Browsing by Author "Basha, Riyaz"
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Item A Robust Model for A Sustainable Diverse Healthcare Community - The Center for Diversity and International Programs, UNT Health Science Center(2019-03-05) Jones, Harlan; Basha, Riyaz; Vishwanatha, Jamboor; Nair, MayaAbout CDIP The Center for Diversity and International Program’s (CDIP) objectives are to broaden partnerships (local, national and international), unify institutional pipeline programs, innovate education and training, and lead diverse constituencies to opportunities in biomedical/behavioral science research and Health Professional career paths. CDIP’S programs A pipe line of programs from “K-12” to “healthcare professionals” are offered by CDIP K – 12 Outreach Stimulate and broaden student’s awareness of biomedical and health professional careers paths by exposing students to clinical and laboratory research environments at UNTHSC. Undergraduate Summer Research Internships Various undergraduate summer research programs at UNTHSC are funded through numerous sources. Participants are created with minority and non-minority-serving institution partners across USA. Graduate and Health Professional Student Training Programs Supports short term and dual degree research training for underrepresented students in health professions. Faculty Grant Writing and Professional Development Provide research and mentoring to underrepresented graduate and heath professional students, post-docs and junior faculty. CDIP’S structure The main pillars of CDIP are constituted with (1) Texas Center for Health Disparities (TCHD): A National Institute of Minority Health and Health Disparities (specialized Center of Excellence in Health Disparities (U54) was announced in 2017. (1) Research (2) Education and Training and (3) Outreach (2) National Research Mentoring Network (NRMN): Develop a culture of mentoring relationships, and more broadly the research workforce. (3) Diversity Training Programs: The plan includes a variety of programs that reach out to students from K-12, through college, and into graduate school and health care professions. (4) Texas Minority Health, Education Research and Outreach: Supports PhD scholars, junior faculty development and scholarship for senior faculty. Impact of CDIP CDIP has pioneered inter professional collaboration at institutional and national levels. 801 students and 201 faculty members from various colleges/schools at UNT Health Science Center and partnering institutions across the nation participated in various programs offered by CDIP and benefiting their educational or professional career. Such collaboration resulted in more than 200 publications and $24.76 Million in research funding. In summary, CDIP functions are in full alignment with the mission of ‘One University’.Item A Small Molecule Derivative as a Targeting Agent for Sp1 and Survivin Effectively Suppresses Pancreatic Cancer Cell Growth(2017-03-14) Sankpal, Umesh; Mahammad, Shahela; Chhabra, Jaya; Brown, Deondra; Gurung, Raj; Holder, Alvin; Basha, Riyaz; Hurtado, Myrna MsBackground: Pancreatic cancer has one of the most fatal malignancies due to its poor prognosis. It currently has a one-year survival rate of 20%. Current standard forms of treatment contain a high level of toxicity, thus preventing an increase in dosage or frequency. This issue poses the need for more effective, yet less toxic agents for treatment. Tolfenamic acid (TA) is most commonly used to treat migraines but has recently been demonstrated to contain anti-cancer properties. It is known to downregulate the Specificity Protein (Sp) transcription factor, Sp1. Sp1 regulates several genes involved in cell proliferation and apoptosis, including survivin, an inhibitor of apoptosis protein. Interestingly, a recent discovery proposed that a copper(II) complex with TA as a ligand can result in higher therapeutic response; however its efficacy was not tested in gastro-intestinal cancers. Purpose: In this study, we assessed the therapeutic efficacy of a Cu(II)- containing complex of TA (Cu-TA) using human pancreatic cancer cell lines. Methods: MIA PaCa-2 and Panc1 cells were treated with increasing concentrations of DMSO (vehicle), equimolar CuCl2 (negative control), TA or Cu-TA and the cell viability was measured at 24 and 48 h post-treatment using CellTiter-Glo kit. CuTA was further tested for its effect on Sp1 and survivin expression by Western blot and quantitative PCR. The activation of apoptosis was determined by measuring the activity of effector caspases using the Caspase 3/7-Glo kit and the apoptotic cell population through flow cytometric analysis using Annexin-V staining. Cell cycle arrest was assessed by flow cytometry with propidium iodide staining. Results: While both TA and Cu-TA inhibited pancreatic cancer cell growth in a dose/time-dependent manner. Cu-TA was highly effective in inhibiting Sp1 and survivin protein expression and showed similar trend for inducing apoptotic markers and causing cell cycle arrest in G2/M phase. The results of qPCR demonstrated that the expression of survivin mRNA was significantly lower following both Cu-TA and TA treatment; however, the mRNA expression of Sp1 remained unchanged. This indicates that TA and Cu-TA could be affecting Sp1 by a similar mechanism. Conclusions: These results