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https://www.readbyqxmd.com/read/28641053/the-discovery-and-development-of-romidepsin-for-the-treatment-of-t-cell-lymphoma
#1
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...
June 22, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28631651/follicular-variant-of-peripheral-t-cell-lymphoma
#2
Archana Lakshmanan, S Annapurneswari, Sheila Nair
Globally, peripheral T-cell lymphomas (PTCLs) constitute about 12% of all non-Hodgkin lymphomas, of which the unspecified category is the most common subtype (30%). Mostly, the unspecified category shows a diffuse pattern of involvement in the lymph nodes. However, rarely, they may show a follicular/nodular pattern mimicking a follicular lymphoma. We report a case of a follicular variant of PTCL, not otherwise specified. This case displayed a striking nodular/follicular pattern with an admixture of small (centrocyte-like) and large (centroblast-like) cells, thus mimicking a follicular lymphoma...
April 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/28631636/profiling-of-peripheral-t-cell-lymphomas-in-kerala-south-india-a-5-year-study
#3
Rekha A Nair, Jayasudha Arundhathi Vasudevan, Priya Mary Jacob, Renu Sukumaran
BACKGROUND: Peripheral T-cell lymphomas (PTCLs) are non-Hodgkin's lymphomas (NHLs) with considerable variation in incidence across the world. They show a wide variety of clinicopathological features and generally associated with poor clinical outcome. Lymphoma data from different geographic regions will definitely aid in routine clinical practice and research work. PTCLs are reported with a higher frequency in Asia as compared to Western countries. OBJECTIVE: The objective of this study was to analyze the frequency and distribution of PTCLs diagnosed in a tertiary care cancer center in Kerala...
April 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/28622960/treatment-of-peripheral-t-cell-lymphoma-in-community-settings
#4
Tatyana Feldman, Charles M Farber, Kelly Choi, Claudio Faria, Andre Goy, Jacqueline Connors, Dhakshila Paramanathan, Sukhi Kaur, Eric Schultz, Michael McGuire, Stuart L Goldberg
BACKGROUND: Peripheral T-cell lymphomas (PTCLs) represent a rare and heterogeneous group of malignancies that do not have consensus treatment recommendations. Strategies extrapolated from B-cell lymphoma have met with limited efficacy, although T-cell-specific salvage therapies have been recently developed. METHODS: To determine treatment patterns and associated outcomes in PTCL not otherwise specified (PTCL-NOS), anaplastic large T-cell lymphoma (ALCL), and angioimmunoblastic T-cell lymphoma (AITL), a retrospective analysis was undertaken at a large US community oncology network among patients treated between January 2010 and April 2015...
June 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28597542/the-efficacy-and-safety-of-gemcitabine-cisplatin-prednisone-thalidomide-versus-chop-in-patients-with-newly-diagnosed-peripheral-t-cell-lymphoma-with-analysis-of-biomarkers
#5
Ling Li, Wenjing Duan, Lei Zhang, Xin Li, Xiaorui Fu, Xinhua Wang, Jingjing Wu, Zhenchang Sun, Xudong Zhang, Yu Chang, Feifei Nan, Jiaqin Yan, Zhaoming Li, Ken H Young, Mingzhi Zhang
We compared the efficacy and safety of gemcitabine, cisplatin, prednisone and thalidomide (GDPT) with standard CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone) for patients with newly diagnosed peripheral T-cell lymphoma (PTCL) in a prospective randomized controlled and open-label clinical trial. Between July 2010 and June 2016, 103 patients were randomly allocated into two groups, of whom 52 were treated with GDPT therapy and 51 with CHOP therapy. The 2-year progression-free survival (PFS) and overall survival (OS) rates were better in the GDPT group than in the CHOP group (57% vs...
June 9, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28534565/lanthanoplatins-emissive-eu-iii-and-tb-iii-complexes-staining-nucleoli-targeted-through-pt-dna-crosslinking
#6
Khushbu Singh, Swati Singh, Payal Srivastava, Sri Sivakumar, Ashis K Patra
Two highly luminescent water-soluble heterometallic LnPt2 complexes, [{cis-PtCl(NH3)2}2Ln(L)(H2O)](NO3)2 (Ln = Eu (1), Tb (2)), have been designed for their selective nucleoli staining through formation of Pt-DNA crosslinks. The complexes showed significant cellular uptake and distinctive nucleoli localization through intrinsic emission from Eu(III) or Tb(III) observed through confocal fluorescence microscopy.
