Objective:To study the relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma.Methods:A total of 297 patients from July 2009 to May 2013 were chosen as ...Objective:To study the relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma.Methods:A total of 297 patients from July 2009 to May 2013 were chosen as objects.EGFR gene mutation were detected with fluorescence quantitative PCR.Relevance of EGFR gene mutation with clinical and pathological features was analyzed,and the prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was compared.Results:In 297 patients.136(45.79%) showed EGFR gene mutation.EGFR gene mutation had no significant relevance with age.gender,smoking history,family history of cancer and clinical stage(P>0.05);there was significant relevance between EGFR gene mutation and blood type,pathologic types,differentiation and diameter of cancer(P<0.05).The difference between prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was statistical significance(P<0.05).Conclusions:EGFR gene mutation has significant relevance with pathological features,the prognosis of EGFRmutant-paticnts is better than that of EGFR- wide type-patients.展开更多
BACKGROUND Chemotherapy and radiotherapy followed by durvalumab is currently the standard treatment for locally advanced node-positive non-small-cell lung cancer(NSCLC).We describe the case of a patient with locally a...BACKGROUND Chemotherapy and radiotherapy followed by durvalumab is currently the standard treatment for locally advanced node-positive non-small-cell lung cancer(NSCLC).We describe the case of a patient with locally advanced node-positive NSCLC(LA-NSCLC)treated in a phase II prospective protocol with chemotherapy,accelerated hypofractionated radiotherapy(AHRT)and surgery in the preimmunotherapy era.CASE SUMMARY A 69-year-old male,ex-smoker(20 PY),with a Karnofsky performance status of 90,was diagnosed with locally advanced squamous cell lung carcinoma.He was staged by total body computed tomography(CT)scanning,and integrated 18Ffluorodeoxyglucose positron emission tomography/CT scan[cT4 cN3 cM0,stage IIIC according to TNM(tumor-node-metastasis)8th edition]and received AHRT between chemotherapy cycles,in accordance with the study protocol(EudractCT registration 2008-006525-14).At the end of the study the patient underwent surgery,which was not part of the protocol,and showed a complete pathological response.CONCLUSION This case report confirms that AHRT can be used successfully to treat primary LA-NSCLC with bilateral mediastinal lymph node involvement.Our case is of particular interest because of the pathological response after AHRT and the lack of surgical complications.We hypothesize that this radiotherapeutic approach,with its proven efficacy,could be delivered as a short course reducing treatment costs,increasing patient compliance and reducing toxicity.We are currently investigating the possibility of combining hypofractionation,chemotherapy and immunotherapy for patients with LA-NSCLC.展开更多
Objective: To investigate the expression of p120ctn in non-small-cell lung cancer (NSCLC) and its relationship with clinicopathological factors and prognosis. Methods: p120ctn expression was tested by immunohistochemi...Objective: To investigate the expression of p120ctn in non-small-cell lung cancer (NSCLC) and its relationship with clinicopathological factors and prognosis. Methods: p120ctn expression was tested by immunohistochemistry for 80 tumors from patients with non-small-cell lung cancer. Correlations were investigated between p120ctn immunostaining in primary tumors and clinicopathological characteristics and survival. Results: Abnormal expression of p120ctn was found in 68/80(85%) tumors in which 43 cases had cytoplasmic staining. Abnormal staining of p120ctn was related with high TNM stage (P=0.003) and nodal metastasis (P=0.024). However, there was no correlation between altered expression with poor differentiation and histological type. According to Kaplan-Meier survival estimate, the expression of p120ctn was related to the poor survival (P=0.015) of patients. A Cox regression analysis revealed that p120ctn expression was a significant independent factor in the prediction of survival for patients with non-small-cell lung cancer (P=0.008). Conclusion: altered expression of p120ctn was found in non-small-cell lung cancers and was correlated with lymph node metastasis and prognosis. From a practical point of view, the expression of p120ctn can be of prognostic value for patients with non-small-cell lung cancer.展开更多
Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advance...Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials.展开更多
Background: The purpose of this study is to evaluate the clinical efficacy and safety of abraxane-based chemotherapy with/without nedaplatin in elderly patients with non-small-cell lung cancer (NSCLC). Materials an...Background: The purpose of this study is to evaluate the clinical efficacy and safety of abraxane-based chemotherapy with/without nedaplatin in elderly patients with non-small-cell lung cancer (NSCLC). Materials and methods: From October 2009 to January 2013, 48 elderly patients (≥65 years) with NSCLC were investigated in this clinical trial. The patients were randomized and equally allocated into arms A and AP- (A) abraxane (130 mg/m2, days 1, 8); (B) abraxane + nedaplatin (20 mg/m2 days 1-3, q3w). The parameters of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and side effects were evaluated between two arms. Results: Over 80% of the patients completed four cycles of chemotherapy. The total ORR was 21.3 %, DCR was 55.3%, PFS 4.5 months and OS 12.6 months. No significant difference was found between arms A and AP in terms of ORR (16.7% vs. 26.1%, P=0.665) or DCR (55.3% vs. 56.5%, P=0.871). The median PFS in arm A was 3.3 months [25-75% confidence interval (CI): 3.1-7.2] and 5.5 months (25-75% CI: 3.2-7.0) in arm AP with no statistical significance (P=0.640). The median OS in arm A was 12.6 months (25-75% CI: 5.7-26.2) and 15.1 months (25-75% CI: 6.4-35.3) in arm AP with no statistical significance (P=0.770). The side effects were mainly grade 1-2. The incidence of grade 3-4 toxicities was 29.1% in arm A and 62.5% in arm AP with a statistical significance (P=0.020). Conclusions: Compared with combined therapy, abraxane alone chemotherapy was beneficial for elderly NSCLC patients with better tolerability and less adverse events, whereas did not significantly differ in terms of ORR, DCR, PFS or OS.展开更多
