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https://www.readbyqxmd.com/read/28062691/activating-mutations-and-translocations-in-the-guanine-exchange-factor-vav1-in-peripheral-t-cell-lymphomas
#1
Francesco Abate, Ana C da Silva-Almeida, Sakellarios Zairis, Javier Robles-Valero, Lucile Couronne, Hossein Khiabanian, S Aidan Quinn, Mi-Yeon Kim, Maria Antonella Laginestra, Christine Kim, Danilo Fiore, Govind Bhagat, Miguel Angel Piris, Elias Campo, Izidore S Lossos, Olivier A Bernard, Giorgio Inghirami, Stefano Pileri, Xosé R Bustelo, Raul Rabadan, Adolfo A Ferrando, Teresa Palomero
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas frequently associated with poor prognosis and for which genetic mechanisms of transformation remain incompletely understood. Using RNA sequencing and targeted sequencing, here we identify a recurrent in-frame deletion (VAV1 Δ778-786) generated by a focal deletion-driven alternative splicing mechanism as well as novel VAV1 gene fusions (VAV1-THAP4, VAV1-MYO1F, and VAV1-S100A7) in PTCL. Mechanistically these genetic lesions result in increased activation of VAV1 catalytic-dependent (MAPK, JNK) and non-catalytic-dependent (nuclear factor of activated T cells, NFAT) VAV1 effector pathways...
January 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28054534/long-term-outcomes-of-peripheral-blood-stem-cell-transplantation-for-38-patients-with-peripheral-t-cell-lymphoma
#2
Jian Bo, Yu Zhao, Songsong Zhang, Wenrong Hua, Shuhong Wang, Chunji Gao, Quanshun Wang, Honghua Li, Li Yu
OBJECTIVE: In this study, to investigate clinical characteristics, response, outcome, and prognosis of peripheral blood stem cell transplantation (PBSCT) for patients with peripheral T-cell lymphoma (PTCL). METHODS: This study retrospectively analyzed the efficacy of PBSCT in 38 patients with PTCL. Kaplan-Meier methods were used in survival analysis, and the Cox regression model was applied in multivariate analysis. There were ten clinical parameters were analyzed...
July 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28053548/recombinant-human-endostatin-in-combination-with-chop-regimen-for-peripheral-t-cell-lymphoma
#3
Qunling Zhang, Junning Cao, Kai Xue, Xiaojian Liu, Dongmei Ji, Ye Guo, Xiaonan Hong
Peripheral T cell lymphoma (PTCL) has a poor prognosis. Overexpression of vascular endothelial growth factor (VEGF) might contribute to the poor prognosis of PTCL and could be the target of novel therapy. The efficacy and safety of recombinant human endostatin (Endostar) in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (ECHOP) have been explored in 15 PTCL patients. The objective response rate was 80%, with 53.3% patients having achieved complete response (CR) rate. The CR rate was 100% (3/3) in angioimmunoblastic T cell lymphoma (AITL) patients compared to only 36...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28040682/t-cell-lymphoma-recent-advances-in-characterization-and-new-opportunities-for-treatment
#4
REVIEW
Carla Casulo, Owen O'Connor, Andrei Shustov, Michelle Fanale, Jonathan W Friedberg, John P Leonard, Brad S Kahl, Richard F Little, Lauren Pinter-Brown, Ranjani Advani, Steven Horwitz
Peripheral T-cell lymphomas (PTCLs) are uncommon, heterogeneous, and aggressive non-Hodgkin's lymphomas. Despite progress in the last several years resulting in a deeper understanding of PTCL biology and pathogenesis, there is currently no accepted single standard of care for newly diagnosed patients, and for those with relapsed or refractory disease, prognosis is dismal. The National Cancer Institute convened a Clinical Trials Planning Meeting to advance the national clinical trial agenda in lymphoma. The objective was to identify unmet needs specific to five major lymphoma subtypes and develop strategies to address them...
