tbuckley/cabot-search huggingface dataset:
Abstract 555: A workflow for enrichment and whole genome amplification (WGA) of circulating tumor cells (CTCs) for next generation sequencing
Authors: Merisa Nisic, Sijie Hao, Ramdane Harouaka, Si-Yang Zheng
Journal: Cancer Research (2015)

Abstract Metastasis is the leading cause of cancer deaths. Circulating tumor cells (CTCs) are thought to be responsible for the seeding of metastases. These tumor cells are heterogeneous with variation occurring at the single-cell level. Using a flexible micro spring array (FMSA) device for label-free mechanical enrichment of CTCs from whole blood samples, we established a workflow from isolation followed by whole genome amplification (WGA) and finally sequencing of circulating tumor cells. Briefly, circulating tumor cells were collected from the FMSA using the Zeiss Laser Capture Microdissection System. Isolated cells underwent whole genome amplification using a commercial WGA kit. The quality of the amplified genomic DNA was analyzed using the TaqMan® Real-Time PCR Assays. Specific loci were then amplified with the Ion AmpliSeq™ Cancer Hotspot Panel v2 and sequenced using the Ion PGM™ System. These studies were performed to understand the genomic heterogeneity observed in circulating tumor cells. Citation Format: Merisa Nisic, Sijie Hao, Ramdane Harouaka, Si-Yang Zheng. A workflow for enrichment and whole genome amplification (WGA) of circulating tumor cells (CTCs) for next generation sequencing. [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 555. doi:10.1158/1538-7445.AM2015-555
The influence of age on intensity of care at the end of life among older patients with advanced cancer.
Authors: J. A. Zerillo, A. K. Smith, M. A. Schonberg, E. P. McCarthy
Journal: Journal of Clinical Oncology (2011)

9099 Background: Little is known about intensity of care or hospice use among the oldest adults dying with advanced cancers. Methods: We analyzed data from 38,747 fee-for-service beneficiaries age 66 and older with advanced cancer diagnoses including non-small cell lung (n=20,185), small cell lung (n=4,252), colorectal (n=7,721), female breast (n=1,877) or prostate (n=4,712) cancer. We studied newly diagnosed patients from 1992 to 1999 in the SEER Program who died by 12/31/2001. Using linked Medicare claims, we examined hospice use and/or receipt of high-intensity care by age. We defined high-intensity care as receipt of chemotherapy, 2+ hospitalizations, >14 days hospitalized, and/or an intensive care unit admission in the last month of life. We also examined time in hospice prior to death and in-hospital death. We adjusted analyses for sociodemographics, tumor characteristics and comorbidities. Results: Overall, 51% of patients were age 66-74, 40% were 75-84, and 9% were 85 and older; 52% (60% of those 85+) died within 6 months of diagnosis. Although receipt of high-intensity care decreased with older age, 28% of patients age 85 and older received some type of high intensity of care. Only 41% of patients used hospice care and a modest decline was observed for those age 85 and older. Results were similar after adjustment. Conclusions: Despite poor prognoses, many older patients with advanced cancer receive high intensity of care at the end of life, even among those age 85 and older. Hospice use is also lower among these patients. These findings highlight opportunities to improve the quality of care at the end of life. Unadjusted indicators of intensity care by age. 66-74 (n=19,853) 75-84 (n=15,315) 85+ (n=3,579) High-intensity care in last month of life 1+ indicators, (%)† 39 34 28 Chemotherapy < 30 days, (%)† 15 10 5 2+ hospitalizations, (%)† 13 11 9 >14 days hospitalized, (%)** 13 12 11 ICU admission, (%)* 13 13 12 Died in-hospital, (%)† 29 26 24 Enrolled in hospice, (%)** 41 41 38 Median hospice stay, days (25th, 75th ) 19 (7-46) 20 (8-51) 21 (8-56) P values for difference by age *<0.05; **<0.01; †0.0001.
