<i>Endostatin</i> Gene Therapy for Endometriosis in Rats

Tt, Zhang; XL, Fang; Gang, Julie

doi:10.1177/030006051204000522

Cited by 8 publications

(4 citation statements)

References 28 publications

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“…Kojima et al explained the potential of endostatin’s ability to treat disorders related to lymphangiogenesis, such as lymphedema [165]. Becker et al and Zhang et al used endostatin to treat endometriosis without affecting the estrous cycles in in vivo and in vitro models [151, 244]. Several disorders and diseases for which the therapeutic potential of endostatin has been demonstrated include melanoma [245], glioblastoma [246], fibroproliferative disorders [247], pancreatic cancer [248], non-Hodgkin’s lymphoma [249], retinoblastoma [250], hypertension [251], and renal cell carcinoma [252]; even more diseases are included in Table 5.…”

Section: Discussionmentioning

confidence: 99%

Endostatin's emerging roles in angiogenesis, lymphangiogenesis, disease, and clinical applications

Walia

Yang

Huang

et al. 2015

Biochimica et Biophysica Acta (BBA) - General Subjects

159

126

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Background Angiogenesis is the process of neovascularization from pre-existing vasculature and is involved in various physiological and pathological processes. Inhibitors of angiogenesis, administered either as individual drugs or in combination with other chemotherapy, have been shown to benefit patients with various cancers. Endostatin, a 20-kDa C-terminal fragment of type XVIII collagen, is one of the most potent inhibitors of angiogenesis. Scope of review We discuss the biology behind endostatin in the context of its endogenous production, the various receptors to which it binds, and the mechanisms by which it acts. We focus on its inhibitory role in angiogenesis, lymphangiogenesis, and cancer metastasis. We also present emerging clinical applications for endostatin and its potential as a therapeutic agent in the form a short peptide. Major conclusions The delicate balance between pro- and anti-angiogenic factors can be modulated to result in physiological wound healing or pathological tumor metastasis. Research in the last decade has emphasized an emerging clinical potential for endostatin as a biomarker and as a therapeutic short peptide. Moreover, elevated or depressed endostatin levels in diseased states may help explain the pathophysiological mechanisms of the particular disease. General significance Endostatin was once sought after as the ‘be all and end all’ for cancer treatment; however, research throughout the last decade has made it apparent that endostatin’s effects are complex and involve multiple mechanisms. A better understanding of newly discovered mechanisms and clinical applications still has the potential to lead to future advances in the use of endostatin in the clinic.

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Section: Discussionmentioning

confidence: 99%

Endostatin's emerging roles in angiogenesis, lymphangiogenesis, disease, and clinical applications

Walia

Yang

Huang

et al. 2015

Biochimica et Biophysica Acta (BBA) - General Subjects

159

126

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“…Several studies have assessed the effect of other types of drugs that suppress angiogenesis in endometriosis with different results. These drugs included endostatin [29, 30, 33, 34], cabergoline [35, 36], and anginex [29]. …”

Section: Discussionmentioning

confidence: 99%

Efficacy of Anti-VEGF/VEGFR Agents on Animal Models of Endometriosis: A Systematic Review and Meta-Analysis

