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Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 80%-85% of all patients with lung cancer, the majority of patients with lung cancer at the time of diagnosis is in the advanced stage. The development of target therapy based on has changed the mode of treatment in patients with advanced NSCLC. In NSCLC, epidermal growth factor receptor mutation (EGFR) fusion with echinoderm microtubule-associated protein-like4-anaplastic lymphoma kinase (EML4-ALK) has been shown to be a powerful biomarker. It is well known that KRAS is also NSCLC one of the most common mutations in oncogenes, although more than 20 years ago KRAS mutation was found in NSCLC. At present, although there are many drugs used to treat NSCLC patients with KRAS mutation, there is no selective or specific inhibitor for the direct elimination of KRAS activity. NSCLC patients with KRAS mutation have poor responsiveness to most systemic therapy. However, individualized therapy for activated signaling pathways with targeted drugs has a good effect on the prognosis of NSCLC patients with KRAS mutation. In addition, the prognostic and predictive role of KRAS mutation in NSCLC remains unclear. In this review, we focus on the research progress of NSCLC with KRAS mutation, including molecular biology, clinicopathological features, prognosis and prediction of KRAS mutation, which will help to improve the understanding of NSCLC in KRAS mutation. .
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Animals , Humans , Carcinoma, Non-Small-Cell Lung , Genetics , Lung Neoplasms , Genetics , Mutation , Proto-Oncogene Proteins p21(ras) , GeneticsABSTRACT
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.
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Objective To analyze the correlative factors of anemia in patients with non-small-cell lung cancer (NSCLC), and to explore the impact of anemia on prognosis.Methods The clinical data of 473 patients with NSCLC treated at the first time from January 2008 to November 2012 in the Fourth Hospital of Hebei Medical University were analyzed retrospectively.Results There were 273 patients (57.72 ％) with anemia.Anemia occurred in different age (x2 =3.459, P =3.459), different albumin level (x2 =70.648, P =70.648), different PS score (x2 =10.222, P =10.222), whether recent surgery (x2 =4.956, P =4.956), whether recent chemotherapy (x2 =3.627, P =0.037), and other factors.By multiple factors analysis, hypoalbuminemia was an independent risk factor for anemia (P ＜ 0.05).The median OS of the anemia patients was shorter than that of the patients without anemia (15 months vs 17 months, P ＜ 0.05).Conclusions Hypoalbuminemia is the independent risk factor for emergence of anemia.Anemia is the prognosis indicator of shorten survival period, which is an independent factor of prognosis in the NSCLC.
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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.
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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.
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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.
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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.
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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
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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.