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https://www.readbyqxmd.com/read/28088788/dual-syk-jak-inhibition-overcomes-ibrutinib-resistance-in-chronic-lymphocytic-leukemia-cerdulatinib-but-not-ibrutinib-induces-apoptosis-of-tumor-cells-protected-by-the-microenvironment
#1
Ailin Guo, Pin Lu, Greg Coffey, Pamela Conley, Anjali Pandey, Y Lynn Wang
Ibrutinib (BTK inhibitor) has generated remarkable responses in CLL. However, the drug, to a large extent, does not cause cell death directly and does not eradicate CLL malignant clones. Inability to eradicate CLL has fostered resistance generation. Once patients become resistant, they do poorly with a median survival of 3-4 months. Novel therapeutic strategies are needed to prevent resistance, improve treatment outcome and ultimately cure the disease. Herein, we explore dual targeting of the BCR and JAK-STAT pathways with a novel single agent, cerdulatinib, which selectively inhibits both SYK (a BCR component) and JAK kinases...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28087047/rational-design-of-low-immunogenic-anti-cd25-recombinant-immunotoxin-for-t-cell-malignancies-by-elimination-of-t-cell-epitopes-in-pe38
#2
Ronit Mazor, Gilad Kaplan, Dong Park, Youjin Jang, Fred Lee, Robert Kreitman, Ira Pastan
LMB-2, is a potent recombinant immunotoxin (RIT) that is composed of scFv antibody that targets CD25 (Tac) and a toxin fragment (PE38). It is used to treat T cell leukemias and lymphomas. To make LMB-2 less immunogenic, we introduced a large deletion in domain II and six point mutations in domain III that were previously shown to reduce T cell activation in other RITs. We found that unlike other RITs, deletion of domain II from LMB-2 severely compromised its activity. Rather than deletion, we identified T cell epitopes in domain II and used alanine substitutions to identify point mutations that diminished those epitopes...
January 5, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28078727/second-cancer-incidence-in-primary-mediastinal-b-cell-lymphoma-treated-with-methotrexate-with-leucovorin-rescue-doxorubicin-cyclophosphamide-vincristine-prednisone-and-bleomycin-regimen-with-or-without-rituximab-and-mediastinal-radiotherapy-results-from-a-monoinstitutional
#3
Vitaliana De Sanctis, Marco Alfò, Alice Di Rocco, Michela Ansuinelli, Eleonora Russo, Mattia F Osti, Maurizio Valeriani, Giuseppe Minniti, Lavinia Grapulin, Daniela Musio, Stefano Bracci, Alessandra Spagnoli, Maria Luisa Moleti, Vincenzo Tombolini, Maurizio Martelli
Our aim is to assess the incidence of second cancer in long-time surviving primary mediastinal B-cell lymphoma (PMBCL) patients treated with combined radiochemoimmunotherapy (standard methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin with rituximab and mediastinal radiation therapy at a dose of 30 to 36 Gy). For this purpose, 92 points were evaluated. After a median overall survival of 137 months (range 76-212), we recorded second cancer in 3 of 80 long-surviving patients (3...
January 12, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28075522/crucial-role-of-carbonic-anhydrase-ix-in-tumorigenicity-of-xenotransplanted-adult-t-cell-leukemia-derived-cells
#4
Kentaro Nasu, Kazunori Yamaguchi, Tomoka Takanashi, Keiichi Tamai, Ikuro Sato, Shoji Ine, Osamu Sasaki, Kennichi Satoh, Nobuyuki Tanaka, Yuetsu Tanaka, Takuya Fukushima, Hideo Harigae, Kazuo Sugamura
Carbonic anhydrase IX (CA9) is a membrane-associated carbonic anhydrase that regulates cellular pH, is upregulated in various solid tumors, and is considered to be a therapeutic target. Here, we describe the essential role of CA9 in the tumorigenicity of cells derived from human adult T-cell leukemia/lymphoma (ATL). We previously established the highly tumorigenic ST1-N6 subline from the ATL-derived ST1 cell line by serial xenotransplantation in NOG mice. In the present study, we first show that CA9 expression is strongly enhanced in ST1-N6 cells...
