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B lymphocyte and cancer

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https://www.readbyqxmd.com/read/28534499/cis-perturbation-of-cancer-drivers-by-the-htlv-1-blv-proviruses-is-an-early-determinant-of-leukemogenesis
#1
Nicolas Rosewick, Keith Durkin, Maria Artesi, Ambroise Marçais, Vincent Hahaut, Philip Griebel, Natasa Arsic, Véronique Avettand-Fenoel, Arsène Burny, Carole Charlier, Olivier Hermine, Michel Georges, Anne Van den Broeke
Human T-cell leukaemia virus type-1 (HTLV-1) and bovine leukaemia virus (BLV) infect T- and B-lymphocytes, respectively, provoking a polyclonal expansion that will evolve into an aggressive monoclonal leukaemia in ∼5% of individuals following a protracted latency period. It is generally assumed that early oncogenic changes are largely dependent on virus-encoded products, especially TAX and HBZ, while progression to acute leukaemia/lymphoma involves somatic mutations, yet that both are independent of proviral integration site that has been found to be very variable between tumours...
May 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28530155/an-oncolytic-adenovirus-encoding-decorin-and-gm-csf-inhibits-tumor-growth-in-a-colorectal-tumor-model-by-targeting-pro-tumorigenic-signals-and-via-immune-activation
#2
Zhao Liu, Yuefeng Yang, Xiaoyan Zhang, Hao Wang, Weidong Xu, Hua Wang, FengJun Xiao, Zhigang Bai, Hongwei Yao, Xuemei Ma, Lan Jin, Chu-Tse Wu, Prem Seth, Zhongtao Zhang, Lisheng Wang
In advanced and metastatic stages of colorectal cancer (CRC), reduced sensitivity to conventional strategies is still a major obstacle to successful treatments. Decorin is an important regulator in the development and progression of various cancers. To examine if CRC patients have altered decorin levels, expression of decorin and its target genes, Met and vascular endothelial growth factor A (VEGFA) were analyzed in their tumors. Compared to normal tissues, decorin expression was reduced in CRC patients' tumors, while, there were increased Met and VEGFA levels...
May 20, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28521429/b-cells-inhibit-the-antitumor-immunity-against-an-established-murine-fibrosarcoma
#3
Andrea Maglioco, Damián G Machuca, María Noel Badano, Paula Nannini, Gabriela V Camerano, Héctor Costa, Roberto Meiss, Raúl A Ruggiero, Mirta Giordano, Graciela I Dran
Despite the classic role of B cells in favoring the immune response, an inhibitory action of B lymphocytes in tumor immunity has emerged in certain studies. In methylcolanthrene-induced murine fibrosarcoma (MCC), the loss of immunogenicity and the establishment of tolerance are paralleled by systemic immune suppression and the appearance of B(+)IL-10(+) cells in tumor-draining lymph nodes. The present study aimed to assess the role of the B(+)IL-10(+) cell population in the immune evasion and tolerance induced by MCC through the depletion of B cells in mice at various times of tumor progression: Prior to or subsequent to tumor implantation...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521284/cytokine-mediated-activation-of-human-ex-vivo-expanded-v%C3%AE-9v%C3%AE-2-t-cells
#4
Eisuke Domae, Yuya Hirai, Takashi Ikeo, Seiji Goda, Yoji Shimizu
Vγ9Vδ2 T cells, the major subset of the human peripheral blood γδ T-cell, respond to microbial infection and stressed cells through the recognition of phosphoantigens. In contrast to the growing knowledge of antigen-mediated activation mechanisms, the antigen-independent and cytokine-mediated activation mechanisms of Vγ9Vδ2 T cells are poorly understood. Here, we show that interleukin (IL) -12 and IL-18 synergize to activate human ex vivo-expanded Vγ9Vδ2 T cells. Vγ9Vδ2 T cells treated with IL-12 and IL-18 enhanced effector functions, including the expression of IFN-γ and granzyme B, and cytotoxicity...
