Downregulation of wild-type p53 protein by HER-2/neu mediated PI3K pathway activation in human breast cancer cells: its effect on cell proliferation and implication for therapy

Overexpression and activation of HER-2/neu (also known as c-erbB-2), a proto-oncogene, was found in about 30% of human breast cancers, promoting cancer growth and making cancer cells resistant to chemo- and radio-therapy. Wild-type p53 is crucial in regulating cell growth and apoptosis and is found to be mutated or deleted in 60-70% of human cancers. And some cancers with a wild-type p53 do not have normal p53 function, suggesting that it is implicated in a complex process regulated by many factors. In the present study, we showed that the overexpression of HER-2/neu could decrease the amount of wild-type p53 protein via activating PI3K pathway, as well as inducing MDM2 nuclear translocation in MCF7 human breast cancer cells. Blockage of PI3K pathway with its specific inhibitor LY294002 caused Gl-S phase arrest, decreased cell growth rate and increased chemo- and radio-therapeutic sensitivity in MCF7 cells expressing wild-type p53. However, it did not increase the sensitivity to adriamycin in MDA-MB-453 breast cancer cells containing mutant p53. Our study indicates that blocking PI3K pathway activation mediated by HER-2/neu overexpression may be useful in the treatment of breast tumors with HER-2/neu overexpression and wild-type p53.

CORRELATION BETWEEN SERUM HER-2 ONCOPROTEIN AND PATIENTS WITH BREAST CANCER

To detect serum HER-2 oncoprotein levels in patients with operable and metastatic breast cancers, and to study the correlations between serum HER-2 level and lymph node status as well as other clinical parameters. Methods A total of 120 women were studied consisting of 10 healthy volunteers, 31 benign breast disease, 53 operable breast cancer, and 26 metastatic breast cancer patients. The levels of serum HER-2 were measured using an enzyme-liked im-munosorbent assay (ELISA). Results The mean serum HER-2 levels were 9.6 ± 1.5 ng/mL in healthy volunteers, 11.9 ± 1.6 ng/mL in benign breast disease, 13.2 ± 4.2 ng/mL in operable breast cancer, and 30.5 ± 30.8 ng/mL in metastatic breast cancer patients. The former is much lower than the latter three (P = 0.02, 0.001, 0.03, respectively). If using 15 ng/mL as a normal baseline, elevated serum HER-2 levels were observed in none of the healthy volunteers as well as patients with benign disease, but in 18.9% (10/53) operable breast cancer patients and 61.5% (16/26) metastatic patients. In patients with operable breast cancer, there was a positive correlation between serum concentrations of HER-2 and the size of primary tumor (P < 0.05), whereas there was no correlation between serum concentration and axillary lymph node or estrogen receptor status. In patients with metastatic dise-ase, there was no correlation with site of metastases (P > 0.05). Conclusion Serum HER-2 level was strongly correlated with tumor loads and clinical stages, thus acting as a promising predictor of cancer recurrence in breast cancer patients.

GENISTEIN INHIBITS EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN HER-2/NEU TRANSFECTED HUMAN BREAST CANCER MCF-7 CELLS

Objective： our previous studies have demonstrated that HER-2/neu gene expression in human breast cancer MCF-7 cells promotes angiogenesis in MCF-7 cells xenograft tumors, and genistein inhibits angiogenesis in MCF-7 cells with HER-2/neu expression xenograft tumors. Here, the effects of genistein on the expression of vascular endothelial growth factor （VEGF） in MCR-7 cells with HER-2/neu expression were further studied for exploring the molecular mechanism of anti-angiogenesis in HER-2/neu-overexpressing breast cancer by genistein. Methods： HER-2/neu-overexpressing MCF-7 cells （MCF-7/HER-2） were established by transfecting HEg-2/neu gene into HER-2/neu negative expression breast cancer MCF-7 cells. Immunocytochemical staining, western blot and reverse transcription-polymerase chain reaction （RT-PCR） were adopted to measure the expression of VEGF in MCF-7/HER-2 cells treated by genistein for 24, 48 and 72h. Results： HER-2/neu expression up-regulated VEGF mRNA and protein in MCF-7 cells, genistein decreased VEGF mRNA and protein level in MCF-7/HER-2 cells in a time-dependent manner. Conclusion： These results suggest that VEGF plays an important role in HER-2/neu gene expression promoted antiogenesis in breast cancer and genistein induced down-regulation of the expression of VEGF may be one of the molecular mechanisms of its anti-angiogenesis in HER-2/neu-overexpressing breast cancer.

