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Article ; Online: Effects of pro-inflammatory cytokines and cell interactions on cell area and cytoskeleton of rheumatoid arthritis synoviocytes and immune cells.

Filali, Samira / Noack, Mélissa / Géloën, Alain / Pirot, Fabrice / Miossec, Pierre

2023 Volume 102, Issue 2, Page(s) 151303

Abstract: Rheumatoid synovitis is infiltrated by immune cells that interact with synoviocytes, leading to the pannus formation. Inflammation or cell interaction effects are mainly evaluated with cytokine production, cell proliferation or migration. Few studies ... ...

Abstract	Rheumatoid synovitis is infiltrated by immune cells that interact with synoviocytes, leading to the pannus formation. Inflammation or cell interaction effects are mainly evaluated with cytokine production, cell proliferation or migration. Few studies interest on cell morphology. Here, the purpose was to deepen some morphological changes of synoviocytes or immune cells under inflammatory conditions. Inflammatory cytokines, IL-17 and TNF that are largely involved in RA pathogenesis, induced a change in synoviocyte morphology, inducing a retracted cell with higher number of pseudopodia. Several morphological parameters decreased in inflammatory conditions: cell confluence, area and motility speed. The same impact on cell morphology was observed in co-culture of synoviocytes and immune cells in inflammatory/non-inflammatory conditions or with cell activation (miming the in vivo situation), affecting both cell types: synoviocytes were retracted and inversely immune cells proliferated, indicating that cell activation induced a morphological change of cells. In contrast, with RA but not control synoviocytes, cell interactions were not sufficient to affect PBMC and synoviocyte morphology. The morphological effect came only from the inflammatory environment. These findings reveal that the inflammatory environment or cell interactions induced massive changes in control synoviocytes, with cell retraction and increase of pseudopodia number, leading to better interactions with other cells. Except in the case of RA, the inflammatory environment was absolutely required for such changes.
MeSH term(s)	Humans ; Synoviocytes/pathology ; Cytokines/pharmacology ; Leukocytes, Mononuclear/pathology ; Arthritis, Rheumatoid/pathology ; Cell Proliferation ; Cells, Cultured ; Cytoskeleton ; Fibroblasts/pathology ; Cell Communication
Chemical Substances	Cytokines
Language	English
Publishing date	2023-03-06
Publishing country	Germany
Document type	Journal Article
ZDB-ID	391967-5
ISSN	1618-1298 ; 0070-2463 ; 0171-9335
ISSN (online)	1618-1298
ISSN	0070-2463 ; 0171-9335
DOI	10.1016/j.ejcb.2023.151303
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Article ; Online: Biological Applications and Toxicity Minimization of Semiconductor Quantum Dots.

Filali, Samira / Pirot, Fabrice / Miossec, Pierre

Trends in biotechnology

2019 Volume 38, Issue 2, Page(s) 163–177

Abstract: The extraordinary potential of semiconductor quantum dots (QDs) has resulted in their widespread application in various fields, from engineering technology and the development of laboratory techniques to biomedical imaging and therapeutic strategies. ... ...

Abstract	The extraordinary potential of semiconductor quantum dots (QDs) has resulted in their widespread application in various fields, from engineering technology and the development of laboratory techniques to biomedical imaging and therapeutic strategies. However, the toxicity of QDs remains a concern and has limited their applications in human health. Better understanding of the behavior of QDs as it relates to their composition will enable the exploration of their limitations and development of a strategy to control their toxicity for potential therapeutic applications. Here, we describe approaches to minimize their toxicities according to the specific cell type, organ, or animal species, summarizing recent promising research at the cellular, organ, and whole-organism level.
MeSH term(s)	Animals ; Diagnostic Imaging/methods ; Ecotoxicology/methods ; Humans ; Invertebrates ; Quantum Dots/chemistry ; Quantum Dots/therapeutic use ; Quantum Dots/toxicity ; Semiconductors ; Stem Cells ; Structure-Activity Relationship ; Tissue Distribution ; Vertebrates
Language	English
Publishing date	2019-08-28
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	47474-5
ISSN	1879-3096 ; 0167-7799
ISSN (online)	1879-3096
ISSN	0167-7799
DOI	10.1016/j.tibtech.2019.07.013
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Article ; Online: In high-grade ovarian carcinoma, platinum-sensitive tumor recurrence and acquired-resistance derive from quiescent residual cancer cells that overexpress CRYAB, CEACAM6, and SOX2.

