Expressions of estrogen receptor subtypes and c-met proto-oncogene in endometrial carcinoma and their correlation

Objective To investigate the expressions of estrogen receptor(ER)subtypes and c-met proto-oncogene in human endometrial carcinomas and to assess the clinical significance of ER and c-met in this carcinoma.Methods Reverse transcription PCR(RT-PCR)was used to detect the expressions of ERα,ERβ and c-met proto-oncogene mRNA in 30 samples of endometrial carcinoma and 11 samples of normal endometrium.Results The expression of ERα in endometrial carcinoma(0.70±0.40)was significantly reduced in comparison to that in normal endometrium(1.14±0.56,P<0.05).A similar finding was made for the expression of ERβ in carcinoma(0.24±0.18)versus normal tissues(0.48±0.20,P<0.05).In contrast,c-met mRNA expression was increased in endometrial carcinoma(1.45±0.72)compared to that in normal endometrium(0.42±0.31,P<0.01).A decrease tendency of the expression of ERα was also found from Stage Ⅰ(0.82±0.41)to a more severe Stag Ⅱ-Ⅲ of endometrial carcinoma(0.42±0.17,P<0.05).The analysis of ERα and ERβ mRNA revealed a decrease tendency from shallow to deep invasion of the uterine muscles(P<0.05).We found that the expressions of ERα and ERβ were negatively correlated with c-met proto-oncogene with a coefficient correlation of-0.63(P<0.01)and-0.32(P<0.05),respectively.Conclusion ERα and ERβ are both involved in mutagenic action of carcinogen.C-met proto-oncogene plays an important role in the carcinogenesis and development of endometrial carcinoma.C-met and ER expressions show a negative correlation in the development of endometrial carcinoma.

黄芪建中汤对脾胃虚寒证胃溃疡大鼠炎症因子及HGF/c-Met信号通路的影响

目的观察黄芪建中汤对脾胃虚寒证胃溃疡大鼠炎症因子及HGF/c-Met信号通路的影响。方法将60只大鼠随机分为4组,即正常组、模型组、黄芪建中汤组[黄芪建中汤6.8 g/(kg·d)]、奥美拉唑组[奥美拉唑肠溶胶囊4.2 mg/(kg·d)],每组15只大鼠。正常组除外,其他组采用耗气破气法结合饥饱失常法进行大鼠脾胃虚寒证模型造模,再采用冰醋酸法建立大鼠胃溃疡模型。比较各组大鼠体质量、溃疡指数;HE染色观察大鼠胃组织病理学变化;采用酶联免疫吸附法检测血清中白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)含量;免疫组化法检测胃组织中肝细胞生长因子(HGF)、肝细胞生长因子受体(c-Met)表达;荧光定量PCR检测胃组织HGF、c-Met m RNA水平。结果与正常组相比,模型组大鼠体质量降低,溃疡指数升高,IL-6、IL-1β、TNF-α含量升高,HGF升高,HGF、c-Met m RNA升高(P<0.05);与模型组相比,黄芪建中汤组和奥美拉唑组大鼠体质量升高,溃疡指数降低,IL-6、IL-1β、TNF-α降低,HGF升高,HGF、c-Met mRNA升高(P<0.05)。结论黄芪建中汤可以通过抑制炎症因子、调节HGF/c-Met通路的表达促进胃黏膜修复。

