tbuckley/cabot-search huggingface dataset:
Abstract P6-01-10: Estrogen receptor β2 and β5 increase expression of ABCG2 and drug resistance of the triple- negative breast cancer cell line SUM159
Authors: M Faria, J-A Gustafsson, A Strom
Journal: Cancer Research (2017)

Abstract Recent clinical studies indicate that estrogen receptor β2 (ERβ2) and β5 (ERβ5) expression in TNBC correlates to worse prognosis. We have expressed ERβ2 and ERβ5 in the triple negative cell line SUM159. Estrogen receptors β2 and β5 are highly similar to estrogen receptor β1, except for a truncated C-terminus making the remaining ligand -binding domain incapable of binding to estrogen. In addition, at the C-terminus, ER β2 and β5 have a unique peptide each of 27 and 4 amino acids in length respectively. Stably expressing ERβ2 and ERβ5 using a transposon integrated, tetracycline- regulated expression system increases expression of the drug resistance gene, ABCG2 in the triple negative SUM159 cells. Furthermore, we also find that the cells become more resistant to treatments with paclitaxel. We find that ERβ2 and ERβ5 interact with HIF-1α and HIF-2α and are recruited to HIF response elements (HRE's) in chromatin. In agreement with this, we find that ERβ2 and ERβ5 are recruited to the ABCG2 promoter, which contains HRE's and is known to be a target of HIF signaling. We propose that ERβ2 and ERβ5 play a role in chemo - resistance of TNBC and that targeting these factors may reduce chemo resistance thus preventing tumor-relapses and their associated mortalities. Citation Format: Faria M, Gustafsson J-A, Strom A. Estrogen receptor β2 and β5 increase expression of ABCG2 and drug resistance of the triple- negative breast cancer cell line SUM159 [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 P6-01-10.
Association of Plasma Cell-Free Hemoglobin with Physiological Measures of Nitric Oxide Responsiveness and Estimated Pulmonary Artery Systolic Pressure: Requirement for Rigorously Optimized Blood Processing Variables
Authors: Laurel G. Mendelsohn, Susan Yuditskaya, Xunde Wang, Wasnard Victor, Katherine Corbin, Shoaib Alam, Darlene Allen, Caterina P. Minniti, James G. Taylor, Gregory J. Kato
Journal: Blood (2012)
Abstract P1-08-07: Assessing the impact of loss of NF1 protein on endocrine therapy resistance
Authors: B Cakar, D Chan, P Yan, Z Zheng, P Singh, JT Lei, S Haricharan, M Ellis, E Chang
Journal: Cancer Research (2017)

Abstract Background: The vast majority of breast cancers belong to the luminal subtype, which expresses the estrogen receptor-α (ER). Although great strides have been made in targeting the ER pathway for treating the ER+ tumors, relapse and death is common and ongoing. In order to identify the cause for treatment resistance, we have conducted a retrospective analyses on the tumor ge­nomes of &amp;gt;600 patients treated by tamoxifen monotherapy in the adjuvant setting with a median follow-up of 10.4 years. Our data have revealed that NF1 (Neuro­fibromatosis type 1) gene loss of function mutations were greatly associated with poor prognosis. NF1 is a tumor suppressor acting mostly as a GAP (GTP ase activating protein) to switch off acti­vated Ras. We aim to define the impact of loss of NF1 protein on patient outcome in ER+ breast cancer patients by establishing an immunohistochemistry (IHC) protocol to detect NF1. Method and results: We have first surveyed commercially available antibodies by Western blot and found one that could efficiently detect endogenous NF1. We then use this to validate inducible shRNA clones against NF1, as well as a breast cancer cell line that is NF1-null. This antibody has high background. We have thus partially purified a commercially available NF1 antibody by preclearing using NF1-null cell lysate. We then performed immunostaining using NF1-silenced and null cells as control and found that NF1 is mostly cytoplasmic and nuclear. To get antibody of high quality, we have decided to make our own antibody by expressing a C-terminal fragment of NF1 as a GST-tagged protein (GST-NF1c). Production of polyclonal and monoclonal antibody is in progress. Conclusion: Our clinical profiling data suggest that loss of NF1 protein, a very common event in a wide range of other cancers, promotes endocrine therapy resistance. An efficient IHC protocol will enable us to firmly validate whether loss of the NF1 protein indeed correlates with poor patient outcome. This method will ultimately enable us to identify high risk NF1 deficient patients and to properly treat them. Citation Format: Cakar B, Chan D, Yan P, Zheng Z, Singh P, Lei JT, Haricharan S, Ellis M, Chang E. Assessing the impact of loss of NF1 protein on endocrine therapy resistance [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 P1-08-07.