demonstrate that Cu-TA is more effective than TA and potentially useful for pancreatic cancer treatment after clinical testing. Studies to understand precise underlying mechanisms are currently under investigation.Item Adverse Effects of Lung Cancer Immunotherapy Among Socioeconomically Marginalized Lung Cancer Patients(2022-08) Nwaogbe, Ogochukwu; Mathew, Stephen O.; Basha, Riyaz; Adorboe, AndrewLung cancer remains a major contributor of cancer-related deaths and account for more than half of lung cancer deaths. In the U.S., lung cancer accounts for almost 25% of all U.S. cancer deaths and certain population groups bear a disproportionate burden. Immunotherapy is a novel treatment for lung cancer that has shown improvements in stalling disease progression and overall survival. But these treatments are associated with a plethora of adverse events that can affect any organ in the body. Most of the evidence on the adverse effects associated with immunotherapy is documented from clinical trials which often exclude the socioeconomically marginalized population. Hence little evidence exists on the incidence and range of adverse events in this population group. This study contributes to the evidence on the frequency and types of immunotherapy side effects experienced by socioeconomically marginalized populations.Item An Analysis of Employee Engagement within the Heart and Lung Transplant and Pulmonary Research Department of the Baylor Scott and White Research Institute at Dallas, TX.(2018-12) Lee, Daniel J.; Mathew, Stephen O.; Basha, Riyaz; Khan, Shafaat A.; Martits-Chalangari, Katalin; Martinez, HoracioIntroduction: Employee engagement is an important construct to measure, with positive employee engagement linked to favorable business outcomes such as increased customer satisfaction, increased productivity, and decreased employee turnover. Employees and interns of the Heart and Lung Transplant and Pulmonary Research Department at Baylor Scott and White Research Institute in Dallas, Texas participated in a survey study to gauge engagement levels and identify any process-improvement initiatives that could be implemented to create a better work environment. Methods: An electronic survey was created to assess various engagement drivers. The survey was then administered to employees and interns to assess how well the department was engaging them; it also provided an opportunity for respondents to bring attention to any issues or concerns they had regarding the department. Results: Due to the brevity of the survey, not all engagement drivers could be measured. However, the short length of the survey resulted in a high response rate. Results also showed the department scored high on all engagement drivers that were measured. The small sample size meant statistical analysis was limited to descriptive measures. Action items were also suggested to address the concerns brought to light by the respondents. Conclusion: The engagement drivers measured in the Heart and Lung Transplant and Pulmonary Research Department of the Baylor Scott and White Research Institute in Dallas, Texas show the staff is positively engaged. However, a survey is only a "snap shot" of one moment in time. It is therefore recommended that another survey be conducted after the action items discussed below have been implemented to measure the effects. Short surveys are ideal to get quick responses and a high participation rate. However, a longer, more thorough survey should also be created to gain further insight into all aspects of engagement of the research department. Further research into employee engagement could also be conducted by looking at such demographic factors as age, gender, and years employed at Baylor Scott and White Medical Center. Further research should also attempt to obtain a higher number of participants for greater generalizability and validity.Item Anti-cancer activity of biogenic silver nanoparticles against Neuroblastoma cells(2018-03-14) Umesh, Sankpal; Ravikumar, Nulakachandanam; Bharathkumar, Bukkapatnam; Basha, Riyaz; Rajasekhar, MaramABSTRACT Purpose: Neuroblastoma (NB) is one of the solid tumors diagnosed in young children. Due to severe side effects associated with the current therapeutic options, it is important to identify less toxic therapies for treating NB patients. Nanoparticles (NPs) are widely used in various medical applications; however, the particle size and preparation methods play critical roles in their activity. Recently use of plant extracts as stabilizing or reducing agents is gaining significance due to higher stability and activity. Biogenic silver nanoparticles (BSNPs) have been tested for their activity in wound healing mechanism and preventing microbial diseases. The objective of this investigation was to prepare BSNPs using plant extracts and silver nanoparticles and evaluate their anti-cancer activity against neuroblastoma (NB) cell lines. BSNPs were prepared using two different plant extracts and characterized. SHSY5Y and LA155n cells were treated with increasing concentrations of BSNPs for 48 h and dose curves obtained. The effect of BSNPs on apoptosis and cell cycle arrest was evaluated to understand the underlying mechanisms. Method: BSNPs were synthesized using silver NPs and herbal reducing agents. These particles were characterized by Atomic Force