EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR AND BASIC FIBROBLAST GROWTH FACTOR IN HUMAN NON-SMALL CELL LUNG CANCER AND THEIR CLINICAL SIGNIFICANCE

Objective: To explore the expression of vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(bFGF) in non-small cell lung cancer(NSCLC) and theIR clinical significance. Methods: The expression of VEGF and bFGF was examined at the protein levels by immunohistochemical staining in 96 NSCLC patients, and in 36 of which at the mRNA levels by reverse transcription-PCR analysis. Results: VEGF mRNAs were expressed predominately as its secretory forms (VEGF121 and VEGF165) in NSCLC tissues. The positive ratios of VEGF121 and VEGF165 were 69.5%(25 of 36) and 41.7%(15 of 36) respectively. The positive ratio of bFGF was 52.8(19 of 36) in the same tumor specimens. The positive ratios of VEGF and bFGF at protein levels were 55.55%(20 of 36) and 58.33%(21 of 36) respectively. A significant positive correlation was observed between VEGF and bFGF expression in NSCLC tissues(P=0.002). No significant interrelationship between VEGF, bFGF expression and clinical data(age, sex, histological subtype differentiation, P-stage, metastasis and survival) was found. Conclusions: VEGF and bFGF may play an important role in angiogenesis and act in a synergistic manner in NSCLC.

Expression of Nerve Growth Factor and Hypoxia Inducible Factor-1α and Its Correlation with Angiogenesis in Non-Small Cell Lung Cancer

Summary： In order to investigate the expression of nerve growth factor （NGF） and hypoxia inducible factor-1α （HIF-1α） and its correlation with angiogenesis in non-small cell lung cancer （NSCLC）, paraffin-embedded tissue blocks from 20 patients with NSCLC were examined. Twenty corresponding para-cancerous lung tissue specimens were obtained to serve as a control. The expression of NGF, HIF-1α, and vascular endothelial growth factor （VEGF） in the NSCLC tissues was detected by using immunohistochemistry. The microvascular density （MVD） was determined by CD31 staining. The resuits showed that the expression levels ofNGF, HIF-1α and VEGF in the NSCLC tissues were remarkably higher than those in the para-cancerous lung tissues （P〈0.05）. There was significant difference in the MVD between the NSCLC tissues （9.19±1.43） and para-cancerous lung tissues （2.23±1.19） （P〈0.05）. There were positive correlations between NGF and VEGF, between HIF-1α and VEGF, and between NGF and HIF-1α in NSCLC tissues, with the spearman correlation coefficient being 0.588, 0.519 and 0.588, respectively. In NSCLC tissues, the MVD had a positive correlation with the three factors （P〈0.05）. Theses results suggest that NGF and HIF-1α are synergically involved in the angiogenesis of NSCLC.

Clinical Significance of VEGF-C and VEGFR-3 Expression in Non-small Cell Lung Cancer

The relationship between vascular endothelial growth factor-C （VEGF-C）/vascular endothelial growth factor receptor 3 （VEGFR-3） expression and clinicopathologic features of the patients with non-small cell lung cancer （NSCLC） was investigated. The expression of VEGF-C and VEGFR-3 was assessed in 65 patients with NSCLC by immunohistochemistry. The significance of VEGF-C and VEGFR-3 expression was analyzed statistically. The results showed that VEGF-C and VEGFR-3 were highly expressed in cytoplasm and membrane in lung cancer tissues with the positive rate being 55.4 % and 52.3 % respectively, while there was no expression in the normal lung tissues. The expression of VEGF-C was significantly increased in adenocacinoma as compared to other types of NSCLC （P〈0.05）. The VEGFR-3 expression was closely related with lymph node metastasis （P〈0.01） and TNM stage （P〈0.05）. There was a positive correlation between the VEGF-C and VEGFR-3 expression in NSCLC patients （r=-0.658, P〈0.01）. It is suggested that VEGFR-3 plays an important role in the lymphatic metastasis of NSCLC. The interaction between VEGF-C and VEGFR-3 may be deeply involved in the mechanism of lung cancer metastasis.

