The combination of an mTORc1/TORc2 inhibitor with lapatinib is synergistic in bladder cancer in vitro.

Objective: To examine the ability of dual mTORc1/c2 inhibitors in conjunction with lapatinib to function in a synergistic manner to inhibit cell proliferation and anchorage-independent growth in bladder cancer cell lines.

Materials And Methods: We examined patient tumor samples for overexpression of pS6, p4EBP1, pAkt, and phosphorylated epidermal growth factor receptor (pEGFR) using a tissue microarray containing 84 cases. Three bladder cancer cell lines, T24, HT1376, and UM-UC-3, were analyzed for cell proliferation after treatment with mTORc1/c2 inhibitors OSI-027 or PP242.

Isolation and characterization of cidofovir resistant vaccinia viruses.

Background: The emergence of drug resistant viruses, together with the possibility of increased virulence, is an important concern in the development of new antiviral compounds. Cidofovir (CDV) is a phosphonate nucleotide that is approved for use against cytomegalovirus retinitis and for the emergency treatment of smallpox or complications following vaccination. One mode of action for CDV has been demonstrated to be the inhibition of the viral DNA polymerase.

An Amsacta moorei entomopoxvirus ortholog of the poly(A) polymerase small subunit exhibits methyltransferase activity and is non-essential for virus growth.

Unlike the heterodimeric poly(A) polymerase (PAP) of vaccinia virus (VACV), the PAP from the Amsacta moorei entomopoxvirus, AMEV, is potentially derived from three subunits: a single large and two small subunits (AMV060 and AMV115). The VACV small subunit serves as a 2'-O-methyltransferase, a processivity factor for mRNA polyadenylation, and a transcription elongation factor. We wished to determine the structure-function relationships of the three putative AMEV PAP subunits.

Cytokine secretion by cystic fibrosis airway epithelial cells.

It is controversial whether mutations in cystic fibrosis transmembrane conductance regulator intrinsically dysregulate inflammation. We characterized passage 2 human tracheobronchial epithelial cell cultures morphologically and physiologically and determined whether cytokine production or nuclear factor-kappaB activation was systematically altered in cystic fibrosis (CF) cells. Non-CF and CF cells originating from a total of 33 and 25 lungs, respectively, were available for culture on plastic or at an air-liquid interface until well differentiated.