tbuckley/cabot-search huggingface dataset:
Abstract 1716: Acquisition of estrogen independence induces TOB1-related mechanisms supporting breast cancer cell proliferation
Authors: Yong-Wei Zhang, Rochelle E. Nasto, Rency Varghese, Sandra A. Jablonski, Ilya G. Serebriiskii, Rishi Surana, Valerie S. Calvert, Ionut Bebu, Joseph Murray, Lu Jin, Michael Johnson, Rebecca Riggins, Habtom Ressom, Emmanuel Petricoin III, Robert Clarke, Erica A. Golemis, Louis M. Weiner
Journal: Cancer Research (2015)

Abstract Approximately 70% of newly diagnosed breast cancers express high levels of estrogen receptor alpha (ERα). However, de novo and acquired drug resistance to anti-estrogen agents limit the treatment of such patients, requiring the use of cytotoxic chemotherapy; many such patients have a poor prognosis. Therefore, resistance to therapies targeting the estrogen pathway remains a challenge in the treatment of estrogen-receptor positive breast cancer. To address this challenge, a system biological approach by screening a library of siRNAs targeting an estrogen receptor- and aromatase-centered network, was used and identified 46 genes that are dispensable in estrogen-dependent MCF7 cells, but are selectively required for the survival of estrogen-independent MCF7-derived cells, and multiple additional estrogen-independent breast cancer cell lines. Integration of this information identified a tumor suppressor gene TOB1 as a critical determinant of estrogen-independent estrogen-receptor positive breast cell survival. Depletion of TOB1 selectively promoted G1 phase arrest and sensitivity to AKT and mTOR inhibitors in estrogen-independent cells but not estrogen-dependent cells. Phosphoproteomic profiles (results from reverse phase protein array, RPPA) under basal conditions and following TOB1 depletion identified significant signaling network reprogramming by TOB1 that differed in estrogen-sensitive and estrogen-resistant cell lines. These data support a novel function for TOB1 in mediating survival of estrogen-independent breast cancers. The translational significance of this new molecular mechanism of estrogen independence in human breast cancer will be fully determined when TOB1 inhibitors are developed to enable in vivo validation studies. These studies also provide evidence for combining TOB1 inhibition and AKT/mTOR inhibition as a therapeutic strategy, which have potential translational significance for the management of patients with estrogen receptor-positive breast cancers. Citation Format: Yong-Wei Zhang, Rochelle E. Nasto, Rency Varghese, Sandra A. Jablonski, Ilya G. Serebriiskii, Rishi Surana, Valerie S. Calvert, Ionut Bebu, Joseph Murray, Lu Jin, Michael Johnson, Rebecca Riggins, Habtom Ressom, Emmanuel Petricoin III, Robert Clarke, Erica A. Golemis, Louis M. Weiner. Acquisition of estrogen independence induces TOB1-related mechanisms supporting breast cancer cell proliferation. [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 1716. doi:10.1158/1538-7445.AM2015-1716
P2-052: Effects of huTNF-α, hIL-2 gene transfection on the expressionof MDR1, LRP gene in lung cancer
Authors: Lei Su, Xiuyi Zhi, Qingsheng Xu, Baodong Liu, Yi Zhang, Ruotian Wang, Mu Hu, Lei Liu, Kun Qian
Journal: Journal of Thoracic Oncology (2007)
An Open-Label Phase 2 Study of Lenalidomide in Combination with Oral Dexamethasone in the Previously Untreated, Symptomatic Patients with Chronic Lymphocytic Leukemia (CLL).
Authors: Christine Chen, Harminder Paul, Luisa Del Rizzo, Lisa W Le, Ellen Nong Wei, Anthea Lau, James B Johnston, Spencer B Gibson, Michelle Brown, Suzanne Trudel
Journal: Blood (2012)
Extracellular vesicles in liver pathobiology: Small particles with big impact
Authors: Petra Hirsova, Samar H. Ibrahim, Vikas K. Verma, Leslie A. Morton, Vijay H. Shah, Nicholas F. LaRusso, Gregory J. Gores, Harmeet Malhi
Journal: Hepatology (2016)