du Manoir, Stanislas / Delpech, Hélène / Orsetti, Béatrice / Jacot, William / Pirot, Nelly / Noel, Jean / Colombo, Pierre-Emmanuel / Sardet, Claude / Theillet, Charles

The Journal of pathology

2022 Volume 257, Issue 3, Page(s) 367–378

Abstract: Most high-grade ovarian carcinomas (HGOCs) are sensitive to carboplatin (CBP)-based chemotherapy but frequently recur within 24 months. Recurrent tumors remain CBP-sensitive and acquire resistance only after several treatment rounds. Recurrences arise ... ...

Abstract	Most high-grade ovarian carcinomas (HGOCs) are sensitive to carboplatin (CBP)-based chemotherapy but frequently recur within 24 months. Recurrent tumors remain CBP-sensitive and acquire resistance only after several treatment rounds. Recurrences arise from a small number of residual tumor cells not amenable to investigation in patients. We developed patient-derived xenografts (PDXs) that allow the study of these different stages of CBP-sensitive recurrence and acquisition of resistance. We generated PDX models from CBP-sensitive and intrinsically resistant HGOC. PDXs were CBP- or mock-treated and tumors were sampled, after treatment and at recurrence. We also isolated models with acquired-resistance from CBP-sensitive PDXs. Tumors were characterized at the histological and transcriptome levels. PDX models reproduced treatment response seen in the patients. CBP-sensitive residual tumors contained nonproliferating tumor cell clusters embedded in a fibrotic mesh. In nontreated PDX tumors and treated CBP-resistant tumors, fibrotic tissue was not prevalent. Residual tumors had marked differences in gene expression when compared to naïve and recurrent tumors, indicating downregulation of the cell cycle and proliferation and upregulation of interferon response and the epithelial-mesenchymal transition. This gene expression pattern resembled that described in embryonal diapause and 'drug-tolerant persister' states. Residual and acquired-resistance tumors share the overexpression of three genes: CEACAM6, CRYAB, and SOX2. Immunostaining analysis showed strong CEACAM6, CRYAB, and SOX2 protein expression in CBP-sensitive residual and acquired-resistance PDX, thus confirming the RNA profiling results. In HGOC PDX, CBP-sensitive recurrences arise from a small population of quiescent, drug-tolerant, residual cells embedded in a fibrotic mesh. These cells overexpress CEACAM6, CRYAB, and SOX2, whose overexpression is also associated with acquired resistance and poor patient prognosis. CEACAM6, CRYAB, and SOX2 may thus serve as a biomarker to predict recurrence and emergence of resistant disease in CBP-treated HGOC patients. © 2022 The Pathological Society of Great Britain and Ireland.
MeSH term(s)	Antigens, CD/biosynthesis ; Antigens, CD/genetics ; Carboplatin/pharmacology ; Carboplatin/therapeutic use ; Carcinoma, Ovarian Epithelial/drug therapy ; Carcinoma, Ovarian Epithelial/genetics ; Carcinoma, Ovarian Epithelial/metabolism ; Cell Adhesion Molecules/biosynthesis ; Cell Adhesion Molecules/genetics ; Drug Resistance, Neoplasm ; Female ; GPI-Linked Proteins/biosynthesis ; GPI-Linked Proteins/genetics ; Humans ; Neoplasm Recurrence, Local ; Neoplasm, Residual ; Ovarian Neoplasms ; Recurrence ; SOXB1 Transcription Factors/biosynthesis ; SOXB1 Transcription Factors/genetics ; Xenograft Model Antitumor Assays ; alpha-Crystallin B Chain/biosynthesis ; alpha-Crystallin B Chain/genetics
Chemical Substances	Antigens, CD ; CEACAM6 protein, human ; CRYAB protein, human ; Cell Adhesion Molecules ; GPI-Linked Proteins ; SOX2 protein, human ; SOXB1 Transcription Factors ; alpha-Crystallin B Chain ; Carboplatin (BG3F62OND5)
Language	English
Publishing date	2022-04-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3119-7
ISSN	1096-9896 ; 0022-3417
ISSN (online)	1096-9896
ISSN	0022-3417
DOI	10.1002/path.5896
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Article ; Online: Preliminary

