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Article: Strategies for Efficient Targeting of Tumor Collagen for Cancer Therapy.

Baldari, Silvia / Di Modugno, Francesca / Nisticò, Paola / Toietta, Gabriele

2022 Volume 14, Issue 19

Abstract: The tumor stroma, which comprises stromal cells and non-cellular elements, is a critical component of the tumor microenvironment (TME). The dynamic interactions between the tumor cells and the stroma may promote tumor progression and metastasis and ... ...

Abstract	The tumor stroma, which comprises stromal cells and non-cellular elements, is a critical component of the tumor microenvironment (TME). The dynamic interactions between the tumor cells and the stroma may promote tumor progression and metastasis and dictate resistance to established cancer therapies. Therefore, novel antitumor approaches should combine anticancer and anti-stroma strategies targeting dysregulated tumor extracellular matrix (ECM). ECM remodeling is a hallmark of solid tumors, leading to extensive biochemical and biomechanical changes, affecting cell signaling and tumor tissue three-dimensional architecture. Increased deposition of fibrillar collagen is the most distinctive alteration of the tumor ECM. Consequently, several anticancer therapeutic strategies have been developed to reduce excessive tumor collagen deposition. Herein, we provide an overview of the current advances and challenges of the main approaches aiming at tumor collagen normalization, which include targeted anticancer drug delivery, promotion of degradation, modulation of structure and biosynthesis of collagen, and targeting cancer-associated fibroblasts, which are the major extracellular matrix producers.
Language	English
Publishing date	2022-09-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14194706
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Article ; Online: Current Biomedical Use of Copper Chelation Therapy.

Baldari, Silvia / Di Rocco, Giuliana / Toietta, Gabriele

International journal of molecular sciences

2020 Volume 21, Issue 3

Abstract: Copper is an essential microelement that plays an important role in a wide variety of biological processes. Copper concentration has to be finely regulated, as any imbalance in its homeostasis can induce abnormalities. In particular, excess copper plays ... ...

Abstract	Copper is an essential microelement that plays an important role in a wide variety of biological processes. Copper concentration has to be finely regulated, as any imbalance in its homeostasis can induce abnormalities. In particular, excess copper plays an important role in the etiopathogenesis of the genetic disease Wilson's syndrome, in neurological and neurodegenerative pathologies such as Alzheimer's and Parkinson's diseases, in idiopathic pulmonary fibrosis, in diabetes, and in several forms of cancer. Copper chelating agents are among the most promising tools to keep copper concentration at physiological levels. In this review, we focus on the most relevant compounds experimentally and clinically evaluated for their ability to counteract copper homeostasis deregulation. In particular, we provide a general overview of the main disorders characterized by a pathological increase in copper levels, summarizing the principal copper chelating therapies adopted in clinical trials.
MeSH term(s)	Chelating Agents/chemistry ; Chelating Agents/pharmacology ; Chelating Agents/therapeutic use ; Chelation Therapy ; Clinical Trials as Topic ; Copper/chemistry ; Copper/metabolism ; Diabetes Mellitus/drug therapy ; Diabetes Mellitus/genetics ; Diabetes Mellitus/metabolism ; Gene Regulatory Networks/drug effects ; Homeostasis ; Humans ; Idiopathic Pulmonary Fibrosis/drug therapy ; Idiopathic Pulmonary Fibrosis/genetics ; Idiopathic Pulmonary Fibrosis/metabolism ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/metabolism ; Parkinson Disease/drug therapy ; Parkinson Disease/genetics ; Parkinson Disease/metabolism ; Structure-Activity Relationship
Chemical Substances	Chelating Agents ; Copper (789U1901C5)
Language	English
Publishing date	2020-02-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21031069
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Article ; Online: The synergism of SMC1A cohesin gene silencing and bevacizumab against colorectal cancer.

Di Nardo, Maddalena / Astigiano, Simonetta / Baldari, Silvia / Pallotta, Maria Michela / Porta, Giovanni / Pigozzi, Simona / Antonini, Annalisa / Emionite, Laura / Frattini, Annalisa / Valli, Roberto / Toietta, Gabriele / Soddu, Silvia / Musio, Antonio

Journal of experimental & clinical cancer research : CR

2024 Volume 43, Issue 1, Page(s) 49

Abstract: Background: SMC1A is a subunit of the cohesin complex that participates in many DNA- and chromosome-related biological processes. Previous studies have established that SMC1A is involved in cancer development and in particular, is overexpressed in ... ...

