Nonsteroidal antiinflammatory drugs differentially suppress endometriosis in a murine model

Efstathiou, Jason A.; Sampson, David A.; Levine, Zalman; Rohan, Richard M.; Zurakowski, David; Folkman, Judah; D’Amato, Robert J.; Rupnick, Maria A.

doi:10.1016/j.fertnstert.2004.06.058

Cited by 86 publications

(63 citation statements)

References 34 publications

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“…46,48 The advantage of the transplantation model is its high reproducibility, the well-defined and rather short time frame and the possibility to measure lesion growth. 39,40,47 In addition, bioimaging is now widely used for many applications such as oncology, gene expression, and immunology. [61][62][63] Implementation of this system should therefore be facilitated by the technical ease of the described procedures.…”

Section: Discussionmentioning

confidence: 99%

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A Novel Noninvasive Model of Endometriosis for Monitoring the Efficacy of Antiangiogenic Therapy

Becker

Wright

Satchi‐Fainaro

et al. 2006

The American Journal of Pathology

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Endometriosis, the presence of ectopic endometrial tissue, is a common disease associated with high morbidity and socioeconomic problems. Angiogenesis, the formation of new blood vessels, plays an important role in the formation and growth of endometriotic lesions. We have created a novel, noninvasive model to monitor the growth of these lesions and the associated angiogenesis in vivo. First, we generated luciferase-expressing transgenic mice by inserting the human ubiquitin C promoter coupled to the firefly luciferase reporter. Injection of luciferin in these mice causes full-body bioluminescence, which can be detected using a lowlight CCD camera. Endometrial tissue from these transgenic mice was surgically implanted into nonluminescent recipients. Bioluminescence of lesions was noninvasively imaged after intravenous or intraperitoneal injection of luciferin. Transabdominal luminescence compared well with the location of the transgenic endometriotic lesions, and lesion size correlated with the intensity of luminescence. Systemic treatment with the angiogenesis inhibitors caplostatin and endostatin peptide mP-1 delayed and suppressed the onset and intensity of the luminescent signal. Caplostatin suppressed the growth of endometriotic lesions by 59% compared with controls. This novel, noninvasive model of endometriosis provides a means to study early angiogenesis in vivo and to monitor endometriotic growth and the efficacy of systemic antiangiogenic therapy.

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Section: Discussionmentioning

confidence: 99%

“…C: At necropsy, endometriotic lesions were measured in two perpendicular diameters (D 1 and D 2 ) with a caliper, and CSA was calculated using the formula for an ellipse (D 1 ϫ D 2 ϫ /4) as previously described. 39,40,47 Bars indicate the SEM. …”

Section: Caplostatin Inhibits Growth Of Endometriotic Lesionsmentioning

confidence: 99%

A Novel Noninvasive Model of Endometriosis for Monitoring the Efficacy of Antiangiogenic Therapy

Becker

Wright

Satchi‐Fainaro

et al. 2006

The American Journal of Pathology

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“…It induces the expression of local P450 aromatase and the anti-apoptotic gene Bcl-2. E 2 also possesses immunosuppressive-mediated activity and inhibits the synthesis of cytokines IFNγ, TNFα, and IL-12, IL-1β-mediated expression of chemokines, the proliferation of T-and B-cells and reduces the cytotoxic activity of NK cells, creating a background of the immunosuppressive characteristic of endometriosis [1][2][3].…”

Section: The Efficacy Of Selective Cyclooxygenase 2 Inhibitors In Thementioning

confidence: 99%

“…17β-эстрадиол, в свою очередь, ин-дуцирует активность ЦОГ-2. Воспалительный процесс в эндометриоидных тканях усиливает продукцию цитокинов (IL-1β, TNF-α) моноци-тами и макрофагами, что также способствует продукции ПГ Е 2 в этой ткани [3]. Кроме того, показано, что ароматаза не только присутству-ет в эндометриоидных гетеротопиях, эутопиче-ском эндометрии больных эндометриозом, но и ее экспрессия повышается под воздействием цитокинов, находящихся в перитонеальной жидкости [10].…”

Section: The Efficacy Of Selective Cyclooxygenase 2 Inhibitors In Theunclassified

