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  1. Article: Wie hätten Sie entschieden? Die Therapievariante von Dr. Nicole Bujara und Dr. Pia Di Cristofano

    Bujara, Nicole / Di Cristofano, Pia

    Dental-Magazin

    2003  Volume 21, Issue 1, Page(s) 46

    Language German
    Document type Article
    ZDB-ID 380595-5
    ISSN 0176-7291
    Database Current Contents Medicine

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  2. Article ; Online: The Year in Basic Thyroid Cancer Research.

    Di Cristofano, Antonio

    Thyroid : official journal of the American Thyroid Association

    2021  Volume 32, Issue 1, Page(s) 3–8

    Abstract: Background: ...

    Abstract Background:
    MeSH term(s) Endocrinology/methods ; Humans ; Research/trends ; Societies/organization & administration ; Societies/trends ; Thyroid Neoplasms/physiopathology ; Thyroid Neoplasms/therapy ; United States
    Language English
    Publishing date 2021-12-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1086044-7
    ISSN 1557-9077 ; 1050-7256
    ISSN (online) 1557-9077
    ISSN 1050-7256
    DOI 10.1089/thy.2021.0561
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: A zebrafish xenotransplant model of anaplastic thyroid cancer to study the tumor microenvironment and innate immune cell interactions

    Michael, Cassia / Di Cristofano, Antonio / de Oliveira, Sofia

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Anaplastic thyroid cancer (ATC) is a rare malignant subtype of thyroid cancer. While ATC is rare it accounts for a disproportionately high number of thyroid cancer-related deaths. Here we developed an ATC xenotransplant model in zebrafish larvae, where ... ...

    Abstract Anaplastic thyroid cancer (ATC) is a rare malignant subtype of thyroid cancer. While ATC is rare it accounts for a disproportionately high number of thyroid cancer-related deaths. Here we developed an ATC xenotransplant model in zebrafish larvae, where we can study tumorigenesis and therapeutic response in vivo. Using both mouse (T4888M) and human (C643) derived fluorescently labeled ATC cell lines we show these cell lines display different engraftment rates, mass volume, proliferation, and angiogenic potential. Next, using a PIP-FUCCI reporter to track proliferation
    Language English
    Publishing date 2023-06-02
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.05.29.541816
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Split Gp41-1 intein splicing as a model to evaluate the cellular location of the oncosuppressor Maspin in an in vitro model of osteosarcoma.

    Mariano, Alessia / Di Cristofano, Samuele / Raimondo, Domenico / Scotto d'Abusco, Anna

    Cell biochemistry and function

    2024  Volume 42, Issue 2, Page(s) e3987

    Abstract: Inteins are proteins involved in the protein splicing mechanism, an autoprocessing event, where sequences (exteins) separated by inteins become ligated each other after recombination. Two kinds of inteins have been described, contiguous inteins and split ...

    Abstract Inteins are proteins involved in the protein splicing mechanism, an autoprocessing event, where sequences (exteins) separated by inteins become ligated each other after recombination. Two kinds of inteins have been described, contiguous inteins and split inteins. The former ones are transcribed and translated as a single peptide along with their exteins, while the latter are fragmented between two different genes and are transcribed and translated separately. The aim of this study is to establish a method to obtain a fluorescent eukaryotic protein to analyze its cellular localization, using the natural split gp41-1 inteins. We chose natural split inteins due to their distribution in all three domains of life. Two constructs were prepared, one containing the N-terminal split intein along with the N-moiety of the Red Fluorescent Protein (RFP) and a second construct containing the C-terminal of split intein, the C-moiety of RFP and the gene coding for Maspin, a tumor suppressor protein. The trans-splicing was verified by transfecting both N-terminal and C-terminal constructs into mammalian cells. The success of the recombination event was highlighted through the fluorescence produced by reconstituted RFP after recombination, along with the overlap of the red fluorescence produced by recombined RFP and the green fluorescence produced by the hybridization of the recombinant Maspin with a specific antibody. In conclusion, we opted to use this mechanism of recombination to obtain a fluorescent Maspin instead to express a large fusion protein, considering that it could interfere with Maspin's structure and function.
    MeSH term(s) Animals ; Humans ; Inteins/genetics ; Protein Splicing ; Serpins/genetics ; Osteosarcoma/genetics ; Mammals
    Chemical Substances SERPIN-B5 ; Serpins
    Language English
    Publishing date 2024-03-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 283643-9
    ISSN 1099-0844 ; 0263-6484
    ISSN (online) 1099-0844
    ISSN 0263-6484
    DOI 10.1002/cbf.3987
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Anaplastic Thyroid Cancer Cells Upregulate Mitochondrial One-Carbon Metabolism To Meet Purine Demand, Eliciting A Critical Targetable Vulnerability.