基于转录组测序探究C-MET表达在非小细胞肺癌中的免疫调控机制

目的通过转录组测序技术分析C-MET表达在非小细胞肺癌中的免疫调控机制。方法使用siRNA分子干扰技术将C-MET高表达肺腺癌细胞株(H1993)、肺鳞癌细胞株(EBC-1)的C-MET表达沉默,利用转录组测序技术检测C-MET沉默前后细胞差异表达的基因(DEGs),通过生物信息学分析挖掘出C-MET可能参与调控的免疫微环境信号通路及相关基因。最后使用人免疫细胞与H1993、EBC-1共培养技术验证C-MET对免疫因子(INF-γ、INF-β、CXCL-10)的影响。结果通过转录组测序技术共检测到505个DEGs,其中H1993的C-MET调控前后表达差异组的表达差异基因共有38个,上调的差异表达基因有24个,下调的差异表达基因有14个。EBC-1的C-MET调控前后表达差异组的表达差异基因共有467个,上调的差异表达基因有347个,下调的差异表达基因121个。差异基因的KEGG分析表明,C-MET表达可能通过白细胞介素(IL-17)信号通路、白细胞分化、细胞因子受体活性、细胞周期、细胞因子-细胞因子受体相互作用参与免疫细胞调节因子的调控。使用肺癌细胞与人免疫细胞共同培养技术验证C-MET对免疫因子分泌的影响,Rt-qPCR检测结果提示:与C-MET高表达组共培养的PBMC中干扰素(INF-γ)的m RNA转录水平是低表达组的77倍、CXCL-10的mRNA转录水平是低表达组的1.6倍,INF-β的mRNA转录水平是低表达组的2倍。结论C-MET表达可能通过IL-17信号通路、白细胞分化、细胞因子受体活性通路参与肿瘤周围免疫微环境调控。

宫颈癌患者癌组织c-Met mRNA与NF-κB mRNA表达的关系及其对预后的影响

目的分析肝细胞生长因子受体原癌基因c-Met mRNA与核因子-κB(NF-κB)mRNA在宫颈癌发病中的关系及对宫颈癌患者预后的影响。方法选取本院宫颈癌患者89例作为癌变组,宫颈癌前病变患者89例作为癌前病变组,因子宫肌瘤行全子宫切除患者89例作为正常宫颈组。采用RT-PCR检测3组宫颈组织中c-Met、NF-κB mRNA相对表达量。采用Spearman/Pearson分析c-Met mRNA与NF-κB mRNA在宫颈癌发病中的关系。采用Kaplan-Meier曲线分析不同c-Met mRNA、NF-κB mRNA表达水平患者的3年生存率。结果宫颈组织中c-Met、NF-κB mRNA相对表达量,癌变组>癌前病变组>正常宫颈组(P<0.05)。癌前病变组、癌变组c-Met mRNA与NF-κB mRNA呈正相关(P<0.001)。c-Met高表达与NF-κB mRNA高表达在宫颈癌发病中呈正向交互作用(P<0.05)。c-Met、NF-κB mRNA与宫颈癌临床分期、淋巴结转移、脉管浸润呈正相关,与分化程度呈负相关(P<0.05)。癌变组c-Met、NF-κB mRNA高表达患者3年生存率低于低表达患者(P<0.05)。结论c-Met mRNA与NF-κB mRNA高表达在宫颈癌发病中呈正向交互作用,与临床分期、淋巴结转移、脉管浸润呈正相关,且宫颈癌患者3年生存率显著降低。

CTC、RON及c-Met在早期三阴性乳腺癌预后预测中的作用

目的 分析循环肿瘤细胞(CTC)、受体酪氨酸激酶(RON)及间质表皮转化因子(c-Met在早期三阴性乳腺癌(TNBC)预后预测中的作用。方法 分析2018年1月至2021年1月于郑州大学第一附属医院进行诊治的1 225例乳腺癌患者资料,根据纳入标准最终选取168例TNBC患者设为研究组,选取患者癌旁3 cm的组织为对照组,另选取同时期在本院进行健康体检者168名为健康组。根据患者治疗后的预后情况将研究组分为预后良好组(n=142)以及预后不良组(n=26)。比较研究组与健康组CTC的表达情况,比较研究组与对照组c-Met与RON的表达情况,采用多元Logistic回归分析影响TNBC预后的独立危险因素;并通过受试者工作特征曲线(ROC)分析c-Met、RON、CTC对TNBC患者预后的预测价值。结果 研究组CTC水平高于健康组,差异有统计学意义(P<0.05);研究组c-Met与RON阳性表达高于对照组,差异有统计学意义(P<0.05);预后良好组、预后不良组年龄、肿瘤直径比较差异无统计学意义(P>0.05),预后良好组、预后不良组腋窝淋巴结、体重指数、糖尿病、RON、c-Met、CTC比较,差异有统计学意义(P<0.05),经非条件多因素logistic回归模型分析显示,腋窝淋巴结转移、CTC阳性、RON阳性、c-Met阳性为TNBC患者预后的危险因素(P<0.05)。CTC、RON及c-Met单独检测以及三者联合检测AUC分别为0.764、0.778、0.776、0.857,其中三者联合检测AUC值最大。结论 联合检测RON、c-MET、CTC水平对TNBC患者预后具有一定的预测价值。

