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https://www.readbyqxmd.com/read/28550183/somatic-mutation-spectrum-in-monoclonal-gammopathy-of-undetermined-significance-indicates-a-less-complex-genomic-landscape-compared-to-multiple-myeloma
#1
Aneta Mikulasova, Christopher P Wardell, Alexander Murison, Eileen M Boyle, Graham H Jackson, Jan Smetana, Zuzana Kufova, Ludek Pour, Viera Sandecka, Martina Almasi, Pavla Vsianska, Evzen Gregora, Petr Kuglik, Roman Hajek, Faith E Davies, Gareth J Morgan, Brian A Walker
Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant precursor of multiple myeloma with a 1% risk of progression per year. Although targeted analyses have shown the presence of specific genetic abnormalities such as IGH translocations, RB1 deletion, 1q gain, hyperdiploidy or RAS genes mutations, little is known about the molecular mechanism of malignant transformation. We have performed whole exome sequencing together with CGH+SNP array analysis in 33 flow-cytometry separated abnormal plasma cell samples from MGUS patients to describe somatic gene mutations and chromosome changes at the genome-wide level...
May 26, 2017: Haematologica
https://www.readbyqxmd.com/read/28533926/concomitant-lymphoplasmacytic-lymphoma-and-plasma-cell-myeloma-a-diagnostic-challenge
#2
Ahmad T Mansour, Alaleh Esmaeili Shandiz, Michelle K Zimmerman, Trenton D Roth, Jiehao Zhou
BACKGROUND: Lymphoplasmacytic lymphoma and plasma cell myeloma are two B cell lymphoproliferative neoplasms derived from mature B-lymphocytes in different differentiation stages. The coexistence of these two tumors in the same patient is exceedingly rare and can be difficult to diagnose. CASE PRESENTATION: A 76-year-old male presented with a pathologic fracture after a fall. Radiography showed a lytic lesion in the pelvis. Serum immunofixation showed distinct IgM kappa and IgA kappa monoclonal protein bands...
2017: American Journal of Blood Research
https://www.readbyqxmd.com/read/28533058/music-therapy-for-symptom-management-after-autologous-stem-cell-transplantation-results-from-a-randomized-study
#3
Debbie Bates, Brian Bolwell, Navneet S Majhail, Lisa Rybicki, Melissa Yurch, Donna Abounader, Joseph Kohuth, Shannon Jarancik, Heather Koniarczyk, Linda McLellan, Jane Dabney, Christine Lawrence, Lisa Gallagher, Matt Kalaycio, Ronald Sobecks, Robert Dean, Brian Hill, Brad Pohlman, Betty K Hamilton, Aaron T Gerds, Deepa Jagadeesh, Hien D Liu
High-dose chemotherapy followed by autologous stem cell transplant (ASCT) is frequently performed in patients with hematologic malignancies. ASCT can result in significant nausea, pain, and discomfort. Supportive care has improved and pharmacologic therapies are frequently employed, but with limitations. Music has been demonstrated to improve nausea and pain in patients undergoing chemotherapy but few data are available regarding the effects of music therapy in the transplant setting. In a prospective study, patients with lymphoma or multiple myeloma undergoing ASCT were randomized to receive either interactive music therapy (MT) with a board-certified music therapist or no music therapy (No MT)...
