Browsing by Author "Cooksey, Luke"
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Item Correlating DCE-MRI Vascular Changes and T2-MRI Contour Changes of the Muscles of Swallowing in Patients with Osteoradionecrosis of the Mandible following Intensity-Modulated Radiation Therapy for Head and Neck Cancers.(2020) Mohamed, Abdallah; Fuller, Clifton; Cooksey, LukePURPOSE: Radiotherapy is a treatment modality that is curative for the treatment of many head and neck cancers and is a mainstay of the standard treatment regimen of these cancers. Though beneficial in most cases, radiotherapy in the head and neck area carries toxicity risks associated with treatment: dysphagia, chronic aspiration pneumonia, and osteoradionecrosis are considered amongst those with the most impact. Osteoradionecrosis (ORN), or death of bone tissue due to radiation, affects only a small percentage of those receiving radiotherapy. However, ORN carries significant risks and detriments to quality-of-life when it does occur. Our work in this area seeks to identify and correlate changes in Dynamic Contrast-Enhanced (DCE) MRI vascular parameters with changes in T2-MRI swallowing muscle contours in patients who have received a diagnosis of ORN following Intensity-Modulated Radiation Therapy (IMRT). METHODS: For 95 patients who received a diagnosis of ORN, swallowing muscles were precisely contoured on pre-treatment and during-treatment T2 MRI images. The images were then compiled with pre-treatment CT-based radiation plans and DCE-MRI images using a software called "Dicompyler." RESULTS/CONCLUSIONS: While the work is still on-going, preliminary observations have indicated it is likely the overall aim to create a registry for assessing patient risk of ORN development is very possible. Future direction should be to continue compiling and registering ORN patient data and to begin preliminary work of establishing parameters and algorithms that can be safely tested in patients for analysis of clinical usefulness.Item Correlating DCE-MRI Vascular Changes and T2-MRI Contour Changes of the Muscles of Swallowing in Patients with Osteoradionecrosis of the Mandible following Intensity-Modulated Radiation Therapy for Head and Neck Cancers.(2021) Cooksey, Luke; Fuller, Clifton; Lai, Stephen; Mohamed, AbdallahPURPOSE: Radiotherapy is a highly-effective mainstay of the standard treatment regimen for head and neck cancers. Though beneficial in most cases, radiotherapy in the head and neck area carries several toxicity risks associated with treatment: dysphagia, chronic aspiration pneumonia, and osteoradionecrosis are considered amongst those with considerable negative impact. Osteoradionecrosis (ORN), or death of bone tissue due to radiation, affects only a small percentage of those receiving radiotherapy. However, ORN carries significant risks and detriments to quality-of-life when it does occur. Our work in this area seeks to identify and correlate changes in Dynamic Contrast-Enhanced (DCE) MRI vascular parameters with changes in T2-MRI swallowing muscle contours in patients who have received a diagnosis of ORN following Intensity-Modulated Radiation Therapy (IMRT). METHODS: For 95 patients who received a diagnosis of ORN, swallowing muscles were precisely contoured on pre-treatment and during-treatment T2 MRI images. The images were then compiled and registered with pre-treatment CT-based radiation plans and DCE-MRI images using a software called "Dicompyler." RESULTS/CONCLUSIONS: While the work is still on-going, preliminary observations have indicated it is likely the overall aim to create a database registry and timeline for assessing patient risk of ORN development is very possible. Future directions, based on preliminary observations, should be to continue compiling and registering ORN patient correlation data and to begin preliminary work of establishing parameters and algorithms that can be safely utilized in patients for analysis of clinical efficacy and effectiveness.Item Glioblastoma multiforme expresses cell surface PCNA, a potential target for NK cell-mediated immunotherapy.