Browsing by Author "Liu, S."

Now showing 1 - 6 of 6
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    Fibroblast Growth Factor 23 Genotype and Cardiovascular Disease in Patients Undergoing Hemodialysis
    (Karger Publishers, 2019-02) Schwantes-An, T.-H.; Liu, S.; Stedman, M.; Decker, B. S.; Wetherill, L.; Edenberg, H. J.; Vatta, M.; Foroud, T. M.; Chertow, G. M.; Moe, S. M.; Medical and Molecular Genetics, School of Medicine
    Background: Elevated serum concentrations of fibroblast growth factor 23 (FGF23) are associated with cardiovascular mortality in patients with chronic kidney disease and those undergoing dialysis. Objectives: We tested the hypotheses that polymorphisms in FGF23, its co-receptor alpha-klotho (KL), and/or FGF23 receptors (FGFR) are associated with cardiovascular events and/or mortality. Methods: We used 1,494 DNA samples collected at baseline from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events Trial, in which patients were randomized to the calcimimetic cinacalcet or placebo for the treatment of secondary hyperparathyroidism. We analyzed European and African Ancestry samples separately and then combined summary statistics to perform a meta-analysis. We evaluated single-nucleotide polymorphisms (SNPs) in FGF23, KL, and FGFR4 as the key exposures of interest in proportional hazards (Cox) regression models using adjudicated endpoints (all-cause and cardiovascular mortality, sudden cardiac death, and heart failure [HF]) as the outcomes of interest. Results: rs11063112 in FGF23 was associated with cardiovascular mortality (risk allele = A, hazard ratio [HR] 1.32, meta-p value = 0.004) and HF (HR 1.40, meta-p value = 0.007). No statistically significant associations were observed between FGF23 rs13312789 and SNPs in FGFR4 or KL genes and the outcomes of interest. Conclusions: rs11063112 was associated with HF and cardiovascular mortality in patients receiving dialysis with moderate to severe secondary hyperparathyroidism.
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    In vitro and In vivo evidence demonstrating chronic absence of Ref-1 Cysteine 65 impacts Ref-1 folding configuration, redox signaling, proliferation and metastasis in pancreatic cancer
    (Elsevier, 2024) Mijit, M.; Kpenu, E.; Chowdhury, N. N.; Gampala, S.; Wireman, R.; Liu, S.; Babb, O.; Georgiadis, M. M.; Wan, J.; Fishel, M. L.; Kelley, M. R.; Pediatrics, School of Medicine
    Ref-1/APE1 (Redox Effector/Apurinic Endonuclease 1) is a multifunctional enzyme that serves as a redox factor for several transcription factors (TFs), e.g., NF-kB, HIF-1α, which in an oxidized state fail to bind DNA. Conversion of these TFs to a reduced state serves to regulate various biological responses such as cell growth, inflammation, and cellular metabolism. The redox activity involves a thiol exchange reaction for which Cys65 (C65) serves as the nucleophile. Using CRISPR editing in human pancreatic ductal adenocarcinoma (PDAC) cells, we changed C65 to Ala (C65A) in Ref-1 to evaluate alteration of Ref-1 redox dynamics as well as chronic loss of Ref-1 redox activity on cell signaling pathways, specifically those regulated by NF-kB and HIF-1α. The redox activity of Ref-1 requires partial unfolding to expose C65, which is buried in the folded structure. Labeling of Ref-1 with polyethylene glycol-maleimide (PEGm) provides a readout of reduced Cys residues in Ref-1 and thereby an assessment of partial unfolding in Ref-1. In comparing Ref-1WT vs Ref-1C65A cell lines, we found an altered distribution of oxidized versus reduced states of Ref-1. Accordingly, activation of NF-kB and HIF-1α in Ref-1C65A lines was significantly lower compared to Ref-1WT lines. The bioinformatic data revealed significant downregulation of metabolic pathways including OXPHOS in Ref-1C65A expressing clones compared to Ref-1WT line. Ref-1C65A also demonstrated reduced cell proliferation and use of tricarboxylic acid (TCA) substrates compared to Ref-1WT lines. A subcutaneous as well as PDAC orthotopic in vivo model demonstrated a significant reduction in tumor size, weight, and growth in the Ref-1C65A lines compared to the Ref-1WT lines. Moreover, mice implanted with Ref-1C65A redox deficient cells demonstrate significantly reduced metastatic burden to liver and lung compared to mice implanted with Ref-1 redox proficient cells. These results from the current study provide direct evidence that the chronic absence of Cys65 in Ref-1 results in redox inactivity of the protein in human PDAC cells, and subsequent biological results confirm a critical involvement of Ref-1 redox signaling and tumorigenic phenotype.
