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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: 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 ; 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: Liraglutide for Lower Limb Perfusion in People With Type 2 Diabetes and Peripheral Artery Disease: The STARDUST Randomized Clinical Trial.

Caruso, Paola / Maiorino, Maria Ida / Longo, Miriam / Porcellini, Chiara / Matrone, Rita / Digitale Selvaggio, Lucia / Gicchino, Maurizio / Carbone, Carla / Scappaticcio, Lorenzo / Bellastella, Giuseppe / Giugliano, Dario / Esposito, Katherine

JAMA network open

2024 Volume 7, Issue 3, Page(s) e241545

Abstract: Importance: Peripheral artery disease (PAD) in diabetes may lead to diabetic foot ulcer and lower-extremities amputation. Glucagon-like peptide 1 receptor agonists have proven cardiovascular benefits in trials of people with type 2 diabetes at high ... ...

Abstract	Importance: Peripheral artery disease (PAD) in diabetes may lead to diabetic foot ulcer and lower-extremities amputation. Glucagon-like peptide 1 receptor agonists have proven cardiovascular benefits in trials of people with type 2 diabetes at high cardiovascular risk. Objective: To examine the effect of liraglutide on peripheral perfusion measured as peripheral transcutaneous oxygen pressure (TcPo2) in individuals with type 2 diabetes and PAD. Design, setting, and participants: This open-label randomized clinical trial was conducted between February 1, 2021, and June 30, 2022, with a final follow-up on December 30, 2022, at University of Campania "Luigi Vanvitelli," Naples, Italy. Fifty-five individuals with type 2 diabetes, PAD, and TcPo2 between 30 and 49 mm Hg were included. Interventions: Patients were randomized to receive 1.8 mg of subcutaneous liraglutide or conventional treatment of cardiovascular risk factors (control group) for 6 months. Main outcomes and measures: Coprimary outcomes were the change from baseline of peripheral perfusion between groups and the comparison of the proportion of individuals who reached 10% increase of TcPo2 from baseline in each group. Results: Fifty-five participants (mean [SD] age, 67.5 [8.5] years; 43 [78%] male) were randomized (27 to the liraglutide group and 28 to the control group) and analyzed. Participants had a median (IQR) hemoglobin A1c level of 6.9% (6.5%-7.8%) and a mean (SD) TcPo2 of 40.3 (5.7) mm Hg. Transcutaneous Po2 increased over time in both groups, with significant differences favoring the liraglutide group after 6 months (estimated treatment difference, 11.2 mm Hg; 95% CI, 8.0-14.5 mm Hg; P < .001). The 10% increase of TcPo2 occurred in 24 participants (89%) in the liraglutide group and 13 (46%) in the control group (relative risk, 1.91; 95% CI, 1.26-2.90; P < .001). Compared with the control group, individuals in the liraglutide group had a significant reduction of C-reactive protein (-0.4 mg/dL; 95% CI, -0.7 to -0.07 mg/dL; P = .02), urinary albumin to creatinine ratio (-119.4 mg/g; 95% CI, -195.0 to -43.8 mg/g; P = .003), and improvement of 6-minute walking distance (25.1 m; 95% CI, 21.8-28.3 m; P < .001). Conclusions and relevance: In this randomized clinical trial of people with type 2 diabetes and PAD, liraglutide increased peripheral perfusion detected by TcPo2 measurement during 6 months of treatment. These results support the use of liraglutide to prevent the clinical progression of PAD in individuals with type 2 diabetes. Trial registration: ClinicalTrials.gov Identifier: NCT04881110.
MeSH term(s)	Male ; Humans ; Aged ; Female ; Liraglutide/therapeutic use ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Perfusion ; Peripheral Arterial Disease/drug therapy ; Lower Extremity
Chemical Substances	Liraglutide (839I73S42A)
Language	English
Publishing date	2024-03-04
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article
ISSN	2574-3805
ISSN (online)	2574-3805
DOI	10.1001/jamanetworkopen.2024.1545
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: Combined Targeting of Glioblastoma Stem-Like Cells by Neutralizing RNA-Bio-Drugs for STAT3.

