Determination of effective mechanical properties of biocomposite on the basis of multilevel modeling

Numerical simulation of biocomposite "zirconia-based ceramics - cortical bone" was performed using multilevel approach. The effective mechanical properties of the ceramic biocomposite were determined

Multiparametric early detection and prediction of cardiotoxicity using myocardial strain, T1 and T2 mapping, and biochemical markers: A longitudinal cardiac resonance imaging study during 2 years of follow-up

BACKGROUND: Our goal was to evaluate the ability of cardiovascular magnetic resonance for detecting and predicting cardiac dysfunction in patients receiving cancer therapy. Left ventricular ejection fraction, global and regional strain utilizing fast-strain-encoded, T1 and T2 mapping, and cardiac biomarkers (troponin and BNP [brain natriuretic peptide]) were analyzed. METHODS: Sixty-one patients (47 with breast cancer, 11 with non-Hodgkin lymphoma, and 3 with Hodgkin lymphoma) underwent cardiovascular magnetic resonance scans at baseline and at regular intervals during 2 years of follow-up. The percentage of all left ventricular myocardial segments with strain ≤-17% (normal myocardium [%]) was analyzed. Clinical cardiotoxicity (CTX) and sub-CTX were defined according to standard measures. RESULTS: Nine (15%) patients developed CTX, 26 (43%) had sub-CTX. Of the 35 patients with CTX or sub-CTX, 24 (69%) were treated with cardioprotective medications and showed recovery of cardiac function. The amount of normal myocardium (%) exhibited markedly higher accuracy for the detection of CTX and sub-CTX compared with left ventricular ejection fraction, T1, and T2 mapping as well as troponin I (Δareas under the curve=0.20, 0.24, and 0.46 for normal myocardium (%) versus left ventricular ejection fraction, troponin I, and T1 mapping, CONCLUSIONS: Normal myocardium (%) derived by fast-strain-encoded cardiovascular magnetic resonance, is an accurate and sensitive tool that can establish cardiac safety in patients with cancer undergoing cardiotoxic chemotherapy not only for the early detection but also for the prediction of those at risk of developing CTX. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03543228

Relationship between quality of life indicators and cardiac status indicators in chemotherapy patients

AIM: With the aim of improving personalized treatment of patients on chemotherapy, the objective of the study was to assess the degree of association between selected Quality of life (QoL) indicators and both clinical and imaging cardiac status indicators when detecting deterioration in QoL of these patients. METHODS: In a cohort clinical study in Hamburg, from August 2017 through October 2020, 59 cancer patients, aged 18-80 years, were evaluated before chemotherapy, and at several follow-ups, using EQ-5D and SF-36 QoL questionnaires, fast strain-encoded (fast-SENC) cardiac magnetic resonance (CMR), conventional CMR, and echocardiography, and further received a clinical and biomarker examination. Data was analyzed using survival analyses. A decline of more than 5% in each observed QoL metric value was defined as the observed event. Patient were separated into groups according to the presentation of cardiotoxicity as per its clinical definition, the establishment of the indication for cardioprotective therapy initiation, and by a worsening in the value of each observed imaging metric by more than 5% in the previous follow-up compared to the corresponding pre-chemotherapy baseline value. RESULTS: Among clinical cardiac status indicators, the indication for cardioprotective therapy showed statistically good association with QoL scores (EQ-5D p=0.028; SF-36 physical component p=0.016; SF-36 mental component p=0.012). In terms of imaging metrics, the MyoHealth segmental myocardial strain score was the only one demonstrating consistently good QoL score association (EQ-5D p=0.005; SF-36 physical component p=0.056; SF-36 mental component p=0.002). CONCLUSIONS: Established fast-SENC CMR scores are capable of highlighting patients with reduced QoL, who require more frequent/optimal management

An expression signature of syndecan-1 (CD138), E-cadherin and c-met is associated with factors of angiogenesis and lymphangiogenesis in ductal breast carcinoma in situ

