Inetetamab combined with tegafur as second-line treatment for human epidermal growth factor receptor-2-positive gastric cancer: A case report

BACKGROUND Human epidermal growth factor receptor-2(HER-2)plays a vital role in tumor cell proliferation and metastasis.However,the prognosis of HER2-positive gastric cancer is poor.Inetetamab,a novel anti-HER2 targeting drug independently developed in China,exhibits more potent antibody-dependent cell-mediated cytotoxicity than trastuzumab,which is administered as the first-line treatment for HER2-positive gastric cancer in combination with chemotherapy.In this case,the efficacy and safety of inetetamab combined with tegafur was investigated as a second-line treatment for HER2-positive gastric cancer.CASE SUMMARY A 52-year-old male patient with HER2-positive gastric cancer presented with abdominal distension,poor appetite,and fatigue two years after receiving six cycles of oxaliplatin combined with tegafur as first-line treatment after surgery,followed by tegafur monotherapy for six months.The patient was diagnosed with postoperative recurrence of gastric adenocarcinoma.He received 17 cycles of a combination of inetetamab,an innovative domestically developed anti-HER2 monoclonal antibody,and tegafur chemotherapy as the second-line treatment(inetetamab 200 mg on day 1,every 3 wk combined with tegafur twice daily on days 1–14,every 3 wk).Evaluation of the efficacy of the second-line treatment revealed that the patient achieved a stable condition and progression-free survival of 17 months.He tolerated the treatment well without exhibiting any grade 3-4 adverse events.CONCLUSION Inetetamab combined with chemotherapy for the treatment of metastatic HER2-positive gastric cancer demonstrates significant survival benefits and acceptable safety.

Human epidermal growth factor receptor 2 expression level and combined positive score can evaluate efficacy of advanced gastric cancer

BACKGROUND Although treatment options for gastric cancer(GC)continue to advance,the overall prognosis for patients with GC remains poor.At present,the predictors of treatment efficacy remain controversial except for high microsatellite instability.AIM To develop methods to identify groups of patients with GC who would benefit the most from receiving the combination of a programmed cell death protein 1(PD-1)inhibitor and chemotherapy.METHODS We acquired data from 63 patients with human epidermal growth factor receptor 2(HER2)-negative GC with a histological diagnosis of GC at the Cancer Hospital,Chinese Academy of Medical Sciences between November 2020 and October 2022.All of the patients screened received a PD-1 inhibitor combined with chemotherapy as the first-line treatment.RESULTS As of July 1,2023,the objective response rate was 61.9%,and the disease control rate was 96.8%.The median progression-free survival(mPFS)for all patients was 6.3 months.The median overall survival was not achieved.Survival analysis showed that patients with a combined positive score(CPS)≥1 exhibited an extended trend in progression-free survival(PFS)when compared to patients with a CPS of 0 after receiving a PD-1 inhibitor combined with oxaliplatin and tegafur as the first-line treatment.PFS exhibited a trend for prolongation as the expression level of HER2 increased.Based on PFS,we divided patients into two groups:A treatment group with excellent efficacy and a treatment group with poor efficacy.The mPFS of the excellent efficacy group was 8 months,with a mPFS of 9.1 months after excluding a cohort of patients who received interrupted therapy due to surgery.The mPFS was 4.5 months in patients in the group with poor efficacy who did not receive surgery.Using good/poor efficacy as the endpoint of our study,univariate analysis revealed that both CPS score(P=0.004)and HER2 expression level(P=0.015)were both factors that exerted significant influence on the efficacy of treatment the combination of a PD-1 inhibitor and chemotherapy in patients with advanced GC(AGC).Finally,multivariate analysis confirmed that CPS score was a significant influencing factor.CONCLUSION CPS score and HER2 expression both impacted the efficacy of immunotherapy combined with chemotherapy in AGC patients who were non-positive for HER2.