A Large Skin Cancer Screening Quality Initiative
Authors: Laura K. Ferris, Melissa I. Saul, Yan Lin, Fei Ding, Martin A. Weinstock, Alan C. Geller, Jian-Min Yuan, Erica Neuren, Spandana Maddukuri, Francis X. Solano, John M. Kirkwood
Journal: JAMA Oncology (2017)

The lack of prospective randomized clinical trials demonstrating that full-body skin examination (FBSE) reduces melanoma morbidity or mortality has prompted an "I" rating from the United States Preventive Services Task Force for population-based skin cancer screening. More data on these screening programs are needed.To describe a skin cancer screening quality initiative in a large health care system and to determine if the intervention was associated with screening of a demographically higher-risk population than previous screening programs and if melanoma incidence and thickness differed in screened vs unscreened patients.This observational evaluation of a prospectively implemented quality initiative was conducted in a large health care system in western Pennsylvania (University of Pittsburgh Medical Center, UPMC) among adults seen in an office visit by a UPMC-employed primary care physician (PCP) in 2014.Implementation of a campaign promoting annual skin cancer screening by FBSE, including training of PCPs, promotion of the initiative to physicians and patients, and modification of the electronic health record (EHR) to include FBSE as a recommended preventive service for patients 35 years or older.Characteristics of screened and unscreened patients and melanomas detected among them.Of 333 735 adult patients seen in an office visit by PCPs in 2014, 53 196 patients (15.9% of the screen-eligible population) received an FBSE, and 280 539 did not. Screened patients were slightly older (median age, 60 vs 57 years; P < .001) but did not differ significantly by sex (43.2% vs 43.1% men; P = .49) from the unscreened population. Fifty melanomas were diagnosed in screened patients and 104 melanomas were diagnosed in unscreened patients. Screened patients were more likely than unscreened patients to be diagnosed with melanoma (adjusted risk ratio [RR], 2.4; 95% CI, 1.7-3.4; P < .001) and to have a thinner invasive melanoma (median thickness, 0.37 mm vs 0.65 mm; P < .001). The incidence of melanoma lesions 1 mm or thicker was similar in screened vs unscreened patients (adjusted RR, 0.7; 95% CI, 02.-2.2; P = .52).Large-scale screening for melanoma within a United States health care system is feasible and can result in increased detection of thinner melanomas. This intervention also resulted in screening of a higher proportion of men and an older patient population than previous screening interventions in which younger individuals and women predominated.
Gender Parity in Critical Care Medicine
Authors: Sangeeta Mehta, Karen E. A. Burns, Flavia R. Machado, Alison E. Fox-Robichaud, Deborah J. Cook, Carolyn S. Calfee, Lorraine B. Ware, Ellen L. Burnham, Niranjan Kissoon, John C. Marshall, Jordi Mancebo, Simon Finfer, Christiane Hartog, Konrad Reinhart, Kathryn Maitland, Renee D. Stapleton, Arthur Kwizera, Pravin Amin, Fekri Abroug, Orla Smith, Jon H. Laake, Gentle S. Shrestha, Margaret S. Herridge
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Clinical practice guidelines are systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances. These documents inform and shape patient care around the world. In this Perspective we discuss the importance of diversity on guideline panels, the disproportionately low representation of women on critical care guideline panels, and existing initiatives to increase the representation of women in corporations, universities, and government. We propose five strategies to ensure gender parity within critical care medicine.
