Phospho-sulindac is a sulindac derivative with promising anticancer activity in lung cancer, but its limited metabolic stability presents a major challenge for systemic therapy. We reasoned that inhalation delivery of phospho-sulindac might overcome first-pass metabolism and produce high levels of intact drug in lung tumors. Here, we developed a system for aerosolization of phospho-sulindac and...

Growth factors and COX-2/PGE2 enhance lung cancer invasion/metastasis via PI3K/Akt and RAS/Raf. Here, we explored their mechanism of action further. We found first that higher levels of migration inducting gene-7 protein (MIG-7) and PHB phosphorylated at threonine 258 (phospho-PHBT258) are positively correlated with advanced stages of human lung cancer in tissue microarray. PGE2 or growth facto...

After dissemination from a primary tumor, cancer cells may resume growth, leading to overt metastasis, or enter a state of protracted dormancy. However, mechanisms that determine their fate, or markers that predict it, are mostly unavailable. We previously showed that in HEp3 human head and neck carcinoma, the extracellular signal-regulated kinase (ERK)/p38 activity ratio predicts whether the c...

Homozygous mutant (Shp-2Delta46-110) embryonic stem (ES) cells exhibit decreased hematopoiesis; however, the point at which Shp-2 is critical for ES cell differentiation to hematopoietic cells is unknown. We characterized the differentiation defect of Shp-2Delta46-110 ES cells by examining early points of differentiation, conducting leukemia inhibitory factor (LIF)-stimulated biochemical analys...

BACKGROUND Cystitis causes considerable neuronal plasticity in the primary afferent pathways. The molecular mechanism and signal transduction underlying cross talk between the inflamed urinary bladder and sensory sensitization has not been investigated. RESULTS In a rat cystitis model induced by cyclophosphamide (CYP) for 48 h, the mRNA and protein levels of the excitatory neurotransmitter ca...

BACKGROUND Study of ERK activation has thus far relied on biochemical assays that are limited to the use of phospho-specific antibodies and radioactivity in vitro, and analysis of whole cell populations in vivo. As with many systems, fluorescence resonance energy transfer (FRET) can be utilized to make highly sensitive detectors of molecular activity. Here we introduce FRET-based ERK Activity S...

Background Irisin is an exercise-linked myokine produced by cleavage of the membrane precursor fibronectin type III domain-containing protein 5 (FNDC5) in skeletal muscle, brain, and other tissues. Recently, irisin has been identified as a key molecule for exercise-induced neuroprotection mouse models Alzheimer’s disease (AD). However, role FNDC5/irisin AD pathology not yet comprehensively expl...

PI3K-Akt and Ras-MAPK pathways were both implicated in cell survival and neurite-outgrowth, respectively. Akt has been suggested to be involved in neuronal survival and MAPK in neurite outgrowth during development. This study investigated if Akt, a component of PI3K-Akt pathway, and MAPK/ERK, a component of Ras-MAPK pathway, were expressed in the normal and regenerating dorsal root ganglia and ...

Apoptosis inhibitor 5 (API5) has recently been identified as a tumor metastasis-regulating gene in cervical cancer cells. However, the precise mechanism of action for API5 is poorly understood. Here, we show that API5 increases the metastatic capacity of cervical cancer cells in vitro and in vivo via up-regulation of MMP-9. Interestingly, API5-mediated metastasis was strongly dependent on the E...