Preliminary Investigation on the Effect of <i>Lactobacillus</i>and Epidermal Growth Factor on Tight Junction Proteins in Experimental Clostridium <i>difficile</i>Infection

Clostridium difficile associated disease (CDAD) is the most common hospital acquired infection, due to exposure to various drugs. C. difficile toxins influence barrier function in intestinal epithelium. Biotherapeutic approaches, employing probiotic and epidermal growth factor (EGF) could help in barrier protein protection and aid in CDAD management. A preliminary investigation on the effect of Lactobacillus acidophilus and EGF on tight junction proteins in experimentally induced C. difficile infection was done. BALB/mice were divided into 5 groups. Group 1 was comprised of healthy controls, whereas animals in Groups 2 - 5 were sub-divided into 3 subgroups (a, b and c) each. Animals in Groups 2 - 5 received C. difficile inoculum either on day 1 (Group 2) or after pretreatment with ampicillin (Group 3), cyclosporine (Group 4) or lansoprazole (Group 5). Additionally animals in subgroups “b” and “c” also received L. acidophilus and EGF inocula respectively after C. difficile challenge. All animals were investigated for the presence of tight junction proteins (occludin, α-actinin and zonula occludens) in their colonic segments. Data were analyzed using the SPSS version 10 software. These three proteins were present in significantly less (P < 0.05) number of animals in the drug receiving animals, whereas they were found in significantly more (P < 0.05) number of animals receiving L. acidophilus and EGF after challenge with ampicillin, cyclosporine and lansoprazole, suggesting their role in protecting intestinal barrier function.

Expression of c-erbB-2 oncogene protein, epidermal growth factor receptor, and TGF-β1 in human pancreatic ductal adenocarcinoma

Objective: To detect the relations of c-erbB-2 onco-gene protein, epidermal growth factor receptor (EG-FR) and transforming growth factor-β1 (TGF-β1)to the progression or metastasis of pancreatic carci-noma.Methods: Using streptavidinbiotin complex (SABC)method, c-erbB-2 oncongene protein, we examinedimmunohistochemically EGFR and TGF-β1 expres-sions in wax-tissue sections from 10 individuals withnormal pancreas (NP), 13 patients with chronic pan-creatitis (CP) and 36 patients with pancreatic ductaladenocarcinoma (PC).Results: The positive expression rates of c-cerbB-2oncogene protein, EGFR and TGF-β1 in the NP, CPand PC groups were 0, 0, 10%; 7.7%, 7.7%,7.7%; and 41.7%, 50.0%, 44.4%, respectively.The positive expression rates of the three specific pro-teins increased more significantly in the PC groupthan in the NP and CP groups (P【0.05). The indi-vidual expression of c-erbB-2, EGFR and TGF-β1was not related to the age and sex of the patients aswell as the site, size and histopathological grade oftumors (P】0.05), but to the clinical stage of tumors(P【0.01). The coexpression rate of the three pro-teins was 27.8 % (10/36). This coexpression in thePC group was correlated with the histopathologicalgrades and clinical stages of tumors (P【0.01).Conclusion: Detection of c-erbB-2 oncogene protein,EGFR, and TGF-β1 expressions in pancreatic tissueis helpful to judge the malignancy, progression, andmetastasis of PC.

Correlation of human epidermal growth factor receptor 2 expression with clinicopathological characteristics and prognosis in gastric cancer