Microscope and Transmission Electron Microscope. Fourier-transform infrared spectroscopy was used to identify the active herbal compounds along with silver nanoparticles. The cell viability of NB cells was measured using Cell Titer-Glo kit. Apoptotic cells distribution were determined by Flow cytometry using annexin V staining The expression of cleaved Poly (ADP-ribose) Polymerase (cPARP) was evaluated by western blot. Results:. The characterization of BSNPs revealed alkynes, amines and alkylhalides as reducing agents and particles were ranged 20-100 nm in size. BSNPs caused significantly more cell growth inhibition when compared to silver NPs which is accompanied by an increase in apoptotic markers, c-PARP expression and annexin-v staining. Conclusion: These preliminary data using different reducing agents suggest the potential anti- proliferative effect of BSNPs against NB cells.Item Anti-proliferative activity of clotam and copper-clotam against T-cell Acute lymphoblastic leukemia cell line CCRF-CEM(2020) Basha, Riyaz; Siraj, Sohail; Sankpal, Umesh; Polu, Rujula; Patel, KrishnaPurpose: Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children younger than 5 years. Patients with ALL have bone marrow that produces immature white blood cells, which are unable to effectively fight infections. NSAIDs are common pain reliving agents that act through COX inhibition, which stops the production of prostaglandins. Clotam (Tolfenamic Acid/TA) is an NSAID that has anti-tumor proliferative effects. It works through targeting specificity protein (Sp) transcription factors that assist cancer cells in inhibiting apoptosis. Our objective is to test TA and copper-TA (Cu-TA), a derivative of TA, to induce an anti-leukemic response. Methods: The T-cell ALL cell line CCRF-CEM was obtained from the American Type Culture Collection (Manassas, VA) and cells were cultured as per the supplier's instructions. A cell viability assay was performed in which cells were plated in a 96-well plate and treated with increasing concentrations of TA and Cu-TA. After 48-hours, the cells were lysed, and the amount of ATP in the cells was measured using luminescence. Using this data, IC50 values were calculated. Results: The IC50 values showed both TA and Cu-TA had anti-cancer proliferative effects. Cu-TA was 15 times more potent than TA in its ability to kill CCRF-CEM cells. Conclusion: Our results demonstrate that Cu-TA is more effective than TA for killing CCRF-CEM cells. This study suggests better implications of Cu-TA in ALL therapy, if further tested using pre-clinical models.Item Anti-Proliferative Effect of Copper Tolfenamic Acid in Neuroblastoma Cell Lines(2019-03-05) Basha, Riyaz; Sankpal, Umesh; Maram, Rajasekhar; Grebennikov, SarahAnti-Proliferative Effect of Copper Tolfenamic Acid in Neuroblastoma Cell Lines Sarah Grebennikov, Yazmin Hernandez, Rajasekhar Maram, Umesh T. Sankpal, and Riyaz Basha Background:Neuroblastoma (NB) is a neuroendocrine tumor of the sympathetic nervous system most commonly found in the adrenal medulla. It is the most common extracranial tumor in infants with an average age of onset of 1 year. While presentation in children over the age of 5 is rare, the prognosis is markedly worse due to the higher likelihood of an aggressive malignancy with metastasis to lymph nodes and bone marrow. Current treatment modalities include surgical resection, chemotherapy, radiotherapy, and autologous stem cell transplant. These treatments are highly efficacious, however there are several associated side effects. Specifically, chemotherapeutic side effects are dose dependent and can range from mild stomach pain to more severe and serious complications including hearing loss, myelosuppression, and neurotoxicity. To limit these side effects, we are investigating anti-cancer agents with limited side-effects. Copper Tolfenamic Acid (Cu-TA) is metallic complex of an anti-cancer Non-Steroidal Anti-inflammatory Drug, Tolfenamic acid which is known to inhibit anti-apoptotic protein, Survivin and inhibits cancer cell growth. Hypothesis: We hypothesize that Cu-TA down-regulates survivin and inhibits neuroblastoma cell growth more effectively than TA. Methods: NB cell lines, SMS-KCNR and LA155n cell lines (from ATCC) were treated with increasing concentrations of Cu-TA or TA (0, 5, 10, 20, 40 and 80 µM). CellTiter-Glo reagent was added to the 96-well plate, and readings were taken at 24 and 48 hours. Using this data, IC50 values were calculated using SigmaPlot software. The effect of Cu-TA on Survivin protein expression was measured using western blot analysis. Results: Cell viability data showed a dose dependent decrease due to Cu-TA treatment in both cell lines. Analysis of the Western Blot confirms that there was a decrease in the survivin protein in the cells treated with Cu-TA. Conclusion:These results demonstrate that Cu-TA is an inhibitor of survivin and more effective at inhibiting NB cancer cells than TA alone. Since survivin is associated with resistance to chemotherapy, if Cu-TA sensitizes NB cells to chemotherapy, it will help reduce the side effects of chemotherapy while maintaining the efficacy of treatment.Item Anti-proliferative effects of a copper(II) complex with a thiosemicarbazone ligand against selected human cancer cells(2023) Fiadjoe, Hope; Lambring, Christoffer