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https://www.readbyqxmd.com/read/29736687/cyclooxygenase-and-lipoxygenase-gene-expression-in-the-inflammogenesis-of-breast-cancer
#1
Brian M Kennedy, Randall E Harris
We examined the expression of major inflammatory genes, cyclooxygenase-1 and 2 (COX1, COX2) and arachidonate 5-lipoxygenase (ALOX5) in 1090 tumor samples of invasive breast cancer from The Cancer Genome Atlas (TCGA). Mean cyclooxygenase expression (COX1 + COX2) ranked in the upper 99th percentile of all 20,531 genes and surprisingly, the mean expression of COX1 was more than tenfold higher than COX2. Highly significant correlations were observed between COX2 with eight tumor-promoting genes (EGR2, IL6, RGS2, B3GNT5, SGK1, SLC2A3, SFRP1 and ETS2) and between ALOX5 and ten tumor promoter genes (CD33, MYOF1, NLRP1, GAB3, CD4, IFR8, CYTH4, BTK, FGR, CD37)...
May 7, 2018: Inflammopharmacology
https://www.readbyqxmd.com/read/29551516/interleukin-6-is-essential-for-glomerular-immunoglobulin-a-deposition-and-the-development-of-renal-pathology-in-cd37-deficient-mice
#2
Angelique L W M M Rops, Erik Jansen, Alie van der Schaaf, Elmar Pieterse, Nils Rother, Julia Hofstra, Henry B P M Dijkman, Anne-Els van de Logt, Jack Wetzels, Johan van der Vlag, Annemiek B van Spriel
Immunoglobulin A (IgA) nephropathy (IgAN), the most common glomerulonephritis worldwide, is characterized by IgA depositions in the kidney. Deficiency of CD37, a leukocyte-specific tetraspanin, leads to spontaneous development of renal pathology resembling IgAN. However, the underlying molecular mechanism has not been resolved. Here we found that CD37 expression on B cells of patients with IgAN was significantly decreased compared to B cells of healthy donors. Circulating interleukin (IL)-6 levels, but not tumor necrosis factor-α or IL-10, were elevated in Cd37-/- mice compared to wild-type mice after lipopolysaccharide treatment...
March 15, 2018: Kidney International
https://www.readbyqxmd.com/read/29470615/pre-dosing-with-lilotomab-prior-to-therapy-with-177-lu-lilotomab-satetraxetan-significantly-increases-the-ratio-of-tumor-to-red-marrow-absorbed-dose-in-non-hodgkin-lymphoma-patients
#3
Caroline Stokke, Johan Blakkisrud, Ayca Løndalen, Jostein Dahle, Anne C T Martinsen, Harald Holte, Arne Kolstad
PURPOSE: 177 Lu-lilotomab satetraxetan is a novel anti-CD37 antibody radionuclide conjugate for the treatment of non-Hodgkin lymphoma (NHL). Four arms with different combinations of pre-dosing and pre-treatment have been investigated in a first-in-human phase 1/2a study for relapsed CD37+ indolent NHL. The aim of this work was to determine the tumor and normal tissue absorbed doses for all four arms, and investigate possible variations in the ratios of tumor to organs-at-risk absorbed doses...
February 22, 2018: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29453628/safety-tolerability-and-preliminary-activity-of-imgn529-a-cd37-targeted-antibody-drug-conjugate-in-patients-with-relapsed-or-refractory-b-cell-non-hodgkin-lymphoma-a-dose-escalation-phase-i-study
#4
Anastasios Stathis, Ian W Flinn, Sumit Madan, Kami Maddocks, Arnold Freedman, Steven Weitman, Emanuele Zucca, Mihaela C Munteanu, M Lia Palomba
Background CD37 is expressed on B-cell lymphoid malignancies, thus making it an attractive candidate for targeted therapy in non-Hodgkin lymphoma (NHL). IMGN529 is an antibody-drug conjugate comprising a CD37-binding antibody linked to the maytansinoid DM1, a potent anti-mitotic agent. Methods This first-in-human, phase 1 trial recruited adult patients with relapsed or refractory B-cell NHL. The primary objective was to determine the maximum tolerated dose (MTD) and recommended phase 2 dose. Secondary objectives were to evaluate safety, pharmacokinetics, and preliminary clinical activity...
