tbuckley/cabot-search huggingface dataset:
The effect of cigarette smoke on therapeutic response in cancer cells.
Authors: Graham Walter Warren, Michelle A Romano, Samantha Lynne Sobus, Sundaravadivel Balasubramanian, Carl Atkinson
Journal: Journal of Clinical Oncology (2015)

e22265 Background: According to the 2014 Surgeon General’s Report, smoking causes adverse outcomes in cancer patients including increased cancer specific mortality. There are no existing biologic models that have evaluated the effects of cigarette smoke (CS) on therapeutic response or the effect of CS removal on restoration of therapeutic response. Methods: Human lung (A549, H460), head/neck (FaDu), breast (MDA-MB231), colon (SW1116) and prostate (PC3) cancer cell lines were exposed to acute, subacute, and chronic dose escalated CS and cell survival was measured following dose escalated treatment with single fraction radiotherapy (RT). The reversible effects of CS exposure were assessed to determine if acute or prolonged removal of CS resulted in restoration of RT response. Results: Exposure of all cell lines to dose escalated CS for up to 12 weeks demonstrated that CS increased survival following RT in all cell lines in a time and dose dependent manner. However, the dose of CS that decreased RT response varied according to cell line with some cell lines exhibiting higher sensitivity to CS than others. High doses of CS resulted in cytotoxicity in all cell lines with dose dependent effects following a similar cell specific response. CS significantly increased survival fraction in all cell lines and more than doubled survival in 5 of 6 cell lines. The reversible effects of CS were tested in H460, A549, and FaDu cells demonstrating that CS exposure for 6 or 9 weeks followed by CS removal for 3-6 weeks resulted in a partial to complete restoration of baseline therapeutic response in a cell specific manner; however, all cell lines required several weeks to achieve a partial or full restoration of response to RT. Conclusions: This CS exposure model reflects clinical observations that smoking reversibly decreases therapeutic response across both tobacco related (lung, head/neck) and non-tobacco related (breast, colon, prostate) cancer cells. The reversible effects of CS exposure on therapeutic response require careful consideration and documentation in clinical trials design, but data suggest that CS broadly decreases therapeutic response and removal of CS does not immediately restore therapeutic response.
Abstract 17153: Do Poor Responders to Cardiac Resynchronization Therapy also Poorly Respond to Exercise Therapy in Heart Failure Patients With Reduced Ejection Fraction?
Authors: Kayo Misumi, Tetsuo Arakawa, Michio Nakanishi, Kazuhiro Nakao, Takuya Hasegawa, Shigefumi Fukui, Masanobu Yanase, Teruo Noguchi, Toshihisa Anzai, Kengo Kusano, Satoshi Yasuda, Yoichi Goto
Journal: Circulation (2017)

Background: While cardiac resynchronization therapy (CRT) improves left ventricular ejection fraction (LVEF), exercise therapy (ET) improves exercise capacity in chronic heart failure patients with...
Abstract 18884: Ryanodine Receptor Hyperphosphorylation Induces Arrhythmias in Diabetes
Authors: Iuliana Popescu, Guo Yin, Sarah Srodulski, Xiaoli Peng, Florin Despa, Sanda Despa
Journal: Circulation (2016)

Background: Type-2 diabetes (T2D) heightens the risk of heart failure, arrhythmias and sudden cardiac death, but the underlying mechanisms are poorly understood. Hypothesis: Spontaneous Ca2+ releas...
Abstract 14067: Adherence to Cardio-protective Medications Prescribed for Secondary Prevention After Hospitalization for an Acute Coronary Syndrome
Authors: Jamal S Rana, Melissa M Parker, Howard H Moffet, Andrew J Karter
Journal: Circulation (2017)