February 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28003262/defining-the-clonality-of-peripheral-t-cell-lymphomas-using-rna-seq
#5
Scott D Brown, Greg Hapgood, Christian Steidl, Andrew P Weng, Kerry J Savage, Robert A Holt
MOTIVATION: In T-cell lymphoma, malignant T cells arising from a founding clone share an identical T cell receptor (TCR) and can be identified by the over-representation of this TCR relative to TCRs from the patient's repertoire of normal T cells. Here, we demonstrate that TCR information extracted from RNA-seq data can provide a higher resolution view of peripheral T cell lymphomas (PTCLs) than that provided by conventional methods. RESULTS: For 60 subjects with PTCL, flow cytometry/FACS was used to identify and sort aberrant T cell populations from diagnostic lymph node cell suspensions...
December 21, 2016: Bioinformatics
https://www.readbyqxmd.com/read/27995879/-comparison-of-allogeneic-or-autologous-hematopoietic-stem-cell-transplant-for-high-risk-peripheral-t-cell-lymphomas
#6
Q L Wang, H W Huang, Z M Jin, X W Tang, H Y Qiu, C C Fu, Y Han, M Miao, H R Chang, A N Sun, D P Wu
Objective: To evaluate the efficacy of auto-HSCT and allo-HSCT in the treatment of high risk peripheral T cell lymphoma (PTCL). Methods: From July 2007 to July 2014, 60 cases of high risk PTCL were analyzed retrospectively. Results: All 60 patients were at high risk group (carried with IPI≥3), with a median age of 31 (12-58) years old. Of the 60 cases, 22 were PTCL-not otherwise specified (PTCL-NOS), 22 ALK negative anaplastic large cell lymphoma (ALK-negative ALCL) and 16 angioimmunoblastic T-cell lymphoma (AITL)...
November 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/27995419/t-cell-lymphoma-epidemiology-the-known-and-unknown
#7
REVIEW
Anh Phan, Rachel Veldman, Mary Jo Lechowicz
T-cell lymphoma, a collection of subtypes of Non-Hodgkin lymphoma, is a rare malignancy. The low prevalence of this disease has made it challenging to identify subtype-specific risk factors. Potential risk factors could enable us to identify high-risk patients and predict patient outcomes. Here, we report on the current epidemiologic and prognostic factors data associated with the individual subtypes both of peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL) found in large cohort and case studies...
December 2016: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/27983760/the-survival-outcome-of-patients-with-relapsed-refractory-peripheral-t-cell-lymphoma-not-otherwise-specified-and-angioimmunoblastic-t-cell-lymphoma
#8
Dai Chihara, Michelle A Fanale, Roberto N Miranda, Mansoor Noorani, Jason R Westin, Loretta J Nastoupil, Fredrick B Hagemeister, Luis E Fayad, Jorge E Romaguera, Felipe Samaniego, Francesco Turturro, Hun J Lee, Sattva S Neelapu, M Alma Rodriguez, Michael Wang, Nathan H Fowler, Richard E Davis, L Jeffrey Medeiros, Chitra Hosing, Yago L Nieto, Yasuhiro Oki
Survival outcome of patients with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL) who experience disease progression/relapse remains very poor. A total of 321 patients, newly diagnosed with PTCL-NOS (n = 180) or AITL (n = 141) between 1999 and 2015, were analysed. Failure-free survival (FFS) and overall survival (OS) were calculated from the time of first disease progression (FFS1, OS1), from second disease progression (FFS2, OS2) and from third progression (FFS3, OS3)...
