tbuckley/cabot-search huggingface dataset:
PP08. SITE-SPECIFIC PHENOTYPES OF CANCER CELLS AND MACROPHAGES IN INTRACRANIAL BREAST CANCER METASTASES
Authors: Mr David Taggart, Dr Nora Rippaus, Dr Tereza Andreou, Ms Jennifer Williams, Dr Heiko Wurdak, Mr Krzysztof Wronski, Dr Mihaela Lorger
Journal: Neuro-Oncology (2017)

Central nervous system (CNS) metastases develop in ~15% of metastatic breast cancer patients and are associated with a very poor prognosis due to the lack of effective therapies. Intracranial metastases are mainly located within the brain parenchyma, at the leptomeninges or at the dura. Although simultaneous involvement of multiple intracranial locations is very common in breast cancer, the experimental studies have been focusing mainly on parenchymal brain metastases. To address the knowledge gap in understanding of metastases at other CNS locations, we developed a preclinical mouse model of intracranial breast cancer metastases with simultaneous involvement of brain parenchyma and the dura. This enabled us to subsequently study and compare cancer cell phenotypes and inflammatory tumour microenvironment at the two intracranial locations. Simultaneous colonization of brain parenchyma and the dura was achieved by administration of cancer cells into the internal carotid artery of mice. This resulted in a significantly higher dural as compared to the parenchymal tumour burden across 3 different breast cancer models. The inflammatory tumour microenvironment in dural and parenchymal brain metastases was subsequently analysed by flow cytometry. Although model-specific differences in metastases-infiltrating immune cell populations were detected, microglia/macrophages were the most abundant cell population across all 3 models. In contrast to primary tumours, the understanding of macrophages within metastases is very limited and comparison of macrophage phenotypes between different metastatic sites is lacking. Through analysis of multiple intra- and extra-cellular markers by flow cytometry, we discovered significant differences in the activation state of metastasis-associated macrophages (MAMs) at the two sites. Interestingly, the phenotype of parenchymal MAMs was causally linked to the metastatic site-specific cancer cell features. Gene expression analysis revealed that cancer cells that have metastasized to brain parenchyma evolved different molecular profiles compared with metastatic cells isolated from the dura. Significant differences in several inflammation-related pathways, NF-kB1 activity and cytokine profiles were detected. The most significantly upregulated cytokine in brain parenchyma- versus dura-derived cancer cells was Lymphotoxin β and a gain-of-function approach demonstrated a direct involvement of this factor in the polarization of parenchymal MAMs towards the M2 state. Because macrophages and their activation state have been implicated in tumor growth and modulation of responses to therapies, the understanding of metastatic site-specific MAM differences is important for the design of treatment strategies that can effectively target metastases at distinct anatomical locations.
Adult patients with acute lymphoblastic leukaemia (ALL) who relapse have a dismal outlook: Results from MRC UKALL XII/ECOG 2993 trial.
Authors: R Chopra, A H Goldstone, G Buck, S M Richards, I Franklin, H M Lazarus, P H Wiernek, M S Tallman, H G Prentice, J Durrant, J M Rowe
Journal: Blood (2003)
Preliminary results of an open-label phase I pharmacokinetic/pharmacodynamic study of JNJ26481585: Early evidence of antitumor activity
Authors: S. Postel-Vinay, R. Kristeleit, P. Fong, B. Venugopal, D. Crawford, L. Van Beÿsterveldt, N. Fourneau, P. Hellemans, J. Evans, J. De-Bono
Journal: Journal of Clinical Oncology (2009)

