Objective To compare the long-term cost-utility of three first-generation EGFR-TKIs targeted drugs, gefitinib, icotinib, and erlotinib as first-line treatments for advanced non-small cell lung cancer (NSCLC). Methods Real-world data were collected from 1 511 patients with advanced NSCLC treated with first-generation EGFR-TKIs as first-line treatment at West China Hospital of Sichuan University from 2009 to 2019. A three-state Markov model was established to evaluate the clinical efficacy, safety and cost-utility of three first-generation EGFR-TKIs targeted drugs. The transition probability of each state was obtained by survival analysis, the direct and indirect costs were calculated by the bottom-up method, the health utility value was obtained through literature research, the incremental cost effectiveness ratio (ICER) and quality-adjusted life years (QALYs) were calculated, and sensitivity analyses and Monte Carlo simulations were performed. Results There was no significant difference in clinical efficacy among the three first-generation EGFR-TKIs in the treatment of NSCLC. The incidence of skin rash and liver injury caused by gefitinib was significantly higher than that caused by icotinib and erlotinib (P<0.05). The average economic burden of patients treated with icotinib was the lowest (CNY 192 535.3) (P<0.01). The cost-utility ratio of icotinib (CNY 132 985.9/QALYs) was much lower than that of gefitinib (CNY 205 005.3/QALYs) and erlotinib (CNY 172 893.1/QALYs). Conclusion Compared with the three first-generation EGFR-TKIs drugs, icotinib is the most cost-effective.
ObjectiveTo reveal the true value of plasma detection of epidermal growth factor receptor (EGFR) mutation for early-stage non-small cell lung cancer (NSCLC) gene diagnosis and to predict survival prognosis. MethodsTissue samples of positive EGFR mutations by using amplification refractory mutation system (ARMS) method were surgically resected from 198 patients with stage I-IV NSCLC between February 2014 and June 2015 in Tangdu hospital. Paired blood samples were collected before surgery. And the cellfree DNA (cfDNA) in plasma was extracted, plasma EGFR mutations were detected by real-time polymerase chain reaction (PCR). Concentration of cfDNA was measured by ultraviolet spectrophotometry. Follow-up observation for stage ⅢA patients was put into force after surgery. Kaplan-Meire was used in survival analysis. ResultsThe sensitivity of EGFR mutation for the 198 paired tissues and plasma samples was 17.2%.The sensitivity was positively correlated with TNM stage and negatively correlated with tumor differentiation. The sensitivity of sage ⅢA was 33.3%, significantly higher than that of the patients at stage ⅠA (1.6%, P=0.000) and stage ⅠB (7.9%, P=0.004). The sensitivity of poor differentiation was 36.8%, significantly higher than that of high differentiation (0.0%, P=0.000) and moderate differentiation (15.7%, P=0.010). There was no correlation between plasma cfDNA concentration and patient characteristics. Survival analysis showed that plasma detection was a vital factor for predicting postoperative survival prognosis of stage ⅢA patients (P=0.014). ConclusionTissue samples cannot be replaced by plasma samples for epidermal growth factor receptor (EGFR) mutation test in early-stage NSCLC patients, currently. When the sensitivity increases dramatically in the plasma samples of stage ⅢA NSCLC and poor differentiation tumor, we recommend using plasma detection for gene diagnosis, dynamic monitoring of EGFR mutations in stage ⅢA or poorly differentiated tumors, especially in NSCLC patients whose tissue samples cannot be obtained by surgery. And plasma EGFR detection is a valuable method of forecasting survival prognosis for locally advanced NSCLC patients.
