The construction and therapy strategy of a CTNF-α-exosome-SPION and the preparation of the CTNF-α-exosome-SPION by gene engineering and dehydration synthesis are described here. The CTNF-α-exosome-SPION displays membrane targeting anticancer activity with the help of magnetic force.

BAY55‐9837, a potential therapeutic peptide in the treatment of type 2 diabetes mellitus (T2DM), is capable of inducing glucose (GLC)‐dependent insulin secretion. However, the therapeutic benefit of BAY55‐9837 is limited by its short half‐life, lack of targeting ability, and poor blood GLC response. How to improve the blood GLC response of BAY55‐9837 is an existing problem that needs to be solved. In this study, a method for preparing BAY55‐9837‐loaded exosomes coupled with superparamagnetic iron oxide nanoparticle (SPIONs) with pancreas islet targeting activity and an enhanced blood GLC response with the help of an external magnetic force (MF) is demonstrated. The plasma half‐life of BAY55‐9837 loaded in exosome‐SPION is 27‐fold longer than that of BAY55‐9837. The active targeting property of SIPONs enables BAY‐exosomes to gain a favorable targeting property, which improves the BAY55‐9837 blood GLC response capacity with the help of an external MF. In vivo studies show that BAY‐loaded exosome‐based vehicle delivery enhances pancreas islet targeting under an external MF and markedly increases insulin secretion, thereby leading to the alleviation of hyperglycemia. The chronic administration of BAY‐exosome‐SPION/MF significantly improves glycosylated hemoglobin and lipid profiles. BAY‐exosome‐SPION/MF maybe a promising candidate for a peptide drug carrier for T2DM with a better blood GLC response.

Objective: To study the effect of Fucoxanthin on PI3K / Akt signaling pathway in human cervical cancer Hela cells. Method:We exposed HeLa cells to different concentrations of Fucoxanthin for 24 hours. The effect of Fucoxanthin on PI3K/Akt signaling pathway related proteins was detected by Western blot. In order to analyze the relationship between nuclear transcription factor activity and Fucoxanthin, the activity of NF-kappa B and AP-1 was determined by luciferase reporter gene assay.Results: Western blot analysis showed that Fucoxanthin inactivated Akt pathway, inhibited Bcl-2 protein level, induced Bax production and caspase-3 cleavage. The Fucoxanthin may inhibit the growth of HeLa cells by inhibiting the PI3K/Akt signaling pathway. Fucoxanthin dose dependently reduced the activation level of NF-kappa B but did not significantly affect AP-1. This indicates that Fucoxanthin inhibits the activation of NF-kappa B in HeLa cells. Conclusion:NF-kappa B may be the mediator of Fucoxanthin-induced apoptosis in HeLa cells. As an ideal target for tumor therapy, NF-kappa B can regulate some genes involved in the development and progression of cervical cancer and inhibit cell apoptosis by activating several antiapoptosis genes.

TGF-β signaling inhibits cell growth in epithelial cells and thus acts as tumor suppressor, yet increased TGF-β signaling often promotes cancer progression through effects on the tumor micro-environment and effects on the carcinoma cells that can lead to epithelial plasticity responses and increased invasion. The responsive epithelial or carcinoma cells can regulate their cell surface levels of TGF-β receptors, and thus enhance their responses to TGF-β. In addition to transcription control of TGF-β receptor expression, the cells can rapidly mobilize TβRII and TβRI from a large intracellular receptor pool to the cell surface, and thus enhance their TGF-β responsiveness. For example, high glucose, as seen in hyperglycemia, rapidly induces high levels of cell surface receptors that increase the cell’s TGF-β responsiveness, resulting in extracellular matrix production and increased cell size. Similarly, increased cell surface TGF-β receptor levels and TGF-β responsiveness also occur in response to insulin, which is therapeutically used against diabetes-associated hyperglycemia. The insulin-induced increase in cell surface levels requires activation of Akt, which then phosphorylates the membrane-associated RabGAP AS160, thus alleviating AS160-mediated retention of vesicles containing TβRII and TβRI, and allowing them to reach the cell surface. Additionally, the levels of functional TGF-β receptor complexes at the cell surface is controlled by TACE-mediated ectodomain shedding, which is activated in response to Erk and p38 MAPK activation. We will discuss the physiological implications of these multiple levels of control of TGF-β receptor cell surface presentation and TGF-β responsiveness in cancer cell behavior and cancer progression. Finally, the epithelial plasticity response to TGF-β is also controlled by the direct interaction of activated Smad3 with a methyltransferase, which consequently controls the histone modifications of the gene encoding the transcription factor Snail, a master regulator that drives epithelial-mesenchymal transition. Thus, Smad-mediated changes of histone methylation complement direct Smad-mediated transcription effects in the control of epithelial-mesenchymal transition. Citation Format: Rik Derynck, Erine Budi, Baby-Periyanayaki Muthusamy, Yoko Katsuno, Dan Du. Control of TGF-β responsiveness and epithelial plasticity. [abstract]. In: Proceedings of the AACR Special Conference: Developmental Biology and Cancer; Nov 30-Dec 3, 2015; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(4_Suppl):Abstract nr IA31.