e13504 Background: JNJ26481585 is a novel orally active pan-histone deacetylase inhibitor (HDACI) which showed potent antitumor efficacy in a wide range of animal tumor models. Methods: A 2-stage accelerated titration design Phase I trial was conducted to characterize safety, establish the maximum tolerated dose (MTD) and determine pharmacokinetics in patients (pts) with refractory solid tumors, of performance status &lt;2 and with adequate hematologic, renal, hepatic and cardiac function. The drug was administered orally, once daily in 3 weekly cycles. Results: To date, 9 pts (median age 59; range 32–74) have been treated at 4 dose levels (DL): 2 (2 pts), 4 (2 pts), 8 (3 pts), and 12 (2 pts) mg. The median number of cycles administered was 2 (range 1–9). Dose-limiting toxicity was seen at 12mg (CTCAE Grade [G] 3 non-sustained ventricular tachycardia [VT] [1 pt] and G3 fatigue [1 pt]) and the 8mg cohort is being expanded. Other toxicity observed at 12mg comprised G2 palpitations with QT prolongation (1 pt), G2 anorexia (1 pt), G2 vomiting (1 pt) and G2 dysgeusia (1 pt). At 8mg, 1 pt on warfarin developed a G2 INR increase. Non-specific ECG changes were observed from the 2mg DL onwards. The drug was generally well tolerated up to 8mg. Exposure to JNJ26481585 increased proportionally over the 2 to 12mg dose range, with a constant metabolite/parent ratio (3.5 for C max ; 7 for AUC). Two partial responses (PR) and one stable disease (SD) have been observed. PR occurred in 2 pts with metastatic melanoma treated at 12mg : one pt had a PR in visceral and complete response in subcutaneous melanoma metastases after 22 days of drug and has ongoing response 5 months after stopping treatment; the second pt had PR in lymph nodes and reduction of cutaneous lesions of melanoma. One non small cell lung cancer pt treated at 4mg showed SD for 9 cycles. Assessment of histone acetylation as a pharmacodynamic biomarker in peripheral blood lymphocytes and hair follicles is ongoing. Conclusions: JNJ26481585 is generally well tolerated at doses up to 8mg daily. Evidence of promising antitumor activity has been observed with 2 PR to date in patients with metastatic melanoma. The 8mg cohort is being expanded with increased cardiac monitoring. Other schedules may be explored in the future. [Table: see text]
Abstract P3-01-06: Visualizing the real difference between 2-D and 3-D specimen mammography
Authors: CS Kaufman, K Zacharias
Journal: Cancer Research (2017)

Abstract BACKGROUND: Specimen mammography aids in the determination 1) if the target lesion has been removed and 2) whether there is a clear margin at excision. In the past, two orthogonal views using 2-D imaging has been considered to be equivalent to a three dimensional perspective. Yet tomosynthesis for screening mammography has demonstrated the value of thin sliced imaging over two view screening mammography. In March, 2015, we began using true 3-D tomosynthesis of breast specimens at lumpectomy and have compared 2-D and 3-D specimen mammography. METHODS: We have examined 125 consecutive breast cancer patients with both 2-D and 3-D imaging of the same specimens since March 2015. The circulating nurse would take the specimen and obtain two orthogonal views using both 2-D and 3-D devices with images sent to the radiology department. It was not felt ethical to blind the surgeon from having both images available to make an intraoperative clinical decision regarding immediate re-excision. We compared the data noted from each method and which method best aided the decision to perform immediate re-excision, and time required to obtain the images. RESULTS: We have studied 125 patients over 11 months since March 2015. Confirmation of complete lesion excision was easier with 3-D tomosynthesis than with 2-D as the 3-D slice did not include overlying skin or dense breast tissue surrounding the lesion in the image, making the target lesion stand out more clearly. Although the 2-D images appear to have higher contrast than the individual 3-D slices, the tomosynthesis 3-D images contained more actionable data than the 2-D. Also decisions to excise more tissue during the procedure were enabled by the additional information included in the 3-D images. In addition, the 3-D images provided the depth of field to enable accurate re-excision using the Z-axis (see figures). Finally, it took about a minute longer to obtain and review the 3D images, although this difference did not delay surgical decisions nor prolong operative time. CONCLUSIONS: 3-D specimen tomosynthesis facilitates the reduction of post-operative re-excision for lumpectomy patients by providing more information than 2-D orthogonal views, providing easier, more accurate confirmation of the extent of the target excision. Additionally, serial 1mm slices of the specimen allowed the integration of Z-axis targeting, ensuring that any necessary margin excision during surgery was accomplished immediately with maximum tissue conservation. More studies are planned to further validate these findings of these first 125 patients. Citation Format: Kaufman CS, Zacharias K. Visualizing the real difference between 2-D and 3-D specimen mammography [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 P3-01-06.
Accelerated Degradation of cFLIP Mediated By Inhibition of Methyltransferases Sensitizes B-Cell Lymphoma Cells to TRAIL-Induced Apoptosis
Authors: Frank K Braun, Rohit Mathur, Lalit Sehgal, Rachel Wilkie-Grantham, Joya Chandra, Zuzana Berkova, Felipe Samaniego
Journal: Blood (2014)
Abstract ES6-2: ES6-2 Surgical considerations in patients receiving neoadjuvant therapy
Authors: TA King
Journal: Cancer Research (2017)

