Malignant Colorectal Cancer in the Rio Grande Valley: A Demographical Study

Background: There is abundant demographical data available that provides an excellent general statistical overview of colorectal cancer (CRC) within the Hispanic population in South Texas. Much is known about the overarching trends regarding incidence, prevalence, mortality and screening rates among this specific population as compared to other racial and ethnic groups at the state and national levels. Despite our understanding of these broad trends, few studies have taken a step inward to provide a closer demographical analysis of a CRC population here in the Rio Grande Valley. In this study, we narrow the scope and take a closer look at this population to better understand its demographical composition and to identify potential disparities specific to this region that may be overlooked by broader studies. Methods: A retrospective medical chart review was performed on 96 patients with a primary diagnosis of malignant colorectal cancer who received care at the UTHealth RGV Surgery & Women’s Specialty Center in Harlingen, Texas between January 1st, 2020 and February 5th, 2021. Data regarding age, gender, race/ethnicity, insurance status, screening usage, comorbid conditions, follow-up rates, cancer stage, tumor location and treatment outcomes were collected. Results & Conclusion: Results for this study are pending due to initial delays in the IRB review process. Data is currently being collected and results will be submitted before the July 27th deadline

Synchronous Gastrointestinal Metastatic Large Cell Neuroendocrine Tumor and Metastatic Colon Adenocarcinoma: Case Report

This article reports a case involving a synchronous silent metastatic rectal adenocarcinoma and metastatic large cell neuroendocrine tumor of the cecum and ascending colon. The patient presented with left sided abdominal pain and hematochezia with a noncontributory family, social, and medical history. This case presents a rare pathology not only due to the low incidence of synchronous gastrointestinal malignancies, but due to the unusual silent patient presentation

Stress and Molecular Drivers for Cancer Progression: A Longstanding Hypothesis

Stress management is becoming very important part of cancer patient care. Chronic stressors lead to boost tumorigenesis and promote cancer development, recurrence, and drug resistant leading to poor health outcomes. The Hypothalamic-Pituitary-Adrenal (HPA) axis, which is activated by stress, also regulates Hypothalamic-Pituitary-Thyroid (HPT) axis. Stress related changes in immune function and inflammatory response also leads to reduced immune surveillance resulting in tumorigenesis. This article explores the hormonal axis impacted by stress and how chronic stress can lead to poor outcome of a cancer patient

Molecular Modelling a Key Method for Potential Therapeutic Drug Discovery

The well-defined and characterized 3D crystal structure of a protein is important to explore the topological and physiological features of the protein. The distinguished topography of a protein helps medical chemists design drugs on the basis of the pharmacophoric features of the protein. Structure-based drug discovery, specifically for pathological proteins that cause a higher risk of disease, takes advantage of this fact. Current tools for studying drug-protein interactions include physical, chromatographic, and electrophoretic methods. These techniques can be separated into either non-spectroscopic (equilibrium dialysis, ultrafiltration, ultracentrifugation, etc.) or spectroscopic (Fluorescence spectroscopy, NMR, X-ray diffraction, etc.) methods. These methods, however, can be time-consuming and expensive. On the other hand, in silico methods of analyzing protein-drug interactions, such as docking, molecular simulations, and High-Throughput Virtual Screenings (HTVS), are heavily underutilized by core drug discovery laboratories. These kinds of approaches have a great potential for the mass screening of potential small drugs molecules. Studying protein-drug interactions is of particular importance for understanding how the structural conformation of protein elements affect overall ligand binding affinity. By taking a bioinformatics approach to analyzing drug-protein interactions, the speed with which we identify potential drugs for genetic targets can be greatly increased

Performing a High-Throughput Virtual Screening (HVTS) to identify potential therapeutic targets of YB-1 protein

Background: Hepatocellular carcinomas (HCCs) is a primary malignancy of the liver. Hispanic-Texans have several risk factors and disparities that compound the risk of HCC diagnosis and treatment. The most used chemotherapeutic drug against HCC is sorafenib, but many liver cancers have developed a resistance to this drug. The knockdown of Y-box binding protein-1 (YB-1) has been shown to greatly increase sensitivity to sorafenib. In this study, we will discuss identification of potential YB-1 inhibitors, which can lead to re-sensitization of liver cancer cells to sorafenib. Methodology: The RCSB protein data bank (pdb) was used to retrieve the crystal structure of YB1, while the DrugBank database was used to obtain a list of experimental and approved drugs. A multiple sequence alignment (MSA) of YB-1 & Lin28 was done by Clustal Omega. Biovia Discovery Studio 2020 was used to visualize 3D models and perform a High-Throughput Virtual Screening (HTVS), which includes rigid docking via the LibDock extension, flexible docking via the CDocker extension, and a pharmacokinetic profiling via an ADMET analysis. Results: The cold shock domain of YB-1 was found to be conserved with Lin28, as a known transcription factor. 22 drug candidates were identified through HTVS. The best six show a decent binding ability in both rigid and flexible dockings and have been previously tested in different cancer types to some extent. Conclusion: We were able to identify six potential drug candidates for inhibiting our protein of interest, YB-1. Studies are in progress to study them on sorafenib-resistant HCC cell lines

Role of POTE-2 in hepatocellular carcinoma progression.

