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Article ; Online: Monitoring of kinetics and exhaustion markers of circulating CAR-T cells as early predictive factors in patients with B-cell malignancies.

García-Calderón, Clara Beatriz / Sierro-Martínez, Belén / García-Guerrero, Estefanía / Sanoja-Flores, Luzalba / Muñoz-García, Raquel / Ruiz-Maldonado, Victoria / Jimenez-Leon, María Reyes / Delgado-Serrano, Javier / Molinos-Quintana, Águeda / Guijarro-Albaladejo, Beatriz / Carrasco-Brocal, Inmaculada / Lucena, José-Manuel / García-Lozano, José-Raúl / Blázquez-Goñi, Cristina / Reguera-Ortega, Juan Luis / González-Escribano, María-Francisca / Reinoso-Segura, Marta / Briones, Javier / Pérez-Simón, José Antonio /

Caballero-Velázquez, Teresa

Frontiers in immunology

2023 Volume 14, Page(s) 1152498

Abstract: Purpose: CAR-T cell therapy has proven to be a disruptive treatment in the hematology field ... inconsistently defined. Here, we aimed to optimize the detection of CD19 CAR-T cells in blood and to identify ... of circulating CAR-T cells from 48 patients treated with Tisa-cel or Axi-cel was performed.: Results ...

Abstract	Purpose: CAR-T cell therapy has proven to be a disruptive treatment in the hematology field, however, less than 50% of patients maintain long-term response and early predictors of outcome are still inconsistently defined. Here, we aimed to optimize the detection of CD19 CAR-T cells in blood and to identify phenotypic features as early biomarkers associated with toxicity and outcomes. Experimental design: In this study, monitoring by flow cytometry and digital PCR (dPCR), and immunophenotypic characterization of circulating CAR-T cells from 48 patients treated with Tisa-cel or Axi-cel was performed. Results: Validation of the flow cytometry reagent for the detection of CAR-T cells in blood revealed CD19 protein conjugated with streptavidin as the optimal detection method. Kinetics of CAR-T cell expansion in blood confirmed median day of peak expansion at seven days post-infusion by both flow cytometry and digital PCR. Circulating CAR-T cells showed an activated, proliferative, and exhausted phenotype at the time of peak expansion. Patients with increased expansion showed more severe CRS and ICANs. Immunophenotypic characterization of CAR-T cells at the peak expansion identified the increased expression of co-inhibitory molecules PD1 and LAG3 and reduced levels of the cytotoxicity marker CD107a as predictors of a better long-term disease control. Conclusions: These data show the importance of CAR-T cells in vivo monitoring and identify the expression of PD1LAG3 and CD107a as early biomarkers of long-term disease control after CAR-T cell therapy.
MeSH term(s)	Humans ; Receptors, Chimeric Antigen/genetics ; Kinetics ; B-Lymphocytes/pathology ; T-Lymphocytes/pathology ; Lymphoma, Large B-Cell, Diffuse/pathology
Chemical Substances	Receptors, Chimeric Antigen
Language	English
Publishing date	2023-04-14
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1152498
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Article ; Online: High-Sensitivity Troponin T

Manuel Antonio Tazón-Varela / Jon Ortiz de Salido-Menchaca / Pedro Muñoz-Cacho / Enara Iriondo-Bernabeu / María Josefa Martos-Almagro / Emma Lavín-López / Ander Vega-Zubiaur / Edgar José Escalona-Canal / Iratxe Alcalde-Díez / Carmen Gómez-Vildosola / Ainhoa Belzunegui-Gárate / Fabiola Espinoza-Cuba / José Antonio López-Cejuela / Alba García-García / Alejandro Torrejón-Cereceda / Elena Sabina Nisa-Martínez / Diana Moreira Nieto / Cintia Hellín-Mercadal / Ander García-Caballero /

Héctor Alonso-Valle

Journal of Personalized Medicine, Vol 12, Iss 520, p

A Potential Safety Predictive Biomarker for Discharge from the Emergency Department of Patients with Confirmed Influenza

2022 Volume 520

Abstract: The purpose of the study was to analyze the relationship between the high-sensitivity troponin T ... during the care process. In addition, a high-sensitivity troponin T cut-off value was sought to allow ... designed in which high-sensitivity troponin T is determined as an exposure factor, patients are followed ...

