Objective To research the promoter methylation level of RAS association domain family 1A (RASSF1A) and RASSF1A gene mRNA expression level in cervical cancer tissue, and to analyze their relationships with clinicopathological parameters of cervical cancer and the clinical significance.Methods The RASSF1A gene promoter methylation and RASSF1A gene mRNA were detected respectively by methylation specific PCR and quantitative real-time PCR method in 40 cases of cervical cancer tissues and corresponding adjacent tissues.Results RASSF1A mRNA expression level in cervical cancer (0.26±0.05) was significantly lower than that in adjacent tissues (0.28±0.03), and the difference was statistically significant (t=2.27, P=0.026).The methylation rate of RASSF1A gene promoter region (0.71%±0.04%) was significantly higher than that in adjacent tissues (0.66%± 0.03%), and the difference was statistically significant (t=6.78, P=0.000).The expression of RASSF1A mRNA was significantly correlated with pathological differentiation (t=3.31, P=0.002), International Federation of Gynecology and Obstetrics (FIGO) stage (t=2.13, P=0.040), lymphatic metastasis (t=2.56, P=0.015).The promoter methylation level of RASSF1A gene was significantly correlated with pathological differentiation (t=2.08, P=0.045), FIGO stage (t=2.66, P=0.011), lymphatic metastasis (t=2.22, P=0.033), depth of invasion (t=2.12, P=0.041).Conclusion The RASSF1A gene promoter region methylation level and the RASSF1A gene mRNA expression level are associated with the malignant degree of cervical carcinoma.The RASSF1A gene promoter region methylation level may be used as a reference indicator for predicting the risk of metastasis of cervical cancer.

Objective To investigate the recent curative effect and adverse reactions of radiotherapy combined with temozolomide in non-small cell lung cancer (NSCLC) patients with brain metastases.MethodsThe clinical date of 51 NSCLC patients with brain metastases were retrospective analyzed in Department of Radiation Oncology of Affiliated Hospital of Hebei University.Patients were divided into experimental group (n=26) and control group (n=25) according to the different treatment methods.The experimental group underwent whole brain and local tumor radiotherapy plus temozolomide.The control group only received whole brain and local tumor radiotherapy.The recent curative effect and adverse reactions of the two groups were analyzed.Results The Karnofsky performance status score of patients in the experimental group was obviously improved than that in the control group (76.2±6.4 vs.72.8±5.3), with a significant difference (t=2.06, P=0.04).The total effective rate in the experimental group was higher than that in the control group (80.8% vs.64.0%), but there was no statistically significant difference (χ2=1.80, P=0.18).Compared with the control group, the incidences of nausea and vomiting (80.8% vs.28.0%) and bone marrow suppression (84.6% vs.24.0%) in the experimental group were significantly higher, with significant differences (χ2=14.33, P=0.00;χ2=18.91, P=0.00).There were similar incidences of headache (69.2% vs.60.1%), liver and kidney damage (73.1% vs.64.0%) in the two groups, with no significant differences (χ2=0.47, P=0.49;χ2=0.47, P=0.49).Conclusion Radiotherapy combined with temozolomide can improve the quality of life in NSCLC patients with brain metastases, which has controllable and tolerable adverse reactions.

