المؤلفون: Knop, S, Engelhardt, M, Liebisch, P, Meisner, C, Holler, E, Metzner, B, Peest, D, Kaufmann, M, Bunjes, D, Straka, C, Fischer, T, Sezer, O, Hentrich, M, Ostermann, H, Bassermann, F, Hess, G, Hertenstein, B, Freund, M, Kropff, M, Schmidt, CA, Wolf, HH, Jung, W, Frickhofen, N, Mielke, S, Bargou, RC, Maschmeyer, G, Svaldi, M, Langer, CH, Gramatzki, M, Hebart, H, Kanz, L, Einsele, H, Dorken, B, Gerecke, C, Fuhrmann, S, Ludwig, WD, Bormann, M, Meyer, R, Naumann, R, Platzbecker, U, Rollig, C, Rosler, W, von Metzler, I, Martin, H, Finke, J, Trumper, L, Dolken, G, Muller, L, Ligeti, K, Kroger, N, Schilling, G, Durk, H, Ganser, A, Pfreundschuh, M, Sayer, H, von Lilienfeld-Toal, M, Mugge, LO, Bentz, M, Bruggemann, M, Wolleschak, D, Reusch, J, Franke, D, Peschel, C, Dechow, T, Wandt, H, Schafer-Eckart, K, Hart, C, Reichle, A, Bottcher, S, Kahl, C, Mergenthaler, HG, Aulitzky, W, Greiner, J, Heidemann, E, Langer, C

المصدر: Leukemia. 33(11):2710-2719

مصطلحات موضوعية: Medicin och hälsovetenskap

الوصول الحر: http://kipublications.ki.se/Default.aspx?queryparsed=id:142256182Test

المؤلفون: Gökbuget, N, Kantarjian, HM, Brüggemann, M, Stein, AS, Bargou, RC, Dombret, H, Fielding, AK, Heffner, L, Rigal-Huguet, F, Litzow, M, O'Brien, S, Zugmaier, G, Gao, S, Nagorsen, D, Forman, SJ, Topp, MS

المصدر: Blood Advances , 3 (20) pp. 3033-3037. (2019)

الوصف: Minimal residual disease (MRD), where leukemic cell levels are lower than the morphologic detection threshold, is the most important prognostic factor for acute lymphoblastic leukemia (ALL) relapse during first-line chemotherapy treatment and is standard of care in treatment monitoring and decision making. Limited data are available on the prognostic value of MRD response after relapse. We evaluated the relationship between MRD response and outcomes in blinatumomab-treated adults with relapsed/refractory (R/R) B-cell precursor ALL. Of 90 patients with complete remission (CR) or CR with partial hematologic recovery (CRh), 64 (71.1%) achieved a complete MRD response (no detectable individual rearrangements of immunoglobulin/T-cell receptor genes by polymerase chain reaction [PCR] at a minimum sensitivity level of 10-4). Eleven patients had MRD <10-4. Therefore, overall, 75 (83.3%) experienced an MRD response (no detectable MRD or detectable MRD) measured by PCR within the first 2 treatment cycles. Overall survival (OS) and relapse-free survival (RFS) were significantly longer in patients who achieved CR/CRh and MRD response (median, 20.6 and 9.0 months, respectively) compared with CR/CRh patients without MRD response (median, 12.5 and 2.3 months, respectively). In conclusion, longer durations of OS and RFS associated with MRD response support the value of achieving MRD response and its use as a prognostic factor for blinatumomab treatment in R/R ALL. This trial was registered at www.clinicaltrials.gov as #NCT01466179.

وصف الملف: text

العلاقة: https://discovery.ucl.ac.uk/id/eprint/10085250/7/Fielding%20advancesadv2019000457.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10085250Test/

الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10085250/7/Fielding%20advancesadv2019000457.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10085250Test/

المؤلفون: Topp MS, Gökbuget N, Stein AS, Zugmaier G, O'Brien S, Bargou RC, Dombret H, Fielding AK, Heffner L, Larson RA, Neumann S, FOA, Roberto, Litzow M, Ribera JM, Rambaldi A, Schiller G, Brüggemann M, Horst HA, Holland C, Jia C, Maniar T, Huber B, Nagorsen D, Forman SJ, Kantarjian H.M.

