Optimizing management of actinic keratosis and photodamaged skin: utilizing a stepwise approach.

PubMed

Lee, Andrew D; Jorizzo, Joseph L

2009-09-01

The incidence of photodamaged skin and skin lesions of all degrees of severity, from actinic keratosis (AK) to skin cancers, has dramatically increased. Actinic keratoses are pathologic, reflecting damage of essential skin cell functions and potentially progressing to invasive squamous cell carcinoma (SCC). The rate of progression is uncertain but may be as high as 10%. Because it is impossible to predict which AKs will progress to SCC, all lesions should be treated. Options include topical therapies, cryotherapy, curettage, and photodynamic therapy. Unfortunately, many individuals do not seek treatment or avoid it because of irritation, discomfort, and concern for scarring. Combining field-directed therapy and cryotherapy has been more effective than cryotherapy alone. Incorporating patient education with treatment may optimize outcomes. We propose a comprehensive 5-step approach for managing AK lesions and photodamaged skin that includes periodic clinical skin examinations; treating AK lesions with a combination of field- and lesion-directed therapy; and patient education regarding sun-protective measures and regular skin self-examinations.

Clinical forms of actinic keratosis and levels of dysplasia of the epidermis.

PubMed

Oshyvalova, Olena O; Kaliuzhna, Lydia D; Kropelnytskyi, Vladislav O

Introduction: Actinic keratosis (AK) is precancerous skin lesion that occurs in the sun-exposedskin areas characterized by local intraepidermal dysplasia of different severity (KIN I, KIN II and KIN III). The aim of this research was to study distribution patterns and morphological features of AK histological types. Materials and Methods: The study included skin biopsy material from 68 patients with different clinical forms of AK. The diagnosis of AK was histologically confirmed in 100% of cases. Results: There were 63.21% of men and 36.8% of women among all patients with AK. The average age of patients was 73.3 ± 8.3.The most common clinico-histological forms of actinic keratosis were typical (41.2%), hypertrophic (16.2%), atrophic (14.7%) and pigmentary (11.7%), bowenoid (8.8%), acantholytic (7.4%). Among the rate of epidermal dysplasia there diagnosed cases of KIN І (50%), KIN ІІ (36.8%) and KIN III (13.2%). Conclusions: It was found a direct correlation between KIN I and typical and pigment forms of AK, KIN II and hypertrophic and bowenoid forms of AK.

Increased number of mast cells in the dermis in actinic keratosis lesions effectively treated with imiquimod.

PubMed

Oyama, Satomi; Funasaka, Yoko; Tsuchiya, Shin-Ichi; Kawana, Seiji; Saeki, Hidehisa

2017-08-01

Actinic keratosis (AK) is a cutaneous cancer in situ which develops as a result of excessive exposure to ultraviolet (UV). Toll-like receptor (TLR)7 agonist imiquimod is a topical immune response modifier and is effective for the treatment of non-melanoma skin cancers. Recently, the diagnostic role of the dermatoscope has been reported in the course of treatment of AK. In addition, mast cells are now considered to contribute to both the innate and adaptive immune systems in topical imiquimod therapy. We assessed the effect of imiquimod treatment by dermatoscopic and immunohistochemical findings in 14 patients with a total of 21 AK lesions. With the dermatoscope, though the mean erythema score was not significantly different between the cured lesions and the unresponsive lesions, the erythema/red pseudo-network ("strawberry") pattern was decreased significantly in the cured lesions. By immunohistochemistry, the number of Ki-67-positive proliferative cells in the epidermis was decreased and that of CD117-positive mast cells in the dermis was increased in the responding lesions. To the best of our knowledge, this is the first study demonstrating that the number of mast cells in the dermis was increased in AK lesions effectively treated with imiquimod. Our present result suggests that mast cells may contribute an antitumor effect in human skin treated with topical imiquimod. © 2017 Japanese Dermatological Association.

A consensus approach to improving patient adherence and persistence with topical treatment for actinic keratosis

PubMed Central

Stockfleth, Eggert; Peris, Ketty; Guillen, Carlos; Cerio, Rino; Basset-Seguin, Nicole; Foley, Peter; Sanches, José; Culshaw, Alex; Erntoft, Sandra; Lebwohl, Mark

2015-01-01

Background Topical therapy is important in the treatment of actinic keratosis, but guidance for improving adherence/persistence during topical therapy is still lacking. Objectives To utilize expert consensus to generate a list of recommendations to improve real-world efficacy when prescribing topical therapy for actinic keratosis. Methods An expert panel of eight dermatologists was convened to generate recommendations based on facilitated discussion and consensus generation using a modified Delphi session. The recommendations were ratified with the expert panel. Results Facilitated discussion generated 31 issues within five themes, which were prioritized using expert voting. Consensus was achieved on the importance of short and simple treatment regimens for maximizing patient compliance, physician awareness of the progression of actinic keratosis to squamous cell carcinoma, provision of appropriate patient information, and the use of effective communication strategies to educate physicians about actinic keratosis. Based on these key findings, eight recommendations were generated. Conclusions The recommendations will assist physicians when prescribing topical actinic keratosis therapy. Further research should focus on the types of patient outcomes that are influenced by the characteristics of topical field therapy. PMID:25865875

MAL Daylight Photodynamic Therapy for Actinic Keratosis: Clinical and Imaging Evaluation by 3D Camera.

PubMed

Cantisani, Carmen; Paolino, Giovanni; Pellacani, Giovanni; Didona, Dario; Scarno, Marco; Faina, Valentina; Gobello, Tommaso; Calvieri, Stefano

2016-07-11

Non-melanoma skin cancer is the most common skin cancer with an incidence that varies widely worldwide. Among them, actinic keratosis (AK), considered by some authors as in situ squamous cell carcinoma (SCC), are the most common and reflect an abnormal multistep skin cell development due to the chronic ultraviolet (UV) light exposure. No ideal treatment exists, but the potential risk of their development in a more invasive form requires prompt treatment. As patients usually present with multiple AK on fields of actinic damage, there is a need for effective, safe, simple and short treatments which allow the treatment of large areas. To achieve this, daylight photodynamic therapy (DL-PDT) is an innovative treatment for multiple mild actinic keratosis, well tolerated by patients. Patients allocated to the PDT unit, affected by multiple mild-moderate and severe actinic keratosis on sun-exposed areas treated with DL-PDT, were clinically evaluated at baseline and every three months with an Antera 3D, Miravex(©) camera. Clinical and 3D images were performed at each clinical check almost every three months. In this retrospective study, 331 patients (56.7% male, 43.3% female) were treated with DL-PDT. We observed a full clearance in more than two-thirds of patients with one or two treatments. Different responses depend on the number of lesions and on their severity; for patients with 1-3 lesions and with grade I or II AK, a full clearance was reached in 85% of cases with a maximum of two treatments. DL-PDT in general improved skin tone and erased sun damage. Evaluating each Antera 3D images, hemoglobin concentration and pigmentation, a skin color and tone improvement in 310 patients was observed. DL-PDT appears as a promising, effective, simple, tolerable and practical treatment for actinic damage associated with AK, and even treatment of large areas can be with little or no pain. The 3D imaging allowed for quantifying in real time the aesthetic benefits of DL

MAL Daylight Photodynamic Therapy for Actinic Keratosis: Clinical and Imaging Evaluation by 3D Camera

PubMed Central

Cantisani, Carmen; Paolino, Giovanni; Pellacani, Giovanni; Didona, Dario; Scarno, Marco; Faina, Valentina; Gobello, Tommaso; Calvieri, Stefano

2016-01-01

Non-melanoma skin cancer is the most common skin cancer with an incidence that varies widely worldwide. Among them, actinic keratosis (AK), considered by some authors as in situ squamous cell carcinoma (SCC), are the most common and reflect an abnormal multistep skin cell development due to the chronic ultraviolet (UV) light exposure. No ideal treatment exists, but the potential risk of their development in a more invasive form requires prompt treatment. As patients usually present with multiple AK on fields of actinic damage, there is a need for effective, safe, simple and short treatments which allow the treatment of large areas. To achieve this, daylight photodynamic therapy (DL-PDT) is an innovative treatment for multiple mild actinic keratosis, well tolerated by patients. Patients allocated to the PDT unit, affected by multiple mild−moderate and severe actinic keratosis on sun-exposed areas treated with DL-PDT, were clinically evaluated at baseline and every three months with an Antera 3D, Miravex© camera. Clinical and 3D images were performed at each clinical check almost every three months. In this retrospective study, 331 patients (56.7% male, 43.3% female) were treated with DL-PDT. We observed a full clearance in more than two-thirds of patients with one or two treatments. Different responses depend on the number of lesions and on their severity; for patients with 1–3 lesions and with grade I or II AK, a full clearance was reached in 85% of cases with a maximum of two treatments. DL-PDT in general improved skin tone and erased sun damage. Evaluating each Antera 3D images, hemoglobin concentration and pigmentation, a skin color and tone improvement in 310 patients was observed. DL-PDT appears as a promising, effective, simple, tolerable and practical treatment for actinic damage associated with AK, and even treatment of large areas can be with little or no pain. The 3D imaging allowed for quantifying in real time the aesthetic benefits of DL

New Topical Treatment Options for Actinic Keratosis: A Systematic Review.

PubMed

Stockfleth, Eggert; Sibbring, Gillian C; Alarcon, Ivette

2016-01-01

This systematic review compared the relative efficacy of 5-fluorouracil 0.5% in salicylic acid 10% (5-FU/SA), ingenol mebutate (IMB) and imiquimod 2.5%/3.75% (IMI) for actinic keratosis on the face, forehead or scalp. Only 11 publications, relating to 7 randomised controlled trials, met inclusion criteria and it was only possible to compare the effect of all 3 treatments on complete clinical clearance, and the effect of 5-FU/SA and IMB on actinic keratosis recurrence rate. Despite a higher vehicle response rate for 5-FU/SA, complete clinical clearance was higher than IMB and IMI (55.4, 42.2, and 25.0-30.6/34.0-35.6%, [corrected] respectively). 5-FU/SA was also associated with lower actinic keratosis recurrence rate than IMB at 12 months post-treatment (32.7 vs. 53.9%). Although qualitative assessment suggested a numerical advantage of 5-FU/SA over IMB and IMI in terms of complete clinical clearance and sustained clearance, clinical data from longer term trials, with comparable outcome measures, are required to corroborate these findings.

A consensus approach to improving patient adherence and persistence with topical treatment for actinic keratosis.

PubMed

Stockfleth, Eggert; Peris, Ketty; Guillen, Carlos; Cerio, Rino; Basset-Seguin, Nicole; Foley, Peter; Sanches, José; Culshaw, Alex; Erntoft, Sandra; Lebwohl, Mark

2015-01-01

Topical therapy is important in the treatment of actinic keratosis, but guidance for improving adherence/persistence during topical therapy is still lacking. To utilize expert consensus to generate a list of recommendations to improve real-world efficacy when prescribing topical therapy for actinic keratosis. An expert panel of eight dermatologists was convened to generate recommendations based on facilitated discussion and consensus generation using a modified Delphi session. The recommendations were ratified with the expert panel. Facilitated discussion generated 31 issues within five themes, which were prioritized using expert voting. Consensus was achieved on the importance of short and simple treatment regimens for maximizing patient compliance, physician awareness of the progression of actinic keratosis to squamous cell carcinoma, provision of appropriate patient information, and the use of effective communication strategies to educate physicians about actinic keratosis. Based on these key findings, eight recommendations were generated. The recommendations will assist physicians when prescribing topical actinic keratosis therapy. Further research should focus on the types of patient outcomes that are influenced by the characteristics of topical field therapy. © 2015 The Authors. International Journal of Dermatology published by John Wiley & Sons Ltd on behalf of International Society of Dermatology.

Ingenol mebutate gel for actinic keratosis: the link between quality of life, treatment satisfaction, and clinical outcomes.

PubMed

Augustin, Matthias; Tu, John H; Knudsen, Kim Mark; Erntoft, Sandra; Larsson, Thomas; Hanke, C William

2015-05-01

Actinic keratosis therapy can elicit unsightly and painful local skin responses; assessment of treatment satisfaction and health-related quality of life (QoL) is important. Ingenol mebutate gel is a novel topical field therapy for actinic keratosis. Post-hoc analyses were performed based on patient-reported outcomes from phase-III trials (n = 1005) to assess the effects of ingenol mebutate on QoL and the relationship between both QoL and treatment satisfaction, and degree of lesion clearance. Patients received ingenol mebutate or vehicle for self-application to a 25-cm(2) contiguous area: 0.015% once daily for 3 consecutive days (face/scalp) or 0.05% once daily for 2 consecutive days (trunk/extremities). QoL (Skindex-16) and Treatment Satisfaction Questionnaire for Medication data were recorded. Significant, positive associations between Treatment Satisfaction Questionnaire for Medication score and degree of clearance were identified for patients in the face/scalp (effectiveness P < .0001 and global satisfaction P = .0002) and trunk/extremities (P < .0001 and P = .0014, respectively) groups. There was a significant association between Skindex-16 score and clearance for patients in the face/scalp group for change in symptoms (P = .0218), emotions (P = .0002), and overall Skindex-16 score (P = .0006) from baseline. Clinical trial population findings may not be generalizable to clinical practice. Ingenol mebutate significantly improved patients' QoL and treatment satisfaction. Improvements were associated with higher degrees of actinic keratosis lesion clearance. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Treatment considerations in actinic keratosis.

PubMed

Goldenberg, G

2017-03-01

The chronic skin condition actinic keratosis (AK) is characterized by the formation of keratotic lesions of variable thickness that are poorly delimited. AK occurs on areas of the skin that have had long-term exposure to the sun or UV radiation. Although AKs may regress, they usually persist and can progress to squamous cell carcinoma (SCC). Clinicians are unable to predict which AKs will progress; therefore, both clinically visible lesions and subclinical, non-visible (i.e. the entire area affected by AK/field cancerization) should be treated. AK treatment options include lesion-directed therapies that target specific AK lesions and field-directed therapies that target multiple clinical lesions and the underlying field damage. This article reviews currently available treatment options in AK, with a focus on patient-applied field therapies, and their suitability according to specific disease characteristics and patient needs. Choice of treatment in AK depends on lesion-, patient- and treatment-related factors and should be individualized. Considerations when choosing a therapy include site of application, treatment duration, surface area of application, tolerability profiles and implications on adherence. Field-directed therapies treat clinical and subclinical damage (i.e. the entire area affected by AK), achieve high rates of sustained clearance of AKs and may reduce the risk of progression to SCC. There is a clear need for field therapies with short duration of treatment and predictable, short-lived, mild local skin reactions that can be used over a large surface area. Therapies with shorter and simpler treatment courses are often associated with better adherence than treatments with longer courses. These may, therefore, represent more appropriate choices in patients for whom convenience and/or adherence are an issue. © 2017 European Academy of Dermatology and Venereology.

Sebaceous carcinoma in association with actinic keratosis: A report of two cases with an immunohistochemical study.

PubMed

Misago, Noriyuki; Kuwashiro, Maki; Tsuruta, Noriko; Narisawa, Yutaka

2015-06-01

We report two cases of sebaceous carcinoma associated with actinic keratosis (AK) with an immunohistochemical study, which suggests the possibility that sebaceous carcinoma really does develop within AK. Case 1 had sebaceous carcinoma arising within the atrophic type AK and case 2 had sebaceous carcinoma associated with bowenoid AK in the periphery and some parts of the overlying epidermis of the lesion. © 2015 Japanese Dermatological Association.

New and current preventive treatment options in actinic keratosis.

PubMed

Arenberger, P; Arenbergerova, M

2017-09-01

Actinic keratosis (AK) is a characteristic skin lesion on skin areas of subjects with mainly phototype I and phototype II, or with specific genetic factors and who are exposed to prolonged ultraviolet radiation. AK may be considered a precursor of in situ squamous cell carcinoma (SCC), a type of non-melanoma skin cancer (NMSC). However, it is still not possible to predict which AK lesions will develop into SCC. Early treatment of AK is therefore recommended. Despite the increasing number of patients with AK developing into SCC, to date, there is still no clear suggestion of therapeutic strategy for AK. Current treatment consists of a multitude of topical lesion-directed or field-directed therapies or a combination of both. Recently, orally administered nicotinamide has shown to significantly reduce rates of new NMSC and AK in high-risk patients. This study aims to provide an update on the most relevant information about AK and to provide an insight into current and new treatment options. © 2017 European Academy of Dermatology and Venereology.

Management of actinic keratosis.

PubMed

2013-07-01

Actinic keratoses are common, often multiple, epidermal lesions found mainly on the sun-exposed skin of fair-skinned middle-aged and older people.(1) Over time, lesions may remain unchanged or may proliferate, regress, reappear or develop into squamous cell carcinoma (SCC).(2) Detectable (spot) lesions are often associated with alteration of the surrounding skin (field) where subclinical lesions might be present.(2) Interventions may target individual or multiple lesions or a whole field.(2) Here, we update our previous review(3) on the prevention and treatment of actinic keratoses, focusing on the licensed treatments most commonly used in the UK and recommended in UK guidelines.

Comparison of three light doses in the photodynamic treatment of actinic keratosis using mathematical modeling

NASA Astrophysics Data System (ADS)

Vignion-Dewalle, Anne-Sophie; Betrouni, Nacim; Tylcz, Jean-Baptiste; Vermandel, Maximilien; Mortier, Laurent; Mordon, Serge

2015-05-01

Photodynamic therapy (PDT) is an emerging treatment modality for various diseases, especially for cancer therapy. Although high efficacy is demonstrated for PDT using standardized protocols in nonhyperkeratotic actinic keratoses, alternative light doses expected to increase efficiency, to reduce adverse effects or to expand the use of PDT, are still being evaluated and refined. We propose a comparison of the three most common light doses in the treatment of actinic keratosis with 5-aminolevulinic acid PDT through mathematical modeling. The proposed model is based on an iterative procedure that involves determination of the local fluence rate, updating of the local optical properties, and estimation of the local damage induced by the therapy. This model was applied on a simplified skin sample model including an actinic keratosis lesion, with three different light doses (red light dose, 37 J/cm2, 75 mW/cm2, 500 s blue light dose, 10 J/cm2, 10 mW/cm2, 1000 s and daylight dose, 9000 s). Results analysis shows that the three studied light doses, although all efficient, lead to variable local damage. Defining reference damage enables the nonoptimal parameters for the current light doses to be refined and the treatment to be more suitable.

Automated Detection of Actinic Keratoses in Clinical Photographs

PubMed Central

Hames, Samuel C.; Sinnya, Sudipta; Tan, Jean-Marie; Morze, Conrad; Sahebian, Azadeh; Soyer, H. Peter; Prow, Tarl W.

2015-01-01

Background Clinical diagnosis of actinic keratosis is known to have intra- and inter-observer variability, and there is currently no non-invasive and objective measure to diagnose these lesions. Objective The aim of this pilot study was to determine if automatically detecting and circumscribing actinic keratoses in clinical photographs is feasible. Methods Photographs of the face and dorsal forearms were acquired in 20 volunteers from two groups: the first with at least on actinic keratosis present on the face and each arm, the second with no actinic keratoses. The photographs were automatically analysed using colour space transforms and morphological features to detect erythema. The automated output was compared with a senior consultant dermatologist’s assessment of the photographs, including the intra-observer variability. Performance was assessed by the correlation between total lesions detected by automated method and dermatologist, and whether the individual lesions detected were in the same location as the dermatologist identified lesions. Additionally, the ability to limit false positives was assessed by automatic assessment of the photographs from the no actinic keratosis group in comparison to the high actinic keratosis group. Results The correlation between the automatic and dermatologist counts was 0.62 on the face and 0.51 on the arms, compared to the dermatologist’s intra-observer variation of 0.83 and 0.93 for the same. Sensitivity of automatic detection was 39.5% on the face, 53.1% on the arms. Positive predictive values were 13.9% on the face and 39.8% on the arms. Significantly more lesions (p<0.0001) were detected in the high actinic keratosis group compared to the no actinic keratosis group. Conclusions The proposed method was inferior to assessment by the dermatologist in terms of sensitivity and positive predictive value. However, this pilot study used only a single simple feature and was still able to achieve sensitivity of detection of 53

Dermatoscopic Findings of Seborrheic Keratosis in Melanoma.

PubMed

Brandão, Maria Luiza; Oliveira Lima, Cíntia Maria; Moura, Heloísa Helena; Ishida, Cleide; Campos-do-Carmo, Gabriella; Cuzzi, Tullia; Ramos-E-Silva, Marcia

2016-06-01

Cutaneous melanoma may in some instances be confused with seborrheic keratosis, which is a very common neoplasia, more often mistaken for actinic keratosis and verruca vulgaris. Melanoma may clinically resemble seborrheic keratosis and should be considered as its possible clinical simulator. We report a case of melanoma with dermatoscopic characteristics of seborrheic keratosis and emphasize the importance of the dermatoscopy algorithm in differentiating between a melanocytic and a non-melanocytic lesion, of the excisional biopsy for the establishment of the diagnosis of cutaneous tumors, and of the histopathologic examination in all surgically removed samples.

Differences in Disease-specific Quality of Life in Patients with Actinic Keratosis in Australia and Denmark.

PubMed

Miller, Iben Marie; Vinding, Gabrielle; Zarchi, Kian; Esmann, Solveig; Murrell, Dedee F; Jemec, Gregor B

2016-04-01

Actinic keratosis (AK) negatively influences patient quality of life as measured by the disease-specific Actinic Keratosis Quality of Life (AKQoL) questionnaire. The quality of life in Australian patients was significantly less affected than in Danish patients. We hypothesize that general factors such as public awareness and cultural connotations of AK, may influence the impact of AK on quality of life (QoL).

Actinic Keratosis and Non-Invasive Diagnostic Techniques: An Update

PubMed Central

Casari, Alice; Chester, Johanna; Pellacani, Giovanni

2018-01-01

Actinic keratosis represents the earliest manifestation of non-melanoma skin cancer. Because of their risk of progression to invasive squamous cell carcinoma, an earlier diagnosis and treatment are mandatory. Their diagnosis sometimes could represent a challenge even for expert dermatologists. Dermoscopy, confocal laser microscopy and optical coherence tomography could help clinicians in diagnosis. PMID:29316678

Actinic keratosis: a cross-sectional study of disease characteristics and treatment patterns in Danish dermatology clinics.

PubMed

Erlendsson, Andrés M; Egekvist, Henrik; Lorentzen, Henrik F; Philipsen, Peter A; Stausbøl-Grøn, Birgitte; Stender, Ida M; Haedersdal, Merete

2016-03-01

The incidence of actinic keratosis (AK) is increasing, and several treatment options are available. The aim of this study was to describe clinical characteristics and treatment patterns in patients with AK treated by Danish dermatologists. A multicenter, non-interventional, cross-sectional study was conducted. Three dermatology hospital departments and seven private dermatology clinics enrolled eligible AK patients consecutively during one week. A total of 312 patients were included. Non-melanoma skin cancer (NMSC) was previously reported in 51.0% of patients and currently suspected in 9.4% of AK-affected anatomical regions. Lesions of AK were located primarily on the face (38.6%), scalp (12.8%), and hands (11.2%). Actinic keratosis commonly presented with multiple AK lesions (38.6%) and field cancerization (38.5%). The treatments used most frequently were cryotherapy (57.7%) and photodynamic therapy (PDT) with methyl aminolevulinate (17.1%) and imiquimod (11.2%). The likelihood of receiving cryotherapy was higher for men (odds ratio [OR] 1.65, 95% confidence interval [CI] 1.10-2.47) and increased with age (2.2% per year, 0.4-4.0%). PDT represented the most frequently applied treatment for severe actinic damage and was more likely to be prescribed to women (OR 4.08, 95% CI 2.22-7.47) and young patients (OR 0.97 per year, 95% CI 0.95-0.99). The prevalence of severe actinic damage (17.3% versus 9.6%) and intake of immunosuppressive medication (29.0 versus 2.0) were higher among hospital patients compared with those treated in private practices (P < 0.0001). The majority of AK patients in Danish dermatology clinics have a history of skin cancer, and NMSC is suspected in almost 10% of AK-affected regions. Cryotherapy is the most frequently used treatment overall, except in instances of severe actinic damage, in which PDT is the first-choice treatment. © 2015 The International Society of Dermatology.

Clinical Response to Ingenol Mebutate in Patients With Actinic Keratoses.

PubMed

Batalla, A; Flórez, Á; Feal, C; Peón, G; Abalde, M T; Salgado-Boquete, L; de la Torre, C

2015-12-01

Cryotherapy is the most common treatment for actinic keratosis, but its effect is limited to individual lesions. Several topical drugs, however, are available that, in addition to treating individual actinic keratoses, target field cancerization and thereby act on subclinical lesions. Examples are 5-fluorouracil, imiquimod, diclofenac, and ingenol mebutate. We report on 17 patients with actinic keratoses treated with ingenol mebutate and describe our findings on treatment effectiveness, adherence, and tolerance. Complete and partial response rates were 35% and 53%, respectively. Ninety-four percent of patients fully adhered to treatment and 18% developed severe local reactions. Ingenol mebutate is an effective treatment for actinic keratosis. Although it has a similar rate of local reactions to other treatments available for actinic keratosis, its short treatment regimen favors better adherence. Copyright © 2014 Elsevier España, S.L.U. y AEDV. All rights reserved.

Spanish-Portuguese consensus statement on use of daylight-mediated photodynamic therapy with methyl aminolevulinate in the treatment of actinic keratosis.

PubMed

Gilaberte, Y; Aguilar, M; Almagro, M; Correia, O; Guillén, C; Harto, A; Pérez-García, B; Pérez-Pérez, L; Redondo, P; Sánchez-Carpintero, I; Serra-Guillén, C; Valladares, L M

2015-10-01

Daylight-mediated photodynamic therapy (PDT) is a new type of PDT that is as effective as conventional PDT in grade 1 and 2 actinic keratosis but with fewer adverse effects, resulting in greater efficiency. The climatic conditions in the Iberian Peninsula require an appropriately adapted consensus protocol. We describe a protocol for the treatment of grade 1 and 2 actinic keratosis with daylight-mediated PDT and methyl aminolevulinate (MAL) adapted to the epidemiological and clinical characteristics of Spanish and Portuguese patients and the climatic conditions of both countries. Twelve dermatologists from different parts of Spain and Portugal with experience in the treatment of actinic keratosis with PDT convened to draft a consensus statement for daylight-mediated PDT with MAL in these countries. Based on a literature review and their own clinical experience, the group developed a recommended protocol. According to the recommendations adopted, patients with multiple grade 1 and 2 lesions, particularly those at risk of developing cancer, are candidates for this type of therapy. Daylight-mediated PDT can be administered throughout the year, although it is not indicated at temperatures below 10°C or at excessively high temperatures. Likewise, therapy should not be administered when it is raining, snowing, or foggy. The procedure is simple, requiring application of a sunscreen with a protection factor of at least 30 based exclusively on organic filters, appropriate preparation of the lesions, application of MAL without occlusion, and activation in daylight for 2hours. This consensus statement represents a practical and detailed guideline to achieve maximum effectiveness of daylight-mediated PDT with MAL in Spain and Portugal with minimal adverse effects. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

Diclofenac Sodium 3% in Hyaluronic Acid 2.5% Gel Significantly Diminishes the Actinic Keratosis Area and Severity Index.

PubMed

Schmitz, Lutz; Gupta, Girish; Segert, Marc Hanno; Kost, Ricarda; Sternberg, Julia; Gambichler, Thilo; Stockfleth, Eggert; Dirschka, Thomas

2018-05-23

Actinic keratosis area and severity index (AKASI) is a new assessment tool to quantify the severity of actinic damage on the head. Thus far, it has not been evaluated in monitoring the efficacy of field-directed topical treatments in actinic keratosis (AK) in routine clinical practice. Thus, the aim of this study was to determine treatment outcomes by using AKASI 3 months after the initiation of topical application of diclofenac sodium 3% in hyaluronic acid 2.5% gel (DFS) in patients with AKs on the head. We performed a retrospective analysis of patients with AKs who had AKASI scores prior to and after treatment with DFS. Of the 24 patients included, 20 (83.3%) showed an improvement in AKASI, 2 (8.3%) a stable AKASI, and 2 (8.3%) a worsening of AKASI after a median (interquartile range) follow-up period of 91.5 days (89.8-104.3). The median AKASI reduction was 31.4% (16.7-59.1). The Wilcoxon test showed significant differences (p = 0.0008) between baseline and posttreatment AKASI values. AKASI is an easy-to-use quantitative tool for assessing the treatment outcome of field-directed therapies. Field-directed therapies of AK should no longer be monitored by assessments based on lesion counts alone. © 2018 S. Karger AG, Basel.

Light emitting fabric for photodynamic treatment of actinic keratosis

NASA Astrophysics Data System (ADS)

Thecua, E.; Vicentini, C.; Vignion, A.-S.; Lecomte, F.; Deleporte, P.; Mortier, L.; Szeimies, R.-M.; Mordon, S.

2017-02-01

The integration of optical fibers into flexible textile structures, by using knitting or weaving processes can allow the development of flexible light sources. The paper aims to present a new technology: Light Emitting Fabrics (LEF), which can be used for example for PDT of Actinic Keratosis in Dermatology. The predetermined macro-bending of optical fibers, led to a homogeneous side emission of light over the entire surface of the fabric. Tests showed that additional curvatures when applying the LEF on non-planar surfaces had no impact on light delivery and proved that LEF can adapt to the human morphology. The ability of the LEF, coupled with a 635nm LASER source, to deliver a homogeneous light to lesions is currently assessed in a clinical trial for the treatment of AK of the scalp by PDT. The low irradiance and progressive activation of the photosensitizer ensure a pain reduction, compared to discomfort levels experienced by patients during a conventional PDT session.

Topical photodynamic therapy of actinic keratosis in renal transplant recipients.

PubMed

Piaserico, S; Belloni Fortina, A; Rigotti, P; Rossi, B; Baldan, N; Alaibac, M; Marchini, F

2007-01-01

Organ transplant recipients (OTRs) show an increased risk of precancerous (mostly actinic keratosis [AK]) and cancerous (mostly squamous cell carcinomas [SCC] and basal cell carcinomas [BCC]) cutaneous lesions. Their frequency increases with time after transplantation. AKs seem to progress more often and faster to invasive SCC in OTRs compared with the general population. The steady increase of risk of cutaneous premalignancies and malignancies with time after transplantation is an alarming figure because the number of organ allograft recipients who live for many years after transplantion is rapidly growing. This points out the need to devote more resources to skin cancer prevention, detection, and management. Various therapies, including cryotherapy, topical 5-fluorouracil, imiquimod, topical diclofenac, curettage, electrosurgery, carbon dioxide laser, and surgical excision, are available for AKs. However, most of these are limited by frequent relapses and the presence of multiple lesions over a wide area. Topical photodynamic therapy (PDT) represents an innovative therapeutic approach for nonsurgical treatment of cutaneous precancerous lesions and skin cancers. In this study we confirmed the usefulness of PDT in the treatment of AKs in OTRs, even in lesions relapsing or unresponsive to conventional treatment. We showed a complete response rate of 71%, after 2 treatments sessions that were 2 weeks apart. The response rate of scalp/facial lesions (72%) was higher compared with acral lesions (40%). Topical PDT could represent a useful therapeutic alternative for AKs in OTRs because large lesions can be treated with excellent cosmetic outcome.

Swiss (German) Version of the Actinic Keratosis Quality of Life questionnaire.

PubMed

Meier, Larissa S; Schubert, Maria; Göksu, Yasemin; Esmann, Solveig; Vinding, Gabrielle R; Jemec, Gregor B E; Hofbauer, Günther F L

2018-04-18

Actinic keratosis (AK) is a sun-induced skin lesion that may progress to invasive squamous cell carcinoma of the skin. Recently, the Actinic Keratosis Quality of Life questionnaire (AKQoL) was designed for patients with AK in Denmark as a specific quality of life instrument for AK patients. The objective of this study was to adapt the AKQoL for the German language region of Switzerland and to evaluate its psychometric properties (validity, reliability). Translation and cultural adaptation of the questionnaire were assessed by using the technique of cognitive interviewing. During the translation process, 34 patients with AK from the Department of Dermatology, University Hospital Zurich, were interviewed in 3 sessions of cognitive interviewing. The translated questionnaire was then distributed together with the Dermatology Life Quality Index (DLQI) to a second group of 113 patients for validation and reliability testing. Within this group, we measured the internal consistency by the Cronbach coefficient α and Spearman correlation coefficient between the AKQoL and the DLQI. The problems encountered during the translation process led to changes in 5 categories as described by Epstein: stylistic changes, change in breadth, change in actual meaning, change in frequency and time frame, change in intensity. We found a Cronbach α of 0.82, an acceptable internal consistency. The Spearman correlation coefficient between total scores of AKQoL and DLQI was 0.57. We culturally adapted and validated a Swiss (German) version of the AKQoL questionnaire applicable for the population of a university center in Switzerland to measure and monitor the quality of life in patients with AK. © 2018 S. Karger AG, Basel.

Dermoscopic clues to differentiate facial lentigo maligna from pigmented actinic keratosis.

PubMed

Lallas, A; Tschandl, P; Kyrgidis, A; Stolz, W; Rabinovitz, H; Cameron, A; Gourhant, J Y; Giacomel, J; Kittler, H; Muir, J; Argenziano, G; Hofmann-Wellenhof, R; Zalaudek, I

2016-05-01

Dermoscopy is limited in differentiating accurately between pigmented lentigo maligna (LM) and pigmented actinic keratosis (PAK). This might be related to the fact that most studies have focused on pigmented criteria only, without considering additional recognizable features. To investigate the diagnostic accuracy of established dermoscopic criteria for pigmented LM and PAK, but including in the evaluation features previously associated with nonpigmented facial actinic keratosis. Retrospectively enrolled cases of histopathologically diagnosed LM, PAK and solar lentigo/early seborrhoeic keratosis (SL/SK) were dermoscopically evaluated for the presence of predefined criteria. Univariate and multivariate regression analyses were performed and receiver operating characteristic curves were used. The study sample consisted of 70 LMs, 56 PAKs and 18 SL/SKs. In a multivariate analysis, the most potent predictors of LM were grey rhomboids (sixfold increased probability of LM), nonevident follicles (fourfold) and intense pigmentation (twofold). In contrast, white circles, scales and red colour were significantly correlated with PAK, posing a 14-fold, eightfold and fourfold probability for PAK, respectively. The absence of evident follicles also represented a frequent LM criterion, characterizing 71% of LMs. White and evident follicles, scales and red colour represent significant diagnostic clues for PAK. Conversely, intense pigmentation and grey rhomboidal lines appear highly suggestive of LM. © 2015 British Association of Dermatologists.

Adaptation and validation of the Spanish version of the Actinic Keratosis Quality of Life questionnaire.

PubMed

Longo Imedio, Isabel; Serra-Guillén, Carlos

2016-01-01

While there are questionnaires for evaluating the effects of skin cancer on patient quality of life, there are no specific questionnaires available in Spanish for evaluating quality of life in patients with actinic keratosis. The aim of this study was to translate and culturally adapt the Actinic Keratosis Quality of Life (AKQoL) questionnaire into Spanish. The original questionnaire was translated into Spanish following the guidelines for the cross-cultural adaptation of self-report measures. Several measures of general reliability and validity were calculated, including Cronbach α for internal consistency and the Spearman rank-order correlation coefficient and a Bland-Altman plot for test-retest reliability. To test concurrent validity, we used the Pearson correlation coefficient to measure the correlation between AKQoL and Skindex-29 scores. The final version of the questionnaire was administered to 621 patients with actinic keratosis, who scored a mean (SD) of 5.25 (4.73) points (total possible score, 0-25). The Cronbach α reliability coefficient analysis was 0.84. The correlation between the mean (SD) score on the Skindex-29 (1.87 [4.07]) and on the AKQoL (1.97 [2.98] was 0.344 (P=.002, Spearman's rho), with a proportion of shared variance of 11.8%. The translation, cross-cultural adaptation, and validation of the original AKQoL produced a reliable, easily understandable questionnaire for evaluating the impact of actinic keratosis on the quality of life of patients in our setting. Copyright © 2016 AEDV. Published by Elsevier España, S.L.U. All rights reserved.

