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https://www.readbyqxmd.com/read/29242879/translesion-dna-synthesis-across-double-base-lesions-derived-from-cross-links-of-an-antitumor-trinuclear-platinum-compound-primer-extension-conformational-and-thermodynamic-studies
#1
O Novakova, N P Farrell, V Brabec
Polynuclear platinum complexes represent a unique structural class of DNA-binding agents of biological significance. They contain at least two platinum coordinating units bridged by a linker, which means that the formation of double-base lesions (cross-links) in DNA is possible. Here, we show that the lead compound, bifunctional [{trans-PtCl(NH3)2}2μ-trans-Pt(NH3)2{H2N(CH2)6NH2}2]4+ (Triplatin or BBR3464), forms in DNA specific double-base lesions which affect the biophysical and biochemical properties of DNA in a way fundamentally different compared to the analogous double-base lesions formed by two adducts of monofunctional chlorodiethylenetriamineplatinum(ii) chloride (dienPt)...
December 15, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29233821/activity-of-the-pi3k-%C3%AE-%C3%AE-inhibitor-duvelisib-in-a-phase-i-trial-and-preclinical-models-of-t-cell-lymphoma
#2
Steven M Horwitz, Raphael Koch, Pierluigi Porcu, Yasuhiro Oki, Alison Moskowitz, Megan Perez, Patricia Myskowski, Adam Officer, Jacob D Jaffe, Sara N Morrow, Kerstin Allen, Mark Douglas, Howard Stern, Jennifer Sweeney, Patrick Kelly, Virginia Kelly, Jon C Aster, David Weaver, Francine M Foss, David M Weinstock
Duvelisib (IPI-145) is an oral inhibitor of phosphoinositide-3-kinase (PI3K)-δ/γ isoforms currently in clinical development. PI3K-δ/γ inhibition may directly inhibit malignant T-cell growth, making Duvelisib a promising candidate for patients with peripheral (PTCL) or cutaneous (CTCL) T-cell lymphoma. Inhibition of either isoform may also contribute to clinical responses by modulating nonmalignant immune cells. We investigated these dual effects in a TCL cohort from a Phase 1, open-label study of Duvelisib in patients with relapsed or refractory PTCL [n=16] and CTCL [n=19], along with in vitro and in vivo models of TCL...
December 12, 2017: Blood
https://www.readbyqxmd.com/read/29217426/composite-lymphoma-of-follicular-b-cell-and-peripheral-t-cell-types-with-distinct-zone-distribution-in-a-75-year-old-male-patient-a-case-study
#3
John Tanaka, Pu Su, Catherine Luedke, Rachel Jug, Lian-He Yang, Kristen Deak, Sarah Horn, Yang Zhang, Marc Delos Angeles, Yi Xie, Endi Wang
Composite lymphoma (CL) of T-/B-cell type is rare, and follicular lymphoma composite with peripheral T-cell lymphoma (PTCL) has not previously been reported. We report such a case with both neoplastic components displaying a unique zone of distribution. A 75-year-old male patient presented with generalized lymphadenopathy. Sections of axillary lymph node demonstrated potentially two clonal processes, PTCL with aberrant CD20 expression and follicular lymphoma. Interestingly, the two neoplastic components were confined to their respective classic distribution zones, with PTCL occupying the interfollicular areas and follicular lymphoma residing in follicles...