Introduction: Adherence to cardio-protective medications prescribed for acute coronary syndrome (ACS) remains a challenge. We estimated adherence to beta-blockers, statins, angiotensin-converting e...
Abstract 18106: 2d Strain is a More Accurate Measure of Systolic Function Than Shortening Fraction and Ejection Fraction in Pediatric Patients Following Orthotopic Heart Transplant
Authors: Meghna D Patel, Georgeann K Groh, Justin Varughese, Craig Myers, Tim Sekarski, Diana Hartman, Joshua J Murphy, Gautam K Singh, Shafkat Anwar
Journal: Circulation (2015)

Introduction: 2D strain by echocardiography is a sensitive technique for assessing LV systolic function in pediatric heart transplant patients, although it is under-utilized clinically. Methods: We prospectively compared 2D LV 4-chamber Lagrangian longitudinal strain (LS) in 34 echo studies against cardiac output indexed to body surface area (cardiac index, Ci) via cardiac catheterization to assess accuracy of LS. Of those echos, 31/34 were simultaneous with cath, and 3/34 were within 10 days of catheterization. Ci was also compared to LV shortening fraction (SF) and single plane ejection fraction (EF). FS via M-mode in parasternal short-axis and EF via 4 chamber were measured. Strain was obtained in the 4 chamber apical view as an average of 6 segments. Right heart catheterization was performed and evaluated by a cardiac interventionalist blinded to echo data. Pearson’s correlation coefficient was used to assess relationships. Results: Mean age was 10.2 years (0.3 - 19 years), 11 males. Mean HR was 99 bpm (64-155) for catheterization, and 97 bpm (66-148) for echocardiography, mean frame rate 72 f/sec (47-109). Mean Ci was 3.8 L/min/m2 (95% CI 1.9 to 5.73). LS was diminished for this cohort, mean -13.7 (95% CI - 4 to -23.3), however, EF and SF were normal (mean EF 59.1% (95% CI 32.58%- 85.6%), mean FS 35.6% (95% CI 24%- 47%)). There was moderate positive correlation between LS and Ci, (r = 0.48, p = 0.002). FS and EF did not correlate with Ci (r = 0.34, p = 0.03, and r = 0.15, p = 0.39 respectively). There was fair positive correlation between LS and EF and LS and SF (r = 0.36, p = 0.03 and r = 0.38, p = 0.02 respectively). Conclusion: 4 chamber LV LS may be a more sensitive and reliable non-invasive method to assess systolic function in pediatric heart transplant patients. Further investigation in a larger sample using global (18 segment) strain is warranted.
The Biological Effects of Double-Dose Alpha-1 Antitrypsin Augmentation Therapy. A Pilot Clinical Trial
Authors: Michael A. Campos, Patrick Geraghty, Gregory Holt, Eliana Mendes, Paul R. Newby, Shuren Ma, Landy V. Luna-Diaz, Gerard M. Turino, Robert A. Stockley
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Augmentation therapy with intravenous AAT (alpha-1 antitrypsin) is the only specific therapy for individuals with pulmonary disease from AAT deficiency (AATD). The recommended standard dose (SD; 60 mg/kg/wk) elevates AAT trough serum levels to around 50% of normal; however, outside of slowing emphysema progression, its effects in other clinical outcomes have not been rigorously proven.Objectives: To evaluate the biological effects of normalizing AAT trough levels with double-dose (DD) therapy (120 mg/kg/wk) in subjects with AATD already receiving SD therapy.Methods: Clinically stable subjects were evaluated after 4 weeks of SD therapy, followed by 4 weeks of DD therapy, and 4 weeks after return to SD therapy. At the end of each phase, BAL fluid (BALF) and plasma samples were obtained.Measurements and Main Results: DD therapy increased trough AAT levels to normal and, compared with SD therapy, reduced serine protease activity in BALF (elastase and cathepsin G), plasma elastase footprint (Aα-Val360), and markers of elastin degradation (desmosine/isodesmosine) in BALF. DD therapy also further downregulated BALF ILs and cytokines including Jak-STAT (Janus kinases-signal transducer and activator of transcription proteins), TNFα (tumor necrosis factor-α), and T-cell receptor signaling pathways, cytokines involved in macrophage migration, eosinophil recruitment, humoral and adaptive immunity, neutrophil activation, and cachexia. On restarting SD after DD treatment, a possible carryover effect was seen for several biological markers.Conclusions: Subjects with AATD on SD augmentation therapy still exhibit inflammation, protease activity, and elastin degradation that can be further improved by normalizing AAT levels. Higher AAT dosing than currently recommended may lead to enhanced clinical benefits and should be explored further.Clinical trial registered with www.clinicaltrials.gov (NCT01669421).
THU-183-Prospective multicenter study of glecaprevir plus pibrentasvir combination therapy for patients with chronic hepatitis C
Authors: Akihiro Tamori, Motoo Iwasa, Kazuaki Inoue, Tatehiro Kagawa, Koichi Takaguchi, Masahito Minami, Yoshiaki Iwasaki, Kazuhiro Nouso, Hai Hoang, Masaru Enomoto, Norifumi Kawada
Journal: Journal of Hepatology (2019)
THU-185-Effectiveness and safety of DAA-based treatment of hepatitis C patients with severe and end stage chronic kidney diseases-EpiTer-2 database analysis
Authors: Krzysztof Tomasiewicz, Beata Lorenc, Tronina Olga, Agnieszka Czauz-Andrzejuk, Ewa Janczewska, Klapaczynski Jakub, Simon Krzysztof, Witold Dobracki, Aleksander Garlicki, Magdalena Tudrujek, Dorota Zarebska-Michaluk, Jerzy Jaroszewicz, Jolanta Citko, Wtodzimierz Mazur, Dorota Dybowska, Waldemar Halota, Rafal Krygier, Piekarska Anna, Jolanta Bialkowska-Warzecha, Matgorzata Pawtowska, Robert Flisiak
Journal: Journal of Hepatology (2019)
Proteomic evidence of specific IGKV1-8 association with cystic lung light chain deposition disease
Authors: Mylène Camus, Sandrine Hirschi, Grégoire Prevot, Marie-Pierre Chenard, Hervé Mal, Marc Stern, Martine Reynaud-Gaubert, Julia Gilhodes, Odile Burlet-Schiltz, Pierre Brousset, Magali Colombat
Journal: Blood (2019)
Lowering the <i>P</i> Value Threshold
Authors: Amin Adibi, Don Sin, Mohsen Sadatsafavi
Journal: JAMA (2019)