    Sugarman, Adam J / Huynh, Luong Do / Shabro, Aidin / Di Cristofano, Antonio

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Anaplastic thyroid cancer (ATC) is one of the most aggressive and lethal tumor types, characterized by loss of differentiation, epithelial-to-mesenchymal transition, extremely high proliferation rate, and generalized resistance to therapy. To identify ... ...

    Abstract Anaplastic thyroid cancer (ATC) is one of the most aggressive and lethal tumor types, characterized by loss of differentiation, epithelial-to-mesenchymal transition, extremely high proliferation rate, and generalized resistance to therapy. To identify novel relevant, targetable molecular alterations, we analyzed gene expression profiles from a genetically engineered ATC mouse model and from human patient datasets, and found consistent upregulation of genes encoding enzymes involved in the one-carbon metabolic pathway, which uses serine and folates to generate both nucleotides and glycine. Genetic and pharmacological inhibition of
    Language English
    Publishing date 2023-04-30
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.04.30.538848
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Anaplastic thyroid cancer cells upregulate mitochondrial one-carbon metabolism to meet purine demand, eliciting a critical targetable vulnerability.

    Sugarman, Adam J / Huynh, Luong Do / Shabro, Aidin / Di Cristofano, Antonio

    Cancer letters

    2023  Volume 568, Page(s) 216304

    Abstract: Anaplastic thyroid cancer (ATC) is one of the most aggressive and lethal tumor types, characterized by loss of differentiation, epithelial-to-mesenchymal transition, extremely high proliferation rate, and generalized resistance to therapy. To identify ... ...

    Abstract Anaplastic thyroid cancer (ATC) is one of the most aggressive and lethal tumor types, characterized by loss of differentiation, epithelial-to-mesenchymal transition, extremely high proliferation rate, and generalized resistance to therapy. To identify novel relevant, targetable molecular alterations, we analyzed gene expression profiles from a genetically engineered ATC mouse model and from human patient datasets, and found consistent upregulation of genes encoding enzymes involved in the one-carbon metabolic pathway, which uses serine and folates to generate both nucleotides and glycine. Genetic and pharmacological inhibition of SHMT2, a key enzyme of the mitochondrial arm of the one-carbon pathway, rendered ATC cells glycine auxotroph and led to significant inhibition of cell proliferation and colony forming ability, which was primarily caused by depletion of the purine pool. Notably, these growth-suppressive effects were significantly amplified when cells were grown in the presence of physiological types and levels of folates. Genetic depletion of SHMT2 dramatically impaired tumor growth in vivo, both in xenograft models and in an immunocompetent allograft model of ATC. Together, these data establish the upregulation of the one-carbon metabolic pathway as a novel and targetable vulnerability of ATC cells, which can be exploited for therapeutic purposes.
    MeSH term(s) Animals ; Mice ; Humans ; Thyroid Carcinoma, Anaplastic/drug therapy ; Thyroid Neoplasms/pathology ; Cell Line, Tumor ; Cell Proliferation ; Glycine/pharmacology ; Glycine/therapeutic use ; Purines/pharmacology
    Chemical Substances Glycine (TE7660XO1C) ; Purines
    Language English
    Publishing date 2023-07-06
    Publishing country Ireland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 195674-7
    ISSN 1872-7980 ; 0304-3835
    ISSN (online) 1872-7980
    ISSN 0304-3835
    DOI 10.1016/j.canlet.2023.216304
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: A zebrafish xenotransplant model of anaplastic thyroid cancer to study the tumor microenvironment and innate immune cell interactions in vivo.

