LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 6 of total 6

Search options

  1. Article ; Online: CAPN2-responsive mesoporous silica nanoparticles: A promising nanocarrier for targeted therapy of pancreatic cancer.

    Slapak, Etienne J / El Mandili, Mouad / Ten Brink, Marieke S / Kros, Alexander / Bijlsma, Maarten F / Spek, C Arnold

    Cancer letters

    2024  Volume 590, Page(s) 216845

    Abstract: Pancreatic adenocarcinoma (PDAC) is highly resistant to conventional chemotherapeutic interventions, resulting in exceptionally low survival rates. The limited efficacy can in part be attributed to dose limitations and treatment cessation urged by ... ...

    Abstract Pancreatic adenocarcinoma (PDAC) is highly resistant to conventional chemotherapeutic interventions, resulting in exceptionally low survival rates. The limited efficacy can in part be attributed to dose limitations and treatment cessation urged by toxicity of currently used chemotherapy. The advent of targeted delivery strategies has kindled hope for circumventing off-target toxicity. We have previously reported a PDAC-specific mesoporous silica nanoparticle (MSN) containing a protease linker responsive to ADAM9, a PDAC-enriched extracellularly deposited protease. Upon loading with paclitaxel these ADAM9-MSNs reduced side effects both in vitro and in vivo, however, disappointing antitumor efficacy was observed in vivo. Here, we propose that an efficient uptake of MSNs by tumor cells might underlie the lack of antitumor efficacy of MSNs functionalized with linker responsive to extracellular proteases. Harnessing this premise to improve antitumor efficacy, we performed an in silico analysis to identify PDAC-enriched intracellular proteases. We report the identification of BACE2, CAPN2 and DPP3 as PDAC enriched intracellular proteases, and report the synthesis of BACE2-, CAPN2- and DPP3-responsive MSNs. Extensive preclinical assessments revealed that paclitaxel-loaded CAPN2- and DPP3-MSNs exhibit high PDAC specificity in vitro as opposed to free paclitaxel. The administration of paclitaxel-loaded CAPN2- and DPP3-MSNs in vivo confirmed the reduction of leukopenia and induced no organ damage. Promisingly, in two mouse models CAPN2-MSNs reduced tumor growth at least as efficiently as free paclitaxel. Taken together, our results pose CAPN2-MSNs as a promising nanocarrier for the targeted delivery of chemotherapeutics in PDAC.
    MeSH term(s) Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/pathology ; Silicon Dioxide/chemistry ; Humans ; Animals ; Paclitaxel/pharmacology ; Paclitaxel/administration & dosage ; Nanoparticles/chemistry ; Cell Line, Tumor ; Calpain/metabolism ; Drug Carriers/chemistry ; Xenograft Model Antitumor Assays ; Mice ; Porosity ; Amyloid Precursor Protein Secretases/metabolism ; Amyloid Precursor Protein Secretases/antagonists & inhibitors ; Mice, Nude ; Female
    Chemical Substances Silicon Dioxide (7631-86-9) ; Paclitaxel (P88XT4IS4D) ; Calpain (EC 3.4.22.-) ; Drug Carriers ; CAPN2 protein, human (EC 3.4.22.53) ; Amyloid Precursor Protein Secretases (EC 3.4.-)
    Language English
    Publishing date 2024-04-06
    Publishing country Ireland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 195674-7
    ISSN 1872-7980 ; 0304-3835
    ISSN (online) 1872-7980
    ISSN 0304-3835
    DOI 10.1016/j.canlet.2024.216845
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1177: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: An optimized retroviral toolbox for overexpression and genetic perturbation of primary lymphocytes.

    van der Donk, Lieve E H / van der Spek, Jet / van Duivenvoorde, Tom / Ten Brink, Marieke S / Geijtenbeek, Teunis B H / Kuijl, Coenraad P / van Heijst, Jeroen W J / Ates, Louis S

    Biology open

    2022  Volume 11, Issue 2

    Abstract: Genetic manipulation of primary lymphocytes is crucial for both clinical purposes and fundamental research. Despite their broad use, we encountered a paucity of data on systematic comparison and optimization of retroviral vectors, the workhorses of ... ...