Abstract	The purpose of the study was to analyze the relationship between the high-sensitivity troponin T levels in patients with confirmed influenza virus infection and its severity determined by mortality during the care process. In addition, a high-sensitivity troponin T cut-off value was sought to allow us to a safe discharge from the emergency department. An analytical retrospective observational study was designed in which high-sensitivity troponin T is determined as an exposure factor, patients are followed until the resolution of the clinical picture, and the frequency of mortality is analyzed. We included patients ≥ 16 years old with confirmed influenza virus infection and determination of high-sensitivity troponin T. One hundred twenty-eight patients were included (96.9% survivors, 3.1% deceased). Mean and median blood levels of high-sensitivity troponin T of survivors were 26.2 ± 58.3 ng/L and 14.5 ng/L (IQR 16 ng/L), respectively, and were statistically different when compared with those of the deceased patients, 120.5 ± 170.1 ng/L and 40.5 ng/L (IQR 266.5 ng/L), respectively, p = 0.012. The Youden index using mortality as the reference method was 0.76, and the cut-off value associated with this index was 24 ng/L (sensitivity 100%, specificity 76%, NPV 100%, PPV 4%) with AUC of 88,8% (95% CI: 79.8–92.2%), p < 0.001. We conclude that high-sensitivity troponin T levels in confirmed virus influenza infection are a good predictor of mortality in our population, and this predictor is useful for safely discharging patients from the emergency department.
Keywords	influenza ; human ; troponin ; biomarkers ; SARS-CoV-2 ; cardiovascular infections ; Medicine ; R
Subject code	616
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Apoptosis-mediated ADAM10 activation removes a mucin barrier promoting T cell efferocytosis.

Drexhage, Linnea Z / Zhang, Shengpan / Dupont, Maeva / Ragaller, Franziska / Sjule, Ellen / Cabezas-Caballero, Jose / Deimel, Lachlan P / Robertson, Helen / Russell, Rebecca A / Dushek, Omer / Sezgin, Erdinc / Karaji, Niloofar / Sattentau, Quentin J

Nature communications

2024 Volume 15, Issue 1, Page(s) 541

Abstract: Efferocytic clearance of apoptotic cells in general, and T cells in particular, is required ... that normal and transformed human T cells express a subset of mucins which are rapidly and selectively removed ... of the plasma membrane. Mucin clearance enhances uptake of apoptotic T cells by macrophages, confirming mucins ...

Abstract	Efferocytic clearance of apoptotic cells in general, and T cells in particular, is required for tissue and immune homeostasis. Transmembrane mucins are extended glycoproteins highly expressed in the cell glycocalyx that function as a barrier to phagocytosis. Whether and how mucins may be regulated during cell death to facilitate efferocytic corpse clearance is not well understood. Here we show that normal and transformed human T cells express a subset of mucins which are rapidly and selectively removed from the cell surface during apoptosis. This process is mediated by the ADAM10 sheddase, the activity of which is associated with XKR8-catalyzed flipping of phosphatidylserine to the outer leaflet of the plasma membrane. Mucin clearance enhances uptake of apoptotic T cells by macrophages, confirming mucins as an enzymatically-modulatable barrier to efferocytosis. Together these findings demonstrate a glycocalyx regulatory pathway with implications for therapeutic intervention in the clearance of normal and transformed apoptotic T cells.
MeSH term(s)	Humans ; Efferocytosis ; Mucins ; T-Lymphocytes/metabolism ; Apoptosis ; Phagocytosis ; ADAM10 Protein/genetics ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Amyloid Precursor Protein Secretases
Chemical Substances	Mucins ; ADAM10 protein, human (EC 3.4.24.81) ; ADAM10 Protein (EC 3.4.24.81) ; Membrane Proteins ; Amyloid Precursor Protein Secretases (EC 3.4.-)
Language	English
Publishing date	2024-01-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-44619-8
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Article ; Online: Icariside II, a Prenyl-Flavonol, Alleviates Inflammatory and Neuropathic Pain by Inhibiting T-Type Calcium Channels and USP5-Cav3.2 Interactions.

Ali, Md Yousof / Gadotti, Vinicius M / Huang, Sun / Garcia-Caballero, Agustin / Antunes, Flavia T T / Jung, Hyun Ah / Choi, Jae Sue / Zamponi, Gerald W

ACS chemical neuroscience

2023 Volume 14, Issue 10, Page(s) 1859–1869

Abstract: Cav3.2 channels play an important role in the afferent nociceptive pathway, which is responsible for both physiological and pathological pain transmission. Cav3.2 channels are upregulated during neuropathic pain or peripheral inflammation in part due to ... ...

