tbuckley/cabot-search huggingface dataset:
The role of claudin-1 in colorectal cancer
Authors: Punita Dhawan, R. Daniel Beauchamp
Journal: Cancer Research (2004)

5080  Tight junctions (TJ) play a pivotal role in compartmentalization in multicellular organisms by sealing the paracellular pathway in epithelial and endothelial cell sheets. Disruption/reduction of tight and adherens junctions is a hallmark of tumor invasion and metastasis. Claudins, recently identified multigene family of 24 members function as major cell adhesion molecules at tight junctions. Although expression of previously known TJ proteins such as occludin and ZO-1 have been found to be decreased in cancer supporting loss of cell-cell junction it is intriguing that some claudin family members expression is highly elevated in various human cancers. However, the relationship between claudin overexpression and cancer initiation or progression is not known. Smad4, a critical component of the TGF-β signaling pathway and a tumor suppressor protein, negatively regulates the growth of epithelial cells. Inactivation of Smad4 has been shown to be a late event in colorectal carcinogenesis. In our preliminary studies, using non-transformed RIE cells and normal colon tissue samples, we observed that claudin-1 protein is not expressed. However, it is highly expressed in colon tumor tissues and the expression increases further in the metastatic colon cell lines and tissue samples. Interestingly, in our preliminary studies, we observed an inverse correlation between smad4 and claudin-1 expression. Also in tissue samples, smad4 expression decreased with increase in claudin-1 expression from normal to metastatic tumor samples. Transient overexpression of Smad4 markedly decreased claudin-1 expression in smad4 deficient cells. Consequently we hypothesize that claudin-1 plays a role in the progression of colorectal carcinoma and smad-4 is involved in regulation of claudin-1 in colon cancer.
Annals Story Slam - Innovations: Practices That Build Trust - Getting Rid of Stupid Stuff
Authors: Melinda Ashton
Journal: Annals of Internal Medicine (2020)

Web Exclusives18 February 2020Annals Story Slam - Innovations: Practices That Build Trust - Getting Rid of Stupid StuffFREEMelinda Ashton, MDMelinda Ashton, MDHawaii Pacific Health (M.A.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W20-0002 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Innovations: Practices That Build Trust - Getting Rid of Stupid Stuff "Innovations: Practices That Build Trust - Getting Rid of Stupid Stuff," by Melinda Ashton, MD (Duration 4:33)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Hawaii Pacific Health (M.A.)Current Author Address: Melinda Ashton, MD; e-mail, melinda.[email protected]org. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 February 2020Volume 172, Issue 4Page: SS1 ePublished: 18 February 2020 Issue Published: 18 February 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.Loading ...
Emerging role of tumor-related functional peptides encoded by lncRNA and circRNA
Authors: Pan Wu, Yongzhen Mo, Miao Peng, Ting Tang, Yu Zhong, Xiangying Deng, Fang Xiong, Can Guo, Xu Wu, Yong Li, Xiaoling Li, Guiyuan Li, Zhaoyang Zeng, Wei Xiong
Journal: Molecular Cancer (2020)

Abstract Non-coding RNAs do not encode proteins and regulate various oncological processes. They are also important potential cancer diagnostic and prognostic biomarkers. Bioinformatics and translation omics have begun to elucidate the roles and modes of action of the functional peptides encoded by ncRNA. Here, recent advances in long non-coding RNA (lncRNA) and circular RNA (circRNA)-encoded small peptides are compiled and synthesized. We introduce both the computational and analytical methods used to forecast prospective ncRNAs encoding oncologically functional oligopeptides. We also present numerous specific lncRNA and circRNA-encoded proteins and their cancer-promoting or cancer-inhibiting molecular mechanisms. This information may expedite the discovery, development, and optimization of novel and efficacious cancer diagnostic, therapeutic, and prognostic protein-based tools derived from non-coding RNAs. The role of ncRNA-encoding functional peptides has promising application perspectives and potential challenges in cancer research. The aim of this review is to provide a theoretical basis and relevant references, which may promote the discovery of more functional peptides encoded by ncRNAs, and further develop novel anticancer therapeutic targets, as well as diagnostic and prognostic cancer markers.
Advances in non-invasive assessment of hepatic fibrosis
Authors: Rohit Loomba, Leon A Adams
Journal: Gut (2020)

