tbuckley/cabot-search huggingface dataset:
Impaired Cyclooxygenase-2 Expression Leads to Aggravated Renal Fibrosis in Response to Unilateral Ureteral Obstruction in Mice
Authors: Kirsten Madsen, Signe Skou Tofteng, Line Nilsson, Boye L. Jensen, Rikke Nørregaard
Journal: Journal of the American Society of Nephrology (2014)
Abstract P3-04-05: Identification of SAR439859, an orally bioavailable selective estrogen receptor degrader (SERD) that has strong antitumor activity in wild-type and mutant ER+ breast cancer models
Authors: M Shomali, J Cheng, M Koundinya, M Weinstein, N Malkova, F Sun, A Hebert, M Cindachao, D Hoffman, J McManus, M Levit, J Pollard, S Vincent, L Besret, F Adrian, C Winter, Y El-Ahmad, F Halley, K Hsu, J Lager, C Garcia-Echeverria, M Bouaboula
Journal: Cancer Research (2017)

Abstract Estrogen receptor positive (ER+) breast cancer accounts for 70% of all breast cancers and is primarily treated with endocrine therapy. Approximately 40% of patients on endocrine therapy will become resistant via a number of mechanisms. There is evidence that in many cases ER continues to play a central role, including mutations in ER leading to a constitutively active receptor. Estrogen receptor degraders like fulvestrant are effective in shutting down ER signaling; however, poor pharmaceutical properties limit fulvestrant clinical activity and prevent it from achieving maximum receptor blockade. We describe the discovery of SAR439859, a novel, orally bioavailable SERD that is a potent antagonist and degrader of ER both in vitro and in vivo. SAR439859 has robust activity in multiple ER+ breast cancer cell lines including cells that are resistant to tamoxifen as well as cell lines harboring ER mutants. Across a large panel of ER+ cells, SAR439859 demonstrated broad and superior ER degradation activity than most SERDs undergoing clinical testing. This leads to a profound inhibition of ER signaling, better inhibition of cell growth and results in improved in vivo efficacy. SAR439859 demonstrated tumor regression in all ER+ BC models including MCF7-ESR1 mutant-Y537S model, as well as patient-derived xenograft model that is resistant to endocrine therapies. Furthermore, SAR439859 displays limited cross-resistance with other class of SERDs. Taken together, these results suggest that SAR439859 would be of therapeutic benefit in metastatic BC setting for patients harboring wild type or mutant ER. SAR439859 is being advanced toward the clinic. Citation Format: Shomali M, Cheng J, Koundinya M, Weinstein M, Malkova N, Sun F, Hebert A, Cindachao M, Hoffman D, McManus J, Levit M, Pollard J, Vincent S, Besret L, Adrian F, Winter C, El-Ahmad Y, Halley F, Hsu K, Lager J, Garcia-Echeverria C, Bouaboula M. Identification of SAR439859, an orally bioavailable selective estrogen receptor degrader (SERD) that has strong antitumor activity in wild-type and mutant ER+ breast cancer models [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-04-05.