Detection of HER-2/neu Amplification on Fine Needle Aspirates of Breast Cancer Using Fluorescence in Situ Hybridization

The accuracy of diagnostic assays for HER-2/neu in breast cancer is extremely important as HER-2/neu status is essential in tailoring adjuvant and/or neoadjuvant treatment in every patient. FNAC is widely practiced in Egypt in preoperative diagnosis of breast cancer for its low cost and high diagnostic accuracy. Since the determination of HER-2/neu protein expression on cytological preparations was previously found to be unreliable for clinical use, we opted for the assessment of HER-2/neu status in fine needle aspirates using FISH. The main objective of this study was to evaluate the reliability of HER-2/neu status assessment by FISH on fine needle aspirates of breast cancers by comparing the results with IHC and FISH on FFPE tissue sections obtained from corresponding surgically resected specimens. Fine needle aspirates from 40 breast cancer patients with pathologically confirmed breast cancer were included in the study. They were submitted for HER-2/neu evaluation by FISH. After surgery, the corresponding FFPE sections were evaluated for HER-2/neu by FISH and by IHC. FNAs from 11 cases proved to be amplified by FISH, while 29 cases were not amplified. Apart from two cases that showed lack of signals, all specimens evaluated by FISH on the corresponding FFPE sections showed matched results. The Measurement of Agreement between FISH on FNAs and FISH on FFPE sections was 86.7%, while that between FISH on FNAs and IHC was 72.5%. The high concordance rate in the present study between FISH evaluation of HER-2/neu gene amplification on FNAC samples and their corresponding FFPE samples indicate that FISH may be a reliable technique for HER-2/neu assessment on FNAs. Furthermore, FISH on FNAs gave us better hybridization signals than their corresponding FFPE tissue sections. Finally, we also conclude that all score (2+) cases by IHC should be reevaluated by FISH which is crucial for the patient management.

Association between Overexpression of Her-2 and Other Clinicopathologic Prognostic Factors in Breast Cancer in Morocco

Background: Breast cancer is the leading cancer among women. The management depends largely on the knowledge of prognostic factors. The aim of our study is to evaluate the overexpression of Her-2/neu in patients with invasive breast carcinoma in Morocco, and to study the association between this overexpression and otherprognostic factors of breast cancer, such as age, tumor size, tumor grade, hormone receptors, vascular space invasion and lymph node status. Methods: This is a transversal study in which we included patients with invasive breast carcinomas treated at University Hospital Ibn Rochd of Casablanca in radiotherapy-oncology departement between January 2008 and December 2010, having had surgery first. Univariate analysis (Chi 2 test and Student’s test) and multivariate (logistic regression) were performed to study this association. Results: The overexpression of Her-2/neu was found in 29.2% of cases. In univariate analysis, Her-2 positive status was significantly correlated with high-grade tumors and large, to a lymph node, vascular space invasion and negative ER/PR. Age alone does not appear as a factor associated with positive Her-2/neu status. In multivariate analysis, the overexpression of Her 2 was significantly associated only with vascular space invasion, high tumor grade and the negativity of estrogen receptors. Conclusion: In our series, only the high grade, the vascular space invasion and the negative hormone receptors are independent factors associated with overexpression of Her 2/neu. Age does not appear as a factor associated with positive Her-2/neu status.

Comparison of Fluorescence in situ Hybridization and Immunohistochemistry for Assessment of HER-2 Status in Breast Cancer Patients

