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https://www.readbyqxmd.com/read/28069569/the-crebbp-acetyltransferase-is-a-haploinsufficient-tumor-suppressor-in-b-cell-lymphoma
#1
Jiyuan Zhang, Sofija Vlasevska, Victoria A Wells, Sarah Nataraj, Antony B Holmes, Romain Duval, Stefanie N Meyer, Tongwei Mo, Katia Basso, Paul K Brindle, Shafinaz Hussein, Riccardo Dalla-Favera, Laura Pasqualucci
Inactivating mutations of the CREBBP acetyltransferase are highly frequent in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), the two most common germinal-center (GC) derived cancers. However, the role of CREBBP inactivation in lymphomagenesis remains unclear. Here we show that CREBBP regulates enhancer/super-enhancer networks with central roles in GC/post-GC cell fate decisions, including genes involved in signal transduction by the B-cell receptor and CD40 receptor, transcriptional control of GC and plasma cell development, and antigen presentation...
January 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28062671/targeting-hdac3-in-crebbp-mutant-lymphomas-counterstrikes-unopposed-enhancer-deacetylation-of-b-cell-signaling-and-immune-response-genes
#2
Uta E Höpken
The cellular phenotype of B-cell lymphomas arising from B cells undergoing germinal center reactions, such as follicular lymphoma and diffuse large B-cell lymphoma, is strongly shaped by mutations in chromatin-modifying genes. The work presented by Jiang and colleagues addresses how somatic mutations in CREBBP disable acetylation and cause unopposed deacetylation by BCL6/SMRT/HDAC3 complexes on enhancers of B-cell signaling and immune response genes. This opens a therapeutic avenue toward targeted inhibition of CREBBP-mutant lymphomas by HDAC inhibitors...
January 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28052023/spermatogonial-stem-cells-and-progenitors-are-refractory-to-reprogramming-to-pluripotency-by-the-transcription-factors-oct3-4-c-myc-sox2-and-klf4
#3
Sébastien Corbineau, Bruno Lassalle, Maelle Givelet, Inès Souissi-Sarahoui, Virginie Firlej, Paul Henri Romeo, Isabelle Allemand, Lydia Riou, Pierre Fouchet
The male germinal lineage, which is defined as unipotent, produces sperm through spermatogenesis. However, embryonic primordial germ cells and postnatal spermatogonial stem cells (SSCs) can change their fate and convert to pluripotency in culture when they are not controlled by the testicular microenvironment. The mechanisms underlying these reprogramming processes are poorly understood. Testicular germ cell tumors, including teratoma, share some molecular characteristics with pluripotent cells, suggesting that cancer could result from an abnormal differentiation of primordial germ cells or from an abnormal conversion of SCCs to pluripotency in the testis...
December 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/28040262/environmental-impact-of-estrogens-on-human-animal-and-plant-life-a-critical-review
#4
REVIEW
Muhammad Adeel, Xiaoming Song, Yuanyuan Wang, Dennis Francis, Yuesuo Yang
BACKGROUND: Since the inception of global industrialization, steroidal estrogens have become an emerging and serious concern. Worldwide, steroid estrogens including estrone, estradiol and estriol, pose serious threats to soil, plants, water resources and humans. Indeed, estrogens have gained notable attention in recent years, due to their rapidly increasing concentrations in soil and water all over the world. Concern has been expressed regarding the entry of estrogens into the human food chain which in turn relates to how plants take up and metabolism estrogens...
December 28, 2016: Environment International
https://www.readbyqxmd.com/read/28008151/tonsillar-cd56brightnkg2a-nk-cells-restrict-primary-epstein-barr-virus-infection-in-b-cells-via-ifn-%C3%AE
#5
Aurelia Jud, Monika Kotur, Christoph Berger, Claudine Gysin, David Nadal, Anna Lünemann
Natural killer (NK) cells constitute the first line of defense against viruses and cancers cells. Epstein-Barr virus (EBV) was the first human virus to be directly implicated in carcinogenesis, and EBV infection is associated with a broad spectrum of B cell lymphomas. How NK cells restrict EBV-associated oncogenesis is not understood. Here, we investigated the efficacies and mechanisms of distinct NK cell subsets from tonsils, the portal of entry of EBV, in limiting EBV infection in naïve, germinal center-associated and memory B cells...