January 11, 2017: Cancer Science
https://www.readbyqxmd.com/read/28074066/preclinical-targeting-of-aggressive-t-cell-malignancies-using-anti-cd5-chimeric-antigen-receptor
#5
K H Chen, M Wada, K G Pinz, H Liu, K-W Lin, A Jares, A E Firor, X Shuai, H Salman, M Golightly, F Lan, L Senzel, L-H Leung, X Jiang, Y Ma
The outlook for T-cell malignancies remain poor due to the lack of effective therapeutic options. Chimeric antigen receptor (CAR) immunotherapy has recently shown promise in clinical trials for B-cell malignancies, however, designing CARs for T-cell based disease remain a challenge due to the shared surface antigen pool between normal and malignant T-cells. Normal T-cells express CD5 but NK (natural killer) cells do not, positioning NK cells as attractive cytotoxicity cells for CD5CAR design. Additionally, CD5 is highly expressed in T cell acute lymphoblastic leukemia (T-ALL) and peripheral T cell lymphomas (PTCLs)...
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28073846/extended-treatment-with-single-agent-ibrutinib-at-the-420-mg-dose-leads-to-durable-responses-in-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma
#6
Steven E Coutré, Richard R Furman, Ian W Flinn, Jan A Burger, Kristie Blum, Jeff Sharman, Jeffrey Jones, William Wierda, Weiqiang Zhao, Nyla A Heerema, Amy J Johnson, Anh Tran, Cathy Zhou, Elizabeth Bilotti, Danelle F James, John C Byrd, Susan O'Brien
PURPOSE: Ibrutinib, a first-in-class, once-daily, oral inhibitor of Bruton tyrosine kinase, promotes apoptosis, and inhibits B-cell proliferation, adhesion, and migration. Ibrutinib has demonstrated single-agent efficacy and acceptable tolerability at doses of 420 and 840 mg in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who were treatment-naïve (TN) or had relapsed/refractory (R/R) CLL after ≥1 prior therapy in a phase Ib/II study (PCYC-1102). Subsequently, the ibrutinib 420 mg dose was approved in CLL...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28068180/clonal-hematopoiesis-associated-with-adverse-outcomes-after-autologous-stem-cell-transplantation-for-lymphoma
#7
Christopher J Gibson, R Coleman Lindsley, Vatche Tchekmedyian, Brenton G Mar, Jiantao Shi, Siddhartha Jaiswal, Alysia Bosworth, Liton Francisco, Jianbo He, Anita Bansal, Elizabeth A Morgan, Ann S Lacasce, Arnold S Freedman, David C Fisher, Eric Jacobsen, Philippe Armand, Edwin P Alyea, John Koreth, Vincent Ho, Robert J Soiffer, Joseph H Antin, Jerome Ritz, Sarah Nikiforow, Stephen J Forman, Franziska Michor, Donna Neuberg, Ravi Bhatia, Smita Bhatia, Benjamin L Ebert
Purpose Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition characterized by somatic mutations in the blood of otherwise healthy adults. We hypothesized that in patients undergoing autologous stem-cell transplantation (ASCT) for lymphoma, CHIP at the time of ASCT would be associated with an increased risk of myelodysplastic syndrome and acute myeloid leukemia, collectively termed therapy-related myeloid neoplasm (TMN), and other adverse outcomes. Methods We performed whole-exome sequencing on pre- and post-ASCT samples from 12 patients who developed TMN after autologous transplantation for Hodgkin lymphoma or non-Hodgkin lymphoma and targeted sequencing on cryopreserved aliquots of autologous stem-cell products from 401 patients who underwent ASCT for non-Hodgkin lymphoma between 2003 and 2010...
