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Richard A. Prinz, M.D.

Richard A. Prinz, M.D.

Richard A. Prinz, M.D.

  • Locations

    NorthShore Medical Group

    1000 Central St.
    Suite 800
    Evanston, IL 60201
    847.570.1700 847.733.5296 fax Get Directions This location is wheelchair accessible.

    NorthShore Medical Group

    757 Park Ave. West
    Suite 2850
    Highland Park, IL 60035
    847.570.1700 847.733.5296 fax Get Directions This location is wheelchair accessible.

    NorthShore Medical Group

    1329 N. Wolf Rd.
    Mount Prospect, IL 60056
    847.570.1700 847.733.5296 fax Get Directions This location is wheelchair accessible.
  • Publications
    • Inhibition of the sonic hedgehog pathway activates TGF-β-activated kinase (TAK1) to induce autophagy and suppress apoptosis in thyroid tumor cells.

      Cell death & disease 2021 May 08

      Authors: Li S, Wang J, Lu Y, Zhao Y, Prinz RA, Xu X
      The sonic hedgehog (Shh) pathway is highly activated in a variety of malignancies and plays important roles in tumorigenesis, tumor growth, drug resistance, and metastasis. Our recent study showed that the inhibitors of the Shh pathway such as cyclopamine (CP), a Smothened (SMO) inhibitor, and GANT61, a Gli1 inhibitor, have modest inhibitory effects on thyroid tumor cell proliferation and tumor growth. The objective of this study was to determine whether autophagy was induced by inhibition of the Shh pathway and could negatively regulate GANT61-induced apoptosis. Here we report that inhibition of the Shh pathway by Gli1 siRNA or by cyclopamine and GANT61 induced autophagy in SW1736 and KAT-18 cells, two anaplastic thyroid cancer cell lines; whereas Gli1 overexpression suppressed autophagy. Mechanistic investigation revealed that inhibition of the Shh pathway activated TAK1 and its two downstream kinases, the c-Jun-terminal kinase (JNK) and AMP-activated protein kinase (AMPK). GANT61-induced autophagy was blocked by TAK1 siRNA and the inhibitors of TAK1 (5Z-7-oxozeaenol, 5Z), JNK (SP600125), and AMPK (Compound C, CC). Inhibition of autophagy by chloroquine and 5Z and by TAK1 and Beclin-1 siRNA enhanced GANT61-induced apoptosis and its antiproliferative activity. Our study has shown that inhibition of the Shh pathway induces autophagy by activating TAK1, whereas autophagy in turn suppresses GANT61-induced apoptosis. We have uncovered a previously unrecognized role of TAK1 in Shh pathway inhibition-induced autophagy and apoptosis.
      PMID: 33966040 [PubMed - as supplied by publisher]
    • Radioactive iodine-125 seed localization as an aid in reoperative neck surgery.

      American journal of surgery 2021 03

      Authors: Bortz MD, Khokar A, Winchester DJ, Moo-Young TA, Ecanow DB, Ecanow JS, Prinz RA
      Scarring and disrupted tissue planes add to already-complex neck anatomy and make localization of nonpalpable pathology difficult in cervical endocrine reoperations. We describe the use of radioactive iodine-125 seed localization (RSL) in 6 patients with metastatic papillary thyroid carcinoma (PTC) and 2 with recurrent hyperparathyroidism.
      Eight patients had 2-D ultrasound-guided RSL of the target lesion, 0-3 days preoperatively. Intraoperative gamma probe (Neoprobe) was used to plan incision placement and localize the implanted seed. Recorded operative variables included: number of lymph nodes (LNs) harvested, estimated blood loss (EBL), operative time, length of stay (LOS) and RSL and operative complications.
      All patients had successful resection of the targeted area and removal of the radioactive seed. There was no seed migration. Two complications occurred in the thyroid group.
      Radioactive iodine 125 seeds facilitate successful localization of endocrine pathology during reoperative cervical procedures.
      PMID: 33546853 [PubMed - as supplied by publisher]
    • Tips for authors of surgical manuscripts from senior reviewers.

