Guoyi Yan, Xinxin Zhong, Lin Yue, Chunlan Pu, Huifang Shan, Suke Lan, Meng Zhou, Xueyan Hou, Jie Yang, Rui Li
Anaplastic lymphoma kinase (ALK) was involved in the development of various cancer types. Although several ALK inhibitors have been advanced to clinical trials, the emergence of drug resistance has limited the clinical application of them. To overcome the drug resistance, proteolysis targeting chimeras (PROTACs) could be an alternative strategy. In this study, a series of ALK degraders were designed and synthesized. The degraders were developed through the conjugation of LDK378 and CRBN E3 ubiquitin ligase ligands...
January 2, 2021: European Journal of Medicinal Chemistry
Cosimo Nardi, Maddalena Tomei, Michele Pietragalla, Linda Calistri, Nicholas Landini, Pierluigi Bonomo, Giuditta Mannelli, Francesco Mungai, Luigi Bonasera, Stefano Colagrande
BACKGROUND AND PURPOSE: Parotid lesions show overlaps of morphological findings, apparent diffusion coefficient (ADC) values and types of time/intensity curve. This research aimed to evaluate the role of diffusion weighted imaging texture analysis in differentiating between benign and malignant parotid lesions and in characterizing pleomorphic adenoma (PA), Warthin tumor (WT), epithelial malignancy (EM), and lymphoma (LY). METHODS: Texture analysis of 54 parotid lesions (19 PA, 14 WT, 14 EM, and 7 LY) was performed on ADC map images...
January 7, 2021: European Journal of Radiology
Andrea C Lo, Ben Chen, Vanessa Samuel, Kerry J Savage, Ciara Freeman, Karen Goddard
PURPOSE: The study objective is to describe and quantify the incidence of treatment-induced late effects in AYA lymphoma patients. METHODS: Consecutive patients diagnosed with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) at 15-24 years of age were identified. All patients in British Columbia who received radiation therapy (RT) from 1974 to 2014 with ≥ 5-year survival post-RT were included. Late effects' analyses included only survivors who received RT to the relevant anatomical site(s) and/or relevant chemotherapy, and were reported as cumulative incidence (CI) ± standard error...
January 16, 2021: Journal of Cancer Survivorship: Research and Practice
Maxens Decavèle, Aliénor Dreyfus, Nicolas Gatulle, Nicolas Weiss, Caroline Houillier, Sophie Demeret, Julien Mayaux, Isabelle Rivals, Martin Dres, Julie Delemazure, Elise Morawiec, Charles-Edouard Luyt, Khe Hoang-Xuan, Sylvain Choquet, Thomas Similowski, Alexandre Demoule
INTRODUCTION: To describe the reasons for intensive care unit (ICU) admission and to evaluate the outcomes and prognostic factors of patients with primary central nervous system lymphoma (PCNSL) admitted to the ICU. PATIENTS AND METHODS: Retrospective observational cohort study of 101 PCNSL patients admitted to 3 ICUs over a two-decade period. RESULTS: Acute respiratory failure, mainly secondary to aspiration pneumonia and Pneumocystis jirovecii pneumonia, was the leading reason for ICU admission (33%)...
January 16, 2021: Journal of Neurology
(no author information available yet)
PURPOSE: The main objective of Repro-Can-OPEN Study Part 2 is to learn more about oncofertility practices in optimum resource settings to provide a roadmap to establish oncofertility best practice models. METHODS: As an extrapolation for oncofertility best practice models in optimum resource settings, we surveyed 25 leading and well-resourced oncofertility centers and institutions from the USA, Europe, Australia, and Japan. The survey included questions on the availability and degree of utilization of fertility preservation options in case of childhood cancer, breast cancer, and blood cancer...
January 16, 2021: Journal of Assisted Reproduction and Genetics
R Pettengell, R Uddin, A Boumendil, R Johnson, B Metzner, A Martín, J Romejko-Jarosinska, I Bence-Bruckler, P Giri, C U Niemann, S P Robinson, E Kimby, N Schmitz, P Dreger, A H Goldstone, S Montoto
We report the 12-year follow-up of the prospective randomized EBMT LYM1 trial to determine whether the benefit of brief duration rituximab maintenance (RM) on progression-free survival (PFS) in patients with relapsed follicular lymphoma (FL) receiving an autologous stem cell transplant (ASCT) is sustained. One hundred and thirty-eight patients received RM with or without purging. The median follow-up after random assignment is 12 years (range 10-13) for the whole series. The 10-year PFS after ASCT is 47% (95% CI 40-54) with only 4 patients relapsing after 7...