Hadda, Zebiri / Hélène, Van Den Berghe / Tom, Paunet / Aurélie, Wolf-Mandroux / Audrey, Bethry / Hubert, Taillades / Noël, Yohan Jean / Pirot, Nelly / Catherine, Botteron / Michel, Chammas / Pierre-Emmanuel, Chammas / Xavier, Garric

Biomaterials science

2022 Volume 10, Issue 7, Page(s) 1776–1786

Abstract: Peritendinous adhesions are complications known to occur up to 6 weeks after surgery and cause chronic pain and disability. Anti-adhesion barriers are currently the best option for prevention. In a previous study, we designed two biodegradable membranes, ...

Abstract	Peritendinous adhesions are complications known to occur up to 6 weeks after surgery and cause chronic pain and disability. Anti-adhesion barriers are currently the best option for prevention. In a previous study, we designed two biodegradable membranes, D-PACO1 and D-PACO
MeSH term(s)	Achilles Tendon/pathology ; Achilles Tendon/surgery ; Animals ; Polyesters ; Polymers ; Rats ; Tissue Adhesions/prevention & control ; Wound Healing
Chemical Substances	Polyesters ; Polymers
Language	English
Publishing date	2022-03-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2693928-9
ISSN	2047-4849 ; 2047-4830
ISSN (online)	2047-4849
ISSN	2047-4830
DOI	10.1039/d1bm01150b
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Article ; Online: Live-stream characterization of cadmium-induced cell death using visible CdTe-QDs.

Filali, Samira / Geloën, Alain / Lysenko, Vladimir / Pirot, Fabrice / Miossec, Pierre

Scientific reports

2018 Volume 8, Issue 1, Page(s) 12614

Abstract: Characterization of cell death currently requires the use of indirect markers, which has largely limited the ability to monitor cell death processes inside the cell. Here, we introduce a new method for the characterization of cell death mechanisms using ... ...

Abstract	Characterization of cell death currently requires the use of indirect markers, which has largely limited the ability to monitor cell death processes inside the cell. Here, we introduce a new method for the characterization of cell death mechanisms using cadmium telluride quantum dots (CdTe-QDs). Using visible CdTe-QDs with mesenchymal cells (e.g. synoviocytes), live-stream imaging allowed for visualization of cadmium-induced cell death, combining characteristics of apoptosis and autophagy. Initially, similar anti-proliferative effect was observed between 10 µg/ml Cd
MeSH term(s)	Apoptosis/drug effects ; Cadmium/adverse effects ; Cadmium/pharmacology ; Cadmium Compounds/chemistry ; Cell Death/drug effects ; Humans ; Molecular Imaging/methods ; Primary Cell Culture ; Quantum Dots/metabolism ; Synoviocytes/drug effects ; Tellurium/chemistry
Chemical Substances	Cadmium Compounds ; Cadmium (00BH33GNGH) ; Tellurium (NQA0O090ZJ) ; cadmium telluride (STG188WO13)
Language	English
Publishing date	2018-08-22
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/s41598-018-31077-2
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Article: Biological Applications and Toxicity Minimization of Semiconductor Quantum Dots

Filali, Samira / Pirot, Fabrice / Miossec, Pierre

Trends in biotechnology. 2019,

2019

Abstract	The extraordinary potential of semiconductor quantum dots (QDs) has resulted in their widespread application in various fields, from engineering technology and the development of laboratory techniques to biomedical imaging and therapeutic strategies. However, the toxicity of QDs remains a concern and has limited their applications in human health. Better understanding of the behavior of QDs as it relates to their composition will enable the exploration of their limitations and development of a strategy to control their toxicity for potential therapeutic applications. Here, we describe approaches to minimize their toxicities according to the specific cell type, organ, or animal species, summarizing recent promising research at the cellular, organ, and whole-organism level.
Keywords	human health ; image analysis ; laboratory techniques ; quantum dots ; therapeutics ; toxicity
Language	English
Publishing place	Elsevier Ltd
Document type	Article
Note	Pre-press version
ZDB-ID	47474-5
ISSN	1879-3096 ; 0167-7799
ISSN (online)	1879-3096
ISSN	0167-7799
DOI	10.1016/j.tibtech.2019.07.013
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Morphological and Mechanical Characterization of Extracellular Vesicles and Parent Human Synoviocytes under Physiological and Inflammatory Conditions.