Abstract Early randomized trials of neoadjuvant chemotherapy failed to show an improvement in overall survival compared to adjuvant therapy, yet it reduces the need for mastectomy and axillary lymph node dissection, thus decreasing the morbidity of surgery, without increasing the risk of locoregional recurrence. It is also now increasingly clear that the impact of neoadjuvant chemotherapy varies by molecular subtype; whereby patients with high-grade estrogen receptor negative and/or HER2 positive breast cancers are more likely to experience pathologic complete response to NAC that those with low-grade, estrogen receptor positive cancers. The increasing rates of pCR following neoadjuvant chemotherapy have had a significant impact on local-regional treatment considerations. However, patient selection for this approach remains critical. Sentinel node biopsy after neoadjuvant chemotherapy accurately stages the axilla and is associated with a low rate of nodal recurrence in patients presenting with a clinically negative axilla. Sentinel node biopsy after neoadjuvant chemotherapy in patients with proven axillary metastases prior to neoadjuvant chemotherapy who become clinically node negative has a false negative rate of less than 10% only when 3 or more sentinel nodes are identified and there are no data on nodal recurrence rates after sentinel node biopsy alone in this population. Hence, strategies to ensure a low false negative rate are critical if sentinel node biopsy is offered to patients with proven axillary metastases prior to neoadjuvant chemotherapy. The relative contribution of pre-treatment stage and post-treatment stage (degree of pathologic response) to local control is also uncertain and tailoring of local therapy based on the degree of response is the subject of ongoing trials. Citation Format: King TA. ES6-2 Surgical considerations in patients receiving neoadjuvant therapy [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 ES6-2.
Abstract IA20: Material-based therapeutic cancer vaccines
Authors: David J. Mooney
Journal: Cancer Research (2017)

Abstract The recent successes of checkpoint blockade therapy demonstrate the power of immunotherapy. The correlation between patient response to these therapies and the extent of T cell infiltration into tumors suggest that vaccines capable of generating robust T cell responses to cancer antigens may lead to a greater fraction of patients responding to checkpoint blockade. Therapeutic cancer vaccines often depend on extensive manipulation of antigen presenting cells in the laboratory, but subsequent cell infusion typically leads to large-scale cell death and limited efficacy. We are instead developing biomaterials that provide controlled delivery of immunomodulatory factors, in certain ways mimicking aspects of microbial infection, to resident dendritic cells in order to bypass the need to manipulate cells in the laboratory. These material strategies allow control over immune cell trafficking and activation, cause tumor regression in preclinical models, and are currently in a Phase I clinical trial. Recent preclinical studies demonstrate synergy between these material-based vaccines and anti-PD1/CTLA4. Citation Format: David J. Mooney. Material-based therapeutic cancer vaccines. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr IA20.
Treatment and Prognosis in Patients with Adult T-Cell Leukemia-Lymphoma (ATL): A Nationwide Survey in Japan
Authors: Yoshitaka Imaizumi, Masako Iwanaga, Kisato Nosaka, Shigeki Ito, Kenji Ishitsuka, Atae Utsunomiya, Yoshiki Tokura, Takeaki Tomoyose, Kazuya Shimoda, Kensei Tobinai, Toshiki Watanabe, Kaoru Uchimaru, Kunihiro Tsukasaki
Journal: Blood (2016)
Abstract S1-04: Optimal duration of extended letrozole treatment after 5 years of adjuvant endocrine therapy; results of the randomized phase III IDEAL trial (BOOG 2006-05)
Authors: EJ Blok, CJH van de Velde, EM Meershoek-Klein Kranenbarg, H Putter, J van den Bosch, E Maartense, AE van Leeuwen-Stok, G-J Liefers, JWR Nortier, EJT Rutgers, JR Kroep
Journal: Cancer Research (2017)