et al. 2016

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Background/ObjectiveVascular endothelial growth factor (VEGF) is the most important promotor of angiogenesis. Some studies indicate that anti-angiogenic agents that interfere with VEGF and its receptor (VEGFR), i.e., anti-VEGF/VEGFR agents, may be applied to treat endometriosis. This meta-analysis investigated the efficacy of anti-VEGF/VEGFR agents in animal models of endometriosis.MethodsA systematic literature search was performed for animal studies published in English or Chinese from January 1995 to June 2016, which evaluated the effect of anti-VEGF/VEGFR agents on endometriosis. The databases were: PubMed, Web of Science, BIOSIS, Embase, and CNKI. The quality of included studies was assessed using the SYRCLE tool. The random-effect models were used to combine the results of selected studies. Heterogeneity was assessed using H2statistic and I2 statistic. Subgroup analyses were performed to determine the source of heterogeneity in endometriosis scores and follicle numbers.ResultsWe identified 13 studies that used anti-VEGF/VEGFR agents in various animal models. The meta-analysis showed that anti-VEGF/VEGFR agents were associated with smaller size (standardized mean difference (SMD) –0.96, 95% CI –1.31 to –0.62; P < 0.0001) and weight (SMD –1.70, 95% CI –2.75 to –0.65; P = 0.002) of endometriosis lesions, relative to the untreated controls, as well as a lower incidence rate of endometriosis (risk ratio 0.26, 95% CI 0.07 to 0.93; P = 0.038) and endometriosis score (SMD –1.17, 95% CI –1.65 to –0.69; P < 0.0001); the number of follicles were similar (SMD –0.78, 95% CI –1.65 to 0.09; P = 0.08).ConclusionsAnti-VEGF/VEGFR agents appeared to inhibit the growth of endometriosis, with no effect on ovarian function. Anti-angiogenic therapy may be a novel strategy in treating endometriosis.

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“…107 Gene therapy with the antiangiogenic endostatin (transfection by intralesional injection) in a rat model reduced lesion size and MMP-2 levels. 119 Although initial infatuation for the development of therapeutic MMP inhibitors, especially against cancer, strongly declined due to the deleterious side effects of broad-spectrum peptidomimetic inhibitors, there is now renewed interest for novel, highly selective agents, ranging from small molecules to antibodies, antisense inhibitors, and engineered N-terminal tissue inhibitors of metalloproteinase domain (remarkably reviewed by Mohan et al 120 ). To gain further insight into the precise role of MMPs in EM and to better evaluate their potential as therapeutic targets, future investigations aimed at testing the effects of these new substances on EM development or progression are urgently needed.…”

Section: Mmps and Timps In Animal Models Of Artificial Endometriosismentioning

confidence: 99%

Are matrix metalloproteinases and their inhibitors reliable diagnosis biomarkers and attractive therapeutic targets in endometriosis?

Henriet¹,

Mon²,

Marbaix³

2016

MNM

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Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are expressed in the human endometrium during the menstrual cycle, in particular to induce substantial extracellular matrix breakdown underlying menstruation. Endometriosis (EM) is characterized by the presence of endometrial tissue at ectopic locations. Because EM is thought to often develop from retrograde menstruation followed by implantation of menstrual tissue fragments at ectopic sites, endometrial MMPs and TIMPs were rapidly suspected as contributors to EM development and progression, generating hope for their use as biomarkers to facilitate EM diagnosis and as potential targets for developing new therapies against EM. Here, we not only summarize a substantial literature supporting the presence of MMPs and TIMPs in eutopic and ectopic endometrium of EM patients but also highlight frequent controversies on expression changes and the difficulty in identifying systematic MMP/TIMP differential regulation associated with the disease. Moreover, by reanalyzing publicly available data from a whole genome transcriptomic study, we show that occasional and unexplained endometrial overexpression of selective MMPs regardless of the disease and phase of the menstrual cycle rather discourages the use of eutopic MMPs and TIMPs as diagnosis biomarkers. However, we also review multiple studies using rodent models that collectively provide strong support to the contribution of MMPs in EM development and progression, and therefore to further investigations aiming at targeting MMP activity, especially in light of recent advances in new MMP inhibitors.

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Endostatin Gene Therapy for Endometriosis in Rats

Cited by 8 publications

References 28 publications

Endostatin's emerging roles in angiogenesis, lymphangiogenesis, disease, and clinical applications

Endostatin's emerging roles in angiogenesis, lymphangiogenesis, disease, and clinical applications

Efficacy of Anti-VEGF/VEGFR Agents on Animal Models of Endometriosis: A Systematic Review and Meta-Analysis

Are matrix metalloproteinases and their inhibitors reliable diagnosis biomarkers and attractive therapeutic targets in endometriosis?

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