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https://www.readbyqxmd.com/read/28714680/correction-to-discovery-of-pyrazolo-1-5-a-pyrimidine-b-cell-lymphoma-6-bcl6-binders-and-optimization-to-high-affinity-macrocyclic-inhibitors
#1
William McCoull, Roman D Abrams, Erica Anderson, Kevin Blades, Peter Barton, Matthew Box, Jonathan Burgess, Kate Byth, Qing Cao, Claudio Chuaqui, Rodrigo J Carbajo, Tony Cheung, Erin Code, Andrew D Ferguson, Shaun Fillery, Nathan O Fuller, Eric Gangl, Ning Gao, Matthew Grist, David Hargreaves, Martin R Howard, Jun Hu, Paul D Kemmitt, Jennifer E Nelson, Nichole O'Connell, D Bryan Prince, Piotr Raubo, Philip B Rawlins, Graeme R Robb, Junjie Shi, Michael J Waring, David Whittaker, Marta Wylot, Xiahui Zhu
No abstract text is available yet for this article.
July 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28712322/is-now-the-time-for-molecular-driven-therapy-for-diffuse-large-b-cell-lymphoma
#2
Alice Di Rocco, Federico De Angelis, Michela Ansuinelli, Robin Foà, Maurizio Martelli
Recent genetic and molecular discoveries regarding alterations in diffuse large B-cell lymphoma (DLBCL) deeply changed the approach to this lymphoproliferative disorder. Novel additional predictors of outcomes and new therapeutic strategies are being introduced to improve outcomes. Areas covered: This review aims to analyse the recent molecular discoveries in DLBCL, the rationale of novel molecular driven treatments and their impact on DLBCL prognosis, especially in ABC-DLBCL and High Grade B Cell Lymphoma...
July 17, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28711572/emerging-strategies-in-treating-double-hit-lymphomas
#3
REVIEW
Chadi Nabhan, Anthony R Mato
Double hit lymphomas (DHLs) are a new category in the World Health Organization newest classification for lymphoid malignancies. DHL encompasses various histologies of lymphomas where the MYC oncogene and either BCL2 or BCL6 oncogenes are present concomitantly. Several observational studies and retrospective series have demonstrated that patients with DHL carry a poor prognosis and respond less and for a shorter duration to standard R-CHOP (rituximab, cyclophosphamide, vincristine, adriamycin, and prednisone)...
June 21, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28710097/germinal-centres-in-diagnostic-labial-gland-biopsies-of-patients-with-primary-sj%C3%A3-gren-s-syndrome-are-not-predictive-for-parotid-malt-lymphoma-development
#4
Erlin A Haacke, Bert van der Vegt, Arjan Vissink, Fred K L Spijkervet, Hendrika Bootsma, Frans G M Kroese
OBJECTIVE: Patients with primary Sjögren's syndrome (pSS) have an increased risk of developing non-Hodgkin's lymphoma (NHL), particularly parotid gland mucosa-associated lymphoid tissue (MALT) lymphomas. Presence of germinal centres (GCs) in labial gland biopsies has been suggested as predictive factor for NHL. We assessed whether presence of GCs is increased in labial gland biopsies from patients with pSS who developed parotid MALT lymphoma, the dominant NHL-subtype in pSS, compared with patients with pSS who did not develop lymphoma...
July 14, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28694329/feminization-of-male-mouse-liver-by-persistent-growth-hormone-stimulation-activation-of-sex-biased-transcriptional-networks-and-dynamic-changes-in-chromatin-states
#5
Dana Lau-Corona, Alexander Suvorov, David J Waxman
Sex-dependent pituitary GH secretory profiles--pulsatile in males and persistent in females--regulate sex-biased, STAT5-dependent expression of hundreds of genes in mouse liver, imparting sex differences in hepatic drug/lipid metabolism and disease risk. Here we examine transcriptional and epigenetic changes induced by continuous-GH infusion (cGH) in male mice, which rapidly feminizes the temporal profile of liver STAT5 activity. cGH repressed 86% of male-biased genes and induced 68% of female-biased genes within 4-days; however, several highly female-specific genes showed weak or no feminization, even after 14-days cGH...
