Since the development of molecular biology,the treatment of advanced non-small cell cancer is shifting from traditional chemotherapy into molecular targeted therapy with genotyping as a guide′s help.The most widely used is epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs).With the appli-cation of EGFR-TKIs,the resistances to EGFR inhibitors are paid more and more attention,in recent years. The main mechanisms of acquired resistances are as follows:secondary mutation of the EGFR gene,amplifica-tion of c-MET,Her2 and other target genes,histological transformation,activation of the bypass mechanisms, loss of p53,the relief of negative feedback loops,overlap of mechanisms,etc.

Objective:To investigate the inhibitory effect of recombinant mutant human tumor necrosis factor(rmhTNF-?)combined with cisplatin(DDP)against transplanted Lewis lung carcinoma(LLC)in mice,and to explore the related mechanism.Methods:LLC cells were subcutaneously inoculated into C57BL/6 mice at the right axilla and the mice were randomly divided into 4 groups:sodium chloride(control group),DDP group,rmhTNF-? group,rmhTNF-? plus DDP group.On the 7th day after inoculation the diameter of the tumor reached 0.6 cm;the corresponding agents were intratumorally injected for 3 d.All mice were sacrificed 1 d later and the tumors were obtained,weighed,and the tumor inhibitory rate was calculated.Flow cytometric analysis was used to examine cells apoptosis and cell cycle.Expression of survivin mRNA was examined by RT-PCR.Results:(1)The tumor inhibitory rates of the DDP plus rmhTNF-? group(36.61%)was significantly higher than those of the DDP group(17.12%)and rmhTNF-? group(15.83%,P

With the rapid growth of incidence of non-small cell lung cancer (NSCLC),more and more studies have been made about its occurrence,development and metastatic mechanism m recent years.Researches about Fas/FasL protein expression and Fas/FasL-mediated apoptosis,immune escape mechanism and their roles in the pathogenesis,progression and prognosis of lung cancer are constantly emerging.Discussion about the roles of Fas/ FasL system in NSCLC could provide evidence for early diagnosis,prognosis prediction and new treatment of NSCLC.

Objective This study aimed at retrospective analysis of some metastatic breast cancer cases,investigated the recurrence of brain metastases of metastatic breast cancer in patients with risk factors,and provided a reference for the implementation of prevention strategies in the treatment plan and a reasonable choice.Methods A total of 796 breast cancer cases was visited,of whom 456 patients with recurrent metastatic breast cancer,in which 61 patients were with brain metastasis.The follow-up data were analyzed with SPSS13.0 software.x2 was used to test the age,estrogen receptor (ER),progesterone receptor (PR),cerbB-2 expression,lymph node metastasis,and brain metastasis.The COX proportional hazard model was used to analyze the recurrence and metastasis in patients with single-factor,multi-factor analysis,in order to obtain the independent prognostic factors.Results The x2 tests that group age ≤ 35 years,hormone receptor-negative,CerbB-2 (2 +)/(3 +) has a higher risk than another group (x2 =24.92,8.28,4.02,P ＜0.01 orP ＜0.05).COX univariate analysis showed that patient age,tumor size,ER and PR expression,CerbB-2 expression,lung metastases were looked.as the first metastatic site and hormone therapy.Those were significant factors whether the patient suffered from brain metastasis (P ＜ 0.05).COX multivariate analysis showed that age,ER and PR expression,CerbB-2 expression,and lung metastases were looked as the first metastatic site acted as an independent prognostic factor for brain metastasis (P ＜0.05).Conclusions Age,ER and PR expression,CerbB-2 expression,lung metastases as the first metastatic site are the independent prognostic factors for brain metastasis.

Molecular markers have been widely used in the treatment of breast cancer. Cell proliferation markers Ki-67 antigen representing breast neoplasms proliferative activity is associated with clinic pathological features and prognosis and has an important predictive value in assessing the effect of neoadjuvant chemotherapy and endocrine therapy. High expression of Ki-67 is a bad prognostic factor of breast cancer, which is highly related to tumor progression, metastasis and prognosis.

In recent years, a number of studies have focused on malignant tumor patients with coagulant function abnormality, which causes thrombus complications, tumor growth, infiltration of closely related cells, transfer, and so on. These factors directly affect prog-nosis. Heparin is a widely known anticoagulant, and anticoagulation drugs have been included in malignant tumor treatment guide-lines. Ameaican Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and American College of Clinical Pharmacy (ACCP) recommend low-molecular-weight heparin as the first choice for the treatment of cancer thrombosis. However, the prophylactic use of anticoagulant drugs in patients with tumor control disease, as well as the prolonged PFS and OS mechanism, is still unclear. The recently publishedReport of incidence and mortality in China(2012) suggests that lung cancer incidence and mortality ranked first place. This review will introduce several aspects of anticoagulant drugs that can be used to control the recurrence of malig-nant tumor metastasis and prolong the survival mechanism of pathophysiology.

The article describes the molecular structure and biological characteristics of thrombin and thrombin receptor.It manly discusses thrombin caused the mechanisms of cerebral edema formation after intracerebral hemorrhage by prormoting cell inflammtory reaction,neuron apoptosis and injurying blood-brain barrier.