B.; Sankpal, Umesh; Alajroush, Duaa; Smith, Chloe; Anderson, Brittney; Mann, Novia; Beebe, Stephen; Holder, Alvin; Basha, RiyazPurpose: The frequent relapse and drug resistance associated with the current cancer chemotherapy treatments necessitate the development of alternative strategies. Thiosemicarbazones are a class of metal chelators that have been explored to treat diverse human diseases, including cancer. Copper, a crucial structural component for many significant enzymes and a key catalytic co-factor in redox processes, is being explored for several medical applications. Additionally, the anti-cancer activity of certain chemotherapeutic agents can be enhanced by the use of copper-containing complexes. This study aimed to evaluate the antiproliferative effects of a copper(II) complex with a thiosemicarbazone ligand (Cu-acetylethTSC or [Cu(acetylethTSC)Cl]Cl·0.25C2H5OH (where acetylethTSC = (E)-N-ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide)) against human cancer cell lines, viz., medulloblastoma (DAOY, D283), glioblastoma (LN-229), Ewing sarcoma (TC205, CHLA10), and acute lymphoblastic leukemia (CCRF-CEM, SUP-B15). Methods: These selected cell lines were cultured using standard protocols. Cell viability was measured using a Cell Titer-Glo kit at 48 h after treatment with various concentrations of Cu-acetylethTSC. Each treatment group and the controls were read in triplicates and the data were plotted as percentage cell viability versus concentration of the complex. Dose-response curves were generated based on the cell viability data obtained, and IC50 values were calculated. Cardiomyocytes (H9C2) were also cultured and used to test cytotoxicity in non-malignant cells. Results: Cell viability was inhibited in a dose-dependent manner in all the selected cancer cell lines whiles that of H9C2 was not significantly affected. Conclusion: This indicates that Cu-acetylethTSC was selective for malignant cells. Further studies are underway to understand the efficacy, protein targets, and underlying mechanisms of the role of Cu- acetylethTSC.Item Assessing elevated liver enzymes as a potential early screen for type II diabetes mellitus in children(2020) Bowman, William; Basha, Riyaz; Hamby, Tyler; Habiba, Nusrath; Das, SiddharthPurpose: As the rise of obesity tracks with the incidence of Type 2 Diabetes Mellitus (T2DM) and nonalcoholic fatty liver diseases (NAFLD), it suggests that metabolic changes in obesity give rise to a clinically significant association between insulin resistance and elevated liver enzymes. This is illustrated in recent adult studies showing a high prevalence of NAFLD in patients with T2DM. Considering the diagnosis of T2DM and NAFLD often occurs late into adulthood, assessing the validity of metabolic-based early screening protocols may identify high-risk individuals in the pediatric population. Our study assesses the prevalence of elevated liver enzymes in children and evaluates the association between elevated liver enzymes and noninvasive risk factors. Methods: Our study enrolled 151 nondiabetic children between the ages 10-14 at the pediatric outpatient clinic at UNTHSC. We recorded noninvasive risk factors and measured liver enzymes. The liver enzymes studied were alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transpeptidase (GGT). Results: Through chi-squared analysis, boys were shown to have a statistically significant relationship between increased BMI and elevated GGT as well a statistically significant relationship between presence of acanthosis nigricans and elevated GGT. It was also shown that young girls and African American children have a higher prevalence of ALP and GGT, respectively. Conclusions: There was significant association between elevated liver enzymes and specific noninvasive risk factors. Furthermore, this study noticed that gender and racial differences may play confounding roles suggesting there is variation within liver enzyme levels inherent in particular subpopulations.Item Assessing the cytotoxicity of investigational agent for cancer therapy against non-malignant cells(2020) Patel, Krishna; Mukka, Lasya; Sankpal, Umesh; Basha, Riyaz; Siraj, SohailBackground: The treatment of cancer requires chemotherapy (ChT). Most of ChT agents exhibit unwanted side-effect and cause damage to healthy cells. Side effects from commonly used ChT agents are leaving pediatric cancer survivors with lasting damage to organ systems, specifically the heart. Studies conducted by our group demonstrated the anti-cancer activity of clotam (tolfenamic acid-TA) and copper-clotam (Cu-TA). Cu-TA is showing higher cytotoxicity against cancer cells even at much lower dose than TA in pancreatic cancer cells. Our long term objective is to test these agents to sensitize cancer cells to ChT. Methods: Cardiomyocytes H9c2 (cell line derived from rat heart tissue) originally obtained from the American Type Culture Collection (Manassas, VA) were cultured as per the supplier's instructions. H9c2 cells were treated with TA or Cu-TA or Doxorubicin and combinations (for example, TA and Doxorubicin) and cell viability assay was measured using CellTiter-Glo (Promega) kit at 48 hours post-treatment following manufacturer's instructions. Results & Conclusion: We found that TA or Cu-TA are not inducing toxicity in H9c2 cells at tested doses. TA kept more