Abstract 12: Physiological Role of Endogenous Adult Cardiac Colony-forming Unit Fibroblasts
Authors: Elvira Forte, Vaibhao Janbandhu, Naisana S Asli, James Cornwell, Dhanushi Abeygunawardena, Munira Xaymardan, Richard P Harvey
Journal: Circulation Research (2015)

Colony-forming unit fibroblasts (CFU-Fs), analogous to those giving rise to bone marrow (BM) mesenchymal stem cells (MSCs), have been identified in different tissues. CFU-Fs are multipotent progenitor cells, with a supportive paracrine and immunomodulatory function. They share the expression of surface antigens, are capable of self-renewal, and to differentiate into osteogenic, adipogenic and chondrogenic lineages in vitro. Our laboratory has isolated, for the first time, CFU-Fs from the adult murine heart. These cells are included within the Sca1+ PDGFRα+ CD31- fraction of interstitial cells, mainly associated with microvessels and the perivascular adventitial niche of larger vessels. Here we show that resident cCFU-Fs, are quiescent in homeostatic conditions, relatively more hypoxic and have a lower metabolic profile compared to other interstitial cells. Treatment with PDGF-AB ligand stimulates cCFU-Fs to exit the quiescent state, potentially making them more responsive to mitogenic and differentiative factors. In a mouse with a H2B-eGFP fusion gene knocked-in the Pdgfrα locus, cCFU-Fs lay in the GFPhigh population. After myocardial infarction, a GFPmed population appears, which has partially lost the expression of Sca1 and PDGFRα proteins, and consists largely of activated myofibroblasts. Likely derived from cCFU-Fs or related stromal fraction, GFPmed cells are significantly reduced by inhibiting PDGFRα signalling and increased by systemic PDGF-AB treatment. Despite augmenting the GFPmed myofibroblasts-like population, short-term PDGF-AB treatment is beneficial, leading to reduced scar, and increased vascular density and ejection fraction. A crucial factor in cardiac repair is the fine balance between pro-inflammatory (type1) and pro-reparative/pro-angiogenic (type2) immune responses, which can be regulated by MSCs. interestingly PDGF-AB treatment seems to be associated with an earlier resolution of the type1 response at 5 days after MI, compared to controls. We hypothesize that the beneficial effects of short term PDGF-AB treatment are due to early activation of cCFU-Fs and stromal cells from quiescence, leading to enhanced pro-angiogenic, anti-apoptotic and immunomodulatory impacts.
The Outcome of Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with Rituximab-CHOP (R-CHOP) Is Not Predicted by 18-FDG-Positron Emission Tomography/Computerized Tomography (PET) Performed at Intermediate In-Course Evaluation, but Only by PET Assessed at the End of Therapy.
Authors: Umberto Vitolo, Annalisa Chiappella, Marilena Bellò, Roberto Passera, Barbara Botto, Giancarlo Castellano, Chiara Ciochetto, Simone Ferrero, Chiara Frairia, Silvia Franceschetti, Francesca Giunta, Marco Ladetto, Massimo Menga, Maura Nicolosi, Giorgio Priolo, Benedetta Puccini, Luigi Rigacci, Flavia Salvi, Luca Vaggelli, Patrizia Pregno, Gianni Bisi
Journal: Blood (2010)
Initial Evaluation of a 48-h Continuous Intravenous Infusion Weekly Regimen of ON 01910.Na in Advanced Myelodysplastic Syndrome (MDS).
Authors: Azra Raza, Naomi Galili, Muhammad Shahzad Ali, Fahad Ali, Alyssa Goodman, Samir Ahmed Qasim, Francois Wilhelm
Journal: Blood (2009)
ASXL1 Mutations Promote Myeloid Transformation Through Inhibition of PRC2-Mediated Gene Repression
Authors: Omar Abdel-Wahab, Mazhar Adli, Lindsay Saunders, Jie Gao, Alan H. Shih, Suveg Pandey, Jake Jaffe, Xinyang Zhao, Fabiana Perna, Martin Carroll, Ari Melnick, Stephen D. Nimer, Iannis Aifantis, Bradley Bernstein, Ross L Levine
Journal: Blood (2011)
PP30. ‘FIND OUT FASTER’: CAN WE ACHIEVE NEW WAITING TIME STANDARDS FOR THE GLIOBLASTOMA PATHWAY?