Objective: Crizotinib is recommended as the first-line therapy for advanced anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC). Despite its initial efficacy, patients ultimately acquire resista...Objective: Crizotinib is recommended as the first-line therapy for advanced anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC). Despite its initial efficacy, patients ultimately acquire resistance to crizotinib within 1 year. In such patients, the optimal sequential therapy after crizotinib treatment remains unknown. This study explored which sequential therapy option confers the greatest benefit.Methods: A total of 138 patients with advanced ALK-positive NSCLC resistant to crizotinib were studied. Based on patterns of disease progression of metastases, patients were divided into 3 groups: brain progression, non-liver progression, and liver progression. Sequential therapies included crizotinib continuation plus local therapy, nextgeneration ALK inhibitors(ALKi's), and chemotherapy. The primary endpoint was overall survival(OS) from the time of crizotinib resistance to death or last follow-up.Results: The 138 patients included 64 cases with progression in brain, 57 cases in non-liver sites and 17 cases in liver. A significant difference in OS was observed among the distinct progression pattern(median OS, 25.4 months in brain, 15.8 months in non-liver, and 10.8 months in liver, respectively, P=0.020). The difference in OS among sequential therapies was statistically significant in the non-liver progression group(median OS, 27.6 months with next-generation ALKi's, 13.3 months with crizotinib continuation, and 10.8 months with chemotherapy,respectively, P=0.019). However, crizotinib continuation plus local therapy seems to provide non-inferior median OS compared with next-generation ALKi's for patients with brain progression(median OS, 28.9 months vs.32.8 months, P=0.204). And no significant differences in OS were found in patients with progression in liver(P=0.061).Conclusions: Crizotinib continuation together with local therapy might be a feasible strategy for patients with progression in brain beyond crizotinib resistance, as well as next-generation ALKi's. Next-generation ALKi's tended to provide a survival benefit in patients with non-liver progression.展开更多
Non-small-cell lung cancer remains a leading cause of death around the world. For most cases, the only chance of cure comes from resection for localised disease, however relapse rates remain high following surgery. Da...Non-small-cell lung cancer remains a leading cause of death around the world. For most cases, the only chance of cure comes from resection for localised disease, however relapse rates remain high following surgery. Data has emerged over recent years regarding the utility of adjuvant chemotherapy for improving disease-free and overall survival of patients following curative resection. This paper reviews the clinical trials that have been conducted in this area along with the studies integrating radiation therapy in the adjuvant setting. The role of prognostic gene signatures are reviewed as well as ongoing clinical trials including those incorporating biological or targeted therapies.展开更多
The purpose of this study was to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel as a rescue regimen in the treatment of patients with advanced non-small-cell lung cancer. We retrospectively ...The purpose of this study was to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel as a rescue regimen in the treatment of patients with advanced non-small-cell lung cancer. We retrospectively reviewed the medical records of 20 patients with stage IV non-small-cell lung cancer. The patients had progressive disease after standard antitumor therapy and subsequently received intravenous albumin-bound paclitaxel at the dose of 100 mg/m2 in weekly schedule. Cumulative findings showed that the overall response rate was 30.0%, the disease control rate amounted to 40%, and the 1 year survival rate was 30%. In addition, the median time to progression and the median survival time reached 5 and 10 months, respectively. Meanwhile, no severe hypersensitivity reactions and grade 4 adverse effects were reported. In summary, weekly-administered albumin-bound paclitaxel seems to be an effective and safe regimen for elderly patients with stage IV non-small-cell lung cancer who were refractory to conventional therapy.展开更多
Non-small-cell lung carcinoma (NSCLC) is one of the most frequently diagnosed malignancies worldwide. Previous studies have shown that microRNA-449b (miR-449b) functions as a tumor suppressor in many cancers. Howe...Non-small-cell lung carcinoma (NSCLC) is one of the most frequently diagnosed malignancies worldwide. Previous studies have shown that microRNA-449b (miR-449b) functions as a tumor suppressor in many cancers. However, the role of miR- 449b in NSCLC is still unknown. In the present study, miR-449b was significantly down- regulated in NSCLC samples and cell lines. Bioinformatics analysis revealed that 3'-UTR region of leucine rich repeat containing G protein-coupled receptor 4 (LGR4) mRNA had putative complementary sequences to miR-449b, which was further confirmed by the luciferase assay. Western blotting showed that restoration of miR-449b in NSCLC cells decreased the expression of LGR4. Interestingly, over-expression of miR-449b inhibited growth and invasion of NSCLC cells in vitro. Furthermore, ectopic expression of LGR4 reversed miR-449b-suppressed proliferation and invasion of NSCLC cells. Therefore, the data of the present study demonstrate that miR-449b inhibits tumor cell growth and invasion by targeting LGR4 in NSCLC.展开更多
Surgery is the first choice of treatment for patients with non-small-cell lung cancer(NSCLC), but few patients can be treated surgically because of either advanced disease or poor pulmonary function. Other therapies i...Surgery is the first choice of treatment for patients with non-small-cell lung cancer(NSCLC), but few patients can be treated surgically because of either advanced disease or poor pulmonary function. Other therapies include radiotherapy and chemotherapy, as well as complementary and alternative therapies, usually with disappointing results. Bronchial artery infusion(BAI) is a manageable and effective method for treating advanced NSCLC. Outcome is good by BAI due to its repeatability and low toxicity. Icotinib hydrochloride is a newly developed and highly specific epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor and has been safely and efficiently used to treat advanced NSCLC. We herein report a 73-year-old patient with chronic cough, who was diagnosed with advanced NSCLC with the EGFR mutation of L858 R substitution in exon 21, and treated with the combination of oral icotinib and BAI chemotherapy as the first-line therapy, which resulted in a satisfactory clinical outcome. Complete remission of advanced NSCLC can be achieved using the combination of oral icotinib and BAI chemotherapy.展开更多
Objective: Crizotinib has demonstrated promising efficacy in patients with anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC) in clinical trials. We conducted this retrospective multicenter stu...Objective: Crizotinib has demonstrated promising efficacy in patients with anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC) in clinical trials. We conducted this retrospective multicenter study to assess the outcomes of crizotinib therapy in, to our knowledge, a large sample cohort of patients with ALKpositive advanced NSCLC.Methods: We reviewed the medical records of 484 unselected ALK-positive NSCLC patients treated with crizotinib at 5 cancer centers in China from January 2013 to November 2017. Clinical data were collected from the initiation of crizotinib therapy to Response Evaluation Criteria in Solid Tumors(RECIST)-defined progressive disease(PD).Results: A total of 428 eligible ALK-positive NSCLC patients were enrolled, 273(63.8%) of whom received crizotinib as first-line treatment. The median progression-free survival(PFS) and overall survival(OS) from the initiation of crizotinib treatment were 14.4 [95% confidence interval(95% CI), 12.4-16.4] months and 53.4(95%CI, 33.7-73.1) months, respectively. In subgroup analyses, patients who received crizotinib as first-line treatment showed a higher disease control rate(DCR) and a longer median OS compared with second-/later-line crizotinib treatment(94.8% and OS not reached vs. 89.0% and 40.5 months, respectively). For 261 patients with RECISTdefined PD, multivariate Cox analysis revealed that in patients who received first-line crizotinib therapy, continued crizotinib beyond progressive disease(CBPD) and next-generation ALK inhibitors after crizotinib failure were associated with improved survival.Conclusions: This study has demonstrated the clinically meaningful benefit of crizotinib treatment in a large cohort of Chinese ALK-positive NSCLC patients. CBPD and next-generation ALK inhibitor treatment may provide improved survival after RECIST-defined progression on crizotinib.展开更多
