Expressions of BMAL1 and CerbB-2 genes in nasopharyngeal carcinoma / 西安交通大学学报(医学版)

【Objective】 To study the expressions of BMAL1 and CerbB-2 genes in nasopharyngeal carcinoma (NPC) and their related mechanisms. 【Methods】 Plasmid transfection, MTT, RT-PCR and Western blotting were used to detect the proliferation of NPC cells, the expressions of BMAL1 and CerbB-2 genes and proteins, and the expression of NF-κB signaling pathway. 【Results】 The MTT results showed that BMAL1 and CerbB-2 could affect the proliferation of NPC cells. RT-PCR results showed that BMAL1 gene was significantly down-regulated in NPC (CK: 2.24±0.22, NPC: 0.63±0.11, P<0.01), while CerbB-2 gene expression was significantly up-regulated (CK: 0.89±0.13, NPC: 2.65±0.25, P<0.01). The p50 and p65 genes in the NF-κB signaling pathway were up-regulated in NPC cells (p50, CK: 0.48±0.12, NPC: 1.45±0.25; p65, CK: 0.52±0.12, NPC: 2.33±0.35, P<0.01). The results of Western blotting were consistent with gene expression, which further confirmed the reliability of the results. 【Conclusion】 This study reveals that BMAL1 and CerbB-2 regulate the invasion and metastasis of NPC cells through the inflammatory pathway NF-κB, providing further theoretical support for the treatment and prevention of NPC.

Expression of Ki67 and CerbB-2 in Gall Bladder, Oesophageal, Small Intestinal and Colorectal Adenocarcinomas: A Study from a Tertiary Care Hospital in Western U.P.

Introduction: Gall bladder cancer is the commonestbiliary tract malignancy with poor prognosis. Oesophagealadenocarcinomas are aggressive with very poor survival.Adenocarcinomas of small intestine are rare, in comparisonto colorectal carcinomas. We studied the expression of twocommonly studied immunohistochemical markers Ki67 andCerbB-2 in gall bladder and gastrointestinal carcinomas, tofind out their prognostic significance.Material and Methods: Histopathologically confirmed casesof adenocarcinomas of gall bladder (19 cases), oesophagus(3 cases), small intestine (3 cases) and colorectal region (8cases) were included. Formalin fixed paraffin embeddedtissue blocks were retrieved and sections were studiedimmunohistochemically for expression of Ki67 and CerbB-2.Tumors of all stages and grades were studied.Results: Our study revealed a significantly high Ki67in neoplastic glands of gall bladder, oesophageal, smallintestinal and colorectal adenocarcinomas as comparedto the non neoplastic areas. The Ki67 labelling index washigher in moderately and poorly differentiated areas as wellas mucinous and signet ring type adenocarcinomas. Therewas no relation with stage/depth of tumor invasion. CerbB-2was significantly overexpressed in gall bladder and colorectaladenocarcinomas. Expression was higher in advanced stageand greater depth of invasion. There was no associationwith tumor grade or type. In esophageal and small intestineadenocarcinomas, expression was not related to either tumorstage or grade.Conclusion: A panel of Ki67 and CerbB-2 in gastrointestinaland biliary tract malignancies may correlate well with differentprognostic indicators in these malignancies, like tumor stage,histologic type and grade.

The relationship study of MRI feature and VEGF & CerbB-2 expression in atypical breast cancer / 实用放射学杂志

Objective To explore the relationship between MRI and VEGF&CerbB-2 expression in atypical breast cancer.Methods 82 cases of atypical breast cancer confirmed by pathology were analyzed retrospectively.The relationship between MRI and VEGF &CerbB-2 expression were compared and analyzed.Results In total patients,57 cases were VEGF positive expression(69.5%,57/82),50 cases were CerbB-2 positive expression(61.0%,50/82).The VEGF positive expression rate was 78.8% in maximum diameter ≥2.0 cm group,which was obviously higher than < 2.0 cm group(P<0.05).Internal necrosis,ADC value and VEGF positive expression were positively correlated (P<0.05).There were not positively correlated relationships between internal reinforcement method,TIC and VEGF positive expression(P>0.05).There were positively correlated relationships between internal necrosis,ADC value and CerbB-2 positive expression (P<0.05).There were not positively correlated relationships between maximum diameter,internal reinforcement method, TIC and CerbB-2 positive expression(P>0.05).Conclusion There are relationships between the maximum diameter,internal necrosis,ADC value and molecular biology (VEGF,CerbB-2)of the atypical breast cancer.