Authors: Mr Jake Weddell, Ms Sarah Hawksby, Prof Philip Kane
Journal: Neuro-Oncology (2017)

INTRODUCTION: The Department of Health has recently developed new targets for waiting times within cancer pathway, which aim to shorten the time between referral for a suspected malignancy and the communication of a definitive diagnosis. The proposed targets in the “Find Out Faster” document include: • 50% of patients to receive communication of a definitive diagnosis within 14 days. • 95% of patients to receive communication of a definitive diagnosis within 28 days. Are these targets achievable for patients referred with a suspected diagnosis of Glioblastoma? METHOD: A retrospective audit was conducted of the pathways of 50 consecutive patients referred to our Brain & CNS tumours MDT between 21/10/2014–31/12/2015 who subsequently received a diagnosis of glioblastoma. RESULTS: Nineteen patients received a radiological diagnosis only and 31 received a histological diagnosis. The median time taken from referral to communication of a diagnosis was 22 days with 30% of patients receiving their diagnosis within 14 days and 74% within 28 days. Factors contributing to delays in the diagnostic pathway included: MDT decision to communication of radiological diagnosis (Median 7 days); MDT decision to admission for surgery (Median 13 days); Histology reported to communication of diagnosis (Median 8 days). CONCLUSION: Clarity is needed within the proposed guidelines regarding the definition of terms such as “definitive diagnosis” and “referral date” which are key points of measurement in the management pathway. Refinement of the current patient pathway is likely to lead to the achievement of the ‘find out faster’ target of 95% of patients to receive communication of a definitive diagnosis within 28 days. Achieving the new standard will impact on job planning for all members of the MDT. The achievement of the secondary target, 50% of patients to receive communication of a definitive diagnosis within 14 days, is unlikely.
High T-Cell Lymphoma Breakpoint 1 (TCL1) Levels Are Associated with Lack of Response and Inferior Outcome Following Fludarabine, Cyclophosphamide, Rituximab (FCR) Frontline Therapy in Patients with Chronic Lymphocytic Leukemia (CLL).
Authors: Ellen Schlette, Constantine S. Tam, Marco Herling, Carlos Bueso-Ramos, William Wierda, Alessandra Ferrajoli, Susan O’Brien, Michael Keating, Dan Jones
Journal: Blood (2008)
Recommended Guidelines for Validation, Quality Control, and Reporting of <i>TP53</i> Variants in Clinical Practice
Authors: Bernard Leroy, Mandy L. Ballinger, Fanny Baran-Marszak, Gareth L. Bond, Antony Braithwaite, Nicole Concin, Lawrence A. Donehower, Wafik S. El-Deiry, Pierre Fenaux, Gianluca Gaidano, Anita Langerød, Eva Hellstrom-Lindberg, Richard Iggo, Jacqueline Lehmann-Che, Phuong L. Mai, David Malkin, Ute M. Moll, Jeffrey N. Myers, Kim E. Nichols, Sarka Pospisilova, Patricia Ashton-Prolla, Davide Rossi, Sharon A. Savage, Louise C. Strong, Patricia N. Tonin, Robert Zeillinger, Thorsten Zenz, Joseph F. Fraumeni, Peter E.M. Taschner, Pierre Hainaut, Thierry Soussi
Journal: Cancer Research (2017)

Accurate assessment of TP53 gene status in sporadic tumors and in the germline of individuals at high risk of cancer due to Li-Fraumeni Syndrome (LFS) has important clinical implications for diagnosis, surveillance, and therapy. Genomic data from more than 20,000 cancer genomes provide a wealth of information on cancer gene alterations and have confirmed TP53 as the most commonly mutated gene in human cancer. Analysis of a database of 70,000 TP53 variants reveals that the two newly discovered exons of the gene, exons 9β and 9γ, generated by alternative splicing, are the targets of inactivating mutation events in breast, liver, and head and neck tumors. Furthermore, germline rearrange-ments in intron 1 of TP53 are associated with LFS and are frequently observed in sporadic osteosarcoma. In this context of constantly growing genomic data, we discuss how screening strategies must be improved when assessing TP53 status in clinical samples. Finally, we discuss how TP53 alterations should be described by using accurate nomenclature to avoid confusion in scientific and clinical reports. Cancer Res; 77(6); 1250-60. ©2017 AACR.
Integrated Analysis of Long Term Safety in Patients (pts) with Chronic Immune Thrombocytopenia (ITP) Treated with Romiplostim.