Expression of VEGFR2 and NRP-1 in non-small cell lung cancer and their clinical significance

Objective： Vascular-targeted therapy is gradually becoming more appealing for patients with lung cancer. It is unclear whether vascular endothelial growth factor receptor 2（VEGFR2） and neuropilin-1（NRP-1） can be biomarkers for clinical treatment. We aimed to investigate the expression levels of VEGFR2 and NRP-1 in human non-small cell lung cancer（NSCLC） and their clinical significance by observing patient prognosis. Methods： VEGFR2 and NRP-1 were assessed by immunohistochemistry（IHC） in 40 patients with NSCLC and in 10 patients with benign lesions of lung; kinase insert domain receptor（KDR） and NRP-1 copy number gain（CNG） was assessed by fluorescence in situ hybridization（FISH）. The distributions of overall survival（OS） and progression-free survival（PFS） were estimated using the Kaplan-Meier method and compared between groups by log-rank test.Results： Rates of positive immunostaining for VEGFR2 and NRP-1 were 58% and 55%, respectively. KDR and NRP-1 CNG（＋） were detected in 32.5% and 30% of tumors, respectively. Levels of both VEGFR2 and NRP-1 in lung tumors were significantly different than in the control tissue（χ2=11.22, P=0.001; χ2=9.82, P=0.001, respectively）; similar results were obtained using CNGs（χ2=4.39, P=0.036; χ2=3.95, P=0.046, respectively）. Statistically significant correlations were observed with histological grade, clinical TNM stage and the lymph node status（P〈0.05）, but not age, gender or pathology type（P〉0.05）. VEGFR2 showed a strong correlation with NRP-1（Rs=0.68, P=0.00）; similar results were observed with KDR and NRP-1 CNG（Rs=0.32, P=0.04）. Significant differences in OS and PFS were observed between the groups with higher VEGFR2 and NRP-1 and those with lower expression（P〈0.05）. Conclusions： According to these data, VEGFR2 and NRP-1 are highly expressed in NSCLC. We can conclude that they play a key role in NSCLC occurrence, development and metastasis and are associated with patient prognosis（P〈0.05 for OS and PFS）. This information will be beneficial for clinical antiangiogenic treatment in NSCLC.

Association of Polymorphic Variants of <i>VEGF</i>and <i>KDR</i>Genes with Development and Metastasing of Non-Small Cell Lung Cancer

Vascular endothelial growth factor (VEGF) is one of the most important and specific factors affecting angiogenesis in tumor development. VEGFR2 is a receptor encoded by the KDR gene. VEGF and VEGFR2 transmit a signal to intracellular tyrosine kinase cascades. Polymorphic variants of the VEGF and KDR genes significantly influence the expression levels of the endothelial growth factor and its receptor, which leads to a change in the activation of angiogenesis in oncopathological processes. In this study, the relationship between the polymorphic variants rs2010963, rs699947 and rs3025039 of the VEGF gene and rs1870377 and rs2071559 of the KDR gene was analyzed with the development of a specific histological type of non-small cell lung cancer and its clinical and morphological characteristics. It was established that the development of squamous cell carcinoma is associated with -634CC genotype of the VEGF gene and the genotypes containing -2578A allele of the VEGF gene reduce the likelihood of this cancer type development. The development of adenocarcinoma is associated with +936CC VEGF/1719TT KDR and +936CT VEGF/1719TT KDR combinations. In women with non-small cell lung cancer, -634GC genotype of the VEGF gene is associated with a greater degree of the primary lesion spread. Genotype -2578СС of the VEGF gene is associated with a higher degree of the primary tumor spread in the general group of patients and with regional metastases in women. Haplotypes -634G/-2578C/+936C are risky for the occurrence of metastases in regional lymph nodes in women.