December 4, 2017: Human Pathology
https://www.readbyqxmd.com/read/29212973/-refractory-cd20-positive-peripheral-t-cell-lymphoma-showing-loss-of-cd20-expression-after-rituximab-therapy-and-gain-of-cd20-expression-after-administration-of-vorinostat-and-gemcitabine
#4
Kazuaki Teshima, Hideaki Ohyagi, Masaaki Kume, Satsuki Takahashi, Masahiro Saito, Naoto Takahashi
A 79-year-old male patient presented with systemic lymphadenopathy. A lymph node biopsy revealed effacement of the normal nodal architecture with diffuse proliferation of medium-sized atypical lymphoid cells. Southern blot analyses demonstrated rearrangement of the T-cell receptor gene but not the immunoglobulin heavy chain gene. He was diagnosed with CD20-positive peripheral T-cell lymphoma (PTCL), NOS. Although he achieved partial remission after six cycles of R-CHOP, he relapse occurred after 2 months. CD20-negative conversion was confirmed in the lymph node, which was positive for CCR4, and the skin at the time of relapse...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29194714/survival-following-salvage-therapy-for-primary-refractory-peripheral-t-cell-lymphomas-ptcl
#5
Janie Y Zhang, Robert Briski, Sumana Devata, Mark S Kaminski, Tycel J Phillips, Tera L Mayer, Nathanael G Bailey, Ryan A Wilcox
Optimal salvage therapy for primary refractory peripheral T-cell lymphomas (PTCL) and the role of hematopoietic stem cell transplant remain poorly defined. We conducted a retrospective review of clinical outcomes and prognostic factors in a single-center cohort of 93 patients with primary refractory PTCL, defined as progression during first-line therapy or relapse within 6 months of its completion. Clinical outcomes were poor in this population, with median event-free survival (EFS) of 3.5 months, median overall survival (OS) of 9...
December 1, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29190917/pretreatment-epstein-barr-virus-dna-in-whole-blood-is-a-prognostic-marker-in-peripheral-t-cell-lymphoma
#6
Yu Ri Kim, Soo-Jeong Kim, June-Won Cheong, Haerim Chung, Ji Eun Jang, Yundeok Kim, Woo-Ick Yang, Yoo Hong Min, Jin Seok Kim
Because there are few studies regarding the clinical impact of circulating EBV-DNA in peripheral T-cell lymphomas (PTCLs), we tried to evaluate the role of EBV-DNA in whole blood as a prognostic factor for PTCL. We retrospectively reviewed 110 PTCL patients with median age of 63 (20-94) years. Forty-seven patients (42.7%) showed positive results for EBV-DNA, and these patients also had stage III/IV disease, elevated lactic dehydrogenase, and low albumin level (P = 0.007, P = 0.004, P = 0.002, respectively)...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29141948/a-phase-i-study-of-romidepsin-and-pralatrexate-reveals-marked-activity-in-relapsed-and-refractory-t-cell-lymphoma
#7
Jennifer E Amengual, Renee Lichtenstein, Jennifer Lue, Ahmed Sawas, Changchun Deng, Emily Lichtenstein, Karen Khan, Laine Atkins, Aishling Rada, Hye A Kim, Codruta Chiuzan, Matko Kalac, Enrica Marchi, Lorenzo Falchi, Mark A Francescone, Lawrence Schwartz, Serge Cremers, Owen A O'Connor
The peripheral T-cell lymphomas (PTCL) are a group of rare malignancies characterized by chemotherapy insensitivity and poor prognosis. Romidepsin and pralatrexate were approved by the U.S. FDA for patients with relapsed/refractory PTCL, exhibiting response rates of 25% and 29% respectively. Based on synergy of the combination in preclinical models of PTCL, we initiated a phase I study of pralatrexate plus romidepsin in patients with relapsed/refractory lymphoma (ClinicalTrials.gov (NCT01947140)). This was a single institution dose-escalation phase I study of pralatrexate plus romidepsin designed to determine the dose limiting toxicities (DLT), maximum tolerated dose (MTD), pharmacokinetic profile and response rates...
November 15, 2017: Blood
https://www.readbyqxmd.com/read/29139160/assessing-the-ligand-properties-of-nhc-stabilized-phosphorus-i-cations
#8
Justin F Binder, Stephanie C Kosnik, Charles Lloyd Bergstrom Macdonald
The isolation and full characterization of a series of cationic metal carbonyl complexes bearing an N-heterocyclic carbene-stabilized phosphorus(I) ligand are reported. Specifically, the mononuclear coordination complexes [LM(CO)₅][BPh₄] (M = Cr, Mo, W), [LFe(CO)₄][BPh₄] and the dinuclear complexes [LMn₂(CO)₈][BPh₄] and [LCo₂(CO)₆][BPh₄], where L = [bis(1,3,4,5-tetramethylimidazol-2-ylidene)phosphanide]+, have all been isolated in the solid state and structurally confirmed by single crystal X-ray diffraction...