Abstract 3371: Periostin secreted by breast cancer cells inhibits macrophage phagocytosis and adhesion to fibronectin
Authors: Michelle M. Coleman, Rachel S. Helms, Didier Dreau
Journal: Cancer Research (2015)

Abstract Interactions between cancer cells and immune cells are critical to the development of breast cancer metastases. We have previously shown that breast cancer cells secrete periostin, an extracellular matrix protein implicated in tumor progression. Here we evaluated 1) the effect of macrophage secretions on 4T1 breast cancer cell production of periostin and 2) the effect of periostin on key macrophage functions. In vitro, periostin secretion by highly metastastic 4T1 mammary cancer cells was investigated by ELISA. Following a 48-hour incubation with conditioned media obtained from J774A-1 monocyte cells, 4T1 cells secreted significantly higher periostin concentrations (p&amp;lt;0.05). Next, the effect of prolonged incubation with periostin on proliferation, adhesion and phagocytosis of macrophages was investigated using mouse J774A-1 and RAW264.7 monocyte cells and mouse primary bone marrow macrophages. In the conditions tested, periostin did not affect macrophage proliferation. Incubation with periostin significantly decreased macrophage adhesion to fibronectin-coated vessels (p&amp;lt;0.05). Incubation with periostin also significantly inhibited macrophage phagocytosis of polymer beads (p&amp;lt;0.05). Together, these observations indicate that the secretion of periostin by 4T1 cells is, in part, stimulated through paracrine communication with macrophages, and that periostin inhibits both macrophage adhesion and phagocytosis. Citation Format: Michelle M. Coleman, Rachel S. Helms, Didier Dreau. Periostin secreted by breast cancer cells inhibits macrophage phagocytosis and adhesion to fibronectin. [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 3371. doi:10.1158/1538-7445.AM2015-3371
A Retrospective Analysis of 344 Fludarabine Melphalan RIC Allogeneic Stem Cell Transplants for Myeloid and Lymphoid Malignancies In Australia and New Zealand 1998–2008,
Authors: Adam J Bryant, Elango Pillai, Glen Kennedy, Anna Kalff, David Ritchie, Biju George, Mark Hertzberg, Sushrut S. Patil, Andrew Spencer, Keith Fay, Paul Cannell, Leanne Berkahn, Richard Doocey, Ruth Spearling, Ian Nivison-Smith, John Moore
Journal: Blood (2011)
The Novel Human Ph+ Acute Lymphoblastic Leukemia Cell Line PhALL3.1 Is Amenable to Retroviral Gene Transfer and Mimics Human Disease Progression in SCID-Beige Mice
Authors: Mark G. Frattini, Elmer Santos, Mark Lawrence Heaney, Peter Maslak, Suresh C Jhanwar, Steven M Larson, Elisa De Stanchina, Bayard Clarkson, Renier J. Brentjens
Journal: Blood (2008)
A 3-Dimensional Co-Culture Model to Investigate Adhesion-Mediated Drug Resistance in Multiple Myeloma
Authors: Omar S. Aljitawi, Yinghua Xiao, Karthik Ramachandran, Brea C. Lipe, Rama Garimella, Amrita Krishnan, Lisa Stehno-Bittel, Linheng Li
Journal: Blood (2012)
First-Line Treatment with R-Chop/21 for Patients with Disseminated Diffuse Large B-Cell Lymphoma (DLCL). Results of a Prospective Series of 128 Patients.
Authors: E. Gonzalez-Barca, E. Domingo-Domenech, J. M. Ribera, J. Briones, A. Salar, L. Gallur, C. Estany, L. Escoda, S. Gardella, J. A. Hernandez, J. Rodriguez, E. Ramila, O. Ramon, M. Garcia-Pinto, I. Español, P. Vivancos, A. Asensio, M. Encuentra, A. Fernandez de Sevilla
Journal: Blood (2004)
Endothelial and Platelet FVIII/VWF Expression - Divergence in Clinical Effect in Murine Models of Hemophilia A with and without FVIII Inhibitory Antibodies.
Authors: Qizhen Shi, Scot A. Fahs, David A. Wilcox, Hartmut Weiler, Sandra L. Haberichter, Robert R. Montgomery
Journal: Blood (2006)
Aberrant Expression of Mir-29b, Mir-181a and Mir-181b in T-Cell Acute Lymphoblastic Leukemia.
