LMO2 Confers Synthetic Lethality to PARP Inhibition in DLBCL

Publication date: Available online 22 August 2019Source: Cancer CellAuthor(s): Salma Parvin, Ariel Ramirez-Labrada, Shlomzion Aumann, XiaoQing Lu, Natalia Weich, Gabriel Santiago, Elena M. Cortizas, Eden Sharabi, Yu Zhang, Isidro Sanchez-Garcia, Andrew J. Gentles, Evan Roberts, Daniel Bilbao-Cortes, Francisco Vega, Jennifer R. Chapman, Ramiro E. Verdun, Izidore S. LossosSummaryDeficiency in DNA double-strand break (DSB) repair mechanisms has been widely exploited for the treatment of different malignances, including homologous recombination (HR)-deficient breast and ovarian cancers. Here we demonstrate that diffuse large B cell lymphomas (DLBCLs) expressing LMO2 protein are functionally deficient in HR-mediated DSB repair. Mechanistically, LMO2 inhibits BRCA1 recruitment to DSBs by interacting with 53BP1 during repair. Similar to BRCA1-deficient cells, LMO2-positive DLBCLs and T cell acute lymphoblastic leukemia (T-ALL) cells exhibit a high sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. Furthermore, chemotherapy and PARP inhibitors synergize to inhibit the growth of LMO2-positive tumors. Together, our results reveal that LMO2 expression predicts HR deficiency and the potential therapeutic use of PARP inhibitors in DLBCL and T-ALL.Graphical Abstract
Source: Cancer Cell - Category: Cancer & Oncology Source Type: research

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Publication date: Available online 19 September 2019Source: Advances in Space ResearchAuthor(s): E.L. Tang, Z.Q. Liang, L.Wang, Y.F. HanAbstractIn view of the objective reality that it takes a long time for debris to locate the impact point when debris impacts the spacecraft bulkhead, timely and accurate determination of the location of the impact source is the premise and basis for damage repair, which is of great significance to the safety of astronauts. In this paper, the experiments of 2A12 aluminium plate impacted by 2A12 aluminium projectile under different impact parameters have been performed by using the self-buil...
Source: Advances in Space Research - Category: Science Source Type: research
Conclusions: The abnormal location of FLT3 caused by different glycosylation status leads to the distinguishing signaling pathways. Targeting on FLT3 glycosylation may provide a new perspective for therapeutic strategies. Abbreviations: ABCG2: ATP-binding cassette transporter breast cancer resistance protein; ATF: activating transcription factor; AML: acute myeloid leukemia; CHOP: CCAAT-enhancer-binding protein homologous protein; 2-DG: 2-deoxy-D-glucose; EFS: event free survival; EPO: erythropoietin; EPOR: erythropoietin receptor; ERS: endoplasmic reticulum stress; FLT3: FMS-like tyrosine kinase 3; GPI: glycosylphosphatid...
Source: Hematology - Category: Hematology Tags: Hematology Source Type: research
Conclusion and Future Perspectives This review illustrates our current knowledge of USP7, including its source and characterization, structure, binding partners and substrates in various biological processes. Besides, how USP7 regulates various aspects of a cell under both normal and pathological states are elaborated in detail. As the processes of ubiquitination and deubiquitination are extremely dynamic and context-specific, a series of studies have linked USP7 to different cancers. The biology, particularly the immune oncology mechanisms, reveal that USP7 inhibitors would be useful drugs, thus it is vital to develop hi...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Yi He†, Wenyong Long† and Qing Liu* Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China Super-enhancers (SEs) refer to large clusters of enhancers that drive gene expressions. Recent data has provided novel insights in elucidating the roles of SEs in many diseases, including cancer. Many mechanisms involved in tumorigenesis and progression, ranging from internal gene mutation and rearrangement to external damage and inducement, have been demonstrated to be highly associated with SEs. Moreover, translocation, formation, deletion, or duplication of SEs themselves co...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusions: CAR T cell therapies have demonstrated the clinical benefits of harnessing our body's own defenses to combat tumor cells. Similar research is being conducted on lesser known modifications and gene-modified immune cells, which we highlight in this review. Introduction Chimeric antigen receptors and engineered T cell receptors (based on previously identified high affinity T cell receptors) function by redirecting T cells to a predefined tumor-specific (or tumor-associated) target. Most of these modifications use retroviral or lentiviral vectors to integrate the construct, and most of the receptors ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Objective: To investigate the clinical features of 2nd hematological malignancies post to the initial cancer treatment.METHODS: A retrospective study was performed to analyze the available clinical data of 116 patients diagnosed with 2nd hematologic malignancies after treatment of various malignant tumors from June 1998 to June 2018 at Sun Yat-sen University cancer center.RESULTS: The characteristics of the 116 patients diagnosed with 2nd hematological cancer post to initial cancer treatment were indicated as following: 62 males and 54 females. The primary tumor category was grouped as (according to ICD-10 International Di...
Source: Blood - Category: Hematology Authors: Tags: 904. Outcomes Research-Malignant Conditions Source Type: research
Conclusion: This study found that sociodemographic factors were associated with the risk of developing medical conditions in AYA NHL, ALL and AML survivors. As expected, the risk of medical conditions varied by cancer type and treatment, with those undergoing SCT having a higher risk of medical conditions regardless of cancer type. NHL and ALL survivors who were uninsured or publicly insured were at a consistently higher risk of developing medical conditions, as were Hispanic ALL survivors and Black AML survivors. Our findings highlight the higher burden of medical conditions in subgroups of cancer survivors that may relat...
Source: Blood - Category: Hematology Authors: Tags: 904. Outcomes Research-Malignant Conditions: Real World Outcomes Source Type: research
CONCLUSION Cognitive impairment can affect daily functioning, quality of life, and capacity to work in patients with cancer and those in remission. Consequently, cognitive assessment is now an important and necessary part of a comprehensive oncological care plan. Cancer-related cognitive impairment might be due to the direct effects of the cancer itself, nonspecific factors, or comorbid conditions that are independent of the disease and/or due to the adverse effects of the treatment or combination of treatments given for the disease. The prevalence and extent of cognitive impairment associated with cancer is recognized but...
Source: Innovations in Clinical Neuroscience - Category: Neuroscience Authors: Tags: Cognition Current Issue Neuro oncology Neurology Review cancer chemotherapy cognitive impairment neuropsychological assessment treatment Source Type: research
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