tbuckley/cabot-search huggingface dataset:
Abstract A09: Understanding the role of colorectal cancer-associated microbes in colorectal cancer
Authors: Dominik Ternes, Martine Schmitz, Léa Grandmougin, Mina Tsenkova, Eric Koncina, Aurélien Ginolhac, Jessica Karta, Diana Kuhn, Javier Ramiro Garcia, Kacy Greenhalgh, Paul Wilmes, Elisabeth Letellier, Serge Haan
Journal: Cancer Research (2020)

Abstract Accumulating evidence suggests that dysbiosis, a state of pathologic imbalance in the human gut microbiome, is present in patients suffering from colorectal cancer (CRC). Several microbiome studies identified specific bacteria that are associated with CRC, among which Fusobacteria were shown to directly interact with cancer or immune cells of their host. However, only a limited number of CRC-associated microbes have been studied for host-microbial interactions; hence, the role of bacteria in the etiology of the disease remains unknown. Accordingly, our work aims at the development of a methodologic workflow for studying CRC-associated bacteria and their role in colon cancer tumor initiation and progression. In a first step, we identified CRC-associated bacteria that are enriched at the tumor site of CRC patients. Therefore, we used publicly available datasets and an in-house patient sample collection. Then, we predicted and optimized bacterial growth in silico by using a genome-scale metabolic reconstruction model combined with a constraint-based modeling approach. Finally, we implemented CRC-associated bacteria together with established primary CRC patient cultures into the microfluidics-based human-microbial crosstalk model (HuMiX). Our workflow allowed to analyze host-microbial interaction mechanisms of CRC-associated bacteria on a transcriptomic, proteomic, and metabolomic level. Citation Format: Dominik Ternes, Martine Schmitz, Léa Grandmougin, Mina Tsenkova, Eric Koncina, Aurélien Ginolhac, Jessica Karta, Diana Kuhn, Javier Ramiro Garcia, Kacy Greenhalgh, Paul Wilmes, Elisabeth Letellier, Serge Haan. Understanding the role of colorectal cancer-associated microbes in colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A09.
Challenges and Special Aspects of Pulmonary Hypertension in Middle- to Low-Income Regions
Authors: Babar Hasan, Georg Hansmann, Werner Budts, Alexandra Heath, Zahra Hoodbhoy, Zhi-Cheng Jing, Martin Koestenberger, Katharina Meinel, Ana Olga Mocumbi, Ganna D. Radchenko, Hannes Sallmon, Karen Sliwa, R. Krishna Kumar
Journal: Journal of the American College of Cardiology (2020)

Challenges and special aspects related to the management and prognosis of pulmonary hypertension (PH) in middle- to low-income regions (MLIRs) range from late presentation to comorbidities, lack of resources and expertise, cost, and rare options of lung transplantation. Expert consensus recommendations addressing the specific challenges for prevention and therapy of PH in MLIRs with limited resources have been lacking. To date, 6 MLIR-PH registries containing mostly adult patients with PH exist. Importantly, the global prevalence of PH is much higher in MLIRs compared with high-income regions: group 2 PH (left heart disease), pulmonary arterial hypertension associated with unrepaired congenital heart disease, human immunodeficiency virus, or schistosomiasis are highly prevalent. This consensus statement provides selective, tailored modifications to the current PH guidelines to address the specific challenges faced in MLIRs, resulting in the first pragmatic and cost-effective consensus recommendations for PH care providers, patients, and their families.
Abstract 17578: Impact of the Adjunct Use of Intra-Aortic Counter Pulsation Devices to Extracorporeal Membrane Oxygenation for Cardiogenic Shock
Authors: Manuel Rivera, Nileshkumar Patel, Gilson Fernandes, Rhanderson Cardoso, Varun Kumar, Amit Badiye, Mauricio Cohen
Journal: Circulation (2017)

