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

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6020
Author(s):  
Francesca Maria Orlandella ◽  
Luigi Auletta ◽  
Adelaide Greco ◽  
Antonella Zannetti ◽  
Giuliana Salvatore

Background: We have conducted a systematic review focusing on the advancements in preclinical molecular imaging to study the delivery and therapeutic efficacy of miRNAs in mouse models of breast cancer. Methods: A systematic review of English articles published in peer-reviewed journals using PubMed, EMBASE, BIOSIS™ and Scopus was performed. Search terms included breast cancer, mouse, mice, microRNA(s) and miRNA(s). Results: From a total of 2073 records, our final data extraction was from 114 manuscripts. The most frequently used murine genetic background was Balb/C (46.7%). The most frequently used model was the IV metastatic model (46.8%), which was obtained via intravenous injection (68.9%) in the tail vein. Bioluminescence was the most used frequently used tool (64%), and was used as a surrogate for tumor growth for efficacy treatment or for the evaluation of tumorigenicity in miRNA-transfected cells (29.9%); for tracking, evaluation of engraftment and for response to therapy in metastatic models (50.6%). Conclusions: This review provides a systematic and focused analysis of all the information available and related to the imaging protocols with which to test miRNA therapy in an in vivo mice model of breast cancer, and has the purpose of providing an important tool to suggest the best preclinical imaging protocol based on available evidence.

2021 ◽  
Author(s):  
Francesca Maria Orlandella ◽  
Luigi Auletta ◽  
Adelaide Greco ◽  
Antonella Zannetti ◽  
Giuliana Salvatore

Abstract Background: miRNAs have been defined as a tumor suppressor or oncogene (oncomiR) in several human cancers. We have conducted a systematic review highlighting and specifically focusing in the advancements in preclinical molecular imaging to study in vivo the delivery and the therapeutic efficacy of miRNAs in mouse models of breast cancer.Methods: A systematic review of English articles published in peer-reviewed journals using PubMed® (including MEDLINE®), EMBASE, BIOSIS™, Scopus was performed. Search terms included breast cancer, mouse, mice, microRNA(s) and miRNA(s). The search was focused on the last five years (2015-2021). All studies using miRNA in breast cancer models which included a preclinical imaging evaluation, both in vivo or ex vivo were analyzed. Result: From a total of 2,073 records, 1,221 papers were assessed for full text eligibility, but excluding all those in which there was no use of mouse models of breast cancer, there was not in vivo imaging or ex vivo on whole organs, and without a clear link to a miRNA, our final data extraction was made on a total of 114 manuscripts. The murine genetic background most used in miRNA studies have been resulted to be the Balb/C (46,7%). Regarding cell lines, MDA-MB-231 parental and derived cells were used in most experiments (62,5%). The most used model was the i.v. metastatic model (46,8%), which was obtained via intravenous injection (68,9%) in the tail vein. The modulation of miRNA was obtained mainly by stable transfection with specific lentiviral plasmid or DNA constructs in luciferase- labelled BC cells (54,4%). Bioluminescence resulted the most used tool (64%) and was used as a surrogate of tumor growth for efficacy treatment or for the evaluation of tumorigenicity in miRNA transfected cells (29,9%); for tracking, evaluation of engraftment and for response to therapy in metastatic models (50,6%).Conclusion: this review provides a systematic and focused analysis of all the information currently available and related to the imaging protocols to test miRNA therapy in in vivo mice model of BC and has the purpose to provide an important tool to suggest the best pre-clinical imaging protocol on currently available evidences.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
G. C. Santin ◽  
D. S. B. Oliveira ◽  
R. Galo ◽  
M. C. Borsatto ◽  
S. A. M. Corona

Background. The aim of this study was to perform a systematic review of the literature on the efficacy of antimicrobial photodynamic therapy (PDTa) on cariogenic dental biofilm.Types of Studies Reviewed. Studiesin vivo,in vitro, andin situwere included. Articles that did not address PDTa, those that did not involve cariogenic biofilm, those that used microorganisms in the plankton phase, and reviews were excluded. Data extraction and quality assessments were performed independently by two raters using a scale.Results. Two hundred forty articles were retrieved; only seventeen of them met the eligibility criteria and were analyzed in the present review. Considerable variability was found regarding the methodologies and application protocols for antimicrobial PDTa. Two articles reported unfavorable results.Practical Implications. The present systematic review does not allow drawing any concrete conclusions regarding the efficacy of antimicrobial PDTa, although this method seems to be a promising option.