Authors: Douglas B. Cines, Terry B. Gernsheimer, Jeffrey Wasser, Bertrand Godeau, Andrew Provan, Roger M. Lyons, Ivy Altomare, Xuena Wang, Paul Woodard
Journal: Blood (2012)
Erratum: IGF-binding protein-1 levels are related to insulin-mediated glucose disposal and are a potential serum marker of insulin resistance (Diabetes Care (2006) 29, (1535-1537))
Authors: B. A. Maddux, A. Chan, E. A. De Filippis, L. J. Mandarino, I. D. Goldfine
Journal: Diabetes Care (2006)
Injectable and thermally contractible hydroxypropyl methyl cellulose/Fe3O4 for magnetic hyperthermia ablation of tumors
Authors: Fengjuan Wang, Yang Yang, Yi Ling, Jianxin Liu, Xiaojun Cai, Xiaohan Zhou, Xiuzhen Tang, Bing Liang, Yini Chen, Hangrong Chen, Dengming Chen, Chunhong Li, Zhigang Wang, Bing Hu, Yuanyi Zheng
Journal: Biomaterials (2017)
PP67. PAEDIATRIC TECTAL PLATE ‘GLIOMAS’: A DECADE’S EXPERIENCE
Authors: Ms Nida Kalyal, Ms Charlotte Burford, Mr Harutomo Hasegawa, Mrs Claire Cairns, Mr Jignesh Tailor, Prof Keyoumars Ashkan, Mr Sanjeev Bassi, Mr Christopher Chandler, Dr Henry Mandeville, Dr Stergios Zacharoulis, Mr Bassel Zebian
Journal: Neuro-Oncology (2017)

OBJECTIVE: Tectal plate ‘gliomas’ are uncommon, indolent lesions. Presentation is usually with hydrocephalus and diagnosis is typically made radiologically without histological confirmation. Long term data guiding management is lacking. METHOD: Retrospective review of all paediatric tectal plate lesions in our unit over the last 10 years. RESULTS: Fifteen patients (13 boys, 2 girls; mean age 8.9 years) were identified and included. Most presented with increased intracranial pressure. Fourteen patients (93%) had hydrocephalus at presentation. In 13 patients (87%) there was no progression of the lesion. CSF diversion was performed in 14 patients (93%). The initial intervention was endoscopic third ventriculostomy (ETV) in 12 (80%) and ventriculoperitoneal shunting in 3 (20%). Four patients (33%) were biopsied; 2 (17%) were WHO grade 1 pilocytic astrocytomas and 2 (17%) had non-diagnostic biopsies. Four patients (33%) received adjuvant therapy, two upfront (due to atypical radiological appearances) and 2 due to progression. Of the 4 patients receiving adjuvant therapy, 1 had chemotherapy only (Carboplatin and Vincristine), 1 had chemotherapy followed by proton beam therapy and 2 patients had focal radiation therapy (59.4 CGE). All patients were alive with stable disease at follow up (average 50.5 months; range 0–120 months). CONCLUSION: Our experience is in line with the published literature on the natural history of tectal plate ‘gliomas’ and supports the notion that these are low grade tumours that can be managed with cerebrospinal fluid diversion and surveillance imaging. Adjuvant therapy is reserved for progression and achieves long term control.
