Nanoparticles carrying fingolimod and methotrexate enables targeted induction of apoptosis and immobilization of invasive thyroid cancer.

Metastatic tumors are the main cause of cancer-related death, as the invading cancer cells disrupt normal functions of distant organs and are nearly impossible to eradicate by traditional cancer therapeutics. This is of special concern when the cancer has created multiple metastases and extensive surgery would be too dangerous to execute. Therefore, combination chemotherapy is often the selected treatment form. However, drug cocktails often have severe adverse effects on healthy cells, whereby the development of targeted drug delivery could minimize side-effects of drugs and increase the efficacy of the combination therapy. In this study, we utilized the folate antagonist methotrexate (MTX) as targeting ligand conjugated onto mesoporous silica nanoparticles (MSNs) for selective eradication of folate receptor-expressing invasive thyroid cancer cells. The MSNs was subsequently loaded with the drug fingolimod (FTY720), which has previously been shown to efficiently inhibit proliferation and invasion of aggressive thyroid cancer cells. To assess the efficiency of our carrier system, comprehensive in vitro methods were employed; including flow cytometry, confocal microscopy, viability assays, invasion assay, and label-free imaging techniques. The in vitro results show that MTX-conjugated and FTY720-loaded MSNs potently attenuated both the proliferation and invasion of the cancerous thyroid cells while keeping the off-target effects in normal thyroid cells reasonably low. For a more physiologically relevant in vivo approach we utilized the chick chorioallantoic membrane (CAM) assay, showing decreased invasive behavior of the thyroid derived xenografts and an increased necrotic phenotype compared to tumors that received the free drug cocktail. Thus, the developed multidrug-loaded MSNs effectively induced apoptosis and immobilization of invasive thyroid cancer cells, and could potentially be used as a carrier system for targeted drug delivery for the treatment of diverse forms of aggressive cancers that expresses folate receptors.

[Serum cathepsin A activity in pregnant, parturient and puerperal patients]. / Die Aktivität des Kathepsins A im Blutserum Schwangerer, Gebärender und Wöchnerinnen.

Cathepsin A activity has been determinal in sera of nonpregnant, pregnant (1st, 2nd and 3rd trimesto), puerperal (first, third and fifth day post partum) and parturient women in second stage (retroplacental blood and blood from umbilical cord) by means of N-Cbz-L-glutamyl-L-tyrosin after incubation with 37 degrees C and pH 5.5. There was an increasing cathepsin A activity with the duration of pregnancy, during labour and in the first puerperal days. Maximum of activity of cathepsin A has been determined in serum of retroplacental blood.

[The activities of cathepsin A in the placenta, fetal membranes and amniotic fluid in physiologic pregnancy and pregnancy complicated by EPH gestosis]. / Die Aktivitäten des Kathepsins A in der Plazenta, den Eihäuten und der Amnionflüssigkeit in der physiologischen und durch EPH-Gestose komplizierten Schwangerschaft.

Activity of cathepsin A was determined in placenta, fetal membranes and amniotic fluid as well in normal pregnancy as in complicated pregnancy by EPH-gestosis. Measurement of activity was done by N-CbZ-L-glutamyl-tyrosine with pH 5.5. Compared with normal pregnancy activity of cathepsin A was lower in the three materials of EPH-gestosis.