Abstract Despite the success of adjuvant endocrine therapy in early breast cancer, approximately 50% of all recurrences still occur after the initial 5 years of follow-up. Earlier studies confirmed that endocrine therapy extension after 5 years of adjuvant tamoxifen with either tamoxifen or aromatase inhibitors up to 10 years leads to an improvement in survival. However, aromatase inhibitors are currently standard of care in the initial 5 years of adjuvant therapy, and the benefit of extended use beyond 5 years of AI based therapy is still debated. The randomized phase III IDEAL trial was designed to study the optimal duration of extended adjuvant endocrine therapy after the initial 5 years of any endocrine therapy. Between April 2007 and November 2011, 1824 postmenopausal, HR-positive early breast cancer patients were included by 74 hospitals in the Netherlands. Enrolled patients earlier received 5 years of any endocrine therapy (87.9% AI based),completed this treatment no longer than 2 years before randomization, and did not have any recurrence at the moment of inclusion. The included patients were randomly allocated to either 2.5 or 5 years of extended letrozole (daily 2.5mg). Primary outcome was disease free survival (DFS), secondary endpoints were overall survival (OS), distant disease free survival (DDFS), contralateral breast cancer and safety. Results &amp; Discussion: Results will become available soon. Citation Format: Blok EJ, van de Velde CJH, Meershoek-Klein Kranenbarg EM, Putter H, van den Bosch J, Maartense E, van Leeuwen-Stok AE, Liefers G-J, Nortier JWR, Rutgers EJT, Kroep JR. Optimal duration of extended letrozole treatment after 5 years of adjuvant endocrine therapy; results of the randomized phase III IDEAL trial (BOOG 2006-05) [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 S1-04.
Intermediate Dose Methotrexate Improves Overall Survival and Progression-Free Survival of Patients with Diffuse Large B Cell Lymphoma Treated with the R-CHOP or CHOP Regimen
Authors: Eldad J Dann, Vered Heffes, Tatiana Mashiach, Noam Benyamini, Irit Avivi, Netanel A Horowitz
Journal: Blood (2015)
Using the National Cancer Database for Outcomes Research
Authors: Daniel J. Boffa, Joshua E. Rosen, Katherine Mallin, Ashley Loomis, Greer Gay, Bryan Palis, Kathleen Thoburn, Donna Gress, Daniel P. McKellar, Lawrence N. Shulman, Matthew A. Facktor, David P. Winchester
Journal: JAMA Oncology (2017)

<h3>Importance</h3> The National Cancer Database (NCDB), a joint quality improvement initiative of the American College of Surgeons Commission on Cancer and the American Cancer Society, has created a shared research file that has changed the study of cancer care in the United States. A thorough understanding of the nuances, strengths, and limitations of the database by both readers and investigators is of critical importance. This review describes the use of the NCDB to study cancer care, with a focus on the advantages of using the database and important considerations that affect the interpretation of NCDB studies. <h3>Observations</h3> The NCDB is one of the largest cancer registries in the world and has rapidly become one of the most commonly used data resources to study the care of cancer in the United States. The NCDB paints a comprehensive picture of cancer care, including a number of less commonly available details that enable subtle nuances of treatment to be studied. On the other hand, several potentially important patient and treatment attributes are not collected in the NCDB, which may affect the extent to which comparisons can be adjusted. Finally, the NCDB has undergone several significant changes during the past decade that may affect its completeness and the types of available data. <h3>Conclusions and Relevance</h3> The NCDB offers a critically important perspective on cancer care in the United States. To capitalize on its strengths and adjust for its limitations, investigators and their audiences should familiarize themselves with the advantages and shortcomings of the NCDB, as well as its evolution over time.
Advanced Glycation End Products (AGEs)-Mediated Cell Growth of Human Acute Myelogenous Leukemia Via Mitogen-Activated Protein (MAP) Kinase Pathways.
Authors: Ju Young Kim, Hyun Ki Park, Jin Sun Yoon, Eun Shil Kim, Kwang Sung Ahn, Sung Soo Yoon, Byoung Kook Kim, Young Lee
Journal: Blood (2005)
Bone Effect of Botezomib in Patients with Relapse and Smoldering Myeloma; A Computer Assisted Image Analysis Study of Bone Marrow Core Biopsies,
Authors: Mohamed E Salama, Graham E. Wagner, Tamara Berno, Jessica Kohan, Fenghuang Zhan, Guido J. Tricot, Maurizio Zangari
Journal: Blood (2011)
Subversion of Pkca and Pkcbii Upregulation Play an Essential Role in Chronic Lymphocytic Leukaemia Development, Inducing Constitutive B Cell Receptor-Mediated Signals
Authors: Anuradha Tarafdar, Ashfia Fatima Khan, Emilio Cosimo, Hothri A. Moka, Karen Dunn, Alison M. Michie
Journal: Blood (2015)
Guideline: A hemoglobin threshold of 7 to 8 g/dL is recommended for hemodynamically stable hospitalized patients
Authors: Thomas DeLoughery
Journal: Annals of Internal Medicine (2017)

