1.Efficacy Differences of First-line EGFR-TKIs Alone vs in Combination with Chemotherapy in Advanced Lung Adenocarcinoma Patients with Sensitive EGFR Mutation and Concomitant Non-EGFR Genetic Alterations.
Guowei ZHANG ; Ruirui CHENG ; Yuanyuan NIU ; Huijuan WANG ; Xiangtao YAN ; Mina ZHANG ; Xiaojuan ZHANG ; Jinpo YANG ; Chunhua WEI ; Zhiyong MA
Chinese Journal of Lung Cancer 2022;25(9):651-657
BACKGROUND:
Epidermal growth factor receptor (EGFR) mutations are often associated with non-EGFR genetic alterations, which may be a reason for the poor efficacy of EGFR tyrosine kinase inhibitors (TKIs). Here we conducted this study to explore whether EGFR-TKIs combined with chemotherapy would benefit advanced lung adenocarcinoma patients with both sensitive EGFR mutation and concomitant non-EGFR genetic alterations.
METHODS:
Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant non-EGFR genetic alterations were retrospectively collected. And the patients were required to receive first-line EGFR-TKIs and chemotherapy combination or EGFR-TKIs monotherapy. Demographic, clinical and pathological data were collected, and the electronic imaging data were retrieved to evaluate the efficacy and time of disease progression. Survival data were obtained through face-to-face or telephone follow-up. The differences between the two groups in objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were investigated.
RESULTS
107 patients were included, including 63 cases in the combination group and 44 cases in the monotherapy group. The ORR were 78% and 50% (P=0.003), and DCR were 97% and 77% (P=0.002), respectively. At a median follow-up of 13.7 mon, a PFS event occurred in 38.1% and 81.8% of patients in the two groups, with median PFS of 18.8 mon and 5.3 mon, respectively (P<0.000,1). Median OS was unreached in the combination group, and 27.8 mon in the monotherapy group (P=0.31). According to the Cox multivariate regression analysis, combination therapy was an independent prognostic factor of PFS CONCLUSIONS: In patients with EGFR-mutant advanced lung adenocarcinoma with concomitant non-EGFR genetic alterations, combination of TKIs and chemotherapy was significantly superior to EGFR-TKIs monotherapy, which should be the preferred treatment option.
Adenocarcinoma of Lung/genetics*
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ErbB Receptors/genetics*
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Humans
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Lung Neoplasms/pathology*
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Mutation
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Protein Kinase Inhibitors/therapeutic use*
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Retrospective Studies
2.Therapeutic effect of nivolumab on non-small-cell lung cancer patients with brain metastases: a retrospective study
Guowei ZHANG ; Ruirui CHENG ; Huijuan WANG ; Yong ZHANG ; Peng LI ; Xiangtao YAN ; Mina ZHANG ; Xiaojuan ZHANG ; Jinpo YANG ; Zhiyong MA
Chinese Journal of Oncology 2020;42(11):961-965
Objective:To preliminarily explore the treatment effect of nivolumab on Chinese non-small-cell lung cancer (NSCLC) patients with brain metastases, and further enrich the evidences of programmed death-ligand 1 (PD-1) monoclonal antibody in the treatment of NSCLC patients with brain metastases.Methods:The clinical and pathological data of 22 NSCLC patients with brain metastases treated with nivolumab were collected. The electronic imaging data were collected to confirm the treatment effect and time point of disease progression, and the survival data of the patients were obtained through follow-up.Results:Twenty-one patients were evaluated for the intracranial treatment effect. The intracerebral objective response rate (IORR) was 28.6%, the intracranial disease control rate (IDCR) was 47.6%. The median intracranial progression-free-survival (iPFS) of all the 22 patients was 5.2 months. Both the 1-year and 2-year survival rates were 56.7%.Conclusions:The treatment effect of PD-1 monoclonal antibody on NSCLC patients with brain metastases is similar as those without brain metastases.
