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https://www.readbyqxmd.com/read/28729399/decitabine-priming-enhances-mucin-1-inhibition-mediated-disruption-of-redox-homeostasis-in-cutaneous-t-cell-lymphoma
#1
Salvia Jain, Abigail Washington, Rebecca Karp Leaf, Parul Bhargava, Rachael A Clark, Thomas S Kupper, Dina Stroopinsky, Athalia Pyzer, Leandra Cole, Myrna Nahas, Arie Apel, Jacalyn Rosenblatt, Jon Arnason, Donald Kufe, David Avigan
Cutaneous T-cell lymphoma (CTCL) is a heterogeneous neoplasm and patients with relapsed/refractory disease exhibit resistance to standard therapies. We have previously demonstrated that the MUC1-C oncoprotein plays a critical role in protection from oxidative stress in CTCL cells. Targeting of MUC1-C with a pharmacologic inhibitor, GO-203, was associated with apoptosis in CTCL. However, disease responses were incomplete underscoring the need for combinatorial strategies that could exploit the vulnerability of CTCL cells to oxidative signals...
July 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28703284/brentuximab-vedotin-in-cd30-cutaneous-lymphoma-how-do-we-treat-how-shall-we-treat-a-review-of-the-literature
#2
REVIEW
R Stranzenbach, E Dippel, M Schlaak, R Stadler
Brentuximab vedotin is an antibody-drug conjugate that brings the antimicrotubule agent monomethyl auristatin E into CD30-expressing cells. Some prior studies could demonstrate good efficacy in cutaneous lymphomas. The standard therapeutic scheme is 1.8mg/kg every 3 weeks. Background of this work is the fact that cutaneous lymphoma has a different pathophysiology, and a dynamic other than systemic lymphoma. The objectives of this review were to get an overview of the currently used therapeutic regimen, and to check whether dose reduction or modified time intervals could benefit in a similar activity with less toxicity...
July 13, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28700333/onc201-selectively-induces-apoptosis-in-cutaneous-t-cell-lymphoma-cells-via-activating-pro-apoptotic-integrated-stress-response-and-inactivating-jak-stat-and-nf-%C3%AE%C2%BAb-pathways
#3
Xiao Ni, Xiang Zhang, Cheng-Hui Hu, Timothy Langridge, Rohinton S Tarapore, Joshua E Allen, Wolfgang Oster, Madeleine Duvic
Cutaneous T-cell lymphomas (CTCLs) are extremely symptomatic and still incurable, and more effective and less toxic therapies are urgently needed. ONC201, an imipridone compound, has shown efficacy in pre-clinical studies in multiple advanced cancers. This study was to evaluate the anti-tumor activity of ONC201 on CTCL cells. The effect of ONC201 on the cell growth and apoptosis were evaluated in CTCL cell lines (n=8) and primary CD4+ malignant T cells isolated from CTCL patients (n=5). ONC201 showed a time-dependent cell growth inhibition in all treated cell lines with a concentration range of 1...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28697338/hdac-inhibitors-finally-open-up-chromatin-accessibility-signatures-of-ctcl
#4
Christopher J Ott, Catherine J Wu
In this issue of Cancer Cell, Qu et al. describe the chromatin accessibility profiles of cutaneous T cell lymphoma, with dynamic assessments of response and resistance to histone deacetylase inhibitor therapy. Their "personal regulome" analysis framework reveals chromatin features that may be predictive of clinical response to epigenetic therapy.
July 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28694326/genomic-analysis-of-220-ctcls-identifies-a-novel-recurrent-gain-of-function-alteration-in-rltpr-p-q575e
#5
Joonhee Park, Jingyi Yang, Alexander T Wenzel, Akshaya Ramachandran, Wung J Lee, Jay C Daniels, Juhyun Kim, Estela Martinez-Escala, Nduka Amankulor, Barbara Pro, Joan Guitart, Marc L Mendillo, Jeffrey N Savas, Titus J Boggon, Jaehyuk Choi
Cutaneous T cell lymphoma (CTCL) is an incurable non-Hodgkin lymphoma of the skin-homing T cell. In early stage disease, lesions are limited to the skin, but in later stage disease, the tumor cells can escape into the blood, the lymph nodes, and at times the visceral organs. To clarify the genomic basis of CTCL, we performed genomic analysis of 220 CTCLs. Our analyses identify 55 putative driver genes, including 17 genes not previously implicated in CTCL. These novel mutations are predicted to affect chromatin (BCOR, KDM6A, SMARCB1, TRRAP), immune surveillance (CD58, RFXAP), MAPK signaling (MAP2K1, NF1), NF-κB signaling (PRKCB, CSNK1A1), PI-3-Kinase signaling (PIK3R1, VAV1), RHOA/cytoskeleton remodeling (ARHGEF3), RNA-splicing (U2AF1), T cell receptor signaling (PTPRN2, RLTPR), and T cell differentiation (RARA)...
July 10, 2017: Blood
https://www.readbyqxmd.com/read/28694325/tcr-cxcr4-signaling-stabilizes-cytokine-mrna-transcripts-via-a-prex1-rac1-pathway-implications-for-ctcl
#6
Kimberly N Kremer, Brittney A Dinkel, Rosalie M Sterner, Douglas G Osborne, Dragan Jevremovic, Karen E Hedin
As with many immunopathologically-driven diseases, the malignant T cells of cutaneous T cell lymphomas (CTCL), such as Sezary Syndrome, display aberrant cytokine secretion patterns that contribute to pathology and disease progression. Targeting this disordered release of cytokines is complicated by the changing cytokine milieu that drives the phenotypic changes of CTCL. Here, we characterize a novel signaling pathway that can be targeted to inhibit the secretion of cytokines by modulating either CXCR4 or CXCR4-mediated signaling...