Extracellular vesicles (EVs) are nanometer-sized, membrane-bound vesicles released by cells into the extracellular milieu. EVs are now recognized to play a critical role in cell-to-cell communication. EVs contain important cargo in the form of proteins, lipids, and nucleic acids and serve as vectors for delivering this cargo from donor to acceptor or target cell. EVs are released under both physiologic and pathologic conditions, including liver diseases, and exert a wide range of effects on target cells. This review provides an overview on EV biogenesis, secretion, cargo, and target cell interactions in the context of select liver diseases. Specifically, the diverse roles of EVs in nonalcoholic steatohepatitis, alcoholic liver disease, viral hepatitis, cholangiopathies, and hepatobiliary malignancies are emphasized. Liver diseases often result in an increased release of EVs and/or in different cargo sorting into these EVs. Either of these alterations can drive disease pathogenesis. Given this fact, EVs represent a potential target for therapeutic intervention in liver disorders. Because altered EV composition may reflect the underlying disease condition, circulating EVs can be exploited for diagnostic and prognostic purposes as a liquid biopsy. Furthermore, ex vivo modified or synthesized EVs can be engineered as therapeutic nano-shuttles. Finally, we highlight areas that merit further investigation relevant to understanding how EVs regulate liver disease pathogenesis. (Hepatology 2016;64:2219-2233).
PD2-3-1: Prognostic significance and origin of plasma KRAS mutations in patients with non-small cell lung cancer (NSCLC)
Authors: Oliver Gautschi, Annemarie Ziegler, Barbara Huegli, Mathias Gugger, Daniel Ratschiller, Philip C. Mack, Hsing-Jien Kung, Rolf A. Stahel, David R. Gandara, Daniel C. Betticher
Journal: Journal of Thoracic Oncology (2007)
Phase I Trial Of The Targeted Alpha-Particle Nano-Generator Actinium-225 (225Ac)-Lintuzumab (Anti-CD33) In Combination With Low-Dose Cytarabine (LDAC) For Older Patients With Untreated Acute Myeloid Leukemia (AML)
Authors: Joseph G. Jurcic, Farhad Ravandi, John M. Pagel, Jae H Park, Dan Douer, Elihu H. Estey, Hagop M Kantarjian, Dragan Cicic, David A. Scheinberg
Journal: Blood (2013)
P3-080: Erlotinib as single agent in men with advanced or metastatic NSCLC: A retrospective analysis
Authors: Manuel Domine, Luis Alfonso Gurpide, Fernando Rosillo, Javier Puertas, Mariano Provencio, Christian Rolfo, Miguel Mendez, Marta Lopez-Brea, Maria Luz Amador, Luis Paz Ares
Journal: Journal of Thoracic Oncology (2007)
Association between electronic cigarette use and changes in quit attempts, success of quit attempts, use of smoking cessation pharmacotherapy, and use of stop smoking services in England: time series analysis of population trends
Authors: Emma Beard, Robert West, Susan Michie, Jamie Brown
Journal: BMJ (2016)