Effect of Pemetrexed combined with cis-platinum chemotherapy on matrix metalloproteinase VEGF, NK cells and immune function in patients with non-squamous non-small cell lung cancer

Objective:To explore effect of Pemetrexed combined with cis-platinum chemotherapy on matrix metalloproteinase (MMPs), vascular esandothelial growth factor (VEGF), NK cells and immune function in patients with non-squamous non-small cell lung cancer.Method:A total of86 cases of non-squamous non-small cell lung cancer patients were divided into control group (n=44) and observation group (n=42), control group was given docetaxel combined cis-platinum chemotherapy, pemetrexed combined cis-platinum chemotherapy, was applied for observation group. Compared MMP-2, MMP-9, VEGF, NK cells and immune function level before and after treatment in both groups.Results: MMP-2, MMP-9, VEGF, NK cells, CD3+, CD4+, CD8+, CD4+/CD8+ level in both groups before treatment was no significant difference. After treatment, MMP-2, MMP-9, VEGF, CD8+level in both groups was significant lower than before treatment intra-group, and observation was lower than control group, there was significant difference. After treatment, NK cells, CD3+, CD4+, CD8+, CD4+/CD8+ level in both groups was increased dramatically than before treatment of intra-group, moreover, NK cells, CD3+, CD4+, CD8+, CD4+/CD8+level in observation group after treatment was obvious higher than in control group after treatment, there was significant difference.Conclusion:Pemetrexed combined with cis-platinum chemotherapy for non-squamous non-small cell lung cancer could effectively decrease serum MMPs, VEGF level and increase NK cell level, regulate immune function, with definite clinical significance.

Molecularly targeted therapies for advanced or metastatic non-small-cell lung carcinoma

Non-small-cell lung cancer(NSCLC)remains the leading cause of cancer-related death in both men and women in the United States.Platinum-based doublet chemotherapy has been a standard for patients with advanced stage disease.Improvements in overall survival and quality of life have been modest.Improved knowledge of the aberrant molecular signaling pathways found in NSCLC has led to the development of biomarkers with associated targeted therapeutics,thus changing the treatment paradigm for many NSCLC patients.In this review,we present a summary of many of the currently investigated biologic targets in NSCLC,discuss their current clinical trial status,and also discuss the potential for development of other targeted agents.

Clinicopathological and Prognostic Significance of Hypoxia-inducible Factor-1 alpha in Lung Cancer: a Systematic Review with Meta-analysis

Hypoxia-inducible factor-1 alpha（HIF-1α） plays a vital role in the initiation, evaluation and prognosis in lung cancer. The prognostic value of HIF-1α reported in diverse study remains disputable. Accordingly, a meta-analysis was implemented to further understand the prognostic role of HIF-1α in lung cancer. The relationship between HIF-1α and the clinicopathological characteristics and prognosis of lung cancer were investigated by a meta-analysis. Pub Med and Embase were searched from their inception to January 2015 for observational studies. Fixed-effects or random-effects meta-analyses were used to calculate odds ratios and 95% confidence intervals of different comparisons. A total of 20 studies met the criteria. The results showed that HIF-1α expression in lung cancer tissues was significantly higher than that in normal lung tissues. Expression of HIF-1α in patients with squamous cell carcinoma was significantly higher than that of patients with adenocarcinomas. Similarly, non-small cell lung cancer（NSCLC） patients had higher HIF-1α expression than small cell lung cancer（SCLC） patients. Moreover, lymph node metastasized tissues had higher HIF-1α expression than non-lymph node metastasized tissues. A high level HIF-1α expression was well correlated with the expression of vascular endothelial growth factor and epidermal growth factor receptor in the NSCLC. Notably, NSCLC or SCLC patients with positive HIF-1α expression in tumor tissues had lower overall survival rate than patients with negative HIF-1α expression. It was suggested that HIF-1α expression may be a prognostic biomarker and a potential therapeutic target for lung cancer.

