Inhibition of fibroblast collagen synthesis and proliferation by levamisole and 5-fluorouracil

Waard, J.W.D. de; Man, Ben M. de; Wobbes, Th.; Linden, C. J. Van Der; Hendriks, T

doi:10.1016/s0959-8049(97)00352-3

Cited by 41 publications

(35 citation statements)

References 26 publications

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“…In most of our experimental groups, loss of strength is indeed accompanied by a significantly reduced hydroxyproline level in the anastomotic segment. Previous results, both in our animal model (de Waard et al, 1995b) and in human subcutaneous grafts (Graf et al, 1994b), have demonstrated that early post-operative intraperitoneal 5-FU treatment may strongly inhibit collagen synthetic capacity, possibly by a direct effect on fibroblast proliferation and collagen synthesis (de Waard et al, 1998). As no direct effects of 5-FU on collagen degradation are known, we suggest that reduced synthesis is primarily responsible for the observed loss of anastomotic strength.…”

Section: Discussionsupporting

confidence: 50%

Is early post-operative treatment with 5-fluorouracil possible without affecting anastomotic strength in the intestine?

et al. 1999

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Early post-operative local or systemic administration of 5-fluorouracil (5-FU) is under investigation as a means to improve outcome after resection of intestinal malignancies. It is therefore quite important to delineate accurately its potentially negative effects on anastomotic repair. Five groups ( n = 24) of rats underwent resection and anastomosis of both ileum and colon: a control group and four experimental groups receiving daily 5-FU, starting immediately after operation or after 1, 2 or 3 days. Within each group, the drug (or saline) was delivered either intraperitoneally ( n = 12) or intravenously ( n = 12). Animals were killed 7 days after operation and healing was assessed by measurement of anastomotic bursting pressure, breaking strength and hydroxyproline content. In all cases, 5-FU treatment from the day of operation or from day 1 significantly ( P < 0.025) and severely suppressed wound strength; concomitantly, the anastomotic hydroxyproline content was reduced. Depending on the location of the anastomosis and the route of 5-FU administration, even a period of 3 days between operation and first dosage seemed insufficient to prevent weakening of the anastomosis. The effects of intravenous administration, though qualitatively similar, were quantitatively less dramatic than those observed after intraperitoneal delivery. Post-operative treatment with 5-FU, if started within the first 3 days after operation, is detrimental to anastomotic strength and may compromise anastomotic integrity. © 1999 Cancer Research Campaign

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Section: Discussionsupporting

confidence: 50%

Is early post-operative treatment with 5-fluorouracil possible without affecting anastomotic strength in the intestine?

et al. 1999

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“…It has been found to have an inhibitory effect on human fibroblast cell lines in culture [9]. It also inhibits proliferation and myofibroblast differentiation in Dupuytren fibroblasts in vitro [10].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Intralesional 5-Fluorouracil in the Treatment of Keloids

Gupta

Kalra²

2002

Dermatology

186

109

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Background: The treatment of keloids remains challenging. Cryosurgery and intralesional corticosteroids have been considered as the mainstream of therapy; however, the long-term use of corticosteroids has been found to be associated with serious side effects. Intralesional 5-fluorouracil (5-FU) has only been used in one study for the treatment of hypertrophic scars and keloids, mostly in combination with other treatments. The efficacy of 5-FU as an individual therapeutic agent is unknown. Objective: To evaluate the efficacy and safety of intralesional injections of 5-FU in the treatment of small keloid lesions. Methods: Twenty-four (12 male, 12 female) consecutive patients with keloids of 6 cm or less in their maximum dimension were treated with intralesional injections of 50–150 mg 5-FU per week for a maximum of 16 injections. Results: One third (8/24, 33.3%) of the patients showed more than 75% flattening of the keloid. Three out of 8 patients (with >75% flattening) required less than 16 (13, 13 and 15) injections for achieving the desired response. Overall, about half of the patients showed more than 50% flattening of the treated keloid. A correlation with the duration of keloid was found. Six (54.5%) out of 11 patients with keloids of ≤5 years duration, in contrast to only 2 (15.4%) out of 13 patients with keloids of >5 years duration showed more than 75% flattening (p < 0.05). Side effects included pain (all patients), hyperpigmentation (all patients) and ulceration (1 patient). No difference in peripheral blood count was noted before, during and after the therapy. Conclusion: Intralesional 5-FU can be safely used for the management of small keloids of shorter duration.

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“…29 5-FU limits keloid growth both in vitro and in vivo. 53,54 However, the overall efficacy of 5-FU is not considered superior to other modalities.…”

Section: -Fluorouracilmentioning

confidence: 99%

Strategic management of keloid disease in ethnic skin: a structured approach supported by the emerging literature

Uddin

Bayat

2013

Br J Dermatol

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SummaryKeloid disease (KD) is a common, benign, dermal fibroproliferative growth of unknown aetiology. Lesions tend to grow over time; they often recur following therapy and do not regress spontaneously. KD causes considerable discomfort due to pain, pruritus and inflammation, and a significant psychosocial impact with reduced quality of life. It is unique to humans and occurrence is higher in individuals with dark, pigmented, ethnic skin. There is a strong familial heritability, with a high ethnic predisposition in individuals of African, Asian and Hispanic descent. High recurrence rates and unknown resolution rates present a major problem for both the patient and clinician. Many treatment modalities exist; however, there is no single advocated therapy. Therefore, the aim of this review was to explore the most current literature regarding the range of treatment options for KD and to offer a structured approach in the management of KD, based on evidence and experience, to aid clinicians in their current practice. A focused history involving careful evaluation of the patient's symptoms, signs, quality of life and psychosocial well-being should direct targeted therapy, complemented with regular follow-up and re-evaluation. Many treatment modalities, such as intralesional steroid injection, silicone gel application, cryotherapy, lasers, 5-fluorouracil and, relatively recently, photodynamic therapy, are currently being used in clinical practice for the management of KD. Combination therapies have also been shown to be beneficial. However, there is a lack of robust, randomized, level-one, evidence-controlled trials evaluating these treatment options. Management of KD in ethnic pigmented skin remains a clinical challenge. Thus, a strategic approach with structured assessment, targeted therapy and focus on prevention of recurrence is highly recommended. Quality evidence is essential in order to tailor treatment effectively for the ethnic patient presenting with KD.What's already known about this topic?• Keloid disease (KD) is a common, benign, fibroproliferative tumour of unknown origin.• With high recurrence rates, treatment of KD remains a challenge for both the patient and clinician.• With lack of level-one evidence, there is no single advocated therapy.What does this study add?• A structured strategic approach for management of KD by utilizing a focused history, targeted therapy and regular follow-up of the patient.• Patients' symptoms, signs, quality of life and psychosocial well-being should be carefully evaluated and managed.

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Inhibition of fibroblast collagen synthesis and proliferation by levamisole and 5-fluorouracil

Cited by 41 publications

References 26 publications

Is early post-operative treatment with 5-fluorouracil possible without affecting anastomotic strength in the intestine?

Is early post-operative treatment with 5-fluorouracil possible without affecting anastomotic strength in the intestine?

Efficacy and Safety of Intralesional 5-Fluorouracil in the Treatment of Keloids

Strategic management of keloid disease in ethnic skin: a structured approach supported by the emerging literature

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