Bestimmung der Knochendichte bei Früh- Und Neugeborenen mittels Ultraschall

Einleitung: Da im letzten Trimenon 80% der Mineralsalze in den fetalen Knochen eingelagert werden, benötigen FG eine optimale postnatale Substitution mit Ca, P und Vit.D, um Osteopenien zu vermeiden. Um die tatsächliche Einlagerung der Mineralsalze im Knochen zu dokumentieren, gilt bei Erwachsenen die sonographische Messung der Transmissionsgeschwindigkeit (UTG) inzwischen als anerkannte Methode. Fragestellung: Ist die Messung der UTG eine geeignete Methode zur Bestimmung der Knochendichte bei Früh- und Neugeborenen? Methodik: Messung der UTG mit Prototyp II-IV-U-Osteoson (Minhorst) zweiwöchentlich bei 172 FG, GA 23-42 Wochen (33,8±5,0), GGW 405-5130g (2132g±1091), mittlere Beobachtungszeit 5,8 Wochen (1-54). Ergebnisse: Die intraindividuelle Reproduzierbarkeit der UTG-Messung betrug 0,62%. Die UTG-Werte lagen zwischen 1621 m/s und 1831 m/s und sind damit vergleichbar mit bereits publizierten Daten von Kindern zwischen 1 und 6 Jahren (1567-1832m/s). Die UTG-Werte der ersten Lebenswoche zeigten einen signifikanten Zusammenhang mit GA und GGW (p=0,001). Die Werte der hypotrophen FG lagen unterhalb der altersentsprechenden Werte der eutrophen FG. Die Verlaufswerte korrelierten positiv mit Alter und Gewicht (p=0,001). Es zeigte sich eine signifikante Korrelation zwischen der UTG und den laborchemischen Parametern des Knochenstoffwechsels sowie den Risikofaktoren für einen reduzierten Knochenaufbau (p=0,001). Schlussfolgerung: Die UTG ist reproduzierbar, einfach durchzuführen, strahlenfrei und wenig belastend. Damit ist sie möglicherweise eine geeignete Methode zum Screening und Therapiemonitoring der Knochendichte bei Früh- und Neugeborenen

Node-positive breast cancer: Which are the best chemotherapy regimens?

Breast cancer-associated mortality has been significantly reduced since the 1990s, mainly because of early diagnosis and systemic therapeutic interventions. All three therapy components-cytostatic therapy, endocrine therapy and targeted antibody therapy-are at present necessary tools for the curative treatment of primary breast cancer. This article reviews the evidence base for the use of various chemotherapy schedules in patients with primary, node-positive breast cancer, including schedules in combination with targeted HER2/neu therapy

Monitoring in metastatic breast cancer: Is imaging outdated in the era of circulating tumor cells?

In clinical practice imaging technologies such as computed tomography (CT), positron emission tomography (PET)/CT and magnetic resonance imaging (MRI) are well-established methods for monitoring metastatic breast cancer (MBC) patients and for assessing therapeutic efficacy. However, several weeks of treatment are required before these technologies can offer any reliable information on effective disease regression, and, in the meanwhile, the patients are exposed to potentially unnecessary therapy. Circulating tumor cells (CTCs) have been shown to be powerful prognostic and predictive markers and provide clinicians with valuable information. However, in one clinical trial, an early change of chemotherapy based on CTC detection did not result in improved survival. Currently, CTC detection outside clinical trials should be limited to selected clinical situations, i.e. increased treatment toxicity or as risk estimation

Circulating microRNAs as blood-based markers for patients with primary and metastatic breast cancer

Introduction: MicroRNAs (miRs) are interesting new diagnostic targets that may provide important insights into the molecular pathogenesis of breast cancer. Here we evaluated, for the first time, the feasibility and clinical utility of circulating miRs as biomarkers for the detection and staging of breast cancer. Methods: The relative concentrations of breast cancer-associated miR10b, miR34a, miR141 and miR155 were measured in the blood serum of 89 patients with primary breast cancer (M0, n = 59) and metastatic disease (M1, n = 30), and 29 healthy women by a TaqMan MicroRNA Assay. Results: The relative concentrations of total RNA (P = 0.0001) and miR155 (P = 0.0001) in serum significantly discriminated M0-patients from healthy women, whereas miR10b (P = 0.005), miR34a (P = 0.001) and miR155 (P = 0.008) discriminated M1-patients from healthy controls. In breast cancer patients, the changes in the levels of total RNA (P = 0.0001), miR10b (P = 0.01), miR34a (P = 0.003) and miR155 (P = 0.002) correlated with the presence of overt metastases. Within the M0-cohort, patients at advanced tumor stages (pT3 to 4) had significantly more total RNA (P = 0.0001) and miR34a (P = 0.01) in their blood than patients at early tumor stages (pT1 to 2). Conclusions: This pilot study provides first evidence that tumor-associated circulating miRs are elevated in the blood of breast cancer patients and associated with tumor progression

