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Book ; Online: Pathologic Conditions of the Human Nervous and Muscular Systems Associated with Mutant Chaperones: Molecular and Mechanistic Aspects

Macario, Everly Conway de / Macario, Alberto J. L.

2018

Abstract: This eBook presents illustrative examples of genetic chaperonopathies affecting primarily nerves and muscles and discusses molecular mechanisms and treatment targeting chaperones, i.e., ... ...

Abstract	This eBook presents illustrative examples of genetic chaperonopathies affecting primarily nerves and muscles and discusses molecular mechanisms and treatment targeting chaperones, i.e., chaperonotherapy
Keywords	Science (General)
Size	1 electronic resource (111 p.)
Publisher	Frontiers Media SA
Document type	Book ; Online
Note	English ; Open Access
HBZ-ID	HT020099649
ISBN	9782889454570 ; 2889454576
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Immunohistochemistry of Human Hsp60 in Health and Disease: Recent Advances in Immunomorphology and Methods for Assessing the Chaperonin in Extracellular Vesicles.

Caruso Bavisotto, Celeste / Cappello, Francesco / Conway de Macario, Everly / Macario, Alberto J L / Rappa, Francesca

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

2023 Volume 2693, Page(s) 263–279

Abstract: The subject matter of this chapter is defined by the title of its two previous editions, "Immunohistochemistry of human Hsp60 in health and disease: From autoimmunity to cancer," the latest of which appeared in 2018. Since then, considerable advances ... ...

Abstract	The subject matter of this chapter is defined by the title of its two previous editions, "Immunohistochemistry of human Hsp60 in health and disease: From autoimmunity to cancer," the latest of which appeared in 2018. Since then, considerable advances have been made in the fields of autoimmunity and cancer and some of them are closely linked to progress in the understanding of the chaperone system (CS). This is a physiological system composed of molecular chaperones, co-chaperones, chaperone cofactors, and chaperone interactors and receptors. The molecular chaperones are the chief members of the CS, and here we focus on one of them, Hsp60. Since extracellular vesicles (EVs) have also emerged as key factors in the functioning of the CS and in carcinogenesis, we have incorporated a detailed section about them. This chapter explains how to assess Hsp60 in tissues and in EVs for application in diagnosis, prognostication, and patient monitoring and, eventually, for developing methods using them as therapeutic targets and tools. We describe immunohistochemical techniques, immunofluorescence and double immunofluorescence-confocal microscopy, and methods for collecting and isolating EVs from blood plasma and for assessing their contents in Hsp60 and related microRNAs (miRNAs). All these procedures have proven to be reliable and useful in the study and management of various types of cancer and inflammatory and autoimmune conditions.
MeSH term(s)	Humans ; Immunohistochemistry ; Extracellular Vesicles ; Neoplasms/diagnosis ; Molecular Chaperones ; Chaperonins ; Chaperonin 60/chemistry
Chemical Substances	Molecular Chaperones ; Chaperonins (EC 3.6.1.-) ; Chaperonin 60
Language	English
Publishing date	2023-08-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-3342-7_20
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Histopathology of Skeletal Muscle in a Distal Motor Neuropathy Associated with a Mutant CCT5 Subunit: Clues for Future Developments to Improve Differential Diagnosis and Personalized Therapy.

Scalia, Federica / Conway de Macario, Everly / Bonaventura, Giuseppe / Cappello, Francesco / Macario, Alberto J L

Biology

2023 Volume 12, Issue 5

Abstract: Genetic chaperonopathies are rare but, because of misdiagnosis, there are probably more cases than those that are recorded in the literature and databases. This occurs because practitioners are generally unaware of the existence and/or the symptoms and ... ...

Abstract	Genetic chaperonopathies are rare but, because of misdiagnosis, there are probably more cases than those that are recorded in the literature and databases. This occurs because practitioners are generally unaware of the existence and/or the symptoms and signs of chaperonopathies. It is necessary to educate the medical community about these diseases and, with research, to unveil their mechanisms. The structure and functions of various chaperones in vitro have been studied, but information on the impact of mutant chaperones in humans, in vivo, is scarce. Here, we present a succinct review of the most salient abnormalities of skeletal muscle, based on our earlier report of a patient who carried a mutation in the chaperonin CCT5 subunit and suffered from a distal motor neuropathy of early onset. We discuss our results in relation to the very few other published pertinent reports we were able to find. A complex picture of multiple muscle-tissue abnormalities was evident, with signs of atrophy, apoptosis, and abnormally low levels and atypical distribution patterns of some components of muscle and the chaperone system. In-silico analysis predicts that the mutation affects CCT5 in a way that could interfere with the recognition and handling of substrate. Thus, it is possible that some of the abnormalities are the direct consequence of defective chaperoning, but others may be indirectly related to defective chaperoning or caused by other different pathogenic pathways. Biochemical, and molecular biologic and genetic analyses should now help in understanding the mechanisms underpinning the histologic abnormalities and, thus, provide clues to facilitate diagnosis and guide the development of therapeutic tools.
Language	English
Publishing date	2023-04-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology12050641
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The chaperone system in cancer therapies: Hsp90.