<b>Objectives</b>&nbsp;To estimate how far changes in the prevalence of electronic cigarette (e-cigarette) use in England have been associated with changes in quit success, quit attempts, and use of licensed medication and behavioural support in quit attempts. <b>Design</b>&nbsp;Time series analysis of population trends. <b>Participants</b>&nbsp;Participants came from the Smoking Toolkit Study, which involves repeated, cross sectional household surveys of individuals aged 16 years and older in England. Data were aggregated on about 1200 smokers quarterly between 2006 and 2015. Monitoring data were also used from the national behavioural support programme; during the study, 8 029 012 quit dates were set with this programme. <b>Setting</b>&nbsp;England. <b>Main outcome measures</b>&nbsp;Prevalence of e-cigarette use in current smokers and during a quit attempt were used to predict quit success. Prevalence of e-cigarette use in current smokers was used to predict rate of quit attempts. Percentage of quit attempts involving e-cigarette use was also used to predict quit attempts involving use of prescription treatments, nicotine replacement therapy (NRT) on prescription and bought over the counter, and use of behavioural support. Analyses involved adjustment for a range of potential confounders. <b>Results</b>&nbsp;The success rate of quit attempts increased by 0.098% (95% confidence interval 0.064 to 0.132; P&lt;0.001) and 0.058% (0.038 to 0.078; P&lt;0.001) for every 1% increase in the prevalence of e-cigarette use by smokers and e-cigarette use during a recent quit attempt, respectively. There was no clear evidence for an association between e-cigarette use and rate of quit attempts (β 0.025; 95% confidence interval −0.035 to 0.085; P=0.41), use of NRT bought over the counter (β 0.006; −0.088 to 0.077; P=0.89), use of prescription treatment (β −0.070; −0.152 to 0.013; P=0.10), or use of behavioural support (β −0.013; −0.102 to 0.077; P=0.78). A negative association was found between e-cigarette use during a recent quit attempt and use of NRT obtained on prescription (β −0.098; −0.189 to −0.007; P=0.04). <b>Conclusion</b>&nbsp;Changes in prevalence of e-cigarette use in England have been positively associated with the success rates of quit attempts. No clear association has been found between e-cigarette use and the rate of quit attempts or the use of other quitting aids, except for NRT obtained on prescription, where the association has been negative. <b>Study registration</b>&nbsp;The analysis plan was preregistered (https://osf.io/fbgj2/).
Re: Claude Schulman, Erik Cornel, Vsevolod Matveev, et al. Intermittent Versus Continuous Androgen Deprivation Therapy in Patients with Relapsing or Locally Advanced Prostate Cancer: A Phase 3b Randomised Study (ICELAND). Eur Urol 2016;69:720–7
Authors: Peihua Liu, Longfei Liu, Xiongbing Zu
Journal: European Urology (2016)
Phase 1/2 Study of Elotuzumab in Combination with Lenalidomide and Low Dose Dexamethasone in Relapsed or Refractory Multiple Myeloma: Interim Results.
Authors: Sagar Lonial, Ravi Vij, Jean-Luc Harousseau, Thierry Facon, Jonathan Kaufman, Amitabha Mazumder, Philippe Moreau, Xavier Leleu, John Fry, Anil Singhal, Sundar Jagannath
Journal: Blood (2009)
Drug‐induced liver and skin reactions: In need of a consensus definition
Authors: Inmaculada Medina‐Cáliz, Mercedes Robles‐Díaz, M. Isabel Lucena, Raul J. Andrade
Journal: Hepatology (2016)