Randomized Trial of Four Financial-Incentive Programs for Smoking Cessation
Authors: Scott D. Halpern, Benjamin French, Dylan S. Small, Kathryn Saulsgiver, Michael O. Harhay, Janet Audrain-McGovern, George Loewenstein, Troyen A. Brennan, David A. Asch, Kevin G. Volpp
Journal: New England Journal of Medicine (2015)

Financial incentives promote many health behaviors, but effective ways to deliver health incentives remain uncertain.We randomly assigned CVS Caremark employees and their relatives and friends to one of four incentive programs or to usual care for smoking cessation. Two of the incentive programs targeted individuals, and two targeted groups of six participants. One of the individual-oriented programs and one of the group-oriented programs entailed rewards of approximately $800 for smoking cessation; the others entailed refundable deposits of $150 plus $650 in reward payments for successful participants. Usual care included informational resources and free smoking-cessation aids.Overall, 2538 participants were enrolled. Of those assigned to reward-based programs, 90.0% accepted the assignment, as compared with 13.7% of those assigned to deposit-based programs (P<0.001). In intention-to-treat analyses, rates of sustained abstinence from smoking through 6 months were higher with each of the four incentive programs (range, 9.4 to 16.0%) than with usual care (6.0%) (P<0.05 for all comparisons); the superiority of reward-based programs was sustained through 12 months. Group-oriented and individual-oriented programs were associated with similar 6-month abstinence rates (13.7% and 12.1%, respectively; P=0.29). Reward-based programs were associated with higher abstinence rates than deposit-based programs (15.7% vs. 10.2%, P<0.001). However, in instrumental-variable analyses that accounted for differential acceptance, the rate of abstinence at 6 months was 13.2 percentage points (95% confidence interval, 3.1 to 22.8) higher in the deposit-based programs than in the reward-based programs among the estimated 13.7% of the participants who would accept participation in either type of program.Reward-based programs were much more commonly accepted than deposit-based programs, leading to higher rates of sustained abstinence from smoking. Group-oriented incentive programs were no more effective than individual-oriented programs. (Funded by the National Institutes of Health and CVS Caremark; ClinicalTrials.gov number, NCT01526265.).
Abstract P2-03-02: Differential mutation pattern between neoadjuvant and metastatic settings in breast cancer patients
Authors: B Xu, C Williams, P De, N Dey, J Klein, K Williams, A McMillan, B Leyland-Jones
Journal: Cancer Research (2017)

Abstract Background: Dysregulated signaling pathways occur in human cancers including breast cancer, making it a rational target for novel genome guided combinatorial personalized therapies. The aim of the present study was to investigate the different genetic mutation pattern between neoadjuvant and metastatic settings in breast cancer patients to guide research and clinical treatment. Material and Methods: 150 breast cancer patients were involved in this study. 38 patients were receiving neoadjuvant treatment and 112 patients were in the metastatic setting. Tumor specimens obtained from the 150 patients were subjected to genetic mutation testing by FoundationOne. Genetic alterations detected by FoundationOne test were collected and analyzed. Results: 96 and 149 different genes where reported by FoundationOne in neoadjuvant and metastatic setting respectively. The average number of non-synonymous mutation was five per case in the neoadjuvant setting and six per case in the metastatic setting. TP53 (58%), MYC (32%), PIK3CA (29%), PTEN (16%), CDH1 (13%), CCND1 (11%), EMSY (11%), LYN (11%) and ZNF703 (11%) were the most seen mutations in neoadjuvant setting. TP53 (40%), PIK3CA (39%), MYC (22%), CCND1 (21%), FGF19 (21%), FGF4 (21%), CDH1 (20%), FGF3 (19%), ERBB2 (17%), ESR1 (14%), FGFR1 (14%), ZNF703 (14%), GATA3 (13%), MYST3 (11%), PTEN (11%), EMSY (10%), NF1 (10%) and ZNF217 (10%) were the most seen mutations in metastatic setting. ESR1 and GATA3, which are seen in 14% and 13% of metastatic breast cancer patients, were not reported in neoadjuvant breast patients. Moreover, among the 16 metastatic breast cancer patients who has ESR1 mutation, 9 (56%) of them presented with PIK3CA or other genetic mutations which are directly involved in the phosphoinositide 3-kinase (PI3K)/AKT pathway. Conclusion: A significantly more mutation in Receptor Tyrosine Kinases (RTKs)/ Growth Factor Signaling ( especially ERBB and FGFR pathways) was reported in the metastatic setting compare to the neoadjuvant setting, suggesting a critical role of the RTKs in metastatic breast cancer patients. The coexisting of ESR1 and PI3K/AKT pathway alteration and the absence of ESR1 in neoadjuvant setting also suggested that in early stage breast cancer patients who have a PI3K pathway alterations; there is a higher chance to develop ESR1 mutation with disease progression. Citation Format: Xu B, Williams C, De P, Dey N, Klein J, Williams K, McMillan A, Leyland-Jones B. Differential mutation pattern between neoadjuvant and metastatic settings in breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-03-02.