ObjectiveTo detect the expressions of signal peptide-CUB-EGF-like domain containing protein 3 (SCUBE3) and specificity protein 1 (SP1) in breast cancer tissues, and explore relations between their protein expressions and clinicopathologic features or prognosis.MethodsFrom February 2013 to October 2015, the breast cancer tissues and the corresponding adjacent normal breast tissues of 80 women patients with breast cancer in the Mianyang Central Hospital were selected, and the expressions of SCUBE3 and SP1 proteins in the tissues were detected by immunohistochemistry. The relations between the expressions of SCUBE3 and SP1 and clinicopathologic parameters of breast cancer were analyzed, the correlation between the SCUBE3 and SP1 was analyzed by Spearman rank correlation analysis. Kaplan-Meier method was used to analyze the survival of patients with breast cancer; and Cox proportional hazards regression model was used to analyze the risk factors of overall survival of patients with breast cancer.ResultsThe positive rates of SCUBE3 and SP1 proteins expressions in the breast cancer tissues were higher than those in the corresponding adjacent normal breast tissues (P<0.05). The positive rates of SCUBE3 and SP1 protein expressions were higher in the breast cancer tissues with lymph node metastasis and molecular subtypes of Luminal A or B (P<0.05), and the positive rates of SCUBE3 protein expression were higher in the breast cancer tissues with TNM stage Ⅱ–Ⅳ and high Ki67 (P<0.05). The retsult of Spearman rank correlation analysis showed that the positive rates of SCUBE3 and SP1 proteins expressions in the breast cancer tissues was positive correlation (χ2=7.979, rs=0.316, P=0.005). Kaplan-Meier curve showed that the overall survival of the patients with positive expression of SCUBE3 or SP1 protein was worse than that of the patients with negative expression (χ2=4.042, P=0.044; χ2=10.676, P=0.001). The Cox proportional hazards regression model multivariate analysis showed that the positive SCUBE3 (HR=6.020, P=0.016), positive SP1 (HR=4.077, P=0.018), lymph node metastasis (HR=3.518, P=0.017), and higher Ki67 expression (HR=7.989, P<0.001) were the independent risk factors of overall survival for the patients with breast cancer.ConclusionPositive rates of SCUBE3 and SP1 proteins expressions in breast cancer tissues are higher and there is a positive correlation between them, which are closely related to clinicopathologic parameters such as lymph node metastasis and molecular subtypes and prognosis of patients with breast cancer.
The resistance of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has been brought into focus. COX-2 signal pathway was found to be closely related to EGFR signal pathway by recent researches, and there has been a growing interest to focus the researches on whether COX-2 pathway inhibition improves the efficacy of EGFR-TKIs in treating advanced NSCLC. In this review, we will illustrate recent advances of combined inhibition of EGFR and COX-2 signal pathways in NSCLC therapy.
Objective To investigate the effects of the recombinant plasmid pIRES-hBMP-2-hVEGF165 on differentiation and maturation of hBMSCs in vitro. Methods The co-expressing vector of hBMP-2 and hVEGF165 was constructed. The BMSCs were isolated and cultured from health adult human denoted marrow. By the l ipofection method, the reconstructed plasmids pIRES-hBMP-2-hVEGF165, pIRES-hBMP-2, pIRES-hVEGF165 and pIRES neo empty vector, weretransfected to hBMSCs (groups A, B, C and D). The untransfected cells were harvested as control group (group E). After4 weeks of culture, RT-PCR was employed to assay the hBMP-2, hVEGF165 and osteocalcin mRNA expression in hBMSCs. The expressions of hBMP-2 and hVEGF165 of BMSCs were assayed by Western blot. The level of ALP activities of BMSCs was determined. Col I was also determined by immunohistochemical staining. Results Compared to group E, the hBMSCs in group A secreted high level of hBMP-2, hVEGF165, Col I and osteocalcin; osteocalcin and Col I expressed at high level in group B, and hVEGF165 expressed at high level in group C. Otherwise, the expression of hVEGF165 in group B and the expressions of hBMP-2 and Col I in group C resemble to that of groups D and E, no expression or few expression was observed. The activities of ALP in groups A, B, C, D and E were 0.91 ± 0.03, 0.90 ± 0.02, 0.64 ± 0.03, 0.67 ± 0.01 and 0.66 ± 0.02, respectively. The activity of ALP of groups A and B were significantly increased compared with that of group E (P lt; 0.05); there was no significant difference among groups C, D and E (P gt; 0.05). Conclusion The recombinant plasmid pIRES-hBMP-2-hVEGF165 can be successfully transfected into BMSCs with cation l iposome-mediated transfection method, the exogenous hBMP-2 and hVEGF165 genes can be expressed constitutively in the transfected BMSCs, and it can enhance the differentiation abil ities of BMSCs.