3.Therapeutic effect of nivolumab on non-small-cell lung cancer patients with brain metastases: a retrospective study
Guowei ZHANG ; Ruirui CHENG ; Huijuan WANG ; Yong ZHANG ; Peng LI ; Xiangtao YAN ; Mina ZHANG ; Xiaojuan ZHANG ; Jinpo YANG ; Zhiyong MA
Chinese Journal of Oncology 2020;42(11):961-965
Objective:To preliminarily explore the treatment effect of nivolumab on Chinese non-small-cell lung cancer (NSCLC) patients with brain metastases, and further enrich the evidences of programmed death-ligand 1 (PD-1) monoclonal antibody in the treatment of NSCLC patients with brain metastases.Methods:The clinical and pathological data of 22 NSCLC patients with brain metastases treated with nivolumab were collected. The electronic imaging data were collected to confirm the treatment effect and time point of disease progression, and the survival data of the patients were obtained through follow-up.Results:Twenty-one patients were evaluated for the intracranial treatment effect. The intracerebral objective response rate (IORR) was 28.6%, the intracranial disease control rate (IDCR) was 47.6%. The median intracranial progression-free-survival (iPFS) of all the 22 patients was 5.2 months. Both the 1-year and 2-year survival rates were 56.7%.Conclusions:The treatment effect of PD-1 monoclonal antibody on NSCLC patients with brain metastases is similar as those without brain metastases.
4.Efficacy of platinum-based doublet chemotherapy versus single-agent chemotherapy as second-line treatment in elderly patients with advanced non-small cell lung cancer
Xiangtao YAN ; Huijuan WANG ; Peng LI ; Guowei ZHANG ; Mina ZHANG ; Jinpo YANG ; Zhiyong MA
Chinese Journal of Geriatrics 2019;38(3):242-245
Objective To compare the efficacy and tolerance of platinum-based doublet chemotherapy versus single-agent chemotherapy as second-line treatment in elderly patients with advanced non-small cell lung cancer(NSCLC).Methods A total of 85 elderly patients with advanced NSCLC after first-line treatment were retrospectively analyzed and divided into the combination therapy group(n=40,taking platinum-based doublet chemotherapy)and the single-agent chemotherapy group(n=45,receiving single-agent second-line chemotherapy).Results There were no significant differences in the objective response rate (ORR)and the disease control rate (DCR)between the combination therapy group and the single-agent chemotherapy group(27.5 % or 11/40 vs.20.0 % or 9/45,60.0% or 24/40 vs.73.3% or 33/45,x2 =0.662 and 1.704,P=0.416 and 0.192).The median progression-free survival(PFS)was 3.8 months for the combination therapy group and 2.8 months for the single-agent chemotherapy group(P =0.045).The rate of grade Ⅲ/Ⅳ hematological toxicity was higher in the combination therapy group than in the single-agent chemotherapy group.Conclusions Platinum-based doublet chemotherapy has longer PFS than the single-agent chemotherapy as secondline treatment in elderly patients with advanced non-small cell lung cancer,and more attention should be paid to its high hematological toxicity.
5.Efficacy and Safety of Bevacizumab Combined with Chemotherapy as Second-line or Later-line Treatment in Advanced Nonsquamous Non-small Cell Lung Cancer.
Xuanxuan ZHENG ; Huijuan WANG ; Guowei ZHANG ; Xiangtao YAN ; Zhiyong MA
Chinese Journal of Lung Cancer 2018;21(7):513-518
BACKGROUND:
Bevacizumab combined with platinum-based chemotherapy has been recommended as the first-line agent in advanced nonsquamous non-small cell lung cancer (NSCLC) without driven gene, but this regimen is not common in the second-line or later-line treatment of non-squamous NSCLC. The aim of this study is to investigate the efficacy and safety of bevacizumab combined with chemotherapy as second-line or later-line treatment in advanced non-squamous NSCLC.
METHODS:
We retrospectively reviewed the clinical data of advanced nonsquamous NSCLC patients who were treated with bevacizumab after first-line treatment failure and they were hospitalized in the Affiliated Cancer Hospital of Zhengzhou University from January 2014 to June 2017, and Kaplan-Meier method, Log-rank test and Cox model were used for analysis.