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
THU-375-Transcription factor TRIM33 controls liver progenitor cell towards hepatocyte differentiation through synergizing with SMAD2/3 following massive parenchymal loss
Authors: Tao Lin, Shanshan Wang, Chen Shao, Xiaodong Yuan, Franziska Wandrer, Heike Bantel, Alexander Marx, Matthias Ebert, Huiguo Ding, Steven Dooley, Honglei Weng
Journal: Journal of Hepatology (2019)
Between-group attack and defence in an ecological setting: Insights from nonhuman animals
Authors: Andrew N. Radford, Susanne Schindler, Tim W. Fawcett
Journal: Behavioral and Brain Sciences (2019)

Attempts to understand the fundamental forces shaping conflict between attacking and defending groups can be hampered by a narrow focus on humans and reductionist, oversimplified modelling. Further progress depends on recognising the striking parallels in between-group conflict across the animal kingdom, harnessing the power of experimental tests in nonhuman species and modelling the eco-evolutionary feedbacks that drive attack and defence.
A specific gene-microbe interaction drives the development of Crohn’s disease–like colitis in mice
Authors: R. Caruso, T. Mathes, E. C. Martens, N. Kamada, A. Nusrat, N. Inohara, G. Núñez
Journal: Science Immunology (2019)

Bacterial dysbiosis is associated with Crohn's disease (CD), a chronic intestinal inflammatory disorder thought to result from an abnormal immune response against intestinal bacteria in genetically susceptible individuals. However, it is unclear whether dysbiosis is a cause or consequence of intestinal inflammation and whether overall dysbiosis or specific bacteria trigger the disease. Here, we show that the combined deficiency of NOD2 and phagocyte NADPH oxidase, two CD susceptibility genes, triggers early-onset spontaneous TH1-type intestinal inflammation in mice with the pathological hallmarks of CD. Disease was induced by Mucispirillum schaedleri, a Gram-negative mucus-dwelling anaerobe. NOD2 and CYBB deficiencies led to marked accumulation of Mucispirillum, which was associated with impaired neutrophil recruitment and killing of the bacterium by luminal neutrophils. Maternal immunoglobulins against Mucispirillum protected mutant mice from disease during breastfeeding. Our results indicate that a specific intestinal microbe triggers CD-like disease in the presence of impaired clearance of the bacterium by innate immunity.
SAT-278-Integrated analysis of dna methylation and mRNA expression to identify mechanisms of non-alcoholic steatohepatitis
Authors: Noemí Cabré, Douglas J. Chapski, Fedra Luciano, Gerard Baiges, Salvador Fernández-Arroyo, Anna Hernández-Aguilera, Jordi Camps, Elisabet Rodríguez, Manuel Rosa-Garrido, Thomas M. Vondriska, Jorge Joven
Journal: Journal of Hepatology (2019)
Long-term safety of fertility preservation by ovarian stimulation and concurrent aromatase inhibitor treatment in women with breast cancer.
Authors: Kutluk Oktay, Volkan Turan, Jayeon Kim
Journal: Journal of Clinical Oncology (2015)