Effect and Mechanism of Ginsenoside Rg3 on Postoperative Life Span of Patients with Non-Small Cell Lung Cancer

Objective： To explore the effect and mechanism of ginsenoside Rg3 （Shenyi Capsule, 参一胶囊） on the postoperative life span of patients with non-small cell lung cancer （NSCLC）. Methods： The prospective, randomized, controlled method was adopted. One hundred and thirty- three patients with NSCLC were randomly assigned to 3 groups： Shenyi Capsule group （43 cases）, combined therapy group （Shenyi Capsule plus chemotherapy, 46 cases）, and chemotherapy group （44 cases）. The survival rates, immune function and the correlation between vascular endothelial growth factor （VEGF） expression and clinical effect were analyzed in the three groups. Results： （1） The 1-year survival rate in the Shenyi group, the combined group and the chemotherapy group was 76.7% （33/43）, 82.6% （38/46）, and 79.5% （35/44）, respectively; the 2-year survival rate was 67.4% （29/43）, 71.7% （33/46）, and 70.5% （31/44）, respectively; and the 3-year survival rate was 46.5% （20/43）, 54.3% （25/46）, and 47.7% （21/44）, respectively. There was no significant difference among the 3 groups （P〉0.05）. （2） NK cells were increased to different degrees and the ratio of CD4/CD8 was normal in the Shenyi Capsule group and the combined group, while the ratio of CD4/CD8 was disproportional in the chemotherapy group. （3） In the chemotherapy group, the 3-year survival rate was lower in patients with positive expression of VEGF than in patients with negative expression （37.0% vs 64.7%, χ^2=17.9, P〈0.01）, but no significant statistical difference was shown in the other two groups （53.6% vs 55.6%, P〉0.05; 44.4% vs 50.0%, P〉0.05）. Conclusion： Shenyi Capsule, especially in combination with chemotherapy, can improve the life span of patients with NSCLC after operation. The mechanism might be correlated with improving the immune function and anti-tumor angiogenesis.

Recombinant human erythropoietin accelerated the proliferation of non-small cell lung cancer cell lines and reduced the expression of VEGF,HIF-1α,and PD-L1 under a simulated hypoxic environment in vitro

Background:As erythropoietin(EPO)has been used to treat anemia in cancer patients,negative controversy has continued.Unfortunately,its effects on non-small-cell lung carcinoma(NSCLC)cell lines are uncertain and the phenomenon of inducing immune escape of tumor cells remains to be explored.This study aimed to provide an important basis for the application of exogenous EPO in the treatment of tumor-associated anemia.Methods:Cells were cultured in 1%O2,5%CO_(2),and 94%N2 to simulate a hypoxic environment of the tumor.A549 cell line(lower expression EPOR)and NCI-H838 cell line(higher expression EPOR)were treated with 2 and 8 U/ml recombinant human EPO(rhEPO).CCK-8 method was used to determine the logarithmic growth phase of the cells and to detect cell proliferation.The expression levels of VEGF,HIF-1α,and PD-L1 were determined by western blot.One-way ANOVA was used for statistical analysis between groups,withp<0.05 indicating a significant difference.Results:Hypoxia itself could decrease the survival rate of NSCLC cells.Under the hypoxic condition,rhEPO induced tumor cells proliferation,especially in the NCI-H838 cell line,where 2 U/ml rhEPO increased the total number of surviving cells(Hypoxia+rhEPO 2 U/ml vs.Hypoxia,p<0.05).Western blot analysis showed that hypoxia upregulated the expression of VEGF,HIF-1α,and PD-L1 in NSCLC cell lines(Normoxia vs.Hypoxia,p<0.05),but may not be dependent on the expression levels of EPOR.RhEPO decreased the expression levels of VEGF and HIF-1α.In the A549 cell line,it depended on the concentration of rhEPO and was particularly obvious in HIF-1α(Hypoxia vs.Hypoxia+rhEPO 2 U/ml vs.Hypoxia+rhEPO 8 U/ml,p<0.05).A low concentration of rhEPO may not reduce VEGF expression.In the NCI-H838 cell line,the effect of rhEPO on VEGF was more obvious,but it may be independent of rhEPO concentrations.The downregulation of PD-L1 expression by rhEPO was only presented in the A549 cell line and required higher rhEPO concentrations(Hypoxia+rhEPO 8 U/ml vs.Hypoxia&Hypoxia+rhEPO 2 U/ml,p<0.05).Conclusion:The effect of prolonged high concentrations of rhEPO under hypoxic conditions resulted in accelerated cells proliferation of non-small-cell lung cancer and was independent of EPOR expression levels on the cell lines surface.Hypoxia resulted in increased expression of VEGF,HIF-1α,and PD-L1 on the NSCLC cell lines.Under normoxic conditions,rhEPO did not affect the expression of VEGF,HIF-1α,and PD-L1;but under hypoxic conditions,the application of rhEPO reduced the expression of VEGF,HIF-1α,and PD-L1,producing an impact on the biological behavior of tumor cells.