RESULTS:
A total of 62 patients were included in the analysis. The total objective response rate (ORR) was 32.2%, and the disease control rate (DCR) was 96.8%. The median progression-free survival (PFS) was 6.4 months (95%CI: 6.05-6.83), and the median overall survival (OS) was 20.4 months (95%CI: 12.98-27.76). In the subgroup analysis, there was no significant difference in median PFS between patients with brain metastases and those without brain metastases (6.2 months vs 6.4 months, P=0.052). Cycles of bevacizumab (>6 or ≤6 cycles) was an independent influencing factor of PFS (P=0.004). The most common adverse events were leukopenia, fatigue, nausea, thrombocytopenia and hypertension.
CONCLUSIONS
In the second-line or later-line treatment, bevacizumab combined with chemotherapy is an effective and safe regimen for advanced non-squamous NSCLC.
Aged
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Bevacizumab
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adverse effects
;
therapeutic use
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Brain Neoplasms
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secondary
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Carcinoma, Non-Small-Cell Lung
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drug therapy
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pathology
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Disease-Free Survival
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Female
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Humans
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Lung Neoplasms
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drug therapy
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pathology
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Male
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Middle Aged
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Retrospective Studies
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Safety
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Treatment Outcome
6.Preparation and In Vitro Release of Curcumin Nanoparticles with A Novel Codendrimer as Stabilizer
Ran LI ; Yanna ZHAO ; Ting WANG ; Meihua HAN ; Xiangtao WANG ; Xueying YAN ; Yifei GUO
Herald of Medicine 2017;36(5):538-543
Objective To enhance the solubility and bioavailability of curcumin (CUR).Methods A novel curcumin nanoparticles were prepared.The CUR-PGD nanoparticles were prepared by the method of ultrasound precipitation combined with high-pressure homogenization using codendrimer PAMAM-co-0.25OEG (PGD) as stabilizer.The stability of CUR-PGD nanoparticles was measured in 0.9% sodium chloride solution,5% glucose, PBS and plasma.Results The drug loading capacity (DL%) of CUR-PGD nanoparticles was 41.2%, the solubility of CUR was increased to 1.5 mg·mL-1 (50 times of CUR bulk powder).The mean diameter of the nanoparticles was 438.0 nm with spherical morphology and the zeta potential was 41.4 mV.The nanoparticles was stable in 0.9% sodium chloride solution,5% glucose, PBS and plasma and there was no hemolytic phenomenon, which meant they were suitable for intravenous administration.The DSC and XRD spectra of CUR-PGD nanoparticles showed that the CUR was presented as crystal morphology in the nanoparticles.The CUR released from nanoparticles was detected in different releasing medium and presented obvious controlled release behavior.Conclusion PGD may be an effective stabilizer for the preparation of CUR-PGD nanoparticles and CUR-PGD nanoparticles are a promising drug delivery system for CUR application in clinic.
7.A descriptive analysis of triage,surge,and medical resource use in a university affiliated hospital ;after 8·12 explosion and burn at Tianjin Port
Guoqiang LI ; Xin YU ; Xiangtao MENG ; Liangliang LIU ; Pengbo YAN ; Mengna TIAN ; Shaolei CHEN ; Huijuan HAN
Chinese Journal of Emergency Medicine 2016;25(9):1119-1125
Objective To analyze the massive explosions and burn at Tianjin Port in 2015 resulted in a mass casualty event,and the entire course of response of a hospital to deal with such major sudden accident in order to find a rational strategy for optimal use of medical resources and reduce the critical mortality.Methods This study was done by a retrospective analysis of data from one trauma center at an academic hospital.Data including outcome,triage,severity and pattern of injuries,patient flow,and medical resources used were obtained by the review of hospital records.Results This disaster caused 165 deaths,8 missing contact,and 797 non-fatal casualties.The Pingjin Hospital admitted 298 casualties,and 29 of them were seriously injured referred to by Tianjin Emergency Medical Center.Excessive triage rate made after transfer to another hospital was 62.07% with 11 of the 29 severely injured patients.Maximum (also the first)surge had 147 injured patients arrived around one hour after incident,the second surge had 31 seriously injured patients occurred around 4 hours after incident.Of them,17 patients needed surgery and 17 patients were admitted to the intensive care unit.Conclusions These data showed that the number of casualties in the first surge was substantially larger than predicted and those casualties had less severe trauma,whereas the number of the injured in the second surge was less but the trauma was more severe.In order to maintain the hospital surge capacity,an effective re-triage and a hospital-wide damage control principle can be used to deal with.