Background: Hepatocellular carcinoma (HCC) accounts for 85-90% of primary liver cancers. The Hispanic population had an incidence of 21.2 per 100,000 in Texas. Particularly, the Rio Grande Valley (RGV) is an underserved area facing disparities that increase risk factors of HCC and thus, yielding higher incidence and mortality. Therefore, early, faster, and inexpensive diagnostic biomarkers and methods are crucial to under-resourced areas such as the RGV. Recently, we have identified an extracellular cancer antigen, POTE-2. Preliminary data indicates high POTE-2 expression in HCC tumors. In this study, we will discuss the role of POTE-2 in HCC progression and its associated regulatory pathways. Methods: The Cancer Genome Atlas (TCGA) database of HCC patients (n=371 tumor; n=50 normal) was analyzed. Liver cancer cells were procured from ATCC. POTE-2 mRNA and protein expression analyzed via RT-PCR and western blot. Absolute copy number was determined using Digital Droplet PCR. Lentiviral-based plasmids were used for overexpression and knockdown studies. Signaling pathways were analyzed using Proteome Profiler array. Results: Comprehensive analysis of TCGA database revealed high POTE-2 expression tumors with upregulation in all stages of HCC. POTE-2 expression increases with nodal metastatic status leading to poor survival. The protein expression for POTE-2 was significantly higher in SK-HEP1 compared to C3A cells. Lentiviral transduction showed significant overexpression and knockdown of the POTE-2 protein. Modulation of POTE-2 expression led to changes in lncRNA and kinase pathways. Conclusion: These studies will help discover novel mechanisms of POTE-2 protein function, signaling pathways and roles in liver cancer progression

Modulation of POTE-2 Expression by ncRNAs in Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) has one of the highest incidents and mortality rates within the Hispanic population of South Texas. The Surveillance, Epidemiology, and End Results (SEER) cancer registry reports a 20.3% 5-year relative survival rate upon HCC diagnoses, which decreases in advanced stage cancers. The disproportionate impact on the Hispanic community and poor prognostics makes the search for better diagnostic measures imperative. A major step in bridging the disparity in HCC occurrence is the identification of potential biomarkers aiding in HCC diagnosis, surveillance, and treatment. POTE ankyrin domain members have been recognized as key promotors of tumorigenesis. POTE-2, a novel protein, has shown to be differentially regulated in liver cancer. Micro-RNAs (miRNAs) regulate protein expression through translational inhibition or mRNA degradation. This study aims to investigate possible role of miRNA-3662 in POTE-2 expression regulation in HCC cell lines. Methods: POTE-2 mRNA and protein were analyzed using RT-PCR and western blot respectively in liver cancer cell lines, SK-HEP1, C3A, HEPG2, and HEP-3B. POTE-2 mRNA was analyzed for potential miRNA binding sites using miRNAdb.org. Identified miRNAs were verified using miRNA specific RT-PCR. Results: SK-HEP1 yielded relatively low mRNA with high protein, and the opposite was observed in C3A cells. SK-HEP1 cells showed higher proliferation, migration, and invasion. Analysis of POTE-2 mRNA using miRNA database identified potential miRNAs binding sites. MiRNA-3662 being the top candidate is being analyzed for its role in POTE-2 regulation. Conclusions: Regulation of POTE-2 mRNA by miRNA-3662 makes it a potential candidate for miRNA-based therapeutics in HCC

Stress induced lncRNA MALAT1 in colorectal cancer health disparity

Background: Health disparities in the lower Rio Grande Valley are well documented and can play a critical role in cancer prognosis. Chronic stress, arguably exacerbated by these disparities, can also lead to a poor outcome after diagnosis through dysregulation of molecular markers known to be involved in cancer progression, resistance, and recurrence. lncRNA have been a relatively recent point of interest in the field of cancer research and play a role in cancer initiation and progression across tissue types. We have found that lncRNA MALAT1 is stress induced through transcription factor NFATc1. Here, we propose to investigate the association of stress factors with NFATc1 and MALAT1 expression, and the role of these novel molecular drivers in CRC progression and metastasis. Methods: CRC tissues of different ethnicities were stained using Novel Z Probe based technology (lncRNA MALAT1) and immunohistochemistry (NFATc1). Stained tissues were scanned on digital scanner and scored. CRC cell lines were profiled for MALAT1 expression using RT-PCR. Lentiviral based overexpression (SW480) and knockdown (SW620) of MALAT1 in CRC cells was performed to study proliferation, invasion, migration, and colony forming capacity Results: MALAT1 and NFATc1 expression was scored to be high in underserved population. MALAT1 expression was lower in less aggressive SW480 cell line as compared to highly metastatic SW620 cell line. Overexpression of MALAT1 in SW480, and knockdown in SW620 resulted in changes in their oncogenic profiles. Conclusions: Understanding the mechanistic roles molecular drivers influenced by biochemical stressors can provide pivotal information pertinent to CRC progression and metastasis

Role of Nutraceuticals in COVID-19 Mediated Liver Dysfunction

COVID-19 is known as one of the deadliest pandemics of the century. The rapid spread of this deadly virus at incredible speed has stunned the planet and poses a challenge to global scientific and medical communities. Patients with COVID-19 are at an increased risk of co-morbidities associated with liver dysfunction and injury. Moreover, hepatotoxicity induced by antiviral therapy is gaining importance and is an area of great concern. Currently, alternatives therapies are being sought to mitigate hepatic damage, and there has been growing interest in the research on bioactive phytochemical agents (nutraceuticals) due to their versatility in health benefits reported in various epidemiological studies. Therefore, this review provides information and summarizes the juncture of antiviral, immunomodulatory, and hepatoprotective nutraceuticals that can be useful during the management of COVID-19