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    Annexin A2 in tumor-derived extracellular vesicles: Molecular contributions in metastatic triple negative breast cancer
    (2023) Trivedi, Rucha; Vishwanatha, Jamboor
    Purpose Tumor-derived extracellular vesicles (TEV) are highly implicated in tissue-specific metastasis. Additionally, TEV interacts with the distant microenvironment to shape a pre-metastatic niche (PMN) for homing the tumor cells. Annexin A2 (AnxA2) is a plasma and endosomal membrane-associated protein. Its high levels have been correlated with poor distant metastasis-free survival and poor overall survival in triple negative breast cancer (TNBC) patients. It is also abundantly present in TEV and recruits TEV-associated cargo such as proteins and microRNAs. Our lab reported that in vivo education with AnxA2 depleted EV led to reduced TNBC metastasis to lungs and brain suggesting a key role in the formation of a PMN. While the presence of AnxA2 in EV has been reported, its contribution in the formation & development of PMN via EV is still unexplored. We aim to evaluate the implications of AnxA2 in EV & elucidate the mechanisms promoting TNBC metastasis. Methods We used shRNA- mediated gene silencing to stably downregulate AnxA2 in organotropic TNBC cell lines derived from the parent MDA MB 231 cells. Differential ultracentrifugation was used to isolate EV from cell culture supernatant & size analysis was done using NTA. Biological characterization was done in concordance with MISEV 2018 guidelines using immunoblotting. Additionally, the EVs will be subjected to quantitative proteomic and transcriptomic analysis to identify differentially expressed proteins and genes upon loss of AnxA2. Results Upon depletion of AnxA2 protein, we observed a significant effect of AnxA2 depletion on its physiological role in plasmin generation. We observed a size distribution of the isolated EV between 30-300 nm. Using immunoblotting we confirmed reduced levels of AnxA2 in EVs derived from AnxA2 depleted TNBC cells. We verified their purity using EV enriched markers - ESCRT, Heat shock proteins & tetraspanins such as CD81, CD9, CD63 & confirmed the absence of negative markers - GM130, calnexin & cytochrome c. Interestingly, we observed a reduced yield of EV with AnxA2 depletion indicating a potential effect on EV biogenesis & release. Conclusion The role of AnxA2 in TEV biogenesis, release and selective cargo loading will lead to potential identification and understanding of the novel secretory and EV protein that may act as a functional regulator in promoting advanced metastasis in TNBC.
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    Looking Beyond Standard Chemotherapy: Peptides in Breast Cancer Treatment
    (2023) Tripathi, Amit K.; Vishwanatha, Jamboor K.
    Background: Chemotherapy is the most established method of treatment that kill fast-dividing cancer cells. However, most cancer drugs have very poor cell selectivity and kill normal cells along with cancer cells indiscriminately. Besides, the continuous use of this therapy increases the possibility of drug resistance in the body along with the chances of recurrence. The usage of peptide-based drugs to combat cancer is gaining significance in the pharmaceutical industry. The collateral damage caused to normal cells due to the use of chemotherapy, radiotherapy, etc. has given an impetus to the search for alternative methods of cancer treatment. Candidate Protein: In the fight against cancer, newer strategies to combat cancer progression are of utmost importance. Peptides derived from naturally occurring proteins are an important strategy to identify lead molecules in the field of cancer therapeutics. Migration and invasion enhancer 1 (MIEN1) is one such candidate protein that is overexpressed in various cancers and plays an important role in cancer cell migration and invasion. Conserved regions of ITAM and prenylation motif in MIEN1 were used as a template to identify anti-cancer peptides. In vitro Results: The two newly identified bioactive peptides (named LA3IK and RP-7) inhibited genes and proteins responsible for cancer cell migration and invasion in both MDA-MB-231 breast cancer. RNA-seq, qPCR analysis and western blots showed changes in the transcriptome and protein expression after peptide treatment. The mechanism of the action of the peptides involves the inhibition of key pathways like Epithelial-Mesenchymal transition and Epidermal Growth Factor-mediated NF-κB pathway to exert their anti-cancer activity. Interestingly, the peptides targeted the same signal transduction pathways followed by parental MIEN1 to show their anti-cancer properties. Thus, the two peptides acted as dominant negative effectors of MIEN1 activity. In vivo results: Additionally, LA3IK and RP-7 peptide treatments induced apoptosis in mice groups bearing tumors derived from MDA-MB-231 cells as evidenced by increased levels of cleaved caspase-3 and PARP proteins in western blots. Intriguingly, the MIEN1 mRNA and protein levels were lowered in the in vivo breast cancer tumor models that remained unchanged in in vitro experiments indicating an improved therapeutic activity in the living system. The peptides did not cause any toxicity in the mice group that received peptides only, at three times the dose used during in vivo assays. Pharmacokinetic studies: The PK studies along with the half-life determination and plasma-binding studies are underway in collaboration with the Preclinical Pharmacology Core of UT Southwestern Medical Center to identify and improve the drug-like characteristics of the MIEN1-protein derived anti-cancer peptides LA3IK and RP-7. IP Status: An intellectual property right application has been filed for LA3IK and RP-7 in August 2022. The patent status is pending. Acknowledgments: The work was supported by The Texas Center for Health Disparities (TCHD) under the award number: U54MD006882
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    Characteristics and Outcomes of Patients With Hepatocellular Carcinoma Diagnosed at John Peter Smith Hospital
    (2023) Hull, Madison; Teigen, Kari; Bullock, Jolonda; Basha, Riyaz; Narra, Kalyani
    Purpose: 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.