July 10, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28688665/b-cells-in-tertiary-lymphoid-structures-are-associated-with-favorable-prognosis-in-gastric-cancer
#6
Chie Sakimura, Hiroaki Tanaka, Takahiro Okuno, Soichiro Hiramatsu, Kazuya Muguruma, Kosei Hirakawa, Hideki Wanibuchi, Masaichi Ohira
BACKGROUND: The role of tumor-infiltrating B cells in the tumor microenvironment is still unclear. Recent studies have reported that B cells and tertiary lymphoid structures (TLSs) that contain B cell follicles correlate with the favorable prognosis of cancer patients. The aim of this study was to investigate the association between tumor-infiltrating B cells and clinicopathological features in gastric cancer. METHODS: Tumor blocks were obtained from 226 patients with stage Ib to stage IV gastric cancer...
July 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28671040/high-expressions-of-bcl6-and-lewis-y-antigen-are-correlated-with-high-tumor-burden-and-poor-prognosis-in-epithelial-ovarian-cancer
#7
Liancheng Zhu, Huilin Feng, Shan Jin, Mingzi Tan, Song Gao, Huiyu Zhuang, Zhenhua Hu, Huimin Wang, Zuofei Song, Bei Lin
Aberrant regulation of BCL6 plays crucial oncogenic roles in various malignant tumors; howbeit, the function of BCL6 in tumorigenesis of ovarian cancer remains unclear. The aim of this study is to investigate the role of BCL6 in ovarian cancer. The methods of immunohistochemical staining, quantitative real-time polymerase chain reaction, immunocytochemical staining, and gene expression profile enrichment analysis were performed to identify the possible role of BCL6 in ovarian cancer. We observed that the expression of BCL6 was significantly higher in ovarian cancer tissues and correlated with higher tumor burden including advanced International Federation of Gynecology and Obstetrics stages, poor differentiation, Type II ovarian cancer, the presence of >1 cm residual tumor size, and appearance of recurrence or death (all p < 0...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28669662/characterization-and-functional-analysis-of-the-paralichthys-olivaceus-prdm1-gene-promoter
#8
Peizhen Li, Bo Wang, Dandan Cao, Yuezhong Liu, Quanqi Zhang, Xubo Wang
PR domain containing protein 1 (Prdm1) is a transcriptional repressor identified in various species and plays multiple important roles in immune response and embryonic development. However, little is known about the transcriptional regulation of the prdm1 gene. This study aims to characterize the promoter of Paralichthys olivaceus prdm1 (Po-prdm1) gene and determine the regulatory mechanism of Po-prdm1 expression. A 2000bp-long 5'-flanking region (translation initiation site designated as +1) of the Po-prdm1 gene was isolated and characterized...
June 29, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/28665415/cryptic-t-3-8-q27-q24-and-or-myc-bcl6-linkage-associated-with-myc-expression-by-immunohistochemistry-is-frequent-in-multiple-hit-b-cell-lymphomas
#9
H Ohno, M Nakagawa, C Kishimori, K Fukutsuka, G Honjo
No abstract text is available yet for this article.
June 30, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28659758/chronic-oxidative-stress-mitochondrial-dysfunction-nrf2-activation-and-inflammation-in-the-hippocampus-accompany-heightened-systemic-inflammation-and-oxidative-stress-in-an-animal-model-of-gulf-war-illness
#10
Geetha A Shetty, Bharathi Hattiangady, Dinesh Upadhya, Adrian Bates, Sahithi Attaluri, Bing Shuai, Maheedhar Kodali, Ashok K Shetty
Memory and mood dysfunction are the key symptoms of Gulf war illness (GWI), a lingering multi-symptom ailment afflicting >200,000 veterans who served in the Persian Gulf War-1. Research probing the source of the disease has demonstrated that concomitant exposures to anti-nerve gas agent pyridostigmine bromide (PB), pesticides, and war-related stress are among the chief causes of GWI. Indeed, exposures to GWI-related chemicals (GWIR-Cs) and mild stress in animal models cause memory and mood impairments alongside reduced neurogenesis and chronic low-level inflammation in the hippocampus...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28656528/chitinase-3-like-1-deficient-splenocytes-deteriorated-the-pathogenesis-of-acute-graft-versus-host-disease-via-regulating-differentiation-of-tfh-cells
#11
Zengyao Li, Hao Lu, Jian Gu, Jing Liu, Qin Zhu, Yunjie Lu, Xuehao Wang
Acute graft-versus-host disease (aGVHD) is an intractable complication in transplant patients, limiting the efficacy of this therapy. Chitinase 3-like-1 (CHI3L1), a member of the glycosyl hydrolase 18 family that lacks chitinase activity, plays a critical role in a variety of inflammatory diseases. Here, we investigated the in vitro and in vivo effects of CHI3L1 on the development of aGVHD. In this study, mixed lymphocyte reactions (MLR) in vitro showed that CHI3L1 deficiency in CD4(+) T cell promoted the production of interferon (IFN)-γ and T follicular helper (Tfh)-related cytokines such as interleukin-6 (IL-6) and interleukin-21 (IL-21)...
