It has been shown that the high expression of human epididymis protein 4(HE4)in most lung cancers is related to the poor prognosis of patients,but the mechanism of pathological transformation of HE4 in lung cancer is ...It has been shown that the high expression of human epididymis protein 4(HE4)in most lung cancers is related to the poor prognosis of patients,but the mechanism of pathological transformation of HE4 in lung cancer is still unclear.The current study is expected to clarify the function and mechanism of HE4 in the occurrence and metastasis of lung adenocarcinoma(LUAD).Immunoblotting evaluated HE4 expression in lung cancer cell lines and biopsies,and through analysis of The Cancer Genome Atlas(TCGA)dataset.Frequent HE4 overexpression was demonstrated in LUAD,but not in lung squamous cell carcinoma(LUSC),indicating that HE4 can serve as a biomarker to distinguish between LUAD and LUSC.HE4 knockdown significantly inhibited cell growth,colony formation,wound healing,and invasion,and blocked the G1-phase of the cell cycle in LUAD cell lines through inactivation of the EGFR signaling downstream including PI3K/AKT/mTOR and RAF/MAPK pathways.The first-line EGFR inhibitor gefitinib and HE4 shRNA had no synergistic inhibitory effect on the growth of lung adenocarcinoma cells,while the third-line EGFR inhibitor osimertinib showed additive anti-proliferative effects.Moreover,we provided evidence that HE4 regulated EGFR expression by transcription regulation and protein interaction in LUAD.Our findings suggest that HE4 positively modulates the EGFR signaling pathway to promote growth and invasiveness in LUAD and highlight that targeting HE4 could be a novel strategy for LUAD treatment.展开更多
Background and objective:Epidermal growth factor receptor(EGFR)mutations are often associated with non-EGFR genetic alterations,which maybe a reason for the poor efficacy of EGFR tyrosine kinase inhibitors(TKIs).Here ...Background and objective:Epidermal growth factor receptor(EGFR)mutations are often associated with non-EGFR genetic alterations,which maybe 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.Materials and methods:Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant nonEGFR 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 of18.8 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.Conclusion: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.展开更多
Objective： We conducted a prospective phase II trial of single-agent salvage chemotherapy with docetaxel in patients with advanced non-small cell lung cancer （NSCLC） after failure of chemotherapy and gefitinib to a...Objective： We conducted a prospective phase II trial of single-agent salvage chemotherapy with docetaxel in patients with advanced non-small cell lung cancer （NSCLC） after failure of chemotherapy and gefitinib to assess the efficacy and toxicity of docetaxel in this setting. Methods： Patients with histologically confirmed NSCLC who were failure of chemotherapy and gefitinib were given docetaxel 75 mg/m^2 intravenously for 30 rain every 3 weeks until the toxicity was unacceptable or disease progressed. The response evaluation criteria in solid tumors （RECIST） guidelines were used for the evaluation of an- titumor activity. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria version 2.0. Results： In total, 31 patients were enrolled in this phase II trial between February 2004 and December 2006, and 84 cycles （average 2.7 cycles） were given. We observed 4 partial responses （PRs） and 10 stable disease （SD） states in 31 eligible patients. The objective response rate was 12.9%, and the disease control rate was 45.2%. The median survival time （MST） was 10 months （95% CI, 5.05-15.08 months）. The 1-year survival rate was 40.6%. The most common toxicities were neutropenia, anemia, and peripheral neuropathy that occurred as follows： 45% of the patients experienced grade 3 or 4 neutropenia, 29% experienced grade 3 anemia, and 25.8% had grade 3 peripheral neuropathy. No patient terminated docetaxel chemotherapy due to toxicity. Conclusion： Docetaxel is beneficial as salvage chemotherapy in patients with advanced NSCLC after failure of cytotoxic agents and gefitinib.展开更多