Background: To determine the safety and therapeutic efficacy of nimotuzumab (h-R3) combined with docetaxel in advanced non-small-cell lung cancer (NSCLC) patients who have failed to respond to prior first-line ch...Background: To determine the safety and therapeutic efficacy of nimotuzumab (h-R3) combined with docetaxel in advanced non-small-cell lung cancer (NSCLC) patients who have failed to respond to prior first-line chemotherapy. Methods: In this single-center, open-label, dose-escalating phase I trial, patients with epidermal growth factor receptor (EGFR)-expressing stage IV NSCLC were treated with nimotuzumab plus doeetaxel according to a dose escalation schedule. The safety and efficacy of the combination treatment were observed and analyzed.Results: There were 12 patients with EGFR-expressing stage IV NSCLC enrolled. The dose of nimotuzumab was escalated from 200 to 600 mg/week. The longest administration of study drug was 40 weeks at the 600 mg/week dose level. Grade Ⅲ-Ⅳ toxicities included neutropenia and fatigue, and other toxicities included rash. Dose-limiting toxicity occurred with Grade 3 fatigue at the 200 mg dose level of nimotuzumab and Grade 4 neutropenia with pneumonia at the 600 mg dose level of nimotuzumab. No objective responses were observed, and stable disease was observed in eight patients (66.7%). The median progression-free survival (PFS) was 4.4 months in all patients, 1.3 months in patients with the EGFR mutation, and 4.4 months in those with wild type EGFR (EGFR WT). The median survival time (MST) was 21.1 months in all patients, 21.1 months in patients with EGFR mutation, and 26.4 months in patients with EGFR WT. Conclusions: Nimotuzumab and docetaxel combination therapy was found to be well tolerated and efficacious. Further study of nimotuzumab is warranted in advanced NSCLC patients.展开更多
Objective: Epidermal growth factor receptor (EGFR) mutations are strong determinants of tumor response to EGFR tyrosine kinase inhibitors in non-small-cell lung cancer (NSCLC) patients. The aim of this study was ...Objective: Epidermal growth factor receptor (EGFR) mutations are strong determinants of tumor response to EGFR tyrosine kinase inhibitors in non-small-cell lung cancer (NSCLC) patients. The aim of this study was to evaluate the correspondence between EGFR mutations in non-small-cell lung cancer tissues and in circulating DNA. Methods: The research was conducted in 50 non-small-cell lung cancer patients who had undergone curative surgery, and in whom both serum and neoplastic tissues were available. Meanwhile sera of 33 cases of advanced NSCLC patients were also analyzed. DNA were extracted from each sample. Mutations of EGFR in exonl8-21 were examined by PCR amplification method and direct sequencing. Results: EGFR mutations were detected in 15 (30%) of 50 neoplastic tissue samples, 6 cases were in-frame deletion del E746-A750 in exonl9, 9 cases were substitution in exon 21 (all were L858R except one was L861Q), but no mutated DNA resulted in paired serum circulating DNA samples of 50 resectable patients. As the 33 advanced NSCLC patients, EGFR mutations were detected in only 2 serum circulating DNA samples, all were L858R mutation in exon 21. Conclusion: These data indicated that it was difficult to identify EGFR mutations in circulating DNA of NSCLC patients. The use of EGFR mutation in serum as a clinical method for decision making of TKI therapy is unsatisfactory.展开更多
Objective: To analyze the outcomes of patients who received TKI immediately after the first-line without progression as maintenance treatment (immediate group) vs. those received delayed treatment upon disease prog...Objective: To analyze the outcomes of patients who received TKI immediately after the first-line without progression as maintenance treatment (immediate group) vs. those received delayed treatment upon disease progression as second-line therapy (delayed group). Methods: The study included 159 no-small-cell lung cancer (NSCLC) patients who received gefitinib or erlotinib as maintenance treatment in the immediate group (85 patients) or as second-line therapy in the delayed group (74 patients). The primary end point was progression-free survival (PFS). EGFR mutation status was detected using denaturing high-performance liquid chromatography (DHPLC). Results: PFS was 17.3 and 16.4 months in the immediate and delayed groups, respectively (hazard ratio [HR], 0.99; 95% Confidence Interval [CI]: 0.69-1.42; P=0.947). In a subgroup analysis that included only patients with EGFR mutation, however, PFS was significantly longer in the immediate group than in the delayed group (HR, 0.48; 95% CI: 0.27-0.85; P=0.012). In patients with wild type EGFR, the risk for disease progression was comparable between the two groups (HR, 1.23; 95% CI: 0.61-2.51; P=0.564). No significant difference was demonstrated between the immediate and delayed group in terms of the overall survival (OS) (26.1 months vs. 21.6 months, respectively; HR=0.53; 95% CI: 0.27 to 1.06; P=0.072). There was also no difference in the incidence of adverse events between the two groups. Conclusions: EGFR TKI maintenance improves PFS in patients with EGFR mutation. Prospectively designed clinical studies that compare TKI immediate vs. delayed treatment after first-line chemotherapy upon disease progression are needed.展开更多
Non-small-cell lung cancer(NSCLC)causes significant mortality worldwide.Patients with chronic renal failure have an increased risk of developing lungcancer.NSCLC Patients with chronic renal failure undergoing hemodial...Non-small-cell lung cancer(NSCLC)causes significant mortality worldwide.Patients with chronic renal failure have an increased risk of developing lungcancer.NSCLC Patients with chronic renal failure undergoing hemodialysis(HD)often exhibit poor performance,and chemotherapy is generally contraindicated.Oral epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs)are effective treatment agents for NSCLC patients.However,the benefits andadverse effects of EGFR-TKIs in NSCLC undergoing HD are known.There are noclinical studies on the effects of EGFR-TKIs on NSCLC patients undergoing HD.We reviewed all previous case reports about EGFR-TKIs in NSCLC patientsundergoing HD.It is difficult to design studies about the effects of EGFR-TKIs inpatients undergoing HD,and this review is quite important.EGFR-TKIs are welltolerated in patients undergoing HD.The main routes of elimination of EGFRTKIsare metabolism via the liver,and renal elimination is minor.Therecommended doses and pharmacokinetics of these EGFR-TKIs for patientsundergoing HD are similar to those for patients with normal renal function.Theplasma protein binding of EGFR-TKIs is very high,and it is not necessary toadjust the dose after HD.In conclusion,EGFR-TKIs are effective and welltolerated in patients undergoing HD.展开更多