June 27, 2017: Inflammation
https://www.readbyqxmd.com/read/28652395/differential-requirements-for-tcf1-long-isoforms-in-cd8-and-cd4-t-cell-responses-to-acute-viral-infection
#12
Jodi A Gullicksrud, Fengyin Li, Shaojun Xing, Zhouhao Zeng, Weiqun Peng, Vladimir P Badovinac, John T Harty, Hai-Hui Xue
In response to acute viral infection, activated naive T cells give rise to effector T cells that clear the pathogen and memory T cells that persist long-term and provide heightened protection. T cell factor 1 (Tcf1) is essential for several of these differentiation processes. Tcf1 is expressed in multiple isoforms, with all isoforms sharing the same HDAC and DNA-binding domains and the long isoforms containing a unique N-terminal β-catenin-interacting domain. In this study, we specifically ablated Tcf1 long isoforms in mice, while retaining expression of Tcf1 short isoforms...
June 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28648593/myc-rearranged-lymphomas-other-than-burkitt-comparison-between-r-chop-and-burkitt-type-immunochemotherapy
#13
Maria Joao Baptista, Gustavo Tapia, José-Ángel Hernández-Rivas, Alejandra Martínez-Trillos, José-Luis Mate, José-Tomás Navarro
BACKGROUND AND OBJECTIVE: MYC-rearranged (MYC-R) lymphomas other than Burkitt lymphoma (BL) are very aggressive, with poor prognosis when treated with standard regimens. We aimed to study the characteristics and outcome of a series of MYC-R lymphomas comparing the treatment results between R-CHOP based and a specific intensive regimen for BL (BURKIMAB). PATIENTS AND METHODS: Retrospective study of patients diagnosed with MYC-R. Translocations of MYC, BCL2 and BCL6 were evaluated by fluorescent in situ hybridization...
June 22, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28628241/aberrant-expression-of-cd10-and-bcl6-in-mantle-cell-lymphoma
#14
Marco Pizzi, Claudio Agostinelli, Simona Righi, Anna Gazzola, Claudia Mannu, Francesca Galuppini, Matteo Fassan, Andrea Visentin, Francesco Piazza, Gianpietro C Semenzato, Massimo Rugge, Elena Sabattini
AIMS: Mantle cell lymphoma (MCL) is characterized by distinctive histologic and molecular features. Aberrant expression of BCL6 and CD10 has occasionally been reported, but the biological features of such cases are largely unknown. This study aimed to define the epidemiologic, histologic and cytogenetic characteristics of BCL6 and CD10-positive MCLs, also investigating possible biological features. METHODS AND RESULTS: 165 cases of cyclin D1 and t(11;14)(q13;q34) positive MCLs were studied for CD10 and BCL6 immunohistochemical expression which was documented in 26/165 (15...
June 19, 2017: Histopathology
https://www.readbyqxmd.com/read/28614202/further-exploration-of-the-complexities-of-large-b-cell-lymphomas-with-myc-abnormalities-and-the-importance-of-a-blastoid-morphology
#15
Erika M Moore, Nidhi Aggarwal, Urvashi Surti, Steven H Swerdlow
The 2016 World Health Organization classification recognized "high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements" (double/triple-hit lymphoma [DTHL]) and "high-grade B-cell lymphoma, not otherwise specified," which includes non-DTHL with a "blastoid" or "intermediate" cytology. Although extensively studied, many questions remain, including which cases belong in these categories, which factors mitigate their adverse prognosis, and when to perform fluorescence in situ hybridization studies...
June 13, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28610450/novel-tumor-markers-provide-improved-prediction-of-survival-after-diagnosis-of-human-immunodeficiency-virus-hiv-related-diffuse-large-b-cell-lymphoma
#16
Chun Chao, Michael J Silverberg, Lie-Hong Chen, Lanfang Xu, Otoniel Martínez-Maza, Donald I Abrams, Hongbin D Zha, Reina Haque, Jonathan Said
Existing prognostic tools for HIV + diffuse large B-cell lymphoma (DLBCL) fail to accurately predict patient outcomes. To develop a novel prognostic algorithm incorporating molecular tumor characteristics and HIV disease factors, we included 80 patients with HIV-related DLBCL diagnosed between 1996 and 2007. Immunohistochemistry staining was used to analyze the expression of 26 tumor markers. Clinical data were collected from medical records. Logistic regression and bootstrapping were used to select and assess stability of the prognostic model, respectively...