Lung cancer, mostly non-small cell carcinoma (NSCLC), is still a major global problem with devastating outcomes. The majority presents at late stages, in which the chance of cure is minimal. With the better understand...Lung cancer, mostly non-small cell carcinoma (NSCLC), is still a major global problem with devastating outcomes. The majority presents at late stages, in which the chance of cure is minimal. With the better understanding of lung cancer biology, there have been several novel targeted approaches against NSCLC. Anti-angiogenesis has been proven to be an important approach in combination with systemic chemotherapy treatment in NSCLC at the first-line setting. The prototypic monoclonal antibody against vascular endothelial growth factor (VEGF), be- vacizumab, is now approved for clinical use in combination with platinum-based chemotherapy in first-line treatment of advanced non-squamous NSCLC, associated with improved response and survival compared with chemotherapy alone. The most notable example of targeted therapy for lung cancer is epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI). There have been extensive evidences supporting the superiority of EGFR TKI (like gefitinib or erlotinib) over standard platinum-based doublet chemotherapy in first-line treatment of advanced NSCLC carrying EGFR activating mutations. Almost following the same path as EGFR TKI, a novel target (anaplastic lymphoma kinase, ALK) has been identified recently with a very promising targeted agent (crizotinib) that has already been approved for clinical use in NSCLC carrying ALK rearrangements. Over the past decade, there have been undoubtedly growing armamentaria in the treatment of NSCLC, focusing on personalized and targeted approach.展开更多
Objective:This paper aims to study the mutation of epidermal growth factor receptor(EGFR)gene in fresh cytological specimens from patients with lung adenocarcinoma,and to determine the prognosis of positive patients b...Objective:This paper aims to study the mutation of epidermal growth factor receptor(EGFR)gene in fresh cytological specimens from patients with lung adenocarcinoma,and to determine the prognosis of positive patients by tyrosine kinase inhibitor(TKI).Methods:A total of 313 specimens from needle aspiration and pleural effusion were collected in the Cancer Detection Center of the Fourth Hospital of Hebei Medical University.After HE and immunocytochemistry stainings,the specimens were diagnosed as lung adenocarcinoma by two cytology pathologists.The mutation of 18-21 exon was detectied using ARMS to observe mutations situation.Then,the objective response rate(ORR)and the progressionfree survival(PFS)between the targeted group and the chemotherapy group of patients were comparedith.Results:Among 313 cases,293 cases of lung adenocarcinoma were diagnosed,and DNA specimens were extracted from 288 cases.The success rate was about 98.3%.130 mutations were found and the rate was 45.1%.EGFR mutation of adenocarcinoma patients mainly occurred to females,nonsmokers,but had nothing to do with age.The ORR was statistically different between the targeted group with chemotherapy(P<0.01),and PFS curve of targeted group was on chemotherapy group.The efficacy and the survival time of targeted group and targeted and chemotherapy group were superior to that of chemotherapy group.The results of the EGFR mutation and the prognosis of the tested positive patients in the fresh cytology samples were consistent with that from previous literatures.Conclusion:The results of the test were accurate,and fresh cytological specimens can be used as a replacement for tumor tissue specimens.展开更多
Objective:To evaluate the clinical efficacy of gefitinib in non-small cell lung cancer.Methods:A total of 45 patients with non-small cell lung cancer who received treatment in Taizhou Second People's Hospital from...Objective:To evaluate the clinical efficacy of gefitinib in non-small cell lung cancer.Methods:A total of 45 patients with non-small cell lung cancer who received treatment in Taizhou Second People's Hospital from January 2018 to January 2020 were selected as the subjects in this study,in which all of them were treated with gefitinib.Its efficacy and safety were evaluated.Results:The objective response rate was 53.33% and the disease control rate was 84.44%.After treatment,the levels of tumor markers were measured again,of which the levels of CA125 and CEA were significantly lower than before(P<0.05).After treatment,the patients'CD_(3)^(+),CD_(4)^(+),and CD_(4)^(+)/CD_(8)^(+) were significantly lower than those before treatment,and CD_(8)^(+) was significantly higher(P<0.05).Conclusion:Gefitinib,which is a targeted therapy for non-small cell lung cancer,can reduce the level of serum tumor markers and improve the immune function.The curative effect is good,but more emphasis should be on the adverse reactions caused by a single drug use.展开更多
基金supported by National Natural Science Foundation of China(82272695)the Key Program of Natural Science Foundation of Zhejiang Province(LZ23H160004)National Undergraduate Training Program for Innovation,and Zhejiang Xinmiao Talents Program,China.
