tbuckley/cabot-search huggingface dataset:
Abstract 2896: A flexible mouse model of malignant pleural mesothelioma
Authors: Jonathan Cooper, Filippo Giancotti
Journal: Cancer Research (2015)

Abstract Patients with advanced malignant pleural mesothelioma (MPM) have extremely limited treatment options. To develop targeted therapies necessary to radically alter the clinical course of MPM, it is important to identify oncogenic mutations and signaling pathways that drive its development and progression. About 75% of MPMs carry inactivating mutations at the NF2 locus, which encodes the FERM domain protein Merlin, and often also have deletions of the CDKN2A locus, encoding the CDK inhibitor p16 and the p53 activator ARF. Since traditional cancer therapies target dysregulated oncogenes, it is important to elucidate the pathogenically relevant proteins that are dysregulated downstream of MPM tumor suppressors. We have developed a flexible and rapid mouse model that can be used to dissect genetics of MPM, to evaluate the preclinical efficacy of novel therapies, and to provide a platform for MPM shRNA genetic screens. We injected into the pleural cavity of mice lentivirus encoding Cre recombinase and miR30-based shRNA cassettes to simultaneously deplete four of the most commonly lost proteins in mesothelioma - Nf2, p16INK4a/ARF, and BAP1. Cre recombinase deletes the Nf2 conditional allele and simultaneously activates a Luciferase reporter gene in the pleural mesothelium, allowing for bioluminescent imaging of infected cells that develop MPM tumors. Lentiviral miR30-based shRNA cassettes simultaneously deplete Ink4a/ARF and Bap1, helping to drive tumorigenesis. To evaluate MPM genetics, mice with conditional alleles for putative drivers of MPM pathogenesis (i.e. Dcaf1 and Ptk2) in addition to the Nf2 conditional allele can be injected with the virus to determine whether these genes are necessary and sufficient for MPM development or progression. Moreover, knockdown of putative MPM drivers can be easily carried out by adding corresponding shRNA cassettes to the lentiviral vector. Using these methods, we have developed a rapid genetically engineered mouse model that recapitulates human MPM and can be used to explore MPM genetics. This flexible MPM mouse model will allow us to unravel MPM genetics and help to identify novel therapeutic targets as well as provide an efficient preclinical test of these therapies. Citation Format: Jonathan Cooper, Filippo Giancotti. A flexible mouse model of malignant pleural mesothelioma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2896. doi:10.1158/1538-7445.AM2015-2896
A multicenter phase II study of S-1 plus bevacizumab in patients with previously treated non-squamous NSCLC
Authors: Hiroaki Takeoka, Kazuhiko Yamada, Masao Itiki, Takehito Shukuya, Yasushi Hisamatu, Koichi Azuma, Takaaki Tokito, Hidenobu Ishii, Tomoaki Hoshino
Journal: Annals of Oncology (2015)
The Global Asthma Network rationale and methods for Phase I global surveillance: prevalence, severity, management and risk factors
Authors: Philippa Ellwood, M. Innes Asher, Nils E. Billo, Karen Bissell, Chen-Yuan Chiang, Eamon M. Ellwood, Asma El-Sony, Luis García-Marcos, Javier Mallol, Guy B. Marks, Neil E. Pearce, David P. Strachan
Journal: European Respiratory Journal (2016)

The Global Asthma Network (GAN), established in 2012, followed the International Study of Asthma and Allergies in Childhood (ISAAC). ISAAC Phase One involved over 700 000 adolescents and children from 156 centres in 56 countries; it found marked worldwide variation in symptom prevalence of asthma, rhinitis and eczema that was not explained by the current understanding of these diseases; ISAAC Phase Three involved over 1 187 496 adolescents and children (237 centres in 98 countries). It found that asthma symptom prevalence was increasing in many locations especially in low- and middle-income countries where severity was also high, and identified several environmental factors that required further investigation. GAN Phase I, described in this article, builds on the ISAAC findings by collecting further information on asthma, rhinitis and eczema prevalence, severity, diagnoses, asthma emergency room visits, hospital admissions, management and use of asthma essential medicines. The subjects will be the same age groups as ISAAC, and their parents. In this first global monitoring of asthma in children and adults since 2003, further evidence will be obtained to understand asthma, management practices and risk factors, leading to further recognition that asthma is an important non-communicable disease and to reduce its global burden.
Identification of dengue type 2 virus in febrile travellers returning from Burkina Faso to France, related to an ongoing outbreak, October to November 2016
Authors: Carole Eldin, Philippe Gautret, Antoine Nougairede, Mélanie Sentis, Laetitia Ninove, Nadia Saidani, Matthieu Million, Philippe Brouqui, Remi Charrel, Philippe Parola
Journal: Eurosurveillance (2016)