The expression and clinical significance of p53,C-myc and CerbB-2 in thyroid papillary carcinoma / 重庆医学

Objective To investigate the expression level and clinical significance of p53 ,C-myc and CerbB-2 in papillary thy-roid carcinoma patients .Methods The expression level of p53 ,C-myc and CerbB-2 were detected in 45 cases of papillary thyroid carcinoma tissue specimens and 45 cases of nodular goiter tissue specimens by using immunohistochemical staining .Their correla-tions with clinic pathological features in papillary thyroid carcinoma were analyzed further .Results The positive expression rates of p53 ,C-myc and CerbB-2 in the papillary thyroid carcinoma tissue specimens were significantly higher than that of the nodular goiter tissue specimens(all P< 0 .01) .The expression of C-myc and CerbB-2 significantly correlated with lymph node metastasis(P< 0 . 05) .The expression of CerbB-2 significantly correlated with tumor size ,local infiltration ,TNM stage ,differentiated degree and lymph node metastasis (all P< 0 .05) .p53 positive expression ,C-myc positive expression and CerbB-2 positive expression were the independent factors of cervical lymph node metastasis .Conclusion p53 ,C-myc and CerbB-2 were highly expressed in papillary thy-roid carcinoma and correlated with cervical lymph nody metastasis .The detection of p53 ,C-myc and CerbB-2 might be helpful for diagnosis of papillary thyroid carcinomas .

Factors predicting lapatinib efficacy in HER-2+ metastatic breast carcinoma: Does it work better in different histologic subtypes.

CONTEXT: Introduction of trastuzumab, a recombinant monoclonal antibody against the extracellular domain of HER‑2, is a cornerstone in the treatment of HER‑2+ breast carcinoma. However, many cancers that have an initial response to trastuzumab will progress some time later. After progression on trastuzumab‑based first‑line treatment, there are several options. Although TDM‑1 (Trastuzumab emtansine) has prolonged progression‑free survival (PFS) and overall survival in patients previously treated with trastuzumab and taxane, it is still not available in Turkey. Patients may be switched to lapatinib (an oral tyrosine kinase inhibitor targeting both HER‑1 and HER‑2), or they may re‑challenge with trastuzumab. There is no clear definition of the patients who should be switched to lapatinib. AIM: In this study, we investigated the factors predicting the efficacy of lapatinib. SUBJECTS AND METHODS: Totally, 94 patients treated with lapatinib for metastatic breast carcinoma was included in our study. Retrospective data including pathology, treatments and treatment results, metastatic sites, and laboratory tests were collected. RESULTS: Progression‑free survival was 9.1 months. Histologic subtypes other than invasive ductal carcinoma and liver metastasis were inversely related with PFS. Overall survival was 22.1 months, and patients with histologic subtypes other than invasive ductal carcinoma and who progress with brain metastasis had a worse prognosis. CONCLUSION: Clinicians should give attention to histologic subtype and metastatic sites when choosing patients for lapatinib treatment.

Analysis of EGFR and HER-2 expressions in ductal carcinomas in situ in canine mammary glands / Análise da expressão de EGFR e HER-2 em carcinomas ductais in situ da glândula mamária canina

Biomolecular evidence has shown that ductal carcinoma in situ (DCIS) may develop into invasive carcinoma of the canine mammary gland, and mutations in proto-oncogenes HER2 and EGFR; two members of the family of epidermal growth factor receptors, may be involved in this process. The purpose of this study was the characterization of the immunohistochemical expression of the EGFR and HER2 proteins in the process of neoplastic transformation, supposedly present in ductal carcinomas in situ in canine mammary glands. Fifteen cases of DCIS were evaluated, with a higher expression of HER2 and EGFR being observed in low-grade carcinomas when compared with high-grade neoplasms, and with a high positive statistical correlation in the latter. Results suggest that aggressive tumors tend to lose the expression of EGFR and HER2 simultaneously. The loss of the expression of these markers may be related to the process of neoplastic progression in canine mammary tumors...

