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https://www.readbyqxmd.com/read/29340116/t-follicular-helper-cells-a-potential-therapeutic-target-in-follicular-lymphoma
#1
REVIEW
Jordi Ochando, Mounia S Braza
Follicular lymphoma (FL), the most common indolent B-cell non-Hodgkin lymphoma (B-NHL), is a germinal center (GC)-derived lymphoma. The mechanisms underlying B-cell differentiation/maturation in GCs could be also involved in their malignant transformation. Moreover, the non-malignant cell composition and architecture of the tumor microenvironment can influence FL development and outcome. Here, we review recent research advances on CD4 helper T cells in FL that highlight the pivotal role of T follicular helper (TFH) cells in a complex multicellular system where they interact with B cells during GC dynamics...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339810/extrahepatic-cancers-and-chronic-hcv-infection
#2
REVIEW
Stanislas Pol, Anaïs Vallet-Pichard, Olivier Hermine
Infectious agents, such as HCV, account for ∼15% of human cancers. HCV infects not only hepatocytes but also extrahepatic cells. Chronic HCV infection can induce chronic inflammation with qualitative and quantitative alterations of the immune repertoire and tissue microenvironment, which could induce various neoplasias. Epidemiological studies and meta-analyses suggest an increased rate of extrahepatic cancers in patients with chronic HCV infection along with a higher risk of intrahepatic cholangiocarcinoma, pancreatic cancer and non-Hodgkin lymphoma (NHL), highlighting the need to screen for HCV infection in patients with these cancers...
January 17, 2018: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29337112/molecular-heterogeneity-in-diffuse-large-b-cell-lymphoma-and-its-implications-in-clinical-diagnosis-and-treatment
#3
REVIEW
Lingchuan Guo, Pei Lin, Hui Xiong, Shichun Tu, Gang Chen
Over half of patients with diffuse large B-cell lymphoma (DLBCL) can be cured by standard R-CHOP treatment (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). However, the remaining patients are refractory and ultimately succumb to progressive or relapsed disease. During the past decade, there has been significant progress in the understanding of molecular mechanisms in DLBCL, largely owing to collaborative efforts in large-scale gene expression profiling and deep sequencing, which have identified genetic alterations critical in lymphomagenesis through activation of key signaling transduction pathways in DLBCL...
January 11, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29335468/aicda-drives-epigenetic-heterogeneity-and-accelerates-germinal-center-derived-lymphomagenesis
#4
Matt Teater, Pilar M Dominguez, David Redmond, Zhengming Chen, Daisuke Ennishi, David W Scott, Luisa Cimmino, Paola Ghione, Jayanta Chaudhuri, Randy D Gascoyne, Iannis Aifantis, Giorgio Inghirami, Olivier Elemento, Ari Melnick, Rita Shaknovich
Epigenetic heterogeneity is emerging as a feature of tumors. In diffuse large B-cell lymphoma (DLBCL), increased cytosine methylation heterogeneity is associated with poor clinical outcome, yet the underlying mechanisms remain unclear. Activation-induced cytidine deaminase (AICDA), an enzyme that mediates affinity maturation and facilitates DNA demethylation in germinal center (GC) B cells, is required for DLBCL pathogenesis and linked to inferior outcome. Here we show that AICDA overexpression causes more aggressive disease in BCL2-driven murine lymphomas...
January 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29330147/genetic-ablation-of-rbm38-promotes-lymphomagenesis-in-the-context-of-mutant-p53-by-downregulating-pten
#5
Jin Zhang, Enshun Xu, Cong Ren, Hee Jung Yang, Yanhong Zhang, Wenqiang Sun, Xiangmudong Kong, Weici Zhang, Mingyi Chen, Eric C Huang, Xinbin Chen
Mutant p53 exerts gain-of-function effects that drive metastatic progression and therapeutic resistance, but the basis for these effects remain obscure. The RNA binding protein RBM38 limits translation of mutant p53 and is often ablated in tumors harboring it. Here we show how loss of Rbm38 significantly alters cancer susceptibility in mutant p53 knock-in mice, by shortening lifespan, altering tumor incidence and promoting T cell lymphomagenesis. Loss of Rbm38 enhanced mutant p53 expression and decreased expression of the tumor suppressor Pten, a key regulator of T cell development...