Matching Dietary Amino Acid Balance to the In Silico-Translated Exome Optimizes Growth and Reproduction without Cost to Lifespan
Authors: Matthew D.W. Piper, George A. Soultoukis, Eric Blanc, Andrea Mesaros, Samantha L. Herbert, Paula Juricic, Xiaoli He, Ilian Atanassov, Hanna Salmonowicz, Mingyao Yang, Stephen J. Simpson, Carlos Ribeiro, Linda Partridge
Journal: Cell Metabolism (2017)
A New Entity of Acute Myeloid Leukemia Driven By Epigenetic and Somatic Dis-Regulation of Uncx, a Novel Homeobox Transcription Factor Gene
Authors: Giulia Daniele, Clelia Tiziana Storlazzi, Cristina Papayannidis, Ilaria Iacobucci, Angelo Lonoce, Margherita Perricone, Mariana Lomiento, Fabiana Mammoli, Elena Marasco, Vilma Mantovani, Hilmar Quentmeier, Giorgia Simonetti, Antonella Padella, Vincenzo Franza, Hans G. Drexler, Jie Ding, Orazio Palumbo, Massimo Carella, Niroshan Nadarajah, Renè Massimiliano Marsano, Antonio Palazzo, Emanuela Ottaviani, Carmen Baldazzi, Nicoletta Testoni, Sergio Ferrari, Giovanni Martinelli
Journal: Blood (2015)
OP01. A PML/POLYCOMB/SLIT AXIS REGULATES MIGRATION OF BOTH NORMAL AND NEOPLASTIC CELLS IN THE CNS
Authors: Mr A Deli, Dr Valeria Amodeo, Dr Joanne Betts, Dr Stefano Bartesaghi, Dr Mikaella Vouri, Dr Rozita Roshani, Dr Sara Galavotti, Ms Ying Zhang, Ms Joanne Lau, Ms Sarah Oberndorfer, Dr Ana Leite, Dr David Dinsdale, Prof Chris Jones, Prof Pierluigi Nicotera, Dr David Michod, Prof Sebastian Brandner, Prof Paolo Salomoni
Journal: Neuro-Oncology (2017)

INTRODUCTION: The control of SVZ neural progenitor/stem cells (NPCs) migration through the rostral migratory stream (RMS) is essential for normal neurogenesis and serve as the fundamental basis of production/replacement of neurons in the adult brain. Alterations of these processes can lead to neoplastic transformation and glioblastoma multiforme (GBM). The ability of GBM cells to migrate through the brain parenchyma represents a key factor underlying GBM aggressiveness. GBM cells use the same routes used by neuroblasts/immature neurons and neural stem cells upon injury, such as vessels and myelin tracts, suggesting that GBM migration may lay its roots in essential cellular processes controlling migration of immature neurons/neuroblasts and neural stem cells (1). However, our understanding of mechanisms regulating cell migration/invasion during brain tumourigenesis remains limited. METHODS: We combined in vivo and in vitro approaches, including the use of genetically modified mice, primary HGG tissues/NPCs (in collaboration with S Brandner, UCL, C Jones, ICR, S Pollard, Edinburgh, and others). RESULTS: Here we report that the stem cell factor and RAS effector Promyelocytic Leukaemia protein (PML) (2,3) regulates cell migration through the epigenetic control of Slit axon guidance genes in normal and neoplastic cells in the central nervous system. Loss of PML leads to impaired NSC and neuroblast migration and a smaller olfactory bulb in the adult mouse brain. PML controls cell migration via Polycomb Repressive 2-dependent regulation of the Slit axon guidance genes. A similar epigenetically controlled PML/Slit axis is functional also upon RAS-driven neoplastic transformation of NSCs and in primary GBM cells. PML expression inversely correlates with Slit1 expression and patient prognosis in GBM and is enriched in the mesenchymal subtype, which is characterized by activation of the RAS/MAPK pathway. Finally, PML loss impairs tumor growth in an orthotopic animal model. CONCLUSIONS: Taken together, these findings disclose a novel molecular axis at the root of cell migration during normal neurogenesis and brain tumourigenesis. Cuddapah VA et al. Nat Rev Neurosci 15: 455–465. Regad T. et al. Nature neuroscience 12: 132–140. Salomoni P. et al. Cell Res 18: 622–640.
