Search results for "ErbB-2"
showing 10 items of 119 documents
Immunophenotype and molecular characterisation of adenocarcinoma of the small intestine
2009
Background: Despite having a dramatically larger surface area than the large intestine, the small intestine is an infrequent site for the development of adenocarcinoma. To better understand the molecular abnormalities in small bowel adenocarcinoma (SBA), we characterised a number of candidate oncogenic pathways and the immunophenotype of this rare cancer. Methods: Tissue microarrays were constructed from tumour samples from 54 patients with all stages of the disease. Immunohistochemistry and microsatellite instability (MSI) testing were conducted. Results: The profile of cytokeratin 20 and 7 coexpression was variable, but expression of caudal type homeobox transcription factor 2 (CDX2) was …
Trastuzumab therapy vs tetracycline controlled ERBB2 downregulation: influence on tumour development in an ERBB2-dependent mouse tumour model
2008
Trastuzumab (Herceptin) has improved therapy of breast cancer. Only patients overexpressing ERBB2 are treated with trastuzumab, whereas its use in tumours without ERBB2 expression is useless. This led to the concept that the subgroup of trastuzumab-sensitive tumours is ‘ERBB2-dependent', meaning that ERBB2 signalling is indispensable for growth of these tumours. We used a mouse model that allows anhydrotetracycline (ATc)-controlled downregulation of ERBB2 in tumour tissue. ERBB2 mRNA and protein expression were downregulated below detection limit leading to a macroscopically complete tumour remission within 14 days. Tumour remission was accompanied by a strong decrease in proliferation, a m…
4-Epidoxycycline: an alternative to doxycycline to control gene expression in conditional mouse models
2004
Since the pioneering work by Gossen and Bujard in 1992 demonstrating the usefulness of the Escherichia coli derived tet resistance operon for regulating gene expression a large collection of doxycycline-controlled transgenic mice has been established. Gene switching in eukaryotic tissue culture cells or mice requires administration of tetracycline, anhydrotetracycline or doxycycline to efficiently inactivate the transactivator protein tTA (TET-OFF system) or alternatively to activate the reverse transactivator protein rtTA (TET-ON system). However, the antibiotic activity of doxycycline can create an imbalance of the intestinal flora, resulting in diarrhoea and in a smaller number of animal…
Dephosphorylation of p-ERK1/2 in relation to tumor remission after HER-2 and Raf1 blocking therapy in a conditional mouse tumor model
2006
Several studies have shown that HER-2/neu (erbB-2) blocking therapy strategies can cause tumor remission. However, the responsible molecular mechanisms are not yet known. Both ERK1/2 and Akt/PKB are critical for HER-2-mediated signal transduction. Therefore, we used a mouse tumor model that allows downregulation of HER-2 in tumor tissue by administration of anhydrotetracycline (ATc). Switching-off HER-2 caused a rapid tumor remission by more than 95% within 7 d of ATc administration compared to the volume before switching-off HER-2. Interestingly, HER-2 downregulation caused a dephosphorylation of p-ERK1/2 by more than 80% already before tumor remission occurred. Levels of total ERK protein…
Intrinsic Subtypes and Gene Expression Profiles in Primary and Metastatic Breast Cancer.
2017
Biological changes that occur during metastatic progression of breast cancer are still incompletely characterized. In this study, we compared intrinsic molecular subtypes and gene expression in 123 paired primary and metastatic tissues from breast cancer patients. Intrinsic subtype was identified using a PAM50 classifier and χ2 tests determined the differences in variable distribution. The rate of subtype conversion was 0% in basal-like tumors, 23.1% in HER2-enriched (HER2-E) tumors, 30.0% in luminal B tumors, and 55.3% in luminal A tumors. In 40.2% of cases, luminal A tumors converted to luminal B tumors, whereas in 14.3% of cases luminal A and B tumors converted to HER2-E tumors. We ident…
DOTAGA-Trastuzumab. A New Antibody Conjugate Targeting HER2/Neu Antigen for Diagnostic Purposes.