Basset, Charbel A / Conway de Macario, Everly / Leone, Lavinia Giovanna / Macario, Alberto J L / Leone, Angelo

Journal of molecular histology

2023 Volume 54, Issue 2, Page(s) 105–118

Abstract: The chaperone system (CS) of an organism is composed of molecular chaperones, chaperone co-factors, co-chaperones, and chaperone receptors and interactors. It is present throughout the body but with distinctive features for each cell and tissue type. ... ...

Abstract	The chaperone system (CS) of an organism is composed of molecular chaperones, chaperone co-factors, co-chaperones, and chaperone receptors and interactors. It is present throughout the body but with distinctive features for each cell and tissue type. Previous studies pertaining to the CS of the salivary glands have determined the quantitative and distribution patterns for several members, the chaperones, in normal and diseased glands, focusing on tumors. Chaperones are cytoprotective, but can also be etiopathogenic agents causing diseases, the chaperonopathies. Some chaperones such as Hsp90 potentiate tumor growth, proliferation, and metastasization. Quantitative data available on this chaperone in salivary gland tissue with inflammation, and benign and malignant tumors suggest that assessing tissue Hsp90 levels and distribution patterns is useful for differential diagnosis-prognostication, and patient follow up. This, in turn, will reveal clues for developing specific treatment centered on the chaperone, for instance by inhibiting its pro-carcinogenic functions (negative chaperonotherapy). Here, we review data on the carcinogenic mechanisms of Hsp90 and their inhibitors. Hsp90 is the master regulator of the PI3K-Akt-NF-kB axis that promotes tumor cell proliferation and metastasization. We discuss pathways and interactions involving these molecular complexes in tumorigenesis and review Hsp90 inhibitors that have been tested in search of an efficacious anti-cancer agent. This targeted therapy deserves extensive investigation in view of its theoretical potential and some positive practical results and considering the need of novel treatments for tumors of the salivary glands as well as other tissues.
MeSH term(s)	Humans ; Phosphatidylinositol 3-Kinases ; Molecular Chaperones/metabolism ; HSP90 Heat-Shock Proteins/metabolism ; Neoplasms/drug therapy
Chemical Substances	Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Molecular Chaperones ; HSP90 Heat-Shock Proteins
Language	English
Publishing date	2023-03-18
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2144021-9
ISSN	1567-2387 ; 1567-2379
ISSN (online)	1567-2387
ISSN	1567-2379
DOI	10.1007/s10735-023-10119-8
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Chaperonins in cancer: Expression, function, and migration in extracellular vesicles.

Macario, Alberto J L / Conway de Macario, Everly

Seminars in cancer biology

2021 Volume 86, Issue Pt 1, Page(s) 26–35

Abstract: The chaperonins CCT and Hsp60 are molecular chaperones, members of the chaperone system (CS). Chaperones are cytoprotective but if abnormal in quantity or quality they may cause diseases, the chaperonopathies. Here, recent advances in the understanding ... ...

