Developmental pathways associated with cancer metastasis: Notch, Wnt, and Hedgehog

Master developmental pathways, such as Notch, Wnt, and Hedgehog, are signaling systems that control proliferation, cell death, motility, migration, and stemness. These systems are not only commonly activated in many solid tumors, where they drive or contribute to cancer initiation, but also in primary and metastatic tumor development. The reactivation of developmental pathways in cancer stroma favors the development of cancer stem cells and allows their maintenance, indicating these signaling pathways as particularly attractive targets for efficient anticancer therapies, especially in advanced primary tumors and metastatic cancers. Metastasis is the worst feature of cancer development. This feature results from a cascade of events emerging from the hijacking of epithelial-mesenchymal transition, angiogenesis, migration, and invasion by transforming cells and is associated with poor survival, drug resistance, and tumor relapse. In the present review, we summarize and discuss experimental data suggesting pivotal roles for developmental pathways in cancer development and metastasis, considering the therapeutic potential. Emerging targeted antimetastatic therapies based on Notch, Wnt, and Hedgehog pathways are also discussed

Activity of aqueous ethanol extract of Euphorbia prostrata ait on Shigella dysenteriae type 1-induced diarrhea in rats

Aim: Euphorbia prostrata   (Euphorbiaceae) is traditionally used in Cameroon for the treatment of many diseases, including diarrhea. We investigated the acute toxicity and effect of the aqueous ethanol extract of the plant on gastrointestinal propulsion, in vitro bacterial growth and in vivo bacillary dysentery. Materials and Methods: Diarrhea was induced by oral administration of 12 x 10 8 Shigella dysenteriae type 1 (Sd1) cells. Diarrheic rats were treated for 5 days with 10, 20 or 40 mg/kg extract or 20 mg/kg norfloxacin. The faeces frequencies and the number of Sd1 were assessed and the death rate recorded. Results: The aqueous ethanol extract of E. prostrata was not toxic. In vitro, the minimal inhibitory and minimal bactericidal concentrations of the extract were 3,500 and 12,000 µg/ml, respectively. In vivo, diarrhea went along with increase in faeces frequency (P < 0.01 by the 3 rd day), increase in the bacterial population to a maximum on the 2 nd day after infection (P < 0.01). The death rate in diarrheic control group was 100% by day 6. E. prostrata extracts (20 and 40 mg/kg), like norfloxacin, reduced the bacterial growth (P < 0.01), so that by the 6 th day Sd1 density was < 100 and no death was recorded. There was a significant (P < 0.01) reduction in faeces frequencies. The extract exhibited notable (P < 0.01) inhibition of intestinal propulsion. Conclusion: The results suggest that E. prostrata possesses bactericidal and antidiarrheic properties and could be a therapeutic alternative for diarrheas of bacterial etiology

Mesenchymal stromal cells’ role in tumor microenvironment: involvement of signaling pathways

International audienceMesenchymal stromal cells (MSCs) are adult multipotent stem cells residing as pericytes in various tissues and organs where they can differentiate into specialized cells to replace dying cells and damaged tissues. These cells are commonly found at injury sites and in tumors that are known to behave like " wounds that do not heal." In this article, we discuss the mechanisms of MSCs in migrating, homing, and repairing injured tissues. We also review a number of reports showing that tumor microenvironment triggers plasticity mechanisms in MSCs to induce malignant neoplastic tissue formation, maintenance, and chemoresistance, as well as tumor growth. The antitumor properties and therapeutic potential of MSCs are also discussed