May 19, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28529614/irf4-mum1-expression-is-associated-with-poor-survival-outcomes-in-patients-with-peripheral-t-cell-lymphoma
#4
Mi Hwa Heo, Ha Young Park, Young Hyeh Ko, Won Seog Kim, Seok Jin Kim
Background: Interferon regulatory factor 4 (IRF4)/multiple myeloma oncogene-1 (MUM1) is a member of the interferon regulatory factor family of transcriptional factors. Although IRF4/MUM1 expression is associated with aggressiveness of B-cell lymphoma and multiple myeloma, the prognostic value of IRF4/MUM1 expression in peripheral T-cell lymphoma (PTCL) is unclear. Methods: We analyzed a tissue array from 69 patients diagnosed with PTCL. The expression levels of IRF4/MUM1 and associated proteins such as MYC and Ikaros were analyzed by immunohistochemistry...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28522749/expansion-of-tumor-infiltrating-cd8-t-cells-expressing-pd-1-improves-the-efficacy-of-adoptive-t-cell-therapy
#5
Sarita M Fernandez-Poma, Diego Salas-Benito, Teresa Lozano, Noelia Casares, José-Ignacio Riezu-Boj, Uxua Mancheño, Edurne Elizalde, Diego Alignani, Natalia Zubeldia, Itziar Otano, Enrique Conde, Pablo Sarobe, Juan J Lasarte, Sandra Hervas-Stubbs
Recent studies have found that tumor-infiltrating lymphocytes (TIL) expressing PD-1 can recognize autologous tumor cells, suggesting that cells derived from PD-1+ TIL can be used in adoptive T cell therapy (ACT). However, no study thus far has evaluated the antitumor activity of PD-1-selected TIL in vivo. In two mouse models of solid tumors, we show that PD-1 allows identification and isolation of tumor-specific TIL without previous knowledge of their antigen specificities. Importantly, despite the high proportion of tumor-reactive T cells present in bulk CD8 TIL before expansion, only T cell products derived from sorted PD-1+, but not from PD-1- or bulk CD8 TIL, specifically recognized tumor cells...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28515094/inhibiting-the-osteocyte-specific-protein-sclerostin-increases-bone-mass-and-fracture-resistance-in-multiple-myeloma
#6
Michelle M McDonald, Michaela R Reagan, Scott E Youlten, Sindhu T Mohanty, Anja Seckinger, Rachael L Terry, Jessica A Pettitt, Marija K Simic, Tegan L Cheng, Alyson Morse, Lawrence M T Le, David Abi-Hanna, Ina Kramer, Carolyne Falank, Heather Fairfield, Irene M Ghobrial, Paul A Baldock, David G Little, Michaela Kneissel, Karin Vanderkerken, J H Duncan Bassett, Graham R Williams, Babatunde O Oyajobi, Dirk Hose, Tri G Phan, Peter I Croucher
Multiple myeloma is a plasma cell cancer that develops in the skeleton causing profound bone destruction and fractures. The bone disease is mediated by increased osteoclastic bone resorption and suppressed bone formation. Treatment with bisphosphonates, which inhibit bone resorption, prevents bone loss but fail to influence bone formation and do not replace lost bone, so patients continue to fracture. Stimulating bone formation to increase bone mass and fracture resistance is a priority; however, targeting tumor-derived modulators of bone formation has had limited success...
May 17, 2017: Blood
https://www.readbyqxmd.com/read/28514770/mm-bmscs-induce-na%C3%A3-ve-cd4-t-lymphocytes-dysfunction-through-fibroblast-activation-protein-%C3%AE
#7
Xiaofei Wu, Yadan Wang, Jian Xu, Ting Luo, Jun Deng, Yu Hu
BACKGROUND: The tumor microenvironment plays a major role in multiple myelomas (MM). MM-BMSCs (bone marrow mesenchymal stromal cells) can support tumor growth and immune surveillance escape. On the other hand, fibroblast activation protein α, expressed by cancer stroma cells including BMSCs, has been shown to potentiate epithelial cancers growth and immune suppression. RESULTS: MM-BMSC inhibited proliferation of T cells (P = 0.0138), promoted senescence of T cells (P < 0...
