tbuckley/cabot-search huggingface dataset:
Circulating Tumor DNA Analyses as Markers of Recurrence Risk and Benefit of Adjuvant Therapy for Stage III Colon Cancer
Authors: Jeanne Tie, Joshua D. Cohen, Yuxuan Wang, Michael Christie, Koen Simons, Margaret Lee, Rachel Wong, Suzanne Kosmider, Sumitra Ananda, Joseph McKendrick, Belinda Lee, Jin Hee Cho, Ian Faragher, Ian T. Jones, Janine Ptak, Mary J. Schaeffer, Natalie Silliman, Lisa Dobbyn, Lu Li, Cristian Tomasetti, Nicholas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein, Peter Gibbs
Journal: JAMA Oncology (2019)

Adjuvant chemotherapy in patients with stage III colon cancer prevents recurrence by eradicating minimal residual disease. However, which patients remain at high risk of recurrence after completing standard adjuvant treatment cannot currently be determined. Postsurgical circulating tumor DNA (ctDNA) analysis can detect minimal residual disease and is associated with recurrence in colorectal cancers.To determine whether serial postsurgical and postchemotherapy ctDNA analysis could provide a real-time indication of adjuvant therapy efficacy in stage III colon cancer.This multicenter, Australian, population-based cohort biomarker study recruited 100 consecutive patients with newly diagnosed stage III colon cancer planned for 24 weeks of adjuvant chemotherapy from November 1, 2014, through May 31, 2017. Patients with another malignant neoplasm diagnosed within the last 3 years were excluded. Median duration of follow-up was 28.9 months (range, 11.6-46.4 months). Physicians were blinded to ctDNA results. Data were analyzed from December 10, 2018, through June 23, 2019.Serial plasma samples were collected after surgery and after chemotherapy. Somatic mutations in individual patients' tumors were identified via massively parallel sequencing of 15 genes commonly mutated in colorectal cancer. Personalized assays were designed to quantify ctDNA.Detection of ctDNA and recurrence-free interval (RFI).After 4 exclusions, 96 eligible patients were eligible; median patient age was 64 years (range, 26-82 years); 49 (51%) were men. At least 1 somatic mutation was identified in the tumor tissue of all 96 evaluable patients. Circulating tumor DNA was detectable in 20 of 96 (21%) postsurgical samples and was associated with inferior recurrence-free survival (hazard ratio [HR], 3.8; 95% CI, 2.4-21.0; P < .001). Circulating tumor DNA was detectable in 15 of 88 (17%) postchemotherapy samples. The estimated 3-year RFI was 30% when ctDNA was detectable after chemotherapy and 77% when ctDNA was undetectable (HR, 6.8; 95% CI, 11.0-157.0; P < .001). Postsurgical ctDNA status remained independently associated with RFI after adjusting for known clinicopathologic risk factors (HR, 7.5; 95% CI, 3.5-16.1; P < .001).Results suggest that ctDNA analysis after surgery is a promising prognostic marker in stage III colon cancer. Postchemotherapy ctDNA analysis may define a patient subset that remains at high risk of recurrence despite completing standard adjuvant treatment. This high-risk population presents a unique opportunity to explore additional therapeutic approaches.
Use of MicroRNA Expression Profiling to Identify Prognostic Subclasses in Mantle Cell Lymphoma: Mir-29 Family as New Prognostic Markers
Authors: Jianhong Lin, Jianjun Zhao, Tint Lwin, Sophie Dessureault, Lynn C. Moscinski, William S. Dalton, Eduardo Sotomayor, Jin Cheng, Jianguo Tao
Journal: Blood (2008)
A Phase II Study of Decitabine Followed By Allogeneic Hematopoietic Stem Cell Transplantation in High-Risk Patients with Myeloid Malignancies
Authors: Christopher R. D'Angelo, Aric C. Hall, Kyungmann Kim, Ryan J. Mattison, Walter L. Longo, Peiman Hematti, Natalie Scott Callander, Mark Juckett
Journal: Blood (2018)
Oncologic services through Project Access and other safety net care coordination programs.