December 16, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27982416/how-i-manage-peripheral-t-cell-lymphoma-not-otherwise-specified-and-angioimmunoblastic-t-cell-lymphoma-current-practice-and-a-glimpse-into-the-future
#9
REVIEW
Norbert Schmitz, Laurence de Leval
Peripheral T-cell lymphoma (PTCL), not otherwise specified (NOS) and angioimmunoblastic T-cell lymphoma (AITL) are the most frequent of more than 20 mature PTCL entities featuring a broad spectrum of morphological, immunophenotypic, molecular and clinical characteristics. Unfortunately, recent progress in understanding the (epi)genetic background of PTCL has not been met with similar advances in treatment. Thus, CHO(E)P [cyclophosphamide, doxorubicin, vincristine, and prednisone (plus etoposide)] remains standard first-line therapy...
December 16, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27981793/responses-to-romidepsin-by-line-of-therapy-in-patients-with-relapsed-or-refractory-peripheral-t-cell-lymphoma
#10
Francine Foss, Barbara Pro, H Miles Prince, Lubomir Sokol, Dolores Caballero, Steven Horwitz, Bertrand Coiffier
Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive non-Hodgkin lymphomas typically associated with poor prognosis. Most patients with PTCL receive chemotherapy as first-line treatment, but many experience rapid relapse. For patients with relapsed/refractory PTCL, responses to treatment and long-term outcomes tend to worsen with increasing lines of therapy. Romidepsin is a potent class I histone deacetylase inhibitor approved by the US Food and Drug Administration for the treatment of PTCL in patients who have received ≥1 prior therapy...
December 16, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27973709/cationic-and-neutral-rotaxanes-having-different-functional-groups-in-the-axle-molecule-and-their-coordination-to-pt-ii
#11
Gilbert Yu, Yuji Suzaki, Kohtaro Osakada
Dibenzo[24]crown-8 (DB24C8) forms rotaxanes with a linear molecule having a dialkylammonium group and a triazole group as well as with the acetylation product of the cationic axle molecule. The former cationic rotaxane is stabilized by multiple intermolecular hydrogen bonding between the NH₂+ and oxyethylene groups. The neutral rotaxane contains the macrocycle in the vicinity of the terminal aryl group. Co-conformation of both the cationic and neutral rotaxanes can be fixed by coordination of the triazole group of the axle molecule to PtCl₂(dmso)₂...
December 14, 2016: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/27943278/frequency-and-clinical-correlates-of-elevated-plasma-epstein-barr-virus-dna-at-diagnosis-in-peripheral-t-cell-lymphomas-ptcl
#12
Bradley M Haverkos, Ying Huang, Alejandro Gru, Preeti Pancholi, Aharon G Freud, Anjali Mishra, Amy S Ruppert, Robert A Baiocchi, Pierluigi Porcu
Epstein Barr virus (EBV)-encoded RNAs (EBER) in tumor tissue and cell-free plasma EBV-DNA (pEBVd) are detected in EBV-associated lymphomas. Studies have suggested that EBER+ peripheral T-cell lymphomas (PTCL) have worse prognosis but the role of EBV in these neoplasms remains unclear. pEBVd is quantitative and more easily amenable to standardization than EBER, but frequency of pEBVd detection, clinical impact, and agreement with EBER status in PTCL are unknown. We retrospectively assessed frequency of detectable pre-treatment pEBVd, presence of EBER in tumor tissue, and outcomes in 61 of 135 EBV-assessable PTCL patients...
December 10, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27935248/cisplatin-primary-complex-with-l-histidine-target-revealed-by-ir-multiple-photon-dissociation-irmpd-spectroscopy
#13
Davide Corinti, Alberto De Petris, Cecilia Coletti, Nazzareno Re, Barbara Chiavarino, Maria E Crestoni, Simonetta Fornarini
The primary complex obtained from cisplatin and l-histidine in water has been detected and isolated by electrospray ionization. The so-obtained cis-[PtCl(NH3 )2 (histidine)](+) complex has been characterized in detail by high-resolution mass spectrometry (MS), tandem MS, IR multiple photon dissociation (IRMPD) spectroscopy, and by quantum chemical calculations. The structural features revealed by IRMPD spectroscopy indicate that platinum binds to the imidazole group, which presents tautomeric forms. Thus, depending on the position of the amino acid pendant on the imidazole ring, isomeric complexes are formed that are remarkably different with respect to the ease with which they undergo fragmentation when activated either by energetic collisions or by multiple IR photon absorption...