(2022) Cooksey, Luke; Mathew, Porunelloor A.Purpose: Glioblastoma multiforme (GBM) is the most common form of primary brain cancer and carries a dreadful five-year survival rate of 9%. Current treatment options include surgery, chemotherapy, and radiation. Recently, there has been a move to pursue immunotherapy options to improve patient outcomes. These therapies often depend on the identification of molecular markers that are distinctive to the tumor cells. Some markers, such as HER2/Neu and EGFR, are overexpressed on a significant percentage of GBM tumors and are used as targets for immunotherapies. However, to address GBM tumors that do not overexpress HER2/Neu and EGFR, our lab set out to identify novel markers on GBM as future candidates for Natural Killer (NK)cell-mediated immunotherapy. Methods: Previously, our lab demonstrated that Lectin-like Transcript-1 (LLT1), membrane-bound Proliferating Cell Nuclear Antigen (PCNA), NKp44 Ligand (NKp44L) and CS1 (CD319) are targets of NK cell-mediated killing of various cancers. Based on these prior studies, we examined their expression on the well-known GBM cell lines LN-229 and LN-18 by flow cytometry using PE-labeled antibodies specific for each marker. Results: PCNA was the lone marker of our panel identified to be highly expressed on both LN-229 and LN-18 cells. Conclusions: Based on our results, we concluded that cell surface PCNA is an ideal candidate for NK cell-mediated immunotherapy for GBM. Currently, we are evaluating blocking inhibitory signals to NK cells from the PCNA-NKp44 interaction to target GBM for NK-mediated killing. Recent findings demonstrating the ability to transiently open the blood-brain barrier further increase the feasibility of targeting GBM by NK cells with monoclonal antibodies in the future.Item Health Literacy: Obstacles to Quality Healthcare in Tarrant County(2019-03-05) Cooksey, Luke; Ahn, Soongjin; Rose, Sushyreta; Hubbard, Daniel; Vo, RussellPurpose: To identify the primary barriers to health literacy and the resources available to community members to optimize health literacy. Background & Conclusion: Health literacy is defined as the degree to which individuals have the capacity to obtain, process, and understand basic health information and the services needed to make appropriate health decisions. According to the U.S. Department of Health & Human Services, only 12% of persons in the United States are classified as proficient, meanwhile more than 25% of persons ([greater than] 77 million people) in the United States experience difficulty with mundane health tasks like following the directions on a prescription label. There are a variety of influencing factors that determine a person’s overall health literacy including demographic factors, biological, and psychosocial factors. There are four main demographic factors that influence health literacy: poverty status, race/ethnicity, education level, and age. Patients that are below the poverty status line, have minority status, have achieved less than a high school education or its equivalent, and/or are above 65 years of age are at an increased risk of possessing less than proficient health literacy. The primary biological and psychosocial aspects that influence health literacy include a patient’s lifestyle and occupation, language competency, culture, and/or cognitive ability. In Tarrant County, there are a number of accessible and expedient resources available to healthcare professionals and members of the community to optimize health literacy and subsequently, health outcomes. The resources available include: United Way of Tarrant County Health Symposium, North Texas Area Community Health Centers, Tarrant County Diabetes Collaboration, Healthy Aging and Independent Living Initiative, Health Education and Literacy Project Consortium, UNT Health Science Center, and of course, your primary care provider.Item LN-229 glioblastoma multiforme cell line expresses CD155 (PVR), a target for Natural Killer Cell-mediated immunotherapy(2024-03-21) Cooksey, Luke; Mathew, Porunelloor; Mangan, EnriquePurpose: Glioblastoma multiforme (GBM) is the most common form of primary brain cancer in adults. Currently, it has a dismal five-year survival rate of less than 7%. Current commonplace treatment options include surgery, chemotherapy, and radiation. In recent years, there has been a major attempt at bringing the immunotherapy revolution into the treatment pillars for GBM. Immunotherapies depend upon targeting molecular antigens that are unique to cancer cells. Our lab is currently working to identify novel antigens on GBM as future candidates for Natural Killer (NK) cell-mediated immunotherapy. In several cancers, the surface antigen known as CD155 (PVR) has been shown to be overexpressed and is important as part of a mechanism for cancer cells to evade NK cell and T cell-mediated immune responses. Typically, CD155 is not highly expressed on healthy cells, making it an attractive immunotherapy target. We set out here to investigate the expression of CD155 on LN-229 cells. Methods: We examined the expression of CD155 on the LN-229 GBM cell line using flow cytometry utilizing PE-labeled antibodies specific for CD155. Our hypothesis: LN-229 cells would show increased detection of fluorescence signal (from anti-CD155 antibodies) when compared to the fluorescence detection of negative control groups (no staining group and PE-isotype control group). Results: CD155 detected on LN-229 cells via the detection of increased fluorescence