Filali, Samira / Darragi-Raies, Nesrine / Ben-Trad, Layth / Piednoir, Agnès / Hong, Saw-See / Pirot, Fabrice / Landoulsi, Ahmed / Girard-Egrot, Agnès / Granjon, Thierry / Maniti, Ofelia / Miossec, Pierre / Trunfio-Sfarghiu, Ana-Maria

International journal of molecular sciences

2022 Volume 23, Issue 21

Abstract: The morphology of fibroblast-like synoviocytes (FLS) issued from the synovial fluid (SF) of patients suffering from osteoarthritis (OA), rheumatoid arthritis (RA), or from healthy subjects (H), as well as the ultrastructure and mechanical properties of ... ...

Abstract	The morphology of fibroblast-like synoviocytes (FLS) issued from the synovial fluid (SF) of patients suffering from osteoarthritis (OA), rheumatoid arthritis (RA), or from healthy subjects (H), as well as the ultrastructure and mechanical properties of the FLS-secreted extracellular vesicles (EV), were analyzed by confocal microscopy, transmission electron microscopy, atomic force microscopy, and tribological tests. EV released under healthy conditions were constituted of several lipid bilayers surrounding a viscous inner core. This "gel-in" vesicular structure ensured high mechanical resistance of single vesicles and good tribological properties of the lubricant. RA, and to a lesser extent OA, synovial vesicles had altered morphology, corresponding to a "gel-out" situation with vesicles surrounded by a viscous gel, poor mechanical resistance, and poor lubricating qualities. When subjected to inflammatory conditions, healthy cells developed phenotypes similar to that of RA samples, which reinforces the importance of inflammatory processes in the loss of lubricating properties of SF.
MeSH term(s)	Humans ; Synoviocytes/physiology ; Synovial Membrane ; Cells, Cultured ; Arthritis, Rheumatoid ; Osteoarthritis ; Fibroblasts ; Extracellular Vesicles
Language	English
Publishing date	2022-10-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232113201
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Article ; Online: Convergent evolution of olfactory and thermoregulatory capacities in small amphibious mammals.

Martinez, Quentin / Clavel, Julien / Esselstyn, Jacob A / Achmadi, Anang S / Grohé, Camille / Pirot, Nelly / Fabre, Pierre-Henri

Proceedings of the National Academy of Sciences of the United States of America

2020 Volume 117, Issue 16, Page(s) 8958–8965

Abstract: Olfaction and thermoregulation are key functions for mammals. The former is critical to feeding, mating, and predator avoidance behaviors, while the latter is essential for homeothermy. Aquatic and amphibious mammals face olfactory and thermoregulatory ... ...

Abstract	Olfaction and thermoregulation are key functions for mammals. The former is critical to feeding, mating, and predator avoidance behaviors, while the latter is essential for homeothermy. Aquatic and amphibious mammals face olfactory and thermoregulatory challenges not generally encountered by terrestrial species. In mammals, the nasal cavity houses a bony system supporting soft tissues and sensory organs implicated in either olfactory or thermoregulatory functions. It is hypothesized that to cope with aquatic environments, amphibious mammals have expanded their thermoregulatory capacity at the expense of their olfactory system. We investigated the evolutionary history of this potential trade-off using a comparative dataset of three-dimensional (3D) CT scans of 189 skulls, capturing 17 independent transitions from a strictly terrestrial to an amphibious lifestyle across small mammals (Afrosoricida, Eulipotyphla, and Rodentia). We identified rapid and repeated loss of olfactory capacities synchronously associated with gains in thermoregulatory capacity in amphibious taxa sampled from across mammalian phylogenetic diversity. Evolutionary models further reveal that these convergences result from faster rates of turbinal bone evolution and release of selective constraints on the thermoregulatory-olfaction trade-off in amphibious species. Lastly, we demonstrated that traits related to vital functions evolved faster to the optimum compared to traits that are not related to vital functions.
MeSH term(s)	Animals ; Biological Evolution ; Body Temperature Regulation/physiology ; Imaging, Three-Dimensional ; Mammals/physiology ; Nasal Cavity/anatomy & histology ; Nasal Cavity/diagnostic imaging ; Nasal Cavity/physiology ; Phylogeny ; Smell/physiology ; Swimming/physiology ; Tomography, X-Ray Computed ; Turbinates/anatomy & histology ; Turbinates/diagnostic imaging ; Turbinates/physiology
Language	English
Publishing date	2020-04-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1917836117
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Article ; Online: Live-stream characterization of cadmium-induced cell death using visible CdTe-QDs