January 15, 2021: Bone Marrow Transplantation
Jisu Park, Hyunwoo Choi, Young Doo Kim, Seo-Hyun Kim, Youbin Kim, Youngdae Gwon, Dong Young Lee, Sung-Hye Park, Won Do Heo, Yong-Keun Jung
Proteinopathy in neurodegenerative diseases is typically characterized by deteriorating activity of specific protein aggregates. In tauopathies, including Alzheimer's disease (AD), tau protein abnormally accumulates and induces dysfunction of the affected neurons. Despite active identification of tau modifications responsible for tau aggregation, a critical modulator inducing tau proteinopathy by affecting its protein degradation flux is not known. Here, we report that anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase, is crucial for the tau-mediated AD pathology...
January 15, 2021: Molecular Psychiatry
Charles E Bullerwell, Philippe Pierre Robichaud, Pierre M L Deprez, Andrew P Joy, Gabriel Wajnberg, Darwin D'Souza, Simi Chacko, Sébastien Fournier, Nicolas Crapoulet, David A Barnett, Stephen M Lewis, Rodney J Ouellette
PAX5 and EBF1 work synergistically to regulate genes that are involved in B lymphocyte differentiation. We used the KIS-1 diffuse large B cell lymphoma cell line, which is reported to have elevated levels of PAX5 expression, to investigate the mechanism of EBF1- and PAX5-regulated gene expression. We demonstrate the lack of expression of hallmark B cell genes, including CD19, CD79b, and EBF1, in the KIS-1 cell line. Upon restoration of EBF1 expression we observed activation of CD19, CD79b and other genes with critical roles in B cell differentiation...
January 15, 2021: Scientific Reports
Sara AlRasbi, Amira H Al-Badi, Abdullah M Al Alawi
A 65-year-old man, a smoker, presented to the emergency department with progressive digital ischaemia, fever and weight loss. The clinical examination revealed generalised lymphadenopathy and ischaemic changes of the right distal phalanges of the second, third and fourth fingers. He had an ultrasound-guided biopsy of the cervical lymph node, which showed histopathological findings of classic Hodgkin's lymphoma. Paraneoplastic acral vascular syndrome (PAVS) is a rare phenomenon and seen more in solid malignancies...
January 15, 2021: BMJ Case Reports
Stephen M Ansell, Michael Maris, Alexander M Lesokhin, Robert Chen, Ian W Flinn, Ahmed Sawas, Mark D Minden, Diego Villa, Mary-Elizabeth M Percival, Anjali S Advani, James M Foran, Steven Horwitz, Matthew Mei, Jasmine Zain, Kerry J Savage, Christiane Querfeld, Oleg E Akilov, Lisa D Johnson, Tina Catalano, Penka S Petrova, Robert A Uger, Eric L Sievers, Anca Milea, Kathleen Roberge, Yaping Shou, Owen A O'Connor
PURPOSE: TTI-621 (SIRPα-IgG1 Fc) is a novel checkpoint inhibitor that activates antitumor activity by blocking the CD47 "don't eat me" signal. This first-in-human phase 1 study (NCT02663518) evaluated the safety and activity of TTI-621 in relapsed/refractory (R/R) hematologic malignancies. EXPERIMENTAL DESIGN: Patients with R/R lymphoma received escalating weekly intravenous TTI-621 to determine the maximum tolerated dose (MTD). During expansion, patients with various malignancies received weekly single-agent TTI‑621 at the MTD; TTI-621 was combined with rituximab in patients with B-cell non-Hodgkin lymphoma (NHL) or nivolumab in patients with Hodgkin lymphoma...
