Preclinical Imaging Evaluation of miRNAs’ Delivery and Effects in Breast Cancer Mouse Models: A Systematic Review

Orlandella, Francesca Maria; Auletta, Luigi; Greco, Adelaide; Zannetti, Antonella; Salvatore, Giuliana

doi:10.3390/cancers13236020

Cited by 5 publications

(3 citation statements)

References 163 publications

(375 reference statements)

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“…Pre-clinical studies evaluating alterations in miRNA expression and function associated with different BC subtypes is based on the use of either in vitro human cancer-derived cell lines or mouse xenograft models. A systematic review focused on the advancements in pre-clinical imaging to study cell-free miRNAs in vitro and in mouse models of BC has recently been published [37].…”

Section: Free Circulating Mirnas: Pre-clinical Studiesmentioning

confidence: 99%

Circulating miRNAs in Breast Cancer Diagnosis and Prognosis

Cardinali

Tasso

Piccioli

et al. 2022

Cancers

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Great improvement has been made in the diagnosis and therapy of breast cancer patients. However, the identification of biomarkers for early diagnosis, prognosis, therapy assessment and monitoring, including drug resistance and the early detection of micro-metastases, is still lacking. Recently, circulating microRNAs (miRNAs), circulating freely in the blood stream or entrapped in extracellular vesicles (EVs), have been shown to have a potential diagnostic, prognostic or predictive power. In this review, recent findings are summarized, both at a preclinical and clinical level, related to miRNA applicability in the context of breast cancer. Different aspects, including clinical and technical challenges, are discussed, describing the potentialities of miRNA use in breast cancer. Even though more methodological standardized studies conducted in larger and selected patient cohorts are needed to support the effective clinical utility of miRNA as biomarkers, they could represent novel and accessible tools to be transferred into clinical practice.

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Section: Free Circulating Mirnas: Pre-clinical Studiesmentioning

confidence: 99%

Circulating miRNAs in Breast Cancer Diagnosis and Prognosis

Cardinali

Tasso

Piccioli

et al. 2022

Cancers

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“…MicroRNAs (miRNAs) are a set of small sequence (18–25 nucleotides) non-coding RNAs that regulate gene expressions at the transcriptional or post-transcriptional level by sequence-specific binding to the 3′ untranslated regions (3′ UTR) of the target gene, leading to the degradation or translation inhibition of the gene (Lv et al 2019 ). Thus, miRNAs have an important role in controlling many biological processes such as cell growth, proliferation, invasion, differentiation, adhesion, apoptosis, and cellular metabolic pathways (Orlandella et al 2021 ; El-Daly et al, 2020 ; Nabih 2020 ; Pedroza-Torres et al 2019 ; Yanwirasti et al 2017 ; Pinweha et al 2016 ). Abnormal alterations of miRNAs expression patterns are frequently observed in various cancers, including BC.…”

Section: Introductionmentioning

confidence: 99%

The diagnostic significance of circulating miRNAs and metabolite profiling in early prediction of breast cancer in Egyptian women

El-Toukhy

El‐Daly

Kamel

et al. 2022

J Cancer Res Clin Oncol

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Objective Breast cancer (BC) is one of the most commonly diagnosed solid malignancies in women worldwide. Purpose Finding new non-invasive circulating diagnostic biomarkers will facilitate the early prediction of BC and provide valuable insight into disease progression and response to therapy using a safe and more accessible approach available every inspection time. Therefore, our present study aimed to investigate expression patterns of potentially circulating biomarkers that can differentiate well between benign, malignant, and healthy subjects. Methods To achieve our target, quantitative analyses were performed for some circulating biomarkers which have a role in the proliferation and tumor growth, as well as, glutamic acid, and human epidermal growth receptor 2 (HER2) in blood samples of BC patients in comparison to healthy controls using qRT-PCR, liquid chromatography/mass spectrometry (LC/MS/MS), and ELISA. Results Our findings showed that the two miRNAs (miRNA-145, miRNA-382) were expressed at lower levels in BC sera than healthy control group, while miRNA-21 was expressed at higher levels in BC patients than control subjects. Area under ROC curves of BC samples revealed that AUC of miRNA-145, miRNA-382, miRNA-21, and glutamic acid was evaluated to equal 0.99, 1.00, 1.00 and 1.00, respectively. Besides, there was a significantly positive correlation between miRNA-145 and miRNA-382 (r = 0.737), and a highly significant positive correlation between miRNA-21 and glutamic acid (r = 0.385). Conclusion Based on our results, we conclude that the detection of serum miRNA-145, -382 and -21 as a panel along with glutamic acid, and circulating HER2 concentrations could be useful as a non-invasive diagnostic profiling for early prediction of breast cancer in Egyptian patients. It can provide an insight into disease progression, discriminate between malignancy and healthy control, and overcome the use limitations (low sensitivity and specificity, repeated risky exposure, and high cost) of other detecting tools, including mammography, magnetic resonance imaging, and ultrasound.