2012
International audience; Improved bifunctional chelating agents (BFC) are required for indium-111 radiolabeling of monoclonal antibodies (mAbs) under mild conditions to yield stable, target-specific agents. 2,2',2″-(10-(2,6-Dioxotetrahydro-2H-pyran-3-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid (DOTAGA-anhydride) was evaluated for mAb conjugation and labeling with indium-111. The DOTA analogue was synthesized and conjugated to trastuzumab-which targets the HER2/neu receptor-in mild conditions (PBS pH 7.4, 25 °C, 30 min) and gave a mean degree of conjugation of 2.6 macrocycle per antibody. Labeling of this immunoconjugate with indium-111 was performed in 75% yield after 1 h a…
Assessing the impact of CMF-like/Anthracycline-based/Anthracycline-Taxane-based/dose-dense chemotherapy in dependency of positive axillary lymph node…
2014
Abstract Aim Adjuvant chemotherapy has changed dramatically in the last decades. Anthracycline-/Taxane-based and dose-dense chemotherapy regimens improved survival in node positive breast cancer. This study tries to answer the following questions: (1)Are there differences in survival dependent on chemotherapy regimens in stratified by number of positive lymph nodes/grading (G)/hormone receptor-status (HR)/T-stage? (2)Is it possible to attribute these effects to chemotherapy by only investigating patients who received 100% guideline-conform surgery, radiotherapy and endocrine therapy? Methods This is a German multi-centre (17 participating hospitals all certified as breast cancer centres) re…
A phase I/II trial of non-pegylated liposomal doxorubicin, docetaxel and trastuzumab as first-line treatment in HER-2-positive locally advanced or me…
2011
Abstract Aim To assess the activity and safety of non-pegylated liposomal doxorubicin (Myocet®) in combination with docetaxel and trastuzumab as first-line treatment of patients with HER-2/neu-positive metastatic breast cancer (MBC). Patients and methods The maximum tolerated dose of the combination was defined in the phase I part of the study. In the phase II part, 45 HER-2/neu-positive MBC patients were enrolled to receive 6–8 cycles of Myocet® 50 mg/m2 (day 1), docetaxel 30 mg/m2 (days 2 and 9) plus trastuzumab (day 2, 4 mg/kg followed by 2 mg/kg/week) every 21 d until unacceptable toxicity or progression occurred. Objective response (primary end-point) and treatment tolerability were as…
Prognostic impact of phosphorylated HER-2 in HER-2+ primary breast cancer.
2011
Abstract Purpose. Tyrosine 1248 is one of the autophosphorylation sites of human epidermal growth factor receptor (HER)-2. We determined the prognostic value of the expression level of tyrosine 1248–phosphorylated HER-2 (pHER-2) in patients with HER-2+ primary breast cancer using a reverse-phase protein array. Patients and Methods. The optimal cutoff value of pHER-2 for segregating disease-free survival (DFS) was determined by receiver operating characteristic (ROC) curve analysis. Five-year DFS for pHER-2 expression level was estimated with the Kaplan-Meier method using both derivation (n = 162) and validation (n = 227) cohorts. Results. Of the 162 patients in the derivation cohort, 26 had…
Long-term outcomes in stage IIIB breast cancer patients who achieved less than a pathological complete response (pCR) after primary chemotherapy.
2009
Abstract Learning Objectives After completing this course, the reader will be able to: Summarize the main risk factors for relapse in patients with T4 breast cancer after neoadjuvant chemotherapy.Evaluate the role of hormone receptors and HER-2 as determinants of risk of relapse after neoadjuvant treatment.Compare the difference in outcomes between patients who achieve less than pCR in relation to receptor status. This article is available for continuing medical education credit at CME.TheOncologist.com. Purpose. Pathological complete response (pCR) to primary chemotherapy is the main determinant for improved disease-free survival (DFS) and overall survival (OS). The primary endpoints of ou…