cells alive in conjunction with Doxorubicin than did the control. Our studies also show that H9c2 cells are not toxic to IC50 values of TA or Cu-TA determined with cancer cells. These results provide evidence that the tested investigational gents are not inducing toxicity in cardiomyocytes at tested doses and supports use of these agents in combination therapy with ChT.Item ASSESSING THE PREVALENCE OF PSYCHOSOCIAL DISTRESS AMONG PEDIATRIC AND ADOLESCENT PATIENTS WITH LEUKEMIA USING THE DISTRESS THERMOMETER TOOL, AN OBSERVATIONAL STUDY(2023-05) Monteverde, Joaquin D.; Basha, Riyaz; Bailey, Laurie; Olivencia-Yurvati, Albert H.A leukemia diagnosis causes psychosocial distress in a significant number of patients. When this psychosocial need goes unattended, it can negatively affect their course of treatment. To prevent this issue, the Distress Thermometer (DT) allows a quick and valid way for patients/parents to self-report distress on a scale of 0-10, including identification of the distress source. This study descriptively evaluates the differences in distress prevalence from different demographic factors such as ethnicity, gender, leukemia type, and age.Item Association of baculoviral inhibitor of apoptosis repeat-containing 5 in the survival of clear cell renal cell carcinoma patients: In silico analysis(2021) Spore, Paul; Basha, Riyaz; Tran, Nora; Ibarra-Aleman, VictoriaPurpose Inhibitor of apoptosis proteins (IAPs) regulate several cellular processes and impacts tumor development, progression and resistance to therapy in several cancers. Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) is a member of the IAP family, which block the release of caspases from the mitochondria, a step in the cell death signaling pathway, allowing uncontrolled growth. Clear cell renal cell carcinoma (ccRCC) is the 4th most common variant of renal cell carcinoma. The objective of this study is to determine the association of BIRC 5 in the survival of ccRCC patients and evaluate the expression of BIRC 5 with the survival of patients of differing race/ethnicity. Methods Data was obtained from the online data sets (The Cancer Genome Atlas utilizing the UALCAN platform). Data of all patients (both genders and all races) revealed that BIRC5 is over-expressed in ccRCC tumors when compared to normal tissue. Results Data analysis showed significant relationship between low BIRC5 expression and higher survival probability than those with tumors that expressed high levels of BIRC5 expression, especially in Caucasians. The African American group did not have a statistical difference in survival probability between the low expression and high expression groups. There was no statistical difference in survival probability when comparing males to females or Caucasians to African Americans with the same level of BIRC5 expression. Conclusion Considering the strong association of BIRC5 with ccRCC, BIRC5 potentially serve as a predictor of prognosis and a target of treatment for improving the outcomes in ccRCC patients.Item Association of Elevated Liver Enzymes with Non-Invasive Risk Factors for Type II Diabetes Mellitus in Children(2017-03-14) Habiba, Nusrath; Hamby, Tyler; Basha, Riyaz; Shah, Deep; Bowman, Paul; Chatrath, AmritpaulPurpose: The obesity epidemic has led to an increased incidence of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) in children. This relationship is significant as the liver is intimately involved in blood glucose homeostasis as insulin resistance triggers glycogenolysis in the liver. However, there is limited research on the association between elevated liver enzymes and risk factors for T2DM in children. The purpose of this study was to assess the prevalence of elevated liver enzymes and their association with non-invasive risk factors for T2DM in non-diabetic children between the ages of 10-14 years without chronic diseases. The liver enzymes studied were alkaline phosphatase (ALP), alanine aminotransferase (ALT), and gamma-glutamyl transpeptidase (GGT). The non-invasive risk factors for T2DM are 1) Body Mass Index (BMI) [greater than] 85th percentile for age and gender, 2) blood pressure [greater than] 95th percentile for height and gender, 3) acanthosis nigricans, 4) race or ethnicity of high risk, and 5) history of T2DM in the family. A race or ethnicity of high risk includes African Americans, Hispanics, American Indians, and Asian/Pacific Islanders. Methods: Following IRB approval, the study was conducted at the outpatient clinics of the University of North Texas Health Science Center, Fort Worth. Children with elevated blood glucose levels, chronic medical conditions, or those who had received systemic corticosteroid therapy within the last year were excluded. Participation was voluntary and 151 children participated in the study who were from the representative races and ethnicities attending the clinics. Results: Results indicated that those with elevated GGT levels had marginally higher BMI (p=0.06) and were significantly more likely to have acanthosis nigricans (p Conclusions: These results suggest that there are meaningful relationships between elevated liver enzymes and non-invasive risk factors for T2DM.Item Association of Specificity Proteins and Survivin in Colon Adenocarcinoma with an Emphasis on Race/Ethnicity(2020) Basha, Riyaz; Kurri, Ananya; Mahajan, AnishaPurpose: Colorectal cancers are the third most common group of cancers worldwide in incidence and mortality, with the most prevalent of those being colon adenocarcinoma (COAD). Mutations in Specificity protein 1 (Sp1) and survivin (baculoviral inhibitor of apoptosis repeat-containing 5) have been well associated with tumorigenesis, however their impact on COAD prognosis remains unclear. The purpose of this study was to evaluate the expression levels of Sp1 and survivin in COAD clinical specimens, their impact on patient survival rates, and association with racial/ethnic disparities. Methods: Data was analyzed using two online databases: 'R2 genomics visualization platform' and 'University of Alabama Cancer Database (UALCAN)'. R2 was used to generate Kaplan-Meier curves for COAD patients with tumors expressing Sp1 and survivin (n=155 patients). UALCAN was used to generate COAD patient survival probabilities in association with race/ethnicity (n=256 patients) of African American (AA), Asian, and Caucasian descent. Results: Sp1 and survivin are overexpressed in COAD tumors and the survival curves demonstrated a link between high levels of Sp1 and survivin expression in COAD patients with a significantly poorer prognosis compared to patients with low levels of expression (Sp1, p=0.0047; survivin, p=0.041). Additionally, the survival curves revealed racial/ethnic disparities. The overexpression of Sp1 and survivin is prevalent among African American patients, correlating with poorer outcomes. Conclusion: The overexpression of Sp1 and survivin is significantly associated with poor prognosis in COAD patients, especially in African Americans. Targeting these markers can improve survival outcomes in COAD patients and address cancer health disparities.Item Association of Specificity Proteins with Hepatocellular Carcinoma Patients Survival(2022) Iloani, Nwamaka Amy; Dulemba, Victoria; Hafeez, Areeba; Bao, Serena; Basha, RiyazPresenter: Nwamaka Amy C. Iloani Authors: Nwamaka Iloani, Victoria Dulemba, Areeba Hafeez, Serena Bao and Riyaz Basha Title: Association of Specificity Proteins with Hepatocellular Carcinoma Patients Survival Background: Liver cancer is one of the most diagnosed cancers worldwide and ranks third in cancer mortality, leading to over 700,000 deaths per year. Of these liver cancers, the most common is hepatocellular carcinoma (HCC), accounting for nearly 80% of all liver cancer diagnoses. Since the current treatment options have limited improvement in prognosis over the years, identifying novel targets to induce therapeutic efficacy and reduce resistance to current therapeutic option is urgently needed. Specificity protein (Sp) transcription factors Sp1 and Sp3 are associated with incidences and poor prognosis of several cancers. Sp1 is implicated in the development and metastasis of HCC by binding to GC-rich sequences of the promoter region. Sp1 influences genetic transcription of the oncogenes encoding for the HCC by binding to gene regions such as RING1 and YY1 Binding Protein (RYBP), Ras guanine nucleotide-releasing protein 1 (RasGRP1) and many others to regulate their genetic expression. Sp3 works in a similar fashion and binds to GC and GT rich sequences in regulatory genes to affect HCC cell expression. The objective of this study is to ascertain the association of Sp1 and Sp3 expression with the survival of HCC patients using publicly available data bases. Method: Information regarding the expression levels of Sp1, Sp3, RYBP, RasGRP1 and Kaplain-Meier curves were obtained from accessing the data in the public data basses, R2 genomics visualization platform and The Cancer Genome Atlas (TCG). These data used to assess the probabilities of HCC patients with high vs low expression of Sp1 or Sp3. Results: The analysis of these data indicated significant findings. When comparing normal liver cell lines and HCC cell lines, HCC cell lines showed increased expression of both Sp1 and Sp3. The high expression of Sp1 or Sp3 is associated with decreased probability and chance of survival in comparison to individuals with decreased expression (Sp1: p< 0.027; Sp3: p< 0.0087). The survival curves of RYBP and RasGRP1 also following similar patten, however the relevance to Sp1 and Sp3 has higher impact and poor prognosis. Conclusion: Higher expressions of Sp1 and Sp3 are typically associated with poorer patient survival rates. These results suggest that the therapeutic interventions that focus on targeting Sp1, Sp3 and their downstream mechanisms have the chance for impeding HCC tumorigenesis. We are investigating the association of Sp1 and Sp3 regulated oncogenes with HCC. Investigational agents with inhibitory effect against Sp1 and Sp3 are also currently being tested against HCC proliferation. Research reported in this publication was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number (R25HL125447). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Item Association of Survivin in Liver Hepatocellular Carcinoma Patient Survival with an Emphasis on Race and Gender(2021) Tran, Nora; Basha, Riyaz; Ibarra-Aleman, Victoria; Spore, PaulPurpose: Liver hepatocellular carcinoma (LIHC) represents the most common type of primary liver cancer in many parts of the world. In LIHC, Survivin is associated with increased tumor aggression and a poorer prognosis. Survivin is a member of the inhibitor of apoptosis (IAP) protein family that inhibits caspases and thus plays a role in several molecular processes, including apoptosis. The objective of this study is to evaluate the association of Survivin expression with LIHC on the basis of race and gender. Methods: In silico analysis was conducted using information from UACLAN: A portal for facilitating tumor subgroup gene expression and survival analyses. UACLAN uses the data from The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC). Results: Analysis showed a significant relationship between high Survivin expression and lower survival probability with Asian patients than those with tumors that expressed low/medium levels of Survivin. No significant relationship in survival probability was found when comparing Survivin expression among African Americans and Caucasians. There was also a significant relationship shown between low/medium and high Survivin expression in females and lower survival probability than in men with high and low/medium expression, respectively. Lastly, a significant relationship between expression of high levels of Survivin and lower survival probability than in men whose tumors expressed low/medium levels of Survivin was shown. Conclusion: Given the significance of Survivin's expression with survival probability in Asians and gender, Survivin is a promising prognostic biomarker and target for improving the prognosis or treatment of LIHC patients.Item Brain Low Grade Gliomas: Association of Specificity Protein Transcription Factor Sp1 and MAOB with Patient Survival(2021) Ibarra-Aleman, Victoria; Basha, Riyaz; Tran, Nora; Spore, PaulPurpose MAOB and SP1 are transcription factors expressed in low-grade gliomas (LGGs). MAOB and SP1 are both involved in the regulation of MAOB and have a positive feedback that leads to increased expression of MAOB in cells. We investigated the relationship between survival times in patients with LGGs and the transcription factors SP1 and MAOB. The levels of these markers in relation to gender and race were also evaluated. Methods Data was obtained through The Cancer Genome Atlas (TCGA) utilizing "UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses". Using Kaplan Meier plots, information was obtained on expression of SP1 and MAOB alone, levels of expression and race, and levels of expression and gender in patients with LGG. Results SP1 and MAOB had lower survival times with high levels of expression. Asians and African Americans had lower survival times than Caucasians with both high and low expressions of SP1 and MAOB. There was a stark difference in survival times between high and low expression of SP1 in females as compared to males. Conclusions It appears that chemotherapeutics that target MAOB could be helpful in extending the survival times for patients with low grade gliomas. Further studies should be done to determine whether the results of gender and race are due to genetic differences or a source of health disparities.Item Characteristics and Outcomes of Patients With Hepatocellular Carcinoma Diagnosed at John Peter Smith Hospital(2023) Hull, Madison; Teigen, Kari; Bullock, Jolonda; Basha, Riyaz; Narra, KalyaniPurpose: The incidence of hepatocellular carcinoma (HCC) is increasing in the US, particularly in individuals infected with hepatitis C (HCV). Although early detection is crucial for better outcomes, at present, there is conflicting evidence regarding HCC screening and its reduction on cancer-related mortality. This study aimed to determine overall survival, prognostic factors influencing survival, and the effects of screening at-risk patients on HCC-related mortality. Methods: A retrospective chart review of patients diagnosed with HCC from 1/1/2018 to 6/4/2021 for the one-year survival analysis and 6/4/2019 for the three-year analysis. Person-time was calculated as the days from the date of diagnosis until the last known encounter or death. The primary exposure of interest was screening within two years prior to the diagnosis date via ultrasound, MRI, and/or CT. Potential covariates were age at diagnosis, race/ethnicity, gender, insurance status, alcohol use disorder, HCV, HBV, and cirrhosis. Kaplan Meier, log rank test, and Cox proportional hazards (CPH) model were used to assess survival curves, survival distributions across screening status, and the effects of additional covariates on prognosis at one and three years, respectively. A backwards stepwise regression was used on the covariates identified via a pre-univariate filtering to construct a multivariable model. Results: There were 165 and 71 patients who met the one- and three- year inclusion criteria, respectively. Survival at one and three years was 38% and 14%, respectively. Median survival for the 165 patients was 265 days (95% CI: 166, 337). Overall, 36% (n=59/163; 2 missing) and 27% (n=19/70; 1 missing) were screened prior to diagnosis. The CPH model showed a statistically significant difference in hazard ratio of death in the first year for those without screening compared to patients with screening (HR: 1.9; 95% CI: 1.2, 3.0; p-value: 0.005). After adjusting for race/ethnicity and insurance type, the CPH model yielded similar results (HR: 2.2; 95% CI: 1.3, 3.6; p-value: 0.002). The CPH model showed a statistically significant difference