Esposito, Carla Lucia / Nuzzo, Silvia / Ibba, Maria Luigia / Ricci-Vitiani, Lucia / Pallini, Roberto / Condorelli, Gerolama / Catuogno, Silvia / de Franciscis, Vittorio

Cancers

2020 Volume 12, Issue 6

Abstract: An important drawback in the management of glioblastoma (GBM) patients is the frequent relapse upon surgery and therapy. A likely explanation is that conventional therapies poorly affect a small population of stem-like cancer cells (glioblastoma stem ... ...

Abstract	An important drawback in the management of glioblastoma (GBM) patients is the frequent relapse upon surgery and therapy. A likely explanation is that conventional therapies poorly affect a small population of stem-like cancer cells (glioblastoma stem cells, GSCs) that remain capable of repopulating the tumour mass. Indeed, the development of therapeutic strategies able to hit GSCs while reducing the tumour burden has become an important challenge to increase a patient's survival. The signal transducer and activator of transcription-3 (STAT3) has been reported to play a pivotal role in maintaining the tumour initiating capacity of the GSC population. Therefore, in order to impair the renewal and propagation of the PDGFRβ-expressing GSC population, here we took advantage of the aptamer-siRNA chimera (AsiC), named Gint4.T-STAT3, that we previously have shown to efficiently antagonize STAT3 in subcutaneous PDGFRβ-positive GBM xenografts. We demonstrate that the aptamer conjugate is able to effectively and specifically prevent patient-derived GSC function and expansion. Moreover, because of the therapeutic potential of using miR-10b inhibitors and of the broad expression of the Axl receptor in GBM, we used the GL21.T anti-Axl aptamer as the targeting moiety for anti-miR-10b, showing that, in combination with the STAT3 AsiC, the aptamer-miR-10b antagonist treatment further enhances the inhibition of GSC sphere formation. Our results highlight the potential to use a combined approach with targeted RNA therapeutics to inhibit GBM tumour dissemination and relapse.
Language	English
Publishing date	2020-05-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12061434
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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: Nucleic Acid Aptamers Targeting Epigenetic Regulators: An Innovative Therapeutic Option.

Catuogno, Silvia / Esposito, Carla Lucia / Ungaro, Paola / de Franciscis, Vittorio

Pharmaceuticals (Basel, Switzerland)

2018 Volume 11, Issue 3

Abstract: Epigenetic mechanisms include DNA methylation, posttranslational modifications of histones, chromatin remodeling factors, and post transcriptional gene regulation by noncoding RNAs. All together, these processes regulate gene expression by changing ... ...

Abstract	Epigenetic mechanisms include DNA methylation, posttranslational modifications of histones, chromatin remodeling factors, and post transcriptional gene regulation by noncoding RNAs. All together, these processes regulate gene expression by changing chromatin organization and DNA accessibility. Targeting enzymatic regulators responsible for DNA and chromatin modifications hold promise for modulating the transcriptional regulation of genes that are involved in cancer, as well as in chronic noncommunicable metabolic diseases like obesity, diabetes, and cardiovascular diseases. Increasingly studies are emerging, leading to the identification of specific and effective molecules targeting epigenetic pathways involved in disease onset. In this regard, RNA interference, which uses small RNAs to reduce gene expression and nucleic acid aptamers are arising as very promising candidates in therapeutic approach. Common to all these strategies is the imperative challenge of specificity. In this regard, nucleic acid aptamers have emerged as an attractive class of carrier molecules due to their ability to bind with high affinity to specific ligands, their high chemical flexibility as well as tissue penetration capability. In this review, we will focus on the recent progress in the field of aptamers used as targeting moieties able to recognize and revert epigenetics marks involved in diseases onset.
Language	English
Publishing date	2018-08-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph11030079
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Article ; Online: Nucleic acids delivering nucleic acids.

