Combined Gene Therapy Using AdsVEGFR2 and AdsTie2 With Chemotherapy Reduces the Growth of Human Ovarian Cancer and Formation of Ascites in Mice

Tuppurainen, Laura; Sallinen, Hanna; Karvonen, Anni; Valkonen, Elina; Laakso, Hanne; Liimatainen, Timo; Hytönen, Elisa; Hämäläinen, Kirsi; Kosma, Veli‐Matti; Anttila, Markku; Ylä‐Herttuala, Seppo

doi:10.1097/igc.0000000000000973

Cited by 15 publications

(12 citation statements)

References 33 publications

(32 reference statements)

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“…It has been shown that a combination of chemotherapy and gene therapy could be synergistically effective for cancer therapy ( Conde et al, 2016 ; Hu et al, 2017 ; Tuppurainen et al, 2017 ; Yang et al, 2017 ). To deliver plasmids carrying therapeutic genes into tumors, a choline derivative-modified co-delivery system has been evaluated which targets ChT; the system was used to deliver a plasmid encoding TRAIL (human tumor necrosis factor-related apoptosis-inducing ligand) and doxorubicin ( Li et al, 2013a ).…”

Section: Transporter-assisted Nano-drug Delivery Systemsmentioning

confidence: 99%

Transporter-Guided Delivery of Nanoparticles to Improve Drug Permeation across Cellular Barriers and Drug Exposure to Selective Cell Types

et al. 2018

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Targeted nano-drug delivery systems conjugated with specific ligands to target selective cell-surface receptors or transporters could enhance the efficacy of drug delivery and therapy. Transporters are expressed differentially on the cell-surface of different cell types, and also specific transporters are expressed at higher than normal levels in selective cell types under pathological conditions. They also play a key role in intestinal absorption, delivery via non-oral routes (e.g., pulmonary route and nasal route), and transfer across biological barriers (e.g., blood–brain barrier and blood–retinal barrier. As such, the cell-surface transporters represent ideal targets for nano-drug delivery systems to facilitate drug delivery to selective cell types under normal or pathological conditions and also to avoid off-target adverse side effects of the drugs. There is increasing evidence in recent years supporting the utility of cell-surface transporters in the field of nano-drug delivery to increase oral bioavailability, to improve transfer across the blood–brain barrier, and to enhance delivery of therapeutics in a cell-type selective manner in disease states. Here we provide a comprehensive review of recent advancements in this interesting and important area. We also highlight certain key aspects that need to be taken into account for optimal development of transporter-assisted nano-drug delivery systems.

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Section: Transporter-assisted Nano-drug Delivery Systemsmentioning

confidence: 99%

Transporter-Guided Delivery of Nanoparticles to Improve Drug Permeation across Cellular Barriers and Drug Exposure to Selective Cell Types

et al. 2018

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“…There is also evidence that a combined Tie-2 targeted gene therapy exerted an antitumor effect in animal models. Co-targeting of VEGFR1, -3 and Tie-2 has been associated with reduced growth of solid human ovarian cancer in mice, and furthermore, combined gene therapy using VEGFR2 and Tie-2 with chemotherapy has reduced the growth of tumors, as well as diminishing the formation of ascites in mice [31].…”

Section: Plos Onementioning

confidence: 99%

High expression of Tie-2 predicts poor prognosis in primary high grade serous ovarian cancer

et al. 2020

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Background Antiangiogenic therapy, although part of standard treatment in ovarian cancer, has variable efficacy. Furthermore, little is known about the prognostic biomarkers and factors influencing angiogenesis in cancer tissue. We evaluated the expression of angiopoietin-2 and two endothelial tyrosine kinase receptors, Tie-1 and Tie-2, and assessed their value in the prediction of survival in patients with malignant epithelial ovarian cancer. We also compared the expression of these factors between primary high grade serous tumors and their distant metastasis. Materials and methods We evaluated 86 women with primary epithelial ovarian cancer. Matched distal omental metastasis were investigated in 18.6% cases (N = 16). The expression levels of angiogenic factors were evaluated by immunohistochemistry in 306 specimens and by qRT-PCR in 111 samples. Results A high epithelial expression level of Tie-2 is a significant prognostic factor in primary high grade serous ovarian cancer. It predicted significantly shorter overall survival both in univariate (p<0.001) and multivariate survival analyses (p = 0.022). Low angiopoietin-2 expression levels in primary ovarian tumors were significantly associated with shorter overall survival (p = 0.015) in the univariate survival analysis. A low expression of angiopoietin-2 was also significantly related to high grade tumors, size of residual tumor after primary surgery and the recurrence of cancer (p = 0.008; p = 0.012; p = 0.018) in the whole study population. The expression of angiopoietin-2 and Tie-2 was stronger in distal omental metastasis than in primary high grade serous tumors in matched-pair analysis (p = 0.001; p = 0.002). Conclusions The angiogenic factor, angiopoietin-2, and its receptor Tie-2 seem to be significant prognostic factors in primary epithelial ovarian cancer. Their expression levels are also increased in metastatic lesions in comparison with primary tumors.

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“…The survival is prolonged if PTX is added to combination gene therapy [ 86 ], being safe in healthy rats [ 87 ]. Furthermore, adenovirus gene therapy with soluble VEGFR2 and Ti2 reducing tumour growth and formation of ascities, enhanced reduction of ascities when gene therapy was combined with PTX and carboplatin, although in this last case, it increased the proliferation of tumour cells [ 88 ].…”

Section: Gene Therapy In Ovarian Cancermentioning

confidence: 99%

Recent Progress in Gene Therapy for Ovarian Cancer

Ayén

Martínez

Marchal

et al. 2018

IJMS

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Ovarian cancer is the most lethal gynecological malignancy in developed countries. This is due to the lack of specific symptoms that hinder early diagnosis and to the high relapse rate after treatment with radical surgery and chemotherapy. Hence, novel therapeutic modalities to improve clinical outcomes in ovarian malignancy are needed. Progress in gene therapy has allowed the development of several strategies against ovarian cancer. Most are focused on the design of improved vectors to enhance gene delivery on the one hand, and, on the other hand, on the development of new therapeutic tools based on the restoration or destruction of a deregulated gene, the use of suicide genes, genetic immunopotentiation, the inhibition of tumour angiogenesis, the alteration of pharmacological resistance, and oncolytic virotherapy. In the present manuscript, we review the recent advances made in gene therapy for ovarian cancer, highlighting the latest clinical trials experience, the current challenges and future perspectives.

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Combined Gene Therapy Using AdsVEGFR2 and AdsTie2 With Chemotherapy Reduces the Growth of Human Ovarian Cancer and Formation of Ascites in Mice

Abstract: Combined inhibition of VEGF/VEGFR2 and Ang/Tie2 pathways provided efficient therapy for ovarian cancer in mice. In addition, antiangiogenic gene therapy has potential as a treatment for the accumulation of ascites.

Cited by 15 publications

References 33 publications

Transporter-Guided Delivery of Nanoparticles to Improve Drug Permeation across Cellular Barriers and Drug Exposure to Selective Cell Types

Transporter-Guided Delivery of Nanoparticles to Improve Drug Permeation across Cellular Barriers and Drug Exposure to Selective Cell Types

High expression of Tie-2 predicts poor prognosis in primary high grade serous ovarian cancer

Recent Progress in Gene Therapy for Ovarian Cancer

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