      Surgery 2021 Jul

      Authors: Malangoni MA, Evans DB, Prinz RA, Hodin RA, Rege R, Harken AH
      PMID: 33494949 [PubMed - as supplied by publisher]
    • In Vitro and In Vivo Antiviral Activity of Gingerenone A on Influenza A Virus Is Mediated by Targeting Janus Kinase 2.

      Viruses 2020 10 08

      Authors: Wang J
      Janus kinase (JAK) inhibitors have been developed as novel immunomodulatory drugs and primarily used for treating rheumatoid arthritis and other inflammatory diseases. Recent studies have suggested that this category of anti-inflammatory drugs could be potentially useful for the control of inflammation "storms" in respiratory virus infections. In addition to their role in regulating immune cell functions, JAK1 and JAK2 have been recently identified as crucial cellular factors involved in influenza A virus (IAV) replication and could be potentially targeted for antiviral therapy. Gingerenone A (Gin A) is a compound derived from ginger roots and a dual inhibitor of JAK2 and p70 S6 kinase (S6K1). Our present study aimed to determine the antiviral activity of Gin A on influenza A virus (IAV) and to understand its mechanisms of action. Here, we reported that Gin A suppressed the replication of three IAV subtypes (H1N1, H5N1, H9N2) in four cell lines. IAV replication was also inhibited by Ruxolitinib (Rux), a JAK inhibitor, but not by PF-4708671, an S6K1 inhibitor. JAK2 overexpression enhanced H5N1 virus replication and attenuated Gin A-mediated antiviral activity. In vivo experiments revealed that Gin A treatment suppressed IAV replication in the lungs of H5N1 virus-infected mice, alleviated their body weight loss, and prolonged their survival. Our study suggests that Gin A restricts IAV replication by inhibiting JAK2 activity; Gin A could be potentially useful for the control of influenza virus infections.
      PMID: 33050000 [PubMed - as supplied by publisher]
    • Inhibition of porcine epidemic diarrhea virus (PEDV) replication by A77 1726 through targeting JAK and Src tyrosine kinases.

      Virology 2020 12

      Authors: Li X, Sun J, Prinz RA, Liu X, Xu X
      Porcine epidemic diarrhea (PED) virus (PEDV) is a coronavirus that primarily infects porcine intestinal epithelial cells and causes severe diarrhea and high fatality in piglets. A77 1726 is the active metabolite of leflunomide, a clinically approved anti-rheumatoid arthritis (RA) drug. A77 1726 inhibits the activity of protein tyrosine kinases (PTKs), p70 S6 kinase (S6K1), and dihydroorotate dehydrogenase (DHO-DHase). Whether A77 1726 can control coronavirus infections has not been investigated. Here we report that A77 1726 effectively restricted PEDV replication by inhibiting Janus kinases (JAKs) and Src kinase activities but not by inhibiting DHO-DHase and S6K1 activities. Overexpression of Src, JAK2 or its substrate STAT3 enhanced PEDV replication and attenuated the antiviral activity of A77 1726. Our study demonstrates for the first time the ability of A77 1726 to control coronavirus replication by inhibiting PTK activities. Leflunomide has potential therapeutic value for the control of PEDV and other coronavirus infections.
      PMID: 32829915 [PubMed - as supplied by publisher]
    • Extrathyroidal extension predicts negative clinical outcomes in papillary thyroid cancer.

