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  1. Article: Netrin-1 binding to Unc5B regulates Blood-Retina Barrier integrity.

    Furtado, Jessica / Geraldo, Luiz Henrique / Leser, Felipe Saceanu / Poulet, Mathilde / Park, Hyojin / Pibouin-Fragner, Laurence / Eichmann, Anne / Boyé, Kevin

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Background: The blood brain barrier (BBB) preserves neuronal function in the central nervous system (CNS) by tightly controlling metabolite exchanges with the blood. In the eye, the retina is likewise protected by the blood-retina barrier (BRB) to ... ...

    Abstract Background: The blood brain barrier (BBB) preserves neuronal function in the central nervous system (CNS) by tightly controlling metabolite exchanges with the blood. In the eye, the retina is likewise protected by the blood-retina barrier (BRB) to maintain phototransduction. We showed that the secreted guidance cue Netrin-1 regulated BBB integrity, by binding to endothelial Unc5B and regulating canonical β-catenin dependent expression of BBB gene expression.
    Objective: Here, we investigated if Netrin-1-binding to endothelial Unc5B also controlled BRB integrity, and if this process involved Norrin/β-catenin signaling, which is the major known driver of BRB development and maintenance.
    Methods: We analyzed Tamoxifen-inducible loss- and gain- of-function alleles of
    Results: Inducible endothelial
    Conclusions: The data identify Netrin1-Unc5B as novel regulators of BRB integrity, with implications for diseases associated with BRB disruption.
    Language English
    Publishing date 2023-01-21
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.01.21.525006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The multiple functions of PrP<sup>C</sup> in physiological, cancer, and neurodegenerative contexts.

    Grimaldi, Izabella / Leser, Felipe Saceanu / Janeiro, José Marcos / da Rosa, Bárbara Gomes / Campanelli, Ana Clara / Romão, Luciana / Lima, Flavia Regina Souza

    Journal of molecular medicine (Berlin, Germany)

    2022  Volume 100, Issue 10, Page(s) 1405–1425

    Abstract: Cellular prion protein (PrP ... C ... ) is a highly conserved glycoprotein, present both anchored in the cell membrane and soluble in the extracellular medium. It has a diversity of ligands and is variably expressed in numerous tissues and cell subtypes, ...

    Abstract Cellular prion protein (PrP<sup>C</sup>) is a highly conserved glycoprotein, present both anchored in the cell membrane and soluble in the extracellular medium. It has a diversity of ligands and is variably expressed in numerous tissues and cell subtypes, most notably in the central nervous system (CNS). Its importance has been brought to light over the years both under physiological conditions, such as embryogenesis and immune system homeostasis, and in pathologies, such as cancer and neurodegenerative diseases. During development, PrP<sup>C</sup> plays an important role in CNS, participating in axonal growth and guidance and differentiation of glial cells, but also in other organs such as the heart, lung, and digestive system. In diseases, PrP<sup>C</sup> has been related to several types of tumors, modulating cancer stem cells, enhancing malignant properties, and inducing drug resistance. Also, in non-neoplastic diseases, such as Alzheimer's and Parkinson's diseases, PrP<sup>C</sup> seems to alter the dynamics of neurotoxic aggregate formation and, consequently, the progression of the disease. In this review, we explore in detail the multiple functions of this protein, which proved to be relevant for understanding the dynamics of organism homeostasis, as well as a promising target in the treatment of both neoplastic and degenerative diseases.
    MeSH term(s) Central Nervous System/metabolism ; Humans ; Neoplasms ; Neoplastic Stem Cells/metabolism ; Neurodegenerative Diseases ; PrPC Proteins/genetics ; PrPC Proteins/metabolism
    Chemical Substances PrPC Proteins
    Language English
    Publishing date 2022-09-03
    Publishing country Germany
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 1223802-8
    ISSN 1432-1440 ; 0946-2716
    ISSN (online) 1432-1440
    ISSN 0946-2716
    DOI 10.1007/s00109-022-02245-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  3. Article ; Online: An Uncommon Lung Neoplasm in a Young Patient: Diagnostic Challenges.

    Leser, Felipe Saceanu / Romano, Lucas Dalsenter / de Resende, Kauê Ruan / Lapa E Silva, José Roberto

    The American journal of case reports

    2020  Volume 21, Page(s) e926038

    Abstract: BACKGROUND Adenosquamous carcinoma of the lung (ASC) is a rare subtype of non-small-cell lung carcinoma (NSCLC), histologically defined by the presence of both squamous cell carcinoma and adenocarcinoma components. This aggressive malignancy has been ... ...