April 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28515726/comparative-analysis-of-immune-checkpoint-molecules-and-their-potential-role-in-the-transmissible-tasmanian-devil-facial-tumor-disease
#5
Andrew S Flies, Nicholas B Blackburn, Alan Bruce Lyons, John D Hayball, Gregory M Woods
Immune checkpoint molecules function as a system of checks and balances that enhance or inhibit immune responses to infectious agents, foreign tissues, and cancerous cells. Immunotherapies that target immune checkpoint molecules, particularly the inhibitory molecules programmed cell death 1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), have revolutionized human oncology in recent years, yet little is known about these key immune signaling molecules in species other than primates and rodents. The Tasmanian devil facial tumor disease is caused by transmissible cancers that have resulted in a massive decline in the wild Tasmanian devil population...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28507808/pro-necrotic-molecules-impact-local-immunosurveillance-in-human-breast-cancer
#6
Gautier Stoll, Yuting Ma, Heng Yang, Oliver Kepp, Laurence Zitvogel, Guido Kroemer
Necrosis culminates in spilling cellular content through the permeabilized plasma membrane, thereby releasing potentially immunostimulatory molecules in the pericellular space of dead cells. Accordingly, molecules involved in necroptotic signaling, such as receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and mixed lineage kinase-like (MLKL) have been found to stimulate anticancer immune responses in mouse models of chemotherapy. mRNAs encoding prominent pro-necrotic gene products (RIPK1, RIPK3, MLKL, PGAM5 and DFNA5) were correlated with immune-related metagenes in several cancer types (breast, colorectal, lung, ovary, melanoma), revealing the strongest associations in breast cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507795/digital-analysis-and-epigenetic-regulation-of-the-signature-of-rejection-in-colorectal-cancer
#7
Viktor H Koelzer, Lena Sokol, Stefan Zahnd, Lucine Christe, Heather Dawson, Martin D Berger, Daniel Inderbitzin, Inti Zlobec, Alessandro Lugli
The immune system plays a pivotal role in the development and progression of colorectal cancer (CRC). Tumor immune rejection has been previously linked to the activation of the interferon-stimulated genes (ISG) STAT1, IRF-5 and IRF-1. Specific immunoregulatory microRNAs (miRNAs) may impact the expression of these ISG in the tumor microenvironment. In this translational study, we develop a digital image analysis protocol to identify the ISG-gene expression signature and investigate miRNA expression in the immediate environment of invading cancer cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28504304/exploiting-scavenger-receptors-in-cancer-immunotherapy-lessons-from-cd5-and-sr-b1
#8
REVIEW
Marcos Vasquez, Inês Simões, Marta Consuegra-Fernández, Fernando Aranda, Francisco Lozano, Pedro Berraondo
Scavenger receptors (SRs) are structurally heterogeneous cell surface receptors characterized by their capacity to remove extraneous or modified self-macromolecules from circulation, thus avoiding the accumulation of noxious agents in the extracellular space. This scavenging activity makes SRs important molecules for host defense and homeostasis. In turn, SRs keep the activation of the steady state immune response in check, and participate as co-receptors in the priming of the effector immune responses when the macromolecules are associated with a threat that might compromise host homeostasis...
May 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28501510/surface-engineering-for-lymphocyte-programming
#9
Elana Ben-Akiva, Randall A Meyer, David R Wilson, Jordan J Green
The once nascent field of immunoengineering has recently blossomed to include approaches to deliver and present biomolecules to program diverse populations of lymphocytes to fight disease. Building upon improved understanding of the molecular and physical mechanics of lymphocyte activation, varied strategies for engineering surfaces to activate and deactivate T-Cells, B-Cells and natural killer cells are in preclinical and clinical development. Surfaces have been engineered at the molecular level in terms of the presence of specific biological factors, their arrangement on a surface, and their diffusivity to elicit specific lymphocyte fates...
May 10, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28500490/effects-of-definitive-and-salvage-radiotherapy-on-the-distribution-of-lymphocyte-subpopulations-in-prostate-cancer-patients
#10
Eva K Sage, Thomas E Schmid, Hans Geinitz, Mathias Gehrmann, Michael Sedelmayr, Marciana N Duma, Stephanie E Combs, Gabriele Multhoff
BACKGROUND: Radiotherapy (RT) is an established treatment for patients with primary and recurrent prostate cancer. Herein, the effects of definitive and salvage RT on the composition of lymphocyte subpopulations were investigated in patients with prostate cancer to study potential immune effects. PATIENTS AND METHODS: A total of 33 prostate cancer patients were treated with definitive (n = 10) or salvage RT (n = 23) after biochemical relapse. The absolute number of lymphocytes and the distribution of lymphocyte subpopulations were analyzed by multiparameter flow cytometry before RT, at the end of RT, and in the follow-up period...