Dengue fever is rarely reported in travellers returning from Africa. We report two cases of dengue fever in travellers returning from Burkina Faso to France. One of them presented a severe dengue fever with ALT &gt; 1,000 IU/L and pericarditis. Serotype 2 was identified. The cases reflect a large ongoing outbreak with over 1,000 reported cases between August and November in the capital city. Clinicians should consider dengue fever in malaria-negative febrile travellers returning from Africa.
Poor Mobilization of CD34+ Stem Cells Predicts Inferior Relapse and Survival Outcomes After Autologous Stem Cell Transplantation for Multiple Myeloma
Authors: Aleksandr Lazaryan, Hien Duong, Lisa Rybicki, Frederic J. Reu, Robert Dean, Ronald Sobecks, Shawnda Tench, Edward A. Copelan, Matt Kalaycio, Brian J. Bolwell
Journal: Blood (2011)
LMO2 Regulates DNA Replication in Hematopoietic Cells
Authors: Marie-Claude Sincennes, Magali Humbert, Benoit Grondin, Christophe Cazaux, Veronique Lisi, Nazar Mashtalir, EL Bachir Affar, Alain Verreault, Trang Hoang
Journal: Blood (2015)
209. Stem Cell/Nanoparticle Constructs for Targeted Ovarian Cancer Therapy
Authors: Pengpeng Cao, Revathiswari Tirughana, Ugochi Nwokafor, Soraya Aramburo, Linda Flores, Jacob Berlin, Karen S. Aboody
Journal: Molecular Therapy (2016)

Intro. Targeted drug delivery is a critical goal for effective cancer therapy. Nanoparticles (NPs) have shown promise as platforms for targeting drugs to tumors, but major challenges remain for controlling the distribution and retention of NPs within tumors. In general, NPs predominantly accumulate in the liver and spleen and have difficulty penetrating poorly vascularized and hypoxic tumor regions. Neural Stem Cells (NSCs) are ideal candidates for use as carriers for NPs in order to overcome these biodistribution challenges. NSCs have demonstrated inherent tumor tropic properties in preclinical invasive and metastatic tumor models, migrating selectively to invasive tumor foci, penetrating hypoxic tumor regions, and even traversing through the blood-brain barrier to access intracranial tumor foci following intravenous administration. We have been pioneers in genetically modifying NSCs to express prodrug activating enzymes for gene therapy, completing a first-in-human safety clinical trial for recurrent glioma in 2013, and demonstrating proof of concept for localized drug delivery (Phase I ongoing). As NSC-based therapies move into the clinic, there is an opportunity to develop complementary NSC-mediated treatment strategies for tumor elimination. We have shown that these clinically relevant NSCs maintain their tumor tropism when transporting either surface-bound or internalized NPs. NSC-NPs selectively penetrate tumor foci (Figure 1 shows NSC-NPs, orange, at tumor foci, green, near liver). The combination of NSCs and NPs offers the potential to realize a modular and general drug targeting system. We now demonstrate that the cisplatin-loaded NPs carried by NSCs is a viable approach for the treatment of Stage III ovarian cancer, where tumors have metastasized to the abdominal cavity. We show that encapsulating cisplatin within silica NPs allows for delayed drug release for 24 hours with minimal leakage, allowing sufficient time for the NSCs to effectively penetrate and distribute through tumor foci. Methods. Ten million NSCs carrying cisplatin-loaded silica NPs (Figure 2) were injected intraperitoneally (IP) into nude mice containing established human ovarian (OVCAR8) peritoneal metastases. Control groups included equivalent levels of free cisplatin or cisplatin-loaded NPs. Results. IP delivery these NSC-NP constructs showed significantly increased concentrations of cisplatin at multiple tumor sites, regardless of size, throughout the peritoneum, as compared to free drug alone or drug-loaded NPs alone. At all timepoints tested, only tumors treated with the NSC-NP constructs had therapeutically significant levels of drug present (Figure 3 shows 6h and 24h timepoints). This allows for concentration of drug at tumor sites, while minimizing toxicities. Long-term efficacy studies are in progress. Our present goal is to generate the efficacy and safety data needed to move toward clinical trials.
Accurate perceptions do not need complete information to reflect reality
Authors: Shabnam Mousavi, David C. Funder
Journal: Behavioral and Brain Sciences (2017)

