tbuckley/cabot-search huggingface dataset:
Abstract LB-355: Loss of keratinocyte desmoglein 1 occurs during melanoma development and alters crosstalk between keratinocytes and melanocytes
Authors: Christopher Arnette, Jodi L. Johnson, Hope E. Burks, Jennifer L. Koetsier, Kathleen J. Green
Journal: Cancer Research (2018)

Abstract Ultraviolet (UV)-induced mutations in melanocytes are a well-established cause of melanoma. However, histologically normal “fields” of altered keratinocytes present in sun-exposed epidermis could also drive initiation and progression of melanoma. We previously demonstrated that UV radiation reduced expression of the keratinocyte desmosomal cadherin, desmoglein 1 (Dsg1), and that loss-of-function mutations in Dsg1 increased keratinocyte cytokine production in Severe dermatitis, multiple Allergies, and Metabolic wasting (SAM) syndrome. Based on these observations we hypothesized that loss of Dsg1 alters the microenvironment through increased cytokine signaling. Here, we show that Dsg1 expression is progressively reduced in regions surrounding human dysplastic nevi, melanoma in situ, and stage I/II melanomas. In contrast, keratinocyte E-cadherin was not significantly altered in early tumors. Dsg1 knockdown in keratinocytes in vitro increased phospho-EGFR, phospho-Stat3, and nuclear NFκB, while increasing keratinocyte mRNAs encoding IL-1α, IL-1β, IL-6 and IL-8 pro-inflammatory cytokines. Re-expressing silencing-resistant Dsg1 returned cytokine levels to control levels. To determine whether Dsg1 loss in keratinocytes elicits paracrine-mediated changes in melanocyte behavior, we treated normal primary melanocytes with conditioned media from Dsg1-silenced keratinocytes. Short-term (overnight) exposure to Dsg1-deficient conditioned media resulted in significantly increased melanocyte dendrite length, similar to morphology changes induced by UV exposure; however, long-term (7 day) exposure resulted in significantly shorter dendrites. Melanocytes exposed to Dsg1-deficient media increased melanin secretion and decreased melanin retention, a phenomenon associated with the process of transformation. Melanocytes incorporated into Dsg1-deficient 3D human skin equivalents exhibited aberrant behavior, including increased numbers and mis-localization to suprabasal layers. Based on these observations, we propose that under homeostatic conditions Dsg1 functions to maintain baseline levels of cytokine signaling, but that Dsg1 loss due to environmental stress disrupts keratinocyte:melanocyte communication through altered paracrine signaling to promote melanoma initiation. Citation Format: Christopher Arnette, Jodi L. Johnson, Hope E. Burks, Jennifer L. Koetsier, Kathleen J. Green. Loss of keratinocyte desmoglein 1 occurs during melanoma development and alters crosstalk between keratinocytes and melanocytes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-355.
Abstract 846: Co-targeting of Axl and MerTK improves radiation response in HNSCC
Authors: Mahyar Abbariki, Mahmoud Toulany, Mari Iida, Alecia Morgan, Kwang Nickel, Nellie McDaniel, Grace Kang, Chunrong Li, Paul Harari, Deric Wheeler
Journal: Cancer Research (2018)