Authors: James Blake Hammock, Courtney Williams, Gabrielle Betty Rocque
Journal: Journal of Clinical Oncology (2019)

126 Background: Since the 1996 formation of Project Access, a nationwide program linking uninsured, low-income, or underserved patients to specialty care, the US has experienced a growth of third-party, safety net care coordination programs that provide sub-specialty care at no or reduced cost. These programs pre-negotiate with local physicians and hospitals to offer pro bono services to patients. Little is known about the provision of oncologic services within these programs. This study evaluated the current landscape of oncologic services within US safety net care coordination programs. Methods: This study reviewed websites via an online search from 04/22/19 - 04/28/19 using keywords “Project Access”, “healthcare”, and individual state names. The websites were reviewed for information on location, services offered, and patient eligibility criteria. Where online data on oncologic services was unavailable, individual programs were called on 05/08/19 for additional information. Five programs were unreachable by phone or e-mail. Results: Websites of 29 safety net care coordination programs in 22 states were identified, serving only approximately 40 counties. Online, one program highlighted "limited" access to oncologic care, while another offered chemotherapy at a reduced cost ($5000/round). When contacted by phone, 55% offered access to oncologic services and 48% assisted with chemotherapy costs. One program provided chemotherapy only if the cancer diagnosis was made after the patient was enrolled in their system. Virtually all programs who offered chemotherapy did so through affiliated large hospital systems. A commonly reported reason for lack of oncology care was a reluctance of oncologists to commit to potential long-term agreements of free care. Online, one program offered PET scans. By phone, 89% offered some imaging. Two programs (7%) explicitly required US citizenship for care. Conclusions: Third-party care coordination centers are increasing in number and provide a novel, and potentially unrecognized, approach to increasing oncology service access. Further research should identify barriers contributing to the relative lack of oncologic services in these programs compared to other specialties.
Abstract 133: Exosomal Transfer of Muscle Specific Mir-499 to Endothelial and Endothelial Progenitor Cells Impairs Angiogenesis in Diabetes
Authors: Zhongjian Cheng, Venkata Naga Srikanth Garikipati, Maria Cimini, May Trungcao, Chunlin Wang, Vandana Mallaredy, Grace Huang, Jia Yu, Cindy Benedict, Suresh K Verma, Raj Kishore
Journal: Circulation Research (2019)

Background: miR-499, a muscle specific-miR, is enhanced in diabetic heart and has been suggested to be a therapeutic target for cardiovascular disease in diabetes. Recent studies provided the evidence that overexpressing miR-499 in ECs inhibits the capillary tube networks. Here, we tested the hypothesis that under diabetic conditions, myocyte-derived exosomes transfer miR-499 to EC/EPCs thereby impairing their angiogenic properties. Methods and Results: miR-499 expression is abundant and enhanced in heart, skeletal muscle, cardiomyocytes and skeletal muscle cells (SKMCs) of db/db mice. We observed that miR-499 level was also increased in diabetic EC/EPCs. In vitro, high D-glucose (25 mM) increased miR-499 level in SKMCs but not in ECs, suggesting that enhanced miR-499 in diabetic EC/EPCs is not regulated by hyperglycemia. To study whether SKMC-derived exosomes transfer miR-499 from SKMCs to EC/EPCs, we first examined the miR-499 levels in diabetic SKMC-derived exosomes and plasma-derived exosomes from db/db mice. We observed that miR-499 levels were greater in diabetic SKMC- and plasma-derived exosomes. Furthermore, by co-culture, we found that diabetic SKMCs increased miR-499 levels in human microvascular endothelial cells (ECs) and impaired EC tube formation and migration which was blocked by exosome inhibitor GW4869 (GW). We also observed that GW partially rescued diabetic SKMC- and plasma-derived exosome-mediated impairment in tube formation and migration of ECs. Overexpression of miR-499 in ECs decreased angiogenic factors and impaired tube formation/migration. Furthermore, in a hind-limb ischemia model of db/db mice, GW treatment improved ischemic hindlimb blood perfusion and angiogenesis. Our study suggests that diabetes-enhanced miR-499 in myocytes can be transferred to ECs via myocyte-derived exosomes thus impairs EC/EPC function. Mechanistically, Sex-determining region Y-box 6 (SOX6), one of the validated target of miR-499, was significantly decreased in diabetic EC/EPCs. Knockdown of SOX6 impairs tube formation and migration of ECs. Conclusions: Our results suggest that exosomal transfer of muscle specific miR-499 to EC/EPCs impairs angiogenesis and ischemic tissue injury repair in diabetes via suppression of SOX6.