Abstract	Background: SMC1A is a subunit of the cohesin complex that participates in many DNA- and chromosome-related biological processes. Previous studies have established that SMC1A is involved in cancer development and in particular, is overexpressed in chromosomally unstable human colorectal cancer (CRC). This study aimed to investigate whether SMC1A could serve as a therapeutic target for CRC. Methods: At first, we studied the effects of either SMC1A overexpression or knockdown in vitro. Next, the outcome of SMC1A knocking down (alone or in combination with bevacizumab, a monoclonal antibody against vascular endothelial growth factor) was analyzed in vivo. Results: We found that SMC1A knockdown affects cell proliferation and reduces the ability to grow in anchorage-independent manner. Next, we demonstrated that the silencing of SMC1A and the combo treatment were effective in increasing overall survival in a xenograft mouse model. Functional analyses indicated that both treatments lead to atypical mitotic figures and gene expression dysregulation. Differentially expressed genes were implicated in several pathways including gene transcription regulation, cellular proliferation, and other transformation-associated processes. Conclusions: These results indicate that SMC1A silencing, in combination with bevacizumab, can represent a promising therapeutic strategy for human CRC.
MeSH term(s)	Animals ; Humans ; Mice ; Bevacizumab/pharmacology ; Bevacizumab/therapeutic use ; Cell Cycle Proteins/metabolism ; Cell Proliferation ; Chromosomal Proteins, Non-Histone/genetics ; Cohesins/genetics ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; Gene Silencing ; Vascular Endothelial Growth Factor A/genetics
Chemical Substances	Bevacizumab (2S9ZZM9Q9V) ; Cell Cycle Proteins ; Chromosomal Proteins, Non-Histone ; Cohesins ; Vascular Endothelial Growth Factor A ; structural maintenance of chromosome protein 1
Language	English
Publishing date	2024-02-16
Publishing country	England
Document type	Journal Article
ZDB-ID	803138-1
ISSN	1756-9966 ; 0392-9078
ISSN (online)	1756-9966
ISSN	0392-9078
DOI	10.1186/s13046-024-02976-2
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Article ; Online: Cancer immunity and immunotherapy beyond COVID-19.

Bellone, Matteo / Brevi, Arianna / Bronte, Vincenzo / Dusi, Silvia / Ferrucci, Pier Francesco / Nisticò, Paola / Rosato, Antonio / Russo, Vincenzo / Sica, Antonio / Toietta, Gabriele / Colombo, Mario Paolo

Cancer immunology, immunotherapy : CII

2023 Volume 72, Issue 7, Page(s) 2541–2548

MeSH term(s)	Humans ; COVID-19 ; Immunotherapy ; Neoplasms/therapy ; Cancer Vaccines
Chemical Substances	Cancer Vaccines
Language	English
Publishing date	2023-03-30
Publishing country	Germany
Document type	Journal Article
ZDB-ID	195342-4
ISSN	1432-0851 ; 0340-7004
ISSN (online)	1432-0851
ISSN	0340-7004
DOI	10.1007/s00262-023-03411-9
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Article: Stem cells under the influence of alcohol: effects of ethanol consumption on stem/progenitor cells

Di Rocco, Giuliana / Baldari, Silvia / Pani, Giovambattista / Toietta, Gabriele

Cellular and molecular life sciences. 2019 Jan., v. 76, no. 2

2019

Abstract: Stem cells drive embryonic and fetal development. In several adult tissues, they retain the ability to self-renew and differentiate into a variety of specialized cells, thus contributing to tissue homeostasis and repair throughout life span. Alcohol ... ...

Abstract	Stem cells drive embryonic and fetal development. In several adult tissues, they retain the ability to self-renew and differentiate into a variety of specialized cells, thus contributing to tissue homeostasis and repair throughout life span. Alcohol consumption is associated with an increased risk for several diseases and conditions. Growing and developing tissues are particularly vulnerable to alcohol’s influence, suggesting that stem- and progenitor-cell function could be affected. Accordingly, recent studies have revealed the possible relevance of alcohol exposure in impairing stem-cell properties, consequently affecting organ development and injury response in different tissues. Here, we review the main studies describing the effects of alcohol on different types of progenitor/stem cells including neuronal, hepatic, intestinal and adventitial progenitor cells, bone-marrow-derived stromal cell, dental pulp, embryonic and hematopoietic stem cells, and tumor-initiating cells. A better understanding of the nature of the cellular damage induced by chronic and episodic heavy (binge) drinking is critical for the improvement of current therapeutic strategies designed to treat patients suffering from alcohol-related disorders.
Keywords	adults ; alcohol drinking ; alcohols ; fetal development ; hematopoietic stem cells ; homeostasis ; intestines ; longevity ; neurons ; patients ; risk ; therapeutics ; tissues ; tooth pulp
Language	English
Dates of publication	2019-01
Size	p. 231-244.
Publishing place	Springer International Publishing
Document type	Article
Note	Review
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-018-2931-8
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Stem cells under the influence of alcohol: effects of ethanol consumption on stem/progenitor cells.