Abstract Social reality of a group emerges from interpersonal perceptions and beliefs put to action under a host of environmental conditions. By extending the study of fast-and-frugal heuristics, we view social perceptions as judgment tools and assert that perceptions are ecologically rational to the degree that they adapt to the social reality. We maintain that the veracity of both stereotypes and base rates, as judgment tools, can be determined solely by accuracy research.
Operating Room Performance Improves after Proficiency-Based Virtual Reality Cataract Surgery Training
Authors: Ann Sofia Skou Thomsen, Daniella Bach-Holm, Hadi Kjærbo, Klavs Højgaard-Olsen, Yousif Subhi, George M. Saleh, Yoon Soo Park, Morten la Cour, Lars Konge
Journal: Ophthalmology (2016)
Structural and Functional Characterization of the NHR2 and Runt Domains of AML1/ETO.
Authors: Matthew D. Cheney, Yizhou Liu, Justin J. Gaudet, Maksymilian Chruszcz, Stephen M. Lukasik, Daisuke Sugiyama, Jeff Lary, James Cole, Zbyszek Dauter, Wladek Minor, Nancy A. Speck, John H. Bushweller
Journal: Blood (2005)
Transplantation for Immunoglobulin Light Chain Amyloidosis. A Statistical Analysis of Factors Predicitng Outcome In Over 400 Patients
Authors: Morie Abraham A. Gertz, Martha Lacy, Angela Dispenzieri, Shaji Kumar, Francis Buadi, David Dingli, Stephen M. Ansell, Dennis Gastineau, David James Inwards, Patrick B Johnston, Mark R. Litzow, Ivana Micallef, Luis Porrata, Nelson Leung, Robert Wolf, William J Hogan, Suzanne R. Hayman
Journal: Blood (2010)
Front-Line Imatinib Mesylate (IM) in Patients with Newly Diagnosed Accelerated Phase (AP)-Chronic Myeloid Leukemia (CML), a Study From the FILMC Group (France Intergroupe Leucemie Myeloide Chronique).
Authors: Delphine Rea, Gabriel Etienne, Franck Emmanuel Nicolini, Pascale Cony-Makhoul, Hyacinthe Johnson-Ansah, Laurence Legros, Francoise Huguet, Michel Tulliez, Martine Gardembas, Krimo Bouabdallah, Philippe Rousselot, Jean-Michel Cayuela, Herve Dombret, François-Xavier Mahon
Journal: Blood (2009)
Mutational analysis and clinical correlation of 185 consecutive metastatic colorectal patients: Similarities and differences between colon and rectal patients.
Authors: A. L. Russo, D. R. Borger, D. P. Ryan, K. C. Fan, H. Lopez, V. Scialabba, L. S. Blaszkowsky, E. L. Kwak, J. W. Clark, J. N. Allen, R. C. Wadlow, A. X. Zhu, R. Wang, D. Dias-Santagata, T. S. Hong, A. J. Iafrate
Journal: Journal of Clinical Oncology (2011)