May 12, 2017: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/28499369/characterization-of-a-splice-site-mutation-in-the-tumor-suppressor-gene-flcn-associated-with-renal-cancer
#11
Malte P Bartram, Tripti Mishra, Nadine Reintjes, Francesca Fabretti, Hakam Gharbi, Alexander C Adam, Heike Göbel, Mareike Franke, Bernhard Schermer, Stefan Haneder, Thomas Benzing, Bodo B Beck, Roman-Ulrich Müller
BACKGROUND: Renal cell carcinoma is among the most prevalent malignancies. It is generally sporadic. However, genetic studies of rare familial forms have led to the identification of mutations in causative genes such as VHL and FLCN. Mutations in the FLCN gene are the cause of Birt-Hogg-Dubé syndrome, a rare tumor syndrome which is characterized by the combination of renal cell carcinoma, pneumothorax and skin tumors. METHODS: Using Sanger sequencing we identify a heterozygous splice-site mutation in FLCN in lymphocyte DNA of a patient suffering from renal cell carcinoma...
May 12, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28497933/scalp-block-for-glioblastoma-surgery-is-associated-with-lower-inflammatory-scores-and-improved-survival
#12
Lan Zheng, Katherine B Hagan, John Villarreal, Visesh Keerty, Jasper Chen, Juan P Cata
BACKGROUND: Regional anesthesia has anti-inflammatory effects. Recent studies suggest that regional anesthesia might improve the survival of patients with cancer. We hypothesized that the use of a scalp block (SB) during craniotomy for glioblastoma (GB) decreases the postoperative systemic and local inflammatory response and extend their survival. METHODS: This retrospective study included 119 patients with GB who underwent tumor resection. We divided patients into 2 groups based on the use of SB during surgery...
May 12, 2017: Minerva Anestesiologica
https://www.readbyqxmd.com/read/28497220/ct-p10-truxima%C3%A2-a-rituximab-biosimilar
#13
Emma D Deeks
CT-P10 (Truxima™) is the first biosimilar of the reference monoclonal anti-CD20 antibody rituximab. It is approved for use in all indications for which reference rituximab is approved, including follicular lymphoma (FL), diffuse large B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukaemia, rheumatoid arthritis (RA), granulomatosis with polyangiitis and microscopic polyangiitis. CT-P10 has similar physicochemical and pharmacodynamic properties to those of reference rituximab, and the pharmacokinetic biosimilarity of the agents has been shown in patients with RA or FL...
May 11, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28496337/immunogenicity-of-oncolytic-vaccinia-viruses-jx-gfp-and-tg6002-in-a-human-melanoma-in-vitro-model-studying-immunogenic-cell-death-dendritic-cell-maturation-and-interaction-with-cytotoxic-t-lymphocytes
#14
B Heinrich, J Klein, M Delic, K Goepfert, V Engel, L Geberzahn, M Lusky, P Erbs, X Preville, M Moehler
Oncolytic virotherapy is an emerging immunotherapeutic modality for cancer treatment. Oncolytic viruses with genetic modifications can further enhance the oncolytic effects on tumor cells and stimulate antitumor immunity. The oncolytic vaccinia viruses JX-594-GFP+/hGM-CSF (JX-GFP) and TG6002 are genetically modified by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF) or transforming 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU). We compared their properties to kill tumor cells and induce an immunogenic type of cell death in a human melanoma cell model using SK29-MEL melanoma cells...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28489849/utilizing-bmp-2-muteins-for-treatment-of-multiple-myeloma
#15
Axel Seher, Charlotte Lagler, Thorsten Stühmer, Urs Dietmar Achim Müller-Richter, Alexander Christian Kübler, Walter Sebald, Thomas Dieter Müller, Joachim Nickel
Multiple myeloma (MM) represents a haematological cancer characterized by the pathological hyper proliferation of antibody-producing B-lymphocytes. Patients typically suffer from kidney malfunction and skeletal disorders. In the context of MM, the transforming growth factor β (TGFβ) member Activin A was recently identified as a promoter of both accompanying symptoms. Because studies have shown that bone morphogenetic protein (BMP)-2-mediated activities are counteracted by Activin A, we analysed whether BMP2, which also binds to the Activin A receptors ActRII and ActRIIB but activates the alternative SMAD-1/5/8 pathway, can be used to antagonize Activin A activities, such as in the context of MM...
2017: PloS One
https://www.readbyqxmd.com/read/28482199/adar-deaminase-a-to-i-editing-of-dna-and-rna-moieties-of-rna-dna-hybrids-has-implications-for-the-mechanism-of-ig-somatic-hypermutation
#16
Edward J Steele, Robyn A Lindley
The implications are discussed of recently published biochemical studies on ADAR-mediated A-to-I DNA and RNA deamination at RNA:DNA hybrids. The significance of these data are related to previous work on strand-biased and codon-context mutation signatures in B lymphocytes and cancer genomes. Those studies have established that there are two significant strand biases at A:T and G:C base pairs, A-site mutations exceed T-site mutations (A>T) by 2.9 fold and G-site mutations exceed C-site mutations (G>C) by 1...