signal (versus negative controls). Conclusions: Based on our results, we concluded that CD155 is overexpressed on the LN-229 cell line and is a sufficient candidate for studying NK cell-mediated immunotherapy in in vitro contexts using LN-229 cells. Currently, we are evaluating blocking inhibitory signals to NK cells mediated through the CD155-TIGIT interaction to target GBM for NK cytotoxicity in LN-229 cells.Item NK-cell target immunotherapy for Hepatocellular carcinoma (HCC)(2022) Allison, Michaela; Mathew, Stephen O.; Mathew, Porunelloor A.; Cooksey, LukeNatural killer (NK) cell immunotherapies have recently been gaining traction for treatment of both hematological and solid tumors due to their innate anti-tumor characteristics. NK cell activity is characterized by a balance of activating and inhibitory receptor interactions rather than antigen recognition, rendering this innate lymphoid cell a promising therapeutic target that does not rely on prior sensitization. Immunotherapies focused on targeting NK cell activity in the form of adoptive transfer, immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) NK cells have shown some success in combating immunosuppressive effects seen during cancer. Significant suppression of NK cells has been identified in the most common type of liver cancer, hepatocellular carcinoma (HCC). NK cells play a pivotal role in the liver by early recognition and lysis of virally infected and cancerous cells introduced through portal circulation and unsurprisingly, dysfunction of this immune cell subset due to the hypoxic HCC microenvironment has been implicated as strongly correlated with poorer prognosis and decreased survival of HCC patients. Research investigating the effects of NK cell suppression has indicated that targeting NK cell suppressive interactions mediates increased lysis of HCC cells. Our research has shown the upregulation of immunosuppressive NK cell ligands on HCC cells that could potentially lead to immune escape mechanisms in HCC cells. Research further elucidating receptor-ligand interactions involved in suppression of NK cell activity during HCC could provide insight into potential therapeutic targets for patients who are untreatable with conventional therapies.Item U-87 MG glioblastoma multiforme cell line expresses cell surface PCNA, a prospective target for Natural Killer Cell-mediated immunotherapy.(2023) Cooksey, Luke; Mathew, Porunelloor A.Purpose: Glioblastoma multiforme (GBM) is the most common form of primary brain cancer in adults and carries a dreadful five-year survival rate of less than 7%. Current commonplace treatment options include surgery, chemotherapy, and radiation. Recently, there has been a move to pursue immunotherapy avenues to improve patient outcomes. These therapies often depend upon the identification of molecular antigens that are particular to cancer cells. Some antigens, such as EGFR, are overexpressed on a significant percentage of GBM tumors and are useful as targets for immunotherapies. However, to address GBM tumors that do not overexpress well-known antigens, our lab set out to identify novel antigens on GBM as future candidates for Natural Killer (NK) cell-mediated immunotherapy. Previously, our lab has demonstrated that cell surface-bound Proliferating Cell Nuclear Antigen (PCNA) can serve as a target of NK cell-mediated killing of several cancers. Cell surface PCNA is not expressed on healthy, non-malignant cells – making it an attractive immunotherapy target. We have also previously shown cell surface PCNA to be expressed on other GBM cell lines (LN-229 and LN-18). We set out here to investigate the potential expression of cell surface PCNA on U-87 MG cells. Methods: Based on the prior studies, we examined the expression of PCNA on the U-87 MG GBM cell line via flow cytometry using PE-labeled antibodies specific for PCNA. For comparison, we did the same experiment in the same setting with LN-18 cells, one of the previously mentioned cell lines that expressed PCNA. Our hypothesis: U-87 MG cells would show increased detection of fluorescence signal of anti-PCNA antibodies when compared to the fluorescence detection of negative control groups (no staining group and PE-isotype control group). Results: PCNA was identified to be expressed on U-87 MG cells via the detection of increased fluorescence signal versus negative controls, though to a lesser degree than that of LN-18 cells. Conclusions: Based on our results, we concluded that cell surface PCNA is expressed on the U-87 MG cell line and is a candidate for studying NK cell-mediated immunotherapy in in vitro contexts using U-87 MG cells. Currently, we are evaluating blocking inhibitory signals to NK cells mediated through the PCNA-NKp44 interaction to target GBM for NK cytotoxicity in U-87 MG cells.