INTRODUCTION: Heparan sulphate proteoglycan syndecan-1 modulates cell proliferation, adhesion, migration and angiogenesis. It is a coreceptor for the hepatocyte growth factor receptor c-met, and its coexpression with E-cadherin is synchronously regulated during epithelial-mesenchymal transition. In breast cancer, changes in the expression of syndecan-1, E-cadherin and c-met correlate with poor prognosis. In this study we evaluated whether coexpression of these functionally linked prognostic markers constitutes an expression signature in ductal carcinoma in situ (DCIS) of the breast that may promote cell proliferation and (lymph)angiogenesis. METHODS: Expression of syndecan-1, E-cadherin and c-met was detected immunohistochemically using a tissue microarray in tumour specimens from 200 DCIS patients. Results were correlated with the expression patterns of angiogenic and lymphangiogenic markers. Coexpression of the three prognostic markers was evaluated in human breast cancer cells by confocal immunofluorescence microscopy and RT-PCR. RESULTS: Coexpression and membrane colocalization of the three markers was confirmed in MCF-7 cells. E-cadherin expression decreased, and c-met expression increased progressively in more aggressive cell lines. Tissue microarray analysis revealed strong positive staining of tumour cells for syndecan-1 in 72%, E-cadherin in 67.8% and c-met in 48.6% of DCIS. E-cadherin expression was significantly associated with c-met and syndecan-1. Expression of c-met and syndecan-1 was significantly more frequent in the subgroup of patients with pure DCIS than in those with DCIS and a coexisting invasive carcinoma. Levels of c-met and syndecan-1 expression were associated with HER2 expression. Expression of c-met significantly correlated with expression of endothelin A and B receptors, vascular endothelial growth factor (VEGF)-A and fibroblast growth factor receptor-1, whereas E-cadherin expression correlated significantly with endothelin A receptor, VEGF-A and VEGF-C staining. CONCLUSION: Syndecan-1, E-cadherin and c-met constitute a marker signature associated with angiogenic and lymphangiogenic factors in DCIS. This coexpression may reflect a state of parallel activation of different signal transduction pathways, promoting tumour cell proliferation and angiogenesis. Our findings have implications for future therapeutic approaches in terms of a multiple target approach, which may be useful early in breast cancer progression

Caveolin-1 expression in benign and malignant lesions of the breast

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Standardisierte AgNOR-Analyse an Adenomen und Hyperplasien der Nebenschilddrüse

Beim primären Hyperparathyreoidismus (HPT) ist die histologische Differenzierung zwischen Adenomen und primären Hyperplasien schwierig. AgNORs sind Nukleolusregionen, die als Marker aktiv transkribierter oder aktiver ribosomaler Gene gelten. In diese Studie wurden 57 Nebenschilddrüsenpräparate (16 Adenome, 7 primäre Hyperplasien und 16 sekundäre/tertiäre HPT-Fälle) eingeschlossen. Nach Silberfärbung wurde der AgNOR-Gehalt der Schnittpräparate mit digitaler Image-Analyse evaluiert. Es zeigten sich signifikant höhere mittlere AgNOR-Flächen (AgA) bei Adenomen als bei Hyperplasien, während kein signifikanter Unterschied bei der AgNOR-Zahl bestand. Dies weist darauf hin, dass die pHPT-Fälle, bei denen eine den AgA-Werten unserer Kontrollgruppe (s/tHPTs) vergleichbare und insofern niedrige AgNOR-Fläche nachgewiesen werden kann, hyperplastischer Genese sind. Im Gegensatz dazu scheinen pHPT-Fälle mit einer größeren AgNOR-Fläche zu der Entität der Adenome zu gehören

The push-out bond strength of calcium silicate-based endodontic sealers

BACKGROUND: The aim was to compare the dislodgement resistance of calcium silicate-based sealers (Total Fill BC Sealer, Endo CPM Sealer, BioRoot RCS) with an epoxy resin-based sealer (AH Plus). METHODS: The root canals of 80 single-rooted human teeth were instrumented with F360 up to size 45.04. All canals were obturated using matching gutta-percha cones according to the single-cone technique in combination with one of the mentioned sealers (n = 20 per group). After eight weeks of incubation (37 °C, 100% humidity), the roots were embedded in resin. Starting with a distance of 7 mm from the apex, four slices of 1 mm thickness were cut. Dislodgement resistance was measured using a universal testing machine and the push-out bond strength was calculated. Specimens were examined under 4×-magnification to determine the mode of bond failure. Statistical analysis was performed using ANOVA and Student-Newman-Keuls-test. RESULTS: Regarding the pooled data of all sections, the push-out bond strength of AH Plus was significantly higher than the push-out bond strength of all calcium silicate-containing sealers (P < 0.05). Out of all calcium silicate-based sealers, Total Fill BC Sealer showed the highest push-out bond strength (P < 0.05). BioRoot RCS had significant higher push-out bond strength than Endo CPM Sealer (P < 0.05). Nearly the same results were found for all four sections. BioRoot RCS only differed significantly from Endo CPM Sealer in the third section (P < 0.05). CONCLUSIONS: The push-out bond strength of the investigated calcium silicate-based sealers was lower than of AH Plus. Total Fill BC showed the highest push-out bond strength of the calcium silicate-based sealers