Authors: Hamilton L. Gimenes-Teixeira, Dalila L. Zanette, Guilherme Augusto S. dos Santos, Priscila S. Scheucher, Leandro F. Dalmazzo, Amélia G. Araújo, Roberto P. Falcao, Wilson A. Silva Júnior, Eduardo M Rego
Journal: Blood (2009)
Biomarker and Ex Vivo Sensitivity Analysis of Venetoclax (ABT-199/GDC-0199) in Combination with Bortezomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma
Authors: Jeremy Ross, Martine Amiot, Brenda Chyla, Lisa Roberts-Rapp, Rasna Goswami, Sun Yan, Xin Huang, Anahita Bhathena, Sari Heitner Enschede, Paulo Maciag, Rod A. Humerickhouse, Evelyn McKeegan
Journal: Blood (2015)
39. FACS-Based Enrichment of a Highly Purified HBB-Targeted Hematopoietic Stem and Progenitor Cell Population Using rAAV6 and CRISPR/Cas9
Authors: Daniel P. Dever, Rasmus O. Bak, Joab Camarena, Nivi Saxena, Andreas Reinisch, Carmencita E. Nicolas, Alec B. Wilkens, Ayal Hendel, Nobuko Uchida, Ravindra Majeti, Kenneth I. Weinberg, Matthew H. Porteus
Journal: Molecular Therapy (2016)

Precise engineered nuclease-mediated gene correction via homologous recombination (HR) in hematopoietic stem and progenitor cells (HSPCs) has the power to transform curative therapies for monogenic diseases of the immune system. Sickle cell disease (SCD) is one of the most common monogenic diseases, affecting millions of people worldwide. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment for patients with SCD; however, immunocompatibility issues, graft-versus-host disease, and graft rejection are major roadblocks for efficacious therapy. In theory, the ideal curative strategy for SCD and most monogenic immune diseases is ex vivo gene correction of patient-derived HSPCs followed by autologous HSCT of a highly purified targeted population to avoid possible complications of competition between unedited and gene-targeted HSPCs in vivo. By supplying a homologous GFP-expressing HBB donor via recombinant adeno-associated virus serotype 6 (rAAV6) in combination with a double strand break created by the CRISPR/Cas9 system, we achieved HR frequencies of 15-49% of HSPCs, and more importantly, identified a population of HBB-targeted HSPCs (HSPCHBB) through a log-fold MFI increase in chromosomal transgene expression. Fluorescence activated cell sorting (FACS) of this population revealed consistent GFP expression in >95% of cells over two weeks in vitro in multiple CD34+ donors isolated from either bone marrow, cord blood or peripheral blood. Single-cell FACS of HSPCHBB into methylcellulose led to both myeloid and lymphoid colony formation, and on-target PCR analysis revealed >95% of these HSPCHBB clones had either a mono or biallelic-targeting event. Notably, a fraction of HSPCHBB displayed the CD34+/CD38-/CD90+/CD45RA-immunophenotype, suggesting successful targeting of long-term repopulating hematopoietic stem cells (LT-HSCs). Furthermore, HSPCHBB displayed long-term engraftment in the bone marrow of immunodeficient NSG mice at 12 weeks post-transplant, where we identified that ~70% of human cells were GFP+ and also produced both myeloid (CD33+) and lymphoid (CD19+) cell types, implying that the HSPCHBB population contains true LT-HSCs that can repopulate a functional immune system. Altogether, these proof-of-concept studies showed that by combining a homologous rAAV6 donor, the CRISPR/Cas9 system, and FACS, it is feasible to generate and enrich a highly purified population of gene-corrected HSPCs that include LT-HSC potentials.