    Michael, Cassia / Mendonça-Gomes, Juliana Moreira / DePaolo, Clinton Walton / Di Cristofano, Antonio / De Oliveira, Sofia

    Endocrine-related cancer

    2024  

    Abstract: Anaplastic thyroid cancer (ATC) is of the most aggressive thyroid cancer. While ATC is rare it accounts for a disproportionately high number of thyroid cancer-related deaths. Here we developed an ATC xenotransplant model in zebrafish larvae, where we can ...

    Abstract Anaplastic thyroid cancer (ATC) is of the most aggressive thyroid cancer. While ATC is rare it accounts for a disproportionately high number of thyroid cancer-related deaths. Here we developed an ATC xenotransplant model in zebrafish larvae, where we can study tumorigenesis and therapeutic response in vivo. Using both mouse (T4888M) and human (C643) derived fluorescently labeled ATC cell lines we show these cell lines display different engraftment rates, mass volume, proliferation, cell death, angiogenic potential and neutrophil and macrophage recruitment and infiltration. Next, using a PIP-FUCCI reporter to track proliferation in-vivo we observed cells in each phase of the cell cycle. Additionally, we performed long-term non-invasive intravital microscopy over 48 hours to understand cellular dynamics in the tumor microenvironment at the single cell level. Lastly, we tested two drug treatments, AZD2014 and a combination therapy of dabrafenib and trametinib to show our model could be used as an effective screening platform for new therapeutic compounds for ATC. Altogether, we show that zebrafish xenotransplants make a great model to study thyroid carcinogenesis and the tumor microenvironment, while also being a suitable model to test new therapeutics in vivo.
    Language English
    Publishing date 2024-04-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 1218450-0
    ISSN 1479-6821 ; 1351-0088
    ISSN (online) 1479-6821
    ISSN 1351-0088
    DOI 10.1530/ERC-23-0195
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: SGK1: The Dark Side of PI3K Signaling.

    Di Cristofano, Antonio

    Current topics in developmental biology

    2017  Volume 123, Page(s) 49–71

    Abstract: Activation of the PI3K pathway is central to a variety of physiological and pathological processes. In these contexts, AKT is classically considered the de facto mediator of PI3K-dependent signaling. However, in recent years, accumulating data point to ... ...

    Abstract Activation of the PI3K pathway is central to a variety of physiological and pathological processes. In these contexts, AKT is classically considered the de facto mediator of PI3K-dependent signaling. However, in recent years, accumulating data point to the existence of additional effectors of PI3K activity, parallel to and independent of AKT, that play critical and unique roles in mediating different developmental, homeostatic, and pathological processes. In this review, I summarize and discuss our current understanding of the function of the serine/threonine kinase SGK1 as a downstream effector of PI3K, and try to separate targets and pathways validated as uniquely SGK1-dependent from those shared with AKT.
    MeSH term(s) Animals ; Cell Differentiation ; Embryonic Development ; Enzyme Stability ; Humans ; Immediate-Early Proteins/metabolism ; Neoplasms/enzymology ; Phosphatidylinositol 3-Kinases/metabolism ; Protein-Serine-Threonine Kinases/metabolism ; Signal Transduction
    Chemical Substances Immediate-Early Proteins ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; serum-glucocorticoid regulated kinase (EC 2.7.11.1)
    Language English
    Publishing date 2017
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 1557-8933 ; 0070-2153
    ISSN (online) 1557-8933
    ISSN 0070-2153
    DOI 10.1016/bs.ctdb.2016.11.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Metabolic Role of PTEN in Insulin Signaling and Resistance.

    Li, Yu Zhe / Di Cristofano, Antonio / Woo, Minna

    Cold Spring Harbor perspectives in medicine

    2020  Volume 10, Issue 8

    Abstract: Phosphatase and tensin homolog (PTEN) is most prominently known for its function in tumorigenesis. However, a metabolic role of PTEN is emerging as a result of its altered expression in type 2 diabetes (T2D), which results in impaired insulin signaling ... ...