Objective To investigate the possible effects and underlying mechanisms of desferroxamine (DFO) preconditioning against hypoxia in neurons. Methods Cortical neurons were cultured in DFO under ischemia condition of oxygen-glucose deprivation (OGD). Cell viability was determined by cell counting kit-8 (CCK-8) method; apoptotic cell ratio was examined with Hoechst 33342 staining; the morphological change was observed. Middle cerebral artery was occluded with or without DFO administration to establish the cerebral ischemia rat model. Infarct sizes were examined by TIC staining, and the neurological severity score was evaluated. Meanwhile immunofluorescent staining was employed to detect the protein synthesis of hypoxia inducible factor-1 (HIF-1) and erythropoietin (EPO), RT-PCR was performed to detect the mRNA expression of HIF-1 and EPO as well Results Neuronal viability kept in 49% (OGD group was 25%, t =8. 544, P<0. 05), the rate of apoptosis was 38% (OGD group was 30%, t = 4. 409, P <0.05 ) after administration of DFO (post-DFO) , the morphology of neurons improved. In the model of focal cerebral ischenfia of 30 mg/kg group, neurological severity score was reduced, the percentage of brain infarct decreased 8.5% (t=4.649, P<0.05) 3 days post-DFO(vs control). In the 100 mg/kg group, neurological severity score was 7.44 ±0.39 (t=2.903, P<0.05 ) ,5.60±0.47 (t=10.143, P < 0.01 ) ,6.97 ±0.73 (t=3.142, P<0.05 ), the percentage of brain infarct decreased 12. 0% (t=5.056, P<0.05), 32.3% (t =10.993, P<0.01), 10.6% (t =4.385, P<0.05)2,3 and7 days post-DFO(vs control), respectively. Immunofluorescent staining found synthesis of HIF-1α and EPO in cultured cortex neurons after DFO pretreated; HIF-1α and EPO were upregulated in the neurons of rat brain after DFO pretreated. The mRNA of HIF-1α and EPO upregulated in vivo and in vitro. Conclusion DFO preconditioning can protect the brain against ischemic damage, which is related to the protective effect on neurons. The mechanism of DFO preconditioning may be involved in the expression of HIF-1α and EPO in vivo and in vitro.

Objective:To investigate the reversing effect of recombinant mutant human tumor necrosis factor (rmh-TNF) on cisplatin(DDP)-resistant human ovarian cancer cell line SKOV3/DDP in vitro and the related mechanism. Methods: DDP-resistant human ovarian cancer cell line SKOV3/DDP was cultured in vitro. The cytotoxic effect of rmh-TNF to SKOV3/DDP cells was examined by MTT assay and the nontoxic dose of rmh-TNF was identified. The changes of DDP resistance was observed after cells were treated with nontoxic dose of rmh-TNF by MTT assay. The expre-ssion of GST-? protein was examined by flow cytometry at different periods after rmh-TNF intervention; RT-PCR was used to analyze the expression of MDR1gene in SKOV3/DDP cells before and after rmh-TNF treatment. Results:(1)rmh-TNF at 50-122.34 U/ml showed no evident inhibitory effect on the growth of SKOV3/DDP cells (the cell survival rate higher than 90%); and 100 U/ml was chosen for the reversing experiment ( nontoxic dose).(2)IC50 values of SKOV3/DDP cells were (23.29?0.43), (8.97?0.69) and (6.43?0.79) ?g/ml after treatment with DDP for 24, 48 and 72 h, respectively; and the values decreased to (19.50?0.50),(4.34?0.43) and (2.44?0.02)?g/ml after combined treatment with 100 U/ml rmh-TNF, respectively.(3)Expression of GST-? protein and MDR1gene decreased with the prolongation of rmh-TNF treatment. Conclusion: rmh-TNF has reversal effect on the DDP-resistant cell line SKOV3/DDP, and the mechanism may be associated with the down-regulation of GST-? protein and MDR1gene expression.

In order to make a report on 90 cases of insomnia treated by the Wei-defensive qi-regulating and brain-strengthening needling technique,as a clinical subject of the multiple center,for assessing the preliminary standardized indications and operating methods and making an initial summary for writing the draft of the technique operation.Methods:By ratio of 1:1,the patients in conformity with the criteria were randomly divided into the experimental group and control group.In the experimental group,45 cases were treated with the Wei-defensive qi-regulating and brain-strengthening needling technique on Baihui (GV 20),Dazhui(GV 14),Shenmai(BL 62),Zhaohai(KI 6),plus ear points.In the control group,45 cases were treated with routine acupuncture on Sishencong(Ex-HN 1),Shenmen (HT 7),Sanyinjiao(SP 6),etc.The therapeutic effects in the two groups were observed and assessed in comparison.Results:The results showed cure in 15 cases.remarkable effect in 27 cases,effect in 42 cases,failure in 6 cases,and the total eriective rate in 94.4% in 90 cases of insomnia.In the three centers,the statistic management was performed based upon PSQI integral and showed significant difference(P＜0.01),and no significant difference among various groups(P＞0.01).Conclusion:The therapeutic effect in the treatment of insomnia by Wei-defensive qi-regulating and brain-strengthening needling technique is better than the control group and the therapeutic effect and methods in various centers are stable.without any deviation.