BK Virus Reactivation After Double Umbilical Cord Blood Transplantation in Adults Correlates with Tregs and Delayed Reconstitution of CD4+ and CD8+ T Effector Cells
Authors: Gowri Satyanarayana, Sarah Hammond, Haesook T Kim, Sean McDonough, Julia Brown, Ioannis Politikos, Lequn Li, Raphael Viscidi, Thomas Broge, Igor Koralnik, Corey Cutler, Karen K. Ballen, Joseph H. Antin, Francisco M Marty, Jerome Ritz, C Sabrina Tan, Vassiliki A. Boussiotis
Journal: Blood (2012)
Abstract 1432: Role of ubiquitin-specific proteases 47 in epithelial-mesenchymal transition
Authors: Bae-Jung Choi, Young-Joon Surh
Journal: Cancer Research (2015)

Abstract Metastatic spread from primary tumor is the last phase of cancer development. Approximately 90% of deaths from cancer are caused by metastasis. During the transition from a benign tumor to a metastatic one, tumor cells lose cell-cell contacts and gain cell motility for invasion. This is called epithelial-mesenchymal transition (EMT). EMT is considered to be a critical contributor of cancer metastasis. Hypoxia, which plays a critical role in development and tumor progression, orchestrates EMT through the coordinated regulation of different EMT regulators. In this study, we found that a series of ubiquitin specific proteases (USP), particularly USP47, were induced in human colon cancer cells (DLD-1, HT-29 and SW-480) under the hypoxic condition based on cDNA microarray data. USPs are a subfamily of deubiquitinating enzymes (DUB) that primarily belong to the cysteine protease family and are known to remove the monoubiquitin and polyubiquitin chains from specific target proteins. Knockdown of USP47 substantially decreased expression of mesenchymal markers. Furthermore, hypoxia-inducible factor (HIF), especially HIF-2α, was found to regulate transcription of USP47. These results suggest USP47 as a novel regulator of EMT under hypoxic conditions. Citation Format: Bae-Jung Choi, Young-Joon Surh. Role of ubiquitin-specific proteases 47 in epithelial-mesenchymal transition. [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 1432. doi:10.1158/1538-7445.AM2015-1432
619. Immunogenicity and Immunomodulatory Effects of the Allogeneic Human Chondrocytes, hChonJ
Authors: Chae-lyul Limg, Yeon-Ju Lee, Sujeong Kim
Journal: Molecular Therapy (2015)

Osteoarthritis is one of the most frequently occurring degenerative diseases in elderly people. The degeneration of articular cartilage is the leading cause of osteoarthritis. However, damaged articular cartilage has a limited capability to heal itself. As one way to overcome this barrier, we have developed TissueGene-C (TG-C, Invossa™) which is a cell-mediated gene therapy for the regeneration of the cartilage tissue. Invossa™ is a mixture of non-transduced human chondrocytes (hChonJ cells) and retrovirally transduced chondrocytes (hChonJb#7 cells), respectively. Since the hChonJ cells are allogeneic, the possibility of immune rejection has been raised. In this study, we investigated the immunological properties of hChonJ cells. First, we showed that hChonJ cells did not express T cell co-stimulatory molecules CD80 and CD86, but expressed the co-inhibitory molecule CD 273 (PD-L2). Even when hChonJ cells were exposed to a pro-inflammatory cytokine IFN-gamma, they did not express co-stimulatory molecules. IFN-gamma treatment induced the expression of CD274 (PD-L1), and up-regulated the expression of PD-L2. Second, we observed that hChonJ cells did not stimulate T cell proliferation with PBMCs from a MHC-mismatched donor. Further, they could suppress the proliferation of activated T cells. We reasoned that co-inhibitory molecules PD-L1 and PD-L2 play an immunosuppressive role against activated T cells, (figure 1) and we demonstrated that the blockade of PD-L1 and/or PD-L2 with specific neutralizing antibody could lead to the restoration of allo-reactive T cell proliferation. In conclusion, we showed that hChonJ cells are not immunogenic but immunosuppressive, and that this phenomenon is mediated by co-inhibitory molecules PD-L1 and PD-L2 on hChonJ cells in a contact-dependent manner. Therefore, because hChonJ cells do not elicit alloantigen-specific T cell proliferation and suppress alloreactive T cells, these findings indicate that allogeneic hChonJ cells might be appropriate for osteoarthritis therapeutics.
