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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
#1
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/29351372/a-preclinical-population-pharmacokinetic-model-for-anti-cd20-cd3-t-cell-dependent-bispecific-antibodies
#2
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/29348373/-immunopathogenesis-of-myalgic-encephalomyelitis-chronic-fatigue-syndrome-me-cfs
#3
Takashi Yamamura, Hirohiko Ono, Wakiro Sato
A recent study on the pathogenesis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has revealed an elevation of inflammatory and anti-inflammatory cytokines in the sera and cerebrospinal fluids of the patients and presence of autoantibodies in subgroups of ME/CFS patients. Furthermore, investigator-initiated clinical trials have proved the efficacy of anti-CD20 antibody (rituximab), that eliminate B cells, in the treatment of ME/CFS. Based on these findings, we hypothesize that immune abnormalities, such as enhanced autoimmune responses, may play an essential role in the neuroinflammatory pathogenesis of ME/CFS...
January 2018: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/29348316/evaluation-of-next-generation-anti-cd20-antibodies-labeled-with-zirconium-89-in-human-lymphoma-xenografts
#4
Jason T Yoon, Mark S Longtine, Bernadette V Marquez-Nostra, Richard L Wahl
Radioimmunotherapies with monoclonal antibodies (mAbs) to the B-lymphocyte antigen 20 (CD20) are effective treatments for B-cell lymphomas, but United States Food and Drug Administration (FDA)-approved radioimmunotherapies exclusively use radiolabeled murine antibodies, potentially limiting re-dosing. The FDA recently approved two unlabeled anti-CD20 monoclonal antibodies, obinutizumab and ofatumumab, termed "next generation" as they are humanized (obinituzumab) or fully human (ofatumumab), thus potentially allowing a greater potential for re-dosing than with previous generation anti-CD20 antibodies, including rituximab (chimeric) and tositumumab (murine) which contain more murine peptide sequences...
January 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29343197/coexpression-of-cd3-and-cd20-in-canine-enteropathy-associated-t-cell-lymphoma
#5
Erica L Noland, Matti Kiupel
The majority of primary intestinal lymphomas in dogs are T-cell lymphomas, with enteropathy-associated T-cell lymphoma (EATL) large cell type (type 1) being the most common. While most T-cell lymphomas express the T-cell marker CD3, there is increasing evidence that some human and canine T-cell lymphomas coexpress the B-cell marker CD20. We describe 3 cases of CD3+, CD20+, Pax5- EATL type 1 in dogs. All 3 cases had clonal rearrangement of T-cell receptor gamma. Initial clinical signs included weight loss, inappetence, diarrhea, and/or vomiting...
January 1, 2018: Veterinary Pathology
https://www.readbyqxmd.com/read/29340126/hepatosplenic-gamma-delta-t-cell-lymphoma-hsgdtcl-two-rare-case-reports-from-western-india
#6
Irappa Madabhavi, Gaurang Modi, Harsha Panchal, Apurva Patel, Swaroop Revannasiddaiah, Asha Anand, Sonia Parikh, Kshitij Joshi, Malay Sarkar
Peripheral T cell lymphomas are a heterogeneous group of post-thymic, mature lymphoid malignancies, accounting for approximately 10-15% of all non-Hodgkin's lymphomas. Hepatosplenic T-cell lymphoma (HSGDTCL) is a rare entity, which is characterized by primary extra nodal disease with typical sinusoidal or sinusal infiltration of the liver and the spleen, respectively by expression of the T-cell receptor γδ chain, and by a number of other frequent clinicopathologic features, including aggressive course of disease...
