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https://www.readbyqxmd.com/read/29353075/btla-marks-a-less-cytotoxic-t-cell-subset-in-diffuse-large-b-cell-lymphoma-with-high-expression-of-checkpoints
#1
Lina Quan, Xiuwen Lan, Yuanyuan Meng, Xiuchen Guo, Yiwei Guo, Lina Zhao, Xue Chen, Aichun Liu
Immunotherapy has shown encouraging results in lymphoma. Pre-clinical and clinical trials have proven checkpoint blockade, such as PD-1 antibody, as an effective treatment for lymphoma, including diffuse large B-cell lymphoma (DLBCL). Combination of checkpoint blockades has emerged as a new way to treat lymphoma, however, the status of checkpoints expression and their function in DLBCL has not been fully elucidated yet. In this study, we examined the expression of BTLA, PD-1, TIM-3, LIGHT and LAG-3 in tumor micro-environmental T cells of DLBCL using flow cytometry, and compared the cytotoxicity and differentiation status of BTLA+ and BTLA- T-cells...
January 15, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29352718/consolidative-radiotherapy-to-residual-masses-after-chemotherapy-is-associated-with-improved-outcome-in-diffuse-large-b-cell-lymphoma-a-retrospective-population-based-study
#2
Øystein Fluge, Bård Mannsåker, Anders Torp, Ingvil Mjaaland, Lars Helgeland, Jan Klos, Olav Mella, Sigbjørn Berentsen, Peter Meyer
BACKGROUND: The role of consolidative radiotherapy (RT) in advanced diffuse large B-cell lymphoma (DLBCL) is not established. PATIENTS AND METHODS: In a population-based retrospective analysis of patients with DLBCL in Western Norway during 2003 to 2008, 170 consecutive patients admitted to Haukeland University Hospital (HUS) and 94 to Stavanger University Hospital (SUS) were included. The mean age was 64 years (range, 17-95 years), 147 patients (56%) were male, 80 patients (30%) had stage I/II, 126 patients (48%) stage III/IV, and 57 patients (22%) had primary extranodal disease...
December 24, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29352717/should-we-use-cell-of-origin-and-dual-protein-expression-in-treating-dlbcl
#3
REVIEW
Peter A Riedell, Sonali M Smith
Treatment outcomes in diffuse large B-cell lymphoma (DLBCL) following standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy is highly variable and dependent on a number of clinical, biologic, and genetic features. The identification of molecular heterogeneity via gene expression profiling dichotomizes patients based on the cell of origin (COO) model into germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subsets, with ABC-DLBCL having a worse outcome...
December 24, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29352515/principles-of-alemtuzumab-immunoablation-in-hematopoietic-cell-transplantation-for-non-malignant-diseases-in-children-a-review
#4
REVIEW
Gregory M T Guilcher, Ravi Shah, Shalini Shenoy
Alemtuzumab is a humanized mAb targeted to CD52. Alemtuzumab is highly immunosuppressive with the ability to deplete T and B cells (in addition to other immune cell lines). A growing understanding of the PKs, dosing, and timing of administration of alemtuzumab has allowed for the study of its use as a conditioning agent for allogeneic HCT. The highly immunosuppressive properties of the drug are particularly appealing in the setting of non-malignant HCT, where GVHD provides no clinical benefit and relapse of malignancy is not applicable...
January 19, 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29352484/melatonin-ameliorates-a%C3%AE-42-induced-alteration-of-%C3%AE-app-processing-secretases-via-the-melatonin-receptor-through-the-pin1-gsk3%C3%AE-nf-%C3%AE%C2%BAb-pathway-in-sh-sy5y-cells
#5
Vorapin Chinchalongporn, Mayuri Shukla, Piyarat Govitrapong
Melatonin is involved in the physiological regulation of the β- amyloid precursor protein (βAPP) cleaving secretases which are responsible for generation of the neurotoxic amyloid beta (Aβ) peptide, one of the hallmarks of Alzheimer's disease (AD) pathology. In this study, we aimed to determine the underlying mechanisms of this regulation under pathological conditions. We establish that melatonin prevents Aβ42 -induced down-regulation of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) as well as up-regulation of β-site APP-cleaving enzyme 1 (BACE1) and presenilin 1 (PS1) in SH-SY5Y cell cultures...
