Small extracellular vesicles (sEVs), mainly exosomes, are nanovesicles that shed from the membrane as intraluminal vesicles of the multivesicular bodies, serve as vehicles that carry cargo influential in modulating the tumor microenvironment for the multi-step process of cancer metastasis. Annexin A2 (AnxA2), a calcium(Ca2+)-dependent phospholipid-binding protein, is among sEV cargoes. sEV-derived AnxA2 (sEV-AnxA2) protein is involved in the process of metastasis in triple-negative breast cancer (TNBC). The objective of the current study is to determine whether sEV-AnxA2 protein and/or mRNA could be a useful biomarkers to predict the responsiveness of chemotherapy in TNBC. Removal of Immunoglobulin G (IgG) from the serum as well as using the System Bioscience’s ExoQuick Ultra kit resulted in efficient sEV isolation and detection of sEV-AnxA2 protein and mRNA compared to the ultracentrifugation method. The standardized method was applied to the twenty TNBC patient sera for sEV isolation. High levels of sEV-AnxA2 protein and/or mRNA were associated with stage 3 and above in TNBC. Four patients who responded to neoadjuvant chemotherapy had high expression of AnxA2 protein and/or mRNA in sEVs, while other four who did not respond to chemotherapy had low levels of AnxA2 protein and mRNA in sEVs. Our data suggest that the sEV-AnxA2 protein and mRNA could be a combined predictive biomarker for responsiveness to chemotherapy in aggressive TNBC.
Bone-metastatic prostate cancer symbolizes the beginning of the later stages of the disease. We designed a cabazitaxel-loaded, poly (lactic-co-glycolic acid) (PLGA) nanoparticle using an emulsion-diffusion-evaporation technique. Bis (sulfosuccinimidyl) suberate (BS3) was non-covalently inserted into the nanoparticle as a linker for the conjugation of a bone-targeting moiety to the outside of the nanoparticle. We hypothesized that the nanoparticles would have the ability to inhibit the epithelial-to-mesenchymal transition (EMT), invasion, and migration in prostate cancer cells. Targeted, cabazitaxel-loaded nanoparticles attenuated the EMT marker, Vimentin, and led to an increased E-cadherin expression. These changes impart epithelial characteristics and inhibit invasive properties in cancer progression. Consequently, progression to distant sites is also mitigated. We observed the reduction of phosphorylated Src at tyrosine 416, along with increased expression of phosphorylated cofilin at serine 3. These changes could affect migration and invasion pathways in cancer cells. Both increased p-120 catenin and inhibition in IL-8 expression were seen in targeted, cabazitaxel-loaded nanoparticles. Overall, our data show that the targeted, cabazitaxel-loaded nanoparticles can act as a promising treatment for metastatic prostate cancer by inhibiting EMT, invasion, and migration, in prostate cancer cells.
In the recent decade, nanomedicine and nanotechnology have been broadly developed leading to a significant advancement in biomedical research as well as clinical practices. The application of several functionalized nanomaterials on the molecular and cellular levels has yielded a lot of promising progresses in various fields of regenerative medicine including disease diagnosis, combinational cell therapy, tissue engineering, and drug and gene delivery. In this review, we will summarize the recent approaches of nanoscale materials utilized in neurological diseases and cancer therapy, with highlights on the most current findings and future prospects of diverse biomedical nanomaterials for tissue regeneration, drug innovations, and the synthesis of delivery system.
The Texas Center for Health Disparities (TCHD) at the University of North Texas Health Science Center is a National Institute on Minority Health and Health Disparities-funded, specialized center of excellence for health disparities. TCHD organized its 12th annual conference focusing on “Evidence-Based Approaches to Reduce Cancer Health Disparities: Discover, Develop, Deliver, and Disseminate.” At this conference, experts in health care, biomedical sciences, and public health gathered to discuss the current status and strategies for reducing cancer health disparities. The meeting was conducted in three sessions on breast cancer, prostate cancer, and colorectal cancer disparities, in addition to roundtable discussions and a poster session. Each session highlighted differences in the effects of cancer, based on factors such as race/ethnicity, gender, socioeconomic status, and geographical location. In each session, expert speakers presented their findings, and this was followed by a discussion panel made up of experts in that field and cancer survivors, who responded to questions from the audience. This article summarizes the approaches to fundamental, translational, clinical, and public health issues in cancer health disparities discussed at the conference.
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