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https://www.readbyqxmd.com/read/28884410/an-7-a-butyric-acid-prodrug-sensitizes-cutaneous-t-cell-lymphoma-cell-lines-to-doxorubicin-via-inhibition-of-dna-double-strand-breaks-repair
#1
Lilach Moyal, Neta Goldfeiz, Batia Gorovitz, Ada Rephaeli, Efrat Tal, Nataly Tarasenko, Abraham Nudelman, Yael Ziv, Emmilia Hodak
We previously found that the novel histone deacetylase inhibitor (HDACI) butyroyloxymethyl diethylphosphate (AN-7) had greater selectivity against cutaneous T-cell lymphoma (CTCL) than SAHA. AN-7 synergizes with doxorubicin (Dox), an anthracycline antibiotic that induces DNA breaks. This study aimed to elucidate the mechanism underlying the effect of AN-7 on Dox-induced double-strand DNA breaks (DSBs) in CTCL, MyLa and Hut78 cell lines. The following markers/assays were employed: comet assay; western blot of γH2AX and p-KAP1; immunofluorescence of γH2AX nuclear foci; Western blot of repair protein; quantification of DSBs-repair through homologous recombination...
September 8, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28853310/responses-to-romidepsin-in-patients-with-cutaneous-t-cell-lymphoma-and-prior-treatment-with-systemic-chemotherapy
#2
Madeleine Duvic, Susan E Bates, Richard Piekarz, Robin Eisch, Youn H Kim, Adam Lerner, Tadeusz Robak, Alexey Samtsov, Jürgen C Becker, William McCulloch, Joel Waksman, Sean Whittaker
Cutaneous T-cell lymphomas (CTCL) are a group of non-Hodgkin lymphomas that typically present in the skin but can progress to systemic involvement. The optimal treatment for patients who relapse from or are refractory to systemic chemotherapy remains unclear. Romidepsin is a potent, class-I selective histone deacetylase inhibitor approved for the treatment of patients with CTCL who have had ≥1 prior systemic therapy. Here, we present a subanalysis of two phase-2 trials (NCT00106431, NCT00007345) of romidepsin in patients with CTCL who had prior treatment with systemic chemotherapy...
August 30, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28845954/phototherapy-of-mycosis-fungoides
#3
Franz Trautinger
Mycosis fungoides (MF), the most common variant of among cutaneous T cell lymphomas (CTCL), is characterised in its early stages by clonal proliferation of malignant T-cells in the skin manifesting as erythematous patches and plaques with a chronic course and progression to cutaneous tumors and extracutaneous organs in some patients. Skin directed therapies (SDT) are primarily used for effective palliation in early stage disease. Phototherapy with ultraviolet A radiation combined with 8-methoxypsoralen (PUVA) and with ultraviolet B radiation (UVB) has a longstanding history in the treatment of MF and are highly effective in inducing remissions...
July 28, 2017: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/28842936/a-single-center-phase-ii-study-of-ixazomib-in-patients-with-relapsed-or-refractory-cutaneous-or-peripheral-t-cell-lymphomas
#4
Philip S Boonstra, Avery Polk, Noah Brown, Alexandra C Hristov, Nathanael G Bailey, Mark S Kaminski, Tycel Phillips, Sumana Devata, Tera Mayer, Ryan A Wilcox
The transcription factor GATA-3, highly expressed in many cutaneous and peripheral T-cell lymphomas, confers resistance to chemotherapy in a cell-autonomous manner. As GATA-3 is transcriptionally regulated by NF-κB, we sought to determine the extent to which proteasomal inhibition impairs NF-κB activation and GATA-3 expression and cell viability in malignant T cells. Proteasome inhibition, NF-κB activity, GATA-3 expression, and cell viability were examined in patient-derived cell lines and primary T-cell lymphoma specimens ex vivo treated with the oral proteasome inhibitor ixazomib...
August 26, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28829215/monoclonal-antibodies-against-cutaneous-t-cell-lymphomas
#5
Mauro Alaibac
Cutaneous T-cell lymphomas (CTCLs) comprise of a group of rare and heterogeneous skin lymphoproliferative disorders derived from skin resident T cells. Treatment of CTCLs is based on skin-directed approaches and/or systemic therapies. Advanced CTCLs are difficult to treat with the currently available treatments as they generally fail to obtain prolonged clinical remission. Recent studies concerning the pathogenetic mechanisms that are operative in CTCL have provided additional potential therapeutic targets for the treatment of these disorders...
