Browsing by Author "Li, Katherine"

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    Identifying Sickle Cell Disease Beyond the Neonatal Period: A Case Series
    (2025-03-28) Gupta, Soumya; Slaughter, Mary; Li, Katherine; Harter, Michaela; Goubeaux, Derrick L.; Drayton Jackson, Meghan
    Background: Sickle Cell Disease (SCD) is an autosomal recessive chronic condition that causes hemolytic anemia and vaso-occlusive episodes that can present as dactylitis, pain, acute chest syndrome (ACS), and other complications. For early detection and intervention, newborn screening (NBS) for SCD is mandated in all 50 states. However, this screening is not readily available in many other areas of the world. Case Description : Three children who immigrated from countries outside the United States were diagnosed with SCD beyond the neonatal period. A 17-year-old female adopted from Kenya presented to the ER with dyspnea after starting oral contraceptives and was found to have a pulmonary embolism. Hemoglobin (Hgb) was 8.1 g/dl. She rapidly deteriorated and required intubation. Bronchoalveolar lavage revealed straw-colored fluid, a rare finding consistent with ACS. Electrophoresis confirmed HbSS. A 7-year-old male from the Dominican Republic presented with pneumonia and pain. Hgb was 8.4 g/dl. There was familial anemia, but he had not received work-up due to insufficient insurance coverage. Electrophoresis showed HbSS. A 7-year-old male from Nigeria presented to the ED after an episode of gross hematuria. His baseline Hgb was 10 g/dl, and his mother had SCD. Electrophoresis showed HbSS. Clinical Significance: Sickle cell disease is a multisystem disorder with complications that can lead to severe illness. Physicians must maintain high clinical suspicion for SCD in patients who did not receive NBS presenting with recurrent pain, severe infection, end organ damage, or anemia. Diagnosis is confirmed with hemoglobin electrophoresis. Conclusion: This case series highlights the need for heightened SCD awareness, particularly in those from areas without universal NBS. Providers must obtain relevant family history, recognize SCD’s diverse presentations, and work to reduce healthcare access barriers to ensure that patients receive timely diagnosis and care.
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    Isopentyl-Deoxynboquinone Induces Mitochondrial Dysfunction and G2/M Phase Cell Cycle Arrest to Selectively Kill NQO1-Positive Pancreatic Cancer Cells
    (Mary Ann Liebert, Inc., 2024) Jiang, Lingxiang; Liu, Yingchun; Tumbath, Soumya; Boudreau, Matthew W.; Chatkewitz, Lindsay E.; Wang, Jiangwei; Su, Xiaolin; Zahid, Kashif Rafiq; Li, Katherine; Chen, Yaomin; Yang, Kai; Hergenrother, Paul J.; Huang, Xiumei; Radiation Oncology, School of Medicine
    Aims: Pancreatic cancer is among the top five leading causes of cancer-related deaths worldwide, with poor overall survival rates. Current therapies for pancreatic cancer lack tumor specificity, resulting in harmful effects on normal tissues. Therefore, developing tumor-specific agents for the treatment of pancreatic cancer is critical. NAD(P)H:quinone oxidoreductase 1 (NQO1), highly expressed in pancreatic cancers but not in associated normal tissues, makes NQO1 bioactivatable drugs a potential therapy for selectively killing NQO1-positive cancer cells. Our previous studies have revealed that the novel NQO1 bioactivatable drug deoxynyboquinone (DNQ) is 10-fold more potent than the prototypic NQO1 bioactivatable drug β-lapachone in killing of NQO1-positive cancer cells. However, DNQ treatment results in high-grade methemoglobinemia, a significant side effect that limits clinical development. Results: Here, we report for the first time on a DNQ derivative, isopentyl-deoxynboquinone (IP-DNQ), which selectively kills pancreatic ductal adenocarcinoma (PDAC) cells in an NQO1-dependent manner with equal potency to the parent DNQ. IP-DNQ evokes massive reactive oxygen species (ROS) production and oxidative DNA lesions that result in poly(ADP-ribose)polymerase-1 (PARP1) hyperactivation, mitochondrial catastrophe, and G2/M phase cell cycle arrest, leading to apoptotic and necrotic programmed cell death. Importantly, IP-DNQ treatment causes only mild methemoglobinemia in vivo, with a threefold improvement in the maximum tolerated dose (MTD) compared with DNQ, while it significantly suppresses tumor growth and extends the life span of mice in subcutaneous and orthotopic pancreatic cancer xenograft models. Innovation and Conclusion: Our study demonstrates that IP-DNQ is a promising therapy for NQO1-positive pancreatic cancers and may enhance the efficacy of other anticancer drugs. IP-DNQ represents a novel approach to treating pancreatic cancer with the potential to improve patient outcomes.