Liver fibrosis should be assessed in all individuals with chronic liver disease as it predicts the risk of future liver-related morbidity and thus need for treatment, monitoring and surveillance. Non-invasive fibrosis tests (NITs) overcome many limitations of liver biopsy and are now routinely incorporated into specialist clinical practice. Simple serum-based tests (eg, Fibrosis Score 4, non-alcoholic fatty liver disease Fibrosis Score) consist of readily available biochemical surrogates and clinical risk factors for liver fibrosis (eg, age and sex). These have been extensively validated across a spectrum of chronic liver diseases, however, tend to be less accurate than more ‘complex’ serum tests, which incorporate direct measures of fibrogenesis or fibrolysis (eg, hyaluronic acid, N-terminal propeptide of type three collagen). Elastography methods quantify liver stiffness as a marker of fibrosis and are more accurate than simple serum NITs, however, suffer increasing rates of unreliability with increasing obesity. MR elastography appears more accurate than sonographic elastography and is not significantly impacted by obesity but is costly with limited availability. NITs are valuable for excluding advanced fibrosis or cirrhosis, however, are not sufficiently predictive when used in isolation. Combining serum and elastography techniques increases diagnostic accuracy and can be used as screening and confirmatory tests, respectively. Unfortunately, NITs have not yet been demonstrated to accurately reflect fibrosis change in response to treatment, limiting their role in disease monitoring. However, recent studies have demonstrated lipidomic, proteomic and gut microbiome profiles as well as microRNA signatures to be promising techniques for fibrosis assessment in the future.
Mercury Poisoning From Skin Cream
Authors: Bridget Kuehn
Journal: JAMA (2020)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
HIV-1-induced cytokines deplete homeostatic innate lymphoid cells and expand TCF7-dependent memory NK cells
Authors: Yetao Wang, Lawrence Lifshitz, Kyle Gellatly, Carol L. Vinton, Kathleen Busman-Sahay, Sean McCauley, Pranitha Vangala, Kyusik Kim, Alan Derr, Smita Jaiswal, Alper Kucukural, Patrick McDonel, Peter W. Hunt, Thomas Greenough, JeanMarie Houghton, Ma Somsouk, Jacob D. Estes, Jason M. Brenchley, Manuel Garber, Steven G. Deeks, Jeremy Luban
Journal: Nature Immunology (2020)
An evolving paradigm of cancer stem cell hierarchies: therapeutic implications
Authors: Alexander J Cole, Adetunji P Fayomi, Vivian I Anyaeche, Shoumei Bai, Ronald J Buckanovich
Journal: Theranostics (2020)

Over a decade of research has confirmed the critical role of cancer stem-like cells (CSCs) in tumor initiation, chemoresistance, and metastasis.Increasingly, CSC hierarchies have begun to be defined with some recurring themes.This includes evidence that these hierarchies are 'flexible,' with both cell state transitions and dedifferentiation events possible.These findings pose therapeutic hurdles and opportunities.Here, we review cancer stem cell hierarchies and their interactions with the tumor microenvironment.We also discuss the current therapeutic approaches designed to target CSC hierarchies and initial clinical trial results for CSC targeting agents.While cancer stem cell targeted therapies are still in their infancy, we are beginning to see encouraging results that suggest a positive outlook for CSC-targeting approaches.
Abstract P3-03-14: Screening strategies for Notch3-degradation-related E3 ligase in breast cancers
Authors: Jing Liu, Man-Li Zhang, Jia-Xin Shen, Ya Xu, Ming-Heng Yuan, Guo-Jun Zhang
Journal: Cancer Research (2020)