Di Rocco, Giuliana / Baldari, Silvia / Pani, Giovambattista / Toietta, Gabriele

Cellular and molecular life sciences : CMLS

2018 Volume 76, Issue 2, Page(s) 231–244

Abstract	Stem cells drive embryonic and fetal development. In several adult tissues, they retain the ability to self-renew and differentiate into a variety of specialized cells, thus contributing to tissue homeostasis and repair throughout life span. Alcohol consumption is associated with an increased risk for several diseases and conditions. Growing and developing tissues are particularly vulnerable to alcohol's influence, suggesting that stem- and progenitor-cell function could be affected. Accordingly, recent studies have revealed the possible relevance of alcohol exposure in impairing stem-cell properties, consequently affecting organ development and injury response in different tissues. Here, we review the main studies describing the effects of alcohol on different types of progenitor/stem cells including neuronal, hepatic, intestinal and adventitial progenitor cells, bone-marrow-derived stromal cell, dental pulp, embryonic and hematopoietic stem cells, and tumor-initiating cells. A better understanding of the nature of the cellular damage induced by chronic and episodic heavy (binge) drinking is critical for the improvement of current therapeutic strategies designed to treat patients suffering from alcohol-related disorders.
MeSH term(s)	Aldehyde Dehydrogenase, Mitochondrial/metabolism ; Ethanol/pharmacology ; Humans ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/drug effects ; Mesenchymal Stem Cells/metabolism ; MicroRNAs/metabolism ; Neoplastic Stem Cells/cytology ; Neoplastic Stem Cells/drug effects ; Neoplastic Stem Cells/metabolism ; Neural Stem Cells/cytology ; Neural Stem Cells/drug effects ; Neural Stem Cells/metabolism ; Reactive Oxygen Species/metabolism ; Stem Cells/cytology ; Stem Cells/drug effects ; Stem Cells/metabolism ; TOR Serine-Threonine Kinases/metabolism
Chemical Substances	MicroRNAs ; Reactive Oxygen Species ; Ethanol (3K9958V90M) ; Aldehyde Dehydrogenase, Mitochondrial (EC 1.2.1.3) ; TOR Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2018-10-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-018-2931-8
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Zs.A 195: Show issues

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Article: Reduction of Cell Proliferation by Acute C

Baldari, Silvia / Manni, Isabella / Di Rocco, Giuliana / Paolini, Francesca / Palermo, Belinda / Piaggio, Giulia / Toietta, Gabriele

Cancers

2021 Volume 13, Issue 19

Abstract: Endogenous acetaldehyde production from the metabolism of ingested alcohol exposes hematopoietic progenitor cells to increased genotoxic risk. To develop possible therapeutic strategies to prevent or reverse alcohol abuse effects, it would be critical to ...

Abstract	Endogenous acetaldehyde production from the metabolism of ingested alcohol exposes hematopoietic progenitor cells to increased genotoxic risk. To develop possible therapeutic strategies to prevent or reverse alcohol abuse effects, it would be critical to determine the temporal progression of acute ethanol toxicity on progenitor cell numbers and proliferative status. We followed the variation of the cell proliferation rate in bone marrow and spleen in response to acute ethanol intoxication in the MITO-Luc mouse, in which NF-Y-dependent cell proliferation can be assessed in vivo by non-invasive bioluminescent imaging. One week after ethanol administration, bioluminescent signals in bone marrow and spleen decreased below the level corresponding to physiological proliferation, and they progressively resumed to pre-treatment values in approximately 4 weeks. Boosting acetaldehyde catabolism by administration of an aldehyde dehydrogenase activity activator or administration of polyphenols with antioxidant activity partially restored bone marrow cells' physiological proliferation. These results indicate that in this mouse model, bioluminescent alteration reflects the reduction of the physiological proliferation rate of bone marrow progenitor cells due to the toxic effect of aldehydes generated by alcohol oxidation. In summary, this study presents a novel view of the impact of acute alcohol intake on bone marrow cell proliferation in vivo.
Language	English
Publishing date	2021-10-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13194999
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Article ; Online: Successful Therapy of Esophageal Fistulas by Endoscopic Injection of Emulsified Adipose Tissue Stromal Vascular Fraction.