文摘It has been shown that the high expression of human epididymis protein 4(HE4)in most lung cancers is related to the poor prognosis of patients,but the mechanism of pathological transformation of HE4 in lung cancer is still unclear.The current study is expected to clarify the function and mechanism of HE4 in the occurrence and metastasis of lung adenocarcinoma(LUAD).Immunoblotting evaluated HE4 expression in lung cancer cell lines and biopsies,and through analysis of The Cancer Genome Atlas(TCGA)dataset.Frequent HE4 overexpression was demonstrated in LUAD,but not in lung squamous cell carcinoma(LUSC),indicating that HE4 can serve as a biomarker to distinguish between LUAD and LUSC.HE4 knockdown significantly inhibited cell growth,colony formation,wound healing,and invasion,and blocked the G1-phase of the cell cycle in LUAD cell lines through inactivation of the EGFR signaling downstream including PI3K/AKT/mTOR and RAF/MAPK pathways.The first-line EGFR inhibitor gefitinib and HE4 shRNA had no synergistic inhibitory effect on the growth of lung adenocarcinoma cells,while the third-line EGFR inhibitor osimertinib showed additive anti-proliferative effects.Moreover,we provided evidence that HE4 regulated EGFR expression by transcription regulation and protein interaction in LUAD.Our findings suggest that HE4 positively modulates the EGFR signaling pathway to promote growth and invasiveness in LUAD and highlight that targeting HE4 could be a novel strategy for LUAD treatment.
文摘Background and objective:Epidermal growth factor receptor(EGFR)mutations are often associated with non-EGFR genetic alterations,which maybe 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.Materials and methods:Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant nonEGFR 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 of18.8 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.Conclusion: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.
基金the Chinese State Key Program for Basic Research (No. 2002BA711A08)the Foundation of Guangzhou Science and Technology Bureau (No. 2001-Z-044-01)the Guangdong Provincial Department of Health, China (No. 2004-199- 25)
文摘Objective： We conducted a prospective phase II trial of single-agent salvage chemotherapy with docetaxel in patients with advanced non-small cell lung cancer （NSCLC） after failure of chemotherapy and gefitinib to assess the efficacy and toxicity of docetaxel in this setting. Methods： Patients with histologically confirmed NSCLC who were failure of chemotherapy and gefitinib were given docetaxel 75 mg/m^2 intravenously for 30 rain every 3 weeks until the toxicity was unacceptable or disease progressed. The response evaluation criteria in solid tumors （RECIST） guidelines were used for the evaluation of an- titumor activity. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria version 2.0. Results： In total, 31 patients were enrolled in this phase II trial between February 2004 and December 2006, and 84 cycles （average 2.7 cycles） were given. We observed 4 partial responses （PRs） and 10 stable disease （SD） states in 31 eligible patients. The objective response rate was 12.9%, and the disease control rate was 45.2%. The median survival time （MST） was 10 months （95% CI, 5.05-15.08 months）. The 1-year survival rate was 40.6%. The most common toxicities were neutropenia, anemia, and peripheral neuropathy that occurred as follows： 45% of the patients experienced grade 3 or 4 neutropenia, 29% experienced grade 3 anemia, and 25.8% had grade 3 peripheral neuropathy. No patient terminated docetaxel chemotherapy due to toxicity. Conclusion： Docetaxel is beneficial as salvage chemotherapy in patients with advanced NSCLC after failure of cytotoxic agents and gefitinib.