Background: The use of endovascular devices as a means of left ventricular volume offloading in patients with cardiogenic shock and requiring extracorporeal membrane oxygenation (ECMO) remains cont...
Hippocampal Network Reorganization Underlies the Formation of a Temporal Association Memory
Authors: Mohsin S. Ahmed, James B. Priestley, Angel Castro, Fabio Stefanini, Ana Sofia Solis Canales, Elizabeth M. Balough, Erin Lavoie, Luca Mazzucato, Stefano Fusi, Attila Losonczy
Journal: Neuron (2020)
TACE-dependent EGFR ligand shedding: A new target in basal breast cancer
Authors: Paraic Kenny, Mina Bissell
Journal: Cancer Research (2008)

297  Epidermal Growth Factor Receptor (EGFR)-positivity has emerged as a common feature of the basal subtype of breast cancer, a clinical entity with poor prognosis and no current targeted therapies. Existing therapeutic strategies in other tissues have focused on targeting the receptor itself, resulting in the approval of drugs such as gefitinib and erlotinib which have proved useful, albeit in relatively small populations of patients.  We have used 3D culture models of breast cancer cell lines representative of the basal phenotype to examine the regulation of EGFR-dependent signaling in this disease. As an alternative approach to inhibiting the receptor directly, we have determined the key regulatory steps upstream of the receptor, on which receptor activation and pro-growth/survival signaling are dependent. We have identified the metalloproteinase TACE/ADAM17 as the key regulator of EGFR ligand shedding in these cell lines, and we have shown using both small molecule inhibitors and siRNAs that inhibition of TACE blocks EGFR signaling by preventing the mobilization of ligands for this receptor. TACE inhibition leads to a downregulation of flux through the EGFR pathway, reduces proliferation and restores the ability to form growth-arrested polarized mammary acinar structures to malignant cells in 3D culture. We report that expression of TACE and the EGFR ligand, TGF-alpha, are positively correlated in human breast cancer samples, in which they are predictive of poor prognosis and that both factors are highly associated with tumors of the basal subtype. Furthermore, we have found that breast cancer cell response to existing EGFR inhibitors, such as gefitinib, is strongly dependent on the levels of free EGFR ligands in the extracellular milieu, which suggests that impeding ligand bioavailability using TACE inhibitors may prove an important means of sensitizing tumors to existing EGFR inhibitors.  These data implicate TACE-dependent TGF-alpha shedding as playing a key role in the proliferation of basal breast cancer cells and provide a strong proof of principle that this important pathway in epithelial tumorigenesis may be effectively inhibited using the strategies we have developed.
分析光照性皮肤病(阳光诱发的皮肤病)患者生活质量和心理影响的研究的回顾
Authors: K.J. Rutter, I. Ashraf, L. Cordingley, L.E. Rhodes
Journal: British Journal of Dermatology (2020)

