tbuckley/cabot-search huggingface dataset:
Abstract 2440: Cross-tissue interactome analyses unravel novel oncogenic roles of SOX2
Authors: Thorsten Schaefer, Silvia Candido, Hui Wang, Thomas Bock, Alexander Schmidt, Claudia Lengerke
Journal: Cancer Research (2017)

Abstract First recognized for its significance in early embryogenesis, SOX2 (sex determining region Y box 2) more recently received major attention as a (i) transcriptional master regulator of stemness driving the re-programming of terminally differentiated somatic cells back into a pluripotent stem cell state and (ii) powerful oncogene of the cancer stem cell (CSC) compartment. We and others have shown that SOX2 expression relies on canonical PI3K/AKT signaling involving direct physical contact and phospho-modification by AKT. Interestingly, we observed that these interactions are highly tissue specific which prompted us to perform a systematic proteomic analysis of co-factors regulating SOX2 biology. The SOX2 interactome was analyzed in human breast carcinoma and glioblastoma cell lines by co-immunoprecipitation (co-IP) and HPLC/MS revealing &amp;gt;900 individual and &amp;gt;70 conserved proteinaceous co-factors, thus underscoring a hitherto underestimated scaffolding function of SOX2. As expected, a major proportion of binding partners cluster in functional categories implicated in DNA binding and/or nucleotide modification (e.g. helicases, transferases, and ligases). However, a near equal share of SOX2 associated factors fall into functional classes formally unrelated to transcription modulation such as cell adhesion, cytoskeletal organization, or metabolic adaptation. Using SOX2 knock-down and overexpression cells generated by lentiviral technology, we confirm co-regulation of SOX2 with selected binding partners. Moreover, we observe co-depletion of SOX2 and protein co-factors in cells of stalled AKT activity, and a molecular restoration of both upon proteasomal inhibition. We conclude that, besides its known significance in DNA activity control, the SOX2 protein engages in various interactions seemingly unrelated to transcription modulation. These newly discovered interactions are likely to synergize with canonical SOX2 functions (i.e. the induction and maintenance of stemness), but involve regulation at post-translational level and of extra-nuclear components. Our efforts thus add an exciting new facet to SOX2 biology and eventually, may open new therapeutic avenues for targeted anti-CSC therapy. Citation Format: Thorsten Schaefer, Silvia Candido, Hui Wang, Thomas Bock, Alexander Schmidt, Claudia Lengerke. Cross-tissue interactome analyses unravel novel oncogenic roles of SOX2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2440. doi:10.1158/1538-7445.AM2017-2440
Room for improvement: a randomised controlled trial with nested qualitative interviews on space, place and treatment delivery
Authors: Louise F Sandal, Jonas B Thorlund, Andrew J Moore, Roger S Ulrich, Paul A Dieppe, Ewa M Roos
Journal: British Journal of Sports Medicine (2017)

Objective Healthcare-oriented design in hospitals can promote better clinical outcomes. Creating optimal facilities may increase treatment effects. We investigated the influence of the treatment room on effects of exercise therapy. Methods In a mixed-method randomised controlled double-blind trial, middle-aged individuals reporting knee or hip pain performed 8 weeks of exercise therapy in (1) a newly built physically enhanced environment, (2) a standard environment or (3) were waitlisted, receiving no intervention. Participants and therapists were blind to study aim. Primary outcome was participants’ Global Perceived Effect (GPE; seven-point Likert scale). Six nested focus group interviews with participants (n=25) and individual interviews with therapists (n=2) explored experiences of the environments. Results 42 people exercised in the physically enhanced environment, 40 in the standard environment, 21 were waitlisted. Contrary to our hypothesis, the treatment response seemed greater in the standard environment for GPE (0.98, 95% CI0.5 to 1.4) than for the physically enhanced environment (0.37, 95% CI −0.2 to 0.9), between-group difference (0.61, 95% CI −0.1 to 1.3) did not reach statistical significance (p=0.07). Waitlist group reported no improvement (−0.05 95% CI −0.5 to 0.4). In interviews, participants from the standard environment expressed greater social cohesion and feeling at home. Qualitative themes identified; reflection, sense of fellowship and transition. Secondary patient-reported outcomes and qualitative findings supported the primary finding, while improvements in muscle strength and aerobic capacity did not differ between exercise groups. Conclusion Results suggest that the physical environment contributes to treatment response. Matching patients’ preferences to treatment rooms may improve patient-reported outcomes. Trial registration number ClinicalTrials.gov identifier: NCT02043613 .
Abstract 172: Oxidative stress and hepatotoxicity induced by graphene oxide in Sprague-Dawley Rats
Authors: Anita K. Patlolla, Paul B. Tchounwou
Journal: Cancer Research (2017)