Evidências biomoleculares sugerem que o carcinoma ductal in situ (CDIS) pode progredir para carcinoma invasor na mama canina e que mutações nos proto-oncogenes HER-2 e EGFR, dois membros da família de receptores para fatores de crescimento epidérmicos, podem estar envolvidas neste processo. A partir disso, este trabalho teve por objetivo caracterizar a expressão imuno-histoquímica das proteínas EGFR e HER-2 no processo de transformação neoplásica supostamente presente em carcinomas ductais in situ da glândula mamária canina. Foram avaliados 15 casos de CDIS, sendo observada maior expressão de HER-2 e EGFR em carcinomas de baixo grau em comparação às neoplasias de alto grau, com correlação estatística positiva alta nestes últimos. Os resultados sugerem que tumores mais agressivos tendem a perder, simultaneamente, a expressão de EGFR e HER-2. A perda na expressão desses marcadores pode estar envolvida no processo de progressão neoplásica em tumores mamários caninos...

Effect of C-erbB-2 shRNA on chemosensitivity of mouse lung adenocarcinoma cells and its mechanism / 吉林大学学报(医学版)

Objective To investigate the effect of C-erbB-2 shRNA on chemosensitivity of mouse lung adenocarcinoma cells and its mechanism,and to find new therapy method for non-small cell lung cancer,especial lung adenocarcinoma.Methods The mouse lung adenocarcinoma Lewis cells were cultured regularly and divided into non-transfected group, pGPU6/RFP/Neo-shNC group and pGPU6/RFP/Neo-erbB-2 group. The plasmids were synthesized and transfected into Lewis cells in each group by Lipofectamine 2000.The expression levels of C-erbB-2 mRNA and protein in the cells in various groups were tested by RT-PCR and Western blotting method, respectively. The Lewis cells were divided into non- transfected group, pGPU6/RFP/Neo-shNC group, carboplatin group, pGPU6/RFP/Neo-erbB-2 group, pGPU6/RFP/Neo-shNC+carboplatin group and pGPU6/RFP/Neo-erbB-2+ carboplatin group. The apoptotic rates of the cells in each group were detected by flow cytometry;the expression levels of Bcl-2 and Bax proteins in each group were determined by Western blotting method.Results The expression levels of C-erbB-2 mRNA and protein in pGPU6/RFP/Neo-erbB-2 group were lower than those in non-transfected group and pGPU6/RFP/Neo-shNC.The apoptotic rate of the cells in pGPU6/RFP/Neo-erbB-2+carboplatin group was the highest in all of the groups (P<0.01);compared with the others, the expression of Bax protein in pGPU6/RFP/Neo-erbB-2+carboplatin group was increased, while the expression level of Bcl-2 protein was decreased.Conclusion C-erbB-2 shRNA can increase the Lewis cells’sensitivity to carboplatin.The mechanism may be that it can enhance the Lewis cells’apoptosis induced by carboplatin through increasing the expression of Bax protein and decreasing the expression of Bcl-2 protein.

Expressions of ER, PR and CerbB-2 in papillary thyroid carcinoma and their clinical significances / 肿瘤研究与临床