光照性皮肤病或光敏感性疾病是一组由日晒引起的皮肤疾病,总体影响大量人群。它们会引起一系列令人痛苦的症状(包括疼痛和烧灼),并可使皮肤出现水疱、鳞片和瘢痕。病情本身以及患者逃避阳光和保护自己避免日晒的需求可能会影响生活质量和心理健康。 这项来自英国的研究旨在了解使用哪种评估方法(工具)来评估光照性皮肤病患者的生活质量和心理健康,并报告对患者的影响。 作者回顾了相关的已发表英语类研究并总结了他们的发现。包括 20 项研究:19 项评估生活质量,3 项评估心理功能。使用 6 种不同的工具评估生活质量,以及 4 种不同的工具来评估心理健康。 研究显示,31‐39% 的光照性皮肤病患者的生活质量受到了非常大的影响。对与雇佣、社交/休闲活动和服装选择有关的问题有特殊影响。 尽管只有少数几项研究关注心理健康,但仍然发现患者出现焦虑和抑郁的比率约为一般人群的两倍。作者还指出,大多数可用工具并非旨在评估间歇性光照性皮肤病的独特影响,而且建议开发更特异的工具可能是有益的。 总之,这项研究证实,光照性皮肤病对患者的生活质量有实质性影响,而且需要更多研究。 本摘要涉及研究:光照性皮肤病对生活质量和心理的影响:一项系统性回顾。
Evolution of Pulmonary Hypertension During Severe Sustained Hypoxia
Authors: Fabian Hoffmann, Ulrich Limper, Vlad G. Zaha, Hannes Reuter, Leonora Zange, Jeanette Schulz-Menger, Marc Hein, Stephan Baldus, Benjamin D. Levine, Jens Jordan, Jens Tank
Journal: Circulation (2020)
Preclinical Evaluation of eFT226, a Novel, Potent and Selective eIF4A Inhibitor with Anti-Tumor Activity in B-Cell Malignancies
Authors: Peggy A Thompson, Boreth Eam, Nathan P Young, Sarah Fish, Joan Chen, Maria Barrera, Haleigh Howard, Ana Parra, Jolene Molter, Jocelyn Staunton, Ivy Nj Hung, Greg S Parker, Gary G Chiang, Chris J Wegerski, Andres Nevarez, Jeff Clarine, Sam Sperry, Alan Xiang, Chinh Tran, Christian Nilewski, Garrick K Packard, Theodore Michels, Paul A Sprengeler, Justin T Ernst, Siegfried H Reich, Kevin R Webster
Journal: Blood (2017)
ERK-Mediated Loss of miR-199a-3p and Induction of EGR1 Act as a “Toggle Switch” of GBM Cell Dedifferentiation into NANOG- and OCT4-Positive Cells
Authors: Fabien Almairac, Laurent Turchi, Nathalie Sakakini, David Nicolas Debruyne, Sarah Elkeurti, Elisabet Gjernes, Beatrice Polo, Laurence Bianchini, Denys Fontaine, Philippe Paquis, Herve Chneiweiss, Marie-Pierre Junier, Patrick Verrando, Fanny Burel-Vandenbos, Thierry Virolle
Journal: Cancer Research (2020)

There is great interest in understanding how the cancer stem cell population may be maintained in solid tumors. Here, we show that tumor cells exhibiting stem-like properties and expression of pluripotency markers NANOG and OCT4 can arise from original differentiated tumor cells freshly isolated from human glioblastomas (GBM) and that have never known any serum culture conditions. Induction of EGR1 by EGFR/ERK signaling promoted cell conversion from a less aggressive, more differentiated cellular state to a self-renewing and strongly tumorigenic state, expressing NANOG and OCT4. Expression of these pluripotency markers occurred before the cells re-entered the cell cycle, demonstrating their capacity to change and dedifferentiate without any cell divisions. In differentiated GBM cells, ERK-mediated repression of miR-199a-3p induced EGR1 protein expression and triggered dedifferentiation. Overall, this signaling pathway constitutes an ERK-mediated "toggle switch" that promotes pluripotency marker expression and stem-like features in GBM cells. SIGNIFICANCE: This study defines an ERK-mediated molecular mechanism of dedifferentiation of GBM cells into a stem-like state, expressing markers of pluripotency.See related commentary by Koncar and Agnihotri, p. 3195.
Mouth-Watering Results: Clinical Need, Current Approaches, and Future Directions for Salivary Gland Regeneration
Authors: Cecilia Rocchi, Elaine Emmerson
Journal: Trends in Molecular Medicine (2020)