Hoxa9 and Meis1 Bind Highly Conserved Elements Near Targets Regulated in Leukemia Cells.
Authors: Kajal V. Sitwala, Yongsheng Huang, Monisha Dandekar, Gordon Robertson, Timothee Cezard, Misha Bilenky, Nina Thiessen, Yongjun Zhao, Thomas Zeng, Martin Hirst, Alfred Hero, Steven Jones, Jay Hess
Journal: Blood (2008)
The prognostic value of polymorphisms in the insulin-like growth factor receptor (IGFR) pathway in patients with locally advanced pancreatic cancer (LAPC)
Authors: R. T. Shroff, M. M. Javle, X. Dong, V. S. Kumar, S. Krishnan, R. A. Wolff, J. L. Abbruzzese, D. Li
Journal: Journal of Clinical Oncology (2009)

4500 Background: The IGFR pathway is activated in pancreatic cancer and may result in aggressive disease course. The study of single nucleotide polymorphisms (SNPs) involved in this pathway may provide prognostic information and predict response to IGFR directed agents. We investigated IGFR pathway SNPs in patients with LAPC. Methods: We evaluated 39 SNPs from 7 candidate genes in the IGFR pathway (IGF1R, IGF2R, IGF1, IGF2, IRS1, IRS2, IGFBP3) in 105 LAPC patients. DNA extraction from whole blood was performed using the Qiagen Flexigene DNA and Promega Maxwell 16 kits. Genotyping was performed using the Sequenom method. Overall survival was measured from date of diagnosis to date of death or last follow-up. Kaplan-Meier plot, log-rank test, and Cox regression were used to compare survival of patients according to genotype corrected for previously identified prognostic factors, including induction chemotherapy, CA 19–9, albumin, LDH, hemoglobin and Karnofsky performance status (KPS). Results: Median survival time (MST) was 15 months (95% CI 13.3–16.7). Induction chemotherapy, LDH, CA 19–9 level, hemoglobin, and KPS were not significantly associated with survival. Serum albumin and three SNPs of the IGF pathway (IGF1R IVS20–3431A&gt;G, IRS1 G971R, and IGF2 *4352A&gt;G) were significantly associated with prognosis ( Table ). Two of the three genotypes remained as significant predictors for survival in Cox regression analysis when adjusted for clinical factors. A significant combined genotype effect was observed wherein patients with all three deleterious alleles had significantly worse survival than those with only two or one (10 vs. 16.3 vs. 21.3 months, p&lt; 0.0001). Conclusions: These data suggest that SNPs in the IGFR pathway genes may have prognostic value for LAPC patients. This information may identify population subgroups that could benefit from IGFR-targeted agents. [Table: see text] No significant financial relationships to disclose.
Pro-Inflammatory Cytokines Drive the Development of a Prothrombotic Platelet Phenotype in Inflammation and Aging
Authors: Pavel Davizon-Castillo, Katrina Ashworth, Kelly Higa, Giovanny Hernandez, Sumitra Acharya, Robert A. Campbell, Matthew Rondina, Colm B. Collins, Anthony Donato, Lisa Lesniewski, James DeGregori, Michael Holer, Nirmal Banda, Jorge Di Paola, Eric Martin Pietras
Journal: Blood (2016)
Points to consider regarding DSM alternatives – Authors' reply
Authors: Stijn Vanheule, Pieter Adriaens, Ariane Bazan, Piet Bracke, Ignaas Devisch, Jean-Louis Feys, Brenda Froyen, Sylvie Gerard, Dorien H. Nieman, Jim Van Os, Marc Calmeyn
Journal: The Lancet Psychiatry (2019)
Conventionally-Defined and PET/CT-Defined Complete Response (CR) to Novel Agent-Based Induction Therapy and Autologous Stem-Cell Transplantation (ASCT) In Multiple Myeloma (MM): A Prospective Study of Clinical and Prognostic Implications
Authors: Elena Zamagni, Cristina Nanni, Francesca Patriarca, Annalisa Pezzi, Beatrice Anna Zannetti, Paola Tacchetti, Emanuela Englaro, Giulia Perrone, Silvia Buttignol, Annamaria Brioli, Lucia Pantani, Francesca Carobolante, Michele Baccarani, Stefano Fanti, Michele Cavo
Journal: Blood (2011)
Phase III Study of VCAP-AMP-VECP vs. Biweekly CHOP in Aggressive Adult T-Cell Leukemia-Lymphoma (ATLL): Japan Clinical Oncology Group Study, JCOG9801.