9521 Background: Cryopreservation of embryos and oocytes after ovarian stimulation (OS) is an established method of fertility preservation (FP). To minimize the elevation of serum estrogen levels, an aromatase inhibitor, letrozole, has been used concurrently with OS. However, long-term safety of this approach is unknown. The objective of this trial was to determine the long-term safety of controlled OS with letrozole supplementation (COSTLES) in women with breast cancer. The impact of BRCA mutations, estrogen-receptor (ER) and operative status on recurrence after COSTLES were also evaluated. Methods: A total of 337 women aged 24-45 with a diagnosis of stage ≤ 3 breast cancer were enrolled during FP consultations. Of those, 120 elected to undergo COSTLES for FP prior to chemotherapy; the remaining 217 served as controls. Results: The baseline characteristics were similar between FP and control groups except for the younger age (P = 0.03) and less frequent lymph node involvement (P = 0.02) in the former. The mean follow-up after diagnosis was 4.9 years (range 1-13) in the FP and 6.2 years (1-14) in the control group. In the FP group, the hazard ratio for recurrence was 0.77 (95% CI: 0.28, 2.13) and the survival was not compromised compared with controls (P = 0.61). Neither BRCA gene mutation status (P = 0.18), nor undergoing FP before breast surgery (P = 0.56) affected survival . Likewise, none of the tumor characteristics including the receptor status affected the survival following COSTLES. Thirty-three women attempted pregnancy with frozen embryos; 15 using a gestational carrier. Seventeen of those 33 had at least one child (FP rate: 51.5%; livebirth/embryo transfer rate: 45.0%). The livebirth rate was similar to an age-matched control group from a national IVF database. There were no recurrences among women who conceived. Conclusions: COSTLES is unlikely to cause substantially increased recurrence risk in breast cancer even in the presence of BRCA gene mutations, and it results in the preservation of fertility in a majority of women. Our data strongly support that FP via COSTLES should be made more widely available for young women with breast cancer even before undergoing breast surgery. Clinical trial information: NCT00504699.
PD-1/PD-L1 immune checkpoint and p53 loss facilitate tumor progression in activated B-cell diffuse large B-cell lymphomas
Authors: Marién Pascual, María Mena-Varas, Eloy Francisco Robles, Maria-Jose Garcia-Barchino, Carlos Panizo, Sandra Hervas-Stubbs, Diego Alignani, Ainara Sagardoy, Jose Ignacio Martinez-Ferrandis, Karen L. Bunting, Stephen Meier, Xavier Sagaert, Davide Bagnara, Elizabeth Guruceaga, Oscar Blanco, Jon Celay, Alvaro Martínez-Baztan, Noelia Casares, Juan José Lasarte, Thomas MacCarthy, Ari Melnick, Jose Angel Martinez-Climent, Sergio Roa
Journal: Blood (2019)
PS-047-HSD17B13 loss of function variant protects from hepatocellular carcinoma developed on alcohol related liver disease
Authors: Jie Yang, Eric Trépo, Pierre Nahon, Christophe Moreno, Eric Letouzé, Sandrine Imbeaud, Thierry Gustot, Jacques Deviere, Paulette Bioulac-Sage, Julien Calderaro, Nathalie Ganne, Alexis Laurent, Jean-Frédéric Blanc, Erwan Guyot, Angela Sutton, Marianne Ziol, Jessica Zucman-Rossi, Jean Charles Nault
Journal: Journal of Hepatology (2019)
Sorting the mixed bag: Tumor grade reassignment of Nottingham Grade II patients using pattern classification techniques.
Authors: Sergey Klimov, Hokyung Shin, Jun Xia, Guilherme Henrique Cantuaria, Xiaoxian Li, Padmashree C.G. Rida, Remus Osan, Ritu Aneja
Journal: Journal of Clinical Oncology (2015)

