tbuckley/cabot-search huggingface dataset:
Clinical outcome according to tumor HER2 status and EGFR expression in advanced gastric cancer patients from the EXPAND study.
Authors: Florian Lordick, Yoon-Koo Kang, Pamela Salman, Sang Cheul Oh, Gyorgy Bodoky, Galina Petrova Kurteva, Constantin D. Volovat, Vladimir Moiseyenko, Akira Sawaki, Joon Oh Park, Vera A. Gorbunova, Heiko Goette, Helena Melezinkova, Christopher Stroh, Markus Moehler
Journal: Journal of Clinical Oncology (2013)

4021 Background: In the EXPAND study adding cetuximab to first-line capecitabine and cisplatin chemotherapy (CT) failed to improve clinical outcome in patients (pts) with advanced gastric or gastroesophageal junction cancer. This analysis assessed treatment outcome according to tumor HER2 status (a pre-defined subgroup) and EGFR expression in EXPAND study pts. Methods: Tumor HER2 status was determined primarily by immunohistochemistry (IHC), HER2 +ve tumors were IHC 3+ or IHC 2+ and fluorescence in situ hybridization (FISH) +ve. EGFR expression was assessed by IHC. A continuous scoring system (scale of 0–300) was used to determine the level of EGFR expression. Biomarker status was correlated with clinical outcome. Results: In both treatment arms, pts with HER2 +ve tumors (n=144) vs HER2 -ve tumors (n=535) had a longer median overall survival (OS): 13.3 (95% CI 10.9–15.5) vs 9.2 (95% CI 8.1–10.5) months in the CT + cetuximab arm and 14.0 (95% CI 11.3–17.1) vs 9.7 (95% CI 8.6–11.0) months in the CT arm, and a better overall response rate, 51.4 (95% CI 39.3–63.3) vs 27.0 (95% CI 21.9–32.6) % and 37.5 (95% CI 26.4–49.7) vs 26.4 (95% CI 21.1–32.3) % respectively. In stepwise multivariable models, pts with HER2 -ve vs HER2 +ve tumors showed an increased risk of death (adjusted hazards ratio 1.552, 95% CI 1.244–1.936) and reduced odds of response (adjusted odds ratio 0.477, 95% CI 0.316–0.720). EGFR tumor expression was evaluable in 774 pts from the intent to treat population (n=904). The EGFR IHC score was low (median 0, range 0–300). No discriminating threshold for the IHC score was identified. However in pt subgroups defined by a series of cut-off points from an IHC score of 10 upwards (rising incrementally by 10), there was a tendency for improved OS, progression-free survival, and tumor response when adding cetuximab to CT in pts with high tumor EGFR IHC scores. Conclusions: In this analysis of EXPAND study pts, those with HER2 +ve tumors were associated with better outcome irrespective of the treatment arm compared with pts with HER2 -ve tumors. Tumor EGFR expression was generally low. Adding cetuximab to CT failed to improve outcome overall, but may benefit a small proportion of pts with high EGFR tumor expression. Clinical trial information: 2007-004219-75.
Coordinated Splicing of Regulatory Detained Introns within Oncogenic Transcripts Creates an Exploitable Vulnerability in Malignant Glioma
Authors: Christian J. Braun, Monica Stanciu, Paul L. Boutz, Jesse C. Patterson, David Calligaris, Fumi Higuchi, Rachit Neupane, Silvia Fenoglio, Daniel P. Cahill, Hiroaki Wakimoto, Nathalie Y.R. Agar, Michael B. Yaffe, Phillip A. Sharp, Michael T. Hemann, Jacqueline A. Lees
Journal: Cancer Cell (2017)
Critical illness-related corticosteroid insufficiency (CIRCI): a narrative review from a Multispecialty Task Force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM)
Authors: Djillali Annane, Stephen M. Pastores, Wiebke Arlt, Robert A. Balk, Albertus Beishuizen, Josef Briegel, Joseph Carcillo, Mirjam Christ-Crain, Mark S. Cooper, Paul E. Marik, Gianfranco Umberto Meduri, Keith M. Olsen, Bram Rochwerg, Sophia C. Rodgers, James A. Russell, Greet Van den Berghe
Journal: Intensive Care Medicine (2017)
The effect of early enteral nutrition (EEN) on immune function of gastric cardia adenocarcinoma postoperative patients.
Authors: Jianmin Chen, Weiguo Zhang, Xiaoshan Feng, Gongping Wang, Canhui Jin, Dan Zhou
Journal: Journal of Clinical Oncology (2014)