Abstract	Cav3.2 channels play an important role in the afferent nociceptive pathway, which is responsible for both physiological and pathological pain transmission. Cav3.2 channels are upregulated during neuropathic pain or peripheral inflammation in part due to an increased association with the deubiquitinase USP5. In this study, we investigated nine naturally occurring flavonoid derivatives which we tested for their abilities to inhibit transiently expressed Cav3.2 channels and their interactions with USP5. Icariside II (ICA-II), one of the flavonols studied, inhibited the biochemical interactions between USP5 and Cav3.2 and concomitantly and effectively blocked Cav3.2 channels. Molecular docking analysis predicts that ICA-II binds to the cUBP domain and the Cav3.2 interaction region. In addition, ICA-II was predicted to interact with residues in close proximity to the Cav3.2 channel's fenestrations, thus accounting for the observed blocking activity. In mice with inflammatory and neuropathic pain, ICA-II inhibited both phases of the formalin-induced nocifensive responses and abolished thermal hyperalgesia induced by injection of complete Freund's adjuvant (CFA) into the hind paw. Furthermore, ICA-II produced significant and long-lasting thermal anti-hyperalgesia in female mice, whereas Cav3.2 null mice were resistant to the action of ICA-II. Altogether, our data show that ICA-II has analgesic activity via an action on Cav3.2 channels.
MeSH term(s)	Female ; Mice ; Animals ; Calcium Channels, T-Type/metabolism ; Molecular Docking Simulation ; Neuralgia/drug therapy ; Neuralgia/metabolism ; Hyperalgesia/metabolism ; Flavonoids ; Flavonols ; Mice, Knockout ; Ubiquitin-Specific Proteases/metabolism
Chemical Substances	Calcium Channels, T-Type ; baohuoside I (113558-15-9) ; prenyl ; Flavonoids ; Flavonols ; Usp5 protein, mouse (EC 3.4.19.12) ; Ubiquitin-Specific Proteases (EC 3.4.19.12)
Language	English
Publishing date	2023-04-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1948-7193
ISSN (online)	1948-7193
DOI	10.1021/acschemneuro.3c00083
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Article ; Online: Allogeneic Stem Cell Transplantation in Mature T Cell and Natural Killer/T Neoplasias: A Registry Study from Spanish GETH/GELTAMO Centers.

Novelli, Silvana / Bento, Leyre / Garcia, Irene / Prieto, Laura / López, Lucía / Gutierrez, Gonzalo / Hernani, Rafael / Pérez, Ariadna / Esquirol, Albert / Solano, Carlos / Bastos, Mariana / Dorado, Nieves / Rodríguez, Nancy / Rodríguez, Guillermo / Piñana, Jose L / Montoro, Juan / Herrera, Pilar / Luna, Alejandro / Parody, Rocío /

Martín, Carmen / García, Estefanía / López, Oriana / Heras, Inmaculada / Zanabili, Joud / Moraleda, Jose M / Yañez, Lucrecia / Gutierrez, Antonio / Zudaire, Teresa / Córdoba, Raúl / Varela, Rosario / Ferra, Christelle / Martínez, Joaquin / Martínez, Carmen / Gonzalez-Barca, Eva / Martino, Rodrigo / Caballero, Dolores

Transplantation and cellular therapy

2021 Volume 27, Issue 6, Page(s) 493.e1–493.e8

Abstract: Despite advances in understanding the biology of mature T and natural killer (NK)/T cell neoplasia ... treatment to date that has been shown to control aggressive T cell neoplasms in the long term is allogeneic ... stem cell transplantation (alloSCT). We aim to report the results of alloSCT for advanced mature T and NK/T neoplasias ...