    Abstract Phosphatase and tensin homolog (PTEN) is most prominently known for its function in tumorigenesis. However, a metabolic role of PTEN is emerging as a result of its altered expression in type 2 diabetes (T2D), which results in impaired insulin signaling and promotion of insulin resistance during the pathogenesis of T2D. PTEN functions in regulating insulin signaling across different organs have been identified. Through the use of a variety of models, such as tissue-specific knockout (KO) mice and in vitro cell cultures, PTEN's role in regulating insulin action has been elucidated across many cell types. Herein, we will review the recent advancements in the understanding of PTEN's metabolic functions in each of the tissues and cell types that contribute to regulating systemic insulin sensitivity and discuss how PTEN may represent a promising therapeutic strategy for treatment or prevention of T2D.
    MeSH term(s) Adipose Tissue/metabolism ; Animals ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/metabolism ; Humans ; Insulin/metabolism ; Mice ; Mice, Knockout ; Muscle, Skeletal/metabolism ; PTEN Phosphohydrolase/metabolism ; Signal Transduction
    Chemical Substances Insulin ; PTEN Phosphohydrolase (EC 3.1.3.67) ; PTEN protein, human (EC 3.1.3.67)
    Language English
    Publishing date 2020-08-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ISSN 2157-1422
    ISSN (online) 2157-1422
    DOI 10.1101/cshperspect.a036137
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Jugular foramen stenosis in external hydrocephalus in infants.

    Cinalli, Giuseppe / Di Martino, Giuliana / Russo, Carmela / Cristofano, Adriana / Picariello, Stefania / Cinalli, Maria Allegra / Mirone, Giuseppe / Mazio, Federica / Quarantelli, Mario / Spennato, Pietro / Covelli, Eugenio

    Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery

    2024  

    Abstract: Objective: To measure the size of jugular foramina in infants affected by external hydrocephalus (EH) and in a control group, to support the hypothesis that a jugular foramen (JF) stenosis may determine dural venous sinus alterations and increased ... ...

    Abstract Objective: To measure the size of jugular foramina in infants affected by external hydrocephalus (EH) and in a control group, to support the hypothesis that a jugular foramen (JF) stenosis may determine dural venous sinus alterations and increased venous outflow resistance as main pathophysiological factor.
    Methods: Minimum, maximum, and mean values of JF areas were measured in a series of phase-contrast magnetic resonance venous angiography (angio MRV PCA3D) performed on 81 infants affected by EH. Results were compared with a group of 54 controls.
    Results: Smaller JF area was significantly smaller in patients versus controls (43.1 ± 14.6 vs. 52.7 ± 17.8; p < 0.001) resulting in a significantly smaller mean JF areas in patients vs. controls (51.6 ± 15.8 vs. 57.0 ± 18.3; p = 0.043). In patients, smaller JF areas were significantly associated with higher venous obstruction grading score (VOGS) both on the right (p = 0.018) and on the left side (p = 0.005). Positional plagiocephaly (cranial vault asymmetry index > 3.5%) was more frequent among EH patients than controls (38/17) but the difference was not significant (p = 0.07). In the 38 plagiocephalic patients, JF area was smaller on the flattened side than the contralateral in a significant number of cases both in right (21/7) and left (9/1) plagiocephaly (p < 0.0005) as well as the mean area (48.2 + 16.4 mm
    Conclusion: In this series of infants affected by EH, the mean size of the ostium of both JF resulted significantly smaller than controls. JF stenosis was significantly associated with higher degrees of venous obstruction on both sides, suggesting a direct extrinsic effect of JF size on dural sinus lumen and possible consequent effect on venous outflow resistance. Positional plagiocephaly, when present, was associated with a decreased JF area and increased VOGS on the flattened side.
    Language English
    Publishing date 2024-04-20
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 605988-0
    ISSN 1433-0350 ; 0302-2803 ; 0256-7040
    ISSN (online) 1433-0350
    ISSN 0302-2803 ; 0256-7040
    DOI 10.1007/s00381-024-06414-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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