Perturbed zinc homeostasis in rural 3-5-y-old Malawian children is associated with abnormalities in intestinal permeability attributed to tropical enteropathy.

Tropical enteropathy and zinc deficiency are major public health problems worldwide. Tropical enteropathy is characterized by reduced mannitol absorption with normal or increased lactulose absorption when a dual sugar absorption test is administered, the results of which are reported as the lactulose:mannitol ratio (L:M). Zinc homeostasis is quantified with a dual stable isotope test.

Bortezomib pre-treatment prolongs interferon-alpha-induced STAT1 phosphorylation in melanoma cells.

Bortezomib is a proteasome inhibitor that can synergize with interferon-alpha (IFN-alpha) to induce apoptosis in melanoma cells in vitro and inhibit tumor growth in vivo. We hypothesized that proteasome inhibition may be an effective means to sensitize melanoma cells to the direct effects of IFN-alpha. Pre-treatment of human melanoma cells with bortezomib led to significantly increased transcription of interferon-stimulated genes as determined by real-time PCR.

IFN-alpha and bortezomib overcome Bcl-2 and Mcl-1 overexpression in melanoma cells by stimulating the extrinsic pathway of apoptosis.

We hypothesized that IFN-alpha would enhance the apoptotic activity of bortezomib on melanoma cells. Combined treatment with bortezomib and IFN-alpha induced synergistic apoptosis in melanoma and other solid tumor cell lines. Apoptosis was associated with processing of procaspase-3, procaspase-7, procaspase-8, and procaspase-9 and with cleavage of Bid and poly(ADP-ribose) polymerase.