Permanent damage to the salivary glands and resulting hyposalivation and xerostomia have a substantial impact on patient health, quality of life, and healthcare costs. Currently, patients rely on lifelong treatments that alleviate the symptoms, but no long-term restorative solutions exist. Recent advances in adult stem cell enrichment and transplantation, bioengineering, and gene transfer have proved successful in rescuing salivary gland function in a number of animal models that reflect human diseases and that result in hyposalivation and xerostomia. By overcoming the limitations of stem cell transplants and better understanding the mechanisms of cellular plasticity in the adult salivary gland, such studies provide encouraging evidence that a regenerative strategy for patients will be available in the near future.
Overexpression and Knockout of Mir-126 Both Promote Leukemogenesis through Targeting Distinct Gene Signaling
Authors: Rui Su, Zejuan Li, Ping Chen, Yuanyuan Li, Hu Chao, Yungui Wang, Stephen Arnovitz, Miao He, Sandeep Gurbuxani, Zhixiang Zuo, Abdel G. Elkahloun, Shenglai Li, Hengyou Weng, Hao Huang, Mary Beth Neilly, Shusheng Wang, Richard A. Larson, Jiwang Zhang, Xi Jiang, Minjie Wei, Jie Jin, Paul P. Liu, Jianjun Chen
Journal: Blood (2015)
Information to cancer patients: A questionnaire survey in three different geographical areas in Italy
Authors: A. Piga, E. Zanon, R. Bracci, V. Barbieri, F. Puglisi, G. Aprile, R. Gesuita, F. Carle, S. Venuta, R. Cellerino
Journal: Journal of Clinical Oncology (2006)

18593 Background: The way information to cancer patients is delivered widely varies among different countries. In Italy, as in other Mediterranean countries, the traditional approach has been of partial disclosure of the truth. Methods: We asked 200 cancer patients in 3 different Centres form Northern, Central and Southern Italy (Udine, Ancona, Catanzaro) to answer a 26-item questionnaire on communication aspects, in order to verify if information received was correct and adequate, and dependent on geographical variations. Statistics included univariate and multiple correspondence analysis, which studies relations between all variables, and provides a graphical representation in which associated variables tend to aggregate spatially. Results: Questionnaires were completed by 587 patients, of median age 60 yrs, 57% females, mainly with gastrointestinal (32%) or breast cancer (30%); 63% had active disease at time of interview. 77% of patients interviewed had a correct knowledge of their diagnosis, with no difference between different Centres. More informed were patients of female gender (p = 0.004), young age, better education, and with breast cancer (all p &lt; 0.001). Patients appropriately informed on prognosis were 41%. More informed were those with good prognosis, breast cancer, and not receiving treatment; less informed patients from Southern Italy and those with advanced disease. Degree of information was not directly related to desire for information, which was more pronounced for patients from Central and Southern Italy. Satisfaction for information received was higher for patients from Northern Italy, not on treatment, with limited disease. Multiple correspondence analysis identified clusters of patients such as those of old age, lower education, male sex, advanced disease, preferred paternalistic approach, characterized by poor level of information; and young age, female sex, high scholarity, breast cancer, patient-centered relationship with their doctor, characterized by high level of information. Conclusions: The cultural attitude towards communication aspects in oncology is changing in Italy. There are still significant differences at different latitudes, but there is a general trend to improving awareness about cancer. No significant financial relationships to disclose.
Use of bone health agents (BHAs) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 (Ra-223) after abiraterone (Abi): An interim review of REASSURE
Authors: C.N. Sternberg, B. Tombal, K. Miller, F. Saad, O. Sartor, J.P. Sade, C. Logothetis, J. Bellmunt, S. Dizdarevic, L.C. Harshman, J. Logue, S. Baldari, T. Richardson, D. Bottomley, M. Schostak, I. Bayh, J. Kalinovsky, C. Higano
Journal: Annals of Oncology (2018)
Pulmonary metastasectomy in colorectal cancer patients with previously resected liver metastasis: Pooled analysis.
Authors: Samer Salah, Francesco Ardissone, Michel Gonzalez, Pascal Gervaz, Marc Riquet, Kazuhiro Watanabe, Jon Zabaleta, Dalia Al-Rimawi, Ehab Massad, Elena Lisi, Osama H Hamed
Journal: Journal of Clinical Oncology (2014)