December 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/28003273/ebi2-overexpression-in-mice-leads-to-b1-b-cell-expansion-and-chronic-lymphocytic-leukemia-cll-like-b-cell-malignancies
#6
Kristine Niss Arfelt, Line Barington, Tau Benned-Jensen, Valentina Kubale, Alexander L Kovalchuk, Viktorija Daugvilaite, Jan Pravsgaard Christensen, Allan Randrup Thomsen, Kristoffer L Egerod, Maria R Bassi, Katja Spiess, Thue W Schwartz, Hongsheng Wang, Herbert C Morse, Peter J Holst, Mette M Rosenkilde
Human and mouse chronic lymphocytic leukemia (CLL) develop from CD5+ B cells that in mice and macaques are known to define the distinct B1a B cell lineage. B1a cells are characterized by lack of germinal center development and the B1a cell population is increased in mice with reduced germinal center formation. As a major mediator of follicular B cell migration, the G protein-coupled receptor (GPCR) Epstein Barr virus-induced gene 2 (EBI2 or GPR183) directs B cell migration in the lymphoid follicles in response to its endogenous ligands, oxysterols...
December 21, 2016: Blood
https://www.readbyqxmd.com/read/27992986/-effect-of-genetics-epigenetics-and-variations-in-the-transcriptional-expression-of-cadherin-e-in-breast-cancer-susceptibility
#7
Andrés Felipe Aristizábal-Pachón, Catarina Satie Takahashi
INTRODUCTION: Cadherin-E (CDH1) is an important regulator of epithelial-mesenchymal transition, invasion and metastasis in many carcinomas. However, germinal epimutations and mutations effect in breast cancer susceptibility is not clear. OBJECTIVE: To evaluate rs334558 polymorphism, promoter methylation status and CDH1 expression profile in breast cancer patients. MATERIALS AND METHODS: We collected peripheral blood samples from 102 breast cancer patients and 102 healthy subjects...
December 1, 2016: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/27902597/whole-exome-sequencing-of-independent-lung-adenocarcinoma-lung-squamous-cell-carcinoma-and-malignant-peritoneal-mesothelioma-a-case-report
#8
Irene Vanni, Simona Coco, Silvia Bonfiglio, Davide Cittaro, Carlo Genova, Federica Biello, Marco Mora, Valeria Rossella, Maria Giovanna Dal Bello, Anna Truini, Barbara Banelli, Dejan Lazarevic, Angela Alama, Erika Rijavec, Giulia Barletta, Francesco Grossi
The presence of multiple primary tumors (MPT) in a single patient has been identified with an increasing frequency. A critical issue is to establish if the second tumor represents an independent primary cancer or a metastasis. Therefore, the assessment of MPT clonal origin might help understand the disease behavior and improve the management/prognosis of the patient.Herein, we report a 73-year-old male smoker who developed 2 primary lung cancers (adenocarcinoma and squamous cell carcinoma) and a malignant peritoneal mesothelioma (PM)...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27869446/-oncopathological-aspects-of-brca1-and-brca2-genes-inactivation-in-tumors-of-ovary-fallopian-tube-and-pelvic-peritoneum
#9
Petr Škapa, Pavel Dundr
Ovarian carcinoma represents a heterogeneous group of malignant epithelial tumors which could be divided into two fundamental groups: Type I (endometrioid carcinoma, clear cell carcinoma, low grade serous carcinoma, mucinous carcinoma and more rare seromucinous carcinoma and malignant Brenner tumor) and type II (high grade serous carcinoma - HGSC). HGSC is the most frequent ovarian carcinoma which may be etiologically linked to inactivation of tumor suppressor genes BRCA1/2 and TP53 and differs from type I carcinomas by higher aggressiveness, tendency to peritoneal spread and worse prognosis...
2016: Ceskoslovenská Patologie
https://www.readbyqxmd.com/read/27866339/recurrent-tp53-missense-mutation-in-cancer-patients-of-arab-descent
#10
Aviad Zick, Luna Kadouri, Sherri Cohen, Michael Frohlinger, Tamar Hamburger, Naama Zvi, Morasha Plaser, Eilat Avital, Shani Breuier, Firase Elian, Azzam Salah, Yael Goldberg, Tamar Peretz
Hereditary cancer comprises more than 10% of all breast cancer cases. Identification of germinal mutations enables the initiation of a preventive program that can include early detection or preventive treatment and may also have a major impact on cancer therapy. Several recurrent mutations were identified in the BRCA1/2 genes in Jewish populations however, in other ethnic groups in Israel, no recurrent mutations were identified to date. Our group established panel sequencing in cancer patients to identify recurrent, founder, and new mutations in the heterogeneous and diverse populations in Israel, We evaluated five breast cancer patients of Arab descent diagnosed with cancer before the age of 50 years and identified the previously described TP53 mutation, c...
