tbuckley/cabot-search huggingface dataset:
Eficacia de la resección endoscópica mucosa para el tratamiento de adenomas colónicos gigantes
Authors: J Rodríguez Sánchez, M Úbeda Muñoz, E De La Santa Belda, P Olivencia Palomar, J Olmedo Camacho
Journal: Endoscopy (2017)

El tamaño de las lesiones se ha considerado tradicionalmente como un factor crucial a la hora de indicar el tratamiento endoscópico. Sin embargo, en los últimos años existe evidencia contrastada que este factor no supone una limitación a la hora de practicar una resección endoscópica con garantías de curación equiparables al tratamiento quirúrgico.
Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy
Authors: Carsten Denkert, Gunter von Minckwitz, Silvia Darb-Esfahani, Bianca Lederer, Barbara I Heppner, Karsten E Weber, Jan Budczies, Jens Huober, Frederick Klauschen, Jenny Furlanetto, Wolfgang D Schmitt, Jens-Uwe Blohmer, Thomas Karn, Berit M Pfitzner, Sherko Kümmel, Knut Engels, Andreas Schneeweiss, Arndt Hartmann, Aurelia Noske, Peter A Fasching, Christian Jackisch, Marion van Mackelenbergh, Peter Sinn, Christian Schem, Claus Hanusch, Michael Untch, Sibylle Loibl
Journal: The Lancet Oncology (2017)
Cytoreductive surgery for ovarian cancer: quality assessment
Authors: A.H. Brand, P.A. DiSilvestro, J. Sehouli, J.S. Berek
Journal: Annals of Oncology (2017)

Surgery is the cornerstone of treatment of ovarian cancer. Given the importance of achieving no or minimal macroscopic residual disease at primary surgery, performing an assessment of the quality of ovarian cancer surgery is crucial. Assessing the quality of care and surgical outcome allows us to establish baseline information, set standards of care and clear priorities, enable benchmarking against peers, and sustain quality improvement. We know that suboptimal care exists and variation in outcomes results. One way to monitor variation in outcomes is through a clinical quality registry (CQR). A CQR collects a defined minimum dataset to measure performance of an individual or center against a range of clinical quality indicators and provides risk-adjusted, benchmarked data to participating institutions. CQR's are an excellent quality assurance measure as they capture all cases (an opt out system). They permit detection and analysis of unwarranted variations in care. This can provide indications of a systems or process problem, thereby motivating health care providers to improve services and care. Several groups have either developed quality indicators for advanced ovarian cancer surgery (The Scottish Cancer Taskforce and the European Society of Gynecological Oncology) or are in the process of doing so (Australian Society of Gynaecological Oncologists). Indicators should be evidence-based and determined by extensive discussion with experts and stakeholders to ensure appropriateness and buy-in. The Scottish Cancer Taskforce and European Society of Gynecological Oncology have set targets for their quality performance measures, which should provide a quantitative framework for improving care in the surgical management of ovarian cancer.
Hepatitis A outbreak in HIV-infected MSM and in PrEP-using MSM despite a high level of immunity, Lyon, France, January to June 2017
Authors: Caroline Charre, Christophe Ramière, Anne-Marie Roque-Afonso, Christian Chidiac, Fabien Zoulim, Matthieu Godinot, Joseph Koffi, Caroline Scholtès, Jean-Michel Livrozet, Laurent Cotte
Journal: Eurosurveillance (2017)

Since 2016, an increase in the number of hepatitis A cases affecting mainly men who have sex with men (MSM) has been reported in low endemic countries in Europe. We calculated the attack rate in Lyon, France, in populations considered at high-risk: HIV-infected MSM and HIV-negative MSM receiving HIV pre-exposure prophylaxis (PrEP). In these populations, high level of immunity did not prevent the outbreak, indicating that vaccination should be reinforced, particularly in younger individuals.
Contributions of maternal lifecourse experience on temporal trends in birthweight in China: an age–period–cohort analysis among 2·5 million newborns
Authors: Jinhua Lu, Jianrong He, Xiaoyan Xia, Weidong Li, Dongmei Wei, Si Tu, Weijian Mo, Ping Wang, Qiong Feng, Huimin Xia, Xiu Qiu
Journal: The Lancet (2017)
Response to ‘Phase IV head-to-head randomized controlled trial comparing ingenol mebutate 0·015% gel with diclofenac sodium 3% gel for the treatment of actinic keratosis on the face or scalp’: reply from the authors
Authors: E. Stockfleth, C.A. Harwood, C. Serra-Guillén, T. Larsson, M.L. Østerdal, T. Skov
Journal: British Journal of Dermatology (2017)

