scholarly journals Development of targeted therapy therapeutics to sensitize triple-negative breast cancer chemosensitivity utilizing bacteriophage phi29 derived packaging RNA

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Long Zhang ◽  
Chaofeng Mu ◽  
Tinghong Zhang ◽  
Dejun Yang ◽  
Chenou Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Targeted Therapy ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Triple Negative ◽  
Sirna Delivery ◽  
Growth Factor Receptor ◽  
Epidermal Growth

Abstract Background To date, triple-negative breast cancer (TNBC) treatment options are limited because of the loss of target receptors and, as a result, are only managed with chemotherapy. What is worse is that TNBC is frequently developing resistance to chemotherapy. By using small interfering RNA (siRNA)-based therapeutics, our recent work demonstrated X-box-binding protein 1 (XBP1) was linked to human epidermal growth factor receptor 2 positive (HER2+) breast cancer development and chemoresistance. Given the instability, off-target effects, net negative charge, and hydrophobicity of siRNA in vivo utilization and clinical transformation, its use in treatment is hampered. Thus, the development of a siRNA-based drug delivery system (DDS) with ultra-stability and specificity is necessary to address the predicament of siRNA delivery. Results Here, we assembled RNase resistant RNA nanoparticles (NPs) based on the 3WJ structure from Phi29 DNA packaging motor. To improved targeted therapy and sensitize TNBC to chemotherapy, the RNA NPs were equipped with an epidermal growth factor receptor (EGFR) targeting aptamer and XBP1 siRNA. We found our RNA NPs could deplete XBP1 expression and suppress tumor growth after intravenous administration. Meanwhile, RNA NPs treatment could promote sensitization to chemotherapy and impede angiogenesis in vivo. Conclusions The results further demonstrate that our RNA NPs could serve as an effective and promising platform not only for siRNA delivery but also for chemotherapy-resistant TNBC therapy.

scholarly journals Development of Targeted Therapy Therapeutics to Sensitize Triple-Negative Breast Cancer Chemosensitivity Utilizing Bacteriophage phi29 Derived Packaging RNA

2020 ◽  
Author(s):  
Long Zhang ◽  
Chaofeng Mu ◽  
Tinghong Zhang ◽  
Dejun Yang ◽  
Chenou Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Targeted Therapy ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Triple Negative ◽  
Sirna Delivery ◽  
Growth Factor Receptor ◽  
Epidermal Growth

Abstract Background To date, triple-negative breast cancer (TNBC) treatment options are limited because of the loss of target receptors and, as a result, are only managed with chemotherapy. What is worse is that TNBC is frequently developing resistance to chemotherapy. By using small interfering RNA (siRNA)-based therapeutics, our recent work demonstrated X-box-binding protein 1 (XBP1) was linked to human epidermal growth factor receptor 2 positive (HER2+) breast cancer development and chemoresistance. Given the instability, off-target effects, net negative charge, and hydrophobicity of siRNA in vivo utilization and clinical transformation, its use in treatment is hampered. Thus, the development of a siRNA-based drug delivery system (DDS) with ultra-stability and specificity is necessary to address the predicament of siRNA delivery.Results Here, we assembled RNase resistant RNA nanoparticles (NPs) based on the 3WJ structure from Phi29 DNA packaging motor. To improved targeted therapy and sensitize TNBC to chemotherapy, the RNA NPs were equipped with an epidermal growth factor receptor (EGFR) targeting aptamer and XBP1 siRNA. We found our RNA NPs could deplete XBP1 expression and suppress tumor growth after intravenous administration. Meanwhile, RNA NPs treatment could promote sensitization to chemotherapy and impede angiogenesis in vivo.Conclusions The results further demonstrate that our RNA NPs could serve as an effective and promising platform not only for siRNA delivery but also for chemotherapy-resistant TNBC therapy.

scholarly journals CD99–PTPN12 Axis Suppresses Actin Cytoskeleton-Mediated Dimerization of Epidermal Growth Factor Receptor

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2895
Author(s):  
Kyoung-Jin Lee ◽  
Yuri Kim ◽  
Min Seo Kim ◽  
Hyun-Mi Ju ◽  
Boyoung Choi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tumor Growth ◽  
Actin Cytoskeleton ◽  
Growth Factor Receptor ◽  
Cytoskeletal Reorganization ◽  
Epidermal Growth

The epidermal growth factor receptor (EGFR), a member of ErbB receptor tyrosine kinase (RTK) family, is activated through growth factor-induced reorganization of the actin cytoskeleton and subsequent dimerization. We herein explored the molecular mechanism underlying the suppression of ligand-induced EGFR dimerization by CD99 agonists and its relevance to tumor growth in vivo. Epidermal growth factor (EGF) activated the formation of c-Src/focal adhesion kinase (FAK)-mediated intracellular complex and subsequently induced RhoA-and Rac1-mediated actin remodeling, resulting in EGFR dimerization and endocytosis. In contrast, CD99 agonist facilitated FAK dephosphorylation through the HRAS/ERK/PTPN12 signaling pathway, leading to inhibition of actin cytoskeletal reorganization via inactivation of the RhoA and Rac1 signaling pathways. Moreover, CD99 agonist significantly suppressed tumor growth in a BALB/c mouse model injected with MDA-MB-231 human breast cancer cells. Taken together, these results indicate that CD99-derived agonist ligand inhibits epidermal growth factor (EGF)-induced EGFR dimerization through impairment of cytoskeletal reorganization by PTPN12-dependent c-Src/FAK inactivation, thereby suppressing breast cancer growth.

Expression of Estrogen, Progesterone Receptors, and Human Epidermal Growth Factor Receptor 2 in Women With Breast Cancer

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S89-S89
Author(s):  
Angela Mlole
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Progesterone Receptors ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth ◽  
The Mean

Abstract Introduction Globally, breast cancer is a leading cause of female cancer-related mortality and most predominant in the premenopausal stage. Expression of hormone receptors and human epidermal growth factor receptor 2, HER2/neu, appears to be different in the premenopausal group. However, there are limited data on hormone receptor expressions among women in Uganda. Therefore, the objective of this study was to determine the expression of estrogen, progesterone receptors, and human epidermal growth factor receptor 2 in women with breast cancer. Methods This was a retrospective descriptive cross-sectional laboratory-based study conducted in the Department of Pathology, Makerere University. Paraffin-embedded tissue blocks were retrieved from the archive and stained with H&E for histological confirmation and establishment of histological grade and type. Immunohistochemistry staining using a mouse-derived monoclonal antibody for hormonal receptors and HER2/neu expression was also done. Data were analyzed using STATA version 13. Results A total of 103 patients’ tissue blocks were analyzed. The mean ± SD age of the cases was 49 ± 15 years. The majority, 55/103 (53.4%), had intermediate cancer grade and 39/103 (37.9%) had triple-negative breast cancer. The majority, 55/103 (53.4%), were positive for ER hormone expression, 48/103 (46.6%) showed positive PR hormone expression, and only 19/103 (18.5%) were HER2/neu positive. Age of the cases showed statistical significance with hormonal receptor expressions and triple-negative breast cancer (P < .05), with high-grade cancers being more common among premenopausal women. Conclusion The study found that the mean age of breast cancer was 49 years, invasive carcinoma of no special type (NST) was the commonest histological type, and the majority were of intermediate cancer grade. In total, 53.4% of patients were ER positive, 46.6% were PR positive, 18.5% were HER2/neu positive, and 37.9% were triple negative. Age was the only factor significantly associated with hormonal receptors and triple-negative breast cancers.

Sign in / Sign up

Export Citation Format

Share Document