Osteopontin and `Melanoma Inhibitory Activity': Comparison of Two Serological Tumor Markers in Metastatic Uveal Melanoma Patients

Background: Evaluation of the protein osteopontin (OPN) as a potential new marker in comparison to melanoma inhibitory activity (MIA) for screening and detection of metastatic uveal melanoma. Methods: Plasma levels of 32 patients with uveal melanoma were analyzed for OPN and MIA by enzyme-linked immunosorbent assay (ELISA). Fourteen of these patients had clinically detectable liver metastases. Results: Median plasma concentration of OPN in patients with metastatic disease was 152.01 ng/ml compared to 47.39 ng/ml in patients without clinically detectable metastases (p < 0.001). The difference between the median MIA plasma levels in patients with (13.11 ng/ml) and patients without (5.64 ng/ml) metastatic disease was also statistically significant (p < 0.001). No correlation could be found between MIA or OPN levels and tumor height in patients without clinically detectable metastases. Conclusion: The proteins MIA and OPN seem to be promising tumor markers for the metastasis screening in patients with uveal melanoma. Copyright (C) 2009 S. Karger AG, Base

Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment

<p>Abstract</p> <p>Background</p> <p>The pathological complete response (pCR) after neoadjuvant chemotherapy is a surrogate marker for a favorable prognosis in breast cancer patients. Factors capable of predicting a pCR, such as the proliferation marker Ki67, may therefore help improve our understanding of the drug response and its effect on the prognosis. This study investigated the predictive and prognostic value of Ki67 in patients with invasive breast cancer receiving neoadjuvant treatment for breast cancer.</p> <p>Methods</p> <p>Ki67 was stained routinely from core biopsies in 552 patients directly after the fixation and embedding process. HER2/neu, estrogen and progesterone receptors, and grading were also assessed before treatment. These data were used to construct univariate and multivariate models for predicting pCR and prognosis. The tumors were also classified by molecular phenotype to identify subgroups in which predicting pCR and prognosis with Ki67 might be feasible.</p> <p>Results</p> <p>Using a cut-off value of > 13% positively stained cancer cells, Ki67 was found to be an independent predictor for pCR (OR 3.5; 95% CI, 1.4, 10.1) and for overall survival (HR 8.1; 95% CI, 3.3 to 20.4) and distant disease-free survival (HR 3.2; 95% CI, 1.8 to 5.9). The mean Ki67 value was 50.6 ± 23.4% in patients with pCR. Patients without a pCR had an average of 26.7 ± 22.9% positively stained cancer cells.</p> <p>Conclusions</p> <p>Ki67 has predictive and prognostic value and is a feasible marker for clinical practice. It independently improved the prediction of treatment response and prognosis in a group of breast cancer patients receiving neoadjuvant treatment. As mean Ki67 values in patients with a pCR were very high, cut-off values in a high range above which the prognosis may be better than in patients with lower Ki67 values may be hypothesized. Larger studies will be needed in order to investigate these findings further.</p

Prognostic Value of [18F]-Fluoro-Deoxy-Glucose PET/CT, S100 or MIA for Assessment of Cancer-Associated Mortality in Patients with High Risk Melanoma

PURPOSE: To assess the prognostic value of FDG PET/CT compared to the tumor markers S100B and melanoma inhibitory activity (MIA) in patients with high risk melanoma. METHODS: Retrospective study in 125 consecutive patients with high risk melanoma that underwent FDG PET/CT for re-staging. Diagnostic accuracy and prognostic value was determined for FDG PET/CT as well as for S100B and MIA. As standard of reference, cytological, histological, PET/CT or MRI follow-up findings as well as clinical follow-up were used. RESULTS: Of 125 patients, FDG PET/CT was positive in 62 patients. 37 (29.6%) patients had elevated S100B (>100 pg/ml) and 24 (20.2%) had elevated MIA (>10 pg/ml) values. Overall specificities for FDG PET/CT, S100B and MIA were 96.8% (95% CI, 89.1% to 99.1%), 85.7% (75.0% to 92.3%), and 95.2% (86.9% to 98.4%), corresponding sensitivities were 96.8% (89.0% to 99.1%), 45.2% (33.4% to 55.5%), and 36.1% (25.2% to 48.6%), respectively. The negative predictive values (NPV) for PET/CT, S100B, and MIA were 96.8% (89.1% to 99.1%), 61.4% (50.9% to 70.9%), and 60.6% (50.8% to 69.7%). The positive predictive values (PPV) were 96.7% (89.0% to 99.1%), 75.7% (59.9% to 86.6%), and 88.0% (70.0% to 95.8%). Patients with elevated S100B- or MIA values or PET/CT positive findings showed a significantly (p<0.001 each, univariate Cox regression models) higher risk of melanoma associated death which was increased 4.2-, 6.5- or 17.2-fold, respectively. CONCLUSION: PET/CT has a higher prognostic power in the assessment of cancer-associated mortality in melanoma patients compared with S100 and MIA

Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the European Scleroderma Trials and Research (EUSTAR) cohort.