贝伐珠单抗与GC化疗方案联合治疗晚期非小细胞肺癌的效果及药物经济学评价

目的 探究贝伐珠单抗联合GC化疗方案(顺铂+吉西他滨)治疗晚期非小细胞肺癌(NSCLC)的效果及药物经济学价值。方法 选取2020年7月—2022年7月收治的86例晚期NSCLC,依据治疗方案分为对照组和观察组,每组43例。对照组给予GC化疗方案,观察组给予贝伐珠单抗联合GC化疗方案。对比2组疗效、毒副反应发生情况以及治疗前后血生化指标,并进行成本-效果分析。结果 观察组客观缓解率58.14%(25/43)、疾病控制率93.02%(40/43)均高于对照组的32.56%(14/43)、72.09%(31/43)(P<0.05)。治疗2、4个疗程,观察组血清癌胚抗原、糖类抗原125、神经元特异性烯醇化酶、血管内皮生长因子、碱性成纤维细胞生长因子均低于对照组(P<0.05)。2组各项毒副反应总发生率比较无显著差异(P>0.05)。观察组总成本高于对照组(P<0.05)。观察组成本-效果比为790.67低于对照组的901.31,且敏感性分析显示,成本-效果分析稳定可靠。结论 贝伐珠单抗联合GC化疗方案治疗晚期NSCLC患者,可下调肿瘤标志物及血管内皮因子水平,提升疗效,且成本-效果优势明显。

奥希替尼联合化疗治疗晚期NSCLC患者EGFR基因突变型的近远期疗效

目的:探讨奥希替尼联合化疗治疗表皮生长因子受体(EGFR)基因突变的晚期非小细胞肺癌(NSCLC)的疗效和安全性。方法:按治疗方案不同将80例晚期NSCLC患者(EGFR突变型)分为联合组(n=38)和单药组(n=42),联合组予以奥希替尼联合化疗治疗,单药组予以奥希替尼单药治疗。比较两组近期疗效和无进展生存期(PFS)、总生存期(OS);比较两组血清癌胚抗原(CEA)、细胞角蛋白19片段(CYFRA21-1)、血管内皮生长因子(VEGF)和胰岛素样生长因子-1(IGF-1)水平,并记录两组不良反应发生情况。结果:联合组ORR为68.42%,高于单药组的54.76%,但差异无统计学意义(P>0.05)。联合组中位PFS为15.2个月,高于单药组的10.3个月(P<0.05);联合组中位OS为25.1个月,高于单药组的18.2个月(P<0.05)。治疗后,联合组血清CEA、CYFRA21-1和VEGF、IGF-1水平均低于单药组(P<0.05)。两组不良反应均以I~II级为主,但联合组白细胞减少发生率高于单药组(P<0.05);两组其他不良反应发生率比较,差异无统计学意义(P>0.05)。结论:奥希替尼联合化疗治疗晚期NSCLC(EGFR突变型)能有效降低血清肿瘤标志物和IGF-1、VEGF水平,使患者生存获益。

贝伐珠单抗联合免疫治疗对非鳞非小细胞肺癌血清学指标及预后的影响

目的探究贝伐珠单抗联合免疫治疗对非鳞非小细胞肺癌(nsNSCLC)血清学指标及预后的影响。方法回顾性分析2018年1月—2020年6月收治94例nsNSCLC的临床资料,根据治疗方案分为对照组和观察组,每组47例。对照组予以纳武利尤单抗治疗,观察组予以贝伐珠单抗联合纳武利尤单抗治疗。探究2组治疗3个周期后临床疗效及血清学指标差异,分析治疗期间不良反应及随访2年生存情况差异。结果观察组治疗3个周期后临床总有效率高于对照组(P<0.05)。治疗3个周期后,2组血清细胞角蛋白19片段抗原21-1(CYFRA21-1)、糖类抗原125(CA125)、血管内皮生长因子、转化生长因子-β1、巨噬细胞移动抑制因子水平均较治疗前降低,且观察组低于对照组(P<0.05)。治疗3个周期后,2组血清载脂蛋白A1较治疗前升高,且观察组高于对照组(P<0.05)。2组治疗期间不良反应发生率以及2年生存率比较差异无统计学意义(P>0.05)。结论贝伐珠单抗联合免疫治疗对nsNSCLC的疗效显著,对血清CYFRA21-1、CA125及生长因子有显著调节作用,且不良反应不会显著增加,但对患者生存期影响不显著。

乐伐替尼对甲状腺癌SW579细胞放射敏感性及血管内皮生长因子、碱性成纤维细胞生长因子、碱性成纤维细胞生长因子受体表达的影响

目的:探究乐伐替尼对甲状腺癌SW579细胞放射敏感性以及对血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)及其受体(bFGFR)表达的影响。方法:体外培养甲状腺癌SW579细胞,筛选最佳放射剂量,取培养至对数生长期的SW579细胞分为对照组(常规培养SW579细胞)、放射组(使用4 Gy X射线照射SW579细胞)、乐伐替尼低(在含SW579细胞的培养基中加入5μmol/L的乐伐替尼后,再使用4 Gy X射线照射SW579细胞)、高(在含SW579细胞的培养基中加入10μmol/L的乐伐替尼后,再使用4 Gy X射线照射SW579细胞)浓度组,培养48 h后。检测SW579细胞存活率、细胞凋亡率和细胞中B细胞淋巴瘤-2相关X(Bax)、B细胞淋巴瘤-2(Bcl-2)、活化胱天蛋白酶3(Cleaved caspase-3)、VEGF、bFGF、bFGFR蛋白表达。结果:随着放射剂量的升高,SW579细胞存活率依次降低(均P<0.05),选取4 Gy X射线进行后续实验;与对照组相比,放射组、乐伐替尼低、高浓度组SW579细胞存活率、Bcl-2、VEGF、bFGF、bFGFR蛋白表达依次降低(均P<0.05),细胞凋亡率、Bax、Cleaved caspase-3蛋白表达依次升高(均P<0.05)。结论:乐伐替尼能增强SW579细胞的放射敏感性,其机制可能与抑制VEGF、bFGF、bFGFR蛋白表达有关。