April 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28512265/chaetocin-enhances-dendritic-cell-function-via-the-induction-of-heat-shock-protein-and-cancer-testis-antigens-in-myeloma-cells
#8
Manh-Cuong Vo, Thanh-Nhan Nguyen-Pham, Hyun-Ju Lee, Sung-Hoon Jung, Nu-Ri Choi, My-Dung Hoang, Hyeoung-Joon Kim, Je-Jung Lee
Dendritic cells (DC)-based vaccines are considered useful in cancer immuno-therapy, and the interactions of DC and dying tumor cells are important and promising for cancer immunotherapy. We investigated whether chaetocin could be used to induce death of myeloma cells, for loading onto DCs can affect DCs function. In this study, we show that the dying myeloma cells treated with chaetocin resulted in the induction of heat shock protein (HSP) 90, which was inhibited by antioxidant N-acetyl cysteine, and showed an increase in the expression of MAGE-A3 and MAGE-C1/CT7...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28508448/a-novel-multi-epitope-vaccine-from-mmsa-1-and-dkk1-for-multiple-myeloma-immunotherapy
#9
Chenyang Lu, Shan Meng, Yanxia Jin, Wanggang Zhang, Zongfang Li, Fang Wang, Feng Wang-Johanning, Yongchang Wei, Hailing Liu, Honglei Tu, Dan Su, Aili He, Xingmei Cao, Fuling Zhou
The identification of novel tumour-associated antigens is urgently needed to improve the efficacy of immunotherapy for multiple myeloma (MM). In this study, we identified a membrane protein MMSA-1 (multiple myeloma special antigen-1) that was specifically expressed in MM and exhibited significantly positive correlation with MM. We then identified HLA-A*0201-restricted MMSA-1 epitopes and tested their cytotoxic T lymphocyte (CTL) response. The MMSA-1 epitope SLSLLTIYV vaccine was shown to induce an obvious CTL response in vitro...
May 16, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28506593/a-rational-strategy-for-reducing-on-target-off-tumor-effects-of-cd38-chimeric-antigen-receptors-by-affinity-optimization
#10
Esther Drent, Maria Themeli, Renée Poels, Regina de Jong-Korlaar, Huipin Yuan, Joost de Bruijn, Anton C M Martens, Sonja Zweegman, Niels W C J van de Donk, Richard W J Groen, Henk M Lokhorst, Tuna Mutis
Chimeric antigen receptors (CARs) can effectively redirect cytotoxic T cells toward highly expressed surface antigens on tumor cells. The low expression of several tumor-associated antigens (TAAs) on normal tissues, however, hinders their safe targeting by CAR T cells due to on-target/off-tumor effects. Using the multiple myeloma (MM)-associated CD38 antigen as a model system, here, we present a rational approach for effective and tumor-selective targeting of such TAAs. Using "light-chain exchange" technology, we combined the heavy chains of two high-affinity CD38 antibodies with 176 germline light chains and generated ∼124 new antibodies with 10- to >1,000-fold lower affinities to CD38...
May 13, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28504661/circulating-tumor-cells-as-a-biomarker-for-response-to-therapy-in-multiple-myeloma-patients-treated-within-the-gmmg-mm5-trial
#11
S Huhn, N Weinhold, J Nickel, M Pritsch, T Hielscher, M Hummel, U Bertsch, B Huegle-Doerr, M Vogel, R Angermund, M Hänel, H J Salwender, K Weisel, J Dürig, M Görner, H Kirchner, N Peter, U Graeven, F Lordick, M Hoffmann, P Reimer, I W Blau, A Jauch, K Dembowsky, T Möhler, P Wuchter, H Goldschmidt
No abstract text is available yet for this article.
May 15, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28504647/identification-of-a-nucleoside-analog-active-against-adenosine-kinase-expressing-plasma-cell-malignancies
#12
Utthara Nayar, Jouliana Sadek, Jonathan Reichel, Denise Hernandez-Hopkins, Gunkut Akar, Peter J Barelli, Michelle A Sahai, Hufeng Zhou, Jennifer Totonchy, David Jayabalan, Ruben Niesvizky, Ilaria Guasparri, Duane Hassane, Yifang Liu, Shizuko Sei, Robert H Shoemaker, J David Warren, Olivier Elemento, Kenneth M Kaye, Ethel Cesarman
Primary effusion lymphoma (PEL) is a largely incurable malignancy of B cell origin with plasmacytic differentiation. Here, we report the identification of a highly effective inhibitor of PEL. This compound, 6-ethylthioinosine (6-ETI), is a nucleoside analog with toxicity to PEL in vitro and in vivo, but not to other lymphoma cell lines tested. We developed and performed resistome analysis, an unbiased approach based on RNA sequencing of resistant subclones, to discover the molecular mechanisms of sensitivity...
