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MicroRNA-Based Therapy in Animal Models of Selected Gastrointestinal Cancers

View Article: PubMed Central - PubMed

ABSTRACT

Gastrointestinal cancer accounts for the 20 most frequent cancer diseases worldwide and there is a constant urge to bring new therapeutics with new mechanism of action into the clinical practice. Quantity of in vitro and in vivo evidences indicate, that exogenous change in pathologically imbalanced microRNAs (miRNAs) is capable of transforming the cancer cell phenotype. This review analyzed preclinical miRNA-based therapy attempts in animal models of gastric, pancreatic, gallbladder, and colorectal cancer. From more than 400 original articles, 26 was found to assess the effect of miRNA mimics, precursors, expression vectors, or inhibitors administered locally or systemically being an approach with relatively high translational potential. We have focused on mapping available information on animal model used (animal strain, cell line, xenograft method), pharmacological aspects (oligonucleotide chemistry, delivery system, posology, route of administration) and toxicology assessments. We also summarize findings in the field pharmacokinetics and toxicity of miRNA-based therapy.

No MeSH data available.


Pie chart of routes of administration of miRNA-based therapy in the selected studies.
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Figure 6: Pie chart of routes of administration of miRNA-based therapy in the selected studies.

Mentions: All selected studies assorted by the organ of cancer cells' origin are summarized in Tables 2–5. Visual summary of therapeutic strategy, type of animal model and routes of administration of miRNA-based therapy is demonstrated in Figures 4–6. We have analyzed 26 studies, 20 of them used the miRNA replacement therapy regimen, and others were miRNA inhibitions. Two studies combined miRNA replacement therapy with chemotherapy, two studies combined miRNA inhibition with either chemotherapy, or immunotherapy. Subcutaneous xenograft model was used in 23 cases, orthotopic xenotransplantation was performed in two experiments, and combination of both was done in one study. In 17 studies, miRNA-based therapeutics were administered locally, i.e., injected intratumorally. Five studies involved systemic administration by tail-vein, or intraperitoneal injection, while four studies combined both routes of administration in a separate substudies, or combined systemic administration of e.g., chemotherapy, with local administration of miRNA-based therapy.


MicroRNA-Based Therapy in Animal Models of Selected Gastrointestinal Cancers
Pie chart of routes of administration of miRNA-based therapy in the selected studies.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037200&req=5

Figure 6: Pie chart of routes of administration of miRNA-based therapy in the selected studies.
Mentions: All selected studies assorted by the organ of cancer cells' origin are summarized in Tables 2–5. Visual summary of therapeutic strategy, type of animal model and routes of administration of miRNA-based therapy is demonstrated in Figures 4–6. We have analyzed 26 studies, 20 of them used the miRNA replacement therapy regimen, and others were miRNA inhibitions. Two studies combined miRNA replacement therapy with chemotherapy, two studies combined miRNA inhibition with either chemotherapy, or immunotherapy. Subcutaneous xenograft model was used in 23 cases, orthotopic xenotransplantation was performed in two experiments, and combination of both was done in one study. In 17 studies, miRNA-based therapeutics were administered locally, i.e., injected intratumorally. Five studies involved systemic administration by tail-vein, or intraperitoneal injection, while four studies combined both routes of administration in a separate substudies, or combined systemic administration of e.g., chemotherapy, with local administration of miRNA-based therapy.

View Article: PubMed Central - PubMed

ABSTRACT

Gastrointestinal cancer accounts for the 20 most frequent cancer diseases worldwide and there is a constant urge to bring new therapeutics with new mechanism of action into the clinical practice. Quantity of in vitro and in vivo evidences indicate, that exogenous change in pathologically imbalanced microRNAs (miRNAs) is capable of transforming the cancer cell phenotype. This review analyzed preclinical miRNA-based therapy attempts in animal models of gastric, pancreatic, gallbladder, and colorectal cancer. From more than 400 original articles, 26 was found to assess the effect of miRNA mimics, precursors, expression vectors, or inhibitors administered locally or systemically being an approach with relatively high translational potential. We have focused on mapping available information on animal model used (animal strain, cell line, xenograft method), pharmacological aspects (oligonucleotide chemistry, delivery system, posology, route of administration) and toxicology assessments. We also summarize findings in the field pharmacokinetics and toxicity of miRNA-based therapy.

No MeSH data available.