BACKGROUND Non-small-cell lung cancer(NSCLC)has the highest morbidity and mortality rates among all malignant tumor types.Although therapies targeting the mutated genes such as KRAS have been used in the clinic for ma...BACKGROUND Non-small-cell lung cancer(NSCLC)has the highest morbidity and mortality rates among all malignant tumor types.Although therapies targeting the mutated genes such as KRAS have been used in the clinic for many years,the prognosis remains poor.Therefore,it is necessary to further study the aberrant expression or mutation of non-target genes affecting the survival and prognosis.AIM To explore the impact of simultaneous abnormalities of multiple genes on the prognosis and survival of patients.METHODS We used R packages to analyze gene expression data and clinical data downloaded from The Cancer Genome Atlas(TCGA)database.We also collected samples from 85 NSCLC patients from the First People’s Hospital of Jingzhou City and retrospectively followed the patients.Multivariate Cox regression analysis and survival analysis were performed.RESULTS Analysis of gene expression data from TCGA revealed that the overexpression of the following single genes affected overall survival:TP53(P=0.79),PTEN(P=0.94),RB1(P=0.49),CTNNB1(P=0.24),STK11(P=0.32),and PIK3CA(P=0.013).However,the probability of multiple genes(TP53,PTEN,RB1,and STK11)affecting survival was 0.025.Retrospective analysis of clinical data revealed that sex(hazard ratio[HR]=1.29;[95%CI:0.64-2.62]),age(HR=1.05;[95%CI:1.02-1.07]),smoking status(HR=2.26;[95%CI:1.16-4.39]),tumor histology(HR=0.58;[95%CI:0.30-1.11]),cancer stage(HR=16.63;[95%CI:4.8-57.63]),epidermal growth factor receptor(EGFR)mutation(HR=1.82;[95%CI:1.05-3.16]),abundance(HR=4.95;[95%CI:0.78-31.36]),and treatment with tyrosine kinase inhibitors(TKIs)(HR=0.58;[95%CI:0.43-0.78])affected patient survival.Co-occurring mutations of TP53,PTEN,RB1,and STK11 did not significantly affect the overall survival of patients receiving chemotherapy(P=0.96)but significantly affected the overall survival of patients receiving TKIs(P=0.045).CONCLUSION Co-occurring mutation or overexpression of different genes has different effects on the overall survival and prognosis of NSCLC patients.Combined with TKI treatment,the co-occurring mutation of some genes may have a synergistic effect on the survival and prognosis of NSCLC patients.展开更多
Objective The aim of this study was to investigate the antitumor and vascular effects of apatinib use combined with chemotherapy on mice with non-small-cell lung cancer(NSCLC).Methods First,60 tumor-bearing nude mice ...Objective The aim of this study was to investigate the antitumor and vascular effects of apatinib use combined with chemotherapy on mice with non-small-cell lung cancer(NSCLC).Methods First,60 tumor-bearing nude mice were randomly divided into control,low-dose,and high-dose groups.Four nude mice per group were sacrificed before administration and on days 1,3,7,and 10 after administration.HIF-1αexpression in tumor tissues was detected.Second,32 nude mice were randomly divided into control,premetrexed,synchronous,and sequential groups.The weights and tumor volumes of mice were recorded.Results(1)HIF-1αexpression decreased significantly on days 3 and 7 after low-dose apatinib treatment.There was no significant difference in HIF-1αexpression in the high-dose apatinib group(P>0.05).MMP-2 and MMP-9 expression levels in the low-dose apatinib group were significantly lower than those in the control group(P<0.05).(2)In the low-dose apatinib group,the microvessel density increased gradually from days 3 to 7 post-treatment,while that in the high-dose apatinib group decreased significantly.(3)The inhibitory effect of sequential therapy using low-dose apatinib and pemetrexed was optimal,while that of synchronous treatment was not better than that of pemetrexed usage alone.Sequential treatment using low-dose apatinib and pemetrexed exerted the best antitumor effect.(4)The expression levels of p-AKT,p-mTOR,p-MEK,and p-ERK in the sequential group were significantly lower than those in the other three groups(P<0.05).Conclusion Apatinib usage involves certain considerations,such as dose requirements and time window for vascular normalization during lung cancer treatment in nude mice,suggesting that dynamic contrast-enhanced magnetic resonance imaging and other tests can be conducted to determine the vascular normalization window in patients with lung cancer and to achieve the optimal anti-vascular effect.展开更多
A tumor suppressor gene, CADM1, encoding an immunoglobulin superfamily cell adhesion molecule, is inactivated in various cancers, including non-small-cell lung cancer (NSCLC). Although promoter methylation is one of t...A tumor suppressor gene, CADM1, encoding an immunoglobulin superfamily cell adhesion molecule, is inactivated in various cancers, including non-small-cell lung cancer (NSCLC). Although promoter methylation is one of the mechanisms to suppress CADM1 expression, about half of tumors lacking CADM1 expression do not show methylation of the gene promoter. We herein investigated the possible involvement of microRNA (miRNA) in the down-regulation of CADM1. Using computational algorithms, miR-214 and miR-375 were identified as candidate miRNAs targeting CADM1. A luciferase reporter assay demonstrated that miR-214 and miR-375 repressed the promoter activity through 3’-UTR of CADM1. Quantitative RT-PCR analysis demonstrated that miR-214 and miR-375 was highly expressed in 21 (62%) and 17 cases (50%) of 34 primary NSCLCs. Notably, increased expression of miR-214 was preferentially observed in tumors with advanced pathological stages and in those lacking CADM1 expression but were not associated with the promoter methylation, suggesting that miR-214-mediated silencing would be another mechanism to suppress CADM1 expression. On the other hand, introduction of miR-214 or miR-375 into NSCLC cells decreased CADM1 protein expression. Furthermore, overexpression of miR-214 enhanced anchorage-independent growth of NSCLC cells, A549, whereas transfection of miRNA inhibitor, miR-214 or miR-375, significantly suppressed the in vitro wound healing activity of HCC827 cells. These findings suggest that overexpression of miR-214 and miR-375 could participate in the malignant features of NSCLC through down-regulating CADM1 and would provide a potential target for the treatment of a subset of NSCLC.展开更多
The effects of atropine, diazepam and pralidoxime were studied for their ability to block the pathological lesions induced by sarin. Rats were exposed to an aerosol of sarin at a concentration of 51.2mg-m for 15 min f...The effects of atropine, diazepam and pralidoxime were studied for their ability to block the pathological lesions induced by sarin. Rats were exposed to an aerosol of sarin at a concentration of 51.2mg-m for 15 min following the pretreatment with one of the following combinations: atropine (10 mg/kg, i.m.) and diazepam (0.5 mg/kg, i.m.); atropine and pralidoxime (25 mg/kg, i.m.); diazepam and pralidoxime; atropine, diazepam and pralidoxime. Lung exposed to sarin aerosols revealed an increased cellular proliferation with progressive diffused interstitial thickening on the 4th day following exposure. On the 16th day, loss of alveolar space and consolidation of large areas of all lobes were observed. Sarin also caused damage to the respiratory bronchioles. All the therapy regime blocked the development of lung lesions in the descending orders: atropine, diazepam and pralidoxime, atropine and diazepam > diazepam and pralidoxime > atropine and pralidoxime. The result suggests that diazepam in combination with atropine and pralidoxime could be an effective drug combination regime for the lung lesions.展开更多