8.Expressions and clinical significances of Hepcidin, BMP6 and HJV in gastric cancer
Rong LI ; Ye LU ; Xu CHENG ; Min YAN ; Xiangtao PAN
Journal of International Oncology 2016;43(3):180-183
Objective To study the expressions of Hepcidin,bone morphogenetic protein 6 (BMP6) and hemojuvelin (HJV) in gastric cancer,and to explore their relationships with clinical pathological characteristics.Methods Hepcidin,BMP6 and HJV were detected by immunohistochemistry in 62 cases of gastric cancer patients,and the relationships among them and clinical pathological features were analyzed.Results Compared with normal gastric mucosa tissues,Hepcidin was highly expressed in gastric cancer tissues (13.3% vs.56.5%,x2 =8.99,P < 0.01),while the differences of the expression of BMP6 and HJV in the two groups were not statistically significant (60.0% vs.40.3 %,x2 =1.89,P > 0.05;93.3% vs.83.9%,x2 =0.88,P > 0.05).The expression of Hepcidin was related to T stage (x2 =6.98,P =0.02),but it was not related to age,sex,lymph node metastasis,distant metastasis and anemia.The expressions of BMP6 and HJV were not related to T stage,age,sex,lymph node metastasis,distant metastasis and anemia.Hepcidin was not related to the expressions of BMP6 and HJV (r=0.13,P>0.05;r=0.15,P>0.05).Conclusion Hepcidin is highly expressed in gastric cancer tissues,which is related to the T staging of gastric cancer,and can be used as an objective indicator of the biological behavior of gastric cancer.There were no differences in the expression of BMP6 and HJV between normal gastric mucosa and gastric cancer tissues.
9.Indirect ELISA with Recombinant GP5 for Detecting Antibodies to Porcine Reproductive and Respiratory Syndrome Virus
Yan CHEN ; Hong TIAN ; Jianhui HE ; Jinyin WU ; Youjun SHANG ; Xiangtao LIU
Virologica Sinica 2011;26(1):61-66
Porcine reproductive and respiratory syndrome is caused by the PRRS virus(PRRSV), which has six structural proteins(GP2, GP3, GP4, GP5, M and N). GP5 and N protein are important targets for serological detection by enzyme-linked immunosorbent assay(ELISA)and other methods. Toward this goal, we developed an indirect ELISA with recombinant GP5 antigens and this method was validated by comparison to the LSI PRRSV-Ab ELISA kit. The results indicated that the optimal concentration of coated recombinant antigen was 0.2 μg/well for a serum dilution of 1:40. The rate of agreement with the LSI PRRSV-Ab kit was 88.7%(266/300). These results support the potential use of recombinant GP5 as an antigen for indirect ELISA to detect PRRSV antibodies in pigs.
10.Application of GP5 Protein to Develop Monoclonal Antibody against Porcine Reproductive and Respiratory Syndrome Virus
Hong TIAN ; Yan CHENG ; Jinyang WU ; Jianhui HE ; Youjun SHANG ; Xiangtao LIU
Virologica Sinica 2011;26(4):267-272
In this study,a panel of monoclonal antibodies (mAbs) against Porcine reproductive and respiratory syndrome virus(PRRSV),named as 8C9 and4B4,were produced by fusing SP2/0 myeloma cells and spleen cells of BALB/c mice immunized with the PRRSV (TCID50=5.5),screened by the indirect ELISA and subjected to several limiting dilutions.mAbs were then identified by biological characterization.Among the two fusion cell strains,8C9 belonged to the IgG1 subclass and 4B4 belonged to the IgG2a subclass.The titers in cell culture supernatant and abdomen liquor reached to 1:104and 1:105,respectively.The specificity test indicated that the two cells had specific reactions for the PRRSV and GP5 protein respectively,and no reaction with Classical swine fever virus (CSFV) or Swine vesicular disease virus (SVDV).The molecular weights of the heavy chain and light chain were about 45.0 kDa and 25.0 kDa,respectively.In neutralization activity tests,the results showed that the prepared mAb 4B4 can protect 50% of cells with no CPE in dilution up to 1:512,but mAB 8C9 has no neutralization activities to PRRSV.

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