The major obstacles to treatment of pancreatic cancer are the highly invasive capacity and resistance to chemo- and radiotherapy. Glycogen synthase kinase 3β (GSK3β) regulates multiple cellular pathways and is implicated in various diseases including cancer. Here we investigate a pathological role for GSK3β in the invasive and treatment resistant phenotype of pancreatic cancer. Pancreatic cancer cells were examined for GSK3β expression, phosphorylation and activity using Western blotting and in vitro kinase assay. The effects of GSK3β inhibition on cancer cell survival, proliferation, invasive ability and susceptibility to gemcitabine and radiation were examined following treatment with a pharmacological inhibitor or by RNA interference. Effects of GSK3β inhibition on cancer cell xenografts were also examined. Pancreatic cancer cells showed higher expression and activity of GSK3β than non-neoplastic cells, which were associated with changes in its differential phosphorylation. Inhibition of GSK3β significantly reduced the proliferation and survival of cancer cells, sensitized them to gemcitabine and ionizing radiation, and attenuated their migration and invasion. These effects were associated with decreases in cyclin D1 expression and Rb phosphorylation. Inhibition of GSK3β also altered the subcellular localization of Rac1 and F-actin and the cellular microarchitecture, including lamellipodia. Coincident with these changes were the reduced secretion of matrix metalloproteinase-2 (MMP-2) and decreased phosphorylation of focal adhesion kinase (FAK). The effects of GSK3β inhibition on tumor invasion, susceptibility to gemcitabine, MMP-2 expression and FAK phosphorylation were observed in tumor xenografts. The targeting of GSK3β represents an effective strategy to overcome the dual challenges of invasiveness and treatment resistance in pancreatic cancer.

Using a sedimentation method, the prevalence of the nodular worm Oesophagostomum stephanostomum (Nematoda: Strongylida) in western lowland gorillas at Moukalaba-Doudou National Park (MDNP), Gabon, was determined in fecal samples collected between January 2007 and October 2011, along with their coprocultures. Concurrently, possible zoonotic Oesophagostomum infections in villagers living near MDNP were assessed from their fecal samples collected during October and November of 2011. In the gorillas, strongylid (Oesophagostomum and/or hookworm) eggs were found in 47 of 235 fecal samples (20.0 %) and Oesophagostomum larvae were detected in 101 of 229 coprocultures (44.1 %). In the villagers, strongylid eggs were found in 9 of 71 fecal samples (12.7 %), but no Oesophagostomum larvae were detected in coprocultures. The internal transcribed spacer (ITS) region of ribosomal RNA gene (rDNA) and cytochrome c oxidase subunit-1 (cox-1) region of mitochondrial DNA (mtDNA) of coprocultured Oesophagostomum larvae were amplified using parasite DNA extracted from 7–25 larvae/sample, cloned into Escherichia coli, and sequenced. Sequenced rDNA contained 353/354-bp long ITS1, 151-bp long 5.8S rDNA, and 227-bp long ITS2. Parts of clones showed variations at 1–3 bases in the ITS1 region at a frequency of 24/68 (35.3 %) and at 1–2 bases in the ITS2 region at a frequency of 7/68 (10.3 %), whereas the 5.8S rDNA was essentially identical. Sequenced cox-1 gene of the parasites, 849 bp in length, showed a higher number of nucleotide variations, mainly at the third nucleotide position of the codon. The majority of clones (27/41 (65.9 %)) had an identical amino acid sequence. These results suggest that at MDNP, Gabon, only a single population of O. stephanostomum with a degree of genetic diversity is prevalent in western lowland gorillas, without zoonotic complication in local inhabitants. The possible genetic variations in the ITS region of rDNA and cox-1gene of mtDNA presented here may be valuable when only a limited amount of material is available for the molecular species diagnosis of O. stephanostomum.