January 9, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28067877/dismal-outcome-of-allogeneic-hematopoietic-stem-cell-transplantation-for-relapsed-adult-t-cell-leukemia-lymphoma-a-japanese-nation-wide-study
#8
H Fujiwara, S Fuji, A Wake, K Kato, Y Takatsuka, T Fukuda, J Taguchi, N Uchida, T Miyamoto, M Hidaka, Y Miyazaki, T Tomoyose, M Onizuka, M Takanashi, T Ichinohe, Y Atsuta, A Utsunomiya
No abstract text is available yet for this article.
January 9, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28067179/cd20-based-immunotherapy-of-b-cell-derived-hematologic-malignancies
#9
Dariush Shanehbandi, Jafar Majidi, Tohid Kazemi, Behzad Baradaran, Leili Aghebati-Maleki
CD20 is a surface antigen which is expressed at certain stages of B-cell differentiation. Targeting the CD20-positive B-cells with therapeutic monoclonal antibodies (MAbs) has been an effectual strategy in the treatment of hematologic malignancies such as non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Initial success with Rituximab (RTX) has encouraged the creation and development of more effective CD20 based therapeutics. However, treatment with conventional MAbs has not been adequate to overcome the problems such as refractory/relapsed disease...
January 9, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28061982/pi3k-signaling-pathway-in-normal-b-cells-and-indolent-b-cell-malignancies
#10
REVIEW
Georgios Pongas, Bruce D Cheson
In chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphomas (NHLs), B-cell receptor signaling leads to activation of the phosphatidylinositol 3-kinase (PI3K) pathway. Idelalisib, a PI3Kδ inhibitor was approved in 2014 by the US Food and Drug Administration (FDA) in combination with rituximab for the treatment of patients with CLL for whom single-agent rituximab would be considered appropriate and as a single agent for patients with relapsed small lymphocytic lymphoma (SLL) and relapsed follicular lymphoma (FL)...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/28061439/synthetic-high-density-lipoproteins-as-targeted-monotherapy-for-chronic-lymphocytic-leukemia
#11
Kaylin M McMahon, Cristina Scielzo, Nicholas L Angeloni, Elad Deiss-Yehiely, Lydia Scarfo, Pamela Ranghetti, Shuo Ma, Jason Kaplan, Federica Barbaglio, Leo I Gordon, Francis J Giles, C. Shad Thaxton, Paolo Ghia
Chronic lymphocytic leukemia (CLL) remains incurable despite the introduction of new drugs. Therapies targeting receptors and pathways active specifically in malignant B cells might provide better treatment options. For instance, in B cell lymphoma, our group has previously shown that scavenger receptor type B-1 (SR-B1), the high-affinity receptor for cholesterol-rich high-density lipoproteins (HDL), is a therapeutic target. As evidence suggests that targeting cholesterol metabolism in CLL cells may have therapeutic benefit, we examined SR-B1 expression in primary CLL cells from patients...
4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28061369/employing-image-processing-techniques-for-cancer-detection-using-microarray-images
#12
Nastaran Dehghan Khalilabad, Hamid Hassanpour
Microarray technology is a powerful genomic tool for simultaneously studying and analyzing the behavior of thousands of genes. The analysis of images obtained from this technology plays a critical role in the detection and treatment of diseases. The aim of the current study is to develop an automated system for analyzing data from microarray images in order to detect cancerous cases. The proposed system consists of three main phases, namely image processing, data mining, and the detection of the disease. The image processing phase performs operations such as refining image rotation, gridding (locating genes) and extracting raw data from images the data mining includes normalizing the extracted data and selecting the more effective genes...