Abstract Graphene oxide (GO) has been extensively explored as a promising nanomaterial for applications in biology because of its unique properties. Therefore, systematic investigation of GO toxicity is essential to determine its fate in the environment and potential adverse health effect. The aim of this study was to investigate the effect of graphene oxide on the induction of reactive oxygen species (ROS), the activity of certain liver enzymes (Alanine ALT, Aspartate AST, alkaline phosphatases ALP), and concentration of lipid hydroperoxide (LHP) in serum and histopathological evaluation of liver tissue in Sprague-Dawley rats. Four groups of five male rats were orally administered GOs, once a day for five days, with doses of 0, 10, 20 and 40 mg/Kg GO. A control group was also made of five rats. Blood and liver were collected 24 h after the last treatment following standard protocols. GO’s exposure increased the induction of ROS, the activities of the liver enzymes (ALT, AST, ALP), concentration of lipid hydroperoxide (LHP) and morphological alterations of the liver tissue in exposed groups compared to control. The highest two doses, 20 and 40 mg/kg, showed statistically significant (p &amp;lt; 0.05) increases in the induction of ROS, activities of ALT, ALP , LHP concentration, and morphological alterations of liver tissue compared to control. However, AST activity showed no effect. Taken together, the results of this study demonstrate that GO is hepatotoxic, and its toxicity may be mediated through oxidative stress. Citation Format: Anita K. Patlolla, Paul B. Tchounwou. Oxidative stress and hepatotoxicity induced by graphene oxide in Sprague-Dawley Rats [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 172. doi:10.1158/1538-7445.AM2017-172
Abstract 4491: Modulation of p63 expression by phosphorylation of RBM38 at S195 via miR-203
Authors: YANHONG ZHANG, WENSHENG YAN, JIN ZHANG, XINBIN CHEN
Journal: Cancer Research (2017)

Abstract p63, a p53 family protein, acts as a sequence-specific DNA-binding transcriptional factor to regulate the expression of target genes involving in various cellular processes, including growth suppression and epithelial development. RBM38, a RNA-binding protein, is a target of p53 family and is known to interact with its target mRNAs and regulate their expression via mRNA stability. Previously, we found that RBM38 negatively regulates p63 mRNA stability through binding to the AU/U-rich element in 3′ untranslated region (3′-UTR). We also found that phosphorylation of RBM38 at Ser195 alters the conformation and function of RBM38 protein. However, it is unclear whether phosphorylation of RBM38 or miR-203 alters the ability of RBM38 to regulate p63 expression. In this study, we found that in both MCF7 and HaCaT cells, wild-type RBM38 and S195A mutant, but not phosphor-mimic S195D mutant, inhibit p63 mRNA stability, suggesting that Ser195 phosphorylation abrogates the ability of RBM38 to repress the expression of p63. Importantly, we found that phosphorylation of RBM38 disrupts the binding of RBM38 to the U-rich element in p63 3′-UTR. Additionally, we found that miR-203 inhibitor increases, whereas miR203 mimic decreases p63 expression through binding to p63 3′-UTR, consistent with a previous report. Interestingly, we found that the ability of RBM38 to repress p63 expression is disrupted by miR-203 inhibitor but enhanced by miR-203 mimic. Furthermore, we found that wild-type RBM38 protein, but not phosphor-mimic S195D mutant, physically interacts with Ago2, indicating that RBM38 may inhibit p63 mRNA stability by modulating Ago2-miR-203 complex to bind to the U-rich element in p63 3′-UTR. Together, we uncovered a novel mechanism by which RBM38 modulates p63 expression via miR-203. Note: This abstract was not presented at the meeting. Citation Format: YANHONG ZHANG, WENSHENG YAN, JIN ZHANG, XINBIN CHEN. Modulation of p63 expression by phosphorylation of RBM38 at S195 via miR-203 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4491. doi:10.1158/1538-7445.AM2017-4491
Hepatitis screening and management before rituximab administration.
Authors: Nataliya Mar, Lisa Holle, Jeffrey S. Wasser, Karen Hook
Journal: Journal of Clinical Oncology (2015)

