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Andreas Suhrbier - One of the best experts on this subject based on the ideXlab platform.
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Tattoo removal with Ingenol Mebutate
Clinical Cosmetic and Investigational Dermatology, 2017Co-Authors: Sarahjane Cozzi, Cini James, Steven M Ogbourne, Thuy T. Le, Andreas SuhrbierAbstract:An increasing number of people are getting tattoos; however, many regret the decision and seek their removal. Lasers are currently the most commonly used method for tattoo removal; however, treatment can be lengthy, costly, and sometimes ineffective, especially for certain colors. Ingenol Mebutate is a licensed topical treatment for actinic keratoses. Here, we demonstrate that two applications of 0.1% Ingenol Mebutate can efficiently and consistently remove 2-week-old tattoos from SKH/hr hairless mice. Treatment was associated with relocation of tattoo microspheres from the dermis into the posttreatment eschar. The skin lesion resolved about 20 days after treatment initiation, with some cicatrix formation evident. The implications for using Ingenol Mebutate for tattoo removal in humans are discussed.; ;
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il 1 contributes to the anti cancer efficacy of Ingenol Mebutate
PLOS ONE, 2016Co-Authors: Thuy T. Le, Kresten Skak, Wayne A Schroder, Glen M Boyle, Carly J Pierce, Kate Schroder, Andreas SuhrbierAbstract:Ingenol Mebutate is approved for the topical treatment of actinic keratoses and may ultimately also find utility in treating skin cancers. Here we show that relapse rates of subcutaneous B16 melanoma tumours treated topically with Ingenol Mebutate were not significantly different in C57BL/6 and Rag1-/- mice, suggesting B and T cells do not play a major role in the anti-cancer efficacy of Ingenol Mebutate. Relapse rates were, however, significantly increased in MyD88-/- mice and in C57BL/6 mice treated with the anti-IL-1 agent, anakinra. Ingenol Mebutate treatment induces a pronounced infiltration of neutrophils, which have been shown to have anti-cancer activity in mice. Herein we provide evidence that IL-1 promotes neutrophil recruitment to the tumour, decreases apoptosis of infiltrating neutrophils and increases neutrophil tumour killing activity. These studies suggest IL-1, via its action on neutrophils, promotes the anti-cancer efficacy of Ingenol Mebutate, with Ingenol Mebutate treatment causing both IL-1β induction and IL-1α released from keratinocytes.
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Relapse and survival following Ingenol Mebutate treatment of B16 tumours grown in MyD88-/- and C57BL/6 mice.
2016Co-Authors: Kresten Skak, Wayne A Schroder, Glen M Boyle, Carly J Pierce, Kate Schroder, Andreas SuhrbierAbstract:(A) Relapse rates following (i) Ingenol Mebutate treatment of B16 tumours grown in MyD88-/- mice (n = 25), (ii) Ingenol Mebutate treatment of B16 tumours grown in C57BL/6 mice (n = 21), (iii) placebo treatment of B16 tumours grown in MyD88-/- mice (n = 18) and (iv) placebo treatment of B16 tumours grown in C57BL/6 mice (n = 19). Mice were scored positive when a tumour was clearly visible (≥1–2 mm in diameter). Data from two independent experiments. Ingenol Mebutate treatment groups were significantly different p = 0.021, log-rank (Mantel-Cox) test. (B) Survival rates of the same mice described in A; mice were euthanized when tumours reached 100 mm2. Ingenol Mebutate treatment groups were significantly different p = 0.018, log-rank (Mantel-Cox) test.
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IL-1α and IL-1β protein levels after Ingenol Mebutate treatment.
