Restoration of apoptosis in serous cancer stem cells sensitizes them to platinum therapy resulting in tumor eradication

Janzen, Deanna M.; Tiourin, E.; Salehi, J. A.; Lü, Jing; Soragni, Alice; Eisenberg, David S.; Pellegrini, Matteo; Memarzadeh, Sanaz

doi:10.1016/j.ygyno.2015.01.004

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“…This nanoparticle system was engineered to increase the cytotoxicity of the doxorubicin six-fold in comparison to the use of free doxorubicin in eliminating CD44+ cancer stem-like cells residing in 3D mammary tumor spheroids (71). Another group tried to target serous cancer stem cells by restoration of apoptosis pathway activity in serous cancer stem cells which dramatically helped sensitize them to platinum therapy resulting in tumor eradication (72). These studies and ours confirm that development of targeted therapies that are toxic to tumor stem cells while sparing normal stem cells could lead to more effective methods for eradicating this ominous population of cells.…”

Section: Discussionmentioning

confidence: 99%

Magnetic nanoparticles as a new approach to improve the efficacy of gene therapy against differentiated human uterine fibroid cells and tumor-initiating stem cells

Shalaby

Khater

Perucho

et al. 2016

Fertility and Sterility

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Uterine fibroid(s) (UF/UFs) are benign tumors commonly found in women of reproductive age. The long-term outcomes of myomectomies are often hampered by high rates of recurrence (up to 60%). Objective To study whether efficient transduction and subsequent elimination of fibroid tumor initiating stem cells during debulking of tumor cells will aid in completely eradicating the tumor as well as decreasing the likelihood of recurrence. Design We have developed a localized non-surgical adenovirus-based alternative for the treatment of UFs. Combining viral based gene delivery with nanotechnology provides an opportunity to develop more efficient targeted viral gene therapy. Magnetic nanoparticles (MNPs) complexed to adenovirus, in the presence of an external magnetic field, accelerate adenovirus transduction. Setting Research laboratory located in Georgia Regents University, an academic research institution. Patients N/A Interventions MNPs complexed to adenovirus (AD GFP) or (AD LacZ) were used to transfect differentiated human fibroid cells in vitro. Main Outcome Measures rate of transduction and tumor growth inhibition. Results We observed a significant increase in transduction efficiency among differentiated human fibroid cells at 2 different multiplicities of infection (MOI); 1 and 10 respectively, with MNPs as compared to adenovirus-alone. Human fibroid stem cells transfected with AD-LacZ expressed β-Galactosidaze at (MOI) of 1, 10, and 50 at percentages of 19%, 62%, and 90%, respectively, which were significantly enhanced with MNPs. Conclusion When applied with adenovirus herpes simplex thymidine kinase, magnetofection significantly suppressed proliferation and induced apoptosis in both cell types. Through the use of magnetofection, we will prove that a lower viral dose will effectively increase the overall safety profile of suicide gene therapy against fibroid tumors.

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Section: Discussionmentioning

confidence: 99%