Abstract BACKGROUND: The Notch pathway is very conserved and used iteratively during development and regulation of cell fates. Deregulation or loss of Notch signaling is associated with a wide range of human disorders, including breast cancer. It is accepted that ubiquitination events are linked to Notch receptors and their ligands where more than 10 E3-ligase and de-ubiquitination enzymes were implicated in this process. In this study, we attempt to apply a workflow to perform an E3-ligase RNAi screen focusing on the degradation system of Notch signaling pathway in breast cancer cells, hoping to further elaborate the pathogenesis of breast cancer and provide new ideas and schemes for its treatment. MATERIALS AND METHODS: Breast cancer cell line MCF7 was treated with cycloheximide (CHX), an inhibitor of protein biosynthesis, to observe the half-life of Notch3 protein. Then a cell-based screening assay was utilized via a 4 × CSL-luc reporter gene, which reacted to a siRNA library targeting E3 ligases that when silenced inhibit proteasome function in Notch signaling pathway. Moreover, Western Blot and Real-Time PCR were conducted to measure various levels of Notch3 after over-expression of potential E3s. Immunoflourescence was checked for co-colonization of potential E3s and Notch3. RESULTS: Since ubiquitination plays a major role in Notch, we performed a siRNA screen targeting human ubiquitin ligases in MCF7 cells. We quantified the activity of 4 × CSL-luc reporter gene as a read-out for Notch3 contents. From the screening results, we identified the APC/C ubiquitin ligase Cdh1 as a potential player in Notch3 degradation. Over-expressed Cdh1 led to decreased Notch3 levels in post-translational level. Moreover, Cdh1-triggered Notch3 led to a reversed accumulation when inhibited by proteasome inhibitor, MG132. CONCLUSION: Taken together, the 4 × CSL-luc reporter system was effective for detecting the potential E3 ligase involved in the degradation of Notch3 through ubiquitination-proteasome system in breast cancer. Citation Format: Jing Liu, Man-Li Zhang, Jia-Xin Shen, Ya Xu, Ming-Heng Yuan, Guo-Jun Zhang. Screening strategies for Notch3-degradation-related E3 ligase in breast cancers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-03-14.
Publisher Correction: Comprehensive molecular characterization of mitochondrial genomes in human cancers
Authors: Yuan Yuan, Young Seok Ju, Youngwook Kim, Jun Li, Yumeng Wang, Christopher J. Yoon, Yang Yang, Inigo Martincorena, Chad J. Creighton, John N. Weinstein, Yanxun Xu, Leng Han, Hyung-Lae Kim, Hidewaki Nakagawa, Keunchil Park, Peter J. Campbell, Han Liang
Journal: Nature Genetics (2020)

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Artificial intelligence in medical imaging: A radiomic guide to precision phenotyping of cardiovascular disease
Authors: Evangelos K Oikonomou, Musib Siddique, Charalambos Antoniades
Journal: Cardiovascular Research (2020)

Rapid technological advances in non-invasive imaging, coupled with the availability of large data sets and the expansion of computational models and power, have revolutionized the role of imaging in medicine. Non-invasive imaging is the pillar of modern cardiovascular diagnostics, with modalities such as cardiac computed tomography (CT) now recognized as first-line options for cardiovascular risk stratification and the assessment of stable or even unstable patients. To date, cardiovascular imaging has lagged behind other fields, such as oncology, in the clinical translational of artificial intelligence (AI)-based approaches. We hereby review the current status of AI in non-invasive cardiovascular imaging, using cardiac CT as a running example of how novel machine learning (ML)-based radiomic approaches can improve clinical care. The integration of ML, deep learning, and radiomic methods has revealed direct links between tissue imaging phenotyping and tissue biology, with important clinical implications. More specifically, we discuss the current evidence, strengths, limitations, and future directions for AI in cardiac imaging and CT, as well as lessons that can be learned from other areas. Finally, we propose a scientific framework in order to ensure the clinical and scientific validity of future studies in this novel, yet highly promising field. Still in its infancy, AI-based cardiovascular imaging has a lot to offer to both the patients and their doctors as it catalyzes the transition towards a more precise phenotyping of cardiovascular disease.
The Lancet Infectious Diseases Commission on antimicrobial resistance: 6 years later
Authors: Ramanan Laxminarayan, Thomas Van Boeckel, Isabel Frost, Samuel Kariuki, Ejaz Ahmed Khan, Direk Limmathurotsakul, D G Joakim Larsson, Gabriel Levy-Hara, Marc Mendelson, Kevin Outterson, Sharon J Peacock, Yong-Guan Zhu
Journal: The Lancet Infectious Diseases (2020)
Prognostic Value of Stress Dynamic Computed Tomography Perfusion With Computed Tomography Delayed Enhancement
Authors: Satoshi Nakamura, Kakuya Kitagawa, Yoshitaka Goto, Masafumi Takafuji, Shiro Nakamori, Tairo Kurita, Kaoru Dohi, Hajime Sakuma
Journal: JACC. Cardiovascular imaging (2020)
Bevacizumab, pertuzumab, and sandostatin for patients (pts) with advanced neuroendocrine cancers (NET).
Authors: Irfan Firdaus, Kent C. Shih, Ahmed Zakari, Evan Z. Lang, Michael McCleod, Kathryn B. Alguire, Nancy Walker Peacock, Douglas B. Flora, Peter Ruehlman, Chris Earwood, Johanna C. Bendell
Journal: Journal of Clinical Oncology (2012)