December 21, 2016: Computers in Biology and Medicine
https://www.readbyqxmd.com/read/28057804/cell-cycle-progression-dictates-the-requirement-for-bcl2-in-natural-killer-cell-survival
#13
Charlotte Viant, Sophie Guia, Robert J Hennessy, Jai Rautela, Kim Pham, Claire Bernat, Wilford Goh, Yuhao Jiao, Rebecca Delconte, Michael Roger, Vanina Simon, Fernando Souza-Fonseca-Guimaraes, Stephanie Grabow, Gabrielle T Belz, Benjamin T Kile, Andreas Strasser, Daniel Gray, Phillip D Hodgkin, Bruce Beutler, Eric Vivier, Sophie Ugolini, Nicholas D Huntington
Natural killer (NK) cells are innate lymphoid cells with antitumor functions. Using an N-ethyl-N-nitrosourea (ENU)-induced mutagenesis screen in mice, we identified a strain with an NK cell deficiency caused by a hypomorphic mutation in the Bcl2 (B cell lymphoma 2) gene. Analysis of these mice and the conditional deletion of Bcl2 in NK cells revealed a nonredundant intrinsic requirement for BCL2 in NK cell survival. In these mice, NK cells in cycle were protected against apoptosis, and NK cell counts were restored in inflammatory conditions, suggesting a redundant role for BCL2 in proliferating NK cells...
January 5, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28056525/venetoclax
#14
Amber C King, Tim J Peterson, Troy Z Horvat, Mabel Rodriguez, Laura A Tang
OBJECTIVE: To review the pharmacology, efficacy, and safety of venetoclax for treatment of lymphoid malignancies. DATA SOURCES: A literature search was performed of PubMed and MEDLINE databases (2005 to September 2016), abstracts from the American Society of Hematology and the American Society of Clinical Oncology, and ongoing studies from clinicaltrials.gov. Searches were performed utilizing the following key terms: venetoclax, ABT-199, GDC-199, obatoclax, GX15-070, BCL-2 inhibitor, navitoclax, ABT-263, and Venclexta...
December 1, 2016: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28056298/-significance-of-cxcl12-cxcr4-expression-in-t-lymphoblastic-lymphoma-leukemia
#15
Z Z Yu, Y F Xi, J Li, W Q Bai, N Gao, P Bu
Objective: To investigate the significance of CXCL12/CXCR4 expression in T lymphoblastic lymphoma/leukemia (T-LBL/ALL) and its prognostic significance. Methods: Using immunohistochemical EnVision method, CXCL12, CXCR4 and Ki-67 expression were evaluated in 72 cases of T-LBL/ALL and 30 selected cases of lymph node reactive hyperplasia (LH) as control. In addition, CXCL12 and CXCR4 mRNA expression levels were examined by real-time reverse transcription polymerase chain reaction (real-time RT-PCR) method. Results: Immunohistochemical results showed that the expression rates of CXCL12 and CXCR4 in T-LBL/ALL were 84...
December 8, 2016: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28056294/-the-understanding-of-epstein-barr-virus-associated-lymphoproliferative-disorder
#16
X G Zhou, Y L Zhang, J L Xie, Y H Huang, Y Y Zheng, W S Li, H Chen, F Liu, H X Pan, P Wei, Z Wang, Y C Hu, K Y Yang, H L Xiao, M J Wu, W H Yin, K Y Mei, G Chen, X C Yan, G Meng, G Xu, J Li, S F Tian, J Zhu, Y Q Song, W J Zhang
In recent years, there are increasing articles concerning Epstein-Barr virus associated lymphoproliferative disorder (EBV+ LPD), and the name of EBV+ LPD is used widely. However, the meaning of EBV+ LPD used is not the same, which triggered confusion of the understanding and obstacles of the communication. In order to solve this problem. Literature was reviewed with combination of our cases to clarify the concept of EBV+ LPD and to expound our understanding about it. In general, it is currently accepted that EBV+ LPD refers to a spectrum of lymphoid tissue diseases with EBV infection, including hyperplasia, borderline lesions, and neoplastic diseases...
