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  1. Article: Editorial: New Roles of Autophagy Pathways in Cancer.

    Martins, Waleska K / Fader, Claudio M / Morselli, Eugenia / Grasso, Daniel

    Frontiers in oncology

    2021  Volume 11, Page(s) 726989

    Language English
    Publishing date 2021-07-07
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2021.726989
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Autophagy-Mediated Exosomes as Immunomodulators of Natural Killer Cells in Pancreatic Cancer Microenvironment.

    Papademetrio, Daniela L / Garcia, María Noé / Grasso, Daniel / Alvarez, Élida

    Frontiers in oncology

    2021  Volume 10, Page(s) 622956

    Abstract: Pancreas ductal adenocarcinoma is a highly aggressive cancer with an incredible poor lifespan. Different chemotherapeutic agents' schemes have been tested along the years without significant success. Furthermore, immunotherapy also fails to cope with the ...

    Abstract Pancreas ductal adenocarcinoma is a highly aggressive cancer with an incredible poor lifespan. Different chemotherapeutic agents' schemes have been tested along the years without significant success. Furthermore, immunotherapy also fails to cope with the disease, even in combination with other standard approaches. Autophagy stands out as a chemoresistance mechanism and is also becoming relevant as responsible for the inefficacy of immunotherapy. In this complex scenario, exosomes have emerged as a new key player in tumor environment. Exosomes act as messengers among tumor cells, including tumor microenvironment immune cells. For instance, tumor-derived exosomes are capable of generating a tolerogenic microenvironment, which in turns conditions the immune system behavior. But also, immune cells-derived exosomes, under non-tolerogenic conditions, induce tumor suppression, although they are able to promote chemoresistance. In that way, NK cells are well known key regulators of carcinogenesis and the inhibition of their function is detrimental for tumor suppression. Additionally, increasing evidence suggests a crosstalk between exosome biogenesis and the autophagy pathway. This mini review has the intention to summarize the available data in the complex relationships between the autophagy pathway and the broad spectrum of exosomes subpopulations in pancreatic cancer, with focus on the NK cells response.
    Language English
    Publishing date 2021-02-19
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2020.622956
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Measuring Autophagy in Pancreatitis.

    Ropolo, Alejandro / Grasso, Daniel / Vaccaro, Maria I

    Methods in molecular biology (Clifton, N.J.)

    2019  Volume 1880, Page(s) 541–554

    Abstract: Acute pancreatitis is one of the first pathological processes where autophagy has been described in a human tissue. Autophagy, autodigestion, and cell death are early cellular events in acute pancreatitis. Recent advances in understanding autophagy ... ...

    Abstract Acute pancreatitis is one of the first pathological processes where autophagy has been described in a human tissue. Autophagy, autodigestion, and cell death are early cellular events in acute pancreatitis. Recent advances in understanding autophagy highlight its importance in pathological conditions. However, methods for monitoring autophagic activity during complex diseases, involving highly differentiated secretory cells, are complicated, and the results are sometimes misinterpreted. Here, we describe methods used to identify autophagic structures and to measure autophagic flux in cultured cell models and animal models of pancreatitis. We also briefly describe the pancreas specific autophagy mouse model that was useful to understand the actual role of autophagy in pancreatitis and to identify a novel selective autophagy pathway named zymophagy. Lastly, we describe the immunomagnetic isolation of autophagosomes and the detection of autophagy in pancreatic tissue samples derived from humans.
    MeSH term(s) Acinar Cells ; Animals ; Autophagosomes/pathology ; Autophagosomes/ultrastructure ; Autophagy ; Cell Culture Techniques/instrumentation ; Cell Culture Techniques/methods ; Cell Line ; Ceruletide/toxicity ; Disease Models, Animal ; Enzyme Precursors/metabolism ; Humans ; Lysosomes/metabolism ; Male ; Mice ; Microscopy, Electron/instrumentation ; Microscopy, Electron/methods ; Microscopy, Fluorescence/instrumentation ; Microscopy, Fluorescence/methods ; Pancreas/cytology ; Pancreas/pathology ; Pancreatectomy ; Pancreatitis/chemically induced ; Pancreatitis/pathology ; Pancreatitis/surgery ; Rats ; Secretory Vesicles/pathology
    Chemical Substances Enzyme Precursors ; Ceruletide (888Y08971B)
    Language English
    Publishing date 2019-01-04
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-8873-0_35
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Initial Steps in Mammalian Autophagosome Biogenesis.