Metabolic syndrome enhances endoplasmic reticulum, oxidative stress and leukocyte–endothelium interactions in PCOS
Authors: Celia Bañuls, Susana Rovira-Llopis, Aranzazu Martinez de Marañon, Silvia Veses, Ana Jover, Marcelino Gomez, Milagros Rocha, Antonio Hernandez-Mijares, Victor M. Victor
Journal: Metabolism (2017)
Evaluation of Bleeding-Related Episodes in Patients with Chronic Immune Thrombocytopenic Purpura (ITP) Receiving Romiplostim or Medical Standard of Care.
Authors: Roberto Stasi, Magaral Murali, Marc Michel, Jean-Francois Viallard, Aristoteles Giagounidis, Ann Janssens, Jason Legg, Mark Danese, Robert Deuson
Journal: Blood (2009)
A Phase II Study of the TNF-α Inhibitor Etanercept and Thrice Weekly Rituximab: Evidence of Clinical Activity in the Absence of del(17p13.1) Genomic Abnormalities.
Authors: Thomas S. Lin, Nyla A. Heerema, Jennifer Swenor, Margaret S. Lucas, Mollie E. Moran, Carolyn M. Cheney, David M. Lucas, Donn Young, Michael A. Caligiuri, Michael R. Grever, John C. Byrd
Journal: Blood (2004)
Targeting the X-Linked Inhibitor of Apoptosis Protein (XIAP) Can Promote Tumor Cell Death, and Increase the Cytotoxic Effects of Chemotherapy Agents in in Vitro and In Vivo Models of Rituximab-Resistant Lymphoma
Authors: Kyle L. Runckel, Cory Mavis, Joseph Skitzki, Juan J Gu, Francisco J. Hernandez-Ilizaliturri, Myron S. Czuczman
Journal: Blood (2015)
Abstract P6-05-05: The expression of lysyl oxidase and fibrotic focus is related to inflammation in breast cancer
Authors: SH Park, YJ Jeong, JG Bong, HK Oh
Journal: Cancer Research (2017)

Abstract Background: Lysyl oxidase (LOX) is an extracellular matrix enzyme that catalyzes the cross-linking of collagens or elastin. Our hypothesis is that LOX contributes to the formation of a fibrotic focus (FF), which is related to inflammation in breast carcinogenesis. In this study, we analyzed the association between the expression LOXs and FF, and investigated prognostic significance in breast cancer. Methods: Tissue microarrarys were constructed from the specimens of 444 patients with primary invasive breast cancer. Immunohistochemical staining for LOX, LOXlike (LOXL)-, LOXL-2 and LOXL-3 was performed. The status of FF within the tumor was assessed. The number of CD4+ T cells, CD8+ T cells, CD68+ macrophages was counted, and intratumoral and peritumoral lymphocyte infiltration were evaluated. The clinicopathologic characteristics of the patients were analyzed. Result: The percentage of positive FF was 39.2% and positive rate of LOX expression was 50% in primary breast cancer tissues. FF was found to be significantly associated with intratumoral and peritumoral inflammation, lymph node metastasis, high histologic grade, larger tumor size. LOX was associated with intratumoral and peritumoral inflammation, CD8+ T cells and menopausal status. LOXL-3 was significantly associated with positive expression of ER and PR, and molecular subtype. Conclusions: FF and the expression of LOX were associated with inflammation in breast cancer in this study. Our results suggest that LOXs may contribute to the formation of a FF indirectly in relation with inflammation in breast cancer. Further studies are needed to clarify the role of LOXs, FF and inflammation in tumorigenesis and prognostic value of them in breast cancer. Citation Format: Park SH, Jeong YJ, Bong JG, Oh HK. The expression of lysyl oxidase and fibrotic focus is related to inflammation in breast cancer [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 P6-05-05.