e15057 Background: Gastric cardia cancer is one of the most common malignancies in Henan, China. Surgery is currently considered as the treatment choice for gastric cardia adenocarcinoma(GCA), Postoperative nutritional support was shown to reduce the incidence of complications and to shorten the length of post operational hospital stay. Recently, early enteral feeding (EEN) has become a standard nutritional support after gastrointestinal surgery. However, the impact of EEN on the immune function of postoperative GCA patients has not yet been elucidated. In this prospective study, we assessed immune function of GCA patients who had undergone surgery according to the postoperative nutritional method between EEN and TPN, and compared the complications and the length of stay of the two modes. Methods: 150 cases of GCA patients were randomly divided EEN group of 80 patients and TPN group of 70 patients. All the patients were given isocaloric and isonitrogenous nutritional support starting the day after operation and for eight days. Peripheral blood total T lymphocyte counts(TLC), lymphocyte subsets of CD3, CD4, CD8 and NK cells as well as immunoglobulin (IgG/IgM/IgA) were determined on one day before surgery, the first day, 2ed day, and 8th day after surgery respectively. Results: On second postoperative day, TLC, CD3, CD4, CD4/CD8 ratio, NK cells as well as immunoglobulin (IgG/IgM/IgA) had decreased compared with preoperative day in both groups; On postoperative day 8, TLC, CD3, CD4, CD4/CD8 ratio and NK cells as well as immunoglobulin (IgG/IgM/IgA) level in both groups had significantly increased compared with postoperative day 2, and those in the EEN group were significantly higher than those in the TPN group (p<0.05). The length of hospital stay in the EEN group is also shorter than TPN group (p<0.05). Conclusions: The stress after surgery in GCA patients can supress their immune function, EEN can improve immune function in these patients and is beneficial for them. It is recommended that EEN should be a standard care of postoperative GCA patients.
R-Spondin1/LGR5 Activates TGFβ Signaling and Suppresses Colon Cancer Metastasis
Authors: Xiaolin Zhou, Liying Geng, Degeng Wang, Haowei Yi, Geoffrey Talmon, Jing Wang
Journal: Cancer Research (2017)

Abstract Leucine-rich repeat containing G-protein–coupled receptor 5 (LGR5), an intestinal stem cell marker, is known to exhibit tumor suppressor activity in colon cancer, the mechanism of which is not understood. Here we show that R-spondin 1 (RSPO1)/LGR5 directly activates TGFβ signaling cooperatively with TGFβ type II receptor in colon cancer cells, enhancing TGFβ-mediated growth inhibition and stress-induced apoptosis. Knockdown of LGR5 attenuated downstream TGFβ signaling and increased cell proliferation, survival, and metastasis in an orthotopic model of colon cancer in vivo. Upon RSPO1 stimulation, LGR5 formed complexes with TGFβ receptors. Studies of patient specimens indicate that LGR5 expression was reduced in advanced stages and positively correlated with markers of TGFβ activation in colon cancer. Our study uncovers a novel cross-talk between LGR5 and TGFβ signaling in colon cancer and identifies LGR5 as a new modulator of TGFβ signaling able to suppress colon cancer metastasis. Cancer Res; 77(23); 6589–602. ©2017 AACR.
Ginsenoside Rg1 Inhibits Glucagon-Induced Hepatic Gluconeogenesis through Akt-FoxO1 Interaction
Authors: Qun Liu, Fei-Ge Zhang, Wen-Song Zhang, An Pan, Yi-Lin Yang, Jin-Feng Liu, Ping Li, Bao-Lin Liu, Lian-Wen Qi
Journal: Theranostics (2017)