Nachira, Dania / Trivisonno, Angelo / Costamagna, Guido / Toietta, Gabriele / Margaritora, Stefano / Pontecorvi, Valerio / Punzo, Giovanni / Porziella, Venanzio / Boškoski, Ivo

Gastroenterology

2021 Volume 160, Issue 4, Page(s) 1026–1028

MeSH term(s)	Adipose Tissue/cytology ; Cell Separation ; Esophageal Fistula/therapy ; Esophagoscopy/methods ; Follow-Up Studies ; Humans ; Stromal Cells/transplantation ; Transplantation, Autologous/methods ; Treatment Outcome
Language	English
Publishing date	2021-01-05
Publishing country	United States
Document type	Journal Article ; Video-Audio Media
ZDB-ID	80112-4
ISSN	1528-0012 ; 0016-5085
ISSN (online)	1528-0012
ISSN	0016-5085
DOI	10.1053/j.gastro.2020.12.063
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Article: Towards Therapeutic Delivery of Extracellular Vesicles: Strategies for

Di Rocco, Giuliana / Baldari, Silvia / Toietta, Gabriele

Stem cells international

2016 Volume 2016, Page(s) 5029619

Abstract: Extracellular vesicles (EVs), such as microvesicles and exosomes, are membranous structures containing bioactive material released by several cells types, including mesenchymal stem/stromal cells (MSCs). Increasing lines of evidences point to EVs as ... ...

Abstract	Extracellular vesicles (EVs), such as microvesicles and exosomes, are membranous structures containing bioactive material released by several cells types, including mesenchymal stem/stromal cells (MSCs). Increasing lines of evidences point to EVs as paracrine mediators of the beneficial effects on tissue remodeling associated with cell therapy. Administration of MSCs-derived EVs has therefore the potential to open new and safer therapeutic avenues, alternative to cell-based approaches, for degenerative diseases. However, an enhanced knowledge about
Language	English
Publishing date	2016-11-23
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	2573856-2
ISSN	1687-9678 ; 1687-966X
ISSN (online)	1687-9678
ISSN	1687-966X
DOI	10.1155/2016/5029619
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Article ; Online: Extracellular Vesicles-Encapsulated MicroRNA-125b Produced in Genetically Modified Mesenchymal Stromal Cells Inhibits Hepatocellular Carcinoma Cell Proliferation.

Baldari, Silvia / Di Rocco, Giuliana / Magenta, Alessandra / Picozza, Mario / Toietta, Gabriele

Cells

2019 Volume 8, Issue 12

Abstract: Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and one of the prominent causes of cancer mortality, leading to approximately 780,000 deaths per year worldwide. Down-regulation of microRNA-125b (miR-125b) is a prognostic ... ...

Abstract	Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and one of the prominent causes of cancer mortality, leading to approximately 780,000 deaths per year worldwide. Down-regulation of microRNA-125b (miR-125b) is a prognostic indicator in HCC patients. Conversely, over-expression of miR-125b in HCC cells induces cell cycle arrest, inhibits proliferation, migration and invasion. Extracellular vesicles (EVs) function as intercellular messengers transferring proteins, RNAs, DNAs, carbohydrates, and lipids. Since EVs protect their cargo from degradation, delivery of therapeutic bioactive molecules, in particular miRNAs, through EVs represents an innovative avenue for cancer therapy. In this study, we evaluated a replacement strategy for the treatment of HCC via delivery of EVs secreted from human adipose tissue-derived mesenchymal stromal/medicinal signaling cells (ASCs) genetically modified with a lentiviral vector expressing miR-125b with a specific ExoMotif sequence tag to enhance the loading into extracellular vesicles. In particular, we determined that the delivery of miR-125b-loaded EVs produced in engineered ASCs specifically reduces HCC cell proliferation in vitro modulating a series of miR-125b targets, which belong to the p53 signaling pathway. This proof-of-concept study supports the development of innovative therapeutic strategies for HCC via EV-mediated miRNA delivery.
MeSH term(s)	Adipose Tissue/metabolism ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/metabolism ; Carcinoma, Hepatocellular/pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Extracellular Vesicles/metabolism ; Humans ; Liver Neoplasms/genetics ; Liver Neoplasms/metabolism ; Liver Neoplasms/pathology ; Mesenchymal Stem Cells/metabolism ; MicroRNAs/genetics ; Transduction, Genetic ; Tumor Suppressor Protein p53
Chemical Substances	MIRN125 microRNA, human ; MicroRNAs ; TP53 protein, human ; Tumor Suppressor Protein p53
Language	English
Publishing date	2019-12-03
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells8121560
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