Adverse reactions affecting both skin and liver can manifest a wide spectrum of heterogeneous clinical presentations, from exanthema or urticaria to Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN). The clinical phenotypes and causative agents of this type of adverse reactions are, however, not well defined. The article of Devarbhavi et al.1 describes the clinical characteristics and outcome of 36 DILI cases associated with SJS/TEN in a cohort of 748 patients, mostly with mixed pattern of damage and attributed mainly to antiepileptic drugs, sulfonamides, and nevirapine. Twenty-one patients (58%) experienced severe drug-induced liver injury (DILI) with an overall mortality of 36%. These results differ from those found by the DILIN group,2 with 9 patients presenting SJS/TEN features of 899 DILI patients. Hepatocellular damage predominated (78%) and 4 patients died (44%). The difference in mortality between these cohorts may be also related to the fact that the Indian Registry included children who had a lower mortality as compared to adults. The spectrum of severe cutaneous adverse reactions (SCARs) also include DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms). DRESS case severity ranges from mild to acute liver failure.3 DRESS has been reported to have a 10% mortality rate, most commonly attributed to fulminant hepatitis with hepatic necrosis.4 Although no consensus criteria are currently available for the definition of DRESS, the International Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) states that DRESS cases must have at least three of the following systemic features: acute skin rash; fever above 38ºC; enlarged lymph nodes; internal organ involvement; or hematological abnormalities, including lymphocytosis, lymphocytopenia, eosinophilia, or thrombocytopenia.5 Genetic risk factors associated with DRESS and SJS/TEN development have been identified and appear to differ depending on the causative drug, as well as patient ethnicity. SCARs encompass a spectrum of different diseases. To compare such cases between different DILI registries, and to identify clinical phenotypes, causative agents, as well as the genetic background, it is necessary to establish common criteria. The study by Devarbhavi et al. may represent a starting point to encourage DILI investigators in pursuing these goals. Inmaculada Medina-Cáliz1,2 Mercedes Robles-Díaz1,2 M. Isabel Lucena1,2 Raul J. Andrade1,2 1Unidad de Gestión Clínica de Aparato Digestivo Servicio de Farmacología Clínica Instituto de Investigación Biomédica de Málaga-IBIMA Hospital Universitario Virgen de la Victoria Universidad de Málaga Málaga, Spain 2Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) Madrid, Spain
Neuregulin-1/ErbB4 Signaling Regulates Visual Cortical Plasticity
Authors: Yanjun Sun, Taruna Ikrar, Melissa F. Davis, Nian Gong, Xiaoting Zheng, Z. David Luo, Cary Lai, Lin Mei, Todd C. Holmes, Sunil P. Gandhi, Xiangmin Xu
Journal: Neuron (2016)
Microaggressions During Medical Training—Reply
Authors: Roberto Montenegro
Journal: JAMA (2016)

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The Prohibitin 3′ Untranslated Region Polymorphisms Are Associated with AML Susceptibility.
Authors: Hye-Ran Kim, Myung-Geun Shin, Sun-Seog Kweon, Hee-Nam Kim, Hyeoung-Joon Kim, Il-Kwon Lee, Jong-Hee Shin, Soon-Pal Suh, Dong-Wook Ryang
Journal: Blood (2009)
Patients with hidradenitis suppurativa have no increased risk of Alzheimer disease
Authors: P. Theut Riis, A. Egeberg, G.H. Gislason, G.B. Jemec
Journal: British Journal of Dermatology (2016)

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease and 30-40% of patients report first-degree relatives with HS [1]. Both familial HS and Alzheimer's disease (AD) are linked to mutations in the γ-secretase complex. [2] The γ-secretase complex consists of presenilin (PS), nicastrin (NCSTN), anterior pharynx defective-1 (APH-1), and pesenilin enchancer-2 (PEN-2). The complex cleaves substrates in the lipid bilayer, most notably amyloid precursor protein (APP) and Notch. [3] Amyloid plaques of the brain are a key step in the pathogenesis of AD [3] and amyloidosis has been described in HS patients [4]. Due to causal mutations in the same complex, researchers have speculated if AD and HS are caused by the same mutations or mutually exclusive. [5] We have therefore studied the risk of AD in patients with HS.

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RAG-induced DNA lesions activate proapoptotic BIM to suppress lymphomagenesis in p53-deficient mice
Authors: Alex R.D. Delbridge, Swee Heng Milon Pang, Cassandra J. Vandenberg, Stephanie Grabow, Brandon J. Aubrey, Lin Tai, Marco J. Herold, Andreas Strasser
Journal: The Journal of Experimental Medicine (2016)