e17747 Background: Rituximab therapy is associated with hepatitis B and, possibly, hepatitis C reactivation. Multiple guidelines recommend hepatitis B screening of patients being considered for anti-CD20 therapy. However, they differ with regards to timing of screening, tests to use, management of carriers, and hepatitis C screening. Due to these inconsistencies, we hypothesized that guideline adherence rates were suboptimal. Methods: Consecutive patients receiving rituximab between 1/2008 and 9/2014 at the University of Connecticut were included. Exclusion criteria were prior rituximab therapy, age < 18 years, and incomplete records. A centralized pharmacy record and patient medical records were analyzed, with results expressed as percentages. Primary endpoint was rates of hepatitis B and C screening before rituximab therapy. Secondary endpoints were rates of gastroenterology referral, antiviral prophylaxis and follow-up serologies in hepatitis carriers as well as reactivation and hepatitis B vaccination in non-immune patients. Results: Of 234 patients, 180 met inclusion criteria. Mean age was 55.8 years with 44.4% males, 3.9% had prior liver disease, and 6.1% had history of alcohol abuse. Rituximab was given for hematologic diagnoses in 63.9% and 56.7% received monotherapy, with a mean of 6.46 treatments [range, 1 - 28]. Screening for hepatitis B occurred in 57.8% and hepatitis C in 48.8% of patients. Screening > 6 months before rituximab administration was documented in 26%, with a mean of 31.6 months [range, 7 - 66]. Of those screened, 55.8% had a complete screening panel. No patients had a positive hepatitis B screen, but 1.9% had an indeterminate result due to an incomplete panel. Positive hepatitis C screen was found in 4.8%. Of those with a positive screen, 40% were referred to gastroenterology, 20% received antiviral prophylaxis, and 0% had follow-up serologic testing. No patients developed hepatitis reactivation. 50% had no evidence of hepatitis B immunity and 0% had vaccination documentation. Conclusions: Hepatitis screening rates before rituximab are suboptimal. A systematic approach to patient management must be adopted among providers. Harmonization of guidelines should contribute to improved compliance and outcomes.
Abstract 4005: HDAC inhibitors regulate M2 tumor-associated macrophage function through histone acetylation
Authors: Amber E. de Groot, Jelani C. Zarif, Kenneth J. Pienta
Journal: Cancer Research (2017)

Abstract Macrophage tumor infiltration in metastatic prostate cancer is a predictor of patient prognosis. Macrophages influence tumors in contrasting ways depending on their polarization: M1 macrophages have anti-tumor functions while M2 macrophages are pro-tumor. The external stimuli influencing macrophage differentiation and M2 polarization have been largely elucidated but the resulting downstream changes remain unknown. There are a number of epigenetic differences between M1 and M2 macrophages that act as important functional determinants. Recent work studying these epigenetic changes has implicated histone deacetylases (HDACs), as critical regulators in macrophage differentiation and in maintaining M1 or M2 function. Pan-HDAC inhibitors (HDIs) such as the clinically utilized suberanilohydroxamic acid (SAHA) target a wide range of HDACs and provide a means for manipulating macrophage histone acetylation. Though HDIs have been found to attenuate inflammatory functions in M1 macrophages, the field has yet to explore effects of histone acetylation in M2 macrophages. Using M2 macrophages derived from human CD14+ monocytes, we found that SAHA regulates M2 macrophage polarization and function through alteration of histone acetylation. Work is ongoing to test expression levels of canonical M2 markers such as the mannose receptor CD206 and scavenger receptor CD163 in M2 macrophages exposed to SAHA either during or after M2 polarization. Additionally, investigation into the ability of these populations to secrete M2 cytokines such as IL-10 and VEG-FA and induce EMT in prostate cancer cells is also being pursued. These results contribute to scientific knowledge of epigenetic regulation in macrophage function and elucidate strategies to decrease the pro-tumor function of tumor-infiltrating M2 macrophages. This work lays the foundation for using epigenetic regulators to modulate the tumor microenvironment and advance cancer medicine. Citation Format: Amber E. de Groot, Jelani C. Zarif, Kenneth J. Pienta. HDAC inhibitors regulate M2 tumor-associated macrophage function through histone acetylation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4005. doi:10.1158/1538-7445.AM2017-4005
Nonsurgical and surgical treatment of periodontitis: how many options for one disease?
Authors: Filippo Graziani, Dimitra Karapetsa, Bettina Alonso, David Herrera
Journal: Periodontology 2000 (2017)

Treatment of periodontitis aims at preventing further disease progression with the intentions to reduce the risk of tooth loss, minimize symptoms and perception of the disease, possibly restore lost periodontal tissue and provide information on maintaining a healthy periodontium. Therapeutic intervention includes introduction of techniques to change behavior, such as: individually tailored oral-hygiene instructions; a smoking-cessation program; dietary adjustment; subgingival instrumentation to remove plaque and calculus; local and systemic pharmacotherapy; and various types of surgery. No single treatment option has shown superiority, and virtually all types of mechanical periodontal treatment benefit from adjunctive antimicrobial chemotherapy. Periodontal treatment, because of the chronic nature of periodontitis, is a lifelong commitment to intricate oral-hygiene techniques, which, when properly implemented, will minimize the risk of disease initiation and progression.
High-Throughput Sequencing as First-Tier Diagnostics in Congenital and Early-Onset Disorders
Authors: Johannes R. Lemke
Journal: JAMA Pediatrics (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Abstract 5539: The phenotypic characterization of Lrig null mouse embryonic fibroblasts
Authors: Carl Herdenberg, Håkan Hedman
Journal: Cancer Research (2017)