January 15, 2021: Clinical Cancer Research
Elifcan Aladag, Sude Hatun Aktimur, Öznur Aydın, Haluk Demiroglu, Yahya Buyukasik, Salih Aksu, Osman Ilhami Ozcebe, Ibrahim Celalettin Haznedaroglu, Nilgun Sayinalp, Mehmet Turgut, Hakan Goker
INTRODUCTION: Acute lymphoblastic leukemia (ALL) is a malign disease with poor prognosis in adults. After remission is achieved by induction therapy, administration of allogeneic hematopoietic stem-cell transplantation (AHSCT) is one of the standard treatment in adult ALL patients. Pediatric-inspired chemotherapy has been demonstrated to improve outcomes of adult ALL. The aim of this study was to compare the Berlin-Frankfurt-Münster-95 chemotherapy (BFM-95) regimen and AHSCT results in ALL patients with first complete remission...
January 12, 2021: Clinical Lymphoma, Myeloma & Leukemia
Sicong Wang, Yaoying Lu, Kyra Woods, Giovanna Di Trapani, Kathryn F Tonissen
Lymphoma is a blood cancer comprising various subtypes. Although effective therapies are available, some patients fail to respond to treatment and can suffer from side effects. Antioxidant systems, especially the thioredoxin (Trx) and glutathione (GSH) systems, are known to enhance cancer cell survival, with thioredoxin reductase (TrxR) recently reported as a potential anticancer target. Since the GSH system can compensate for some Trx system functions, we investigated its response in three lymphoma cell lines after inhibiting TrxR activity with [Au(d2pype)2]Cl, a known TrxR inhibitor...
January 13, 2021: Antioxidants (Basel, Switzerland)
Raphael Wilhelm, Timon Eckes, Gergely Imre, Stefan Kippenberger, Markus Meissner, Dominique Thomas, Sandra Trautmann, Jean-Philippe Merlio, Edith Chevret, Roland Kaufmann, Josef Pfeilschifter, Alexander Koch, Manuel Jäger
Cutaneous T cell lymphomas (CTCLs) represent a heterogeneous group of T cell lymphomas that primarily affect the skin. The most frequent forms of CTCL are mycosis fungoides and Sézary syndrome. Both are characterized by frequent recurrence, developing chronic conditions and high mortality with a lack of a curative treatment. In this study, we evaluated the effect of short-chain, cell-permeable C6 Ceramide (C6Cer) on CTCL cell lines and keratinocytes. C6Cer significantly reduced cell viability of CTCL cell lines and induced cell death via apoptosis and necrosis...
January 13, 2021: Cancers
Hesong Shen, Xiaoqian Yuan, Daihong Liu, Yuanying Huang, Yu Wang, Shixi Jiang, Jiuquan Zhang
OBJECTIVES: To determine the optimal kiloelectron volt of noise-optimized virtual monoenergetic images [VMI (+)] for visualization of nasopharyngeal carcinoma (NPC) and nasopharyngeal lymphoma (NPL), and to explore the clinical value of quantitative parameters derived from dual-energy computed tomography (DECT) for distinguishing the two entities. MATERIALS AND METHODS: Eighty patients including 51 with NPC and 29 with NPL were enrolled. The VMIs (+) at 40-80 keV with an interval of 10 keV were reconstructed by contrast enhanced images...
January 10, 2021: European Journal of Radiology
Martijn Kerkhofs, Rita La Rovere, Kirsten Welkenhuysen, Ann Janssens, Peter Vandenberghe, Muniswamy Madesh, Jan B Parys, Geert Bultynck
Anti-apoptotic Bcl-2 critically controls cell death by neutralizing pro-apoptotic Bcl-2-family members at the mitochondria. Bcl-2 proteins also act at the endoplasmic reticulum, the main intracellular Ca2+ -storage organelle, where they inhibit IP3 receptors (IP3 R) and prevent pro-apoptotic Ca2+ -signaling events. IP3 R channels are targeted by the BH4 domain of Bcl-2. Some cancer types rely on the IP3 R-Bcl-2 interaction for survival. We previously developed a cell-permeable, BH4-domain-targeting peptide that can abrogate Bcl-2's inhibitory action on IP3 Rs, named Bcl-2 IP3 receptor disrupter-2 (BIRD-2)...