MACC1与c-Met基因在胰腺癌组织中的表达及预后意义

目的探究MACC1与c-Met基因在胰腺癌组织中的表达及预后意义。方法应用免疫组化法检测各标本中MACCI和c-Met蛋白的表达情况,统计学分析MACC1和c-Met表达水平与临床病理特征的关系;分别检测MACC1和c-Met在各细胞系中的表达情况,并选取高表达MACC1与c-Met的两组细胞株,通过RNA干扰技术抑制MACC1表达,48H后采用RT-PCR技术检测MACC1与c-Met;分别采用流式细胞仪、划痕实验及Transwell实验检测干扰后两组细胞的细胞增殖、凋亡、迁移及侵袭能力的变化;采用免疫印迹法检测干扰后两组细胞的MACC1与c-Met蛋白变化,并进一步研究相关信号通路的变化。结果MACC1和c-Met蛋白在胰腺癌组织中的高表达率明显增加(P<0.05),且随着肿瘤分期的增高及淋巴结的转移,其表达量均有所增加(P<0.05)。在RNA干扰后,MACCI和c-Met蛋白表达水平较对照组均明显降低(P<0.05);且细胞增殖、细胞迁移和侵袭能力均明显降低,细胞凋亡率明显增多。此外,下调MACC1表达抑制了Notch1、Hey1、Hes1等Notch信号通路相关蛋白的表达,同时,p53、MDM2等p53信号通路相关蛋白表达也明显改变。结论在胰腺癌中,MACC1和c-Met高表达与肿瘤分期及淋巴结转移密切相关。下调MACC1可以抑制凋亡蛋白的表达、胰腺癌细胞的增殖、迁移和侵袭,促进癌细胞凋亡,还可抑制Ras/ERK、Notch以及p53信号通路。MACC1和c-Met与胰腺癌的发生发展密切相关,可作为判断胰腺癌患者预后的重要指标。

Effects of Cadmium on Hepatocellular DNA Damage,Proto-Oncogene Expression and Apoptosis in Rats

Objective To study the effects of cadmium on hepatocellular DNA damage, expression of proto-oncogenes c-myc, c-fos, and c-jun as well as apoptosis in rats. Methods Cadmium chloride at the doses of 5, 10, and 20 μmol/kg was given to rats by i.p. and there were 5 male SD rats in each group. Hepatocellular DNA damage was measured by single cell gel electrophoresis （or comet assay）, while expression of proto-oncogenes c-myc, c-fos, and c-jun in rat hepatocytes were measured by Northern dot hybridization. C-Myc, c-Fos, and c-Jun were detected with immuno-histochemical method. Hepatocellular apoptosis was determined by TUNEL （TdT-mediated dUTP Nick End Labelling） and flow cytometry. Results At the doses of 5, 10, and 20 μmol/kg, cadmium chloride induced DNA damage in rat hepatocytes and the rates of comet cells were 50.20%, 88.40%, and 93.80%, respectively. Results also showed an obvious dose-response relationship between the rates of comet cells and the dose of cadmium chloride （r=0.9172, P〈0.01）. Cadmium chloride at the doses of 5, 10, and 20 μmol/kg induced expression of proto-oncogenes c-myc, c-fos, and c-jun. The positive brown-yellow signal for c-myc, c-fos, and c-jun was mainly located in the cytoplasm of hepatocytes with immunohistochemical method. TUNEL-positive cells were detected in cadmium-treated rat livers. Apoptotic rates （%） of cadmium-treated liver cells at the doses of 5, 10, and 20 μmol/kg were （17.24 ±2.98）, （20.58± 1.35）, and （24.06±1.77） respectively, being significantly higher than those in the control. The results also displayed an obvious dose-response relationship between apoptotic rates and the dose of cadmium chloride （r=0.8619, P〈0.05）. Conclusion Cadmium at 5-20 μmol/kg can induce hepatocellular DNA damage, expression of proto-oncogenes c-myc, c-fos, and c-jun as well as apoptosis in rats.