3553 Background: Data addressing the outcomes and patterns of recurrence following pulmonary metastasectomty (PM) in patients with colorectal cancer (CRC) and previously resected liver metastasis are very limited. Methods: We searched the PubMed for studies assessing PM in CRC and gathered individual data for patients who had PM and a previous curative liver resection. The influence of potential factors on overall survival (OS) was analyzed through univariate and multivariate analysis. Furthermore, the influence of patterns of recurrence following PM on post-recurrence survival was investigated. Results: Between 1983 and 2009, 146 patients from five studies underwent PM and had previous liver resection. The median interval from resection of liver metastasis until detection of lung metastasis and the median follow up from PM were 23 and 48 months respectively. Sixty seven (46%) underwent intra-operative thoracic lymph node (LN) sampling; nine of them (13%) had pathologically confirmed LN involvement, and 48 (33%) received perioperative chemotherapy. Five-year OS and recurrence free survival following PM were 54% and 29% respectively. Factors predicting inferior OS in univariate analysis included thoracic LN involvement and size of largest lung nodule ≥ two cm. In multivariate analysis, thoracic LN involvement was the only independent factor (HR 4.86, 95% CI: 1.56-15.14, P = 0.006). Ninety-three patients had recurrence following PM. Data on dates and pattern of recurrence was available for 74 patients, the five-year post- recurrence survival for patients with lung only recurrence treated with repeated PM (n=21), lung only recurrence treated with chemotherapy (n=20), liver only recurrence (n=10), and all other patterns of recurrence (n=23) were 60%, 0%, 18%, and 5% respectively, p < 0.0001. Conclusions: PM offers a chance for long term survival in selected patients with CRC and previously resected liver metastasis. Thoracic LN involvement predicted poor prognosis; therefore, significant efforts should be undertaken for adequate staging of the mediastinum prior to PM. Also, adequate intra-operative LN sampling allows proper prognostic stratification and enrollment in novel adjuvant therapy trials.
Effects of germline DHFR and FPGS variants on methotrexate metabolism and relapse of leukemia
Authors: Morten Tulstrup, Takaya Moriyama, Chuang Jiang, Marie Grosjean, Jacob Nersting, Jonas Abrahamsson, Kathrine Grell, Lisa Lyngsie Hjalgrim, Ólafur Gísli Jónsson, Jukka Kanerva, Bendik Lund, Stine Nygaard Nielsen, Rikke Linnemann Nielsen, Ulrik Overgaard, Petter Quist-Paulsen, Kaie Pruunsild, Goda Vaitkeviciene, Benjamin Ole Wolthers, Hui Zhang, Ramneek Gupta, Jun J. Yang, Kjeld Schmiegelow
Journal: Blood (2020)
Development and Chemical Specificity of Neurons, M. Cuénod, G. W. Kreutzberg, F. E. Bloom (Eds.), in: Progress in Brain Research, Volume 51. Elsevier/North-Holland Biomedical Press, New York, Chichester, Brisbane and Toronto (1979), xv +513, ISBN 0 444 80128 6
Authors: Marcus Jacobson
Journal: Trends in Neurosciences (1980)
Phase I combination study of trabectedin (T) and capecitabine (C) in patients with advanced malignancies
Authors: L. Gore, E. Rivera, K. Lavallee, S. Holden, S. Grolnic, D. Cleere, S. L. Moulder, Y. A. Elsayed, S. Eckhardt
Journal: Journal of Clinical Oncology (2006)

