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Article ; Online: Directing in Vitro Selection towards G-quadruplex-forming Aptamers to Inhibit HMGB1 Pathological Activity.

Napolitano, Ettore / Criscuolo, Andrea / Riccardi, Claudia / Esposito, Carla L / Catuogno, Silvia / Coppola, Gabriele / Roviello, Giovanni N / Montesarchio, Daniela / Musumeci, Domenica

Angewandte Chemie (International ed. in English)

2024 Volume 63, Issue 16, Page(s) e202319828

Abstract: In the search for novel, effective inhibitors of High-Mobility Group Box1 (HMGB1)-a protein involved in various inflammatory and autoimmune diseases as well as in cancer-we herein discovered a set of anti-HMGB1 G-quadruplex(G4)-forming aptamers by using ... ...

Abstract	In the search for novel, effective inhibitors of High-Mobility Group Box1 (HMGB1)-a protein involved in various inflammatory and autoimmune diseases as well as in cancer-we herein discovered a set of anti-HMGB1 G-quadruplex(G4)-forming aptamers by using an in vitro selection procedure applied to a doped library of guanine-rich oligonucleotides. The selected DNA sequences were then studied in a pseudo-physiological buffer mimicking the extracellular medium, where HMGB1 exerts its pathological activity, using spectroscopic, electrophoretic, and chromatographic techniques. All the oligonucleotides proved to fold into monomeric G4s and in some cases also dimeric species, stable at physiological temperature. Remarkably, the protein preferentially recognized the sequences forming dimeric parallel G4 structures, as evidenced by a properly designed chemiluminescent binding assay which also highlighted a good selectivity of these aptamers for HMGB1. Moreover, all aptamers showed anti-HMGB1 activity, inhibiting protein-induced cell migration. The acquired data allowed identifying L12 as the best anti-HMGB1 aptamer, featured by high thermal and enzymatic stability, no toxicity at least up to 5 μM concentration on healthy cells, along with potent anti-HMGB1 activity (IC
MeSH term(s)	HMGB1 Protein ; Aptamers, Nucleotide/pharmacology ; Aptamers, Nucleotide/chemistry ; G-Quadruplexes
Chemical Substances	HMGB1 Protein ; Aptamers, Nucleotide
Language	English
Publishing date	2024-03-06
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2011836-3
ISSN	1521-3773 ; 1433-7851
ISSN (online)	1521-3773
ISSN	1433-7851
DOI	10.1002/anie.202319828
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The Small RNA Landscape in NSCLC: Current Therapeutic Applications and Progresses.

Ciccone, Giuseppe / Ibba, Maria Luigia / Coppola, Gabriele / Catuogno, Silvia / Esposito, Carla Lucia

International journal of molecular sciences

2023 Volume 24, Issue 7

Abstract: Non-small-cell lung cancer (NSCLC) is the second most diagnosed type of malignancy and the first cause of cancer death worldwide. Despite recent advances, the treatment of choice for NSCLC patients remains to be chemotherapy, often showing very limited ... ...

Abstract	Non-small-cell lung cancer (NSCLC) is the second most diagnosed type of malignancy and the first cause of cancer death worldwide. Despite recent advances, the treatment of choice for NSCLC patients remains to be chemotherapy, often showing very limited effectiveness with the frequent occurrence of drug-resistant phenotype and the lack of selectivity for tumor cells. Therefore, new effective and targeted therapeutics are needed. In this context, short RNA-based therapeutics, including Antisense Oligonucleotides (ASOs), microRNAs (miRNAs), short interfering (siRNA) and aptamers, represent a promising class of molecules. ASOs, miRNAs and siRNAs act by targeting and inhibiting specific mRNAs, thus showing an improved specificity compared to traditional anti-cancer drugs. Nucleic acid aptamers target and inhibit specific cancer-associated proteins, such as "nucleic acid antibodies". Aptamers are also able of receptor-mediated cell internalization, and therefore, they can be used as carriers of secondary agents giving the possibility of producing very highly specific and effective therapeutics. This review provides an overview of the proposed applications of small RNAs for NSCLC treatment, highlighting their advantageous features and recent advancements in the field.
MeSH term(s)	Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; RNA, Small Interfering/genetics ; Oligonucleotides/therapeutic use ; Oligonucleotides, Antisense ; MicroRNAs/genetics ; RNA, Messenger ; Aptamers, Nucleotide/genetics ; Aptamers, Nucleotide/therapeutic use ; Aptamers, Nucleotide/metabolism
Chemical Substances	RNA, Small Interfering ; Oligonucleotides ; Oligonucleotides, Antisense ; MicroRNAs ; RNA, Messenger ; Aptamers, Nucleotide
Language	English
Publishing date	2023-03-24
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/ijms24076121
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Stick-Based Methods for Aptamer-Mediated siRNA Targeted Delivery.