HGF及其受体c-Met基因在损伤修复的马鹿茸组织中的表达特征

为了探求鹿茸损伤修复的分子机制,本试验收集了意外折断修复50 d和65 d后的鹿茸样品,利用qRT-PCR技术和免疫组织化学技术检测HGF和c-Met基因在损伤修复的鹿茸与健康鹿茸组织中的表达。结果表明,HGF及c-Met基因在损伤茸总组织中的相对表达量显著高于健康鹿茸,在茸皮、间充质、软骨和骨四个组织中,茸皮组织相对表达量最高,间充质组织的相对表达量最低;与健康鹿茸组织相比,损伤茸茸皮组织中HGF及c-Met基因的相对表达量极显著降低(P<0.01),而在损伤茸间充质组织中的相对表达量极显著增加(P<0.01),损伤茸与健康茸的软骨和骨组织相对表达量差异不显著(P>0.05)。在损伤修复过程中,HGF及c-Met基因随损伤修复进程的继续表达量也随之上升。因此,HGF及c-Met基因对马鹿茸组织损伤修复及再发育可能具有促进作用。

Current concepts in ameloblastoma-targeted therapies in B-raf proto-oncogene serine/threonine kinase V600E mutation: Systematic review

BACKGROUND Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies.Different signaling pathways that participate in the progression of these tumors have been identified.B-raf proto-oncogene serine/threonine kinase(BRAF)is a protein involved in the behavior of ameloblastomas,and it is related to many cell mechanisms.BRAF gene mutations have been identified in ameloblastomas,of which the BRAF V600E(valine substituted by glutamic acid at amino acid 600)mutation has been the most common and can be present concomitantly with other mutations that may be involved in its behavior.Targeted therapies have been used as an alternative in the case of resistance or contraindications to conventional treatments.AIM To document the presence of BRAF V600E and additional mutations,their behavior,and targeted therapies in these tumors.METHODS An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE,Cochrane,EMBASE,and SpringerLink using the terms“ameloblastomas”,“BRAF V600E”,“additional mutations”,and“targeted therapies”.Ameloblastomas were classified according to WHO guidelines.Inclusion criteria were articles in English,published not more than 10 years ago,and studies with laboratory works related to BRAF V600E.Articles were evaluated by two independent reviewers and retrieved for full-text evaluation.The EBLIP Critical Appraisal Checklist was used to evaluate the quality of the eligible studies.Descriptive statistical analysis was performed.RESULTS Two independent reviewers,with a substantial concordance indicated by a kappa coefficient of k=0.76,evaluated a total of 19 articles that were included in this study.The analysis registered 521 conventional ameloblastomas(AM),81 unicystic ameloblastomas(UA),13 ameloblastic carcinomas(AC),three metastatic ameloblastomas(MA),and six peripheral ameloblastomas(PA),of which the histopathological type,anatomic location,laboratory tests,expression of BRAF mutation,and additional mutations were registered.The BRAF V600E mutation was found in 297 AM(57%),63 UA(77.7%),3 AC(23%),1 MA(50%),and 5 PA(83.3%).Follicular type predominated with a total of 116 cases(40%),followed by plexiform type with 63 cases(22.1%).Furthermore,both types presented additional mutations,in which alterations in JAK3 P132T,SMARCB1,PIK3CA,CTNNB1,SMO,and BRAF G606E genes were found.Four case reports were found with targeted therapy to BRAF V600E.CONCLUSION The identification of BRAF V600E and additional mutations as an aid in targeted therapies has been a breakthrough in alternative treatments of ameloblastomas where surgical treatments are contraindicated.