June 13, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28604718/the-transcription-factor-runx3-guards-cytotoxic-cd8-effector-t-cells-against-deviation-towards-follicular-helper-t-cell-lineage
#17
Qiang Shan, Zhouhao Zeng, Shaojun Xing, Fengyin Li, Stacey M Hartwig, Jodi A Gullicksrud, Samarchith P Kurup, Natalija Van Braeckel-Budimir, Yao Su, Matthew D Martin, Steven M Varga, Ichiro Taniuchi, John T Harty, Weiqun Peng, Vladimir P Badovinac, Hai-Hui Xue
Activated CD8(+) T cells differentiate into cytotoxic effector (TEFF) cells that eliminate target cells. How TEFF cell identity is established and maintained is not fully understood. We found that Runx3 deficiency limited clonal expansion and impaired upregulation of cytotoxic molecules in TEFF cells. Runx3-deficient CD8(+) TEFF cells aberrantly upregulated genes characteristic of follicular helper T (TFH) cell lineage, including Bcl6, Tcf7 and Cxcr5. Mechanistically, the Runx3-CBFβ transcription factor complex deployed H3K27me3 to Bcl6 and Tcf7 genes to suppress the TFH program...
August 2017: Nature Immunology
https://www.readbyqxmd.com/read/28600336/diagnosis-and-classification-of-hematologic-malignancies-on-the-basis-of-genetics
#18
Justin Taylor, Wenbin Xiao, Omar Abdel-Wahab
Genomic analysis has greatly influenced the diagnosis and clinical management of patients affected by diverse forms of hematologic malignancies. Here we review how genetic alterations define subclasses of patients with acute leukemias, myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), non-Hodgkin lymphomas and classical Hodgkin lymphoma. These include new subtypes of acute myeloid leukemia defined by mutations in RUNX1 or BCR-ABL1 translocations as well as a constellation of somatic structural DNA alterations in acute lymphoblastic leukemia...
June 9, 2017: Blood
https://www.readbyqxmd.com/read/28594133/diagnostic-value-of-stmn1-lmo2-hgal-aid-expression-and-1p36-chromosomal-abnormalities-in-primary-cutaneous-b-cell-lymphomas
#19
Evelyne Verdanet, Olivier Dereure, Céline René, Ariane Tempier, Assia Benammar-Hafidi, Mathieu Gallo, Eric Frouin, Luc Durand, Isabelle Gazagne, Valérie Costes-Martineau, Valère Cacheux, Vanessa Szablewski
INTRODUCTION: distinction between primary cutaneous follicular lymphoma (PCFL) and primary cutaneous marginal zone lymphoma (PCMZL) is challenging as clear-cut immunophenotypic and cytogenetic criteria to segregate both entities are lacking. MATERIALS AND METHODS: to better characterize PCFL and PCMZL and to define criteria helpful for the differential diagnosis, we compared expression of immunohistochemical markers (LMO2, HGAL, STMN1, AID, MNDA) and the presence of cytogenetic abnormalities previously described in nodal follicular lymphoma (BCL2 and BCL6 breaks, 1p36 chromosomal region deletion (del 1p36)) in a series of 48 cutaneous follicular and marginal zone lymphomas (CFL and CMZL)...
June 8, 2017: Histopathology
https://www.readbyqxmd.com/read/28589362/determining-the-origin-of-human-germinal-center-b-cell-derived-malignancies
#20
Marc Seifert, Ralf Küppers
Most human B cell lymphomas originate from germinal center (GC) B cells. This is partly caused by the high proliferative activity of GC B cells and the remodeling processes acting at the immunoglobulin (Ig) loci of these cells, i.e., somatic hypermutation and class-switching. Mistargeting of these processes can cause chromosomal translocations, and the hypermutation machinery may also target non-Ig genes. As somatic hypermutation is exclusively active in GC B cells, the presence of somatic mutations in rearranged IgV genes is a standard criterium for a GC or post-GC B cell origin of lymphomas...
2017: Methods in Molecular Biology
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