Linked Article: Stockfleth et al. Br J Dermatol 2018; https://doi.org/10.1111/bjd.16048
Stromal Lkb1 deficiency leads to gastrointestinal tumorigenesis involving the IL-11–JAK/STAT3 pathway
Authors: Saara Ollila, Eva Domènech-Moreno, Kaisa Laajanen, Iris P.L. Wong, Sushil Tripathi, Nalle Pentinmikko, Yajing Gao, Yan Yan, Elina H. Niemelä, Timothy C. Wang, Benoit Viollet, Gustavo Leone, Pekka Katajisto, Kari Vaahtomeri, Tomi P. Mäkelä
Journal: Journal of Clinical Investigation (2017)

Germline mutations in the gene encoding tumor suppressor kinase LKB1 lead to gastrointestinal tumorigenesis in Peutz-Jeghers syndrome (PJS) patients and mouse models; however, the cell types and signaling pathways underlying tumor formation are unknown. Here, we demonstrated that mesenchymal progenitor- or stromal fibroblast–specific deletion of Lkb1 results in fully penetrant polyposis in mice. Lineage tracing and immunohistochemical analyses revealed clonal expansion of Lkb1-deficient myofibroblast-like cell foci in the tumor stroma. Loss of Lkb1 in stromal cells was associated with induction of an inflammatory program including IL-11 production and activation of the JAK/STAT3 pathway in tumor epithelia concomitant with proliferation. Importantly, treatment of LKB1-defcient mice with the JAK1/2 inhibitor ruxolitinib dramatically decreased polyposis. These data indicate that IL-11–mediated induction of JAK/STAT3 is critical in gastrointestinal tumorigenesis following Lkb1 mutations and suggest that targeting this pathway has therapeutic potential in Peutz-Jeghers syndrome.
Interactome Analysis of Microtubule-Targeting Agents Reveals Cytotoxicity Bases in Normal Cells
Authors: Andrés Julián Gutiérrez-Escobar, Gina Méndez-Callejas
Journal: Genomics Proteomics & Bioinformatics (2017)

Cancer causes millions of deaths annually and microtubule-targeting agents (MTAs) are the most commonly-used anti-cancer drugs. However, the high toxicity of MTAs on normal cells raises great concern. Due to the non-selectivity of MTA targets, we analyzed the interaction network in a non-cancerous human cell. Subnetworks of fourteen MTAs were reconstructed and the merged network was compared against a randomized network to evaluate the functional richness. We found that 71.4% of the MTA interactome nodes are shared, which affects cellular processes such as apoptosis, cell differentiation, cell cycle control, stress response, and regulation of energy metabolism. Additionally, possible secondary targets were identified as client proteins of interphase microtubules. MTAs affect apoptosis signaling pathways by interacting with client proteins of interphase microtubules, suggesting that their primary targets are non-tumor cells. The paclitaxel and doxorubicin networks share essential topological axes, suggesting synergistic effects. This may explain the exacerbated toxicity observed when paclitaxel and doxorubicin are used in combination for cancer treatment.
Abstract B35: Runx3 contributes for the defense against endogenous level of oncogenic K-Ras-induced tumorigenesis
Authors: Xin-Zi Chi, You-Soub Lee, Suk-Chul Bae
Journal: Cancer Research (2017)

Abstract Recent studies demonstrated that p53 affects only adenocarcinomas in K-RasG12V knockin mice leaving untouched adenomas which are likely to progress into adenocarcinomas (1, 2). These observations raised a fundamental question regarding whether cells can defend against endogenous level of oncogenic signal (3). Runx3, which plays pivotal roles in lineage determination and functions as a tumor suppressor, is frequently inactivated by promoter hypermethylation in various types of human tumors (4). Previously, we showed that deletion of Runx3 markedly enhanced K-Ras-G12V-induced lung tumorigenesis and led to early death (5). In this study, we found that immortalized Runx3-/- mouse embryonic fibroblast cells (MEFs) were tumorigenic. In addition, Runx3 was silenced by promoter hypermethylation in K-Ras-G12V-knockin MEFs. Expression of Runx3 in the K-Ras-G12V MEFs abolished their tumorigenesity. In mice, knockin of K-Ras-G12V in limited number of cells failed to induce tumor, but combination of K-Ras-G12V-knockin and Runx3-knockout by the same targeting method rapidly induced severe lung adenocarcinomas, lymphomas and skin carcinomas (median survival, 48 days). RUNX3 was silenced in all cases of K-Ras-activated human non-small cell lung cancers (n=20). Our results demonstrate that mammalian cells can defend against endogenous oncogenic K-Ras and Runx3 plays a key role in the defense mechanism. References 1. Feldser et al. (2010). Nature 468, 572-575. 2. Junttila et al. (2010). Nature 468, 567-571. 3. Berns A. (2010). Nature 468:519-20 4. Ito Y, Bae S-C, Chuang LS. (2015). Nat Rev Cancer. 15:81-95. 5. Lee et al., (2013). Cancer Cell. 24(5):603-16. Citation Format: Xin-Zi Chi, You-Soub Lee, Suk-Chul Bae. Runx3 contributes for the defense against endogenous level of oncogenic K-Ras-induced tumorigenesis [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B35.
Abstract B08: Differential regulation of Protein Kinase D isoforms in oxidative stress conditions via tyrosine phosphorylation in the activation segment
Authors: Mathias Cobbaut, Rita Derua, Etienne Waelkens, Peter Störz, Veerle Janssens, Johan Van Lint
Journal: Cancer Research (2017)