2079 Background: T binds to the minor groove of DNA, synergizes with functional nuclease excision repair and targets inducible transcription. T is active in several tumor types and exhibits preclinical synergy with C. The primary objective of this study is to determine the maximum tolerated dose (MTD) of T in combination with C. Secondary objectives include safety and pharmacokinetic (PK) analyses. Methods: Pts with advanced cancer, performance status 0–1 and adequate organ function are eligible. Pts received T starting at 0.4 mg/m 2 over 3 hours on day 1 followed by C on days 2 through 15. The initial dose of C was 2000 mg/m 2 /day and was reduced to 1600 mg/m 2 /day due to GI dose-limiting toxicity. Dose escalation of T continued. Cycles are repeated every 3 weeks, with PK sampling included. Standard “3+3” dose escalation design, definitions of dose limiting toxicity (DLT), and dose modification for toxicity are implemented. Results: To date, 30 patients have received 112 cycles (range 1–12, median 4) of treatment at 7 dose levels. Two of 3 pts at dose level 4 (C 2000 mg/m 2 /d and T 0.9 mg/m 2 ) and 2/6 pts at dose level 3 (C 2000 mg/m 2 /d and T 0.75 mg/ m 2 ) developed gastrointestinal DLT (emesis, diarrhea, pancreatitis). C was subsequently reduced to 1600 mg/m 2 /d and a new T dose escalation was initiated at 0.6 mg/m 2 . Treatment has been well tolerated with C 1600 mg/m 2 /d and T up to the current dose of 0.9 mg/m 2 (dose level 4a), with 1of 6 subjects experiencing grade 1 alkaline phosphatase. The most frequently reported related grade 3–4 adverse events (AEs) are diarrhea (23%), neutropenia (20%), nausea (16.6%), hand-foot syndrome (16.6%) and vomiting (13%). Anti-tumor activity to date includes a confirmed partial response lasting 8 months (m) in a patient with cholangiocarcinoma, and prolonged stable disease in 2 patients with breast cancer (6 and 7m), ovarian cancer (11m) and chondrosarcoma (9m). Conclusions: The combination of C 1600mg/m 2 /d and T up to 0.9mg/m 2 is tolerable and has promising activity in several tumor types. Dose escalation of T continues at 1.1 mg/m 2 . Biologic and pharmacokinetic analyses will be presented. [Table: see text]
Idiopathic Pulmonary Fibrosis
Authors: Athol U. Wells, Sujal R. Desai, Michael B. Rubens, Nicole S. L. Goh, Derek Cramer, Andrew G. Nicholson, Thomas V. Colby, Roland M. du Bois, David M. Hansell
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

In idiopathic pulmonary fibrosis, the quantitation of disease severity using pulmonary function tests is often confounded by emphysema. We have identified the composite physiologic index (CPI) most closely reflecting the morphologic extent of pulmonary fibrosis. Consecutive patients with a clinical/computed tomography (CT) diagnosis of idiopathic pulmonary fibrosis (n = 212) were divided into group I (n = 106) and group II (n = 106). The CPI was derived in group I (by fitting pulmonary function tests against disease extent on CT) and was tested in Group II. The formula for the CPI was as follows: extent of disease on CT = 91.0 - (0.65 x percent predicted diffusing capacity for carbon monoxide [DLCO]) - (0.53 x percent predicted FVC) + (0.34 x percent predicted FEV1). In group II, the CPI correlated more strongly with disease extent on CT (r2 = 0.51) than the individual pulmonary function test (DLCO the highest value, r2 = 0.38). A subanalysis demonstrated that the better fit of the CPI was ascribable to a correction of the confounding effects of emphysema. Mortality was predicted more accurately by the CPI than by a pulmonary function test in all clinical subgroups, including a separate cohort of 36 patients with histologically proven usual interstitial pneumonia (CPI, p < 0.0005; FVC, p = 0.002; PO2, p = 0.002). In conclusion, a new CPI, derived against CT and validated using split sample testing, is a more accurate prognostic determinant in usual interstitial pneumonia than an individual pulmonary function test.
Insurance Status But Not Race and Ethnicity Are Associated With Outcomes in a Large Hospitalized Cohort of Patients With Cirrhosis
Authors: Jasmohan S. Bajaj, Jacqueline G. O’Leary, Puneeta Tandon, Florence Wong, Patrick S. Kamath, Scott W. Biggins, Guadalupe Garcia-Tsao, Jennifer Lai, Michael B. Fallon, Paul J. Thuluvath, Hugo E. Vargas, Benedict Maliakkal, Ram M. Subramanian, Leroy R. Thacker, K. Rajender Reddy
Journal: Clinical Gastroenterology and Hepatology (2020)