February 17, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29323537/investigational-therapies-targeting-cd37-for-the-treatment-of-b-cell-lymphoid-malignancies
#5
REVIEW
Magdalena Witkowska, Piotr Smolewski, Tadeusz Robak
While chemotherapy still remains a cornerstone of oncologic therapy, immunotherapy with monoclonal antibodies has steadily improved the treatment strategy for several hematologic malignancies. New treatment options need to be developed for relapsed and refractory non-Hodgkin lymphoma (NHL) patients. Currently, novel agents targeting specific molecules on the surface of lymphoma cells, such as anti-CD37 antibodies, are under considerable investigation. Here we report on anti-CD37 targeting for the treatment of patients with B-cell NHL...
February 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29188602/-rare-thalassemia-mutations-among-southern-chinese-population
#6
Fen Lin, Liye Yang, Min Lin, Xiangbian Zheng, Min Lu, Meilan Qiu, Liejun Li, Longxu Xie
OBJECTIVE: To detect rare types of thalassemia mutations among southern Chinese population. METHODS: Peripheral blood samples from 327 patients from various regions of southern China were collected. The patients were suspected as rare-type thalassemia for their inconsistency between hematological phenotypes and results of routine mutation screening. The samples were further analyzed with GAP-PCR and DNA sequencing. RESULTS: One hundred and eight cases were diagnosed as rare types of thalassemia...
December 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/29100377/secreted-gelsolin-desensitizes-and-induces-apoptosis-of-infiltrated-lymphocytes-in-prostate-cancer
#7
Chun-Chi Chen, Shiow-Her Chiou, Cheng-Lin Yang, Kuan-Chih Chow, Tze-Yi Lin, Hui-Wen Chang, Weir-Chiang You, Hisu-Wen Huang, Chien-Min Chen, Nien-Cheng Chen, Fen-Pi Chou, Ming-Chih Chou
Loss of immunosurveillance is a major cause of cancer progression. Here, we demonstrate that gelsolin, a constituent of ejaculate, induces apoptosis of activated lymphocytes in prostate cancer. Gelsolin was highly expressed in prostate cancer cells, and was associated with tumor progression, recurrence, metastasis, and poor prognosis. In vitro , secreted gelsolin inactivated CD4+ T cells by binding to CD37, and induced apoptosis of activated CD8+ T lymphocytes by binding to Fas ligand during cell contact dependent on major histocompatibility complex I...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029255/plasmids-can-transfer-to-clostridium-difficile-cd37-and-630%C3%AE-erm-both-by-a-dnase-resistant-conjugation-like-mechanism-and-a-dnase-sensitive-mechanism
#8
Ladan Khodadoost, Haitham Hussain, Peter Mullany
Broad host range conjugative plasmids that replicate in Escherichia coli have been widely used to mobilise smaller replicons, bearing their cognate origin of transfer (oriT) into a variety of organisms that are less tractable genetically, such as Clostridium (Clostridioides) difficile. In this work we demonstrated that the oriT region of pMTL9301 (derived from RK2) is not required for transfer between E. coli and C. difficile strains 630Δerm and CD37 and that this oriT-independent transfer is abolished in the presence of DNase when CD37 is the recipient...
November 15, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28880937/differential-expression-of-tetraspanin-superfamily-members-in-dendritic-cell-subsets
#9
Malou Zuidscherwoude, Kuntal Worah, Alie van der Schaaf, Sonja I Buschow, Annemiek B van Spriel
Dendritic cells (DCs), which are essential for initiating immune responses, are comprised of different subsets. Tetraspanins organize dendritic cell membranes by facilitating protein-protein interactions within the so called tetraspanin web. In this study we analyzed expression of the complete tetraspanin superfamily in primary murine (CD4+, CD8+, pDC) and human DC subsets (CD1c+, CD141+, pDC) at the transcriptome and proteome level. Different RNA and protein expression profiles for the tetraspanin genes across human and murine DC subsets were identified...
2017: PloS One
https://www.readbyqxmd.com/read/28753442/the-antitumor-activity-of-imgn529-a-cd37-targeting-antibody-drug-conjugate-is-potentiated-by-rituximab-in-non-hodgkin-lymphoma-models
#10
Stuart W Hicks, Katharine C Lai, L Cristina Gavrilescu, Yong Yi, Surina Sikka, Prerak Shah, Meghan E Kelly, Jenny Lee, Leanne Lanieri, Jose F Ponte, Callum M Sloss, Angela Romanelli
Naratuximab emtansine (IMGN529) is an investigational antibody-drug conjugate consisting of a CD37-targeting antibody conjugated to the maytansine-derived microtuble disruptor, DM1. IMGN529 has shown promising preclinical and clinical activity in non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL). Due to the aggressive nature of the disease, DLBCL is often treated with combination therapies to maximize clinical outcomes; therefore, we investigated the potential of combining IMGN529 with both standard-of-care and emerging therapies against multiple oncology-relevant targets and pathways...