2021 ◽  
Author(s):  
Soheila Moeini ◽  
Ehsan Karimi ◽  
Ehsan Oskoueian

Abstract Background: This research was performed to synthesize nanophytosomes-loaded high phenolic fraction (HPF) from Juniperus polycarpos fruit extract and investigate its antiproliferation effects against breast cancer in mice model. Results: The nanophytosomes-loaded HPF from Juniperus polycarpos fruit extract was synthesized. The mice trial was conducted to determine the possible toxic effects of the synthesized nanophytosomes. The anticancer, pro-apoptotic, and antioxidative activities of the nanophytosomes were determined. The nanophytosomes-loaded HPF had a spherical structure with a size of 176 nm and a polydispersity index coefficient of 0.24. The in-vivo study manifested that nanophytosomes-loaded HPF significantly improved weight gain and food intake compared to the negative control group (p<0.05). The nanophytosomes-loaded HPF significantly enhanced the expression of bax (3.4-fold) and caspase-3 (2.7-fold) genes but reduced bcl2 (3.6-fold) gene expression in tumor cells. The average tumor size was significantly decreased in mice treated with nanophytosomes-loaded HPF (p<0.05). The expression of GPX (2.3-fold) and SOD (2.7-fold) antioxidants in the liver of mice supplemented with nanophytosomes-loaded HPF was significantly developed compared to the negative control (p<0.05). The nanophytosomes-loaded HPF did not show toxicity on normal cells. Conclusion: Our results indicated that nanophytosomes-loaded HPF might be a potential anticancer agent for the breast cancer treatment.


2021 ◽  
Author(s):  
Palma-Gutierrez Edgardo ◽  
Espinoza-Rado Erika ◽  
Zafra-Tanaka Jessica Hanae

ABSTRACTBackgroundIt is known that cancer can cause loss of body weight and muscle protein wasting, which leads to a state of malnutrition, which in turn worsens the prognosis and health of the cancer patient. It has been suggested that the promoting mechanism of this state is systemic inflammation, for which reason several clinical trials have used omega-3 fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as adjuvants to antineoplastic treatment, mainly due to its anti-inflammatory effects. However, few systematic reviews and meta-analyzes have analyzed the effects of omega-3s in patients with breast cancer.ObjectiveThe aim of this study is to assess the effect of the supplementation with omega-3 fatty acids on nutritional and clinical outcomes in patients with breast cancer receiving medical treatment.MethodsA systematic review will be conducted, starting with a search in PubMed, CENTRAL and EMBASE using search terms related to omega-3 fatty acids and breast cancer. We will include only randomized controlled trials that assess the effects of omega-3 in patients with breast cancer receiving medical treatment.. Data will be extracted in a spread sheet. Study selection and data extraction will be conducted by two reviewers independently and the Cochrane Risk of Bias Tool for RCT will be used for assessment of risk of bias. Discrepancies will be reviewed with a third reviewer.ConclusionThis systematic review aims to provide an analysis on the outcomes of the usage of the intervention with omega-3 fatty acids on nutritional and clinical aspects in patients with breast cancer receiving medical treatment.