AIM:To investigate human epidermal growth factor receptor 2(HER2) gene amplification and protein expression in Chinese patients with resectable gastric cancer and the association with clinicopathological characteristics and survival.METHODS:One hundred and ninety-seven gastric cancer patients who underwent curative surgery procedures were enrolled into this study.HER2 gene amplification and protein expression were examined using fluorescence in-situ hybridization(FISH) and immunohistochemistry(IHC) analysis on formalin-fixed paraffinembedded gastric cancer samples from all patients.For scoring,Hofmann's HER2 gastric cancer scoring system was adopted.All cases showing IHC3+ or FISH positiv-ity were defined as HER2 positive.Patient clinicopathological data and survival information were collected.Finally,χ 2 statistical analysis was performed to analyze the HER2 positivity rate amongst the subgroups with different clinicopathological characteristics including;gender,age,tumor location,Lauren classification,differentiation,TNM staging,depth of invasion,lymph node metastases and distant metastasis.The probability of survival for different subgroups with different clinicopathological characteristics was calculated using the Kaplan-Meier method and survival curves plotted using log rank inspection.RESULTS:According to Hofmann's HER2 gastric cancer scoring criteria,31 cases(15.74%) were identified as HER2 gene amplified and 19 cases(9.64%) were scored as strongly positive for HER2 membrane staining(3+),25 cases(12.69%) were moderately positive(2+) and 153 cases(77.66%) were HER2 negative(0/1+).The concordance rate between IHC and FISH analyses was 88.83%(175/197).Thirty-six cases were defined as positive for HER2 gene amplification and/or protein expression,with 24 of these cases being eligible for Herceptin treatment according to United States recommendations,and 29 of these cases eligible according to EU recommendations.Highly consistent results were detected between IHC3+,IHC0/1 and FISH(73.68% and 95.42%),but low consistency was observed between IHC2+ and FISH(40.00%).The positivity rates in intestinal type and well-differentiated gastric cancer were higher than those in diffuse/mixed type and poorly-differentiated gastric cancer respectively(28.57% vs 13.43%,P = 0.0103;37.25% vs 11.64%,P < 0.0001),but were not correlated with gender,age,tumor location or TNM stage,depth of invasion,lymph node metastases and distant metastasis.In poorly-differentiated gastric cancer patients,those without lymph node metastasis showed a higher HER2 positivity rate than those with lymph node metastasis(26.47% vs 7.14%,P = 0.0021).This association was not present in thosepatients with well-differentiated gastric cancer(28.57% vs 43.33%,P = 0.2832).Within our patient cohort,26 cases were lost to follow-up.The median survival time for the remaining 171 patients was 18 mo.The median survival times of the HER2 positive and negative groups were 17 and 18.5 mo respectively.Overall survival was not significantly different between HER2-positive and negative groups(χ 2 = 0.9157,P = 0.3386),but in patients presenting well-differentiated tumors,the overall survival of the HER2-positive group was significantly worse than that of the HER2-negative group(P = 0.0123).In contrast,patients with poorly differentiated and diffuse/mixed subtype gastric cancers showed no significant differences in overall survival associated with HER2.Furthermore,the median survival time of the HER2 positive group did not show any statistically significant differences when compared to the subgroups of gender,age,tumor location,TNM classification,lymph node metastases and distant metastasis.CONCLUSION:Patients with intestinal type gastric cancer(GC),well-differentiated GC and poorly-differentiated GC without lymph node metastasis,may all represent suitable candidates for targeted therapy using Herceptin.

Epidermal growth factor prevents gut atrophy and maintains intestinal integrity in rats with acute pancreatitis

INTRODUCTIONThere is abundant evidence that stressful insults suchas acute pancreatitis may significantly alter themetabolism of the gut mucosa and therefore itsbarrier integrity,resulting in an increase in mucosalpermeability and subsequent translocation of entericbacteria and their cndotoxins.The fact thatmost bacteria associated with acute pancreatic andperipancreatic infections are of enteric originimplies that the gut plays a major role in

Epidermal growth factor receptor and K-Ras in non-small cell lung cancer-molecular pathways involved and targeted therapies

Lung cancer is currently the leading cause of cancer death in Western nations.Non-small cell lung cancer(NSCLC)represents 80%of all lung cancers,and adenocarcinoma is the predominant histological type.Despite the intensive research carried out on this field and therapeutic advances,the overall prognosis of these patients remains unsatisfactory,with a 5-year overall survival rate of less than 15%.Nowadays,pharmacogenetics and pharmacogenomics represent the key to successful treatment.Recent studies suggest the existence of two distinct molecular pathways in the carcinogenesis of lung adenocarcinoma:one associated with smoking and activation of the K-Ras oncogene and the other not associated with smoking and activation of the epidermal growth factor receptor(EGFR).The K-ras mutation is mainly responsible for primary resistance to new molecules which inhibit tyrosine kinase EGFR(erlotinib and gefitinib)and most of the EGFR mutations are responsible for increased tumor sensitivity to these drugs.This article aims to conduct a systematic review of the literature regarding the molecular pathways involving the EGFR,K-Ras and EGFR targeted therapies in NSCLC tumor behavior.