Abstract Axl and MerTK are members of the TAM family (Tyro, Axl and MerTK) of receptor tyrosine kinases and have been reported to be altered in several types of cancer including Head and Neck Squamous Carcinoma (HNSCC). It is well known that aberrant expression or activity of Axl is associated with resistance to various therapies. Therefore, the translational potential of targeting AXL in HNSCC is worthy, however poorly defined. We recently identified an adaptive feedback mechanism of resistance to AXL-targeting agents mediated by upregulation of MerTK that reveals a direct role for MerTK in resistance to Axl inhibition. In this study, we investigated potential radiosensitization by dual targeting of Axl and MerTK in combination with radiation in human HNSCC cell lines and xenografts (SCC47 and TU138). Immunoblot analysis demonstrated that endogenous levels of Axl or MerTK expression were distinct between these two cell lines. SCC47 cells expressed higher endogenous levels of Axl compared to Tu138. Tu138 expressed higher levels of MerTK compared to SCC47 cells. Radiation induced Axl phosphorylation in SCC47 cells but not in Tu138 cells in vitro. Next, inhibitors of Axl (R428) and/or MerTK (UNC2025) were utilized in combination with single dose radiation in vitro. Clonogenic assays showed that the Axl inhibitor alone acted as a potent radiosensitizer in SCC47 cells. To better define Axl's role in radiation response in HNSCC, we developed HN30-Vector and HN30-Axl stable cells and exposed them to radiation. Phosphorylation of Axl was increased 1 hour post-radiation in Axl overexpressed HN30 compared to parental HN30-Vector which expresses low endogenous levels of Axl. We also found that the HN30-Axl cell line was associated with radioresistance by clonogenic assays. Tumor xenograft studies demonstrated that the combination of R428 and UNC2025 inhibitors improved the efficacy of radiation in Tu138 but not in SCC47. Interestingly, radiation therapy alone was more effective in SCC47 tumors than TU138 tumors. These results reveal that the co-targeting of Axl and MerTK enhanced tumor growth delay in TU138 xenograft mouse models in vivo. Mechanisms of radiosensitization are currently under investigation. Citation Format: Mahyar Abbariki, Mahmoud Toulany, Mari Iida, Alecia Morgan, Kwang Nickel, Nellie McDaniel, Grace Kang, Chunrong Li, Paul Harari, Deric Wheeler. Co-targeting of Axl and MerTK improves radiation response in HNSCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 846.
Abstract 692: Systemic inflammation and survival in colon and rectal cancer patients: Results from the ColoCare Study
Authors: Jennifer Ose
Journal: Cancer Research (2018)

Abstract BACKGROUND Systemic inflammation is an established risk marker for colorectal cancer that may also predict survival. We investigated associations between systemic inflammation and overall survival in a prospectively followed cohort of colorectal cancer patients. METHODS Pre-operatively collected serum samples from n=228 newly diagnosed colorectal cancer patients (stage I-IV) from the ColoCare Study were utilized to measure CRP, SAA, IL-6, IL-8, sICAM-1 and sVCAM-1 (Meso Scale Discovery platform). We used Cox proportional hazard models to investigate associations of biomarkers with overall survival after 24 months follow-up overall, and in analyses stratified by colon (n=92) and rectal tumors (n=136). Analyses were adjusted for age, sex, tumor stage and neo-adjuvant therapy (y/n). RESULTS After 24 months follow-up n=45 patients (20%) were deceased. CRP was significantly associated with increased risk of death in colon (HR:1.27; 95% CI: 1.03-1.57; pValue=0.02) but not rectal cancer (HR:1.06; 95% CI: 0.87-1.29; pValue=0.55). A doubling of circulating sICAM and sVCAM concentrations was significantly associated with increased risk of death in colorectal cancer (sICAM: HR:2.82; 95% CI: 1.57-5.05; pValue=0.0005; sVCAM: HR:3.70; 95% CI: 1.93-7.10; pValue&amp;lt;0.0001). For both biomarkers we observed stronger associations in rectal compared to colon cancer (e.g., sVCAM: rectal cancer (HR:8.13; 95% CI: 3.13-21.11; pValue&amp;lt;0.0001); colon cancer (HR:1.42; 95% CI: 0.68-2.98; pValue=0.35). Circulating IL-6 and IL-8 were not associated with increased risk of death in colon and/or rectal cancer. CONCLUSIONS Inflammatory biomarkers are significantly associated with increased risk of death in colorectal cancer patients. Our data suggest that the role of inflammation in disease progression may be particularly strong relevant in rectal cancer. Keywords: colorectal cancer; inflammation, biomarkers, overall survival, Citation Format: Jennifer Ose. Systemic inflammation and survival in colon and rectal cancer patients: Results from the ColoCare Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 692.
Abstract 14772: Cardiac Vagal Control in Knock-in Mouse model of Dilated Cardiomyopathy
Authors: DongYun Zhan, ChengKun Du, Tsuyoshi Akiyama, Sachio Morimoto, Shuji Shimizu, Toru Kawada, Mikiyasu Shirai, James T Pearson
Journal: Circulation (2016)

