Objective To investigate the roles of NF-κB and EGFR in hepatolithiasis associated with intrahepatic cholangiocarcinoma. Methods Ninety cases of liver tissue specimens from hepatectomies performed in the 2nd Affiliated Hospital of Sun Yat-sen University between August 1989 and June 2009 were enrolled in the study. Among them, 33 cases of hepatolithiasis associated with intrahepatic cholangiocarcinoma were considered as observing group, 32 cases of hepatolithiasis as control group, and 25 cases of normal bile duct tissues as normal control group. The SP method of immunohistochemical staining was applied to detect the expressions of NF-κB and EGFR in intrahepatic biliary ducts epithelial cells, and their relations with clinicopathologic factors and the accumulated survival rate of hepatolithiasis associated with intrahepatic cholangiocarcinoma were analyzed. Results Expression rates of NF-κB and EGFR were gradually raised from normal control group, control group to observing group (Plt;0.01). Expression of EGFR in tumor patients was related to histopathologic differentiation grading and the depth of tumor invasion (Plt;0.05), but not to gender, age, or lymph node metastasis (Pgt;0.05)； there were no significant relationships between the expression of NF-κB and factors described above (Pgt;0.05). The survival rate of patients with tumor expressed EGFR was significantly lower than that of patients with tumor non-expressed EGFR (Plt;0.01). Conclusions NF-κB expression is in the early stage during intrahepatic cholangiocarcinoma genesis. NF-κB and EGFR play cooperating roles during hepatolithiasis carcinogenesis process. Over expression of EGFR is related with poor differentiation and prognosis of tumor.
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.
ObjectiveTo summarize the biological characteristics of human epidermal growth factor receptor 2 (HER-2/neu) gene, the expression and meaning of HER-2/neu gene in gastric cancer, and clinical application of targeted medicine of HER-2/neu gene in gastric cancer. MethodsRelated literatures about HER-2/neu gene and gastric cancer were retrieved for a review. ResultsHER-2/neu gene encoded human epidermal growth factor receptor, and it participated in the gene regulation of tumor cell proliferation, invasion, and metastasis through the downstream signal transduction pathway. Amplification of HER-2/neu gene or overexpression of HER-2 was closely bound up to the occurrence and development of gastric cancer, however, whether it could be used as independent prognostic factors of gastric cancer remained to be controversial. Several targeted medicine of HER-2/neu gene had applied to clinical at present, and all of them obtained good short-term effect. ConclusionHER-2/neu gene is a reliable target of gastric cancer and targeted medicine of HER-2/neu gene has a promising prospect.
Objective To analyze the factors associated with the adoption of targeted therapy in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer and to generate evidence to inform decision-making on public security policy regarding innovative anticancer medicines for the benefit of patients. Methods The study population comprised female patients diagnosed with HER2-positive breast cancer and treated at Fujian Cancer Hospital from 2014 to 2020. The patients were eligible for targeted therapy. The demographic and sociological characteristics and clinical information of patients were extracted from the hospital information system. We performed binary logistic regression analysis of factors associated with the adoption of targeted therapy in patients with HER2-positive breast cancer. We also divided the participants into two groups according to their tumor stage for subgroup analysis. Results A total of 1 041 female patients with HER2-positive breast cancer were included, among them, 803 received targeted therapy. In September 2017, molecular-targeted medicines for HER2-positive breast cancer began to be included in the local basic health insurance program. Only 282 (35.1%) patients adopted targeted therapy before September 2017, after which this number increased to 521 (64.9%). Among the patients who adopted targeted therapy, most were formally employed (45.8%) and enrollees of the urban employee health insurance program (66.0%). Among those who did not adopt targeted therapy, most were unemployed (42.4%) and enrollees of the resident health insurance program (50.0%). Binary logistic regression analysis revealed that patient occupation, gene expression of estrogen receptor, tumor stage, surgery or not, radiotherapy or not, and undergoing treatment before or after September 2017 were correlated with the adoption of targeted therapy (P<0.05). Conclusions Inclusion of targeted medicines for HER2-positive breast cancer in the health insurance program substantially increased the overall administration of these therapies. Individual affordability is a critical factor associated with the application of targeted therapy in eligible patients. Future policies should enhance the public security of patients with a relatively weak ability to pay and provide insurance coverage for innovative anti-cancer medicines.