Melanoma in-situ arising in seborrheic keratosis: a case report

PubMed Central

Repertinger, Susan; Wang, Jeff; Adickes, Edward; Sarma, Deba P

2008-01-01

Background Seborrheic keratosis is a very common benign skin tumor in man. Melanoma is rare but is the most dreaded of all malignant skin tumors. A melanoma arising in a seborrheic keratosis is distinctly rare. We are reporting such a case occurring in an 86-year-old man. Case presentation An-86-year-old male with a history of multiple actinic keratoses and seborrheic keratoses of the head and trunk presented with a mid-back skin lesion. The lesion was poorly circumscribed, flat, and gray, with a pink-tan, well-circumscribed scaly nodule within it. The biopsied lesion was composed of the usual features of hyperkeratotic seborrheic keratosis, but with focal atypical melanocytic proliferation with nesting along the dermal-epidermal junction. We interpreted this lesion as a melanoma in-situ arising within a seborrheic keratosis. Conclusion It is not uncommon for many physicians to remove a typical seborrheic keratosis without a confirmatory microscopic confirmation. We urge that all such lesions be examined by the pathologist to avoid missing another concomitant malignant lesion such as melanoma which needs adequate resection and close follow-up. PMID:18947402

Dermatological Feasibility of Multimodal Facial Color Imaging Modality for Cross-Evaluation of Facial Actinic Keratosis

PubMed Central

Bae, Youngwoo; Son, Taeyoon; Nelson, J. Stuart; Kim, Jae-Hong; Choi, Eung Ho; Jung, Byungjo

2010-01-01

Background/Purpose Digital color image analysis is currently considered as a routine procedure in dermatology. In our previous study, a multimodal facial color imaging modality (MFCIM), which provides a conventional, parallel- and cross-polarization, and fluorescent color image, was introduced for objective evaluation of various facial skin lesions. This study introduces a commercial version of MFCIM, DermaVision-PRO, for routine clinical use in dermatology and demonstrates its dermatological feasibility for cross-evaluation of skin lesions. Methods/Results Sample images of subjects with actinic keratosis or non-melanoma skin cancers were obtained at four different imaging modes. Various image analysis methods were applied to cross-evaluate the skin lesion and, finally, extract valuable diagnostic information. DermaVision-PRO is potentially a useful tool as an objective macroscopic imaging modality for quick prescreening and cross-evaluation of facial skin lesions. Conclusion DermaVision-PRO may be utilized as a useful tool for cross-evaluation of widely distributed facial skin lesions and an efficient database management of patient information. PMID:20923462

Evaluation of the therapeutic results of actinic keratosis treated with topical 5% fluorouracil by reflectance confocal laser microscopy: preliminary study*

PubMed Central

Ishioka, Priscila; Maia, Marcus; Rodrigues, Sarita Bartholomei; Marta, Alessandra Cristina; Hirata, Sérgio Henrique

2015-01-01

Topical treatment for actinic keratosis with 5% fluorouracil has a recurrence rate of 54% in 12 months of follow-up. This study analyzed thirteen actinic keratoses on the upper limbs through confocal microscopy, at the time of clinical diagnosis and after 4 weeks of treatment with fluorouracil. After the treatment was established and evidence of clinical cure was achieved, in two of the nine actinic keratoses, confocal microscopy enabled visualization of focal areas of atypical honeycomb pattern in the epidermis indicating therapeutic failure. Preliminary data suggest the use of confocal microscopy as a tool for diagnosis and therapeutic control of actinic keratosis. PMID:26131881

A 12-Day Course of Imiquimod 5% for the Treatment of Actinic Keratosis: Effectiveness and Local Reactions.

PubMed

Serra-Guillén, C; Nagore, E; Llombart, B; Sanmartín, O; Requena, C; Calomarde, L; Guillén, C

2018-04-01

Imiquimod is an excellent option for patients with actinic keratosis, although its use may be limited by the long course of treatment required (4 weeks) and the likelihood of local skin reactions. The objectives of the present study were to demonstrate the effectiveness of a 12-day course of imiquimod 5% for the treatment of actinic keratosis and to examine the association between treatment effectiveness and severity of local reactions. We included patients with at least 8 actinic keratoses treated with imiquimod 5% cream for 12 consecutive days. Local reactions were classified as mild, moderate, or severe. The statistical analysis of the association between local reactions and clinical response was based on the Pearson χ 2 test and the Spearman rank correlation test. Sixty-five patients completed the study. Complete response was recorded in 52.3% and partial response in 75.4%. We found a statistically significant association between severity of the local reaction and response to treatment in both the Pearson χ 2 test and the Spearman rank correlation test. A 12-day course of imiquimod 5% proved effective for the treatment of actinic keratosis. Severity of local reactions during treatment was correlated with clinical response. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Comparative study of trichloroacetic acid vs. photodynamic therapy with topical 5-aminolevulinic acid for actinic keratosis of the scalp.

PubMed

Di Nuzzo, Sergio; Cortelazzi, Chiara; Boccaletti, Valeria; Zucchi, Alfredo; Conti, Maria Luisa; Montanari, Paola; Feliciani, Claudio; Fabrizi, Giuseppe; Pagliarello, Calogero

2015-09-01

Photodynamic therapy with 5-methyl-aminolevulinate and photodynamic therapy with trichloroacetic acid 50% are the two techniques utilized in the management of actinic keratosis. This study was planned to compare the efficacy, adverse effects, recurrence and cosmetic outcome of these option therapies in patients with multiple actinic keratosis of the scalp. Thirteen patients with multiple actinic keratosis were treated with one of the two treatments on half of the scalp at baseline, while the other treatment was performed on the other half 15 days apart, randomly. Efficacy, adverse effects, cosmetic outcome and recurrence were recorded at follow-up visit at 1, 3, 6 and 12 months. Photodynamic therapy with 5 methyl-aminolevulinate was more effective than trichloroacetic acid although less tolerated by patients as it was more painful. Early adverse effects were almost the same even if trichloroacetic acid leads also to crust formation and to a worse cosmetic outcome characterized by hypopigmentation. Recurrence was lower in the area treated with photodynamic therapy. Trichloroacetic acid 50% is less effective than photodynamic therapy with 5 methyl-aminolevulinate in the treatment of multiple actinic keratosis of the scalp although better tolerated by patients. As this technique is less painful and less expensive than photodynamic therapy, we hypothesize and suggest that more sequential treatments could lead to better results. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dermoscopy of Pigmented Actinic Keratosis of the Face: A Study of 232 Cases.

PubMed

Kelati, A; Baybay, H; Moscarella, E; Argenziano, G; Gallouj, S; Mernissi, F Z

2017-11-01

The diagnosis of pigmented actinic keratosis (PAK) is often challenging because of overlapping features with lentigo maligna. To investigate dermoscopic patterns of PAK according to their different evolutionary stages, and to correlate the pattern with clinical characteristics of the patients. Descriptive and analytical study of 232 PAK. Dermoscopic patterns were divided into two categories: the follicule surroundings' abnormalities (FSA) and follicular keratosis' abnormalities (FKA). FSA and FKA dermoscopic patterns were related to male gender, except for star-like appearance, double white clods and dermoscopic horn (p≤0.04). Rhomboidal, annular granular pattern, gray halo, white circle and double clods were dermoscopic pattern significantly related to xeroderma pigmentosum's type of skin. Based on the evolutionary stages of PAK, the jelly sign was significantly related to thin patches of PAK. Central crusts and scales were related to thick plaques and the star-like appearance to hypertrophic PAK. The presence of 2 or more dermoscopic signs in both FSA and FKA was noticed in 99.1% of lesions. The dermoscopic diagnosis of PAK vary according to the evolutionary stages of the disease, this will increase the diagnosis accuracy, with therapeutic implications. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Protein expression of MMP-2 and MT1-MMP in actinic keratosis, squamous cell carcinoma of the skin, and basal cell carcinoma.

PubMed

de Oliveira Poswar, Fabiano; de Carvalho Fraga, Carlos Alberto; Gomes, Emisael Stênio Batista; Farias, Lucyana Conceição; Souza, Linton Wallis Figueiredo; Santos, Sérgio Henrique Souza; Gomez, Ricardo Santiago; de-Paula, Alfredo Maurício Batista; Guimarães, André Luiz Sena

2015-02-01

Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are 2 skin neoplasms with distinct potentials to invasion and metastasis. Actinic keratosis (AK) is a precursor lesion of SCC. Immunohistochemistry was performed to evaluate the expression of MMP-2 and MT1-MMP in samples of BCC (n = 29), SCC (n = 12), and AK (n = 13). The ratio of positive cells to total cells was used to quantify the staining. Statistical significance was considered under the level P < .05. We found a higher expression of MMP-2 in tumor stroma and parenchyma of SCC as compared to BCC. The expression of this protein was also similar between SCC and its precursor actinic keratosis, and it was higher in the stroma of high-risk BCC when compared to low-risk BCC. MT1-MMP, which is an activator of MMP-2, was similarly expressed in all groups. Our results suggest that MMP-2 expression may contribute to the distinct invasive patterns seen in SCC and BCC. © The Author(s) 2014.

Photodynamic therapy in the management of actinic keratosis: Retrospective evaluation of outcome.

PubMed

Jerjes, Waseem; Hamdoon, Zaid; Abdulkareem, Ali A; Hopper, Colin

2017-03-01

Photodynamic therapy (PDT) is a minimally invasive intervention used in the management of tissue disorders. In this retrospective study, a total of 62 patients with actinic keratosis (AKs) were treated with surface illumination PDT. Comparisons with the clinical features, rate of recurrence as well as malignant transformation and overall outcome were made. The medical records of 62 consecutive patients who presented with suspicious skin lesions and diagnosed with AKs were examined. These patients with 178 AKs lesions were treated with surface illumination methyl aminolevulinate-photodynamic therapy (MAL-PDT). The 16% strength cream (MAL) was applied topically 3h prior to tissue illumination. A single-channel 628nm diode laser was used for illumination and light was delivered at 100J/cm 2 per site. These patients were followed-up for a mean of 7.4 years. Eight recurrences were reported after the first round of MAL-PDT, and two recurrences after the second round. Malignant transformation to squamous cell carcinoma (SCC) was noted in 2 patients only. The 3-year outcome resulted in 60 patients with complete response (CR), and this was maintained at the final outcome (last clinic review). Assessment of lesional outcome vs. response showed that 175/178 treated lesions had complete response (CR) at 3-year follow-up, which increased to 176/178 lesions at the last clinic follow-up. MAL-PDT offers an effective treatment for AKs lesions with excellent cosmetic outcome. Copyright © 2016 Elsevier B.V. All rights reserved.

Clinical effect of imiquimod 5% cream in the treatment of actinic keratosis.

PubMed

Persaud, Andrea N; Shamuelova, Eleonora; Sherer, Daniel; Lou, Wendy; Singer, Giselle; Cervera, Christina; Lamba, Sumedha; Lebwohl, Mark G

2002-10-01

Actinic keratosis (AK) is the earliest clinical manifestation of squamous cell carcinoma. Metastatic SCC causes the majority of the 1300 to 2300 deaths attributed to nonmelanoma skin cancer in the United States each year. Recent studies have shown that intralesional administration of interferon can be used successfully in the treatment of AK. Imiquimod is an immune response modifier, currently approved for the treatment of genital warts. The topically applied immune response modifier acts by up-regulating interferon and other cytokines involved in the cell-mediated immune response at the site of application. The aim of this was to determine the efficacy and safety of imiquimod 5% cream for the treatment of AK. Twenty-two patients with AK lesions were treated with imiquimod 5% cream, initially at 3 times per week for 8 weeks, or until total clearance of lesions. Patients applied imiquimod to lesions on one side of the body and vehicle cream to the other side. A total of 17 patients who completed treatment were evaluated for number of lesions and adverse reactions before treatment and at weeks 2, 4, 6, and 8 after initiation of treatment. AK lesions were also assessed 4 and 8 weeks after treatment. A significant reduction in the average number of lesions per patient was observed for patients treated with imiquimod. The most frequent reactions to treatment were erythema, itching, and scabbing; however, all adverse events were mild to moderate. Imiquimod 5% cream may be a promising treatment for AK.

Photodynamic therapy effective for the treatment of actinic keratosis and basal cell carcinoma in bullous pemphigoid patients.

PubMed

Canavan, Theresa N; de la Feld, Salma Faghri; Huang, Conway; Sami, Naveed

2017-06-01

Treating skin cancers and extensive actinic keratosis in patients with bullous pemphigoid (BP) can be challenging. Treatment options pose unique risks in these patients as surgical wounds can have delayed wound healing and photodynamic therapy (PDT) may exacerbate their blistering disease. We report the successful use of PDT to treat actinic keratosis and skin cancers in two patients with BP, both of whom had excellent response to PDT and tolerated treatment without any bullous disease flares. Carefully selected patients with skin cancers and stable, well controlled BP can be safely considered for treatment using PDT. Copyright © 2017 Elsevier B.V. All rights reserved.

Physicians' opinions and clinical practice patterns for actinic keratosis management in Italy.

PubMed

Peris, K; Neri, L; Calzavara Pinton, P; Catricalà, C; Pellacani, G; Pimpinelli, N; Peserico, A

2014-04-01

We report dermatologists' opinions and clinical practice patterns about clinical factors driving decision making in the management of actinic keratosis (AK) in Italy. We carried out a cross-sectional survey among 33 Italian dermatologists. Physicians were asked to report their management choices in consecutive patients with AK seen at their practice within 2 weeks since study initiation. We collected patients' clinical and socio-demographic characteristics with a standardized data collection form and assessed physicians' opinions on AK management with a self-reported questionnaire. Six hundred fifty-seven patients with new, single AK lesions without evidence of photo-damaged skin in the surrounding areas, were predominantly treated with lesion-directed therapies (primarily cryotherapy). In contrast, physicians preferentially prescribed field-directed therapies to patients with multiple lesions and evidence of photo-damaged skin in AK surrounding areas. However we observed a wide variation in treatment choices and physicians' opinions on AK management. Dermatologists underlined the importance of fostering patients' adherence and minimize therapy side effects. Overall, our results show that current guidelines regarding management of AK are only partially integrated in dermatology practice. The active dissemination of up-to-date national guidelines might help harmonize clinical decision making in this complex and fast growing therapeutic area.

[Actinic keratosis: New concept and therapeutic update].

PubMed

Carmena-Ramón, Rafael; Mateu-Puchades, Almudena; Santos-Alarcón, Sergio; Lucas-Truyols, Sofía

2017-10-01

Actinic keratosis (AK) is a common reason for consultation in both Primary Care and Specialised Care. It is the third or fourth most common reason for consultation in dermatology, accounting for up to 5-6% of patients attended. It has also been observed that its prevalence has been increasing in the last 10years, compared to other dermatoses. This is also expected to continue to increase due to longer life expectancy, and by the changes in sun exposure habits since the middle of the last century. The aim of this article is to update the concepts of AK, cancerisation field and to present the currently available therapeutic tools. Copyright © 2017. Publicado por Elsevier España, S.L.U.

Laser-mediated Photodynamic Therapy: An Alternative Treatment for Actinic Keratosis?

PubMed

Kessels, Janneke P H M; Nelemans, Patty J; Mosterd, Klara; Kelleners-Smeets, Nicole W J; Krekels, Gertruud A M; Ostertag, Judith U

2016-03-01

Photodynamic therapy (PDT) with light emitting diode (LED) illumination is a frequently used treatment modality for actinic keratosis (AK) with excellent cosmetic outcome. A major disadvantage, however, is the high pain score. Pulsed dye laser (PDL) illumination has been suggested, but the long-term efficacy of this treatment is unknown. In this split-face study we prospectively treated 61 patients with AK, with both LED-PDT and PDL-PDT. The mean change in the number of lesions between the end of follow-up and start of therapy was -4.25 (95% confidence interval (95% CI) -5.07; -3.43) for LED-PDT and -3.88 (95% CI -4,76; -2.99) for PDL-PDT, with a non-significant difference (p = 0.258) of -0.46 (95% CI -1.28; 0.35). The percentage decrease from baseline in the total number of AK was 55.8% and 47.8%, respectively, at 12-month follow-up. Visual analogue scale pain score was lower after PDL (mean 2.64) compared with LED illumination (mean 6.47). These findings indicate that PDL-PDT is an effective alternative illumination source fo.

The challenge of diagnosing seborrheic keratosis by reflectance confocal microscopy.

PubMed

Guo, A; Chen, J; Yang, C; Ding, Y; Zeng, Q; Tan, L

2018-05-24

Seborrheic keratosis (SK) is one of the most common skin tumors seen by dermatologists. It should be differentiated with many diseases, especially skin tumors. Reflectance confocal microscopy (RCM) has been applied for evaluation of SK. There are a few studies that describe the RCM of SK. The aim of the study was to find the challenge of diagnosing seborrheic keratosis by reflectance confocal microscopy. A total of 390 patients with a clinical suspicious diagnosis of seborrheic keratosis were enrolled in this study, and lesions from each patient were imaged with RCM. Thirty-seven of these patients performed a biopsy in order to be given a histological diagnosis. We retrospectively analyzed the outcomes of RCM diagnosis and histological diagnosis, and then found the RCM characteristics of biopsy-proven lesions. According to RCM images, 258 of 390 (66.2%) patients were diagnosed with SK, 97 of 390 (24.9%) patients could not be diagnosed by the dermatologist according to RCM. Of all 37 biopsied lesions, 23 were SK, 6 were actinic keratosis, 2 were basal cell carcinoma, and 2 were squamous cell carcinoma. It is challenge to diagnose seborrheic keratosis by reflectance confocal microscopy. It may due to the variable clinical and RCM appearances of SK, and limited depth of RCM. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Increased expression of enhancer of Zeste Homolog 2 (EZH2) differentiates squamous cell carcinoma from normal skin and actinic keratosis.

PubMed

Xie, Qiang; Wang, Hongbei; Heilman, Edward R; Walsh, Michael G; Haseeb, M A; Gupta, Raavi

2014-01-01

Enhancer of Zeste Homolog 2 (EZH2) is a polycomb group protein that has been shown to be involved in the progression of multiple human cancers including melanoma. The expression of EZH2 in normal skin and in pre-malignant and malignant cutaneous squamous cell carcinoma (SCC) has not been studied. We examined the expression of EZH2 in normal skin, actinic keratosis (AK), SCC in situ, well-differentiated (SCC-WD), moderately-differentiated (SCC-MD) and poorly-differentiated SCC (SCC-PD) to ascertain whether EZH2 expression differentiates these conditions. Immunohistochemical staining for EZH2 was performed on formalin-fixed paraffin-embedded biopsies and a tissue microarray containing normal skin, AK, SCC in situ, and SCC of different grades. In comparison to the normal skin, EZH2 expression in actinic keratosis was increased (p=0.03). Similarly, EZH2 expression in all of the neoplastic conditions studied (SCC in situ, SCC-WD, SCC-MD and SCC-PD) was greatly increased in comparison to both the normal skin and actinic keratosis (p≤0.001). EZH2 expression increases incrementally from normal skin to AK and further to SCC, suggesting a role for EZH2 in the progression and differentiation of SCC. EZH2 expression may be used as a diagnostic marker for differentiating SCC from AK or normal skin.

Number of Langerhans cells is decreased in premalignant keratosis and skin cancers.

PubMed

Shevchuk, Z; Filip, A; Shevchuk, V; Kashuba, E

2014-03-01

It was shown earlier that a number of CD207 positive Langerhans cells was lower in basal cell carcinomas than in the normal epidermis. Moreover, benign skin lesions presented a higher number of Langerhans cells when they were compared to malignant tumors. To count Langerhans cells, assessing expression levels of CD1A and CD207 markers in actinic keratosis, basal and squamous cell carcinomas, compared with the normal skin. Comparison of Langerhans cells might give a valuable prognostic marker for skin cancer. Immunohistochemistry and methods of statistics were used. Expression of CD1A and CD207 markers was assessed in tumor samples of actinic keratosis, cutaneous basal and squamous cell carcinomas, in comparison with the normal skin. In each cohort there were 40 patients (and 11 healthy individuals). We have shown that the number of Langerhans cells is considerably lower in cutaneous basal and squamous cell carcinomas, compared with their number in the normal skin (p < 0.0001). CD1A expression correlated with CD207 expression only in the control group. There was no correlation in actinic keratosis, basal and squamous cell carcinoma. This may suggest an alteration of Langerhans cells phenotype in skin neoplastic diseases, making the number of Langerhans cells a valuable prognostic factor for skin tumors.

Cost-Effectiveness and Cost-Utility Analysis of Ingenol Mebutate Versus Diclofenac 3% and Imiquimod 5% in the Treatment of Actinic Keratosis in Spain.

PubMed

Elías, I; Ortega-Joaquín, N; de la Cueva, P; Del Pozo, L J; Moreno-Ramírez, D; Boada, A; Aguilar, M; Mirada, A; Mosquera, E; Gibbons, C; Oyagüez, I

2016-01-01

To perform a cost-effectiveness and cost-utility analysis of ingenol mebutate in the treatment of actinic keratosis in Spain. We used an adapted Markov model to simulate outcomes in a cohort of patients (mean age, 73 years) with actinic keratosis over a 5-year period. The comparators were diclofenac 3% and imiquimod 5%. The analysis was performed from the perspective of the Spanish National Health System based on direct costs (2015 retail price plus value added tax less the mandatory discount). A panel of experts estimated resources, taking unit costs from national databases. An annual discount rate of 3% was applied. Deterministic and probabilistic sensitivity analyses were performed. The effectiveness of ingenol mebutate-with 0.192 and 0.129 more clearances gained in treatments for face and scalp lesions and trunk and extremity lesions, respectively-was superior to diclofenac's. The total costs of treatment with ingenol mebutate were lower at € 551.50 (face and scalp) and € 622.27 (trunk and extremities) than the respective costs with diclofenac (€ 849.11 and € 844.93). The incremental cost-effectiveness and cost-utility ratios showed that ingenol mebutate was a dominant strategy vs diclofenac. Ingenol mebutate also proved to be more effective than imiquimod, based on 0.535 and 0.503 additional clearances, and total costs of € 551.50 and € 527.89 for the two drugs, respectively. The resulting incremental cost-effectiveness ratio was € 728.64 per clearance gained with ingenol mebutate vs imiquimod. Ingenol mebutate was a dominant treatment option vs diclofenac and was efficient vs imiquimod (i.e., more effective at a higher cost, achieving an incremental cost-utility ratio of<€30000/quality-adjusted life-years). Copyright © 2016 AEDV. Published by Elsevier España, S.L.U. All rights reserved.

Colonisation of basal cell carcinoma and actinic keratosis by malignant melanoma in situ in a patient with xeroderma pigmentosum variant

PubMed Central

Smith, Louise J.; Husain, Ehab A.

2012-01-01

Although malignant melanoma (MM) and both basal cell carcinoma (BCC) and actinic keratosis (AK) are sun-induced lesions, the coexistence of these entities at the same anatomical site (collision tumour) is exceedingly rare. We report the case of a 54-year-old woman with a known history of xeroderma pigmentosum variant (XPV) who presented with 2 separate skin lesions over the middle and upper right forearm, respectively. The clinical impression was that of BCCs or squamous cell lesions. On histological examination, both specimens showed features of melanoma in situ (MIS). In the first lesion, MIS merged with and colonised a superficial and focally invasive BCC. In the second lesion, MIS merged with an AK. No separate invasive nests of malignant melanoma were seen in either specimen. The atypical melanocytes were highlighted by Melan-A and HMB-45 immunostaining, whereas the epithelial cells in both the BCC and AK stained with the pancytokeratin MNF-116. The patient had a previous history of multiple MMs and non-melanomatous skin cancers and finally developed widespread metastatic malignant melanoma, which proved fatal. The rare and interesting phenomenon of collision tumours may pose diagnostic difficulties. To our knowledge, this is the first reported simultaneous presentation of cytologically malignant collision tumours in a patient with XPV. PMID:24765446

Genomic instability in human actinic keratosis and squamous cell carcinoma

PubMed Central

Cabral, Luciana Sanches; Neto, Cyro Festa; Sanches, José A; Ruiz, Itamar R G

2011-01-01

OBJECTIVE: To compare the repetitive DNA patterns of human actinic keratoses and squamous cell carcinomas to determine the genetic alterations that are associated with malignant transformation. INTRODUCTION: Cancer cells are prone to genomic instability, which is often due to DNA polymerase slippage during the replication of repetitive DNA and to mutations in the DNA repair genes. The progression of benign actinic keratoses to malignant squamous cell carcinomas has been proposed by several authors. MATERIAL AND METHODS: Eight actinic keratoses and 24 squamous cell carcinomas (SCC), which were pair-matched to adjacent skin tissues and/or leucocytes, were studied. The presence of microsatellite instability (MSI) and the loss of heterozygosity (LOH) in chromosomes 6 and 9 were investigated using nine PCR primer pairs. Random Amplified Polymorphic DNA patterns were also evaluated using eight primers. RESULTS: MSI was detected in two (D6S251, D9S50) of the eight actinic keratosis patients. Among the 8 patients who had squamous cell carcinoma-I and provided informative results, a single patient exhibited two LOH (D6S251, D9S287) and two instances of MSI (D9S180, D9S280). Two LOH and one example of MSI (D6S251) were detected in three out of the 10 patients with squamous cell carcinoma-II. Among the four patients with squamous cell carcinoma-III, one patient displayed three MSIs (D6S251, D6S252, and D9S180) and another patient exhibited an MSI (D9S280). The altered random amplified polymorphic DNA ranged from 70% actinic keratoses, 76% squamous cell carcinoma-I, and 90% squamous cell carcinoma-II, to 100% squamous cell carcinoma-III. DISCUSSION: The increased levels of alterations in the microsatellites, particularly in D6S251, and the random amplified polymorphic DNA fingerprints were statistically significant in squamous cell carcinomas, compared with actinic keratoses. CONCLUSION: The overall alterations that were observed in the repetitive DNA of actinic keratoses and

Eyebrow hairs from actinic keratosis patients harbor the highest number of cutaneous human papillomaviruses

PubMed Central

2013-01-01

Background Cutaneous human papillomavirus (HPV) infections seem to be associated with the onset of actinic keratosis (AK). This study compares the presence of cutaneous HPV types in eyebrow hairs to those in tissues of normal skin and skin lesions of 75 immunocompetent AK patients. Methods Biopsies from AK lesions, normal skin and plucked eyebrow hairs were collected from each patient. DNA from these specimens was tested for the presence of 28 cutaneous HPV (betaPV and gammaPV) by a PCR based method. Results The highest number of HPV prevalence was detected in 84% of the eyebrow hairs (63/75, median 6 types) compared to 47% of AK lesions (35/75, median 3 types) (p< 0.001) and 37% of normal skin (28/75, median 4 types) (p< 0.001), respectively. A total of 228 HPV infections were found in eyebrow hairs compared to only 92 HPV infections in AK and 69 in normal skin. In all three specimens HPV20, HPV23 and/or HPV37 were the most prevalent types. The highest number of multiple types of HPV positive specimens was found in 76% of the eyebrow hairs compared to 60% in AK and 57% in normal skin. The concordance of at least one HPV type in virus positive specimens was 81% (three specimens) and 88-93% of all three combinations with two specimens. Conclusions Thus, eyebrow hairs revealed the highest number of cutaneous HPV infections, are easy to collect and are an appropriate screening tool in order to identify a possible association of HPV and AK. PMID:23618013

Eyebrow hairs from actinic keratosis patients harbor the highest number of cutaneous human papillomaviruses.

PubMed

Schneider, Ines; Lehmann, Mandy D; Kogosov, Vlada; Stockfleth, Eggert; Nindl, Ingo

2013-04-24

Cutaneous human papillomavirus (HPV) infections seem to be associated with the onset of actinic keratosis (AK). This study compares the presence of cutaneous HPV types in eyebrow hairs to those in tissues of normal skin and skin lesions of 75 immunocompetent AK patients. Biopsies from AK lesions, normal skin and plucked eyebrow hairs were collected from each patient. DNA from these specimens was tested for the presence of 28 cutaneous HPV (betaPV and gammaPV) by a PCR based method. The highest number of HPV prevalence was detected in 84% of the eyebrow hairs (63/75, median 6 types) compared to 47% of AK lesions (35/75, median 3 types) (p< 0.001) and 37% of normal skin (28/75, median 4 types) (p< 0.001), respectively. A total of 228 HPV infections were found in eyebrow hairs compared to only 92 HPV infections in AK and 69 in normal skin. In all three specimens HPV20, HPV23 and/or HPV37 were the most prevalent types. The highest number of multiple types of HPV positive specimens was found in 76% of the eyebrow hairs compared to 60% in AK and 57% in normal skin. The concordance of at least one HPV type in virus positive specimens was 81% (three specimens) and 88-93% of all three combinations with two specimens. Thus, eyebrow hairs revealed the highest number of cutaneous HPV infections, are easy to collect and are an appropriate screening tool in order to identify a possible association of HPV and AK.

Long-term use of a new topical formulation containing piroxicam 0.8% and sunscreen: efficacy and tolerability on actinic keratosis. A proof of concept study.

PubMed

Babino, Graziella; Diluvio, Laura; Bianchi, Luca; Orlandi, Augusto; Di Prete, Monia; Chimenti, Sergio; Milani, Massimo; Campione, Elena

2016-08-01

Cyclooxygenase (COX) 1 and 2 enzyme up-regulation is involved in the pathogenetic process of actinic keratosis (A.K.) and non-melanoma skin cancers. Diclofenac, a non-steroidal anti-inflammatory (N.S.A.I.D.) drug, is used as topical treatment of A.K. Piroxicam is a N.S.A.I.D. characterized by a high COX-1 inhibition activity. We conducted an 18 month exploratory open-label study on A.K., to assess the efficacy and tolerability of a new topical formulation of piroxicam and sunscreen in A.K. Enrolled subjects applied a galenic formulation of piroxicam 0.8%, vehiculated in a topical product containing sun filters with high (50+) and broad spectrum (UVA) actions, twice a day for 6 months. Subjects were then followed up for additional 12 months. Thirty-eight subjects with a total of 69 A.K. lesions participated in the trial. The primary outcome was the evolution of the Actinic Keratosis Erythema Scale Atrophy (A.K.E.S.A) score assessing erythema, scale, and atrophy of a target A.K. lesion. Secondary outcomes were the percentage of treated lesions with complete (100%) or partial (≥75%) clearance and the evaluation skin tolerability. A.K.E.S.A. mean (S.D.) score at baseline was 7.5 (1.2). After 6 months of treatment, A.K.E.S.A. score decreased to 0.9 (1.1), a -88% reduction versus baseline. At the end of follow-up, A.K.E.S.A. score was 0.8 (1.2). A complete response was achieved in 38 of the 69 lesions (55%, 95% C.I.: 43% to 66%) and clearance was maintained 1 year post-treatment. A partial clearance was observed in 57 of 69 treated lesions (83%, 95% C.I.: 73% to 91%). Adverse events were limited to mild local irritation. Our experience suggests that 6 month topical piroxicam 0.8% is efficacious and well tolerated in A.K. Clinical efficacy is maintained 1 year post-treatment. The main limitation of our study is that it was an open label non-controlled trial. Future controlled trials are warranted in order to compare the efficacy and tolerability of this topical

PDT and emerging therapies for Actinic Keratosis-A resource letter.

PubMed

Filho, José D Vollet; Andrade, Cintia T; Buzza, Hilde H; Blanco, Kate; Carbinatto, Fernanda; Bagnato, Vanderlei S; Allison, Ron R

2017-03-01

Aktinic Keratosis is common and if left untreated may develop into life threatening squamous cell carcinoma. Therefore early intervention is the standard of care. While many treatments are available PDT continues to move to the for - front for this indication (Brito et al., 2016 [31]). Topical PS is commercially available that are able to reliably ablate these lesions. Innovative protocols including sunlight, large volume LED arrays and maneuvers to improve treatment parameters and cosmesis continue to make this a worldwide treatment of choice for AK. Copyright © 2016 Elsevier B.V. All rights reserved.

Predisposing factors of actinic keratosis in a North-West German population.

PubMed

Hensen, Peter; Müller, Marcel L; Haschemi, Ramin; Ständer, Hartmut; Luger, Thomas A; Sunderkötter, Cord; Schiller, Meinhard

2009-01-01

The growing incident rates of skin cancer and their corresponding precursor lesions, e.g. actinic keratosis (AK), among Caucasians have become an important public health problem. A multicenter case-control study was conducted to identify the risk factors of AK of a prototypical Central European population. The study population comprised a total of 331 cases and 383 controls. Using multivariate analysis we identified ten independent variables predicting the AK risk. The five most crucial were age (OR 1.11; 95% CI 1.08-1,14), gender (OR 3.92; 95% CI 2.42-6.36), history of previous skin malignancies (OR 6.47; 95% CI 3.21-13.03), pale skin phototype (OR 2.5; 95% CI 1.53-4.06), and sun exposure for occupational reasons (OR 1.72; 95% CI 1.01-2.92). Additionally, sun exposure for recreational reasons, denial of the use of sunscreens, painful sunburn episodes before the age of 20, and a familial history of skin malignancies are also significant independent correlates of AK. Our epidemiological data suggest that constitutional susceptibility and sunlight exposure are equally involved in the onset of AK. Additional prophylactic and educational efforts should focus on increasing sun protection policies and educational programs especially aimed at outdoor workers, men, fair skinned individuals and patients with a history of previous skin malignancies. These measures should be able to reduce the excessive incidence rates of AK among Caucasians in Central Europe.

A randomized comparative study of tolerance and satisfaction in the treatment of actinic keratosis of the face and scalp between 5% imiquimod cream and photodynamic therapy with methyl aminolaevulinate.

PubMed

Serra-Guillen, C; Nagore, E; Hueso, L; Llombart, B; Requena, C; Sanmartín, O; Botella-Estrada, R; Guillen, C

2011-02-01

Photodynamic therapy (PDT) and imiquimod are two excellent treatments for actinic keratosis but are often not well tolerated by patients. To ascertain which treatment is better tolerated and which produces greater patient satisfaction. A secondary objective was to determine the factors related to the patient's tolerance to each treatment. Patients with at least five actinic keratosis lesions on the face and scalp were selected. The patients were randomized to receive treatment with PDT with methyl aminolaevulinate or treatment with imiquimod. Tolerance, satisfaction and predisposition to repeat the treatment were evaluated. Most patients exhibited good or acceptable tolerance to both PDT and imiquimod treatment. There was a higher percentage of patients treated with PDT (93%) who were very satisfied compared with imiquimod (62%) (P=0·004). Most patients treated with either one of the two options would repeat the same treatment. No significant relationship was found between age, sex, working time exposed to the sun, phototype and hair colour and the tolerance to both treatments. Both PDT and imiquimod are treatments that are generally well tolerated. While both treatments provide a high level of satisfaction, PDT appears to be slightly superior in this regard. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

[Immunohistochemical study of the specific features of expression of matrix metalloproteinases 1, 9 in the photoaged skin, the foci of actinic keratosis and basal cell carcinoma].