Neoplastic transformation is driven by oncogenic lesions that facilitate unrestrained cell expansion and resistance to antiproliferative signals. These oncogenic DNA lesions, acquired through errors in DNA replication, gene recombination, or extrinsically imposed damage, are thought to activate multiple tumor suppressive pathways, particularly apoptotic cell death. DNA damage induces apoptosis through well-described p53-mediated induction of PUMA and NOXA. However, loss of both these mediators (even together with defects in p53-mediated induction of cell cycle arrest and cell senescence) does not recapitulate the tumor susceptibility observed in p53−/− mice. Thus, potentially oncogenic DNA lesions are likely to also trigger apoptosis through additional, p53-independent processes. We found that loss of the BH3-only protein BIM accelerated lymphoma development in p53-deficient mice. This process was negated by concomitant loss of RAG1/2-mediated antigen receptor gene rearrangement. This demonstrates that BIM is critical for the induction of apoptosis caused by potentially oncogenic DNA lesions elicited by RAG1/2-induced gene rearrangement. Furthermore, this highlights the role of a BIM-mediated tumor suppressor pathway that acts in parallel to the p53 pathway and remains active even in the absence of wild-type p53 function, suggesting this may be exploited in the treatment of p53-deficient cancers.
Endoscopic ultrasound-guided transgastric drainage of a complex multiloculated peritoneal fluid collection as rare complication of lupus peritonitis
Authors: Farid Jalali, Jason Samarasena, John Lee
Journal: Endoscopy (2016)

A 23-year-old woman with an 8-year history of systemic lupus erythematosus (SLE) complicated by recurrent peritonitis presented with abdominal pain and distension.
Ofatumumab Monotherapy for Treatment of Patients with Relapsed/Progressive Diffuse Large B-Cell Lymphoma: Results From a Multicenter Phase II Study
Authors: Bertrand Coiffier, André Bosly, Ka Lung Wu, Gregor Verhoef, Van Eygen Koen, Giovanni Martinelli, Gabriela Barca, Andrew Davies, Eve Gallop-Evans, Swaminathan Padmanabhan, Ira V. Gupta, Thomas S. Lin, Randy L. Davis, Nedjad Losic, Steen Lisby, John A. Radford
Journal: Blood (2010)
Prognostic significance of tumor-infiltrating CD8+ and FOXP3+ lymphocytes in residual tumors and alterations in these parameters after neoadjuvant chemotherapy in triple-negative breast cancer.
Authors: Minoru Miyashita, Hironobu Sasano, Kentaro Tamaki, Hisashi Hirakawa, Gou Watanabe, Hiroshi Tada, Akihiko Suzuki, Takanori Ishida, Chikashi Ishioka, Noriaki Ohuchi
Journal: Journal of Clinical Oncology (2015)

510 Background: A reliable marker is needed to identify high-risk patients eligible for post-neoadjuvant trials of new investigational drugs for breast cancer. We investigated the prognostic value of CD8+ TILs and FOXP3+ TILs in residual tumors after neoadjuvant chemotherapy (NAC) and changes in these parameters before and after NAC in patients with triple-negative breast cancer (TNBC). Methods: One hundred and thirty-one TNBC patients who received NAC were identified. CD8+ TIL and FOXP3+ TIL in residual tumors and biopsy specimens were investigated. The CD8+ TIL and FOXP3+ TIL status of the residual tumors was assessed, and the rates of changes in these cancers caused by NAC were calculated. Results: TNBC patients with high CD8+ TIL levels or a high CD8/FOXP3 ratio in residual tumors had significantly better recurrence-free survival (RFS) and breast cancer-specific survival (BCSS) than patients with low values of these parameters. In multivariate analyses, CD8+ TIL exhibited strong prognostic significance for RFS, with a hazard ratio (HR) of 3.44 (95%CI, 1.74-7.19, P = 0.0003). The CD8/FOXP3 ratio was also significantly correlated with RFS (HR = 2.00, 95%CI, 1.01-4.26, P = 0.049). TNBC with larger residual tumor size and positive lymph node status was independently associated with worse RFS (P = 0.0032 and P = 0.0090, respectively). High CD8+ TIL levels were a markedly powerful indicator of improved BCSS, with an HR of 3.58 (95%CI, 1.48-9.58, P = 0.004). Nodal status was also associated with BCSS (P = 0.003). TNBC with a high rate of CD8+ TIL changes was associated with significantly better RFS compared to the low group (P = 0.011). Higher rates of changes in the CD8/FOXP3 ratio were significantly correlated with both better RFS and BCSS compared to lower rates (P = 0.011 and P = 0.023, respectively). Conclusions: This study is the first to demonstrate that high CD8+ TIL and a high CD8/FOXP3 ratio in residual tumors and increases in these parameters after NAC accurately predict improved prognosis in TNBC patients with non-pCR following NAC. These parameters may be a surrogate for adjuvant treatment in patients with residual disease in the neoadjuvant setting.
Improving the accuracy of FNA lung biopsies in a community hospital.
Authors: A. Higgins, A. R. Calvo, R. Pelstring
Journal: Journal of Clinical Oncology (2010)