October 1, 2017: International Journal of Hematology-oncology and Stem Cell Research
https://www.readbyqxmd.com/read/29340095/tumoral-immune-infiltrate-if-pd-l1-expression-and-role-of-cd8-tia-1-lymphocytes-in-localized-osteosarcoma-patients-treated-within-protocol-isg-os1
#7
Emanuela Palmerini, Claudio Agostinelli, Piero Picci, Stefano Pileri, Teresa Marafioti, Pier-Luigi Lollini, Katia Scotlandi, Alessandra Longhi, Maria Serena Benassi, Stefano Ferrari
Background: We hypothesized that immune-infiltrates were associated with superior survival, and examined a primary osteosarcoma tissue microarrays (TMAs) to test this hypothesis. Methods: 129 patients (pts) with localized osteosarcoma treated within protocol ISG-OS1 were included in the study. Clinical characteristics, expression of CD8, CD3, FOXP3, CD20, CD68/CD163 (tumor associated macrophage, TAM), Tia-1 (cytotoxic T cell), CD303 (plasmacytoid dendritic cells: pDC), Arginase-1 (myeloid derived suppressor cells: MDSC), PD-1 on immune-cells (IC), and PD-L1 on tumoral cells (TC) and IC were analysed and correlated with outcome...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29338562/targeted-microbubbles-with-ultrasound-irradiation-and-pd-1-inhibitor-to-increase-antitumor-activity-in-b-cell-lymphoma
#8
Shiya Zheng, Dan Song, Xiaoxiao Jin, Haijun Zhang, Mohanad Aldarouish, Yan Chen, Cailian Wang
AIM: Severe cardiac toxicity of doxorubicin and an immunosuppressive tumor micro-environment become main obstacles for the effective treatment of B-cell lymphoma. In this research, rituximab-conjugated and doxorubicin-loaded microbubbles (RDMs) were designed for exploring a combination approach of targeted microbubbles with ultrasound (US) irradiation and PD-1 inhibitor to overcome obstacles mentioned above. METHODS: In vivo studies were performed on SU-DHL-4 cell-grafted mice and ex vivo studies were performed on CD20+ human SU-DHL-4 cells and human T cells...
January 17, 2018: Nanomedicine
https://www.readbyqxmd.com/read/29337452/-neurology
#9
Isabelle Chopard, David Benninger, Jean-François Demonet, Renaud Du Pasquier, Lorenz Hirt, Thierry Kuntzer, Patrik Michel, Bernard Nater, Jan Novy, Andrea Rossetti, Olivier Rouaud, Philippe Ryvlin, Myriam Schluep, Marie Theaudin
Ocrelizumab (Ocrevus), an anti-CD20 monoclonal antibody, has been approved for the treatment of multiple sclerosis. Eculizumab (Soliris) has been approved in several countries for refractory forms of generalized seropositive severe myasthenia gravis. A form of gene therapy, patisiran, has shown positive results in transthyretin familial amyloidosis. In the treatment of headaches, particularly migraines, non-pharmacological approaches have shown some interesting results. The criteria for Lewy body dementia have been revised...
January 10, 2018: Revue Médicale Suisse
https://www.readbyqxmd.com/read/29333888/primary-diffuse-large-b-cell-lymphoma-of-the-ciliary-body
#10
Hayyam Kiratli, Abdullah Ağın, Berrin Büyükeren, Figen Söylemezoğlu
PURPOSE: To report an unusual case of an eye with primary ciliary body lymphoma which came to enucleation allowing detailed histopathological examination. METHODS: A 50-year-old man presented with a painful loss of vision in the left eye. The clinical, imaging, and immunohistopathological features of this case were reviewed. RESULTS: The vision in the left eye was light perception. There were keratic precipitates, an irregular and thickened iris with neovascularization...