January 20, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29352371/innate-and-adaptive-t-cells-in-influenza-disease
#6
REVIEW
Simone Nüssing, Sneha Sant, Marios Koutsakos, Kanta Subbarao, Thi H O Nguyen, Katherine Kedzierska
Influenza is a major global health problem, causing infections of the respiratory tract, often leading to acute pneumonia, life-threatening complications and even deaths. Over the last seven decades, vaccination strategies have been utilized to protect people from complications of influenza, especially groups at high risk of severe disease. While current vaccination regimens elicit strain-specific antibody responses, they fail to generate cross-protection against seasonal, pandemic and avian viruses. Moreover, vaccines designed to generate influenza-specific T-cell responses are yet to be optimized...
January 20, 2018: Frontiers of Medicine
https://www.readbyqxmd.com/read/29352235/systems-modeling-accurately-predicts-responses-to-genotoxic-agents-and-their-synergism-with-bcl-2-inhibitors-in-triple-negative-breast-cancer-cells
#7
Federico Lucantoni, Andreas U Lindner, Norma O'Donovan, Heiko Düssmann, Jochen H M Prehn
Triple negative breast cancer (TNBC) is an aggressive form of breast cancer which accounts for 15-20% of this disease and is currently treated with genotoxic chemotherapy. The BCL2 (B-cell lymphoma 2) family of proteins controls the process of mitochondrial outer membrane permeabilization (MOMP), which is required for the activation of the mitochondrial apoptosis pathway in response to genotoxic agents. We previously developed a deterministic systems model of BCL2 protein interactions, DR_MOMP that calculates the sensitivity of cells to undergo mitochondrial apoptosis...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352223/zeb1-confers-chemotherapeutic-resistance-to-breast-cancer-by-activating-atm
#8
Xiang Zhang, Zhen Zhang, Qing Zhang, Quansheng Zhang, Peiqing Sun, Rong Xiang, Guosheng Ren, Shuang Yang
Although zinc finger E-box binding homeobox 1 (ZEB1) has been identified as a key factor in the regulation of breast cancer differentiation and metastasis, its potential role in modulating tumor chemoresistance has not been fully understood. Here, through the study of specimens from a large cohort of human breast cancer subjects, we showed that patients with tumors that expressed high levels of ZEB1 responded poorly to chemotherapy. Moreover, ZEB1 expression was positively correlated with expression of B-cell lymphoma-extra large (Bcl-xL) and cyclin D1, which are key components of tumor chemoresistant mechanisms...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352142/fbxl10-contributes-to-the-development-of-diffuse-large-b-cell-lymphoma-by-epigenetically-enhancing-erk1-2-signaling-pathway
#9
Xiujuan Zhao, Xing Wang, Qian Li, Wanbiao Chen, Na Zhang, Yu Kong, Junqiang Lv, Lei Cao, Dan Lin, Xi Wang, Guogang Xu, Xudong Wu
Epigenetic modifiers have emerged as critical factors governing the biology of different cancers. Herein we show that FBXL10 (also called KDM2B or JHDM1B), an important member of Polycomb repressive complexes, is overexpressed in human diffuse large B-cell lymphoma (DLBCL) tissues and the derived cell lines. Knocking down FBXL10 by specific short hairpin RNAs in DLBCL cells inhibits cell proliferation and induces apoptosis in vitro. Moreover, FBXL10 depletion in DLBCL cells abrogates tumor growth in mouse xenograft models...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352124/hbv-infection-potentiates-resistance-to-s-phase-arrest-inducing-chemotherapeutics-by-inhibiting-chk2-pathway-in-diffuse-large-b-cell-lymphoma
#10
Xinying Zhao, Xudong Guo, Libo Xing, Wenqin Yue, Haisen Yin, Miaoxia He, Jianmin Wang, Jianmin Yang, Jie Chen
A considerable number of diffuse large B-cell lymphoma (DLBCL) patients are infected with hepatitis B virus (HBV), which is correlated with their poor outcomes. However, the role of HBV infection in DLBCL treatment failure remains poorly understood. Here, our data demonstrated that HBV infection was closely associated with poorer clinical prognosis independent of its hepatic dysfunction in germinal center B-cell type (GCB type) DLBCL patients. Interestingly, we found that DLBCL cells expressing hepatitis B virus X protein (HBX) did not exhibit enhanced cell growth but did show reduced sensitivity to methotrexate (MTX) and cytarabine (Ara-C), which induced S-phase arrest...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352101/activation-of-disease-during-therapy-with-alemtuzumab-in-3-patients-with-multiple-sclerosis
#11
Thomas Wehrum, Lena-Alexandra Beume, Oliver Stich, Irina Mader, Mathias Mäurer, Adam Czaplinski, Cornelius Weiller, Sebastian Rauer
OBJECTIVE: To report 3 patients with multiple sclerosis showing severe activation of disease during immunotherapy with alemtuzumab. METHODS: Retrospective case series. RESULTS: Patient 1, a 21-year-old woman, developed severe cognitive impairment, sight deterioration, severe gait ataxia, urinary retention, and extensive progression of cerebral lesion load, including new lesions that exhibited gadolinium ring enhancement and dominance of CD19/20-positive B lymphocytes, 6 months after induction of alemtuzumab...