e22165 Background: Breast tumor grading via the Nottingham Grading System (NGS) involves microscopic evaluation of three histological parameters (nuclear grade, tubularity, and Mitotic index) to estimate risk, stratify patients into prognostic subgroups and suggest treatment protocols based on estimated efficacy in those subgroups. While treatment decisions for Nottingham Grade (NG)I (lowest risk) and NGIII (highest risk) patients may be relatively unambiguous, 30-60% of patients may be designated as NGII (intermediate risk) for whom therapeutic decisions are unclear. In this study we asked if stratification by NGS can be improved to clarify treatment decisions for a larger proportion of NGII patients. Using Multiple Discriminant Analysis (MDA) and clustering methods we examined how well NGS segments patients after inclusion of more histological variables, and whether this refinement enhances prognostic discrimination of the “mixed bag” of NGII patients. Methods: MDA was carried out using classical NGS components alongside receptor status (PR, ER, Her2), and proliferative markers (Ki67 and the Ki67-Adjusted Mitotic Score which reflects ratio of mitotic to proliferative cells). After performing supervised learning of NGs based on these features, class membership was evaluated for data points that were excluded from the training data set. Results: Using MDA, 17% of the patients were shown to be misclassified, with NGII needing the largest grade adjustment (34% of NGII patients). Thus, when additional variables are considered, NGs overlap to a significant degree, and many patients in NGII need to be reassigned to NGI or NGIII. We noted an increase in both the hazard ratios (from 2.034 and 3.456 in NGII and NGIII to 3.649 and 3.492, respectively) and a decrease in all 3 model fit statistics (from 2125.69 -2Log likelihood, 2129.69 AIC, and 2135.7 SBC to 2119.55, 2123.55, 2129.56 respectively). Conclusions: MDA analysis revealed the need to (a) reassign NGs of a significant proportion of NGII patients, and (b) include receptor statuses and proliferative markers for more accurate stratification. Improved fit statistics validated our grade adjustment strategy.
Recent advances on anti-angiogenesis receptor tyrosine kinase inhibitors in cancer therapy
Authors: Shuang Qin, Anping Li, Ming Yi, Shengnan Yu, Mingsheng Zhang, Kongming Wu
Journal: Journal of Hematology & Oncology (2019)