    Grasso, Daniel / Renna, Felipe Javier / Vaccaro, Maria Ines

    Frontiers in cell and developmental biology

    2018  Volume 6, Page(s) 146

    Abstract: During the last decade, autophagy has been pointed out as a central process in cellular homeostasis with the consequent implication in most cellular settings and human diseases pathology. At present, there is significant data available about molecular ... ...

    Abstract During the last decade, autophagy has been pointed out as a central process in cellular homeostasis with the consequent implication in most cellular settings and human diseases pathology. At present, there is significant data available about molecular mechanisms that regulate autophagy. Nevertheless, autophagy pathway itself and its importance in different cellular aspects are still not completely clear. In this article, we are focused in four main aspects: (a)
    Keywords covid19
    Language English
    Publishing date 2018-10-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2018.00146
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Sesquiterpene Lactones as Promising Candidates for Cancer Therapy: Focus on Pancreatic Cancer.

    Laurella, Laura Cecilia / Mirakian, Nadia Talin / Garcia, Maria Noé / Grasso, Daniel Héctor / Sülsen, Valeria Patricia / Papademetrio, Daniela Laura

    Molecules (Basel, Switzerland)

    2022  Volume 27, Issue 11

    Abstract: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease which confers to patients a poor prognosis at short term. PDAC is the fourth leading cause of death among cancers in the Western world. The rate of new cases of pancreatic cancer ( ... ...

    Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease which confers to patients a poor prognosis at short term. PDAC is the fourth leading cause of death among cancers in the Western world. The rate of new cases of pancreatic cancer (incidence) is 10 per 100,000 but present a 5-year survival of less than 10%, highlighting the poor prognosis of this pathology. Furthermore, 90% of advanced PDAC tumor present KRAS mutations impacting in several oncogenic signaling pathways, many of them associated with cell proliferation and tumor progression. Different combinations of chemotherapeutic agents have been tested over the years without an improvement of significance in its treatment. PDAC remains as one the more challenging biomedical topics thus far. The lack of a proper early diagnosis, the notable mortality statistics and the poor outcome with the available therapies urge the entire scientific community to find novel approaches against PDAC with real improvements in patients' survival and life quality. Natural compounds have played an important role in the process of discovery and development of new drugs. Among them, terpenoids, such as sesquiterpene lactones, stand out due to their biological activities and pharmacological potential as antitumor agents. In this review, we will describe the sesquiterpene lactones with in vitro and in vivo activity against pancreatic tumor cells. We will also discuss the mechanism of action of the compounds as well as the signaling pathways associated with their activity.
    MeSH term(s) Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Carcinoma, Pancreatic Ductal/pathology ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Lactones/pharmacology ; Lactones/therapeutic use ; Pancreatic Neoplasms/pathology ; Sesquiterpenes/pharmacology ; Sesquiterpenes/therapeutic use ; Pancreatic Neoplasms
    Chemical Substances Antineoplastic Agents ; Lactones ; Sesquiterpenes
    Language English
    Publishing date 2022-05-29
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules27113492
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.MO 81: Show issues

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  6. Article: Metagenómica: un viaje a las estrellas.

    Grasso, Daniel

    Revista Argentina de microbiologia

    2006  Volume 38, Issue 4, Page(s) 189

    Title translation Metagenomics: a trip to the stars.
    MeSH term(s) Ecosystem ; Genome, Archaeal/genetics ; Genome, Bacterial/genetics ; Genome, Fungal/genetics ; Genomics/organization & administration ; Genomics/trends
    Language Spanish
    Publishing date 2006-10
    Publishing country Argentina
    Document type Editorial
    ZDB-ID 731952-6
    ISSN 0325-7541
    ISSN 0325-7541
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4243: 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)
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  7. Article: Macroautophagy and the oncogene-induced senescence.