No Effect of Individualized Nutrition on Quality of Life, Acute Graft-Versus-Host Disease or Oral Mucositis after Allogeneic Stem Cell Transplantation: A Randomized Controlled Trial
Authors: Kristin J. Skaarud, Marianne J. Hjermstad, Asta Bye, Marit B. Veierød, Anne M. Gudmundstuen, Knut E. A Lundin, Sonia Distante, Lorentz Brinch, Geir E. Tjønnfjord, Per O. Iversen
Journal: Blood (2016)
Resveratrol Induces Erythroid Maturation by Activating FOXO3 and Improves in Vivo Erythropoiesis in Normal and Beta -Thalassemic Mice
Authors: Sara Santos Franco, Luigia De Falco, Saghi Ghaffari, Carlo Brugnara, David Sinclair, Achille Iolascon, Mohandas Narla, Mariarita Bertoldi, Christophe Lebouf, Anne Janin, Angela Siciliano, Pauline Rimmele, Maria Domenica Cappellini, Shady Michan, Elisa Zoratti, Lucia De Franceschi
Journal: Blood (2012)
Polatuzumab Vedotin Combined with Bendamustine (B) and Rituximab (R) or Obinutuzumab (G) in Patients with Relapsed or Refractory (R/R) Follicular Lymphoma (FL) or Diffuse Large B-Cell Lymphoma (DLBCL): Preliminary Results of a Phase Ib/II Dose-Escalation Study
Authors: Alex F Herrera, Matthew J. Matasar, Sarit Assouline, Manali Kamdar, Amitkumar Mehta, Isabelle Fleury, Won Seog Kim, Tae Min Kim, Francesc Bosch, John A Radford, Lilian Bu, Wan-Jen Hong, Laurie H Sehn
Journal: Blood (2016)
Incident opioid use is associated with risk of respiratory harm in non-palliative COPD
Authors: Nicholas T. Vozoris, Denis E. O'Donnell, Chaim Bell, Sudeep S. Gill, Paula A. Rochon
Journal: European Respiratory Journal (2017)

We thank M. Ekström and co-workers for their interest in our manuscript [1] and for their contributions to the important topic of opioid drug use in chronic obstructive pulmonary disease (COPD). M. Ekström and co-workers stress the efficacy of selective use of opioids for refractory breathlessness in COPD. We acknowledged in our manuscript [1] that several clinical studies demonstrate that opioids are efficacious in selected COPD patients for relieving refractory breathlessness. However, we have previously outlined reasons why such trials of drug efficacy have limited ability to comprehensively evaluate for possible drug harms [1–3]. Furthermore, chronic musculoskeletal pain, and not respiratory symptoms, is likely the more common reason why individuals with COPD use opioid drugs [3, 4]. Indeed, M. Ekström and co-workers recently published data showing that 97% of opioid prescriptions among Swedes with advanced COPD were for pain [5]. Several Cochrane reviews have suggested there is insufficient evidence to support the use of opioids for chronic musculoskeletal pain [6–8]. The potential for respiratory-related harm needs to be considered when using opioid drugs in non-palliative COPD <http://ow.ly/i5W03095MKV>
Searching for e-cadherin gene mutation in hereditary diffuse gastric cancer in Korea: A preliminary report.