December 9, 2016: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
https://www.readbyqxmd.com/read/27934299/interaction-of-the-hiv-ncp7-protein-with-platinum-ii-and-gold-iii-complexes-containing-tridentate-ligands
#14
Victor H F Bernardes, Yun Qu, Zhifeng Du, James Beaton, Maria D Vargas, Nicholas P Farrell
The human immunodeficiency virus (HIV) nucleocapsid protein (NCp7) plays significant roles in the virus life cycle and has been targeted by compounds that could lead to its denaturation or block its interaction with viral RNA. Herein, we describe the interactions of platinum(II) and gold(III) complexes with NCp7 and how the reactivity/affinity of potential inhibitors can be modulated by judicious choice of ligands. The interactions of [MCl(N3)](n+) (M = Pt(2+) (n = 1) and Au(3+) (n = 2); N3 = tridentate chelate ligands: bis(2-pyridylmethyl)methylamine (Mebpma, L(1)) and bis(2-pyridylmethyl)amine (bpma, L(2)) with the C-terminal zinc finger of NCp7 (ZF2) were investigated by electrospray ionization-mass spectroscopy (ESI-MS)...
November 7, 2016: Inorganic Chemistry
https://www.readbyqxmd.com/read/27928587/prognosis-of-patients-with-peripheral-t-cell-lymphoma-who-achieve-complete-response-after-chop-chop-like-chemotherapy-without-autologous-stem-cell-transplantation-as-an-initial-treatment
#15
Hideaki Kitahara, Dai Maruyama, Akiko Miyagi Maeshima, Shinichi Makita, Ken-Ichi Miyamoto, Suguru Fukuhara, Wataru Munakata, Tatsuya Suzuki, Yukio Kobayashi, Kinuko Tajima, Takashi Terauchi, Hiroaki Kurihara, Hirokazu Taniguchi, Norio Komatsu, Kensei Tobinai
Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)/CHOP-like chemotherapy has been mostly applied to patients with untreated peripheral T cell lymphoma (PTCL). Because the long-term outcome of patients with PTCL, especially those achieving complete response (CR), has not been fully elucidated, we retrospectively analyzed 78 consecutive patients initially treated with CHOP/CHOP-like chemotherapy, without high-dose chemotherapy followed by autologous stem cell transplantation (HDC/auto-SCT). Median overall and progression-free survivals in all 78 patients were 44 and 17 months, respectively, with a median follow-up of 62 months...
December 7, 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27921272/bcl6-locus-is-hypermethylated-in-angioimmunoblastic-t-cell-lymphoma
#16
Shoko Nishizawa, Mamiko Sakata-Yanagimoto, Keiichiro Hattori, Hideharu Muto, Tran Nguyen, Koji Izutsu, Kenichi Yoshida, Seishi Ogawa, Naoya Nakamura, Shigeru Chiba
BCL6, a master transcription factor for differentiation of follicular helper T (TFH) cells, is highly expressed in angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphomas (PTCL) containing tumor cells with TFH features. TET2, encoding an epigenetic regulator, is frequently mutated in AITL/PTCL. We previously reported that Tet2 knockdown mice developed T-cell lymphomas with TFH features. Hypermethylation of the Bcl6 locus followed by BCL6 upregulation was thought to be the key event for lymphoma development in mice...