Rationale: Glucagon is involved in hepatic gluconeogenesis, playing a key role in type 2 diabetes.Ginsenosides are reported to have antidiabetic activities.Ginsenoside Rg1 is a major propanaxatriol-type saponin in ginseng.This study aims to investigate the regulatory effects of Rg1 on glucagon-induced hepatic glucose production.Methods: The effects of Rg1 were investigated in high-fat-diet (HFD)-fed mice and glucagon-challenged C57BL/6J mice.Glucose metabolism was evaluated by oral glucose tolerance test and pyruvate tolerance test.The role of Rg1 on the regulation of Akt-FoxO1 interaction was performed using immunofluorescence, immunoprecipitation, siRNA silencing, pharmacological inhibitor and active-site mutant in primary hepatocytes or HepG2 cells.Results: Abnormally elevated fasting glucagon levels were observed in HFD-fed mice, contributing significantly to increased fasting plasma glucose levels.Inappropriate fasting glucagon secretion inactivated Akt and promoted hepatic glucose production via upregulation of FoxO1 activity.Rg1 preserved glucagon-impaired Akt activation partly by binding to Akt at Ser473 site.Rg1 also promoted Akt binding to FoxO1 and inactivated FoxO1 by phosphorylation.Consequently, Rg1 decreased the hepatic glucose production through a decrease in transcription of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase).Both siRNA silencing of Akt and Akt inhibitor triciribine attenuated the effects of Rg1 in response to fasting hormone glucagon.Conclusion: Akt phosphorylation at Ser473 by ginsenoside Rg1 is critical for its gluconeogenesis-lowering effect, suggesting a potential for pharmaceutical intervention in response to fasting hormone glucagon.
A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota
Authors: Henry Watson, Suparna Mitra, Fiona C Croden, Morag Taylor, Henry M Wood, Sarah L Perry, Jade A Spencer, Phil Quirke, Giles J Toogood, Clare L Lawton, Louise Dye, Paul M Loadman, Mark A Hull
Journal: Gut (2017)

Objective Omega-3 polyunsaturated fatty acids (PUFAs) have anticolorectal cancer (CRC) activity. The intestinal microbiota has been implicated in colorectal carcinogenesis. Dietary omega-3 PUFAs alter the mouse intestinal microbiome compatible with antineoplastic activity. Therefore, we investigated the effect of omega-3 PUFA supplements on the faecal microbiome in middle-aged, healthy volunteers (n=22). Design A randomised, open-label, cross-over trial of 8 weeks’ treatment with 4 g mixed eicosapentaenoic acid/docosahexaenoic acid in two formulations (soft-gel capsules and Smartfish drinks), separated by a 12-week ‘washout’ period. Faecal samples were collected at five time-points for microbiome analysis by 16S ribosomal RNA PCR and Illumina MiSeq sequencing. Red blood cell (RBC) fatty acid analysis was performed by liquid chromatography tandem mass spectrometry. Results Both omega-3 PUFA formulations induced similar changes in RBC fatty acid content, except that drinks were associated with a larger, and more prolonged, decrease in omega-6 PUFA arachidonic acid than the capsule intervention (p=0.02). There were no significant changes in α or β diversity, or phyla composition, associated with omega-3 PUFA supplementation. However, a reversible increased abundance of several genera, including Bifidobacterium , Roseburia and Lactobacillus was observed with one or both omega-3 PUFA interventions. Microbiome changes did not correlate with RBC omega-3 PUFA incorporation or development of omega-3 PUFA-induced diarrhoea. There were no treatment order effects. Conclusion Omega-3 PUFA supplementation induces a reversible increase in several short-chain fatty acid-producing bacteria, independently of the method of administration. There is no simple relationship between the intestinal microbiome and systemic omega-3 PUFA exposure. Trial registration number ISRCTN18662143.
Heterophilic Type II Cadherins Are Required for High-Magnitude Synaptic Potentiation in the Hippocampus
Authors: Raunak Basu, Xin Duan, Matthew R. Taylor, E. Anne Martin, Shruti Muralidhar, Yueqi Wang, Luke Gangi-Wellman, Sujan C. Das, Masahito Yamagata, Peter J. West, Joshua R. Sanes, Megan E. Williams
Journal: Neuron (2017)
Long-term Intra-articular Steroid Injections and Knee Cartilage
Authors: William J. Maloney, David S. Jevsevar, Kevin G. Shea
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Characteristics of Novel Therapeutics and Postmarket Safety Events
Authors: Tetsuya Tanimoto, Jinichi Mori, Yasuo Oshima
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
YouTube videos promote positive images of alcohol, finds study
Authors: Susan Mayor
Journal: BMJ (2017)

YouTube videos featuring alcohol products that are popular with underage drinkers attract large numbers of viewers and often associate drinking with fun and attractive characters, a new study has found.1

Researchers analysed the content and use of 137 YouTube videos published between 2006 and 2013 that featured alcohol brands popular with underage drinkers, ranging from beer to vodka.