4127 Background: Targeted agents are used to treat well-differentiated NET. Octreotide binds somatostatin receptors and improves time to progression (TTP) of carcinoid tumors, and VEGF pathway targeting improves TTP of pancreatic NET. HER2 overexpression is reported in NET, and pertuzumab blocks HER2 receptor dimerization. This phase II trial combined bevacizumab, pertuzumab, and octreotide LAR for pts with advanced NET. Methods: Pts with advanced well-differentiated NET were enrolled. Pts had ECOG 0-1, and normal end-organ function, including left ventricular ejection fraction (LVEF) ≥50%. Pts received bevacizumab 15 mg/kg IV, pertuzumab 420 mg IV (following an 840 mg loading dose) day 1 of a 21 day cycle, and octreotide LAR 30 mg IM every 28 days. Primary endpoint was objective response rate (ORR). Results: Between 6/10 and 4/11, 43 pts enrolled. 22 M/21 F, med age 62 (33-88), 32 (74%) carcinoid, 11 (26%) PNET. 26% had prior sandostatin, 72% prior surgery, 19% prior radiation, 23% with &gt; 2 previous systemic therapies. Treatment-related grade 3 toxicities included: hypertension (28%), LVEF dysfunction (9%) (reversible with trial drug hold), and diarrhea (7%). No grade 4 toxicity was reported. Median treatment duration was 38 weeks (range: 0 – 76). Chromogranin A values were elevated in 27 pts; 59% had decreases during treatment. Seven pts (16%) achieved objective response [CR: 1 carcinoid (2%), PR: 6 (4 carcinoid, 2 PNET) (14%)]. ORR for carcinoid pts was 15.6%. Median PFS for the entire group was 8.2 months (95% CI: 6.3 – NA). PFS for carcinoid pts was 8.5 months (95% CI: 6.3 – NA); PFS for PNET pts was 6.4 months (95% CI: 3.9 – NA). Median OS has not been reached at 14.3 months followup. Conclusions: The ORR of the combination of bevacizumab, pertuzumab, and octreotide LAR in NET pts was encouraging. Particularly the response rate in carcinoid pts appears higher than historical data, warranting further investigation of this regimen in these pts.
Cell-intrinsic adrenergic signaling controls the adaptive NK cell response to viral infection
Authors: Carlos Diaz-Salazar, Regina Bou-Puerto, Adriana M. Mujal, Colleen M. Lau, Madlaina von Hoesslin, Dietmar Zehn, Joseph C. Sun
Journal: The Journal of Experimental Medicine (2020)

Natural killer (NK) cells are innate lymphocytes that exhibit adaptive features, such as clonal expansion and memory, during viral infection. Although activating receptor engagement and proinflammatory cytokines are required to drive NK cell clonal expansion, additional stimulatory signals controlling their proliferation remain to be discovered. Here, we describe one such signal that is provided by the adrenergic nervous system, and demonstrate that cell-intrinsic adrenergic signaling is required for optimal adaptive NK cell responses. Early during mouse cytomegalovirus (MCMV) infection, NK cells up-regulated Adrb2 (which encodes the β2-adrenergic receptor), a process dependent on IL-12 and STAT4 signaling. NK cell–specific deletion of Adrb2 resulted in impaired NK cell expansion and memory during MCMV challenge, in part due to a diminished proliferative capacity. As a result, NK cell-intrinsic adrenergic signaling was required for protection against MCMV. Taken together, we propose a novel role for the adrenergic nervous system in regulating circulating lymphocyte responses to viral infection.
Abstract P4-12-12: Outcomes of exclusive radiation therapy for breast cancer in older women according to age and comorbidity status: An observational retrospective study
Authors: Lorraine Waechter, Kim Cao, Matthieu Carton, Youlia Kirova, Alain Fourquet
Journal: Cancer Research (2020)