المساهمون: Topp, M, Gökbuget, N, Stein, A, Zugmaier, G, O'Brien, S, Bargou, Rc, Dombret, H, Fielding, Ak, Heffner, L, Larson, Ra, Neumann, S, Foa, Roberto, Litzow, M, Ribera, Jm, Rambaldi, A, Schiller, G, Brüggemann, M, Horst, Ha, Holland, C, Jia, C, Maniar, T, Huber, B, Nagorsen, D, Forman, Sj, Kantarjian, H. M.

مصطلحات موضوعية: bispecific T-cell engager antibody

الوصف: Background Adults with relapsed or refractory B-precursor acute lymphoblastic leukaemia have an unfavourable prognosis. Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19, an antigen consistently expressed on B-lineage acute lymphoblastic leukaemia cells. We aimed to confirm the activity and safety profile of blinatumomab for acute lymphoblastic leukaemia. Methods In a multicentre, single-arm, open-label phase 2 study, we enrolled adult patients with Philadelphia-chromosome- negative, primary refractory or relapsed (first relapse within 12 months of first remission, relapse within 12 months after allogeneic haemopoietic stem-cell transplantation [HSCT], or no response to or relapse after first salvage therapy or beyond) leukaemia. Patients received blinatumomab (9 mu g/day for the first 7 days and 28 mu g/day thereafter) by continuous intravenous infusion over 4 weeks every 6 weeks (up to five cycles), per protocol. The primary endpoint was complete remission (CR) or CR with partial haematological recovery of peripheral blood counts (CRh) within the first two cycles. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT01466179. Findings Between Jan 13, 2012, and Oct 10, 2013, 189 patients were enrolled and treated with blinatumomab. After two cycles, 81 (43%, 95% CI 36-50) patients had achieved a CR or CRh: 63 (33%) patients had a CR and 18 (10%) patients had a CRh. 32 (40%) of patients who achieved CR/CRh underwent subsequent allogeneic HSCT. The most frequent grade 3 or worse adverse events were febrile neutropenia (48 patients, 25%), neutropenia (30 patients, 16%), and anaemia (27 patients, 14%). Three (2%) patients had grade 3 cytokine release syndrome. Neurologic events of worst grade 3 or 4 occurred in 20 (11%) and four (2%) patients, respectively. Three deaths (due to sepsis, Escherichia coli sepsis, and Candida infection) were thought to be treatment-related by the investigators. Interpretation Single-agent blinatumomab showed ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/25524800; info:eu-repo/semantics/altIdentifier/wos/WOS:000346912800045; volume:1; issue:16; firstpage:57; lastpage:66; numberofpages:10; journal:THE LANCET ONCOLOGY; http://hdl.handle.net/11573/780918Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84926099033

الإتاحة: https://doi.org/10.1016/S1470-2045Test(14)71170-2
http://hdl.handle.net/11573/780918Test

المؤلفون: Chatterjee, M, Bargou, RC, Heimberger, T, Andrulis, M, Stuhmer, T, Steinbrunn, T, Einsele, H

المصدر: Clinical Lymphoma and Myeloma ; volume 9, page S140 ; ISSN 1557-9190

مصطلحات موضوعية: Cancer Research, Oncology, Hematology, General Medicine

الإتاحة: https://doi.org/10.1016/s1557-9190Test(11)70747-8
https://api.elsevier.com/content/article/PII:S1557919011707478?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1557919011707478?httpAccept=text/plainTest

المؤلفون: Chatterjee, M, Rancso, C, Heimberger, T, Thorsten, S, Einsele, H, Bargou, RC

المصدر: Clinical Lymphoma and Myeloma ; volume 9, page S140 ; ISSN 1557-9190

مصطلحات موضوعية: Cancer Research, Oncology, Hematology, General Medicine

الإتاحة: https://doi.org/10.1016/s1557-9190Test(11)70748-x
https://api.elsevier.com/content/article/PII:S155791901170748X?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S155791901170748X?httpAccept=text/plainTest