3536 Background: Cancers of the colon and rectum are largely considered to be molecularly comparable diseases, harboring activating mutations in KRAS, BRAF, NRAS, and PIK3CA. These mutations have an impact on both prognosis and therapeutic options. In this study, we used a multiplexed clinical assay (SNaPshot) (Dias-Santagata D, EMBO Mol Med. 2010 May;2(5):146-58) performed on nucleic acid derived from formalin-fixed tissue which tests for 120 previously described mutations across 13 cancer genes and examined the relationship with clinical features and disease site. Methods: 185 consecutive metastatic colorectal patients were identified in our clinic and underwent testing with SNaPshot in an IRB approved protocol. Mutational analysis was performed across 13 genes, including KRAS codons 12 and 13, NRAS codons 12, 13, and 61, BRAF codon 600, and PIK3CA codons 88, 542, 545-546, 1047, and 1049. Patient charts were reviewed for demographic data, primary site, metastatic sites at presentation and last follow-up. Fisher’s exact test was performed to determine statistical significance. Results: Of the 185 patients, 51 (38%) had a rectal primary and 134 (62%) had a colon primary. Median age was 55 years (29-83). There were 78 females (42%). Comparative mutation rate for rectal vs colon primary (respectively) was: KRAS -33% vs 36% (NS), BRAF – 2% vs 11% (P=0.07), PIK3CA - 12% vs 13% (NS), dual PIK3CA/KRAS- 8% vs 5% (NS), and NRAS - 14% vs 1% (P=0.001). The single colon patient with an NRAS mutation had a sigmoid colon primary. Rectal primary was associated with a higher rate of lung metastases at presentation (43%) than colon (21%), P=0.003. NRAS mutation was associated with an 88% (7/8) rate of lung metastases and a 0% rate of bone and CNS metastases. Conclusions: Rectal and colon patients have similar rates of KRAS and PIK3CA mutations. However, BRAF mutations are more common in colon cancer. NRAS mutations are exclusively found in rectosigmoid cancers and may have a different biology than other colorectal cancers. These data suggest that primary tumor location may provide a means to enrich a population for a genotype-directed study.
Abstract 1774: The effects of diarylthiourea analogs on triple negative breast cancer cell growth
Authors: Deborah Nambi, Maggie C. Louie, Shengquan Liu
Journal: Cancer Research (2015)

Abstract Breast cancer is the most common cancer occurring in women and the second leading cause of cancer death in women after lung cancer. Breast cancer is often classified at the molecular level in terms of whether the cancer expresses the estrogen receptor, progesterone receptor and human epidermal growth factor 2 receptor. Hormone receptor positive breast cancer accounts for 75-80% of all breast cancer and the remaining 20-25% accounts for the most aggressive types of cancer which are negative for all three receptors– known as triple negative breast cancer (TNBC). The current treatment used to manage TNBC is chemotherapy. Although chemotherapy has been effective in improving patients’ prognosis, a significant number of patients either relapse or develop resistance to these drugs. There is a significant interest in developing new therapeutic drugs aimed at improving outcomes in TNBC patients. Many studies have shown that flexible heteroarotinoids (Flex-Het) are a promising new class of drugs due to their ability to regulate growth, differentiation and apoptosis in a variety of cancer cells without activating the nuclear retinoic acid receptors. Previous studies have shown ShetA2 as the leading Flex-Het anti-cancer drug with the greatest efficacy in treating various types of cancer cells (Liu et al. 2004, Benbrook et al. 2005, and Liu et al. 2007). Some of the limitations of the ShetA2 are its high lipophilicity, toxic side effects and the low yields associated with the laborious synthesis. Therefore, efforts have been made to develop 2nd generation diarylthiourea compounds that retain anti-cancer activity, but with minimal side effects. The objective of this study was to examine the effects of two 2nd generation drugs SL1-18 and SL1-09 on various TNBC cell lines including MDA-MB-453, MDA-MB-231 and MDA-MB-468. Our preliminary data shows that exposure to micromolar levels of the diarylthiourea compounds effectively inhibited cancer cell growth in all three TNBC cell lines; however additional studies are necessary to understand the molecular mechanism of how SL1-18 and SL1-09 work to block cell growth and whether these anti-cancer drugs are promising therapeutic leads for the treatment of triple negative breast cancer. Citation Format: Deborah Nambi, Maggie C. Louie, Shengquan Liu. The effects of diarylthiourea analogs on triple negative breast cancer cell growth. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1774. doi:10.1158/1538-7445.AM2015-1774
Paper acceptance time in respiratory research: room for improvement?
Authors: Andreas Ronit, Jørgen Vestbo
Journal: European Respiratory Journal (2016)