June 1, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28529614/irf4-mum1-expression-is-associated-with-poor-survival-outcomes-in-patients-with-peripheral-t-cell-lymphoma
#7
Mi Hwa Heo, Ha Young Park, Young Hyeh Ko, Won Seog Kim, Seok Jin Kim
Background: Interferon regulatory factor 4 (IRF4)/multiple myeloma oncogene-1 (MUM1) is a member of the interferon regulatory factor family of transcriptional factors. Although IRF4/MUM1 expression is associated with aggressiveness of B-cell lymphoma and multiple myeloma, the prognostic value of IRF4/MUM1 expression in peripheral T-cell lymphoma (PTCL) is unclear. Methods: We analyzed a tissue array from 69 patients diagnosed with PTCL. The expression levels of IRF4/MUM1 and associated proteins such as MYC and Ikaros were analyzed by immunohistochemistry...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28504033/salvage-chemotherapy-and-autologous-stem-cell-transplantation-for-peripheral-t-cell-lymphoma-a-subset-analysis-of-the-canadian-cancer-trials-group-ly-12-randomized-phase-3-study
#8
Tanya Skamene, Michael Crump, Kerry J Savage, Tony Reiman, John Kuruvilla, David Good, David LeBrun, Ralph M Meyer, Laurie H Sehn, Denis Soulières, Julie Stakiw, Nicole Laferriere, Stefano Luminari, Lois E Shepherd, Marina Djurfeldt, Liting Zhu, Bingshu E Chen, Annette E Hay
Peripheral T-cell lymphoma (PTCL) is a rare, heterogeneous malignancy. Of the 619 patients with relapsed and refractory (R/R) aggressive lymphoma enrolled in the Canadian Cancer Trials Group LY.12 phase 3 trial, 59 (9.5%) had PTCL. Among these, 81% had advanced stage disease, 41% had an International Prognostic Score ≥3, and 41% were refractory to primary therapy. Within the PTCL cohort, the overall response rate after two cycles of salvage chemotherapy was 36%; no difference was observed between dexamethasone, cytarabine, cisplatin (10/30, 33%), and gemcitabine, cisplatin, dexamethasone (11/29, 38%) therapy...
May 15, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28485973/unmasking-the-catalytic-activity-of-a-platinum-complex-with-a-lewis-acidic-non-innocent-antimony-ligand
#9
Di You, François P Gabbaï
With the view of developing self-activating electrophilic catalysts, we are now investigating complexes with a Lewis acidic moiety in the immediate vicinity of the transition metal center. Toward this end, we have synthesized a platinum complex in which the metal is connected to a Lewis acidic bis(triflato)stiboranyl ligand. This complex, ((o-(Ph2P)C6H4)2SbOTf2)PtCl (2), which was obtained by treatment of ((o-(Ph2P)C6H4)2SbCl2)PtCl (1) with 2 equiv of AgOTf, is surprisingly air stable. Yet, it promptly reacts with cyclohexylisocyanide to afford the dicationic chlorostibine complex [((o-(Ph2P)C6H4)2SbCl)PtCNCy](2+) ([3](2+)) as a bis-triflate salt...
May 16, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28474339/impact-of-comorbidity-on-survival-in-peripheral-t-cell-lymphomas-a-swedish-lymphoma-registry-study
#10
Fredrik Ellin, Mats Jerkeman, Jenny Törnqvist, Lars Brudin, Thomas Relander
Comorbidity impacts survival in B-cell lymphoma patients, but the influence in peripheral T-cell lymphomas (PTCLs) has been little studied. To investigate the impact of comorbidity on outcome in PTCL, we identified adult patients with newly diagnosed PTCL from 2000 to 2009 in the Swedish Lymphoma Registry. Data on comorbidity at diagnosis were retrospectively collected according to the Charlson Comorbidity Index (CCI). Comorbid conditions were present in 263 out of 694 (38%) patients. A CCI score of ≥2 was associated with inferior overall survival (OS) (hazard ratio [HR] 1...