Patients with early-stage non-small-cell lung cancer(NSCLC)are candidates for curative surgery;however,despite multiple advances in lung cancer management,recurrence rates remain high.Adjuvant chemotherapy has been de...Patients with early-stage non-small-cell lung cancer(NSCLC)are candidates for curative surgery;however,despite multiple advances in lung cancer management,recurrence rates remain high.Adjuvant chemotherapy has been demonstrated to significantly prolong overall survival(OS),but this benefit is modest and there is an urgent need for effective new therapies to provide a cure for more patients.The high efficacy of tyrosine kinase inhibitors(TKIs)against epidermal growth factor receptor-mutated(EGFR)in patients with advanced EGFR-mutated NSCLC has led to the evaluation of these agents in early stages of the disease.Multiple clinical trials have evaluated the safety and efficacy of EGFR TKIs as an adjuvant treatment,in patients with resected EGFR-mutated NSCLC,and shown that they significantly prolong disease-free survival(DFS),but this benefit does not translate to OS.Recently,an interim analysis of the ADAURA trial demonstrated that,surprisingly,osimertinib improved DFS.This led to the study being stopped early,leaving many unanswered questions about its potential effect on OS and its incorporation as a standard adjuvant treatment in this patient subgroup.These targeted agents are also being evaluated in locally-advanced disease,with promising results,although prospective studies with larger sample sizes are needed to confirm these results.In this article,we review the most relevant studies on the role of EGFR TKIs in the management of early-stage EGFR-mutated NSCLC.展开更多
基金supported by Project Development Plan of Yantai city Science and Technology(No.2013WS229)
文摘Objective:To study the relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma.Methods:A total of 297 patients from July 2009 to May 2013 were chosen as objects.EGFR gene mutation were detected with fluorescence quantitative PCR.Relevance of EGFR gene mutation with clinical and pathological features was analyzed,and the prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was compared.Results:In 297 patients.136(45.79%) showed EGFR gene mutation.EGFR gene mutation had no significant relevance with age.gender,smoking history,family history of cancer and clinical stage(P>0.05);there was significant relevance between EGFR gene mutation and blood type,pathologic types,differentiation and diameter of cancer(P<0.05).The difference between prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was statistical significance(P<0.05).Conclusions:EGFR gene mutation has significant relevance with pathological features,the prognosis of EGFRmutant-paticnts is better than that of EGFR- wide type-patients.
文摘BACKGROUND Chemotherapy and radiotherapy followed by durvalumab is currently the standard treatment for locally advanced node-positive non-small-cell lung cancer(NSCLC).We describe the case of a patient with locally advanced node-positive NSCLC(LA-NSCLC)treated in a phase II prospective protocol with chemotherapy,accelerated hypofractionated radiotherapy(AHRT)and surgery in the preimmunotherapy era.CASE SUMMARY A 69-year-old male,ex-smoker(20 PY),with a Karnofsky performance status of 90,was diagnosed with locally advanced squamous cell lung carcinoma.He was staged by total body computed tomography(CT)scanning,and integrated 18Ffluorodeoxyglucose positron emission tomography/CT scan[cT4 cN3 cM0,stage IIIC according to TNM(tumor-node-metastasis)8th edition]and received AHRT between chemotherapy cycles,in accordance with the study protocol(EudractCT registration 2008-006525-14).At the end of the study the patient underwent surgery,which was not part of the protocol,and showed a complete pathological response.CONCLUSION This case report confirms that AHRT can be used successfully to treat primary LA-NSCLC with bilateral mediastinal lymph node involvement.Our case is of particular interest because of the pathological response after AHRT and the lack of surgical complications.We hypothesize that this radiotherapeutic approach,with its proven efficacy,could be delivered as a short course reducing treatment costs,increasing patient compliance and reducing toxicity.We are currently investigating the possibility of combining hypofractionation,chemotherapy and immunotherapy for patients with LA-NSCLC.
基金This work was supported by a grant from the Scientific Research Foundation of the Ministry ofEducation of PR China (No. 2002-247). *
文摘Objective: To investigate the expression of p120ctn in non-small-cell lung cancer (NSCLC) and its relationship with clinicopathological factors and prognosis. Methods: p120ctn expression was tested by immunohistochemistry for 80 tumors from patients with non-small-cell lung cancer. Correlations were investigated between p120ctn immunostaining in primary tumors and clinicopathological characteristics and survival. Results: Abnormal expression of p120ctn was found in 68/80(85%) tumors in which 43 cases had cytoplasmic staining. Abnormal staining of p120ctn was related with high TNM stage (P=0.003) and nodal metastasis (P=0.024). However, there was no correlation between altered expression with poor differentiation and histological type. According to Kaplan-Meier survival estimate, the expression of p120ctn was related to the poor survival (P=0.015) of patients. A Cox regression analysis revealed that p120ctn expression was a significant independent factor in the prediction of survival for patients with non-small-cell lung cancer (P=0.008). Conclusion: altered expression of p120ctn was found in non-small-cell lung cancers and was correlated with lymph node metastasis and prognosis. From a practical point of view, the expression of p120ctn can be of prognostic value for patients with non-small-cell lung cancer.
文摘Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials.
文摘Background: The purpose of this study is to evaluate the clinical efficacy and safety of abraxane-based chemotherapy with/without nedaplatin in elderly patients with non-small-cell lung cancer (NSCLC). Materials and methods: From October 2009 to January 2013, 48 elderly patients (≥65 years) with NSCLC were investigated in this clinical trial. The patients were randomized and equally allocated into arms A and AP- (A) abraxane (130 mg/m2, days 1, 8); (B) abraxane + nedaplatin (20 mg/m2 days 1-3, q3w). The parameters of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and side effects were evaluated between two arms. Results: Over 80% of the patients completed four cycles of chemotherapy. The total ORR was 21.3 %, DCR was 55.3%, PFS 4.5 months and OS 12.6 months. No significant difference was found between arms A and AP in terms of ORR (16.7% vs. 26.1%, P=0.665) or DCR (55.3% vs. 56.5%, P=0.871). The median PFS in arm A was 3.3 months [25-75% confidence interval (CI): 3.1-7.2] and 5.5 months (25-75% CI: 3.2-7.0) in arm AP with no statistical significance (P=0.640). The median OS in arm A was 12.6 months (25-75% CI: 5.7-26.2) and 15.1 months (25-75% CI: 6.4-35.3) in arm AP with no statistical significance (P=0.770). The side effects were mainly grade 1-2. The incidence of grade 3-4 toxicities was 29.1% in arm A and 62.5% in arm AP with a statistical significance (P=0.020). Conclusions: Compared with combined therapy, abraxane alone chemotherapy was beneficial for elderly NSCLC patients with better tolerability and less adverse events, whereas did not significantly differ in terms of ORR, DCR, PFS or OS.