2016Co-Authors: Kresten Skak, Wayne A Schroder, Glen M Boyle, Carly J Pierce, Kate Schroder, Andreas SuhrbierAbstract:(A, B) C57BL/6 and MyD88-/- mice with B16 tumours were treated topically with Ingenol Mebutate day 0 and 1, treatment sites were excised and IL-1α and IL-1β levels were measured in extracts using BD BD™ Cytometric Bead Array (n = 6 mice per group and time point). Statistics by Kolmogorov-Smirnov tests (differences in variance >4). (C) Cultured adult human keratinocytes were treated with the indicated concentration of Ingenol Mebutate for 16 hours and the supernatants analysed by Western using an anti-IL-1α antibody. Arrow indicates the position of the 18 kDa bioactive form of IL-1α.
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effective treatment of squamous cell carcinomas with Ingenol Mebutate gel in immunologically intact skh1 mice
Archives of Dermatological Research, 2013Co-Authors: Sarahjane Cozzi, Cini James, Steven M Ogbourne, Thuy T. Le, Andreas SuhrbierAbstract:Ingenol Mebutate has recently been approved by the Federal Drug Administration (USA) as a topical treatment for actinic keratoses. Herein, we describe the efficacy of Ingenol Mebutate for the topical treatment of squamous cell carcinoma (SCC) using a wild-type mouse model (SKH1) and the UV-induced mouse SCC cell line, T7. Daily treatment for 2 days with 0.25 % Ingenol Mebutate gel produced a cure rate of 70 %, with 0 % for placebo gel. Electron microscopy revealed swelling of cancer cell mitochondria within 1 h, with disruption of the inner mitochondrial membranes evident at 6 h post treatment. Primary necrosis of cancer cells was clearly evident by 24 h. Treatment was associated with local haemorrhage and a prodigious neutrophil infiltrate, with anti-T7 antibodies also detected. This is the first report of the successful treatment of SCC tumours with Ingenol Mebutate gel in wild-type mice, and supports the view that Ingenol Mebutate induces primary necrosis and activates the immune system.
Steven M Ogbourne - One of the best experts on this subject based on the ideXlab platform.
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Tattoo removal with Ingenol Mebutate
Clinical Cosmetic and Investigational Dermatology, 2017Co-Authors: Sarahjane Cozzi, Cini James, Steven M Ogbourne, Thuy T. Le, Andreas SuhrbierAbstract:An increasing number of people are getting tattoos; however, many regret the decision and seek their removal. Lasers are currently the most commonly used method for tattoo removal; however, treatment can be lengthy, costly, and sometimes ineffective, especially for certain colors. Ingenol Mebutate is a licensed topical treatment for actinic keratoses. Here, we demonstrate that two applications of 0.1% Ingenol Mebutate can efficiently and consistently remove 2-week-old tattoos from SKH/hr hairless mice. Treatment was associated with relocation of tattoo microspheres from the dermis into the posttreatment eschar. The skin lesion resolved about 20 days after treatment initiation, with some cicatrix formation evident. The implications for using Ingenol Mebutate for tattoo removal in humans are discussed.; ;
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effective treatment of squamous cell carcinomas with Ingenol Mebutate gel in immunologically intact skh1 mice
Archives of Dermatological Research, 2013Co-Authors: Sarahjane Cozzi, Cini James, Steven M Ogbourne, Thuy T. Le, Andreas SuhrbierAbstract:Ingenol Mebutate has recently been approved by the Federal Drug Administration (USA) as a topical treatment for actinic keratoses. Herein, we describe the efficacy of Ingenol Mebutate for the topical treatment of squamous cell carcinoma (SCC) using a wild-type mouse model (SKH1) and the UV-induced mouse SCC cell line, T7. Daily treatment for 2 days with 0.25 % Ingenol Mebutate gel produced a cure rate of 70 %, with 0 % for placebo gel. Electron microscopy revealed swelling of cancer cell mitochondria within 1 h, with disruption of the inner mitochondrial membranes evident at 6 h post treatment. Primary necrosis of cancer cells was clearly evident by 24 h. Treatment was associated with local haemorrhage and a prodigious neutrophil infiltrate, with anti-T7 antibodies also detected. This is the first report of the successful treatment of SCC tumours with Ingenol Mebutate gel in wild-type mice, and supports the view that Ingenol Mebutate induces primary necrosis and activates the immune system.