Apoptosis-related deregulation of proteolytic activities and high serum levels of circulating nucleosomes and DNA in blood correlate with breast cancer progression

<p>Abstract</p> <p>Background</p> <p>As cell-free circulating DNA exists predominantly as mono- and oligonucleosomes, the focus of the current study was to examine the interplay of circulating nucleosomes, DNA, proteases and caspases in blood of patients with benign and malignant breast diseases.</p> <p>Methods</p> <p>The concentrations of cell-free DNA and nucleosomes as well as the protease and caspase activities were measured in serum of patients with benign breast disease (n = 20), primary breast cancer (M0, n = 31), metastatic breast cancer (M1, n = 32), and healthy individuals (n = 28) by PicoGreen, Cell Death Detection ELISA, Protease Fluorescent Detection Kit and Caspase-Glo^®3/7 Assay, respectively.</p> <p>Results</p> <p>Patients with benign and malignant tumors had significantly higher levels of circulating nucleic acids in their blood than healthy individuals (p = 0.001, p = 0.0001), whereas these levels could not discriminate between benign and malignant lesions. Our analyses of all serum samples revealed significant correlations of circulating nucleosome with DNA concentrations (p = 0.001), nucleosome concentrations with caspase activities (p = 0.008), and caspase with protease activities (p = 0.0001). High serum levels of protease and caspase activities associated with advanced tumor stages (p = 0.009). Patients with lymph node-positive breast cancer had significantly higher nucleosome levels in their blood than node-negative patients (p = 0.004). The presence of distant metastases associated with a significant increase in serum nucleosome (p = 0.01) and DNA levels (p = 0.04), and protease activities (p = 0.008).</p> <p>Conclusion</p> <p>Our findings demonstrate that high circulating nucleic acid concentrations in blood are no indicators of a malignant breast tumor. However, the observed changes in apoptosis-related deregulation of proteolytic activities along with the elevated serum levels of nucleosomes and DNA in blood are linked to breast cancer progression.</p

M+D: conceptual guidelines for compiling a materials library

This article proposes to present a study conducted by the Raw Materials research group, the results of which comprise the conceptual guidelines for compiling an M+D material library. The study includes the topic, materials and design taking the impact of the changes that came into being in the post industrial era on project methodologies and the search for information regarding materials. Taking into account the importance and complexity that these relationships have taken on currently, we have studied the issue of materials based on Manzini (1983) and Ashby and Johnson (2002). Afterward different databases and materials libraries located in the Brazil, the United States, France and Italy geared toward design professionals and students were analyzed to understand what information and means of access to them were available. The project methodologies were approached based on Löbach (1991), Bürdeck (1994), Schulmann (1994), Baxter (1998), Dantas (1998 and 2005) and Papanek (1995 and 2000). This study sought to identify the key elements of the role of materials in the project process today, to serve as a parameter for the analysis of the models studied. A comparative analysis of the models investigated enabled identification of positive and negative aspects to adapt to the needs previously mentioned and identify conceptual guidelines for compiling a collection of materials for use in design projects. Keywords: Design, Materials, Project Methodology, Library</p

Fluorescence Analysis of Vitamin D Receptor Status of Circulating Tumor Cells (CTCS) in Breast Cancer: From Cell Models to Metastatic Patients

The Vitamin D receptor (VDR) expressed in normal breast tissue and breast tumors has been suggested as a new prognostic biomarker in breast cancer (BC). Besides, increasing evidence supports the view that the detection of circulating tumor cells (CTCs) predicts outcome in early and metastatic BC. Consequently, an evaluation of VDR expression in the CTCs of BC patients may allow optimization of their treatment. As an attempt to profile and subtype the CTCs of metastatic patients, we established an innovative fluorescence technique using nine BC cell lines to visualize, define, and compare their individual VDR status. Afterwards, we tested the CTC presence and VDR expression in blood samples (cytospins) collected from 23 metastatic BC patients. The results demonstrated major differences in the VDR levels among the nine cell lines, and VDR positive CTCs were detected in 46% of CTC-positive patients, with a total of 42 CTCs individually analyzed. Due to the limited number of patients in this study, no correlation between VDR expression and BC subtype classification (according to estrogen receptor (ER), progesterone receptor (PR) and HER2) could be determined, but our data support the view that VDR evaluation is a potential new prognostic biomarker to help in the optimization of therapy management for BC patients