2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoli Hu ◽  
Yang Liu ◽  
Zhitong Bing ◽  
Qian Ye ◽  
Chengcheng Li

Owing to metastases and drug resistance, the prognosis of breast cancer is still dismal. Therefore, it is necessary to find new prognostic markers to improve the efficacy of breast cancer treatment. Literature shows a controversy between moesin (MSN) expression and prognosis in breast cancer. Here, we aimed to conduct a systematic review and meta-analysis to evaluate the prognostic relationship between MSN and breast cancer. Literature retrieval was conducted in the following databases: PubMed, Web of Science, Embase, and Cochrane. Two reviewers independently performed the screening of studies and data extraction. The Gene Expression Omnibus (GEO) database including both breast cancer gene expression and follow-up datasets was selected to verify literature results. The R software was employed for the meta-analysis. A total of 9 articles with 3,039 patients and 16 datasets with 2,916 patients were ultimately included. Results indicated that there was a significant relationship between MSN and lymph node metastases (P &lt; 0.05), and high MSN expression was associated with poor outcome of breast cancer patients (HR = 1.99; 95% CI 1.73–2.24). In summary, there is available evidence to support that high MSN expression has valuable importance for the poor prognosis in breast cancer patients.Systematic Review Registrationhttps://inplasy.com/inplasy-2020-8-0039/.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15047-e15047
Author(s):  
Surender Kharbanda ◽  
Anees Mohammad ◽  
Sachchidanand Tiwari ◽  
Neha Mehrotra ◽  
Sireesh Appajosyula ◽  
...  

e15047 Background: Triple negative breast cancer (TNBC) accounts for about 10-15% of all breast cancers and differ from other types of invasive breast cancers in that they grow and spread faster. TNBCs have limited treatment options and a worse prognosis. Therapy with anthracyclines considered to be one of the most effective agents in the treatment. Unfortunately, resistance to anthracycline therapy is very common due to drug efflux mediated by overexpression of ABC transporter. Pirarubicin (PIRA), an analogue of doxorubicin (DOX), is approved in Japan, Korea and China and is shown to be less cardiotoxic than DOX. Recent studies suggest that cancer stem cells (CSCs) play an important role in tumorigenesis and biology of TNBC. Targeting CSCs may be a promising, novel strategy for the treatment of this aggressive disease. Recent studies have shown that salinomycin (SAL) preferentially targets the viability of CSCs. Methods: SAL and PIRA were co-encapsulated in polylactic acid (PLA)-based block copolymeric nanoparticles (NPs) to efficiently co-deliver these agents to treat TNBC cells. Results: Generated SAL-PIRA co-encapsulated dual drug-loaded NPs showed an average diameter of 110 ± 7 nm, zeta potential of -12.5 mV and PDI of less than 0.25. Both of these anti-cancer agents showed slow and sustained release profile in non-physiological buffer (PBS, pH 7.4) from these dual drug-encapsulated NPs. Additionally, multiple ratios (PIRA:SAL = 3:1, 1:1, 1:3) were encapsulated to generate diverse dual drug-loaded NPs. The results demonstrate that, in contrast to 1:1 and 3:1, treatment of TNBC cells with 1:3 ratio of PIRA:SAL dual drug-loaded NPs, was associated with significant inhibition of growth in vitro in multiple TNBC cell lines. Interestingly, PIRA:SAL (1:3) was synergistic as compared to either SAL- or PIRA single drug-loaded NPs. The IC50 of PIRA and SAL in single drug-encapsulated NPs is 150 nM and 700 nM respectively in MDA-MB-468. Importantly, the IC50 of PIRA in dual drug-encapsulated NPs dropped down to 30 nM (5-fold). Similar results were obtained in SUM-149 TNBC cell line. Studies are underway to evaluate in vivo biological activity of PIRA:SAL (1:3) on tumor growth in a TNBC xenograft mice model. Conclusions: These results demonstrate that a novel dual drug-loaded NP formulation of PIRA and SAL in a unique ratio of 1:3 represents an approach for successful targeting of CSCs and bulk tumor cells in TNBC and potentially other cancer types.


2008 ◽  
pp. 357-375
Author(s):  
Kathleen Gabrielson ◽  
Teresa Southard ◽  
Yi Xu ◽  
Frank C. Marini ◽  
Brett M. Hall ◽  
...  

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 434
Author(s):  
Ilona Rybinska ◽  
Marco Sandri ◽  
Francesca Bianchi ◽  
Rosaria Orlandi ◽  
Loris De Cecco ◽  
...  

