Potential of Peptide Nucleic Acids in Future Therapeutic Applications

Montazersaheb, Soheila; Hejazi, Mohammad Saeid; Charoudeh, Hojjatollah Nozad

doi:10.15171/apb.2018.064

Cited by 59 publications

(56 citation statements)

References 78 publications

(62 reference statements)

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“…Since PNA is not negatively charged, there is no electrostatic repulsion between DNA and RNA, PNA is more effective than ODN in binding to the mRNA of a target gene. 21 Against this background, we designed an anti-CITED1-PNA that was complementary to the first 10 codons of the open reading frame of CITED1 mRNA. This probe stimulates degradation of CITED1 mRNA and inhibits further protein synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…20 Considering the unique properties of PNA, including resistance to enzymatic digestion, inhibition of gene expression of interest appears to be an effective method of cancer treatment. 21 Different from 99m Tc, 177 Lu is a long half-life (6.7d) nuclide that can simultaneously emit β-particles and γ-rays for targeted radionuclide therapy (TRT) and single-photon emission computed tomography (SPECT). 22 For patients who are not susceptible to conventional 131-iodine therapy or who have distant metastases, 177 Lu may constitute a good alternative nuclide for the treatment of iodine-insensitive PTC.…”

Section: Introductionmentioning

confidence: 99%

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Preparation and SPECT/CT Imaging of 177Lu-Labeled Peptide Nucleic Acid (PNA) Targeting CITED1: Therapeutic Evaluation in Tumor-Bearing Nude Mice

Li¹,

Zhang²,

Li³

et al. 2020

OTT

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The expression of Cbp/p300-interacting transactivator with Glu/Asp-rich carboxyterminal domain 1 (CITED1) is upregulated in papillary thyroid carcinoma (PTC) and mediates cell proliferation and migration. To facilitate early diagnosis and monitoring of recurrent or metastatic PTC, we designed 177 Lu-labeled antisense peptide nucleic acid (PNA) targeting CITED1 mRNA to evaluate the therapeutic potential, while analyzing its distribution in nude mice and the characteristics withsingle-photon emission-computed tomography/ computed tomography (SPECT/CT) imaging. Materials and Methods: 177 Lu-DOTA-anti-CITED1-PNA (177 Lu-asPNA) was obtained by indirect labeling. High-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC) were used to determine the labeling rate and radiochemical purity. The stability of 177 Lu-asPNA was evaluated by TLC, and the radioactivity count was measured by a γ counter to calculate its uptake capacity in K1 cells. To analyze the distribution of 177 Lu-asPNA in body tissues and organs of nude mice, static single-photon emission-computed tomography (SPECT) imaging and SPECT/CT image fusion were performed. Then, the therapeutic effects of probes were explored by tumor growth curves and survival analysis. Results: Our probe showed a radiochemical purity of 96.5±0.15% at 1 hr and specific activity of 8.7±0.53 MBq/μg. The uptake rate in the 177 Lu-asPNA group was much higher than that in the 177 Lu-DOTA-nonsense-PNA (177 Lu-nonsense-PNA) and 177 Lu-DOTA groups (P<0.05). The biological distribution showed that the tumor/muscle ratio was at its highest at 24 h (4.98±0.34) post-inoculation, with SPECT/CT imaging showing clear tumor development. By measuring tumor volume of tumor-bearing nude mice, the 177 Lu-asPNA group showed a significant difference in tumor size 9 days after injection (P < 0.05). Kaplan-Meier survival curves showed that the overall survival rate in the 177 Lu-asPNA group was significantly different from those in the DOTA-anti-CITED1-PNA (asPNA) and saline groups (P = 0.002, log-rank test). Conclusion: 177 Lu-asPNA was developed successfully, showing a high labeling rate and good stability. SPECT/CT imaging demonstrated tumor growth in nude mice, which was effectively inhibited by our probe, thus prolonging survival.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Preparation and SPECT/CT Imaging of 177Lu-Labeled Peptide Nucleic Acid (PNA) Targeting CITED1: Therapeutic Evaluation in Tumor-Bearing Nude Mice

Li¹,

Zhang²,

Li³

et al. 2020

OTT

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“…Another way of targeting DNA and RNA moieties is by using peptide nucleic acids (PNA). These are synthetic analogues of DNA that are highly stable and have a hybridization affinity toward natural DNA and RNA, and are therefore a potential approach for the modification of gene expression and epigenetic states 176 . This approach has been applied to the targeting of the lncRNA HOTAIR to block its interaction with EZH2, resulting in reduced invasiveness and increased sensitivity to chemotherapy 177 .…”

