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https://www.readbyqxmd.com/read/29450576/immunopet-imaging-of-cd38-in-murine-lymphoma-models-using-89-zr-labeled-daratumumab
#1
Lei Kang, Dawei Jiang, Christopher G England, Todd E Barnhart, Bo Yu, Zachary T Rosenkrans, Rongfu Wang, Jonathan W Engle, Xiaojie Xu, Peng Huang, Weibo Cai
PURPOSE: CD38 is considered a potential biomarker for multiple myeloma (MM) and has shown a strong link with chronic lymphocytic leukemia due to high and uniform expression on plasma cells. In vivo evaluation of CD38 expression may provide useful information about lesion detection and prognosis of treatment in MM. In this study, immunoPET imaging with 89 Zr-labeled daratumumab was used for differentiation of CD38 expression in murine lymphoma models to provide a potential non-invasive method for monitoring CD38 in the clinic...
February 15, 2018: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29445583/deep-sustained-response-to-daratumumab-monotherapy-associated-with-t-cell-expansion-in-triple-refractory-myeloma
#2
Saad Z Usmani, Imran Khan, Christopher Chiu, David Foureau, Lawrence J Druhan, Katherine Rigby, Tineke Casneuf, A Kate Sasser
Background: Daratumumab, a human CD38 monoclonal antibody that has direct on-tumor and immunomodulatory mechanisms of action, demonstrated clinical benefit as monotherapy or in combination with established regimens in patients with multiple myeloma with one or more prior lines of therapy. Case presentation: A male patient, who was 70 years of age at the time of diagnosis of multiple myeloma in 2011, relapsed after five lines of therapy, including autologous stem cell transplantation...
2018: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29438096/fda-approval-summary-lenalidomide-as-maintenance-therapy-after-autologous-stem-cell-transplant-in-newly-diagnosed-multiple-myeloma
#3
Elizabeth Dianne Pulte, Andrew Dmytrijuk, Lei Nie, Kirsten B Goldberg, Amy E McKee, Ann T Farrell, Richard Pazdur
On February 22, 2017, the U.S. Food and Drug Administration (FDA) granted approval for the use of lenalidomide as maintenance therapy after autologous hematopoietic stem cell transplantation (auto-HSCT) for patients with multiple myeloma. The approval was based on evidence from two randomized, blinded trials of maintenance lenalidomide versus placebo in patients with myeloma who had undergone auto-HSCT along with a third trial of lenalidomide versus no therapy. Each of the trials demonstrated superior progression-free survival for the patients treated with lenalidomide...
February 7, 2018: Oncologist
https://www.readbyqxmd.com/read/29435173/crispr-knock-out-of-programmed-cell-death-protein-1-enhances-anti-tumor-activity-of-cytotoxic-t-lymphocytes
#4
Zhilong Zhao, Long Shi, Wei Zhang, Jinsheng Han, Shaohui Zhang, Zexian Fu, Jianhui Cai
Programmed cell death protein 1 (PD-1) is an immune checkpoint receptor that functions to attenuate T cell activation. In this study, we knocked out (KO) PD-1 in cytotoxic T lymphocytes (CTLs) using CRISPR-Cas9 system to evaluate its effect on the anti-tumor activity of the CTLs against multiple myeloma (MM). Results show that PD-1 KO CTLs facilitate apoptosis and caspase activation of the co-cultured MM cells and enhanced MM cell death by 36% compared with the control. PD-1 KO also increased TNF-α and IFN-γ secretion of the CTLs by 2...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29432497/autologous-t-cells-expressing-the-oncogenic-transcription-factor-klf6-sv1-prevent-apoptosis-of-chronic-lymphocytic-leukemia-cells
#5
Parviz Kokhaei, Mohammad Hojjat-Farsangi, Fariba Mozaffari, Ali Moshfegh, Fatemeh Pak, Ali Rashidy-Pour, Marzia Palma, Lotta Hansson, Anders Österborg, Håkan Mellstedt
Crosstalk between leukemic cells and the tumor microenvironment is of importance in chronic lymphocytic leukemia (CLL). T cells seem to sustain the survival of CLL cells by various mechanisms. The Krüppel-like family of transcription factors (KLFs) are identified as regulators of proliferation and cell death. In the present study, we analyzed the expression of the wild type (WT) gene KLF6 and the oncogenic splice variant 1 (KLF6-SV1) at the mRNA level in subsets of T cells from CLL patients (n = 29), multiple myeloma patients (n = 6) and normal donors (n = 10)...