Abstract Introduction: This study aimed to assess the efficacy, tolerance and impact of comorbidities on outcomes in older women treated by exclusive radiation therapy (RT) for non-metastatic breast cancer (BC). Material and methods: We studied retrospectively female patients older 70 years at diagnosis, treated by exclusive RT for their BC between 2003 and 2013 in our Department. We analysed overall survival (OS), progression free survival (PFS), and specific survival (SS). Comorbidities were evaluated with the Charlson Comorbidity Index (CCI), and toxicities with the CCTCAE v3.0. Results: Between 2003 and 2013, there were 978 patients older than 70 treated for BC in our Hospital, and 817 received RT. Hypofractionated RT was delivered in 90.2% of patients. Of them, 66 patients underwent exclusive RT after refusal of surgery. The median age was 84.8 [71.3-91.7]. The median follow-up was 51.9 months [0.5- 99]. OS, SS and PFS at 5 years were 65.5% CI 95% [54.1-79.3], 86.3% CI 95% [77.2-96.4]), and 58.4% CI 95% [46.9-72.7], respectively. Five-year OS was statistically different according to age younger or older than 85 years: 72.9% CI 95% [58.4-91.1] and 57.1%, IC 95% [40.8-79.8], (p = 0.0026). Similar results were found for 5-year PFS: 64.5% CI 95% [49.5-84.1] and 51.6% CI 95% [35.8-74.5] (p = 0.014). The 5-year OS was also statistically different according to CCI score, respectively 70.8% CI 95% [57.0-87.9] and 59.8% CI 95 % [42.4-84.3] (p = 0.039) for a score of 0 or ≥ 1. Median CCI score was 1. There were 10.6% of the patients who experienced no toxicities; there were 59% who presented grade 1 and 2 radiodermatitis. Late toxicities were mainly fibrosis, observed in 39.4% of the patients, mostly of grade 1 and 2.Conclusion: Exclusive radiation therapy for non-metastatic BC in older women is feasible and well tolerated when adapted techniques are used, but the prognostic is strongly impacted by age and comorbidities. Citation Format: Lorraine Waechter, Kim Cao, Matthieu Carton, Youlia Kirova, Alain Fourquet. Outcomes of exclusive radiation therapy for breast cancer in older women according to age and comorbidity status: An observational retrospective study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-12.
Hemolytic anemia associated with dapsone PCP prophylaxis in GBM patients with normal G6PD activity
Authors: Lisa R Rogers, Peter Oppelt, Lalitha Nayak
Journal: Neuro-Oncology (2020)

Hemolytic anemia associated with dapsone PCP prophylaxis in GBM patients with normal G6PD activityAntibiotic prophylaxis against pneumocystis pneumonia (PCP; Pneumocystis jirovecii ) is standard for glioblastoma (GBM) patients receiving concurrent radiation and temozolomide.Accepted antibiotics include trimethoprim-sulfamethoxazole (TMP-SMX), dapsone (4-4′-diaminophenylsulfone), atovaquone, and inhaled pentamadine.A hemolytic anemia (HA) due to oxidant damage is well described in patients deficient for glucose-6-phosphate dehydrogenase (G6PD) treated with dapsone.There are limited data regarding HA with normal G6PD enzyme activity in GBM patients.We conducted a retrospective review of patients with newly diagnosed GBM treated with concurrent radiation and temozolomide between 2009 and 2014 at University Hospitals Cleveland Medical Center.Patients were identified by the Ohio Brain Tumor Study institutional review board-approved protocol. 1Patients were stratified based on choice of PCP prophylaxis.Hemoglobin and mean corpuscular volume (MCV) were recorded for patients prior to and during therapy.Fifty-two patients were identified.PCP prophylaxis included TMP-SMX (n = 23), pentamadine (n = 17), and dapsone (n = 12).Anemia (≥2.0 g/dL drop in hemoglobin from baseline) occurred in 13%, 24%, and 58% of patients, respectively.Of the 7 who developed anemia on dapsone, 4 had macrocytosis (mean corpuscular volume of 100-110 femtoliters [fL]).Lactate dehydrogenase levels were elevated in 3 patients (range, 312-414 U/L).Average drop in hemoglobin was 3.6 g/dL.Peripheral smears demonstrated degmacytes ("bite cells") (Fig. 1) in each of 5 available samples.Temozolomide was temporarily held in 3 patients, 1 of who required a blood transfusion.Anemia resolved upon discontinuation of dapsone in each.All dapsonetreated patients had normal pretreatment G6PD activity.GBM patients treated with concurrent temozolomide and radiation had a markedly higher rate of anemia on dapsone compared with other PCP prophylactic agents.Anemia was characterized by low-grade hemolysis and "bite cells." Dapsone is commonly implicated in drug-induced HA in G6PD-deficient patients.Dapsone-induced HA is considered uncommon with normal G6PD activity but is reported in patients undergoing stem cell or lung transplants.A retrospective study by Olteanu and colleagues identified a high