PubMed

Kuznetsova, E V; Snarskaya, E S; Zavalishina, L E; Tkachenko, S B

Matrix metalloproteinases (MMPs) mediate the degradation of all types of collagens and other extracellular matrix components (elastin, proteoglycans, and laminin), their synthesis and accumulation play a key role in the hydrolysis of basement membrane. MMPs are involved in a wide range of proteolytic processes in the presence of different physiological and pathological changes, including inflammation, wound healing, angiogenesis, and carcinogenesis. to study the specific features of MMP-1 and MMP-9 expression in different stages of skin photoaging, in the foci of actinic keratosis and basal cell carcinoma by immunohistochemical examination. 12 samples of the healthy skin (6 samples of the eyelid skin with Glogau grade II photoaging; 6 ones of eyelid skin with Glogau grades III-IV photoaging) and biopsies from 8 foci of actinic keratosis and from 8 ones of basal cell carcinoma were examined. A positive reaction to MMPs was shown as different brown staining intensity in the cytoplasm of keratinocytes/tumor cells. MMP-1 and MMP-9 expression was recorded in 67% of the histological specimens of the Glogau grade III photoaged skin and in 100% of those of Glogau grade IV. In the foci of actinic keratosis, the expression of MMP-1 was observed in 62.5% of cases and that of MMP-9 was seen in 87.5%. In basal cell carcinoma, the expression of MMP-1 and MMP-9 was detected in all investigated samples. The immunomorphological findings are indicative of the important role of the level of MMP-1 and MMP-9 expression that is associated with the degree of progression of skin photoaging processes. Minimal MMP-1 and MMP-9 expression was recorded even in grades III-IV photoaging and in the foci of actinic keratosis. Intense MMP-1 and MMP-9 expression was detected in malignant skin epithelial neoplasms as different clinicomorphological types of basal cell carcinoma.

Comparison of the Treatment Guidelines for Actinic Keratosis: A Critical Appraisal and Review.

PubMed

Fleming, Patrick; Zhou, Stephanie; Bobotsis, Robert; Lynde, Charles

There are currently several reputable guidelines on the treatment of actinic keratosis (AK) from groups in Canada, the United Kingdom, and Europe. These recommendations, based on evidence or expert consensus, offer clinicians a variety of treatment options for the different clinical presentations of AKs. Although the guidelines are similar in some regards, variations exist in treatment options, duration, and strength of recommendation. Some guidelines also lack input on specific therapies and certain types of AK, such as hypertrophic or thin presentations. The purpose of this article is to review and compare guidelines published by Canadian, UK, and European groups for the management of AKs in patients.

The association between osteoporotic hip fractures and actinic lesions as a biomarker for cumulative sun exposure in older people-a retrospective case-control study in Argentina.

PubMed

Perroud, H A; Dagatti, M S; Amigot, B; Levit, G P; Tomat, M F; Morosano, M E; Masoni, A M; Pezzotto, S M

2017-05-01

The aim of this study was to analyze the association between the presence of actinic lesions (solar keratosis and non-melanoma skin cancer) and osteoporotic hip fractures in older patients. Both pathologies are common conditions in this age group. Since cumulative sun exposure is difficult to quantify, the presence of actinic lesions can be used to indirectly analyze the association between ultraviolet radiation and osteoporotic hip fractures. This was an observational case-control study. We reviewed the centralized medical records of patients with hip fracture (cases, n = 51) and patients with other diseases hospitalized in the same institution and period (controls, n = 59). The mean age of the patients was 80 ± 8.3 years (range 50-103 years). Differences in maternal hip fracture history were found between cases and controls (14.8 and 8 %, respectively; p = 0.047). Falls history in the past year was higher in cases than in controls (p < 0.0001). Actinic lesions were observed in 32.7 % of patients (prevalence rate 23.5 % in cases, 40.7 % in controls; p = 0.04). When considering patients with actinic lesions, controls have a higher FRAX score compared with cases. Although sun exposure is recommended for bone health, it represents a risk factor for actinic lesions. The presence of actinic lesions may indicate a lower osteoporotic hip fracture risk. A balance between adequate lifetime sun exposure and protection against its adverse effects is required for each patient, in the context of geographic location.

Evaluation of T-lymphocyte subpopulations in actinic keratosis, in situ and invasive squamous cell carcinoma of the skin.

PubMed

Stravodimou, Aristea; Tzelepi, Vassiliki; Papadaki, Helen; Mouzaki, Athanasia; Georgiou, Sophia; Melachrinou, Maria; Kourea, Eleni P

2018-05-01

Tumor infiltrating lymphocytes (TILs) represent important regulators of carcinogenesis. Cutaneous invasive squamous cell carcinoma (inSCC) develops through precursor lesions, namely in situ squamous cell carcinoma (isSCC) and actinic keratosis (AK), representing a natural model of carcinogenesis. The study evaluates TIL subpopulations in inSCC and its precursors by comparing 2 semiquantitative scoring systems, and assesses the presence of regulatory T-cells (Tregs) in these lesions. Paraffin sections from 33 cases of AK, 19 isSCCs and 34 inSCCs with adjacent precursor lesions or normal skin (NS) were immunostained for CD3, CD4, CD8 and Foxp3. TIL subgroups were evaluated by the semiquantitative Klintrup-Mäkinen (K-M) score, and by a more detailed modification of this system. Treg counts were assessed by image analysis quantification. An increase of all TIL subpolulations from precursor lesions toward inSCC was shown by both scoring systems. Treg counts progressively increased from NS to AK and isSCC, but decreased in inSCC. Tregs were more numerous in pT2 and around indolent inSCCs compared to T1 and aggressive subtypes. T-cells and cytotoxic T-cells progressively increase in cutaneous squamous cell carcinogenesis, while Treg counts diminish in inSCC. The K-M score is an appropriate, easily applicable TIL scoring system in cutaneous inSCC. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The continued use of sunscreen prevents the development of actinic keratosis in aged Japanese subjects.

PubMed

Kunimoto, Kayo; Furukawa, Fukumi; Uede, Mikiko; Mizuno, Makoto; Yamamoto, Yuki

2016-08-01

It is well known that the trigger for actinic keratosis (AK) mainly depends on UV exposure. We evaluated the effects of long-term use of sunscreen on the histopathological and dermoscopic changes of AK in aged patients. Eighteen months use of sunscreen produced no change in the number of actinic keratoses or the advancement of histological grade. Although a significant decrease was not observed in the number of positive cells of p53, Ki-67 and COX-2 of the subjects who used sunscreen for 18 months, the downward tendencies of these proteins were observed. The continued use of sunscreen decreased the number of CD31-positive vessels significantly using the Chalkley method, and a significant improvement in scaling and vessel dots was found by dermoscopic study. Moreover, a relationship was found in the amount of sunscreen use and the number of actinic keratoses. Considering these results, it was thought that application of sunscreen reduces the risk of advancement of AK to higher grade AK and squamous cell carcinoma. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Diagnostic accuracy of optical coherence tomography in actinic keratosis and basal cell carcinoma.

PubMed

Olsen, J; Themstrup, L; De Carvalho, N; Mogensen, M; Pellacani, G; Jemec, G B E

2016-12-01

Early diagnosis of non-melanoma skin cancer (NMSC) is potentially possible using optical coherence tomography (OCT) which provides non-invasive, real-time images of skin with micrometre resolution and an imaging depth of up to 2mm. OCT technology for skin imaging has undergone significant developments, improving image quality substantially. The diagnostic accuracy of any method is influenced by continuous technological development making it necessary to regularly re-evaluate methods. The objective of this study is to estimate the diagnostic accuracy of OCT in basal cell carcinomas (BCC) and actinic keratosis (AK) as well as differentiating these lesions from normal skin. A study set consisting of 142 OCT images meeting selection criterea for image quality and diagnosis of AK, BCC and normal skin was presented uniformly to two groups of blinded observers: 5 dermatologists experienced in OCT-image interpretation and 5 dermatologists with no experience in OCT. During the presentation of the study set the observers filled out a standardized questionnaire regarding the OCT diagnosis. Images were captured using a commercially available OCT machine (Vivosight ® , Michelson Diagnostics, UK). Skilled OCT observers were able to diagnose BCC lesions with a sensitivity of 86% to 95% and a specificity of 81% to 98%. Skilled observers with at least one year of OCT-experience showed an overall higher diagnostic accuracy compared to inexperienced observers. The study shows an improved diagnostic accuracy of OCT in differentiating AK and BCC from healthy skin using state-of-the-art technology compared to earlier OCT technology, especially concerning BCC diagnosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Quality of Life, Behaviour and Attitudes towards Actinic Keratosis in Spain: The PIQA Study.

PubMed

Longo, I; Serra-Guillén, C

2018-05-01

This study was aimed to examine patients' knowledge, behaviours and attitudes regarding actinic keratosis (AK) lesions and the impact of the disease on patients' quality of life (QoL). Observational study of patients with AK lesions in Spain. QoL was evaluated with the validated version of Spanish AKQoL questionnaire. Skin self-examination, sun-exposure, habits and attitudes towards AK's treatment were recorded using different questionnaires. The adherence was assessed by means of the Morisky-Green test. Among other variables, QoL and adherence to treatment were compared by using Pearson's χ 2 test and one-way ANOVA tests. Inferential analysis regarding such factors and length of treatment were also performed. A total of 1240 patients (73.6 [10.5] years old) were recruited. Overall, patients that showed higher levels of concern were also showed a higher impairment on QoL. AK had greater effects on women's QoL and those who performed skin self-examination, think that AK is a disease and/or believe that moisturizers can prevent skin aging (P<.05). Adherence and length of treatment were strongly related, since patients with treatments intended for <1week were more likely to show good adherence and complete remission of AK (Odds Ratio [95%CI]: 6.25 [4.55-8.33] and 2.63 [1.96-3.45]), respectively). Concerns due to AK are mainly related to sex and to the consideration of AK as a disease. More concerned patients tend to have lower QoL and good adherence to treatment. Short length of treatment was associated with better adherence and complete remission of AK lesions. Copyright © 2018 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Ingenol mebutate gel treatment for actinic cheilitis: report of four cases.

PubMed

Barrado Solís, Nerea; Molés Poveda, Paula; Lloret Ruiz, César; Pont Sanjuan, Virginia; Velasco Pastor, Manel; Quecedo Estébanez, Esther; Miquel Miquel, Javier

2015-01-01

Actinic cheilitis (AC) are premalignant lesions that have an increased risk of malignant transformation. Their treatment, therefore, is essential to prevent carcinogenesis. However, optimal therapy is not well established and different modalities yield variable results. Ingenol mebutate gel has recently been approved by the US Food and Drug Administration for topical treatment of actinic keratosis, with high clearance rates. On the basis of these findings, we report our experience with this drug for the treatment of AC. © 2014 Wiley Periodicals, Inc.

Using photodynamic therapy to estimate effectiveness of innovative combined diclofenac and tazaroten therapy of disseminated actinic keratosis.

PubMed

Osiecka, Beata J; Jurczyszyn, Kamil; Nockowski, Piotr; Lipinski, Artur; Sieja, Agnieszka; Ziółkowski, Piotr

2015-01-01

Early diagnosis and therapy of precancerous lesions and malignant tumors belong to the most challenging tasks in modern medicine. Photodynamic diagnosis can help diagnose both precancerous lesions and early carcinoma. Actinic keratosis (AK) is the most common precancerous lesion of the skin. The available data show a high effectiveness of diclofenac in treating multifocal AK. We report a case of a 52-year-old woman who complained of multiple disseminated AK lesions predominantly on the lower limbs and trunk with a significant exacerbation within the last 6 months. Due to the spreading of disease and a high number of AK foci, as well as technical problems with visiting the hospital (PDT Laboratory), photodynamic therapy was not applied. The patient was treated for 2 months with a combination of local administration of 3% diclofenac and 0.1% tazaroten and 3% diclofenac only as a half side (left-right) comparison. The effects of therapy were later clinically evaluated and verified by means of photodynamic diagnosis (PDD) directly after therapy and at a follow-up examination 3 months later. The evaluation of treatment was blinded. Treatment with diclofenac only on the right side of the body resulted in clearing of 55% of all treated lesions, which increased to 60% three months after finishing therapy. On the left side of the body, where combined therapy (diclofenac 2 times daily on uneven dates and diclofenac once a day + tazaroten once a day on even dates) was used, 77.5% pathologic lesions disappeared, but this did not increase at follow up. The treatment of multifocal, disseminated AK is a difficult task and also burdensome for the patient due to side effects like scarring or burning and itching which occur during most therapies. Combined therapy with diclofenac and tazaroten supported by PDD may improve the effects of routine treatment of AK.

Ingenol mebutate in low amounts for the treatment of actinic keratosis in Korean patients.

PubMed

Joe, Hyun Jae; Oh, Byung Ho

2017-01-01

Ingenol mebutate (IM), a novel agent for field therapy of actinic keratosis (AK), has a drawback of inducing local skin reactions (LSRs), which may cause discomfort in patients. To reduce the LSRs, we tried the application of IM in low amounts. The purpose of this study was to review Korean patients with AK being treated with IM and evaluate the LSRs and therapeutic outcomes of low amounts of IM. We retrospectively reviewed 47 patients with AK on the face. A total of 20 and 27 patients were treated by applying recommended amount of 18.8 mg/cm 2 and the lower amount of 10 mg/cm 2 , respectively. The mean composite LSR score for the low amount group (LAG; 12.18±3.29) was significantly lower than that for the recommended amount group (RAG; 15.45±2.70) ( P <0.01, independent sample t -test). The 2-month clearance rate calculated by the number of AKs before and after treatment in each patient was significantly higher for RAG (88.16%), compared with 75.56% for LAG ( P <0.001). Low amount of IM for the treatment of facial AK significantly reduced LSRs in Korean patients. Minimizing LSRs may allow for a secondary targeting treatment of IM for the residual lesions, depending on initial treatment outcomes.

Dysplastic nevus associated with seborrheic keratosis*

PubMed Central

Botelho, Luciane Francisca Fernandes; Michalany, Nilceo Schwery; Enokihara, Milvia Maria Simões e Silva; Hirata, Sergio Henrique

2014-01-01

Seborrheic keratosis is a common skin lesion which may coincidentally be associated melanocytic nevi. The authors describe a case of dysplastic nevus associated with seborrheic keratosis and discuss the clinical, dermoscopic, and histological findings of this association. They also discuss the association between seborrheic keratosis and other benign and malignant tumours. PMID:24626665

Treatment of Grade II and III Actinic Keratosis Lesions with a Film-Forming Medical Device Containing Sunscreen/Piroxicam 0.8% and a Retinoic Acid/Glycolic Gel: A Pilot Trial.

PubMed

Puviani, Mario; Milani, Massimo

2018-05-31

Lesion and field-targeted treatments of actinic keratosis (AK) are commonly indicated for grade I and II type lesions. Grade III lesions are in general more difficult to treat. A film-forming medical device containing piroxicam 0.8% and sunscreen (SPF 50+) (PS) has been shown to be effective in the treatment of grade I and II AK lesions. Topical and oral retinoids have been utilized in AK and non-melanoma skin cancers. Topical glycolic acid promotes keratolysis and stimulates collagen synthesis for repair and skin rejuvenation and could be useful in AK treatment strategies. A gel containing retinoid acid (0.02%) and glycolic acid (4%) (RC) is commercially available. The objective of the study was to evaluate the efficacy and local tolerability of a combined treatment approach with PS and RC in subjects with multiple grade II and III AK lesions. Twenty-two subjects (16 males and 6 females; mean age 68 years) with more than five AK lesions were enrolled after obtaining their informed consent in a 3-month trial. PS cream was applied twice daily every day and RC gel was applied twice daily for 2 consecutive days every week. The primary endpoint was the evolution of the AK mean number from baseline to the end of the trial. Secondary endpoints were the thickness of the target lesion (expressed in mm 3 ) and the erythema score (hemoglobin content), evaluated using a standardized computer-based image acquisition analysis system (Anthera 3D). At baseline, the mean (SD) lesion number was 7.7 (3) for grade II and 1.4 (1) for grade III AK. At the end of the study, a significant (P = 0.001) reduction was observed for both grade II (- 81%; from 7.7 to 1.5) and grade III (- 22%) lesions. Six grade III lesions out of 31 (20%), presented at baseline, completely disappeared at month 3. For grade III lesions, a significant mean thickness reduction of 51% was observed at month 3. The erythema score (all lesions) was reduced by 70%. Four patients out of 22 (18%) were

Rosettes in actinic keratosis and squamous cell carcinoma: distribution, association to other dermoscopic signs and description of the rosette pattern.

PubMed

Lozano-Masdemont, B; Polimón-Olabarrieta, I; Marinero-Escobedo, S; Gutiérrez-Pecharromán, A; Rodríguez-Lomba, E

2018-01-01

Rosettes, a dermoscopic structure characterized by four white points arranged as a 4-leaf clover, supports the dermoscopic diagnosis of actinic keratosis (AK) or squamous cell carcinoma (SCC). The association of rosettes with other dermoscopic structures in AK or SCC and their distribution has not been analysed yet. We conducted a prospective study of patients with histologically proven AK or SCC who presented dermoscopic rosettes at initial evaluation. A total of 56 tumours were collected (94.6% AK and 5.4% SCC). Thirty-seven (66.1%) lesions were non-pigmented and 19 (33.9%) pigmented. The most common dermoscopic findings were erythema (53; 94.6%) and scale (42; 75%). White circles were present in 21 lesions (37.5%); pigmented pseudonetwork in 18 (32.1%) and multiple grey to brown dots and globules in 14 (25%). Rosettes were distributed focally in 9 (16.1%) and generalized in 47 (83.9%). The rosette pattern (rosettes as the main structure) was observed only in AK (19; 35.8%). The analysis was not blinded. The distinction between focal distribution (up to 3 rosettes) or generalized could be considered arbitrary. The rosette pattern identified in AK may be a specific pattern for AK. © 2017 European Academy of Dermatology and Venereology.

Electrospun poly-l-lactide scaffold for the controlled and targeted delivery of a synthetically obtained Diclofenac prodrug to treat actinic keratosis.

PubMed

Piccirillo, Germano; Bochicchio, Brigida; Pepe, Antonietta; Schenke-Layland, Katja; Hinderer, Svenja

2017-04-01

Actinic Keratosis' (AKs) are small skin lesions that are related to a prolonged sun-damage, which can develop into invasive squamous cell carcinoma (SCC) when left untreated. Effective, specific and well tolerable therapies to cure AKs are still of great interest. Diclofenac (DCF) is the current gold standard for the local treatment of AKs in terms of costs, effectiveness, side effects and tolerability. In this work, an electrospun polylactic acid (PLA) scaffold loaded with a synthetic DCF prodrug was developed and characterized. Specifically, the prodrug was successfully synthetized by binding DCF to a glycine residue via solid phase peptide synthesis (SPPS) and then incorporated in an electrospun PLA scaffold. The drug encapsulation was verified using multiphoton microscopy (MPM) and its scaffold release was spectrophotometrically monitored and confirmed with MPM. The scaffold was further characterized with scanning electron microscopy (SEM), tensile testing and contact angle measurements. Its biocompatibility was verified by performing a cell proliferation assay and compared to PLA scaffolds containing the same amount of DCF sodium salt (DCFONa). Finally, the effect of the electrospun scaffolds on human dermal fibroblasts (HDFs) morphology and metabolism was investigated by combining MPM with fluorescence lifetime imaging microscopy (FLIM). The obtained results suggest that the obtained scaffold could be suitable for the controlled and targeted delivery of the synthesized prodrug for the treatment of AKs. Electrospun scaffolds are of growing interest as materials for a controlled drug delivery. In this work, an electrospun polylactic acid scaffold containing a synthetically obtained Diclofenac prodrug is proposed as a novel substrate for the topical treatment of actinic keratosis. A controlled drug delivery targeted to the area of interest could enhance the efficacy of the therapy and favor the healing process. The prodrug was synthesized via solid phase

Seborrheic Keratosis of the Conjunctiva: A Case Report

PubMed Central

Kim, Ji Hyun; Bae, Hyoung Won; Lee, Kwang Kil; Kim, Tae Im

2009-01-01

Seborrheic keratosis is a benign epithelial neoplasia that occurs mainly in the skin of the eyelids and face. We describe a case of seborrheic keratosis of the conjunctiva confirmed by histopathology. A 72-year-old man presented with a recurrent conjunctival mass involving the nasal side of his right eye. Clinically, a diagnosis of conjunctival papilloma was made, and a mass excision was performed. The histopathological analysis evidenced a conjunctival-covering epithelium with papillomatous changes and irregular acanthosis, at the expense of a proliferation of basaloid cells. In addition, the lesion exhibited multiple pseudohorn cysts containing keratin. With the above findings, a diagnosis of conjunctival seborrheic keratosis was established. The occurrence of seborrheic keratosis on the conjunctiva is rare. In this case, seborrheic keratosis was confirmed by pathologic report despite its similar appearance with papilloma. Seborrheic keratosis should be considered in the differential diagnosis of conjunctival lesions. PMID:20046694

GIANT PEDUNCULATED SEBORRHEIC KERATOSIS OF PENIS

PubMed Central

Thakur, Jagdeep S; Thakur, Anamika; Chauhan, C G S; Diwana, Vijay K; Chauhan, D C

2008-01-01

Seborrheic keratosis of the penis is a rare entity. It has been mistaken as genital warts and differentiation is only made on histopathology. We are reporting a case presenting as multiple giant polypoidal lesions on the penile skin for the last 20 years. Seborrheic keratosis should be considered in the differential diagnosis of pedunculated lesions of the penis. The histopathology after shave excision will be diagnostic. PMID:19967020

The current role of in vivo reflectance confocal microscopy within the continuum of actinic keratosis and squamous cell carcinoma: a systematic review.

PubMed

Nguyen, Kim P; Peppelman, Malou; Hoogedoorn, Lisa; Van Erp, Piet E J; Gerritsen, Marie-Jeanne P

2016-12-01

Clinical differentiation between actinic keratosis (AK), squamous cell carcinoma (SCC) in situ, and invasive SCC and its variants may be difficult. Reflectance confocal microscopy (RCM) is a non-invasive technique for in vivo skin imaging. To explicate the diagnostic and monitoring use of RCM within the spectrum of AK and SCC, and evaluate the accuracy of RCM for these diagnoses relative to histopathology. A systematic literature search was performed in PubMed, EMBASE, the Cochrane Library, and Web of Science databases. The quality was assessed using the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist. Twenty-five eligible studies were included. Different diagnostic RCM features have been described for AK, actinic cheilitis (AC), erythroplasia of Queyrat, Bowen disease, invasive SCC, and keratoacanthoma (KA). The overall range of sensitivity and specificity of RCM for the diagnosis of SCC, AK, SCC in situ, and KA was 79-100% and 78-100%, respectively. The current literature describes the use of RCM for diagnosing AK, AC, erythroplasia of Queyrat, Bowen disease, invasive SCC, and KA, as well as for monitoring treatments of AK, with good accuracy. Unfortunately, studies with high methodological quality are lacking. Pre-treatment of hyperkeratotic lesions and uniform definitions of RCM features are required to simplify the differentiation between AKs, SCC in situ, and SCC and its variants in clinical practice.

Actinic keratosis modelling in mice: A translational study

PubMed Central

Vandenberghe, Isabelle; Cartron, Valérie; Cèbe, Patrick; Blanchet, Jean-Christophe; Sibaud, Vincent; Guilbaud, Nicolas; Audoly, Laurent; Lamant, Laurence; Kruczynski, Anna

2017-01-01

Background Actinic keratoses (AK) are pre-malignant cutaneous lesions caused by prolonged exposure to ultraviolet radiation. As AKs lesions are generally accepted to be the initial lesions in a disease continuum that progresses to squamous cell carcinoma (SCC), AK lesions have to be treated. They are also the second most common reason for visits to the dermatologist. Several treatments are available but their efficacy still needs to be improved. The UV-B-induced KA lesion mouse model is used in preclinical studies to assess the efficacy of novel molecules, even though it is often more representative of advanced AK or SCC. Objectives Here we report on a translational study, comparing the various stages of AK development in humans and in the UV-B irradiated mouse model, as well as the optimization of photograph acquisition of AK lesions on mouse skin. Methods Human and mouse skin lesions were analysed by histology and immunohistochemistry. Mouse lesions were also assessed using a digital dermatoscope. Results An histological and phenotypic analysis, including p53, Ki67 and CD3 expression detection, performed on human and mouse AK lesions, shows that overall AK modelling in mice is relevant in the clinical situation. Some differences are observed, such as disorganization of keratinocytes of the basal layer and a number of atypical nuclei which are more numerous in human AK, whereas much more pronounced acanthosis is observed in skin lesion in mice. Thanks to this translational study, we are able to select appropriate experimental conditions for establishing either early or advanced stage AK or an SCC model. Furthermore, we optimized photograph acquisition of AK lesions on mouse skin by using a digital dermatoscope which is also used in clinics and allows reproducible photograph acquisition for further reliable assessment of mouse lesions. Use of this camera is illustrated through a pharmacological study assessing the activity of CARAC®. Conclusion These data

Clinical and histopathologic study of benign lichenoid keratosis on the face.

PubMed

Kim, Han Su; Park, Eun Joo; Kwon, In Ho; Kim, Kwang Ho; Kim, Kwang Joong

2013-10-01

Benign lichenoid keratosis is a cutaneous entity that consists of a nonpruritic papule or slightly indurated plaque that is histologically characterized by a band-like inflammatory infiltrate with interface involvement. The purpose of this study was to investigate the clinical and histopathologic features of benign lichenoid keratosis localized on the face. Fourteen benign lichenoid keratosis patients diagnosed clinically and histopathologically in our clinic during the 10-year period from 2002 to 2012 were studied. Thirteen female and 1 male patients were included. The mean age at diagnosis was 46.5 years. The color of most of the lesions was brown (10 cases, 71%). The cheek was the most commonly involved area (10 cases, 71%). All of the lesions were single. There were 9 (64%) flat lesion cases and 5 (36%) raised lesion cases. Most patients denied having any symptoms; 3 had mild pruritus. The histopathological findings indicated that all the cases exhibited lichenoid inflammatory infiltrate obscuring the dermal-epidermal junction and vacuolar alteration of basal cell layer. The lesions showed focal parakeratosis (79%), melanophages (79%), hyperkeratosis (71%), and necrotic keratinocytes (71%). Solar elastosis (50%) and acanthosis (43%) were also seen frequently. Diagnosis of benign lichenoid keratosis should be made by a combination of clinical manifestations and histopathological findings. In particular, benign lichenoid keratosis should be considered if a middle-aged patient presents a solitary asymptomatic brown lesion on the face. We think benign lichenoid keratosis may be a specific disorder rather than the inflammatory stage of regressing solar lentigines, large cell acanthoma or reticulated seborrheic keratosis.

Bowenoid transformation in seborrheic keratosis: A retrospective analysis of 429 patients

PubMed Central

Rajabi, Parvin; Adibi, Neda; Nematollahi, Pardis; Heidarpour, Mitra; Eftekhari, Mehdi; Siadat, Amir Hossein

2012-01-01

Background: Seborrheic keratosis is a common, benign skin tumor. Numerous reports have shown its possibility of malignant transformation. This study was designed to demonstrate the occurrence of concomitant seborrheic keratosis and skin cancers. Materials and Methods: Data was retrospectively reviewed from all patients with a diagnosis of seborrheic keratosis in pathology department of Alzahra Hospital and a private pathology laboratory in Isfahan, Iran over a 4-year period. We classified all demographic data and associated dysplasia or Bowen's disease and analyzed them by student-t or chi-square tests. Results: From all 429 specimens, 5 (1.2%) were found to be associated with Bowen's disease and one (0.2%) with mild dysplasia in squamous epithelium. All cases arose within the clinically, atypical seborrheic keratosis. More men were affected with lesions alone and with malignancy (230/423 (54.4%) and 5/6 (83.3%), respectively) compared to women. The average age of patients suffering from lesions with and without associated malignancy was 57 and 54 years, respectively. The common site of lesion alone was head and neck but lesions with malignancy involved lower extremities. The two lesions were significantly different in site of occurrence (p < 0.001). Conclusion: Generally, although the association between seborrheic keratosis and skin malignancy appears to be accidental, it must always be in mind. Therefore, histopathologic examination of all seborrheic keratosis should be considered, especially when seborrheic keratosis has atypical clinical manifestations. PMID:23267371

Thermographic diagnostics to discriminate skin lesions: a clinical study

NASA Astrophysics Data System (ADS)

Stringasci, Mirian Denise; Moriyama, Lilian Tan; Salvio, Ana Gabriela; Bagnato, Vanderlei Salvador; Kurachi, Cristina

2015-06-01

Cancer is responsible for about 13% of all causes of death in the world. Over 7 million people die annually of this disease. In most cases, the survival rates are greater when diagnosed in early stages. It is known that tumor lesions present a different temperature compared with the normal tissues. Some studies have been performed in an attempt to establish new diagnosis methods, targeting this temperature difference. In this study, we aim to investigate the use of a handheld thermographic camera to discriminate skin lesions. The patients presenting Basal Cell Carcinoma, Squamous Cell Carcinoma, Actinic Keratosis, Pigmented Seborrheic Keratosis, Melanoma or Intradermal Nevus lesions have been investigated at the Skin Departament of Amaral Carvalho Hospital. Patients are selected by a dermatologist, and the lesion images are recorded using an infrared camera. The images are evaluated taken into account the temperature level, and differences into lesion areas, borders, and between altered and normal skin. The present results show that thermography may be an important tool for aiding in the clinical diagnostics of superficial skin lesions.

Cryotherapy - skin

MedlinePlus

... skin; Warts - freezing; Warts - cryotherapy; Actinic keratosis - cryotherapy; Solar keratosis - cryotherapy ... warts Destroy precancerous skin lesions (actinic keratoses or solar keratoses) In rare cases, cryotherapy is used to ...

Regulatory T cells in the actinic cheilitis.

PubMed

Gasparoto, Thaís Helena; de Souza Malaspina, Tatiana Salles; Damante, José Humberto; de Mello, Edgard Franco; Ikoma, Maura Rosane Valério; Garlet, Gustavo Pompermaier; Costa, Maria Renata Sales Nogueira; Cavassani, Karen Angélica; da Silva, João Santana; Campanelli, Ana Paula

2014-11-01

Actinic cheilitis (AC) is an oral potentially malignant lesion which is the counterpart of actinic keratosis of the skin and has potential to develop into squamous cell carcinoma. Regulatory T cells (Tregs) have a critical role in modulating the antitumor immune responses. The presence of regulatory T cells in potentially malignant lesions has not been described. We chose investigate the involvement of regulatory T cells in potentially malignant lesions. The frequency, phenotype, and activity of CD4+CD25+ T cells isolated from blood and lesion of AC patients were analyzed by flow cytometry. Cytokines were quantified by ELISA. Data were compared with samples from healthy subjects. The frequency and suppressor activity of circulating CD4+CD25+ T cells was similar in AC patients and control subjects. However, the frequencies of IL-10-positive Tregs were higher in AC patients, and these cells inhibited interferon-gamma (IFN-γ) and increased interleukin (IL)-10 productions in co-cultures. Furthermore, CD4+CD25+ T cells accumulate in AC lesions. Lesions-derived regulatory T cells suppressed lymphocyte proliferation and pro-inflammatory cytokine production. Moreover, high levels of IL-10 and transforming growth factor-β (TGF-β), and low IFN-γ were detected in the potentially malignant lesions. Therefore, our data show that Tregs accumulate in AC lesions, and these cells could be suppressing immune responses in a potentially malignant microenvironment. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Intraepidermal proliferation of Merkel cells within a seborrheic keratosis: Merkel cell carcinoma in situ or Merkel cell hyperplasia?

PubMed

McFalls, Jeanne; Okon, Lauren; Cannon, Sarah; Lee, Jason B

2017-05-01

Intradepidermal proliferation of Merkel cells without any dermal component has been interpreted as either a hyperplastic process secondary to chronic ultraviolet radiation or a neoplastic process, namely Merkel cell carcinoma (MCC) in situ. The recent criteria that have been proffered to diagnose MCC in situ, unfortunately, are identical to those that have been applied to Merkel cell hyperplasia in the past, posing a diagnostic quandary when faced with an intraepidermal proliferation of Merkel cells. Most previously reported cases of MCC in situ have occurred within associated epithelial lesion that includes solar (actinic) keratosis and squamous-cell carcinoma in situ. Similarly, Merkel cell hyperplasia has been reported to occur in association with a variety of epithelial lesions as well as on chronically sun-damaged skin. Herein, a case of an intraepidermal proliferation of Merkel cells within a seborrheic keratosis is presented accompanied by a discussion on whether the proliferation represents another case of Merkel cell carcinoma in situ or an incidental hyperplastic process on chronically sun-damaged skin. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Actinic keratosis-related signs predictive of squamous cell carcinoma in renal transplant recipients: a nested case-control study.

PubMed

Jiyad, Z; O'Rourke, P; Soyer, H P; Green, A C

2017-04-01

Squamous cell carcinoma (SCC) and intraepidermal carcinoma (IEC) commonly arise in actinically damaged skin. To identify clinical features of actinic change that correlate with an increased risk of SCC or IEC in the short-to-medium term as guidance for prioritizing field treatment. In a nested case-control study, cases were renal transplant recipients who developed an incident SCC or IEC within 18 months following baseline examination and photography. Controls without SCC or IEC were matched to cases on age, sex and duration of immunosuppression. Predefined skin sites on the head, neck and upper limbs were examined using baseline photographs to assess objectively the following features of actinic damage: presence of actinic keratosis (AK) patch (defined as AK > 1 cm 2 ), number of AK patches, number of AKs and area affected by AK. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using McNemar's test to identify differences in SCC/IEC risk combined and SCC risk alone between case and control skin sites. Thirty-nine cases were matched to 39 controls. Significant associations with the presence of an AK patch, number of AK patches, number of AKs and area affected by AKs were identified. The presence of an AK patch conferred an 18-fold increased risk of SCC (OR 18·00, 95% CI 2·84-750) and more than a sixfold increased risk of SCC/IEC combined (OR 6·60, 95% CI 2·56-21·66). AK patches are predictive of SCC/IEC development within 18 months. This can be used to guide site selection for field treatment in patients with widespread actinic damage. © 2016 British Association of Dermatologists.

Lichenoid keratosis is frequently misdiagnosed as basal cell carcinoma.

PubMed

Maor, D; Ondhia, C; Yu, L L; Chan, J J

2017-08-01

Lichenoid keratosis (LK), also known as benign lichenoid keratosis or lichen planus-like keratosis, is a solitary, pink to red-brown scaly plaque representing a host immunological response to a variety of precursor lesions. LK is often misdiagnosed as a dermatological malignancy owing to its clinical resemblance to basal cell carcinoma (BCC) or Bowen disease. We performed a retrospective analysis of the pathology records of a series of LK lesions with reference to the demographic features and accuracy of clinical diagnosis. The pathology records from 2008 to 2009 of 263 consecutive patients with a histological diagnosis of LK from a specialized skin laboratory were retrieved. Data relating to clinical diagnosis, age, sex, anatomical location, time of year of presentation and any coexistent pathological lesions adjacent to the LK were recorded. Mean age at presentation was 64 years (range 34-96), and 58% of patients were female. The most common anatomical site was the chest/anterior torso, followed by the back and legs. The most common coexisting lesion was solar keratosis at 14%, followed by seborrhoeic keratosis (SK) at 7.8%. The correct clinical diagnosis of LK was made in 29.5% of cases. The most common clinical diagnosis was BCC (47%), while SK was the preferred diagnosis in 18%. A clinical diagnosis was not given in 5.5% of cases. In conclusion, it appears that LK is frequently misdiagnosed, with misdiagnosis occurring in > 70% of cases in this study. © 2017 British Association of Dermatologists.

Effectiveness of cross polarized light and fluorescence diagnosis for detection of sub-clinical and clinical actinic keratosis during imiquimod treatment.

