsThis meta-analysis shows that PG is superior to PJ for reducing the incidence of POPF, but there were no differences in other complications or mortality. Therefore, it may be considered as an alternative to PJ and further RCTs are needed to prove our findings.

Superparamagnetic iron oxide magnetic nanomaterial-labeled bone marrow mesenchymal stem cells for rat liver repair after hepatectomy.

BACKGROUNDnSuperparamagnetic iron oxide magnetic nanomaterials (SPIO) are tracers used for treatment of central nervous and cardiovascular system complications in animal models. The present study investigated survival and proliferation of SPIO-labeled bone marrow mesenchymal stem cells (BMSCs) to determine their potential therapeutic value in liver repair.nnnMETHODSnSurface antigens of BMSCs were measured using flow cytometry. BMSCs viability, growth curve, and SPIO (0-100 μg/mL) labeling rate were evaluated using trypan blue staining, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and Prussian blue staining, respectively. SPIO-labeled BMSCs were transplanted via liver or spleen injection in rats undergoing 70% hepatectomy. Distribution of SPIO-labeled BMSCs in liver and spleen, and liver repair were evaluated by magnetic resonance imaging (MRI), and serum alanine aminotransferase, aspartate aminotransferase, albumin, and total bilirubin levels.nnnRESULTSnCD29(+)/CD90(+)/CD45(-) BMSCs were successfully isolated from rats. Labeling rate of SPIO in 25 μg/mL was 94.9%. SPIO labeling did not affect BMSCs survival and proliferation. MRI showed that BMSCs colonized in the liver, whether via spleen or liver injection. Serum levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin in the transplanted rats were significantly lower than in the hepatectomy group at days 1, 3, and 7 after hepatectomy (all P < 0.05), whereas serum albumin levels were significantly higher in the transplanted rats on posthepatectomy day 3 (both P < 0.05). These indicators were not significantly different between the spleen and liver injection approaches.nnnCONCLUSIONSnBMSCs transplantation via liver or spleen injection could significantly accelerate liver healing. In vivo MRI of SPIO-labeled BMSCs can be used to trace real-time liver healing during clinical treatment after hepatectomy.

Clinical, pathological and prognostic characteristics of gastroenteropancreatic neuroendocrine neoplasms in China: a retrospective study

BackgroundGastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare neuroendocrine tumors, and lack of data in Asian populations especially in China. The aim of this retrospective study was to assess the clinical, pathological and prognostic characteristics of GEP-NENs in China.MethodsWe collected clinical and pathological data of 168 patients diagnosed with GEP-NENs and treated at the First and Second Affiliated Hospitals of Dalian Medical University between January 2003 and December 2012. Kaplan-Meier method and log rank analysis was used to analyze the prognostic significance of clinical and pathological characteristics.ResultsMean age was 51.83u2009±u200914.03 and the male-to-female ratio was 1.5:1. Primary sites were the rectum (58.93%), pancreas (13.69%), stomach (9.52%), duodenum (5.36%), colon (4.76%), appendix (4.76%), ileum (2.38%) and jejunum (0.60%). Most patients (95.83%) presented non-functional tumors with non-specific symptoms such as abdominal or back pain (29.17%) and gastrointestinal bleeding (25.60%). Based on the 2010 World Health Organization (WHO) classification, patients were diagnosed with neuroendocrine tumor (NET) (24.40%) or neuroendocrine carcinoma (NEC) (7.14%). The estimated mean survival was 8.94u2009±u20090.28xa0years (95% CI: 8.40-9.48). Male gender, young age, small tumor size and NET tumor type were favorable prognostic factors.ConclusionChinese GEP-NENs patients present characteristics that are similar to American and European patients. However, there is an urgent need to establish a national database for understanding the clinical and epidemiological features of GEP-NENs in China.

Better operative outcomes achieved with the prone jackknife vs. lithotomy position during abdominoperineal resection in patients with low rectal cancer

BackgroundLithotomy (LT) and prone jackknife positions (PJ) are routinely used for abdominoperineal resection (APR). The present study compared the clinical, pathological, and oncological outcomes of PJ-APR vs. LT-APR in low rectal cancer patients in order to confirm which position will provide more benefits to patients undergoing APR.MethodsThis is a retrospective study of consecutive patients with low rectal cancer who underwent curative APR between January 2002 and December 2011. Patients were matched 1:2 (PJ-APRu2009=u200974 and LT-APRu2009=u200937 patients) based on gender and age. Perioperative data, postoperative outcomes, and survival were compared between the two approaches.ResultsHospital stay was shorter with PJ-APR compared with LT-APR (Pu2009<u20090.05). Compared with LT-APR, duration of anesthesia (234u2009±u200950.8 vs. 291u2009±u200969xa0min, Pu2009=u20090.022) and surgery (183u2009±u200944.8 vs. 234u2009±u200960xa0min, Pu2009=u20090.016) was shorter with PJ-APR, and estimated blood losses were smaller (549u2009±u2009218 vs. 674u2009±u2009350xa0mL, Pu2009<u20090.001). Blood transfusions were required in 37.8% of LT-APR patients and in 8.1% of PJ-APR patients (Pu2009<u20090.001). There was no difference in the distribution of N stages (Pu2009=u20090.27). Median follow-up was 47.1 (13.6–129.7) months. Postoperative complications were reported by fewer patients after PJ-APR compared with LT-APR (14.9% vs. 32.4%, Pu2009=u20090.030). There were no significant differences in overall survival, disease-free survival, local recurrence, and distant metastasis (Pu2009>u20090.05).ConclusionsThe PJ position provided a better exposure for low rectal cancer and had a lower operative risk and complication rates than LT-APR. However, there was no difference in rectal cancer prognosis between the two approaches. PJ-APR might be a better choice for patients with low rectal cancer.