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    Expression of Specificity protein 1 in tumor tissues and its impact on the prognosis of cancer patients with an emphasis on race/ethnicity
    (2023) Qadri, Syed; Rama, Kush
    Title: Expression of Specificity protein 1 in tumor tissues and its impact on the prognosis of cancer patients with an emphasis on race/ethnicity Background: Specificity protein (Sp) transcription factors (eg., Sp1, Sp3 and Sp4) play a vital role in growth and development. Sp1 is known to regulate genes that are critical for angiogenesis, tumor growth and metastasis. The overexpression of Sp1 is associated with poor prognosis in some cancers for all populations, however, it may vary depending on the demographic background. Objective: The objective of this project is to analyze the expression of Sp1 in various tumor tissues and evaluate the association with the prognosis of cancer patients using the publicly available online data sets. The other goal is to understand the impact on prognosis with race/ethnicity. Methods: Data was obtained from the publicly available resources, The Cancer Genome Atlas (TCGA) (a landmark cancer genomics program developed by the National Cancer Institute and the National Human Genome Research Institute). Information was collected for 34 cancers and screened for the expression status (upregulated or downregulated), significance and relevance to prognosis of all patients and in relation to race/ethnicity. Results: The information on the level of Sp1 expression was not available for 11 of the cancers in the database. The results are presented for the cancers that TCGA provided Sp1 expression information for. In 60% of the 23 cancers screened, Sp1 expression significantly impacted patient survival resulting in a poorer prognosis. The significance range was between 1.2E-02 to 4.43E-10. In a third of cancers evaluated, Sp1 expression affected the prognosis of patients depending on race/ethnicity. Interestingly, the association of Sp1 with poorer prognosis was found in certain racial/ethnic patients, despite there being no significant effect on the prognosis when combining the data for all patients. Glioblastoma, lung squamous cell carcinoma and prostate cancer are among the cancers that showed relevance to prognosis based on race/ethnicity even though there was no response on the overall survival of all patients combined. Conclusion: These preliminary observations suggest an association between Sp1 expression in tumor tissues with the prognosis of some cancers. The results also suggest that Sp1 can differentially affect the population and may contribute to a poorer prognosis for patients belonging to a certain race/ethnicity in some cancers.
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    In Silico Analysis to Determine the Association of Specificity Protein (Sp) Transcription Factors, Sp1 and Sp3 and Survivin Expression with the Prognosis of Cancers Affecting Women
    (2023) Patel, Pooja; Dutta, Arpam
    Background: Breast cancer is the most common invasive cancer in women worldwide. Studies have shown that breast cancer shares risk factors and genetic mutations with ovarian and uterine cancers which are also analyzed to be increasing in incidence. Clinically, diagnosis of concurrent genetically shared cancers like breast, ovarian, and uterine would have an impact on the treatment options and its course. Dysregulation of transcription factors like Specificity protein (Sp) 1 and 3 which remodel chromatin is responsible for many cancers. While the expression of Sp1 is documented to be upregulated in breast and ovarian cancer, and Sp3 only in breast; uterine cancer lacks such evidence. Baculoviral IAP repeat-containing 5 (BIRC5), also known as survivin, is an inhibitor of the apoptotic pathway and is found to be upregulated in breast, ovarian, and uterine cancer. Sp1, Sp3 and survivin are all associated with high expression in numerous cancers and lead to poor prognosis. Objective: The objective of this study is to analyze the expression of Sp1, Sp3 and survivin in breast invasive carcinoma, ovarian serous cystadenocarcinoma, and uterine corpus endometrial carcinoma to evaluate the prognosis (in all patients and by race/ethnicity) of cancer patients using the data deposited in a public database. Methods: Relevant data and Kaplain-Meier curves were obtained from accessing the public database, The Cancer Genome Atlas (TCGA) (a landmark cancer genomics program developed by the National Cancer Institute and the National Human Genome Research Institute). This data was used to screen for the expression status (upregulated or downregulated), significance and relevance to prognosis for all patients and in relation to race/ethnicity for breast invasive carcinoma, ovarian serous cystadenocarcinoma, and uterine corpus endometrial carcinoma. Results: Sp1, Sp3, and survivin expression significantly impacted patient survival in breast invasive carcinoma (n=1211), ovarian serous cystadenocarcinoma (n=302), and uterine corpus endometrial carcinoma (n=581). When looking at Sp1 and combining data for all patients, there was a relevance in prognosis in ovarian serous cystadenocarcinoma (p=0.045). Additionally, there was an association between the marker and poor prognosis for race/ethnicity when looking at breast invasive carcinoma and uterine corpus endometrial carcinoma. Sp3 and survivin presented similarly when looking at combined and racial/ ethnic prognosis. Both Sp3 and survivin indicated a poorer prognosis for overall population survival in uterine corpus endometrial carcinoma (p=0.018 and p=0.015 respectively). They also presented with a worse prognosis when looking at race/ethnicity for all three listed cancers. Conclusion: The findings from this study suggest an association of Sp1, Sp3, and survivin expression in breast invasive carcinoma, ovarian serous cystadenocarcinoma, and uterine corpus endometrial carcinoma and their prognosis. The results also suggest that these markers may contribute to poor prognosis for patients in certain racial/ethnic groups.
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    Developing a nanoparticle platform for selective delivery of the anti-cancer drug MIH 2.4Bl to breast cancer cells
    (2023) Debnath, Dipti; Petty, Roland; Kapic, Ammar; Sabnis, Nirupama; Lacko, Andras G.; da Silva Souza, Helivaldo Diógenes; de Athayde Filho, Petrônio Filgueiras; Mathis, J. Michael
    Based on data from the World Health Organization, breast cancer is the most common cancer among women, accounting for about 15% of all cancer-related deaths. Thus, new treatment options are urgently needed to decrease this mortality rate. In recent years, mesoionic compounds have shown promising potential as anti-cancer agents due to their unique structure and reaction properties. We reported that a 1,3-thiazolium-5-thiolate mesoionic compound (MIH 2.4Bl) inhibited the growth of most of the breast cancer cell lines tested compared with normal human mammary epithelial cells. Treatment of MCF-7 breast cancer cells with MIH 2.4Bl resulted in alterations in cell cycle distribution with an increased proportion of cells in the G2/M phase compared with untreated cells. MCF-7 cells treated with MIH 2.4Bl also showed morphological changes consistent with apoptotic cell death. In addition, treating MCF-7 cells with MIH 2.4Bl resulted in a significant reduction in all mitochondrial respiratory parameters compared with the control cells, indicative of an overall decrease in mitochondrial membrane potential. These findings suggest that MIH 2.4Bl is a promising candidate for treating breast cancer. However, cancer therapy's primary challenge is the selective destruction of malignant cells while sparing normal cells to preserve tissue integrity. The development and use of drug delivery systems is a recognized approach to improving the efficacy of chemotherapy agents. However, drug delivery systems have been unexplored in mesoionic compounds. The reconstituted high-density lipoprotein (rHDL) nanoparticles have several advantages, including enhanced safety, efficacy, and biocompatibility. The payload, which is contained in the core of the HDL particle, is taken up by SR-B1 receptors, making this method particularly useful for targeted cancer chemotherapy. The upregulation of the SR-B1 receptor by tumor cells and tissues might be helpful in cancer treatment by specifically delivering drug-loaded nanoparticles to the tumors. In this preliminary work, we present an improved delivery strategy of a newly developed formulation of MIH 2.4Bl compound with rHDL nanoparticles as the delivery agent. Initial synthesis, optimization, physicochemical characterization, drug loading, and drug release assessment of the nanoparticles were performed. These studies support the potential therapeutic use of MIH 2.4Bl in treating breast cancer. To advance potential translational studies for monitoring in vitro drug delivery and colocalization of the drug in the cells, we have begun studies of the fluorescence properties of MIH 2.4Bl, using steady-state and time-resolved fluorescence techniques. The fluorescence characteristics of free MIH 2.4Bl was evaluated using UV/VIS and fluorescence spectroscopy. The steady-state and time-resolved measurements were designed to understand the optical properties of MIH 2.4Bl in solution for monitoring in vitro drug delivery and cellular colocalization. All samples, dissolved in various solvents, exhibited maximum absorbance between 440 and 480 nm; excitation at 440 nm elicited the highest emission at approximately 580 nm in methanol. These results may allow future detection and localization of MIH 2.4Bl in vitro and in vivo. Follow-up studies utilizing fluorescence confocal microscopy are anticipated to reveal drug accumulation's site(s) in situ and how cytotoxicity is induced in cancer cells.
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    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.
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    Targeting Sp1 in Ewing Sarcoma: A multi-approach method for the utilization of Mithramycin
    (2023) Lambring, Christoffer B.; Basha, Riyaz; Sankpal, Umesh; Fiadjoe, Hope; Ray, Anish
    Purpose: Ewing Sarcoma (ES) is a bone and soft tissue cancer affecting young adults and children. ES mostly occurs in the bones or soft tissue of the arms, legs, and pelvis. Localized ES presents with 5-year survival rate of 70%, but metastatic 5-year survival rate is between 15% and 30%. Our laboratory is interested in combination treatments using less toxic agents to induce sensitization to chemotherapy in ES. The anti-cancer activity of an antineoplastic antibiotic, Mithramycin, against ES cells has been shown. Mithramycin inhibits Specificity protein 1 (Sp1) a marker associated with aggressive cancer cell growth and resistance to chemo/radiation therapies. However, its mechanistic effects on other oncogenic proteins have yet to be elucidated in ES. The purpose of this study is to evaluate the effectiveness of Mithramycin and various combinations with other chemotherapeutic agents, Etoposide and Vincristine, to inhibit ES cell growth and assess the effect on key cancer related proteins regulated by Sp1. Future studies will include expanding upon Mithramycin’s mechanism of action in Ewing Sarcoma utilizing RNA sequencing and various computational methods. Methods: Cell lines were obtained from Children’s Oncology Group (COG). Anti-proliferative activity of Mithramycin and/or Vincristine and Etoposide against ES cell lines, TC205 and CHLA10, was evaluated using CellTiterGlo kit. Dose curves were plotted and IC50 values were determined by Sigma-Plot software. The expression of Sp1 and survivin was determined by Western blot analysis. The specific type of effect (additive/antagonistic/ synergistic) of the combination treatments were determined by analyzing the combination index obtained via Calcusyn software. Nude mice were injected with TC205 cells and treated over two weeks with either Mithramycin (1mg/kg per week) and/or Etoposide (5mg/kg per week) and tumor volume was compared. Protein models were obtained from RCSB PDB and homology tests were performed using the Swiss-model workspace. Results: Mithramycin, etoposide, and vincristine decreased ES cell line viability in TC205 and CHLA10 cells as monotherapies, but more effectively in combination. Tumor volume was greatly attenuated upon Mithramycin and/or etoposide introduction, but more significantly when used in combination. Mithramycin showed the ability to reduce the expression of Sp1 and offer differing effects on survivin expression, indicative of anti-apoptotic mechanisms being implemented in the ES cell lines. Decreases in viability upon chemotherapeutic and Mithramycin introduction were drastically increased when used in combination and this effect was mirrored in further decreases in Sp1 expression. Synergistic drug responses were shown in the combination of Mithramycin with both Vincristine and Etoposide (CI <1). Sp1 and survivin protein models were established and homology verification using Ramachandran plots and QMEAN Z-scores indicated quality protein models for further computational studies. Conclusions: Mithramycin may effectively sensitize ES cells and improve the response of chemotherapy while lowering necessary effective dosages. Studies to understand the mechanism of action of Mithramycin on Sp1, survivin, and other proteins involved in Ewing Sarcoma are underway.
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    Higher expression of Annexin A2 in bladder urothelial carcinoma promotes migration and invasion.
    (2023) Guo, Christina; Chaudhary, Pankaj
    Purpose:Bladder cancer is a prevalent and often aggressive malignancy, precipitating high morbidity and mortality rates in the US. The paucity of non-invasive and low-cost methods for detection necessitates investigation into improved surveillance assays for bladder urothelial carcinoma (BLCA). Annexin A2 (AnxA2) is a phospholipid-binding protein involved in malignant processes in several cancers but has yet to be studied in association with bladder carcinoma. This study aims to investigate the association of AnxA2 in BLCA and establish its role in the metastasis of bladder cancer cells. Results:The Cancer Genome Atlas Data analysis demonstrated that AnxA2 mRNA expression was significantly increased in BLCA tumor tissue compared to normal bladder tissue. Higher AnxA2 mRNA expression was significantly associated with high pathological grades, stages, and non-papillary tumor histology and poor overall survival, progression-free survival, and disease-specific survival. Similarly, we found that AnxA2 expression was higher in bladder cancer cells derived from high-grade metastatic carcinoma than in cells derived from low-grade urothelial carcinoma. In addition, expression of AnxA2 was significantly mobilized to the surface of bladder cancer cells that were highly metastatic versus cancer cells derived from low-grade tumors. This expression was also associated with high plasmin generation and AnxA2 secretion. Downregulation of AnxA2 cells significantly inhibited proliferation, migration, and invasion in bladder cancer and decreased expression of proangiogenic growth factors and cytokines. Conclusion: Results of this study show that higher expression of AnxA2 is involved in proliferation, migration, and invasion in bladder cancer and is associated with poor prognosis of patients with BLCA. These findings demonstrate the potential for AnxA2 as a prognostic marker and therapeutic target for BLCA. Funding: This research was partly supported by the NIH grants CA233355 and HL125447. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
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    Analysis of Key Cellular Changes of Triple Negative Breast Cancer Cells in Response to Kinase-Inhibiting BI2536 and Associated Derivatives
    (2023) Baker, Christopher; Rinderle, Caroline; Bunnell, Bruce
    Purpose: Triple Negative Breast Cancer (TNBC) is a subtype of breast cancer that grows quickly and has higher rates of metastasis and reoccurrence relative to other Breast Cancer subtypes that make it, in general, a much more dangerous subtype of breast cancer. The Kinase Chemogenomic Set (KCGS) is a collection of 187 kinase-inhibiting compounds with broad activity across 215 different kinases. We hypothesize that this plate contains compounds with the potential to inhibit TNBC and that exploring the transcriptomic and proteomic changes in TNBC cells may give insights into novel treatment targets. Methods: To test this hypothesis, we have utilized two main cell lines, the MDA-MB-231 line and a patient-derived xenograft line, the TuX-BxC-4IC cell line. Measurements have been taken at various time points up until 72 hours at various concentrations of a compound of interest, BI2536, between 1nM and 1uM. Primarily, data will be collected using qRT-PCR to gain insight into the transcriptomic changes during the potential EMT changes. Additionally, various other experiments related to migration, staining, and other essential markers will be conducted on the compound of interest and derivatives of the compound. Results: Initial results and prior work indicate that the compound of interest has moderate success in slowing cancer cell growth. Additionally, initial findings indicate that the compound may succeed in halting and potentially even reversing the EMT process. Conclusion: With this primary data set, we believe that the kinases targeted by the compound may hold potential key targets for the treatment of TNBC.
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    MIEN1 promoter ablation provides novel evidence for colorectal cancer genome editing-based therapeutics.
    (2023) Ranade, Payal
    Purpose: Colorectal cancer (CRC) is one of the leading causes of cancer associated mortalities worldwide. It starts with hyperproliferation of epithelial cells forming a polyp & leads to stages 3 & 4 which are associated with acquisition of metastasis. Chemotherapy majorly focuses on attenuating symptoms with no promising cure. Hence, studying the underlying mechanism of CRC progression & identifying novel therapeutic targets is critical for early diagnosis & treatment. The process of metastasis involves a complex interplay of signaling pathways, where various proteins play crucial roles. One such important protein that aids the process of migration is Migration & Invasion ENhancer 1 (MIEN1). In CRC, MIEN1 expression is predominantly upregulated in cancerous tissue in comparison to normal colorectal tissue, which is closely associated with invasive behavior. But the exact mechanism involved in the process of metastasis is yet unexplored. Methods: It is established that MIEN1 overexpression is a result of 17q12 chromosomal amplification, & such dysregulated expression is linked to the trans-regulation of its minimal promoter region. Therefore, we aim to investigate the effect of MIEN1 promoter ablation on CRC migration properties. CRISPR-Cas9 gene editing technology was used for deleting MIEN1 promoter region in the CRC cell line HT29. RNA seq & bioinformatics tools were employed to assess the transcriptomic consequences of genome-editing. Several DEGs discerned by RNA seq analysis were involved in different biological processes & molecular pathways such as cell adhesion, migration, invasion, & angiogenesis. Out of these the genes vital to CRC biogenesis were evaluated at both RNA & protein levels. Results: We analyzed the effect of MIEN1 knock-out on CRC metastatic potential using functional assays such as wound healing, Matrigel invasion, hanging drop cell – cell adhesion, & found that migration potential of HT29 cells was significantly reduced in absence of MIEN1 protein. We also successfully demonstrated that MIEN1 deletion disrupts the cytoskeletal rearrangement by affecting F-actin reorganization using phalloidin staining. Confocal staining of different proteins participating in actin cytoskeleton rearrangement such as paxillin, FAK, MIEN1 gave us an insight about the role of MIEN1 in mediating phosphorylation of FAK at different phosphorylation sites such as Tyr 397 & 925. Immunoblotting analysis of an array of proteins further confirmed the role of MIEN1 in actin cytoskeleton dynamics. Conclusion: MIEN1 is an important metastatic protein that is specifically overexpressed in cancerous cells. Taken together, our results prove that MIEN1 is involved in different signaling pathways responsible for CRC migration & its deletion leads to perturbation of several biological processes especially the actin cytoskeleton rearrangement, involved in metastasis. Hence, targeting MIEN1 would be a potentially effective therapeutic strategy for CRC patients.
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    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, Riyaz
    Purpose: 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.
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    Barriers to in-Person Focus Group Participation during the Third-Year of COVID-19 Pandemic: A Case Study of Colorectal Cancer (CRC) Screening in Underrepresented Groups
    (2023) Kamt, Sulin; Rasu, Rafia; Miller-Wilson, Lesley-Ann; White, Annesha; Chhetri, Shlesma; Hittson-Smith, Rachal; Fernandez, Denise; Sambamoorthi, Usha
    PURPOSE: In the process of conducting research to understand barriers to colorectal cancer (CRC) screening in underrepresented groups such as Blacks and Hispanics, it became evident that there were also barriers to recruitment in this population. This study assesses the challenges faced in recruitment of focus group participants regarding CRC screening practices among underrepresented groups. Since the COVID-19 pandemic, qualitative research participants have primarily been interviewed through online video or audio interactions. However, as restrictions on in-person interactions have been lifted, in-person focus groups are being increasingly considered. METHODS: The study investigators began recruitment through community health workers in August 2022, when COVID-19 vaccines were available for all adults (age>18 years). Eligible individuals were: age 45-75, Black or Hispanic, with Medicaid or no insurance, and no family history of CRC or diagnosis of certain colon-related diseases. We combined in-person and virtual recruitment strategies, including posting flyers in communities, advertising our study at health fairs, and on social media. Participants would receive a $50 gift card. RESULTS: Fifty-five met the eligibility criteria among 144 respondents, and 45 subjects (29 women and 16 men) agreed to be contacted. An average of 2.5 attempts were made per eligible subject. Unfortunately, we were able to recruit only four women (3 Hispanic and one non-Hispanic black). Traveling to the research site was a barrier to participation. Many subjects (49%) requested virtual participation (online video or audio interactions); some declined because the topic was too sensitive (considered taboo), and eligible men were reluctant to participate in-person. CONCLUSIONS: The requirement of in-person participation affected our recruitment goals, suggesting that COVID-19 has shifted the preferences of research participants to virtual interaction. In response to the eligible participant preferences, the study protocol has been revised to re-contact patients and schedule virtual FG sessions.
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    ystematic Review of Focus Group Discussions & Mixed Method Surveys Regarding Colorectal Cancer Screening
    (2023) Sakowski, Ross; Mathai, Jacob; White, Annesha; Rasu, Rafia; Sambamoorthi, Usha
    Background: Colorectal cancer (CRC) screening has a significant potential to decrease mortality from CRC. Many published studies have used either focus groups or structured interviews to identify barriers and facilitators of CRC. However, a systematic review of methods and findings from focus groups is lacking. Objective: The objective of this study was to conduct a systematic literature review that describes the characteristics of focus group participants and synthesize major themes of CRC screening barriers and facilitators. A secondary objective was to identify the impact of barriers related to social determinants of health (SDoH) factors. Methods: A systematic review of qualitative studies was conducted on CRC screening focus groups following ENTREQ guidelines and the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). Our inclusion criteria were as follows: (1) empirical scientific studies with a qualitative focus group or mixed methods study design; (2) that have been published in a peer-reviewed journal; (3) from January 1, 2012, and August 12, 2022; (4) in English; (5) exploring the attitudes, beliefs and behaviors related to adults and colon cancer screening; (6) face-to-face and online format. Keyword searches were conducted in the electronic databases PubMed and SCOPUS. After review, 31 studies contributing to our research questions were found eligible for inclusion. Results: Findings revealed that the number of participants per focus group (where reported) ranged from 2 to 23 participants with a median of 6 participants. There was a range of 20 to 232 total focus group participants per study while the mixed method studies ranged from 25 to 492. Most of the studies utilized education, income level, and access to healthcare as social determinants of health factors. The most commonly reported SDoH variable noted as a barrier to CRC screening was the lack of recommendation or education of a screening by their healthcare provider (15 of 31, 48%) with embarrassment or disgust regarding the procedure as a secondary barrier (11 of 31, 35%). Conclusions: Main themes for barriers and facilitators that emerged from the review were insurance status and awareness of the benefits of screening. Commonly reported concerns for barriers were embarrassment or disgust regarding the procedure and lack of trust in their provider relationship. Previous awareness of this disease through family history was a common facilitator. Opportunities to increase CRC screening arise in ensuring education and access to alternatives that provoke less embarrassment, such as FIT or FOBT tests. Sponsorship: None
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    Multiple Myeloma in a Cadaver: A Case Report
    (2023) Kalman, Kyra; Judd, Dallin; Hochberg, Dovey; Johnson, Darrian; Jewell, Lauren
    Introduction: Multiple Myeloma (MM) is a malignant neoplasm characterized by the abnormal proliferation of monoclonal immunoglobulin producing plasma cells within the bone marrow. The risk of developing MM is 0.76%; however, risk factors include age, BMI, gender, and race. Common complications include destructive bony lesions and renal insufficiency. Extraosseous myelomatous masses are a rare finding, identified in less than 5% of patients with MM, and its presence is associated with more aggressive, advanced stage disease and poor prognosis. These masses can impact many organ systems but most commonly involve the spleen, lymph nodes, liver, and kidneys. Pancreatic involvement, however, is extremely rare. Infiltration of the pancreas by myeloma cells has an incidence of 2.3% based on autopsy studies. Case Information: A medical dissection of a 58 year old woman was performed in the UNTHSC Center for Anatomical Sciences. The donor was 5’4”, 114 pounds, with a BMI of 22.3. The donor presented with a history of chronic tobacco use at 2 packs/day, unspecified broken bones, MM, and chemotherapy. The examination of the cadaveric specimen yielded insight into the systemic ramifications of MM, uncovering various pathological deviations. The donor's lung tissue exhibited signs consistent with prolonged usage of tobacco, as evidenced by the presence of discoloration and mottling. The kidneys displayed extensive scarring and a significant presence of adipose tissue. Most significantly, a large pancreatic tumor measuring 17 x 5.8 x 4 cm and weighing 167.65 g was found encasing the splenic artery. The sectioned tissue sample looked uniformly tan-white, firm, and mottled. Further dissection revealed an additional neoplastic growth on the posterolateral wall of the pelvic cavity. This tumor was situated anterior to a bony lesion on the sacrum and was found to be impinging upon the surrounding neurovasculature. Conclusion: This case exemplifies the complexities and nuances of Multiple Myeloma, highlighting the systemic nature of the disease and the need for a comprehensive understanding of its potential complications. Identification of scarring in the cadaver's kidney indicated that the patient's MM had caused the congregation of monoclonal immunoglobulins in the renal tissue, triggering profibrotic mechanisms and impaired renal function. The sacral bony lesion is a characteristic MM manifestation of heightened bone reabsorption and elevated osteoclast activity. Furthermore, this may have also led to the donor’s history of unspecified fractures in the arm and leg. The discovery of a large pancreatic neoplasm in this case is an extremely rare complication of MM, with an incidence of only 2.3%. Metastatic pancreatic involvement is not normally diagnosed as an aspect of the clinical progressive course of MM and is associated with poorer prognoses. Therefore, this case serves as a call to action for the medical community to continue to explore and understand the underlying mechanisms of extraosseous myelomatous masses and their presentation to improve the diagnosis and treatment of patients with MM. It is a testament to the ongoing need for research, education, and awareness in the fight against this debilitating disease.
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    A Rare Case of Synchronous Familial Adenomatous Polyposis and Endometrial Carcinoma
    (2023) Nguyen, Khanh; Nguyen, My; Barrera, David
    Familial adenomatous polyposis (FAP) is a rare autosomal dominant disease characterized by numerous polyps in the colon. It is caused by a germline mutation of the adenomatous polyposis coli (APC) gene. Patients have a guaranteed risk of having colorectal cancer and can also develop multiple extra-intestinal manifestations, including cutaneous lesions, brain tumors, desmoid tumors, osteomas, and thyroid cancer. Thus, extensive screenings for both colorectal cancer and the manifestations mentioned above are recommended on a frequent basis. Ovarian and endometrial malignancies are not known to be associated with FAP. Here, we present a case of synchronous FAP and endometrial carcinoma. A 51-year-old female with family history of autosomal-dominant-patterned colon cancer, subtotal colectomy at 17 due to multiple polyps, ileostomy with a J-pouch at 35, and recent upper endoscopy suspicious for ampullary adenoma, presented with one-month history of fatigue and night sweats. Review of system was positive for heartburn and easy bruising. The patient did not have formal genetic testing. She has close follow-ups with yearly surveillance upper GI endoscopy (EGD), flexible sigmoidoscopy, and thyroid ultrasound. At 44, she underwent dilation and curettage due to menorrhagia; samples revealed endometrial cancer, which led her to undergo a bilateral salpingo-oophorectomy. Reports of endometrial and ovarian cancers in FAP are rare. In another case, a 57-year-old female with FAP was found to have bilateral ovarian microcystic stromal tumors (MCSTs), papillary thyroid carcinoma, and endometrial carcinoma. Histopathology from the MCSTs and thyroid was positive for beta-catenin, an important marker in FAP. MCST is a rare subtype of ovarian cancer that has been found concurrent with FAP on several occasions. Although our patient did not have genetic testing, the large number of polyps and autosomal dominant pattern of inheritance are consistent with FAP, rather than Lynch or MUTYH-associated polyposis (MAP) syndromes, which could present similarly. It would be important to look at histopathology in our patient to determine whether there is overlapping genetic expression with FAP. Nevertheless, our case represents another rare instance of co-occurrence of endometrial cancer and FAP. More research needs to be done to explore the potential association between endometrial/ovarian malignancies and FAP. Holistic care is an integral part of osteopathic medicine, thus it is important for osteopathic physicians to provide well-rounded care for every patient. This case gives evidence that there might be benefits in future screening of endometrial/ovarian cancer in patients with FAP that could potentially increase life expectancy in these patients.