PubMed

Ortonne, Jean-Paul; Gupta, Girish; Ortonne, Nicolas; Duteil, Luc; Queille, Catherine; Mallefet, Pascal

2010-07-01

During treatment of actinic keratosis (AK) lesions with imiquimod sub-clinical lesions often become visible. It is, however, unclear whether these sub-clinical lesions would be detectable beforehand. The aim of this pilot study was to compare two techniques, cross polarized light photography (CPL) and fluorescence diagnosis (FD) using methyllevulinic acid and illumination with Wood's lamp for their ability to detect sub-clinical lesions. These findings were also compared with biopsy results taken before and after treatment with imiquimod 5% cream or vehicle. Twelve patients with at least five clinically visible AK lesions in a single contiguous 20 cm(2) area on the head were recruited. Patient eligibility was determined at the screening visit, when they were randomized to treatment. The randomization was 3:1, active to vehicle (nine treated with imiquimod, three with vehicle cream) for a total duration of 24 weeks (six clinic visits). Patients were assessed for baseline AK lesion counts (clinical and sub-clinical) at the screening visit and final counts at week 20. The number of clinically observed AK lesions was significantly lower at week 12 and week 20 compared with baseline following imiquimod treatment versus vehicle. The number of counted lesions were significantly higher using the CPL method compared with clinical counting with imiquimod treatment at baseline (8.3 +/- 3.4 vs 5.8 +/- 1.3; P = 0.027) and week 20 (4.8 +/- 2.4 vs 3.0 +/- 1.7; P = 0.02) but not in the vehicle group. The FD lesion counting method did not show a significant increase in the number of detected lesions compared with clinical analysis in the imiquimod and placebo groups but when comparisons were performed using pooled data (treatments and visits combined) the results were significant. The number of sub-clinical and clinical AK lesions detected during treatment with imiquimod can be better demonstrated using the methods of CPL and FD, but statistical significance was reached only using

Cost-effectiveness of Ingenol Mebutate Gel for the Treatment of Actinic Keratosis in Greece.

PubMed

Athanasakis, Kostas; Boubouchairopoulou, Nadia; Tarantilis, Filippos; Tsiantou, Vasiliki; Kontodimas, Stathis; Kyriopoulos, John

2017-05-01

The present study aimed to perform a cost-effectiveness analysis of ingenol mebutate (IM) versus other topical alternatives for the treatment of actinic keratosis (AK). The analysis used a decision tree to calculate the clinical effects and costs of AK first-line treatments, IM (2-3 days), diclofenac 3% (for 8 or 12 weeks), imiquimod 5% (for 4 or 8 weeks), during a 24-month horizon, using discrete intervals of 6 months. A hypothetical cohort of immunocompetent adult patients with clinically confirmed AK on the face and scalp or trunk and extremities was considered. Clinical data on the relative efficacy were obtained from a network meta-analysis. Inputs concerning resource use derived from an expert panel. All costs were calculated from a Greek third-party payer perspective. IM 0.015% and 0.05% were both cost-effective compared with diclofenac and below a willingness-to-pay threshold of €30,000 per quality-adjusted life-year (QALY) (€199 and €167 per QALY, respectively). Comparing IM on the face and scalp AK lesions for 3 days versus imiquimod for 4 weeks resulted in an incremental cost-effectiveness ratio of €10,868 per QALY. IM was dominant during the 8-week imiquimod period. IM use on the trunk and extremities compared with diclofenac (8 or 12 weeks) led to incremental cost-effectiveness ratios estimated at €1584 and €1316 per QALY accordingly. Results remained robust to deterministic and probabilistic sensitivity analyses. From a social insurance perspective in Greece, IM 0.015% and IM 0.05% could be the most cost-effective first-line topical field treatment options in all cases for AK treatment. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

A case of keratosis lichenoid chronica.

PubMed

Baczewski, Natasha; Albano, Brian

2012-01-01

Keratosis lichenoid chronica is a rare dermatologic anomaly believed to be a variant of lichen planus. It presents as violaceous, nodular lesions usually on the dorsal aspects of the extremities and the trunk. The disease is refractory to treatment although psoralen ultraviolet A therapy and oral retinoids have been proven useful in some cases. Here we present the case of a 58-year-old male diagnosed with keratosis lichenoid chronica.

Association between melanocytic neoplasms and seborrheic keratosis: more than a coincidental collision?

PubMed Central

DeFazio, Jennifer; Zalaudek, Iris; Busam, Klaus J.; Cota, Carlo; Marghoob, Ashfaq

2012-01-01

Clinical observations and an expanding knowledge of cell-to-cell communication have led us to speculate that the finding of a melanocytic nevus in conjunction with a seborrheic keratosis is more than a coincidental collision of two lesions. Here we present five cases demonstrating dermoscopic features of both melanocytic lesions and seborrheic keratoses with corresponding histology. Four cases demonstrate dermoscopic features of a melanocytic nevus and seborrheic keratosis, and the final case a melanoma arising in association with a seborrheic keratosis. PMID:23785597

Quality of life and side effects in patients with actinic keratosis treated with ingenol mebutate: a pilot study.

PubMed

Jubert-Esteve, E; Del Pozo-Hernando, L J; Izquierdo-Herce, N; Bauzá-Alonso, A; Martín-Santiago, A; Jones-Caballero, M

2015-10-01

Actinic keratosis (AK) lesions are in situ squamous cell carcinoma. These lesions have a low risk of progressing to invasive disease but significant impact on patients' quality of life (QoL). The aim of this study was to assess QoL and side effects in patients with AK receiving treatment with ingenol mebutate. This was a prospective, non-randomized pilot study carried out in Spain. The target population was adults with a clinical diagnosis of AK affecting any part of the body. Outcomes were assessed on the basis of a QoL questionnaire (Skindex-29), local skin response, the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4), and clinical response. A total of 19 patients were studied. Most of the participants were men (89.5%) and mean age was 76.2 years. After treatment with ingenol mebutate, significant improvement was observed in the Skindex-29 subscales relating to symptom severity (P=.041), the patients' emotional state (P=.026), and in the overall score (P=.014). Erythema, crusting, and flaking or scaling were the local skin responses with highest median score (2.0 in all 3 cases). Imiquimod 5% and ingenol mebutate achieved higher median scores for effectiveness and global satisfaction than any other previous treatments (as measured by TSQM 1.4). In the patients' assessment of convenience, ingenol mebutate had a higher median score than previous treatments. Over half of the patients (52.6%) had an improvement of at least 75% at month 3. QoL in patients with AK improves after treatment with ingenol mebutate. The presence of side effects did not affect QoL or patient satisfaction with treatment. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

Imiquimod 5% cream for the treatment of actinic keratosis: results from two phase III, randomized, double-blind, parallel group, vehicle-controlled trials.

PubMed

Lebwohl, Mark; Dinehart, Scott; Whiting, David; Lee, Peter K; Tawfik, Naji; Jorizzo, Joseph; Lee, James H; Fox, Terry L

2004-05-01

The immune system plays a critical role in the development and pathogenesis of actinic keratosis (AK). Imiquimod has been shown to stimulate the cutaneous immune response and be effective for the treatment of nonmelanoma skin cancers. Two phase III, randomized, double-blind, vehicle-controlled studies evaluated the efficacy of imiquimod 5% cream compared with vehicle in the treatment of AK lesions on the face and balding scalp. A total of 436 participants at 24 centers in the United States and Canada were randomized to either imiquimod 5% or vehicle cream. Study cream was applied one time per day, 2 days per week for 16 weeks. Clearance of AK lesions was clinically assessed at an 8-week posttreatment visit. The complete clearance rate was 45.1% for the imiquimod group and 3.2% for the vehicle group. The difference in complete clearance rates (imiquimod minus vehicle) was 41.9% with a 95% confidence interval of 34.9% to 49%. The partial (> or =75%) clearance rate was 59.1% for the imiquimod group and 11.8% for the vehicle group. The difference in partial clearance rates (imiquimod minus vehicle) was 47.3% with a 95% confidence interval of 39.5% to 55.1%. The median percent reduction in AK lesions was 83.3% for the imiquimod group and 0% for the vehicle group. Local skin reactions were common. Severe erythema was reported by 17.7% of participants who received imiquimod and 2.3% of participants who received vehicle. Overall, imiquimod was very well tolerated. Imiquimod 5% cream used 2 times per week for 16 weeks is an effective and well-tolerated treatment for AK.

Cost for the treatment of actinic keratosis on the rise in Australia

PubMed Central

Perera, Eshini; McGuigan, Sean; Sinclair, Rodney

2014-01-01

Objectives: To report the burden and cost of actinic keratosis (AK) treatment in Australia and to forecast the number of AK treatments and the associated costs to 2020. Design and setting: A retrospective study of data obtained from medicare Australia for AK treated by cryotherapy between 1 January 1994 and 31 December 2012, by year and by state or territory. Results: The total number of AK cryotherapy treatments increased from 247,515 in 1994 to 643,622 in 2012, and we estimate that the number of treatments will increase to 831,952 (95% CI 676,919 to 986,987) by 2020. The total Medicare Benefits Schedule (MBS) benefits paid out for AK in 2012 was $19.6 million and we forecast that this will increase to $24.7 million by 2020 (without inflation). Conclusion: The number of AK cryotherapy treatments increased by 160% between 1994 and 2012. we forecast that the number of treatments will increase by 30% between 2012 and 2020. The rates of non-melanoma skin cancer (NMSC) and AK appear to be increasing at the same rate. During the period 2010 to 2015 AK is anticipated to increase by 17.8% which follows a similar trend to published data that forecasts an increase in NMSC treatments of 22.3%. PMID:25309734

Cytological diagnosis of basal cell carcinoma and actinic keratosis, using Papanicolaou and May-Grünwald-Giemsa stained cutaneous tissue smear.

PubMed

Christensen, E; Bofin, A; Gudmundsdóttir, I; Skogvoll, E

2008-10-01

Cytology may become the diagnostic method of choice with the advent of new non-invasive treatments for non-melanoma skin cancer, as the sampling technique for cytology entails little tissue disfiguration. The aim of this study was to compare and evaluate the diagnostic performance of scrape cytology using two different cytological staining techniques, and to evaluate additional touch imprint cytology, with that of histopathology of basal cell carcinoma (BCC) and actinic keratosis (AK). We investigated 50 BCC and 28 AK histologically verified lesions, from 41 and 25 patients, respectively. Two separate skin scrape samples and one touch imprint sample were taken from each lesion. The smears were stained with Papanicolaou (Pap) or May-Grünwald-Giemsa (MGG) stains. All cytological specimens were examined in random order by pathologists without knowledge of the histology. Cytodiagnostic results were compared with the histopathological report. Scrape cytodiagnosis agreed with histopathology in 48 (Pap) and 47 (MGG) of the 50 BCC cases, and in 26 of 28 (Pap) and 21 of 26 (MGG) AK cases, yielding sensitivities of 96%, 94%, 93% and 81%, respectively. No significant difference in sensitivity between the two staining methods was found but a trend towards higher Pap sensitivity for AK was noted (P = 0.10). Touch imprint cytology confirmed histopathology in 38 of the 77 cases of BCC and AK. Cytological diagnosis with either Pap or MGG stain for BCC and AK is reliable, and differentiates well between BCC and AK. Imprint cytology proved to be non-diagnostic in half of the examined cases.

Efficacy of Photodynamic Therapy in the Short and Medium Term in the Treatment of Actinic Keratosis, Basal Cell Carcinoma, Acne Vulgaris and Photoaging: Results from Four Clinical Trials

PubMed Central

Martínez-Carpio, PA; Alcolea-López, JM; Vélez, M

2012-01-01

Objective: To determine the clinical efficacy of methyl-aminolevulinate (MAL)-Photodynamic Therapy (PDT) in the treatment of actinic keratosis (AK), basal cell carcinoma (BCC), acne vulgaris (AV) and photoaging (PA), in the short and medium term. Subjects and methods: Four separate prospective studies were designed on patients with AK (n=25), BCC (n=20), AV (n=20) and PA (n=25). Two PDT protocols were applied, and different clinical efficacy criteria were established, including lesion count and size. Two semi-quantitative and four analogue visual scales were completed for the evaluation of results according to the therapist, the patient and two independent experts. Results: In the AK and BCC studies, full clinical remission was observed in 84.7% and 75.7% of lesions, respectively. In the AV study, the number of inflammatory and non-inflammatory lesions fell significantly (p<0.001, p<0.05). In the PA study a reduction in Dover scale scores (3.19 vs. 2.14, p<0.001) was proven. The percentages of satisfied or very satisfied patients were: AK=88%, BCC=90%, AV=89% and PA=80%. A year later, none of the AK or BCC lesions had reappeared, and the cases of AV and PA remained stable, with a tendency towards improvement. Conclusion: the MAL-PDT procedures used produced efficacious, safe and satisfactory results in KA, BCC, AV and PA in the short and medium term. PMID:24511190

Switching From Conventional Photodynamic Therapy to Daylight Photodynamic Therapy For Actinic Keratoses: Systematic Review and Meta-analysis.

PubMed

Tomás-Velázquez, A; Redondo, P

2017-05-01

Actinic keratosis is a precursor lesion to the most common nonmelanoma skin cancer. Conventional photodynamic therapy (PDT) has been shown to be effective, but the procedure is time-consuming, can be very painful, and requires infrastructure. These shortcomings led to the emergence of daylight PDT. To obtain a global estimate of efficacy, we undertook a systematic literature review and performed a meta-analysis of the available evidence on the efficacy and safety of daylight PDT as compared to conventional PDT in the treatment of actinic keratosis and/or field cancerization. The conclusion is that the difference in efficacy is clinically negligible (global estimate of the mean response rate difference, -3.69%; 95% CI, -6.54% to -0.84%). The adverse effects of daylight PDT are mild and localized (79% of patients report no discomfort), and patients report less pain (P<.001). Daylight PDT gives good to excellent cosmetic results in more than 90% of patients, and patient satisfaction is greater (P<.001). Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Randomized, Controlled Trial of Fractional Carbon Dioxide Laser Resurfacing Followed by Ultrashort Incubation Aminolevulinic Acid Blue Light Photodynamic Therapy for Actinic Keratosis.

PubMed

Alexiades, Macrene

2017-08-01

Aminolevulinic acid (ALA) photodynamic therapy (PDT) is an established treatment option for actinic keratosis (AK), and recently fractional carbon dioxide (CO2) laser was shown to improve outcomes; but studies of short incubation photosensitizer are lacking. Assess the efficacy of short incubation ALA followed by blue light PDT with and without previous fractional CO2 treatment for the treatment of AK. Randomized, paired split-design, controlled trial of fractional CO2 followed by ultrashort 15-minute versus 30-minute incubation ALA and blue light PDT for the treatment of AK on the face. The complete clearance rates (CRs) at 8 weeks after ALA PDT with and without FxCO2 at 30- and 15-minute ALA incubation times were 89.78% (+FxCO2) versus 71.20% CR (-FxCO2) at 30', and 86.38% (+FxCO2) versus 69.23% (-FxCO2) at 15' ALA incubation. All lesion improvements were statistically significant. This randomized, comparative paired group controlled clinical study demonstrates that ultrashort 15- and 30-minute incubation ALA PDTs are of limited efficacy for the treatment of AK. Pretreatment with fractional ablative resurfacing yields statistically significant greater AK clearance with ALA-PDT at ultrashort ALA incubations followed by blue light.

Use of reflectance confocal microscopy to evaluate 5-fluorouracil 0.5%/salicylic acid 10% in the field-directed treatment of subclinical lesions of actinic keratosis: subanalysis of a Phase III, randomized, double-blind, vehicle-controlled trial.

PubMed

Ulrich, M; Reinhold, U; Falqués, M; Rodriguez Azeredo, R; Stockfleth, E

2018-03-01

Actinic keratosis (AK) is a common skin disorder that can progress to invasive squamous-cell carcinoma. AK can present as clinical (visible) or subclinical (invisible) lesions within areas of chronic sun damage. The importance of treating subclinical AK is gaining support. We present a subanalysis of a previously published Phase III, double-blind, vehicle-controlled study (NCT02289768), to assess 5-fluorouracil (5-FU) 0.5%/salicylic acid 10% treatment of subclinical AK lesions, based on reflectance confocal microscopy (RCM). To determine the efficacy of 5-FU 0.5%/salicylic acid 10% as field-directed treatment for subclinical AK lesions using RCM. For inclusion in this subanalysis, patients had to have at least three subclinical AK lesions within a 25 cm 2 area of skin. Subclinical AK lesions were diagnosed according to the presence of three key RCM criteria: architectural disarray; keratinocyte atypia and pleomorphism at the basal, spinous and granular layer. Subclinical AK lesions were evaluated by RCM at baseline, after 4, 6 and 12 weeks of 5-FU 0.5%/salicylic acid 10% treatment or vehicle, and 8 weeks following the end of treatment. Twenty-seven patients were included: 17 [mean age = 72.2 years, standard deviation (SD) = 6.3] received 5-FU 0.5%/salicylic acid 10% treatment and 10 (mean age = 76.4 years, SD = 3.9) received vehicle. Eight weeks following the end of treatment, the mean number of subclinical lesions declined (from 3.0 at baseline) to 0.3 (95% confidence interval [CI] 0.06-0.57) for the 5-FU 0.5%/salicylic acid 10% group and 1.6 (95% CI 0.52-2.68) in the vehicle group (reductions of 90% [95% CI 72.1-107.1] vs. 47% [95% CI 24.8-69.5], respectively; P = 0.005). The proportion of patients receiving 5-FU 0.5%/salicylic acid 10% showing complete clearance of three preselected subclinical AK lesions was numerically greater than in the vehicle group (69% vs. 40%, respectively; P = 0.183). To the best of our knowledge, this is the first randomized, vehicle

Microspectroscopic Analysis Of HpD Fluorescence In Bioptic Samples From Human Pre-Malignant And Malignant Lesions Of The Skin

NASA Astrophysics Data System (ADS)

Bottiroli, G.; Dell'Acqua, R.; Jucci, A.; Ricevuti, G.; Sacchi, A. S.

1987-07-01

Microfluorometric analysis was performed on bioptic samples of pre-malignant and malignant cutanous lesions present in the same patients, 48 h after i.v. injection of HpD. Data obtained indicate that actinic keratosis and squamous celle carcinoma show a preferential accumulation if compared to normal skin. The two lesions differ for both intensity and spectral shape of HpD fluorescence. This difference is correlated with a different clinical response to HpD laser phototherapy.

Prevalence of actinic keratosis among dermatology outpatients in Spain.

PubMed

Ferrándiz, C; Plazas, M J; Sabaté, M; Palomino, R

2016-10-01

Actinic keratoses (AKs) are common skin lesions associated with an increased risk of developing squamous cell carcinoma. Few studies in Europe have focused on AK prevalence. To determine the point prevalence of AKs in a dermatology outpatient population in Spain, to describe the clinical characteristics of these lesions and to characterise the profile of AK patients. Observational, cross-sectional, multicentre study conducted in 19 hospitals (dermatology outpatient services) around Spain. A total of 204 consecutive patients per hospital who were ≥45 years old were screened for the presence of AKs. 3877 patients were assessed and the overall AKs prevalence was 28.6%. Prevalence was significantly higher in men than women (38.4% vs. 20.8%, p<0.0001) and increased with age for both sexes (45.2% in 71-80 years). Scalp and ear lesion locations were significantly more frequent in men (51.9% vs. 2.7% and 16.9% vs. 2.4%, respectively, p<0.0001 both cases) and the cheek, nose and neckline in women (46.3% vs. 34.0% [p<0.0001], 43.0% vs. 24.8% [p<0.0001] and 5.3% vs. 1.8% [p=0.002]). Men showed a significantly higher frequency of ≥2 affected areas than women (42.7% vs. 20.3%, p<0.0001). Among patients with AK lesions, only 65% confirmed that they were the reason for the visit to the clinic. Approximately a quarter of the dermatology outpatient population in Spain aged ≥45 years old have AKs, with the prevalence rate being highest in men and in older age groups. AK is underdiagnosed and a proactive strategy is needed for the diagnosis and early treatment of these lesions. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Skin lesion removal

MedlinePlus

... benign; Cryosurgery - skin, benign; BCC - removal; Basal cell cancer - removal; Actinic keratosis - removal; Wart - removal; Squamous cell - removal; Mole - removal; Nevus - removal; Nevi - removal; Scissor ...

Two cases of seborrheic keratosis with basal clear cells.

PubMed

Anan, Takashi; Fukumoto, Takaya; Kimura, Tetsunori

2017-03-01

Seborrheic keratosis with basal clear cells (SKBCC) is an extremely rare histopathological variant of seborrheic keratosis that has histological similarities to melanoma in situ. We herein report two cases of SKBCC and provide the first description of the dermoscopic features of this condition, in addition to the histopathological findings. Both of the two lesions showed typical histological architectures of seborrheic keratosis with rows or focal clusters of monomorphic clear cells with abundant pale cytoplasm and small round nucleus in the basal layer. Immunohistochemical examination revealed that most clear cells were positive for high molecular weight cytokeratin (34βE12) in a peripheral pattern but were negative tor Melan-A. Dermoscopy revealed typical features of ordinary seborrheic keratosis, while unfortunately did not reflect the presence of basal clear cells. © 2016 Japanese Dermatological Association.

A survey of office visits for actinic keratosis as reported by NAMCS, 1990-1999. National Ambulatory Medical Care Survey.

PubMed

Gupta, Aditya K; Cooper, Elizabeth A; Feldman, Steven R; Fleischer, Alan B

2002-08-01

Although actinic keratosis (AK) has been linked to the development of nonmelanoma skin cancer (NMSC), particularly squamous cell carcinoma (SCC), increased awareness regarding diagnosis and treatment may be an important component for reducing morbidity and even mortality from AK and NMSC. We used the National Ambulatory Medical Care Survey (NAMCS) data from 1990 to 1999 to evaluate the diagnosis and treatment of AKs among a wide variety of patients by physicians across the United States. To our knowledge, no widespread surveys of North American populations have been performed recently to determine the epidemiology of AK. AK was diagnosed in more than 47 million visits over the 10-year period surveyed and was found to occur in 14% of patients visiting dermatologists. The diagnosis of AK as determined by NAMCS does not reflect the true prevalence of AK because only patients seeking physician diagnosis were surveyed. This suggests that the actual number of patients in the United States with AK is much higher than 14%. Rates of AK diagnosis in the standard metropolitan statistical areas (SMSAs) and non-standard metropolitan statistical areas (non-SMSAs) of the West states are higher than in other states, but geographic location may not be a direct risk factor for the development of AKs. Procedures were undertaken at 70% of visits where AK was the primary diagnosis. Destruction of lesions was the most frequently performed procedure found in the survey considering only the 1993 and 1994 NAMCS data. Biopsy was the second most frequently performed procedure.

Comparison of 10 efficient protocols for photodynamic therapy of actinic keratosis: How relevant are effective light dose and local damage in predicting the complete response rate at 3 months?

PubMed

Vignion-Dewalle, Anne-Sophie; Baert, Gregory; Thecua, Elise; Lecomte, Fabienne; Vicentini, Claire; Abi-Rached, Henry; Mortier, Laurent; Mordon, Serge

2018-04-18

Topical photodynamic therapy is an established treatment modality for various dermatological conditions, including actinic keratosis. In Europe, the approved protocols for photodynamic therapy of actinic keratosis involve irradiation with either an Aktilite CL 128 lamp or daylight, whereas irradiation with the Blu-U illuminator is approved in the United States. Many other protocols using irradiation by a variety of light sources are also clinically efficient. This paper aims to compare 10 different protocols with clinically proven efficacy for photodynamic therapy of actinic keratosis and the available spectral irradiance of the light source. Effective irradiance, effective light dose, and local damage are compared. We also investigate whether there is an association between the complete response rate at 3 months and the effective light dose or local damage. The effective irradiance, also referred to as protoporphyrin IX-weighted irradiance, is obtained by integrating the spectral irradiance weighted by the normalized absorption spectrum of protoporphyrin IX over the wavelength. Integrating the effective irradiance over the irradiation time yields the effective light dose, which is also known as the protoporphyrin IX-weighted light dose. Local damage, defined as the total cumulative singlet oxygen molecules produced during treatment, is estimated using mathematical modeling of the photodynamic therapy process. This modeling is based on an iterative procedure taking into account the spatial and temporal variations in the protoporphyrin IX absorption spectrum during treatment. The protocol for daylight photodynamic therapy on a clear sunny day, the protocol for daylight photodynamic therapy on an overcast day, the photodynamic therapy protocol for a white LED lamp for operating rooms and the photodynamic therapy protocol for the Blu-U illuminator perform better than the six other protocols-all involving red light illumination-in terms of both effective light dose and

[Increased glucose uptake by seborrheic keratosis on PET scan].

PubMed

Merklen-Djafri, C; Truntzer, P; Hassler, S; Cribier, B

2017-05-01

Positron emission tomography (PET) is an examination based upon the uptake of a radioactive tracer by hypermetabolic cells. It is primarily used in tandem with tomodensitometry (PET-TDM) for cancer staging because of its high sensitivity and specificity for the detection of metastases. However, unusually high uptake may occur with benign tumours, including skin tumours. Herein, we report an extremely rare case of pathological uptake levels resulting from seborrhoeic keratosis. A 55-year-old male patient with oesophageal squamous-cell carcinoma was referred to us following the discovery of an area of high marker uptake following PET-TDM and corresponding to a pigmented skin lesion. No other areas of suspect high uptake were seen. The lesion was surgically excised and histological examination indicated seborrhoeic keratosis. The histological appearance was that of standard seborrhoeic keratosis without any notable mitotic activity. PET-TDM is an examination that enables diagnosis of malignancy. However, rare cases have been described of increased marker uptake by benign cutaneous tumours such as histiocytofibroma, pilomatricoma and condyloma. To date, there have only been only very few cases of increased uptake due to seborrhoeic keratosis. This extremely unusual case of increased glucose uptake in PET-TDM due to seborrhoeic keratosis confirms that the hypermetabolic activity detected by this examination is not necessarily synonymous with malignancy and that confirmation by clinical and histological findings is essential. The reasons for increased metabolic activity within such benign tumours are not known. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Photodamage: all signs lead to actinic keratosis and early squamous cell carcinoma.

PubMed

Wei, Jerry; Kok, Lai Fong; Byrne, Scott N; Halliday, Gary M

2015-01-01

Ultraviolet (UV) radiation is likely to drive the initiation and progression of skin cancer from actinic keratosis to squamous cell carcinoma. Signs of photodamage occur at multiple steps. UV radiation damages many cellular constituents, including lipids, proteins and DNA, all of which are likely to contribute to UV-induced skin cancer. Two biological events culminating from photodamage are mutations in the genes critical to the control of cell division, differentiation and invasion and immunosuppression. DNA photodamage, if unrepaired prior to cell division, can result in the incorporation of an incorrect nucleotide into newly synthesised DNA. Mutations in critical genes contribute to carcinogenesis. Photodamage to proteins such as those involved in DNA repair or proteins or lipids involved in cellular signalling can interfere with this repair process and contribute to mutagenesis. Mutations in key genes, including TP53, BRM, PTCH1, and HRAS, contribute to skin carcinogenesis. UV also damages immunity. Photodamage to DNA and signalling lipids as well as other molecular changes are detrimental to the key cells that regulate immunity. Photodamaged dendritic cells and altered responses by mast cells lead to the activation of T and B regulatory cells that suppress immunity to the protein products of UV-mutated genes. This stops the immune response from its protective function of destroying mutated cells, enabling the transformed cells to progress to skin cancer. UV appears to play a pivotal role at each of these steps, and therefore, signs of photodamage point to the development of skin cancer. © 2015 S. Karger AG, Basel.

Variation in the Cost of Managing Actinic Keratosis

PubMed Central

Gregory, Tanner; Liu, Guodong; Leslie, Douglas L.; Miller, Jeffrey J.

2017-01-01

Importance Actinic keratosis (AK), a skin growth induced by ultraviolet light exposure, requires chronic management because a small proportion can progress into squamous cell skin cancer. Spending for AK management was more than $1 billion in 2004. Investigating geographic variation in AK spending presents an opportunity to decrease waste or recoup excess spending. Objective To evaluate geographic variation in health care cost for management of AKs and the association with patient-related and health-related factors. Design, Setting, and Participants This retrospective cohort study was performed using data from the MarketScan medical claims database of 488 324 continuously enrolled members with 2 or more claims for AK. Data from January 1, 2008, to December 31, 2012, was used. Main Outcomes and Measures Annual costs of care were calculated for outpatient visits, AK destruction, and medications for AKs, and the total of these components. Costs were adjusted for inflation to 2014 US dollars. To display cost variation, we calculated the ratio of mean cost in the highest quintile (Q5) relative to the mean in the lowest quintile (Q1), or the Q5:Q1 ratio; Q5:Q1 ratios were adjusted based on age, sex, history of nonmelanoma skin cancer, US geographic region, and population density (metropolitan statistical area). Results Overall, data from 488 324 continuously enrolled members (mean [SD] age, 53.1 [7.5] years; 243 662 women) with 2 or more claims for AK were included. Overall, patients had 1 085 985 claims related to AK, and dermatologists accounted for 71.0% of claims. The 2-year total cost was $111.5 million, with $52.4 million in 2011 and $59.1 million in 2012. The unadjusted Q5:Q1 ratios for total annual cost per patient ranged from 9.49 to 15.10. Adjusted ratios ranged from 1.72 to 1.80. Conclusions and Relevance There is variation in AK management cost within and between regions. This is not fully explained by differences in patient characteristics such as

Evaluation of the efficacy and tolerability of 0.5% fluorouracil cream and 5% fluorouracil cream applied to each side of the face in patients with actinic keratosis.

PubMed

Loven, Keith; Stein, Linda; Furst, Katharine; Levy, Sharon

2002-06-01

A new 0.5% fluorouracil cream has been developed that provides an alternative to the more highly concentrated topical formulations of fluorouracil that are currently available. This was a comparison of the tolerability and efficacy of the 0.5% and 5% fluorouracil creams in the treatment of actinic keratosis (AK). During this single-blind, randomized study, patients with > or =6 AK lesions were treated for 4 weeks with the 0.5% (once daily) and 5% (twice daily) fluorouracil creams applied to opposite sides of the face. After the end of treatment, patients were followed for an additional 4 weeks. Efficacy variables included absolute and percent reductions in AK lesions from baseline and total clearance of AK lesions. A questionnaire was used to evaluate patients' treatment preferences. Tolerability was evaluated through continuous monitoring of adverse events. Treatment with 0.5% fluorouracil cream reduced the number of AK lesions from 11.3 at baseline to 2.5 at the end of the 4-week follow-up phase, compared with a reduction from 10.3 to 4.2 lesions after treatment with 5% fluorouracil cream. The reduction was significantly greater with the 0.5% cream compared with the 5% cream (P = 0.044). The 0.5% cream was as effective as the 5% cream in terms of the percent reduction in AK lesions from baseline (67% and 47%, respectively) and in achieving total clearance of AK lesions (both treatments, approximately 43% of patients). Both treatments were associated with similar degrees of investigator-rated irritation; however, patients preferred the 0.5% cream because they felt it was more tolerable (P = 0.003), easier to apply, and had a once-daily application schedule. Although all patients experienced facial irritation in association with both creams, fewer patients treated with the 0.5% cream reported symptoms of facial irritation. In this study, 0.5% fluorouracil cream once daily was at least as effective as 5% fluorouracil cream twice daily in terms of the percent

[Photodynamic therapy for actinic cheilitis].

PubMed

Castaño, E; Comunión, A; Arias, D; Miñano, R; Romero, A; Borbujo, J

2009-12-01

Actinic cheilitis is a subtype of actinic keratosis that mainly affects the lower lip and has a higher risk of malignant transformation. Its location on the labial mucosa influences the therapeutic approach. Vermilionectomy requires local or general anesthetic and is associated with a risk of an unsightly scar, and the treatment with 5-fluorouracil or imiquimod lasts for several weeks and the inflammatory reaction can be very intense. A number of authors have used photodynamic therapy as an alternative to the usual treatments. We present 3 patients with histologically confirmed actinic cheilitis treated using photodynamic therapy with methyl aminolevulinic acid as the photosensitizer and red light at 630 nm. The clinical response was good, with no recurrences after 3 to 6 months of follow-up. Our experience supports the use of photodynamic therapy as a good alternative for the treatment of actinic cheilitis.

Expression of matrix metalloproteinase-1, -2 and -3 in squamous cell carcinoma and actinic keratosis

PubMed Central

Tsukifuji, R; Tagawa, K; Hatamochi, A; Shinkai, H

1999-01-01

Matrix metalloproteinase (MMP) plays an important role in extracellular matrix degradation associated with cancer invasion. An expression of MMP-1 (interstitial collagenase), MMP-2 (72-kDa type IV collagenase) and MMP-3 (stromelysin-1) was investigated in squamous cell carcinoma (SCC) and its precancerous condition, actinic keratosis (AK), using in situ hybridization techniques. MMP-1 mRNA was detected in tumour cells and/or in stromal cells in all cases of SCC, four of six AKs adjacent to SCC and four of 16 AKs. MMP-2 and MMP-3 mRNAs were detected in SCC but not in AK. The expression of MMP-3 correlated to that of MMP-1 (P = 0.03) localized at the tumour mass and stroma of the invasive area, while MMP-2 mRNA was detected widely throughout the stroma independent of MMP-1 expression. Our results indicated that the expression of MMP-1, -2 and -3 showed different localization patterns, suggesting a unique role of each MMP in tumour progression. Moreover, MMP-1 expression could be an early event in the development of SCC, and AK demonstrating MMP-1 mRNA, might be in a more advanced dysplastic state, progressing to SCC. © 1999 Cancer Research Campaign PMID:10362121

Defining the actinic keratosis field: a literature review and discussion.

PubMed

Figueras Nart, I; Cerio, R; Dirschka, T; Dréno, B; Lear, J T; Pellacani, G; Peris, K; Ruiz de Casas, A

2018-04-01

Despite the chronic and increasingly prevalent nature of actinic keratosis (AK) and existing evidence supporting assessment of the entire cancerization field during clinical management, a standardized definition of the AK field to aid in the understanding and characterization of the disease is lacking. The objective of this review was to present and appraise the available evidence describing the AK cancerization field, with the aim of determining a precise definition of the AK field in terms of its molecular (including genetic and immunological), histological and clinical characteristics. Eight European dermatologists collaborated to conduct a review and expert appraisal of articles detailing the characteristics of the AK field. Articles published in English before August 2016 were identified using PubMed and independently selected for further assessment according to predefined preliminary inclusion and exclusion criteria. In addition, a retrospective audit of patients with AK was performed to define the AK field in clinical terms. A total of 32 review articles and 47 original research articles provided evidence of sun-induced molecular (including genetic and immunological) and histological skin changes in the sun-exposed area affected by AK. However, the available literature was deemed insufficient to inform a clinical definition of the AK field. During the retrospective audit, visible signs of sun damage in 40 patients with AK were assessed. Telangiectasia, atrophy and pigmentation disorders emerged as 'reliable or very reliable' indicators of AK field based on expert opinion, whereas 'sand paper' was deemed a 'moderately reliable' indicator. This literature review has revealed a significant gap of evidence to inform a clinical definition of the AK field. Therefore, the authors instead propose a clinical definition of field cancerization based on the identification of visible signs of sun damage that are reliable indicators of field cancerization based on expert

Optical coherence tomography in the diagnosis of actinic keratosis-A systematic review.