Angiogenesis has always been the topic of major scientific interest in the field of malignant tumors. Nowadays, targeting angiogenesis has achieved success in various carcinomas by several mechanisms, including the use of anti-angiogenic small molecule receptor tyrosine kinase inhibitors (TKIs). The development of TKIs targeting pro-angiogenic receptors, mainly vascular endothelial growth factor receptor (VEGFR) family, have significantly improved the outcome of certain types of cancers, like renal cell carcinoma, hepatocellular carcinoma, and colorectal carcinoma. However, the general response rate is not very satisfactory. The particular toxicity profile and resistance to anti-angiogenic targeted agents are unavoidable, and no specific marker is available to screen responsive patients to TKIs for precision therapy. To date, about 11 anti-angiogenic TKIs with different binding capacities to angiogenic receptor tyrosine kinase have been approved for the treatment of patients with advanced cancers. This review presents all approved anti-angiogenic small molecule receptor TKIs so far with an emphasis on their indications and clinical efficacy. We also discuss the combination between TKIs and immune checkpoint blockade inhibitors based on the most recent exciting outcome in immunotherapy.
Neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9) as markers of response rate to chemotherapy in lung adenocarcinoma.
Authors: Jose Manuel Ruiz Morales, Rita Dorantes Heredia, Oscar Arrieta, Norberto Carlos Chavez Tapia, Daniel Motola
Journal: Journal of Clinical Oncology (2015)

e19146 Background: Prognosis in patients with lung cancer is poor. Neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase – 9 (MMP – 9) are proteins involved in the invasion and metastases of cancer. Objective.To determine if there is a relationship between tumor expression of NGAL and MMP – 9 in lung adenocarcinoma patients with response rate to chemotherapy in advanced or metastatic lung cancer. Methods: Retrospective analysis was made of patients with lung adenocarcinoma treated at Medica Sur Hospital between 2005 and 2013. Tumor tissue was analyzed for NGAL and MMP – 9 expression by immunohistochemistry. Results: We identified a total of 41 patients. Mean over expression in tumoral tissue of NGAL was 70% and 30% for MMP – 9. Only 30 patients of our cohort received chemotherapy for advanced or metastatic disease and had measurable disease. Most patients received Paclitaxel + carboplatin (n=18) and Pemetrexed + Carboplatin (n=5). We found no difference in response related to gender, differentiation, vascular permeation, perineural invasion or expression of MMP – 9. We found a trend in response to chemotherapy in favor to those patients that expressed NGAL ≥70% that was not statistically significant (p=0.065). Conclusions: Tumoral tissue expression of NGAL ≥70% confers a better response to platinum - based chemotherapy, but it was not statistically significant. A prospective, multi – institutional study is currently being performed to confirm these results. Overall response. Variable Overall Response P Yes No Gender Female 7/17 (41.2%) 10/17 (58.8%) 0.785 Male 6/13 (46.2%) 7/13 (53.8%) Differentiation Well 0/2 (0%) 2/2 (100%) 0.439 Moderately 9/7 (47.1%) 9/17 (52.9%) Poor 5/11 (45.5%) 6/11 (54.5%) Vascular permeation No 3/9 (33%) 6/9 (66.7%) 0.469 Yes 10/21 (47.6%) 11/21 (52.4%) Perineural invasion No 13/29 (44.8%) 16/29 (55.2%) 1.00 Yes 0/1 (0%) 1/1 (100%) NGAL <70% 9/15 (60.0%) 6/12 (40%) 0.065 ≥70% 4/15 (26.7%) 11/15 (73.3%) MMP – 9 <30% 6/15 (40%) 9/15 (60%) 0.713 ≥30% 7/15 (46.7%) 8/15 (53.3%)
FRI-133-HCV neutralizing antibody responses in natural infections mapped by metric multi-dimensional scaling reveals new insights into HCV antigenicity and broadly neutralzing antibodies
Authors: Dorothea Bankwitz, Akash Bahai, Tanvi Khera, Corinne Ginkel, Daniel Todt, Mandy Doepke, Leona Dold, Florian Klein, Alice Mchardy, Thomas Pietschmann
Journal: Journal of Hepatology (2019)