The accurate assessment ofa proto-oncogene, human epidermal growth factor receptor-2 gene （HER-2）, is extremely important for the therapy and prognosis of breast cancer. Currently, immunohistochemistry （IHC） is the method widely used for the detection of HER-2 protein. Fluorescence in situ hybridization （FISH） has been suggested to be a golden standard assay for HER-2 amplification. This study examined the expression and amplification of HER-2 in paraffin-embedded sections of breast cancer tissues, and compared the two methods on the measurement of HER-2 status. HER-2 gene and protein were determined in breast cancer samples from 52 Chinese women by FISH and IHC respectively. The findings indicated that the HER-2 gene amplification was found in 18 cases （34.6%） by FISH and the HER-2 protein over-expression （score 3＋） in 15 cases （28.8%） by IHC. hnmunohistochemically, 28.6% of the cases scored as 2＋ and 93.3% of the cases scored as 3＋ were HER-2-positive by FISH. There was a significant correlation between the HER-2 gene amplification and HER-2 protein over-expression in breast cancer （P〈0.005）. No correlation was noted between the HER-2 gene amplification and any of the clinicopathological parameters examined, including age, menopausal status, menarche age, tumor size, histological tumor type, histological grade, lymph node status, and the expression of ER and PR. It was concluded that the detection of HER-2 gene amplification in breast cancer by FISH is valuable and can compare with HER-2 protein detection by IHC.

Correlations of β-catenin,Ki67 and Her-2/neu with gastric cancer

Objective:To study the clinical pathologic characteristics ofβ-catenin,Ki67 and Her-2/neu in gastric cancer and the correlation ofβ-catenin and Ki67 to the protein expression and gene conditions of Her-2/Neu.Methods:The protein expression ofβ-catenin,Ki67 and Her-2/Neu was detected by immunohistochemistry in 101 cases of gastric cancer and the gene conditions of Her-2/Neu by fluorescence in situ hybridization(FISH).Results:The protein expression ofβ-catenin,Ki67 and Her-2/Neu had close relationship with the clinical pathologic characteristics of gastric cancer.Theβ-catenin and Ki67 had obvious correlation to the differentiation,infiltration and lymphatic metastasis of the gastric cancer(P<0.05).The Ki67 had close relationship with the tumor-node-metastasis staging staging of gastric cancer(P<0.05).Her-2/Neu had close relationship with the differentiation and tumor-node-metastasis staging of gastric cancer(P<0.05)but had no relationship with the infiltration and lymphatic metastasis of the gastric cancer(P<0.05).The protein expression of Ki67 had significantly positive correlation to the protein expression and gene amplification conditions of Her-2/Neu(r=0.567,P<0.05 for protein;r=0.304,P<0.05 for gene).Conclusions:Combined detection ofβ-catenin,Ki67 and Her-2/Neu can be used as a reliable method to help the observation of biological behavior,diagnosis and prognosis of gastric cancer,and Ki67 can be used to serve the preliminary screening of Her-2/Neu gene state.

HER-2,P53 and Hormonal Receptors Protein Expression as Predictive Factors in Breast Cancer Prognosis

OBJECTIVE Breast cancer is a heterogeneous disease with vari-able biological and clinical characteristics.We conducted a studyto evaluate P53,HER-2/neu and hormonal receptor expression aspredictors of prognosis in breast cancer.METHODS In a prospective study,we recruited 81 consecutivepatients with primary operable breast cancer who were treatedwith mastectomy followed by locoregional radiotherapy or che-motherapy and studied the presence of P53,HER-2/neu andhormonal receptors (ER/PR) expression in tumor tissues by im-munohistochemical staining.Associations between these markersexpression and clinical outcomes,including local and regionalrecurrence and metastasis were evaluated.Statistical analysis wasperformed with the SPSS software.RESULTS The mean time of follow-up was (47.3±4.6) months.Expression of P53,HER-2/neu,Estrogen receptors and progester-one receptors were observed in 31.1%,38.5%,31.8% and 51.7% ofthe patients,respectively.P53,HER-2/neu and Negative ER statuswere potent predictors of local-regional recurrence (P=0.034,0.038,0.044,respectively).Also HER-2/neu,Negative ER and NegativePR status were strong predictors of metastasis (P=0.001,0.042,0.054,respectively).CONCLUSION P53 and HER-2/neu expression and also steroidreceptors status (ER/PR status) have an important role in predict-ing the outcome of breast cancer and thus may be of value in se-lecting suitable therapeutic strategy and determining prognosis inthese patients.