PubMed

Friis, K B E; Themstrup, L; Jemec, G B E

2017-06-01

Optical coherence tomography (OCT) is a real-time non-invasive imaging tool, introduced in dermatology in the late 1990s. OCT uses near-infrared light impulses to produce images which can be displayed in cross-sectional and en-face mode. The technique has been used to image skin diseases especially non-melanoma skin cancer including actinic keratosis (AK). Morphological characteristics of AK can be visualized in OCT images and can be used for diagnosis as well as disease monitoring. A systematic review of original papers on AK and OCT was performed on 31.03.16 and 24.10.16 in the major databases Pubmed, MEDLINE, EMBASE, Cochrane and Svemed. Through database search and other sources, we identified 1366 titles of which 21 studies met the inclusion criteria and were used for further investigation. 16/16 Conventional OCT (cross-sectional images) studies described disruption of layers consistent with absence of normal layered architecture in the skin. Thickened epidermis was found in 14/16 studies and white (hyperreflective) streaks and dots were described in 11/16 studies. In High-definition optical coherence tomography (HD-OCT) images disarranged epidermis (cross-sectional images) along with an atypical honeycomb pattern (en-face images) was found in 5/5 studies and well-demarcated dermo-epithelial junction (DEJ) (cross-sectional images) was described in 3/5 studies. Several morphological characteristics of AKs were identified using Conventional OCT and HD-OCT. It is suggested that these may be used in the diagnosis of AK. Additional validation is however required to establish consensus on the optimal diagnostic criteria. Copyright © 2017 Elsevier B.V. All rights reserved.

Pharmacoeconomy of drugs used in the treatment of actinic keratoses

PubMed Central

Nisticò, S; Torchia, V; Gliozzi, M; Bottoni, U; Del Duca, E; Muscoli, C

2016-01-01

Actinic keratosis (AK) represents an emerging issue in the area of skin diseases which undergo high risk for developing squamous cell carcinoma (SCC). Recently, evidence has been accumulated that 3% diclofenac sodium and ingenol mubetate may efficiently counteract the development of progressive AK even if the pharmacoeconomic impact of such a treatment remains poorly defined. With the objective of assessing the efficacy of 3% diclofenac sodium versus ingenol mebutate, a comparative cost-efficacy analysis was performed between both pharmacological treatments. In the present analysis, data of efficacy of clinical studies were combined with information on the quality of life associated with AK lesions based on available literature data. Furthermore, the cost associated with the management of these lesions in Italy has been taken into account. To this purpose, we carried out a literature survey on the clinical and economic data among clinical reports available in Italy based on the assessment of related expenditure of public resources and their relationship with the subsequent health benefits. PMID:27207444

Acantholytic squamous cell carcinoma is usually associated with hair follicles, not acantholytic actinic keratosis, and is not "high risk": Diagnosis, management, and clinical outcomes in a series of 115 cases.

PubMed

Ogawa, Toru; Kiuru, Maija; Konia, Thomas H; Fung, Maxwell A

2017-02-01

Acantholytic squamous cell carcinoma (aSCC) is regarded as a high-risk variant of cutaneous squamous cell carcinoma (SCC). Acantholytic actinic keratosis (aAK) has been regarded as a precursor risk factor for aSCC. However, supporting evidence is limited. We sought to document clinical features, histologic features, management, and outcomes in a series of aSCC cases. Definitions of aSCC, aAK, and aSCC arising in association with aAK were applied to a consecutive series of aSCC cases. Clinical characteristics and outcomes were obtained from electronic medical records. Of 115 aSCC cases (103 patients, mean age 71.8 years), actinic keratosis was present in 23% (27/115) but only 7.8% (9/115) exhibited associated aAK. Ten cases (10/115, 9%) fulfilled strict histologic criteria for follicular SCC as previously defined, but 50 of 115 (43%) of our aSCC cases exhibited predominant involvement of follicular epithelium rather than epidermis. Clinical outcome (median follow-up, 36 months) was available in 106 of 115 (92%). One patient experienced regional extension (parotid), and 1 patient experienced a local recurrence (nose). No disease-related metastases or deaths were documented. This was a single-institution retrospective study from the United States. The presence of acantholysis in cutaneous SCC does not specifically confer aggressive behavior, a finding that may inform clinical practice guidelines. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Factors influencing response to ingenol mebutate therapy for actinic keratosis of face and scalp

PubMed Central

Skroza, Nevena; Proietti, Ilaria; Bernardini, Nicoletta; Balduzzi, Veronica; Mambrin, Alessandra; Marchesiello, Anna; Tolino, Ersilia; Zuber, Sara; La Torre, Giuseppe; Potenza, Concetta

2017-01-01

AIM To determine factors independently influencing response to ingenol mebutate therapy and assess efficacy on clinical setting of non-hypertrophic non-hyperkeratotic actinic keratosis (AK). METHODS Consecutive patients affected by non-hypertrophic non-hyperkeratotic AKs of the face or scalp were enrolled to receive ingenol mebutate 0.015% gel on a selected skin area of 25 cm2 for 3 consecutive days. Local skin reactions were calculated at each follow up visit using a validated composite score. Efficacy was evaluated by the comparison of clinical and dermoscopic pictures before the treatment and at day 57, and classified as complete, partial and poor response. RESULTS A number of 130 patients were enrolled, of which 101 (77.7%) were treated on the face, while 29 (22.3%) on the scalp. The great majority of our study population (n = 119, 91.5%) reached at least a 75% clearance of AKs and, in particular, 58 patients (44.6%) achieved a complete response while 61 (46.9%) a partial one. Logistic backward multivariate analysis showed that facial localization, level of local skin reaction (LSR) at day 2, the highest LSR values and level of crusts at day 8 were factors independently associated with the achievement of a complete response. CONCLUSION Ingenol mebutate 0.015% gel, when properly applied, is more effective on the face than on the scalp and efficacy is directly associated to LSR score. PMID:29067277

Actinic keratosis and diabetes complications: A nationwide population-based study in South Korea (2009-2015).

PubMed

Lee, YoungBok; Lee, JiHyun; Choi, JinYoung; Yu, DongSoo; Han, KyungDo; Park, Yong-Gyu

2017-11-29

As the associations between actinic keratosis (AK) and diabetes complications in patients with diabetes mellitus (DM) have never been investigated, this study aimed to evaluate any such associations in patients with DM. This retrospective cohort study analyzed clinical data for DM patients aged>40 years who had undergone the health examination recommended by the South Korea National Health Insurance Program between 2009 and 2012 (n=2,056,580). All of these patients were classified according to the presence of diabetic retinopathy (DR), end-stage renal disease (ESRD) and history of DVD; myocardial infarction, stroke, transient ischaemic attacks. Newly diagnosed AK was identified using claims data from baseline to the date of diagnosis or 31 December 2015, whichever came first. Of the 2,056,580 patients with DM, 6404 (0.31%) developed AK. Those patients in the DR, ESRD and CVD groups were more likely to be diagnosed with AK (P<0.001, by log-rank test). After adjusting for age and gender, the risks for AK were significantly higher in the DR, ESRD and CVD groups: HR (95% CI): 1.29 (1.21-1.39), HR: 4.24 (3.28-5.47) and HR: 1.22 (1.13-1.31), respectively. This study has revealed that the incidence of AK is higher in diabetes patients with ocular, renal and cardiovascular complications. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Acantholytic squamous cell carcinoma is usually associated with hair follicles, not acantholytic actinic keratosis, and is not “high risk”: Diagnosis, management, and clinical outcomes in a series of 115 cases

PubMed Central

Ogawa, Toru; Kiuru, Maija; Konia, Thomas H.; Fung, Maxwell A.

2017-01-01

Background Acantholytic squamous cell carcinoma (aSCC) is regarded as a high-risk variant of cutaneous squamous cell carcinoma (SCC). Acantholytic actinic keratosis (aAK) has been regarded as a precursor risk factor for aSCC. However, supporting evidence is limited. Objective We sought to document clinical features, histologic features, management, and outcomes in a series of aSCC cases. Methods Definitions of aSCC, aAK, and aSCC arising in association with aAK were applied to a consecutive series of aSCC cases. Clinical characteristics and outcomes were obtained from electronic medical records. Results Of 115 aSCC cases (103 patients, mean age 71.8 years), actinic keratosis was present in 23% (27/115) but only 7.8% (9/115) exhibited associated aAK. Ten cases (10/115, 9%) fulfilled strict histologic criteria for follicular SCC as previously defined, but 50 of 115 (43%) of our aSCC cases exhibited predominant involvement of follicular epithelium rather than epidermis. Clinical outcome (median follow-up, 36 months) was available in 106 of 115 (92%). One patient experienced regional extension (parotid), and 1 patient experienced a local recurrence (nose). No disease-related metastases or deaths were documented. Limitations This was a single-institution retrospective study from the United States. Conclusions The presence of acantholysis in cutaneous SCC does not specifically confer aggressive behavior, a finding that may inform clinical practice guidelines. PMID:27889291

Aminolevulinic Acid Topical

MedlinePlus

... in combination with photodynamic therapy (PDT; special blue light) to treat actinic keratoses (small crusty or scaly ... photosensitizing agents. When aminolevulinic acid is activated by light, it damages the cells of actinic keratosis lesions.

Topical photodynamic therapy with 5-aminolevulinic acid in the treatment of actinic keratoses: a first clinical study

NASA Astrophysics Data System (ADS)

Karrer, Sigrid; Szeimies, Rolf-Markus; Sauerwald, Angela; Landthaler, Michael

1996-01-01

In this first clinical study performed according to GCP- (good clinical practice) guidelines, efficacy, and tolerability of topical photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) were tested in the treatment of actinic keratoses. Ten patients (6 f, 4 m) with 36 lesions (19 located on hands and arms, 17 on the head) received ALA-PDT once. Five to six hours after occlusive application of ALA (water-in-oil-emulsion containing 10% ALA) irradiation was performed with an incoherent light source. Up to 3 months after treatment patients were monitored. A score evaluating infiltration and keratosis of treated actinic keratoses allowed us to estimate therapeutic efficacy. Compared to the initial score (100%) significantly lower score-sums were observed at the 28 day follow-up at both localizations (head: 15%; hand: 67%). Complete remission (score sum 0) resulted in 71% of actinic keratoses localized on the head. Except for slight pain and burning sensations during and after irradiation there were no notable side effects. This study proved good efficacy and tolerability of topical PDT in the treatment of actinic keratoses. Whether PDT is able to compete with established treatment modalities remains to be shown in further studies.

Expression of lumican in hidroacanthoma simplex and clonal-type seborrheic keratosis as a potent differential diagnostic marker.

PubMed

Takayama, Ryoko; Ansai, Shin-Ichi; Ishiwata, Toshiyuki; Yamamoto, Tetsushi; Matsuda, Yoko; Naito, Zenya; Kawana, Seiji

2014-08-01

Lumican, a member of the small leucine-rich proteoglycan family, regulates the assembly and diameter of collagen fibers in the extracellular matrix of various tissues. The lumican expression correlates with pathological conditions and the growth and metastasis of various malignancies. In cutaneous neoplasms, the lumican expression is lower in advanced-stage malignant melanomas that invade the dermis than in early-stage melanomas. Furthermore, we have recently reported that the expression pattern of lumican is different from that of actinic keratosis and the Bowen disease. Lumican is positive in the poroid cells of intraepidermal sweat ducts; therefore, we examined the expression patterns of lumican in acanthotic-type seborrheic keratosis and Pinkus-type poroma followed by clonal-type seborrheic keratosis and hidroacanthoma simplex. The neoplastic cells of acanthotic-type seborrheic keratosis exhibited positive immunostaining in only 1 of 31 cases (3.23%), whereas the poroid cells of Pinkus-type poroma exhibited positive immunoreactivity in 26 of 28 patients (92.8%). In the hidroacanthoma simplex cases, lumican was expressed in poroid cells forming intraepidermal nests in 22 of 28 patients (78.6%), whereas the neoplastic cells in most cases of clonal-type seborrheic keratosis were negative for lumican. In some seborrheic keratosis cases that were positive for lumican in neoplastic cells, lumican was observed in squamoid cells but not in basaloid cells. Therefore, it is necessary to evaluate the immunoreactivity of lumican in seborrheic keratosis and in basaloid cells. These findings suggest that lumican is a potent differential diagnostic marker that distinguishes hidroacanthoma simplex from clonal-type seborrheic keratosis.

Efficacy and safety of topical SR-T100 gel in treating actinic keratosis in Taiwan: A Phase III randomized double-blind vehicle-controlled parallel trial.

PubMed

Yang, Chao-Chun; Wong, Tak-Wah; Lee, Chih-Hung; Hong, Chien-Hui; Chang, Chung-Hsing; Lai, Feng-Jie; Lin, Shang-Hung; Chi, Ching-Chi; Lin, Tzu-Kai; Yen, Hsi; Wu, Chin-Han; Sheu, Hamm-Ming; Lan, Cheng-Che E

2018-06-01

Currently available topical treatments for actinic keratosis (AK) are associated with substantial side-effects. To evaluate the efficacy and safety of topical SR-T100 gel in treating AK. A multicenter, randomized, double-blinded phase III trial was conducted. Patients with at least two clinically visible AK were enrolled and a punch biopsy was performed on one of the AK to confirm the diagnosis. This study consisted of up to 16-week treatment and 8-week post-treatment periods. Medication was applied daily with occlusive dressing. 123 subjects were recruited and 113 were randomized. 76 subjects were in the SR-T100 and 37 in the vehicle arms. In SR-T100 and vehicle groups, 32.39% and 17.14% of subjects achieved complete clearance, respectively. For 75% partial clearance of lesions, 71.83% and 37.1% of subjects achieved this goal in SR-T100 and vehicle group, respectively. When comparing SR-T100 to vehicle, the odds ratio of complete clearance was 2.14 (p = 0.111), and odds ratio of partial clearance was 4.36 (p < 0.001). Severe local reactions were reported by only one subject using SR-T100. The imitation of the study was that not all the treated AK lesions were confirmed by histopathology. The diagnostic uncertainty may contribute to the high partial clearance rate in the vehicle group since the clinical-diagnosed AK showed higher clearance rate compared to histopathology-confirmed AK. The use of occlusive dressing was another possible explanation for high placebo effects. The results suggested that topical SR-T100 gel may be an effective and safe treatment for field therapy of AK. Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Keratosis pilaris and prevalence of acne vulgaris: a cross-sectional study.

PubMed

Schmitt, Juliano Vilaverde; Lima, Brunno Zeni de; Souza, Monique Carolina Meira do Rosário de; Miot, Hélio Amante

2014-01-01

Acne vulgaris has an important genetic predisposition, as well as keratosis pilaris. Clinical observations suggest that patients with keratosis pilaris have less frequent or less severe acne breakouts; however, we found no studies on this regard To determine if the presence of keratosis pilaris is associated with lower prevalence and severity of acne. A cross-sectional study was conducted with dermatology outpatients aged between 14 and 35 years. We evaluated history and clinical grade of acne, demographic variables, history of atopy, smoking, and use of hormonal contraceptives. Two groups were defined by the presence or absence of moderate to severe keratosis pilaris on the arms and were compared by bivariate analysis and by conditional multiple logistic regression. We included 158 patients (66% women), with a median age of 23 ± 11 years. Twenty-six percent of them had keratosis pilaris, which was associated with a history of atopy (odds ratio [OR]=2.80 [1.36 to 5.75]; p<0.01). Acne was present in 66% of subjects, and was related to family history of acne (OR=5.75 [2.47 to 13.37]; p<0.01). In bivariate and multivariate analysis, the group with keratosis pilaris had a less frequent history of acne (OR=0.32 [0.14 to 0.70]; p<0.01). The presence of moderate to severe keratosis pilaris on the arms was associated with lower prevalence of acne vulgaris and lower severity of facial lesions in adolescents and young adults.

A new, objective, quantitative scale for measuring local skin responses following topical actinic keratosis therapy with ingenol mebutate.

PubMed

Rosen, Robert; Marmur, Ellen; Anderson, Lawrence; Welburn, Peter; Katsamas, Janelle

2014-12-01

Local skin responses (LSRs) are the most common adverse effects of topical actinic keratosis (AK) therapy. There is currently no method available that allows objective characterization of LSRs. Here, the authors describe a new scale developed to quantitatively and objectively assess the six most common LSRs resulting from topical AK therapy with ingenol mebutate. The LSR grading scale was developed using a 0-4 numerical rating, with clinical descriptors and representative photographic images for each rating. Good inter-observer grading concordance was demonstrated in peer review during development of the tool. Data on the use of the scale are described from four phase III double-blind studies of ingenol mebutate (n = 1,005). LSRs peaked on days 4 (face/scalp) or 8 (trunk/extremities), with mean maximum composite LSR scores of 9.1 and 6.8, respectively, and a rapid return toward baseline by day 15 in most cases. Mean composite LSR score at day 57 was generally lower than at baseline. The LSR grading scale is an objective tool allowing practicing dermatologists to characterize and compare LSRs to existing and, potentially, future AK therapies.

Atopic dermatitis is not associated with actinic keratosis: cross-sectional results from the Rotterdam study.

PubMed

Hajdarbegovic, E; Blom, H; Verkouteren, J A C; Hofman, A; Hollestein, L M; Nijsten, T

2016-07-01

Epidermal barrier impairment and an altered immune system in atopic dermatitis (AD) may predispose to ultraviolet-induced DNA damage. To study the association between AD and actinic keratosis (AK) in a population-based cross-sectional study. AD was defined by modified criteria of the U.K. working party's diagnostic criteria. AKs were diagnosed by physicians during a full-body skin examination, and keratinocyte cancers were identified via linkage to the national pathology database. The results were analysed in adjusted multivariable and multinomial models. A lower proportion of subjects with AD had AKs than those without AD: 16% vs. 24%, P = 0·002; unadjusted odds ratio (OR) 0·60, 95% confidence interval (CI) 0·42-0·83; adjusted OR 0·74, 95% CI 0·51-1·05; fully adjusted OR 0·69, 95% CI 0·47-1·07. In a multinomial model patients with AD were less likely to have ≥ 10 AKs (adjusted OR 0·28, 95% CI 0·09-0·90). No effect of AD on basal cell carcinoma or squamous cell carcinoma was found: adjusted OR 0·71, 95% CI 0·41-1·24 and adjusted OR 1·54, 95% CI 0·66-3·62, respectively. AD in community-dwelling patients is not associated with AK. © 2016 British Association of Dermatologists.

Dermal changes in superficial basal cell carcinoma, melanoma in situ and actinic keratosis and their implications

PubMed Central

Kazlouskaya, Viktoryia; Malhotra, Saurabh; Navarro, Raquel; Wu, Karen Nguyen; Shvartsbeyn, Marianna; Shengli, Chen; Gui, Jiang; Elston, Dirk M.

2018-01-01

Background Basal cell carcinoma (BCC) has a characteristic stroma, but less is known about the dermal characteristics associated with melanoma in situ (MIS) and actinic keratosis (AK). Materials and methods Dermal changes were studied in 301 specimens of AK, BCC and MIS. Subsequently, blinded images of dermal changes from 90 randomly selected cases of those entities were used to assess the predictive value of the dermal changes. Agreement with the final diagnosis was calculated using kappa coefficient (κ). Results Fibromyxoid stroma was present in 82% of BCC cases; fibrous stroma was seen in 25% of BCC, 58% of MIS and 35.6% of AK specimens (p <0.05). A lichenoid inflammatory infiltrate was frequently associated with AK and a perifollicular infiltrate with periadnexal fibrosis with MIS. Blinded evaluation of images of the dermal changes associated with the tumors yielded the correct diagnosis in (54.4, 41.1 and 27.8%; average 41.2%) by the three appraisers. Coefficient of agreement in blinded imaged evaluation with the actual diagnosis was higher in the BCC and MIS compared with AK (κ = 0.37, p = 0.0001; κ = 0.2, p = 0.0005 and κ = −0.06, p = 0.84, respectively). Conclusion Dermal features may be helpful in predicting the correct diagnosis when tumor is not visible. PMID:24117926

Keratosis pilaris and prevalence of acne vulgaris: a cross-sectional study*

PubMed Central

Schmitt, Juliano Vilaverde; de Lima, Brunno Zeni; de Souza, Monique Carolina Meira do Rosário; Miot, Hélio Amante

2014-01-01

BACKGROUND Acne vulgaris has an important genetic predisposition, as well as keratosis pilaris. Clinical observations suggest that patients with keratosis pilaris have less frequent or less severe acne breakouts; however, we found no studies on this regard OBJECTIVE To determine if the presence of keratosis pilaris is associated with lower prevalence and severity of acne. METHODS A cross-sectional study was conducted with dermatology outpatients aged between 14 and 35 years. We evaluated history and clinical grade of acne, demographic variables, history of atopy, smoking, and use of hormonal contraceptives. Two groups were defined by the presence or absence of moderate to severe keratosis pilaris on the arms and were compared by bivariate analysis and by conditional multiple logistic regression. RESULTS We included 158 patients (66% women), with a median age of 23±11 years. Twenty-six percent of them had keratosis pilaris, which was associated with a history of atopy (odds ratio [OR]=2.80 [1.36 to 5.75]; p<0.01). Acne was present in 66% of subjects, and was related to family history of acne (OR=5.75 [2.47 to 13.37]; p<0.01). In bivariate and multivariate analysis, the group with keratosis pilaris had a less frequent history of acne (OR=0.32 [0.14 to 0.70]; p<0.01). CONCLUSION The presence of moderate to severe keratosis pilaris on the arms was associated with lower prevalence of acne vulgaris and lower severity of facial lesions in adolescents and young adults. PMID:24626653

Differentiation of seborrheic keratosis from basal cell carcinoma, nevi and melanoma by RGB autofluorescence imaging

PubMed Central

Lihachev, Alexey; Lihacova, Ilze; Plorina, Emilija V.; Lange, Marta; Derjabo, Alexander; Spigulis, Janis

2018-01-01

A clinical trial on the autofluorescence imaging of skin lesions comprising 16 dermatologically confirmed pigmented nevi, 15 seborrheic keratosis, 2 dysplastic nevi, histologically confirmed 17 basal cell carcinomas and 1 melanoma was performed. The autofluorescence spatial properties of the skin lesions were acquired by smartphone RGB camera under 405 nm LED excitation. The diagnostic criterion is based on the calculation of the mean autofluorescence intensity of the examined lesion in the spectral range of 515 nm–700 nm. The proposed methodology is able to differentiate seborrheic keratosis from basal cell carcinoma, pigmented nevi and melanoma. The sensitivity and specificity of the proposed method was estimated as being close to 100%. The proposed methodology and potential clinical applications are discussed in this article. PMID:29675324

Differentiation of seborrheic keratosis from basal cell carcinoma, nevi and melanoma by RGB autofluorescence imaging.

PubMed

Lihachev, Alexey; Lihacova, Ilze; Plorina, Emilija V; Lange, Marta; Derjabo, Alexander; Spigulis, Janis

2018-04-01

A clinical trial on the autofluorescence imaging of skin lesions comprising 16 dermatologically confirmed pigmented nevi, 15 seborrheic keratosis, 2 dysplastic nevi, histologically confirmed 17 basal cell carcinomas and 1 melanoma was performed. The autofluorescence spatial properties of the skin lesions were acquired by smartphone RGB camera under 405 nm LED excitation. The diagnostic criterion is based on the calculation of the mean autofluorescence intensity of the examined lesion in the spectral range of 515 nm-700 nm. The proposed methodology is able to differentiate seborrheic keratosis from basal cell carcinoma, pigmented nevi and melanoma. The sensitivity and specificity of the proposed method was estimated as being close to 100%. The proposed methodology and potential clinical applications are discussed in this article.

Red light photodynamic therapy for actinic keratosis using 37 J/cm2 : Fractionated irradiation with 12.3 mW/cm2 after 30 minutes incubation time compared to standard continuous irradiation with 75 mW/cm2 after 3 hours incubation time using a mathematical modeling.

PubMed

Vignion-Dewalle, Anne-Sophie; Baert, Gregory; Devos, Laura; Thecua, Elise; Vicentini, Claire; Mortier, Laurent; Mordon, Serge

2017-09-01

Photodynamic therapy (PDT) is an emerging treatment modality for various diseases, especially for dermatological conditions. Although, the standard PDT protocol for the treatment of actinic keratoses in Europe has shown to be effective, treatment-associated pain is often observed in patients. Different modifications to this protocol attempted to decrease pain have been investigated. The decrease in fluence rate seems to be a promising solution. Moreover, it has been suggested that light fractionation significantly increases the efficacy of PDT. Based on a flexible light-emitting textile, the FLEXITHERALIGHT device specifically provides a fractionated illumination at a fluence rate more than six times lower than that of the standard protocol. In a recently completed clinical trial of PDT for the treatment of actinic keratosis, the non-inferiority of a protocol involving illumination with the FLEXITHERALIGHT device after a short incubation time and referred to as the FLEXITHERALIGHT protocol has been assessed compared to the standard protocol. In this paper, we propose a comparison of the two above mentioned 635 nm red light protocols with 37 J/cm 2 in the PDT treatment of actinic keratosis: the standard protocol and the FLEXITHERALIGHT one through a mathematical modeling. This mathematical modeling, which slightly differs from the one we have already published, enables the local damage induced by the therapy to be estimated. The comparison performed in terms of the local damage induced by the therapy demonstrates that the FLEXITHERALIGHT protocol with lower fluence rate, light fractionation and shorter incubation time is somewhat less efficient than the standard protocol. Nevertheless, from the clinical trial results, the FLEXITHERALIGHT protocol results in non-inferior response rates compared to the standard protocol. This finding raises the question of whether the PDT local damage achieved by the FLEXITHERALIGHT protocol (respectively, the standard protocol

Surgical attitude in premalignant lesions and malignant tumors of the lower lip

PubMed Central

Calcaianu, N; Popescu, SA; Diveica, D; Lascar, I

2015-01-01

Introduction. Malignant tumors of the lower lip may have a variety of histopathology forms. The diagnosis and treatment of premalignant lesions are extremely important to avoid their malignant evolution. The lower lip tumor diagnosis is based on a series of correlations: anamnestic, clinical, laboratory and histopathological (the latter giving the certain diagnose). Material and methods. This study was carried out by selecting the cases with lower lip tumors operated between January 2012 and July 2014, in the Plastic Surgery and Reconstructive Microsurgery Clinic of Bucharest Clinical Emergency Hospital. The variables considered in the study were the following: age, gender, exposure to risk factors, diagnosis, and histopathology. Results. The histopathological examination revealed 63% squamous cell carcinoma, 30% basal cell carcinomas, 5% keratoacanthoma and 2% actinic keratosis. Men were the predominantly affected genre, with a percentage of 70%. In the group of patients studied, 66% were smokers. Discussions. The rate of the malignant transformation of premalignant lesion was 32.6% for keratoacanthoma, 16.9% for actinic cheilitis, 10% for actinic keratoses. Conclusions. There were no clinical or laboratory features to plead for the pre-malignant or malignant character of the of a lower lip tumor, consequently histopathological examination was used for the diagnosis of the lesion. Due to the high percentage of malignant transformation of precancerous lesions, particularly in the form of squamous cell carcinoma, the surgical attitude intending to eradicate a lower lip tumor from an oncological point of view was the excision with oncologic safety margins followed by a lip reconstruction. PMID:25914752

Keratosis Pilaris Revisited: Is It More Than Just a Follicular Keratosis?

PubMed Central

Thomas, Mary; Khopkar, Uday Sharadchandra

2012-01-01

Background: Keratosis pilaris (KP) is characterized by keratinous plugs in the follicular orifices and varying degrees of perifollicular erythema. The most accepted theory of its pathogenesis proposes defective keratinization of the follicular epithelium resulting in a keratotic infundibular plug. We decided to test this hypothesis by doing dermoscopy of patients diagnosed clinically as keratosis pilaris. Materials and Methods: Patients with a clinical diagnosis of KP seen between September 2011 and December 2011 were included in the study. A clinical history was obtained and examination and dermoscopic evaluation were performed on the lesions of KP. Results: The age of the patients ranged from 6-38 years. Sixteen patients had history of atopy. Nine had concomitant ichthyosis vulgaris. All the 25 patients were found to have coiled hair shafts within the affected follicular infundibula. The hair shafts were extracted with the help of a sterile needle and were found to retain their coiled nature. Perifollicular erythema was seen in 11 patients; perifollicular scaling in 9. Conclusion: Based on our observations and previously documented histological data of KP, we infer that KP may not be a disorder of keratinization, but caused by the circular hair shaft which ruptures the follicular epithelium leading to inflammation and abnormal follicular keratinization. PMID:23766609

Anogenital giant seborrheic keratosis.

PubMed

Wollina, Uwe; Chokoeva, Anastasiya; Tchernev, Georgi; Heinig, Birgit; Schönlebe, Jacqueline

2017-08-01

Seborrheic keratosis (SK) are very common benign epidermal tumors. Giant seborrheic keratosis (GSK) is a rare variant with clinical characteristics, which leads very often to misdiagnosis. A genital site of SK is very unusual clinical manifestation and although the cause is still unknown, current literature data point to a possible pathogenetic role of chronic friction and HPV infection. The rare genital localization makes Buschke-Löwenstein tumor and verrucous carcinoma important differential diagnoses. GSK may also show some clinical features of a melanoacanthoma, which makes cutaneous melanoma as another possible differential diagnosis. The clinical diagnosis of genital GSK is often a very difficult one, because the typical clinical features of GSK disappear and the most common dermoscopic features of GSK are usually not seen in the genital region lesions. The diagnosis of GSK of the anogenital area should be made only and always after the exact histological verification and variety of differential diagnosis should be carefully considered. The treatment of GSK is primary surgically. We present a rare case of GSK with concomitant HPV infection in the anogenital region of 72-year-old patient. Surgical approach was performed with excellent outcome.

Clinical practice trends in cryosurgery: a retrospective study of cutaneous lesions

PubMed Central

Erkan, Ceren Dagar; Karaca, Semsettin

2015-01-01

Introduction Cryosurgery is an alternative treatment for many benign, premalignant, and malignant lesions of the skin. Aim To review the indications of cryosurgery for cutaneous lesions. Material and methods The retrospective study was based on the assessment of medical records of 1031 dermatology patients who had cryosurgery. Results One thousand two hundred and forty-four sessions of cryosurgery were applied to the total of 1031 patients. Of the 1031 patients, the most frequent indication for cryosurgery was common warts which were present in 535 (61.59%) patients, followed by anogenital warts in 119 (11.54%) patients, callosity in 81 (7.85%) patients, actinic keratosis in 77 (7.46%) patients, molluscum contagiosum in 35 (3.39%) patients, and other benign or malignant skin lesions. Conclusions Cryosurgery is still a valuable treatment of choice in various benign, premalignant, and malignant skin diseases but seems to be underused for indications other than viral warts. PMID:26015777

Treatment of pigmented keratosis pilaris in Asian patients with a novel Q-switched Nd:YAG laser.

PubMed

Kim, Sangeun

2011-06-01

Treatment for most cases of keratosis pilaris requires simple reassurance and general skin care recommendations. Many Asian patients find lesions due to pigmented keratosis pilaris to be cosmetically unappealing. Treatment of post-inflammatory hyperpigmentation using a 1064-nm Q-switched Nd:YAG laser with low fluence is reported. To investigate the efficacy of a novel Q-switched Nd:YAG laser for the treatment of pigmented keratosis pilaris in Asian patients. Ten patients with pigmented keratosis pilaris underwent five weekly treatments using a Q-switched Nd:YAG laser (RevLite(®); HOYA ConBio(®), Freemont, CA, USA) at 1064 nm with a 6-mm spot size and a fluence of 5.9 J/cm(2). Photographic documentation was obtained at baseline and 2 months after the final treatment. Clinical improvement was achieved in all 10 patients with minimal adverse effects. For the treatment of keratosis pilaris, the use of a Q-switched Nd:YAG laser can be helpful for improving cosmetic appearance as it can improve pigmentation.

Long-term (6 and 12 months) follow-up of two prospective, randomized, controlled phase III trials of photodynamic therapy with BF-200 ALA and methyl aminolaevulinate for the treatment of actinic keratosis

PubMed Central

Dirschka, T; Radny, P; Dominicus, R; Mensing, H; Brüning, H; Jenne, L; Karl, L; Sebastian, M; Oster-Schmidt, C; Klövekorn, W; Reinhold, U; Tanner, M; Gröne, D; Deichmann, M; Simon, M; Hübinger, F; Hofbauer, G; Krähn-Senftleben, G; Borrosch, F; Reich, K; Berking, C; Wolf, P; Lehmann, P; Moers-Carpi, M; Hönigsmann, H; Wernicke-Panten, K; Hahn, S; Pabst, G; Voss, D; Foguet, M; Schmitz, B; Lübbert, H; Szeimies, R-M

2013-01-01

Background Two phase III trials of photodynamic therapy (PDT) with BF-200 ALA, a recently approved nanoemulsion formulation of 5-aminolaevulinic acid (ALA) demonstrated high clearance rates in mild-to-moderate actinic keratosis (AK). The comparison to a registered methyl aminolaevulinate (MAL) cream demonstrated significantly superior total patient clearance rates. Objectives To evaluate long-term efficacy and safety of PDT for AK 6 and 12 months after the last PDT with BF-200 ALA, MAL or placebo. Methods The follow-up phase (FUP) was performed with patients of two phase III studies. Both studies compared BF-200 ALA with placebo, one of the studies additionally with MAL. Overall recurrence rates and various subgroups (light source, lesion severity, lesion location, complete responders after first PDT) were assessed 6 and 12 months after the last PDT. Results Recurrence rates were similar for BF-200 ALA and MAL, with a tendency to lower recurrence rates for BF-200 ALA. The proportion of patients who were fully cleared during PDT and remained completely clear for at least 12 months after PDT were 47% for BF-200 ALA (both studies) and 36% for MAL treatment. The subgroup that was illuminated with narrow wavelength LED lamps reached 69% and 53% for BF-200 ALA (both studies, respectively) and 41% for MAL. No safety concerns were reported. Conclusions The FUP data confirmed the high efficacy and safety of PDT with BF-200 ALA. The slightly lower recurrence rates after BF-200 ALA treatment compared with MAL treatment enhanced the better treatment outcome due to the significantly superior efficacy. PMID:23252768

Reduced degree of irritation during a second cycle of ingenol mebutate gel 0.015% for the treatment of actinic keratosis.

PubMed

Jim On, Shelbi C; Haddican, Madelaine; Yaroshinsky, Alex; Singer, Giselle; Lebwohl, Mark

2015-01-01

Ingenol mebutate gel is a topical field treatment of actinic keratosis (AK). One of several proposed mechanisms of action for ingenol mebutate is induction of cell death in proliferating keratinocytes, suggesting a preferential action on AKs rather than healthy skin. Local skin reactions (LSRs) during 2 sequential 4-week cycles of AK treatment with ingenol mebutate gel 0.015% on the face or scalp were evaluated to test the hypothesis that reapplication of the study product would produce lower LSR scores than during the first treatment cycle. In this unblinded study, 20 participants with AKs on the face or scalp were treated with ingenol mebutate gel 0.015% once daily for 3 days in 2 sequential 4-week cycles. Composite LSR scores were evaluated during both cycles. The composite LSR score during the second cycle was found to be significantly lower than the first cycle (P=.0002). The proportion of participants who experienced LSRs in the second treatment cycle was less than the first cycle. Ingenol mebutate gel 0.015% may cumulatively reduce the burden of sun-damaged skin over 2 treatment cycles by targeting and removing transformed keratinocytes.

Efficacy of iontophoresis-assisted ablative fractional laser photodynamic therapy with short incubation time for the treatment of actinic keratosis: 12-month follow-up results of a prospective, randomised, comparative trial.