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Ingenol Mebutate field directed treatment of uvb damaged skin reduces lesion formation and removes mutant p53 patches
Journal of Investigative Dermatology, 2012Co-Authors: Sarahjane Cozzi, Cini James, Steven M Ogbourne, Blake Ferguson, Joy Gardner, Frank R De Gruijl, Heggert Rebel, Thibaut Larcher, Andreas SuhrbierAbstract:Skin cancer is the most prevalent cancer worldwide and is primarily caused by chronic UV exposure. Here, we describe the topical field-directed treatment of SKH1/hr mice with UVB-damaged skin with Ingenol Mebutate, a new topical drug shown to be effective for the treatment of actinic keratosis (AK). Application of 0.05% Ingenol Mebutate gel to photo-damaged skin resulted in a ≈70% reduction in the number of skin lesions that subsequently emerged compared with placebo treatment. Ingenol Mebutate treatment also reduced the number of mutant p53 keratinocyte patches by ≈70%. The treatment resulted in epidermal cell death, acute inflammation, recruitment of neutrophils, hemorrhage, and eschar formation, all of which resolved over several weeks. Ingenol Mebutate field-directed treatment might thus find utility in the removal of subclinical precancerous cells from UV-damaged skin. Field-directed treatment may be particularly suitable for patients who have AKs surrounded by UV-damaged skin.
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Ingenol Mebutate field-directed treatment of UVB damaged skin reduces lesion formation and removes mutant p53 patches
Journal of Investigative Dermatology, 2012Co-Authors: Sarahjane Cozzi, Cini James, Steven M Ogbourne, Blake Ferguson, Joy Gardner, Frank R De Gruijl, Heggert Rebel, Thibaut Larcher, Thuy T. Lee, Andreas SuhrbierAbstract:Skin cancer is the most prevalent cancer worldwide and is primarily caused by chronic UV exposure. Here, we describe the topical field-directed treatment of SKH1/hr mice with UVB-damaged skin with Ingenol Mebutate, a new topical drug shown to be effective for the treatment of actinic keratosis (AK). Application of 0.05% Ingenol Mebutate gel to photo-damaged skin resulted in a E70% reduction in the number of skin lesions that subsequently emerged compared with placebo treatment. Ingenol Mebutate treatment also reduced the number of mutant p53 keratinocyte patches by E70%. The treatment resulted in epidermal cell death, acute inflammation, recruitment of neutrophils, hemorrhage, and eschar formation, all of which resolved over several weeks. Ingenol Mebutate field-directed treatment might thus find utility in the removal of subclinical precancerous cells from UV-damaged skin. Field-directed treatment may be particularly suitable for patients who have AKs surrounded by UV-damaged skin.
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pep005 Ingenol Mebutate gel for the topical treatment of superficial basal cell carcinoma results of a randomized phase iia trial
Australasian Journal of Dermatology, 2010Co-Authors: Greg Siller, Peter Welburn, Janelle Katsamas, Robert Rosen, Michael Freeman, Steven M OgbourneAbstract:Objectives: To evaluate the safety of two applications of PEP005 (Ingenol Mebutate) gel in superficial basal cell carcinoma. Efficacy was a secondary end-point. Methods: Randomized, vehicle-controlled, phase IIa study conducted at eight private dermatology clinics in Australia. A total of 60 patients with histologically confirmed superficial basal cell carcinoma (lesion size, 4–15 mm) were randomized to treatment on days 1 and 2 (Arm A) or days 1 and 8 (Arm B) and, within each arm, to Ingenol Mebutate gel, 0.0025%, 0.01% or 0.05%, or vehicle gel. The main outcome measures were the incidence and severity of adverse events and local skin responses in Arms A and B; lesion clearance at day 85 was a secondary measure. Results: The incidence of adverse events was low. One patient treated with Ingenol Mebutate gel, 0.05% in Arm A experienced severe flaking/scaling/dryness extending beyond the application site. Non-severe, potentially treatment-related events included erythema extending beyond the application site, application-site pain and headache in two patients each. Six patients in Arm A had one or more severe local skin responses. Efficacy appeared to be dose-related and there was a trend towards higher clinical and histological lesion clearance rates in Arm A compared with Arm B. Histological clearance occurred in five of eight patients (63%) randomized to Ingenol Mebutate gel, 0.05% in Arm A. Conclusions: Two applications of Ingenol Mebutate gel, 0.05%, are safe and have efficacy in patients with superficial basal cell carcinoma.
