Folic acid (FA)-conjugated mesoporous silica nanoparticles combined with MRP-1 siRNA improves the suppressive effects of myricetin on non-small cell lung cancer (NSCLC).

Non-small cell lung cancer (NSCLC) is a common diagnosed cancer disease worldwide and its management remains a challenge. Synergistic cancer therapeutic strategy is interesting for multiple advantages, such as excellent targeting accuracy, low side effects, and promoted therapeutic efficiency. In the present study, myricetin (Myr)-loaded mesoporous silica nanoparticles (MSN) combined with multidrug resistance protein (MRP-1) siRNA was prepared. The surface of the synthesized nanoparticles was modified with folic acid (FA) to promote the therapeutic efficiency of Myr for the treatment of NSCLC. The collected particles were nano-sized and showed a sustained release of Myr in the physiological conditions. FA-conjugated nanoformulations displayed a significant uptake in lung cancer cells compared with that of the non-targeted nanoparticles. The in vitro drug release results suggested a sustained release in FA-conjugated MSN with Myr and MRP-1 nanoparticles compared to the free Myr and MSN combined with MRP-1/Myr. Treatments with FA-conjugated MSN combined with Myr and MRP-1 markedly reduced the cell viability of lung cancer cell lines, including A549 and NCI-H1299, which was accompanied with the decreased number of colony formation. In addition, FA-conjugated MSN loaded with Myr and MRP-1 significantly induced apoptosis in lung cancer cells, along with up-regulated expression levels of cleaved Caspase-3 and PARP. In vivo fluorescence results demonstrated that FA-conjugated MSN with Myr and MRP-1 nanoparticles could specifically accumulate at tumor sites. Compared with free Myr and MSN combined with MRP-1/Myr nanoparticles, FA-conjugated MSN loaded with Myr and MRP-1 nanoparticles could more effectively suppress tumor growth with little side effects. Overall, FA-conjugated nanoparticulate system could provide a novel and effective platform for the treatment of NSCLC.

Hepatic resection for post-operative solitary liver metastasis from oesophageal squamous cell carcinoma.

BACKGROUND: Liver metastasis is common in patients with oesophageal cancer. The effect of operative intervention for post-operative solitary liver metastasis from oesophageal squamous cell carcinoma (ESCC) has not previously been examined. This research was to compare the effect of surgery and non-surgical therapy in patients with post-operative solitary liver metastasis from ESCC. METHODS: We retrospectively analysed the clinical data of 69 consecutive patients with solitary hepatic metastasis who had undergone oesophagectomy for ESCC and were subsequently referred to the First Affiliated Hospital of Zhengzhou University from January 2005 to December 2013. The survival rates of the surgical and non-surgical groups were compared. RESULTS: There were 26 patients in the surgical group and 43 patients in the non-surgical group. There was no operative death in the surgical group. Post-operative complications were observed in six patients, and all of these patients recovered after additional treatments. Patients in the surgical group had 1- and 2-year cumulative survival rates of 50.8 and 21.2%, respectively, which were significantly higher than the 31.0 and 7.1% survival rates of patients in the non-surgical group (P < 0.05). In each group, the patients with a disease-free interval (DFI) lasting >12 months had a better survival rate than those with a DFI lasting ≤12 months (all P < 0.05). CONCLUSIONS: Operative intervention is a better treatment choice for patients with post-operative solitary liver metastasis from ESCC, especially for patients with a DFI lasting >12 months. Patients selected for hepatic resection should be considered on an individual basis through a multidisciplinary team of specialists.

Genetic Polymorphisms in Long Noncoding RNA H19 Are Associated With Susceptibility to Breast Cancer in Chinese Population.

H19, a maternally expressed imprinted gene transcribing a long noncoding RNA, has previously been reported to be involved in tumorigenesis and cancer progression. However, the association between the H19 polymorphisms and breast cancer (BC) susceptibility has remained elusive. The aim of this study was to evaluate the associations between 2 H19 haplotype tagging SNPs (rs3741219 T>C, rs217727 C>T) and the risk of breast cancer. Our study comprised 464 BC patients and 467 cancer-free controls in China. rs3741219 and rs217727 were genotyped with polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) and created restriction site PCR (CRS-RFLP) assays, respectively. False-positive report probability (FPRP) was calculated to test the false-positive association. On performing univariate analysis, no significant association between H19 polymorphisms (rs3741219 and rs217727) and BC was observed. However, in further stratified analyses, CT+TT genotypes of rs217727 had a significantly lower risk of breast cancer among women with number of pregnancy >2 (OR = 0.79; 95% CI = 0.55-0.97). CT genotype of rs217727 was associated with ER positivity (OR = 2.19; 95 % CI = 1.07-4.45) and HER-2 positivity (OR = 1.34; 95 % CI = 1.05-2.12). It was proved that our results were less likely to be false positives according to false-positive report probability calculation. Our findings extend available data on the association of H19 polymorphisms and BC susceptibility. Further validation in large population or cohort studies is needed.

Quantitative assessment of the association between DNMT3B-579G>T polymorphism and cancer risk.