Effects of epidermal growth factor on the growth of human gastric cancer cell and the implanted tumor of nude mice

AIM: Epidermal growth factor (EGF) plays an important role in the regulation of gastrointestinal tissue growth and development, and it can stimulate epithelial proliferation, cell differentiation and growth. It has been established that the EGF can promote gastric cytoprotection and ulcer healing. But the potential ability of EGF to regulate the gastric cancer growth is unknown. This study is to investigate the influence of EGF on human gastric cancer cell and the implanted tumor growth of nude mice. METHODS: The cell growth rates of human gastric adenocarcinoma cell lines MKN-28, MKN-45, SGC-7901 and normal human gastric epithelial cells 3T3 were assessed when incubated with recombinant human EGF (rhEGF, 0.05, 0.1, 0.5, 1.0, 10, 50, 100 mg.L(-1)) using MTT method. The cells of MKN-28, MKN-45, SGC-7901 (gastric cancer tissue 1.5mm(3)) were implanted in the BALB/cA nude mice for 10 days.The EGF was given intraperitoneally (15, 30, 60 microg.kg(-1)) for 3 weeks. The body weights of the tumor-bearing animals and their tumor mass were measured afterwards to assess the mitogenic effect of rhEGF in the nude mice. RESULTS: Within the concentration range of 0.05-100mg.L(-1), rhEGF could increase the cell growth of normal 3T3 cells (cell growth rate 100% vs 102.8%, P【0.05), but partially restrain the gastric cancer cell growth. The latter effect was related to cell differentiation. In 15-60 microg/kg rhEGF groups, the mean implanted tumor mass of MKN-28 cell were 1.75 g, 1.91 g, 2.08 g/NS group 1.97 g (P】0.05), the mean tumor mass of SGC-7901 cell were 1.53 g, 1.07 g, 1.20 g/NS group 1.07 g (P】0.05), and for MKN-45 cell, the tumor mass were respectively 1.92 g, 1.29 g, 1.77 /NS group 1.82 g (P】0.05). So rhEGF had no obvious effect on implanted MKN-28, SGC-7901 and MKN-45 tumor growth. CONCLUSION: EGF has no stimulating effect on the human gastric cancer cell growth neither in vitro nor in vivo.

Knockdown of HE4 suppresses tumor growth and invasiveness in lung adenocarcinoma through regulation of EGFR signaling

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.

真菌球型鼻窦炎的临床特征及BMP-2、EGF与骨质重塑的关系

目的分析真菌球型鼻窦炎的临床特征及骨形态发生蛋白-2(BMP-2)、表皮生长因子(EGF)与骨质重塑的关系。方法以2021年1月至2023年10月秦皇岛第一医院收治的行鼻内镜手术治疗的109例患者为研究对象,其中35例真菌球型鼻窦炎患者为真菌球组,43例慢性鼻-鼻窦炎患者为鼻窦炎组,31例鼻中隔偏曲患者为对照组。统计并比较3组临床特征、影像学特征及BMP-2、EGF水平,采用Pearson相关分析真菌球型鼻窦炎患者影像学特征相关指标水平与BMP-2、EGF水平的相关性。结果鼻窦炎组、真菌球组流脓涕、鼻腔异味患者比例均明显高于对照组(P<0.05)。鼻窦炎组、真菌球组改良整体骨炎评分(GOSS)、Lund-mackay评分、CT值、骨质厚度均大于对照组,且真菌球组改良GOSS、Lund-mackay评分、CT值、骨质厚度均大于鼻窦炎组,差异均有统计学意义(P<0.05);鼻窦炎组、真菌球组BMP-2、EGF水平均高于对照组,但真菌球组BMP-2、EGF水平均低于鼻窦炎组,差异均有统计学意义(P<0.05)。Pearson相关性分析结果显示,真菌球型鼻窦炎患者改良GOSS、Lund-mackay评分、CT值、骨质厚度与BMP-2、EGF水平均呈正相关(P<0.05)。结论真菌球型鼻窦炎患者影像学特征及BMP-2、EGF水平存在明显关系,且BMP-2、EGF水平与骨质重塑密切相关。

Trefoil factors:Tumor progression markers and mitogens via EGFR/MAPK activation in cholangiocarcinoma