July 25, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28718418/novel-insights-into-membrane-targeting-of-b-cell-lymphoma
#11
REVIEW
Charlotte M de Winde, Suraya Elfrink, Annemiek B van Spriel
Standard therapy of patients with B cell non-Hodgkin lymphoma (B-NHL) predominantly consists of chemotherapy combined with anti-CD20 (e.g., rituximab) immunotherapy. However, relapse of aggressive B-NHL occurs frequently, and this may coincide with therapy resistance. This demonstrates the urgent need for exploring new lymphoma-targeted therapies. We review here recent insights in the pathophysiology of B-NHL and discuss CD20 and three alternative membrane targets (B cell receptor, immune checkpoints PD-1/PD-L1, tetraspanin CD37) that are currently in the spotlight for B-NHL treatment...
June 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28602860/a-role-for-the-tetraspanin-proteins-in-salmonella-infection-of-human-macrophages
#12
Noha A Hassuna, Peter N Monk, Fawwaz Ali, Robert C Read, Lynda J Partridge
OBJECTIVE: Infected macrophages play a role in the dissemination of Salmonella and may serve as a reservoir of infection in asymptomatic carriers. However, relatively little is known about the early molecular interactions of the bacteria with these cells. We have recently shown that members of the tetraspanin family of membrane proteins are involved in the initial adhesion of a range of bacteria to host cells. This study investigated the role of tetraspanins in Salmonella enterica subsp...
August 2017: Journal of Infection
https://www.readbyqxmd.com/read/28034866/staining-the-target-cd37-expression-in-lymphomas
#13
COMMENT
Francesco Bertoni, Anastasios Stathis
No abstract text is available yet for this article.
December 29, 2016: Blood
https://www.readbyqxmd.com/read/27977057/randomized-phase-2-study-of-otlertuzumab-and-bendamustine-versus-bendamustine-in-patients-with-relapsed-chronic-lymphocytic-leukaemia
#14
RANDOMIZED CONTROLLED TRIAL
Tadeusz Robak, Andrzej Hellmann, Janusz Kloczko, Javier Loscertales, Ewa Lech-Maranda, John M Pagel, Anthony Mato, John C Byrd, Farrukh T Awan, Holger Hebart, Jose A Garcia-Marco, Brian T Hill, Michael Hallek, Amy J Eisenfeld, Scott C Stromatt, Ulrich Jaeger
Otlertuzumab (TRU-016) is a humanized anti-CD37 protein therapeutic that triggers direct caspase-independent apoptosis of malignant B cells and induces antibody-dependent cell-mediated cytotoxicity. Patients with relapsed chronic lymphocytic leukaemia (CLL) received either otlertuzumab (20 mg/kg) weekly by IV infusion for two 28-day cycles then every 14 days for four 28-day cycles and IV bendamustine (70 mg/m2 ) on Days 1 and 2 of each cycle for up to six 28-day cycles or bendamustine alone. Thirty-two patients were treated with otlertuzumab and bendamustine and 33 with bendamustine alone...
February 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/27899962/new-emerging-therapies-in-the-management-of-chronic-lymphocytic-leukemia
#15
Xiao-Lin Li, Ci-Xian Zhang
Chronic lymphocytic leukemia (CLL) is considered incurable despite advances in management strategies. New drugs targeting cell pathways are currently being developed for the efficient management of CLL. Various strategies involving different targets have been developed, or are currently in the developing stage. A search was conducted in the electronic database PubMed, for pre-clinical as well as clinically controlled trials reporting various strategies against CLL currently under investigation. Novel strategies included use of antibodies, small cell inhibitors, such as spleen tyrosine kinase, LYN, cyclin-dependent kinase, and histone deacetylase inhibitors...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27834943/idelalisib-improves-cd37-antibody-bi-836826-cytotoxicity-against-chemo-resistant-relapse-initiating-cll-cells-a-rationale-for-combination-treatment
#16
S Betrian, L Ysebaert, K H Heider, J P Delord, J J Fournié, A Quillet-Mary
No abstract text is available yet for this article.