المؤلفون: Lentzsch, S, Chatterjee, M, Gries, M, Bommert, K, Gollasch, H, Dörken, B, Bargou, RC, Dörken, B, Bargou, R C

المصدر: Leukemia (08876924); Nov2004, Vol. 18 Issue 11, p1883-1890, 8p

مصطلحات موضوعية: INTERLEUKIN-6, MULTIPLE myeloma, CANCER cells, BONE marrow, APOPTOSIS, CELL lines

مستخلص: IL-6 has been reported to play a central role in growth and survival of multiple myeloma (MM) cells. However, recently we have demonstrated that in the presence of bone marrow stromal cells, survival of MM cells becomes independent of the IL-6/gp130/STAT3 pathway questioning the singular role of IL-6 in MM. Therefore, it was the aim of this study to identify additional factors and signaling pathways that might contribute to the growth and survival of MM cells. We found that in addition to IL-6 a number of bone marrow derived cytokines such as LIF, VEGF, bFGF, MIP-1alpha, SDF-1alpha, IL-1beta, SCF and IL-3 activate the MAPK pathway and induce proliferation of MM.1S and RPMI-8226 MM cells. In addition, these cytokines independently phosphorylate the forkhead family member FKHR via PI3-K/AKT and support survival of primary human MM cells. Inhibition of these pathways induces apoptosis in MM cell lines and primary MM cells. Thus, we provide evidence that in addition to IL-6 a number of different factors trigger important growth-promoting pathways to support the proliferation and survival of MM cells. Therefore, blocking such pathways, rather than blocking a single factor, might be a promising approach for the development of novel treatment strategies in MM. [ABSTRACT FROM AUTHOR]

: Copyright of Leukemia (08876924) is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Bargou, RC, Leng, C, Krappmann, D, Emmerich, F, Mapara, MY, Bommert, K, Royer, HD, Scheidereit, C, Dorken, B

المصدر: Blood; May 1996, Vol. 87 Issue: 10 p4340-4347, 8p

مستخلص: There is a considerable lack of understanding about the common molecular defects that form the basis for the occurrence of Hodgkin's lymphoma. Despite a number of molecular tools used thus far in immunophenotypic and karyotypic studies, it has not been possible to establish a single common trait among various Hodgkin (H)-cell lines or primary tumor cells that would allow classification into a particular hematopoietic lineage. With this study, we demonstrate that a characteristic expression pattern of transcription factors provides a unifying principle. Seven different cell lines derived from patients with Hodgkin's disease (HD), as well as primary H/Reed-Sternberg (RS) cells isolated from the pericardial fluid of a patient with HD, were compared with a number of hematopoietic and nonhematopoietic cell lines for the expression of Oct-2, a tissue-specific transcription factor normally restricted to B cells, and nuclear factor kappa B (NF-kappa B), an inducible transcription factor. Regardless of the heterogeneous phenotypes and genotypes of the H cell lines, which varied inconsistently between B-cell-, T-cell-, or monocyte-like properties, all H cells tested displayed expression of Oct-2 protein at levels comparable to those seen in B cells. Furthermore, all cell lines showed an abundant constitutive nuclear NF-kappa B activity. Interestingly, anaplastic large-cell lymphoma (ALCL) cell lines, which have many features in common with H/RS cells, were devoid constitutive nuclear NF- kappa B activity. Unlike the constitutive NF-kappa B activity known for B cells, which mainly consists of the p50 and c-Rel or RelB subunits, we demonstrate by antibody supershifting experiments that H cells contain constitutive nuclear p50 and p65, the dimeric NF-kappa B normally observed only for limited time intervals after stimulation with diverse inducers. Additionally, some H-cell lines also displayed nuclear c-Rel activity, whereas RelB or p52 were not detected as part of the constitutive activity. The expression pattern of Oct-2 and NF- kappa B appears to be a unifying and characteristic property of H cells and might explain the deregulated expression of various cytokines leading to the clinical and pathologic manifestations of HD.