Abstract The protein kinase D (PKD) family of kinases belongs to the CAMK group and consists of three highly homologous enzymes. They play a versatile role in cancer cell signaling, primarily downstream of PKC isoforms. Classically PKDs are activated upon co-localization with PKC at DAG containing membranes, where PKC phosphorylates the PKD activation loop, generating active PKD. Besides this, PKDs are also activated in oxidative stress conditions, where PKD1 protects against cellular damage via signaling to NF-kB. While the three isoforms are highly homologous, they are not redundant in their biological function and oncogenic potential. A picture has emerged which associates PKD1 expression and activity with decreased migration and inhibition of epithelial mesenchymal transition (EMT). PKD2 and PKD3 on the other hand are upregulated in various cancers, and show oncogenic potential e.g. via enhanced ECM breakdown and potentiation of angiogenesis. While non-redundant biological roles continue to surface, the biochemical mechanisms behind these discrepant functions remain mostly elusive. Here, we identify an isoform specific regulation of PKD2 in oxidative stress conditions via the phosphorylation of a key Tyrosine residue in the substrate binding loop of the activation segment which is highly conserved in most Ser/Thr kinases. Phosphorylation of this residue selectively occurs in PKD2 (and not in PKD1). While wild-type PKD1 signals to NF-kB in oxidative stress, we could show that wild-type PKD2 signaling to NF-kB is impeded in these conditions. Substitution of the activation segment Tyr-717 in PKD2 with a non-phosphorylatable Phe restores signaling to NF-kB, indicating that Tyr-717 phosphorylation is a key determinant for the signaling outcome of PKDs in oxidative stress. Note: This abstract was not presented at the conference. Citation Format: Mathias Cobbaut, Rita Derua, Etienne Waelkens, Peter Störz, Veerle Janssens, Johan Van Lint. Differential regulation of Protein Kinase D isoforms in oxidative stress conditions via tyrosine phosphorylation in the activation segment [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B08.
Aggressive intravenous hydration with lactated Ringer’s solution for prevention of post-ERCP pancreatitis: a prospective randomized multicenter clinical trial
Authors: Chang-Hwan Park, Woo Paik, Eun Park, Chan Shim, Tae Lee, Changdon Kang, Myung Noh, Sun Yi, Jong Lee, Jong Hyun, Jun Lee
Journal: Endoscopy (2017)

Abstract Background and study aims The present study aimed to determine the type of intravenous hydration that is best suited to reducing the incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Patients and methods In a prospective randomized multicenter trial, average-to-high risk patients who underwent first-time ERCP were randomly assigned to three groups (1:1:1) who received: aggressive intravenous hydration (3 mL/kg/h during ERCP, a 20-mL/kg bolus and 3 mL/kg/h for 8 hours after ERCP) with either lactated Ringer’s solution (LRS) or normal saline solution (NSS), or standard intravenous hydration with LRS (1.5 mL/kg/h during and for 8 hours after ERCP). The primary end point was post-ERCP pancreatitis (PEP). Results 395 patients were enrolled, and 385 completed the protocols. The three groups showed no significant differences in demographic characteristics. There was a significant difference in the intention-to-treat (ITT) PEP rate between the aggressive LRS group (3.0 %, 95 % confidence interval [CI] 0.1 % – 5.9 %; 4 /132), the aggressive NSS group (6.7 %, 95 %CI 2.5 % – 10.9 %; 9 /134) and the standard LRS group (11.6 %, 95 %CI 6.1 % – 17.2 %; 15 /129; P = 0.03). In the two-group comparisons, the ITT PEP rate was significantly lower for the aggressive LRS group than for the standard LRS group (relative risk [RR] 0.26, 95 %CI 0.08 – 0.76; P = 0.008). There was no significant difference in the ITT PEP rate between the aggressive NSS group and the standard LRS group (RR 0.57, 95 %CI 0.26 – 1.27; P = 0.17). Conclusion Aggressive hydration with LRS is the best approach to intravenous hydration for the prevention of PEP in average-to-high risk patients.
Leading doctors back legal action to force UK government to cut carbon emissions
Authors: Zosia Kmietowicz
Journal: BMJ (2017)