“Although many studies have investigated the effect of alcohol advertisements on Facebook, Twitter and Instagram, little research has been done on video sharing platforms such as YouTube,” wrote the researchers, led by Brian Primack, director of the University of …
Antitumor effects of a nanoparticle-based vaccine targeted at human aspartyl (Asparaginyl) β-hydroxylase (HAAH).
Authors: Hossein A. Ghanbari, Michael Saul Lebowitz, Solomon Stewart, Kanam Malhotra, Steven Fuller
Journal: Journal of Clinical Oncology (2014)

3100 Background: HAAH is an established target for cancer therapy. It is over-expressed on cancer cells and plays a role in cancer cell growth, motility and invasiveness. Treatment of cancer cells to inhibit HAAH expression (siRNA) or neutralize its activity (mAb) returns cells to a normal phenotype. Moreover, tumor growth in xenograft models of human cancer is significantly (>80%) inhibited by anti-HAAH mAbs. HAAH is an oncofetal protein, important during development but not adult life, and thus, is a promising target for immunotherapy. However, as a self antigen, standard vaccination methods are ineffective in eliciting a sufficient immune response. Methods: We have designed and developed a nanoparticle based anti-cancer vaccine targeting HAAH. This vaccine incorporates a segment of the extracellular domain of HAAH fused to the gpD protein of λ-phage which is known to help to overcome immune tolerance. Results: The manufactured vaccine demonstrated high levels of immunogenicity in mice. Animals injected with 5x107-5x109 nanoparticles showed dose-dependent HAAH-specific antibody responses after 3 injections (day 0, 7, and 14). Sera from these animals demonstrated antigen specific binding to HAAH presented as either recombinant protein (ELISA) or on the surface of tumor cells (ELISA and FACS). The nanoparticle-based vaccine was further tested for efficacy against a mouse hepatocellular cancer line (BNLT3) injected subcutaneously into BALB/c mice in both a prophylactic and treatment modality. In the prophylactic model, mice (n=20) were vaccinated with 5 subcutaneous doses of nanoparticles (5x1010) on days 0, 7, 14, 46, and 62 and were challenged with 5x104 BNLT3 cells on day 46. By day 70, 100% of control mice (n=5) had developed tumors with a mean tumor volume of >300mm3. In contrast, only 85% of vaccinated mice had tumors, with a mean tumor volume of <100mm3. In the treatment model, tumor cells (5x103) and vaccine (1010) were co-administered on day 0 and animals were boosted on days 7 and 14. By day 50, 60% of control mice (n=5) had developed tumors with a mean volume of >20mm3, while none of the vaccinated mice had palpable tumors. Conclusions: These data support further development of this novel nanoparticle vaccine.
Partial versus radical nephrectomy in the elderly: A surgical conundrum.
Authors: Ramkishen Narayanan, Rebecca Leigh O'Malley, Katherine Brewer, Matthew H. Hayn, Diana Mehedint, Mohab W. Safwat, Hyung Lae Kim, Willie Underwood, Thomas Schwaab
Journal: Journal of Clinical Oncology (2012)