PubMed

Choi, Seung-Hwan; Kim, Tae-Hoon; Song, Ki-Hoon

2017-06-01

Iontophoresis is a transdermal drug-delivery technique that enhances the transport of ionic species across membranes and may have significant benefit for the treatment of actinic keratosis (AK) by ablative fractional laser-primed photodynamic therapy (AFL-PDT). The aims of this study were to compare the efficacy, recurrence rate, cosmetic outcome and safety of iontophoresis-assisted AFL-PDT with 2h of incubation vs. those of conventional AFL-PDT with 2- and 3-h incubation in patients with facial and scalp AK. Patients were randomly assigned to iontophoresis-assisted AFL-PDT with a 2-h incubation time (group A) and conventional AFL-PDT with a 2-h (group B) and 3-h (group C) incubation time. All patients underwent AFL-PDT, and group A patients were assigned to treatment with iontophoresis after methyl-aminolevulinate (MAL) application. After 2 or 3h, MAL-applied lesions were irradiated using a red light. Patients were followed up at 1-week, 3 months and 12 months after treatment. Efficacy, cosmetic outcomes and adverse events were assessed. In total, 41 patients (160 AK lesions) completed the study and were evaluated. Efficacy was significantly higher in Group A (88.7%) than in Group B (73.2%); the efficacy of groups A and C (92.2%) at 3 months follow-up was comparable. The recurrence rates were not significantly different between the groups at 12 months (P=0.841). The three groups did not differ in terms of cosmetic outcomes and safety. Iontophoresis-assisted AFL-PDT showed higher efficacy than AFL-PDT with short incubation time. Iontophoresis may effectively reduce the incubation time in AFL-PDT. Copyright © 2017 Elsevier B.V. All rights reserved.

Role of linoleic acid in arsenical palmar keratosis.

PubMed

Ahmed, Tarafder S; Misbahuddin, Mir

2016-03-01

Chronic arsenic exposure can lead to palmoplantar keratosis. In the stratum corneum of skin, linoleic acid is of the utmost importance to the inflammation, keratinization, and regeneration processes. The aims of this study were: (i) to present quantitative information on the linoleic acid fraction of intercorneocyte lipids, and (ii) to elucidate the role of linoleic acid in the pathophysiology of arsenical keratosis. Lipid extracts were collected from keratotic lesions in seven patients, seven arsenic-exposed subjects, and seven non-exposed control subjects. Linoleic acid levels of the specimens were estimated by reverse-phase high-performance liquid chromatography (RP-HPLC). There was a significant (P < 0.001) increase in mean ± standard error (SE) linoleic acid levels in arsenical keratosis patients (palm: 25.66 ± 4.95 μg/cm(2); dorsum: 28.25 ± 6.20 μg/cm(2)) compared with arsenic-exposed (palm: 2.75 ± 0.85 μg/cm(2); dorsum: 1.96 ± 0.64 μg/cm(2)) and non-exposed (palm: 1.52 ± 0.61 μg/cm(2); dorsum: 1.28 ± 0.39 μg/cm(2)) control subjects. There was no significant difference (P = 0.556) in linoleic acid concentration in the non-affected skin of the dorsum of the hand (28.25 ± 6.20 μg/cm(2)) compared with that in the palmar sites (25.66 ± 4.95 μg/cm(2)) in the patient group. The change in linoleic acid levels in the arsenic-exposed control group did not differ from that in non-exposed controls (P = 1.000). Linoleic acid concentration is elevated in arsenical keratosis; this finding warrants further investigation to ascertain whether linoleic acid plays a direct role in the pathophysiology of arsenical keratosis. © 2015 The International Society of Dermatology.

Alveolar ridge keratosis - a retrospective clinicopathological study

PubMed Central

2013-01-01

Background Alveolar ridge keratosis (ARK) is a distinct, benign clinicopathological entity, characterized by a hyperkeratotic plaque or patch that occurs on the alveolar edentulous ridge or on the retromolar trigone, considered to be caused by chronic frictional trauma. The aim of this retrospective study is to present the clinicopathological features of 23 consecutive cases of ARK. Material and methods The 23 biopsy samples of ARK were selected and pathological features were revised (keratosis, acanthosis, surface architecture, and inflammation). Factors such as the patient’s gender, age, anatomical location, tobacco and alcohol use were analyzed. Results Sixteen out of the 23 cases studied were men and 7 women with a mean age of 55.05 (age ranged from 17 to 88 years). Thirteen cases had a history of tobacco habit, amongst whom, 4 also presented alcohol consumption. All the cases presented only unilateral lesions. Nineteen cases involved the retromolar trigone while 4 cases involved edentulous alveolar ridges. When observed microscopically, the lesions were mainly characterized by moderate to important hyperorthokeratosis. Inflammation was scanty or absent. In four of the cases, the presence of melanin pigment in the superficial corium or in the cytoplasm of macrophages was detected. None of the cases showed any features of dysplasia. Conclusion Our results reveal that ARK is a benign lesion. However, the high prevalence of smokers amongst the patients might suggest that some potentially malignant disorders such as tobacco associated leukoplakia may clinically mimic ARK. PMID:23587097

Alveolar ridge keratosis--a retrospective clinicopathological study.

PubMed

Bellato, Lorenzo; Martinelli-Kläy, Carla P; Martinelli, Celso R; Lombardi, Tommaso

2013-04-16

Alveolar ridge keratosis (ARK) is a distinct, benign clinicopathological entity, characterized by a hyperkeratotic plaque or patch that occurs on the alveolar edentulous ridge or on the retromolar trigone, considered to be caused by chronic frictional trauma. The aim of this retrospective study is to present the clinicopathological features of 23 consecutive cases of ARK. The 23 biopsy samples of ARK were selected and pathological features were revised (keratosis, acanthosis, surface architecture, and inflammation). Factors such as the patient's gender, age, anatomical location, tobacco and alcohol use were analyzed. Sixteen out of the 23 cases studied were men and 7 women with a mean age of 55.05 (age ranged from 17 to 88 years). Thirteen cases had a history of tobacco habit, amongst whom, 4 also presented alcohol consumption. All the cases presented only unilateral lesions. Nineteen cases involved the retromolar trigone while 4 cases involved edentulous alveolar ridges. When observed microscopically, the lesions were mainly characterized by moderate to important hyperorthokeratosis. Inflammation was scanty or absent. In four of the cases, the presence of melanin pigment in the superficial corium or in the cytoplasm of macrophages was detected. None of the cases showed any features of dysplasia. Our results reveal that ARK is a benign lesion. However, the high prevalence of smokers amongst the patients might suggest that some potentially malignant disorders such as tobacco associated leukoplakia may clinically mimic ARK.

Claudins 1, 2, 3, 4, 5 and 7 in solar keratosis and squamocellular carcinoma of the skin

PubMed Central

Hintsala, Hanna-Riikka; Siponen, Maria; Haapasaari, Kirsi-Maria; Karihtala, Peeter; Soini, Ylermi

2013-01-01

Claudins are tight junction proteins regulating the paracellular permeability of cell layers. We investigated the expression of claudins 1, 2, 3, 4, 5 and 7 in a sample set consisting of a total of 93 cases representing normal skin, actinic keratoses and squamous cell carcinomas of the skin. There were several changes found in claudin expression. Claudin 1 appeared to be progressively decreased in solar keratosis and skin squamous cell carcinomas compared to normal skin while expression of claudin 2 was increased. With claudins 3 and 5 occasional immunoreactivity was found in squamous cell carcinomas. Claudins 4 and 7 were variably expressed in skin neoplasia compared to normal skin. According to the results expression of claudins 1 and 2 change in parallel with the severity of the epidermal preneoplastic and neoplastic lesions thus probably influencing the disturbed epithelial polarity characteristic of these lesions. Claudin 1 under- and claudin 2 overexpression also lead to a leakier epithelial barrier function of the skin with a resulting damage to skin epithelial resistance. Other claudins investigated in this study did not show progressive changes even though occasional overexpression of them was found in skin squamous cell carcinoma. PMID:24294371

Influence of Information Framing on Patient Decisions to Treat Actinic Keratosis.

PubMed

Berry, Katherine; Butt, Melissa; Kirby, Joslyn S

2017-05-01

Actinic keratosis (AK) is a skin growth induced by UV light exposure that requires long-term management because a small proportion of the disease can progress to squamous cell carcinoma. The influence of how clinicians frame or present information to patients may affect decision making about AK. To evaluate the differences in patients' decisions on whether to receive treatment for AK related to information presentation or choice framing. A prospective survey study was performed from June 1 to July 31, 2016, in participants who were able to read English. Participants were recruited through the Penn State Milton S. Hershey Dermatology Clinic and an online survey site. The survey was conducted through an online portal. A total of 571 individuals were recruited. Regression analysis, correlation coefficient analysis, and test-retest validation were conducted. The proportions of patients choosing to receive treatment for AK. Analyses were performed to adjust for age, sex, educational level, history of skin cancer, and history of AK. Of the 571 recruited participants, 539 (94.4%) returned completed surveys. The mean (SD) age of respondents was 42.9 (17.8) years; 306 (56.8%) were women. The decision to receive treatment for AK varied from 57.7% (n = 311) to 92.2% (n = 497) for the 5 scenarios presented in the questions (P < .001). The question that presented AK as a "precancer" had the highest proportion of participants who preferred treatment (497 [92.2%]). Two questions that presented the risk of AK as not progressing to cancer had the lowest proportion of individuals who chose treatment (311 [57.7%] and 328 [60.9%]). Participants from the clinic and from the online portal were significantly different in age (mean [SD] age, 56.1 [17.6] vs 33.3 [10.0] years), sex (145 [63.6%] vs 161 [51.8%] were females), educational level (40 [17.5%] vs 80 [25.7%] had completed some graduate school), history of AK (46 [20.2%] vs 19 [6.1%] answered yes), and history of skin

Neoplastic Multifocal Skin Lesions: Biology, Etiology, and Targeted Therapies for Nonmelanoma Skin Cancers.

PubMed

Fernandes, Ana R; Santos, Ana C; Sanchez-Lopez, Elena; Kovačević, Andjekla B; Espina, Marta; Calpena, Ana C; Veiga, Francisco J; Garcia, Maria L; Souto, Eliana B

2018-01-01

Neoplastic skin lesions are multifocal, diffuse skin infiltrations of particular relevance in the differential diagnosis of ulcerative, nodular, or crusting skin lesions. Nonmelanoma skin cancers (NMSCs), namely, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and also actinic keratosis (AK), are the most common malignant tumors in humans. BCCs do not proliferate rapidly and most of the times do not metastasize, while SCCs are more infiltrative, metastatic, and destructive. AKs are precursor lesions of cutaneous SCCs. The classical therapy of NMSCs makes use of photodynamic therapy associated with chemotherapeutics. With improved understanding of the pathological mechanisms of tumor initiation, progression, and differentiation, a case is made towards the use of targeted chemotherapy with the intent to reduce the cytotoxicity of classical treatments. The present review aims to describe the current state of the art on the knowledge of NMSC, including its risks factors, oncogenes, and skin carcinogenesis, discussing the classical therapy against new therapeutic options. © 2017 S. Karger AG, Basel.

Long-term (6 and 12 months) follow-up of two prospective, randomized, controlled phase III trials of photodynamic therapy with BF-200 ALA and methyl aminolaevulinate for the treatment of actinic keratosis.

PubMed

Dirschka, T; Radny, P; Dominicus, R; Mensing, H; Brüning, H; Jenne, L; Karl, L; Sebastian, M; Oster-Schmidt, C; Klövekorn, W; Reinhold, U; Tanner, M; Gröne, D; Deichmann, M; Simon, M; Hübinger, F; Hofbauer, G; Krähn-Senftleben, G; Borrosch, F; Reich, K; Berking, C; Wolf, P; Lehmann, P; Moers-Carpi, M; Hönigsmann, H; Wernicke-Panten, K; Hahn, S; Pabst, G; Voss, D; Foguet, M; Schmitz, B; Lübbert, H; Szeimies, R-M

2013-04-01

Two phase III trials of photodynamic therapy (PDT) with BF-200 ALA, a recently approved nanoemulsion formulation of 5-aminolaevulinic acid (ALA) demonstrated high clearance rates in mild-to-moderate actinic keratosis (AK). The comparison to a registered methyl aminolaevulinate (MAL) cream demonstrated significantly superior total patient clearance rates. To evaluate long-term efficacy and safety of PDT for AK 6 and 12 months after the last PDT with BF-200 ALA, MAL or placebo. The follow-up phase (FUP) was performed with patients of two phase III studies. Both studies compared BF-200 ALA with placebo, one of the studies additionally with MAL. Overall recurrence rates and various subgroups (light source, lesion severity, lesion location, complete responders after first PDT) were assessed 6 and 12 months after the last PDT. Recurrence rates were similar for BF-200 ALA and MAL, with a tendency to lower recurrence rates for BF-200 ALA. The proportion of patients who were fully cleared during PDT and remained completely clear for at least 12 months after PDT were 47% for BF-200 ALA (both studies) and 36% for MAL treatment. The subgroup that was illuminated with narrow wavelength LED lamps reached 69% and 53% for BF-200 ALA (both studies, respectively) and 41% for MAL. No safety concerns were reported. The FUP data confirmed the high efficacy and safety of PDT with BF-200 ALA. The slightly lower recurrence rates after BF-200 ALA treatment compared with MAL treatment enhanced the better treatment outcome due to the significantly superior efficacy. © 2012 Biofrontera Bioscience GmbH BJD © 2012 British Association of Dermatologists.

Actikerall™ (5-Fluorouracil 0.5% and Salicylic Acid 10%) Topical Solution for Patient-directed Treatment of Actinic Keratoses.

PubMed

Nguyen, H P; Rivers, J K

2016-05-01

Actinic keratosis (AK), a common cutaneous lesion with the potential to transform into squamous cell carcinoma, has traditionally been treated with ablative and/or surgical procedures. Recently, a topical formulation combining 0.5% 5-fluorouracil with 10% salicylic acid (5-FU-SA) was introduced in Europe under the trade name Actikerall™ for the treatment of grade I/II AKs. In a single randomized phase III trial, 5-FU-SA was shown to be superior to diclofenac 3% gel in hyaluronic acid, as measured by the histological clearance of one defined lesion (72% vs. 59.1%) and by complete clinical clearance (55.4% vs. 32.0%). 5-FU-SA should be applied once daily to a total area of up to 25 cm(2), which may include the lesion(s) and a small area of surrounding skin (rim of healthy skin should not exceed 0.5 cm), for up to 12 weeks. The most common side effects are local inflammation and pruritus at the application site, and no serious adverse effects have been reported to date. Now commercially available in Canada, 5-FU-SA represents a patientapplied therapeutic option for the treatment of both overt and subclinical AKs.

Efficacy of a film-forming medical device containing sunscreen (50+) and piroxicam 0.8% in actinic keratosis and field cancerization: a multicenter, assessor-blinded, 3 month trial.

PubMed

Puviani, Mario; Galloni, Chiara; Marchetti, Silvia; Sergio Pavone, Paolo; Lovati, Silvia; Pistone, Giuseppe; Caputo, Valentina; Tilotta, Giovanna; Scarcella, Giuseppe; Campione, Elena; Diluvio, Laura; Garofalo, Virginia; Bianchi, Luca; Milani, Massimo

2017-07-01

Sunscreen protection in subjects with actinic keratosis (AK) is highly recommended to prevent clinical evolution of this in situ skin cancer condition. Use of topical anti-cyclooxygenase drugs such as diclofenac and piroxicam reduces the number of lesions and improves the cancerization field. A film-forming medical device in a cream formulation containing organic and inorganic sun-filters (50+ SPF) and piroxicam 0.8% (ACTX) has shown in a pilot, single-center, open trial to reduce AK lesions improving the cancerization field. We evaluated in a multicenter, assessor-blinded, 3 month trial the efficacy of ACTX in AK. A total of 70 subjects with at least three AK lesions on the scalp or face were enrolled after written informed consent. Primary outcomes of the study were the clinical evolution of number of AK lesions on a target zone area and the evolution of dermoscopy features of the target lesion, assessing erythema, scaling, pigmentation, and follicular plug, using a 5 point score (from 0 to 4; maximum score: 16). Lesion count and dermoscopy score were evaluated in a blind fashion assessing digital color high definition coded images. A secondary outcome was the Investigator Global Score (IGS) of clinical evolution of the target area using a 7 point scale from -2 (significantly worse) to +4 (completely cured). IGS was evaluated in an open fashion. Subjects were instructed to apply the cream twice daily on the target area, using one finger-tip unit for the treatment of a 35 cm 2 area. All but one subject (40 men and 30 women, mean age 73 years) concluded the study period. At baseline the mean (±SD) number of AK lesions in the target area were 7.0 (5.9) with a median value of 5 and the dermoscopy score of the target lesion was 7.0 (2.3) with a median value of 7.0. ACTX treatment reduced AK lesions to 3.2 (2.9), (p = .0001; Wilcoxon Test), representing a 55% relative reduction. Dermoscopy score was reduced to 3.3 (2.6) (p = .0001) (a reduction of 53%). The

Arsenic-related Bowen's disease, palmar keratosis, and skin cancer.

PubMed Central

Cöl, M; Cöl, C; Soran, A; Sayli, B S; Oztürk, S

1999-01-01

Chronic arsenical intoxication can still be found in environmental and industrial settings. Symptoms of chronic arsenic intoxication include general pigmentation or focal "raindrop" pigmentation of the skin and the appearance of hyperkeratosis of the palms of the hands and soles of the feet. In addition to arsenic-related skin diseases including keratosis, Bowen's disease, basal-cell-carcinoma, and squamous-cell carcinoma, there is also an increased risk of some internal malignancies. Arsenic-related diseases are common in areas of the world where the drinking water has a high arsenic content. In this paper, we describe a 35-year-old male patient who had arsenic-related keratosis, squamous-cell carcinoma in the palmar area of his left hand, and Bowen's disease on his left thigh. The patient worked in a borax mine for 15 years, so he was exposed to arsenic in drinking water, airborne arsenic in his workplace, and had direct contact. The patient was treated for 11 months for arsenic-related keratosis until an axillary lymph node metastasis occurred; the lesion was excised and diagnosed to be malignant. Bowen's disease was detected when the patient was being treated for cancer. No other malignancy was found. The patient is still receiving regular follow-up care. Images Figure 1 Figure 2 PMID:10417369

Influence of Information Framing on Patient Decisions to Treat Actinic Keratosis

PubMed Central

Berry, Katherine; Butt, Melissa

2017-01-01

Importance Actinic keratosis (AK) is a skin growth induced by UV light exposure that requires long-term management because a small proportion of the disease can progress to squamous cell carcinoma. The influence of how clinicians frame or present information to patients may affect decision making about AK. Objective To evaluate the differences in patients’ decisions on whether to receive treatment for AK related to information presentation or choice framing. Design, Setting, and Participants A prospective survey study was performed from June 1 to July 31, 2016, in participants who were able to read English. Participants were recruited through the Penn State Milton S. Hershey Dermatology Clinic and an online survey site. The survey was conducted through an online portal. A total of 571 individuals were recruited. Regression analysis, correlation coefficient analysis, and test-retest validation were conducted. Main Outcomes and Measures The proportions of patients choosing to receive treatment for AK. Analyses were performed to adjust for age, sex, educational level, history of skin cancer, and history of AK. Results Of the 571 recruited participants, 539 (94.4%) returned completed surveys. The mean (SD) age of respondents was 42.9 (17.8) years; 306 (56.8%) were women. The decision to receive treatment for AK varied from 57.7% (n = 311) to 92.2% (n = 497) for the 5 scenarios presented in the questions (P < .001). The question that presented AK as a “precancer” had the highest proportion of participants who preferred treatment (497 [92.2%]). Two questions that presented the risk of AK as not progressing to cancer had the lowest proportion of individuals who chose treatment (311 [57.7%] and 328 [60.9%]). Participants from the clinic and from the online portal were significantly different in age (mean [SD] age, 56.1 [17.6] vs 33.3 [10.0] years), sex (145 [63.6%] vs 161 [51.8%] were females), educational level (40 [17.5%] vs 80 [25.7%] had completed

Non-invasive diagnosis and monitoring of actinic cheilitis with reflectance confocal microscopy.

PubMed

Ulrich, M; González, S; Lange-Asschenfeldt, B; Roewert-Huber, J; Sterry, W; Stockfleth, E; Astner, S

2011-03-01

Actinic cheilitis (AC) represents the equivalent of actinic keratosis on the lip. Various treatment modalities are available and the efficacy of diclofenac in hyaluronic acid has recently been described. Reflectance confocal microscopy (RCM) is a non-invasive imaging technique which has recently been applied for the diagnosis of actinic keratoses. Herein, we describe the applicability of RCM for the diagnosis of AC and for monitoring of treatment response of AC to diclofenac in hyaluronic acid. Ten Caucasian patients with clinical suspicion for AC were included in this study. To obtain a non-invasive diagnosis, RCM was performed at baseline, followed by biopsy and respective confocal-histopathological correlation. Six patients with a histological diagnosis of AC were treated with diclofenac in hyaluronic acid, whereby monitoring was performed by RCM. Reflectance confocal microscopy was able to correctly identify 6/7 cases of AC and 3/3 cases of benign lesions. The most important RCM criteria for diagnosis of AC were cellular atypia at the stratum spinosum and granulosum with atypical honeycomb pattern. One patient with AC was misclassified as inflammatory cheilitis by RCM as it showed marked inflammatory response and lacked clear signs of cellular atypia on RCM imaging. Following topical treatment with diclofenac gel, 5/6 patients (83%) showed a good treatment response with regression of dysplasia on consecutive RCM examination. Reflectance confocal microscopy is a promising tool for the non-invasive diagnosis and monitoring of actinic cheilitis. However, marked inflammation represents a potential diagnostic pitfall. In this regard, biopsy should be performed in doubtful cases. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

Dual-channel red/blue fluorescence dosimetry with broadband reflectance spectroscopic correction measures protoporphyrin IX production during photodynamic therapy of actinic keratosis

NASA Astrophysics Data System (ADS)

Kanick, Stephen Chad; Davis, Scott C.; Zhao, Yan; Hasan, Tayyaba; Maytin, Edward V.; Pogue, Brian W.; Chapman, M. Shane

2014-07-01

Dosimetry for aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy of actinic keratosis was examined with an optimized fluorescence dosimeter to measure PpIX during treatment. While insufficient PpIX generation may be an indicator of incomplete response, there exists no standardized method to quantitate PpIX production at depths in the skin during clinical treatments. In this study, a spectrometer-based point probe dosimeter system was used to sample PpIX fluorescence from superficial (blue wavelength excitation) and deeper (red wavelength excitation) tissue layers. Broadband white light spectroscopy (WLS) was used to monitor aspects of vascular physiology and inform a correction of fluorescence for the background optical properties. Measurements in tissue phantoms showed accurate recovery of blood volume fraction and reduced scattering coefficient from WLS, and a linear response of PpIX fluorescence versus concentration down to 1.95 and 250 nM for blue and red excitations, respectively. A pilot clinical study of 19 patients receiving 1-h ALA incubation before treatment showed high intrinsic variance in PpIX fluorescence with a standard deviation/mean ratio of >0.9. PpIX fluorescence was significantly higher in patients reporting higher pain levels on a visual analog scale. These pilot data suggest that patient-specific PpIX quantitation may predict outcome response.

Clinical study of a retinoic acid-loaded microneedle patch for seborrheic keratosis or senile lentigo.

PubMed

Hirobe, Sachiko; Otsuka, Risa; Iioka, Hiroshi; Quan, Ying-Shu; Kamiyama, Fumio; Asada, Hideo; Okada, Naoki; Nakagawa, Shinsaku

2017-01-01

Pigmented lesions such as of seborrheic keratosis and senile lentigo, which are commonly seen on skin of people>50years of age, are considered unattractive and disfiguring because of their negative psychological impact. Drug therapy using all-trans retinoic acid (ATRA) is an attractive option for self-treatment at home. We have developed an ATRA-loaded microneedle patch (ATRA-MN) and confirmed the pharmacological effects of ATRA-MN application in mice. Here, we describe a clinical study to evaluate the safety and efficacy of ATRA-MN in subjects with seborrheic keratosis or senile lentigo. ATRA-MN was applied to the lesion site of each subject for 6h once per week for 4weeks. The skin irritation reaction was scored to assess adverse reactions and blood tests were performed to evaluate the presence of systemic adverse reactions. To assess the treatment effect using ATRA-MN, the desquamation and whitening ability of the investigational skin was observed. Desquamation of the stratum corneum was observed following four ATRA-MN applications at 1-week intervals, but ATRA-MN applications did not induce severe local or systemic adverse effects. These results showed that ATRA-MN treatment is promising as a safe and effective therapy for seborrheic keratosis and senile lentigo. Copyright © 2016 Elsevier Inc. All rights reserved.

A randomized pilot comparative study of topical methyl aminolevulinate photodynamic therapy versus imiquimod 5% versus sequential application of both therapies in immunocompetent patients with actinic keratosis: clinical and histologic outcomes.

PubMed

Serra-Guillén, Carlos; Nagore, Eduardo; Hueso, Luis; Traves, Victor; Messeguer, Francesc; Sanmartín, Onofre; Llombart, Beatriz; Requena, Celia; Botella-Estrada, Rafael; Guillén, Carlos

2012-04-01

Photodynamic therapy (PDT) and imiquimod are the treatments of choice for actinic keratosis (AK). As they have different mechanisms of action, it seems reasonable to assume that applying both treatments sequentially would be efficacious. We sought to determine which of these therapeutic modalities provides a better clinical and histologic response in patients with AK and whether sequential use of both was more efficacious than each separately. Patients were randomly assigned to one treatment group: group 1, PDT only; group 2, imiquimod only; or group 3, sequential use of PDT and imiquimod. The primary outcome measure was complete clinical response. Partial clinical response was defined as a reduction of more than 75% in the initial number of lesions. A complete clinicopathologic response was defined as lack of evidence of AK in the biopsy specimen. In all, 105 patients completed the study (group 1, 40 patients; group 2, 33 patients; group 3, 32 patients). Sequential application of PDT and imiquimod was more efficacious in all the outcome measures. More patients were satisfied with PDT than with the other two modalities (P = .003). No significant differences were observed among the 3 modalities and tolerance to treatment. Only one cycle of imiquimod was administered. The follow-up period was brief. Sequential application of PDT and imiquimod provides a significantly better clinical and histologic response in the treatment of AK than PDT or imiquimod monotherapy. It also produces less intense local reactions and better tolerance and satisfaction than imiquimod monotherapy. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Inverted follicular keratosis: dermoscopic and reflectance confocal microscopic features.

PubMed

Armengot-Carbo, M; Abrego, A; Gonzalez, T; Alarcon, I; Alos, L; Carrera, C; Malvehy, J; Puig, S

2013-01-01

Inverted follicular keratosis (IFK) is a rare benign tumor which usually appears as a firm papule on the face. The diagnosis is generally made by histopathology because the clinical appearance is difficult to differentiate from other lesions. Dermoscopic features of IFK have not been established to date. Herein we describe the dermoscopic findings of 4 cases of IFK. Radial peripheral hairpin vessels surrounded by a whitish halo arranged around a central white-yellowish amorphous area were observed in 3 cases, and glomerular vessels were present in the central area of one of them. The fourth case also presented a central white amorphous area but showed arborizing vessels. Reflectance confocal microscopy (available in 1 case) revealed a broadened honeycomb pattern, epidermal projections and hairpin and glomerular vessels. To our knowledge this is the first case series describing the dermoscopic features of inverted follicular keratosis and the first confocal microscopy description of this entity.

Italian guidelines and therapeutic algorithm for actinic keratoses.

PubMed

Rossi, R; Calzavara-Pinton, P G; Giannetti, A; Peserico, A; Santucci, M; Vena, G A; Lotti, T

2009-12-01

The prevalence of actinic keratosis (AK) continues to rise among white people throughout the world and it is necessary to increase the level of attention paid to it from a diagnostic and a preventive point of view. Today, AK must be considered an in situ squamous cell carcinoma and as such, must be managed using one of the available approved therapeutic alternatives. However, when multiple AKs develop on severely photodamaged skin, the treatment of the lesion together with that of the field of cancerization is part of an optimal strategy that aims not only to solve alterations clinically evident but also those in the surrounding skin field cancerization, that most likely hosts genetic alterations and is the site of initial gradual replacement of normal cells with tumoral cells. This paper reports the most recent evidences from a careful review of the literature's key articles of the treatment of AKs and suggests guidelines for the clinicians. The guidelines indicated by the authors have also been based on practical evaluations and their own clinical experience. The present conclusions may be modified by new findings in the field of oncologic research.

Interventions for actinic keratoses.

PubMed

Gupta, Aditya K; Paquet, Maryse; Villanueva, Elmer; Brintnell, William

2012-12-12

Actinic keratoses are a skin disease caused by long-term sun exposure, and their lesions have the potential to develop into squamous cell carcinoma. Treatments for actinic keratoses are sought for cosmetic reasons, for the relief of associated symptoms, or for the prevention of skin cancer development. Detectable lesions are often associated with alteration of the surrounding skin (field) where subclinical lesions might be present. The interventions available for the treatment of actinic keratoses include individual lesion-based (e.g. cryotherapy) or field-directed (e.g. topical) treatments. These might vary in terms of efficacy, safety, and cosmetic outcomes. To assess the effects of topical, oral, mechanical, and chemical interventions for actinic keratosis. We searched the following databases up to March 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2010), and LILACS (from 1982). We also searched trials registers, conference proceedings, and grey literature sources. Randomised controlled trials (RCTs) comparing the treatment of actinic keratoses with either placebo, vehicle, or another active therapy. At least two authors independently abstracted data, which included adverse events, and assessed the quality of evidence. We performed meta-analysis to calculate a weighted treatment effect across trials, and we expressed the results as risk ratios (RR) and 95% confidence intervals (CI) for dichotomous outcomes (e.g. participant complete clearance rates), and mean difference (MD) and 95% CI for continuous outcomes (e.g. mean reduction in lesion counts). We included 83 RCTs in this review, with a total of 10,036 participants. The RCTs covered 18 topical treatments, 1 oral treatment, 2 mechanical interventions, and 3 chemical interventions, including photodynamic therapy (PDT). Most of the studies lacked descriptions of some methodological details, such as the generation of the randomisation

Morphometric analysis of suprabasal cells in oral white lesions.

PubMed Central

Shabana, A H; el-Labban, N G; Lee, K W; Kramer, I R

1989-01-01

Surgical specimens from the cheek mucosa of 73 patients with white lesions were studied to determine various morphometric parameters that would help differentiate between the various types of oral mucosal white lesions that carry a risk of malignant change. Four cell types were represented: traumatic keratosis, leucoplakia, candidal leucoplakia and lichen planus, in addition to a control group of normal mucosa. The shape and size of the epithelial cells in two cell compartments, parabasal and spinous, were investigated by an interactive image analysis system (IBAS-1). The results showed an increase in the cell size in the parabasal cell compartment of all the white lesions compared with the normal mucosa. In the spinous cell compartment there was an increase in the cell size in lichen planus and traumatic keratosis; leucoplakia and candidal leucoplakia showed a slight decrease in cell size compared with the normal mucosa. Attempts to discriminate between the four groups of white lesions showed that these parameters can provide a high level of separation between lichen planus and the three other groups, but not between leucoplakia, candidal leucoplakia, and traumatic keratosis. PMID:2703543

Keratosis pilaris on the cheek (image)

MedlinePlus

Keratosis pilaris occurs most commonly during childhood and produces small, rough spots. called papules, that are typically ... especially during winter months, makes the condition worse. Keratosis pilaris tends to be inherited and may be ...

Dual-channel red/blue fluorescence dosimetry with broadband reflectance spectroscopic correction measures protoporphyrin IX production during photodynamic therapy of actinic keratosis

PubMed Central

Kanick, Stephen Chad; Davis, Scott C.; Zhao, Yan; Hasan, Tayyaba; Maytin, Edward V.; Pogue, Brian W.; Chapman, M. Shane

2014-01-01

Abstract. Dosimetry for aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy of actinic keratosis was examined with an optimized fluorescence dosimeter to measure PpIX during treatment. While insufficient PpIX generation may be an indicator of incomplete response, there exists no standardized method to quantitate PpIX production at depths in the skin during clinical treatments. In this study, a spectrometer-based point probe dosimeter system was used to sample PpIX fluorescence from superficial (blue wavelength excitation) and deeper (red wavelength excitation) tissue layers. Broadband white light spectroscopy (WLS) was used to monitor aspects of vascular physiology and inform a correction of fluorescence for the background optical properties. Measurements in tissue phantoms showed accurate recovery of blood volume fraction and reduced scattering coefficient from WLS, and a linear response of PpIX fluorescence versus concentration down to 1.95 and 250 nM for blue and red excitations, respectively. A pilot clinical study of 19 patients receiving 1-h ALA incubation before treatment showed high intrinsic variance in PpIX fluorescence with a standard deviation/mean ratio of >0.9. PpIX fluorescence was significantly higher in patients reporting higher pain levels on a visual analog scale. These pilot data suggest that patient-specific PpIX quantitation may predict outcome response. PMID:24996661

Improved detection reveals active β-papillomavirus infection in skin lesions from kidney transplant recipients.

PubMed

Borgogna, Cinzia; Lanfredini, Simone; Peretti, Alberto; De Andrea, Marco; Zavattaro, Elisa; Colombo, Enrico; Quaglia, Marco; Boldorini, Renzo; Miglio, Umberto; Doorbar, John; Bavinck, Jan N Bouwes; Quint, Koen D; de Koning, Maurits N C; Landolfo, Santo; Gariglio, Marisa

2014-08-01

The aim of this study was to determine whether detection of β-HPV gene products, as defined in epidermodysplasia verruciformis skin cancer, could also be observed in lesions from kidney transplant recipients alongside the viral DNA. A total of 111 samples, corresponding to 79 skin lesions abscised from 17 kidney transplant recipients, have been analyzed. The initial PCR analysis demonstrated that β-HPV-DNA was highly present in our tumor series (85%). Using a combination of antibodies raised against the E4 and L1 proteins of the β-genotypes, we were able to visualize productive infection in 4 out of 19 actinic keratoses, and in the pathological borders of 1 out of 14 squamous cell carcinomas and 1 out of 31 basal cell carcinomas. Increased expression of the cellular proliferation marker minichromosome maintenance protein 7 (MCM7), that extended into the upper epithelial layers, was a common feature of all the E4-positive areas, indicating that cells were driven into the cell cycle in areas of productive viral infections. Although the present study does not directly demonstrate a causal role of these viruses, the detection of E4 and L1 positivity in actinic keratosis and the adjacent pathological epithelium of skin cancer, clearly shows that β-HPV are actively replicating in the intraepidermal precursor lesions of kidney transplant recipients and can therefore cooperate with other carcinogenic agents, such as UVB, favoring skin cancer promotion.

Keratosis reduces sensitivity of anal cytology in detecting anal intraepithelial neoplasia.

PubMed

ElNaggar, Adam C; Santoso, Joseph T; Xie, Huiwen Bill

2012-02-01

To identify factors that may contribute to poor sensitivity of anal cytology in contrast to the sensitivity of anoscopy in heterosexual women. We analyzed 324 patients with biopsy confirmed diagnosis of genital intraepithelial neoplasia (either vulva, vaginal, or cervical) from 2006 to 2011 who underwent both anal cytology and anoscopy. Cytology, anoscopy, and biopsy results were recorded. Biopsy specimens underwent independent analysis for quality of specimen. Also, biopsy specimens were analyzed for characteristics that may contribute to correlation, or lack thereof, between anal cytology and anoscopic directed biopsy. 133 (41%) patients had abnormal anoscopy and underwent directed biopsy. 120 patients with normal anal cytology had anoscopy directed biopsies, resulting in 58 cases of AIN (sensitivity 9.4%; 0.039-0.199). This cohort was noted to have extensive keratosis covering the entire dysplastic anal lesion. 18 patients yielded abnormal anal cytology. Of these patients, 13 had anoscopic directed biopsies revealing 6 with AIN and absent keratosis (specificity 88.6%; 0.78-0.95). The κ statistic for anal cytology and anoscopy was -0.0213 (95% CI=-0.128-0.086). Keratosis reduces the sensitivity of anal cytology. Furthermore, anal cytology poorly correlates with anoscopy in the detection of AIN (κ statistic=-0.0213). Copyright © 2011 Elsevier Inc. All rights reserved.