Evaluation of the effect of screening on the detection of good and poor prognosis breast cancers
Authors: L. J. van 't Veer, L. J. Esserman, S. Linn, E. Rutgers, M. Knauer, V. Retel, S. E. Davis, C. Lin
Journal: Journal of Clinical Oncology (2009)

1525 Background: Since the advent of screening, breast cancer incidence has significantly increased in the United States as well as other countries. SEER data from the US shows that the increase is largely in localized disease without a concomitant or significant decrease in regionalized disease. In addition, the increase has occurred essentially in women over 50. We asked whether molecular characterization of tumors would shed light on the types of tumors detected in screening and in locally advanced breast cancers (LABC). Methods: We identified two groups of patients from European studies before and after the introduction of population based screened (in 1995) where the 70-gene prognosis test (MammaPrint) results were available. The first source is the European Validation Study (EVS) (Buyse et al, J Natl Cancer Inst. 2006). The second was a prospective implementation trial of MammaPrint in the Netherlands (RASTER study) (Bueno de Mesquita et al, Lancet Oncol. 2007). The source of LABC patients comes from the multicenter I-SPY TRIAL (CALGB 150007/150012) who underwent routine screening (prior mammogram within 2 years of diagnosis). Results: In women age 50–60, the fraction of cancers that were MammaPrint good prognosis were 40% and 60% prior to and after the introduction of screening, respectively. For women 50–60 who were actually undergoing screening, the fraction of tumors that were MammaPrint good prognosis was 67%. For patients aged 30–40 with stage I and II lymph node-negative disease, who did not undergo screening in either period, the fraction of MammaPrint good prognosis tumors did not change (29% and 31%, for EVS and Raster, respectively). For patients with LABC, from the I-SPY TRIAL, the fraction of tumors that are MammaPrint good prognosis is 7% and 29% for women aged 30–40 and 50–60, respectively. Of the LABC patients undergoing screening, 80% presented clinically during the interval between routine mammograms. Conclusions: Current screening programs are increasing the burden of low-risk cancers. Screening programs should consider including molecular profiles at the time of diagnosis to reduce overtreatment. The majority of LABCs have high-risk molecular profiles and do not present as screen detected cancers. New strategies are needed for early detection of LABC. [Table: see text]
Abstract #4313: Evaluation of angiogenesis using micro-computed tomography in a xenograft mouse model of lung cancer
Authors: Rajkumar Savai, Alexander Langheinrich, Ralph Schermuly, Soni Pullamsetti, Rio Dumitrascu, Horst Traupe, Wigbert Rau, Werner Seeger, Friedrich Grimminger, Gamal Banat
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Quantitative evaluation of lung tumor angiogenesis using immunohistochemical techniques has been limited by difficulties in generating reproducible data. To analyze intrapulmonary tumor angiogenesis, we used high-resolution micro-computed tomography (micro-CT) of lung tumors of mice inoculated with mouse Lewis lung carcinoma (LLC1) or human adenocarcinoma (A549) cell lines. The lung vasculature was filled with the radiopaque silicone rubber, Microfil, via the jugular vein ( in vivo application) or pulmonary artery ( ex vivo application). In addition, human adenocarcinoma lung tumor bearing mice treated site-specifically with humanized monoclonal antibody (Bevacizumab) against vascular endothelial growth factor (VEGF). Quantitative analysis of lung tumor microvessels imaged with micro-CT showed that more vessels (mainly small, <0.02 mm2) were filled using the in vivo (5.4%) compared with the ex vivo (2.1%) method. Furthermore bevacizumab treated , lung tumor bearing mice showed significantly reduced lung tumor volume and lung tumor angiogenesis compared to untreated mice as assessed by micro-CT. Interestingly microvascularization mainly the smaller vessels (<0.02 mm2) were reduced following bevacizumab treatment. This observation with micro-CT was nicely correlated with immunohistochemical measurement of microvessels. Therefore, micro-CT is a novel method investigating lung tumor angiogenesis and might be considered as an additional complementary tool for precise quantification of angiogenesis.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4313.
Higher Incidence of Secondary AML and Adverse Molecular Markers, Together with Lower CR and Higher AML Related Death Rates in Elderly Compared to Younger Patients: Results from 2435 Patients Included in the Two German AML Intergroup Studies
Authors: Dietger Niederwieser, Verena Sophia Hoffmann, Utz Krug, Rainer Krahl, Christina Sauerland, Karsten Spiekermann, Stefan K. Bohlander, Ute Hegenbart, Wolfram Poenisch, Vladan Vucinic, Michael Cross, Nadja Jaekel, Markus Pfirrmann, Antje Schulze, Alwin Kraemer, Georg Maschmeyer, Christian Junghanss, Sebastian Scholl, Christian Jakob, Thomas Heinicke, Detlev Haehling, Norma Peter, Ute Kreibich, Christoph Busemann, Haifa Kathrin Al-Ali, Ahmet H. Elmaagacli, B Opitz, Hans-Heinrich Wolf, Wolfgang Hiddemann, Wolfgang E Berdel, Thomas Buechner
Journal: Blood (2015)
Pretransplant PET Positivity Predicts Early Relapse with Poor Outcome in Patients of Multiple Myeloma Undergoing Autologous Stem Cell Transplantation
Authors: Bhausaheb Bagal, Hasmukh Jain, Uma Dangi, Manju Sengar, Sadhana Kannan, Venkatesh Rangarajan, Hari Menon, Navin Khattry
Journal: Blood (2014)