المؤلفون: Mapara, MY, Bommert, K, Bargou, RC, Leng, C, Beck, C, Ludwig, WD, Gierschik, P, Dorken, B

المصدر: Blood; April 1995, Vol. 85 Issue: 7 p1836-1842, 7p

مستخلص: Recently G alpha 16, a new guanosine triphosphate (GTP) binding protein alpha subunit has been described to be specifically expressed in human hematopoietic cells. Expression of G alpha 16 was observed in human cell lines of myelomonocytic and T-lymphocytic origin, but not in human B-cell lines Raji and IM9. We studied the expression of G alpha 16 in human B cells corresponding to different stages of B-cell differentiation by means of reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. The human Burkitt's lymphoma cell lines Raji, Ramos, BJAB, the lymphoblastoid cell line SKW6.4, and the plasmocytoma cell line U266 were devoid of G alpha 16. In contrast, G alpha 16 was detected in the human progenitor B cell lines Reh and Nalm-6. Using the mu+, k-cell line BLIN-1 (pre-B cell phenotype) and its derived subclone 1E8 (surface mu+, k+; B-cell phenotype) G alpha 16 expression was found to disappear on transition from pre-B to B-cell differentiation stage. The analysis of a broad panel of human neoplastic B lymphocytes ranging from progenitor B-acute lymphatic leukemia (pre-pre-B-ALL), common acute leukemias (cALL), pre-B-ALL, mature B-ALL to low grade B-cell lymphoma (chronic lymphocytic leukemia of B-cell type, leukemic centrocytic non-Hodgkins lymphoma [NHL], hairy cell leukemia) showed that G alpha 16 expression is limited to progenitor and pre-B-ALL cells. Therefore, we conclude that within B-cell differentiation, G alpha 16 is expressed solely during early B cell ontogeny and downregulated during differentiation. Thus, G alpha 16 might be an important regulator involved in signaling processes in progenitor B cells.

المؤلفون: Ding, QQ, Xia, WY, Liu, JC, Yang, JY, Lee, DF, Xia, JH, Bartholomeusz, G, Li, Y, Pan, Y, Li, Z, Bargou, RC, Qin, J, Lai, CC, Tsai, FJ, Tsai, CH, Hung, MC

المساهمون: 附設醫院, Univ Texas, MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA, Univ Texas, Grad Sch Biomed Sci, Houston, TX 77030 USA, Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Surg, Union Hosp, Wuhan 430022, Peoples R China, Humboldt Univ, Max Delbruck Ctr Mol Med, Robert Rossle Canc Clin, HELIOS Clin, D-13125 Berlin, Germany, Humboldt Univ, Max Delbruck Ctr Mol Med, Dept Hematol Oncol & Tumor Immunol, D-13125 Berlin, Germany, Baylor Coll Med, Dept Biochem, Houston, TX 77030 USA, China Med Univ Hosp, Taichung 404, Taiwan

الوصف: In the present study, role of guanosine-3',5'-cyclic monophosphate (cGMP) in the vasodilatation of tetramethylpyrazine (TMP), one of the active ingredients of the Chinese herb Chuang-xion, was investigated. We found that the TMP could decrease the vascular tone of isolated rat aorta precontracted with phenylephrine (10(-8) M) in a concentration-dependent manner from 10(-5) M to 10(-3) M. Also, the TMP-induced relaxation was reduced by 1H-(1,2,4)-oxadiazol-(4,3-a)-quinoxalin-1-one (ODQ) or methylene blue, the inhibitor of soluble guanylyl cyclase. Moreover, the vasodilative response to TMP was enhanced significantly in the presence of sildenafil, a well-known inhibitor of phosphodiestrase type 5 that is sensitive to cGMP. In addition, TMP could increase the cGMP level in the isolated aortic rings and TMP-induced vasodilatation was deleted by cGMP-dependent protein kinases (PKG) blockade. These results suggest that relaxation of rat aortic strip by TMP is induced in the cGMP-dependent manner. (c) 2005 Elsevier Inc. All rights reserved.

العلاقة: MOLECULAR CELL 19(2):159-170; http://ir.cmu.edu.tw/ir/handle/310903500/28975Test

الإتاحة: http://ir.cmu.edu.tw/ir/handle/310903500/28975Test