文摘Objective: Crizotinib is recommended as the first-line therapy for advanced anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC). Despite its initial efficacy, patients ultimately acquire resistance to crizotinib within 1 year. In such patients, the optimal sequential therapy after crizotinib treatment remains unknown. This study explored which sequential therapy option confers the greatest benefit.Methods: A total of 138 patients with advanced ALK-positive NSCLC resistant to crizotinib were studied. Based on patterns of disease progression of metastases, patients were divided into 3 groups: brain progression, non-liver progression, and liver progression. Sequential therapies included crizotinib continuation plus local therapy, nextgeneration ALK inhibitors(ALKi's), and chemotherapy. The primary endpoint was overall survival(OS) from the time of crizotinib resistance to death or last follow-up.Results: The 138 patients included 64 cases with progression in brain, 57 cases in non-liver sites and 17 cases in liver. A significant difference in OS was observed among the distinct progression pattern(median OS, 25.4 months in brain, 15.8 months in non-liver, and 10.8 months in liver, respectively, P=0.020). The difference in OS among sequential therapies was statistically significant in the non-liver progression group(median OS, 27.6 months with next-generation ALKi's, 13.3 months with crizotinib continuation, and 10.8 months with chemotherapy,respectively, P=0.019). However, crizotinib continuation plus local therapy seems to provide non-inferior median OS compared with next-generation ALKi's for patients with brain progression(median OS, 28.9 months vs.32.8 months, P=0.204). And no significant differences in OS were found in patients with progression in liver(P=0.061).Conclusions: Crizotinib continuation together with local therapy might be a feasible strategy for patients with progression in brain beyond crizotinib resistance, as well as next-generation ALKi's. Next-generation ALKi's tended to provide a survival benefit in patients with non-liver progression.
文摘Non-small-cell lung cancer remains a leading cause of death around the world. For most cases, the only chance of cure comes from resection for localised disease, however relapse rates remain high following surgery. Data has emerged over recent years regarding the utility of adjuvant chemotherapy for improving disease-free and overall survival of patients following curative resection. This paper reviews the clinical trials that have been conducted in this area along with the studies integrating radiation therapy in the adjuvant setting. The role of prognostic gene signatures are reviewed as well as ongoing clinical trials including those incorporating biological or targeted therapies.
文摘The purpose of this study was to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel as a rescue regimen in the treatment of patients with advanced non-small-cell lung cancer. We retrospectively reviewed the medical records of 20 patients with stage IV non-small-cell lung cancer. The patients had progressive disease after standard antitumor therapy and subsequently received intravenous albumin-bound paclitaxel at the dose of 100 mg/m2 in weekly schedule. Cumulative findings showed that the overall response rate was 30.0%, the disease control rate amounted to 40%, and the 1 year survival rate was 30%. In addition, the median time to progression and the median survival time reached 5 and 10 months, respectively. Meanwhile, no severe hypersensitivity reactions and grade 4 adverse effects were reported. In summary, weekly-administered albumin-bound paclitaxel seems to be an effective and safe regimen for elderly patients with stage IV non-small-cell lung cancer who were refractory to conventional therapy.
文摘Non-small-cell lung carcinoma (NSCLC) is one of the most frequently diagnosed malignancies worldwide. Previous studies have shown that microRNA-449b (miR-449b) functions as a tumor suppressor in many cancers. However, the role of miR- 449b in NSCLC is still unknown. In the present study, miR-449b was significantly down- regulated in NSCLC samples and cell lines. Bioinformatics analysis revealed that 3'-UTR region of leucine rich repeat containing G protein-coupled receptor 4 (LGR4) mRNA had putative complementary sequences to miR-449b, which was further confirmed by the luciferase assay. Western blotting showed that restoration of miR-449b in NSCLC cells decreased the expression of LGR4. Interestingly, over-expression of miR-449b inhibited growth and invasion of NSCLC cells in vitro. Furthermore, ectopic expression of LGR4 reversed miR-449b-suppressed proliferation and invasion of NSCLC cells. Therefore, the data of the present study demonstrate that miR-449b inhibits tumor cell growth and invasion by targeting LGR4 in NSCLC.
文摘Surgery is the first choice of treatment for patients with non-small-cell lung cancer(NSCLC), but few patients can be treated surgically because of either advanced disease or poor pulmonary function. Other therapies include radiotherapy and chemotherapy, as well as complementary and alternative therapies, usually with disappointing results. Bronchial artery infusion(BAI) is a manageable and effective method for treating advanced NSCLC. Outcome is good by BAI due to its repeatability and low toxicity. Icotinib hydrochloride is a newly developed and highly specific epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor and has been safely and efficiently used to treat advanced NSCLC. We herein report a 73-year-old patient with chronic cough, who was diagnosed with advanced NSCLC with the EGFR mutation of L858 R substitution in exon 21, and treated with the combination of oral icotinib and BAI chemotherapy as the first-line therapy, which resulted in a satisfactory clinical outcome. Complete remission of advanced NSCLC can be achieved using the combination of oral icotinib and BAI chemotherapy.
文摘Objective: Crizotinib has demonstrated promising efficacy in patients with anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC) in clinical trials. We conducted this retrospective multicenter study to assess the outcomes of crizotinib therapy in, to our knowledge, a large sample cohort of patients with ALKpositive advanced NSCLC.Methods: We reviewed the medical records of 484 unselected ALK-positive NSCLC patients treated with crizotinib at 5 cancer centers in China from January 2013 to November 2017. Clinical data were collected from the initiation of crizotinib therapy to Response Evaluation Criteria in Solid Tumors(RECIST)-defined progressive disease(PD).Results: A total of 428 eligible ALK-positive NSCLC patients were enrolled, 273(63.8%) of whom received crizotinib as first-line treatment. The median progression-free survival(PFS) and overall survival(OS) from the initiation of crizotinib treatment were 14.4 [95% confidence interval(95% CI), 12.4-16.4] months and 53.4(95%CI, 33.7-73.1) months, respectively. In subgroup analyses, patients who received crizotinib as first-line treatment showed a higher disease control rate(DCR) and a longer median OS compared with second-/later-line crizotinib treatment(94.8% and OS not reached vs. 89.0% and 40.5 months, respectively). For 261 patients with RECISTdefined PD, multivariate Cox analysis revealed that in patients who received first-line crizotinib therapy, continued crizotinib beyond progressive disease(CBPD) and next-generation ALK inhibitors after crizotinib failure were associated with improved survival.Conclusions: This study has demonstrated the clinically meaningful benefit of crizotinib treatment in a large cohort of Chinese ALK-positive NSCLC patients. CBPD and next-generation ALK inhibitor treatment may provide improved survival after RECIST-defined progression on crizotinib.