    Grasso, Daniel / Vaccaro, Maria I

    Frontiers in endocrinology

    2014  Volume 5, Page(s) 157

    Abstract: The oncogene-induced senescence is emerging as a potent tumor suppressor mechanism and as a possible therapeutic target. Macroautophagy is intimately linked to the senescence condition setup, although its role has not been elucidated yet. Here, we ... ...

    Abstract The oncogene-induced senescence is emerging as a potent tumor suppressor mechanism and as a possible therapeutic target. Macroautophagy is intimately linked to the senescence condition setup, although its role has not been elucidated yet. Here, we discuss up-to-date concepts of senescence-related macroautophagy and evaluate the current trend of this growing research field, which has relevance in future perspectives toward therapeutic options against cancer.
    Language English
    Publishing date 2014-09-29
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2014.00157
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Autophagy in Human T-Cell Leukemia Virus Type 1 (HTLV-1) Induced Leukemia.

    Ducasa, Nicolás / Grasso, Daniel / Benencio, Paula / Papademetrio, Daniela L / Biglione, Mirna / Kashanchi, Fatah / Berini, Carolina / Garcia, Maria Noé

    Frontiers in oncology

    2021  Volume 11, Page(s) 641269

    Abstract: Viruses play an important role in the development of certain human cancers. They are estimated to contribute 16% to all human cancers. Human T-cell leukemia virus type 1 (HTLV-1) was the first human retrovirus to be discovered and is the etiological ... ...

    Abstract Viruses play an important role in the development of certain human cancers. They are estimated to contribute 16% to all human cancers. Human T-cell leukemia virus type 1 (HTLV-1) was the first human retrovirus to be discovered and is the etiological agent of adult T-cell leukemia/lymphoma (ATLL), an aggressive T-cell malignancy with poor prognosis. HTLV-1 viral proteins interact with mechanisms and proteins present in host cells for their own benefit, evading the immune system and promoting the establishment of disease. Several viruses manipulate the autophagy pathway to achieve their infective goals, and HTLV-1 is not the exception. HTLV-1 Tax viral protein engages NF-κB and autophagy pathways prone favoring viral replication and T cell transformation. In this review we focus on describing the relationship of HTLV-1 with the autophagy machinery and its implication in the development of ATLL.
    Language English
    Publishing date 2021-03-31
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2021.641269
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Autophagy-targeted therapy to modulate age-related diseases: Success, pitfalls, and new directions.

    Martins, Waleska Kerllen / Silva, Maryana do Nascimento da / Pandey, Kiran / Maejima, Ikuko / Ramalho, Ercília / Olivon, Vania Claudia / Diniz, Susana Nogueira / Grasso, Daniel

    Current research in pharmacology and drug discovery

    2021  Volume 2, Page(s) 100033

    Abstract: Autophagy is a critical metabolic process that supports homeostasis at a basal level and is dynamically regulated in response to various physiological and pathological processes. Autophagy has some etiologic implications that support certain pathological ...

    Abstract Autophagy is a critical metabolic process that supports homeostasis at a basal level and is dynamically regulated in response to various physiological and pathological processes. Autophagy has some etiologic implications that support certain pathological processes due to alterations in the lysosomal-degradative pathway. Some of the conditions related to autophagy play key roles in highly relevant human diseases, e.g., cardiovascular diseases (15.5%), malignant and other neoplasms (9.4%), and neurodegenerative conditions (3.7%). Despite advances in the discovery of new strategies to treat these age-related diseases, autophagy has emerged as a therapeutic option after preclinical and clinical studies. Here, we discuss the pitfalls and success in regulating autophagy initiation and its lysosome-dependent pathway to restore its homeostatic role and mediate therapeutic effects for cancer, neurodegenerative, and cardiac diseases. The main challenge for the development of autophagy regulators for clinical application is the lack of specificity of the repurposed drugs, due to the low pharmacological uniqueness of their target, including those that target the PI3K/AKT/mTOR and AMPK pathway. Then, future efforts must be conducted to deal with this scenery, including the disclosure of key components in the autophagy machinery that may intervene in its therapeutic regulation. Among all efforts, those focusing on the development of novel allosteric inhibitors against autophagy inducers, as well as those targeting autolysosomal function, and their integration into therapeutic regimens should remain a priority for the field.
    Language English
    Publishing date 2021-06-01
    Publishing country Netherlands
    Document type Journal Article ; Review
    ISSN 2590-2571
    ISSN (online) 2590-2571
    DOI 10.1016/j.crphar.2021.100033
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: SUFU promotes GLI activity in a Hedgehog-independent manner in pancreatic cancer.