January 19, 2018: Neurology
https://www.readbyqxmd.com/read/29352038/microenvironment-induced-cd44v6-promotes-early-disease-progression-in-chronic-lymphocytic-leukemia
#12
Julia C Gutjahr, Eva Szenes, Lisa Tschech, Daniela Asslaber, Michaela Schlederer, Simone Roos, Xiaobing Yu, Tamara Girbl, Christina Sternberg, Alexander Egle, Fritz Aberger, Ronen Alon, Lukas Kenner, Richard Greil, Veronique Orian-Rousseau, Tanja N Hartmann
Chronic lymphocytic leukemia (CLL) outgrowth depends on signals from the microenvironment. We have previously found that in vitro reconstitution of this microenvironment induces specific variant isoforms of the adhesion molecule CD44, which confer human CLL with high affinity to hyaluronan (HA). Here, we determined the in vivo contribution of standard CD44 and its variants to leukemic B-cell homing and proliferation in Tcl1 transgenic mice with a B-cell-specific CD44 deficiency. In these mice, leukemia onset was delayed and leukemic infiltration of spleen, liver, and lungs, but not of bone marrow was decreased...
January 19, 2018: Blood
https://www.readbyqxmd.com/read/29351999/mll1-promotes-il-7-responsiveness-and-survival-during-b-cell-differentiation
#13
Tao Gan, Bin E Li, Bibhu P Mishra, Kenneth L Jones, Patricia Ernst
B lymphocyte differentiation is an exquisitely regulated homeostatic process resulting in continuous production of appropriately selected B cells. Relatively small changes in gene expression can result in deregulation of this process, leading to acute lymphocytic leukemia (ALL), immune deficiency, or autoimmunity. Translocation of MLL1 (KMT2A) often results in a pro-B cell ALL, but little is known about its role in normal B cell differentiation. Using a Rag1-cre mouse knock-in to selectively delete Mll1 in developing lymphocytes, we show that B cell, but not T cell, homeostasis depends on MLL1...
January 19, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29351985/tocilizumab-tacrolimus-and-methotrexate-for-the-prevention-of-acute-graft-versus-host-disease-low-incidence-of-lower-gastrointestinal-tract-disease
#14
William R Drobyski, Aniko Szabo, Fenlu Zhu, Carolyn Keever-Taylor, Kyle M Hebert, Renee Dunn, Sharon Yim, Bryon Johnson, Anita D'Souza, Mary Eapen, Timothy S Fenske, Parameswaran Hari, Mehdi Hamadani, Mary M Horowitz, J Douglas Rizzo, Wael Saber, Nirav Shah, Bronwen Shaw, Marcelo Pasquini
We conducted a phase 2 study in which patients undergoing allogeneic hematopoietic stem cell transplantation received Tocilizumab in addition to standard immune suppression with tacrolimus and methotrexate for graft versus host disease prophylaxis. Thirty-five patients were enrolled between January 2015 and June 2016. The median age of the cohort was 66 (range 22-76). All patients received busulfan-based conditioning, and were transplanted with HLA-matched related or matched unrelated bone marrow or peripheral stem cell grafts...
January 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29351920/exceptional-response-to-pembrolizumab-in-a-metastatic-chemotherapy-radiation-resistant-ovarian-cancer-patient-harboring-a-cd274-pd-l1-genetic-rearrangement
#15
Stefania Bellone, Natalia Buza, Jungmin Choi, Luca Zammataro, Laurie Gay, Julia A Elvin, David L Rimm, Yuting Liu, Elena Ratner, Peter E Schwartz, Alessandro D Santin
PURPOSE: Ovarian carcinoma no longer responsive to surgery and chemotherapy remains an incurable disease. Alternative therapeutic options remain desperately needed. EXPERIMENTAL DESIGN: We describe a heavily pretreated ovarian cancer patient with recurrent disease experiencing a remarkable clinical response to treatment with the anti-PD1 immune check-point inhibitor pembrolizumab. The clinical, pathological, and genomic characteristics of this exceptional ovarian cancer responder were carefully investigated using immunohistochemistry (IHC), quantitative multiplex fluorescence methods (ie, automated quantitative analysis, AQUA) and whole exome sequencing (WES) techniques...