in hazard ratio of death in three years for those without screening compared to patients with screening (HR: 3.4; 95% CI: 1.7, 7.1; p-value: 0.001). After adjusting for gender, HBV, and race/ethnicity, the CPH model yielded similar results (HR: 2.2; 95% CI: 1.2, 4.0; p-value: 0.009). Conclusion: Overall survival in patients diagnosed with HCC at JPS, a safety-net hospital, is similar to national statistics. Screening in patients at-risk for HCC shows improved survival at one and three years. Further evaluation based on the extent of disease at the time of diagnosis, treatment decisions, and type/timing of screening could be beneficial in determining the outcomes in HCC patients.Item Clinical Significance of Annexin A2 in Predicting Poor Prognosis in African American Women with Triple-Negative Breast Cancer(2017-05) Gibbs, Lee D.; Vishwanatha, Jamboor K.; Basha, Riyaz; Lovely, Rehana S.; Mathew, Porunelloor A.; Singh, MeharvanTriple-negative breast cancers (TNBC) are identified by the absence of these three major receptors that drive most breast cancer subtypes. TNBC is the most aggressive breast cancer subtype and studies have shown that the incidence of TNBC is much higher in premenopausal African American (AA) women and woman of African descent in comparison to woman of European descent. TNBC in AA women has been associated with worst overall survival after controlling for socioeconomic factors, treatment latency, and tumor receptor expression. This suggests that the clinical outcome of TNBC in AA women may result more from biological differences than access to adequate healthcare. Utilizing a large archived breast cancer cohort of genome sequencing information and the evaluation of these targets in breast tissue and serum can lead to recognition of reliable biological markers that have tremendous potential to enhance detection, treatment, and prognosis. Our previous studies have shown that Annexin A2 (AnxA2), a 36 kda calcium-dependent phospholipid binding protein, is abundantly expressed in TNBC. We have shown AnxA2 to play multiple roles in TNBC by regulating cellular functions; including plasminogen activation, angiogenesis, proliferation, migration, invasion, and metastasis. AnxA2 is one of the most identified proteins expressed in exosomes (small vesicles that are secreted from tumors as metastatic regulators). We have previously demonstrated exosomal AnxA2 contribution to metastasis of TNBC cells in vivo. The proposed study will determine the correlation of AnxA2 with poor prognoses in AA TNBC patients, and establish the clinical significance of exosomal AnxA2 in contributing to the poor clinical outcomes seen in AA TNBC patients. Three specific aims were addressed in this work. Aim 1- Determine the association of secreted exosomal AnxA2 with TNBC amongst AA patients. Aim 2 - Evaluate AnxA2 expression in TNBC tissue samples amongst a breast cancer patient cohort of various breast subtypes. Aim 3 - Determine the correlation of AnxA2 gene expression with poor pathological, prognostic variables and race/ethnicity in TNBC patients through in silico analysis.Item Combination of Mithramycin and Standard Chemotherapeutic Agents Induces Anti-proliferative activity in Ewing Sarcoma cell lines(2018-03-14) Hunter, Abigail; Lout, Holly; Dunlap, Elissa; Sankpal, Umesh; Bowman, W. Paul; Basha, Riyaz; Ray, Anish; Albeer, LinaBackground/Hypothesis: Ewing sarcoma (ES) is a small, round, blue cell tumor found primarily in bones of adolescents. The EWS-FLI1 transcription factor is associated with proliferation of cancer cells and is over-expressed in [greater than] 85% of Ewing sarcoma cases. Mithramycin (MIT) is an antibiotic with antineoplastic properties and has been shown to inhibit EWS-FLI1. A recent trial of MIT treatment in ES patients found that hepatotoxicity precluded the administration of MIT at a dose required to inhibit EWS-FLI1 ([greater than]50nmol/L). We hypothesize that the efficacy of adjunct treatment can be enhanced if MIT is used along with standard chemotherapeutic agents such as Vincristine (VIN) and Etoposide (ETO). Combination treatment will reduce the effective dose of both Mithramycin and the standard agent thereby decreasing the therapeutic dose range and side effects. Methods: ES cells, CHLA10 and TC205 were cultured in the presence of vehicle or MIT or VIN or ETO or in combinations (MIT+VIN or MIT+ETO). After 2 days, cell viability was measured using The CellTiter-Glo® Luminescent Cell Viability Assay kit. The apoptosis induced by each of the above-mentioned treatments on the ES cells was measured by Flow cytometry using Annexin V Apoptosis Detection Kit. The expression of cleaved-Poly (ADP-ribose) polymerase (c-PARP), a marker for apoptosis was determined by Western blot analysis. Results: While all treatments showed ES cell growth inhibition, the combination treatment of MIT+ETO was more effective (significant at p Conclusion: The combination MIT+ETO caused more cell growth inhibition when compared to individual treatments in the TC205 and CHLA10 cell lines. These results demonstrate that MIT in combination with standard chemotherapeutic agents potentially increases therapeutic efficacy in ES. However, these results are limited to in vitro studies and need to be tested in an animal model to determine reproducibility and assess the toxicity.