AIM:To investigate trefoil factor(TFF) gene copy number,mRNA and protein expression as potential biomarkers in cholangiocarcinoma(CCA).METHODS:TFF mRNA levels,gene copy number and protein expression were determined respectively by quantitative reverse transcription polymerase chain reaction(PCR),quantitative PCR and immunohistochemistry in bile duct epithelium biopsies collected from individuals with CCA,precancerous bile duct dysplasia and from disease-free controls.The functional impact of recombinant human(rh) TFF2 peptide treatment on proliferation and epidermal growth factor receptor(EGFR) /mitogenactivated protein kinase(MAPK) signaling was assessed in the CCA cell line,KMBC,by viable cell counting and immunoblotting,respectively.RESULTS:TFF1,TFF2 and TFF3 mRNA expression was significantly increased in CCA tissue compared to disease-free controls,and was unrelated to gene copy number.TFF1 immunoreactivity was strongly increased in both dysplasia and CCA,whereas TFF2 immunoreactivity was increased only in CCA compared to diseasefree controls.By contrast,TFF3 immunoreactivity was moderately decreased in dysplasia and further decreased in CCA.Kaplan-Meier analysis found no association of TFF mRNA,protein and copy number with age,gender,histological subtype,and patient survival time.Treatment of KMBC cells with rhTFF2 stimulated proliferation,triggered phosphorylation of EGFR and downstream extracellular signal related kinase(ERK),whereas co-incubation with the EGFR tyrosine kinase inhibitor,PD153035,blocked rhTFF2-dependent proliferation and EGFR/ERK responses.CONCLUSION:TFF mRNA/protein expression is indicative of CCA tumor progression,but not predictive for histological sub-type or survival time.TFF2 is mitogenic in CCA via EGFR/MAPK activation.

Protein tyrosine phosphatase 1B regulates migration of ARPE-19 cells through EGFR/ERK signaling pathway

AIMTo evaluate whether protein tyrosine phosphatase 1B (PTP1B) contributed to initiate human retinal pigment epithelium cells (A)-19 migration and investigate the signaling pathways involved in this process.METHODSARPE-19 cells were cultured and treated with the siRNA-PTP1B. Expression of PTP1B was confirmed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). AG1478 [a selective inhibitor of epidermal growth factor receptor (EGFR)] and PD98059 (a specific inhibitor of the activation of mitogen-activated protein kinase) were used to help to determine the PTP1B signaling mechanism. Western blot analysis verified expression of EGFR and extracellular signal-regulated kinase (ERK) in ARPE-19 cells. The effect of siRNA-PTP1B on cell differentiation was confirmed by immunostaining for &#x003b1;-smooth muscle actin (&#x003b1;-SMA) and qRT-PCR. Cell migration ability was analyzed by transwell chamber assay.RESULTSThe mRNA levels of PTP1B were reduced by siRNA-PTP1B as determined by qRT-PCR assay. SiRNA-PTP1B activated EGFR and ERK phosphorylation. &#x003b1;-SMA staining and qRT-PCR assay demonstrated that siRNA-PTP1B induced retinal pigment epithelium (RPE) cells to differentiate toward better contractility and motility. Transwell chamber assay proved that PTP1B inhibition improved migration activity of RPE cells. Treatment with AG1478 and PD98059 abolished siRNA-PTP1B-induced activation of EGFR and ERK, &#x003b1;-SMA expression and cell migration.CONCLUSIONPTP1B inhibition promoted myofibroblast differentiation and migration of ARPE-19 cells, and EGFR/ERK signaling pathway played important role in migration process.

Inhibition of EGFR attenuates EGF-induced activation of retinal pigment epithelium cell via EGFR/AKT signaling pathway

AIM:To explore the effect of epidermal growth factor receptor(EGFR)inhibition by erlotinib and EGFR siRNA on epidermal growth factor(EGF)-induced activation of retinal pigment epithelium(RPE)cells.METHODS:Human RPE cell line(ARPE-19 cells)was activated by 100 ng/mL EGF.Erlotinib and EGFR siRNA were used to intervene EGF treatment.Cellular viability,proliferation,and migration were detected by methyl thiazolyl tetrazolium(MTT)assay,bromodeoxyuridine(BrdU)staining assay and wound healing assay,respectively.EGFR/protein kinase B(AKT)pathway proteins and N-cadherin,α-smooth muscle actin(α-SMA),and vimentin were tested by Western blot assay.EGFR was also determined by immunofluorescence staining.RESULTS:EGF treatment for 24h induced a significant increase of ARPE-19 cells’viability,proliferation and migration,phosphorylation of EGFR/AKT proteins,and decreased total EGFR expression.Erlotinib suppressed ARPE-19 cells’viability,proliferation and migration through down regulating total EGFR and AKT protein expressions.Erlotinib also inhibited EGF-induced an increase of proliferative and migrative ability in ARPE-19 cells and clearly suppressed EGF-induced EGFR/AKT proteins phosphorylation and decreased expression of N-cadherin,α-SMA,and vimentin proteins.Similarly,EGFR inhibition by EGFR siRNA significantly affected EGF-induced an increase of cell proliferation,viability,and migration,phosphorylation of EGFR/AKT proteins,and up-regulation of N-cadherin,α-SMA,and vimentin proteins.CONCLUSION:Erlotinib and EGFR-knockdown suppress EGF-induced cell viability,proliferation,and migration via EGFR/AKT pathway in RPE cells.EGFR inhibition may be a possible therapeutic approach for proliferative vitreoretinopathy(PVR).

ANTIPROLIFERATIVE ACTIVITY OF HUMAN IFN-γ-EGF_3 FUSION PROTEIN ARE RELATED TO ITS EGF RECEPTOR COMPETITION

The relationship between antiproliferative effect of human IFN γ EGF 3 fusion protein and the influence of EGF receptor binding activity has been studied on A431 cell line. Antiproliferative activity of human IFN γ EGF 3 was higher than that of its parent IFN γ. In the 125 I EGF receptor competition experiment, the inhibition of EGF receptor binding capacity on the target cells was observed in the treatments of human IFN γ or IFN γ EGF 3, but the later was more significant. Our data suggests that the antiproliferative effects by IFN γ and its fusion protein are closely related to their EGF receptor competitions.

p-AKT与VEGF、HER-2在膀胱浸润性尿路上皮癌中的表达及其与患者预后关系研究

目的探讨磷酸化蛋白激酶B(p-AKT)与血管内皮生长因子(VEGF)、人表皮生长因子受体2(HER-2)在膀胱浸润性尿路上皮癌中的表达及其与患者预后的关系。方法用免疫组织化学染色(IHC)和荧光原位杂交(FISH)检测69例膀胱浸润性尿路上皮癌、20例膀胱黏膜良性组织(慢性炎症、乳头状瘤组织)中p-AKT、VEGF、HER-2蛋白的表达。结果膀胱浸润性尿路上皮癌中p-AKT、VEGF、HER-2表达均显著高于膀胱良性组织的表达(P<0.05);p-AKT、VEGF和HER-2在高级别浸润性尿路上皮癌中的表达均显著高于低级别浸润性尿路上皮癌中的表达(P<0.05);p-AKT在后期复发的患者中的表达高于未复发患者(P<0.05);浸润性尿路上皮癌患者中p-AKT与VEGF、HER-2的表达均呈显著正相关(P<0.05);p-AKT、VEGF和HER-2蛋白表达阳性的患者生存率均明显低于阴性表达患者的生存率(P<0.05)。结论p-AKT、VEGF及HER-2蛋白均可能参与了膀胱浸润性尿路上皮癌的发生发展,并且与患者的预后相关,可能成为膀胱尿路上皮癌的预后指标;膀胱浸润性尿路上皮癌中p-AKT与VEGF、HER-2可能存在相互调节关系。