Catuogno, Silvia / Esposito, Carla Lucia / Giangrande, Paloma H

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

2021 Volume 2282, Page(s) 31–42

Abstract: Despite the therapeutic utility of small interfering RNA (siRNA) molecules, the development of a safe and reliable method to selectively target diseased organs and tissues is still a critical need for their translation to the clinic. Here we describe how ...

Abstract	Despite the therapeutic utility of small interfering RNA (siRNA) molecules, the development of a safe and reliable method to selectively target diseased organs and tissues is still a critical need for their translation to the clinic. Here we describe how nucleic acid-based aptamers against cell surface epitopes may be used to address this issue. We discuss the most recent examples and advances in the field of aptamer siRNA delivery and provide a fast and simple protocol for the design and generation of aptamer-siRNA chimeras. The described approach is based on the annealing of the targeting aptamer, and the antisense strand through "stick" complementary sequences elongated at their 3' end, and the subsequent paring with the sense strand. Such a protocol allows a modular non-covalent generation of the constructs and permits an efficient delivery of the siRNA moiety into aptamer target cells.
MeSH term(s)	Aptamers, Nucleotide/genetics ; Aptamers, Nucleotide/metabolism ; Brain Neoplasms/genetics ; Brain Neoplasms/metabolism ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Gene Transfer Techniques ; Glioblastoma/genetics ; Glioblastoma/metabolism ; Humans ; RNA Interference ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Receptor, Platelet-Derived Growth Factor beta/genetics ; Receptor, Platelet-Derived Growth Factor beta/metabolism ; Research Design ; STAT3 Transcription Factor/genetics ; STAT3 Transcription Factor/metabolism ; Workflow
Chemical Substances	Aptamers, Nucleotide ; RNA, Small Interfering ; STAT3 Transcription Factor ; STAT3 protein, human ; PDGFRB protein, human (EC 2.7.10.1) ; Receptor, Platelet-Derived Growth Factor beta (EC 2.7.10.1)
Language	English
Publishing date	2021-04-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1298-9_3
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The Small RNA Landscape in NSCLC

Giuseppe Ciccone / Maria Luigia Ibba / Gabriele Coppola / Silvia Catuogno / Carla Lucia Esposito

International Journal of Molecular Sciences, Vol 24, Iss 6121, p

Current Therapeutic Applications and Progresses

2023 Volume 6121

Abstract	Non-small-cell lung cancer (NSCLC) is the second most diagnosed type of malignancy and the first cause of cancer death worldwide. Despite recent advances, the treatment of choice for NSCLC patients remains to be chemotherapy, often showing very limited effectiveness with the frequent occurrence of drug-resistant phenotype and the lack of selectivity for tumor cells. Therefore, new effective and targeted therapeutics are needed. In this context, short RNA-based therapeutics, including Antisense Oligonucleotides (ASOs), microRNAs (miRNAs), short interfering (siRNA) and aptamers, represent a promising class of molecules. ASOs, miRNAs and siRNAs act by targeting and inhibiting specific mRNAs, thus showing an improved specificity compared to traditional anti-cancer drugs. Nucleic acid aptamers target and inhibit specific cancer-associated proteins, such as “nucleic acid antibodies”. Aptamers are also able of receptor-mediated cell internalization, and therefore, they can be used as carriers of secondary agents giving the possibility of producing very highly specific and effective therapeutics. This review provides an overview of the proposed applications of small RNAs for NSCLC treatment, highlighting their advantageous features and recent advancements in the field.
Keywords	NSCLC ; aptamer ; ASO ; RNAi ; targeted therapy ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: STAT3 silencing by an aptamer-based strategy hampers the crosstalk between NSCLC cells and cancer-associated fibroblasts.

Ibba, Maria L / Ciccone, Giuseppe / Rotoli, Deborah / Coppola, Gabriele / Fiorelli, Alfonso / Catuogno, Silvia / Esposito, Carla L

Molecular therapy. Nucleic acids

2023 Volume 32, Page(s) 111–126

Abstract: The identification of new effective therapeutic options for non-small-cell lung cancer (NSCLC) represents a crucial challenge in oncology. Recent studies indicate that cancer-associated fibroblasts (CAFs) participate in tumor progression by establishing ... ...