We previously identified an extracellular matrix (ECM) gene expression pattern in breast cancer (BC), called ECM3, characterized by a high expression of genes encoding structural ECM proteins. Since ECM is reportedly implicated in response to therapy of BCs, the aim of this work is to investigate the prognostic and predictive value of ECM3 molecular classification in HER2-positive BCs. ECM3 resulted in a robust cluster that identified a subset of 25–37% of HER2-positive tumors with molecular aggressive features. ECM3 was significantly associated with worse prognosis in two datasets of HER2-positive BCs untreated with adjuvant therapy. Analyses carried out on two of our cohorts of patients treated or not with adjuvant trastuzumab showed association of ECM3 with worse prognosis only in patients not treated with trastuzumab. Moreover, investigating a dataset that includes gene profile data of tumors treated with neoadjuvant trastuzumab plus chemotherapy or chemotherapy alone, ECM3 was associated with increased pathological complete response if treated with trastuzumab. In the in vivo experiments, increased diffusion and trastuzumab activity were found in tumors derived from injection of HER2-positive cells with Matrigel that creates an ECM-rich tumor environment. Taken together, these results indicate that HER2-positive BCs classified as ECM3 have an aggressive phenotype but they are sensitive to trastuzumab treatment.


Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2918
Author(s):  
Simone Borgoni ◽  
Emre Sofyalı ◽  
Maryam Soleimani ◽  
Heike Wilhelm ◽  
Karin Müller-Decker ◽  
...  

Breast cancer is one of the leading causes of death for women worldwide. Patients whose tumors express Estrogen Receptor α account for around 70% of cases and are mostly treated with targeted endocrine therapy. However, depending on the degree of severity of the disease at diagnosis, 10 to 40% of these tumors eventually relapse due to resistance development. Even though recent novel approaches as the combination with CDK4/6 inhibitors increased the overall survival of relapsing patients, this remains relatively short and there is a urgent need to find alternative targetable pathways. In this study we profiled the early phases of the resistance development process to uncover drivers of this phenomenon. Time-resolved analysis revealed that ATF3, a member of the ATF/CREB family of transcription factors, acts as a novel regulator of the response to therapy via rewiring of central signaling processes towards the adaptation to endocrine treatment. ATF3 was found to be essential in controlling crucial processes such as proliferation, cell cycle, and apoptosis during the early response to treatment through the regulation of MAPK/AKT signaling pathways. Its essential role was confirmed in vivo in a mouse model, and elevated expression of ATF3 was verified in patient datasets, adding clinical relevance to our findings. This study proposes ATF3 as a novel mediator of endocrine resistance development in breast cancer and elucidates its role in the regulation of downstream pathways activities.


2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
M. F. Fiordelisi ◽  
L. Auletta ◽  
L. Meomartino ◽  
L. Basso ◽  
G. Fatone ◽  
...  

Precision and personalized medicine is gaining importance in modern clinical medicine, as it aims to improve diagnostic precision and to reduce consequent therapeutic failures. In this regard, prior to use in human trials, animal models can help evaluate novel imaging approaches and therapeutic strategies and can help discover new biomarkers. Breast cancer is the most common malignancy in women worldwide, accounting for 25% of cases of all cancers and is responsible for approximately 500,000 deaths per year. Thus, it is important to identify accurate biomarkers for precise stratification of affected patients and for early detection of responsiveness to the selected therapeutic protocol. This review aims to summarize the latest advancements in preclinical molecular imaging in breast cancer mouse models. Positron emission tomography (PET) imaging remains one of the most common preclinical techniques used to evaluate biomarker expression in vivo, whereas magnetic resonance imaging (MRI), particularly diffusion-weighted (DW) sequences, has been demonstrated as capable of distinguishing responders from nonresponders for both conventional and innovative chemo- and immune-therapies with high sensitivity and in a noninvasive manner. The ability to customize therapies is desirable, as this will enable early detection of diseases and tailoring of treatments to individual patient profiles. Animal models remain irreplaceable in the effort to understand the molecular mechanisms and patterns of oncologic diseases.


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