January 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29312557/involvement-of-the-oncogene-b-cell-lymphoma-6-in-the-fusion-and-differentiation-process-of-trophoblastic-cells-of-the-placenta
#6
Britta Jasmer, Cornelia Muschol-Steinmetz, Nina-Naomi Kreis, Alexandra Friemel, Ulrikke Kielland-Kaisen, Dörthe Brüggmann, Lukas Jennewein, Roman Allert, Christine Solbach, Juping Yuan, Frank Louwen
The oncogene B-cell lymphoma 6 (BCL6) is associated with lymphomagenesis. Intriguingly, its expression is increased in preeclamptic placentas. Preeclampsia is one of the leading causes of maternal and perinatal mortality and morbidity. Preeclamptic placentas are characterized by various defects like deregulated differentiation and impaired fusion of trophoblasts. Its pathogenesis is however not totally understood. We show here that BCL6 is present throughout the cell fusion process in the fusogenic trophoblastic cell line BeWo...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29311309/signaling-by-the-epstein-barr-virus-lmp1-protein-induces-potent-cytotoxic-cd4-and-cd8-t-cell-responses
#7
Il-Kyu Choi, Zhe Wang, Qiang Ke, Min Hong, Yu Qian, Xiujuan Zhao, Yuting Liu, Hye-Jung Kim, Jerome Ritz, Harvey Cantor, Klaus Rajewsky, Kai W Wucherpfennig, Baochun Zhang
The B-lymphotropic Epstein-Barr virus (EBV), pandemic in humans, is rapidly controlled on initial infection by T cell surveillance; thereafter, the virus establishes a lifelong latent infection in the host. If surveillance fails, fatal lymphoproliferation and lymphomagenesis ensue. The initial T cell response consists of predominantly CD8+ cytotoxic T cells and a smaller expansion of CD4+ cells. A major approach to treating EBV-associated lymphomas is adoptive transfer of autologous or allogeneic T cells that are stimulated/expanded on EBV-transformed B cells...
January 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29284789/activating-and-sustaining-c-myc-by-depletion-of-mir-144-451-gene-locus-contributes-to-b-lymphomagenesis
#8
Lan Ding, Yanqing Zhang, Lingling Han, Lei Fu, Xia Mei, Jijun Wang, Jacobi Itkow, Afaf Elabid Ibrahim Elabid, Lei Pang, Duonan Yu
Hyper activity of protooncogene c-Myc is one of the hallmarks of highly aggressive lymphomas. However, the mechanism of how c-Myc is subjected to activation and amplification is still not well defined. In this study, we use gene knockout strategy to show that targeted depletion of a well-conserved microRNA gene locus miR-144/451 initiates tumorigenesis including B-lymphoma development in aged mice. This is due, at least in part, to the direct activation of the c-Myc gene by loss of miR-144/451 expression in hematopoietic cells...
December 29, 2017: Oncogene
https://www.readbyqxmd.com/read/29260925/effective-management-strategies-for-patients-with-marginal-zone-lymphoma
#9
Cecilia B Rosand, Kelly Valla, Christopher R Flowers, Jean L Koff
Marginal zone lymphoma (MZL) is an uncommon indolent lymphoma classified into subtypes based on primary site of involvement: splenic, nodal and extranodal. MZLs' relative rarity has largely precluded adoption of a standard management strategy. Here, we provide an overview of the epidemiology, clinical behavior and therapeutic approaches for each subtype. Biologic insights into lymphomagenesis have identified B-cell receptor signaling as a rational therapeutic target. Recent clinical data suggest that novel agents targeting this pathway, including the Bruton's tyrosine kinase inhibitor, ibrutinib, show significant promise in treatment of relapsed MZL...