Janelle Katsamas - One of the best experts on this subject based on the ideXlab platform.
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pep005 Ingenol Mebutate gel for the topical treatment of superficial basal cell carcinoma results of a randomized phase iia trial
Australasian Journal of Dermatology, 2010Co-Authors: Greg Siller, Peter Welburn, Janelle Katsamas, Robert Rosen, Michael Freeman, Steven M OgbourneAbstract:Objectives: To evaluate the safety of two applications of PEP005 (Ingenol Mebutate) gel in superficial basal cell carcinoma. Efficacy was a secondary end-point. Methods: Randomized, vehicle-controlled, phase IIa study conducted at eight private dermatology clinics in Australia. A total of 60 patients with histologically confirmed superficial basal cell carcinoma (lesion size, 4–15 mm) were randomized to treatment on days 1 and 2 (Arm A) or days 1 and 8 (Arm B) and, within each arm, to Ingenol Mebutate gel, 0.0025%, 0.01% or 0.05%, or vehicle gel. The main outcome measures were the incidence and severity of adverse events and local skin responses in Arms A and B; lesion clearance at day 85 was a secondary measure. Results: The incidence of adverse events was low. One patient treated with Ingenol Mebutate gel, 0.05% in Arm A experienced severe flaking/scaling/dryness extending beyond the application site. Non-severe, potentially treatment-related events included erythema extending beyond the application site, application-site pain and headache in two patients each. Six patients in Arm A had one or more severe local skin responses. Efficacy appeared to be dose-related and there was a trend towards higher clinical and histological lesion clearance rates in Arm A compared with Arm B. Histological clearance occurred in five of eight patients (63%) randomized to Ingenol Mebutate gel, 0.05% in Arm A. Conclusions: Two applications of Ingenol Mebutate gel, 0.05%, are safe and have efficacy in patients with superficial basal cell carcinoma.
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randomized double blind double dummy vehicle controlled study of Ingenol Mebutate gel 0 025 and 0 05 for actinic keratosis
Journal of The American Academy of Dermatology, 2009Co-Authors: Lawrence Anderson, George J Schmieder, Philip W Werschler, Eduardo Tschen, Dow Stough, Maurice H. T. Ling, Janelle KatsamasAbstract:Background There is a need for improved medical approaches to the treatment of actinic keratosis. Ingenol Mebutate, a diterpene ester extracted and purified from the plant Euphorbia peplus , is being evaluated as a topical therapy for actinic keratosis. Objective Assess the efficacy and safety of Ingenol Mebutate (formerly PEP005) gel at 3 dosing regimens for the treatment of actinic keratosis. Methods Patients with non-facial actinic keratoses applied vehicle gel for 3 days, Ingenol Mebutate gel, 0.025% for 3 days, or Ingenol Mebutate gel, 0.05% for 2 or 3 days, with an 8-week follow-up period. Results All 3 active treatments were significantly more effective than vehicle at clearing actinic keratosis lesions, with a dose response observed. The partial clearance rate (primary efficacy end point) for patients treated with Ingenol Mebutate gel ranged from 56.0% to 75.4% compared with 21.7% for vehicle gel ( P = .0002 to P P ≤ .0006) for patients in the Ingenol Mebutate gel treatment groups (range: 40.0% to 54.4%) compared with vehicle (11.7%), as was the baseline clearance rate (range: 42.0% to 57.9% for Ingenol Mebutate gel compared with 13.3% for vehicle, P P Limitations Local skin responses may have suggested active treatment to investigators. Conclusions Short-course, field-directed therapy with Ingenol Mebutate gel for actinic keratoses on non-facial sites seems to be effective with a favorable safety profile and potential benefits over topical agents that require a more prolonged course of treatment.
