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In Vitro MicroRNA Expression Profile Alterations Under CDK4/6 Therapy in Breast Cancer
Abstract: Background: Breast cancer is the most common type of cancer worldwide. Cyclin-dependent kinase inhibition is one of the backbones of metastatic breast cancer therapy. However, there are a significant number of therapy failures. This study evaluates the biomarker potential of microRNAs for the prediction of a therapy response under cyclin-dependent kinase inhibition. Methods: This study comprises the analysis of intracellular and extracellular microRNA-expression-level alterations of 56 microRNAs under palbociclib mono as well as combination therapy with letrozole. Breast cancer cell lines BT-474, MCF-7 and HS-578T were analyzed using qPCR. Results: A palbociclib-induced microRNA si...
The Epigenetics of Breast Cancer - Opportunities for Diagnostics, Risk Stratification and Therapy
Abstract: The stage and molecular pathology-dependent prognosis of breast cancer, the limited treatment options for triple-negative carcinomas, as well as the development of resistance to therapies illustrate the need for improved early diagnosis and the development of new therapeutic approaches. Increasing data suggests that some answers to these challenges could be found in the area of epigenetics. In this study, we focus on the current research of the epigenetics of breast cancer, especially on the potential of epigenetics for clinical application in diagnostics, risk stratification and therapy. The differential DNA methylation status of specific gene regions has been used in the past to ...
Evaluation of Circulating MicroRNAs as Non-invasive Biomarkers in the Diagnosis of Ovarian Cancer: a Case-control Study
Abstract: Purpose Ovarian cancer is the seventh most frequent form of malignant diseases in women worldwide and over 150,000 women die from it every year. More than 70 percent of all ovarian cancer patients are diagnosed at a late-stage disease with poor prognosis necessitating the development of sufficient screening biomarkers. MicroRNAs displayed promising potential as early diagnostics in various malignant diseases including ovarian cancer. The presented study aimed at identifying single microRNAs and microRNA combinations detecting ovarian cancer in vitro and in vivo. Methods Intracellular, extracellular and urinary microRNA expression levels of twelve microRNAs (let-7a, let-7d, miR-10a,...
Comparison of Intraoperative Radiotherapy as a Boost Vs. Simultaneously Integrated Boosts After Breast-conserving Therapy for Breast Cancer
Abstract: Background: Currently, there are no data from randomized trials on the use of intraoperative radiotherapy (IORT) as a tumor bed boost in women at high risk of local recurrence. The aim of this retrospective analysis was to compare the toxicity and oncological outcome of IORT or simultaneous integrated boost (SIB) with conventional external beam radiotherapy (WBI) after breast conserving surgery (BCS). Methods: Between 2009 and 2019, patients were treated with a single dose of 20 Gy IORT with 50 kV photons, followed by WBI 50 Gy in 25 or 40.05 in 15 fractions or WBI 50 Gy with SIB up to 58.80-61.60 Gy in 25-28 fractions. Toxicity was compared after propensity score matching. Overall...
Gastrin-releasing Peptide Receptor Imaging in Breast Cancer Using the Receptor Antagonist 68Ga-RM2 and PET
Abstract: Introduction: The gastrin-releasing peptide receptor (GRPR) is overexpressed in breast cancer. The present study evaluates GRPR imaging as a novel imaging modality in breast cancer by employing positron emission tomography (PET) and the GRPR antagonist 68Ga-RM2. Methods: Fifteen female patients with biopsy confirmed primary breast carcinoma (3 bilateral tumors; median clinical stage IIB) underwent 68Ga-RM2-PET/CT for pretreatment staging. In vivo tumor uptake of 68Ga-RM2 was correlated with estrogen (ER) and progesterone (PR) receptor expression, HER2/neu status and MIB-1 proliferation index in breast core biopsy specimens. Results: 13/18 tumors demonstrated strongly increased 68Ga...
Circulating Non-coding RNA-biomarker Potential in Neoadjuvant Chemotherapy of Triple Negative Breast Cancer?.
Abstract: Due to the positive association between neoadjuvant chemotherapy (NACT) and the promising early response rates of patients with triple negative breast cancer (TNBC), including probabilities of pathological complete response, NACT is increasingly used in TNBC management. Liquid biopsy-based biomarkers with the power to diagnose the early response to NACT may support established monitoring tools, which are to a certain extent imprecise and costly. Simple serum- or urine-based analyses of non-coding RNA (ncRNA) expression may allow for fast, minimally-invasive testing and timely adjustment of the therapy regimen. The present study investigated breast cancer-related ncRNAs [microRNA (m...
Exometabolom Analysis of Breast Cancer Cell Lines: Metabolic Signature
Abstract: Cancer cells show characteristic effects on cellular turnover and DNA/RNA modifications leading to elevated levels of excreted modified nucleosides. We investigated the molecular signature of different subtypes of breast cancer cell lines and the breast epithelial cell line MCF-10A. Prepurification of cell culture supernatants was performed by cis-diol specific affinity chromatography using boronate-derivatized polyacrylamide gel. Samples were analyzed by application of reversed phase chromatography coupled to a triple quadrupole mass spectrometer. Collectively, we determined 23 compounds from RNA metabolism, two from purine metabolism, five from polyamine/methionine cycle, one fro...
Accuracy of Cone-beam Computed Tomography, Digital Mammography and Digital Breast Tomosynthesis for Microcalcifications and Margins to Microcalcifications in Breast Specimens
Abstract: Accurate determination of resection margins in breast specimens is important as complete removal of malignancy is a prerequisite for patients' outcome. Mammography (DM) as 2D-technique provides only limited value in margin assessment. Therefore, we investigated whether cone-beam computed tomography (CBCT) or digital breast tomosynthesis (DBT) has incremental value in assessing margins to microcalcifications. Three independent readers investigated breast specimens for presence of microcalcifications and the smallest distance to margins. Histopathology served as gold standard. Microcalcifications were detected in 15 out of 21 included specimens (71%). Pooled sensitivity for DM, DBT and CBCT for microcalcifications compared to preoperative DM was 0.98 (CI 0.94-0.99), 0.83 (CI 0.73-0.94) and 0.94 (CI 0.87-0.99), pooled specificity was 0.99 (CI 0.99-0.99), 0.73 (CI 0.51-0.96) and 0.60 (CI 0.35-0.85). Mean measurement error for margin determination for DM, DBT and CBCT was 10 mm, 14 mm and 6 mm (p = 0.002) with significant difference between CBCT and the other devices (p
