Browsing by Author "Jiang, Lan"

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    Death effector domain-containing protein induces vulnerability to cell cycle inhibition in triple-negative breast cancer
    (Springer Nature, 2019-06-28) Ni, Yingjia; Schmidt, Keon R.; Werner, Barnes A.; Koenig, Jenna K.; Guldner, Ian H.; Schnepp, Patricia M.; Tan, Xuejuan; Jiang, Lan; Host, Misha; Sun, Longhua; Howe, Erin N.; Wu, Junmin; Littlepage, Laurie E.; Nakshatri, Harikrishna; Zhang, Siyuan; Surgery, IU School of Medicine
    Lacking targetable molecular drivers, triple-negative breast cancer (TNBC) is the most clinically challenging subtype of breast cancer. In this study, we reveal that Death Effector Domain-containing DNA-binding protein (DEDD), which is overexpressed in > 60% of TNBCs, drives a mitogen-independent G1/S cell cycle transition through cytoplasm localization. The gain of cytosolic DEDD enhances cyclin D1 expression by interacting with heat shock 71 kDa protein 8 (HSC70). Concurrently, DEDD interacts with Rb family proteins and promotes their proteasome-mediated degradation. DEDD overexpression renders TNBCs vulnerable to cell cycle inhibition. Patients with TNBC have been excluded from CDK 4/6 inhibitor clinical trials due to the perceived high frequency of Rb-loss in TNBCs. Interestingly, our study demonstrated that, irrespective of Rb status, TNBCs with DEDD overexpression exhibit a DEDD-dependent vulnerability to combinatorial treatment with CDK4/6 inhibitor and EGFR inhibitor in vitro and in vivo. Thus, our study provided a rationale for the clinical application of CDK4/6 inhibitor combinatorial regimens for patients with TNBC.
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    Variation in statin prescription among veterans with HIV and known atherosclerotic cardiovascular disease
    (Elsevier, 2022) Erqou, Sebhat; Papaila, Alexa; Halladay, Christopher; Ge, Augustus; Liu, Michael A.; Jiang, Lan; Lally, Michelle; Menon, Anupama; Shah, Nishant R.; Miech, Edward; Virani, Salim S.; Zullo, Andrew R.; Shireman, Theresa I.; Longenecker, Christopher T.; Ross, David; Sullivan, Jennifer L.; Wu, Wen-Chih; Rudolph, James L.; Emergency Medicine, School of Medicine
    Background: People with HIV have increased atherosclerotic cardiovascular disease (ASCVD) risk, worse outcomes following incident ASCVD, and experience gaps in cardiovascular care, highlighting the need to improve delivery of preventive therapies in this population. Objective: Assess patient-level correlates and inter-facility variations in statin prescription among Veterans with HIV and known ASCVD. Methods: We studied Veterans with HIV and existing ASCVD, ie, coronary artery disease (CAD), ischemic cerebrovascular disease (ICVD), and peripheral arterial disease (PAD), who received care across 130 VA medical centers for the years 2018-2019. We assessed correlates of statin prescription using two-level hierarchical multivariable logistic regression. Median odds ratios (MORs) were used to quantify inter-facility variation in statin prescription. Results: Nine thousand six hundred eight Veterans with HIV and known ASCVD (mean age 64.3 ± 8.9 years, 97% male, 48% Black) were included. Only 68% of the participants were prescribed any-statin. Substantially higher statin prescription was observed for those with diabetes (adjusted odds ratio [OR] = 2.3, 95% confidence interval [CI], 2.0-2.6), history of coronary revascularization (OR = 4.0, CI, 3.2-5.0), and receiving antiretroviral therapy (OR = 3.0, CI, 2.7-3.4). Blacks (OR = 0.7, CI, 0.6-0.9), those with non-coronary ASCVD, ie, ICVD and/or PAD only, (OR 0.53, 95% CI: 0.48-0.57), and those with history of illicit substance use (OR=0.7, CI, 0.6-0.9) were less likely to be prescribed statins. There was significant variation in statin prescription across VA facilities (10th, 90th centile: 55%, 78%), with an estimated 20% higher likelihood of difference in statin prescription practice for two clinically similar individuals treated at two comparable facilities (adjusted MOR = 1.21, CI, 1.18-1.24), and a greater variation observed for Blacks or those with non-coronary ASCVD or history of illicit drug use. Conclusion: In an analysis of large-scale VA data, we found suboptimal statin prescription and significant interfacility variation in statin prescription among Veterans with HIV and known ASCVD, particularly among Blacks and those with a history of non-coronary ASCVD.