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Randomized, double-blind, double-dummy, vehicle-controlled study of Ingenol Mebutate gel 0.025% and 0.05% for actinic keratosis.
Journal of The American Academy of Dermatology, 2009Co-Authors: Lawrence Anderson, George J Schmieder, Eduardo Tschen, Dow Stough, W. Philip Werschler, Mark Ling, Janelle KatsamasAbstract:Background There is a need for improved medical approaches to the treatment of actinic keratosis. Ingenol Mebutate, a diterpene ester extracted and purified from the plant Euphorbia peplus , is being evaluated as a topical therapy for actinic keratosis. Objective Assess the efficacy and safety of Ingenol Mebutate (formerly PEP005) gel at 3 dosing regimens for the treatment of actinic keratosis. Methods Patients with non-facial actinic keratoses applied vehicle gel for 3 days, Ingenol Mebutate gel, 0.025% for 3 days, or Ingenol Mebutate gel, 0.05% for 2 or 3 days, with an 8-week follow-up period. Results All 3 active treatments were significantly more effective than vehicle at clearing actinic keratosis lesions, with a dose response observed. The partial clearance rate (primary efficacy end point) for patients treated with Ingenol Mebutate gel ranged from 56.0% to 75.4% compared with 21.7% for vehicle gel ( P = .0002 to P P ≤ .0006) for patients in the Ingenol Mebutate gel treatment groups (range: 40.0% to 54.4%) compared with vehicle (11.7%), as was the baseline clearance rate (range: 42.0% to 57.9% for Ingenol Mebutate gel compared with 13.3% for vehicle, P P Limitations Local skin responses may have suggested active treatment to investigators. Conclusions Short-course, field-directed therapy with Ingenol Mebutate gel for actinic keratoses on non-facial sites seems to be effective with a favorable safety profile and potential benefits over topical agents that require a more prolonged course of treatment.
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randomized double blind double dummy vehicle controlled study of Ingenol Mebutate gel 0 025 and 0 05 for actinic keratosis
Journal of The American Academy of Dermatology, 2009Co-Authors: Lawrence L Anderson, George J Schmieder, Philip W Werschler, Eduardo Tschen, Dow Stough, Mark Ling, Janelle KatsamasAbstract:Background There is a need for improved medical approaches to the treatment of actinic keratosis. Ingenol Mebutate, a diterpene ester extracted and purified from the plant Euphorbia peplus, is being evaluated as a topical therapy for actinic keratosis. Objective Assess the efficacy and safety of Ingenol Mebutate (formerly PEP005) gel at 3 dosing regimens for the treatment of actinic keratosis. Methods Patients with non-facial actinic keratoses applied vehicle gel for 3 days, Ingenol Mebutate gel, 0.025% for 3 days, or Ingenol Mebutate gel, 0.05% for 2 or 3 days, with an 8-week follow-up period. Results All 3 active treatments were significantly more effective than vehicle at clearing actinic keratosis lesions, with a dose response observed. The partial clearance rate (primary efficacy end point) for patients treated with Ingenol Mebutate gel ranged from 56.0% to 75.4% compared with 21.7% for vehicle gel (P = .0002 to P Limitations Local skin responses may have suggested active treatment to investigators. Conclusions Short-course, field-directed therapy with Ingenol Mebutate gel for actinic keratoses on non-facial sites seems to be effective with a favorable safety profile and potential benefits over topical agents that require a more prolonged course of treatment.