ObjectiveTo investigate the expression of tumor metastasis associated genes-1 (MTA1) and vascular endothelial growth factor-C (VEGF-C) in esophageal squamous cell carcinoma (ESCC) and the relationship between them and lymphangiogenesis. MethodA total of 107 patients who received excision for ESCC in the Cardiothoracic Surgery Department of Suining Central Hospital from March 2013 through January 2014 were enrolled. And the paraffinembedded esophageal tissues in 56 healthy persons were collected. The expression of MTA1 and VEGF-C in ESCC was detected using the immunohistochemical method. And D2-40 was used to label the micro-lymphatic endothelial cells of the tumor tissues while the micro-lymphatic vessel density (LVD) was counted. Meanwhile, a statistical analysis was performed for the relationship between MTA1 with VEGF-C and clinical pathological parameters. ResultsThe expression rates of MTA1 protein and VEGF-C protein in ESCC (50.4% and 58.8%, respectively) were higher than those in normal esophageal tissues with a statistical difference (P<0.05). Besides, their high expression rates in stage T3/T4 ESCC and lymph node metastasis group were significantly higher than those in stage T1/T2 ESCC and metastasisfree group, with statistical differences (P<0.05). The high expression rates of MTA1 and VEGF-C protein in ESCC with different TNM stages were compared using Kruskal-Wallis test with statistical differences (P<0.05). Moreover, a positive correlation existed in the expression level between MTA1 protein and VEGF-C protein of ESCC (Spearman coefficient r=0.512, P=0.000). And LVD of the high expression group for MTA1 protein and VEGF-C protein was statistically different from that of the low expression group (P<0.05). ConclusionThe expression of MTA1 is positively correlated with the expression of VEGF-C in ESCC. And they may co-promote lymphangiogenesis and lymphatic metastasis in ESCC. Therefore, both can be used as the laboratory indicators to determine the prognosis of ESCC.
To construct the recombinant adeno-associated virus (rAAV) vector co-expressinghVEGF165 and hBMP-7 depending on internal ribosome entry site (IRES) sequence, to measure the virus titer and to ver ify the correct recombination. Methods The AAV helper-free system was used to generate the rAAV co-expressing hVEGF165 and hBMP-7 genes. The IRES sequence from the bicistronic eukaryotic expression plasmid pIRES was cut down and subcloned into the ITR/MCS containing vector pAAV-MCS to get pAAV-MCS A-IRES-MCS B, in which upstream MCS A and downstream MCS B was constructed. The hVEGF165 and hBMP-7 genes were ampl ified by PCR and inserted into MCS A and MCS B respectively. The recombinant expression plasmid pAAV-hVEGF165-IRES-hBMP-7 was co-transfected into AAV-293 cells with pHelper and pAAV-RC for packaging of recombinant AAV. The green fluorescent protein (GFP) labeled rAAVIRES GFP was simultaneously packaged by using the parallel plasmid pAAV-IRES-GFP. The efficiency of rAAV packagingwas monitored under fluorescent microscope and recombinant viral particles were harvested from infected AAV-293 cells.The virus titer was measured through infecting AAV-HT1080 cells, and the recombinant rAAV-hVEGF165-IRES-hBMP-7was verified by PCR of the exogenous interest genes of hVEGF165 and hBMP-7. Results The recombinant plasmid pAAVhVEGF165- IRES-hBMP-7 was verified by double digestion. Using the AAV helper-free system, GFP expression could be observed under fluorescent microscope 72 hours after triple plasmid co-transfection and the system provided a high packing ratio of 95%-100%. The rAAV has a high purity and high titer of 5.5 × 1011vp/mL, and AAV-HT1080 cell could be infected at a ratio of 90%. The recombinant virus was confirmed by PCR of exogenous hBMP-7 and hVEGF165 genes. Conclusion Re combinant rAAV-hVEGF165-IRES-hBMP-7 was successfully constructed with a high virus titer, which may offer the basement