Leading doctors are backing legal action against UK government ministers on the grounds they have not fulfilled their commitments to cutting carbon emissions in line with the Climate Change Act of 2008 and the Paris Agreement objective of limiting warming to 1.5°C or “well below” 2°C.

In an open letter published in The BMJ ,1 18 health professionals, including The BMJ ’s editor in chief Fiona Godlee, are supporting campaign group Plan B’s legal challenge to force the government …
Application of Large-Scale Aptamer-Based Proteomic Profiling to Planned Myocardial Infarctions
Authors: Jaison Jacob, Debby Ngo, Nancy Finkel, Rebecca Pitts, Scott Gleim, Mark D. Benson, Michelle J. Keyes, Laurie A. Farrell, Thomas Morgan, Lori L. Jennings, Robert E. Gerszten
Journal: Circulation (2017)

Emerging proteomic technologies using novel affinity-based reagents allow for efficient multiplexing with high-sample throughput. To identify early biomarkers of myocardial injury, we recently applied an aptamer-based proteomic profiling platform that measures 1129 proteins to samples from patients undergoing septal alcohol ablation for hypertrophic cardiomyopathy, a human model of planned myocardial injury. Here, we examined the scalability of this approach using a markedly expanded platform to study a far broader range of human proteins in the context of myocardial injury.
Abstract IA19: Clinical and imaging methods for grading and predicting dysphagia in patients with head and neck cancer
Authors: Katherine A. Hutcheson
Journal: Clinical Cancer Research (2017)

Abstract Dysphagia is a priority issue in head and neck cancer care. Swallowing is a complex function tied both to psychosocial well-being and health in cancer survivorship. Much of our understanding of dysphagia relies on the method of measuring swallowing function along the continuum of care. Options to grade dysphagia are many and varied. Patient-reported outcome (PRO) questionnaires have been widely adopted both in research studies and increasingly in clinical practice with the goal of understanding the patients' perception of swallowing abilities. Yet, sensory aberrations and individual coping make it such that PROs are often found discordant with physical swallowing function on imaging studies, such as radiographic modified barium swallow (MBS) studies, particularly in long-term survivors. For these reasons, many groups advocate for multimodal or multidimensional swallowing outcome panels to comprehensively assess dysphagia in head and neck cancer survivorship. This session will review performance, psychometrics, and predictive yield of various dysphagia classification methods for the head and neck cancer population. Citation Format: Katherine A. Hutcheson. Clinical and imaging methods for grading and predicting dysphagia in patients with head and neck cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr IA19.
Nomogram to Predict Survival of Patients With Recurrence of Hepatocellular Carcinoma After Surgery
Authors: Wei He, Baogang Peng, Yunqiang Tang, Junpin Yang, Yun Zheng, Jiliang Qiu, Ruhai Zou, Jingxian Shen, Binkui Li, Yunfei Yuan
Journal: Clinical Gastroenterology and Hepatology (2017)
First-in-Class Oral Small Molecule Against the Tyrosine Kinase ROR1 (KAN0439834) Induced Significant Apoptosis of Chronic Lymphocytic Leukemia Cells
Authors: Mohammad Hojjat-Farsangi, Amir Hossein Daneshmanesh, Fariba Mozaffari, Lotta Hansson, Jan Vågberg, Styrbjörn Byström, Elisabeth Olsson, Charlotta Löfberg, Charlotta Carina Norström, Johan Schultz, Martin Norin, Thomas Olin, Anders Österborg, Ali Moshfegh, Hakan Mellstedt
Journal: Blood (2017)
Mitochondrial Inhibition Augments the Efficacy of Imatinib by Resetting the Metabolic Phenotype of Gastrointestinal Stromal Tumor
Authors: Gerardo A. Vitiello, Benjamin D. Medina, Shan Zeng, Timothy G. Bowler, Jennifer Q. Zhang, Jennifer K. Loo, Nesteene J. Param, Mengyuan Liu, Alec J. Moral, Julia N. Zhao, Ferdinand Rossi, Cristina R. Antonescu, Vinod P. Balachandran, Justin R. Cross, Ronald P. DeMatteo
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Imatinib dramatically reduces gastrointestinal stromal tumor (GIST) 18F-FDG uptake, providing an early indicator of treatment response. Despite decreased glucose internalization, many GIST cells persist, suggesting that alternative metabolic pathways are used for survival. The role of mitochondria in imatinib-treated GIST is largely unknown. Experimental Design: We quantified the metabolic activity of several human GIST cell lines. We treated human GIST xenografts and genetically engineered KitV558del/+ mice with the mitochondrial oxidative phosphorylation inhibitor VLX600 in combination with imatinib and analyzed tumor volume, weight, histology, molecular signaling, and cell cycle activity. In vitro assays on human GIST cell lines were also performed. Results: Imatinib therapy decreased glucose uptake and downstream glycolytic activity in GIST-T1 and HG129 cells by approximately half and upregulated mitochondrial enzymes and improved mitochondrial respiratory capacity. Mitochondrial inhibition with VLX600 had a direct antitumor effect in vitro while appearing to promote glycolysis through increased AKT signaling and glucose transporter expression. When combined with imatinib, VLX600 prevented imatinib-induced cell cycle escape and reduced p27 expression, leading to increased apoptosis when compared to imatinib alone. In KitV558del/+ mice, VLX600 alone did not induce tumor cell death, but had a profound antitumor effect when combined with imatinib. Conclusions: Our findings show that imatinib alters the metabolic phenotype of GIST, and this may contribute to imatinib resistance. Our work offers preclinical proof of concept of metabolic targeting as an effective strategy for the treatment of GIST. Clin Cancer Res; 24(4); 972–84. ©2017 AACR.
Ipilimumab for stage unresectable III/IV melanoma: Brazilian experience in an expanded access program.
Authors: Rafael Schmerling, Daniel Herchenhorn, Jose Augusto Rinck, Veridiana Pires De Camargo, Johnny Camargo, Sergio Vicente Serrano, Sergio Jobim Azevedo, Carlos H. Barrios, Jose Getulio Martins Segalla, Vanessa Dybal Bertoni, Antonio C. Buzaid
Journal: Journal of Clinical Oncology (2014)