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pep005 Ingenol Mebutate gel a novel agent for the treatment of actinic keratosis results of a randomized double blind vehicle controlled multicentre phase iia study
Australasian Journal of Dermatology, 2009Co-Authors: Greg Siller, Peter Welburn, Janelle Katsamas, Kurt Gebauer, Steven M OgbourneAbstract:The sap of the plant Euphorbia peplus is a traditional remedy for skin conditions, including actinic keratosis. The active constituent of the sap is Ingenol Mebutate (Ingenol-3-angelate), formerly known as PEP005. This randomized, double-blind, vehicle-controlled, phase IIa study investigated the safety (and secondarily the efficacy) of two applications of Ingenol Mebutate gel in 58 patients with biopsy-confirmed actinic keratosis. Five preselected lesions were treated with Ingenol Mebutate gel, 0.0025%, 0.01% or 0.05%, or vehicle gel, on days 1 and 2 (Arm A) or days 1 and 8 (Arm B). There were no significant differences in tolerability or efficacy between Arms A and B. Treatment was well tolerated. The most common local skin responses were dose-related erythema, flaking/scaling/dryness and scabbing/crusting. Efficacy was greatest with Ingenol Mebutate gel, 0.05%, which resulted in complete clinical clearance of 71% of treated lesions (P < 0.0001 vs vehicle gel). In addition, 67% of patients treated with Ingenol Mebutate gel, 0.05% had clinical clearance of at least four of five treated lesions (P = 0.0185 vs vehicle gel). Ingenol Mebutate gel is being developed as a short-course topical therapy for actinic keratosis and non-melanoma skin cancer.
James Q. Del Rosso - One of the best experts on this subject based on the ideXlab platform.
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Ingenol Mebutate Topical Gel A Status Report On Clinical Use Beyond Actinic Keratosis.
The Journal of clinical and aesthetic dermatology, 2016Co-Authors: James Q. Del RossoAbstract:: Ingenol Mebutate is available as a topical gel formulation approved for the treatment of actinic keratosis. Two different concentrations are available for treatment of actinic keratoses at specific anatomic sites with the advantages of short durations of therapy and limited "down time" related to visible inflammation as compared to other topical agents. Due to the various modes of action of Ingenol Mebutate, it has also been used for treatment of disease states other than actinic keratosis. This manuscript discusses the suggested modes of action of Ingenol Mebutate and reviews publications on the use of Ingenol Mebutate gel for cutaneous disorders other than actinic keratosis, including squamous cell carcinoma in-situ, basal cell carcinoma, actinic cheilitis, anogenital warts, and others. Author commentaries are also included with the goal of providing relevant clinical insights.
Sarahjane Cozzi - One of the best experts on this subject based on the ideXlab platform.