November 14, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29119842/outcomes-following-front-line-chemotherapy-in-peripheral-t-cell-lymphoma-10-year-experience-at-the-royal-marsden-and-the-christie-hospital
#9
Mary Gleeson, Clare Peckitt, David Cunningham, Adam Gibb, Eliza A Hawkes, Morgan Back, Binnaz Yasar, Kate Foley, Rebecca Lee, Joanna Dash, Hannah Johnson, Catherine O'Hara, Andrew Wotherspoon, Ayoma Attygalle, Lia Menasce, Patrick Shenjere, Mike Potter, Mark E Ethell, Claire Dearden, John Radford, Ian Chau, Kim Linton
We evaluated the outcomes for patients with peripheral T-cell lymphoma (PTCL) undergoing front-line chemotherapy at our institutions between 2002 and 2012. One hundred and fifty-six patients were eligible, comprising PTCL not otherwise specified (NOS) (n = 50, 32.0%), angioimmunoblastic T-cell lymphoma (AITL) (n = 44, 28.2%), anaplastic large-cell lymphoma (ALCL) ALK negative (n = 23, 14.7%), ALCL ALK positive (n = 16, 10.3%), and other (n = 23, 14.7%). Most patients received CHOP (66.0%) and 13...
November 9, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29103138/a-new-prognostic-score-comprising-lactate-dehydrogenase-albumin-and-neutrophil-to-lymphocyte-ratio-to-predict-sensitivity-to-first-line-chemotherapy-in-patients-with-peripheral-t-cell-lymphomas
#10
Satoshi Kaito, Yusuke Kanemasa, Yuki Sasaki, Toshihiro Okuya, Tsukasa Yamaguchi, Chikako Funasaka, Tatsu Shimoyama, Yasushi Omuro, Tsunekazu Hishima, Yoshiharu Maeda
No standard therapy for peripheral T-cell lymphomas (PTCLs) has been established, and treatment outcomes are poor. Upfront stem cell transplantation has been investigated in several studies, some of which have reported promising outcomes. However, some patients maintain long-term remission after chemotherapy alone. It is thus important to predict sensitivity to first-line chemotherapy to optimize treatment strategies. In the present study, we retrospectively analyzed time to treatment failure (TTF) of first-line chemotherapy in 59 patients with PTCLs...
November 4, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29100307/elevated-serum-interleukin-10-level-and-m2-macrophage-infiltration-are-associated-with-poor-survival-in-angioimmunoblastic-t-cell-lymphoma
#11
Jun Soo Ham, Ha Young Park, Kyung Ju Ryu, Young Hyeh Ko, Won Seog Kim, Seok Jin Kim
Interleukin-10 (IL-10) induces an immunosuppressive microenvironment including M2 macrophages, inhibiting anti-tumor immunity. The aim of this study was to evaluate whether serum IL-10 level at diagnosis and tissue infiltration of M2 macrophages could predict survival outcome of patients with angioimmunoblastic T-cell lymphoma (AITL). We measured serum levels of IL-5, IL-10, IL-12, and interferon-gamma (IFN-γ) at diagnosis in AITL and other common subtypes of nodal T-cell lymphoma including peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), ALK-negative anaplastic large cell lymphoma (ALCL) or ALK-positive ALCL between September 2008 and December 2014...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29081194/-prognostic-significance-of-nccn-international-prognostic-index-nccn-ipi-for-patients-with-peripheral-t-cell-lymphoma-treated-with-chop-based-chemotherapy
#12
M C Zhang, P P Xu, H J Zhong, X Zhao, W L Zhao, S Cheng
Objective: To validate the prognostic value of NCCN-International Prognostic Index (NCCN-IPI) for patients with peripheral T-cell lymphoma (PTCL) treated with CHOP-based chemotherapy. Methods: A retrospective analysis in 162 PTCL patients who were initially diagnosed and treated in Rui Jin Hospital from January 2003 to May 2013 was conducted. Baseline characteristics were collected, and survival analysis was performed according to the IPI and NCCN-IPI model. Results: The estimated 5-year overall survival (OS) rate and progression free survival (PFS) rate were 33% and 20%, with median OS and PFS of 17...