Abstract	The chaperonins CCT and Hsp60 are molecular chaperones, members of the chaperone system (CS). Chaperones are cytoprotective but if abnormal in quantity or quality they may cause diseases, the chaperonopathies. Here, recent advances in the understanding of CCT and Hsp60 in cancerology are briefly discussed, focusing on breast and brain cancers. CCT subunits, particularly CCT2, were increased in breast cancer cells and this correlated with tumor progression. Experimental induction of CCT2 increase was accompanied by an increase of CCT3, 4, and 5, providing another evidence for the interconnection between the members of the CS and the difficulties expected while manipulating one member with therapeutic purposes. Another in silico study demonstrated a direct correlation between the increase in the tumor tissue of the mRNA levels of all CCT subunits, except CCTB6, with bad prognosis. Studies with glioblastomas demonstrated an increase in the CCT subunits in the tumor tissue and in extracellular vesicles (EVs) derived from them. Expression levels of CCT1, 2, 6A, and 7 were the most increased and markers of bad prognosis, particularly CCT6A. A method for measuring Hsp60 and related miRNA in exosomes from blood of patients with glioblastomas or other brain tumors was discussed, and the results indicate that the triad Hsp60-related miRNAs-exosomes has potential regarding diagnosis and patient monitoring. All these data provide a strong foundation for future studies on the role played by chaperonins in carcinogenesis and for fully developing their theranostics applications along with exosomes.
MeSH term(s)	Humans ; Glioblastoma/genetics ; Glioblastoma/metabolism ; Extracellular Vesicles/genetics ; Extracellular Vesicles/metabolism ; Chaperonin Containing TCP-1/genetics ; Chaperonin Containing TCP-1/metabolism ; Chaperonin 60/genetics ; Chaperonin 60/metabolism ; Prognosis ; Brain Neoplasms/metabolism ; MicroRNAs/genetics
Chemical Substances	Chaperonin Containing TCP-1 (EC 3.6.1.-) ; Chaperonin 60 ; MicroRNAs ; CCT6A protein, human
Language	English
Publishing date	2021-06-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1033980-2
ISSN	1096-3650 ; 1044-579X
ISSN (online)	1096-3650
ISSN	1044-579X
DOI	10.1016/j.semcancer.2021.05.029
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Hsp70 and Calcitonin Receptor Protein in Extracellular Vesicles from Glioblastoma Multiforme: Biomarkers with Putative Roles in Carcinogenesis and Potential for Differentiating Tumor Types.

Alberti, Giusi / Sánchez-López, Christian M / Marcilla, Antonio / Barone, Rosario / Caruso Bavisotto, Celeste / Graziano, Francesca / Conway de Macario, Everly / Macario, Alberto J L / Bucchieri, Fabio / Cappello, Francesco / Campanella, Claudia / Rappa, Francesca

International journal of molecular sciences

2024 Volume 25, Issue 6

Abstract: Glioblastoma multiforme (GBM) is a malignancy of bad prognosis, and advances in early detection and treatment are needed. GBM is heterogenous, with varieties differing in malignancy within a tumor of a patient and between patients. Means are needed to ... ...

Abstract	Glioblastoma multiforme (GBM) is a malignancy of bad prognosis, and advances in early detection and treatment are needed. GBM is heterogenous, with varieties differing in malignancy within a tumor of a patient and between patients. Means are needed to distinguish these GMB forms, so that specific strategies can be deployed for patient management. We study the participation of the chaperone system (CS) in carcinogenesis. The CS is dynamic, with its members moving around the body in extracellular vesicles (EVs) and interacting with components of other physiological systems in health and disease, including GBM. Here, we describe the finding of high amounts of Hsp70 (HSPA1A) and the calcitonin receptor protein (CTR) in EVs in patients with GBM. We present a standardized protocol for collecting, purifying, and characterizing EVs carrying Hsp70 and CTR in plasma-derived EVs from patients with GBM. EVs from GBM patients were obtained just before tumor ablative surgery (T0) and 7 days afterwards (T1); Hsp70 was highly elevated at T0 and less so at T1, and CTR was greatly increased at T0 and reduced to below normal values at T1. Our results encourage further research to assess Hsp70 and CTR as biomarkers for differentiating tumor forms and to determine their roles in GBM carcinogenesis.
MeSH term(s)	Humans ; Glioblastoma/metabolism ; Receptors, Calcitonin/metabolism ; Cell Line, Tumor ; Extracellular Vesicles/metabolism ; Biomarkers, Tumor/metabolism ; Carcinogenesis/metabolism ; Brain Neoplasms/metabolism
Chemical Substances	Receptors, Calcitonin ; Biomarkers, Tumor
Language	English
Publishing date	2024-03-18
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/ijms25063415
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Putative Roles and Therapeutic Potential of the Chaperone System in Amyotrophic Lateral Sclerosis and Multiple Sclerosis.

Noori, Leila / Saqagandomabadi, Vahid / Di Felice, Valentina / David, Sabrina / Caruso Bavisotto, Celeste / Bucchieri, Fabio / Cappello, Francesco / Conway de Macario, Everly / Macario, Alberto J L / Scalia, Federica

Cells

2024 Volume 13, Issue 3

Abstract: The putative pathogenic roles and therapeutic potential of the chaperone system (CS) in amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) are reviewed to provide a bibliographic and conceptual platform for launching research on the ... ...