e15046 Background: Whether increased risk of complication (Cx) is balanced by the renal preserving benefits of partial nephrectomy (PN) in those with shortened lifespan is unclear. We compared Cx and renal function outcomes of PN and radical nephrectomy (RN) in the elderly. Methods: From a prospectively maintained renal tumor database, we retrospectively identified patients ≥ 75 years old who had RN or PN for a solitary, localized tumor ≤ 7cm and a normal contralateral kidney. CKD-EPI formula estimated glomerular filtration rate (eGFR). Propensity analysis was used to account for population selection bias: probability of RN was calculated by multivariate logistic regression, including variables thought to influence selection for nephrectomy type, yielding a propensity score based on quintile of RN probability. Odds ratios for any Cx, high grade Cx and postoperative stage ≥ 4 chronic kidney disease [CKD4] by nephrectomy type were recalculated using logistic regression adjusting for propensity score. Other statistical tests used were Student′s t, Wilcoxon rank-sum and Fisher′s exact. Results: 57 patients met inclusion criteria: 47% and 53% had PN and RN, respectively. Age, gender, baseline Cr, BMI and Charlson index were similar between the PN and RN groups. In both groups, surgical approach was minimally invasive in 93%. Mean tumor size with RN was larger than with PN (4.6 v. 3.6 cm, p&lt;0.01). EBL was higher with PN (360 v. 122 mL, p=0.02), although intraoperative transfusion rate was similar (p=0.13). With similar preoperative eGFR between groups, mean postoperative eGFR was lower in the RN group (36 v. 50 ml/min/1.73m2, p&lt;0.01). Propensity analysis showed likelihood of CKD4 was significantly higher with RN (OR 5.5, p=0.04). Cx rate was similar between PN and RN (30% v.37%, p=0.39), but most high grade Cxs were seen with PN (56% v. 23%, p=0.01). Propensity analysis supported these data in that risk of total Cxs was not increased with PN (p=0.46) but risk of high grade Cxs was significantly higher with PN (OR 9.2, p&lt;0.01). Conclusions: Risk of significant renal dysfunction following RN was 5-fold that of PN, but risk of high grade complications with PN is 9-fold that of RN. Evaluating the clinical impact of these risks should be done on an individual patient basis.
Abstract 12684: Cpr Quality During Out- Of- Hospital Cardiac Arrest Transport
Authors: Sheldon Cheskes, Cathy Zhan, Adam Byers, Richard Verbeek, Ian Drennan, Steve Lin, Ahmed Taher, Steven Brooks, Jason Buick, Laurie J Morrison
Journal: Circulation (2016)

Background: Previous studies have demonstrated significant associations between cardiopulmonary resuscitation (CPR) quality metrics and survival to hospital discharge following out-of- hospital cardiac arrest (OHCA). No large study has explored the relationship between location of resuscitation (scene vs. transport) and CPR quality. Objective: We sought to determine the impact of CPR location on CPR quality metrics during OHCA. Methods: We performed a retrospective cohort study of prospectively collected data from the Toronto RescuNET Epistry- cardiac arrest database. We analyzed CPR quality data from all treated adult OHCA occurring over a 39 month period beginning January 1, 2013. We included OHCA patients who underwent resuscitation by emergency medical services and had CPR quality metric data for both scene and transport phases of the resuscitation. Based on 2010 American Heart Association guidelines, high quality CPR was defined as chest compression fraction (CCF)&gt; 0.70, compression rate &gt;100/min and compression depth &gt; 5.0 cm. Scene and transport CPR quality metrics were compared for each patient using a Wilcoxon rank-sum paired-samples test . The proportion of patients who received high quality CPR (defined as meeting all 3 CPR quality benchmarks) was compared between resuscitation locations using a chi-square statistic. Results: Amongst 842 included patients (69.5% male, mean (SD) age 66.8±17.0), median compression rate was statistically higher on scene compared to transport (105.8 vs. 102.0 ; Δ 3.8; 95% CI: 2.5, 4.0), while median compression depth (5.56 vs. 5.33; Δ 0.23; 95% CI: 0.12, 0.26) and median CCF (0.95 vs. 0.87; Δ 0.08; 95% CI: 0.07, 0.08) were statistically higher during the transport phase. The proportion of patients with high quality CPR was similar on scene compared to during transport (45.8% vs. 42.5%; Δ 3.3; 95% CI: -1.4, 8.1). Conclusions: High quality CPR metrics were identified in both (scene and transport) locations of resuscitation and exceeded current CPR quality benchmarks. These results suggest that high quality, manual compressions can be performed by well-trained EMS systems regardless of location. Further study is required to determine whether these metrics can be replicated in other EMS jurisdictions.