December 20, 2017: Future Oncology
https://www.readbyqxmd.com/read/29245936/podocalyxin-promotes-proliferation-and-survival-in-mature-b-cell-non-hodgkin-lymphoma-cells
#10
Estíbaliz Tamayo-Orbegozo, Laura Amo, Marta Riñón, Naiara Nieto, Elena Amutio, Natalia Maruri, Miren Solaun, Arantza Arrieta, Susana Larrucea
Podocalyxin (PCLP1) is a CD34-related sialomucin expressed by some normal cells and a variety of malignant tumors, including leukemia, and associated with the most aggressive cancers and poor clinical outcome. PCLP1 increases breast tumor growth, migration and invasion; however, its role in hematologic malignancies still remains undetermined. The purpose of this study was to investigate the expression and function of PCLP1 in mature B-cell lymphoma cells. We found that overexpression of PCLP1 significantly increases proliferation, cell-to-cell interaction, clonogenicity, and migration of B-cell lymphoma cells...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29221181/analysis-of-ctcl-cell-lines-reveals-important-differences-between-mycosis-fungoides-s%C3%A3-zary-syndrome-vs-htlv-1-leukemic-cell-lines
#11
Elena Netchiporouk, Jennifer Gantchev, Matthew Tsang, Philippe Thibault, Andrew K Watters, John-Douglas Matthew Hughes, Feras M Ghazawi, Anders Woetmann, Niels Ødum, Denis Sasseville, Ivan V Litvinov
HTLV-1 is estimated to affect ~20 million people worldwide and in ~5% of carriers it produces Adult T-Cell Leukemia/Lymphoma (ATLL), which can often masquerade and present with classic erythematous pruritic patches and plaques that are typically seen in Mycosis Fungoides (MF) and Sézary Syndrome (SS), the most recognized variants of Cutaneous T-Cell Lymphomas (CTCL). For many years the role of HTLV-1 in the pathogenesis of MF/SS has been hotly debated. In this study we analyzed CTCL vs. HTLV-1+ leukemic cells...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29204260/the-evolving-role-of-targeted-biological-agents-in-the-management-of-indolent-b-cell-lymphomas
#12
REVIEW
Trent Peng Wang, John Harwood Scott, Stefan Klaus Barta
Improved understanding of the mechanisms of lymphomagenesis has resulted in a surge of development for new targeted agents. An impressive number of biological agents targeting different steps in the pathways of tumor proliferation, survival and apoptosis have become available. The management of patients with indolent non-Hodgkin lymphomas (iNHLs) is rapidly transforming with incorporation of those targeted biological agents into the front-line and relapsed/refractory setting. This review highlights several categories of novel biological agents and will discuss their potential role in the contemporary management of patients with iNHLs...
December 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29202805/clinical-significance-of-pcdh10-promoter-methylation-in-diffuse-large-b-cell-lymphoma
#13
Wenting Huang, Xuemin Xue, Ling Shan, Tian Qiu, Lei Guo, Jianming Ying, Ning Lu
BACKGROUND: PCDH10, one of the non-clustered protocadherins, is identified as a tumor suppressor gene in many tumors. Recently, promoter methylation of PCDH10 was found in diffuse large B-cell lymphoma (DLBCL) but not in normal lymph nodes, suggesting that its epigenetic aberrance is essential to the lymphomagenesis. However, there are few studies on the clinicopathological relevance and prognostic significance of PCDH10 methylation status in DLBCL. METHODS: One hundred-seven cases of DLBCL between Jan 2009 and Jul 2010 were selected to extract genomic DNA and perform bisulfite modification...
December 4, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29200394/-the-igh-3-rr-doctor-jekyll-and-mister-hyde-of-b-cell-maturation-and-lymphomagenesis
#14
Alexis Saintamand, Nour Ghazzaui, Hussein Issaoui, Yves Denizot
The four transcriptional enhancers located in the 3' regulatory region (3'RR) of the IgH locus control the late phases of B-cell maturation, namely IgH locus transcription, somatic hypermutation and class switch recombination. Doctor Jekyll by nature, the 3'RR acts as Mister Hyde in case of oncogenic translocation at the IgH locus taking under its transcriptional control the translocated oncogene. The aim of this review is to show this duality on the basis of the latest scientific advances in the structure and function of the 3'RR and to hIghlight the targeting of the 3'RR as a potential therapeutic approach in mature B-cell lymphomas...
November 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/29192350/serum-cholesterol-trajectories-in-the-10-years-prior-to-lymphoma-diagnosis
#15
Sharon Hensley Alford, George Divine, Chun Chao, Laurel A Habel, Nalini Janakiraman, Yun Wang, Heather Spencer Feigelson, Delia Scholes, Doug Roblin, Mara M Epstein, Lawrence Engel, Suzanne Havstad, Karen Wells, Marianne Ulcickas Yood, Joan Fortuny, Christine Cole Johnson
PURPOSE: Many studies suggest a role for cholesterol in cancer development. Serum cholesterol levels have been observed to be low in newly diagnosed lymphoma cases. The objective of these analyses was to examine the time-varying relationship of cholesterol with lymphomagenesis in the 10 years prior to diagnosis by lymphoma subtype. METHODS: Participants were selected from the combined membership of six National Cancer Institute-funded Cancer Research Network health plans from 1998 to 2008, excluding members with human immunodeficiency virus, cancer (except lymphoma), or organ transplants...