Background:  It has been reported that cardiac vagal nerve activity is reduced in heart failure, but cardiac vagal nerve activity in heart failure has only been evaluated by indirect methods in mice.   Objective:  To evaluate cardiac vagal nerve activity and identify the abnormality of cardiac vagal control in heart failure using a knock-in mouse model of dilated cardiomyopathy (DCM) with ΔK210 mutation in the cardiac troponin T gene.   Methods:  Microdialysis technique was applied to the left ventricular myocardium of anesthetized mice and myocardial interstitial acetylcholine (ACh) levels were measured by HPLC as an index of ACh release from cardiac vagal nerve endings. The effects of electrical stimulation of left cervical vagal nerves at 5 and 10 Hz (peripheral vagal control) and alpha-2 adrenergic stimulation by intravenous medetomidine at 0.1 mg/kg (central vagal control) were examined in wild-type (WT) mice (n=7) and DCM mice (n=7).   Results:  At baseline, heart rate was lower (390 ± 8 vs. 415 ± 4 bpm,  P  P  P    Conclusion:  In a mouse model of DCM, peripheral vagal control including ACh release from vagal nerve endings and heart rate control was preserved, but central vagal control through alpha-2 adrenergic receptors was impaired.
Post-translational buffering leads to convergent protein expression levels between primates
Authors: Sidney H. Wang, Chiaowen Joyce Hsiao, Zia Khan, Jonathan K. Pritchard
Journal: Genome biology (2018)

Differences in gene regulation between human and closely related species influence phenotypes that are distinctly human. While gene regulation is a multi-step process, the majority of research concerning divergence in gene regulation among primates has focused on transcription.To gain a comprehensive view of gene regulation, we surveyed genome-wide ribosome occupancy, which reflects levels of protein translation, in lymphoblastoid cell lines derived from human, chimpanzee, and rhesus macaque. We further integrated messenger RNA and protein level measurements collected from matching cell lines. We find that, in addition to transcriptional regulation, the major factor determining protein level divergence between human and closely related species is post-translational buffering. Inter-species divergence in transcription is generally propagated to the level of protein translation. In contrast, gene expression divergence is often attenuated post-translationally, potentially mediated through post-translational modifications.Results from our analysis indicate that post-translational buffering is a conserved mechanism that led to relaxation of selective constraint on transcript levels in humans.
Investigating the Role of Micronutrients in Brain Development and Psychiatric Disorders via Magnetic Resonance Imaging
Authors: Tomáš Paus
Journal: JAMA Psychiatry (2018)

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 Psychiatry 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 Psychiatry journal
Double-balloon platform-assisted rectal endoscopic submucosal dissection
Authors: Shawn Shah, Sam Sharma, Qais Dawod, Kaveh Hajifathalian, Monica Saumoy, Toyooki Sonoda, Reem Sharaiha
Journal: Endoscopy (2018)

A 69-year-old woman with complicated diverticular disease post-partial left colectomy was referred for evaluation of hematochezia. Index colonoscopy showed a large rectal polyp, and polypectomy was incomplete. Biopsy showed a traditional serrated adenoma. The case was referred to the advanced endoscopy service for further management.
Exercise in cirrhosis: Translating evidence and experience to practice
Authors: Puneeta Tandon, Kathleen Patricia Ismond, Kenneth Riess, Andres Duarte-Rojo, Bandar Al-Judaibi, Michael Andrew Dunn, Jennifer Holman, Nancy Howes, Mark Joseph Franklin Haykowsky, Deborah Ann Josbeno, Margaret McNeely
Journal: Journal of Hepatology (2018)
Abstract 5843: The efficacy of a histone deacetylase inhibitor in combination with a MEK inhibitor in lung cancer cells harboring RAS mutations
Authors: Tadaaki Yamada, Joseph M. Amann, Azusa Tanimoto, Hirokazu Taniguchi, Takehito Shukuya, Seiji Yano, Koichi Takayama, David P. Carbone
Journal: Cancer Research (2018)