Objectives To determine whether progressive skin fibrosis is associated with visceral organ progression and mortality during follow-up in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods We evaluated patients from the European Scleroderma Trials and Research database with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, valid mRSS at 12±3 months after baseline and ≥1 annual follow-up visit. Progressive skin fibrosis was defined as an increase in mRSS &gt;5 and ≥25% from baseline to 12±3 months. Outcomes were pulmonary, cardiovascular and renal progression, and all-cause death. Associations between skin progression and outcomes were evaluated by Kaplan-Meier survival analysis and multivariable Cox regression. Results Of 1021 included patients, 78 (7.6%) had progressive skin fibrosis (skin progressors). Median follow-up was 3.4 years. Survival analyses indicated that skin progressors had a significantly higher probability of FVC decline ≥10% (53.6% vs 34.4%; p&lt;0.001) and all-cause death (15.4% vs 7.3%; p=0.003) than non-progressors. These significant associations were also found in subgroup analyses of patients with either low baseline mRSS (≤22/51) or short disease duration (≤15 months). In multivariable analyses, skin progression within 1 year was independently associated with FVC decline ≥10% (HR 1.79, 95% CI 1.20 to 2.65) and all-cause death (HR 2.58, 95% CI 1.31 to 5.09). Conclusions Progressive skin fibrosis within 1 year is associated with decline in lung function and worse survival in dcSSc during follow-up. These results confirm mRSS as a surrogate marker in dcSSc, which will be helpful for cohort enrichment in future trials and risk stratification in clinical practice

Differential in situ expression of IL-17 in skin diseases

Background: Interleukin (IL)-17 is a key molecule for epithelial immunity and inflammation. Objectives: To quantify IL-17 expression in situ in a large panel of cutaneous diseases. Materials &amp; Methods: 289 samples of the 30 most common cutaneous infectious, autoimmune, inflammatory and tumor diseases were stained for IL-17 immunohistochemically. Results: IL-17 expression strongly varied between the diseases, but was conserved within each disease. The major cellular sources of IL-17 were T cells and granulocytes. Skin diseases caused by extracellular microbials were infiltrated by many IL-17+ cells, while intracellular infections were scarcely positive for IL-17. While autoimmune diseases were mostly accompanied by IL-17+ T cells, IL-17+ granulocytes were dominant in neutrophilic dermatoses. Conclusion: Cutaneous diseases show a characteristic pattern of IL-17+ cellular infiltrate. These patterns are relevant for the clinician, since therapeutic approaches targeting differentiation of Th17 cells as well as direct targeting of IL-17 are or will become available

Einsatz von kohlestaemmigem Pyrolysegas als Reduktionsbrennstoff Schlussbericht

Das Forschungsprojekt verfolgte das Ziel mit 6 deutschen und australischen Kohlen die Stickoxidemissionen aus Kohlestaubfeuerungen durch Brennstoffstufung mit Pyrolysegas als Reduktionsbrennstoff zu verringern. Das erreichte Ziel war der Nachweis, dass mit dem beschriebenen Verfahren NO_x-Emissionswerte von 200 mg/m&quot;3 erreicht und unterschritten werden koennen. Die Brennstoffstufung unter Verwendung von kohlestaemmigen Gasen wurde experimentell im Hinblick auf die wichtigsten Verfahrensparameter, wie z.B. die Kohleart, Entgasungsrate, Temperatur, Verweilzeit und Stoechiometrie untersucht. In einem Flugstrom- und einem Wirbelschichtreaktor wurde der Einfluss der Entgasungstemperatur auf Restkohle und Pyrolyseprodukte, die Verteilung des Brennstoffstickstoffs, die Gas- und Teerqualitaet und deren Auswirkungen auf die NO_x-Bildung und Reduktion bei der gestuften Verbrennung bestimmt. Die Validierung des mathematischen Simulationsmodells erfolgte mit den experimentell gewonnenen Daten. Als wesentliche Kriterien fuer die erreichbare NO_x-Minderung werden Temperatur, Luftzahl und Verweilzeit in der Reduktionszone des Verbrennungsreaktors angesehen. Die Pyrolyseversuche zeigten den starken Einfluss der Kohleart und der Entgasungsbedingungen auf die Zusammensetzung der Gase und auf die erreichbare NO_x-Minderung. Die in den Pyrolysegasen enthaltenen Teere mit ihren Stickstoffverbindungen verbessern die Reduktionswirkung vorhandener Stickstoffoxide. Durch den Einsatz der Pyrolysegase als Reduktionsbrennstoff koennen NO_x-Emissionen unter 200 mg/m&quot;3 bei Luftzahlen um 0,95 erreicht und unterschritten werden. (orig./SR)The research project's aim was to reduce nitrogen emissions from pulverized-coal furnaces by fuel staging with pyrolysis gas from coal. The test fuels were 6 German and Australian coals. The aim achieved has been the statement that the described method is an adequate means to attain to and remain below emission values of 200 mg/m&quot;3. The method of fuel staging using coal-original gases was investigated with tests focussing the most important process parameters such as coal type, devolatilization ratio, temperature, residence time, and stoichiometry. The relevant features determined with an entrained flow reactor and with a fluidized-bed reactor were the impact of devolatilization temperatures on carbonized residue and pyrolysis products, the distribution of fuel nitrogen, and the quality of gas and tar, including the respective effects on NO_x formation and reduction in staged combustion. The validation of the mathematical model was done with the experimentally obtained data. The criteria considered fundamental for achieving the NO_x reduction level are temperature, air ratio, and residence time in the reduction zone of the furnace. The pyrolysis tests manifested the strong influence of the coal type and the devolatilization conditions on the composition of the gases and the attainable NO_x reduction. The tars in the pyrolysis gases, with their nitrogen compounds, improve the reducing effect of available nitrogen oxides. By using pyrolysis gases from coal as reburning fuel, NO_x emissions of less than 200 mg/m&quot;3 can be obtained at air ratios around 0.95. (orig./SR)Available from TIB Hannover: F97B1363+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman