Browsing by Author "Wang, Z."

Now showing 1 - 5 of 5
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    Epigenetic Modulations and Lineage Plasticity in Advanced Prostate Cancer
    (Elsevier, 2020-04) Ge, R.; Wang, Z.; Montironi, R.; Jiang, Z.; Cheng, M.; Santoni, M.; Huang, K.; Massari, F.; Lu, X.; Cimadamore, A.; Lopez-Beltran, A.; Cheng, L.; Pathology and Laboratory Medicine, School of Medicine
    Prostate cancer is the most common cancer and second leading cause of cancer-related death in American men. Antiandrogen therapies are part of the standard of therapeutic regimen for advanced or metastatic prostate cancers; however, patients who receive these treatments are more likely to develop castration-resistant prostate cancer (CRPC) or neuroendocrine prostate cancer (NEPC). In the development of CRPC or NEPC, numerous genetic signaling pathways have been under preclinical investigations and in clinical trials. Accumulated evidence shows that DNA methylation, chromatin integrity, and accessibility for transcriptional regulation still play key roles in prostate cancer initiation and progression. Better understanding of how epigenetic change regulates the progression of prostate cancer and the interaction between epigenetic and genetic modulators driving NEPC may help develop a better risk stratification and more effective treatment regimens for prostate cancer patients.
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    Genetic variant predicts bevacizumab-induced hypertension in ECOG-5103 and ECOG-2100
    (Nature Publishing Group, 2014-09-09) Schneider, B. P.; Li, L.; Shen, F.; Miller, K. D.; Radovich, M.; O'Neill, A.; Gray, R. J.; Lane, D.; Flockhart, D. A.; Jiang, G.; Wang, Z.; Lai, D.; Koller, D.; Pratt, J. H.; Dang, C. T.; Northfelt, D.; Perez, E. A.; Shenkier, T.; Cobleigh, M.; Smith, M. L.; Railey, E.; Partridge, A.; Gralow, J.; Sparano, J.; Davidson, N. E.; Foroud, T.; Sledge, G. W.; Department of Medicine, IU School of Medicine
    Background: Bevacizumab has broad anti-tumour activity, but substantial risk of hypertension. No reliable markers are available for predicting bevacizumab-induced hypertension. Methods: A genome-wide association study (GWAS) was performed in the phase III bevacizumab-based adjuvant breast cancer trial, ECOG-5103, to evaluate for an association between genotypes and hypertension. GWAS was conducted in those who had experienced systolic blood pressure (SBP) >160 mm Hg during therapy using binary analysis and a cumulative dose model for the total exposure of bevacizumab. Common toxicity criteria (CTC) grade 3–5 hypertension was also assessed. Candidate SNP validation was performed in the randomised phase III trial, ECOG-2100. Results: When using the phenotype of SBP>160 mm Hg, the most significant association in SV2C (rs6453204) approached and met genome-wide significance in the binary model (P=6.0 × 10−8
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    Identification and Mechanistic Investigation of Drug-Drug Interactions Associated With Myopathy: A Translational Approach
    (Wiley Blackwell (John Wiley & Sons), 2015-09) Han, X.; Quinney, S. K.; Wang, Z.; Zhang, P.; Duke, J.; Desta, Z.; Elmendorf, J. S.; Flockhart, D. A.; Li, L.; Department of Medical & Molecular Genetics, IU School of Medicine
    Myopathy is a group of muscle diseases that can be induced or exacerbated by drug-drug interactions (DDIs). We sought to identify clinically important myopathic DDIs and elucidate their underlying mechanisms. Five DDIs were found to increase the risk of myopathy based on analysis of observational data from the Indiana Network of Patient Care. Loratadine interacted with simvastatin (relative risk 95% confidence interval [CI] = [1.39, 2.06]), alprazolam (1.50, 2.31), ropinirole (2.06, 5.00), and omeprazole (1.15, 1.38). Promethazine interacted with tegaserod (1.94, 4.64). In vitro investigation showed that these DDIs were unlikely to result from inhibition of drug metabolism by CYP450 enzymes or from inhibition of hepatic uptake via the membrane transporter OATP1B1/1B3. However, we did observe in vitro synergistic myotoxicity of simvastatin and desloratadine, suggesting a role in loratadine-simvastatin interaction. This interaction was epidemiologically confirmed (odds ratio 95% CI = [2.02, 3.65]) using the data from the US Food and Drug Administration Adverse Event Reporting System.
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    Immune signatures underlying post-acute COVID-19 lung sequelae
    (AAAS, 2021-11) Cheon, I. S.; Li, C.; Son, Y. M.; Goplen, N. P.; Wu, Y.; Cassmann, T.; Wang, Z.; Wei, X.; Tang, J.; Li, Y.; Marlow, H.; Hughes, S.; Hammel, L.; Cox, T. M.; Goddery, E.; Ayasoufi, K.; Weiskopf, D.; Boonyaratanakornkit, J.; Dong, H.; Li, H.; Chakraborty, R.; Johnson, A. J.; Edell, E.; Taylor, J. J.; Kaplan, M. H.; Sette, A.; Bartholmai, B. J.; Kern, R.; Vassallo, R.; Sun, J.; Microbiology and Immunology, School of Medicine
    Severe coronavirus disease 2019 (COVID-19) pneumonia survivors often exhibit long-term pulmonary sequelae, but the underlying mechanisms or associated local and systemic immune correlates are not known. Here, we have performed high-dimensional characterization of the pathophysiological and immune traits of aged COVID-19 convalescents, and correlated the local and systemic immune profiles with pulmonary function and lung imaging. We found that chronic lung impairment was accompanied by persistent respiratory immune alterations. We showed that functional severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific memory T and B cells were enriched at the site of infection compared with those of blood. Detailed evaluation of the lung immune compartment revealed that dysregulated respiratory CD8+ T cell responses were associated with the impaired lung function after acute COVID-19. Single-cell transcriptomic analysis identified the potential pathogenic subsets of respiratory CD8+ T cells contributing to persistent tissue conditions after COVID-19. Our results have revealed pathophysiological and immune traits that may support the development of lung sequelae after SARS-CoV-2 pneumonia in older individuals, with implications for the treatment of chronic COVID-19 symptoms.
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    Loophole-free tests of the Bell inequalities by distributing ion-photon entanglement through hybrid quantum network
    (Office of the Vice Chancellor for Research, 2013-04-05) Luo, L.; Wang, Z.; Cao, D. Y.; Huang, Y.; Li; Han, Y.
    We are developing a long term program to implement loophole-free tests of the Bell inequalities by generating entangled ion-photon pairs over long distances. Time-like interval and high detection efficiency are two essential components for a loophole-free test of the Bell inequalities. In our scheme, a pair of entangled photons (local and remote photon) from narrow-band spontaneous parametric down conversion (SPDC) will be used to produce time-like interval through a telecom fiber linking two cities separated by a distance of over 100 km in Anhui, China. Then an up-conversion quantum interface will coherently transfer the qubit stored in the local SPDC photon to another photon at 370 nm which coincides the spontaneous emitted photon from trapped Yb ions. We will then implement a herald entanglement scheme by a joint measurement of both the up-conversion photon and the spontaneous emitted photon which is entangled with a trapped Yb ion. Thus ion-photon entanglement can be generated between the remote SPDC photon and the trapped ion. Assuming perfect detection efficiency of the ion, minimum detection efficiency 0.50 of the SPDC photon is required to close the detection loophole. We will present an analysis of this experimental scheme and report the current experimental progress.