基于EGFR/MAPK/ERK信号通路探讨鳖甲煎丸对MHCC-97H肝癌细胞皮下瘤的抑瘤作用

目的基于表皮生长因子受体(epidermal growth factior receptor,EGFR)/丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)/细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)信号通路探究鳖甲煎丸对MHCC-97H肝癌细胞皮下瘤的抑瘤作用及作用机制。方法选取30只雄性BLAB/c裸鼠,建立MHCC-97H肝癌细胞皮下瘤模型。造模成功后随机分为模型组,鳖甲煎丸低、中、高剂量组(0.55、1.1、2.2 g/kg),西药组(乐伐替尼4 mg/kg+吉非替尼80 mg/kg),每组6只。鳖甲煎丸低、中、高剂量组灌胃2次/d,西药组每周灌胃5 d,模型组予以等量生理盐水2次/d灌胃,每组连续干预2周。观察大鼠一般情况;计算各组大鼠抑瘤率;HE染色观察病理形态学变化;RT-qPCR检测瘤体组织中EGFR、丝裂原活化蛋白质激酶激酶(mitogen-activated protein kinase kinase,MEK)、ERK1、ERK2 mRNA表达水平;Western blot检测EGFR、磷酸化的EGFR(p-EGFR)、MEK、磷酸化的MEK(p-MEK)、ERK1、ERK2、磷酸化的ERK1/2(p-ERK1/2)、基质金属蛋白酶-1(matrix metalloproteinase-1,MMP-1)、细胞周期蛋白D1(cell cycle protein D1,Cyclin D1)、神经型钙黏附蛋白(N-cadherin)、上皮型钙黏附蛋白(E-cadherin)相对表达水平。结果与模型组比较,鳖甲煎丸低、中、高剂量组及西药组精神、反应、进食饮水等情况均明显改善。与第0天比较,各组第14天体质量明显降低(P<0.01)。与模型组、鳖甲煎丸低剂量组比较,鳖甲煎丸中、高剂量组和西药组瘤体质量减轻(P<0.05,P<0.01)。鳖甲煎丸低、中、高剂量组和西药组抑瘤率分别为20%、47.73%、55.91%、75.45%。与模型组比较,鳖甲煎丸低、中、高剂量组及西药组肿瘤细胞排列疏松,边界模糊,细胞核固缩、破裂,其中西药组最明显。与模型组比较,鳖甲煎丸低、中、高剂量组和西药组EGFR、MEK、ERK1、ERK2 mRNA表达水平明显下降(P<0.01);与鳖甲煎丸低剂量组比较,鳖甲煎丸高剂量组和西药组EGFR、MEK、ERK1、ERK2 mRNA表达水平显著降低(P<0.01),鳖甲煎丸中剂量组ERK1 mRNA表达水平显著降低(P<0.01);与鳖甲煎丸中剂量组比较,西药组EGFR、ERK2 mRNA表达水平降低(P<0.05,P<0.01)。与模型组比较,鳖甲煎丸中、高剂量组和西药组p-EGFR/EGFR、p-MEK/MEK、p-ERK1/ERK1、p-ERK2/ERK2、MMP-1、Cyclin D1、N-cadherin蛋白相对表达水平下降(P<0.05,P<0.01),E-cadherin蛋白相对表达水平明显升高(P<0.01)。与鳖甲煎丸高剂量组比较,西药组p-EGFR/EGFR、p-ERK1/ERK1、MMP-1、Cyclin D1、N-cadherin蛋白相对表达水平明显下降(P<0.01),E-cadherin蛋白相对表达水平升高(P<0.05)。结论鳖甲煎丸可能通过抑制EGFR/MAPK/ERK信号通路激活,从而下调MMP-1、Cyclin D1、N-cadherin蛋白,上调E-cadherin蛋白表达,进而对MHCC-97H肝癌细胞皮下瘤产生显著的抑制作用。

乳腺癌组织中EGFR、GATA-3、E-Cad的表达及其与预后的关系

目的探讨表皮生长因子受体(EGFR)、GATA结合蛋白3(GATA-3)、上皮性钙黏附蛋白(E-cad)在乳腺癌组织内的表达及其与患者预后的关系。方法选取89例乳腺癌患者,术中采集所有患者的癌组织与癌旁正常组织(距离病灶边缘≥3 cm),将其分别纳入观察组、对照组,统计对比2组EGFR、GATA-3、E-Cad阳性表达差异。另随访1年,统计对比不同EGFR、GATA-3、E-Cad表达患者的生存率。结果观察组EGFR、GATA-3阳性表达率高于对照组,E-Cad阳性表达率低于对照组,差异有统计学意义(P<0.05);EGFR、GATA-3、E-Cad表达与患者肿瘤的分化程度、淋巴结转移、临床分期有关,差异有统计学意义(P<0.05)。EGFR、GATA-3阳性表达患者的生存率低于阴性表达患者,E-Cad阴性表达患者的生存率低于阳性表达患者,差异有统计学意义(P<0.05)。结论EGFR、GATA-3在乳腺癌组织内呈高表达,E-Cad呈低表达,三者表达与乳腺癌患者的生存率具有紧密联系。