Abstract	Despite advances in understanding the biology of mature T and natural killer (NK)/T cell neoplasia, current therapies, even the most innovative ones, are still far from ensuring its cure. The only treatment to date that has been shown to control aggressive T cell neoplasms in the long term is allogeneic stem cell transplantation (alloSCT). We aim to report the results of alloSCT for advanced mature T and NK/T neoplasias performed in centers from our national GELTAMO/GETH (Grupo Español de Linfoma y Trasplante de Médula Ósea/Grupo Español de Trasplante Hematopoyético y Terapia Celular) over the past 25 years. As a secondary objective, we analyzed the results of alloSCT from haploidentical donors. We performed a retrospective analysis of all patients who received an alloSCT in Spanish centers (n = 201) from September 1995 to August 2018. The 2-year overall survival (OS) and disease-free survival (DFS) were 65.5% and 58.2%, respectively. The univariate for OS and DFS showed statistically different hazard ratios for conditioning intensity, response pre-alloSCT, comorbidity index, donor/receptor cytomegalovirus status and Eastern Cooperative Oncology Group (ECOG) pre-alloSCT, but only a better ECOG pre-alloSCT remained significant in the multivariate analysis. There was an increased incidence of relapse in those patients who did not develop chronic graft-versus-host disease (GVHD) and an increased risk of death in those developing moderate to severe acute GVHD. The 1-year nonrelapse mortality was 21.9% and was mainly due to GVHD (30%) and bacterial infections (17%). When comparing unrelated donors with haploidentical donors, we found similar results in terms of OS and DFS. There was, however, a reduction of acute GVHD in the haploidentical group (P = .04) and trend to a reduction of chronic GVHD. In conclusion, alloSCT is the only curative option for most aggressive T cell neoplasias. Haploidentical donors offer similar results to related donors in terms of survival with a reduction of acute GVHD.
MeSH term(s)	Hematopoietic Stem Cell Transplantation ; Humans ; Killer Cells, Natural ; Neoplasm Recurrence, Local ; Registries ; Retrospective Studies ; Transplantation Conditioning
Language	English
Publishing date	2021-03-15
Document type	Journal Article
ZDB-ID	3062231-1
ISSN	2666-6367
ISSN (online)	2666-6367
DOI	10.1016/j.jtct.2021.03.014
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Article ; Online: Combined treatment of graft versus host disease using donor regulatory T cells and ruxolitinib.

Rodríguez-Gil, Alfonso / Escamilla-Gómez, Virginia / Nufer, Melanie / Andújar-Sánchez, Félix / Lopes-Ramos, Teresa / Bejarano-García, José Antonio / García-Guerrero, Estefanía / Calderón-Cabrera, Cristina / Caballero-Velázquez, Teresa / García-Calderón, Clara Beatriz / Hernández-Díaz, Paola / Reguera-Ortega, Juan Luis / Rodríguez-Torres, Nancy / Martínez-Cibrián, Nuria / Rodríguez-Barbosa, José Ignacio / Villadiego, Javier / Pérez-Simón, José Antonio

Scientific reports

2022 Volume 12, Issue 1, Page(s) 8348

Abstract: Donor derived regulatory T lymphocytes and the JAK1/2 kinase inhibitor ruxolitinib are currently ... mouse model. Our results show that ruxolitinib favors the ratio of thymic regulatory T ... cells to conventional T cells in culture, without affecting the suppressive capacity of these Treg. The combination ...

Abstract	Donor derived regulatory T lymphocytes and the JAK1/2 kinase inhibitor ruxolitinib are currently being evaluated as therapeutic options in the treatment of chronic graft versus host disease (cGvHD). In this work, we aimed to determine if the combined use of both agents can exert a synergistic effect in the treatment of GvHD. For this purpose, we studied the effect of this combination both in vitro and in a GvHD mouse model. Our results show that ruxolitinib favors the ratio of thymic regulatory T cells to conventional T cells in culture, without affecting the suppressive capacity of these Treg. The combination of ruxolitinib with Treg showed a higher efficacy as compared to each single treatment alone in our GvHD mouse model in terms of GvHD incidence, severity and survival without hampering graft versus leukemia effect. This beneficial effect correlated with the detection in the bone marrow of recipient mice of the infused donor allogeneic Treg after the adoptive transfer.
MeSH term(s)	Animals ; Disease Models, Animal ; Graft vs Host Disease/drug therapy ; Mice ; Nitriles ; Pyrazoles ; Pyrimidines ; T-Lymphocytes, Regulatory/transplantation
Chemical Substances	Nitriles ; Pyrazoles ; Pyrimidines ; ruxolitinib (82S8X8XX8H)
Language	English
Publishing date	2022-05-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-12407-x
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Article ; Online: Post-mortem neuropathologic examination of a 6-case series of CAR T-cell treated patients.