Authors: Kunihiro Tsukasaki, Takuya Fukushima, Atae Utsunomiya, Syuichi Ikeda, Masato Masuda, Kensei Tobinai, Haruhiko Fukuda, Masanori Shimoyama, Masao Tomonaga, Tomomitu Hotta
Journal: Blood (2005)
Clinical Efficacy of Therapies for Transfusion-Dependent Non-Severe Aplastic Anemia: A Retrospective Cohort Study in Multiple Hospitals
Authors: Shengyun Lin, Yan Yang, Hua Yin, Chang Huang, Jian Chen, Liqiang Wu, Jianping Shen, Baodong Ye, Zhiping Hu, Yiping Shen, Zhiyin Zheng, Wenyi Shen, Xingyu Lu, Xuemei Wu, Guangsheng He, Jianyong Li
Journal: Blood (2018)
Abstract 437: PRMT5-induced Arginine Methylation Mediates Energy Stress-induced Autophagy in the Heart
Authors: Risa Mukai, Toshiro Saito, Peiyong Zhai, Junichi Sadoshima
Journal: Circulation Research (2019)

Autophagy is a self-degradative process that is important for protecting cells and organisms against stress and plays a protective role in the heart. However, the underlying mechanism by which autophagy protects the heart against stress is poorly understood. ATG proteins are required for autophagy and modulated by post-translational modifications (PTMs) such as phosphorylation, ubiquitination, and acetylation. The level of arginine methylation, another form of PTM, is altered in the heart in response to stress. Our hypothesis is that arginine methylation plays an important role in the regulation of autophagy in the heart during stress. To this end, we examined the level of arginine methylation in response to energy stress in vivo . We observed a time-dependent increase in arginine methylation in the mouse heart under starvation conditions for 24 to 48 hours. Arginine methylation was increased (2.32-fold, p&lt;0.01) after 48 hours of fasting compared to in those without fasting. Expression of protein arginine methyltransferase 5 (PRMT5) was increased at both the mRNA and protein level (1.6- and 1.72-fold, p&lt;0.05) in the mouse heart after 48 hours of starvation. In order to investigate the role of endogenous PRMT5, we knocked down PRMT5 with adenovirus harboring sh-RNA. LC3-II, a marker of autophagy activity, was increased during glucose deprivation in sh-scramble-treated cardiomyocytes (CMs) (2.14-fold, p&lt;0.01), but not in sh-PRMT5-treated CMs. Arginine methylation was reduced in response to glucose deprivation in CMs when PRMT5 was downregulated. Mice were also injected intraperitoneally with a PRMT5-specific inhibitor (EPZ015666, 2 mg/kg) and hearts were harvested after 48 hours of starvation. Both arginine methylation levels and autophagy activity in the heart were decreased in the presence of EPZ015666 compared to in non-treated mice. Increased arginine methylation was also observed in the mouse heart in response to 1 hour of myocardial ischemia (1.87-fold, p&lt;0.01), which was accompanied by upregulation of PRMT5 (1.54-fold, p&lt;0.05). Taken together, these data suggest that arginine methylation mediated through PRMT5 may play a key role in mediating autophagy during energy stress conditions such as starvation and ischemia.