Egfr amplification specific gene expression in phyllodes tumours of the breast, Cell. Oncol

Abstract. Background: Recently, we were able to show that amplifications of the epidermal growth factor receptor (egfr) gene and the overexpression of EGFR were associated with the initiation and progression of phyllodes tumours. Methods: In order to gain further insights into regulation mechanisms associated with egfr amplifications and EGFR expression in phyllodes tumours, we performed global gene expression analysis (Affymetrix A133.2) on a series of 10 phyllodes tumours, of these three with and seven without amplifications of an important regulatory repeat in intron 1 of egfr (CA-SSR I). The results were verified and extended by means of immunohistochemistry using the tissue microarray method on an extensively characterized series of 58 phyllodes tumours with antibodies against caveolin-1, eps15, EGF, TGF-α, pErk, pAkt and mdm2. Results: We were able to show that the presence of egfr CA-SSR I amplifications in phyllodes tumours was associated with 230 differentially expressed genes. Caveolin-1 and eps15, involved in EGFR turnover and signalling, were regulated differentially on the RNA and protein level proportionally to egfr gene dosage. Further immunohistochemical analysis revealed that the expression of caveolin-1 and eps15 were also significantly correlated with the expression of pAkt (p &lt; 0.05), pERK (p &lt; 0.05), mdm2 (p &lt; 0.01) and EGF (p &lt; 0.001 for caveolin-1). Eps15 and pERK were further associated with tumour grade (p &lt; 0.01 and p &lt; 0.001, respectively). Conclusion: Our results show that amplifications within regulatory sequences of egfr are associated with the expression of eps15 and caveolin-1, indicating an increased turnover of EGFR. The interplay between EGFR and caveolin-1, eps15, pAkt, mdm2 and pERK therefore seems to present a major molecular pathway in carcinogenesis and progression of breast phyllodes tumours

Egfr Amplification Specific Gene Expression in Phyllodes Tumours of the Breast

Background: Recently, we were able to show that amplifications of the epidermal growth factor receptor (egfr) gene and the overexpression of EGFR were associated with the initiation and progression of phyllodes tumours. Methods: In order to gain further insights into regulation mechanisms associated with egfr amplifications and EGFR expression in phyllodes tumours, we performed global gene expression analysis (Affymetrix A133.2) on a series of 10 phyllodes tumours, of these three with and seven without amplifications of an important regulatory repeat in intron 1 of egfr (CA-SSR I). The results were verified and extended by means of immunohistochemistry using the tissue microarray method on an extensively characterized series of 58 phyllodes tumours with antibodies against caveolin-1, eps15, EGF, TGF-α, pErk, pAkt and mdm2. Results: We were able to show that the presence of egfr CA-SSR I amplifications in phyllodes tumours was associated with 230 differentially expressed genes. Caveolin-1 and eps15, involved in EGFR turnover and signalling, were regulated differentially on the RNA and protein level proportionally to egfr gene dosage. Further immunohistochemical analysis revealed that the expression of caveolin-1 and eps15 were also significantly correlated with the expression of pAkt (p < 0.05), pERK (p < 0.05), mdm2 (p < 0.01) and EGF (p < 0.001 for caveolin-1). Eps15 and pERK were further associated with tumour grade (p < 0.01 and p < 0.001, respectively). Conclusion: Our results show that amplifications within regulatory sequences of egfr are associated with the expression of eps15 and caveolin-1, indicating an increased turnover of EGFR. The interplay between EGFR and caveolin-1, eps15, pAkt, mdm2 and pERK therefore seems to present a major molecular pathway in carcinogenesis and progression of breast phyllodes tumours