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https://www.readbyqxmd.com/read/28625481/chromatin-accessibility-landscape-of-cutaneous-t-cell-lymphoma-and-dynamic-response-to-hdac-inhibitors
#1
Kun Qu, Lisa C Zaba, Ansuman T Satpathy, Paul G Giresi, Rui Li, Yonghao Jin, Randall Armstrong, Chen Jin, Nathalie Schmitt, Ziba Rahbar, Hideki Ueno, William J Greenleaf, Youn H Kim, Howard Y Chang
Here, we define the landscape and dynamics of active regulatory DNA in cutaneous T cell lymphoma (CTCL) by ATAC-seq. Analysis of 111 human CTCL and control samples revealed extensive chromatin signatures that distinguished leukemic, host, and normal CD4(+) T cells. We identify three dominant patterns of transcription factor (TF) activation that drive leukemia regulomes, as well as TF deactivations that alter host T cells in CTCL patients. Clinical response to histone deacetylase inhibitors (HDACi) is strongly associated with a concurrent gain in chromatin accessibility...
June 1, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28599078/non-lesional-atopic-dermatitis-skin-shares-similar-t-cell-clones-with-lesional-tissues
#2
Patrick M Brunner, Ryan O Emerson, Christopher Tipton, Sandra Garcet, Saakshi Khattri, Israel Coats, James G Krueger, Emma Guttman-Yassky
BACKGROUND: Atopic dermatitis (AD) is characterized by robust immune activation. Various T-cell subsets, including Th2/Th22 cells, are increased in lesional and non-lesional skin. However, there is conflicting literature on the diversity of the T-cell receptor (TCR) repertoire in lesional AD, and its relation to non-lesional skin remains unclear. METHODS: We performed high-throughput deep sequencing of the β-TCR repertoire in 29 lesional and 19 non-lesional AD biopsies, compared to 6 healthy control and 6 cutaneous T-cell lymphoma (CTCL) samples from previously published cohorts...
June 9, 2017: Allergy
https://www.readbyqxmd.com/read/28597022/increased-interleukin-19-expression-in-cutaneous-t-cell-lymphoma-and-atopic-dermatitis
#3
Tomonori Oka, Makoto Sugaya, Naomi Takahashi, Rina Nakajima, Sayaka Otobe, Miyoko Kabasawa, Hiraku Suga, Tomomitsu Miyagaki, Yoshihide Asano, Shinichi Sato
Interleukin-19 (IL-19), a pro-inflammatory cytokine known to stimulate the production of T helper type 2 (Th2) cytokines, is induced by IL-17A and highly expressed in the lesional skin of psoriasis and atopic dermatitis (AD). This aim of this study was to investigate whether IL-19 is involved in cutaneous T-cell lym-phoma (CTCL) and AD. IL-19 levels were significantly higher in the sera of patients with AD and those with advanced-stage CTCL than in normal controls, correlating significantly with clinical disease markers...
June 9, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28593508/bet-bromodomain-inhibitor-jq1-decreases-cd30-and-ccr4-expression-and-proliferation-of-cutaneous-t-cell-lymphoma-cell-lines
#4
Hiroaki Kamijo, Makoto Sugaya, Naomi Takahashi, Tomonori Oka, Tomomitsu Miyagaki, Yoshihide Asano, Shinichi Sato
Bromodomain and external domain (BET) proteins regulate cell growth, proliferation, cell cycle, and differentiation in various cancers. Therefore, they have emerged as interesting targets. The effect of BET inhibitor on cutaneous T-cell lymphoma (CTCL), however, is yet to be known. Here, we examined the effect of BET inhibitor JQ1 on four cell lines (MyLa, SeAx, Hut78 and HH cells). CTCL cell lines were treated with JQ1 and cell number, cell cycle, frequency of apoptosis, and expressions of CD25, CD30 and CCR4 on the cell surface were evaluated by flow cytometry...
June 7, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28578360/cutaneous-t-cell-lymphoma-in-saudi-arabia-retrospective-single-center-review
#5
Yousef Binamer
BACKGROUND: Cutaneous T-cell lymphoma (CTCL) is an uncommon disease with various clinical presentations. The hypopigmented type is more common in individuals with a dark skin complexion. Moreover, childhood CTCL is more common in Mediterranean populations in comparison to the West. OBJECTIVE: To describe CTCL in the Saudi population. DESIGN: A retrospective collection of data on all cases of CTCL from 2010-2016. SETTING: Dermatology clinic at a tertiary center in Riyadh, Saudi Arabia...