Abstract Purpose: Non-small-cell lung cancer (NSCLC) can be identified by precise molecular subsets based on genomic alterations that drive tumorigenesis and include mutations in EGFR, KRAS, and various ALK fusions. However, despite effective treatment for EGFR and ALK, promising therapeutics have not been developed for patients with KRAS mutations. Therefore, novel therapeutic strategies for KRAS mutated cancer based on molecular mechanisms are needed to improve their prognosis. It has been reported that one way the RAS-ERK pathway contributes to tumorigenesis is by affecting stability and localization of FOXO3a protein, an important regulator of cell death and the cell cycle. Experimental Design: We used NSCLC cells with RAS mutation to evaluate the effect of a MEK inhibitor in combination with a HDAC inhibitor through the expression and localization of FOXO proteins in vitro and in vivo. Protein expression was examined by Western blotting. Results: Combined treatment with a MEK inhibitor and a HDAC inhibitor showed synergistic effects on cell viability of RAS mutated lung cancer cells through activation of FOXOs, with a subsequent increase in BIM and cell cycle inhibitors. Moreover, in a mouse xenograft model, the combination of belinostat and trametinib significantly decreases tumor formation through FOXOs by increasing BIM and increase in cell cycle inhibitors p21 and p27. Conclusions: These findings demonstrate that FOXOs might be one of the critical pathways in RAS driven lung cancer cells, suggesting that the dual molecular targeted therapy for MEK and HDACs may be promising as novel therapeutic strategy in NSCLC with specific populations of RAS mutations. Citation Format: Tadaaki Yamada, Joseph M. Amann, Azusa Tanimoto, Hirokazu Taniguchi, Takehito Shukuya, Seiji Yano, Koichi Takayama, David P. Carbone. The efficacy of a histone deacetylase inhibitor in combination with a MEK inhibitor in lung cancer cells harboring RAS mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5843.
Abstract 17322: Can Statins Reduces the Risk of Contrast-Induced Nephropathy Post Cardiac Catheterization?- A Network Meta-Analysis
Authors: Muhammad U Khan, Safi U Khan, Hammad Rahman, Muhammad Z Khan
Journal: Circulation (2017)

Introduction: Contrast-induced nephropathy (CIN) is a major cause of mortality and morbidity including increased incidence of hemodialysis, length of hospitalization and healthcare costs. Studies h...
Endoscopic ultrasound-guided transrectal pelvic abscess drainage using a lumen-apposing metal stent
Authors: Shawn Shah, Salem Karadesh, Enad Dawod, Monica Saumoy, Cheguevara Afaneh, Reem Sharaiha
Journal: Endoscopy (2018)

A 31-year-old woman with asthma presented with 1 week of lower abdominal pain and fevers after a recent emergency room discharge for appendicitis that had been managed conservatively with antibiotics. Upon presentation, she underwent a computed tomography (CT) scan of the abdomen and pelvis, which revealed a multiloculated pelvic abscess measuring approximately 7.3 × 4.7 × 7.0 cm ([Fig. 1]). The collection was thought to be unamenable to drainage by interventional radiology.
CircNT5E Acts as a Sponge of miR-422a to Promote Glioblastoma Tumorigenesis
Authors: Renjie Wang, Sai Zhang, Xuyi Chen, Nan Li, Jianwei Li, Ruichao Jia, Yuanqing Pan, Haiqian Liang
Journal: Cancer Research (2018)

Circular RNA and long noncoding RNA function as efficient miRNA sponges that regulate gene expression in eukaryotes. However, the sponges of functional miRNAs in glioblastoma remain largely unknown. Here, we identify a subset of circRNAs and lncRNAs that are specifically increased in miR-422a-downregulated glioblastoma tissues. We characterized a novel circRNA derived from NT5E, named circNT5E, that is regulated by ADARB2 binding to sites flanking circRNA-forming introns. We hypothesized that circNT5E may serve as a sponge against miR-422a in glioblastoma tumorigenesis. circNT5E controlled multiple pathologic processes, including cell proliferation, migration, and invasion. circNT5E directly bound miR-422a and inhibited miR-422a activity. Furthermore, circNT5E was observed to sponge other miRNAs, exhibiting tumor suppressor-like features in glioblastoma. Taken together, these findings highlight a novel oncogenic function of circRNA in glioblastoma tumorigenesis.Significance: Microarray profiling of circRNA/lncRNA/mRNA in glioblastoma identifies circNT5E as an oncogenic circular RNA and a sponge of miR-422a. Cancer Res; 78(17); 4812-25. ©2018 AACR.
Abstract 5689: Characterization of immune infiltrate and checkpoint protein expression patterns in murine syngeneic tumors via multiplex immunohistochemistry
Authors: Jennifer Ziello, Sarah Klein, Katherine Crosby
Journal: Cancer Research (2018)