7639 Background: Until 2008 it was believed that outcomes in NSCLC were independent of histologic type. Until then, all doublet combinations of platinum compounds showed comparable efficacy in the treatment of NSCLC, and there was no urge for pathologists to differentiate the specific histologic subtypes. There is now data to support improved efficacy with agents such as pemetrexed in non-squamous cell carcinoma or gemcitabine in squamous cell histology. We evaluated the rate of non-specific NSCLC diagnosis in FNA biopsies in our institution before and after raising awareness among our pathologists and interventional radiologists and making changes in the immunoperoxidase panel used in lung cancer samples. Methods: We evaluated all FNA biopsies of lung cancer patients obtained in 2008 classifying them in adenocarcinoma; squamous cell ca; SCLC; NSCLC NOS and neuroendocrine carcinoma. For 2009 some changes were implemented by pathology including: increased awareness of the therapeutic importance of a specific diagnosis in NSCLC, addition of CK5/CK6, MOC-31 and BerEP4 immunoperoxidase stains and making a habit for the pathologist present at the lung biopsies to request more tissue if deemed appropriate. We did not include in our analysis the cases designated non-diagnostic due to insufficient sample size. Results: In 2008 there were 83 cases of FNA lung biopsies, and of the cases designated primary lung carcinoma 44% were NSCLC NOS, 9% adenocarcinoma, 3% mesothelioma, 28% squamous cell, 13% SCLC and 3% large cell neuroendocrine carcinoma. In 2009 we had 111 cases of FNA lung biopsies, and of the cases allocated primary lung carcinoma, 23% were NSCLC NOS, 29% adenocarcinoma, 22% squamous cell carcinoma, 20% SCLC and 6% large cell neuroendocrine carcinoma. Conclusions: The rate of NSCLC NOS decreased from 44% to 23%. We were able to document a significant decrease in nonspecific NSCLC FNA diagnosis by making simple and inexpensive changes. We noticed a personal variation among pathologists as to how often a complete immunoperoxidase panel was applied. Most pathologists were not aware of the predictive value of NSCLC histology in therapeutic decisions at the time our study was started. Sampling issues continue to be an obstacle to a firm histologic diagnosis. No significant financial relationships to disclose.
D2-07: Mechanisms of activating PI3K signaling in lung cancers that become resistant EGFR tyrosine kinase inhibitors
Authors: Jeffrey A. Engelman, Kreshnik Zejnullahu, Tetsuya Mitsudomi, Courtney Hyland, Joon Oh Park, Neal Lindeman, Christopher-Michael Gale, Xiaojun Zhao, James Christensen, Rogers M. Rogers, Federico Cappuzzo, Tony Mok, Charles Lee, Johnson E. Bruce, Lewis C. Cantley, Pasi A. Jänne
Journal: Journal of Thoracic Oncology (2007)