    Paradise, Brooke D / Gainullin, Vladimir G / Almada, Luciana L / Sigafoos, Ashley N / Sen, Sandhya / Vera, Renzo E / Raja Arul, Glancis Luzeena / Toruner, Murat / Pease, David R / Gonzalez, Alina L / Mentucci, Fatima M / Grasso, Daniel H / Fernandez-Zapico, Martin E

    The Biochemical journal

    2023  Volume 480, Issue 15, Page(s) 1199–1216

    Abstract: Aberrant activation of the Hedgehog (Hh) signaling pathway, through which the GLI family of transcription factors (TF) is stimulated, is commonly observed in cancer cells. One well-established mechanism of this increased activity is through the ... ...

    Abstract Aberrant activation of the Hedgehog (Hh) signaling pathway, through which the GLI family of transcription factors (TF) is stimulated, is commonly observed in cancer cells. One well-established mechanism of this increased activity is through the inactivation of Suppressor of Fused (SUFU), a negative regulator of the Hh pathway. Relief from negative regulation by SUFU facilitates GLI activity and induction of target gene expression. Here, we demonstrate a novel role for SUFU as a promoter of GLI activity in pancreatic ductal adenocarcinoma (PDAC). In non-ciliated PDAC cells unresponsive to Smoothened agonism, SUFU overexpression increases GLI transcriptional activity. Conversely, knockdown (KD) of SUFU reduces the activity of GLI in PDAC cells. Through array PCR analysis of GLI target genes, we identified B-cell lymphoma 2 (BCL2) among the top candidates down-regulated by SUFU KD. We demonstrate that SUFU KD results in reduced PDAC cell viability, and overexpression of BCL2 partially rescues the effect of reduced cell viability by SUFU KD. Further analysis using as a model GLI1, a major TF activator of the GLI family in PDAC cells, shows the interaction of SUFU and GLI1 in the nucleus through previously characterized domains. Chromatin immunoprecipitation (ChIP) assay shows the binding of both SUFU and GLI1 at the promoter of BCL2 in PDAC cells. Finally, we demonstrate that SUFU promotes GLI1 activity without affecting its protein stability. Through our findings, we propose a novel role of SUFU as a positive regulator of GLI1 in PDAC, adding a new mechanism of Hh/GLI signaling pathway regulation in cancer cells.
    MeSH term(s) Humans ; Repressor Proteins/genetics ; Repressor Proteins/metabolism ; Zinc Finger Protein GLI1/genetics ; Hedgehog Proteins/genetics ; Hedgehog Proteins/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Pancreatic Neoplasms/genetics ; Proto-Oncogene Proteins c-bcl-2 ; Pancreatic Neoplasms
    Chemical Substances Repressor Proteins ; Zinc Finger Protein GLI1 ; Hedgehog Proteins ; Transcription Factors ; Proto-Oncogene Proteins c-bcl-2 ; SUFU protein, human
    Language English
    Publishing date 2023-07-21
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2969-5
    ISSN 1470-8728 ; 0006-2936 ; 0306-3275 ; 0264-6021
    ISSN (online) 1470-8728
    ISSN 0006-2936 ; 0306-3275 ; 0264-6021
    DOI 10.1042/BCJ20220439
    Database MEDical Literature Analysis and Retrieval System OnLINE

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