Vidal-Robau, Nuria / Caballero, Gabriela / Archilla, Ivan / Ladino, Andrea / Fernández, Sara / Ortiz-Maldonado, Valentín / Rovira, Montserrat / Gómez-Hernando, Marta / Delgado, Julio / Suárez-Lledó, María / Fernández de Larrea, Carlos / Balagué, Olga / Frigola, Gerard / Muñoz, Abel / Ortiz, Estrella / Ribalta, Teresa / Martinez, Miguel J / Angeles-Marcos, Maria / Español-Rego, Marta /

González, Azucena / Benitez-Ribas, Daniel / Martinez-Hernandez, Eugenia / Castro, Pedro / Aldecoa, Iban

Free neuropathology

2022 Volume 3

Abstract: Introduction: ...

Abstract	Introduction:
Language	English
Publishing date	2022-10-27
Publishing country	Germany
Document type	Journal Article
ISSN	2699-4445
ISSN (online)	2699-4445
DOI	10.17879/freeneuropathology-2022-4365
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Article ; Online: Impact of disease burden and late loss of B cell aplasia on the risk of relapse after CD19 chimeric antigen receptor T Cell (Tisagenlecleucel) infusion in pediatric and young adult patients with relapse/refractory acute lymphoblastic leukemia: role of B-cell monitoring.

Molinos-Quintana, Águeda / Alonso-Saladrigues, Anna / Herrero, Blanca / Caballero-Velázquez, Teresa / Galán-Gómez, Víctor / Panesso, Melissa / Torrebadell, Montserrat / Delgado-Serrano, Javier / Pérez de Soto, Concepción / Faura, Anna / González-Martínez, Berta / Castillo-Robleda, Ana / Diaz-de-Heredia, Cristina / Pérez-Martínez, Antonio / Pérez-Hurtado, José María / Rives, Susana / Pérez-Simón, José Antonio

Frontiers in immunology

2024 Volume 14, Page(s) 1280580

Abstract: Introduction: Loss of B-cell aplasia (BCA) is a well-known marker of functional loss of CD19 CAR-T ... Most relapses and loss of BCA occur in the first months after CD19 CAR-T infusion. In addition, high ...

Abstract	Introduction: Loss of B-cell aplasia (BCA) is a well-known marker of functional loss of CD19 CAR-T. Most relapses and loss of BCA occur in the first months after CD19 CAR-T infusion. In addition, high tumor burden (HTB) has shown to have a strong impact on relapse, especially in CD19-negative. However, little is known about the impact of late loss of BCA or the relationship between BCA and pre-infusion tumor burden in patients infused with tisagenlecleucel for relapsed/refractory B-cell acute lymphoblastic leukemia. Therefore, the optimal management of patients with loss of BCA is yet to be defined. Methods: We conducted a Spanish, multicentre, retrospective study in patients infused with tisagenlecleucel after marketing authorization. A total of 73 consecutively treated patients were evaluated. Results: Prior to infusion, 39 patients had HTB (≥ 5% bone marrow blasts) whereas 34 had a low tumor burden (LTB) (<5% blasts). Complete remission was achieved in 90.4% of patients, of whom 59% relapsed. HTB was associated with inferior outcomes, with a 12-month EFS of 19.3% compared to 67.2% in patients with LTB (p<0.001) with a median follow-up of 13.5 months (95% CI 12.4 - 16.2). In the HTB subgroup relapses were mainly CD19-negative (72%) whereas in the LTB subgroup they were mainly CD19-positive (71%) (p=0.017). In the LTB group, all CD19-positive relapses were preceded by loss of BCA whereas only 57% (4/7) of HTB patients experienced CD19-positive relapse. We found a positive correlation between loss of BCA and CD19-positive relapse (R-squared: 74) which persisted beyond six months post-infusion. We also explored B-cell recovery over time using two different definitions of loss of BCA and found a few discrepancies. Interestingly, transient immature B-cell recovery followed by BCA was observed in two pediatric patients. In conclusion, HTB has an unfavorable impact on EFS and allo-SCT might be considered in all patients with HTB, regardless of BCA. In patients with LTB, loss of BCA preceded all CD19-positive relapses. CD19-positive relapse was also frequent in patients who lost BCA beyond six months post-infusion. Therefore, these patients are still at significant risk for relapse and close MRD monitoring and/or therapeutic interventions should be considered.
MeSH term(s)	Humans ; Child ; Young Adult ; Receptors, Chimeric Antigen/therapeutic use ; Retrospective Studies ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Recurrence ; T-Lymphocytes ; Cost of Illness ; Receptors, Antigen, T-Cell ; Salicylates
Chemical Substances	tisagenlecleucel (Q6C9WHR03O) ; Receptors, Chimeric Antigen ; 4-trifluoromethylsalicylic acid (328-90-5) ; Receptors, Antigen, T-Cell ; Salicylates
Language	English
Publishing date	2024-01-16
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1280580
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Article ; Online: Corrigendum: Impact of disease burden and late loss of B cell aplasia on the risk of relapse after CD19 chimeric antigen receptor T Cell (Tisagenlecleucel) infusion in pediatric and young adult patients with relapse/refractory acute lymphoblastic leukemia: role of B-cell monitoring.