“…Будучи медиатором воспаления, простагландин Е 2 участвует во всех воспалительных процессах, индуцирует локальную экспрессию ароматазы Р450 и антиапоптотического гена Bcl-2. Обладает опосредованным иммуносупрессивным действием, ингибируя синтез цитокинов IFN-γ, TNF-α, IL-12, IL-1β-опосредованную экс-прессию хемокинов, пролиферацию Т-и В-клеток, снижает цитотоксическую активность NK-клеток, создавая иммуносупрессивный фон, характерный для эндометриоза [1][2][3]. Целью исследования явилась оценка эффек-тивности и безопасности применения ингибитора ЦОГ-2 целекоксиба в схемах комбинированной и монотера-пии НГЭ.…”

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The efficacy of selective cyclooxygenase 2 inhibitors in the treatment of genital endometriosis

et al. 2018

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External genital endometriosis is characterized by the processes of angiogenesis, neurogenesis, impaired apoptosis, local inflammation of the tissues, secretion of estradiol, and cell proliferation. In a similar manner, prostaglandin E2 affects tissues. The safest drugs that overwhelm COX-2 activity and inhibit the expression of prostaglandin E2 are selective COX-2 inhibitors. As a mediator of inflammation, prostaglandin E2 is involved in all inflammatory processes. It induces the expression of local P450 aromatase and the anti-apoptotic gene Bcl-2. E2 also possesses immunosuppressive-mediated activity and inhibits the synthesis of cytokines IFNγ, TNFα, and IL-12, IL-1β-mediated expression of chemokines, the proliferation of T- and B-cells and reduces the cytotoxic activity of NK cells, creating a background of the immunosuppressive characteristic of endometriosis [1–3]. This study included 100 patients of reproductive age (aged 22-35 years) with a confirmed diagnosis of external genital endometriosis of degree II–IV. Fifty patients received 100 mg of celecoxib in monotherapy and in combination with 2 mg of dienoguest. The control group included 50 people receiving monotherapy with 2 mg of dienogest. The effectiveness of therapy was assessed using the visual analog scale (VAS) and on the basis of the dynamics of algodismenorrhea, pain during coitus, clinical examination, and the patient’s subjective assessment of the degree of irritability and severity of depressive syndrome. The effectiveness of the treatment was evaluated according to MRI and ultrasound of the pelvic organs throughout the study. To control for possible complications of the therapy, the patients performed a comprehensive dynamic survey assessing the indicators of general blood analysis and the blood coagulation system. In the group with the combined application of celecoxib and dienoguest, a clinically significant reduction in pain syndrome and a decrease in the degree of irritability and depressive syndrome were noted relative to the control group. No side effects of celecoxib on the body systems were identified throughout the study. Thus, celecoxib can be recommended as a safe and effective combination therapy for endometriosis.

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Novel therapeutics with enhanced biological activity generated by the strategic introduction of silicon isosteres into known drug scaffolds

Gately

West

2007

Drug Development Research

146

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The strategic replacement of carbon with silicon within biologically prevalidated drug scaffolds can generate focused libraries of pharmaceutically relevant agents with novel, durable and marketable intellectual property. This approach can be cost-effective and of lower developmental risk because known drugs have recognized pharmacology and toxicity profiles, proven safety in humans, and established manufacturing and formulation methods. The change in shape, charge, and lipophilicity that can result from the addition of silicon can favorably alter the biological activity and toxicology of the parent drug. Silicon-containing derivatives of indomethacin are COX-2 selective, suggesting they will not be associated with the classical toxicities associated with nonselective inhibition of the cyclooxygenases. The silicon-indomethacin derivatives also demonstrated superior anti-cancer activity at clinically achievable concentrations when tested in vitro against a human pancreatic cancer cell line, MiaPaCa-2, and a panel of 14 human multiple myeloma cell lines. Bioorganosilicon chemistry represents an attractive approach for emerging biopharmaceutical organizations seeking to rapidly develop a portfolio of novel pharmacological agents that have the potential for enhanced therapeutic and pharmacological benefit. Drug Dev Res 68: [156][157][158][159][160][161][162][163] 2007 r2007 Wiley-Liss, Inc.

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Nonsteroidal antiinflammatory drugs differentially suppress endometriosis in a murine model

Cited by 86 publications

References 34 publications

A Novel Noninvasive Model of Endometriosis for Monitoring the Efficacy of Antiangiogenic Therapy

A Novel Noninvasive Model of Endometriosis for Monitoring the Efficacy of Antiangiogenic Therapy

The efficacy of selective cyclooxygenase 2 inhibitors in the treatment of genital endometriosis

Novel therapeutics with enhanced biological activity generated by the strategic introduction of silicon isosteres into known drug scaffolds

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