Dendrosome mediated topical gene silencing by PLK-1 specific siRNA: implication in treatment of skin cancer in mouse model

RSC Advances ◽  
2016 ◽  
Vol 6 (8) ◽  
pp. 6843-6857
Author(s):  
Mohd. Asif Sherwani ◽  
Saba Tufail ◽  
Aijaz Ahmed Khan ◽  
Mohammad Owais

Topical application of PLK-1 siRNA bearing dendrosomes on DMBA induced skin papillomas in mice exhibit potent anti-cancer effect. The treatment leads to reduced number and sizes of papillomas.

Nanoscale ◽  
2015 ◽  
Vol 7 (9) ◽  
pp. 3903-3914 ◽  
Author(s):  
Venkata Vamsi K. Venuganti, ◽  
Manju Saraswathy ◽  
Chandradhar Dwivedi ◽  
Radhey S. Kaushik ◽  
Omathanu P. Perumal

Topical iontophoretic delivery of a dendrimer–antisense oligonucleotide nanocomplex demonstrates the potential for developing gene silencing therapy for skin diseases.


2008 ◽  
Vol 111 (2) ◽  
pp. 356-364 ◽  
Author(s):  
Amy L. Jonson ◽  
Lisa M. Rogers ◽  
Sundaram Ramakrishnan ◽  
Levi S. Downs

2018 ◽  
Vol 25 (6) ◽  
pp. 677-686 ◽  
Author(s):  
Shani Avniel-Polak ◽  
Gil Leibowitz ◽  
Victoria Doviner ◽  
David J Gross ◽  
Simona Grozinsky-Glasberg

Patients with neuroendocrine neoplasms (NENs) often require systemic treatment, which is frequently limited by the emergence of drug resistance. mTOR inhibitors (mTORi), such as RAD001 (everolimus), have been shown to inhibit neoplasm progression. mTORi stimulates autophagy, a degradation pathway that might promote the survival of neoplasm cells that are exposed to anti-cancer therapy. Chloroquine (CQ), a well-known anti-malarial and anti-rheumatic drug, suppresses autophagy. Based on our previous results, we hypothesized that CQ may enhance the anti-tumorigenic effects of mTORi by inhibiting autophagy and we aimed to examine the anti-tumorigenic effect of CQ, alone or in combination with RAD001. We established a NEN subcutaneous xenograft mouse model and evaluated the effect of the drugs on tumor growth, mTOR pathway, autophagy and apoptosis. CQ alone and in combination with RAD001 significantly decreased neoplasm volume. Histopathological analysis revealed that the combination of CQ and RAD001 markedly inhibited mTOR activity and neoplasm cell growth, along with accumulation of autophagosomes and increased apoptosis. In conclusion, CQ enhances the anti-tumorigenic effect of RAD001 in vivo by inhibiting autophagy. Clinical trials addressing the effects of CQ therapy on neoplasm progression in patients with NENs, mainly in those treated with mTORi, are warranted.


eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Kent Riemondy ◽  
Xiao-jing Wang ◽  
Enrique C Torchia ◽  
Dennis R Roop ◽  
Rui Yi

In many mouse models of skin cancer, only a few tumors typically form even though many cells competent for tumorigenesis receive the same oncogenic stimuli. These observations suggest an active selection process for tumor-initiating cells. Here, we use quantitative mRNA- and miR-Seq to determine the impact of HrasG12V on the transcriptome of keratinocytes. We discover that microRNA-203 is downregulated by HrasG12V. Using a knockout mouse model, we demonstrate that loss of microRNA-203 promotes selection and expansion of tumor-initiating cells. Conversely, restoration of microRNA-203 using an inducible model potently inhibits proliferation of these cells. We comprehensively identify microRNA-203 targets required for Hras-initiated tumorigenesis. These targets include critical regulators of the Ras pathway and essential genes required for cell division. This study establishes a role for the loss of microRNA-203 in promoting selection and expansion of Hras mutated cells and identifies a mechanism through which microRNA-203 antagonizes Hras-mediated tumorigenesis.


2011 ◽  
Vol 9 (1) ◽  
Author(s):  
Natasja K van den Engel ◽  
Dominik Rüttinger ◽  
Margareta Rusan ◽  
Robert Kammerer ◽  
Wolfgang Zimmermann ◽  
...  

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