Abstract Murine syngeneic tumor models are increasingly utilized for preclinical immuno-oncology studies as immunotherapeutic strategies continue to make clinical strides. However, the immunologic features of the tumor microenvironment (TME) in these models remain largely undefined. In this study, we applied a 7-color multiplex immunohistochemistry panel to visualize and quantify the immune infiltrate within formalin-fixed, paraffin-embedded RENCA, CT26.WT, and LL/2 tumor tissues derived from subcutaneous mouse models of renal cell carcinoma, colon carcinoma, and lung carcinoma, respectively. Additionally, we applied this panel to a 4T1 orthotropic primary mammary tumor and lung metastasis formed via tail vein injection. The multiplex panel included antibodies detecting CD3 and CD8 as T cell markers, F4/80 as a myeloid cell marker, the immunosuppressive receptor PD-1 as well as its ligand PD-L1, pan-keratin as a tumor mask, and DAPI as a nuclear counterstain. We characterized the tissue localization of tumor-infiltrating immune cells and analyzed the trends in co-expression and frequency patterns of immunosuppressive proteins. This study strives to better understand the underlying differences in the immunologic landscapes of these tumors, which in turn has implications for researchers studying responses to immunotherapeutic approaches and combination strategies. Citation Format: Jennifer Ziello, Sarah Klein, Katherine Crosby. Characterization of immune infiltrate and checkpoint protein expression patterns in murine syngeneic tumors via multiplex immunohistochemistry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5689.
Abstract 830: ISU104, a fully human antibody targeting a specific epitope on the ErbB3, displays potent inhibition of tumor growth in multiple xenograft tumor models
Authors: Miyoung Kim, Youngmi Hur, Sohyeon Seo, Heynjeong Lim, Kyungyong Kim, Youngsoo Sohn, Seung-Beom Hong, Donggoo Bae
Journal: Cancer Research (2018)

Abstract Members of the epidermal growth factor receptor family (ErbB family) are known as potent mediators in the development and progression of cancer. Activated ErbBs recruit various adaptors and signaling molecules through the phosphorylated cytoplasmic domain, which further leads to activation of downstream oncogenic signaling pathways. There are approved therapeutics for ErbB1 (EGFR) and ErbB2 (HER2) in the treatment of human cancers, while monoclonal antibodies targeting ErbB3 are just undergoing clinical trials. ISU104 is a fully human anti-ErbB3 antibody isolated from phage display antibody library. We performed the hydrogen/deuterium exchange mass spectrometry (HDX-MS) analysis with ErbB3 extracellular domain and ISU104, and that indicated that ISU104 mainly binds with domain 3 and weakly interacts with domain 1 of ErbB3. The binding property of ISU104 induced dose-dependent inhibition of ligand (heregulin, HRG) binding, blocking of dimerization of ErbB3 with other ErbBs and subsequently inactivated the downstream signaling of ErbB3. Also, ISU104 occasioned internalization of ErbB3 from plasma membrane, and downregulated the expression level of ErbB3. We demonstrated the biologic effect of ISU104 in several ErbB3-expressing cancer cell lines, including head and neck squamous cell carcinoma (HNSCC) and breast cancers. ISU104 completely suppressed the HRG-induced ErbB3/AKT phosphorylation, reduced cell proliferation and survival. Next, we evaluated efficacy of ISU104 in multiple xenograft models. Mice were treated with 10 mg/kg of ISU104 twice weekly. ISU104 regressed tumor growth in FaDu HNSCC model, and showed more than 70% tumor growth inhibition (TGI) in CAL27 (HNSCC), BxPC3 (pancreatic cancer), MDA-MB-468 (breast cancer), A549 (skin cancer), and BT474 (breast cancer) models. Our results suggest that ISU104 effectively blocks activation of ErbB3 and the downstream pathway by ErbB3, and may provide clinical benefit to ErbB3-activated patients. Citation Format: Miyoung Kim, Youngmi Hur, Sohyeon Seo, Heynjeong Lim, Kyungyong Kim, Youngsoo Sohn, Seung-Beom Hong, Donggoo Bae. ISU104, a fully human antibody targeting a specific epitope on the ErbB3, displays potent inhibition of tumor growth in multiple xenograft tumor models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 830.