Objective To explore the effect of membrane surface nucleolin （NCL） on activation of epidermal growth factor receptor （EGFR） signaling. Methods Immunohistochemistry was used to identify the expressions of membrane surface NCL or EGFR in pallilary thyroid carcinoma （PTC） tissues. The level of phosphorlated EGFR in TPC-1 cells was observed by Western blot. TPC-1 cells invasion capacity was detected by Transwell assay. Results The posi-tive expression rates of membrane surface NCL and EGFR in PTC tissues were 100% （56/56） and 80.4% （45/56） respe-ctively， while the expressions of NCL and EGFR were related with lymph node metastasis （P＜0.05）. There was posi-tive correlation between the expressions of NCL and EGFR （r=0.635， P＜0.01）. Western blot showed that anti-NCL or anti-EGFR of TPC-1 cells could inhibit the expression of phosphorlation EGFR （P＜0.01）. Transwell assay showed the number of membrane-invading cells were reduced significantly in anti-NCL group anti-EGFR group （P＜0.01）. Conclusions Membrane surface NCL may be a kind of indispensable component in activation of EGFR signaling， by which EGFR can participate in growth and invasion of tumors. NCL can be used as a target for developing a new field of tumor treatment.
Objective To evaluate the clinical significance of epidermal growth factor receptor EGFR) mutations in the treatment of non-small cell lung cancer ( NSCLC) . Methods Plasma DNAs solated fromblood specimens of 170 NSCLC patients, who were admitted in the First Affiliated Hospital of uangzhou Medical College from December 2005 to December 2007, were subjected to the test of EGFR utant-enriched PCR. The correlation of mutant detection with clinical characteristics was analyzed as well.Results Out of the total 170 patients, EGFR mutations were identified in 77 cases ( 77 /170, 45. 3% ) .EGFR mutations were more frequent in the patients with adenocarcinoma ( P lt; 0. 001) and in the nonsmokers P =0. 001) . In the 33 patients treated with gefitinib, those with mutations ( + ) showed a higher esponse rate and prolonged progression-free survival after the treatment compared with those with mutations( - ) ( P =0. 001 and 0. 001, respectively) . Conclusions EGFR active mutations can be specifically and ensitively detected by EGFR mutant enriched PCR assay. Plasma EGFR mutants detection is valuable in uiding clinical decision.
ObjectiveTo investigate the value of serum soluble CD146 (sCD146) in determining acquired epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance in lung adenocarcinoma.MethodsA total of 144 lung adenocarcinoma EGFR sensitive patients in People’s Hospital of Zhengzhou University diagnosed from January 2016 to December 2016 were recruited in the study. According to the different time of taking drugs, the patients were divided into a non-medication group (31 cases), a 1 to 3 month treatment group (25 cases), a 4 to 6 month treatment group (19 cases), a 7 to 12 month treatment group (25 cases), a drug-resistant group (24 cases), and a nonresistant group up to 1 year of treatment (20 cases). The serum levels of sCD146, carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) were measured by ELISA and chemiluminescence and compared between different period of medication. The relationship of serum sCD146 with tumor markers (CEA, NSE) and tumor related clinical parameters (age, gender, tumor stage, metastasis, tumor diameter, number of the lesions) were analyzed.ResultsThe serum sCD146 level was minimum in the non-medication group that did not receive pioglitazone treatment, highest in the 1 to 3 month treatment group (early treatment period), and declined with duration of medication until resistance occurred without significant difference (P>0.05). The level of sCD146 of the drug-resistant group was significantly lower than that of all nonresistant groups, with significant difference (allP<0.05), but still higher than that of the non-medication group (P<0.05). The serum sCD146 levels in the nonresistant patients with medication over 1 year and within 1 year were similar (P>0.05), and significantly higher than the non-medication group and drug-resistance group (allP<0.05). The serum CEA levels did not differ significantly between 6 groups (P>0.05). The serum NSE level of the 4 to 6 month treatment group was lower than that of the 7 to 12 month treatment group (P<0.05), but both in the normal reference range. The NSE levels did not differ in any other groups (P>0.05). Serum sCD146 was associated with metastasis (P<0.05), but not associated with serum CEA or NSE, nor with sex, age, tumor staging, tumor diameter or lesion number (allP>0.05).ConclusionsCD146 may be involved in the mechanism of TKI killing tumor cells and the mechanism of TKI resistance, and may be a serological marker for monitoring the efficacy of TKI and judging the resistance of TKI.
Objective
To analyze the relationship between the epidermal growth factor receptor(EGFR) gene mutation and malignant pulmonary focal ground-glass lesion (fGGL).
Methods
We retrospectively collected the clinical data of 86 patients with surgical treatment in the department of cardiothoracic surgery of Changzheng Hospital from August 2012 to February 2015. There were 26 males and 60 females with a mean age of 56.14±10.55 years. We analyzed the relationship between the EGFR gene mutation and the related clinical data.