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    Addressing Age-Appropriate Cancer Care for Adolescents and Young Adults
    (2023) Tran, Kylie; Elledge, Daniel; Hoeft, Alice; Albritton, Karen
    Purpose: Adolescents and young adults (AYAs), normally defined as patients between 15 and 39 years of age, are often lost in the healthcare system that concentrates primarily on pediatric and adult cancers1. AYA cancer presentation can differ and treatments are less established compared to pediatric and adult cancers2. Many AYA patients are treated in pediatric facilities, which can lead to age-appropriate needs not being met. The goal of this project is to examine the AYA patient experience and assess if AYAs receive age-appropriate care at Cook Children’s Hospital in Fort Worth, Texas. Methods: Patient reported outcomes surveys were administered to AYA patients diagnosed between 1/1/2016 and 1/1/2020 with at least one of the following cancers: acute lymphoblastic leukemia, acute myeloblastic leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, testicular germ cell tumor, ovarian germ cell tumor, or sarcoma. Eighty-five patients were eligible to participate in the study. The survey and chart review included information pertaining to demographics, socioeconomic factors, treatment, and diagnosis-related questions. Results: Seventeen patients have completed the survey. Patients rated age-appropriateness and quality of care on a five-point Likert scale. On average, patients rated the following aspects of their care as highly satisfactory for age-appropriateness: communication with medical staff (M = 4.80, SD = 0.40), staff recognition of life events (M = 4.71, SD = 0.46), provider attitude (M = 4.86, SD = 0.37), and support provided to their families (M = 4.82, SD = 0.40). Although still highly rated, the physical environment (M= 4.38, SD = 0.91) and recreational activities (M= 4.35, SD = 0.87) were reported to be slightly lower than the other categories for age-appropriateness. Conclusions: AYA patients face unique challenges related to their cancer presentation and psychosocial needs. Interactions between patients, their physicians, and their environment all contribute to the patients' treatment experience and providing comprehensive, age-appropriate care is important. Overall, patients reported receiving age-appropriate care at Cook Children’s Hospital but reported slightly less satisfaction with the facilities and age-related activities. Based on these findings, continuing to establish age-appropriate resources and physical spaces for AYA patients can greatly enhance their quality of care and treatment experience. Beginning in 2016, Cook Children’s AYA clinic had already initiated changes to establish more supportive resources for AYAs, including creating and renovating a designated AYA lounge and implementing more programmatic psychosocial care through psychological interventions and AYA-specific support groups. References 1. Alvarez, The Lancet Oncology, 2022 2. Smith, Pediatric Blood & Cancer, 2019
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    Recognizing the Central Nervous System as a Site of Pediatric Sarcoma Relapse: A 3-Patient Series
    (2023) Smith, Danielle; Hamby, Tyler; Heym, Kenneth; Mohamed, Ashraf; Vallance, Kelly; Ray, Anish
    Background: Sarcomas are diverse malignancies derived from primitive mesenchymal cells that are difficult to diagnose and treat. Advances in local control techniques, chemotherapy regimens, and imaging modalities have led to improvements in both morbidity and mortality in pediatric patients. However, one-third of patients develop disease relapse. Previously, intracranial metastasis was thought to be rare. The incidence of sarcoma brain metastasis is thought to have increased and is associated with grim outcomes. Case Information: Case 1 – A male Asian infant was born with a mass involving lower left extremity requiring through the knee amputation shortly after birth. Pathology confirmed infantile fibrosarcoma (IF). He was started an IF-based regimen after pulmonary biopsy confirmed metastatic disease. Two months after chemotherapy completion, 5.6 x 7.2 x 6.3 cm intracranial tumor was found with pathology confirming metastatic IF. Despite salvage chemotherapy and entrectinib, he continued to have increased neurological symptoms and died. Case 2 - Ten-year-old Caucasian female presented with 8-month history of progressively enlarging right foot mass measuring 6.2 x 4.5 x 4.2 cm, consistent with Ewing Sarcoma upon biopsy. PET scan showed bilateral pulmonary metastatic disease with lymph node involvement. Chemotherapy and radiation therapy (XRT) were started. After completion of cycle 6, she had increased neurological symptoms and imaging showed 5 x 6 cm temporal mass with hemorrhage. Brain XRT, palliative chemotherapy, and Ruxolitnib were started; however, the patient subsequently died. Case 3 – Six-year-old Hispanic female with large mass arising from right proximal humeral metaphysis with evidence of bilateral pulmonary metastasis. Biopsy confirmed metastatic osteosarcoma and chemotherapy was started. Although the patient was treated further with methotrexate, salvage chemotherapy, palliative XRT, and Pazopanib, she began to develop neurological symptoms over several weeks before passing. Conclusions: We note this is the only report of IF brain metastasis, a rare report of sarcoma lymph node metastasis, and each patient was treated with an immunotherapy agent. Caregivers in cases 2 and 3 reported new-onset neurological manifestations prior to identification of new brain metastasis, indicating a lag in detection of new intracranial relapse in asymptomatic sarcoma patients. We suggest implementing a brief review of systems screening tool focused on concerning neurological manifestations to screen for brain metastasis.
