1,721,038 research outputs found
Uso di small interfering RNA (SIRNA) per il trattamento di patologie caratterizzate da iperproliferazione cellulare
No full textTherapeutic potential of small interfering RNAs/micro interfering RNA in hepatocellular carcinoma
Full text linkHepatocellular carcinoma (HCC) is the predominant
form of primary liver cancer and represents the third
leading cause of cancer-related death worldwide.
Current available therapeutic approaches are poorly
effective, especially for the advanced forms of the
disease. In the last year, short double stranded RNA
molecules termed small interfering RNAs (siRNAs) and
micro interfering RNAs (miRNA), emerged as interesting
molecules with potential therapeutic value for HCC.
The practical use of these molecules is however limited
by the identification of optimal molecular targets and
especially by the lack of effective and targeted HCC
delivery systems. Here we focus our discussion on the
most recent advances in the identification of siRNAs/
miRNAs molecular targets and on the development of
suitable siRNA/miRNAs delivery systems
siRNA, Ribozyme and Aptamer Oligonucleotides as Molecular Tools for the Control of Cell Proliferation in the Perspective of Supporting Therapies
No full textAptamers as nano-targeting delivery devices or anti-cancer drugs for fighting tumours
No full textAptamer researches applied to the treatment of human cancers have increased since their discovery in 1990. This is due to different factors including: 1) the technical possibility to select, by SELEX-based procedures, specific aptamers targeting virtually any given molecule, 2) the aptamer favorable bio-activity in vivo, 3) the low production costs and 4) the ease synthesis and storage for the marketing. In the field of cancer treatments, aptamers have been studied as tumor-specific agents driving drugs into cancer cells; additionally they have been used as anti-neoplastic agents per se, able to inhibit tumor cell growth and dissemination when administered alone or in combination with conventional anti-neoplastic drugs. Aptamers are gaining an increased interest for pharmaceutical companies and some of them are under clinical evaluation trials.
In this review we update the findings about the use of aptamers as “escort" molecules able to drive drugs into the cells and as anti-neoplastic drugs per se. Current anti-neoplastic treatments suffer for the intrinsic toxicity related to the un-specific targeting of both normal and tumorigenic proliferating cells. The aptamers could be useful to improve: 1) the selective targeting of molecules essential for the viability and expansion of tumor cells and/or the selective driving of chemiotherapics into tumor cells, thus resulting in higher effectiveness and lower systemic side-effects compared to conventional anti-neoplastic drugs alone and 2) to improve the therapeutic index of currently used chemiotherapics. Even if some problems related to the in vivo stability and pharmacokinetic/dynamics of aptamers remain to be improved, their potential use in the treatment of different human cancers is getting closer and closer to a practical therapeutic use
Thermo-responsive hydrogels from cellulose-based polyelectrolytes and catanionic vesicles for biomedical application
No full textIn this study, negatively charged catanionic vesicles/hydrophobically modified hydroxyethylcellulose polymers thermo-responsive hydrogels have been fabricated. Vesicular aggregates were found to act as multifunctional junctions for networking of modified-cellulose water solutions. The contributions of the electrostatic and hydrophobic interactions were evaluated by changing either vesicles composition or the polymer hydrophobic substitution. Thermal-induced size and lamellarity of hydrogelenclosed vesicles were detected, with further polygonal shape changes induced by cellulose-based polymer addition. The thermal transition was also found to tune hydrogel mechanical behaviour. The network formation was further assessed through molecular insights, which allow to determine the arrangement of the polymer chains on the vesicles’ surface. The examined systems exhibited interesting thermo-responsive characteristics. Thus, vesicularly crosslinked hydrogels herein presented can offer a wide variety of applications, i.e. in biomedical field, as multi-drug delivery systems, thanks to their ability to provide for different environments to guest molecules, comprising bulk water, vesicles’ interior and bilayers, sites on polymeric chains
Aptamer targeting of the elongation factor 1A impairs hepatocarcinoma cells viability and potentiates bortezomib and idarubicin effects
Full text linkThe high morbidity and mortality of hepatocellular carcinoma (HCC) is mostly due to the limited efficacy
of the available therapeutic approaches. Here we explore the anti-HCC potential of an aptamer targeting
the elongation factor 1A (eEF1A), a protein implicated in the promotion of HCC. As delivery methods, we
have compared the effectiveness of cationic liposome and cholesterol-mediated approaches.
A75 nucleotide long aptamer containing GT repetition (GT75) was tested in three HCC cell lines, HepG2,
HuH7 and JHH6. When delivered by liposomes, GT75 was able to effectively reducing HCC cells viability
in a dose and time dependent fashion. Particular sensitive were JHH6 where increased apoptosis with no
effects on cell cycle were observed. GT75 effect was likely due to the interference with eEF1A activity as
neither the mRNA nor the protein levels were significantly affected. Notably, cholesterol-mediated
delivery of GT75 abrogated its efficacy due to cellular mis-localization as proven by
fluorescence and
confocal microscopic analysis. Finally, liposome-mediated delivery of GT75 improved the therapeutic
index of the anticancer drugs bortezomib and idarubicin.
In conclusion, liposome but not cholesterol-mediated delivery of GT75 resulted in an effective delivery
of GT75, causing the impairment of the vitality of a panel of HCC derived cells
Novel hepatocellular carcinoma molecules with prognostic and therapeutic potentials
No full textHepatocellular carcinoma (HCC) is the third leading cause of cancer-related death. The modest efficacy of the therapeutic approaches also depends on the fact that the diagnosis often occurs in the late stages of the disease. Thus, the identification of early markers of onset and progression could be of significant benefit. Here we mainly focus on the latest data pointing the attention towards: (1) biochemical cellular markers; (2) micro-interfering RNA; (3) epigenetic variations; and (4) tumor stroma. The integration of these different lines of investigations should represent promising strategies to identify effective HCC markers
2D DYNAMICAL SIMULATION OF A VIBRATIONAL MILL
No full text2D DYNAMICAL SIMULATION OF A VIBRATIONAL MIL
Mathematical modeling of drug release from natural polysaccharides based matrices
No full textThe new concept of personalized medicine and the affirmation of Nucleic Acid Based Drugs (NABDs), an emerging class of bio-drugs constituted by short sequences of either DNA or RNA, represent a new challenge for the mathematical modelling in the drug delivery and adsorption field. Indeed, whether patient uniqueness asks for the use of theoretical tools enabling a rational approach adapting to each patient, NABDs delivery brings to our attention new aspects of drug delivery due to the NABDs fragile nature and way of action. This review aims to present and discuss the mathematical modelling of drug release from natural polysaccharides matrices with particular care to the description of the chemical and physical phenomena ruling drug deliver
Hydrogels mesh size evaluation
No full textThe importance of hydrogels in the biomedical and biotechnological
fields induced researchers to experimentally and theoretically
study their properties. Among them, one of the most important
is represented by the mesh size distribution of their polymeric
network. Indeed, this characteristic heavily rules the mass exchange
processes between the hydrogel and the surrounding. The aim of
this chapter is to present and discuss some techniques devoted to
the estimation of the polymeric network mesh size. In particular, attention
will be focused on rheology, low-field NMR, crioporosimetry,
and release test
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