初治肺腺癌患者EGFR基因突变和C-MET基因扩增共存的临床病理及预后分析

目的探讨初治肺腺癌患者驱动基因EGFR突变和C-MET扩增共存的临床病理特征、预后。方法复阅病理切片,应用扩增阻遏突变系统—实时荧光定量聚合酶链反应检测EGFR基因突变,应用荧光原位杂交检测C-MET扩增,回顾性分析EGFR突变和C-MET扩增共存初治肺腺癌的临床病理及随访资料。结果11例EGFR突变合并C-MET扩增的送检组织中除1例难以评估组织结构的细胞块,其他10例均出现复杂腺体和实性的高级别成分。临床Ⅳ期的EGFR突变合并C-MET扩增组患病率显著高于EGFR突变组和C-MET扩增组,差异有统计学意义(P均<0.001);而EGFR突变组和C-MET扩增组在各临床分期的患病率差异均无统计学意义(P均>0.05)。EGFR基因和C-MET扩增组间的生存率变化差异无统计学意义(χ^(2)=0.042,P=0.838),而EGFR突变合并C-MET扩增组患者的生存状况显著差于EGFR突变组(χ^(2)=246.72,P<0.001)和C-MET扩增组(χ^(2)=236.41,P<0.001)。结论EGFR突变叠加C-MET扩增的初治肺腺癌组织学分化较差、进展快、预后差,首诊时往往已经是癌症晚期,临床需重视这种并发的不良驱动分子事件,随着C-MET靶向抑制剂的可及性增加,这部分叠加分子事件的肺腺癌患者将可能从EGFR与C-MET双靶用药中获益。

清肠汤联合心身同治疗法对热盛血瘀型溃疡性结肠炎HGF/c-MET表达的影响

目的探讨清肠汤联合心身同治疗法对热盛血瘀型溃疡性结肠炎患者肝细胞生长因子(hepatocyte growth factor,HGF)/肝细胞生长因子受体(cellular-mesenchymal to epithelial transition factor,c-MET)表达影响。方法选取于2019年5月—2021年5月医院内科门诊确诊的热盛血瘀型溃疡性结肠炎(ulcerative colitis)患者146例,根据前瞻队列研究按照1∶1原则分为对照组与研究组两组,每组73例。对照组给予口服美沙拉嗪缓释颗粒,4 g/d,治疗组在对照组治疗基础上给予清肠汤和心身同治疗法。两组患者治疗疗程均为3个月,治疗结束后随访3个月,治疗后评价两组患者疗效,分析治疗前后两组患者的中医症状积分(腹泻、黏液脓血便、腹痛、里急后重)和肠黏膜组织HGF、c-MET的免疫组化结果。结果经比较,治疗后研究组患者治疗总有效率(97.26%,71/73)显著高于对照组(86.30%,63/73),差异具有统计学意义(P<0.05)。两组腹泻、黏液脓血便、腹痛、里急后重中医症状积分均显著降低(P<0.05),但研究组治疗后各症状积分及总积分均显著低于对照组(P<0.05)。经治疗后,两组HGF及c-MET阳性率均显著增高(P<0.05),但研究组HGF及c-MET阳性率均显著高于对照组(P<0.05)。结论清肠汤联合心身同治疗法对热盛血瘀型溃疡性结肠炎具有较好的临床疗效,可以提高肠黏膜组织上的HGF/c-MET的表达。