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    Analysis of survivin expression in black and white breast cancer patient tissue
    (2023) Brown, Kerrie; Fang, Yisheng V.; Sankpal, Umesh T.
    Purpose: Survivin is a protein that belongs to the inhibitor of apoptosis family. It inhibits the activation of caspases and is also involved in the regulation of the cell cycle. Survivin is normally expressed during development with no expression detected in most adult differentiated tissues. However, high expression of this protein is found in many cancers which correlates with poor prognosis. Breast cancer disproportionately affects black women who have significantly higher mortality rates compared to white women with breast cancer. We hypothesize that higher expression of Survivin in Black cancer patients correlates with their higher mortality rates. In this project, we compared the level of expression of survivin in breast tumor tissue from Black and White cancer patients. This was done using immunohistochemical (IHC) staining technique of tumor tissue sections and analysis of The Cancer Genome Atlas database. Detecting differential expression of Survivin between the two racial groups and within different subtypes of breast cancer could lead to the development of Survivin as a diagnostic and/or prognostic marker as well as a possible therapeutic target. Methods: Our first approach was to analyze the TCGA database to confirm our hypothesis that there is differential expression of survivin between the two racial groups and within different subtypes of breast cancer. This involved RNA-seq data analysis using various tools available online. Secondly, breast tumor tissue, representing different subtypes of breast cancer, from Black and White patients, was analyzed by immunohistochemistry (IHC) using survivin specific antibodies. The protocol for nuclear and cytoplasmic Survivin detection was standardized. The IHC data, in the form of percent staining (nuclear and cytoplasmic), was then analyzed by semi-quantitative methods using H-score and Allred scores. Results and Conclusions: Results from the analysis of TCGA database and our IHC data indicate significantly higher expression of survivin in tumors from Black patients compared to White. Differential expression was also observed between different subgroups of breast cancer, with high expression in the most aggressive triple negative (TNBC) form of breast cancer. Coincidently, the occurrence of TNBC is higher in Black women compared to White women. We also observed higher nuclear expression in Black patients compared to White patients, which has been associated with poor outcomes. Based on the vast literature suggesting that survivin plays a key role in cancer progression, we believe that survivin could be a useful diagnostic and/or prognostic marker or a therapeutic target to combat the racial disparity in breast cancer.
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    (2023) Levitt, Mike; Siebert, Garland; Hamby, Tyler; Hill, Rachel; Mohamed, Ashraf
    RETROSPECTIVE ANALYSIS OF A HYPERGLYCEMIA SCREENING PROTOCOL IN PEDIATRIC PATIENTS WITH ALL AND LLY Mike Levitt, MSa Garland Siebert, MSa Rachel Hill, RD, CSO, LD, CNSCb Tyler Hamby, PhDa,c Ashraf Mohamed, MDb aUniversity of North Texas Health Science Center, Texas College of Osteopathic Medicine bCook Children’s Health Care System, Department of Pediatric Hematology/Oncology cCook Children’s Health Care System, Department of Research Operations Background: Approximately 4-35% of pediatric patients undergoing treatment for acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LLy) develop drug-induced hyperglycemia. Hyperglycemia is associated with poor outcomes including increased infections, weight loss, diabetic ketoacidosis, and greater mortality. However, no guidelines for identifying drug-induced hyperglycemia currently exist and the time course of hyperglycemia development remains relatively uncharacterized past induction therapy. Objective: The present study aims to evaluate a hyperglycemia screening protocol (HSP) that was implemented to identify hyperglycemia more promptly and to further describe the time course of hyperglycemia during ALL and LLy therapy. Design/Methods: A retrospective medical records review of 154 patients diagnosed with ALL or LLy at Cook Children’s Medical Center between March 2018 and April 2022 was performed. The HSP included more frequent blood glucose monitoring, criteria for removal of dextrose from IV fluids, consultation with other providers (case management, patient educator, registered dietitian), and robust care coordination between the hematology-oncology and endocrinology teams. Predictors of hyperglycemia were examined with univariate Cox regression. Results: The HSP was ordered for 88 (57%) of the patients. Fifty-four (35%) patients developed hyperglycemia: 28 (52%) during induction therapy and 26 (48%) patients after induction therapy. Enrollment in the HSP increased the likelihood of a hyperglycemia diagnosis compared to those not enrolled (41% vs. 27%, HR=1.76, p<0.050). Age ³10 years was an independent predictor of hyperglycemia development (HR=3.72, p<0.0001). Patients who did not gain weight during the induction period were more likely to also have hyperglycemia (weight loss: HR=5.42, p=0.001; weight steady: HR=3.48, p=0.012). The development of pancreatitis was also associated with drug-induced hyperglycemia (HR=2.45, p=0.007). Blood glucose values were significantly more likely to be ³ 200 mg/dL during days 5-8 of induction therapy compared to days 1-4 (29% vs. 10%, OR=4.18, p<0.001). Compared to blood glucose measurements taken in the morning (10%), values were more likely to be ≥200 mg/dL when acquired overnight (20%, OR=4.42, p<0.001), in the afternoon (16%, OR=2.34, p=0.011), and in the evening (38%, OR=10.57, p<0.001). Conclusion: Implementation of the HSP helped detect hyperglycemia more frequently in enrolled patients compared to controls and readily identified individuals at the greatest risk of developing hyperglycemia. These findings highlight a population of patients that develop hyperglycemia past induction therapy and give guidance on the timing of continued blood glucose monitoring in at-risk patients.