Anti-Cripto Mab inhibit tumour growth and overcome MDR in a human leukaemia MDR cell line by inhibition of Akt and activation of JNK/SAPK and bad death pathways

Doxorubicin (DOX) selection of CCRF-CEM leukaemia cell line resulted in multidrug resistance (MDR) CEM/A7R cell line, which overexpresses MDR, 1 coded P-glycoprotein (Pgp). Here, we report for the first time that oncoprotein Cripto, a founding member of epidermal growth factor-Cripto-FRL, 1-Criptic family is overexpressed in the CEM/A7R cells, and anti-Cripto monoclonal antibodies (Mab) inhibited CEM/A7R cell growth both in vitro and in an established xenograft tumour in severe combined immunodeficiency mice. Cripto Mab synergistically enhanced sensitivity of the MDR cells to Pgp substrates epirubicin (EPI), daunorubicin (DAU) and non-Pgp substrates nucleoside analogue cytosine arabinoside (AraC). In particular, the combination of anti-Cripto Mab at less than 50% of inhibition concentrations with noncytotoxic concentrations of EPI or DAU inhibited more than 90% of CEM/A7R cell growth. Cripto Mab slightly inhibited Pgp expression, and had little effect on Pgp function, indicating that a mechanism independent of Pgp was involved in overcoming MDR. We demonstrated that anti-Cripto Mab-induced CEM/A7R cell apoptosis, which was associated with an enhanced activity of the c-Jun N-terminal kinase/stress-activated protein kinase and inhibition of Akt phosphorylation, resulting in an activation of mitochondrial apoptosis pathway as evidenced by dephosphorylation of Bad at Ser136, Bcl-2 at Ser70 and a cleaved caspase-9

EMI shielding properties of polymer blends with inclusion of graphene nano platelets

Polymer blends of poly vinyle chloride (PVC) and polyaniline (PANI) with the inclusion of graphene nano platelets (GNP) are fabricated to enhance the EMI shielding effectiveness. The initial assessment with cyclic voltammetry has shown improved electrical conductivity both for PVC/PANI blends and PVC/PANI/GNP composites. The capacitive effect of the blends and composites is evaluated at lower frequency region (100 Hz-5 MHz). EMI shielding measurements of PVC/PANI/GNP composites is performed in the frequency range 10 MHz-20 GHz. In case of PVC/PANI (15 wt%) blends, a maximum attenuation of similar to 27 dB is attained which is enhanced to similar to 51 dB (max.) with the inclusion of 5 wt% GNP, mainly due to the absorption phenomena. The enhanced shielding effectiveness is achieved mainly in the frequency range 11-20 GHz. The dispersion state, fillers nature and their interaction may be the main aspects for the enhanced EMI shielding effectiveness of hybrid polymeric nanocomposites.publishedVersionPeer reviewe