胃苏颗粒联合泮托拉唑对非萎缩性胃炎患者胃肠激素及血清MCP-1、EGF的影响

目的探讨胃苏颗粒联合泮托拉唑对非萎缩性胃炎患者胃肠激素及血清单核细胞趋化因子-1(MCP-1)、表皮生长因子(EGF)的影响。方法选取2020年1月~2023年1月在我院就诊的非萎缩性胃炎患者116例,按照随机数字表法分为观察组和对照组,每组58例。对照组给予泮托拉唑20mg,2次/d,连续4周;观察组在对照组基础上加用胃苏颗粒5g,3次/d,连续4周。比较两组患者治疗前后胃肠激素(胃泌素、胆囊收缩素、生长抑素、血清素)及血清MCP-1、EGF的水平变化,以及临床疗效和不良反应。结果治疗后,两组患者的胃泌素和生长抑素水平明显升高,胆囊收缩素和血清素水平明显降低(P<0.001);血清MCP-1水平明显降低、EGF水平明显升高,两组相比差异有统计学意义(P=0.007、0.008)。治疗后观察组的临床症状总分低于对照组(P<0.001)。观察组的总有效率为93.10%,显著高于对照组(74.14%),差异有统计学意义(P=0.009)。两组患者均未出现严重不良反应。结论胃苏颗粒联合泮托拉唑能够有效调节非萎缩性胃炎患者的胃肠激素及血清MCP-1、EGF水平,改善胃黏膜的修复和保护功能,提高临床疗效,安全性好。

miRNA-7-EGFR/ERK通路用于卵巢癌治疗的研究进展

卵巢癌(OC)在女性生殖系统肿瘤中致死率最高,治疗多选择手术切除加辅助化疗,然而易出现耐药性,导致患者预后差。miRNA-7在卵巢癌细胞中低表达,通过靶向表皮生长因子受体(EGFR)/细胞外调节蛋白激酶(ERK)信号通路发挥抗肿瘤作用。本综述介绍miRNA-7-EGFR/ERK通路在卵巢癌治疗中的作用,为卵巢癌的治疗提供新的思路。

超声多模态检查联合血清Egfl7、VEGF、OPN对肝癌微血管侵犯的诊断价值及预后价值分析

目的探讨与分析超声多模态检查联合血清表皮生长因子样结构域蛋白7(epidermal growth factor-like domain protein 7,EGFL7)、血管内皮生长因子(vascular endothelial growth factor,VEGF)、骨桥蛋白(osteopontin,OPN)对肝癌微血管侵犯的诊断价值及预后价值。方法2018年2月到2021年5月选择在本院诊治的肝癌患者78例作为研究对象,所有患者都给予超声多模态检查联合血清Egfl7、VEGF、OPN检测,同时给予手术病理检查,判断微血管侵犯状况,随访患者的预后并进行预测价值分析。结果78例患者中检出微血管侵犯阳性28例,占比35.9%。阳性组的肝癌血管分级、血管分布与阴性组对比有明显差异(P<0.05)。阳性组的血清Egfl7、VEGF、OPN含量都明显高于阴性组(P<0.05)。所有患者随访到2022年10月1日,平均随访时间28.47±2.10个月,死亡22例,死亡率为78.6%。多因素Logistic回归分析显示微血管侵犯、血管分级、血管分布与血清Egfl7、VEGF、OPN含量都为影响患者随访死亡的重要因素(P<0.05)。结论肝癌微血管侵犯患者多表现为超声多模态血管分级程度高与混合血流状况,伴随有血清Egfl7、VEGF、OPN的高表达,超声与联合血清Egfl7、VEGF、OPN对肝癌微血管侵犯的诊断预后预测都有很好的价值。