ACP Journal Club21 February 2017Guideline: A hemoglobin threshold of 7 to 8 g/dL is recommended for hemodynamically stable hospitalized patientsThomas DeLoughery, MD, MACP, FAWMThomas DeLoughery, MD, MACP, FAWMOregon Health & Science University, Portland, Oregon, USA (T.D.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2017-166-4-015 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationCarson JL, Guyatt G, Heddle NM, et al. Clinical practice guidelines from the AABB: red blood cell transfusion thresholds and storage. JAMA. 2016;316:2025-35. https://pubmed.ncbi.nlm.nih.gov/27732721Clinical Impact RatingsEmergency Med: Hospitalists: Hematology: Critical Care: References1 Adams C, Lundy JS. Anesthesia in cases of poor surgical risk—some suggestions for decreasing the risk. Surg Gynec Obstet 1942;74:1011–19. Google Scholar2 Carson JL, Terrin ML, Noveck H, et al; FOCUS Investigators. Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med. 2011;365:2453-62. [PMID: 22168590] Google Scholar3 Heddle NM, Cook RJ, Arnold DM, et al. Effect of short-term vs. long-term blood storage on mortality after transfusion. N Engl J Med. 2016;375:1937-45. [PMID: 27775503] Google Scholar Author, Article, and Disclosure InformationAffiliations: Oregon Health & Science University, Portland, Oregon, USA (T.D.)This article was published at Annals.org on 7 February 2017. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 21 February 2017Volume 166, Issue 4Page: JC15KeywordsBloodGrading of Recommendations Assessment Development and EvaluationHematology and oncologyHemoglobinIron deficiencyMortalityOrthopedic surgeryRed blood cellsRelative risk ePublished: 21 February 2017 Issue Published: 21 February 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Correct Data and Meta-analytic Approaches Show the Reduced Risk of Concussion for Athletes Playing at Higher Altitudes—Reply
Authors: Gerald S. Zavorsky, James M. Smoliga
Journal: JAMA Neurology (2017)

In Reply We appreciate the 2 letters concerning our recent meta-analysis.1 These letters were essentially from the same research group, and include individuals holding a licensed patent on technology aiming to replicate the supposedly protective effects of “high” altitude.
TET2 Is Essential for Survival in Mice, and Decreased TET2 Expression Enlarges HSC Compartment and Alters Cell Differentiation
Authors: Kotaro Shide, Takuro Kameda, Haruko Shimoda, Ayako Kamiunten, Masaaki Sekine, Tomonori Hidaka, Keiko Katayose, Yoko Kubuki, Akira Kitanaka, Kazuya Shimoda
Journal: Blood (2011)
Erratum to ‘‘Combining different types of multifunctional liposomes loaded with ammonium bicarbonate to fabricate microneedle arrays as a vaginal mucosal vaccine adjuvant-dual delivery system (VADDS)’’ [J. Control. Release 246 (2017) 12–29]
Authors: Ning Wang, Yuanyuan Zhen, Yiguang Jin, Xueting Wang, Ning Li, Shaohong Jiang, Ting Wang
Journal: Journal of Controlled Release (2017)
ATG5 Dependent Autophagy Uncouples T Cell Functions and Modulates Experimental Graft-Versus-Host Disease
Authors: Katherine Oravecz-Wilson, Corinne Rossi, Chen Liu, Tomomi Toubai, Hiroya Tamaki, Cynthia Zajac, Stuart Brabbs, Nathan Mathewson, Julia Wu, Yaping Sun, Pavan Reddy
Journal: Blood (2015)
Comparable Results of HLA-Mismatched Vs HLA-Matched Unrelated Donors for Allogeneic Stem Cell Transplantation Using Pre-Transplant ATG.
Authors: Nicolaus Kroeger, Tatjana Zabelina, Thomas Binder, Francis Ayuk, Ulrike Bacher, Gitta Amtsfeld, Alexander Muth, Heinrich Lellek, Rudolf Erttmann, Christine Wolschke, Thomas Eiermann, Axel R. Zander
Journal: Blood (2008)
Dynamic Changes in Aortic Vascular Stiffness in Patients Bridged to Transplant With Continuous-Flow Left Ventricular Assist Devices
Authors: Amit C. Patel, R. Blair Dodson, William K. Cornwell, Kendall S. Hunter, Joseph C. Cleveland, Andreas Brieke, JoAnn Lindenfeld, Amrut V. Ambardekar
Journal: JACC Heart Failure (2017)
Antifungal Prophylaxis with Itraconazole in Patients with Acute Leukemia and after Stem Cell Transplantation (SZT): High Plasma Concentrations with a Loading Dose Strategy.
Authors: Michael Sandherr, Michael Vogeser, Carsten Hartig, Christoph Aulmann, Stefanie Fuhrmann, Linda Wondzinski, Daniel Oruzio, Guenter Schlimok
Journal: Blood (2004)