HER-2 expression after neoadjuvant chemotherapy of the breast cancers

Objective:The aim of this study was to study changes of HER-2 expression after neoadjuvant chemotherapy in the breast cancer cases.Methods:One hundred and thirty-seven female patients with primary breast cancers,who received neoadjuvant chemotherapy,underwent core needle puncture and Mammotome biopsy before chemotherapy,and the biopsy results were used as the basis of histological diagnosis,fluorescence in situ hybridization (FISH) was performed to test HER2 status of tumor tissues before and after chemotherapy.All patients underwent FEC,TE,or AC neoadjuvant chemotherapy of 2-6 cycles before surgery.Results:Twenty-two patients were positive according to FISH test among 137 preoperative patients,8 patients achieved pathological complete remission after chemotherapy (three HER-2 positive patients and five negative patients),91 patients achieved partial remission,24 patients were stable,and 14 cases were invalid.Twenty-two patients were positive according to FISH test (8 patients with pathological complete remission did not undergo test),and positive patients still expressed positively after chemotherapy before neoadjuvant chemotherapy.Three negative patients were converted to be positive,and changes before and after chemotherapy had no statistical difference (P>0.05).Conclusion:Neoadjuvant chemotherapy makes no influence on patients with HER-2 positive expression,while patients with negative expression can be converted to be positive,but without significant difference.

The expression of HER-2/neu gene in colon cancer tissues and its clinical significance

Objective：The article aims to detect the expression of HER-2/neu gene in colon cancer tissues and adjacent tissues, to analyze the relationship between dif erent pathologic types and clinical features, also to invest the distribution of patients with positive expression of HER-2 gene. Methods：The expression of HER-2 gene in the 223 samples with colon can-cer was detected by immunochemical approach. The expression of HER-2 gene in colon cancer tissues and adjacent tissues and dif erent pathologic types was analyzed byχ2 test. The correlation between the expression of HER-2 gene and clinical features was analyzed by Spearman. Results：The number of positive expression of HER-2 gene in colon cancer tissues and adjacent tissues were 74 and 0 respectively, the dif erence has statistical significance. The number of papil ary or tubular adenocarcinoma was 182, among them, 60 cases were positive expression. The number of mucinous adenocarcinoma was 41, among them, 14 cases were positive expression. The expression of HER-2/neu gene has no correlation with sex, age, the maximum diameter, general classification, degree of dif erentiation and depth of invasion, which has no statistical significance. However, the expression of HER-2/neu gene has correlation with metastasis of lymph node and Dukes stage, which has statistical significance. The expression of HER-2/neu gene was positive correlation with metastasis of lymph node and Dukes stage. The correlated coef icient index was 0.320 and 0.320 respectively. In the 74 patients with positive expression of HER-2 gene, 59.4%of them were 60-74 years old. And there was 97.3%of the patients without family history of adenocarcinoma. Conclusion：The expression of HER-2/neu gene in colon cancer tissues was higher than in adjacent tissues. The expression of HER-2/neu gene has no correlation with sex, age, the maximum diameter, general classification, degree of dif erentiation and depth of invasion, but has correlation with metastasis of lymph node and Dukes stage. The expression of HER-2/neu gene was positive correlation with metastasis of lymph node and Dukes stage. The expression of HER-2/neu gene with age of 60-74 years old and without family history of adenocarcinoma was higher than other groups.

Geldanamycin inhibits proliferation and motility of Her2/neu-overexpressing SKBr3 breast cancer cells

Objective Benzoquinone ansamycin antibiotic, geldanamycin (GA), is a new anticancer agent that could inhibit Hsp90 by occupying its NH2-terminal ATP-binding site. This study was to investigate the antitumor efficacy of GA on Her2/neu tyrosine kinase overexpressing human breast cancer cell line SKBr3. Methods The degradation of Her2/neu tyrosine kinase was analyzed by Western blotting, the proliferation index was determined by MTT assay, cell cycle distribution was detected by flow cytometry, Cyclin D1 mRNA transcription was measured by RT-PCR and real-time PCR, and cell motility was evaluated by the cell culture insert model. Results GA induced a dose-and a time-dependent degradation of the Her2/neu tyrosine kinase protein and concurrently, the inhibition of cancer cell proliferation. The antitumor effects mediated by GA included: GA treatment decreased the survival rates of cancer cells, and led to a dose-dependent G1 arrest. Furthermore, this antitumor effect was proved to be related to declined transcription of Cyclin D1. Concurrently, the motility of cancer cells was reduced by GA. Conclusion GA treatment could induce the degradation of Her2/neu tyrosine kinase efficiently, inhibit cancer cell proliferation and reduce motility in Her2/neu tyrosine kinase overexpressed human breast cancer cell line SKBr3.