2018: PloS One
https://www.readbyqxmd.com/read/29427804/escmid-study-group-for-infections-in-compromised-hosts-esgich-consensus-document-on-the-safety-of-targeted-and-biological-therapies-an-infectious-diseases-perspective-immune-checkpoint-inhibitors-cell-adhesion-inhibitors-sphingosine-1-phosphate-receptor-modulators
#6
REVIEW
Gil Redelman-Sidi, Olivier Michielin, Carlos Cervera, Camillo Ribi, José María Aguado, Mario Fernández-Ruiz, Oriol Manuel
BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of immune checkpoint inhibitors, LFA-3-targeted agents, cell adhesion inhibitors, sphingosine-1-phosphate receptor modulators and proteasome inhibitors and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family...
February 7, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29424538/development-of-a-targeted-mass-spectrometry-serum-assay-to-quantify-m-protein-in-the-presence-of-therapeutic-monoclonal-antibodies
#7
Marina Zajec, Joannes F M Jacobs, Patricia J T A Groenen, Corrie M de Kat Angelino, Christoph Stingl, Theo M Luider, Yolanda B De Rijke, Martijn M VanDuijn
M-protein diagnostics can be compromised for patients receiving therapeutic monoclonal antibodies as treatment in multiple myeloma. Conventional techniques are often not able to distinguish between M-proteins and therapeutic monoclonal antibodies administered to the patient. This may prevent correct response assessment and can lead to overtreatment. We have developed a serum-based targeted mass spectrometry assay to detect M-proteins, even in the presence of three therapeutic monoclonal antibodies (daratumumab, ipilimumab and nivolumab)...
February 9, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29421983/emerging-immune-targets-for-the-treatment-of-multiple-myeloma
#8
Atif Sohail, Adeela Mushtaq, Ahmad Iftikhar, Zabih Warraich, Sandra E Kurtin, Pavan Tenneti, Ali McBride, Faiz Anwer
We reviewed emerging immune strategies for multiple myeloma (MM) therapy excluding US FDA approved drugs. In relapsed refractory MM, isatuximab (anti-CD38) monotherapy achieved overall response (OR) of 24%. Other monoclonal antibodies that have shown efficacy in combination therapy include siltuximab (OR: 66%), indatuximab (OR: 78%), isatuximab (OR: 64.5%), pembrolizumab (OR: 60%), bevacizumab (OR: 70%), dacetuzumab (OR: 39%) and lorvotuzumab (OR: 56.4%). No OR was observed with monotherapy using BI-505, siltuximab, bevacizumab, AVE-1642, figitumumab, atacicept, milatuzumab, dacetuzumab, lucatumumab, IPH2101, lorvotuzumab, BT062 and nivolumab...
February 1, 2018: Immunotherapy
https://www.readbyqxmd.com/read/29416605/human-dkk1-and-human-hsp70-fusion-dna-vaccine-induces-an-effective-anti-tumor-efficacy-in-murine-multiple-myeloma
#9
Ting-Ting Liu, Yang Wu, Ting Niu
Dickkopf-1 (DKK1) is an ideal target for the immunotherapy of multiple myeloma. Heat Shock protein70 (HSP70) is a class of important molecular chaperone to promote antigen presentation. Homologous xenogeneic antigens can enhance immunogenicity and induce stronger anti-tumor immune response than that of allogeneic ones. Therefore, we constructed human DKK1 and human HSP70 DNA fusion vaccine (hDKK1-hHSP70), and then determined its anti-tumor immuno- genicity and anti-tumor effects on immunizing BALB/c mice already inoculated with NS-1 murine multiple myeloma cells in prophylactic and therapeutic models using cytotoxic T lymphocytes, enzyme-lined immunosorbent assay, flow cytometry, immunohistochemistry and Hochest staining...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29410180/plerixafor-plus-granulocyte-colony-stimulating-factor-for-patients-with-non-hodgkin-s-lymphoma-and-multiple-myeloma-long-term-follow-up-report
#10
Ivana N Micallef, Patrick J Stiff, Auayporn P Nademanee, Richard T Maziarz, Mitchell E Horwitz, Edward A Stadtmauer, Jonathan L Kaufman, John M McCarty, Rita Vargo, Peter D Cheverton, Martin Struijs, Brian Bolwell, John F DiPersio
The purpose of this report is to analyze long-term clinical outcomes of patients exposed to plerixafor plus granulocyte colony-stimulating factor (G-CSF) for stem cell mobilization. This was a study of patients with non-Hodgkin's lymphoma (NHL, n = 167) and multiple myeloma (MM, n = 163) who were enrolled in the long-term follow-up of 2 pivotal phase III studies (NCT00741325 and NCT00741780) of 240 µg/kg plerixafor plus 10 µg/kg G-CSF, or placebo plus 10 µg/kg G-CSF to mobilize and collect CD34+ cells for auto-HSCT...