January 15, 2018: Ocular Immunology and Inflammation
https://www.readbyqxmd.com/read/29327714/a-comprehensive-flow-cytometry-based-immunophenotypic-characterization-of-burkitt-like-lymphoma-with-11q-aberration
#11
Grzegorz Rymkiewicz, Beata Grygalewicz, Magdalena Chechlinska, Katarzyna Blachnio, Zbigniew Bystydzienski, Joanna Romejko-Jarosinska, Renata Woroniecka, Michalina Zajdel, Katarzyna Domanska-Czyz, David Martin-Garcia, Ferran Nadeu, Pawel Swoboda, Jolanta Rygier, Barbara Pienkowska-Grela, Jan Konrad Siwicki, Monika Prochorec-Sobieszek, Itziar Salaverria, Reiner Siebert, Jan Walewski
We previously described a subset of MYC translocation-negative aggressive B-cell lymphomas resembling Burkitt lymphoma, characterized by proximal gains and distal losses in chromosome 11. In the 2016 WHO classification, these MYC-negative lymphomas were recognized as a new provisional entity, 'Burkitt-like lymphoma with 11q aberration'. Here we present an immunophenotype analysis of Burkitt-like lymphomas with 11q aberration. Cells were acquired by fine needle aspiration biopsy from 10 young adult patients, 80% of whom presented recurrence-free 5-year survival...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29327711/cd3-positive-plasmablastic-b-cell-neoplasms-a-diagnostic-pitfall
#12
Zenggang Pan, Mingyi Chen, Qianyun Zhang, Endi Wang, Liqun Yin, Youyuan Xu, Qin Huang, Youzhong Yuan, Xiaohui Zhang, Gang Zheng, Ji Yuan
Rare B-cell neoplasms with plasmablastic differentiation may aberrantly express CD3 by immunohistochemical staining, which places a great challenge for diagnosis. We here studied 17 cases of CD3+ plasmablastic B-cell neoplasms, including 12 plasmablastic lymphomas and 5 plasmablastic plasma cell myelomas. All 17 cases occurred in the extranodal sites with a male predominance (13/17). Four cases were initially misinterpreted by outside institutions, among which three were diagnosed as 'peripheral T-cell lymphoma, not otherwise specified' and one was classified as 'poorly differentiated neuroendocrine carcinoma'...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29325249/-clinicopathologic-features-of-primary-hepatic-marginal-zone-lymphoma-of-mucosa-associated-lymphoid-tissue-and-hepatic-pseudolymphoma
#13
C Liu, X Li, H Li, Q X Gong, Y Li, Z Wang, Z H Zhang
Objective: To study the clinicopathological features of primary hepatic extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT lymphoma) and hepatic pseudolymphoma, and to discuss their differential diagnosis, treatment and prognosis. Methods: Three primary hepatic MALT lymphomas and two hepatic pseudolymphomas collected from January 2012 to March 2017 in the First Affiliated Hospital of Nanjing Medical University were evaluated by HE and immunohistochemistry(IHC), in-situ hybridization and immunoglobulin (Ig) gene rearrangement detection, and the relevant literature reviewed...
January 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29325247/-impact-of-prdm1-gene-inactivation-on-c-myc-regulation-in-diffuse-large-b-cell-lymphoma
#14
X Y Zhang, Z P Ma, W L Cui, X L Pang, R Chen, L Wang, W Zhang, X X Li
Objective: To investigate the role of PRDM1 gene inactivaion in the regulation of C-MYC in diffuse large B-cell lymphoma (DLBCL), and to explore the correlation of its immunophenotype and prognosis. Methods: 100 cases paraffin-embedded DLBCL tissues were collected from January 2009 to December 2015 at the First Affiliated Hospital of Xinjiang Medical University along with 20 cases of reactive proliferative lymph nodes as control. Immunohistochemical methods were used to detect the expression of CD20, CD10, MUM1, Ki-67, bcl-6, PRDM1/Blimp1, C-MYC and PAX5 protein...
January 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29324849/the-b-cell-death-function-of-obinutuzumab-hdel-produced-in-plant-nicotiana-benthamiana-l-is-equivalent-to-obinutuzumab-produced-in-cho-cells
#15
Jin Won Lee, Woon Heo, Jinu Lee, Narae Jin, Sei Mee Yoon, Ki Youl Park, Eun Yu Kim, Woo Taek Kim, Joo Young Kim
Plants have attracted attention as bio-drug production platforms because of their economical and safety benefits. The preliminary efficacy of ZMapp, a cocktail of antibodies produced in N. benthamiana (Nicotiana benthamiana L.), suggested plants may serve as a platform for antibody production. However, because the amino acid sequences of the Fab fragment are diverse and differences in post-transcriptional processes between animals and plants remain to be elucidated, it is necessary to confirm functional equivalence of plant-produced antibodies to the original antibody...
