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The inflammatory state of tumor microenvironment play an important role in non-small cell lung cancer (NSCLC) drug resistance. As the key signal pathway connecting inflammation and tumor, activated signal transduction and transcriptional activation factor 3 (STAT3) leads togenetic abnormal expression, gene silencing, genomic instability, etc. in tumor cells, and induces therapeutic resistance. STAT3 has thepotential to be a new target for reversal of resistance. In this review, we summarize the progress of STAT3 in acquired drug resistance of NSCLC, explore the possibility of STAT3 as a new target to reverse drug resistance, and provide basic theories for the new clinical treatment strategy of acquired drug resistance in NSCLC. .
ABSTRACT
BACKGROUND@#Epidermal growth factor receptor (EGFR) mutation non-small cell lung cancer (NSCLC) is an important subtype of lung cancer. The incidence of malignant pericardial effusion (MPCE) in EGFR-mutant NSCLC patients is high. However, there are few researches on the treatmentof this type of patients.@*METHODS@#We collected data on clinical characteristics and treatment of advanced NSCLC patients who harboring EGFR mutants and MPCE between January 2010 and December 2016. The treatments were divided into three groups: oral gefitinib combined with pericardial perfusion of hydroxycamptotheci (HCPT) group (gefitinib/HCPT); intravenous chemotherapy combined with pericardial perfusion of HCPT group (chemotherapy/HCPT) and gefitinib monotherapy group. And we retrospectively analyzed patients' outcomes in three groups.@*RESULTS@#In 273 advanced NSCLC patients with EGFR mutations, 29 cases had pericardial effusion, among which 6 patients with small amount of pericardial effusion were excluded, and 23 patients were analyzed. Median pericardium progression free survival (PFS) was 247 days. PFS for gefitinib/HCPT group (460 days) was superior to PFS for chemotherapy/HCPT group (94 days, P=0.008) and gefitinib monotherapy group (131 days, P=0.032). As for the efficacy of primary pulmonary lesions, the efficacy in gefitinib/ HCPT group was superior to chemotherapy/HCPT group [objective response rate (ORR): 33.3% vs 12.5%; disease control rate (DCR): 86.7% vs 62.5%]. There is no difference of ORR and DCR between gefitinib/HCPT group and gefitinib monotherapy group. No obvious adverse reaction was observed in all three groups.@*CONCLUSIONS@#First-line gefitinib therapy combined with pericardial perfusion of HCPT can improve pericardium PFS for advanced NSCLC patients who harboring EGFR mutants andmalignantpericardial effusion. This finding should be confirmed further through multicenter, prospective clinical trials with large sample size.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Carcinoma, Non-Small-Cell Lung , Drug Therapy , Metabolism , Pathology , Disease-Free Survival , ErbB Receptors , Metabolism , Gefitinib , Lung Neoplasms , Drug Therapy , Metabolism , Pathology , Perfusion , Pericardial Effusion , Pericardium , Quinazolines , Therapeutic Uses , Retrospective Studies , Treatment OutcomeABSTRACT
MicroRNAs(miRNAs)are a class of small(22 nucleotides)non-coding RNAs which play important roles in diverse biological and pathological processes.The dysregulation of miRNA expression is closely related to the development and progression of malignant tumors in humans.DNA methylation is a kind of epigenetic modification in human genome.Both hypermethylation and hypomethylation of DNA are closely related to different kinds of tumors,including gastric cancer.
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Angiogenesis plays a critical role in growth and metastasis of lung cancer.The strongest tumor angiogenesis factor known is the vascular endothelial growth factor (VEGF).Therefore,anti-VEGF therapy which can restrain tumor angiogenesis is an important form of the targeted therapy of lung cancer.The expression of VEGF is also significant to the prognosis of lung cancer.
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Targeted therapy combined with chemotherapy has achieved great success in palliative treatment for metastatic colorectal cancer.Recent studies gave more emphasis on new fields,such as maintenance treatment,adjuvant treatment and the prognostic & predictive biomarker.These advances have been gradually changing the treatment strategies for colorectal cancer.The latest advances on the targeted therapy for colorectal cancer from the 2010 Annual Meeting of American Society of Clinical Oncology are reviewed below.
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Objective To elucidate the molecular mechanisms of sorafenib inhibitting human pe-ripheral blood T cells. Methods CFSE(5, 6-carboxyfluorescein diacetate succinimidyl ester) proliferation assay and MTS [3-(4, 5-diethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl) -2-( 4-sulfophenyl) -2H-etrazoli-um, inner salt] assay were used to examine the proliferation and the viability of T cells; Annexin V-FITC and PI staining was used to detect apoptosis; Flow cytometry was used to detect the expression of CD25, CD69; Western blot was used to detect the expression of cell cycle proteins; ELISA was used to detect the level of IL-2; Picryl chloride-induced delayed-type hypersensitivity model to be used to for the evaluation of in vivo immunocompetency. Results Sorafenib inhibited proliferation of human peripheral blood T cells in-duced by phytohemagglutinin(PHA) in a dose-dependent manner without inducing their apeptosis. Sorafenib caused human blood T cells arrest in the G_0/G_1 phase of the ceLl cycle. Sorafenib decreased CD25 and CD69 expressions and IL-2 production in human T cells. Sorafenib inhibited picryl chloride-induced delayed-type hypersensitivity in mice. Conclusion Sorafenib could inhibit proliferation and activation of peripheral blood T cells. These finding indicated that long term administration of sorafenib might lead to immunosuppressive effects.
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Objective To observe humoral and cellular immunogenecity of nucleic acid vaccine of hepatitis B core antigen (HBcAg) in rhesus monkeys. Methods Rhesus monkeys of the experimental group and the control group received intramuscular injections of a HBcAg nucleic acid vaccine(pJW4303/HBc) and a control plasmid (pJW4303), respectively. Anti HBc titers, isotypes of anti HBc IgG in sera of the rhesus monkeys pre and post vaccinations, and IFN ? as well as IL 4 levels in the culture supernatant of PBMC isolated from the monkeys were detected by an enzyme linked immunoabsorbent assay. HBcAg specific proliferation activities of PBMC in the monkeys were measured by 3H TdR incorporation assay. Results It was observed in rhesus monkeys of experimental group an obvious anti HBc response after immunization with HBcAg nucleic acid vaccine. The major isotypes of anti HBc IgG was IgG2 and IFN ? was predominant compared with IL 4 in the culture supernatant of rhesus monkeys' PBMC, both indicating Th1 type of immune responses. HBcAg specific proliferation activities of PBMC in the experimental group were significantly stronger than those in the control group. Conclusions The nucleic acid vaccine based on HBcAg shows a good humoral and cellular immunogenecity in rhesus monkeys.