August 28, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28805086/brentuximab-vedotin-therapy-for-cd30-positive-cutaneous-t-cell-lymphoma-a-targeted-approach-to-management
#6
Julia J Scarisbrick
CD30-positive primary cutaneous T-cell lymphoma (CTCL) includes mycosis fungoides, anaplastic large-cell lymphoma and lymphomatoid papulosis type A. Brentuximab vedotin (BV) consists of an antibody targeting CD30 with a protease-cleavable linker to vedotin. CD30 binding allows internalization of BV inducing cell-cycle arrest and apoptosis. Response rates >75% with manageable adverse effects in refractory Hodgkin lymphoma and systemic anaplastic large-cell lymphoma led to accelerated approval for both. Phase II studies in CD30-expressing CTCL followed and showed similar efficacy, which was ratified in a Phase III trial of BV versus physician's choice (methotrexate or bexarotene) showing significant improved responses without increase in severe adverse effects although peripheral neuropathy is frequent...
August 14, 2017: Future Oncology
https://www.readbyqxmd.com/read/28795194/-treatment-of-rare-cutaneous-t%C3%A2-cell-lymphoma-and-blastic-plasmacytoid-dendritic-cell-neoplasm
#7
REVIEW
U Wehkamp, M Weichenthal
Among the group of primary cutaneous lymphomas several subtypes have very low incidence rates. Based on the revision of the WHO classification for lymphoid neoplasms (2016), an overview of rare cutaneous T‑cell lymphoma (CTCL) subtypes is given and therapeutic approaches are detailed. The prognosis of the different subtypes is highly variable underlining the importance of adequate stage and subtype adapted treatment. In cases of indolent subtypes topical treatment, e. g. topical corticosteroids or UV phototherapy are often sufficient...
August 9, 2017: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
https://www.readbyqxmd.com/read/28770285/-treatment-of-mycosis-fungoides-and-s%C3%A3-zary-syndrome
#8
REVIEW
J P Nicolay, C Assaf
Adequate therapeutic management of cutaneous T-cell lymphoma (CTCL) requires the identification of the exact CTCL stage and entity within the current WHO classification. There is no curative therapy for CTCL yet, so that treatment currently aims at improving symptoms and quality of life as well as reducing relapse rates. The treatment has to be stage-adapted. Therapeutic options comprise skin-directed as well as systemic treatment. In early stages, phototherapy and local steroids are the first-line therapeutic options...
August 2, 2017: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
https://www.readbyqxmd.com/read/28762479/brentuximab-vedotin-in-cd30-primary-cutaneous-t-cell-lymphomas-a-review-and-analysis-of-existing-data
#9
Tyler H Enos, Lawrence S Feigenbaum, Heather W Wickless
BACKGROUND: The utility of brentuximab vedotin (BV) in CD30(+) systemic lymphomas is established, however evidence for treating primary cutaneous lymphoma remains limited. This study aimed to evaluate BV in treating CD30(+) transformed mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (PC-ALCL). METHODS: A literature review was conducted, and we analyzed data from published trials and case reports obtained via search of Ovid-MEDLINE(®) and PubMed databases...
August 1, 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/28748653/oral-bexarotene-for-post-transplant-cutaneous-t-cell-lymphoma
#10
Daniel J Lewis, Simo Huang, Madeleine Duvic
Organ transplant recipients receiving immunosuppression have an increased risk of developing post-transplant lymphoproliferative diseases (PTLDs). Traditionally, PTLDs refer to Epstein-Barr virus (EBV)-induced B-cell lymphoma. However, post-transplant T-cell lymphoma may also occur and tends to have a poorer response to reduced immunosuppressive therapy. As such, additional therapy is often needed for post-transplant T-cell lymphoma, including post-transplant cutaneous T-cell lymphoma (PT-CTCL). We present only the third case of PT-CTCL occurring after liver transplantation...
July 26, 2017: Dermatologic Therapy
https://www.readbyqxmd.com/read/28729399/decitabine-priming-enhances-mucin-1-inhibition-mediated-disruption-of-redox-homeostasis-in-cutaneous-t-cell-lymphoma
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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 (CTCLs), such as Sézary 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 CTCLs. 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...
August 24, 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
#17
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
#18
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
#19
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
#20
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
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