July 10, 2017: Blood
https://www.readbyqxmd.com/read/28685851/risk-of-cutaneous-t-cell-lymphoma-in-patients-with-chronic-lymphocytic-leukemia-and-other-subtypes-of-non-hodgkin-lymphoma
#7
Timothy W Chang, Amy L Weaver, Tait D Shanafelt, Thomas M Habermann, Cooper C Wriston, James R Cerhan, Timothy G Call, Jerry D Brewer
BACKGROUND: Second hematologic cancers in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) are well documented and include Hodgkin lymphoma, therapy-related acute myeloid leukemia/myelodysplastic syndromes, and transformation to diffuse large B-cell lymphoma. Although cutaneous T-cell lymphoma (CTCL) has been reported in patients with CLL, the incidence and comparison to expected rates are unknown. We evaluated the incidence of CTCL among patients with CLL or other non-Hodgkin lymphoma (NHL) subtypes using data from the Surveillance, Epidemiology, and End Results (SEER) Program...
July 7, 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/28664499/romidepsin-in-japanese-patients-with-relapsed-or-refractory-peripheral-t-cell-lymphoma-a-phase-i-ii-and-pharmacokinetics-study
#8
Dai Maruyama, Kensei Tobinai, Michinori Ogura, Toshiki Uchida, Kiyohiko Hatake, Masafumi Taniwaki, Kiyoshi Ando, Kunihiro Tsukasaki, Takashi Ishida, Naoki Kobayashi, Kenichi Ishizawa, Yoichi Tatsumi, Koji Kato, Toru Kiguchi, Takayuki Ikezoe, Eric Laille, Tokihiro Ro, Hiromi Tamakoshi, Sanae Sakurai, Tomoko Ohtsu
This phase I/II multicenter study evaluated romidepsin treatment in Japanese patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL). Patients aged ≥20 years received romidepsin via a 4-h intravenous infusion on days 1, 8, and 15 of each 28-day cycle. Phase I used a 3 + 3 design to identify any dose-limiting toxicity (DLT) for regimens of romidepsin 9 and 14 mg/m(2). The primary endpoints for phase I and II were DLT and overall response rate (ORR), respectively...
June 29, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28644551/erythema-multiforme-like-lesions-in-primary-cutaneous-aggressive-cytotoxic-epidermotropic-cd8-t-cell-lymphoma-a-diagnostic-and-therapeutic-challenge
#9
Carlo Tomasini, Mauro Novelli, Daniele Fanoni, Emilio Francesco Berti
Primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma (pCAECD8+ CTCL), is an extremely rare, rapidly progressing cutaneous lymphoma, with frequent systemic involvement, first recognized as a distinct clinicopathologic entity by Berti et al in 1999. (1) As the name suggests, this entity has an aggressive behavior and exhibits marked epidermotropism on histopathologic analysis. Conventional treatment modalities for classic CTCL are often ineffective and the prognosis is poor with a median survival of 12 months...
June 23, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/28641053/the-discovery-and-development-of-romidepsin-for-the-treatment-of-t-cell-lymphoma
#10
REVIEW
Piotr Smolewski, Tadeusz Robak
Romidepsin is a potent and selective inhibitor of histone deacetylases (HDCAi). It is also the only bicyclic inhibitor to undergo clinical assessment and is considered a promising drug for the treatment of T-cell lymphomas. The cellular action of romidepsin results in enhanced histone acetylation, as well as the acetylation of other nuclear or cytoplasmic proteins, influencing cell cycle, apoptosis, and angiogenesis. In phase II studies involving patients with relapsed or refractory of cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL), romidepsin produced overall response rates (ORR) of 34-35% and 25-38%, with complete response (CR) rates of 6% and 15-18%, respectively...
August 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28638728/gene-expression-analysis-in-cutaneous-t-cell-lymphomas-ctcl-highlights-disease-heterogeneity-and-potential-diagnostic-and-prognostic-indicators
#11
Ivan V Litvinov, Michael T Tetzlaff, Philippe Thibault, Pamela Gangar, Linda Moreau, Andrew K Watters, Elena Netchiporouk, Kevin Pehr, Victor G Prieto, Elham Rahme, Nathalie Provost, Martin Gilbert, Denis Sasseville, Madeleine Duvic
Cutaneous T-Cell Lymphomas (CTCL) are rare, but potentially devastating malignancies, whose pathogenesis remains poorly elucidated. Unfortunately, currently it is not possible to predict based on the available criteria in which patients the cancer will progress and which patients will experience an indolent disease course. Furthermore, at early stages this malignancy often masquerades as psoriasis, chronic eczema or other benign inflammatory dermatoses. As a result, it takes on average 6 y to diagnose this lymphoma since its initial presentation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28625481/chromatin-accessibility-landscape-of-cutaneous-t-cell-lymphoma-and-dynamic-response-to-hdac-inhibitors
#12
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...
July 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28599078/non-lesional-atopic-dermatitis-skin-shares-similar-t-cell-clones-with-lesional-tissues
#13
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
#14
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
#15
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...
August 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28578360/cutaneous-t-cell-lymphoma-in-saudi-arabia-retrospective-single-center-review
#16
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
#17
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
#18
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
#19
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
#20
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
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