    Abstract BACKGROUND Adenosquamous carcinoma of the lung (ASC) is a rare subtype of non-small-cell lung carcinoma (NSCLC), histologically defined by the presence of both squamous cell carcinoma and adenocarcinoma components. This aggressive malignancy has been rarely described in young female patients. Due to its low incidence and difficult-to-establish preoperative diagnosis, little is known about the complete clinical course for young patients with this specific NSCLC subtype. Moreover, a history of smoking is positively associated with ASC, but evidence for an association with exposure to secondhand smoke is sparse. CASE REPORT We present the case of a previously healthy 29-year-old woman with a long-standing history of secondhand smoke exposure, who was ultimately diagnosed with advanced ASC via fiberoptic bronchoscopy with transbronchial biopsy after a number of different investigations and treatments performed outside our service. She had visited many clinicians in 4 months of symptoms, initially presented as thoracic pain and cough thought to be due to a complicated pneumonia. Symptoms progressed despite empiric treatment and eventually included low back pain, weight loss, and night sweats. The hypothesis of tuberculosis was then investigated and discarded, at which point, 3 months after the onset of symptoms, she had a CT scan of the chest, revealing a pulmonary mass. She was referred to our hospital to further investigate this finding via fiberoptic bronchoscopy with transbronchial biopsy. During the procedure, she experienced an acute exacerbation of the low back pain, which prompted her admission in the Emergency Department, and she was later admitted to our pneumology ward. An extensive treatment plan including chemotherapy and radiotherapy was initially started, but could not be completed due to rapid disease progression, defined by pulmonary and spine metastatic implants, which limited treatment to palliative care. The patient died 6 months after the initial onset of symptoms. CONCLUSIONS This case report shows the clinical course of a difficult and rare diagnosis, and demonstrates the high level of suspicion required for the early diagnosis of lung neoplasms in young patients.
    MeSH term(s) Adult ; Bronchoscopy ; Carcinoma, Non-Small-Cell Lung ; Female ; Humans ; Lung ; Lung Neoplasms/diagnosis ; Tomography, X-Ray Computed
    Language English
    Publishing date 2020-10-16
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 2517183-5
    ISSN 1941-5923 ; 1941-5923
    ISSN (online) 1941-5923
    ISSN 1941-5923
    DOI 10.12659/AJCR.926038
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: CCL21-CCR7 signaling promotes microglia/macrophage recruitment and chemotherapy resistance in glioblastoma.

    Geraldo, Luiz Henrique / Garcia, Celina / Xu, Yunling / Leser, Felipe Saceanu / Grimaldi, Izabella / de Camargo Magalhães, Eduardo Sabino / Dejaegher, Joost / Solie, Lien / Pereira, Cláudia Maria / Correia, Ana Helena / De Vleeschouwer, Steven / Tavitian, Bertrand / Canedo, Nathalie Henriques Silva / Mathivet, Thomas / Thomas, Jean-Leon / Eichmann, Anne / Lima, Flavia Regina Souza

    Cellular and molecular life sciences : CMLS

    2023  Volume 80, Issue 7, Page(s) 179

    Abstract: Glioblastoma (GBM) is the most common and fatal primary tumor of the central nervous system (CNS) and current treatments have limited success. Chemokine signaling regulates both malignant cells and stromal cells of the tumor microenvironment (TME), ... ...

    Abstract Glioblastoma (GBM) is the most common and fatal primary tumor of the central nervous system (CNS) and current treatments have limited success. Chemokine signaling regulates both malignant cells and stromal cells of the tumor microenvironment (TME), constituting a potential therapeutic target against brain cancers. Here, we investigated the C-C chemokine receptor type 7 (CCR7) and the chemokine (C-C-motif) ligand 21 (CCL21) for their expression and function in human GBM and then assessed their therapeutic potential in preclinical mouse GBM models. In GBM patients, CCR7 expression positively associated with a poor survival. CCL21-CCR7 signaling was shown to regulate tumor cell migration and proliferation while also controlling tumor associated microglia/macrophage recruitment and VEGF-A production, thereby controlling vascular dysmorphia. Inhibition of CCL21-CCR7 signaling led to an increased sensitivity to temozolomide-induced tumor cell death. Collectively, our data indicate that drug targeting of CCL21-CCR7 signaling in tumor and TME cells is a therapeutic option against GBM.
    MeSH term(s) Animals ; Mice ; Humans ; Microglia ; Glioblastoma/drug therapy ; Receptors, CCR7/genetics ; Macrophages ; Central Nervous System ; Tumor Microenvironment ; Chemokine CCL21
    Chemical Substances Receptors, CCR7 ; CCR7 protein, human ; CCL21 protein, human ; Chemokine CCL21
    Language English
    Publishing date 2023-06-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-023-04788-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 195: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  5. Article ; Online: The multiple functions of the co-chaperone stress inducible protein 1.

    da Fonseca, Anna Carolina Carvalho / Matias, Diana / Geraldo, Luiz Henrique Medeiros / Leser, Felipe Saceanu / Pagnoncelli, Iohana / Garcia, Celina / do Amaral, Rackele Ferreira / da Rosa, Barbara Gomes / Grimaldi, Izabella / de Camargo Magalhães, Eduardo Sabino / Cóppola-Segovia, Valentín / de Azevedo, Evellyn Mayla / Zanata, Silvio Marques / Lima, Flavia Regina Souza

    Cytokine & growth factor reviews

    2020  Volume 57, Page(s) 73–84

    Abstract: Stress inducible protein 1 (STI1) is a co-chaperone acting with Hsp70 and Hsp90 for the correct client proteins' folding and therefore for the maintenance of cellular homeostasis. Besides being expressed in the cytosol, STI1 can also be found both in the ...

    Abstract Stress inducible protein 1 (STI1) is a co-chaperone acting with Hsp70 and Hsp90 for the correct client proteins' folding and therefore for the maintenance of cellular homeostasis. Besides being expressed in the cytosol, STI1 can also be found both in the cell membrane and the extracellular medium playing several relevant roles in the central nervous system (CNS) and tumor microenvironment. During CNS development, in association with cellular prion protein (PrP
    MeSH term(s) Heat-Shock Proteins ; Humans ; Molecular Chaperones ; Tumor Microenvironment
    Chemical Substances Heat-Shock Proteins ; Molecular Chaperones
    Language English
    Publishing date 2020-06-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1330534-7
    ISSN 1879-0305 ; 1359-6101
    ISSN (online) 1879-0305
    ISSN 1359-6101
    DOI 10.1016/j.cytogfr.2020.06.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2653: Show issues Location:
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