April 21, 2017: DNA Repair
https://www.readbyqxmd.com/read/28476198/copy-number-alterations-associated-with-acute-lymphoblastic-leukemia-in-mexican-children-a-report-from-the-mexican-inter-institutional-group-for-the-identification-of-the-causes-of-childhood-leukemia
#17
Beatriz Rosales-Rodríguez, Fernando Fernández-Ramírez, Juan Carlos Núñez-Enríquez, Ana Claudia Velázquez-Wong, Aurora Medina-Sansón, Elva Jiménez-Hernández, Janet Flores-Lujano, José Gabriel Peñaloza-González, Rosa Martha Espinosa-Elizondo, María Luisa Pérez-Saldívar, José Refugio Torres-Nava, Jorge Alfonso Martín-Trejo, Gabriela Bibiana Martínez-Morales, Vilma Carolina Bekker-Méndez, Juan Manuel Mejía-Aranguré, Haydee Rosas-Vargas
B-cell precursor acute lymphocytic leukemia (B-ALL) represents a worldwide public health issue. Particularly, Mexico is one of the countries with the highest incidence of ALL in children. Between the multiple factors involved in ALL etiology, genetic alterations are clearly one of the most relevant features. In this work, a group of 24 B-ALL patients, all negative for the four most frequent gene fusions (ETV6-RUNX1, BCR-ABL1, TCF3-PBX1 and MLL-AF4), were included in a high-resolution microarray analysis in order to evaluate genomic copy-number alterations (CNAs)...
November 2016: Archives of Medical Research
https://www.readbyqxmd.com/read/28475442/investigating-histological-aspects-of-scars-in-children
#18
I Westra, P D H M Verhaegen, H Ibrahim Korkmaz, K I Braam, G J L Kaspers, H W M Niessen, F B Niessen
OBJECTIVE: Very little is known about histological aspects of paediatric scars and the possible role of the immune system during their formation. In this study, the histology thoracic scars caused by the placement of an implantable central venous access device in children who underwent treatment for cancer was assessed. METHOD: The amount and type of collagen, the collagen orientation, the type of elastic fibres, the vascularsation, and the count of neutrophils, macrophages, and lymphocytes were analysed...
May 2, 2017: Journal of Wound Care
https://www.readbyqxmd.com/read/28474673/single-cell-rna-seq-enables-comprehensive-tumour-and-immune-cell-profiling-in-primary-breast-cancer
#19
Woosung Chung, Hye Hyeon Eum, Hae-Ock Lee, Kyung-Min Lee, Han-Byoel Lee, Kyu-Tae Kim, Han Suk Ryu, Sangmin Kim, Jeong Eon Lee, Yeon Hee Park, Zhengyan Kan, Wonshik Han, Woong-Yang Park
Single-cell transcriptome profiling of tumour tissue isolates allows the characterization of heterogeneous tumour cells along with neighbouring stromal and immune cells. Here we adopt this powerful approach to breast cancer and analyse 515 cells from 11 patients. Inferred copy number variations from the single-cell RNA-seq data separate carcinoma cells from non-cancer cells. At a single-cell resolution, carcinoma cells display common signatures within the tumour as well as intratumoral heterogeneity regarding breast cancer subtype and crucial cancer-related pathways...
May 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28471657/discovery-of-a-b-cell-lymphoma-6-protein-protein-interaction-inhibitor-by-a-biophysics-driven-fragment-based-approach
#20
Yusuke Kamada, Nozomu Sakai, Satoshi Sogabe, Koh Ida, Hideyuki Oki, Kotaro Sakamoto, Weston Lane, Gyorgy Snell, Motoo Iida, Yasuhiro Imaeda, Junichi Sakamoto, Junji Matsui
B-cell lymphoma 6 (BCL6) is a transcriptional factor that expresses in lymphocytes and regulates the differentiation and proliferation of lymphocytes. Therefore, BCL6 is a therapeutic target for autoimmune diseases and cancer treatment. This report presents the discovery of BCL6-corepressor interaction inhibitors by using a biophysics-driven fragment-based approach. Using the surface plasmon resonance (SPR)-based fragment screening, we successfully identified fragment 1 (SPR KD = 1200 μM, ligand efficiency (LE) = 0...
May 11, 2017: Journal of Medicinal Chemistry
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