scholarly journals Direct Comparison of Chol-siRNA Polyplexes and Chol-DsiRNA Polyplexes Targeting STAT3 in a Syngeneic Murine Model of TNBC

2022 ◽  
Vol 8 (1) ◽  
pp. 8
Author(s):  
Zhen Ye ◽  
Mai Mohamed Abdelmoaty ◽  
Stephen M. Curran ◽  
Shetty Ravi Dyavar ◽  
Devendra Kumar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Rna Interference ◽  
Cancer Therapy ◽  
Solid Tumors ◽  
Diblock Copolymer ◽  
Murine Model ◽  
Target Gene ◽  
Breast Tumors ◽  
Final Dose ◽  
Polymer Complexes

RNA interference (RNAi) molecules have tremendous potential for cancer therapy but are limited by insufficient potency after intravenous (IV) administration. We previously found that polymer complexes (polyplexes) formed between 3′-cholesterol-modified siRNA (Chol-siRNA) or DsiRNA (Chol-DsiRNA) and the cationic diblock copolymer PLL[30]-PEG[5K] greatly increase RNAi potency against stably expressed LUC mRNA in primary syngeneic murine breast tumors after daily IV dosing. Chol-DsiRNA polyplexes, however, maintain LUC mRNA suppression for ~48 h longer after the final dose than Chol-siRNA polyplexes, which suggests that they are the better candidate formulation. Here, we directly compared the activities of Chol-siRNA polyplexes and Chol-DsiRNA polyplexes in primary murine 4T1 breast tumors against STAT3, a therapeutically relevant target gene that is overexpressed in many solid tumors, including breast cancer. We found that Chol-siSTAT3 polyplexes suppressed STAT3 mRNA in 4T1 tumors with similar potency (half-maximal ED50 0.3 mg/kg) and kinetics (over 96 h) as Chol-DsiSTAT3 polyplexes, but with slightly lower activity against total Stat3 protein (29% vs. 42% suppression) and tumor growth (11.5% vs. 8.6% rate-based T/C ratio) after repeated IV administration of equimolar, tumor-saturating doses every other day. Thus, both Chol-siRNA polyplexes and Chol-DsiRNA polyplexes may be suitable clinical candidates for the RNAi therapy of breast cancer and other solid tumors.

scholarly journals Direct Comparison of Chol-siRNA Polyplexes and Chol-DsiRNA Polyplexes Targeting STAT3 in a Syngeneic Murine Model of TNBC

2021 ◽  
Author(s):  
Zhen Ye ◽  
Mai Mohamed Abdelmoaty ◽  
Stephen M. Curran ◽  
Shetty Ravi Dyavar ◽  
Devendra Kumar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Rna Interference ◽  
Cancer Therapy ◽  
Solid Tumors ◽  
Diblock Copolymer ◽  
Murine Model ◽  
Target Gene ◽  
Breast Tumors ◽  
Final Dose ◽  
Polymer Complexes

RNA interference (RNAi) molecules have tremendous potential for cancer therapy but are limited by insufficient potency after i.v. administration. We previously found that polymer complexes (polyplexes) formed between 3’-cholesterol-modified siRNA (Chol-siRNA) or DsiRNA (Chol-DsiRNA) and the cationic diblock copolymer PLL[30]-PEG[5K] greatly increase RNAi potency against stably expressed LUC mRNA in primary syngeneic murine breast tumors after daily i.v. dosing. Chol-DsiRNA Polyplexes, however, maintain LUC mRNA suppression ~48 h longer after the final dose than Chol-siRNA Polyplexes, suggesting they are a better candidate formulation. Here, we directly compared the activities of Chol-siRNA and Chol-DsiRNA Polyplexes in primary murine 4T1 breast tumors against STAT3, a therapeutically relevant target gene overexpressed in many solid tumors including breast cancer. We found that Chol-siSTAT3 Polyplexes suppressed STAT3 mRNA in 4T1 tumors with similar potency (half-maximal ED50 0.3 mg/kg) and kinetics over 96 hours as Chol-DsiSTAT3 Polyplexes but with slightly lower activity against total Stat3 protein (29% vs. 42% suppression) and tumor growth (11.5% vs. 8.6% rate-based T/C ratio) after repeated i.v. administration of tumor-saturating doses every other day. Thus, both Chol-siRNA Polyplexes and Chol-DsiRNA Polyplexes may be suitable clinical candidates for RNAi therapy of breast cancer and other solid tumors.