沙参麦冬汤加减联合贝伐珠单抗对非小细胞肺癌患者血清VEGF、bFGF水平及免疫功能的影响

目的探讨非小细胞肺癌(NSCLC)患者应用沙参麦冬汤加减联合贝伐珠单抗治疗的效果。方法采用随机数字表法将本院2019年12月至2021年12月收治的NSCLC患者102例分为两组,每组各51例。对照组予以GP化疗方案,观察组加用沙参麦冬汤加减联合贝伐珠单抗治疗,均连续治疗6周。比较两组临床疗效、中医证候积分、血清学指标、免疫功能指标及不良反应。结果与对照组比,观察组临床总有效率及CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平较高,各项中医证候积分及血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)水平较低,有统计学差异(P<0.05)。两组不良反应发生率比较,无统计学差异(P>0.05)。结论NSCLC患者应用沙参麦冬汤加减联合贝伐珠单抗治疗效果较佳,改善临床症状和免疫功能,抑制新生血管生成,且安全性好,值得推广。

克唑替尼联合沙利度胺治疗非小细胞肺癌的效果观察

目的分析非小细胞肺癌(NSCLC)疾病特点,评价克唑替尼联合沙利度胺治疗的效果。方法86例NSCLC患者,采取随机数字表法分为对照组与观察组,各43例。对照组患者采取克唑替尼治疗,观察组患者在对照组基础上联合沙利度胺治疗。比较两组患者治疗效果、不良反应发生情况及肿瘤坏死因子-α(TNF-α)、血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)水平。结果观察组患者治疗总有效率46.51%及临床控制率79.07%均高于对照组的23.26%、48.84%,差异具有统计学意义(P<0.05)。两组患者不良反应发生率比较,差异无统计学意义(P>0.05)。观察组患者TNF-α、VEGF、bFGF水平分别为(10.45±2.99)、(384.59±70.50)、(8.65±2.45)pg/ml,低于对照组的(17.35±4.05)、(488.33±70.50)、(14.50±2.60)pg/ml,差异具有统计学意义(P<0.05)。结论克唑替尼联合沙利度胺治疗NSCLC具有安全性、有效性价值,有助于抑制肿瘤发展、转移。

沙利度胺对肺癌患者血清VEGF、bFGF和TNF-α水平的影响及临床意义

背景与目的:沙利度胺具有抗血管生成作用,本研究的目的在于评价沙利度胺联合化疗治疗晚期非小细胞肺癌的临床疗效并比较治疗前后血清VEGF、bFGF和TNF-α的变化。方法:66例晚期非小细胞肺癌随机分为2组各33例,联合组:NP+沙利度胺治疗。d1,8静脉滴注长春瑞滨25mg/m2,d1静脉滴注DDP70～80mg/m2;沙利度胺200mg/d,口服,第1天起连续给药。化疗组:单化疗,用NP方案,剂量同上。采用酶联免疫法检测40例(两组各前20例)患者治疗前后血清VEGF、bFGF和TNF-α的含量。结果:联合组有效率(CR+PR)为51.5%;化疗组有效率为36.4%。两组有效率无显著差异(P>0.05)。联合组治疗有效的NSCLC患者血清VEGF水平显著下降(P<0.05)。化疗组治疗有效的NSCLC患者治疗前后血清VEGF对比差异无显著性(P>0.05)。两组化疗无效的患者治疗后血清VEGF、bFGF水平均比治疗前显著升高(P<0.05)。联合组治疗后血清TNF-α水平显著低于治疗前水平(P<0.05)。化疗组治疗前后血清TNF-α水平比较差异无显著性(P>0.05)。结论:沙利度胺联合NP能改善晚期非小细胞肺癌患者的有效率;沙利度胺能够抑制肿瘤细胞VEGF和TNF-α的产生,从而降低血清VEGF和TNF-α的水平。

