Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.24.3 (collagenase)
18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Currently, surgical intervention is the only efficacious treatment for Peyronie's disease (PD), a fibromatosis of the tunica albuginea of the penis. Therapies based on the molecular pathways for this disease could provide alternatives to surgical treatment but only recently has the pathophysiology of the Peyronie's disease plaque been investigated at the molecular level. In this review, we examine the current knowledge of gene expression in the PD plaque and the relationship of PD with other fibrotic conditions such as Dupytren's disease. TGFbeta1, along with other growth factors, pro-fibrotic genes, and collagen, are expressed in fibroblasts and myofibroblasts. Myofibroblasts are normally involved in wound contracture and largely eliminated via apoptosis during the late stages of wound remodeling. In the PD plaque, however, these cells persist and may play an important role in the PD plaque fibrosis. The expression levels of TGFbeta1 and pro- and anti-fibrotic gene products, along with the nitric oxide/reactive oxygen species (NO/ROS) ratio in the tunica albuginea, appear to be essential for the formation and progression of the PD plaque and effect the expression of multiple genes. This can be assessed with the recently developed DNA-based chip arrays and results with the PD plaque have been encouraging. OSF-1 (osteoblast recruitment), MCP-1 (macrophage recruitment), procollagenase IV (collagenase degradation), and other fibrotic genes have been identified as being possible candidate regulatory genes. Finally, possible therapeutic avenues for gene-based therapy in the treatment of PD are discussed that may eventually reduce the need for surgical intervention.
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PMID:Gene expression in Peyronie's disease. 1245 87

Dupuytren's contracture is a fibroproliferative disorder characterized by progressive deposition of mature collagen fibers. In other fibrotic diseases affecting organs such as the liver, lung, heart, and skin, matrix metalloproteinases (MMPs) and their natural inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), play an important role. In this study, serum concentrations of MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 were determined in 22 patients (five women and 17 men; average age, 67 +/- 11 years) with Dupuytren's disease using an enzyme-linked immunosorbent assay. Tissue samples were obtained for standard histological and immunohistochemical analyses. Sera and samples of palmar fascia from 20 patients (13 women and seven men; average age, 60 +/- 15 years) who had undergone hand surgery for carpal tunnel syndrome were used as the control group. Statistical analysis was performed using the Mann-Whitney test. Patients with Dupuytren's contracture presented with a TIMP-1 concentration of 437 +/- 160 ng/ml, a significantly higher TIMP-1 concentration than that seen in the control patients, who had a concentration of 321 +/- 70 ng/ml (p < 0.05). Patients with a proliferative active disease (n = 14) had a significantly higher TIMP-1 concentration (525 +/- 136 ng/ml) than patients (n = 8) with a contracture in the late involutional and residual phase (286 +/- 41 ng/ml; p < 0.05). There were no significant differences in the TIMP-2, MMP-1, MMP-2, and MMP-9 serum concentrations between patients with palmar fibromatosis and the control group. Patients with Dupuytren's disease had a significantly lower MMP-to-TIMP ratio (1.1 +/- 0.3; p < 0.05) than the control group (1.5 +/- 0.35). Patients with an active palmar fibromatosis presented a significantly (p < 0.05) reduced ratio (1 +/- 0.2) compared with those in later phases (1.4 +/- 0.3). TIMP-1 and TIMP-2 could be detected in tissue of patients with Dupuytren's contracture, with an accumulation in proliferative areas. MMPs could be detected locally in Dupuytren's tissue in a few patients, with less positive staining than for TIMPs. In the control group, there was just little or no staining for TIMPs and MMPs. The data indicate that the physiological balance between MMPs and their natural inhibitors is disturbed in patients with a proliferative active Dupuytren's disease. The decrease in the systemic MMP-to-TIMP ratio can cause increased synthesis and deposition of collagen, leading to palmar fibromatosis.
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PMID:Matrix metalloproteinases and tissue inhibitors of metalloproteinases in sera and tissue of patients with Dupuytren's disease. 1450 11