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“…To date, C57Bl mice were the most often used strain in studies evaluating effect of letrozle on spatial learning (Meng et al, 2011; Liu et al, 2019; Vierk et al, 2015). Since our goal was to evaluate the effect of prolonged exposure to letrozole on cognitive functions in an animal model used in breast cancer research (Orlandella et al, 2021), the present study used female BALB/c mice. The BALB/c mice are significantly different form C57BL mice in their emotionality (Brinks et al, 2007) and neurochemistry (Bach et al, 2011), therefore their evaluation may provide additional information about effects of letrozole on cognitive behavior.…”

Section: Introductionmentioning

confidence: 99%

Letrozole delays acquisition of water maze task in female BALB/c mice: possible involvement of anxiety

Mamczarz

Lane

Merchenthaler

2022

Preprint

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Letrozole, an aromatase inhibitor (AI), is used as an adjuvant therapy in estrogen receptor-positive (ER+) breast cancer patients. Similar to other AIs, it induces many side effects, including impaired cognition. Despite its negative effect in humans, results from animal models are inconsistent and suggest that letrozole can either impair or improve cognition. Here we studied effects of letrozole on cognitive behavior of adult female BALB/c mice, a relevant animal model for breast cancer studies. Mice were continuously treated with once-a-day subcutaneous (s.c.) injections of letrozole (0.1 or 0.3 mg/kg/day) or vehicle and subjected to behavioral testing starting on day 21 after treatment initiation. During the treatments, vaginal smears were taken from the mice to evaluate estrous cyclicity. Both doses of letrozole suspended cyclicity and the smears showed that the mice were in constant metestrus. Exposure to letrozole did not significantly affect response to novelty measured as a locomotor activity in open field. However, repeated testing in open field (4 days x 15 min) revealed that letrozole 0.3 mg/kg facilitated locomotor habituation (a form of non-associative learning), significantly reducing locomotor activity on 3rd and 4th day of testing. These findings suggest that certain doses of letrozole may have positive effects on cognitive behavior. Training to find a hidden platform in the Morris water maze (15 days x 4 trials), however, indicated that letrozole 0.1 mg/kg-treated mice had significant learning impairment, as, throughout the training, they swam longer times than vehicle-treated mice to reach the hidden platform. Similarly, in a probe test performed 72 h after the last day of the training, letrozole 0.1 mg/kg-treated mice did not show preference for the training platform zones. These results indicate that cognitive impairments reported by women treated with letrozole can be captured in BALB/c mice treated with clinically relevant doses of the drug. Interestingly, most of the letrozole 0.1 mg/kg-treated mice were able to learn the new platform position in reversal training and performed similar to control mice in a reversal probe test. Results of the reversal test suggest that letrozole did not completely disrupt spatial navigation but rather delayed acquisition of spatial information. The current study shows that letrozole dose dependently modulates behavioral response and that its effects are task dependent.

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Preclinical Imaging Evaluation of miRNAs’ Delivery and Effects in Breast Cancer Mouse Models: A Systematic Review

Cited by 5 publications

References 163 publications

Circulating miRNAs in Breast Cancer Diagnosis and Prognosis

Circulating miRNAs in Breast Cancer Diagnosis and Prognosis

The diagnostic significance of circulating miRNAs and metabolite profiling in early prediction of breast cancer in Egyptian women

Letrozole delays acquisition of water maze task in female BALB/c mice: possible involvement of anxiety

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