文摘Background: To determine the safety and therapeutic efficacy of nimotuzumab (h-R3) combined with docetaxel in advanced non-small-cell lung cancer (NSCLC) patients who have failed to respond to prior first-line chemotherapy. Methods: In this single-center, open-label, dose-escalating phase I trial, patients with epidermal growth factor receptor (EGFR)-expressing stage IV NSCLC were treated with nimotuzumab plus doeetaxel according to a dose escalation schedule. The safety and efficacy of the combination treatment were observed and analyzed.Results: There were 12 patients with EGFR-expressing stage IV NSCLC enrolled. The dose of nimotuzumab was escalated from 200 to 600 mg/week. The longest administration of study drug was 40 weeks at the 600 mg/week dose level. Grade Ⅲ-Ⅳ toxicities included neutropenia and fatigue, and other toxicities included rash. Dose-limiting toxicity occurred with Grade 3 fatigue at the 200 mg dose level of nimotuzumab and Grade 4 neutropenia with pneumonia at the 600 mg dose level of nimotuzumab. No objective responses were observed, and stable disease was observed in eight patients (66.7%). The median progression-free survival (PFS) was 4.4 months in all patients, 1.3 months in patients with the EGFR mutation, and 4.4 months in those with wild type EGFR (EGFR WT). The median survival time (MST) was 21.1 months in all patients, 21.1 months in patients with EGFR mutation, and 26.4 months in patients with EGFR WT. Conclusions: Nimotuzumab and docetaxel combination therapy was found to be well tolerated and efficacious. Further study of nimotuzumab is warranted in advanced NSCLC patients.
文摘Objective: Epidermal growth factor receptor (EGFR) mutations are strong determinants of tumor response to EGFR tyrosine kinase inhibitors in non-small-cell lung cancer (NSCLC) patients. The aim of this study was to evaluate the correspondence between EGFR mutations in non-small-cell lung cancer tissues and in circulating DNA. Methods: The research was conducted in 50 non-small-cell lung cancer patients who had undergone curative surgery, and in whom both serum and neoplastic tissues were available. Meanwhile sera of 33 cases of advanced NSCLC patients were also analyzed. DNA were extracted from each sample. Mutations of EGFR in exonl8-21 were examined by PCR amplification method and direct sequencing. Results: EGFR mutations were detected in 15 (30%) of 50 neoplastic tissue samples, 6 cases were in-frame deletion del E746-A750 in exonl9, 9 cases were substitution in exon 21 (all were L858R except one was L861Q), but no mutated DNA resulted in paired serum circulating DNA samples of 50 resectable patients. As the 33 advanced NSCLC patients, EGFR mutations were detected in only 2 serum circulating DNA samples, all were L858R mutation in exon 21. Conclusion: These data indicated that it was difficult to identify EGFR mutations in circulating DNA of NSCLC patients. The use of EGFR mutation in serum as a clinical method for decision making of TKI therapy is unsatisfactory.
基金supported by the grants from the China National Funds for Distinguished Young Scientists (No. 81025012)the Capital Development Foundation (No. 30772472)
文摘Objective: To analyze the outcomes of patients who received TKI immediately after the first-line without progression as maintenance treatment (immediate group) vs. those received delayed treatment upon disease progression as second-line therapy (delayed group). Methods: The study included 159 no-small-cell lung cancer (NSCLC) patients who received gefitinib or erlotinib as maintenance treatment in the immediate group (85 patients) or as second-line therapy in the delayed group (74 patients). The primary end point was progression-free survival (PFS). EGFR mutation status was detected using denaturing high-performance liquid chromatography (DHPLC). Results: PFS was 17.3 and 16.4 months in the immediate and delayed groups, respectively (hazard ratio [HR], 0.99; 95% Confidence Interval [CI]: 0.69-1.42; P=0.947). In a subgroup analysis that included only patients with EGFR mutation, however, PFS was significantly longer in the immediate group than in the delayed group (HR, 0.48; 95% CI: 0.27-0.85; P=0.012). In patients with wild type EGFR, the risk for disease progression was comparable between the two groups (HR, 1.23; 95% CI: 0.61-2.51; P=0.564). No significant difference was demonstrated between the immediate and delayed group in terms of the overall survival (OS) (26.1 months vs. 21.6 months, respectively; HR=0.53; 95% CI: 0.27 to 1.06; P=0.072). There was also no difference in the incidence of adverse events between the two groups. Conclusions: EGFR TKI maintenance improves PFS in patients with EGFR mutation. Prospectively designed clinical studies that compare TKI immediate vs. delayed treatment after first-line chemotherapy upon disease progression are needed.
基金the Taipei Tzu Chi Hospital,Buddhist Tzu Chi Medical Foundation,No.TCRD-TPE-108-RT-4(3/3)and No.TCRD-TPE-109-59.
文摘Non-small-cell lung cancer(NSCLC)causes significant mortality worldwide.Patients with chronic renal failure have an increased risk of developing lungcancer.NSCLC Patients with chronic renal failure undergoing hemodialysis(HD)often exhibit poor performance,and chemotherapy is generally contraindicated.Oral epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs)are effective treatment agents for NSCLC patients.However,the benefits andadverse effects of EGFR-TKIs in NSCLC undergoing HD are known.There are noclinical studies on the effects of EGFR-TKIs on NSCLC patients undergoing HD.We reviewed all previous case reports about EGFR-TKIs in NSCLC patientsundergoing HD.It is difficult to design studies about the effects of EGFR-TKIs inpatients undergoing HD,and this review is quite important.EGFR-TKIs are welltolerated in patients undergoing HD.The main routes of elimination of EGFRTKIsare metabolism via the liver,and renal elimination is minor.Therecommended doses and pharmacokinetics of these EGFR-TKIs for patientsundergoing HD are similar to those for patients with normal renal function.Theplasma protein binding of EGFR-TKIs is very high,and it is not necessary toadjust the dose after HD.In conclusion,EGFR-TKIs are effective and welltolerated in patients undergoing HD.
基金Supported by the Natural Science Foundation of Hubei Province,No. 2017CFB786the Hubei Province Health and Family Planning Scientific Research Project,No. WJ2016Y10+1 种基金the Jingzhou Science and Technology Bureau Project,No. 2017-93the College Students Innovative Entrepreneurial Training Program in Yangtze University,No. 2019376
文摘BACKGROUND Non-small-cell lung cancer(NSCLC)has the highest morbidity and mortality rates among all malignant tumor types.Although therapies targeting the mutated genes such as KRAS have been used in the clinic for many years,the prognosis remains poor.Therefore,it is necessary to further study the aberrant expression or mutation of non-target genes affecting the survival and prognosis.AIM To explore the impact of simultaneous abnormalities of multiple genes on the prognosis and survival of patients.METHODS We used R packages to analyze gene expression data and clinical data downloaded from The Cancer Genome Atlas(TCGA)database.We also collected samples from 85 NSCLC patients from the First People’s Hospital of Jingzhou City and retrospectively followed the patients.Multivariate Cox regression analysis and survival analysis were performed.RESULTS Analysis of gene expression data from TCGA revealed that the overexpression of the following single genes affected overall survival:TP53(P=0.79),PTEN(P=0.94),RB1(P=0.49),CTNNB1(P=0.24),STK11(P=0.32),and PIK3CA(P=0.013).However,the probability of multiple genes(TP53,PTEN,RB1,and STK11)affecting survival was 0.025.Retrospective analysis of clinical data revealed that sex(hazard ratio[HR]=1.29;[95%CI:0.64-2.62]),age(HR=1.05;[95%CI:1.02-1.07]),smoking status(HR=2.26;[95%CI:1.16-4.39]),tumor histology(HR=0.58;[95%CI:0.30-1.11]),cancer stage(HR=16.63;[95%CI:4.8-57.63]),epidermal growth factor receptor(EGFR)mutation(HR=1.82;[95%CI:1.05-3.16]),abundance(HR=4.95;[95%CI:0.78-31.36]),and treatment with tyrosine kinase inhibitors(TKIs)(HR=0.58;[95%CI:0.43-0.78])affected patient survival.Co-occurring mutations of TP53,PTEN,RB1,and STK11 did not significantly affect the overall survival of patients receiving chemotherapy(P=0.96)but significantly affected the overall survival of patients receiving TKIs(P=0.045).CONCLUSION Co-occurring mutation or overexpression of different genes has different effects on the overall survival and prognosis of NSCLC patients.Combined with TKI treatment,the co-occurring mutation of some genes may have a synergistic effect on the survival and prognosis of NSCLC patients.