scholarly journals CD133 in Breast Cancer Cells: More than a Stem Cell Marker

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Federica Brugnoli ◽  
Silvia Grassilli ◽  
Yasamin Al-Qassab ◽  
Silvano Capitani ◽  
Valeria Bertagnolo
Keyword(s):  
Breast Cancer ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Breast Tumors ◽  
Surface Expression ◽  
Stem Cell Marker ◽  
Industrialized Countries ◽  
Triple Negative Phenotype

Initially correlated with hematopoietic precursors, the surface expression of CD133 was also found in epithelial and nonepithelial cells from adult tissues in which it has been associated with a number of biological events. CD133 is expressed in solid tumors as well, including breast cancer, in which most of the studies have been focused on its use as a surface marker for the detection of cells with stem-like properties (i.e., cancer stem cells (CSCs)). Differently with other solid tumors, very limited and in part controversial are the information about the significance of CD133 in breast cancer, the most common malignancy among women in industrialized countries. In this review, we summarize the latest findings about the implication of CD133 in breast tumors, highlighting its role in tumor cells with a triple negative phenotype in which it directly regulates the expression of proteins involved in metastasis and drug resistance. We provide updates about the prognostic role of CD133, underlining its value as an indicator of increased malignancy of both noninvasive and invasive breast tumor cells. The molecular mechanisms at the basis of the regulation of CD133 levels in breast tumors have also been reviewed, highlighting experimental strategies capable to restrain its level that could be taken into account to reduce malignancy and/or to prevent the progression of breast tumors.

Docetaxel-loaded nanoparticles based on star-shaped mannitol-core PLGA-TPGS diblock copolymer for breast cancer therapy

2013 ◽  
Vol 9 (11) ◽  
pp. 8910-8920 ◽  
Author(s):  
Wei Tao ◽  
Xiaowei Zeng ◽  
Ting Liu ◽  
Zhongyuan Wang ◽  
Qingqing Xiong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Diblock Copolymer ◽  
Breast Cancer Therapy

scholarly journals Global transcriptional analysis identifies a novel role for SOX4 in tumor-induced angiogenesis

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Stephin J Vervoort ◽  
Olivier G de Jong ◽  
M Guy Roukens ◽  
Cynthia L Frederiks ◽  
Jeroen F Vermeulen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Poor Prognosis ◽  
Target Gene ◽  
Gene Selection ◽  
Mammary Tumorigenesis ◽  
Breast Tumors ◽  
Transcriptional Analysis

The expression of the transcription factor SOX4 is increased in many human cancers, however, the pro-oncogenic capacity of SOX4 can vary greatly depending on the type of tumor. Both the contextual nature and the mechanisms underlying the pro-oncogenic SOX4 response remain unexplored. Here, we demonstrate that in mammary tumorigenesis, the SOX4 transcriptional network is dictated by the epigenome and is enriched for pro-angiogenic processes. We show that SOX4 directly regulates endothelin-1 (ET-1) expression and can thereby promote tumor-induced angiogenesis both in vitro and in vivo. Furthermore, in breast tumors, SOX4 expression correlates with blood vessel density and size, and predicts poor-prognosis in patients with breast cancer. Our data provide novel mechanistic insights into context-dependent SOX4 target gene selection, and uncover a novel pro-oncogenic role for this transcription factor in promoting tumor-induced angiogenesis. These findings establish a key role for SOX4 in promoting metastasis through exploiting diverse pro-tumorigenic pathways.

Iron oxide and gold bimetallic radiosensitizers for synchronous tumor chemoradiation therapy in 4T1 breast cancer murine model

2021 ◽  
Author(s):  
Hamed Nosrati ◽  
Yasamin Baghdadchi ◽  
Reza Abbasi ◽  
Murat Barsbay ◽  
Mohammadreza Ghaffarlou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Iron Oxide ◽  
Cancer Therapy ◽  
Therapeutic Effect ◽  
Murine Model ◽  
Chemoradiation Therapy ◽  
Synchronous Tumor ◽  
Multifunctional Nanomaterials ◽  
4T1 Breast Cancer

The development of highly integrated multifunctional nanomaterials with a superadditive therapeutic effect and good safety is an urgent but challenging task in cancer therapy research.

(TA)MUC1 as a potential new target for breast cancer therapy

2020 ◽  
Author(s):  
AS Heimes ◽  
P Fries ◽  
N Stergiou ◽  
R Attariya ◽  
A Hasenburg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Breast Cancer Therapy
Sign in / Sign up

Export Citation Format

Share Document