Research of vitamin E succinate combined with paclitaxel on the apoptosis of Her-2 over-expressing breast cancer cells

Objective： The aim of this study was to detect apoptosis rates of Her-2 overexpression breast cancer cells, which were administrated with vitamin E succinate （VES） combined with paclitaxel at different dosages, or administrated alone; to discuss the mechanism of their actions. Methods： Using immunohistochemical method to detect Her-2 expression of MDA- MB-453 cells. Using TUNEL assay to detect apoptosis rates of MDA-MB-453 ceils, with the concentrations at 10, 20 mg/L of VES and 50, 100 nmol/L of paclitaxel, and also combined together for 24 or 48 h. Then compared apoptosis action of various combinations. Results： The expression rate of 95% Her-2 was interval （63.32%, 69.60%）; VES and paclitaxel both induced apoptosis of MDA-MB-453 cells, and it is dose to time dependence. It was strongest in apoptosis at 10 mg/L VES and 100 nmol/L paclitaxel in MDA-MB-453 cells 48 h later. Conclusion： VES and paclitaxel both induced apoptosis of MDA-MB-453 cells. It is stronger when the two drugs are administrated together. The mechanism is probably related to reduction of bcl-2 expression, so as to be more sensitive to paclitaxel. Synergistic effect is also possible for the two drugs influence tumor cells in different growing phases.

Impressive Objective Response to Nab-Paclitaxel plus Trastuzumab as Fifth Line Therapy in an Elderly HER-2 Positive Breast Cancer Patient

Background: Agent targeting HER-2 pathway plus chemotherapy has represented a major progress in the management of patients with breast cancer. However, the role of late-line treatment in heavily pretreated patients is still largely unclear. In the last decade, nab-paclitaxel has shown significant activity and good toxicity profile in metastatic breast cancer. Case Presentation: We report the case of a 76-year-old Caucasian woman with metastatic HER-2 positive ductal infiltrating breast carcinoma treated with a combination of weekly nab-paclitaxel and trastuzumab as fifth-line therapy. She had previously received first-line paclitaxel and trastuzumab, second-line vinorelbine and trastuzumab, third-line TDM1 and fourth-line oral capecitabine and lapatinib. Clinical and radiological staging showed progression at bone, skin and soft-tissue. The patient received weekly nab-paclitaxel plus trastuzumab. Massive objective response was clinically and PET documented which lasted 8 months. Tolerance to treatment was fairly good as well as cardiac safety. Conclusion: To the best of our knowledge, this is the first reported case of efficacy of nab-paclitaxel in combination with trastuzumab as fifth-line of treatment in a patient with metastatic HER-2 positive breast cancer.

Relationship between expression of ER, PR, Her-2, Ki-67 and neoadjuvant chemotherapy effect in breast cancer

Objective: The purpose of the study was to investigate the relationship between the expression of estrogen receptor(ER), progestogen receptor(PR), human epidermal growth factor receptor(Her-2), Ki-67 and the effect of neoadjuvant chemotherapy in breast cancer. Methods: The expression of ER, PR, Her-2 and Ki-67 in 45 breast cancers which received neoadjuvant chemotherapy was detected by immunohistochemistry. Results: The effective rates in ER negative and PR negative groups were higher than those in ER positive and PR positive groups(83.3% vs 59. 4%, 82.4% vs 60.6%). There was no significant difference of the effective rate between Her-2 overexpressed group and Her-2 non-overexpressed group(81.8% vs 64.1%), and the same thing happened between Ki-67 negative group and Ki-67 positive group(67.7% vs 63.2%). Conclusion: In the patients with breast cancer, ER, PR negative ones were more sensitive to neoadjuvant chemotherapy. These patients may get more benefits from chemotherapy. ER, PR could be feasible markers for predicting the effective rate of neoadjuvant chemotherapy.