We recently submitted a paper to a top five respiratory journal in terms of average citations per article. The paper was swiftly sent for peer review. A month later, the review was in, and the paper was now “awaiting associate editor decision”. After another 6 weeks, and at the time of writing this letter, the paper is still with the handling editor. Like us, many authors have probably at this stage speculated when it would be reasonable to contact the editorial office and enquire about the status. This letter analyses paper acceptance time in respiratory journals and discusses novel ways to disseminate research <http://ow.ly/b9uX306esnA> We would like to acknowledge D.S. Himmelstein (bioinformationist; University of Pennsylvania, Philadelphia, PA, USA) for allowing us to analyse data.
Abstract 1935: Gene expression analysis reveals distinct pathways of resistance to antiangiogenic therapy in ovarian cancer
Authors: Bharat Kumar Devapatla, Pharavee Jaiprasart, Sukyung Woo
Journal: Cancer Research (2015)

Abstract Purpose: The rapid development of resistance after an initial response phase is a major challenge of antiangiogenic therapies. The molecular mechanisms underlying clinical resistance to antiangiogenic therapies are not yet well understood. We aimed to identify potential mediators of resistance to antiangiogenic therapy, with a view toward eventually developing therapeutic approaches to improve antiangiogenic therapies. Methods: We developed preclinical in vivo phenotypic resistance models of antiangiogenic therapy using human ovarian carcinoma cells. We used two representative anti-VEGF agents to block VEGF (bevacizumab, 10 mg/kg BIW, IP) or its receptor (sorafenib, 30 mg/kg daily, PO). The treatment was given until tumors showed a long-term trend toward continued progression after an initial response (resistant tumor). Whereas treatment-sensitive tumors were defined by a long-term trend toward stable disease or regression. We conducted next generation sequencing to compare changes in the gene expression in resistant and sensitive tumors, distinguishing their origin (tumor vs stroma cells). To get a more detailed perspective of the overall changes in gene expression, Gene Set Enrichment Analysis (GSEA) was performed by pair-wise comparison according to treatment outcome (resistant vs sensitive) with respect to bevacizumab and sorafenib, of which the entire MSigDB collections were compared to. Further, significantly enriched pathways were validated with clinical gene expression profiling studies of various tumor types deposited in GEO and ArrayExpress. Results: Our GSEA analysis revealed significant differences (FDR&amp;lt;0.25) in enrichment of various pathways between sensitive and resistant tumors. We observed ERK, P38 MAPK, ATP dependent helicase activity, and phosphatidylinositide 3-kinases pathways are differentially enriched between sensitive and resistant phenotypes of bevacizumab-treated group. In sorafenib-resistant group, six pathways were enriched including E2F1, KRAS and PDGF regulated pathways. Conclusions: Here, we report distinct pathways of response to bevacizumab and sorafenib in preclinical ovarian cancer models, which may provide critical insights into ovarian tumor's adaption during anti-VEGF blockade. These pathways may also provide important clues for identifying synergistic therapeutic strategies to overcome or delay resistance to antiangiogenic agents. Citation Format: Bharat Kumar Devapatla, Pharavee Jaiprasart, Sukyung Woo. Gene expression analysis reveals distinct pathways of resistance to antiangiogenic therapy in ovarian cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1935. doi:10.1158/1538-7445.AM2015-1935
T3 : A Multicenter Phase IB Dose Escalation Study to Evaluate the Safety, Feasibility and Efficacy of the Temsirolimus (Torisel™)-CHOP-Rituximab (T-R-CHOP), Temsirolimus (Torisel™)-FC-Rituximab (T-R-FC) and Temsirolimus (Torisel™)- DHA-Rituximab (T-R-DHA) for the Treatment of Patients with Relapsed/Refractory Mantle Cell Lymphoma (MCL), a Lysa Study
Authors: Steven Le Gouill, Krimo Bouabdallah, Guillaume Cartron, Remy Gressin, Thierry Lamy, Bertrand Coiffier, Catherine Thieblemont, Corinne Haioun, Olivier Casasnovas, Emmanuel Gyan, Olivier Hermine
Journal: Blood (2014)
Paediatrician is denied permission to appeal against manslaughter conviction
Authors: Clare Dyer
Journal: BMJ (2016)

A paediatrician who was convicted of manslaughter after a 6 year old patient died of septic shock has failed to persuade three senior judges to give her permission to appeal against her conviction.1

Hadiza Bawa-Garba, who was a specialist registrar in paediatrics at Leicester Royal Infirmary, was found guilty of manslaughter in November 2015 over the death of Jack Adcock, who had Down’s syndrome. …