November 19, 2016: Familial Cancer
https://www.readbyqxmd.com/read/27863842/development-of-t-follicular-helper-cells-and-their-role-in-disease-and-immune-system
#11
REVIEW
Sadegh Eivazi, Salman Bagheri, Mohammad Sadegh Hashemzadeh, Majdedin Ghalavand, Elmira Safaie Qamsari, Ruhollah Dorostkar, Maryam Yasemi
The T follicular helper cells (TFH) are a subset of CD4+ T cells specialized to regulate antibody responses. The production of these cells is associated with the dendritic cells (DCs) and B cells. TFH cells help B cells form germinal centers (GC) differentiate into memory and plasma cells (antibody-secreting cells) as humoral responses. In addition, there is strong evidence that TFH cells play a pivotal role in the development of long-lived humoral immunity. Molecular factors such as transcription factors, surface receptors, cytokine and micro RNAs are involved in the formation of TFH cells...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27803184/a-class-1-histone-deacetylase-with-potential-as-an-antifungal-target
#12
Ingo Bauer, Divyavaradhi Varadarajan, Angelo Pidroni, Silke Gross, Stefan Vergeiner, Birgit Faber, Martin Hermann, Martin Tribus, Gerald Brosch, Stefan Graessle
: Histone deacetylases (HDACs) remove acetyl moieties from lysine residues at histone tails and nuclear regulatory proteins and thus significantly impact chromatin remodeling and transcriptional regulation in eukaryotes. In recent years, HDACs of filamentous fungi were found to be decisive regulators of genes involved in pathogenicity and the production of important fungal metabolites such as antibiotics and toxins. Here we present proof that one of these enzymes, the class 1 type HDAC RpdA, is of vital importance for the opportunistic human pathogen Aspergillus fumigatus Recombinant expression of inactivated RpdA shows that loss of catalytic activity is responsible for the lethal phenotype of Aspergillus RpdA null mutants...
November 1, 2016: MBio
https://www.readbyqxmd.com/read/27799872/potential-of-cells-and-cytokines-chemokines-to-regulate-tertiary-lymphoid-structures-in-human-diseases
#13
REVIEW
Feifeng Jing, Eun Young Choi
Tertiary lymphoid structures (TLS) are ectopic lymphoid tissues involved in chronic inflammation, autoimmune diseases, transplant rejection and cancer. They exhibit almost all the characteristics of secondary lymphoid organs (SLO), which are associated with adaptive immune responses; as such, they contain organized B-cell follicles with germinal centers, distinct areas containing T cells and dendritic cells, high endothelial venules, and lymphatics. In this review, we briefly describe the formation of SLO, and describe the cellular subsets and molecular cues involved in the formation and maintenance of TLS...
October 2016: Immune Network
https://www.readbyqxmd.com/read/27781290/low-dose-radiotherapy-in-diffuse-large-b-cell-lymphoma
#14
Carlo Furlan, Vincenzo Canzonieri, Michele Spina, Mariagrazia Michieli, Anna Ermacora, Roberta Maestro, Sara Piccinin, Riccardo Bomben, Michele Dal Bo, Marco Trovo, Valter Gattei, Umberto Tirelli, Giovanni Franchin, Pietro Bulian
Low-dose radiotherapy (LDRT) given in 2 × 2 Gy is a highly effective and safe treatment for palliation of indolent lymphomas. Otherwise, very little regarding the use of LDRT for diffuse large B-cell lymphoma (DLBCL) has been investigated. We designed a phase 2 trial of LDRT in patients with DLBCL with indication for palliative radiation. Low-dose radiotherapy was administered on symptomatic areas only. Clinical response was assessed 21 days after LDRT and defined as reduction >50% of maximum diameter of the radiated lesions...