Objective To explore the expressions of ER,PR and CerbB-2 in human papillary thyroid carcinoma,and their correlation with the clinical features.Methods The expressions of ER,PR and CerbB-2 were detected by immunohistochemistry in 89 papillary thyroid carcinoma samples and 13 nodular goiter samples.Results In papillary thyroid carcinoma samples,ER,PR and CerbB-2 were detected for 50.56 ％(45/89),43.82 ％ (39/89),24.72 ％ (22/89),respectively.In nodular goiter,ER,PR and CerbB-2 were detected for 15.38 ％ (2/13),7.69 ％ (1/13),0,respectively,there were significant differences between the two groups (x2 =5.649,P=0.017,x2 =6.211,P=0.013,x2 =4.097,P=0.043).The positive rates of PR were 56.26 ％(26/46) in without lymph node metastasis,compared with those lymph node metastasis 30.2 3％ (13/43) were significantly higher,the difference was statistically significant (x2 =6.239,P =0.012).Conclusion The expressions of ER,PR and CerbB-2 are significant higher in papillary thyroid carcinoma.The detection of ER,PR and CerbB-2 might be helpful for early diagnosis and prognosis of papillary thyroid carcinoma.

Expression and amplification of CerbB-2 oncogene in gastric adenocarcinoma and its significance / 肿瘤研究与临床

Objective To investigate the significance of CerbB-2 oncogene in the occurrence and development of gastric adenocarcinoma. Methods By using immunohistochemistry and fluorescence in situ hybridization, 60 cases of gastric adenocarcinoma tissue, 60 cases of normal margin of mucosal tissue and 30 cases of normal gastric mucosa tissue were detected for the expression and amplification of CerbB-2. Results The positive rate of CerbB-2 expression in gastric adenocarcinoma tissues, normal margin of mucosal tissues and normal gastric mucosa tissues were 31.7 %, 8.33 % and 3.33 %; The positive rate of CerbB-2 amplification of these were 28.3 %, 5 % and 0. There were significant differences between gastric adenocarcinoma tissues and the others in the expression and amplification of CerbB-2. The expression and amplification of CerbB-2 in gastric adenocarcinoma tissues had no correlation with age,gender,tumor size or tumor differentiation degree of patients' (P >0.05), but were correlated with the extent of tumor invasion, lymph node metastasis, distant metastasis and clinical stage(P <0.05). Conclusion CerbB-2 is closely related to the occurrence and development of gastric adenocarcinoma, and can be considered as an important index for determining the biological behavior of gastric cancer.

Avaliação digital comparativa da expressão tecidual da proteína cerbB-2 em mulheres portadoras de doenças tumorais da mama / Comparative digital evaluation of tissue expression of the cerbB-2 protein in women with breast tumoral diseases

A imuno-histoquímica (IHC) para expressão da proteína Her-2/neu tornou-se um dos mais atrativos testes de rotina, devido a custo, conveniência e relevância biológica. Contudo, têm sido relatados problemas quanto à variabilidade das marcações em IHC, além da subjetividade na interpretação dos métodos de IHC convencionais. Assim, o presente estudo objetiva quantificar morfometricamente a imunomarcação da proteína cerbB-2 expressa em tumores de mama. Fragmentos de tecido mamário normal (n = 10) e com doença tumoral (carcinoma ductal invasivo [CDI], n = 51 e fibroadenoma, [FA], n = 21) foram fixados em formalina, submetidos à rotina histológica para inclusão em parafina. Cortes histológicos (4 µm), corados em hematoxilina e eosina foram examinados para confirmar o diagnóstico. Os cortes foram incubados em solução de anticorpo anti-cerbB-2 por 60 minutos em temperatura ambiente. A marcação foi visualizada após reação da peroxidase do cromógeno diaminobenzidina associado ao peróxido de hidrogênio. A análise morfométrica foi realizada utilizando uma estação de análise digital de imagens por meio do software de análise Optimas®. A partir dos resultados obtidos, pode-se concluir que a superexpressão do cerbB-2 em casos de CDI é um fenômeno condizente com o estágio de proliferação das células neoplásicas e, quando analisados os casos de FA, esse marcador não exibiu qualquer correlação ou padrão específico; ao contrário, apresentaram resultados semelhantes ao tecido mamário normal. Não houve diferenças significativas entre os diferentes score qualitativos (1+, 2+ e 3+) e a análise morfométrica digital (áreas médias marcadas). Esses achados demonstram a necessidade de estudos mais acurados a fim de resolver essa dificuldade de interpretação.