    Abstract Genetic manipulation of primary lymphocytes is crucial for both clinical purposes and fundamental research. Despite their broad use, we encountered a paucity of data on systematic comparison and optimization of retroviral vectors, the workhorses of genetic modification of primary lymphocytes. Here, we report the construction and validation of a versatile range of retroviral expression vectors. These vectors can be used for the knockdown or overexpression of genes of interest in primary human and murine lymphocytes, in combination with a wide choice of selection and reporter strategies. By streamlining the vector backbone and insert design, these publicly available vectors allow easy interchangeability of the independent building blocks, such as different promoters, fluorescent proteins, surface markers and antibiotic resistance cassettes. We validated these vectors and tested the optimal promoters for in vitro and in vivo overexpression and knockdown of the murine T cell antigen receptor. By publicly sharing these vectors and the data on their optimization, we aim to facilitate genetic modification of primary lymphocytes for researchers entering this field.
    MeSH term(s) Animals ; Genetic Vectors/genetics ; Humans ; Lymphocytes ; Mice ; Promoter Regions, Genetic ; Retroviridae/genetics
    Language English
    Publishing date 2022-03-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2632264-X
    ISSN 2046-6390 ; 2046-6390
    ISSN (online) 2046-6390
    ISSN 2046-6390
    DOI 10.1242/bio.059032
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: C3a signaling is not involved in eosinophil migration during experimental allergic lung inflammation in mice.

    Yang, Jack / Van't Veer, Cornelis / Ten Brink, Marieke S / de Vos, Alex F / van der Poll, Tom

    Allergy

    2019  Volume 75, Issue 4, Page(s) 934–936

    MeSH term(s) Alveolitis, Extrinsic Allergic ; Animals ; Eosinophils ; Hypersensitivity/etiology ; Inflammation ; Lung ; Mice ; Pneumonia/etiology ; Pulmonary Eosinophilia
    Language English
    Publishing date 2019-09-03
    Publishing country Denmark
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/all.14021
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.150: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 125: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: PAR1 signaling on tumor cells limits tumor growth by maintaining a mesenchymal phenotype in pancreatic cancer.

    Tekin, Cansu / Shi, Kun / Daalhuisen, Joost B / Ten Brink, Marieke S / Bijlsma, Maarten F / Spek, C Arnold

    Oncotarget

    2018  Volume 9, Issue 62, Page(s) 32010–32023

    Abstract: Protease activated receptor-1 (PAR1) expression is associated with disease progression and overall survival in a variety of cancers. However, the importance of tumor cell PAR1 in pancreatic ductal adenocarcinomas (PDAC) remains unexplored. Utilizing ... ...

    Abstract Protease activated receptor-1 (PAR1) expression is associated with disease progression and overall survival in a variety of cancers. However, the importance of tumor cell PAR1 in pancreatic ductal adenocarcinomas (PDAC) remains unexplored. Utilizing orthotopic models with wild type and PAR1-targeted PDAC cells, we show that tumor cell PAR1 negatively affects PDAC growth, yet promotes metastasis. Mechanistically, we show that tumor cell-specific PAR1 expression correlates with mesenchymal signatures in PDAC and that PAR1 is linked to the maintenance of a partial mesenchymal cell state. Indeed, loss of PAR1 expression results in well-differentiated pancreatic tumors
    Language English
    Publishing date 2018-08-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2560162-3
    ISSN 1949-2553 ; 1949-2553
    ISSN (online) 1949-2553
    ISSN 1949-2553
    DOI 10.18632/oncotarget.25880
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article ; Online: Comparison of inhibitory effects of irreversible and reversible Btk inhibitors on platelet function.

    Tullemans, Bibian M E / Karel, Mieke F A / Léopold, Valentine / Ten Brink, Marieke S / Baaten, Constance C F M J / Maas, Sanne L / de Vos, Alex F / Eble, Johannes A / Nijziel, Marten R / van der Vorst, Emiel P C / Cosemans, Judith M E M / Heemskerk, Johan W M / Claushuis, Theodora A M / Kuijpers, Marijke J E

    EJHaem

    2021  Volume 2, Issue 4, Page(s) 685–699

    Abstract: All irreversible Bruton tyrosine kinase (Btk) inhibitors including ibrutinib and acalabrutinib induce platelet dysfunction and increased bleeding risk. New reversible Btk inhibitors were developed, like MK-1026. The mechanism underlying increased ... ...

