Adenovirus-mediated overexpression of human tissue plasminogen activator prevents peritoneal adhesion formation/reformation in rats

Atta, Hussein M.; Al-Hendy, Ayman; Elrehany, Mahmoud A.; Dewerchin, Mieke; Raheim, Salama R. Abdel; Ghany, Hend Abdel; Fouad, Rasha

doi:10.1016/j.surg.2009.02.018

Cited by 12 publications

(6 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Local molecular therapy is inherently limited; therefore an alternative strategy using gene therapy has recently been employed to correct molecular aberrations induced by surgical trauma [31]. In five studies based on rat models, different vectors were used to express therapeutic nucleic acids (transgenes or small interfering RNAs) in peritoneal tissue [31,40,55-59]. …”

Section: Articlementioning

confidence: 99%

Peritoneal adhesion index (PAI): proposal of a score for the “ignored iceberg” of medicine and surgery

et al. 2013

View full text Add to dashboard Cite

Peritoneal adhesions describe a condition in which pathological bonds form between the omentum, the small and large bowels, the abdominal wall, and other intra-abdominal organs. Different classification systems have been proposed, but they do not resolve the underlying problem of ambiguity in the quantification and definition of adhesions. We therefore propose a standardized classification system of adhesions to universalize their definition based on the macroscopic appearance of adhesions and their diffusion to different regions of the abdomen. By scoring with these criteria, the peritoneal adhesion index (PAI) can range from 0 to 30, unambiguously specifying precise adhesion scenarios. The standardized classification and quantification of adhesions would enable different studies to more meaningfully integrate their results, thereby facilitating a more comprehensive approach to the treatment and management of this pathology.

show abstract

Section: Articlementioning

confidence: 99%

Peritoneal adhesion index (PAI): proposal of a score for the “ignored iceberg” of medicine and surgery

et al. 2013

View full text Add to dashboard Cite

show abstract

“…It is worth noting that some protective role for tPA in inhibiting peritoneal adhesion formation has also been previously demonstrated. 36 The results with the genetically altered mice, either deficient for EPCR or devoid of PAR1, together with those of APC derivatives suggest that the EPCR-dependent signaling function of APC is essential for the ability of APC to prevent postsurgical adhesion band formation. This is evidenced by the observation that APC-2Cys, which has dramatically decreased anticoagulant activity, exhibited a normal protective activity in both in vitro and in vivo assays; however, APC did not exhibit any activity in the same assays in EPCR d/d mice.…”

Section: Discussionmentioning

confidence: 97%

Intraperitoneal administration of activated protein C prevents postsurgical adhesion band formation

Dinarvand

Hassanian

Weiler

et al. 2015

Blood

View full text Add to dashboard Cite

show abstract

“…As such, we believe that our cell model used in this study is appropriate. In addition to preventing de novo adhesion formation, this strategy is being proposed to prevent adhesion reformation, in which the cell phenotype has already acquired the adhesion profile as we have described before [15]. In a clinical setting, a physical barrier anchored with modified Ad vectors could possibly be administered into the pelvic cavity at the end of surgical manipulations to prevent/reduce the development of postoperative adhesion.…”

Section: Discussionmentioning

confidence: 99%

“…The broad tropism of Ad allows the virus to infect many cell types and is responsible for virus dissemination to distant organs. In our previous work, we have shown that a first-generation replication-incompetent Ad vector encoding htPA can be successfully used for regulating levels of tPA/PAI without increasing the risk of postoperative bleeding, mortality, or postoperative complications, and decreasing de novo and recurrent peritoneal adhesion formation in a rat model [15]. Since then, various modifications of the Ad vector have been developed to improve its selective cell targeting and gene delivery ability in various cell types.…”

Section: Introductionmentioning

confidence: 99%

Towards Gene Therapy of Postoperative Adhesions: Fiber and Transcriptional Modifications Enhance Adenovirus Targeting towards Human Adhesion Cells

Nair

Saed

Atta

et al. 2013

Gynecol Obstet Invest

View full text Add to dashboard Cite

Postoperative abdominal/pelvic peritoneal adhesions are a major source of morbidity (bowel obstruction, infertility, ectopic gestation as well as chronic pelvic pain) in women. In this study, we screened various transduction and transcription modifications of adenovirus (Ad) to identify those that support maximal Ad-mediated gene delivery to human adhesion fibroblasts, which in turn would enhance the efficacy of this novel treatment/preventative strategy for postoperative adhesions. We transduced primary cultures of human peritoneal adhesion fibroblasts with fiber-modified Ad vectors Ad5-RGD-luc, Ad5-Sigma-luc, Ad5/3-luc and Ad5-CAV2-luc as well as transcriptional targeting viruses Ad5-survivin-luc, Ad5-heparanase-luc, Ad5-mesothelin (MSLN)-CRAd-luc and Ad5-secretory leukoprotease inhibitor (SLPI)-luc, and compared their activity to wild-type Ad5-luc. At 48 h, luciferase activity was measured and normalized to the total protein content in the cells. Among the fiber-modified Ad vectors, Ad5-Sigma-luc and among the transcriptional targeting modified Ad vectors, Ad5-MSLN-CRAd-luc showed significantly increased expression levels of luciferase activity at 5, 10 and 50 plaque forming units/cell in adhesion fibroblast cells compared with wild-type Ad5-luc (p < 0.05). Specific modifications of Ad improve their gene delivery efficiency towards human peritoneal adhesion fibroblasts. Developing a safe localized method to prevent/treat postoperative adhesion formation would have a major impact on women health.

show abstract

Adenovirus-mediated overexpression of human tissue plasminogen activator prevents peritoneal adhesion formation/reformation in rats

Cited by 12 publications

References 21 publications

Peritoneal adhesion index (PAI): proposal of a score for the “ignored iceberg” of medicine and surgery

Peritoneal adhesion index (PAI): proposal of a score for the “ignored iceberg” of medicine and surgery

Intraperitoneal administration of activated protein C prevents postsurgical adhesion band formation

Towards Gene Therapy of Postoperative Adhesions: Fiber and Transcriptional Modifications Enhance Adenovirus Targeting towards Human Adhesion Cells

Contact Info

Product

Resources

About