文摘Lung cancer, mostly non-small cell carcinoma (NSCLC), is still a major global problem with devastating outcomes. The majority presents at late stages, in which the chance of cure is minimal. With the better understanding of lung cancer biology, there have been several novel targeted approaches against NSCLC. Anti-angiogenesis has been proven to be an important approach in combination with systemic chemotherapy treatment in NSCLC at the first-line setting. The prototypic monoclonal antibody against vascular endothelial growth factor (VEGF), be- vacizumab, is now approved for clinical use in combination with platinum-based chemotherapy in first-line treatment of advanced non-squamous NSCLC, associated with improved response and survival compared with chemotherapy alone. The most notable example of targeted therapy for lung cancer is epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI). There have been extensive evidences supporting the superiority of EGFR TKI (like gefitinib or erlotinib) over standard platinum-based doublet chemotherapy in first-line treatment of advanced NSCLC carrying EGFR activating mutations. Almost following the same path as EGFR TKI, a novel target (anaplastic lymphoma kinase, ALK) has been identified recently with a very promising targeted agent (crizotinib) that has already been approved for clinical use in NSCLC carrying ALK rearrangements. Over the past decade, there have been undoubtedly growing armamentaria in the treatment of NSCLC, focusing on personalized and targeted approach.
文摘Objective:This paper aims to study the mutation of epidermal growth factor receptor(EGFR)gene in fresh cytological specimens from patients with lung adenocarcinoma,and to determine the prognosis of positive patients by tyrosine kinase inhibitor(TKI).Methods:A total of 313 specimens from needle aspiration and pleural effusion were collected in the Cancer Detection Center of the Fourth Hospital of Hebei Medical University.After HE and immunocytochemistry stainings,the specimens were diagnosed as lung adenocarcinoma by two cytology pathologists.The mutation of 18-21 exon was detectied using ARMS to observe mutations situation.Then,the objective response rate(ORR)and the progressionfree survival(PFS)between the targeted group and the chemotherapy group of patients were comparedith.Results:Among 313 cases,293 cases of lung adenocarcinoma were diagnosed,and DNA specimens were extracted from 288 cases.The success rate was about 98.3%.130 mutations were found and the rate was 45.1%.EGFR mutation of adenocarcinoma patients mainly occurred to females,nonsmokers,but had nothing to do with age.The ORR was statistically different between the targeted group with chemotherapy(P<0.01),and PFS curve of targeted group was on chemotherapy group.The efficacy and the survival time of targeted group and targeted and chemotherapy group were superior to that of chemotherapy group.The results of the EGFR mutation and the prognosis of the tested positive patients in the fresh cytology samples were consistent with that from previous literatures.Conclusion:The results of the test were accurate,and fresh cytological specimens can be used as a replacement for tumor tissue specimens.
文摘Objective:To evaluate the clinical efficacy of gefitinib in non-small cell lung cancer.Methods:A total of 45 patients with non-small cell lung cancer who received treatment in Taizhou Second People's Hospital from January 2018 to January 2020 were selected as the subjects in this study,in which all of them were treated with gefitinib.Its efficacy and safety were evaluated.Results:The objective response rate was 53.33% and the disease control rate was 84.44%.After treatment,the levels of tumor markers were measured again,of which the levels of CA125 and CEA were significantly lower than before(P<0.05).After treatment,the patients'CD_(3)^(+),CD_(4)^(+),and CD_(4)^(+)/CD_(8)^(+) were significantly lower than those before treatment,and CD_(8)^(+) was significantly higher(P<0.05).Conclusion:Gefitinib,which is a targeted therapy for non-small cell lung cancer,can reduce the level of serum tumor markers and improve the immune function.The curative effect is good,but more emphasis should be on the adverse reactions caused by a single drug use.