January 12, 2021: Cell Calcium
Danchen Wu, Asish Dasgupta, Austin D Read, Rachel E T Bentley, Mehras Motamed, Kuang-Hueih Chen, Ruaa Al-Qazazi, Jeffrey D Mewburn, Kimberly J Dunham-Snary, Elahe Alizadeh, Lian Tian, Stephen L Archer
The homeostatic oxygen sensing system (HOSS) optimizes systemic oxygen delivery. Specialized tissues utilize a conserved mitochondrial sensor, often involving NDUFS2 in complex I of the mitochondrial electron transport chain, as a site of pO2 -responsive production of reactive oxygen species (ROS). These ROS are converted to a diffusible signaling molecule, hydrogen peroxide (H2 O2 ), by superoxide dismutase (SOD2). H2 O2 exits the mitochondria and regulates ion channels and enzymes, altering plasma membrane potential, intracellular Ca2+ and Ca2+ -sensitization and controlling acute, adaptive, responses to hypoxia that involve changes in ventilation, vascular tone and neurotransmitter release...
January 12, 2021: Free Radical Biology & Medicine
Katarina Lopusna, Pawel Nowialis, Jana Opavska, Ajay Abraham, Alberto Riva, Staci L Haney, Rene Opavsky
DNA methylation regulates gene transcription and is involved in various physiological processes in mammals, including development and hematopoiesis. It is catalyzed by DNA methyltransferases including Dnmt1, Dnmt3a and Dnmt3b. For Dnmt3b, its effects on transcription can result from its own DNA methylase activity, the recruitment of other Dnmts to mediate methylation, or transcription repression in a methylation-independent manner. Low frequency mutations in human DNMT3B are found in hematologic malignancies including cutaneous T-cell lymphomas, Hairy cell leukemia and Diffuse Large B-cell lymphomas...
January 12, 2021: Journal of Biological Chemistry
Sugeshnee Pather, Thembi Mashele, Pascale Willem, Moosa Patel, Yvonne Perner, Mantoa Motaung, Natasha Nagiah, Faadil Waja, Vinitha Philip, Atul Lakha, Martin J Hale
AIMS: We utilised dual-colour chromogenic and fluorescent in situ hybridisation (CISH and FISH) to evaluate c-MYC gene copy numbers and rearrangements within HIV-associated plasmablastic lymphomas (PBL). Thereafter, clinicopathological features were explored. METHODS AND RESULTS: Sixty-seven patients (N=67) were included from October 2013 to June 2017. Dual-colour CISH, FISH and immunohistochemistry were performed on formalin-fixed paraffin-embedded tumour sections...
January 15, 2021: Histopathology
Joseph Chen, Brett Houk, Yazdi K Pithavala, Ana Ruiz-Garcia
Lorlatinib, a selective inhibitor of anaplastic lymphoma kinase (ALK) and c-ROS oncogene 1 (ROS1) tyrosine kinase, is indicated for the treatment of ALK-positive metastatic non-small cell lung cancer (NSCLC) following progression on crizotinib and at least one other ALK inhibitor, or alectinib/ceritinib as the first ALK inhibitor therapy for metastatic disease. The population pharmacokinetics (popPK) of lorlatinib was conducted by nonlinear mixed effects modeling of data from 330 patients with ALK- or ROS1-positive NSCLC and 95 healthy participants from six Phase 1 studies in healthy volunteers; demographic, metabolizer phenotype, and patient prognostic factors were evaluated as covariates...
January 15, 2021: CPT: Pharmacometrics & Systems Pharmacology
N Sun, W Qiao, Y Xing, T Wang, J Yang, J Zhao
PURPOSE: We aimed to evaluate the prognostic value of 18 F-FDG PET/CT in patients with relapsed or refractory T-Lymphoblastic lymphoma (T-LBL) undergoing hematopoietic stem cell transplantation (HSCT). METHODS: PET/CT was performed in 21 consecutive relapsed or refractory T-LBL patients scheduled for HSCT. All PET/CT images were assessed using the Deauville criteria, and patients were divided into negative (Deauville ≤ 3) and positive (Deauville > 3) groups for comparison...
January 15, 2021: Clinical & Translational Oncology
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