November 30, 2017: Cancer Causes & Control: CCC
https://www.readbyqxmd.com/read/29186126/erratum-pd-1-is-a-haploinsufficient-suppressor-of-t-cell-lymphomagenesis
#16
Tim Wartewig, Zsuzsanna Kurgyis, Selina Keppler, Konstanze Pechloff, Erik Hameister, Rupert Öllinger, Roman Maresch, Thorsten Buch, Katja Steiger, Christof Winter, Roland Rad, Jürgen Ruland
This corrects the article DOI: 10.1038/nature24649.
November 29, 2017: Nature
https://www.readbyqxmd.com/read/29167438/checkpoint-kinase-1-is-essential-for-normal-b-cell-development-and-lymphomagenesis
#17
Fabian Schuler, Johannes G Weiss, Silke E Lindner, Michael Lohmüller, Sebastian Herzog, Simon F Spiegl, Philipp Menke, Stephan Geley, Verena Labi, Andreas Villunger
Checkpoint kinase 1 (CHK1) is critical for intrinsic cell cycle control and coordination of cell cycle progression in response to DNA damage. Despite its essential function, CHK1 has been identified as a target to kill cancer cells and studies using Chk1 haploinsufficient mice initially suggested a role as tumor suppressor. Here, we report on the key role of CHK1 in normal B-cell development, lymphomagenesis and cell survival. Chemical CHK1 inhibition induces BCL2-regulated apoptosis in primary as well as malignant B-cells and CHK1 expression levels control the timing of lymphomagenesis in mice...
November 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/29143824/pd-1-is-a-haploinsufficient-suppressor-of-t-cell-lymphomagenesis
#18
Tim Wartewig, Zsuzsanna Kurgyis, Selina Keppler, Konstanze Pechloff, Erik Hameister, Rupert Öllinger, Roman Maresch, Thorsten Buch, Katja Steiger, Christof Winter, Roland Rad, Jürgen Ruland
T cell non-Hodgkin lymphomas are a heterogeneous group of highly aggressive malignancies with poor clinical outcomes. T cell lymphomas originate from peripheral T cells and are frequently characterized by genetic gain-of-function variants in T cell receptor (TCR) signalling molecules. Although these oncogenic alterations are thought to drive TCR pathways to induce chronic proliferation and cell survival programmes, it remains unclear whether T cells contain tumour suppressors that can counteract these events...
December 7, 2017: Nature
https://www.readbyqxmd.com/read/29141798/ecotropic-viral-integration-site-5-evi5-variants-are-associated-with-multiple-sclerosis-in-iranian-population
#19
Mehrdokht Mazdeh, Soudeh Ghafouri-Fard, Rezvan Noroozi, Arezou Sayad, Maryam Khani, Mohammad Taheri, Mir Davood Omrani
BACKGROUND: Multiple sclerosis (MS) is a multifactorial disorder with immunological basis. Numerous genetic and environmental factors contribute in its pathogenesis. Several genetic loci have been shown to be associated with MS risk. Among genes whose participation in MS has been evaluated is Ecotropic Viral Integration Site 5 (EVI5). EVI5 is a common site of retroviral integration with a possible role in T-cell lymphomagenesis. METHODS: In the current study, we aimed to confirm association of the single nucleotide polymorphisms (SNPs) within EVI5 gene with MS in 410 relapsing-remitting MS patients and 410 controls from Iranian population...
November 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29137176/ebv-and-apoptosis-the-viral-master-regulator-of-cell-fate
#20
REVIEW
Leah Fitzsimmons, Gemma L Kelly
Epstein-Barr virus (EBV) was first discovered in cells from a patient with Burkitt lymphoma (BL), and is now known to be a contributory factor in 1-2% of all cancers, for which there are as yet, no EBV-targeted therapies available. Like other herpesviruses, EBV adopts a persistent latent infection in vivo and only rarely reactivates into replicative lytic cycle. Although latency is associated with restricted patterns of gene expression, genes are never expressed in isolation; always in groups. Here, we discuss (1) the ways in which the latent genes of EBV are known to modulate cell death, (2) how these mechanisms relate to growth transformation and lymphomagenesis, and (3) how EBV genes cooperate to coordinately regulate key cell death pathways in BL and lymphoblastoid cell lines (LCLs)...
November 13, 2017: Viruses
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