February 1, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29409124/current-developments-in-immunotherapy-in-the-treatment-of-multiple-myeloma
#11
REVIEW
Martin Köhler, Christine Greil, Michael Hudecek, Sagar Lonial, Noopur Raje, Ralph Wäsch, Monika Engelhardt
Multiple myeloma (MM) is the second most common hematologic malignancy and represents approximately 10% of all hematological neoplasms. Standard therapy consists of induction therapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) or, if ASCT cannot be performed, standard doublet, triplet, or quadruplet, novel agent-containing induction treatment until progression. Although MM is still regarded as mostly incurable by current standards, the development of several novel compounds, combination therapies, and immunotherapy approaches has raised great hopes about transforming MM into an indolent, chronic disease and possibly achieving a cure for individual patients...
February 6, 2018: Cancer
https://www.readbyqxmd.com/read/29397841/-effects-of-thalidomide-on-the-ratio-of-th17-to-treg-cells-in-peripheral-blood-and-expression-of-il-17-and-il-35-in-patients-with-multiple-myeloma
#12
Ling-Jun Zhao, Song Gao, Xiao Li
OBJECTIVE: To explore the effects of thalidomide on the ratio of Th17 to Treg cells in peripheral blood and expression of IL-17 and IL-35 in patients with multiple myeloma(MM), so as to provide reference for the clinical treatment of patients with MM. METHODS: A total of 82 MM patients treated with thalidomide from January 2014 to December 2016 were enrolled in MM group, 30 healthy subjects were selected as control (control group). The ratio of T cell subsets and Treg cells accounted for CD4 + T cell were detected by flow cytometer...
February 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29397346/single-center-experience-in-treating-patients-with-t-4-14-multiple-myeloma-with-and-without-planned-frontline-autologous-stem-cell-transplantation
#13
Henry Chan, Madeline Phillips, Manjula Maganti, Sophia Farooki, Giovanni Piza Rodriguez, Esther Masih-Khan, Christine Chen, Anca Prica, Donna Reece, Rodger Tiedemann, Suzanne Trudel, Vishal Kukreti
BACKGROUND: Translocation t(4;14) has traditionally been classified as a high-risk cytogenetic feature in patients with multiple myeloma with shortened progression-free (PFS) and overall survival (OS) despite initial response to treatment. Recent data have shown an improved long-term survival in these patients treated with novel agents, such as bortezomib. PATIENTS AND METHODS: We conducted a retrospective study on our patients with t(4;14) multiple myeloma treated with bortezomib-based induction between July 1, 2006 and June 30, 2014 to assess the real-world outcomes of these patients in a tertiary center...
January 5, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29381435/selective-inhibition-of-nuclear-export-with-oral-selinexor-for-treatment-of-relapsed-or-refractory-multiple-myeloma
#14
Dan T Vogl, David Dingli, Robert Frank Cornell, Carol Ann Huff, Sundar Jagannath, Divaya Bhutani, Jeffrey Zonder, Rachid Baz, Ajay Nooka, Joshua Richter, Craig Cole, Ravi Vij, Andrzej Jakubowiak, Rafat Abonour, Gary Schiller, Terri L Parker, Luciano J Costa, David Kaminetzky, James E Hoffman, Andrew J Yee, Ajai Chari, David Siegel, Rafael Fonseca, Scott Van Wier, Gregory Ahmann, Ilsel Lopez, Michael Kauffman, Sharon Shacham, Jean-Richard Saint-Martin, Carla D Picklesimer, Cassandra Choe-Juliak, A Keith Stewart
Purpose Selinexor, a first-in-class, oral, selective exportin 1 (XPO1) inhibitor, induces apoptosis in cancer cells through nuclear retention of tumor suppressor proteins and the glucocorticoid receptor, along with inhibition of translation of oncoprotein mRNAs. We studied selinexor in combination with low-dose dexamethasone in patients with multiple myeloma refractory to the most active available agents. Patients and Methods This phase II trial evaluated selinexor 80 mg and dexamethasone 20 mg, both orally and twice weekly, in patients with myeloma refractory to bortezomib, carfilzomib, lenalidomide, and pomalidomide (quad-refractory disease), with a subset also refractory to an anti-CD38 antibody (penta-refractory disease)...
January 30, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29380550/distinct-predictive-impact-of-fish-abnormality-in-proteasome-inhibitors-and-immunomodulatory-agents-response-redefining-high-risk-multiple-myeloma-in-asian-patients
#15
Ja Min Byun, Dong-Yeop Shin, Junshik Hong, Inho Kim, Hyun Kyung Kim, Dong Soon Lee, Youngil Koh, Sung-Soo Yoon
For risk-adaptive therapeutic approaches in multiple myeloma (MM) treatment, we analyzed treatment outcome according to in situ hybridization (FISH) profiles to investigate the prognostic and predictive values of structural variations in a large series of Asian population. A total of 565 newly diagnosed patients with multiple myeloma between January 2005 and June 2015 were evaluated. FISH results showed del(17p13) in 8.8% (29/331), del(13q14) in 35.5% (184/519), t(14;16) in 2.5% (8/326), t(4;14) in 27.9% (109/390), IgH rearrangement in 47...