      Surgery 2021 Jan

      Authors: Bortz MD, Kuchta K, Winchester DJ, Prinz RA, Moo-Young TA
      The eighth edition American Joint Committee on Cancer tumor-node-metastasis staging for well-differentiated thyroid cancers, no longer considers "minimal" extrathyroidal extension for tumor staging. This change prompted us to examine the effect of extrathyroidal extension on patient outcomes.
      Patients (n = 177,497) in the 2016 National Cancer Database with classic papillary thyroid cancer were evaluated to determine the effect of extrathyroidal extension on overall survival and risk for nodal and distant metastases. Kaplan-Meier curves with the log-rank test were used to evaluate survival differences. Multivariable Cox and logistic regression analyses included relevant clinicopathologic variables (e.g. age, sex, race, and Charlson Comorbidity Index).
      Patients with "minimal" extrathyroidal extension had worse survival versus patients with no extrathyroidal extension (10-year survival 89.3% vs 93.1%, hazard ratio 1.23; 95% confidence interval, 1.13-1.35; P < .001). Any extrathyroidal extension was associated with higher risks for lymph node (odds ratio 2.78; 95% confidence interval, 2.69-2.87) and distant metastasis (odds ratio 3.5; 95% confidence interval, 3.05-4.04). These associations persisted when comparing "micro" (extension into the thyroid capsule) versus none for nodal risk (odds ratio 1.25; 95% confidence interval, 1.18-1.33) and distant metastasis (OR 1.52; 95% confidence interval, 1.11-2.09).
      All levels of extrathyroidal extension, including microscopic, were associated with increased risk for nodal and distant metastasis. Both minimal and macroscopic extrathyroidal extension were also associated with decreased overall survival. Such findings have the potential to affect the clinical decision making for patients diagnosed with papillary thyroid cancer.
      PMID: 32682508 [PubMed - as supplied by publisher]
    • H1N1 Influenza Virus Cross-Activates Gli1 to Disrupt the Intercellular Junctions of Alveolar Epithelial Cells.

      Cell reports 2020 06 30

      Authors: Ruan T, Sun J, Liu W, Prinz RA, Peng D, Liu X, Xu X
      Influenza A virus (IAV) primarily infects the airway and alveolar epithelial cells and disrupts the intercellular junctions, leading to increased paracellular permeability. Although this pathological change plays a critical role in lung tissue injury and secondary infection, the molecular mechanism of IAV-induced damage to the alveolar barrier remains obscure. Here, we report that Gli1, a transcription factor in the sonic hedgehog (Shh) signaling pathway, is cross-activated by the MAP and PI3 kinase pathways in H1N1 virus (PR8)-infected A549 cells and in the lungs of H1N1 virus-infected mice. Gli1 activation induces Snail expression, which downregulates the expression of intercellular junction proteins, including E-cadherin, ZO-1, and Occludin, and increases paracellular permeability. Inhibition of the Shh pathway restores the levels of Snail and intercellular junction proteins in H1N1-infected cells. Our study suggests that Gli1 activation plays an important role in disrupting the intercellular junctions and in promoting the pathogenesis of H1N1 virus infections.
      PMID: 32610119 [PubMed - as supplied by publisher]
    • A77 1726, the active metabolite of the anti-rheumatoid arthritis drug leflunomide, inhibits influenza A virus replication in vitro and in vivo by inhibiting the activity of Janus kinases.

      FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2020 08

      Authors: Wang J, Sun J
      The newly reassorted IAV subtypes from zoonotic reservoirs respond poorly to current vaccines and antiviral therapy. There is an unmet need in developing novel antiviral drugs for better control of IAV infection. The cellular factors that are crucial for virus replication have been sought as novel molecular targets for antiviral therapy. Recent studies have shown that Janus kinases (JAK), JAK1, and JAK2, play an important role in IAV replication. Leflunomide is an anti-inflammatory drug primarily used for treating rheumatoid arthritis (RA). Prior studies suggest that A77 1726, the active metabolite of leflunomide, inhibits the activity of JAK1 and JAK3. Our current study aims to determine if A77 1726 can function as a JAK inhibitor to control IAV infection. Here, we report that A77 1726 inhibited the replication of three IAV subtypes(H5N1, H1N1, H9N2)in three cell types (chicken embryonic fibroblasts, A549, and MDCK). A77 1726 inhibited JAK1, JAK2, and STAT3 tyrosine phosphorylation. Similar observations were made with Ruxolitinib (Rux), a JAK-specific inhibitor. JAK2 overexpression enhanced H5N1 virus replication and compromised the antiviral activity of A77 1726. Leflunomide inhibited virus replication in the lungs of IAV-infected mice, alleviated their body weight loss, and prolonged their survival. Our study demonstrates for the first time the ability of A77 1726 to inhibit JAK2 activity and suggests that inhibition of JAK activity contributes to its antiviral activity.
      PMID: 32598086 [PubMed - as supplied by publisher]
    • The Gli1-Snail axis contributes to Salmonella Typhimurium-induced disruption of intercellular junctions of intestinal epithelial cells.