Objective To systematically review the efficacy of intravitreal injection of anti-vascular endothelial growth factors (anti-VEGF) on macular edema (ME) secondary to retinal vein occlusion (RVO). Methods Databases including PubMed, EMbase, Web of Science, The Cochrane Library, CNKI, WanFang Data and VIP were electronically searched to identify randomized controlled trials on different anti-VEGF drugs in the treatment of RVO-ME from inception to September 17th 2021. Two reviewers independently screened literature, extracted data, and assessed the risk bias of the included studies. Meta-analysis was then performed using RevMan 5.3 software. Results A total of 11 RCTs were included. Data from these studies included 2 436 eyes, of which 1 682 involved central retinal vein occlusion and 754 involved branch retinal vein occlusion. The results of meta-analysis showed that at 6 months of follow-up, anti-VEGF drug treatment of RVO-ME improved corrected visual acuity (MD=14.97, 95%CI 10.09 to 19.86, P<0.000 01) and reduced central retinal thickness (MD= ?218.21, 95%CI ?295.56 to ?140.86, P<0.000 01) compared with control groups. At 12 months, anti-VEGF treatment of RVO-ME showed better improvement in corrected visual acuity compared with control group (MD=5.70, 95%CI 3.90 to 7.50, P<0.000 01). No statistically differences were observed in the improvements corrected visual acuity with different anti-VEGF drugs. However, for central retinal vein occlusion, different anti-VEGF drugs improved the central retinal thickness including aflibercept vs. bevacizumab (MD=?46.79, 95%CI ?83.12 to ?10.46, P=0.01), and bevacizumab vs. ranibizumab (MD=76.03, 95%CI 30.76 to 121.30, P=0.001) had significant differences. Conclusions The current evidence shows that anti-VEGF drugs can improve vision and reduce macular edema in the treatment of RVO-ME. Bevacizumab may be an effective alternative to ranibizumab or aflibercept. Existing evidence cannot determine differences between the improvement of best-corrected vision and the reduction of central retinal thickness during the long-term treatment of RVO, which requires to be verified by further research.
The 2025 American Society of Clinical Oncology (ASCO) Annual Meeting was held in Chicago. At the meeting, researches on the treatment of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) once again took the spotlight. Combination therapy strategies have demonstrated the potential to overcome resistance to EGFR tyrosine kinase inhibitor (EGFR-TKI) and prolong survival. Meanwhile, progress has also been made in individualized treatment strategies for young patients and those with fibrotic interstitial lung disease. However, the complexity of resistance mechanisms, special treatment considerations for different populations, and the impact of socioeconomic factors on treatment accessibility remain challenges in the field of EGFR-mutant NSCLC treatment. In the future, it is necessary to further explore more effective treatment regimens and expand the accessibility of precision medicine to maximize patient benefits.
Objective To construct a green fluorescent protein expression plasmid pEGFP-C3-anti-TAG72 scFv-CD28, containing anti-TAG72 single chain variable fragment (scFv) fused into the transmembrane and intracellular domain of the signal-transducing chain of CD28 gene, and to transfect it into peripheral blood mononuclear cells． Methods Recombinant transmembrane and intracellular domain of CD28 cDNA and anti-TAG72 scFv cDNA fragment was subcloned into pEGFP-C3 vector. Recombinant clones were selected by Kanamyein， and then identified by PCR， enzyme digestion analysis and DNA sequencing. The recombinant plasmid was transfected into peripheral blood mononuclear cells by means of lipofection. The recombinant protein expression was confirmed by immunocytochemistry, laser scanning confocal microscope, PCR and Western blot analysis. Results The fused gene fragment of anti-TAG72 scFv-CD28 was successfully inserted into pEGFP-C3 plasmid, and it was confirmed by enzyme digestion and DNA sequencing. The fused anti-TAG72 scFv-CD28 gene and its protein was identified in peripheral blood mononuclear cells． Conclusion The eukaryotic expression plasmid pEGFP-C3-anti-TAG72 scFv-CD28 was successfully constructed and transiently expressed in peripheral blood mononuclear cells， which would lay a foundation for further studies on the role of it to activate tumor-associated antigen-specific T lymphocyte, for generating of modified T lymphocytes targeting gastrointestinal tumors.