Results
Postoperative pathology showed atypical adenomatous hyperplasia (AAH) combined with focal adenocarcinoma in situ (AIS) or AIS in 10 patients, minimally invasive adenocarcinoma (MIA) in 15, and lepidic predominant adenocarcinoma (LPA) in 61. The EGFR gene mutation reports showed the exon 19 19-del mutation in 14 patients, exon 21 L858R mutation in 27, and exon 21 L861Q mutation in 2. There was no difference between the mutation of EGFR gene and clinical factors except age and smoking (P>0.05). Till June 30, 2015, all patients were alive and follow-up was 440.48±186.61 days.
Conclusion
The EGFR gene in patients with malignant pulmonary fGGL shows a higher mutation rate, which provides important clinical reference data for the basic research and the clinical treatment.
Objective To detect the expressions of epidermal growth factor receptor (EGFR), epidermal growth factor receptor-2 (C-erbB-2), vascular endothelial growth factor (VEGF) and cyclooxgenase-2 (COX-2) in gastric cancer tissues, and to analyze the relationship among them and the clinicopathologic factors of gastric cancer. Methods The SP immunohistochemical stain was used to detect EGFR, C-erbB-2, VEGF and COX-2 protein expressions in sample of 68 gastric cancer tissues. And their corresponding clinical data were analyzed retrospectively. Results The expression rates of EGFR, C-erbB-2, VEGF and COX-2 protein in gastric cancer tissue were 38.2% (26/68), 42.6% (29/68), 52.9% (36/68) and 60.3% (41/68) corresponding. An obvious increasing tendency as the differentiation of the cancer degraded, invasion depth deepened, lymphatic metastasis occurred and TNM stage upgraded was showed by the positive expression rates of them （P＜0.05，P＜0.01）; but there was no correlation with the patient’s sex, age, tumour site and size （Pgt;0.05）. There was a stable positive correlation among EGFR, C-erbB-2, VEGF and COX-2 expressions in gastric cancer tissue, respectively （P＜0.05）. Conclusion EGFR, C-erbB-2, VEGF and COX-2 expressions participate in the development, invasion and metastasis process of gastric cancer. Joint detection of them can be looked as an important symbol for judging the prognosis of gastric cancer and screening the high-risk metastasis patients, and guiding the molecular targeting therapy of gastric cancer.
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.
Objective To observe the effect of gefitinib on expression of epidermal growth factor receptor (EGFR) in bile duct epithelial cells, and the feasibility of inhibiting hyperplasia of bile duct epithelial cells with gefitinib. Methods Sixty-one patients with hepatolithiasis having to be in hospital for surgery from the First People’s Hospital of Shuangliu county were selected, with 25-65 years old, average 46.92 years. The patients were randomly divided into therapy group and control group. There were 30 cases in therapy group, in which fine duct was placed on lesion bile duct during operation, and through whom gefitinib solution was perfused after operation. There were 31 cases in control group with only T tube drainage after operation. The bile duct sample was obtained respectively during the operation and 6 weeks and 12 weeks after operation. The histology and expression change of EGFR were observed by HE staining, immunohistochemistry and RT-PCR method respectively. Results There were no significant differences in pathohistology changes of bile duct and the EGFR protein and mRNA expression between therapy group and control group during operation. The hyperplasia of epithelium mucosae and submucosal gland in the therapy group were obviously decreased as compared with those in control group, the EGFR mRNA and protein expression in therapy group were weaker than those of control group （Plt;0.05） 6 weeks and 12 weeks after gefitinib treatment. Conclusion EGFR is overexpressed in the chronic proliferative cholangitis, and continuously local application of gefitinib after operation can specifically interrupt the activation and expression of EFGR and then effectively inhibit the hyperplasia of bile duct epithelial cells.