Correlation of Hormonal Receptors Estrogen Receptor, Progesterone Receptor and Her-2/Neu with Tumor Characteristics in Breast Carcinoma: Study of 100 Consecutive Cases

Introduction-Breast cancer is the most common cancer and leading cause of death in women. In India, its incidence is rapidly rising over last few decades. Present study is aimed to study the pattern of expression of hormonal receptors and Her-2/neu in invasive breast carcinoma and to correlate estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu expressions with various clinicopathological parameters. Material and methods: The present study was carried out in Department of Pathology, S.C.B. Medical College, Cuttack in the year 2013 taking consecutive 100 cases. Routine H&E staining for histological diagnosis and IHC analysis for ER, PR and Her 2/neu was carried out in all 100 cases of breast malignancies. Results: 99% of cases are invasive breast carcinoma, not otherwise specify (IDC-NOS). The age ranges from 23 years to 72 years. Majority of tumors are of grade 2 (70%) followed by grade 3 (30%). ER PR and Her-2/neu expression are seen in 45%, 35% and 30% respectively. Triple negative cases comprise 35%. Higher number of grade 2 tumor shows ER, PR positivity as compared to grade 3 tumors. Her-2/neu expression does not show any significant correlation with age or lymph node status of the patient. Conclusion: ER and PR expression in breast cancers in the current study are found to be comparable to the findings of other authors, but the frequency of HER-2/neu expression is slightly higher. Significant correlation is observed between hormonal receptor status and the grade of the tumor. Inverse relationship is found between Her-2/neu expression and ER, PR receptor status. Her-2/neu expression is increased with size and high grade of tumor.

Evaluation of Tobacco Use and Her-2 Receptor Expression in Breast Cancer in an Ethnically Diverse Inner-City Population

Background: Tobacco is linked to most cancers however despite overwhelming biological plausibility and decades of epidemiological studies, no association has been established between tobacco and breast cancer. Although estrogen receptor status has been looked at as a variable there has been no evaluation of the role of Her-2 and smoking in breast cancer. Methods: Review of records from patients treated at the University of Miami/Jackson Memorial Hospital from 1998-2012. The incidence of smoking and Her-2 expression in1255 women was evaluated. Data was analyzed by age, race, ethnic group, menopausal status, tumor stage, and ER/PR/Her-2 receptor status. Results: 1255 charts were analyzed with 1094 having full information. Overall rate of Her-2 expression 18.1%. The rate of Her-2 expression was 21.4% in smokers and 17.0% in non-smokers (p = 0.10). The rate of Her-2 expression was 10.8% in Caucasian smokers and 9.8% in Caucasian non-smokers (p = 0.88);24.5% in smokers of African descent and 17.3% in non-smokers of African descent (p = 0.24);22.9% in Latino smokers and 17.4% in Latino non-smokers (p = 0.10). The rate of Her-2/ER expression was 9.4% in smokers and 7.9% in non-smokers (p = 0.42);5.4% in Caucasian smokers and 4.9% in Caucasian non-smokers (p = 0.916);12.2% in smokers of African descent and 5.9% in non-smokers of African descent (p = 0.11);9.5% in Latin smokers and 8.8% in Latin non-smokers (p = 0.77). Conclusions: We found non-statistically significant positive associations in all analyses between Her-2 expression with or without ER expression and tobacco exposure when analyzed by ethnicity.

The Role of HER2/Neu and BRCA1 Genes in the Diagnosis of Breast Cancer among Sudanese Women

Background: Knowledge of HER2/Neu and BRCA1 Genes might be helpful for development of strategies for decreasing the burden of risk of breast cancer. Therefore, the aim of this study to detect the role of HER2/Neu and BRCA1 Genes expression in diagnosis of breast cancer in Sudanese women. Methodology: A total of 100 tissue samples obtained from patients with breast cancer in addition to 50 tissue samples obtained from patients with benign breast lesions, were detected the expression of HER2/Neu and BRCA1 Genes by Polymerase Chain Reaction (PCR). Results: The prevalence of HER2/Neu and BRCA1 Genes, among cases was 6%, and 10% respectively. Conclusion: HER2/Neu and BRCA1 Genes have a considerable contribution to etiology of breast cancer in Sudan that requires further consideration.

