Gemcitabine anti-proliferative activity significantly enhanced upon conjugation with cell-penetrating peptides

Vale, Nuno; Ferreira, Abigail; Fernandes, Iva; Araújo, Maria João; Mateus, Nuno; Gomes, Paula

doi:10.1016/j.bmcl.2017.04.086

Cited by 31 publications

(25 citation statements)

References 29 publications

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“…Gemcitabine (2′,2-difluorodeoxycytidine) is a nucleoside analogue which requires intracellular phosphorylation to produce the nucleotides gemcitabine diphosphate (dFdCDP) and triphosphate (dFdCTP), which are then incorporated into DNA and RNA [111]. A phase III trial noticed that the addition of gemcitabine to paclitaxel does improve the complete response in neoadjuvant chemotherapy [112].…”

Section: Main Textmentioning

confidence: 99%

“…A phase III trial noticed that the addition of gemcitabine to paclitaxel does improve the complete response in neoadjuvant chemotherapy [112]. In BC, it is an effective drug for metastatic disease, but around 30% of patients did not response this drug [111]. In this regard, it was described that miR-21 overexpression mediates resistance to gemcitabine.…”

Section: Main Textmentioning

confidence: 99%

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Micro-RNAs as Potential Predictors of Response to Breast Cancer Systemic Therapy: Future Clinical Implications

Campos‐Parra

Cuamani-Mitznahuatl

Pedroza-Torres

et al. 2017

IJMS

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Despite advances in diagnosis and new treatments such as targeted therapies, breast cancer (BC) is still the most prevalent tumor in women worldwide and the leading cause of death. The principal obstacle for successful BC treatment is the acquired or de novo resistance of the tumors to the systemic therapy (chemotherapy, endocrine, and targeted therapies) that patients receive. In the era of personalized treatment, several studies have focused on the search for biomarkers capable of predicting the response to this therapy; microRNAs (miRNAs) stand out among these markers due to their broad spectrum or potential clinical applications. miRNAs are conserved small non-coding RNAs that act as negative regulators of gene expression playing an important role in several cellular processes, such as cell proliferation, autophagy, genomic stability, and apoptosis. We reviewed recent data that describe the role of miRNAs as potential predictors of response to systemic treatments in BC. Furthermore, upon analyzing the collected published information, we noticed that the overexpression of miR-155, miR-222, miR-125b, and miR-21 predicts the resistance to the most common systemic treatments; nonetheless, the function of these particular miRNAs must be carefully studied and further analyses are still necessary to increase knowledge about their role and future potential clinical uses in BC.

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Section: Main Textmentioning

confidence: 99%

Section: Main Textmentioning

confidence: 99%

Micro-RNAs as Potential Predictors of Response to Breast Cancer Systemic Therapy: Future Clinical Implications

Campos‐Parra

Cuamani-Mitznahuatl

Pedroza-Torres

et al. 2017

IJMS

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“…Cell invasion assay. This assay was done by using a chamber system based procedure of the literature 31 .…”

Section: Methodsmentioning

confidence: 99%

Exploring the action of RGDV-gemcitabine on tumor metastasis, tumor growth and possible action pathway

Zhang

et al. 2020

Sci Rep

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The coupling of Arg-Gly-Asp-Val (RGDV) and gemcitabine led to a hypothesis that the conjugate (RGDV-gemcitabine) could inhibit tumor metastasis. To confirm this hypothesis the activities of RGDV-gemcitabine inhibiting tumor metastasis in vitro and in vivo were presented for the first time. AFM (atomic force microscopy) imaged that RGDV-gemcitabine was able to adhere onto the surface of serum-starved A549 cells, to block the extending of the pseudopodia. Thereby RGDV-gemcitabine was able to inhibit the invasion, migration and adhesion of serum-starved A549 cells in vitro. On C57BL/6 mouse model RGDV-gemcitabine dose dependently inhibited the metastasis of planted tumor towards the lung and the minimal dose was 0.084 µmol/kg/3 days. The decrease of serum TNF-α (tumor necrosis factor), IL-8 (interleukin-8), MMP-2 (matrix metalloprotein-2) and MMP-9 (matrix metalloprotein-9) of the treated C57BL/6 mice was correlated with the action pathway of RGDV-gemcitabine inhibiting the metastasis of the planted tumor towards lung.

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“…The results revealed a significant increase of antiproliferative activity of novel CPP-drug conjugates on three cell lines in vitro. In addition, their half-lives were also increased to approximately 9.6 days and 42 h. Taken together, these results demonstrated that conjugation of 40 with CPP might be a valuable strategy for the development of novel prodrugs for an accurate delivery on cancer cells, improving the efficacy of parent drug and alleviate the adverse effects induced on patients [ 87 ].…”

Section: Drugs and Diseasesmentioning

confidence: 95%

Amino Acids in the Development of Prodrugs

Vale

Ferreira

Matos³

et al. 2018

Molecules

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Although drugs currently used for the various types of diseases (e.g., antiparasitic, antiviral, antibacterial, etc.) are effective, they present several undesirable pharmacological and pharmaceutical properties. Most of the drugs have low bioavailability, lack of sensitivity, and do not target only the damaged cells, thus also affecting normal cells. Moreover, there is the risk of developing resistance against drugs upon chronic treatment. Consequently, their potential clinical applications might be limited and therefore, it is mandatory to find strategies that improve those properties of therapeutic agents. The development of prodrugs using amino acids as moieties has resulted in improvements in several properties, namely increased bioavailability, decreased toxicity of the parent drug, accurate delivery to target tissues or organs, and prevention of fast metabolism. Herein, we provide an overview of models currently in use of prodrug design with amino acids. Furthermore, we review the challenges related to the permeability of poorly absorbed drugs and transport and deliver on target organs.

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Gemcitabine anti-proliferative activity significantly enhanced upon conjugation with cell-penetrating peptides

Cited by 31 publications

References 29 publications

Micro-RNAs as Potential Predictors of Response to Breast Cancer Systemic Therapy: Future Clinical Implications

Micro-RNAs as Potential Predictors of Response to Breast Cancer Systemic Therapy: Future Clinical Implications

Exploring the action of RGDV-gemcitabine on tumor metastasis, tumor growth and possible action pathway

Amino Acids in the Development of Prodrugs

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