Cancer
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/30804
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Browsing Cancer by Author "Bao, Serena"
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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 Investigational Agents to Target Specificity Protein1 Transcription Factor and Survivin for Inhibiting Medulloblastoma Cells Growth(2022) Bao, Serena; Kishinchandani, Sachi; Lambring, Christoffer B.; Basha, Riyaz; Sankpal, Umesh; Nwamaka, IloaniAbstract Presenter: Serena Bao Authors: Serena Bao, Sachi Kishinchandani, Briggs Lambring, Umesh Sankpal, Iloani Nwamaka, Riyaz Basha Title: Investigational Agents to Target Specificity Protein1 Transcription Factor and Survivin for Inhibiting Medulloblastoma Cells Growth Background: Medulloblastoma (MB) is a brain cancer predominantly arising in children. It accounts for 20% of all childhood brain tumors. The treatment for MB includes a combination of surgery and radiation therapy. Although around 70% of the patients have shown remission with treatment today, these therapies are associated with significant morbidity, especially in the youngest patients. Therefore, widespread interest is shown to develop more successful treatments. One potential target of cancer treatment is a protein known as survivin. Survivin inhibits cell death and is upregulated in most cancers, including MB. A transcription factor known as Sp1 upregulates survivin by binding to its promoter region. Therefore, suppressing Sp1 activities indirectly down-regulates survivin and can serve as a target for MB therapy. Our aim is to find and test appropriate investigational agents that inhibit Sp1, thereby inhibit survivin and cancer cell growth. In addition, we want to use an in silico analysis to determine the expression of Specificity protein1 (Sp1) and survivin in MB patients, and see how it correlates with the survival of these patients. It has been previously determined that the investigational agents Tolfenamic acid (TA) and its derivative copper-tolfenamic acid (CuTA) are effective at inhibiting Sp1 in some cancer cells. In this project, we investigated the growth inhibitory effect of TA and CuTA using DAOY cell line. Method: DAOY cell lines (purchased from a commercial source, American Type Culture Collection, Manassas, Virginia; IBC-2016-0038) were cultured and seeded (2,000 cells per well) in a 96 well plate. Cells were treated using increasing concentrations (0, 10, 20, 40, 80 µM) of TA or Cu-TA. After a 48-hour incubation, the viability of the sample was measured via a luminance assay using the CellTiterGlo. Dose curves were generated, and the dose required to inhibit 50% of the viability (IC50 value) was determined using Graphpad Prism Software. Data from the R2 genomics visualization platform was used to generate Kaplain-Meier curves. The presented curves compare survival probabilities in Medulloblastoma patients with high vs. low expression of Sp1 and survivin. Results: The in silico analyses using R2 genomics visualization platform demonstrated MB patients who express higher levels of Sp1 is associated with low survival time(p = 0.033). Similarly, MB patients with higher levels of survivin expression show poor prognosis (p = 0.049) As per the IC50 values, Cu-TA is 3.6 times more effective against MB cells without affecting non-cancerous cells than TA Conclusion: Higher expression of Sp1 or survivin is associated with low survival time in medulloblastoma patients. Both TA and Cu-TA are inhibiting DAOY cell growth, however, Cu-Ta is more effective than TA against MB cell line. With increased resistance to standard therapies, TA and Cu-TA potentially enhance the therapeutic efficacy of chemotherapy and radiation.