Abstract	The identification of new effective therapeutic options for non-small-cell lung cancer (NSCLC) represents a crucial challenge in oncology. Recent studies indicate that cancer-associated fibroblasts (CAFs) participate in tumor progression by establishing a favorable microenvironment that promotes cancer progression. Therefore, the development of strategies inhibiting the interplay between CAFs and cancer cells is considered a winning approach for the development of effective anti-cancer drugs. Among other factors, the signal transducer and activator of transcription-3 (STAT3) has been reported as a key mediator of CAF oncogenic actions, representing a promising therapeutic target. Here, we applied an aptamer-based conjugate (named Gint4.T-STAT3), containing a STAT3 siRNA linked to an aptamer binding and inhibiting the platelet-derived growth factor receptor (PDGFR)β, to obtain STAT3-specific silencing and interfere with CAF pro-tumorigenic functions. We demonstrated that this molecule effectively delivers the STAT3 siRNA in NSCLC cells, and blocks CAF-induced cancer cell growth and migration and reduced spheroid dimension. In addition, we found that Gint4.T-STAT3 alters CAF phenotype, thus functioning as a double-acting molecule able to inhibit the entire tumor bulk. Our data provide a proof of principle for the targeting of CAF pro-tumor functions through an aptamer-based drug, and can open innovative horizons in NSCLC therapy.
Language	English
Publishing date	2023-03-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2662631-7
ISSN	2162-2531
ISSN	2162-2531
DOI	10.1016/j.omtn.2023.03.003
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Aptamer Cell-Based Selection: Overview and Advances.

Catuogno, Silvia / Esposito, Carla Lucia

Biomedicines

2017 Volume 5, Issue 3

Abstract: Aptamers are high affinity single-stranded DNA/RNA molecules, produced by a combinatorial procedure named SELEX (Systematic Evolution of Ligands by Exponential enrichment), that are emerging as promising diagnostic and therapeutic tools. Among selection ... ...

Abstract	Aptamers are high affinity single-stranded DNA/RNA molecules, produced by a combinatorial procedure named SELEX (Systematic Evolution of Ligands by Exponential enrichment), that are emerging as promising diagnostic and therapeutic tools. Among selection strategies, procedures using living cells as complex targets (referred as "cell-SELEX") have been developed as an effective mean to generate aptamers for heavily modified cell surface proteins, assuring the binding of the target in its native conformation. Here we give an up-to-date overview on cell-SELEX technology, discussing the most recent advances with a particular focus on cancer cell targeting. Examples of the different protocol applications and post-SELEX strategies will be briefly outlined.
Language	English
Publishing date	2017-08-14
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines5030049
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Article ; Online: Advances in mRNA non-viral delivery approaches.

Ibba, Maria L / Ciccone, Giuseppe / Esposito, Carla L / Catuogno, Silvia / Giangrande, Paloma H

Advanced drug delivery reviews

2021 Volume 177, Page(s) 113930

Abstract: Messenger RNAs (mRNAs) present a great potential as therapeutics for the treatment and prevention of a wide range of human pathologies, allowing for protein replacement, vaccination, cancer immunotherapy, and genomic engineering. Despite advances in the ... ...

Abstract	Messenger RNAs (mRNAs) present a great potential as therapeutics for the treatment and prevention of a wide range of human pathologies, allowing for protein replacement, vaccination, cancer immunotherapy, and genomic engineering. Despite advances in the design of mRNA-based therapeutics, a key aspect for their widespread translation to clinic is the development of safe and effective delivery strategies. To this end, non-viral delivery systems including peptide-based complexes, lipidic or polymeric nanoparticles, and hybrid formulations are attracting growing interest. Despite displaying somewhat reduced efficacy compared to viral-based systems, non-viral carriers offer important advantages in terms of biosafety and versatility. In this review, we provide an overview of current mRNA therapeutic applications and discuss key biological barriers to delivery and recent advances in the development of non-viral systems. Challenges and future applications of this novel therapeutic modality are also discussed.
MeSH term(s)	Animals ; Drug Delivery Systems ; Gene Transfer Techniques ; Humans ; RNA, Messenger/administration & dosage
Chemical Substances	RNA, Messenger
Language	English
Publishing date	2021-08-14
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	639113-8
ISSN	1872-8294 ; 0169-409X
ISSN (online)	1872-8294
ISSN	0169-409X
DOI	10.1016/j.addr.2021.113930
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Article: Selection of RNA aptamers targeting hypoxia in cancer.