May 2017: Annals of Saudi Medicine
https://www.readbyqxmd.com/read/28557175/psoriasis-in-patients-with-mycosis-fungoides-%C3%AE-clinicopathological-study-of-25-patients
#6
V Nikolaou, L Marinos, E Moustou, E Papadavid, A Economidi, E Christofidou, M Gerochristou, A Tasidou, E Economaki, A Stratigos, C Antoniou
BACKGROUND: It has been reported that patients with psoriasis are at increased risk for developing lymphoma including cutaneous T cell lymphomas (CTCL). However, the comorbidity and the histopathologic correlation of psoriasis and Mycosis Fungoides (MF) have been less studied. OBJECTIVE: The objective of the current study was to investigate the relation between mycosis fungoides (MF) and psoriasis. METHODS: We retrospectively reviewed and reevaluated all MF cases diagnosed and followed in a 16 year period who carried both MF and psoriasis diagnoses...
May 30, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28557110/dose-escalation-study-evaluating-pegylated-interferon-alpha-2a-in-patients-with-cutaneous-t-cell-lymphoma
#7
M Schiller, A Tsianakas, W Sterry, R Dummer, A Hinke, D Nashan, R Stadler
BACKGROUND: This open-label, multicenter, dose-escalation study evaluated the safety, tolerability, and efficacy of subcutaneous pegylated (40 kD) interferon α-2a (PEG-IFN α-2a) in patients with cutaneous T-cell lymphoma (CTCL). PATIENTS AND METHODS: PEG-IFNα-2a was administered subcutaneously at 180 (n=4), 270 (n=6), or 360 μg (n=3) once weekly for 12 weeks. Efficacy was assessed by the proportion of patients with complete response (CR) or partial response (PR)...
May 30, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28551309/ontak-like-human-il-2-fusion-toxin
#8
Zhaohui Wang, Qian Zheng, Huiping Zhang, Roderick T Bronson, Joren C Madsen, David H Sachs, Christene A Huang, Zhirui Wang
Ontak® is a FDA-approved diphtheria toxin-based recombinant fusion toxin for treatment of human CD25(+) cutaneous T cell lymphoma (CTCL). However, it has been discontinued clinically due to the production issue related to the bacterial expression system with difficult purification. Recently we have developed monovalent and bivalent human IL-2 fusion toxins targeting human CD25(+) cells using advanced unique diphtheria toxin resistant yeast Pichia Pastoris expression system. In vitro efficacy characterization using human CD25(+) HUT102/6TG cells demonstrated that both monovalent and bivalent isoforms are potent and the bivalent isoform is approximately two logs more potent than the monovalent isoform...
May 24, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28540671/multidisciplinary-management-of-mycosis-fungoides-s%C3%A3-zary-syndrome
#9
REVIEW
Sara Berg, Jennifer Villasenor-Park, Paul Haun, Ellen J Kim
PURPOSE OF REVIEW: Diagnosis and management of mycosis fungoides and Sézary syndrome (MF/SS) require accurate clinicopathological correlation and a multidisciplinary approach. We reviewed major advances in the field regarding diagnostic and prognostic tools as well as skin-directed therapies (SDTs) and systemic agents for MF/SS published in the past 2 years. RECENT FINDINGS: Improved technology (T-cell receptor high-throughput sequencing) and increased multicenter collaboration (Cutaneous Lymphoma International Consortium) have led to diagnostic/prognostic advances...
June 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28537899/nras-mutations-in-cutaneous-t-cell-lymphoma-ctcl-sensitize-tumors-towards-treatment-with-the-multikinase-inhibitor-sorafenib
#10
Michael K Kießling, Jan P Nicolay, Tabea Schlör, Claus-Detlev Klemke, Dorothee Süss, Peter H Krammer, Karsten Gülow
Therapy of cutaneous T cell lymphoma (CTCL) is complicated by a distinct resistance of the malignant T cells towards apoptosis that can be caused by NRAS mutations in late-stage patients. These mutations correlate with decreased overall survival, but sensitize the respective CTCL cells towards MEK-inhibition-induced apoptosis which represents a promising novel therapeutic target in CTCL. Here, we show that the multi-kinase inhibitor Sorafenib induces apoptosis in NRAS-mutated CTCL cells. CTCL cell lines and to a minor extent primary T cells from Sézary patients without NRAS mutations are also affected by Sorafenib-induced apoptosis suggesting a sensitizing role of NRAS mutations for Sorafenib-induced apoptosis...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28512419/successful-treatment-of-primary-cutaneous-peripheral-t-cell-lymphoma-presenting-acquired-ichthyosis-with-oral-bexarotene-monotherapy