October 25, 2016: Hematological Oncology
https://www.readbyqxmd.com/read/27769169/unexpected-effects-of-different-genetic-backgrounds-on-identification-of-genomic-rearrangements-via-whole-genome-next-generation-sequencing
#15
Zhangguo Chen, Katherine Gowan, Sonia M Leach, Sawanee S Viboolsittiseri, Ameet K Mishra, Tanya Kadoishi, Katrina Diener, Bifeng Gao, Kenneth Jones, Jing H Wang
BACKGROUND: Whole genome next generation sequencing (NGS) is increasingly employed to detect genomic rearrangements in cancer genomes, especially in lymphoid malignancies. We recently established a unique mouse model by specifically deleting a key non-homologous end-joining DNA repair gene, Xrcc4, and a cell cycle checkpoint gene, Trp53, in germinal center B cells. This mouse model spontaneously develops mature B cell lymphomas (termed G1XP lymphomas). RESULTS: Here, we attempt to employ whole genome NGS to identify novel structural rearrangements, in particular inter-chromosomal translocations (CTXs), in these G1XP lymphomas...
October 21, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27752256/understanding-immune-cells-in-tertiary-lymphoid-organ-development-it-is-all-starting-to-come-together
#16
REVIEW
Gareth W Jones, David G Hill, Simon A Jones
Tertiary lymphoid organs (TLOs) are frequently observed in tissues affected by non-resolving inflammation as a result of infection, autoimmunity, cancer, and allograft rejection. These highly ordered structures resemble the cellular composition of lymphoid follicles typically associated with the spleen and lymph node compartments. Although TLOs within tissues show varying degrees of organization, they frequently display evidence of segregated T and B cell zones, follicular dendritic cell networks, a supporting stromal reticulum, and high endothelial venules...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27703207/novel-population-of-small-tumour-initiating-stem-cells-in-the-ovaries-of-women-with-borderline-ovarian-cancer
#17
Irma Virant-Klun, Martin Stimpfel
Small stem cells with diameters of up to 5 μm previously isolated from adult human ovaries indicated pluripotency and germinal lineage, especially primordial germ cells, and developed into primitive oocyte-like cells in vitro. Here, we show that a comparable population of small stem cells can be found in the ovarian tissue of women with borderline ovarian cancer, which, in contrast to small stem cells in "healthy" ovaries, formed spontaneous tumour-like structures and expressed some markers related to pluripotency and germinal lineage...
October 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27696265/role-of-the-immune-response-in-disease-progression-and-therapy-in-multiple-myeloma
#18
Susan J Lee, Ivan Borrello
Multiple myeloma (MM) is a hematologic cancer derived from malignant plasma cells within the bone marrow. Unlike most solid tumors, which originate from epithelial cells, the myeloma tumor is a plasma cell derived from the lymphoid cell lineage originating from a post-germinal B-cell. As such, the MM plasma cell represents an integral component of the immune system in terms of both antibody production and antigen presentation, albeit not efficiently. This fundamental difference has significant implications when one considers the implications of immunotherapy...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27693615/variegated-rhoa-mutations-in-human-cancers
#19
Keisuke Kataoka, Seishi Ogawa
RHOA is one of the most extensively investigated members of the Rho GTPase family of proteins and has long been implicated in malignant transformation as well as tumor invasion and metastasis. Recently, revolutionized sequencing platforms have revealed frequent RHOA mutations in a wide variety of human cancers, including angio-immunoblastic T-cell lymphoma, adult T-cell leukemia/lymphoma, germinal center B-cell lymphoma, diffuse-type gastric cancer, and other solid tumors. With their discrete positional distributions and types of amino acid substitution depending on cancer type, different RHOA mutations seem to have unique functional and biological properties...
September 29, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27693350/loss-of-the-hvem-tumor-suppressor-in-lymphoma-and-restoration-by-modified-car-t-cells
#20
Michael Boice, Darin Salloum, Frederic Mourcin, Viraj Sanghvi, Rada Amin, Elisa Oricchio, Man Jiang, Anja Mottok, Nicolas Denis-Lagache, Giovanni Ciriello, Wayne Tam, Julie Teruya-Feldstein, Elisa de Stanchina, Wing C Chan, Sami N Malek, Daisuke Ennishi, Renier J Brentjens, Randy D Gascoyne, Michel Cogné, Karin Tarte, Hans-Guido Wendel
The HVEM (TNFRSF14) receptor gene is among the most frequently mutated genes in germinal center lymphomas. We report that loss of HVEM leads to cell-autonomous activation of B cell proliferation and drives the development of GC lymphomas in vivo. HVEM-deficient lymphoma B cells also induce a tumor-supportive microenvironment marked by exacerbated lymphoid stroma activation and increased recruitment of T follicular helper (TFH) cells. These changes result from the disruption of inhibitory cell-cell interactions between the HVEM and BTLA (B and T lymphocyte attenuator) receptors...
October 6, 2016: Cell
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