Nuzzo, Silvia / Iaboni, Margherita / Ibba, Maria Luigia / Rienzo, Anna / Musumeci, Domenica / Franzese, Monica / Roscigno, Giuseppina / Affinito, Alessandra / Petrillo, Gianluca / Quintavalle, Cristina / Ciccone, Giuseppe / Esposito, Carla Lucia / Catuogno, Silvia

Frontiers in molecular biosciences

2022 Volume 9, Page(s) 956935

Abstract: Hypoxia plays a crucial role in tumorigenesis and drug resistance, and it is recognised as a major factor affecting patient clinical outcome. Therefore, the detection of hypoxic areas within the tumour micro-environment represents a useful way to monitor ...

Abstract	Hypoxia plays a crucial role in tumorigenesis and drug resistance, and it is recognised as a major factor affecting patient clinical outcome. Therefore, the detection of hypoxic areas within the tumour micro-environment represents a useful way to monitor tumour growth and patients' responses to treatments, properly guiding the choice of the most suitable therapy. To date, non-invasive hypoxia imaging probes have been identified, but their applicability
Language	English
Publishing date	2022-09-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2022.956935
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Article: Emerging Therapeutic RNAs for the Targeting of Cancer Associated Fibroblasts.

Santana-Viera, Laura / Ibba, Maria L / Rotoli, Deborah / Catuogno, Silvia / Esposito, Carla L

Cancers

2020 Volume 12, Issue 6

Abstract: Tumor mass consists of a complex ensemble of malignant cancer cells and a wide variety of resident and infiltrating cells, secreted factors, and extracellular matrix proteins that are referred as tumor microenvironment (TME). Cancer associated ... ...

Abstract	Tumor mass consists of a complex ensemble of malignant cancer cells and a wide variety of resident and infiltrating cells, secreted factors, and extracellular matrix proteins that are referred as tumor microenvironment (TME). Cancer associated fibroblasts (CAFs) are key TME components that support tumor growth, generating a physical barrier against drugs and immune infiltration, and contributing to regulate malignant progression. Thus, it is largely accepted that therapeutic approaches aimed at hampering the interactions between tumor cells and CAFs can enhance the effectiveness of anti-cancer treatments. In this view, nucleic acid therapeutics have emerged as promising molecules. Here, we summarize recent knowledge about their role in the regulation of CAF transformation and tumor-promoting functions, highlighting their therapeutic utility and challenges.
Language	English
Publishing date	2020-05-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12061365
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Article ; Online: Advances in Oligonucleotide Aptamers for NSCLC Targeting.

Rotoli, Deborah / Santana-Viera, Laura / Ibba, Maria L / Esposito, Carla L / Catuogno, Silvia

International journal of molecular sciences

2020 Volume 21, Issue 17

Abstract: Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer worldwide, with the highest incidence in developed countries. NSCLC patients often face resistance to currently available therapies, accounting for frequent relapses and poor ... ...

Abstract	Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer worldwide, with the highest incidence in developed countries. NSCLC patients often face resistance to currently available therapies, accounting for frequent relapses and poor prognosis. Indeed, despite great recent advancements in the field of NSCLC diagnosis and multimodal therapy, most patients are diagnosed at advanced metastatic stage, with a very low overall survival. Thus, the identification of new effective diagnostic and therapeutic options for NSCLC patients is a crucial challenge in oncology. A promising class of targeting molecules is represented by nucleic-acid aptamers, short single-stranded oligonucleotides that upon folding in particular three dimensional (3D) structures, serve as high affinity ligands towards disease-associated proteins. They are produced in vitro by SELEX (systematic evolution of ligands by exponential enrichment), a combinatorial chemistry procedure, representing an important tool for novel targetable biomarker discovery of both diagnostic and therapeutic interest. Aptamer-based approaches are promising options for NSCLC early diagnosis and targeted therapy and may overcome the key obstacles of currently used therapeutic modalities, such as the high toxicity and patients' resistance. In this review, we highlight the most important applications of SELEX technology and aptamers for NSCLC handling.
MeSH term(s)	Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Aptamers, Nucleotide/chemistry ; Aptamers, Nucleotide/pharmacology ; Carcinoma, Non-Small-Cell Lung/diagnosis ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Drug Delivery Systems/methods ; Humans ; Lung Neoplasms/diagnosis ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Nanostructures/chemistry ; RNA/chemistry ; SELEX Aptamer Technique/methods
Chemical Substances	Antineoplastic Agents ; Aptamers, Nucleotide ; RNA (63231-63-0)
Language	English
Publishing date	2020-08-23
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/ijms21176075
Database	MEDical Literature Analysis and Retrieval System OnLINE

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