Samira Filali / Alain Geloën / Vladimir Lysenko / Fabrice Pirot / Pierre Miossec

Scientific Reports, Vol 8, Iss 1, Pp 1-

2018 Volume 10

Abstract: Abstract Characterization of cell death currently requires the use of indirect markers, which has largely limited the ability to monitor cell death processes inside the cell. Here, we introduce a new method for the characterization of cell death ... ...

Abstract	Abstract Characterization of cell death currently requires the use of indirect markers, which has largely limited the ability to monitor cell death processes inside the cell. Here, we introduce a new method for the characterization of cell death mechanisms using cadmium telluride quantum dots (CdTe-QDs). Using visible CdTe-QDs with mesenchymal cells (e.g. synoviocytes), live-stream imaging allowed for visualization of cadmium-induced cell death, combining characteristics of apoptosis and autophagy. Initially, similar anti-proliferative effect was observed between 10 µg/ml Cd2+ and CdTe-QDs at 24 h (cell index/cell density ratio decreased from 0.6 to −16.6, p < 0.05) using techniques that do not require the capacity of CdTe-QDs. Apoptosis was confirmed by the quantification of morphological parameters (reduced surface area, increased cell thickness) and positive labeling with annexin V. Autophagy was confirmed by monodansylcadaverine staining, identifying similar autophagic vacuoles with both Cd2+ and CdTe-QD. However, QD imaging allowed for visualization of cadmium elements inside cell structures and their kinetic changes leading to cell death. Cell death characteristics were similar in inflammatory and non-inflammatory environment but were induced up to 4 h earlier in the former. Therefore, live-stream imaging of a visible cytotoxic agent has useful applications not currently possible with indirect methods, including chronological monitoring of cell death.
Keywords	Medicine ; R ; Science ; Q
Subject code	500
Language	English
Publishing date	2018-08-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
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Article ; Online: Design and selection of optimal ErbB-targeting bispecific antibodies in pancreatic cancer.

Frontiers in immunology

2023 Volume 14, Page(s) 1168444

Abstract: The ErbB family of receptor tyrosine kinases is a primary target for small molecules and antibodies for pancreatic cancer treatment. Nonetheless, the current treatments for this tumor are not optimal due to lack of efficacy, resistance, or toxicity. Here, ...

Abstract	The ErbB family of receptor tyrosine kinases is a primary target for small molecules and antibodies for pancreatic cancer treatment. Nonetheless, the current treatments for this tumor are not optimal due to lack of efficacy, resistance, or toxicity. Here, using the novel BiXAb™ tetravalent format platform, we generated bispecific antibodies against EGFR, HER2, or HER3 by considering rational epitope combinations. We then screened these bispecific antibodies and compared them with the parental single antibodies and antibody pair combinations. The screen readouts included measuring binding to the cognate receptors (mono and bispecificity), intracellular phosphorylation signaling, cell proliferation, apoptosis and receptor expression, and also immune system engagement assays (antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity). Among the 30 BiXAbs™ tested, we selected 3Patri-1Cetu-Fc, 3Patri-1Matu-Fc and 3Patri-2Trastu-Fc as lead candidates. The in vivo testing of these three highly efficient bispecific antibodies against EGFR and HER2 or HER3 in pre-clinical mouse models of pancreatic cancer showed deep antibody penetration in these dense tumors and robust tumor growth reduction. Application of such semi-rational/semi-empirical approach, which includes various immunological assays to compare pre-selected antibodies and their combinations with bispecific antibodies, represents the first attempt to identify potent bispecific antibodies against ErbB family members in pancreatic cancer.
MeSH term(s)	Animals ; Mice ; Antibodies, Bispecific ; Cell Line, Tumor ; ErbB Receptors/metabolism ; Signal Transduction ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/pathology ; Pancreatic Neoplasms
Chemical Substances	Antibodies, Bispecific ; ErbB Receptors (EC 2.7.10.1)
Language	English
Publishing date	2023-04-20
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.2023.1168444
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