Objective To investigate the clinicopathological characteristics of HER2 protein expression in different degrees in human epidermal growth factor receptor 2 (HER2) negative breast cancer and the factors related to the efficacy of neoadjuvant chemotherapy in breast cancer with low HER2 expression. Methods The clinicopathological data of 161 patients with HER2-negative breast cancer who received neoadjuvant chemotherapy in the Department of Breast Surgery, Affiliated Hospital of Southwest Medical University from March 2019 to March 2022 were retrospectively collected. The difference of clinical and pathological characteristics of patients with different levels of HER2 protein expression were analyzed, and the factors influencing the pathological complete remission (pCR) rate of breast cancer patients with low HER2 expression after neoadjuvant chemotherapy with unconditional logistic regression model were analyzed. Results Among 161 HER2 negative breast cancer patients, 108 cases were low HER2 expression, accounting for 67.1%. Compared with those with zero expression of HER2 [immunohistochemistry (IHC) 0], the patients with low HER2 expression had higher axillary lymph node metastasis rate (P=0.048), lower histological grade (P=0.006), and higher proportion of positive hormone receptor expression (P<0.001). There was no significant difference in pCR rate among the HER2 IHC 0, IHC 1+ and IHC 2+ / in situ hybridization (ISH)– (P=0.099) , and the pCR rate of low expression of HER2 was lower than that of zero expression of HER2 in the general population and Luminal subgroup, and the difference was statistically significant (P<0.05). There was no significant difference in triple negative breast cancer subgroup (P=0.814). The logistic regression analysis showed that age, histological grade and estrogen receptor expression status were independent influencing factors for pCR rate after neoadjuvant chemotherapy with low HER2 expression (P<0.05). Conclusions Different degrees of HER2 protein expressions in patients with HER2-negative breast cancer have unique clinicopathological characteristics. The pCR rate of neoadjuvant chemotherapy in patients with low HER2-expression breast cancer is lower than that in patients with zero HER2-expression breast cancer. Age, histological grade and estrogen receptor expression status are independent factors influencing the pCR rate of neoadjuvant chemotherapy in patients with low HER2-expression breast cancer.
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.
目的 探讨不同分子分型乳腺浸润性导管癌手术病例标本中P53、表皮生长因子受体（EGFR）和Ki-67的表达及临床意义。 方法 采用免疫组织化学链霉菌抗生物素蛋白-过氧化物酶连接法法对2010年1月－2011年7月446例乳腺浸润性导管癌患者标本进行分子分型，并同时检测其P53、EGFR、Ki-67等的表达。 结果 P53和Ki-67在人类表皮生长因子受体2（HER2）过表达型、基底细胞样型、未分类型中的表达明显强于管腔A型及管腔B型（P＜0.05）；HER2过表达型和未分类型中的EGFR表达明显强于管腔A型及管腔B型（P＜0.05）。 结论 在使用雌激素受体、c-erbB-2等指标对浸润性导管癌进行分子分型时同时检测P53、EGFR及Ki-67等标记物，有助于更加精准的评估肿瘤的生物学行为及预后 ，对靶向药物的个体化治疗提供参考和疗效预测有重要意义。
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 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 compare the efficacy and safety of different cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) for the treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced or metastatic breast cancer. Methods Randomized controlled trials (RCTs) on CDK4/6i for the treatment of HR+/HER2− metastatic or advanced breast cancer were retrieved from databases including PubMed, EMbase, Web of Science, The Cochrane Library, CNKI, Wanfang, VIP, and SinoMed, with the search period ranging from database inception to August 2023. Bayesian network meta-analysis was conducted using R 4.2.0 software. Results A total of 18 RCTs from 25 articles, involving 8 031 patients and 11 treatment regimens, were included. There was no significant difference in progression-free survival (PFS) or overall survival (OS) among different CDK4/6i+ET combinations. The highest cumulative probability for PFS was observed with dalpiciclib (DAL)+fulvestrant (FUL), while ribociclib (RIB)+FUL ranked first for OS. In terms of efficacy, abemaciclib (ABE)+aromatase inhibitors (AI) and ABE+FUL ranked first in objective response rate and clinical benefit rate, respectively. Regarding safety, statistically significant difference in grade 3-4 adverse events was observed among certain types of CDK4/6i (P<0.05). Conclusion Current evidence suggests that CDK4/6i+ET is superior to ET alone for the treatment of HR+/HER2− advanced/metastatic breast cancer. Different CDK4/6i+ET combinations demonstrate comparable or similar efficacy; however, the incidence of adverse reactions is higher with combination therapy. Treatment regimens should be selected based on individual conditions.