Immunohistochemistry for HER-2/neu protein expression has become the most attractive routine test due to its cost, convenience and biological relevance. However, problems as to IHC staining variability and subjectivity in the interpretation of IHC conventional methods have been reported. Thus, this study aims to quantify morphometrically cerbB-2 protein immunostaining expressed in breast tumors. Mammary fragments of normal breast tissue (n = 10) and with tumoral disease (invasive ductal carcinoma, IDC, n = 51 and fibroadenoma, FA, n = 21) were fixed in formalin, processed histologically and embedded in paraffin. Hematoxylin and eosin stained sections (4 mm) were examined to confirm the diagnosis. Afterwards, they were incubated with anti-cerbB-2 antibody solution for 60 minutes at room temperature. The staining was visualized after the peroxidase reaction with diaminobenzidine chromogen associated with hydrogen peroxide. Morphometric analysis was carried out using a digital image analysis workstation based on OPTIMAS® software. From these results it may be concluded that cerbB-2 over expression in IDC cases is a phenomenon closely related to the stage of neoplastic cell proliferation. When FA cases were analyzed , this marker did not show any correlation with the staining pattern. On the contrary, FA and normal mammary tissue analysis yielded similar results. There were no significant differences between the different qualitative scores (1+, 2+ and 3+) and digital morphometric analysis (marked mean areas). These findings suggest the necessity for more accurate studies in order to clarify this interpretation issue.

CerbB-2 Expression and Significance in Patients with Nasopharyngeal Carcinoma / 中国肿瘤临床

Objective: To investigate the biological significance of CerbB-2 expression in nasopharyn-geal carcinoma. Methods: The expression of CerbB-2 was detected in 90 nasopharyngeal carcinoma tissues and 22 nasopharyngitis tissues by SP immunohistochemical method. The relationship between CerbB-2 ex-pression and clinicopathological characteristics of nasopharyngeal carcinoma was investigated. Results: The positive expression rate of CerbB-2 protein was 65.56% in nasopharyngeal carcinoma tissues, and 31.82% in nasopharyngitis tissues, with a significant difference (P<0.05). The ratio of expression was 81.0% in patients of N_2 and N_3 lymth node stage, significantly different from that in patients of N_0 and N_1 lymph node stage (52.1%, P<0.05). The expression of CerbB-2 gene was not correlated with age, gender, clinical stage, T stage and distant metastasis of nasopharyngeal carcinoma (P>0.05). Conclusion: There is a high expression of CerbB-2 in nasopharyngeal carcinoma tissues, which might be an important event in the pathogenesis and progression of nasopharyngeal carcinoma.

Expression and clinical slgnificance of CerbB——2 and p53 protein in cervical squamous carcinoma / 中国基层医药

Objective To explore the expression and clinical significance of two oncogenes,CerbB-2 and p53,on cervical squamous carcinoma.Methods The immunohistochemical S-P process was performed on 45 cases of cervical squamous carcinoma.The expressions of CerbB-2 and p53 on 15 cases of CIN(cervical intraepithelial neoplasia)and on 10 cases of normal cervical tissues were chosen and the relationship between the expressions and the related clinicopathological factors were analyzed.Results The positive expression rate of CerbB-2 on normal cervical tissues, CIN and cervical squamous carcinoma was 0,26.7% and 66.7%, respectively; that of p53 was 0,13.3% and 68.9% ,respectively.From the normal cervical epithelium to the CIN and to the cervical squamous carcinoma,the positive rate of CerbB-2 and p53 was increased significantly(P<0.05);the positive rate of CerbB-2 was associated with the pathological grade and the metastasis of lymph node(P <0.05) and that showed no statistic significance with the clinical stage ,the diameter of tumour,the infiltration of vessel and infiltrative depth(P > 0.05) ;the positive rate of p53 is only associated with the pathological grade(P <0.05) ;the difference between the CerbB-2 and p53 expressions on cervical squamous carcinoma were not statistically significant(P> 0.05).Conclusion The expressions of CerbB-2 and p53 have some practical values on the occurrence, the development and the clinical prognostic evaluation for the cervical squamons carcinoma.

