Browsing by Subject "biomarker"
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Item Combination of Small Extracellular Vesicle-Derived Annexin A2 Protein and mRNA as a Potential Predictive Biomarker for Chemotherapy Responsiveness in Aggressive Triple-Negative Breast Cancer(MDPI, 2023-01-09) Desai, Priyanka P.; Narra, Kalyani; James, Johanna D.; Jones, Harlan P.; Tripathi, Amit K.; Vishwanatha, Jamboor K.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(Ca(2+))-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.Item Investigation of Anterior Cruciate Ligament Fibroblast Biomarkers for Cell Characterization by Immunohistochemistry(2015-12-01) Lerma, Tanya; Geoffrey Guttmann; Rehana S. Lovely; Rustin E. ReevesApproximately 200,000 anterior cruciate ligament (ACL) injuries occur in the United States per year. This ligament is also the most commonly injured ligament of the knee joint. Surgical reconstruction using autografts from the patient is the main method of treatment to date; however, cadaver tendon allografts may also be used. A less invasive and more promising method for repair is ligament engineering. Growth factors, a proper matrix, and suitable cells, are a few of the necessary components of a ligament construct. A common protocol to engineer a ligament is to use ACL fibroblasts and to seed them into a matrix or scaffold that allows the creation of a similar tissue. However, to date no successful construct has been engineered. In order for an engineered construct to be successful and resemble a human ACL, an understanding of the cellular components of the ACL fibroblasts is necessary. The existence and role of the cellular components in the human ACL allows for the ligament to maintain its mechanical properties. Therefore, it is necessary to investigate every aspect of this tissue, including using reliable biomarkers to properly characterize human ACL fibroblasts. In this study, we will identify a combination of biomarkers specific to these fibroblasts using the method of immunohistochemistry. The central hypothesis of this study is that the biomarkers of interest, vimentin, fibronectin, alpha-smooth muscle actin(α-SMA), Fibroblast Growth Factor Receptor 1 (FGFR1), and collagen III will be a suitable and reliable combination of markers to characterize anterior cruciate ligament (ACL) fibroblasts because 100% of the cells are expected to stain positive for these biomarkers by the method of immunohistochemistry. However, our results indicate that none of the biomarkers were detected in cells at a rate of 100%. Fibronectin and collagen III abundance in the ECM made it difficult to determine specific production by an isolated fibroblast. However, both biomarkers were detected in abundance by fluorescence intensity. FGFR1 and vimentin stained positive in over 50% of cells, but less than 95%. Alpha-SMA was more variable due to two of the ligaments having 0% of cells stain positive for this biomarker. However, samples that did show expression of alpha-SMA that stained over 46% of cells.Item Post-transcriptional and Epigenetic Regulation of MIEN1 in Prostate Cancer(2014-08-01) Rajendiran, Smrithi; Vishwanatha, Jamboor K.; Basu, Alakananda; Berg, Rance E.Migration and invasion enhancer 1 (MIEN1), a gene located in the 17q12 region of the human chromosome, enhances migratory and invasive potential of cancer cells via two mechanisms; activating the Akt dependent NF-κB downstream signaling and facilitating filopodia formation; thereby playing an important role in cancer progression. MIEN1 is highly expressed in many cancers including prostate and breast, but its expression is very basal to null in a variety of normal tissues making it a plausible target for cancer therapy. Though the functions of MIEN1 are known, the reasons for its increased expression in cancer is unknown. Determining the molecular gene regulatory mechanisms by which expression of MIEN1 is curtailed in normal cells will help in developing better targeting strategies. Among the different gene regulatory mechanisms including transcriptional regulation, post-transcriptional modifications and histone and DNA alterations, here we focus on post transcriptional and DNA methylation based regulation of MIEN1. We show that MIEN1 is downregulated post-transcriptionally by miRNA-940 which itself is present in low amounts in cancer cells and tissues compared to the normal counterparts. The miR-940 also contributes to inhibition of cancer progression by attenuating the migration, invasion, anchorage-independent growth and epithelial-to-mesenchymal transition, when ectopically re-introduced into cancer cells. The miR-940 can be detected in circulation and its elevated levels in serum from cancer patients than normal subjects, suggest its potential as a biomarker for prostate cancer diagnosis. MIEN1, like urokinase plasminogen activator, is also suppressed by DNA methylation in normal cells. On the contrary, hypomethylation in cancer, results in its overexpression. The current approach of using global demethylating agents to activate the expression of hypermethylated tumor suppressor genes may in the long run activate tumor promoting genes like MIEN1. Thus, our study supports the notion that gene-centric hypomethylating agents may be a better epigenetic targeting approach to treat cancer. In conclusion, our data confirm the role of post-transcriptional and DNA methylation mediated mechanisms in the regulation of MIEN1.Item Salivary Exosomes in Health and Disease: Future Prospects in the Eye(MDPI, 2023-04-14) Liu, Angela; Hefley, Brenna; Escandon, Paulina; Nicholas, Sarah E.; Karamichos, DimitriosExosomes are a group of vesicles that package and transport DNA, RNA, proteins, and lipids to recipient cells. They can be derived from blood, saliva, urine, and/or other biological tissues. Their impact on several diseases, such as neurodegenerative, autoimmune, and ocular diseases, have been reported, but not fully unraveled. The exosomes that are derived from saliva are less studied, but offer significant advantages over exosomes from other sources, due to their accessibility and ease of collection. Thus, their role in the pathophysiology of diseases is largely unknown. In the context of ocular diseases, salivary exosomes have been under-utilized, thus creating an enormous gap in the literature. The current review discusses the state of exosomes research on systemic and ocular diseases and highlights the role and potential of salivary exosomes as future ocular therapeutic vehicles.