乳腺癌患者血清与肿瘤组织中Her-2/neu表达的相关性研究

目的 :建立一种检测血清Her 2 /neu的快速、简单的方法 ,并从临床的角度探讨了血清Her 2 /neu与组织Her 2 /neu表达及其他因素的相关性。方法 :收集初治乳腺癌 5 3例 ,采用ELISA方法检测血清Her 2 /neu水平 ,并采用免疫组化方法对术后标本进行组织Her 2 /neu表达的检测 ;同时设立了 10例正常人、31例乳腺良性病变为对照。结果 :早期乳腺癌中 ,10 / 5 3(19% )血清Her 2 /neu水平高于正常 ,组织Her 2 /neu表达阳性者中 32 %血清Her 2 /neu阳性 ,而组织表达阴性者中仅7%血清阳性 ,二者有相关性 (P <0 0 5 )。血清Her 2 /neu水平与肿瘤大小有相关性 (P <0 5 ) ,与淋巴结、受体状况无关。结论 :血清Her 2 /neu与组织Her 2 /neu有一致性 ,前者可作为后者的补充。

乳腺癌患者血清HER-2/neu浓度与组织HER-2表达水平的相关性

目的探讨化学发光法检测可手术乳腺癌患者血清HER-2/neu ECD浓度与组织HER-2表达水平的相关性。方法采用西门子化学发光仪检测2012年12月至2013年12月收治的84例可手术乳腺癌患者血清HER-2/neu ECD水平,并采用同期的58例乳腺良性病变患者及56例健康体检女性作为对照;同时对84例可手术乳腺癌患者进行组织HER-2表达的检测。结果可手术乳腺癌患者血清HER-2/neu ECD水平及阳性率分别为(15.56±6.79)ng/ml、19.05%,明显高于乳腺良性病变患者的(6.21±3.21)ng/ml、0.00%,及健康体检者的(5.13±2.25)ng/ml、0.00%,P均<0.05。34例组织HER-2表达阳性的可手术乳腺癌中有14例血清HER-2/neu阳性,阳性符合率为41.2%;50例组织HER-2表达阴性的可手术乳腺癌中有48例血清HER-2/neu阴性,阴性符合率为96.0%;血清HER-2/neu水平与组织HER-2表达状态具有较好的一致性,(kappa=0.406,P<0.05)。结论化学发光法检测可手术乳腺癌患者血清HER-2/neu浓度与组织HER-2表达水平具有较好的一致性。因此,乳腺癌患者在系统治疗期间,可通过化学发光法动态监测患者血清HER-2/neu ECD水平,可弥补组织HER-2检测的不足,在乳腺癌随访、疗效监测尤其是用Herceptin治疗后的疗效监测中发挥其独到作用。

SUCI02选择性抑制HER-2/neu受体酪氨酸激酶磷酸化及其对HER-2/neu过表达乳腺癌细胞生长的影响

背景与目的:HER-2/neu受体过度表达与肿瘤的发生发展、对化疗的敏感性以及患者预后有关;我们通过大量筛选,发现SUCI02犤N-(4-乙氧苯基)-2-羟基酸胺犦能抑制HER2/neu受体酪氨酸激酶磷酸化。本研究拟探讨SUCI02对HER-2/neu过度表达的肿瘤细胞生长的影响。方法:用免疫沉淀、免疫印迹法检测HER-2/neu受体酪氨酸激酶磷酸化、酪氨酸激酶蛋白水平的变化;MTT法检测SUCI02对乳腺癌细胞的抑制作用。结果:SUCI02能抑制HER-2/neu受体的自身磷酸化,在乳腺癌MDA-MB-453m1细胞中,SUCI02对HER-2/neu受体自身磷酸化的IC50为4.34μg/ml,对HER-2/neu的表达没有任何影响。在用SUCI02处理MDA-MB-453m1细胞30min后,用培养液洗掉药物,继续培养不同时间,结果可见洗掉药物后30min,SUCI02对HER-2/neu受体磷酸化的抑制就开始恢复。SUCI02处理MDA-MB-453m1细胞后其下游靶分子MAPK和AKT激活明显受抑制,呈现剂量依赖性。SUCI02对EGFR受体酪氨酸磷酸化在最高剂量用到40μg/ml下没有明显的抑制作用。应用MTT法检测了SUCI02对过度表达HER-2/neu的MDA-MB-453m1细胞的生长抑制作用,同时应用过表达EGFR的乳腺癌MDA-MB-468细胞作为对照,结果可见SUCI02对HER-2/neu过表达的肿瘤细胞相对于过表达EGFR的肿瘤细胞有更明显的抑制作用。结论:SUCI02?