We defined the immunocytochemical expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in benign soft tissue neoplasms, fibromatoses, and sarcomas, together with the activity of gelatinase MMPs and TIMPs measured by zymography and reverse zymography in a subset of cases. The most strongly expressed MMP in all tumors was MMP-1, with weaker expression of MMP-10, MMP-11, and MMP-14 in most tumors. Nuclear expression of MMP-1, MMP-8, and MMP-13 was an unusual feature. TIMP-2 was expressed in all tumors, with stronger expression in fibromatoses than in sarcomas. Fibromatoses and high-grade sarcomas showed greater MMP-1 expression than other groups, and endothelial MMP-2 expression was more extensive in sarcomas. Differences in MMP and TIMP expression might be linked to the biologic behavior of soft tissue neoplasms. The activation of endothelial MMP-2 linked to widespread MMP-14 expression provides a mechanism for sarcomas to modulate their matrix and facilitate angiogenesis.
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PMID:Matrix metalloproteinase expression is related to angiogenesis and histologic grade in spindle cell soft tissue neoplasms of the extremities. 1571 37

Dupuytren's disease is a progress fibromatosis of unknown origin first described in 1831. Nonoperative treatment options have been suggested involving radiation therapy, vitamin E, local injection therapy suing calcium channel blockers, interferon, corticosteroids or collagenase. Transforming growth factor-beta1 (TGF-beta1) and its downstream Smad signalling system is well established as a key player during fibrogenesis. A number of in vitro experiments have been assessed the blockade of TGF-beta1 and TGF-beta 2. Clinically, a number of antifibrotic agents are available such as N-acetyl-L-cysteins (NAC) as well as angiotensin-converting enzyme (ACE) inhibitors or AT II antagonists. However, to date none of the well known substances has been tested clinically in fibromatosis such as Dupuytren's disease especially to prevent recurrences after surgical release. Antifibrotic medication using a combination of N-acetyl-L-cystein (NAC) and ACE inhibitor can prevent the recurrence of Dupyutren's disease. Given the fact that recurrence rate in Dupuytren's disease is high and unpredictable after surgical release, an antifibrotic intervention might be worthwhile to consider in the clinical setting. Antifibrotic agents inhibit TGF-beta1, which play a key role in fibromatosis. Thus, antifibrotic medication might reduce the recurrence rate in fibromatosis such as Dupuytren's disease in a clinical significant way.
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PMID:Antifibrotic medication using a combination of N-acetyl-L-cystein (NAC) and ACE inhibitors can prevent the recurrence of Dupuytren's disease. 1972 37

Dupuytren's disease (DD) is a type of fibromatosis which progressively results in the shortening and thickening of the fibrous tissue of the palmar fascia. This condition which predominantly affects white-northern Europeans has been identified since 1614. DD can affect certain activities of daily living such as face washing, combing hair and putting hand in a glove. The origin of Dupuytren's contracture is still unknown, but there are a number of treatments that doctors have come across throughout the years. Historically surgery has been the mainstay treatment for DD but not the only one. The objective is to make a structured review of the most recent advances in treatment of DD including the surgical and medical interventions. We have looked at the most relevant published articles regarding the various treatment options for DD. This review has taken 55 articles into consideration which have met the inclusion criteria. The most recent treatments used are multi-needle aponeurotomy, extensive percutaneous aponeurotomy and lipografting, injecting collagenase Clostridium histolyticum, INF-gamma and shockwave therapy as well as radiotherapy. Each of these treatments has certain advantages and drawbacks and cannot be used for every patient. In order to prevent this condition, spending more time and money in the topic is required to reach better and more consistent treatments and ultimately to eradicate this disease.
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PMID:Recent Surgical and Medical Advances in the Treatment of Dupuytren's Disease - A Systematic Review of the Literature. 2243 52

Dupuytren's disease is a benign fibromatosis affecting the palmar and digital fascia and causing flexion contracture of the affected fingers. Up to date, this affection has no curative treatment available. The author is presenting an updated review of the therapeutic arsenal available for Dupuytren's disease cords correction. Open fasciectomy remains the "gold standard" surgical treatment of the disease but enzymatic treatment of the cords by injected collagenase clostridium histolyticum represents a promising new therapeutic. Recent published data are showing that this procedure gives comparable results to the published ones for segmental fasciectomy in terms of cords correction and recurrence prevention but with the advantage of a quicker recovery with a minimal morbidity.
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PMID:[News in the treatment of Dupuytren's disease: from surgery to collagenase's injection]. 2419 41