Relationship between expression of p53、cerbB-2 and the effect of neoadjuvant chemotherapy using taxinol and epirubicin in breast cancer / 重庆医科大学学报

Objective:To study the correlation of p53、cerbB-2 expression in breast cancer with the clinical response to TE regimen neoadjuvant chemotherapy,and search for biological markers to guide therapy and predict effect of neoadjuvant chemotherapy. Methods:The expression of the p53,cerbB-2 was examined by immunohistoehemical assay in samples of breast cancer tissue before neoadjuvant chemotherapy which taken from 57 case of breast cancer patients.Results:The overall response rate to neoadjuvant chemotherapy was 73.7%.The effect of neoadjuvant chemotherapy was not related to types of tumor and TNM stage. The effect of neoadjuvant chemotherapy had a significantly negative correlation with p53 expression. There was no significant diference between the response to neoadjuvant chemotherapy and cerbB-2 expression.Of the 11 patients who obtained a complete clinical response,Only one was classified as p53 positive(P

The analysis of the relationship between the clinical effect,pathological changes and the neoadjuvant chemotherapy containing THP and docetaxel on breast cancer / 中国癌症杂志

Background and purpose:Neoadjuvant chemotherapy is one of the hot studied area in breast cancer research.Our aim was to explore the relationship between the clinical effect,pathological changes and the neoadjuvant chemotherapy containing THP and docetaxel on breast cancer.Methods:The expression of ER, PR and CerbB-2 in breast cancer tissue of patients who had received neoadjuvant chemotherapy were detected by immunohistochemistry method.The relationship of age,ER,PR,CerbB-2,pathological stage and axillary lymph node metastasis with pathological complete response(pCR) was analysed.Results:For the patients after neoadjuvant chemotherapy,the pCR of the positive ER(0%),PR(9.38%) was lower than that of negative ER(20.27),PR(90.63%) respectively.The pCR of the positive CerbB-2(33.33%) was higher than that of negative CerbB-2(9.74%,P

Study the relationship between TCM spleen def iciency syndromes and gastric precancerous lesion / 中华中医药杂志

Objective:To explore the relationship between the pathophysiological changes in TCM spleen de ciency syndromes and precancerous lesion of gastric mucosa.Method:160 cases with spleen de ciency syndromes accompanied by gastric mucosa intestinal metaplasia,IM and / or atypical hyperplasia,AHP,(spleen de ciency is divided into spleen qi de ciency or SQD,spleen yin de ciency or SyinD and spleen de ciency with qi stagnation or SDQS) and 22 cases in health control group were taken as the study object.The detection was conducted on such trace elements as Zn,Cu of gastric mucosa epithelial cell nuclei and mitochondrion under the direct view of CM200FEG –TEM by adopting 9100/60 -Energy Dispersion X-ray Analyzers;detection was conducted on epithelial cell nucleus DNA by using IBAS2000 image analyzer;detection was conducted on the expression of P53,Ki67,CerbB2,P21ras in gastric mucosa tissue slices by adopting ElivisionTM Plus'.Result:The quantitative changes of gastric mucosa epithelial cell nucleus DNA,Zn,Cu and the positive expression rates of P53,P21ras,CerbB2 and Ki67 increased in the sequence of SQD group,SyinD group and SDQS group,while mitochondrial Cu,Zn decreased in the same sequence,there was signi cant di erence between the groups(P

Investigation of expression of c-erbB-2 and DPC4 in tissues of colonic schistosomiasis and colorectal carcinoma / 中国普通外科杂志

Objective To determine the relationship between chronic colonic schistosomiasis and colorectal carcinoma.Methods Expression levels of c-erbB-2 and DPC4 were detected by two-step and SP immunohistochemical method respectively in normal colonic mucosa of 15 cases,in colonic mucosa of 15 cases with simple schistosomiasis,20 cases of colorectal carcinoma with schistosomiasis and 20 cases of colorectal carcinoma without schistosomiasis.Results c-erbB-2 was expressed in each group with different levels,but the level in colonic mucosa with schistosomiasis was the highest compared to other groups,which had statistical significance(P