Development of Potency Assays for Quality Assessment of an Advanced Therapy Medicinal Product: Mitomycin C-Induced Peripheral Blood Mononuclear Cell (MIC) Product
Authors: Ming NI, Lei Wang, Christian Kleist, Peter Terness, Gerhard Opelz, Christian Morath, Matthias Schaier, Carsten Müller-Tidow, Martin Zeier, Michael Schmitt, Anita Schmitt
Journal: Blood (2018)
Dynamic Prognostic Model to Identify Patients with Primary or Post-Polycythemia Vera/Essential Thrombocythemia Myelofibrosis (Mf) At the Highest Risk of Death and Transformation to Acute Myeloid Leukemia
Authors: Alfonso Quintás-Cardama, Jenny Shan, Sherry Pierce, Hagop M. Kantarjian, Srdan Verstovsek
Journal: Blood (2011)
Human Mesenchymal Stroma Cells (hMSCs) Expanded with Human Platelets Lysate Are Safe and Effective For the Treatment of Graft Versus Host Disease
Authors: Martino Introna, Ettore Biagi, Chiara Capelli, Agnese Salvadè, Giovanna D’Amico, Attilio Rovelli, Anna Grassi, Adriana Balduzzi, Josee Golay, Andrea Biondi, Alessandro Rambaldi
Journal: Blood (2008)
Mitochondrial Metabolic Reprogramming by CD36 Signaling Drives Macrophage Inflammatory Responses
Authors: Yiliang Chen, Moua Yang, Wenxin Huang, Wenjing Chen, Yiqiong Zhao, Marie L. Schulte, Peter Volberding, Zachary Gerbec, Michael T. Zimmermann, Atefeh Zeighami, Wendy Demos, Jue Zhang, Darcy A. Knaack, Brian C. Smith, Weiguo Cui, Subramaniam Malarkannan, Komal Sodhi, Joseph I. Shapiro, Zijian Xie, Daisy Sahoo, Roy L. Silverstein
Journal: Circulation Research (2019)

Rationale: A hallmark of chronic inflammatory disorders is persistence of proinflammatory macrophages in diseased tissues. In atherosclerosis, this is associated with dyslipidemia and oxidative stress, but mechanisms linking these phenomena to macrophage activation remain incompletely understood. Objective: To investigate mechanisms linking dyslipidemia, oxidative stress, and macrophage activation through modulation of immunometabolism and to explore therapeutic potential targeting specific metabolic pathways. Methods and Results: Using a combination of biochemical, immunologic, and ex vivo cell metabolic studies, we report that CD36 mediates a mitochondrial metabolic switch from oxidative phosphorylation to superoxide production in response to its ligand, oxidized LDL (low-density lipoprotein). Mitochondrial-specific inhibition of superoxide inhibited oxidized LDL-induced NF-κB (nuclear factor-κB) activation and inflammatory cytokine generation. RNA sequencing, flow cytometry, 3H-labeled palmitic acid uptake, lipidomic analysis, confocal and electron microscopy imaging, and functional energetics revealed that oxidized LDL upregulated effectors of long-chain fatty acid uptake and mitochondrial import, while downregulating fatty acid oxidation and inhibiting ATP5A (ATP synthase F1 subunit alpha)—an electron transport chain component. The combined effect is long-chain fatty acid accumulation, alteration of mitochondrial structure and function, repurposing of the electron transport chain to superoxide production, and NF-κB activation. Apoe null mice challenged with high-fat diet showed similar metabolic changes in circulating Ly6C + monocytes and peritoneal macrophages, along with increased CD36 expression. Moreover, mitochondrial reactive oxygen species were positively correlated with CD36 expression in aortic lesional macrophages. Conclusions: These findings reveal that oxidized LDL/CD36 signaling in macrophages links dysregulated fatty acid metabolism to oxidative stress from the mitochondria, which drives chronic inflammation. Thus, targeting to CD36 and its downstream effectors may serve as potential new strategies against chronic inflammatory diseases such as atherosclerosis.
