Showing papers by "Jerry S.H. Lee published in 2023"

Detection and visualization of HER2 clustering using an Aggregation Induced Emission based fluorescent probe molecule

Abstract: The spatio-temporal organization of proteins within the cell membrane can govern various cellular functions, ultimately playing a role in disease progression. One interesting example is the human epidermal growth factor receptor 2 (HER2), a member of the epidermal growth factor receptor (EGFR) family. HER2 is known to be over-expressed in certain cancer types. In some sub-types of breast cancer, it is known that overexpressed HER2s are non-homogenously distributed on the cell membrane surface, forming HER2 clusters that consist of HER2s in close proximity to each other. One therapeutic strategy is to disrupt this clustering behavior. However, given the nanometer lengthscales involved, detecting these subtle changes has proven challenging. In this work, we propose and demonstrate a new fluorophore for imaging HER2 clustering behaviour based on the organic molecule Tetraphenylethylene (TPE). This molecule undergoes aggregation induced emission (AIE), a unique photophysical behaviour that results in an increase in fluorescent signal when the molecular motion of the TPE-containing molecule is restricted. By conjugating the fluorophore to a HER2 specific antibody, HER2 clustering disruption in HER2 over-expressing breast cancer cells in response to the introduction of an FDA-approved therapeutic is detected. While this antibody-conjugated fluorophore system is optimized for the detection of HER2, the imaging agent forms a modular platform that is adaptable by changing the targeting moeity. This imaging system will find applications in a wide range of membrane protein spatio-temporal investigations.

Chemotherapy Treatment Costs and Clinical Outcomes of Colon Cancer in the U.S. Military Health System's Direct and Private Sector Care Settings.

Abstract: INTRODUCTION Identifying low-value cancer care may be an important step in containing costs associated with treatment. Low-value care occurs when the medical services, tests, or treatments rendered do not result in clinical benefit. These may be impacted by care setting and patients' access to care and health insurance. We aimed to study chemotherapy treatment and the cost paid by the Department of Defense (DoD) for treatment in relation to clinical outcomes among patients with colon cancer treated within the U.S. Military Health System's direct and private sector care settings to better understand the value of cancer care. MATERIALS AND METHODS A cohort of patients aged 18 to 64 years with primary colon cancer diagnosed between January 1, 1999, and December 31, 2014, were identified in the Military Cancer Epidemiology database. Multivariable time-dependent Cox proportional hazards regression models were used to assess the relationship between chemotherapy treatment and the cost paid by the DoD (in quartiles, Q) and the outcomes of cancer progression, cancer recurrence, and all-cause death modeled as adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs). The Military Cancer Epidemiology data were approved for research by the Uniformed Services University of the Health Sciences' Institutional Review Board. RESULTS The study included 673 patients using direct care and 431 patients using private sector care. The median per patient chemotherapy costs in direct care ($111,202) were lower than in private sector care ($350,283). In direct care, higher chemotherapy costs were associated with an increased risk of any outcome but not with all-cause death. In private sector care, higher chemotherapy costs were associated with a higher risk of any outcome and with all-cause death (aHR, 2.67; 95% CI, 1.20-5.92 for Q4 vs. Q1). CONCLUSIONS The findings in the private sector may indicate low-value care in terms of the cost paid by the DoD for chemotherapy treatment and achieving desirable survival outcomes for patients with colon cancer in civilian health care. Comprehensive evaluations of value-based care among patients treated for other tumor types may be warranted.