Abstract The LRIG gene family consists of LRIG1, LRIG2 and LRIG3. The most studied of these is LRIG1, which is a tumor suppressor gene. The LRIG1 protein is downregulated in various types of cancer and it negatively regulates receptor tyrosine kinases including the EGF- and PDGF-receptors. Lrig1 also regulates stem cell homeostasis in mouse skin and intestine. The functions of LRIG2 and LRIG3 are less known, but some findings imply that they might antagonize LRIG1. Intriguingly, the sole LRIG homolog in C. elegans, Sma-10, positively regulates BMP signaling. Thus, it is not known to what degree the LRIG proteins have the same, overlapping, or opposing functions, and the molecular mechanisms involved are poorly characterized. To elucidate the functions of the three LRIG proteins we generated a series of wildtype and LRIG-null (Lrig1-/-;Lrig2-/-;Lrig3-/-) mouse embryonic fibroblast (MEF) lines. These cell lines were created from homozygous Lrig1flox/flox;Lrig2flox/flox;Lrig3flox/flox mouse embryos. The FLOXed Lrig genes were then deleted with CRE-recombinase, thereby creating Lrig-null MEFs. ddPCR analysis showed that the Lrig-null MEF lines were contaminated with less than 1% of cells carrying wildtype Lrig3 alleles. Lrig-null MEFs showed a higher proliferation rate and migrated more in trans-well chambers than the wildtype cells. These cell lines will also be useful to investigate the importance of Lrig proteins for other cellular functions such as, signal transduction, lipidomics, transcriptomics, secretomics, metabolomics, and oxidative stress sensitivity. We also transduced the Lrig-null cells with individual inducible Lrig-genes thus creating a powerful system for the examination of the biology of the specific Lrig proteins. Citation Format: Carl Herdenberg, Håkan Hedman. The phenotypic characterization of Lrig null mouse embryonic fibroblasts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5539. doi:10.1158/1538-7445.AM2017-5539
Abstract 3491: A role for the long non-coding RNA <i>GHRLOS</i> in cancer
Authors: Esha T. Shah, Penny Jeffery, Patrick Thomas, Inge Seim, Lisa Chopin
Journal: Cancer Research (2017)

Abstract Long non-coding RNA (lncRNA) genes are abundant in the human genome, and many are now recognized as oncogenes and/or tumor suppressors. We previously characterized the structure of GHRLOS, an antisense gene on the opposite strand of the multifunctional ghrelin gene (GHRL), however, its expression and function in disease has not been described. To this end, using The Cancer Genome Atlas (TCGA) data set, we revealed that GHRLOS is differentially expressed in a number of cancers. In particular, expression was elevated in endometrial cancer (1.2 - fold; P = 7.1 x 10-3 Welch's two-sample t-test; n = 24 vs. n = 175) and prostate cancer (1.2-fold; P = 3.7 x 10-6; n = 52 vs. n = 498) compared to normal tissues. Using qRT-PCR (and commercial cDNA panels) we confirmed that GHRLOS expression was upregulated in endometrial cancer (1.96-fold, P = 0.005 Welch’s two-sample t-test, n = 5 vs. n = 17) and prostate cancer (2.46-fold, P = 0.0045 Welch’s two-sample t-test, n = 5 vs. n = 21) compared to normal tissues. Initial studies, using siRNA designed to silence endogenous GHRLOS expression, significantly reduced cell migration in the PC3 prostate cancer cell line (0.47-fold change, P = 0.042 Kruskal-Wallis test, n = 2) conversely, preliminary data using forced GHRLOS overexpression increased migration and proliferation. Taken together, we show that the long non-coding RNA GHRLOS is differentially expressed in tumor tissue and regulates cell migration and proliferation; possibly by modulating alternative splicing of the overlapping, multifunctional ghrelin gene locus. Targeting GHRLOS could provide a valuable and novel way to target the ghrelin axis in disease. Ongoing studies aim to validate in vitro functional results in complementary mouse xenograft models and identify genes and pathways regulated by this novel lncRNA. Citation Format: Esha T. Shah, Penny Jeffery, Patrick Thomas, Inge Seim, Lisa Chopin. A role for the long non-coding RNA GHRLOS in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3491. doi:10.1158/1538-7445.AM2017-3491
Extracts from responses
Authors: James A Cave
Journal: BMJ (2008)

The article on otalgia does not offer some really useful short cuts to help with ear pain.1


Wiggling the pinna is sore in otitis externa, not otitis media (sometimes difficult to differentiate if the external auditory meatus is full of debris).


Getting patients to “pop” their ears is a useful way of seeing if the pain is middle ear in origin.


A negative Rinne test is helpful when diagnosing otitis media (how can they have otitis media with an air filled middle ear?).