Effect of bone marrow mesenchymal stem cells on hepatocellular carcinoma in microcirculation.

This study aims t explore the effect and application of bone marrow mesenchymal stem cells (BMSCs) on hepatocellular carcinoma in microcirculation by observing the angiogenesis of hepatocellular carcinoma in transplanted area. BMSCs were isolated and cultured primarily using the method of whole bone marrow culture and identifying surface antigens of third-generation bone marrow-derived mesenchymal stem cells using flow cytometry. Hepatoma cells cultured with BMSCs-conditioned medium (BMSCs-CM) were assayed using the cell proliferation rate of the MTT method. Nude mice were divided into control group (group A), BMSCs cell transplantation group (group B), HepG-2 cell group (group C), and combined BMSCs and HepG-2 cell cotransplanted group (group D). The result showed that the microvascular density was not significantly different in groups A and B. However, the microvascular density at 14xa0days was higher than 0xa0day in group C (Pu2009<u20090.05). In group D, the microvascular density at 14xa0days was higher than that of 7 and 0xa0days (Pu2009<u20090.05) and 7xa0days was higher than 0xa0days (Pu2009<u20090.05). It was showed that the microvascular density did not get significant difference at 0 and 7xa0days in the four groups (Pu2009>u20090.05). But the microvascular density of group C was higher than groups A and B at 14xa0days (Pu2009<u20090.05), group D was higher than groups A and B at 14xa0days (Pu2009<u20090.05) and group D was higher than group C at 14xa0days (Pu2009<u20090.05). BMSCs could promote the growth of microvascular in hepatoma cells in a transplanted area.

Differential hepatic stem cell proliferation and differentiation after partial hepatectomy in rats

Stem cell‑derived hepatocyte precursor cells represent a promising model for clinical transplantation to diseased livers, as well as for establishment of in vitro systems for drug metabolism and toxicology studies. The present study aimed to establish a new method of induction of hepatocyte differentiation using various factors and evaluate the effect of different partial hepatectomies and the duration of collagenase perfusion on hepatic stem cell proliferation and differentiation. A rat model of hepatic oval cell proliferation was established by partial hepatectomy (PH). Following 73.1 and 83.4% PH, rats underwent perfusion with IV collagenase for 10, 20 and 30 min. Density gradient centrifugation was performed and cells in the supernatant were cultured in various combinations of factors to induce oval cells to differentiate into mature hepatocytes. Cells were characterized for hepatocyte marker expression by morphology, flow cytometry, immunofluorescence and western blot analysis. Hepatic oval cells isolated from rats at 7 and 14 days post‑PH exhibited properties of hepatic stem/progenitor cells. Following culturing in RPMI‑1640 medium with hepatocyte growth factor and fibroblast growth factor‑4, the cells resembled primary human hepatocytes with regard to morphology and expression of the hepatocyte markers, cytokeratin 18 (CK‑18) and α‑1‑fetoprotein (AFP). Optimal differentiation of hepatic stem cells to CK‑18‑ and AFP‑positive cells was observed when stem cells isolated from 83.4% PH rats (7 days following surgery) were perfused with IV collagenase for 20 min. The results of this study provide novel insights into characteristics of rat hepatic stem cells.

Osthole inhibits the tumorigenesis of hepatocellular carcinoma cells

Hepatocellular carcinoma (HCC) accounts for approximately 90% of all cases of primary liver cancer, and the majority of patients with HCC are deprived of effective curative methods. Osthole is a Chinese herbal medicine which has been reported to possess various pharmacological functions, including hepatocellular protection. In the present study, we investigated the anticancer activity of osthole using HCC cell lines. We found that osthole inhibited HCC cell proliferation, induced cell cycle arrest, triggered DNA damage and suppressed migration in HCC cell lines. Furthermore, we demonstrated that osthole not only contributed to cell cycle G2/Mxa0phase arrest via downregulation of Cdc2 and cyclinxa0B1 levels, but also induced DNA damage via an increase in ERCC1 expression. In addition, osthole inhibited the migration of HCC cell lines by significantly downregulating MMP-2 and MMP-9 levels. Finally, we demonstrated that osthole inhibited epithelial-mesenchymal transition (EMT) via increasing the expression of epithelial biomarkers E-cadherin and β-catenin, and significantly decreasing mesenchymal N-cadherin and vimentin protein expression. These results suggest that osthole may have potential chemotherapeutic activity against HCC.

Modulation of transport and metabolism of bile acids and bilirubin by chlorogenic acid against hepatotoxicity and cholestasis in bile duct ligation rats: involvement of SIRT1-mediated deacetylation of FXR and PGC-1α

The purpose of the present study was to investigate the effect and potential mechanism of chlorogenic acid (CA) on liver injury induced by cholestasis in a rat model of bile duct ligation (BDL).

Additional file 1: Figure S1. of Integrin-β5, a miR-185-targeted gene, promotes hepatocellular carcinoma tumorigenesis by regulating β-catenin stability

MHCC-97xa0L cell lysates were incubated with IgG (control) or ITGB5 antibody. The bounded proteins were eluted, resolved by SDS-PAGE, and visualized by CBB staining (upper panel). The band in the ITGB5 lane was identified as β-catenin by mass spectrometry. The obtained peptide sequences by mass spectrometry analysis were shown on the right.(B-D)The RNA levels of miR-185 were analysed by q-RT-PCR. (TIFF 552xa0kb)