玻璃酸钠通过干扰HGF/c-Met介导的MEK/ERK和PI3K/AKT信号通路抑制胃癌细胞增殖

目的 分析玻璃酸钠影响肝细胞生长因子(HGF)受体(c-Met)介导的人胃癌(GC)AGS细胞增殖及其作用机制。方法 应用不同浓度的玻璃酸钠作用于AGS细胞。应用HGF激活c-Met。细胞增殖与毒性检测试剂盒(CVTK)测定细胞增殖;Western印迹测定c-Met酪氨酸(Tyr)1234位点磷酸化(p-c-Met-Y1234)、磷酸化丝裂原活化蛋白激酶(p-MEK)、磷酸化细胞外调节激酶(p-ERK)1/2、磷酸化磷脂酰肌醇-3激酶(p-PI3K)、磷酸化蛋白激酶B(p-AKT)相对蛋白表达。结果 HGF明显促进AGS细胞增殖,并诱导细胞内p-c-Met(Y1234)、p-MEK1/2、p-ERK1/2、p-PI3K、p-AKT明显高表达(P<0.05);不同浓度玻璃酸钠作用细胞后,由HGF引起的细胞增殖明显受到抑制,p-c-Met(Y1234)、p-MEK1/2、p-ERK1/2、p-PI3K、p-AKT表达水平显著降低(P<0.05)。结论 璃酸钠通过抑制人AGS细胞的c-Met酪氨酸磷酸化,调控HGF/c-Met介导的MEK/ERK和PI3K/AKT信号通路,进而抑制人AGS细胞的增殖。

THE PRELIMINARY APPLICATION OF IN SITU HYBRIDI-ZATION IN DETECTING PROTO-ONCOGENES EXPRESSION IN HUMAN LEUKEMIC CELLS

An in situ hybridization technique with 35S labelled proto-oncogene probes (c-myc & c-fes) was used to detect their expression in bone marrow cells of 22 cases of leukemia of various types and immature granulocytes and erythroblasts of 16 nomal myelograms as controls. Both c-myc and c-fes were detectable in leukemic cells as well as in immature granulocytes and erythroblasts of normal bone marrow, but the expression extent varied in different cases. The levels of c-myc expression in leukemic cells were higher than those in controls (P<0.001). There was no difference of c-fes expression in two groups of bone marrow cells (P>0.05). This technique provides us a new method in studying variations of proto-oncogene expression in leukemic cells.

Malignant pheochromocytoma in neurofibromatosis; mutation screening of RET proto-oncogene, VHL and SDH gene

AIM: To investigate pathogenic mutations related to malignant pheochromocytoma in neurofibromatosis(NF).METHODS: We present a patient with NF and metastatic pheochromocytoma in whom genetic screening for presence of pathogenic mutations in RET protooncogene, von Hippel-Lindau(VHL) and succinate dehydrogenase complex subunits B(SDHB) genes were investigated. RET proto-oncogene mutation screening for exons 10, 11, 13, 14, 15, 16 were examined by polymerase chain reaction(PCR) and direct DNA sequencing in patient. Mutation screening for exons 1, 2, 3 of VHL gene was carried out. Both forward and reverse strandswere subjected to direct sequencing after PCR amplification. The entire coding sequence of SDHB gene was screened for the presence of pathogenic mutations by PCR-sequencing.RESULTS: A 45-year-old man presented with abdominal pain and hypertension over the previous year. The patient was a known case of neurofibromatosis type 1(NF1) who presented at the age of 15 years with hyperpigmented and hypopigmented lesions. After complete evaluation for hypertension, biochemical tests and imagings indicated a malignant pheochromocytoma of 120 mm × 70 mm in size. The patient underwent left adrenalectomy, nephrectomy and splenectomy. After surgery the symptoms improved and blood pressure was controlled. After 5 years he was admitted again for evaluation of hypertensive crisis. Biochemical tests were again consistent with pheochromocytoma and disease relapse. Imaging studies and liver biopsy confirmed metastatic pheochromocytoma to the liver and para-aortic area. 131 Iodine-metaiodobenzylguanidine therapy was carried out. Genetic screening of VHL(exons 1, 2, 3), RET proto-oncogene(exons 10, 11, 13, 14, 15, 16) and SDH complex subunits revealed no pathogenic mutation. CONCLUSION: We conclude that mutations in the NF1 gene are responsible for the patient's clinical findings. However, would be helpful to further examine somatic mutations for a more precise study of genotypephenotype correlation.