Objective To establish the subcutaneous transplantation tumor models with Lewis lung adenocarcinoma in C57BL/6 mice, and to observe the influence of oHSV2, DDP and drug combination on tumor volume, median survival time and weight of tumor-burdened mice.Methods Subcutaneous transplantation tumor models were established with Lewis lung adenocarcinoma in tumor-burdened mice.Tumor-burdened mice were randomly divided into the control group, oHSV2 group, DDP group, oHSV2/DDP sequential group, DDP/oHSV2 sequential group and oHSV2+DDP combination group with 12 rats in each group using the random number table method.The tumor size and weight of mice were measured every 3 days.Results On the 21st day, the tumor size of tumor-burdened mice in every group was as follows: control group (1.82±0.06)cm3, oHSV2 group (0.63±0.05)cm3, DDP group (0.58±0.03)cm3, oHSV2/DDP sequential group (0.49±0.05)cm3, DDP/oHSV2 sequential group (0.42±0.04)cm3, and the difference was statistically significant (F=1 359.01, P=0.000).The data in oHSV2+DDP group were put away because of premature death in mice.The differences were statistically significant between control group and oHSV2 group (P=0.000), control group and DDP group (P=0.000), control group and oHSV2/DDP sequential group (P=0.000), control group and DDP/oHSV2 sequential group (P=0.000), oHSV2 group and DDP group (P=0.017), DDP group and DDP/oHSV2 sequential group (P=0.000), oHSV2/DDP sequential group and DDP/oHSV2 sequential group (P=0.001).The weight of tumor-burdened mice in every group was listed as follows: control group (21.64±0.40)g, oHSV2 group (21.34±0.37)g, DDP group (15.96±0.43)g, oHSV2/DDP sequential group (19.04±0.31)g, DDP/oHSV2 sequential group (16.34±0.30)g, and the difference was statistically significant (F=588.67, P=0.000).The difference was not statistically significant between control group and oHSV2 group (P=0.076).However, the differences were statistically significant between control group and DDP group (P=0.000), control group and oHSV2/DDP sequential group (P=0.000), control group and DDP/oHSV2 sequential group (P=0.000), oHSV2 group and DDP group (P=0.000), oHSV2 group and oHSV2/DDP sequential group (P=0.000), DDP group and DDP/oHSV2 group (P=0.013), oHSV2/DDP sequential group and DDP/oHSV2 sequential group (P=0.000).The median survival time of tumor-burdened mice in every group was displayed as follows: control group 23 d , oHSV2 group 32 d, DDP group 30 d, oHSV2/DDP sequential group 37 d, DDP/oHSV2 sequential group 39 d, oHSV2+DDP combination group 16 d, and the difference was statistically significant (χ2=120.81, P=0.000).The differences were statistically significant between control group and oHSV2 group (χ2=10.88, P=0.001), control group and DDP group (χ2=10.69, P=0.001), oHSV2 group and DDP/oHSV2 sequential group (χ2=10.09, P=0.001), DDP group and DDP/oHSV2 sequential group (χ2=9.67, P=0.002).However, the differences were not statistically significant between oHSV2 group and DDP group (χ2=0.00, P=0.996), oHSV2/DDP sequential group and DDP/oHSV2 sequential group (χ2=2.70, P=0.100).Conclusion On the premise of that the weight of mice is no affected, oHSV2 can inhibit the tumor size and prolong the median survival time of tumor-burdened mice effectively, and the effect of DDP/oHSV2 sequential group is the most significant.This article provides an experimental basis for exploring therapeutic methods of lung adenocarcinoma.

Objective To investigate the relationship between the expression of vascular endothelial growth factor C (VEGF-C) and vascular endothelial growth factor receptor-3 (VEGF-R3) in peripheral blood of patients with lung cancer and the pathological characteristics, and to assess the ability to evaluate lymphatic and distant metastasis of the two marks.Methods VEGF-C and VEGF-R3 were detected by enzyme-linked immunosorbent assay (ELISA) in 124 patients with lung cancer and 30 normal controls, and used to analyze the relationship with the pathological characteristics of lung cancer.Results The serum levels [M(QR)] of VEGF-C and VEGF-R3 in patients with lung cancer were 283.57 (120.70) pg/ml and 62.72 (43.02) ng/ml, significantly higher than the control whose VEGF-C and VEGF-R3 were 234.62 (129.20) ng/ml and 43.08 (17.07) pg/ml, respectively (Z=-2.840, P=0.005;Z=-3.834, P<0.001).No correlation was found between the expression of VEGF-C and age, sex, primary tumor site, T stage (Z=-0.949, P=0.343;Z=-0.454, P=0.649;Z=-1.168, P=0.243;Z=-1.694, P=0.090).But the expression of VEGF-C was significantly related with pathologic type, N stage and M stage (χ2=8.829, P=0.012;χ2=27.148, P<0.001;Z=-2.221, P=0.026).However, the expression of VEGF-R3 was not correlated with age, sex, the site of the primary lesion, pathological type and T, N, M stage (Z=-0.558, P=0.577;Z=-0.599, P=0.549;Z=-0.703, P=0.482;χ2=1.166, P=0.558;Z=-0.680, P=0.496;χ2=0.353, P=0.950;Z=-1.523, P=0.128).Conclusion The expressions of VEGF-C and VEGF-R3 in patients with lung cancer are higher than those in normal control, and the expression of VEGF-C is related with patho-logic type, N stage and M stage.The detection of VEGF-C in peripheral blood of lung cancer is expected to be an assistant marker for the evaluation of lymph node metastasis and blood metastasis, but VEGF-R3 does not show its value.