e20045 Background: Expanded Access Programs (EAP) for ipilimumab (IPI) were established around the world in order to provide appropriate drug access. This abstract reports the experience with IPI in major melanoma treatment centers in Brazil. Methods: Patients (pts) with unresectable stage III/IV melanoma who had either failed or were intolerant to previous therapy were eligible to receive intravenous IPI therapy (3mg/kg every 3 weeks for 4 cycles), in an open-label, multicenter prospective program. Re-induction was allowed. Data on demographics, survival, and safety were collected. Results: From March 2011 to November 2012, 450 pts across 11 centers were included and treated with at least 1 IPI dose in Brazilian EAP. This analysis includes data until database lock in October 2013 (maximum follow up: 30 months). Median age was 56 years (min-max: 18-88), 59.1% were males, 19.3% had brain metastases, 8.4% ocular melanoma and 8.0% mucosal melanoma. In total, 58.0% presented drug-related adverse event (AE) of any grade; 38 pts (8.4%) with grade 3-4 AEs. 27 pts (6.0%) had drug-related Serious AEs, 20 of them (4.4%) grade 3-4: gastrointestinal (GI) disorders (11 pts, 7 with diarrhea), pain, anemia and rash (2 pts each), hypopituitarism, hypophysitis, adrenal insufficiency, diabetes mellitus and hyponatremia (1 pt each). Any grade immune-related AEs (irAEs) were reported in 197 pts (43.8%), with 26 (5.8%) presenting grade 3-4 AEs. Serious irAEs were seen in 20 pts (4.4%), 15 (3.3%) of which grade 3-4: GI disorders (11 pts, 7 with diarrhea), endocrine disorders (3 pts) and rash (2 pts). Deaths within 70 days of last dose were reported in 127 pts (28.2%), none related to IPI toxicity. 55 pts received re-induction. Discontinuation rate was 82.9% with disease progression as the most common reason (67.6%). Median overall survival (OS) was 9.0 months (95%CI 8.1-10.5). One-year OS rate was 40% (95%CI 35-45%) for the overall population. Pts with cutaneous melanoma but no CNS/ocular/mucosal involvement (n=300) had a one-year OS of 42% (95%CI 36-47%). Conclusions: In this EAP experience with 450 Brazilian pts, IPI demonstrated an acceptable safety profile. One year OS rate of 40% for this experience is consistent with Phase III trial MDX-020. Clinical trial information: NCT00495066.