Objective To explore the effects of prolonged inhalation of Aspergillus fumigatus ( Af)spores on epithelial cell injury and expression of epidermal growth factor receptor( EGFR) in airways of asthmatic rats. Methods 64 male Wistar rats were randomly divided into 8 groups, ie. chronic asthma group ( group A) , chronic asthma plus Af spores inhalation for 1 week ( group B) , 3 weeks ( group C) and 5 weeks ( group D) , chronic asthma plus saline inhalation for 5 weeks ( group E) , OVA-sensitized and salinechallenged group ( group F) , and OVA-sensitized and saline-challenged plus Af spores inhalation for 5 weeks ( group G) ( each n =8) . The airway resistance ( Raw) and change of Raw after acetylcholine provocation were detected using a computerized system. The concentrations of epidermal growth factor ( EGF) andtransforming growth factor alpha( TGF-α) in BALF were measured by ELISA. The extents of epithelial cell injury and goblet cell hyperplasia were evaluated on hematoxylin and eosin-stained( HE) and periodic acidschiff ( PAS) stained lung sections. The expression of EGFR in airway epithelia was demonstrated byimmunohistochemistry, and the level of EGFR protein in the rat lung tissues was measured by western blot.Results The concentration of EGF( pg/mL) ( 51. 72 ±8. 54, 68. 12 ±7. 85, 86. 24 ±9. 12, respectively)and TGF-α( pg/mL) ( 55. 26 ±9. 30, 75. 58 ±11. 56, 96. 75 ±14. 66, respectively) , detached/ inner perimeter of epithelium( % ) ( 11. 25 ±3. 12, 26. 45 ±5. 56, 28. 50 ±7. 50, respectively) , the ratio of goblet cell area to epithelial cell area ( % ) ( 16. 42 ±5. 24, 22. 64 ±6. 82, 36. 38 ±9. 21, respectively) , the integrated optical density ( IOD) of EGFR positive stain in airway epithelial cells ( 82 ±15,120 ±19, 165 ±21, respectively) , and the EGFR protein levels in lung tissues ( 0. 91 ±0. 26, 1. 61 ±0. 52, 2. 52 ±0. 78,respectively) in group B, C, and D were higher than those in group A, E, F and G( P lt; 0. 05 or P lt;0. 01) .The change rates of Raw( % ) ( 61. 91 ±5. 26, 84. 69 ±6. 38) in group C and D were higher than those in group A, E, F and G ( P lt; 0. 05 or P lt;0. 01) . The IOD of EGFR was positively correlated with detached/inner perimeter of epithelium( % ) and the ratio of goblet cell area to epithelial cell area( % ) ( r = 0. 692,P lt;0. 01; r = 0. 657, P lt; 0. 01, respectively) . Conclusion Prolonged inhalation of Aspergillus fumigatus spores can aggravate airway epithelial cell injury, up-regulate the expression of EGFR in airway epithelial cell and induce goblet cell hyperplasia, thus increase the airway responsiveness in rats with chronic asthma.
Objective
To assess the efficacy of a kind of new material lipid magnetic particle for isolation and detection of lung cancer circulating tumor cells (CTCs).
Methods
Immune lipid magnetic particles were prepared with reverse evaporation method and they were assembled into kits with EpCAM and EGFR antibody respectively. Their efficacy were evaluated by detecting A549 cells in group A (A549 cells mixed in phosphated buffer solution) and group B (A549 cells mixed in blood from healthy volunteers). Lung cancer CTCs of hospitalized patients were also detected with both immune magnetic particals. Then the detecting efficacy was compared between EpCAM immune lipid magnetic particles and the conventional CellsearchTM system.
Results
The immune lipid magnetic particles had high capture efficiency for CTCs isolation and identification. The median of EpCAM immune lipid magnetic particles method in detecting A549 cells in group A was 92%, and EGFR was 90%. The median of EpCAM immune lipid magnetic particles method in detecting A549 cells in group B was 85%, and EGFR was 81%. In 13 patients with lung cancer, CTCs can be detected with both immune lipid magnetic particles methods and both medians were 5; In negative control, the medians of both methods were 0 (P＜0.05). EpCAM immune lipid magnetic particles method can detect more CTCs than conventional CellsearchTM system in 3 lung cancer patients.
Conclusions
Immune lipid magnetic particles have good efficacy for lung cancer CTCs detection and has promising clinical application value. The EpCAM immune lipid magnetic particles have equal efficiency in detecting lung cancer CTCs with EGFR. There is a trend that EpCAM immune lipid magnetic particles is superior to the conventional CellsearchTM system.
ObjectiveTo explore expression of epidermal growth factor receptor(EGFR) in triple-negative breast cancer(TNBC).
Method The published articles about expression of EGFR in TNBC according to the inclusion and exclusion criteria from PubMed, Elsevier-Science Direct, and Web of Science databases were retrieved. The meta-analysis was performed with RevMan 5.2 software.
ResultsA total of 8 articles were eligible for the meta-analysis. Among them, 1 006 patients in the TNBC group and 2 945 cases in the non-TNBC group. The result of meta-analysis showed that the positive rate of EGFR expression in the TNBC group was significantly higher than that in the non-TNBC group(OR=6.57, 95% CI 3.42-12.61, P < 0.000 01). The result of race subgroup analysis showed that the positive rate of EGFR expression of TNBC patients in Caucasian(OR=8.93, 95% CI 4.16-19.17, P < 0.000 01) or Xanthoderm(OR=2.79, 95% CI 0.99-7.89, P=0.05) was significantly increased as compared with non-TNBC patients.
ConclusionThe positive rate of EGFR expression in TNBC patients is higher than that of non-TNBC patients, which might become an important marker of TNBC and an effective therapeutic target.