Dupuytren's disease is a fibromatosis affecting the hand. The disease affects the hand and fingers and may present with a contracture causing increasing disability of the hand. We can treat the symptoms but not its cause. In this article we review the background, diagnosis and methods of treatment of the disease. Although the mainstay of treatment accepted by most is surgical, use of collagenase injections aimed at chemically disintegrating pathologic cords may emerge as an important addition to the armamentarium of treatments for Dupuytren's disease.
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PMID:[Dupuytren's disease]. 2460 2

Fibrosis is a common lesion in different pathologic diseases and defined by the excessive accumulation of collagen. Different approaches have been used to treat different conditions characterized by fibrosis. The FDA and EMA approved the use of collagenase to treat palmar fibromatosis (Dupuytren's contracture). The EMA approved additionally its use in severe Peyronie's disease, but it has been used off label in other conditions [1,2]. The approved treatment includes up to three (in palmar fibromatosis) or up to eight (in penile fibromatosis) injections followed by finger extension or penile modeling procedures, typically causing severe pain. Frequent single injections are adequate to treat palmar fibromatosis [3]. The need to repeatedly inject doses of this enzyme can be due to the labile nature of collagenase, which exhibits a complete activity loss after a short period of time. This study presents a novel strategy to manage this enzyme based on the synthesis of polymeric nanocapsules that contain collagenase encapsulated within their matrix. These nanocapsules have been engineered for achieving a gradual release of the encapsulated enzyme for a longer time, which can be up to ten days. The efficacy of these nanocapsules has been tested in a murine model of local dermal fibrosis, and the results demonstrate a reduction in fibrosis greater than that with the injection of free enzyme; this type of treatment showed a significant improvement compared to conventional therapy of free collagenase.
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PMID:Collagenase nanocapsules: An approach to fibrosis treatment. 2973 7

Fibromatoses are a group of benign connective tissue tumors characterized by the infiltrative, aggressive proliferation of well-differentiated fibroblasts, leading to frequent local recurrence. Within this heterogeneous disease group, superficial fibromatoses show slower growth and more benign infiltration of surrounding tissues than deep fibromatoses. Superficial fibromatoses relevant to dermatology include palmar, plantar, and penile fibromatosis, knuckle pads, pachydermodactyly and infantile digital fibromatosis. They present clinically with subcutaneous nodules or cords that lead to local infiltration and limited mobility of the affected areas. Treatment options vary from watchful waiting, non-invasive methods such as radiotherapy and intralesional corticosteroid/collagenase injections to radical surgical procedures. Early intervention may disrupt disease progression and may even restore functional ability. These disorders should therefore be recognized and treated early in the course of the disease.
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PMID:Clinical features and management of superficial fibromatoses. 3086 79

Plantar fibromatosis, also known as Ledderhose's disease, is a rare disorder of benign fibroblast proliferation involving the plantar aponeurosis (i.e., plantar fascia). Traditionally, surgical intervention has been the most common treatment for plantar fibromatosis. However, numerous studies have reported high recurrence rates of plantar fibromatosis after surgical intervention, as well as wound healing difficulties and nerve injury. Plantar fibromatosis often coexists with other superficial fibrous diseases such as Dupuytren's contracture and Peyronie's disease; immunohistochemical and ultrastructural analyses suggest a relationship between Ledderhose's disease and Dupuytren's contracture. The US Food and Drug Administration approved collagenase Clostridium histolyticum for the treatment of Dupuytren's contracture in 2010 and Peyronie's disease in 2013. This case study presents the successful treatment of Ledderhose's disease almost 4 years (45.5 months) after off-label use of collagenase C. histolyticum injection in a 22-year-old white female who had recurrent plantar fibromatosis after surgical intervention.
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PMID:The Effects of Collagenase Clostridium histolyticum on Plantar Fibromatosis: A Case Study. 3167 81


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