December 5, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27911989/a-prospective-cohort-study-of-patients-with-peripheral-t-cell-lymphoma-in-the-united-states
#17
Steven M Horwitz, Lauren C Pinter-Brown, Steven T Rosen, Barbara Pro, Eric D Hsi, Massimo Federico, Christian Gisselbrecht, Marc Schwartz, Lisa A Bellm, Mark A Acosta, Andrei R Shustov, Ranjana H Advani, Tatyana A Feldman, Mary Jo Lechowicz, Sonali M Smith, Frederick Lansigan, Anil Tulpule, Michael D Craig, John P Greer, Brad S Kahl, Joseph W Leach, Neil Morganstein, Carla Casulo, Steven I Park, Francine M Foss
BACKGROUND: Long-term survival in patients with aggressive peripheral T-cell lymphoma (PTCL) is generally poor, and there currently is no clear consensus regarding the initial therapy used for these diseases. Herein, the authors analyzed treatment patterns and outcomes in a prospectively collected cohort of patients with a new diagnosis of nodal PTCL in the United States. METHODS: Comprehensive Oncology Measures for Peripheral T-cell Lymphoma Treatment (COMPLETE) is a prospective multicenter cohort study designed to identify the most common prevailing treatment patterns used for patients newly diagnosed with PTCL in the United States...
December 2, 2016: Cancer
https://www.readbyqxmd.com/read/27898263/genetic-alterations-affecting-gtpases-and-t-cell-receptor-signaling-in-peripheral-t-cell-lymphomas
#18
Rebecca L Boddicker, Gina L Razidlo, Andrew L Feldman
Peripheral T-cell lymphomas (PTCLs) are rare, heterogeneous tumors with poor response to standard therapy and few targeted treatments available. The identification of mutations in the T-cell receptor (TCR) signaling pathway that either directly or indirectly affect Ras- and Rho-family GTPases is an emerging theme across PTCL subtypes. This review summarizes the role of GTPases in TCR signaling and highlights the constellation of mutations in this pathway among PTCLs. In particular, focus is given to the functional impact of the mutations and opportunities for targeted therapy...
November 29, 2016: Small GTPases
https://www.readbyqxmd.com/read/27885817/serum-ferritin-level-is-a-prognostic-marker-in-patients-with-peripheral-t-cell-lymphoma
#19
S Koyama, S Fujisawa, R Watanabe, M Itabashi, D Ishibashi, Y Ishii, Y Hattori, Y Nakajima, K Motohashi, H Takasaki, R Kawasaki, C Hashimoto, E Yamazaki, H Koharazawa, S Takemura, N Tomita, R Sakai, S Motomura, H Nakajima
INTRODUCTION: The prognostic value of serum ferritin level in patients with peripheral T-cell lymphoma (PTCL) remains unknown. METHODS: We retrospectively analyzed clinical data from 78 consecutive patients with newly diagnosed PTCL that were treated with anthracycline-containing regimens between 1998 and 2011. RESULTS: The patients consisted of 50 males and 28 females with a median age of 64 years (range, 16-83 years). The subtypes of PTCL were 39 PTCL, not otherwise specified and 39 angioimmunoblastic T-cell lymphoma (AITL)...
November 24, 2016: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/27873737/erythroderma-and-non-hodgkin-t-cell-lymphoma-what-else-apart-from-mycosis-fungoides-and-s%C3%A3-zary-syndrome
#20
Alessandro Pileri, Cinzia Pellegrini, Claudio Agostinelli, Vieri Grandi, Annalisa Patrizi, Pier Luigi Zinzani, Nicola Pimpinelli
BACKGROUND: Peripheral T-cell lymphomas, not otherwise specified (PTCL-NOS), are a rare condition characterised by specific histology, nodal presentation, and a poor prognosis. In total, 10-18% of patients present with cutaneous involvement which is regarded as a poor prognostic marker. However, cutaneous PTCL-NOS lesions have been rarely reported in the literature. OBJECTIVES: We sought to describe PTCL-NOS cases characterised by erythrodermic dissemination to the skin...
November 21, 2016: European Journal of Dermatology: EJD
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