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    Predictors of Nodal and Metastatic Failure in Early Stage Non-Small Cell Lung Cancer after Stereotactic Body Radiation Therapy
    (Elsevier, 2019) Cerra-Franco, Alberto; Liu, S.; Azar, M.; Shiue, Kevin; Freije, S.; Hinton, J.; Deig, Christopher R.; Edwards, D.; Estabrook, Neil C.; Ellsworth, S. G.; Huang, K.; Diab, K.; Langer, Mark P.; Zellars, Richard; Kong, Feng-Ming; Wan, Jun; Lautenschlaeger, Tim; Radiation Oncology, School of Medicine
    Introduction/Background Many early-stage non-small cell lung cancer (ES-NSCLC) patients undergoing stereotactic body radiation therapy (SBRT) develop metastases, which is associated with poor outcomes. We sought to identify factors predictive of metastases after lung SBRT and created a risk stratification tool. Materials and Methods We included 363 patients with ES-NSCLC who received SBRT; median follow-up was 5.8 years. The following patient and tumor factors were retrospectively analyzed for their association with metastases (defined as nodal and/or distant failure): sex; age; lobe involved; centrality; previous NSCLC; smoking status; gross tumor volume (GTV); T-stage; histology; dose; minimum, maximum, and mean GTV dose; and parenchymal lung failure. A metastasis risk-score linear-model using beta coefficients from a multivariate Cox model was built. Results A total of 111/406 (27.3%) lesions metastasized. GTV volume and dose were significantly associated with metastases on univariate and multivariate Cox proportional hazards modeling (p<0.001 and HR=1.02 per mL, p<0.05 and HR=0.99 per Gy, respectively). Histology, T-stage, centrality, lung parenchymal failures, and previous NSCLC were not associated with development of metastasis. A metastasis risk-score model using GTV volume and prescription dose was built: [risk score=(0.01611 x GTV)–(0.00525 x dose (BED10))]. Two risk-score cutoffs separating the cohort into low-, medium-, and high-risk subgroups were examined. The risk-score identified significant differences in time to metastases between low-, medium-, and high-risk patients (p<0.001), with 3-year estimates of 81.1%, 63.8%, and 38%, respectively. Conclusion GTV volume and radiation dose are associated with time to metastasis and may be used to identify patients at higher risk of metastasis after lung SBRT.
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    Preface "Water, climate, and vegetation: ecohydrology in a changing world"
    (2012-12) Wang, Lixin; Liu, J.; Sun, G.; Wei, X.; Liu, S.; Dong, Q.
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    ROLE OF OSTEOCLASTS IN THE BIOCORROSION OF METAL IMPLANTS
    (Office of the Vice Chancellor for Research, 2011-04-08) Theriac, Haili; Dodge, Todd; Largura, Heather; Hara, A.; Liu, S.; Bruzzaniti, Angela
    Mini implants (MIs), typically composed of stainless steel (SS) or titanium alloy (Ti), have recently emerged as superior alternatives to traditional dental and orthopedic implants. When a metal implant is inserted into bone, a process called bone remodeling is triggered near the implant. Bone remodeling involves the activity of osteoblasts (OBs), which produce new bone tissue, and osteoclasts (OCs), which degrade and digest bone. OCs degrade bone by acidifying the extracellular environment and secreting hydrolytic enzymes that degrade the extracellular matrix. However, the acidification of the extracellular environment can potentially lead to the biological corrosion of metal implants after implantation. This may have important consequences such as cell toxicity, decreased osseointegration of the implant, and implant loosening. The objective of this study is to determine if implants made from Ti are more resistant to OC-mediated biocorrosion than stainless steel (SS) implants. We hypothesize that biocorrosive activity by OCs will be greater on SS than titanium. To assess the biocorrosive effects of OCs on SS and Ti, the top face of 150 µm thick sections of each metal were scanned using a Proscan 2000 Scantron to provide accurate three dimensional surface measurements of the metals before introduction of OCs. OC precursors were isolated from the bone marrow of C57/bl6 mice and differentiated with macrophage colony stimulating factor and receptor activator of NF-kappaB ligand for 7 days in the presence of either SS or Ti metals. The metals discs were then removed and rescanned with the Proscan Scantron and changes in the surface measurements before and after OC growth was calculated. OCs were fixed and stained for tartrate-resistant acid phosphatase, a marker of mature OCs, and counted. Our preliminary findings revealed that the surface roughness of SS was reduced to a greater extent than Ti metals. OC number was also reduced in cultures containing SS compared with Ti. These findings suggest SS may be more susceptible to OC-mediated biocorrosion than Ti-based metal implants. Although the physiological implications are unclear, we speculate that sustained corrosion of SS can negatively affect the long-term stability of implants in vivo.
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    Three-dimensional airway volumes and most constricted areas in children
    (Office of the Vice Chancellor for Research, 2012-04-13) Kula, K.; Ahn, E.J.; Liu, S.; Stewart, K.; Eckert, G.; Halum, S.; Dillehay, J.; Eraso, F.; Ghoneima, A.
    Objective: The objectives of this retrospective study using cone beam computed tomography (CBCT) were to determine if there are differences in the volume of various airway segments and the most constricted area (MCA) of children with different dentoskeletal patterns. Methods: The initial CBCTs of 83 orthodontic patients (30 Angle’s Class I; 26 Class II; and 27 Class III) were collected from a private orthodontic office. Following reliability studies, various parameters of the craniofacial complex, airway volume, and MCA were measured utilizing Dolphin 3D software. Comparisons among the three dental and the skeletal malocclusion classes were performed using one-way ANOVA and Fishers Protected Least Significant. Associations of the airway volumes and the MCA with other parameters were determined using correlation coefficients, accepting p < 0.05 as significant for all tests. Results: Maxillary right sinus volume was the only airway segment showing significant difference among different dental classes. Maxillary sinus volume also correlated moderately with anterior facial height and mandibular length. No significant differences were found between the MCA and different dentoskeletal classifications. Conclusions: The only significant difference in airway parameters among the dentoskeletal classes was that the dental Class II subjects had greater right sinus volume than the other classes. Shorter anterior facial height or mandibular length could be indicators for decreased airway volume in children. Funding: IUSD Graduate Research Committee, IUPUI Three-Dimensional Imaging of the Craniofacial Complex Center, Jarabak Endowed Professorship