文摘Objective The aim of this study was to investigate the antitumor and vascular effects of apatinib use combined with chemotherapy on mice with non-small-cell lung cancer(NSCLC).Methods First,60 tumor-bearing nude mice were randomly divided into control,low-dose,and high-dose groups.Four nude mice per group were sacrificed before administration and on days 1,3,7,and 10 after administration.HIF-1αexpression in tumor tissues was detected.Second,32 nude mice were randomly divided into control,premetrexed,synchronous,and sequential groups.The weights and tumor volumes of mice were recorded.Results(1)HIF-1αexpression decreased significantly on days 3 and 7 after low-dose apatinib treatment.There was no significant difference in HIF-1αexpression in the high-dose apatinib group(P>0.05).MMP-2 and MMP-9 expression levels in the low-dose apatinib group were significantly lower than those in the control group(P<0.05).(2)In the low-dose apatinib group,the microvessel density increased gradually from days 3 to 7 post-treatment,while that in the high-dose apatinib group decreased significantly.(3)The inhibitory effect of sequential therapy using low-dose apatinib and pemetrexed was optimal,while that of synchronous treatment was not better than that of pemetrexed usage alone.Sequential treatment using low-dose apatinib and pemetrexed exerted the best antitumor effect.(4)The expression levels of p-AKT,p-mTOR,p-MEK,and p-ERK in the sequential group were significantly lower than those in the other three groups(P<0.05).Conclusion Apatinib usage involves certain considerations,such as dose requirements and time window for vascular normalization during lung cancer treatment in nude mice,suggesting that dynamic contrast-enhanced magnetic resonance imaging and other tests can be conducted to determine the vascular normalization window in patients with lung cancer and to achieve the optimal anti-vascular effect.
文摘A tumor suppressor gene, CADM1, encoding an immunoglobulin superfamily cell adhesion molecule, is inactivated in various cancers, including non-small-cell lung cancer (NSCLC). Although promoter methylation is one of the mechanisms to suppress CADM1 expression, about half of tumors lacking CADM1 expression do not show methylation of the gene promoter. We herein investigated the possible involvement of microRNA (miRNA) in the down-regulation of CADM1. Using computational algorithms, miR-214 and miR-375 were identified as candidate miRNAs targeting CADM1. A luciferase reporter assay demonstrated that miR-214 and miR-375 repressed the promoter activity through 3’-UTR of CADM1. Quantitative RT-PCR analysis demonstrated that miR-214 and miR-375 was highly expressed in 21 (62%) and 17 cases (50%) of 34 primary NSCLCs. Notably, increased expression of miR-214 was preferentially observed in tumors with advanced pathological stages and in those lacking CADM1 expression but were not associated with the promoter methylation, suggesting that miR-214-mediated silencing would be another mechanism to suppress CADM1 expression. On the other hand, introduction of miR-214 or miR-375 into NSCLC cells decreased CADM1 protein expression. Furthermore, overexpression of miR-214 enhanced anchorage-independent growth of NSCLC cells, A549, whereas transfection of miRNA inhibitor, miR-214 or miR-375, significantly suppressed the in vitro wound healing activity of HCC827 cells. These findings suggest that overexpression of miR-214 and miR-375 could participate in the malignant features of NSCLC through down-regulating CADM1 and would provide a potential target for the treatment of a subset of NSCLC.
文摘The effects of atropine, diazepam and pralidoxime were studied for their ability to block the pathological lesions induced by sarin. Rats were exposed to an aerosol of sarin at a concentration of 51.2mg-m for 15 min following the pretreatment with one of the following combinations: atropine (10 mg/kg, i.m.) and diazepam (0.5 mg/kg, i.m.); atropine and pralidoxime (25 mg/kg, i.m.); diazepam and pralidoxime; atropine, diazepam and pralidoxime. Lung exposed to sarin aerosols revealed an increased cellular proliferation with progressive diffused interstitial thickening on the 4th day following exposure. On the 16th day, loss of alveolar space and consolidation of large areas of all lobes were observed. Sarin also caused damage to the respiratory bronchioles. All the therapy regime blocked the development of lung lesions in the descending orders: atropine, diazepam and pralidoxime, atropine and diazepam > diazepam and pralidoxime > atropine and pralidoxime. The result suggests that diazepam in combination with atropine and pralidoxime could be an effective drug combination regime for the lung lesions.
文摘Patients with early-stage non-small-cell lung cancer(NSCLC)are candidates for curative surgery;however,despite multiple advances in lung cancer management,recurrence rates remain high.Adjuvant chemotherapy has been demonstrated to significantly prolong overall survival(OS),but this benefit is modest and there is an urgent need for effective new therapies to provide a cure for more patients.The high efficacy of tyrosine kinase inhibitors(TKIs)against epidermal growth factor receptor-mutated(EGFR)in patients with advanced EGFR-mutated NSCLC has led to the evaluation of these agents in early stages of the disease.Multiple clinical trials have evaluated the safety and efficacy of EGFR TKIs as an adjuvant treatment,in patients with resected EGFR-mutated NSCLC,and shown that they significantly prolong disease-free survival(DFS),but this benefit does not translate to OS.Recently,an interim analysis of the ADAURA trial demonstrated that,surprisingly,osimertinib improved DFS.This led to the study being stopped early,leaving many unanswered questions about its potential effect on OS and its incorporation as a standard adjuvant treatment in this patient subgroup.These targeted agents are also being evaluated in locally-advanced disease,with promising results,although prospective studies with larger sample sizes are needed to confirm these results.In this article,we review the most relevant studies on the role of EGFR TKIs in the management of early-stage EGFR-mutated NSCLC.