May 5, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28466815/the-study-of-cd14-hla-dr-low-myeloid-drived-suppressor-cell-mdsc-in-peripheral-blood-of-peripheral-t-cell-lymphoma-patients-and-its-biological-function
#11
J Du, X Sun, Y Song
Peripheral T-cell lymphoma is the generic term of a group of heterogeneous disease in non-Hodgkin's lymphoma. To investigate the quantity of CD14+HLA-DR-/low MDSC and T cell subsets in peripheral blood of peripheral T cell lymphoma (PTCL) patients, and explore the biological functions of CD14+HLA-DR-/low MDSC in peripheral T-cell lymphoma. Flow cytometry was used to determine CD14+HLA-DR-/low MDSC and T cell subsets in peripheral blood of 33 peripheral T-cell lymphoma patients and 23 healthy cases; CD3 +T cells, CD14+HLA-DR-/low MDSC cells and HLA-DR+ cells were selected with magnetic activated cell sorting; Biotin-labeled micro magnetic beads (CD2 / CD3 / CD28) were used to stimulate amplification of CD3 + T cells, which were co-cultured and analyzed by flow cytometry for the effect of different concentrations of CD14+HLA-DR-/low MDSC on the proliferative activity of autologous CD3+ T cells...
March 31, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28448876/study-on-electronic-properties-thermodynamic-and-kinetic-parameters-of-the-selected-platinum-ii-derivatives-interacting-with-guanine
#12
Filip Šebesta, Jaroslav V Burda
Interaction of hydrated forms of several potential anticancer agents (PtCl2(diaminocyclohexane), trans-[PtCl2(NH3)(thiazole)], cis-[PtCl2(NH3)(piperidine)], and cis-PtCl2(NH3)(cyclohexylamine) complexes) with guanine are explored and compared with an analogous interaction of cisplatin. Basic electronic properties, binding and stabilization energies are determined and energy profiles for the aquation reaction are estimated at the B3LYP/6-311++G(2df,2pd) level of theory. It is found that the substitution reaction is an exothermic and exergonic process with ΔG slightly less negative than -20kcal/mol...
April 12, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28447074/chidamide-tablets-hdac-inhibition-to-treat-lymphoma
#13
REVIEW
Y Xu, P Zhang, Y Liu
Chidamide is the first oral subtype-selective histone deacetylase inhibitor (HDACI) approved in China as well as the first HDACI of the benzamide class approved for the treatment of relapsed and refractory peripheral T-cell lymphoma (PTCL). This review addresses detailed information regarding chidamide, including the mechanism of action, preclinical pharmacology, pharmacokinetics and metabolism, clinical studies and application, safety, drug interactions and ongoing clinical trials. Although twice-weekly chidamide monotherapy has been recommended based on the evidence from preclinical and clinical studies with tolerable toxicities, its clinical efficacy could be further increased by combination with multidrug chemotherapy or chemo-free regimens...
March 2017: Drugs of Today
https://www.readbyqxmd.com/read/28426230/photophysics-and-excited-state-properties-of-cyclometalated-iridium-iii-platinum-ii-and-iridium-iii-iridium-iii-bimetallic-complexes-bridged-by-dipyridylpyrazine
#14
Yang-Jin Cho, So-Yoen Kim, Chang Min Choi, Nam Joon Kim, Chul Hoon Kim, Dae Won Cho, Ho-Jin Son, Chyongjin Pac, Sang Ook Kang
We investigated the electrochemical and excited-state properties of 2,3-bis(2-pyridyl)pyrazine (dpp)-bridged bimetallic complexes, (L)2Ir-dpp-PtCl [1, L = 2-(4',6'-difluorophenyl)pyridinato-N,C(2) (dfppy); 2, L = 2-phenylpyridinato-N,C(2) (ppy)] and [(L)2Ir]2(dpp) [3, L = dfppy; 4, L = ppy] compared to monometallic complexes, (L)2Ir-dpp (5, L = dfppy; 6, L = ppy) and dpp-PtCl (dpp-Pt(II)Cl2; 7). The single-crystal X-ray crystallographic structures of 1, 3, 5, and 6 showed that 1 and 3 have approximately coplanar structures of the dpp unit, while the noncoordinated pyridine ring of dpp in 5 and 6 is largely twisted with respect to the pyrazine ring...