May 15, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28498418/identification-and-expression-of-mmsa-8-and-its-clinical-significance-in-multiple-myeloma
#13
Rui He, Nan Yang, Pengyu Zhang, Jie Liu, Junhui Li, Fulin Zhou, Wanggang Zhang
In our previous studies, we identified 12 multiple myeloma (MM)-associated antigens by serological analysis of tumor-associated antigens with a recombinant cDNA expression library (SEREX) on MM. MM-associated antigen-8 (MMSA-8) was one of the new antigens identified. We determined the 3'- and 5'-ends of MMSA-8 using SMART-rapid amplification of cDNA ends (RACE) and then cloned its full-length cDNA in the U266 cell line. The full cDNA sequence revealed that MMSA-8 is RPS27A-related transcript variant 1 that is specifically associated with MM...
April 28, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28495913/longitudinal-fluorescence-in-situ-hybridization-reveals-cytogenetic-evolution-in-myeloma-relapsing-after-autologous-transplantation
#14
Maximilian Merz, Anna Jauch, Thomas Hielscher, Elias K Mai, Anja Seckinger, Dirk Hose, Uta Bertsch, Kai Neben, Marc S Raab, Hans Salwender, Igor W Blau, Hans-Walter Lindemann, Ingo Schmidt-Wolf, Christof Scheid, Mathias Haenel, Katja Weisel, Hartmut Goldschmidt, Jens Hillengass
To investigate cytogenetic evolution after upfront autologous stem cell transplantation for newly diagnosed myeloma we retrospectively analyzed fluorescence in situ hybridization results of 128 patients with paired bone marrow samples at primary diagnosis and relapse. High-risk cytogenetic abnormalities (deletion 17p and/or gain1q21) occurred more frequently after relapse (odds ratio: 6.33; 95% confidence interval: 1.86,33.42;p<0.001). No significant changes were observed for defined IgH translocations (t(4;14); t(11;14); t(14;16)) or hyperdiploid karyotypes between primary diagnosis and relapse...
May 11, 2017: Haematologica
https://www.readbyqxmd.com/read/28495797/ixazomib-enhances-parathyroid-hormone-pth-induced-%C3%AE-catenin-t-cell-factor-tcf-signaling-by-dissociating-%C3%AE-catenin-from-the-pth-receptor
#15
Yanmei Yang, Hong Lei, Ya-Wei Qiang, Bin Wang
The anabolic action of PTH in bone is mostly mediated by cAMP/PKA and Wnt-independent activation of β-catenin/T-cell factor (TCF) signaling. β-catenin switches the PTH receptor (PTHR) signaling from cAMP/PKA to PLC/PKC activation by binding to the PTHR. Ixazomib (Izb) is the first orally administered proteasome inhibitor that was approved recently for the treatment of multiple myeloma in part through inhibition of pathologic bone destruction. Proteasome inhibitors were reported to stabilize β-catenin by ubiquitin-proteasome pathway...
May 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28490813/leptin-receptor-antagonism-of-inkt-cell-function-a-novel-strategy-to-combat-multiple-myeloma
#16
M Favreau, E Menu, D Gaublomme, K Vanderkerken, S Faict, K Maes, E De Bruyne, S Govindarajan, M Drennan, S Van Calenbergh, X Leleu, L Zabeau, J Tavernier, K Venken, D Elewaut
A hallmark of bone marrow changes with aging is the increase in adipocyte composition, but how this impacts development of multiple myeloma (MM) is unknown. Here, we report the role of the adipokine leptin as master regulator of anti-myeloma tumor immunity by modulating the invariant natural killer T (iNKT) cell function. A marked increase in serum leptin levels and leptin receptor (LR) expression on iNKT cells in MM patients and the 5T33 murine MM model was observed. MM cells and leptin synergistically counteracted anti-tumor functionality of both murine and human iNKT cells...