September 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29072976/international-assessment-of-event-free-survival-at-24-months-and-subsequent-survival-in-peripheral-t-cell-lymphoma
#13
Matthew J Maurer, Fredrik Ellin, Line Srour, Mats Jerkeman, N Nora Bennani, Joseph M Connors, Graham W Slack, Karin E Smedby, Stephen M Ansell, Brian K Link, James R Cerhan, Thomas Relander, Kerry J Savage, Andrew L Feldman
Purpose Peripheral T-cell lymphomas (PTCLs) have aggressive clinical behavior. We have previously shown that event-free survival (EFS) at 24 months (EFS24) is a clinically useful end point in diffuse large B-cell lymphoma. Here, we assess EFS24 and subsequent overall survival (OS) in large, multinational PTCL cohorts. Patients and Methods Patients with systemic PTCL newly diagnosed from 2000 to 2012 and treated with curative intent were included from the United States and Sweden (initial cohorts) and from Canada (replication cohort)...
October 26, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28953629/clinical-characteristics-of-angioimmunoblastic-t-cell-lymphoma-in-china-and-c-reactive-protein-as-an-independent-prognostic-factor
#14
Ying Li, Chunmei Yang, Liping Mao, Jinghan Wang, Chenying Li, Wenbin Qian
Angioimmunoblastic T-cell lymphoma (AITL) is a major subtype of peripheral T-cell lymphoma (PTCL). Due to its low incidence, the characteristics of AITL are still not well understood. The prognostic evaluation of this disease has not been established.We retrospectively analyzed 52 patients with newly diagnosed AITL in China between January 2008 and September 2016.Among these patients, the median age at diagnosis was 62 (40-83) and 58% (30/52) of the patients were older than 60 years. Thirty-five patients were male, accounting for 67...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28946015/peripheral-t-cell-lymphomas-focusing-on-novel-agents-in-relapsed-and-refractory-disease
#15
REVIEW
Alessandro Broccoli, Lisa Argnani, Pier Luigi Zinzani
Patients with relapsed or refractory peripheral T-cell lymphoma display a dismal prognosis and their therapy represents an unmet medical need, as the best treatment strategy is yet to be determined. Exciting data on novel targeted agents are now emerging from recently concluded and ongoing clinical trials in patients with relapsed and refractory PTCL. Four recently approved compounds are used as single agents: pralatrexate, a novel antifolate agent; romidepsin and belinostat, both histone deacetylase (HDAC) inhibitors; brentuximab vedotin, an anti-CD30 drug-conjugated monoclonal antibody...
November 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28940014/clinicopathological-analysis-in-ptcl-nos-with-cadm1-expression
#16
Takeharu Kato, Hiroaki Miyoshi, Seiichiro Kobayashi, Noriaki Yoshida, Yoshitaka Imaizumi, Masao Seto, Kaoru Uchimaru, Yasushi Miyazaki, Koichi Ohshima
Peripheral T cell lymphoma, not otherwise specified (PTCL-NOS), is a heterogeneous disease with respect to clinicopathological features. Cell adhesion molecule 1 (CADM1) has been reported to be ectopically expressed in adult T cell leukaemia/lymphoma (ATLL). However, the frequency of CADM1 expression remains unknown in peripheral T cell lymphomas. In the current study, CADM1 expression was analysed in 88 PTCL-NOS patients. CADM1 was expressed in 14 of 88 (15.9%) PTCL-NOS cases, and its expression was associated with C-C chemokine receptor type 4 (CCR4) expression and nuclear atypia...