Section: Translational Relevance Of Csc Epigeneticsmentioning

confidence: 99%

Epigenetic regulation of cancer stem cell formation and maintenance

French

Pauklin

2020

Intl Journal of Cancer

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Cancerous tumours contain a rare subset of cells with stem-like properties that are termed cancer stem cells (CSCs). CSCs are defined by their ability to divide both symmetrically and asymmetrically, to initiate new tumour growth and to tolerate the foreign niches required for metastatic dissemination. Accumulating evidence suggests that tumours arise from cells with stem-like properties, the generation of CSCs is therefore likely to be an initiatory event in carcinogenesis. Furthermore, CSCs in established tumours exist in a dynamic and plastic state, with nonstem tumour cells thought to be capable of de-differentiation to CSCs. The regulation of the CSC state both during tumour initiation and within established tumours is a desirable therapeutic target and is mediated by epigenetic factors. In this review, we will explore the epigenetic parallels between induced pluripotency and the generation of CSCs, and discuss how the epigenetic regulation of CSCs opens up novel opportunities for therapeutic intervention. K E Y W O R D S cancer stem cells, cancer therapy, early detection of cancer, epigenetics, induced pluripotent stem cells, tumorigenesis 1 | INTRODUCTION As with adult tissues, cancerous tumours also contain a rare subset of cells with stem-like properties that can function to regenerate the heterogeneous cell populations observed therein. These cancer stem cells (CSCs) are defined by their ability to divide both symmetrically and asymmetrically, to initiate new tumour growth and to tolerate the foreign niches required for metastatic dissemination. As the tumourinitiating population, CSCs underpin the very nature of malignancy and studying their regulation is essential for understanding tumour formation, metastasis and relapse after therapy. As it is not possible to isolate CSCs based on functional properties, CSC identification can be achieved by FACs sorting based on surrogate cell surface marker profiles and subsequent transplantation into immune-compromised mice to demonstrate enhanced tumourigenic potential. Using this strategy, CSCs have been identified in most cancers, first in acute myeloid leukaemia (AML) followed by breast cancer and other solid malignancies such as brain, colon and pancreatic cancer, and are purported to account for only a few per cent of the total cell population.

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“…Because the pattern of mRNA expression varies with protein content and researchers found that RNA may have function without translation to the protein, 23 we also measured expression of survivin and phosphorylated survivin on Thr34 (p-survivin) in PBMCs by western blot analysis. Therefore, although, analyses showed similar expression patterns of survivin in PBMCs of BD patients We next classified patients into two groups: patients with active disease and patients with inactive disease.…”

Section: Birc5 Gene Is Overexpressed In Pbmcs In Bdmentioning

confidence: 99%

Phosphorylation Modulates Survivin Function in Behcet’s Disease

et al. 2020

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Purpose: Survivin is critical for proliferation, maturation, homeostasis and differentiation of effector and memory lymphocytes. In this study the baculoviral inhibitors of apoptosis proteins (IAPs) repeat containing 5 (BIRC5) mRNA, survivin, and phosphorylated survivin expression were evaluated in peripheral blood mononuclear cells (PBMCs), and plasma of patients with Behcet’s disease (BD). Methods: In this study, 26 Iranian Azari patients diagnosed with BD and 30 healthy controls were recruited. Total RNA was extracted from PBMCs. The expression level of survivin was measured by quantitative real-time polymerase chain reaction (PCR). Survivin plasma levels were measured using survivin Enzyme-linked immunosorbent assays. Also, western blotting analysis was performed to measure phosphorylated-survivin and survivin levels in PBMCs and plasma of patients with BD. Results: In a pilot study, we showed that BIRC5 gene expression increased in BD patients compared with healthy controls (P<0.05). Western blotting analysis indicated that there was an increase in phosphorylated survivin expression in PBMCs of BD patients. Our data from western blot analysis showed survivin level in plasma samples of BD patients was similar to healthy controls. No significant differences were observed between plasma survivin levels in the BD patients compared with control group (P>0.05). The expression of phosphorylated survivin at Thr34 in PBMCs of BD patients with active disease was increased. Plasma phosphorylated survivin levels in having BD patients were also downregulated compared to healthy individuals. Conclusion: Analysis of PBMCs indicated increasing expression level of phosphorylated survivin in PBMCs of BD patients. There was also a downregulation in phosphorylated survivin levels in plasma of BD patients.

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Potential of Peptide Nucleic Acids in Future Therapeutic Applications

Cited by 59 publications

References 78 publications

<p>Preparation and SPECT/CT Imaging of <sup>177</sup>Lu-Labeled Peptide Nucleic Acid (PNA) Targeting CITED1: Therapeutic Evaluation in Tumor-Bearing Nude Mice</p>

<p>Preparation and SPECT/CT Imaging of <sup>177</sup>Lu-Labeled Peptide Nucleic Acid (PNA) Targeting CITED1: Therapeutic Evaluation in Tumor-Bearing Nude Mice</p>

Epigenetic regulation of cancer stem cell formation and maintenance

Phosphorylation Modulates Survivin Function in Behcet’s Disease

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