Abstract 773: Neonatal and Adult Cardiac Transcriptome Analysis Reveals Distinct Mechanisms in Noncompaction Dilated Cardiomyopathy Development Induced by p.K69R-MLP (Muscle Lim Protein) Mutation i <i>n vivo</i>
Authors: Enkhsaikhan Purevjav, Fuyi Xu, Undral Munkhsaikhan, Neely Alberson, Ramona Sabau, Lu Lu, Jeffrey A Towbin
Journal: Circulation Research (2019)

Introduction: Pediatric and adult dilated cardiomyopathy (DCM) represent distinct pathological entities, however, the basis of this phenomena remains obscure. The pathogenic variant p.K69R in MLP/ CSRP3 induced DCM in adult Mlp K69R knock-in mice. A noncompacted ventricular wall and dilated ventricles were seen in embryonic and neonatal Mlp K69R hearts, reminiscent of that seen in infant variant carriers. Hypothesis: Mlp- K69R associated genetic modifiers govern DCM phenotypes in neonatal and adult heart. The study was to find genetic modifiers associated with divergent neonatal and adult phenotypes induced by Mlp- K69R. Methods: RNA extracted from neonatal and adult Mlp K69R and Mlp WT mouse myocardium was applied to Affymetrix microarray and QPCR analysis. Data were normalized, subjected to differentially expression genes and gene set enrichment analysis. Results: We found 1024 genes in adult and 252 genes in neonatal heart that were significantly altered in Mlp K69R vs WT littermates. 23 of these genes were mutually altered in adult and neonatal mutants. In adult mutants, 15 sarcomeric genes were significantly over-expressed compared to WT littermates. The mutation altered expression of genes involved in sarcolemmal and desmosomes unity. Calcium handling, integrin-associated networks, and heart failure-associated genes were upregulated in mutants vs WT littermates. In neonates, genes involved in cardiac and vascular development ( Rhox2c, Tbx3, Mir23a, Tbc1d7 ), cell adhesion and migration ( Tff2 ), and apoptosis ( Mir297a-2 ) were significantly altered. Two cardio-protective miRNAs, Mir98 and Mir451a , were highly reciprocally altered in both, adult and neonatal, mutant vs WT hearts. Their expression was increased in mutant adult hearts, but decreased in neonatal mutant hearts, suggesting novel candidates associated with K69R-MLP-induced DCM and noncompaction phenotypes. Conclusions: Differential transcriptomes in neonatal and adult hearts suggest that pathogenic K69R-MLP variant induces DCM and noncompaction phenotypes via distinct underlying genetic modifiers. Contrary to mutant adult mice, mutant newborn hearts show significant decrease in Mir98 and Mir451a, which may predispose them to developing myocardial noncompaction.
Excellent Outcome of Nodular Lymphocyte Predominant Hodgkin Lymphoma in the Eastern Province of Saudi Arabia. a Real-World Case Series of 49 Consecutive Patients Treated at a Referral Center from 2006 to 2017
Authors: John Apostolidis, Nihad Mokhtar, Mohammed Darweesh, Enas Mutahar, Manar Abdulbaqi, Salman Harbi, Eshrak Shaibani, Mohammed Kawari, Ayman Abulhassan, Jenifer Bacal, Heba Raslan, Afrah Dawood, Asif Moinuddid, Ahmed Buali, Eman Debawy, Taghreed Hindi, Ayed Garni, Mohammed Rahal, Panagiotis Kaloyannidis, Khalid Anezi, Hani Hassan Al Hashmi
Journal: Blood (2018)
Increased Age-Related B-Cells in Patients with Aplastic Anemia
Authors: Elena E. Solomou, Eva Plakoula, Argiris Symeonidis, Athanasios Galanopoulos, Athina Vyniou, Giannakoulas Nikolaos, Maria D. Palasopoulou, Evgenia Verigou, George Vassilopoulos, Haralambos Gogos, Antonis Kattamis, Stamatis-Nick Liossis
Journal: Blood (2018)
Results of a Phase I Study of GRN163L, a Direct Inhibitor of Telomerase, in Patients with Relapsed and Refractory Multiple Myeloma (MM)
Authors: Asher Alban Chanan-Khan, Nikhil C. Munshi, Mohamad A. Hussein, Laurence Elias, Fabio Benedetti, Jennifer Smith, Soo-Peang Khor, Carol A. Huff
Journal: Blood (2008)