#11
Kayo Tanita, Taku Fujimura, Yota Sato, Takanori Hidaka, Sadanori Furudate, Yumi Kambayashi, Akira Tsukada, Akira Hashimoto, Setsuya Aiba
Acquired ichthyosis (AI) is a reactive cutaneous manifestation that can be associated with malignant hematological disease, including cutaneous T-cell lymphoma (CTCL). Since it is difficult to distinguish AI from ichthyosiform mycosis fungoides, to select the treatment for CTCL with ichthyosis-like appearance and to evaluate its efficacy is sometimes challenging. In this report, we describe a case of primary cutaneous peripheral T-cell lymphoma not otherwise specified presenting AI successfully treated with oral bexarotene...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28493286/comprehensive-analysis-of-cutaneous-t-cell-lymphoma-ctcl-incidence-and-mortality-in-canada-reveals-changing-trends-and-geographic-clustering-for-this-malignancy
#12
Feras M Ghazawi, Elena Netchiporouk, Elham Rahme, Matthew Tsang, Linda Moreau, Steven Glassman, Nathalie Provost, Martin Gilbert, Sara-Elizabeth Jean, Kevin Pehr, Denis Sasseville, Ivan V Litvinov
BACKGROUND: Previous reports of geographic clustering of cutaneous T-cell lymphoma (CTCL) in Texas, Pittsburgh, and Sweden as well as the occurrence of CTCL in married couples and family members raise a possibility of the existence of an external and potentially preventable trigger(s) for this rare skin cancer. METHODS: The authors studied CTCL incidence and mortality in Canada using 3 distinct population-based cancer databases. Data on patients' sex, age at the time of diagnosis, subtype of CTCL malignancy, reporting province, city, and postal code were analyzed...
May 10, 2017: Cancer
https://www.readbyqxmd.com/read/28468739/a-phase-iii-study-of-lenalidomide-maintenance-after-debulking-therapy-in-patients-with-advanced-cutaneous-t-cell-lymphoma-eortc-21081-nct01098656-results-and-lessons-learned-for-future-trial-designs
#13
Martine Bagot, Baktiar Hasan, Sean Whittaker, Marie Beylot-Barry, Robert Knobler, Emad Shah, Sandrine Marreaud, Stephen Morris, Stephane Dalle, Octavio Servitje, Richard Cowan, Liisa Väkevä, Guillaume Chaby, Constanze Jonak, Christopher P Fox, Diana Ritchie, Maarten H Vermeer, Rudolf Stadler, Pablo L Ortiz Romero, Julia Scarisbrick, Pietro Quaglino
EORTC 21081 was a randomized phase III study of observation alone versus lenalidomide maintenance (25 mg po for 21 days) after debulking therapy in patients with advanced-stage cutaneous T-cell lymphomas (CTCLs). The aim was to investigate whether maintenance treatment with lenalidomide prolonged response after debulking in patients who had not been previously treated with intravenous chemotherapy. A total of 26 centres from 10 different European countries registered 30 patients with advanced CTCL. Twenty-one patients were randomized (20% of the 105 patients initially deemed necessary for the study; the study was terminated early following withdrawal of funding support from Celgene)...
May 3, 2017: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/28447489/forodesine-in-the-treatment-of-cutaneous-t-cell-lymphoma
#14
REVIEW
Daniel J Lewis, Madeleine Duvic
Cutaneous T-cell lymphoma (CTCL) is characterized by the accumulation of neoplastic CD4+ T lymphocytes in the skin. Given the lack of curative treatments for CTCL, there is a significant need for new, superior therapies. Forodesine is a transition-state analogue that inhibits purine nucleoside phosphorylase. Because it selectively targets T lymphocytes, it represents a drug of interest for the treatment of CTCL. Areas covered: Phase I/II dose-ranging studies of intravenous (IV) and oral forodesine demonstrated its activity, safety, and tolerability for refractory CTCL...