      Cellular microbiology 2020 08

      Authors: Liu W, Ruan T, Ji X, Ran D, Sun J
      Salmonella enterica serovar Typhimurium (S. Typhimurium) is a facultative intracellular pathogen that damages gastrointestinal tissue and causes severe diarrhoea. The mechanisms by which Salmonella disrupts epithelial barrier and increases the paracellular permeability are incompletely understood. Our present study aims to determine the role of Gli1, a transcription factor activated in the sonic hedgehog (Shh) pathway, in decreasing the levels of apical junction proteins in a Salmonella-infected human colonic epithelial cancer cell line, Caco-2, and in the intestinal tissue of Salmonella-infected mice. Here, we report that S. Typhimurium increased the mRNA and protein levels of Gli1 and Snail, a downstream transcription factor that plays an important role in the epithelial-to-mesenchymal transition (EMT). S. Typhimurium also decreased the levels of E-cadherin and three tight junction proteins (ZO-1, claudin-1, and occludin). Gli1 siRNA and GANT61, a Gli1-specific inhibitor, blocked S. Typhimurium-induced Snail expression, restored the levels of E-cadherin and tight junction proteins, and prevented S. Typhimurium-increased paracellular permeability. Further study showed that Gli1 was cross-activated by the MAP and PI-3 kinase pathways. S. Typhimurium devoid of sopB, an effector of the Type 3 secretion system (T3SS) responsible for AKT activation, was unable to induce Snail expression and to decrease the expression of apical junction proteins. Our study uncovered a novel role of Gli1 in mediating the Salmonella-induced disruption of the intestinal epithelial barrier.
      PMID: 32329192 [PubMed - as supplied by publisher]
    • Trends in nonoperative management of papillary thyroid microcarcinoma.

      Journal of surgical oncology 2020 May

      Authors: Holoubek SA, Yan H, Kuchta KM, Winchester DJ
      In 2010, a Japanese trial of nonoperative management for papillary thyroid microcarcinomas (PTmC) was published. This study determines if the prevalence of nonoperative management in the United States has changed and if there are predictors of this approach.
      Patients treated for PTmC between 2004 and 2015 in the National Cancer Data Base were identified. Inclusion criteria were: classic or follicular variant papillary cancer histology, tumor size 1 to 10 mm, cN0 disease and no extrathyroidal extension or metastatic disease. Nonoperative management was assessed over time and compared between 2004-2010 and 2010-2015. Logistic regression identified factors associated with nonoperative management.
      Of 65 381 PTmC patients, 344 (0.5%) were treated nonoperatively. The annual rate of nonoperative management was similar at 0.6% in 2004 to 0.4% in 2010 (P = .755) but increased to 0.9% in 2015 (P < .001). There was no difference in patient age, race, comorbidities, or reason for nonoperative management between the two periods. Academic centers managed more patients nonoperatively. Multivariable logistic regression suggests older age, facility type, location, Hispanic, Asian, and Native American ethnicity were associated with nonoperative management.
      The vast majority of PTmC in the United States is treated with an operation. A small but significant increase in nonoperative management occurred between 2004-2010 and 2010-2015.
      PMID: 32189361 [PubMed - as supplied by publisher]