November 11, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27760757/assessment-of-cd37-b-cell-antigen-and-cell-of-origin-significantly-improves-risk-prediction-in-diffuse-large-b-cell-lymphoma
#17
Zijun Y Xu-Monette, Ling Li, John C Byrd, Kausar J Jabbar, Ganiraju C Manyam, Charlotte Maria de Winde, Michiel van den Brand, Alexandar Tzankov, Carlo Visco, Jing Wang, Karen Dybkaer, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L Richards, Eric D Hsi, William W L Choi, Jooryung Huh, Maurilio Ponzoni, Andrés J M Ferreri, Michael B Møller, Ben M Parsons, Jane N Winter, Michael Wang, Frederick B Hagemeister, Miguel A Piris, J Han van Krieken, L Jeffrey Medeiros, Yong Li, Annemiek B van Spriel, Ken H Young
CD37 (tetraspanin TSPAN26) is a B-cell surface antigen widely expressed on mature B cells. CD37 is involved in immune regulation and tumor suppression but its function has not been fully elucidated. We assessed CD37 expression in de novo diffuse large B-cell lymphoma (DLBCL), and investigated its clinical and biologic significance in 773 patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and 231 patients treated with CHOP. We found that CD37 loss (CD37- ) in ∼60% of DLBCL patients showed significantly decreased survival after R-CHOP treatment, independent of the International Prognostic Index (IPI), germinal center B-cell-like (GCB)/activated B-cell-like (ABC) cell of origin, nodal/extranodal primary origin, and the prognostic factors associated with CD37- , including TP53 mutation, NF-κBhigh , Mychigh , phosphorylated STAT3high , survivinhigh , p63- , and BCL6 translocation...
December 29, 2016: Blood
https://www.readbyqxmd.com/read/27739922/characterization-and-prognostic-relevance-of-circulating-microvesicles-in-chronic-lymphocytic-leukemia
#18
Luciana De Luca, Giovanni D'Arena, Vittorio Simeon, Stefania Trino, Ilaria Laurenzana, Antonella Caivano, Francesco La Rocca, Oreste Villani, Giovanna Mansueto, Silvia Deaglio, Idanna Innocenti, Luca Laurenti, Stefano Molica, Giuseppe Pietrantuono, Angelo De Stradis, Luigi Del Vecchio, Pellegrino Musto
Microvescicles (MV) are shedding particles released by normal and neoplastic cells, whose levels in biological fluids highlight their potential role as disease biomarkers and therapeutic targets. By analyzing 131 newly diagnosed chronic lymphocytic leukemia (CLL), we found that the absolute number of serum CLL MV was significantly higher than in controls, in particular in advanced stages of disease. In addition, CD19 + and CD37+, B-cell derived MV, significantly correlated with high tumor burden. Absolute MV number cutoff selected by ROC analysis distinguished Rai stage 0 patients with shorter time to treatment (TTT) from those with more stable disease...
June 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27587710/red-marrow-absorbed-dose-for-non-hodgkin-lymphoma-patients-treated-with-177lu-lilotomab-satetraxetan-a-novel-anti-cd37-antibody-radionuclide-conjugate
#19
Johan Blakkisrud, Ayca Løndalen, Jostein Dahle, Simon Turner, Harald Holte, Arne Kolstad, Caroline Stokke
Red marrow (RM) is often the primary organ at risk in radioimmunotherapy; irradiation of marrow may induce short- and long-term hematologic toxicity. (177)Lu-lilotomab satetraxetan is a novel anti-CD37 antibody-radionuclide conjugate currently in phase 1/2a. Two predosing regimens have been investigated, one with 40 mg of unlabeled lilotomab antibody (arm 1) and one without (arm 2). The aim of this work was to compare RM-absorbed doses for the two arms and to correlate absorbed doses with hematologic toxicity...
January 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27493270/tumor-absorbed-dose-for-non-hodgkin-lymphoma-patients-treated-with-the-anti-cd37-antibody-radionuclide-conjugate-177lu-lilotomab-satetraxetan
#20
Johan Blakkisrud, Ayca Løndalen, Anne C T Martinsen, Jostein Dahle, Jon E Holtedahl, Tore Bach-Gansmo, Harald Holte, Arne Kolstad, Caroline Stokke
(177)Lu-lilotomab satetraxetan is a novel antibody radionuclide conjugate currently tested in a phase 1/2a first-in-human dosage escalation trial for patients with relapsed CD37+ indolent non-Hodgkin lymphoma. The aim of this work was to develop dosimetric methods and calculate tumor-absorbed radiation doses for patients treated with (177)Lu-lilotomab satetraxetan. METHODS: Patients were treated at escalating injected activities (10, 15 and 20 MBq/kg) of (177)Lu-lilotomab satetraxetan and with different predosing, with or without 40 mg of unlabeled lilotomab...
January 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
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