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Order Articulavirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
When the influenza VLPs generated in mammalian cells from HA, NA, and HIV-1 Gag fused to GFP were characterized by nano-LC-MS/MS analysis to identify the possible protein cargo, nucleolin appeared as the most abundant cellular protein present in VLPs (Venereo-Sánchez et al. 2019). It is worth mentioning that the LC/MS/MS technique was used for the first time by the characterization of the influenza H3N2 and H5N1 VLPs that were generated in Vero cells and consisted of the four proteins: HA, NA, M1, and M2 (Wu et al. 2010). Now, the high-resolution LC-MS methods allow precise quantitation of both HA and NA protein concentrations in influenza VLP vaccine candidates (Guo J et al. 2020).
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
It was postulated that immediate disruption of the nucleolin ribosomal RNA G-quadruplex interaction by quarfloxin led to selective inhibition of Pol I-driven transcription. Also, the re-localization of nucleolin to the nucleoplasm was known to be a common response to cellular stress, resulting in selective apoptosis through various different pathways. Interestingly, it has been shown that nucleolin has significant selectivity for the myc G-quadruplex, where it inhibits myc transcription. In early experiments, although quarfloxin did not inhibit myc gene expression in A549 cells growing in vitro after 2 hours of exposure, in other studies the molecule was shown to inhibit myc mRNA expression by 85% in HCT-116 tumor cells isolated from mice after treatment with quarfloxin.
The Ultrastructure And Pathobiology Of Urinary Bladder Cancer
Published in George T. Bryan, Samuel M. Cohen, The Pathology of Bladder Cancer, 2017
Bendicht U. Pauli, Joseph Alroy, Ronald S Weinstein
The nuclei of transitional cell carcinoma cells are frequently pleomorphic.2,3,23,40,222,226 Degree of nuclear pleomorphism is used to determine the histopathological grade of human bladder tumors. Uniform size and shape of nuclei are observed in low-grade (Grade I) tumors (see Figure 28), while extreme pleomorphism is characteristic of high-grade (Grade III) tumors (see Figure 27). Pleomorphic nuclei display one or multiple infoldings of the nuclear envelope and clumping of the chromatin along the nuclear membrane. There are multiple nucleoli. The number of nuclear pores per unit area of nuclear membrane in human bladder carcinoma cells is generally greater than in normal bladder epithelium, as determined in freeze-fracture studies413 (see Figure 29). This increase may be indicative of a higher level of metabolic transport between the nucleus and cytoplasm in malignant tumor cells. The nuclear/cytoplasmic ratio of high-grade transitional cell carcinomas is greater than that of low-grade tumors or normal bladder epithelium. In studies on a small series of biopsies from normal and neoplastic human bladder epithelia, this ratio increased from 0.25 in normal epithelium to 0.27 in low-grade transitional cell carcinomas and to 0.41 in high-grade transitional cell carcinomas, as determined by morphometric techniques from light micrographs.414
Cell-directed aptamer therapeutic targeting for cancers including those within the central nervous system
Published in OncoImmunology, 2022
Jun Wei, Renduo Song, Aria Sabbagh, Anantha Marisetty, Neal Shukla, Dexing Fang, Hinda Najem, Martina Ott, James Long, Lijie Zhai, Maciej S. Lesniak, Charles David James, Leonidas Platanias, Michael Curran, Amy B. Heimberger
Nucleolin is a non-ribosomal phosphoprotein that influences a wide range of cellular activities such as cell adhesion, cell division and migration, regulation of rRNA transcription, modification, and processing of nascent pre-rRNA, telomerase maintenance, and DNA repair.14 Nucleolin is highly expressed in a broad range of human and murine cancers,15 and its cellular distribution is often altered in tumors.16 Because of its high-level expression across cancers, nucleolin has been suggested as a potential target for the delivery of therapy to tumors.17 The nucleolin-targeting aptamer, AS1411, was developed and has been used for this purpose, and is reactive with human and murine target proteins. This 26-mer DNA aptamer with G-quadruplex structure, renders the aptamer heat stable and resistant to DNase/RNase degradation.18
Nucleic acid therapeutics: a focus on the development of aptamers
Published in Expert Opinion on Drug Discovery, 2021
Swati Jain, Jaskirat Kaur, Shivcharan Prasad, Ipsita Roy
Overexpression of P-glycoprotein (P-gp) can remove cytotoxic drugs from the cell and is a major reason for the development of chemoresistance in cancer therapy. In a recent report, the small molecule doxorubicin was delivered to the multi-drug resistant MCF-7/ADR breast cancer cells via a targeting aptamer in a liposome-based formulation [269]. The mechanism of cytotoxic action of doxorubicin was used to intercalate it into the double stranded arm of AS1411, the nucleolin-specific aptamer. Nucleolin is overexpressed on cancer cells and rapidly migrates to the nucleus. An aptamer-doxorubicin complex bound to nucleolin would reach the nucleus without being subjected to efflux by Pgp and thus resistance will not develop. AS1411 was localized to the nucleus and explained the reason for about four times lower IC50 for the formulation than the free drug [269].
Recent advances in the combination delivery of drug for leukemia and other cancers
Published in Expert Opinion on Drug Delivery, 2020
Thikrayat Al-Attar, Sundararajan V. Madihally
Monoclonal antibodies have been explored due to overexpression of certain differentiation antigens and growth factors on tumor cells, e.g. epidermal growth factor. Antibodies have several affect target cells by many mechanisms, such as agonist activity upon binding to the surface receptor, triggering immune pathways, or stromal ablation [57]. While folate receptor expression is significantly lower in normal cells, it is overexpressed in many tumor cells, such as ovarian, breast, and lung cancer, among others. Folate activates certain cellular pathways, upon binding to the receptor, which eventually acts upon the nucleus, directly affecting transcription [58]. Nucleolin is another recent targeting method for liposomes and other nanoparticles, to deliver drugs such as siRNA and doxorubicin. Nucleolin is a ribonucleoprotein, which is overexpressed in cancer cells and is associated with cell proliferation and apoptosis [59]. It has shown successful inhibition of tumor growth, with no observed nonspecific binding [60]. Aptamers which are oligonucleotides or peptides with high binding specificity due to small size, high stability, and low immunogenicity, have shown enhanced targeting in cancer treatment and imaging. Aptamers are [61,62]. Due to these properties, aptamers have shown enhanced cancer treatment by reducing side effects and off-targeting [63].