January 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29351631/atypical-radiological-presentation-of-pulmonary-invasion-of-diffuse-large-b-cell-lymphoma-mimicking-pneumocystis-jiroveci-pneumonia
#16
Ryoko Inaba Higashiyama, Shinichi Makita, Akiko Miyagi Maeshima, Dai Maruyama
No abstract text is available yet for this article.
January 17, 2018: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29351623/development-of-sugar-chain-binding-single-chain-variable-fragment-antibody-to-adult-t-cell-leukemia-cells-using-glyco-nanotechnology-and-phage-display-method
#17
Kaname Muchima, Taro Todaka, Hiroyuki Shinchi, Ayaka Sato, Arisa Tazoe, Rikiya Aramaki, Yuhei Kakitsubata, Risa Yokoyama, Naomichi Arima, Masanori Baba, Masahiro Wakao, Yuji Ito, Yasuo Suda
Adult T-cell leukemia (ATL) is an intractable blood cancer caused by the infection of human T-cell leukemia virus type-1, and effective medical treatment is required. It is known that the structure and expression levels of cell surface sugar chains vary depending on cell states such as inflammation and cancer. Thus, it is expected that the antibody specific for ATL cell surface sugar chain would be an effective diagnostic tool and a strong candidate for the development of an anti-ATL drug. Here, we developed a stable sugar chain binding single chain variable fragment antibody (scFv) that can bind to ATL cells using a fiber type Sugar Chip and phage display method...
January 17, 2018: Journal of Biochemistry
https://www.readbyqxmd.com/read/29351372/a-preclinical-population-pharmacokinetic-model-for-anti-cd20-cd3-t-cell-dependent-bispecific-antibodies
#18
Gregory Z Ferl, Arthur Reyes, Liping L Sun, Melissa Cheu, Amy Oldendorp, Saroja Ramanujan, Eric G Stefanich
CD20 is a cell-surface receptor expressed by healthy and neoplastic B cells and is a well-established target for biologics used to treat B-cell malignancies. Pharmacokinetic (PK) and pharmacodynamic (PD) data for the anti-CD20/CD3 T-cell-dependent bispecific antibody BTCT4465A were collected in transgenic mouse and nonhuman primate (NHP) studies. Pronounced nonlinearity in drug elimination was observed in the murine studies, and time-varying, nonlinear PK was observed in NHPs, where three empirical drug elimination terms were identified using a mixed-effects modeling approach: i) a constant nonsaturable linear clearance term (7 mL/day/kg); ii) a rapidly decaying time-varying, linear clearance term (t½  = 1...
January 19, 2018: Clinical and Translational Science
https://www.readbyqxmd.com/read/29351194/involvement-of-bax-and-bcl-2-in-induction-of-apoptosis-by-essential-oils-of-three-lebanese-salvia-species-in-human-prostate-cancer-cells
#19
Alessandra Russo, Venera Cardile, Adriana C E Graziano, Rosanna Avola, Maurizio Bruno, Daniela Rigano
Prostate cancer is one of the most common forms of cancer in men, and research to find more effective and less toxic drugs has become necessary. In the frame of our ongoing program on traditionally used Salvia species from the Mediterranean Area, here we report the biological activities of Salvia aurea, S. judaica and S. viscosa essential oils against human prostate cancer cells (DU-145). The cell viability was measured by 3(4,5-dimethyl-thiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) test and lactate dehydrogenase (LDH) release was used to quantify necrosis cell death...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29351100/sudden-unexpected-death-from-unusually-large-primary-cardiac-b-cell-lymphoma
#20
Julius Tikka, Samuli Vaittinen, Lasse Pakanen, Philippe Lunetta
Primary cardiac lymphomas represent approximately 1% to 2% of primary cardiac neoplasms and 5% of malignant cardiac neoplasms. Here we present a case of sudden unexpected death of a middle-aged male resulting from an unusually large cardiac B-cell lymphoma. The neoplasm infiltrated the myocardium of the right atrium and ventricle and, to a lesser extent, the wall of the left atrium and pulmonary trunk. Extensive infiltration of the heart by the primary cardiac lymphoma, combined with the complete lack of symptoms, makes this case unusual...
January 18, 2018: American Journal of Forensic Medicine and Pathology
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