Breastfeeding keratosis: this frictional keratosis of newborns may mimic thrush.

PubMed

Kiat-Amnuay, Sudarat; Bouquot, Jerry

2013-09-01

We report the first example, to our knowledge, of a frictional keratosis from exuberant sucking in a breastfeeding infant. A 2-month-old girl was referred for evaluation of a well-demarcated, nonsloughing white keratotic plaque of the lower lip mucosa, just inside the vermilion border. The plaque had a slightly irregular surface, had no surrounding erythema, and was the only such plaque in the mouth. It had been present for at least 3 weeks and had been unsuccessfully treated by her pediatrician via oral Mycostatin (nystatin). Her parents sought a second opinion when the infant was prescribed a full course of oral Diflucan (fluconazole). A cytopathology smear (Papanicolaou test) revealed abundant mature keratinocytes with no evidence of Candida. The mother admitted that the infant "worked hard" at sucking during breastfeeding and continued sucking long after feeding. The parents were unaware of any other habit or potential irritation of the lips. After 3 months of age the infant's sucking pattern became more "normal" and the keratosis disappeared; it did not recur during 3 years of follow-up. We propose the term "breastfeeding keratosis" for this entity.

Psoriasiform keratosis - case report.

PubMed

Pires, Carla Andréa Avelar; Sousa, Brena Andrade de; Nascimento, Carla do Socorro Silva do; Moutinho, Ana Thais Machado; Miranda, Mario Fernando Ribeiro de; Carneiro, Francisca Regina Oliveira

2014-01-01

Psoriasiform Keratosis is a rare clinic entity. The etiopathogenesis remains unknown and the disease is characterized by a solitary, scaly or keratotic papule, or plaque mainly located on the extremities. Histopathological features closely resemble those of psoriasis. We report the case of a 70-year-old woman presenting a solitary and asymptomatic keratotic plaque, located on the back of the left leg, unresponsive to topical corticosteroids. We performed an excisional biopsy and histopathology was consistent with psoriasiform keratosis.

Psoriasiform Keratosis - Case report*

PubMed Central

Pires, Carla Andréa Avelar; de Sousa, Brena Andrade; do Nascimento, Carla do Socorro Silva; Moutinho, Ana Thais Machado; de Miranda, Mario Fernando Ribeiro; Carneiro, Francisca Regina Oliveira

2014-01-01

Psoriasiform Keratosis is a rare clinic entity. The etiopathogenesis remains unknown and the disease is characterized by a solitary, scaly or keratotic papule, or plaque mainly located on the extremities. Histopathological features closely resemble those of psoriasis. We report the case of a 70-year-old woman presenting a solitary and asymptomatic keratotic plaque, located on the back of the left leg, unresponsive to topical corticosteroids. We performed an excisional biopsy and histopathology was consistent with psoriasiform keratosis. PMID:24770510

Evaluation of Resource Utilization and Treatment Patterns in Patients with Actinic Keratosis in the United States.

PubMed

Asche, Carl V; Zografos, Panagiotis; Norlin, Jenny M; Urbanek, Bill; Mamay, Carl; Makin, Charles; Erntoft, Sandra; Chen, Chi-Chang; Hines, Dionne M; Mark Siegel, Daniel

2016-01-01

To compare health care resource utilization and treatment patterns between patients with actinic keratosis (AK) treated with ingenol mebutate gel (IngMeb) and those treated with other field-directed AK therapies. A retrospective, propensity-score-matched, cohort study compared refill/repeat and adding-on/switching patterns and outpatient visits and prescriptions (health care resource utilization) over 6 months in patients receiving IngMeb versus those receiving imiquimod, 5-fluorouracil, diclofenac sodium, and methyl aminolevulinate or aminolevulinic acid photodynamic therapy (MAL/ALA-PDT). The final sample analyzed included four matched treatment cohort pairs (IngMeb and comparator; n = 790-971 per treatment arm). Refill rates were similar except for imiquimod (15% vs. 9% for imiquimod and IngMeb, respectively; P < 0.05). MAL/ALA-PDT treatment repetition rates were higher than IngMeb refill rates (20% vs. 10%; P < 0.05). Topical agent add-on/switch rates were comparable. PDT had higher switch rates than did IngMeb (5% vs. 2%; P < 0.05). The IngMeb cohort had a significantly lower proportion of patients with at least one AK-related outpatient visit during the 6-month follow-up than did any other cohort: versus imiquimod (50% vs. 66%; P < 0.0001), versus 5-fluorouracil (50% vs. 69%; P < 0.0001), versus diclofenac sodium (51% vs. 56%; P = 0.034), and versus MAL/ALA-PDT (50% vs. 100%; P < 0.0001). There were significantly fewer AK-related prescriptions among patients receiving IngMeb than among patients in other cohorts. Results based on the first 6 months after treatment initiation suggested that most field-directed AK therapies had clinically comparable treatment patterns except imiquimod, which was associated with higher refill rates, and PDT, which was associated with significantly more frequent treatment sessions and higher switching rates. IngMeb was also associated with significantly fewer outpatient visits than were other field-directed therapies. Copyright �

Seborrheic Keratosis-like Lesions of the Cervix and Vagina: Report of a New Entity Possibly Related to Low-risk Human Papillomavirus Infection.

PubMed

Talia, Karen L; McCluggage, W Glenn

2017-04-01

We report a series of 7 unusual and morphologically distinct cervical or upper vaginal lesions in women aged 41 to 70 years. The lesions involved the cervix in 3 cases, the upper vagina in 2, the cervix and vagina in 1, and in 1 case the site of origin could not be determined. The lesions had a consistent morphologic appearance with a surface "plaque-like" or "stuck-on" configuration apparent in those cases where surrounding normal tissues were present. Broad coalescing solid sheets and interconnecting trabeculae of cytologically bland cells with a rather "basaloid" appearance emanated from the surface and there were scattered squamous eddies. Other features included peripheral palisading and a stroma containing hyalinized basement membrane-like material. Immunohistochemically, the lesions were diffusely positive with p63, CK5/6, and 34βE12 and focally positive with CK7, but largely negative with CK20, EMA, CEA, and BerEP4. p16 was negative or exhibited nonblock-type immunoreactivity and GATA3 was negative or weakly positive. Molecular testing detected human papillomavirus type 42 in 3 of 7 cases, with no virus detected in the remaining 4 cases. Rarely, similar cases have been reported previously as inverted transitional papilloma of the cervix or vagina, but based on the morphology and immunophenotype we do not feel these represent transitional lesions. We suggest the term seborrheic keratosis-like lesions to designate this new and rare entity, which may be associated with low-risk human papillomavirus infection. Limited follow-up in a small number of cases suggests that these lesions follow a benign clinical course.

Swiss clinical practice guidelines on field cancerization of the skin.

PubMed

Hofbauer, Günther; Anliker, Mark; Boehncke, Wolf-Henning; Brand, Christoph; Braun, Ralph; Gaide, Olivier; Hafner, Jürg; Hunger, Robert; Itin, Peter; Kaeuper, Gina; Lautenschlager, Stephan; Mainetti, Carlo; Streit, Markus

2014-01-01

Actinic keratosis (AK) affects millions of people worldwide, and its prevalence continues to increase. AK lesions are caused by chronic ultraviolet radiation exposure, and the presence of two or more AK lesions along with photodamage should raise the consideration of a diagnosis of field cancerization. Effective treatment of individual lesions as well as field cancerization is essential for good long-term outcomes. The Swiss Registry of Actinic Keratosis Treatment (REAKT) Working Group has developed clinical practice guidelines for the treatment of field cancerization in patients who present with AK. These guidelines are intended to serve as a resource for physicians as to the most appropriate treatment and management of AK and field cancerization based on current evidence and the combined practical experience of the authors. Treatment of AK and field cancerization should be driven by consideration of relevant patient, disease, and treatment factors, and appropriate treatment decisions will differ from patient to patient. Prevention measures and screening recommendations are discussed, and special considerations related to management of immunocompromised patients are provided.

Online consensus conferences for clinical guidelines development - a survey among participants from the International Guidelines for the Treatment of Actinic Keratosis.

PubMed

Werner, Ricardo N; Jacobs, Anja; Rosumeck, Stefanie; Nast, Alexander

2014-12-01

Guideline development requires considerable time and financial resources. New technical devices such as software for online conferences may help to reduce time and financial efforts of guidelines development. The present survey may serve as an explorative pilot for a future study to determine the technical feasibility, acceptability and possible weaknesses of online consensus conferences for clinical guidelines development. An anonymous online survey was conducted among participants in the online consensus conference of the International League of Dermatological Societies (ILDS) Guidelines for the Treatment of Actinic Keratosis. The majority of participants reported no technical problems with the participation in the online consensus conference; one participant had substantial technical problems accountable to a regional telephone breakdown. The majority of participants would not have preferred a traditional face-to-face conference, and all participants rated online consensus conferences for international guidelines as absolutely acceptable. Rates of acceptance were particularly high among those participants with prior experience with consensus conferences. Certain aspects, particularly the possibilities of debating, were rated as possibly superior in face-to-face conferences by some participants. The data from the online survey indicate that online consensus conferences may be an appropriate alternative to traditional face-to-face consensus conferences, especially within the frame of international guidelines that would require high travel costs and time. Further research is necessary to confirm the data from this explorative pilot study. © 2014 John Wiley & Sons, Ltd.

Efficacy of ablative fractional laser-assisted photodynamic therapy with short-incubation time for the treatment of facial and scalp actinic keratosis: 12-month follow-up results of a randomized, prospective, comparative trial.

PubMed

Choi, S H; Kim, K H; Song, K H

2015-08-01

Photodynamic therapy (PDT) using methyl aminolevulinate (MAL) is an effective first-line treatment for actinic keratosis (AK). Erbium:yttrium-aluminium-garnet (Er:YAG) ablative fractional laser-assisted MAL-PDT (AFL-PDT) has shown significant benefit for the treatment of AK. The objectives of this study were to compare the efficacy, recurrence rate, cosmetic outcome and safety between AFL-PDT with 2 and 3 h of incubation vs. Conventional MAL-PDT in patients with facial and scalp AK. This prospective randomized trial initially enrolled 440 facial and scalp AK lesions in 93 patients. Patients were randomly assigned to AFL-PDT with a 2-h incubation time (2h-AFL-PDT), 3h-AFL-PDT and 3h-MAL-PDT. All patients underwent one session of MAL-PDT using a red light-emitting diode lamp at 37 J/cm(2) , and AFL-PDT groups were assigned to pretreatment with Er:YAG AFL. Patients were followed up at 1 week, 3 months and 12 months post treatment. Efficacy, cosmetic outcomes and adverse events were assessed. Finally, 427 facial AK lesions in 88 patients were analysed in this study. Three months after the last treatment session, 3h-AFL-PDT (91.7%) was significantly more effective than 2h-AFL-PDT (76.8%) and 3h-MAL-PDT (65.6%, P < 0.001), and differences in efficacy remained significant at the 12-month follow-up. The recurrence rate was significantly lower for 3h-AFL-PDT (7.5%) than for 3h-MAL-PDT (22.1%) at 12 months (P = 0.002);however, no significant difference was found between 2h-AFL-PDT and 3h-MAL-PDT. No significant difference was found in cosmetic outcomes or safety between the three groups. We recommend 3h-AFL-PDT rather than classic MAL-PDT or short-incubation AFL-PDT for treating AK. © 2015 European Academy of Dermatology and Venereology.

Actinic lesions in fishermen’s lower lip: clinical, cytopathological and histopathologic analysis

PubMed Central

Piñera-Marques, Karine; Lorenço, Silvia Vanessa; da Silva, Luiz Fernando Ferraz; Sotto, Mirian Nacagami; Carneiro, Paulo Campos

2010-01-01

INTRODUCTION Actinic cheilitis (AC) is considered to be a pre-malignant lesion or an incipient and superficial form of lip squamous cell carcinoma. It is commonly found in individuals whose occupational activities are related to chronic sun exposure and the definitive diagnosis is performed with biopsy. Althoug Exfoliative cytology has been used as a screening procedure to evaluate cancer of the oral cavity no studies have proposed the use of exfoliative cytologic analysis to evaluate and diagnose AC. OBJECTIVE The purpose of this study was to evaluate lower lip lesions on fishermen related to chronic solar exposure using clinical, cytologic and histopathologic analyses. PATIENTS AND METHODS Smears taken from the vermilion of the lower lips of 125 fishermen and 30 control individuals were subjected to cytologic analysis. RESULTS The harvested cells were sufficient for cytologic analysis in 83.2% of the samples. Sixteen fishermen exhibited prominent lower lip lesions that justified biopsy and histological studies. In total, 4 specimens were malignant (3.2%), and 12 displayed epithelial dysplasia, demonstrating that the prevalence of epithelial dysplasia and malignant lesions was high among the fishermen population. These conditions were strongly associated with infiltration and blurring of the vermilion margin of the lower lip. CONCLUSION The cytologic analysis was not useful for detecting epithelial dysplasia or malignant alterations. PMID:20454492

Topical photodynamic therapy with methylaminolevulinate for the treatment of actinic keratosis and reduction of photodamage in organ transplant recipients: a case-series of 16 patients.

PubMed

Hasson, Ariel; Navarrete-Dechent, Cristián; Nicklas, Claudia; de la Cruz, Claudia

2012-01-01

Organ transplant recipients (OTR) are at high risk of developing cutaneous neoplasms. Topical photodynamic therapy (PDT) has been used for the treatment of actinic keratosis (AK) in OTR. The objective was to evaluate the efficacy of PDT with methylaminolevulinate (MAL) in the treatment of facial AK in OTR. As a secondary objective, we wanted to evaluate the usefulness of topical PDT in the reduction of photodamage in OTR. A prospective, single center, single arm study was made. 16 OTR were included. Topical PDT was applied for 1 or 2 cycles depending on the patient's characteristics. An evaluation of AK was made at visits pre-treatment, at 12 weeks and at 24 weeks. Photodamage was measured with multispectral image technique (SkinCare). A complete response rate of 100% was achieved for AK in all patients; it persisted without change at 12 and 24 weeks of follow-up. 62.5% of patients improved their photodamage as measured by SkinCare®, but this result was not statistically significant (P = 0.12). All patients had high level of satisfaction at the end of the therapy. MAL-PDT is an effective therapy for the treatment of AK in OTRs. It can reduce photodamage in this group of patients, but these results were not statistically significant.

Treatment options for actinic keratoses.

PubMed

McIntyre, William J; Downs, Michael R; Bedwell, Sondra A

2007-09-01

Actinic keratoses are rough, scaly lesions that commonly occur on sun-exposed areas of the skin. The prevalence of the condition increases with age. Actinic keratoses are thought to be carcinomas in situ, which can progress to squamous cell carcinomas. The decision to treat can be based on cosmetic reasons; symptom relief; or, most importantly, the prevention of malignancy and metastasis. Treatment options include ablative (destructive) therapies such as cryosurgery, curettage with electrosurgery, and photodynamic therapy. Topical therapies are used in patients with multiple lesions. Fluorouracil has been the traditional topical treatment for actinic keratoses, although imiquimod 5% cream and diclofenac 3% gel are effective alternative therapies. There are too few controlled trials comparing treatment modalities for physicians to make sound, evidence-based treatment decisions.

Follicular keratosis of the chin treated with 1.24R-dihydroxyvitamin D3 ointment.

PubMed

Yanagihara, Makoto; Takeda, Kiminobu; Tanabe, Hiroshi; Abe, Shinya; Ishizaki, Hiroshi

2007-01-01

In follicular keratosis of the chin, keratotic follicular papules occur on the chin and jaw due to localized prolonged pressure and friction on the naked skin. We present one patient with this disorder. The dermatoscopic examination revealed many well-demarcated yellow spindle bodies in the patchy lesion. Therapy with 1.24R-dihydroxyvitamin D3 ointment was effective during the treatment but had no residual positive effect.

Solar keratosis, pterygium, and squamous cell carcinoma of the conjunctiva in Malawi.

PubMed Central

Clear, A S; Chirambo, M C; Hutt, M S

1979-01-01

The histological features of 234 conjunctival biopsies from Africans in Malawi have been re-examined. The appearances of solar keratosis, pinguecula, and pterygium are presented as part of a continuous spectrum of the same pathological process and aetiology, which may lead to carcinomatous change. The results are discussed with regard to the specific geographical distribution of such lesions found by other workers, with particular emphasis on ultraviolet radiation as the main aetiological factor. Images PMID:427069

Papular, profuse, and precocious keratosis pilaris.

PubMed

Castela, Emeline; Chiaverini, Christine; Boralevi, Franck; Hugues, Rosalind; Lacour, Jean Philippe

2012-01-01

Keratosis pilaris (KP) is a frequent and benign condition in children characterized by the presence of rough, follicular papules and varying degrees of erythema. Different variants have been described, including simple KP and red KP. Between September 2007 and October 2010, 11 children with profuse and precocious KP seen at the department of pediatric dermatology were included. They defined an underemphasized clinical variant of childhood KP: the papular, profuse, and precocious KP characterized by early age of onset (<18 mos), extensive involvement of the limbs and cheeks, and papular nature of lesions. No clinical association has been found. The main complication was episodes of folliculitis. Diagnosis was delayed for all patients. Treatment is difficult, but association between emollient and keratolytic agents can provide some help. © 2011 Wiley Periodicals, Inc.

Actinic comedonal plaque.

PubMed

Eastern, J S; Martin, S

1980-12-01

Solitary plaques developed on the sun-exposed and damaged skin of five elderly, fair-skinned individuals. The lesions, erythematous to bluish confluent nodules and plaques with a cribriform appearance and comedone-like structures, presented a distinctive histologic picture of dilated, keratin-filled follicles within a matrix of amorphous, damaged collagen. We believe these cases demonstrate a distinct entity within the realm of actinic dermatoses, for which the name "actinic comedonal plaque" seems appropriate.

Statistical Properties of Echosignal Obtained from Human Dermis In Vivo

NASA Astrophysics Data System (ADS)

Piotrzkowska, Hanna; Litniewski, Jerzy; Nowicki, Andrzej; Szymańska, Elżbieta

The paper presents the classification of the healthy skin and the skin lesions (basal cell carcinoma and actinic keratosis), basing on the statistical parameters of the envelope of ultrasonic echoes. The envelope was modeled using Rayleigh and non-Rayleigh (K-distribution) statistics. Furthermore, the characteristic parameter of the K-distribution, the effective number of scatterers was investigated. Also the attenuation coefficient was used for the skin lesion assessment.

The role of immunosuppression in squamous cell carcinomas arising in seborrheic keratosis.

PubMed

Conic, Ruzica Z; Napekoski, Karl; Schuetz, Heidi; Piliang, Melissa; Bergfeld, Wilma; Atanaskova Mesinkovska, Natasha

2017-06-01

Seborrheic keratoses (SK) are common skin neoplasms considered to be benign. Reports of associated squamous cell carcinoma arising within seborrheic keratosis (SCC-SK) have been described. To describe the histopathologic characteristics of SCC-SK and identify predisposing factors in formation of these rare lesions. There were 162 cases of SCC-SK in a span of a decade (2003-2014). All of the histopathologic specimens and medical records were reviewed. Data from these patients were compared to a control group with seborrheic keratosis who were matched by age, sex, and location of lesion from the same time period (n = 162). SCC-SK has the classic histopathologic features of SK, such as hyperkeratosis, parakeratosis, papillomatosis, and pseudohorn cysts. The areas of squamous cell carcinoma were characterized by areas of squamous dysplasia (100%), hypogranulosis (79.6%), squamous eddies (79.6%), solar elastosis (80.9%), and brown pigmentation (59.9%). Patients with a history of immunosuppression had an increased risk for developing SCC-SK (19% vs 3%; P < .01), particularly when inhibition was transplant-associated (10% vs 0%; P < .01). This was a single center, retrospective study. SCC-SK occurs more often in elderly men with a history of immunosuppression associated with organ transplants. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy

PubMed Central

Cunningham, Trevor J.; Tabacchi, Mary; Eliane, Jean-Pierre; Tuchayi, Sara Moradi; Manivasagam, Sindhu; Mirzaalian, Hengameh; Turkoz, Ahu; Kopan, Raphael; Schaffer, Andras; Saavedra, Arturo P.; Wallendorf, Michael; Cornelius, Lynn A.; Demehri, Shadmehr

2016-01-01

BACKGROUND. Actinic keratosis is a precursor to cutaneous squamous cell carcinoma. Long treatment durations and severe side effects have limited the efficacy of current actinic keratosis treatments. Thymic stromal lymphopoietin (TSLP) is an epithelium-derived cytokine that induces a robust antitumor immunity in barrier-defective skin. Here, we investigated the efficacy of calcipotriol, a topical TSLP inducer, in combination with 5-fluorouracil (5-FU) as an immunotherapy for actinic keratosis. METHODS. The mechanism of calcipotriol action against skin carcinogenesis was examined in genetically engineered mouse models. The efficacy and safety of 0.005% calcipotriol ointment combined with 5% 5-FU cream were compared with Vaseline plus 5-FU for the field treatment of actinic keratosis in a randomized, double-blind clinical trial involving 131 participants. The assigned treatment was self-applied to the entirety of the qualified anatomical sites (face, scalp, and upper extremities) twice daily for 4 consecutive days. The percentage of reduction in the number of actinic keratoses (primary outcome), local skin reactions, and immune activation parameters were assessed. RESULTS. Calcipotriol suppressed skin cancer development in mice in a TSLP-dependent manner. Four-day application of calcipotriol plus 5-FU versus Vaseline plus 5-FU led to an 87.8% versus 26.3% mean reduction in the number of actinic keratoses in participants (P < 0.0001). Importantly, calcipotriol plus 5-FU treatment induced TSLP, HLA class II, and natural killer cell group 2D (NKG2D) ligand expression in the lesional keratinocytes associated with a marked CD4+ T cell infiltration, which peaked on days 10–11 after treatment, without pain, crusting, or ulceration. CONCLUSION. Our findings demonstrate the synergistic effects of calcipotriol and 5-FU treatment in optimally activating a CD4+ T cell–mediated immunity against actinic keratoses and, potentially, cancers of the skin and other organs. TRIAL

A case of new onset keratosis pilaris after discontinuation of erlotinib.

PubMed

Okereke, Uchenna R; Colozza, Sara; Cohen, David E

2014-11-01

Keratosis pilaris and keratosis pilaris-like eruptions have been reported in association with RAF inhibitors sorafenib and vemurafenib. We describe herein what is to our knowledge the first reported case of new onset keratosis pilaris after discontinuation of EGFR inhibitor erlotinib. A 60 year-old female with stage IV lung cancer was treated with erlotinib (100 mg/d). The patient elected to discontinue erlotinib after four years secondary to adverse systemic reactions. However, five months later small, monomorphic, rough, folliculocentric papules with surrounding mild erythema characteristic of keratosis pilaris were noted on upper back and arms. This serves as the first documented case of new onset keratosis pilaris in a patient after discontinuation of erlotinib. We report the present case to show the possible association of keratosis pilaris with not only RAF inhibitors, but also the EGFR inhibitor erlotinib. Further investigation will determine whether this is a class effect with other systemic EGFR inhibitors.

Basal Cell Carcinoma Arising within Seborrheic Keratosis

PubMed Central

Yurdakul, Cüneyt; Güçer, Hasan; Sehitoglu, Ibrahim

2014-01-01

Malignant tumour development within a seborrheic keratosis (SK) is extremely rare. Though the most commonly developed malignant tumour is the basal cell carcinoma (BCC), other tumour types have also been reported in literature. Herein, we will report a superficial type BCC case developed within SK localized in hairy skin of a 78-year-old female patient. In immunohistochemical evaluation, diffuse positive staining with CK19 and over-expression in p53 compared with non-neoplastic areas were determined in neoplastic basaloid islands. It is always not easy to differentiate especially superficial type BCC cases from non-neoplastic epithelium of SK with histopathological evaluation. As far as this reason we believe that in difficult differentiation of these 2 lesions, in order to show the differentiation in basal epithelium, immunohistochemical evaluation may be helpful. PMID:25177624

Effective photodynamic therapy of actinic keratoses on the head and face with a novel, self-adhesive 5-aminolaevulinic acid patch.

PubMed

Hauschild, Axel; Popp, Georg; Stockfleth, Eggert; Meyer, Karl-Gustav; Imberger, Dirk; Mohr, Peter; Itschert, Götz; Kaufmann, Roland; Neuber, Karsten; Frambach, Yvonne; Gollnick, Harald; Brunnert, Marcus; Stocker, Marcus; Ortland, Christoph; Karrer, Sigrid

2009-02-01

Photodynamic therapy (PDT) is increasingly used for the treatment of actinic keratosis (AK). To investigate both the efficacy of different application times and the safety of a novel patch (PD P 506 A) containing aminolaevulinic acid in the PDT of mild to moderate AK. Applications of PD P 506 A for 0.5, 1, 2 and 4 h were compared in a multicentre, randomized, blinded-observer, parallel-group study. After patch removal, study lesions were illuminated with red light (lambda(em) approximately 630 nm; 37 J/cm(2)). Study lesions were not pretreated (e.g. by curettage) prior to PDT. Efficacy was evaluated 4 and 8 weeks after treatment. Safety and tolerability were determined through laboratory analyses and documentation of both local reactions and adverse events. A total of 149 patients were initially enrolled. Of these, 140 patients (520 lesions) completed the study according to protocol. Eight weeks after treatment, 86% of the AK lesions (74% of the patients) treated with 4-h patch application showed complete clearance. The complete clearance rates of lesions (patients) for the 2-, 1- and 0.5-h treatment arms were 73% (47%), 72% (50%) and 51% (24%), respectively. Statistically, the 4-h application was identified as the 'best treatment'. Patients with clearance seemed to experience local reactions to a greater extent than patients without clearance. Local reactions to study treatments did not exceed the expected range. The results of this first clinical efficacy study suggest excellent therapeutic outcomes with a single PD P 506 A PDT with a 4-h application.

Actinic prurigo of the lip: Two case reports

PubMed Central

Miranda, Ana MO; Ferrari, Thiago M; Werneck, Juliana T; Junior, Arley Silva; Cunha, Karin S; Dias, Eliane P

2014-01-01

Actinic prurigo is a photodermatosis that can affect the skin, conjunctiva and lips. It is caused by an abnormal reaction to sunlight and is more common in high-altitude living people, mainly in indigenous descendants. The diagnosis of actinic prurigo can be challenging, mainly when lip lesions are the only manifestation, which is not a common clinical presentation. The aim of this article is to report two cases of actinic prurigo showing only lip lesions. The patients were Afro-American and were unaware of possible Indian ancestry. Clinical exam, photographs, videoroscopy examination and biopsy were performed, and the diagnosis of actinic prurigo was established. Topical corticosteroid and lip balm with ultraviolet protection were prescribed with excellent results. The relevance of this report is to show that although some patients may not demonstrate the classical clinical presentation of actinic prurigo, the associated clinical and histological exams are determinants for the correct diagnosis and successful treatment of this disease. PMID:25133153

Keratosis follicularis spinulosa decalvans and acne keloidalis nuchae.

PubMed

Goh, Michelle S Y; Magee, Jill; Chong, Alvin H

2005-11-01

A 27-year-old man presented with a 10-year history of scarring alopecia on the vertex of the scalp associated with follicular crusting and pustule formation, and a papular eruption on the posterior neck. Additionally, there was keratosis pilaris on the cheeks, eyebrows and thighs. Histology from the vertex showed scarring with a mixed perifollicular inflammatory infiltrate and foci of acute suppurative folliculitis. With clinical correlation, the diagnosis of keratosis follicularis spinulosa decalvans and concurrent acne keloidalis nuchae was made. The association of keratosis follicularis spinulosa decalvans with acne keloidalis nuchae has not previously been described. The patient responded to treatment with oral isotretinoin 20 mg (0.25 mg/kg) daily for 12 months.

FGFR3, PIK3CA and RAS mutations in benign lichenoid keratosis.

PubMed

Groesser, L; Herschberger, E; Landthaler, M; Hafner, C

2012-04-01

Benign lichenoid keratoses (BLKs) are solitary skin lesions which have been proposed to represent a regressive form of pre-existent epidermal tumours such as solar lentigo or seborrhoeic keratosis. However, the genetic basis of BLK is unknown. FGFR3, PIK3CA and RAS mutations have been shown to be involved in the pathogenesis of seborrhoeic keratosis and solar lentigo. We thus investigated whether these mutations are also present in BLK. After manual microdissection and DNA isolation, 52 BLKs were screened for FGFR3, PIK3CA and RAS hotspot mutations using SNaPshot(®) multiplex assays. We identified 6/52 (12%) FGFR3 mutations, 10/52 (19%) PIK3CA mutations, 6/52 (12%) HRAS mutations and 2/52 (4%) KRAS mutations. FGFR3 and RAS mutations were mutually exclusive. One BLK showed a simultaneous PIK3CA and HRAS mutation. In nine BLKs with a mutation, nonlesional control tissue from the epidermal margin and the dermal lymphocytic infiltrate were wild-type, indicating that these mutations are somatic. To demonstrate that these findings are specific, 10 samples of lichen planus were analysed without evidence for FGFR3, PIK3CA or RAS mutations. Our results indicate that FGFR3, PIK3CA and RAS mutations are present in approximately 50% of BLKs. These findings support the concept on the molecular genetic level that at least a proportion of BLKs represents regressive variants resulting from former benign epidermal tumours such as seborrhoeic keratosis and solar lentigo. © 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.

Actinic keratosis

MedlinePlus

... near surfaces that reflect light, such as water, sand, concrete, and areas painted white. Sunlight is more ... A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among ...

Management of actinic cheilitis using ingenol mebutate gel: A report of seven cases.

PubMed

Flórez, Ángeles; Batalla, Ana; de la Torre, Carlos

2017-03-01

Actinic cheilitis (AC) can precede the development of squamous cell carcinoma of the lip, a location with high risk of invasiveness and metastasis. We communicate the good results that we obtained when treating seven patients suffering from AC with ingenol mebutate (IM) 0,015% concentration gel on three consecutive days. Three patients achieved complete clearance and four significant improvement. IM is a topical field treatment approved for actinic keratosis. To our knowledge, reported experience in the management of AC with IM is very limited. Local skin responses grade 3 were the main adverse event observed and they resolved in all patients without specific therapy within 1 to 2 weeks. IM is characterized by its rapid clinical effect, its favorable safety profile and its dosing period of only 3 days, shorter than with other field therapies. All these facts make it an attractive new therapy for AC, with need for further study.

mHealth App for Risk Assessment of Pigmented and Nonpigmented Skin Lesions-A Study on Sensitivity and Specificity in Detecting Malignancy.

PubMed

Thissen, Monique; Udrea, Andreea; Hacking, Michelle; von Braunmuehl, Tanja; Ruzicka, Thomas

2017-12-01

With the advent of smartphone devices, an increasing number of mHealth applications that target melanoma identification have been developed, but none addresses the general context of melanoma and nonmelanoma skin cancer identification. In this study a smartphone application using fractal and classical image analysis for the risk assessment of skin lesions is systematically evaluated to determine its sensitivity and specificity in the diagnosis of melanoma and nonmelanoma skin cancer along with actinic keratosis and Bowen's disease. In the Department of Dermatology, Catharina Hospital Eindhoven, The Netherlands, 341 melanocytic and nonmelanocytic lesions were imaged using SkinVision app; 239 underwent histopathological examination, while the rest of 102 lesions were clinically diagnosed as clearly benign and not removed. The algorithm has been calibrated using the images of the first 233 lesions. The calibrated version of the algorithm was used in a subset of 108 lesions, and the obtained results were compared with the medical findings. On the 108 cases used for evaluation the algorithm scored 80% sensitivity and 78% specificity in detecting (pre)malignant conditions. Although less accurate than the dermatologist's clinical eye, the app may offer support to other professionals who are less familiar with differentiating between benign and malignant lesions. An mHealth application for the risk assessment of skin lesions was evaluated. It adds value to diagnosis tools of its type by taking into consideration pigmented and nonpigmented lesions all together and detecting signs of malignancy with high sensitivity.

Merkel cell carcinoma with seborrheic keratosis: A unique association.

PubMed

Anand, Murthy S; Krishnamurthy, Shantha; Ravindranath, Suvarna; Ranganathan, Jyothi

2018-01-01

Merkel cell carcinoma (MCC) is a rare, clinically aggressive neuroendocrine carcinoma of the skin; MCC is 40 times less common as compared to melanoma. The most frequently reported sites have been the head and neck, extremities, and trunk. Potential mimics include malignant melanoma, lymphoma, or metastatic small cell (neuroendocrine) carcinomas. Histopathology of MCC resembles small cell carcinoma both morphologically and on IHC. The possible cell of origin was proposed as the Merkel cell, which functions as a mechanoreceptor. It has a high chance of local recurrence, regional and distant spread. In recent times, Merkel cell polyomavirus has been implicated as the causative agent for this tumor. The same agent has a reported etiologic association with other skin lesions, including seborrheic keratosis.

Expression of matrix metalloproteinases 9 and 12 in actinic cheilitis

PubMed Central

Poulopoulos, Athanasios K; Andreadis, Dimitrios; Markopoulos, Anastasios K

2013-01-01

AIM: To investigate the role of matrix-degrading metalloproteinases 9, 12 (MMPs), as mediators of functional connective tissue damage in actinic cheilitis. METHODS: Thirty five formalin-fixed, paraffin embedded specimens of actinic cheilitis, and twelve specimens of normal lower lip vermillion, which were obtained by the archives of the Department of Oral Medicine and Maxillofacial Pathology, were examined. From each block, 5 μm thick sections were cut and routinely stained with Hematoxylin and Eosin. Immunohistochemical studies were performed on 4-μm thick sections of formalin-fixed paraffin embedded actinic cheilitis lesions and of normal lower lip vermillion, for MMP-9 and MMP-12 in serial sections of our specimens. Appropriate positive and negative controls were performed to confirm the specificity of the staining reaction. MMP immunohistochemistry was evaluated using a semiquantitative immunoreactive score. RESULTS: Haematoxylin and eosin staining revealed in actinic cheilitis lesions atrophic stratified squamous cell epithelium, or focally and irregularly hyperplastic of variable thickness, in some areas was observed marked keratin production. Varying degrees of epithelial dysplasia were noticed with a wide spectrum of change within the same specimen. Characteristic was the appearance of chronic inflammatory infiltration, and a band of amorphous acellular, basophilic change like solar elastosis (elastin replacement of collagen). In normal lower lip specimens weak and scanty positive expression of MMP-9 and MMP-12 was observed. Anti-MMP-9 antibody showed a weak reaction, in actinic cheilitis lesions, focal in the elastotic material, in chronic inflammatory cells and mostly in macrophages and neutrophils. Strong and in some cases diffused immunohistochemical expression of MMP-12 was detected in actinic cheilitis lesions in the areas of the fragmented, distorted and thickened elastic fibers. MMP-12 was also expressed in chronic inflammatory cells and mostly

Characterization and Modulation of Proteins Involved in SM Vesication

DTIC Science & Technology

2005-05-01

shown to be the major etiological factor leading to the precancerous stage of actinic keratosis (AK) and to induction and progression of skin cancers...representing a transient regression-prone precancerous stage equivalent to actinic keratosis . To further examine which caspases are apical and

A Network Meta-Analysis of the Relative Efficacy of Treatments for Actinic Keratosis of the Face or Scalp in Europe

PubMed Central

Vegter, Stefan; Tolley, Keith

2014-01-01

Background Several treatments are available for actinic keratosis (AK) on the face and scalp. Most treatment modalities were compared to placebo and therefore little is known on their relative efficacy. Objectives To compare the different treatments for mild to moderate AK on the face and scalp available in clinical practice in Europe. Methods A network meta-analysis (NMA) was performed on the outcome “complete patient clearance”. Ten treatment modalities were included: two 5-aminolaevulinic acid photodynamic therapies (ALA-PDT), applied as gel (BF-200 ALA) or patch; methyl-aminolevulinate photodynamic therapy (MAL-PDT); three modalities with imiquimod (IMI), applied as a 4-week or 16-week course with 5% imiquimod, or a 2–3 week course with 3.75% imiquimod; cryotherapy; diclofenac 3% in 2.5% hyaluronic acid; 0.5% 5-fluorouracil (5-FU); and ingenol mebutate (IMB). The only data available for 5% 5-FU was from one small study and was determined to be too limited to be reliably included in the analysis. For BF-200 ALA and MAL-PDT, data from illumination with narrow-band lights were selected as these are typically used in clinical practice. The NMA was performed with a random-effects Bayesian model. Results 25 trials on 5,562 patients were included in the NMA. All active treatments were significantly better than placebo. BF-200 ALA showed the highest efficacy compared to placebo to achieve total patient clearance. BF-200 ALA had the highest probability to be the best treatment and the highest SUCRA score (64.8% and 92.1%), followed by IMI 5% 4 weeks (10.1% and 74.2%) and 5-FU 0.5% (7.2% and 66.8%). Conclusions This NMA showed that BF-200 ALA, using narrow-band lights, was the most efficacious treatment for mild to moderate AK on the face and scalp. This analysis is relevant for clinical decision making and health technology assessment, assisting the improved management of AK. PMID:24892649

Case for diagnosis. Actinic prurigo.