Catuogno, Silvia / Esposito, Carla Lucia / Condorelli, Gerolama / de Franciscis, Vittorio

Advanced drug delivery reviews

2018 Volume 134, Page(s) 79–93

Abstract: Nucleic acid therapeutics, including siRNAs, miRNAs/antimiRs, gRNAs and ASO, represent innovative and highly promising molecules for the safe treatment of a wide range of pathologies. The efficiency of systemic treatments is impeded by 1) the need to ... ...

Abstract	Nucleic acid therapeutics, including siRNAs, miRNAs/antimiRs, gRNAs and ASO, represent innovative and highly promising molecules for the safe treatment of a wide range of pathologies. The efficiency of systemic treatments is impeded by 1) the need to overcome physical and functional barriers in the organism, and 2) to accumulate in the intracellular active site at therapeutic concentrations. Although oligonucleotides either as modified naked molecules or complexed with delivery carriers have revealed to be effectively delivered to the affected target cells, this is restricted to topic treatments or to a few highly vascularized tissues. Therefore, the development of effective strategies for therapeutic nucleic acid selective delivery to target tissues is of primary importance in order to reduce the occurrence of undesired effects on non-target healthy tissues and to permit their translation to clinic. Due to their high affinity for specific ligands, high tissue penetration and chemical flexibility, short single-stranded nucleic acid aptamers are emerging as very attractive carriers for various therapeutic oligonucleotides. Yet, different aptamer-based bioconjugates, able to provide accumulation into target tissues, as well as efficient processing of therapeutic oligonucleotides, have been developed. In this respect, nucleic acid aptamer-mediated delivery strategies represent a powerful approach able to increase the therapeutic efficacy also highly reducing the overall toxicity. In this review, we will summarize recent progress in the field and discuss achieved objectives and optimization of aptamers as delivery carriers of short oligonucleotides.
MeSH term(s)	Aptamers, Nucleotide/chemistry ; Drug Carriers/chemistry ; Drug Delivery Systems ; Humans ; Oligonucleotides/administration & dosage ; Oligonucleotides/chemistry ; Oligonucleotides/pharmacology
Chemical Substances	Aptamers, Nucleotide ; Drug Carriers ; Oligonucleotides
Language	English
Publishing date	2018-04-06
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	639113-8
ISSN	1872-8294 ; 0169-409X
ISSN (online)	1872-8294
ISSN	0169-409X
DOI	10.1016/j.addr.2018.04.006
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Article ; Online: Nucleic Acid Aptamers Targeting Epigenetic Regulators

Silvia Catuogno / Carla Lucia Esposito / Paola Ungaro / Vittorio de Franciscis

Pharmaceuticals, Vol 11, Iss 3, p

An Innovative Therapeutic Option

2018 Volume 79

Abstract	Epigenetic mechanisms include DNA methylation, posttranslational modifications of histones, chromatin remodeling factors, and post transcriptional gene regulation by noncoding RNAs. All together, these processes regulate gene expression by changing chromatin organization and DNA accessibility. Targeting enzymatic regulators responsible for DNA and chromatin modifications hold promise for modulating the transcriptional regulation of genes that are involved in cancer, as well as in chronic noncommunicable metabolic diseases like obesity, diabetes, and cardiovascular diseases. Increasingly studies are emerging, leading to the identification of specific and effective molecules targeting epigenetic pathways involved in disease onset. In this regard, RNA interference, which uses small RNAs to reduce gene expression and nucleic acid aptamers are arising as very promising candidates in therapeutic approach. Common to all these strategies is the imperative challenge of specificity. In this regard, nucleic acid aptamers have emerged as an attractive class of carrier molecules due to their ability to bind with high affinity to specific ligands, their high chemical flexibility as well as tissue penetration capability. In this review, we will focus on the recent progress in the field of aptamers used as targeting moieties able to recognize and revert epigenetics marks involved in diseases onset.
Keywords	epigenetics ; aptamers ; targeted therapy ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
Subject code	570
Language	English
Publishing date	2018-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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