Effect of cisplatin-based concurrent radiochemotherapy on malignant degree of advanced cervical cancer and expression of proto-oncogene and tumor suppressor genes

Objective:To study the effect of cisplatin-based concurrent radiochemotherapy on the malignant degree of advanced cervical cancer and the expression of proto-oncogene and tumor suppressor genes.Methods: A total of 82 patients with advanced cervical cancer who were treated in our hospital between July 2013 and December 2016 were collected and divided into control group and observation group according to random number table, with 41 cases in each group. The control group of patients received radiotherapy alone, while the observation group of patients received cisplatin-based concurrent radiochemotherapy. Tumor marker levels in serum as well as proto-oncogene and tumor suppressor gene expression in tumor tissue were compared between two groups of patients before and after treatment.Results:Before treatment, differences in tumor marker levels in serum as well as proto-oncogene and tumor suppressor gene expression in tumor tissue were not statistically significant between two groups of patients. After treatment, serum tumor markers SCC, CA50, CA724 and CEA levels of observation group were significantly lower than those of control group;proto-oncogene DEK, c-myc and PIK3CA mRNA expression in tumor tissue were significantly lower than those of control group;tumor suppressor genes p53, SOCS-1, FHIT and PTEN mRNA expression in tumor tissue were significantly higher than those of control group.Conclusions:Cisplatin-based concurrent radiochemotherapy can effectively reduce the tumor malignancy and balance the proto-oncogene / tumor suppressor gene expression in patients with advanced cervical cancer.

小分子c-Met激酶抑制剂Foretinib的合成

Foretinib是处于临床研究阶段的小分子c-Met激酶抑制剂,而现有的合成路线普遍存在总收率较低的问题。本文以4'-羟基-3'-甲氧基苯乙酮(2)作为起始原料,经醚化、硝化、亲核取代、缩合、还原环合、氯代、醚化、还原和酰化反应制得目标化合物Foretinib(1),总收率为26.06%,纯度为99.40%。Foretinib及反应中间体的结构经1H NMR和MS(ESI)确征。上述合成路线反应条件温和,操作简便且收率高,适合工业化生产。

eEF1A1通过HGF/c-MET通路调控肝癌细胞的迁移和侵袭能力

目的探讨真核翻译延长因子1A1(eukaryotic translation elongation factor 1α1,eEF1A1)对肝癌细胞的侵袭、迁移和HGF/c-MET通路的影响及作用机制。方法采用qRT-PCR和Western bolt检测肝癌细胞和组织中eEF1A1表达。构建eEF1A1敲除载体转染HLF和Alex肝癌细胞,CCK-8和Transwell实验检测细胞的增殖、侵袭和迁移能力。KM plotter分析患者的总体预后。通过eEF1A1基因敲除的转录组测序,Western bolt检测HGF、c-MET和p-c-MET蛋白的表达。裸鼠皮下成瘤实验检测eEF1A1对肝癌肿瘤的影响。结果eEF1A1在肝癌细胞和组织中显著升高,敲低eEF1A1能抑制HCC细胞的增殖、迁移和侵袭。eEF1A1高表达与肝癌的不良预后相关。此外,敲除eEF1A1显著降低HGF和p-c-MET蛋白水平,抑制肝癌肿瘤的生长,但c-MET蛋白水平无显著差异。结论eEF1A1通过抑制HGF/c-MET信号通路抑制肝癌细胞迁移和侵袭。

RET proto-oncogene mutation analysis in a pedigree with multiple endocrine neoplasia 2A