Frontiers in immunology

2024 Volume 15, Page(s) 1373852

Abstract: This corrects the article DOI: 10.3389/fimmu.2023.1280580.]. ...

Abstract	[This corrects the article DOI: 10.3389/fimmu.2023.1280580.].
Language	English
Publishing date	2024-02-07
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1373852
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Article ; Online: Peripheral T-cell lymphoma: molecular profiling recognizes subclasses and identifies prognostic markers.

Rodríguez, Marta / Alonso-Alonso, Ruth / Tomás-Roca, Laura / Rodríguez-Pinilla, Socorro M / Manso-Alonso, Rebeca / Cereceda, Laura / Borregón, Jennifer / Villaescusa, Teresa / Córdoba, Raúl / Sánchez-Beato, Margarita / Fernández-Miranda, Ismael / Betancor, Isabel / Bárcena, Carmen / García, Juan F / Mollejo, Manuela / García-Cosio, Mónica / Martin-Acosta, Paloma / Climent, Fina / Caballero, Dolores /

de la Fuente, Lorena / Mínguez, Pablo / Kessler, Linda / Scholz, Catherine / Gualberto, Antonio / Mondéjar, Rufino / Piris, Miguel A

Blood advances

2021 Volume 5, Issue 24, Page(s) 5588–5598

Abstract: Peripheral T-cell lymphoma (PTCL) is a clinically aggressive disease, with a poor response ... Seattle, WA) that includes 208 genes associated with T-cell differentiation, oncogenes and ... histological types of PTCL (angioimmunoblastic T-cell lymphoma [AITL]; PTCL with T follicular helper [TFH ...

Abstract	Peripheral T-cell lymphoma (PTCL) is a clinically aggressive disease, with a poor response to therapy and a low overall survival rate of approximately 30% after 5 years. We have analyzed a series of 105 cases with a diagnosis of PTCL using a customized NanoString platform (NanoString Technologies, Seattle, WA) that includes 208 genes associated with T-cell differentiation, oncogenes and tumor suppressor genes, deregulated pathways, and stromal cell subpopulations. A comparative analysis of the various histological types of PTCL (angioimmunoblastic T-cell lymphoma [AITL]; PTCL with T follicular helper [TFH] phenotype; PTCL not otherwise specified [NOS]) showed that specific sets of genes were associated with each of the diagnoses. These included TFH markers, cytotoxic markers, and genes whose expression was a surrogate for specific cellular subpopulations, including follicular dendritic cells, mast cells, and genes belonging to precise survival (NF-κB) and other pathways. Furthermore, the mutational profile was analyzed using a custom panel that targeted 62 genes in 76 cases distributed in AITL, PTCL-TFH, and PTCL-NOS. The main differences among the 3 nodal PTCL classes involved the RHOAG17V mutations (P < .0001), which were approximately twice as frequent in AITL (34.09%) as in PTCL-TFH (16.66%) cases but were not detected in PTCL-NOS. A multivariate analysis identified gene sets that allowed the series of cases to be stratified into different risk groups. This study supports and validates the current division of PTCL into these 3 categories, identifies sets of markers that can be used for a more precise diagnosis, and recognizes the expression of B-cell genes as an IPI-independent prognostic factor for AITL.
MeSH term(s)	Humans ; Immunoblastic Lymphadenopathy ; Lymphoma, T-Cell, Peripheral/diagnosis ; Lymphoma, T-Cell, Peripheral/genetics ; Mutation ; Phenotype ; Prognosis
Language	English
Publishing date	2021-09-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2021005171
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