Annexin V-Directed Enzyme Prodrug Therapy Plus Docetaxel for the Targeted Treatment of Pancreatic Cancer

Guillen, Katrin P.; Restuccia, Antonietta; Kurkjian, Carla; Harrison, Roger G.

doi:10.1097/mpa.0000000000000343

Cited by 4 publications

(3 citation statements)

References 39 publications

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“…Experiments in vitro revealed that the growth of the prostate cancer cell line was effectively inhibited by docetaxel, a drug whose anticancer activity is higher than taxol because of higher intracellular drug level and longer retention time (13). Besides, docetaxel is free of serious adverse reactions, particularly to the heart (14). With the effects of inhibiting prostate specific antigen increments, relieving pain and reducing adverse reactions from chemotherapy, docetaxel can delay tumor progression, reduce the symptoms and significantly prolong patient lives (15).…”

Section: Introductionmentioning

confidence: 99%

Anticancer effect of docetaxel induces apoptosis of prostate cancer via the cofilin-1 and paxillin signaling pathway

Xiao

Chun-wen

et al. 2016

Molecular Medicine Reports

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Prostate cancer is a common multiple malignant tumor occurring in males. Prostate cancer mortality is the 2nd most common of all tumor types in Western countries and the mortality of morbidity is 13% in the USA. The present study aimed to investigate the anticancer effect of docetaxel on inducing the apoptosis of prostate cancer via the cofilin‑1 and paxillin signaling pathway. Treatment with docetaxel (1‑50 nM) disposed the human LNCaP prostate cancer cells for 24 h. Cell growth and cytotoxicity were subsequently measured using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and lactate dehydrogenase assay, respectively. Docetaxel-induced cell death was analyzed using flow cytometric and caspase-3 assays. Reverse transcription‑quantitative polymerase chain reaction analysis was used to detect the gene expression of cofilin‑1 and western blots were used to determine the protein expression of paxillin. Treatment with docetaxel inhibited cell growth, promoted cytotoxicity, activated apoptosis and increased caspase‑3 activity in the LNCaP cells. Notably, administration of docetaxel reduced the gene expression of cofilin‑1 and the protein expression of paxillin in the LNCaP cells. Additionally, knockdown of cofilin‑1 advanced the anticancer effect of docetaxel against LNCaP cells through suppression of the paxillin pathway. The present findings demonstrated that the anticancer effect of docetaxel induces the apoptosis of prostate cancer via the suppression of the cofilin‑1 and paxillin signaling pathways, which will assist in setting a stage for the clinical treatment of prostate cancer.

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Section: Introductionmentioning

confidence: 99%

Anticancer effect of docetaxel induces apoptosis of prostate cancer via the cofilin-1 and paxillin signaling pathway

Xiao

Chun-wen

et al. 2016

Molecular Medicine Reports

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“…DEPT strategies use an enzyme–substrate pair to convert a systemically administered prodrug into cytotoxic payload within an enzyme‐enriched tumor microenvironment. This results in tumoricidal effects that can be applied in synergy with existing chemotherapies . However, all current DEPT strategies are susceptible to the bystander effect, whereby the cytotoxic payload also interacts with neighboring bystander cells to cause off‐target cytotoxicity (Figure a) .…”

Section: Figurementioning

confidence: 99%

“…[14,15] DEPT strategies use an enzyme-substrate pair to convertasystemically administered prodrug into cytotoxic payload within an enzyme-enriched tumor microenvironment.T his results in tumoricidal effects that can be applied in synergy with existing chemotherapies. [16] However, all current DEPT strategies are susceptible to the bystander effect, [17] whereby the cytotoxic payload also interacts with neighboring bystander cells to causeo ff-target cytotoxicity ( Figure 1a). [18] We envisioned that the use of an enzyme-directed pro-immunostimulant would exploit the bystander effect;d iffusion of active immunostimulant away from enzyme-enriched cancer cells would enablea ctivation of bystanderi mmune cells within the tumor microenvironment ( Figure 1b).…”

mentioning

confidence: 99%

An Enzyme‐Directed Imidazoquinoline for Cancer Immunotherapy

et al. 2016

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Herein we report the synthesis and activity of an enzyme-directed immunostimulant with immune cell activation mediated by β-galactosidase, either exogenously added, or on B16 melanoma cells. Covalent attachment of a β-galactopyranoside to an imidazoquinoline immunostimulant at a position critical for activity resulted in a pro-immunostimulant that could be selectively converted by β-galactosidase into an active immunostimulant. The pro-immunostimulant exhibited β-galactosidase-directed immune cell activation as measured by NF-κB transcription in RAW-Blue macrophages or cytokine production (TNF, IL-6, IL-12) in JAWSII monocytes. Conversion of the pro-immunostimulant into an active immunostimulant was also found to occur using β-galactosidase-enriched B16 melanoma cells. In co-culture experiments with either immune cell line, β-galactosidase-enriched B16 cells effected activation of bystander immune cells.

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Annexin A5 as a targeting agent for cancer treatment

Woodward¹,

Faria²,

Harrison³

2022

Cancer Letters

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Annexin V-Directed Enzyme Prodrug Therapy Plus Docetaxel for the Targeted Treatment of Pancreatic Cancer

Abstract: Strong binding of fusion proteins to PDAC cells and effective cytotoxicity demonstrate the potential applicability of enzyme prodrug therapy to the treatment of PDAC.

Cited by 4 publications

References 39 publications

Anticancer effect of docetaxel induces apoptosis of prostate cancer via the cofilin-1 and paxillin signaling pathway

Anticancer effect of docetaxel induces apoptosis of prostate cancer via the cofilin-1 and paxillin signaling pathway

An Enzyme‐Directed Imidazoquinoline for Cancer Immunotherapy

Annexin A5 as a targeting agent for cancer treatment

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