December 8, 2016: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28053195/tcr-based-therapy-for-multiple-myeloma-and-other-b-cell-malignancies-targeting-intracellular-transcription-factor-bob1
#17
Lorenz Jahn, Pleun Hombrink, Renate S Hagedoorn, Michel G D Kester, Dirk M van der Steen, Tania Rodriguez, Tsvetelina Pentcheva-Hoang, Arnoud H de Ru, Marjolein P Schoonakker, Miranda H Meeuwsen, Marieke Griffioen, Peter A van Veelen, J H Frederik Falkenburg, Mirjam H M Heemskerk
Immunotherapy of hematological malignancies or solid tumors by administration of monoclonal antibodies or T-cells engineered to express chimeric antigen receptors or T-cell receptors (TCRs) has demonstrated clinical efficacy. However, antigen-loss tumor escape variants and the absence of currently targeted antigens on several malignancies hampers the widespread application of immunotherapy. We have isolated a TCR targeting a peptide of the intracellular B-cell specific transcription factor BOB1 presented in the context of HLA-B*07:02...
January 4, 2017: Blood
https://www.readbyqxmd.com/read/28052939/no-association-between-radiation-dose-from-pediatric-ct-scans-and-risk-of-subsequent-hodgkin-lymphoma
#18
Amy Berrington de Gonzalez, Neige Journy, Choonsik Lee, Lindsay M Morton, Richard Harbron, Douglas R Stewart, Louise Parker, Alan W Craft, Kieran McHugh, Mark Little, Mark Pearce
BACKGROUND: We examined the relationship between estimated radiation dose from CT scans and subsequent Hodgkin lymphoma in the UK pediatric CT scans cohort. METHODS: A retrospective, record linkage cohort included patients aged 0-21 years who underwent CT scans between 1980 and 2002 and were followed up for cancer or death until 2008. Poisson regression analysis was used to evaluate the relationship between estimated radiation dose (lagged by two years) and incident Hodgkin lymphoma diagnosed at least two years after the first CT scan...
January 4, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28051888/the-benefits-and-burdens-of-cancer-a-prospective-longitudinal-cohort-study-of-adolescents-and-young-adults
#19
Joelle P Straehla, Krysta S Barton, Joyce P Yi-Frazier, Claire Wharton, Kevin Scott Baker, Kira Bona, Joanne Wolfe, Abby R Rosenberg
BACKGROUND: Adolescents and early young adults (AYAs) with cancer are at high risk for poor outcomes. Positive psychological responses such as benefit-finding may buffer the negative impacts of cancer but are poorly understood in this population. OBJECTIVE: We aimed to prospectively describe the content and trajectory of benefit- and burden-finding among AYAs to develop potential targets for future intervention. PATIENTS AND METHODS: One-on-one semistructured interviews were conducted with English-speaking AYA patients (aged 14-25 years) within 60 days of diagnosis of a noncentral nervous system malignancy requiring chemotherapy, 6-12 and 12-18 months later...
January 4, 2017: Journal of Palliative Medicine
https://www.readbyqxmd.com/read/28051344/trends-in-cancer-mortality-among-adolescents-and-young-adults-in-brazil
#20
Nathalie Vieira Balmant, Rejane de Souza Reis, Marceli de Oliveira Santos, Julio Pinto Oliveira, Beatriz de Camargo
PURPOSE: Adolescents and young adults (AYA) with cancer comprise an intermediate age group between pediatric and adult oncology, and have a spectrum of different types of cancers. Survival among this group has not improved as much as in younger children with cancer. The aim of this study was evaluate the trends in cancer mortality of AYA aged 15-29 years in Brazil. METHODS: Data were extracted from the Atlas of Cancer Mortality databases from 1979 to 2013. Age-specific mortality rates were calculated based on the deaths from each type of cancer and the period via a direct method using the proposed world population age groups...
January 4, 2017: Journal of Adolescent and Young Adult Oncology
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