Objective To investigate the function of tripartite motif protein 22 (TRIM22) and the interaction with eukaryotic translation initiation factor-4E (eIF4E) in the differentiation of NB4 cells, one kind of acute promyelocytic leukemia cells, which elucidates the mechanism of TRIM22 targeting to regulate eIF4E.Methods The model of NB4 cells inducing differentiation was established in vitro.The expression changes of gene and protein of TRIM22 and eIF4E were detected by using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting.In addition, the effect on cell function and protein expression level of eIF4E after adopting electroporation technology to depress or over-express TRIM22 was detected by CCK-8 and flow cytometry.Finally, the interaction of TRIM22 and eIF4E was verified by using co-immunoprecipitation (CO-IP).Results The mRNA relative expression level of TRIM22 was gradually increasing from 1.01±0.15 to 30.98±2.79 (F=280.700, P=0.000), and the protein relative expression level was gradually increasing from 0.22±0.03 to 0.51±0.05 (F=51.430, P=0.000) after the all-trans-retinoic acid (ATRA) induction for NB4 cell.However, the mRNA relative expression level of eIF4E was gradually decreasing from 1.01±0.09 to 0.47±0.06 (F=20.520, P=0.000), with the same trend, the protein relative expression level was gradually decreasing from 0.97±0.02 to 0.64±0.09 (F=14.700, P=0.001).The expression level of PE-CD11b in the TRIM22 over-expression group with ATRA detected by flow cytometry [(78.80±2.00)%] was higher than that in the transfection group of empty vetor with ATRA [(58.70±2.70)%] (t=9.535, P=0.000) and the cotransfection group with ATRA [(61.60±3.80)%] (t=8.187, P=0.000).Meanwhile, the protein level of eIF4E changed reversely after over-expressing the gene level of TRIM22 (t=4.985, P=0.007).The CO-IP experiment was used to verify the interaction of TRIM22 and eIF4E.ConclusionTRIM22 is able to promote the cell differentiation during the process of NB4 cells differentiation.Furthermore, eIF4E is a target of TRIM22 for binding with, which plays an important role in depressing the expression of eIF4E.

Pancreatic cancer is one of the most malignant tumors.Targeted therapy has become an important part of the treatment of pancreatic cancer.The signaling pathways such as hepatocyte growth factor/c-MET (HGF/c-MET) signaling pathway, inhibition of which may exerts an antitumor effect, play extremely important roles in the occurrence and development of pancreatic cancer.Therefore, the research of HGF/c-MET targeted inhibitors opens up a new avenue for treatment of pancreatic cancer.

The development of cholangiocarcinoma is slow, but its metastasis is extremely quick.When the tumor is found, the patients often have missed optimal operation period, and there is a lack of effective diagnostic indexes at present.In recent years, with the rapid development of molecular biology, studies find that microRNAs (miRNAs) are closely associated with cholangiocarcinoma.Because of miRNAs have great stability in various types of body fluids, so miRNAs in serum/plasma and bile are expected to become potential biomarkers in the diagnosis of cholangiocarcinoma.

As the leading cause of death among lung cancer patients, brain metastasis occurs in approximately 10 percent of non-small cell lung cancer (NSCLC) patients at first diagnosis.Whole-brain radiation therapy (WBRT) is still the standard treatment for patients with brain metastasis, however, the efficacy of WBRT reaches a plateau.It has been proved that tyrosine kinase inhibitors (TKIs) make considerable therapeutic effect for NSCLC patients with brain metastasis.The combination therapy of TKIs with WBRT may provide new major treatment for epidermal growth factor receptor (EGFR) mutant NSCLC with brain metastasis.

Small cell lung cancer (SCLC) is a highly malignant tumor, which is very sensitive to first-line chemotherapy, but easy to recurrence and metastasis early.So it always has poor prognosis.Second-line therapy for SCLC develops slowly.Topotecan is the only drug approved by US Food and Drug Administration as a second-line chemoradiotherapy.Numerous studies on molecular targeted therapy and immunotherapy are being carried out, but most of them have no or little benefit.Rovalpituzumab tesirine (Rova-T) targeted antibody-drug conjugate (ADC) which is published at the 2016 American Society of Clinical Oncology Annual Meeting shows a good anti-tumor activity, which seems to bring a new dawn of molecular targeted therapy.

The radiation techniques for lung cancer stereotactic body radiotherapy (SBRT) include intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT).Concerning the target conformity and dosimetric homogeneity index, HT and VMAT technologies are superior to IMRT.On the contrary, HT and VMAT technology can increase low dose area irradiated of lung.Comparing to other two technologies, VMAT can obviously shorten the treatment time.At present, there is no consensus how to choose individually optimized radiotherapy technology for different location and stages lung tumors.