2018: PloS One
https://www.readbyqxmd.com/read/29323085/cd19-negative-b-lineage-acute-lymphoblastic-leukemia-a-diagnostic-and-therapeutic-challenge
#16
Shashi Bansal, Upendra Sharma, Akansha Jain, Richa Sharma, Bhargav Yagnik
B-lineage acute lymphoblastic leukemia (B-ALL) is an aggressive neoplasm of B-lymphocyte precursors that express the pan B-cell marker CD19 in all the cases. Rarely, a case may be assigned as B-lineage even if CD19 is negative. Here, a 16-year-old male presented with complaints of pain abdomen, on and off fever, joint pain, and hepatosplenomegaly for 2 months. Bone marrow examination was suggestive of acute leukemia with numerous leukoblasts on aspiration. On flow cytometry, gated blast population was negative for CD19, cytoCD3, and myeloperoxidase MPO and positive for CD34, TdT, HLA-DR, CD22, CD79a, and CD10...
October 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/29319177/characterization-of-ectopic-lymphoid-structures-in-different-types-of-acute-renal-allograft-rejection
#17
Kitty de Leur, Marian C Clahsen-van Groningen, Thierry P P van den Bosch, Gretchen N de Graav, Dennis A Hesselink, Janneke N Samsom, Carla C Baan, Karin Boer
BACKGROUND: We hypothesize that T cells such as IL-21+BCL6+ T follicular helper cells can regulate B cell mediated immunity within the allograft during acute T-cell mediated rejection, this process may feed chronic allograft rejection on long term. To investigate this mechanism we determined the presence and activation status of organized T and B cells in so-called ectopic lymphoid structures (ELSs) in different types of acute renal allograft rejection. METHODS: Biopsies showing the following primary diagnosis were included: acute/active antibody-mediated rejection, C4d+ (a/aABMR), acute T cell-mediated rejection grade I (aTCMRI), and acute T cell-mediated rejection grade II (aTCMRII)...
January 10, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29317666/single-very-low-rituximab-doses-in-healthy-volunteers-a-pilot-and-a-randomized-trial-implications-for-dosing-and-biosimilarity-testing
#18
Christian Schoergenhofer, Michael Schwameis, Christa Firbas, Johann Bartko, Ulla Derhaschnig, Robert M Mader, Raute Sunder Plaßmann, Petra Jilma-Stohlawetz, Kalpna Desai, Priya Misra, Ulrich Jäger, Bernd Jilma
There are no  dose-finding trials available for rituximab that could guide dosing in non-malignant diseases. We hypothesized that currently used doses (≥375 mg/m2) exceed several hundred-fold the half-maximal effective dose, which is most sensitive for detecting putative differences between biosimilars and important for dose finding. In an open label, exploratory trial healthy volunteers received single infusions of rituximab at doses of 0.1, 0.3 or 1.0 mg/m2. Subsequently, in a double-blind, randomized trial healthy volunteers received single infusions of two rituximab products at doses of 0...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29314206/follicular-lymphoma-2018-update-on-diagnosis-and-management
#19
Arnold Freedman
DISEASE OVERVIEW: Follicular lymphoma is generally an indolent B cell lymphoproliferative disorder of transformed follicular center B cells. Follicular lymphoma (FL) is characterized by diffuse lymphadenopathy, bone marrow involvement, splenomegaly and less commonly other extranodal sites of involvement. In general, cytopenias can occur but constitutional symptoms of fever, nightsweats, and weight loss are uncommon. DIAGNOSIS: Diagnosis is based on histology of preferably a biopsy of a lymph node...
February 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29313699/post-transplant-lymphoproliferative-disease-after-liver-transplantation
#20
José Ignacio Herrero, Carlos Panizo
We have read the article "Post-transplant lymphoproliferative disease in liver transplant recipients" with great interest. This article reports a series of liver transplant recipients with post-transplant lymphoproliferative disease (PTLD). The effect on patient survival and the potential benefit of rituximab-based therapy are highlighted. Rituximab is a chimeric antibody against the CD20 surface marker. This marker is found in most PTLD of a B cell origin. A recent study from our center also highlighted the role of rituximab in PTLD therapy (3)...
January 9, 2018: Revista Española de Enfermedades Digestivas
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