BACKGROUND: DNA methyltransferase 3B (DNMT3B) has been discovered to play an important role in tumorigenesis. However, the association between DNMT3B-579G>T and the cancer risk has not been demonstrated. OBJECTIVE: The aim of this study is to provide a precise quantification for the association between DNMT3B-579G>T and the cancer susceptibility. METHODS: We performed a systematic literature review and assessed the methodological quality of included case-control designed studies based on Newcastle-Ottawa Scale (NOS). Pooled odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) were calculated to assess the strengths of the association. RESULTS: We identified 18 studies for pooled analyses. Overall, the results demonstrated that the DNMT3B-579G>T polymorphism was significantly associated with a subtly decreased cancer risk (GT vs TT: OR = 0.78, 95%CI: 0.70-0.87, P< 0.01; GT + GG vs TT: OR = 0.81, 95%CI: 0.68-0.97, P= 0.02), especially in the Asian population and in colorectal cancer subgroup. In addition, when stratified for source of controls, the results of population-based subgroup showed the GT genotype might have a significantly decreased cancer risk, but not hospital-based subgroups. CONCLUSIONS: DNMT3B-579G>T polymorphism might contribute to the susceptibility of cancers especially in the Asian population and for colorectal cancer.

Expression heterogeneity research of ITGB3 and BCL-2 in lung adenocarcinoma tissue and adenocarcinoma cell line.

OBJECTIVE: To analyze expression heterogeneity of Integrin beta 3 (ITGB3) and B-cell lymphoma 2 (BCL-2) in lung adenocarcinoma tissue and adenocarcinoma cell line and further provide theoretical direction for molecular biological research of lung adenocarcinoma. METHODS: Tissue microarray was used to observe relation among expression, heterogeneitpy and clinical characteristics of ITGB3 and BCL-2 in lung cancer. RESULTS: ITGB3 and BCL-2 increased significantly in A549 cells in CAFs group withß-actin as control; the expression level of BCL-2 also increased in ITGB3 transfected cells with GFP plasmid transfected A549 cells as control; immunohistochemistry staining showed that positive rates of ITGB3, ITGB1 and BCL-2 in normal lung tissues were 0, the positive rates in lung adenocarcinoma were 7.04%, 84.51% and 4.23%, respectively; in the results of immunohistochemistry staining, the expression of Girdin protein in lung adenocarcinoma was homogeneous, however protein expression of ITGB3, ITGB1 and BCL-2 showed different patterns in the same location with significant heterogeneity; majority of ITGB3, ITGB1 or BCL-2 positive tissue showed heterogeneity that expression in trailing edge was higher than that of trailing edge in lung adenocarcinoma tissue, the patients with BCL-2 heterogeneity showed higher lymph node metastasis ratio and lower clinical stage (P<0.05); and the expression of ITGB3 and the clinical characteristics of patients were not significant related (P>0.05). CONCLUSIONS: Expression of ITGB3 and BCL-2 in lung adenocarcinoma and adenocarcinoma cell line showed heterogeneity that expression in trailing edge was higher than that of trailing edge, which may play an important role in promoting tumor lymph node metastasis and vascular invasion, and provides a new research direction for exploration of lung adenocarcinoma metastasis mechanism.

[KRAS and epidermal growth factor receptor gene mutation in non-small cell lung cancer].

OBJECTIVE: To study KRAS and epidermal growth factor receptor (EGFR) mutations in primary non-small cell lung cancer (NSCLC) and their association with the effects of targeted therapy. METHODS: Gene mutations of KRAS and EGFR in both primary tumors and local lymph node metastases from 150 patients with NSCLC were analyzed by direct sequencing. Twelve of the patients were given gefitinib as neoadjuvant therapy after EGFR-TKI sensitive mutations had been detected in biopsies of mediastinal lymph node metastases. RESULTS: Two primary tumors and 10 metastases were identified to have KRAS mutations, while 35 primary tumors and 44 metastases were found to have EGFR mutations. KRAS and EGFR mutation status was different between primary tumors and corresponding metastases in 6.7% (10/150) and 8.67% (13/150) patients, respectively. One patient with no TKI sensitive mutations in the primary tumor showed disease progression with gefitinib therapy. CONCLUSIONS: Our results suggest that a considerable proportion of NSCLC in Chinese patients showed discrepancy in KRAS and EGFR mutation status between primary tumors and corresponding metastases. This observation may have important implications for the use of targeted TKI therapy in the treatment of NSCLC patients.

[Effect of extract of ginkgo biloba leaves on the precondition of liver graft in rat liver transplantation].

OBJECTIVE: To explore the effect of extract of ginkgo biloba leaves on the precondition of liver graft in rat liver transplantation. METHODS: Male Sprague-Dawley rats were used as donors and recipients of orthotopic liver transplantation (OLT), and were randomly divided into extract of ginkgo biloba leaves group (Egb), NS control group (NS), and sham operation group (SO) according to whether the extract of ginkgo biloba leaves was injected by the venous (40 mg/kg) 1 h before the liver grafts harvesting. The rats were killed at 2 h, 6 h, and 24 h after the ischemia/reperfusion. The serum concentrations of ALT and AST were determined and the liver tissue were sampled to observe the expression of TNF-alpha and IL-1. RESULTS: After the ischemia/reperfusion the serum concentration of ALT and AST and expressions of TNF-alpha and IL-1 in the hepatic tissue in the NS group significantly increased (p<0.01), and the hepatocytic morphologic change was obvious compared with the SO group. The treatment of ginkgo biloba extract significantly decreased the serum concentration of ALT and AST and the expressions of TNF-alpha and IL-1 in the hepatic tissue in EGb group compared with the NS group (p<0.01), and relieved the hepatocyte swelling and necrosis. CONCLUSION: Ginkgo bilobA extract may decrease the release of TNF-alpha and IL-1 by inhibiting activation of kuffer cells and regulate the cell factors to protect the live.