Objective To discuss clinical diagnosis and treatment of multiple endocrine neoplasia ( MEN) 2A,and report the mutation of RET proto-oncogene in a pedigree of three patients with MEN 2A. Methods Bilateral adrenalectomy was performed on two of the three

克唑替尼与AP化疗方案治疗EGFR-TKIs耐药c-Met扩增阳性晚期肺腺癌的疗效比较

目的比较克唑替尼与培美曲塞联合卡铂(AP)化疗方案治疗表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)耐药间质表皮转化因子(c-Met)扩增阳性晚期肺腺癌的疗效。方法选取2019年6月—2022年6月赣州市肿瘤医院收治的EGFR-TKIs耐药c-Met扩增阳性晚期肺腺癌患者72例,按照随机数字表法分为对照组与试验组,各36例。对照组予以AP化疗方案,试验组予以克唑替尼胶囊,2组均以21 d为1个周期,持续治疗2个周期。比较2组临床疗效,治疗前及治疗2个周期后肿瘤标志物[血管内皮生长因子(VEGF)、癌胚抗原(CEA)、糖类抗原125(CA125)]、免疫指标(CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+))、卡氏功能状态量表(KPS)评分,无进展生存时间(PFS)、总生存时间(OS)、不良反应。结果试验组与对照组疾病控制率比较,差异无统计学意义(88.89%vs.75.00%,χ^(2)=2.347,P=0.126)。治疗前及治疗2个周期后,2组血清VEGF、CEA、CA125水平比较,差异无统计学意义(P>0.05);治疗2个周期后,2组血清VEGF、CEA、CA125水平低于治疗前(P<0.01)。治疗前及治疗2个周期后,2组CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)比较,差异无统计学意义(P>0.05);治疗2个周期后,对照组CD3^(+)、CD8^(+)及试验组CD8^(+)低于治疗前,试验组CD4^(+)/CD8^(+)高于治疗前(P<0.05或P<0.01)。治疗2个周期后,2组KPS评分高于治疗前,且试验组高于对照组(P<0.01)。2组PFS、OS比较,差异无统计学意义(P>0.05)。试验组不良反应总发生率低于对照组(13.89%vs.38.89%,χ^(2)=5.792,P=0.016)。结论EGFR-TKIs耐药c-Met扩增阳性晚期肺腺癌患者采用克唑替尼或AP化疗方案治疗均能获得一定效果,均能够降低肿瘤标志物水平,延缓病情进展,延长生存期,且对患者免疫功能损伤较小,但克唑替尼不良反应更少,能够提升患者生存质量。

MACC1和c-met在非小细胞肺癌中的表达及其预后价值

背景与目的已有的研究表明结肠癌转移相关基因1(metastasis-associated in colon cancer1,MACC1)是一个与肿瘤浸润转移相关的新基因,该基因能够调节肝细胞生长因子受体(hepatocyte growth factor receptor,c-met)的表达。本研究旨在探讨MACC1和c-met在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中的表达及其与浸润转移和预后的关系。方法采用免疫组化检测103例NSCLC组织及40例癌旁正常组织中MACC1和c-met蛋白的表达。结果 MACC1和c-met在NSCLC组中的阳性表达率均明显高于正常肺组织(P<0.001)。MACC1和c-met阳性率均与肺癌的分化程度、T分期、淋巴结转移和TNM分期相关(P<0.05),而与性别、年龄、吸烟及组织学类型等无关(P>0.05)。MACC1和c-met的表达呈正相关(r=0.403,P<0.001)。Kaplan-Meier生存曲线显示MACC1和c-met阳性组5年生存率均明显低于阴性组(P<0.05)。Cox多因素分析显示MACC1是NSCLC的独立预后因素(P=0.026)。结论 MACC1和c-met的表达与肺癌的分化、浸润和转移密切相关,两者均对生存期有一定的影响,MACC1是NSCLC的独立预后危险因素。