The Jak2 Kinase Inhibitor, G6, Reduces the Mutant Burden and Reverses Marrow Fibrosis in a Mouse Model of Jak2-V617F Mediated PMF,
Authors: Peter P. Sayeski, Annet Kirabo, Sung Park, Meghanath Gali, Mary Reinhard, Heather L Wamsley, Zhizhuang Joe Zhao, Kirpal S Bisht, Christopher R Cogle, Gyorgy M Keseru
Journal: Blood (2011)
Abstract IA29: Eliminating racial disparities in colorectal cancer
Authors: Stephen Grubbs
Journal: Cancer Research (2017)

Abstract The Delaware Cancer Advisory Council was convened in 2001 by Governor Ruth Ann Minner to develop a statewide cancer control program. Rather than reporting a comprehensive cancer control program, the Council in 2002 recommended a limited number of achievable deliverables to reduce Delaware's high rates of cancer incidence and mortality. The Delaware Legislature and the Governor Minner accepted the recommendations and fully funded the program. Three key elements of the program include a statewide coordinated colorectal screening program with coverage of the uninsured, a cancer treatment program providing for the uninsured, and an emphasis of African American cancer disparity reduction. The screening program featured statewide nurse navigation, colonoscopy promotion, statewide marketing, and coverage for both screening and up to two years of cancer treatment for the uninsured. Over the next ten years, the program eliminated the Caucasian and African American colorectal cancer disparities between by raising screening rates, lowering the stage at diagnosis, reducing the incidence, and finally eliminating the mortality disparity. All Delaware populations achieved improved colorectal cancer outcomes with the greatest gain in the African American community that closed the disparity gaps. Delaware can be viewed as a model for success, achieved when all parties including government, health care systems, providers, and the public are determined together to improve health and tackle health disparities. Citation Format: Stephen Grubbs. Eliminating racial disparities in colorectal cancer. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr IA29.
Impact of Serum Soluble LR11 on Survival in Newly Diagnosed Diffuse Large B-Cell Lymphoma: A Multicenter Prospective Study
Authors: Yasumasa Sugita, Chikako Ohwada, Takeharu Kawaguchi, Tomoya Muto, Shokichi Tsukamoto, Yusuke Takeda, Naoya Mimura, Masahiro Takeuchi, Emiko Sakaida, Naomi Shimizu, Hiroaki Tanaka, Daijiro Abe, Motoharu Fukazawa, Takeaki Sugawara, Nobuyuki Aotsuka, Kaichi Nishiwaki, Akira Yokota, Hiroyuki Ebinuma, Kengo Fujimura, Hideaki Bujo, Chiaki Nakaseko
Journal: Blood (2014)
A Novel Cancer Vaccine Strategy In Previously Untreated Patients with Stage III/IV Follicular Lymphoma Generates Tumor-Reactive T Cells and Clinical Response
Authors: Arne Kolstad, Shraddha Kumari, Gunnar Kvalheim, Trond Velde Bogsrud, Ulf Madsbu, Trond Hagtvedt, Gustav Gaudernack, Grethe Lauvvang, Harald Holte, Johanna Olweus
Journal: Blood (2010)
Corrigendum re: “TMPRSS2-ERG in Blood and Docetaxel Resistance in Metastatic Castration-resistant Prostate Cancer” [Eur Urol 2016;70:709–13]
Authors: Òscar Reig, Mercedes Marín-Aguilera, Gemma Carrera, Natalia Jiménez, Laia Paré, Susana García-Recio, Lydia Gaba, Maria Verónica Pereira, Pedro Fernández, Aleix Prat, Begoña Mellado
Journal: European Urology (2017)
Early Results of the Clinical Collection and Genetic Correction of Fanconi Complement Type A Hematopoietic Stem Cells.
Authors: Patrick Kelly, B. Balcik, K. Bohn, R. Mueller, I. Jurickova, T. Schuesler, L. Reeves, T. Leemhuis, R. Harris, S. M. Davies, F. O. Smith, C. von Kalle, D. A. Williams
Journal: Blood (2005)