April 20, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28420721/phase-i-study-of-fenretinide-delivered-intravenously-in-patients-with-relapsed-or-refractory-hematologic-malignancies-a-california-cancer-consortium-trial
#15
Ann Mohrbacher, Allen S Yang, Susan Groshen, Shivaani Kummar, Martin E Gutierrez, Min H Kang, Denice Tsao-Wei, C Patrick Reynolds, Edward Newman, Barry J Maurer
A phase I study was conducted to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetics of fenretinide delivered as an intravenous emulsion in relapsed/refractory hematologic malignancies. <br /><br />Experimental Design: Fenretinide (80 - 1810 mg/m(2)/day) was administered by continuous infusion on Days 1 - 5, in 21-day cycles, using an accelerated titration design. <br /><br />Results: Twenty-nine patients, treated with a median of three prior regimens (range, 1 to 7), were enrolled and received test drug...
April 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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
#16
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/28387513/heteroleptic-cycloplatinated-n-heterocyclic-carbene-complexes-a-new-approach-to-highly-efficient-blue-light-emitters
#17
Sara Fuertes, Andrés J Chueca, Lorenzo Arnal, Antonio Martín, Umberto Giovanella, Chiara Botta, Violeta Sicilia
New heteroleptic compounds of platinum(II)-containing cyclometalated N-heterocyclic carbenes, [PtCl(R-C^C*)(PPh3)] [R-CH^C*-κC* = 3-methyl-1-(naphthalen-2-yl)-1H-imidazol-2-ylidene (R-C = Naph; 1A), 1-[4-(ethoxycarbonyl)phenyl]-3-methyl-1H-imidazol-2-ylidene (R = CO2Et; 1B), and [Pt(R-C^C*)(py)(PPh3)]PF6 (py = pyridine; R-C = Naph, 2A; R = CO2Et, 2B], have been prepared and fully characterized. All of them were obtained as the trans-(C*,PPh3) isomer in high yields. The selectivity of their synthesis has been explained in terms of the degree of transphobia (T) of pairs of ligands in trans positions...
April 7, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28382854/lymphoma-classification-in-goats
#18
Patti K Kiser, Christiane V Löhr
Lymphoma has been described in individual cases for goats but not systematically characterized in a larger cohort. This study aimed to subtype caprine lymphoma based on topographic and subgross distribution, immunophenotype, and cellular morphology following the World Health Organization classification system for hematopoietic tumors in domestic animals. Fifteen caprine lymphoma cases were assessed with 6 submitted as biopsy and 9 for postmortem examination. Goats were predominantly young adult (median 3 years) and dwarf breeds (Pygmy and Pygora)...
July 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28375859/primary-cutaneous-follicular-helper-t-cell-lymphoma-a-case-series-and-review-of-the-literature
#19
James Y Wang, Giang Huong Nguyen, Jia Ruan, Cynthia M Magro
Primary cutaneous follicular helper T-cell (Tfh) lymphoma is a recently described variant of peripheral T-cell lymphoma-not otherwise specified. This particular variant, usually presenting as a sudden onset of multiple plaques and nodules, is characterized by tumoral atypical T cells that express an array of Tfh markers, such as inducible T-cell costimulator, Bcl-6, CXCL13, PD-1, and CD10. The authors now present 3 patients whose known clinical skin findings are consistent with PTCL of Tfh origin (PTCL-Tfh)...
May 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28340883/novel-agents-in-the-treatment-of-relapsed-or-refractory-peripheral-t-cell-lymphoma
#20
REVIEW
Enrica Marchi, Alexander G Raufi, Owen A O'Connor
Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of mature T-cell malignancies associated with exceptionally poor prognoses. Currently, chemotherapy remains the standard of care, but outcomes are suboptimal, with 5-year survival rates ranging from 15% to 25%. In recent years, several novel agents, including pralatrexate, romidepsin, belinostat, and brentuximab vedotin, have been approved for the treatment of relapsed/refractory PTCL. In addition, numerous other therapies with different mechanisms of action and targets are currently under investigation...
April 2017: Hematology/oncology Clinics of North America
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