November 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28932400/mediastinal-peripheral-t-cell-lymphoma-diagnosed-by-repeated-biopsies-after-an-initial-diagnosis-of-fibrosing-mediastinitis
#17
Naoko Kakuta, Mitsuhiro Sumitani, Arata Sugitani, Kenji Nakahama, Yuzo Miki, Seichi Syoji
We report a case of mediastinal peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) diagnosed by repeated biopsies. A 44-year-old man was admitted to our hospital with a 2-week history of facial swelling, neck distension, and dyspnoea on exertion. Computed tomography of the chest showed a mediastinal mass. Initial needle biopsy and video-assisted thoracoscopic biopsy revealed the pathological diagnosis of fibrosing mediastinitis (FM). Glucocorticoid therapy (prednisolone) was temporarily effective in reducing tumour size...
November 2017: Respirology Case Reports
https://www.readbyqxmd.com/read/28900149/assessment-of-t-cell-receptor-repertoire-and-clonal-expansion-in-peripheral-t-cell-lymphoma-using-rna-seq-data
#18
Qiang Gong, Chao Wang, Weiwei Zhang, Javeed Iqbal, Yang Hu, Timothy C Greiner, Adam Cornish, Jo-Heon Kim, Raul Rabadan, Francesco Abate, Xin Wang, Giorgio G Inghirami, Timothy W McKeithan, Wing C Chan
T-cell clonality of peripheral T-cell lymphoma (PTCL) is routinely evaluated with a PCR-based method using genomic DNA. However, there are limitations with this approach. The purpose of this study was to determine the utility of RNA-seq for assessing T-cell clonality and T-cell antigen receptor (TCR) repertoire of the neoplastic T-cells in 108 PTCL samples. TCR transcripts, including complementarity-determining region 3 (CDR3) sequences, were assessed. In normal T cells, the CDR3 sequences were extremely diverse, without any clonotype representing more than 2% of the overall TCR population...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28883272/peripheral-t-cell-lymphoma-not-otherwise-specified-a-retrospective-single-center-analysis
#19
Takaharu Suzuki, Keisuke Kawamoto, Suguru Tamura, Shun Uemura, Akane Kaihatsu, Hiroki Nemoto, Hironori Kobayashi, Takashi Ushiki, Kyoko Fuse, Yasuhiko Shibazaki, Masato Moriyama, Masayoshi Masuko, Miwako Narita, Hirohito Sone, Sadao Aoki, Naoya Nakamura, Koichi Oshima, Jun Takizawa
We retrospectively analyzed clinical and pathological features, treatments, and prognoses in 28 patients with newly diagnosed peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) in Niigata University Medical and Dental Hospital. Of them, 16 were males and 12 were females, and their median age was 62.5 (range, 26-88) years. The International Prognostic Index was high-intermediate/high in 68% of patients. Twelve patients were treated with CHOP/THP-COP and nine with third-generation chemotherapy regimens...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28876340/cisplatin-and-transplatin-interaction-with-methionine-bonding-motifs-assayed-by-vibrational-spectroscopy-in-the-isolated-ionic-complexes
#20
Roberto Paciotti, Davide Corinti, Alberto De Petris, Alessandra Ciavardini, Susanna Piccirillo, Cecilia Coletti, Nazzareno Re, Philippe Maitre, Bruno Bellina, Perdita Barran, Barbara Chiavarino, Maria Elisa Crestoni, Simonetta Fornarini
Cisplatin and transplatin (cis- and trans-[PtCl2(NH3)2]) have been allowed to react with methionine (Met) in water solution in a study aimed to characterize the monofunctional complex primarily formed. The thioether function of methionine is known to have a very high affinity for square planar platinum(ii) and sulfur-containing biomolecules have been proposed as a cisplatin drug reservoir on the way to platination at DNA. Both cisplatin and transplatin yield [PtCl(NH3)2Met](+) complexes, delivered by electrospray ionization in the gas phase and sampled as isolated species using tools based on mass spectrometry...
October 11, 2017: Physical Chemistry Chemical Physics: PCCP
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