Authors: Hwoon-Yong Jung, Eun Jeong Gong, Woochang Lee, Ji Yong Ahn, Kwi-Sook Choi, Do Hoon Kim, Jeong Hoon Lee, Kee Don Choi, Ho June Song, Gin Hyug Lee, Jin-Ho Kim
Journal: Journal of Clinical Oncology (2014)

e15016 Background: Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant cancer syndrome and is associated with germline mutation of the E-cadherin (CDH1) gene. Despite of its high penetrance and cumulative risk of developing gastric cancer, HDGC has rarely been reported in Asia. Methods: We performed polymerase chain reaction-direct sequencing to investigate the mutation status of the CDH1 gene in 70 Korean patients fulfilling the screening criteria of the updated consensus guidelines prosed by the International Gastric Cancer Linkage Consortium. Results: Of the 70 patients with HDGC, 5 patients (7.1%) tested positive. Among 33 patients with two cases of gastric cancer with at least one case of diffuse gastric cancer (DGC) and a diagnosis prior to 50 years, 3 patients (9.1%) had CDH1 germline mutations. Two were nonsense mutation (c.1003C>T, p.Arg335*, exon 7) in a 43 year-old female and 59 year-old male, and the other was missense mutation (c.182C>T, p.The61Ile, exon 3) in a 36-year old female. Of the 37 patients diagnosed with DGC prior to 40 years, 2 patients (5.4%) had CDH1 gene variations (c.715G>A, p.Gly239Arg, exon 6 in a 28-year old male and c.2494G>A, p.Val832Met, exon 16 in a 35-year old female). There was no patient with both diffuse gastric cancer and lobular breast cancer. Conclusions: Although the incidence of sporadic gastric cancer is relatively high in Asia, the possibility of HDGC and the evaluation of CDH1 gene mutation status should be considered in individuals with diffuse gastric cancer.
Abstract B22: Establishment of Patient-Derived Xenograft (PDX) Models of Ovarian Cancer
Authors: Li Liang, Imelda Mercado-Uribe, Na Niu, Yi Jiang, Wenjun Cheng, Russell Broaddus, Robert Bast, Gordon Mills, Anil K. Sood, Jinsong Liu
Journal: Clinical Cancer Research (2016)

Abstract Ovarian cancer is the most lethal gynecological malignancy. The majority of ovarian cancer patients are diagnosed at an advanced stage of disease, and the lack of good early screening and diagnostic tests is one of the reasons for the low overall survival rate. Moreover, there is no good marker to predict patients' response to chemotherapy. Patient-derived xenografts (PDXs) have become the most promising preclinical model for gynecologic malignances. We have successfully established 22 PDX models derived from ovarian cancer patients' surgical specimens implanted into severe combined immunodeficient (SCID) mice, non-obese diabetic (NOD)-SCID or Nude mice. The majority of the PDX models were generated from patients' samples diagnosed with high-grade serous carcinoma including 3 with BRCA1/2 mutations, as well as less common types of ovarian cancers such as low-grade serous, endometrioid, mucinous carcinomas, and carcinosarcoma. PDXs have been established from solid masses as well as from ascites. We have optimized protocol for establishing ovarian PDXs including implantation and collection methods, tumor type (solid versus ascites), and type of mouse strains used. Using SCID mice, our success rate exceeded 80% and recent data indicated that the success rate in NOD/SCID mice was higher. The link between the pathology and PDX core, the “triage protocol” and ongoing PARP inhibitor trials will provide an important array of PDXs including pre- and post-treatment PDXs for exploration for biomarkers as well as for co-clinical trials to validate the utility of rational drug combinations. All models were validated using short tandem repeats (STR) and compared to the H&amp;E and immunohistochemistry stains from the matching patient's tissue. We also examined the expression of B7-H4, a novel member of the B7 family immune checkpoint regulators, in 9 patient-derived xenografts (PDXs) of high-grade ovarian serous carcinoma. Our data showed that B7-H4 proteins were expressed in 8 of 9 PDX models of high-grade serous carcinoma, suggesting that PDXs may be useful for studying immunotherapy. Citation Format: Li Liang, Imelda Mercado-Uribe, Na Niu, Yi Jiang, Wenjun Cheng, Russell Broaddus, Robert Bast, Gordon Mills, Anil K. Sood, Jinsong Liu. Establishment of Patient-Derived Xenograft (PDX) Models of Ovarian Cancer. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr B22.