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Tattoo removal with Ingenol Mebutate
Clinical Cosmetic and Investigational Dermatology, 2017Co-Authors: Sarahjane Cozzi, Cini James, Steven M Ogbourne, Thuy T. Le, Andreas SuhrbierAbstract:An increasing number of people are getting tattoos; however, many regret the decision and seek their removal. Lasers are currently the most commonly used method for tattoo removal; however, treatment can be lengthy, costly, and sometimes ineffective, especially for certain colors. Ingenol Mebutate is a licensed topical treatment for actinic keratoses. Here, we demonstrate that two applications of 0.1% Ingenol Mebutate can efficiently and consistently remove 2-week-old tattoos from SKH/hr hairless mice. Treatment was associated with relocation of tattoo microspheres from the dermis into the posttreatment eschar. The skin lesion resolved about 20 days after treatment initiation, with some cicatrix formation evident. The implications for using Ingenol Mebutate for tattoo removal in humans are discussed.; ;
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effective treatment of squamous cell carcinomas with Ingenol Mebutate gel in immunologically intact skh1 mice
Archives of Dermatological Research, 2013Co-Authors: Sarahjane Cozzi, Cini James, Steven M Ogbourne, Thuy T. Le, Andreas SuhrbierAbstract:Ingenol Mebutate has recently been approved by the Federal Drug Administration (USA) as a topical treatment for actinic keratoses. Herein, we describe the efficacy of Ingenol Mebutate for the topical treatment of squamous cell carcinoma (SCC) using a wild-type mouse model (SKH1) and the UV-induced mouse SCC cell line, T7. Daily treatment for 2 days with 0.25 % Ingenol Mebutate gel produced a cure rate of 70 %, with 0 % for placebo gel. Electron microscopy revealed swelling of cancer cell mitochondria within 1 h, with disruption of the inner mitochondrial membranes evident at 6 h post treatment. Primary necrosis of cancer cells was clearly evident by 24 h. Treatment was associated with local haemorrhage and a prodigious neutrophil infiltrate, with anti-T7 antibodies also detected. This is the first report of the successful treatment of SCC tumours with Ingenol Mebutate gel in wild-type mice, and supports the view that Ingenol Mebutate induces primary necrosis and activates the immune system.
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Ingenol Mebutate field directed treatment of uvb damaged skin reduces lesion formation and removes mutant p53 patches
Journal of Investigative Dermatology, 2012Co-Authors: Sarahjane Cozzi, Cini James, Steven M Ogbourne, Blake Ferguson, Joy Gardner, Frank R De Gruijl, Heggert Rebel, Thibaut Larcher, Andreas SuhrbierAbstract:Skin cancer is the most prevalent cancer worldwide and is primarily caused by chronic UV exposure. Here, we describe the topical field-directed treatment of SKH1/hr mice with UVB-damaged skin with Ingenol Mebutate, a new topical drug shown to be effective for the treatment of actinic keratosis (AK). Application of 0.05% Ingenol Mebutate gel to photo-damaged skin resulted in a ≈70% reduction in the number of skin lesions that subsequently emerged compared with placebo treatment. Ingenol Mebutate treatment also reduced the number of mutant p53 keratinocyte patches by ≈70%. The treatment resulted in epidermal cell death, acute inflammation, recruitment of neutrophils, hemorrhage, and eschar formation, all of which resolved over several weeks. Ingenol Mebutate field-directed treatment might thus find utility in the removal of subclinical precancerous cells from UV-damaged skin. Field-directed treatment may be particularly suitable for patients who have AKs surrounded by UV-damaged skin.
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Ingenol Mebutate field-directed treatment of UVB damaged skin reduces lesion formation and removes mutant p53 patches
Journal of Investigative Dermatology, 2012Co-Authors: Sarahjane Cozzi, Cini James, Steven M Ogbourne, Blake Ferguson, Joy Gardner, Frank R De Gruijl, Heggert Rebel, Thibaut Larcher, Thuy T. Lee, Andreas SuhrbierAbstract:Skin cancer is the most prevalent cancer worldwide and is primarily caused by chronic UV exposure. Here, we describe the topical field-directed treatment of SKH1/hr mice with UVB-damaged skin with Ingenol Mebutate, a new topical drug shown to be effective for the treatment of actinic keratosis (AK). Application of 0.05% Ingenol Mebutate gel to photo-damaged skin resulted in a E70% reduction in the number of skin lesions that subsequently emerged compared with placebo treatment. Ingenol Mebutate treatment also reduced the number of mutant p53 keratinocyte patches by E70%. The treatment resulted in epidermal cell death, acute inflammation, recruitment of neutrophils, hemorrhage, and eschar formation, all of which resolved over several weeks. Ingenol Mebutate field-directed treatment might thus find utility in the removal of subclinical precancerous cells from UV-damaged skin. Field-directed treatment may be particularly suitable for patients who have AKs surrounded by UV-damaged skin.