STAT3、pSTAT3、VEGF和bFGF在非小细胞肺癌中的表达

目的探讨信号转导及转录活化因子3(STAT3)及其磷酸化形式pSTAT3与血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)在非小细胞肺癌(NSCLC)组织中的表达及关系。方法应用免疫组织化学方法检测68例NSCLC和27例正常肺组织中STAT3、pSTAT3、VEGF、bFGF的表达,并分析其与各临床病理参数之间的关系。结果STAT3、pSTAT3、VEGF、bFGF在NSCLC组织的阳性表达率均高于正常肺组织(P<0.05);NSCLC中pSTAT3、VEGF、bFGF三者之间的表达呈正相关(P<0.05)。STAT3、pSTAT3在低分化NSCLC中的表达高于中、高分化者,在TNM Ⅲ+Ⅳ期NSCLC中的表达高于Ⅰ+Ⅱ期,有淋巴结转移者高于无淋巴结转移者,差异均有统计学意义(P<0.05)。VEGF、bFGF在TNM Ⅲ+Ⅳ期NSCLC中的表达高于Ⅰ+Ⅱ期(P<0.05),有淋巴结转移者VEGF表达高于无淋巴结转移者(P<0.05)。结论STAT3、pSTAT3、VEGF和bFGF在非小细胞肺癌中高表达,并与肿瘤的侵袭和转移有关。

非小细胞肺癌患者血清VEGF和bFGF检测的临床意义

目的探讨非小细胞肺癌(NSCLC)患者血清血管内皮细胞生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)的水平与临床病理特征的关系,比较它们在肺癌诊治中的临床价值。方法采用ELISA法检测40例晚期NSCLC患者化疗前后血清VEGF和bFGF的含量。结果Ⅳ期NSCLC患者的血清VEGF含量显著高于Ⅲ期(P<0.05)。吸烟指数≥400组血清VEGF水平显著高于吸烟指数<400组(P<0.01)。低分化癌血清bFGF水平显著高于高、中分化癌(P<0.01)。吸烟指数≥400组血清bFGF水平显著高于吸烟指数<400组(P<0.05)。VEGF与bFGF之间存在显著正相关(P<0.05)。肺癌化疗无效的患者化疗后血清VEGF和bFGF水平均比化疗前升高(P<0.05)。结论根据血清VEGF水平可推测病情进展;VEGF和bFGF在NSCLC血管形成过程中具有协同作用;血清VEGF和bFGF水平可作为NSCLC患者疗效预测的参考指标。

刺芒柄花素对老年晚期肺癌患者胸水及血清中内皮抑素、VEGF、MMP-2、bFGF及肿瘤标志物的影响

目的探讨刺芒柄花素对老年晚期肺癌患者胸水及血清中内皮抑素(endostatin,ES)、血管内皮素生长因子(vascular endothelial growth factor,VEGF)、基质金属蛋白酶2(matrix metalloproteinases 2,MMP-2)、碱性成纤维细胞生长因子(basic fibroblast growth factor,b FGF)及肿瘤标志物的影响。方法选取河南省南阳市中心医院诊治的老年晚期肺癌患者67例,根据随机数字表法随机分为2组:对照组33例,行临床常规NP方案化疗;实验组34例,在对照组相同的临床常规治疗基础上加用刺芒柄花素予以治疗,比较2组患者胸水和血清中ES、VEGF、MMP-2、b FGF、肿瘤标志物水平以及生存质量评分变化。结果与对照组比较,实验组胸水和血清中ES、VEGF、MMP-2、b FGF含量均明显降低(P<0.05);实验组血清癌胚抗原(carcino embryonie antigen,CEA)、神经元特异性烯醇化酶(neuron specific enolase,NSE)、细胞角蛋白19片段(cytokeratin-19-fragments,CYFRA21-1)、糖类抗原125(carbohydrate antigen125,CA125)水平明显降低(P<0.05);实验组患者生存质量评分情况明显优于对照组(χ2=4.96,P<0.05)。结论刺芒柄花素对老年晚期肺癌患者治疗具有较好的临床疗效,且能有效改善患者生存质量,降低胸水和血清中ES、VEGF、MMP-2、b FGF等指标和肿瘤标志物水平,对临床治疗老年晚期肺癌具有重要意义。