January 29, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29368256/immunopathogenesis-and-immunotherapy-of-multiple-myeloma
#16
REVIEW
Hideto Tamura
Despite the advent of novel therapies and improvements in survival, multiple myeloma (MM) remains an incurable disease. Thus, new treatment strategies including immunotherapies are needed for MM patients with stable disease after induction chemotherapy as well as for disease control in patients with advanced disease. However, profound immune dysregulation not only of B cells, but also of other immune cells such as natural killer cells, T cells, and dendritic cells and increase in the number of immunosuppressive cells, i...
January 24, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29365400/-effects-of-psmb5-on-proliferation-and-bortezomib-chemo-resistance-in-human-myeloma-cells-and-its-related-molecular-mechanisms
#17
H M Mo, Q Y Wu, D Y Han, R Liu, X Ma, P Zhou, K L Xu
Objective: To investigate the effects of proteasome beta 5 subunit (PSMB5) on proliferation and bortezomib (BTZ) chemo-sensitivity of multiple myeloma (MM) and its related molecular mechanisms. Methods: We used two MM cell lines, RPMI 8226 and BTZ drug-resistant cell line RPMI 8226/BTZ100 (hereinafter referred to as BTZ100) , as the research object. PSMB5 was overexpressed or knocked down in two myeloma cell lines via lentivirus transfection. CCK8 assay was used to detect the impact of PSMB5 on cell viability and bortezomib sensitivity in human myeloma cells; Using flow cytometry to test the effects of PSMB5 on apoptosis rate of human myeloma cells under the treatment of bortezomib; Apoptosis-related gene expression of Bax, Bcl-2, p-Akt and cleaved caspase-3 were detected by Western blot...
December 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29344579/prognostic-significance-of-cytogenetic-heterogeneity-in-patients-with-newly-diagnosed-multiple-myeloma
#18
Maximilian Merz, Anna Jauch, Thomas Hielscher, Tilmann Bochtler, Stefan Olaf Schönland, Anja Seckinger, Dirk Hose, Uta Bertsch, Kai Neben, Marc Steffen Raab, Jens Hillengass, Hans Salwender, Igor Wolfgang Blau, Hans-Walter Lindemann, Ingo G H Schmidt-Wolf, Christof Scheid, Mathias Haenel, Katja C Weisel, Hartmut Goldschmidt
We investigated subclonal cytogenetic aberrations (CA) detected by interphase fluorescence in situ hybridization (iFISH) in patients with newly diagnosed multiple myeloma (MM) enrolled in the Haemato Oncology Foundation for Adults in the Netherlands (HOVON)-65/German-Speaking MM Group (GMMG)-HD4 phase 3 trial. Patients were either treated with 3 cycles of vincristine, Adriamycin, and dexamethasone or bortezomib, Adriamycin, and dexamethasone and then thalidomide or bortezomib maintenance after tandem autologous transplantation...
January 9, 2018: Blood Advances
https://www.readbyqxmd.com/read/29327711/cd3-positive-plasmablastic-b-cell-neoplasms-a-diagnostic-pitfall
#19
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/29327244/antibody-based-delivery-of-tumor-necrosis-factor-l19-tnf%C3%AE-and-interleukin-2-l19-il2-to-tumor-associated-blood-vessels-has-potent-immunological-and-anticancer-activity-in-the-syngeneic-j558l-balb-c-myeloma-model
#20
Hans D Menssen, Ulf Harnack, Ulrike Erben, Dario Neri, Burkhard Hirsch, Horst Dürkop
PURPOSE: To analyze the impact of TNFα or IL2 on human lymphocytes in vitro and the anti-tumor and immune-modifying effects of L19-IL2 and L19-TNFα on subcutaneously growing J558L myeloma in immunocompetent mice. METHODS: PBMCs from three healthy volunteers were incubated with IL2, TNFα, or with IL2 plus addition of TNFα (final 20 h). BALB/c J558L mice with subcutaneous tumors were treated with intravenous L19-TNFα plus L19-IL2, or controls. Tumor growth and intra- and peri-tumoral tissues were analyzed for micro-vessel density, necrosis, immune cell composition, and PD1 or PD-L1 expressing cells...
January 11, 2018: Journal of Cancer Research and Clinical Oncology
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