May 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28490812/hdac3-regulates-dnmt1-expression-in-multiple-myeloma-therapeutic-implications
#17
T Harada, H Ohguchi, Y Grondin, S Kikuchi, M Sagawa, Y-T Tai, R Mazitschek, T Hideshima, K C Anderson
Epigenetic signaling pathways are implicated in tumorigenesis and therefore histone deacetylases (HDACs) represent novel therapeutic targets for cancers including multiple myeloma (MM). Although non-selective HDAC inhibitors show anti-MM activities, unfavorable side effects limit their clinical efficacy. Isoform- and/or class-selective HDAC inhibition offers the possibility to maintain clinical activity while avoiding adverse events attendant to broad non-selective HDAC inhibition. We have previously reported that HDAC3 inhibition, either by genetic knockdown or selective inhibitor BG45, abrogates MM cell proliferation...
May 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28487543/kdm6b-modulates-mapk-pathway-mediating-multiple-myeloma-cell-growth-and-survival
#18
H Ohguchi, T Harada, M Sagawa, S Kikuchi, Y-T Tai, P G Richardson, T Hideshima, K C Anderson
Recent studies have delineated cancer type-specific roles of histone 3 lysine 27 (H3K27) demethylase KDM6B/JMJD3 depending on its H3K27 demethylase activity. Here we show that KDM6B is expressed in multiple myeloma (MM); and that shRNA-mediated knockdown and CRISPR-mediated knockout of KDM6B abrogate MM cell growth and survival. TNFα or bone marrow stromal cell culture supernatants induce KDM6B, which is blocked by IKKβ inhibitor MLN120B, suggesting KDM6B is regulated by NF-κB signaling in MM cells. RNA-sequencing and subsequent ChIP-qPCR analyses reveal that KDM6B is recruited to the loci of genes encoding components of MAPK signaling pathway including ELK1 and FOS, and upregulates these genes expression without affecting H3K27 methylation level...
May 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28483281/preclinical-data-support-leveraging-cs1-chimeric-antigen-receptor-t-cell-therapy-for-systemic-light-chain-amyloidosis
#19
Michael Rosenzweig, Ryan Urak, Miriam Walter, Laura Lim, James F Sanchez, Amrita Krishnan, Stephen Forman, Xiuli Wang
BACKGROUND AIMS: Light chain amyloidosis (AL) is a protein deposition disorder that is a result of a plasma cell dyscrasia, similar to multiple myeloma (MM). Immunotherapy is an attractive approach because of the low burden of disease, but the optimal target for AL is unclear. CS1 and B-cell maturation antigen (BCMA) are two potential targets because they are expressed on normal plasma cells and MM cells. METHODS: We performed a prospective study evaluating bone marrow specimens of 20 patients with plasma cell diseases, 10 with AL and 10 with MM...
May 5, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28471126/multiple-myeloma-with-an-unusual-oral-presentation
#20
Anjali Nayak, Meghanand T Nayak
Multiple myeloma (MM) is a dyscrasia caused by neoplastic proliferation of somatically mutated plasma cells. Myeloma cells divide and expand within the bone marrow affecting multiple locations in the body where bone marrow is present. Oral manifestations, though common are usually not diagnosed. This report describes rare oral manifestations of multiple myeloma like oral petechiae and gingival swelling presented in a 40-year-old male patient. The diagnosis was established by blood examination & skeletal survey, while oral findings were later correlated with the diagnosis of MM...
July 2016: Journal of Experimental Therapeutics & Oncology
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