    Abstract All irreversible Bruton tyrosine kinase (Btk) inhibitors including ibrutinib and acalabrutinib induce platelet dysfunction and increased bleeding risk. New reversible Btk inhibitors were developed, like MK-1026. The mechanism underlying increased bleeding tendency with Btk inhibitors remains unclear. We investigated the effects of ibrutinib, acalabrutinib and MK-1026 on platelet function in healthy volunteers, patients and Btk-deficient mice, together with off-target effects on tyrosine kinase phosphorylation. All inhibitors suppressed GPVI- and CLEC-2-mediated platelet aggregation, activation and secretion in a dose-dependent manner. Only ibrutinib inhibited thrombus formation on vWF-co-coated surfaces, while on collagen this was not affected. In blood from Btk-deficient mice, collagen-induced thrombus formation under flow was reduced, but preincubation with either inhibitor was without additional effects. MK-1026 showed less off-target effects upon GPVI-induced TK phosphorylation as compared to ibrutinib and acalabrutinib. In ibrutinib-treated patients, GPVI-stimulated platelet activation, and adhesion on vWF-co-coated surfaces were inhibited, while CLEC-2 stimulation induced variable responses. The dual inhibition of GPVI and CLEC-2 signalling by Btk inhibitors might account for the increased bleeding tendency, with ibrutinib causing more high-grade bleedings due to additional inhibition of platelet-vWF interaction. As MK-1026 showed less off-target effects and only affected activation of isolated platelets, it might be promising for future treatment.
    Language English
    Publishing date 2021-08-10
    Publishing country United States
    Document type Journal Article
    ISSN 2688-6146
    ISSN (online) 2688-6146
    DOI 10.1002/jha2.269
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  6. Article ; Online: Betulinic acid delivered in liposomes reduces growth of human lung and colon cancers in mice without causing systemic toxicity.

    Mullauer, Franziska B / van Bloois, Louis / Daalhuisen, Joost B / Ten Brink, Marieke S / Storm, Gert / Medema, Jan Paul / Schiffelers, Raymond M / Kessler, Jan H

    Anti-cancer drugs

    2011  Volume 22, Issue 3, Page(s) 223–233

    Abstract: Betulinic acid (BetA) is a plant-derived pentacyclic triterpenoid with potent anticancer capacity that targets the mitochondrial pathway of apoptosis. BetA has a broad efficacy in vitro against prevalent cancer types, including lung, colorectal, prostate, ...

    Abstract Betulinic acid (BetA) is a plant-derived pentacyclic triterpenoid with potent anticancer capacity that targets the mitochondrial pathway of apoptosis. BetA has a broad efficacy in vitro against prevalent cancer types, including lung, colorectal, prostate, cervix and breast cancer, melanomas, neuroblastomas, and leukemias. The cytotoxic effects of the compound against healthy cells are minimal, rendering BetA a promising potential anticancer drug. However, because of the weak hydrosolubility of BetA, it has been difficult to study its efficacy in vivo and a pharmaceutical formulation is not yet available. We report the development of a liposome formulation of BetA and show its successful application in mice. Large liposomes, assembled without cholesterol to reduce their rigidity, efficiently incorporated BetA. Nude mice xenografted with human colon and lung cancer tumors were treated intravenously with the BetA-containing liposomes. Tumor growth was reduced to more than 50% compared with the control treatment, leading to an enhanced survival of the mice. Oral administration of the liposomal formulation of BetA also slowed tumor growth. Any signs of systemic toxicity caused by BetA treatment were absent. Thus, liposomes are an efficient formulation vehicle for BetA, enabling its preclinical development as a nontoxic compound for the treatment of cancers.
    MeSH term(s) Administration, Oral ; Animals ; Antineoplastic Agents, Phytogenic/administration & dosage ; Antineoplastic Agents, Phytogenic/chemistry ; Antineoplastic Agents, Phytogenic/toxicity ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Colonic Neoplasms/drug therapy ; Colonic Neoplasms/pathology ; Drug Delivery Systems ; Drug Stability ; Female ; Humans ; Injections, Intravenous ; Liposomes/chemistry ; Lung/pathology ; Lung Neoplasms/drug therapy ; Lung Neoplasms/pathology ; Mice ; Mice, Nude ; Mitochondria/drug effects ; Rhodamines ; Triterpenes/administration & dosage ; Triterpenes/chemistry ; Triterpenes/toxicity
    Chemical Substances Antineoplastic Agents, Phytogenic ; Liposomes ; Rhodamines ; Triterpenes ; betulinic acid (4G6A18707N)
    Language English
    Publishing date 2011-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1065301-6
    ISSN 1473-5741 ; 0959-4973
    ISSN (online) 1473-5741
    ISSN 0959-4973
    DOI 10.1097/CAD.0b013e3283421035
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 3125: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top