June 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28412739/retinoic-acid-receptor-alpha-drives-cell-cycle-progression-and-is-associated-with-increased-sensitivity-to-retinoids-in-t-cell-lymphoma
#15
Xueju Wang, Surendra Dasari, Grzegorz S Nowakowski, Konstantinos N Lazaridis, Eric D Wieben, Marshall E Kadin, Andrew L Feldman, Rebecca L Boddicker
Peripheral T-cell lymphomas (PTCLs) are aggressive non-Hodgkin lymphomas with generally poor outcomes following standard therapy. Few candidate therapeutic targets have been identified to date. Retinoic acid receptor alpha (RARA) is a transcription factor that modulates cell growth and differentiation in response to retinoids. While retinoids have been used to treat some cutaneous T-cell lymphomas (CTCLs), their mechanism of action and the role of RARA in CTCL and other mature T-cell lymphomas remain poorly understood...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405495/biological-and-clinical-significance-of-tryptophan-catabolizing-enzymes-in-cutaneous-t-cell-lymphomas
#16
Pilvi Maliniemi, Kirsi Laukkanen, Liisa Väkevä, Katja Dettmer, Tuomas Lipsanen, Leila Jeskanen, Alban Bessede, Peter J Oefner, Marshall E Kadin, Annamari Ranki
Indoleamine 2,3-deoxygenase 1 (IDO1) induces immune tolerance in the tumor microenvironment (TME) and is recognized as a potential therapeutic target. We studied the expression of both IDO1 and the related tryptophan 2,3-dioxygenase (TDO) in several different subtypes of cutaneous T-cell lymphoma (CTCL), and evaluated the kynurenine (KYN) pathway in the local TME and in patient sera. Specimens from the total of 90 CTCL patients, including mycosis fungoides (MF, n = 37), lymphomatoid papulosis (LyP, n = 36), primary cutaneous anaplastic large cell lymphoma (pcALCL, n = 4), subcutaneous panniculitis-like T-cell lymphoma (SPTCL n = 13), and 10 patients with inflammatory lichen ruber planus (LRP), were analyzed by immunohistochemistry (IHC), immunofluorescence (IF), quantitative PCR, and/or liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28400642/cd3-cd56-cd4-cd8-cd20-cd30-peripheral-t-cell-non-hodgkin-s-lymphoma-a-rare-case-report
#17
Ashish Jagati, Bela J Shah, Sonal Tibrewal, Trusha Gajjar
Cutaneous T-cell lymphoma (CTCL) commonly presents as mycosis fungoides or Sezary syndrome, both having CD4 positivity. A subset of CTCL which lacks CD4 surface marker is classified as cutaneous γ and δ-T-cell lymphoma (CGD-TCL). Because of its rarity and inability to study large number of patients, the impact of immunophenotype on the clinical outcome of primary CTCL in patients is limited. We report a case of primary CGD-TCL in a 71-year-old male because of this rarity and to emphasize its aggressive nature...
March 2017: Indian Journal of Dermatology
https://www.readbyqxmd.com/read/28400633/new-targeted-treatments-for-cutaneous-t-cell-lymphomas
#18
Martine Bagot
Cutaneous T-cell lymphomas (CTCLs) represent a group of rare and heterogeneous diseases that are very difficult to treat at advanced stages. The development of monoclonal antibodies is a new hope for the treatment of these diseases. Alemtuzumab (Campath) is a humanized IgG1 kappa monoclonal antibody specific for CD52, an antigen expressed by most T and B lymphocytes. Alemtuzumab may frequently induce long-term remissions in patients with Sezary syndrome but high-dose treatments lead to severe cytopenia, immune depletion, and opportunistic infections...
March 2017: Indian Journal of Dermatology
https://www.readbyqxmd.com/read/28395975/increased-soluble-cd226-in-sera-of-patients-with-cutaneous-t-cell-lymphoma-mediates-cytotoxic-activity-against-tumor-cells-via-cd155
#19
Naomi Takahashi, Makoto Sugaya, Hiraku Suga, Tomonori Oka, Makiko Kawaguchi, Tomomitsu Miyagaki, Hideki Fujita, Takashi Inozume, Shinichi Sato
Immune checkpoint therapy, which targets regulatory pathways in T cells to enhance antitumor immune responses, has led to important clinical advances. CD155 is expressed in various types of cancer, and this surface molecule on tumor cells functions either as a co-stimulatory molecule or a co-inhibitory molecule, depending on its receptor. CD226, a CD155 ligand, is mainly expressed on natural killer cells and CD8(+) T cells, playing important roles in natural killer cell-mediated cytotoxicity. In this study, we investigated the expression and function of CD155 and CD226 in cutaneous T-cell lymphoma (CTCL)...
April 7, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28391645/hematopoietic-stem-cell-transplantation-in-advanced-cutaneous-t-cell-lymphoma
#20
Hiroshi Saruta, Chika Ohata, Ikko Muto, Taichi Imamura, Eijiro Oku, Koichi Ohshima, Koji Nagafuji, Takekuni Nakama
We retrospectively reviewed data pertaining to five patients with cutaneous T-cell lymphoma (CTCL) who had received hematopoietic stem cell transplantation (HSCT) between 2004 and 2015 at Kurume University Hospital, along with their clinical data until March 2016. For patients with advanced CTCL eligible for HSCT, autologous HSCT was performed when they responded well to chemotherapy, and allogeneic HSCT was selected for patients with advanced mycosis fungoides (MF)/Sézary syndrome (SS) and CTCL other than MF/SS with poor chemosensitivity...
April 9, 2017: Journal of Dermatology
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