Abstract	The putative pathogenic roles and therapeutic potential of the chaperone system (CS) in amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) are reviewed to provide a bibliographic and conceptual platform for launching research on the diagnostic and therapeutic applications of CS components. Various studies suggest that dysfunction of the CS contributes to the pathogenesis of ALS and MS, and here, we identify some of the implicated CS members. The physiology and pathophysiology of the CS members can be properly understood if they are studied or experimentally or clinically manipulated for diagnostic or therapeutic purposes, bearing in mind that they belong to a physiological system with multiple interacting and dynamic components, widespread throughout the body, intra- and extracellularly. Molecular chaperones, some called heat shock protein (Hsp), are the chief components of the CS, whose canonical functions are cytoprotective. However, abnormal chaperones can be etiopathogenic factors in a wide range of disorders, chaperonopathies, including ALS and MS, according to the data reviewed. Chaperones typically form teams, and these build functional networks to maintain protein homeostasis, the canonical role of the CS. However, members of the CS also display non-canonical functions unrelated to protein homeostasis. Therefore, chaperones and other members of the CS, if abnormal, may disturb not only protein synthesis, maturation, and migration but also other physiological processes. Thus, in elucidating the role of CS components in ALS and MS, one must look at protein homeostasis abnormalities and beyond, following the clues emerging from the works discussed here.
MeSH term(s)	Humans ; Amyotrophic Lateral Sclerosis/metabolism ; Multiple Sclerosis/therapy ; Molecular Chaperones/metabolism ; Heat-Shock Proteins/metabolism
Chemical Substances	Molecular Chaperones ; Heat-Shock Proteins
Language	English
Publishing date	2024-01-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells13030217
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Histopathology of Skeletal Muscle in a Distal Motor Neuropathy Associated with a Mutant CCT5 Subunit: Clues for Future Developments to Improve Differential Diagnosis and Personalized Therapy

Scalia, Federica / Conway de Macario, Everly / Bonaventura, Giuseppe / Cappello, Francesco / Macario, Alberto J. L.

Biology (Basel). 2023 Apr. 23, v. 12, no. 5

2023

Abstract	Genetic chaperonopathies are rare but, because of misdiagnosis, there are probably more cases than those that are recorded in the literature and databases. This occurs because practitioners are generally unaware of the existence and/or the symptoms and signs of chaperonopathies. It is necessary to educate the medical community about these diseases and, with research, to unveil their mechanisms. The structure and functions of various chaperones in vitro have been studied, but information on the impact of mutant chaperones in humans, in vivo, is scarce. Here, we present a succinct review of the most salient abnormalities of skeletal muscle, based on our earlier report of a patient who carried a mutation in the chaperonin CCT5 subunit and suffered from a distal motor neuropathy of early onset. We discuss our results in relation to the very few other published pertinent reports we were able to find. A complex picture of multiple muscle-tissue abnormalities was evident, with signs of atrophy, apoptosis, and abnormally low levels and atypical distribution patterns of some components of muscle and the chaperone system. In-silico analysis predicts that the mutation affects CCT5 in a way that could interfere with the recognition and handling of substrate. Thus, it is possible that some of the abnormalities are the direct consequence of defective chaperoning, but others may be indirectly related to defective chaperoning or caused by other different pathogenic pathways. Biochemical, and molecular biologic and genetic analyses should now help in understanding the mechanisms underpinning the histologic abnormalities and, thus, provide clues to facilitate diagnosis and guide the development of therapeutic tools.
Keywords	apoptosis ; atrophy ; chaperonins ; computer simulation ; histology ; histopathology ; muscles ; mutants ; mutation ; patients ; peripheral nervous system diseases ; skeletal muscle ; therapeutics
Language	English
Dates of publication	2023-0423
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology12050641
Database	NAL-Catalogue (AGRICOLA)

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Article: Unexpected tumor reduction in metastatic colorectal cancer patients during SARS-Cov-2 infection: effect of ACE-2 expression on tumor cells or molecular mimicry phenomena? Two not mutually exclusive hypotheses.

Cappello, Francesco / Burgio, Stefano / Conway de Macario, Everly / Macario, Alberto J L

Therapeutic advances in medical oncology

2021 Volume 13, Page(s) 17588359211027825

Language	English
Publishing date	2021-06-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2503443-1
ISSN	1758-8359 ; 1758-8340
ISSN (online)	1758-8359
ISSN	1758-8340
DOI	10.1177/17588359211027825
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Editorial: Pathologic Conditions of the Human Nervous and Muscular Systems Associated with Mutant Chaperones: Molecular and Mechanistic Aspects.

Macario, Alberto J L / Conway de Macario, Everly

Frontiers in molecular biosciences

2018 Volume 5, Page(s) 14

Language	English
Publishing date	2018-02-16
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2018.00014
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