PubMed

Daldon, Patricia Erica Christofoletti; Pascini, Mirella; Correa, Mariane

2010-01-01

A 13-year-old black boy had pruritic papular and nodular lesions on his forearms associated to edema of the lower lip, photophobia, conjunctivitis and pterygium. Skin biopsy of the lower lip revealed acanthosis, spongiosis with dermal perivascular mononuclear cell infiltration composed by lymphocytes, plasma cells and eosinophils consistent with actinic prurigo. Lesions improved considerably with the use of thalidomide 100mg/ day.

Actinic cheilitis: aesthetic and functional comparative evaluation of vermilionectomy using the classic and W-plasty techniques.

PubMed

Rossoe, Ed Wilson Tsuneo; Tebcherani, Antonio José; Sittart, José Alexandre; Pires, Mario Cezar

2011-01-01

Chronic actinic cheilitis is actinic keratosis located on the vermilion border. Treatment is essential because of the potential for malignant transformation. To evaluate the aesthetic and functional results of vermilionectomy using the classic and W-plasty techniques in actinic cheilitis. In the classic technique, the scar is linear and in the W-plasty one, it is a broken line. 32 patients with clinical and histopathological diagnosis of actinic cheilitis were treated. Out of the 32 patients, 15 underwent the W-plasty technique and 17 underwent the classic one. We evaluated parameters such as scar retraction and functional changes. A statistically significant association between the technique used and scar retraction was found, which was positive when using the classic technique (p = 0.01 with Yates' correction). The odds ratio was calculated at 11.25, i.e., there was a greater chance of retraction in patients undergoing the classic technique. Both techniques revealed no functional changes. We evaluated postoperative complications such as the presence of crusts, dry lips, paresthesia, and suture dehiscence. There was no statistically significant association between complications and the technique used (p = 0.69). We concluded that vermilionectomy using the W-plasty technique shows better cosmetic results and similar complication rates.

Dermoscopy-pathology relationship in seborrheic keratosis.

PubMed

Minagawa, Akane

2017-05-01

Making a definitive diagnosis of seborrheic keratosis (SK) can be challenging for the naked eye due to its wide variation in clinical features. Fortunately, however, most cases of SK exhibit the typical dermoscopic findings of fissures and ridges, hairpin vessels with white halo, comedo-like openings, and milia-like cysts, all of which are helpful to distinguish SK from melanoma, melanocytic nevus, squamous cell carcinoma, basal cell carcinoma (BCC) and other skin tumors. Histopathologically, these dermoscopic characteristics correspond to papillomatous surface of the epidermis, enlarged capillaries of the dermal papillae, pseudohorn cysts in the epidermis opened to the surface of the lesion and intraepidermal cysts, respectively. Clinicians should bear in mind that the clonal type of SK dermoscopically mimics melanoma and BCC by the presence of globule-like structures, while regressing SK exhibits a granular pattern that is similar to the peppering found in melanoma. Furthermore, milia-like cysts alone are insufficient for a conclusive diagnosis of SK because melanoma in rare cases displays cysts along with other SK-like dermoscopic findings. © 2017 Japanese Dermatological Association.

Heterogeneity of keratin expression and actin distribution in benign and malignant mammary diseases.

PubMed

Wada, T; Yasutomi, M; Yamada, K; Hashimura, K; Kunikata, M; Tanaka, T; Huang, J W; Mori, M

1991-01-01

Immunoreactivity of monoclonal anti-cytokeratin KL1, PKK1, K8.12 and anti-actin antibodies in 101 cases of diseased human breast lesions showed irregular keratin distribution in luminal cells of terminal ductal-lobular unit and basal layer cells of the interlobular and main duct. Actin staining was confined to myoepithelial cells. Benign lesions showed great heterogeneity in luminal cells of the terminal ductal-lobular units. Breast carcinoma showed a reduced staining for keratins, heterogeneity of keratin expression was found in solid tubular carcinoma, and actin was usually absent: however, papillo-ductal or comedo type had actin positive myoepithelial cells around carcinoma foci.

Keratosis lichenoides chronica: Case-based review of treatment options.

PubMed

Pistoni, Federica; Peroni, Anna; Colato, Chiara; Schena, Donatella; Girolomoni, Giampiero

2016-08-01

Keratosis lichenoides chronica (KLC) is a rare dermatological condition characterized by keratotic papules arranged in a parallel linear or reticular pattern and facial lesions resembling seborrheic dermatitis or rosacea. The clinical, histological and therapeutic information on 71 patients with KLC retrieved through a PubMed search plus one our new case were analyzed. KLC affects patients of all ages, with a modest male predominance. Pediatric cases represent about one quarter of patients. Diagnosis is usually delayed and histologically confirmed. All patients have thick, rough and scaly papules and plaques arranged in a linear or reticular pattern, on limbs (>80%) and trunk (about 60%). Face involvement is described in two-thirds of patients. Lesions are usually asymptomatic or mildly pruritic. Other manifestations, such as palmoplantar keratoderma, mucosal involvement, ocular manifestations, nail dystrophy, are reported in 20-30% of patients. Children present more frequently alopecia. No controlled trials are available. Results from small case series or single case reports show that the best treatment options are phototherapy and systemic retinoids, alone or in combination, with nearly half of patients reaching complete remission. Systemic corticosteroids as well as antibiotics and antimalarials are not effective.

Paying more than lip service to lip lesions.

PubMed Central

Bentley, Janna M.; Barankin, Benjamin; Lauzon, Gilles J.

2003-01-01

OBJECTIVE: To review the epidemiology, etiology, diagnosis, management, and prognosis of the most common, potentially lethal, lip lesions: leukoplakia, actinic cheilitis, and squamous cell carcinoma (SCC). QUALITY OF EVIDENCE MEDLINE: was searched from 1966 to 2002 for English-language articles on prevalence of lip lesions. No articles for a family physician audience were found. MEDLINE was searched again using the terms "leukoplakia," "actinic cheilitis," and "squamous cell carcinoma." Randomized, controlled trials were selected; non-blinded trials, population-based studies, and systematic reviews were also used. MAIN MESSAGE: Leukoplakia, actinic cheilitis, and SCC of the lips are relatively common presentations that can cause substantial morbidity and, more rarely, mortality. Any abnormality of the lips can be an embarrassment. Because of the seriousness and frequency of lip disease, it is important to look for, diagnose, and treat lip lesions to prevent morbidity and mortality and also to maintain social acceptance and self-esteem. CONCLUSION: Knowledge of leukoplakia, actinic cheilitis, and SCC of the lips will aid family physicians in diagnosing and managing these lesions and in preventing associated morbidity and mortality. PMID:14526863

Actin, actin-binding proteins, and actin-related proteins in the nucleus.

PubMed

Kristó, Ildikó; Bajusz, Izabella; Bajusz, Csaba; Borkúti, Péter; Vilmos, Péter

2016-04-01

Extensive research in the past decade has significantly broadened our view about the role actin plays in the life of the cell and added novel aspects to actin research. One of these new aspects is the discovery of the existence of nuclear actin which became evident only recently. Nuclear activities including transcriptional activation in the case of all three RNA polymerases, editing and nuclear export of mRNAs, and chromatin remodeling all depend on actin. It also became clear that there is a fine-tuned equilibrium between cytoplasmic and nuclear actin pools and that this balance is ensured by an export-import system dedicated to actin. After over half a century of research on conventional actin and its organizing partners in the cytoplasm, it was also an unexpected finding that the nucleus contains more than 30 actin-binding proteins and new classes of actin-related proteins which are not able to form filaments but had evolved nuclear-specific functions. The actin-binding and actin-related proteins in the nucleus have been linked to RNA transcription and processing, nuclear transport, and chromatin remodeling. In this paper, we attempt to provide an overview of the wide range of information that is now available about actin, actin-binding, and actin-related proteins in the nucleus.

Proteomic profiling reveals candidate markers for arsenic-induced skin keratosis.

PubMed

Guo, Zhiling; Hu, Qin; Tian, Jijing; Yan, Li; Jing, Chuanyong; Xie, Heidi Qunhui; Bao, Wenjun; Rice, Robert H; Zhao, Bin; Jiang, Guibin

2016-11-01

Proteomics technology is an attractive biomarker candidate discovery tool that can be applied to study large sets of biological molecules. To identify novel biomarkers and molecular targets in arsenic-induced skin lesions, we have determined the protein profile of arsenic-affected human epidermal stratum corneum by shotgun proteomics. Samples of palm and foot sole from healthy subjects were analyzed, demonstrating similar protein patterns in palm and sole. Samples were collected from the palms of subjects with arsenic keratosis (lesional and adjacent non-lesional samples) and arsenic-exposed subjects without lesions (normal). Samples from non-exposed healthy individuals served as controls. We found that three proteins in arsenic-exposed lesional epidermis were consistently distinguishably expressed from the unaffected epidermis. One of these proteins, the cadherin-like transmembrane glycoprotein, desmoglein 1 (DSG1) was suppressed. Down-regulation of DSG1 may lead to reduced cell-cell adhesion, resulting in abnormal epidermal differentiation. The expression of keratin 6c (KRT6C) and fatty acid binding protein 5 (FABP5) were significantly increased. FABP5 is an intracellular lipid chaperone that plays an essential role in fatty acid metabolism in human skin. This raises a possibility that overexpression of FABP5 may affect the proliferation or differentiation of keratinocytes by altering lipid metabolism. KRT6C is a constituent of the cytoskeleton that maintains epidermal integrity and cohesion. Abnormal expression of KRT6C may affect its structural role in the epidermis. Our findings suggest an important approach for future studies of arsenic-mediated toxicity and skin cancer, where certain proteins may represent useful biomarkers of early diagnoses in high-risk populations and hopefully new treatment targets. Further studies are required to understand the biological role of these markers in skin pathogenesis from arsenic exposure. Copyright © 2016 Elsevier Ltd

Potentially malignant oral lesions: clinicopathological correlations

PubMed Central

Maia, Haline Cunha de Medeiros; Pinto, Najara Alcântara Sampaio; Pereira, Joabe dos Santos; de Medeiros, Ana Miryam Costa; da Silveira, Éricka Janine Dantas; Miguel, Márcia Cristina da Costa

2016-01-01

ABSTRACT Objective To determine the incidence of potentially malignant oral lesions, and evaluate and correlate their clinical and pathological aspects. Methods The sample consisted of cases clinically diagnosed as oral leukoplakia, oral erythroplakia, erythroleukoplakia, actinic cheilitis, and oral lichen planus treated at a diagnostic center, between May 2012 and July 2013. Statistical tests were conducted adopting a significance level of 5% (p≤0.05). Results Out of 340 patients, 106 (31.2%) had potentially malignant oral lesions; and 61 of these (17.9%) were submitted to biopsy. Actinic cheilitis was the most frequent lesion (37.5%) and the lower lip was the most affected site (49.6%). Among 106 patients in the sample, 48 (45.3%) reported nicotine consumption, 35 (33%) reported alcohol intake and 34 (32.1%) sun exposure while working. When clinical and histopathological diagnoses were compared, oral erythroplakia and atypical ulcer were the lesions that exhibited greater compatibility (100% each). Conclusion In most cases, clinical and histopathological diagnoses were compatible. An association between the occurrence of erythroplakia, leukoplakia and erythroleukoplakia with smoking was observed. Similarly, an association between actinic cheilitis and sun exposure was noted. Erythroleukoplakia presented the highest malignancy grade in this study. Finally, dental surgeons should draw special attention to diagnosis of potentially malignant oral lesions, choose the best management, and control the lesions to avoid their malignant transformation. PMID:27074232

Value of videoroscopy in the detection of alterations of  Actinic Cheilitis and the selection of biopsy areas

PubMed Central

Miranda, Ana-Maria; Ferrari, Thiago; Domingos, Tabata; Cunha, Karin; Dias, Eliane

2015-01-01

Background To demonstrate the value of videoroscopy in identifying lesions and alterations not seen by oroscopy and to select the area for biopsy. Material and Methods Eighty patients were subjected to anamnesis, physical exam, videoroscopy exam, toluidine blue test and biopsy. A diagram of the lips was created to record the exact location where the lesion was found. Results Physical exam identified 287 lesions, and videoroscopy identified 587 lesions; erythema and white lesions were the most common lesions associated with actinic cheilitis. Of the 59 performed biopsies, 32 (52.4%) cases were identified by videoroscopy that showed lesions that were not detected during physical examination. Conclusions The establishment of a diagram of the lip permitted registration of the precise location of the lesion. Videoroscopy was effective in locating lesions not seen by oroscopy. Both videoroscopy and the diagram of the lips allowed for better and earlier diagnosis and better patient follow-up for those with actinic cheilitis. Key words: Actinic cheilitis, potentially malignant disorder, videoroscopy, dermatoscopy, lip. oroscopy, diagram of lip. PMID:25662549

Dermoscopy of inverted follicular keratosis: study of 12 cases.

PubMed

Llambrich, A; Zaballos, P; Taberner, R; Terrasa, F; Bañuls, J; Pizarro, A; Malvehy, J; Puig, S

2016-07-01

Inverted follicular keratosis (IFK) is an uncommon benign tumour of the follicular infundibulum, which is often misdiagnosed clinically as other keratinizing tumours, and commonly diagnosed correctly by histopathology. There are few reports about the dermoscopic findings of this lesion. To evaluate the dermoscopic features of IFK. The dermoscopic structures and patterns in digital dermoscopic images of 12 histopathologically confirmed cases of IFK collected from 5 hospitals in Spain were evaluated. A keratoacanthoma (KA)-like pattern composed of central keratin surrounded by hairpin vessels in a radial arrangement was the most common pattern in IFK (58.3%). The second most common pattern was composed of a yellowish-white amorphous central area surrounded by vascular structures in a radial arrangement (33.3%). The remaining case showed a pattern composed of a yellowish-white amorphous central area with milky red globules. Vascular structures were present in all cases, with a monomorphic pattern in seven cases and a polymorphic pattern in five, mainly with radial arrangement. Arborizing vessels, linear irregular vessels, corkscrew vessels and milky red globules were present in some cases. We describe the two main patterns of IFK. Lesions with a KA-like pattern are clinically and dermoscopically undistinguishable from KA and squamous cell carcinoma. Cases with a polymorphic vascular pattern could be confused with malignant tumours, including basal cell carcinoma and amelanotic melanoma. © 2016 British Association of Dermatologists.

Overexpression of Amyloid Precursor Protein Promotes the Onset of Seborrhoeic Keratosis and is Related to Skin Ageing.

PubMed

Li, Yuanying; Wang, Yu; Zhang, Wei; Jiang, Leiwei; Zhou, Wenming; Liu, Zhi; Li, Shijun; Lu, Hongguang

2018-02-28

Seborrhoeic keratosis is an age-related skin disease. Amyloid precursor protein (APP) plays an important role in the pathogenesis of age-related Alzheimer's disease. The aim of this study was to elucidate the expression characteristics of APP in seborrhoeic keratosis tissues (n = 50), and explore whether the production of APP is related to the onset of seborrhoeic keratosis and skin ageing, including ultraviolet (UV)-induced ageing, as observed in normal skin (n = 79). The results of immunohistochemistry, Western blotting and quantitative real-time PCR showed that APP and its downstream products (i.e. amyloid-β42) were more highly expressed in seborrhoeic keratosis than in paired adjacent normal skin tissues. In contrast, the expression of its key secretase (i.e. β-secretase1) was generally low. Furthermore, APP expression was higher in UV-exposed than non-exposed skin sites, and expression in the older age group (61-85 years) was greater than that in the younger age group (41-60 years) in seborrhoeic keratosis tissues (p<0.05). APP expression correlated positively with age in epidermis (p<0.05), but not in dermis. These findings suggest that overexpression of APP may promote the onset of seborrhoeic keratosis and is a marker of skin ageing and UV damage. Further research will elucidate whether therapeutic mitigation of increased levels of APP in the skin might delay the onset of seborrhoeic keratosis and skin ageing.

[Retrospective, descriptive, observational study of treatment of multiple actinic keratoses with topical methyl aminolevulinate and red light: results in clinical practice and correlation with fluorescence imaging].

PubMed

Fernández-Guarino, M; Harto, A; Sánchez-Ronco, M; Pérez-García, B; Marquet, A; Jaén, P

2008-12-01

Actinic keratosis (AK) is one of the most common skin diseases seen in clinical practice. In the last 5 years, several studies assessing the efficacy of photodynamic therapy in the treatment of multiple AKs have been published. We aimed to assess the clinical outcomes of photodynamic therapy in patients with multiple AKs and the correlation of those outcomes with fluorescence imaging. In this retrospective, descriptive, observational study of 57 patients treated in our hospital with photodynamic therapy for multiple AKs, we recorded age, sex, and lesion site (face, scalp, and dorsum of the hands). All patients were treated in the same way: methyl aminolevulinic acid (Metvix) was applied for 3 hours and the skin then irradiated with red light at 630 nm, 37 J/cm(2), for 7.5 minutes (Aktilite). The response, remission duration, tolerance, number of sessions, and fluorescence images were recorded by site. The chi(2) test was used to assess between-site differences and the correlation between fluorescence imaging and clinical response. The greatest improvements were obtained for facial lesions; these required fewer sessions and remission lasted longer than lesions at other sites. The treatment was best tolerated on the dorsum of the hands. The fluorescence area and the reduction in intensity on applying treatment were found to be strongly and significantly correlated with the extent of clinical response. Overall, the outcomes of treatment of multiple AKs with photodynamic therapy are better for the face than for the scalp and dorsum of the hands. Fluorescence imaging may be an effective tool for predicting response to treatment.

Biopsy guided by dermoscopy in cutaneous pigmented lesion - Case report*

PubMed Central

Bomm, Lislaine; Benez, Marcela Duarte Villela; Maceira, Juan Manuel Piñeiro; Succi, Isabel Cristina Brasil; Scotelaro, Maria de Fatima Guimarães

2013-01-01

It may be clinically difficult to differentiate early-stage melanoma from benign tumors, specially pigmented seborrheic keratosis. Dermoscopy can help; however, the findings are not always conclusive. Therefore, histopathology may be necessary for a correct diagnosis. We describe a melanocytic lesion with dubious clinic and dermoscopic findings. An incisional biopsy of a suspicious area, guided by dermoscopy, was performed to clarify the findings. PMID:23539018

Systemic retinoids for the chemoprevention of cutaneous squamous cell carcinoma and verrucal keratosis in a cohort of patients on BRAF inhibitors.

PubMed

Anforth, R; Blumetti, T C M P; Clements, A; Kefford, R; Long, G V; Fernandez-Peñas, P

2013-12-01

The treatment of metastatic melanoma has changed greatly with the development of inhibitors targeted at the mutated BRAF kinase present in up to 50% of metastatic melanoma cases. These agents, vemurafenib and dabrafenib, have been shown to increase median survival. Unfortunately, they have also been associated with the development of verrucal keratosis (VK) and cutaneous squamous cell carcinoma (cuSCC). These lesions require surgical excision, and when a large number of these lesions need to be treated, it can significantly affect the patient's quality of life. To determine if acitretin is suitable as a chemopreventative agent against the development of verrucal keratosis and cuSCC, in patients on BRAF inhibitors. Patients treated with a BRAF inhibitor, vemurafenib or dabrafenib, for stage IV metastatic melanoma, who had undergone more than five surgical excisions to remove lesions suggestive of cuSCC, were offered the opportunity to commence acitretin as a chemopreventative agent. Patients were evaluated every 4 weeks. Clinical and histological data were collected. Eight patients, who had a total of 24 cuSCC removed, were included in the study. After commencement of acitretin, only five cuSCC were excised from two patients. The most significant reduction was in a patient who had developed 13 cuSCC over 10 months and only two cuSCC 3 months after commencing acitretin. No modifications in the dose of the BRAF inhibitor were made as a result of cuSCC in any of these patients. Acitretin should be considered as a chemopreventative agent for VK and cuSCC in patients taking BRAF inhibitors, before considering dosage reductions. © 2013 British Association of Dermatologists.

Actinous enigma or enigmatic actin

PubMed Central

Povarova, Olga I; Uversky, Vladimir N; Kuznetsova, Irina M; Turoverov, Konstantin K

2014-01-01

Being the most abundant protein of the eukaryotic cell, actin continues to keep its secrets for more than 60 years. Everything about this protein, its structure, functions, and folding, is mysteriously counterintuitive, and this review represents an attempt to solve some of the riddles and conundrums commonly found in the field of actin research. In fact, actin is a promiscuous binder with a wide spectrum of biological activities. It can exist in at least three structural forms, globular, fibrillar, and inactive (G-, F-, and I-actin, respectively). G-actin represents a thermodynamically instable, quasi-stationary state, which is formed in vivo as a result of the energy-intensive, complex posttranslational folding events controlled and driven by cellular folding machinery. The G-actin structure is dependent on the ATP and Mg2+ binding (which in vitro is typically substituted by Ca2+) and protein is easily converted to the I-actin by the removal of metal ions and by action of various denaturing agents (pH, temperature, and chemical denaturants). I-actin cannot be converted back to the G-form. Foldable and “natively folded” forms of actin are always involved in interactions either with the specific protein partners, such as Hsp70 chaperone, prefoldin, and the CCT chaperonin during the actin folding in vivo or with Mg2+ and ATP as it takes place in the G-form. We emphasize that the solutions for the mysteries of actin multifunctionality, multistructurality, and trapped unfolding can be found in the quasi-stationary nature of this enigmatic protein, which clearly possesses many features attributed to both globular and intrinsically disordered proteins. PMID:28232879

The application of 5-aminolevulinic acid in the treatment of precancerous lesions, skin cancer, and a new approach to the control of therapy

NASA Astrophysics Data System (ADS)

Kulas, Zbigniew; Bereś-Pawlik, Elżbieta; Bieniek, Andrzej; Matusiak, Łukasz

2009-02-01

The aim of our work was to determine a therapeutic effect of photodynamic therapy (PDT). Twenty five patients with the Bowen's disease, actinic keratosis and basal cell carcinoma (superficial, nodular) were examined. They were treated with photosensitizer - aminolevulinic acid (metabolized in protoporphyrin IX), and the new red light source built of high-power diodes. A new method, based on numerical analysis of fluorescence imaging of tissues, was proposed as a way for controlling therapy.

Evidence- and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis - International League of Dermatological Societies in cooperation with the European Dermatology Forum - Short version.

PubMed

Werner, R N; Stockfleth, E; Connolly, S M; Correia, O; Erdmann, R; Foley, P; Gupta, A K; Jacobs, A; Kerl, H; Lim, H W; Martin, G; Paquet, M; Pariser, D M; Rosumeck, S; Röwert-Huber, H-J; Sahota, A; Sangueza, O P; Shumack, S; Sporbeck, B; Swanson, N A; Torezan, L; Nast, A

2015-11-01

Actinic keratosis (AK) is a frequent health condition attributable to chronic exposure to ultraviolet radiation. Several treatment options are available and evidence based guidelines are missing. The goal of these evidence- and consensus-based guidelines was the development of treatment recommendations appropriate for different subgroups of patients presenting with AK. A secondary aim of these guidelines was the implementation of knowledge relating to the clinical background of AK, including consensus-based recommendations for the histopathological definition, diagnosis and the assessment of patients. The guidelines development followed a pre-defined and structured process. For the underlying systematic literature review of interventions for AK, the methodology suggested by the Cochrane Handbook for Systematic Reviews of Interventions, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was adapted. All recommendations were consented during a consensus conference using a formal consensus methodology. Strength of recommendations was expressed based on the GRADE approach. If expert opinion without external evidence was incorporated into the reasoning for making a certain recommendation, the rationale was provided. The Guidelines underwent open public review and approval by the commissioning societies. Various interventions for the treatment of AK have been assessed for their efficacy. The consenting procedure led to a treatment algorithm as shown in the guidelines document. Based on expert consensus, the present guidelines present recommendations on the classification of patients, diagnosis and histopathological definition of AK. Details on the methods and results of the systematic literature review and guideline development process have been published separately. International guidelines are intended to be adapted to national or regional

Mutational analysis of cutaneous squamous cell carcinomas and verrucal keratosis in patients taking BRAF inhibitors.

PubMed

Anforth, Rachael; Tembe, Varsha; Blumetti, Tatiana; Fernandez-Peñas, Pablo

2012-09-01

B-RAF inhibitors (BRAFi) have been shown to improve rates of overall and progression-free survival in patients with stage IV metastatic melanoma positive for the BRAF V600E mutation. However, the main drawback is the development of verrucal keratosis (hyperkeratotic papules with verruca-like characteristics with benign histological findings) and cutaneous squamous cell carcinomas (cuSCC). We have found upstream mutations in RAS as well as PIK3CA in both verrucal keratosis and cuSCC. This suggests that verrucal keratosis is an early clinical presentation of cuSCC in patients on BRAFi. © 2012 John Wiley & Sons A/S.

Oral mucosal lesions in denture wearers.

PubMed

Jainkittivong, Aree; Aneksuk, Vilaiwan; Langlais, Robert P

2010-03-01

To determine the prevalence of oral mucosal lesions (OMLs) and denture-related mucosal lesions (DMLs) in denture wearers and to co-relate the prevalence with age, gender, type of denture and any systemic conditions. Dental records of 380 denture wearers were retrospectively reviewed for OMLs and DMLs. We found 45% of the denture wearers had DMLs and 60.8% had OMLs not related to denture wearing. Although the prevalence of DMLs was higher in complete denture wearers than in partial denture wearers (49% vs. 42.2%), this difference was not significant. The most common DMLs were traumatic ulcer (19.5%) and denture-induced stomatitis (18.1%). When analysed by type, traumatic ulcer, denture hyperplasia, frictional keratosis and candidiasis were more common in complete denture wearers, whereas denture-induced stomatitis was more common in partial denture wearers. Frictional keratosis was more common in men than in women. The prevalence of OMLs not related to denture wearing was higher in complete denture wearers than in partial denture wearers, and the most common OML was fissured tongue (27.6%). No association between DMLs and systemic conditions or xerostomic drugs was noted. No differences in the prevalence of DMLs in association with denture type were found. The prevalence of OMLs not related to denture wearing was higher in complete denture wearers than in partial denture wearers. This difference was affected by age, and the data were similar to the findings observed in the elderly.

Clinical characteristics of keratosis obturans and external auditory canal cholesteatoma.

PubMed

Park, So Young; Jung, Young Hoon; Oh, Jeong-Hoon

2015-02-01

Keratosis obturans (KO) and external auditory canal cholesteatoma (EACC) have been considered separate entities. While the disorders are distinct, they share many overlapping characteristics, making a correct diagnosis difficult. In the present study, we compared their clinical characteristics and radiological features to clarify the diagnostic criteria. Retrospective case series. Academic medical center. The clinical data of 23 cases of EACC and KO were retrospectively reviewed. The following clinical characteristics were compared between the 2 groups: sex, age, onset of symptoms, follow-up period, audiometric results, and imaging findings on temporal bone computed tomography including bilaterality, location, and the presence of extension to adjacent tissue. The mean age of the EACC group was significantly older than that of the KO group. All of the cases of EACC occurred unilaterally, and bilateral occurrences of KO were observed in 4 of 9 cases. All of the lesions in the KO group were circumferential, and no lesion in the EACC group invaded the superior canal wall. No significant differences in symptoms, such as acute otalgia, otorrhea, and hearing loss, were noted between the 2 groups. The incidence of conductive hearing impairment more than 10 dB was higher in the KO group than in the EACC group. Thus, KO and EACC are 2 distinct disease entities that share common features in clinical characteristics except for predominant age and bilaterality. Conservative treatment with meticulous cleaning of the lesion was successful in most cases with a long-term follow-up. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

Value of videoroscopy in the detection of alterations of actinic cheilitis and the selection of biopsy areas.

PubMed

Miranda, Ana-Maria; Ferrari, Thiago; Leite, Taiana; Domingos, Tabata; Cunha, Karin; Dias, Eliane

2015-05-01

To demonstrate the value of videoroscopy in identifying lesions and alterations not seen by oroscopy and to select the area for biopsy. Eighty patients were subjected to anamnesis, physical exam, videoroscopy exam, toluidine blue test and biopsy. A diagram of the lips was created to record the exact location where the lesion was found. Physical exam identified 287 lesions, and videoroscopy identified 587 lesions; erythema and white lesions were the most common lesions associated with actinic cheilitis. Of the 59 performed biopsies, 32 (52.4%) cases were identified by videoroscopy that showed lesions that were not detected during physical examination. The establishment of a diagram of the lip permitted registration of the precise location of the lesion. Videoroscopy was effective in locating lesions not seen by oroscopy. Both videoroscopy and the diagram of the lips allowed for better and earlier diagnosis and better patient follow-up for those with actinic cheilitis.

Actin-induced dimerization of palladin promotes actin-bundling

PubMed Central

Vattepu, Ravi; Yadav, Rahul; Beck, Moriah R

2015-01-01

A subset of actin binding proteins is able to form crosslinks between two or more actin filaments, thus producing structures of parallel or networked bundles. These actin crosslinking proteins interact with actin through either bivalent binding or dimerization. We recently identified two binding sites within the actin binding domain of palladin, an actin crosslinking protein that plays an important role in normal cell adhesion and motility during wound healing and embryonic development. In this study, we show that actin induces dimerization of palladin. Furthermore, the extent of dimerization reflects earlier comparisons of actin binding and bundling between different domains of palladin. On the basis of these results we hypothesized that actin binding may promote a conformational change that results in dimerization of palladin, which in turn may drive the crosslinking of actin filaments. The proximal distance between two actin binding sites on crosslinking proteins determines the ultrastructural properties of the filament network, therefore we also explored interdomain interactions using a combination of chemical crosslinking experiments and actin cosedimentation assays. Limited proteolysis data reveals that palladin is less susceptible to enzyme digestion after actin binding. Our results suggest that domain movements in palladin are necessary for interactions with actin and are induced by interactions with actin filaments. Accordingly, we put forth a model linking the structural changes to functional dynamics. PMID:25307943

[Arsenical keratosis treated by dermatome shaving].

PubMed

Kjerkegaard, Ulrik Knap; Heje, Jens Martin; Vestergaard, Christian; Stausbøl-Grøn, Birgitte; Stolle, Lars Bjørn

2014-05-05

Cutaneous malignancy in association with arsenic exposure is a rare but well-documented phenomenon. Signs of chronic arsenic exposure are very rare in Denmark today. However, arsenic was used in the medical treatment of psoriasis vulgaris up till the 1980's and several patients suffer from this arsenic treatment today. This case report shows that arsenical keratosis can be treated by dermatome shaving, a superficial destructive therapy.

Diclofenac Topical (actinic keratosis)

MedlinePlus

... growths on the skin caused by too much sun exposure). Diclofenac is in a class of medications ... plan to avoid exposure to real and artificial sunlight (sun lamps) and to wear protective clothing and ...

Standard guidelines of care: CO2 laser for removal of benign skin lesions and resurfacing.

PubMed

Krupashankar, D S

2008-01-01

Resurfacing is a treatment to remove acne and chicken pox scars, and changes in the skin due to ageing. MACHINES: Both ablative and nonablative lasers are available for use. CO 2 laser is the gold standard in ablative lasers. Detailed knowledge of the machines is essential. INDICATIONS FOR CO 2 LASER: Therapeutic indications: Actinic and seborrheic keratosis, warts, moles, skin tags, epidermal and dermal nevi, vitiligo blister and punch grafting, rhinophyma, sebaceous hyperplasia, xanthelasma, syringomas, actinic cheilitis angiofibroma, scar treatment, keloid, skin cancer, neurofibroma and diffuse actinic keratoses. CO 2 laser is not recommended for the removal of tattoos. AESTHETIC INDICATIONS: Resurfacing for acne, chicken pox and surgical scars, periorbital and perioral wrinkles, photo ageing changes, facial resurfacing. PHYSICIANS' QUALIFICATIONS: Any qualified dermatologist (DVD or MD) may practice CO 2 laser. The dermatologist should possess postgraduate qualification in dermatology and should have had specific hands-on training in lasers either during postgraduation or later at a facility which routinely performs laser procedures under a competent dermatologist/plastic surgeon, who has experience and training in using lasers. For the use of CO 2 lasers for benign growths, a full day workshop is adequate. As parameters may vary in different machines, specific training with the available machine at either the manufacturer's facility or at another centre using the machine is recommended. CO 2 lasers can be used in the dermatologist's minor procedure room for the above indications. However, when used for full-face resurfacing, the hospital operation theatre or day care facility with immediate access to emergency medical care is essential. Smoke evacuator is mandatory. Detailed counseling with respect to the treatment, desired effects, possible postoperative complications, should be discussed with the patient. The patient should be provided brochures to study and

Actin Polymerization is Stimulated by Actin Crosslinking Protein Palladin

PubMed Central

Gurung, Ritu; Yadav, Rahul; Brungardt, Joseph G.; Orlova, Albina; Egelman, Edward H.; Beck, Moriah R.

2016-01-01

The actin scaffold protein palladin regulates both normal cell migration and invasive cell motility, processes that require the coordinated regulation of actin dynamics. However, the potential effect of palladin on actin dynamics has remained elusive. Here we show that the actin binding immunoglobulin-like domain of palladin, which is directly responsible for both actin binding and bundling, also stimulates actin polymerization in vitro. Palladin eliminated the lag phase that is characteristic of the slow nucleation step of actin polymerization. Furthermore, palladin dramatically reduced depolymerization, slightly enhanced the elongation rate, and did not alter the critical concentration. Microscopy and in vitro crosslinking assays reveal differences in actin bundle architecture when palladin is incubated with actin before or after polymerization. These results suggest a model whereby palladin stimulates a polymerization-competent form of G-actin, akin to metal ions, either through charge neutralization or conformational changes. PMID:26607837

Differentiating regressed melanoma from regressed lichenoid keratosis.

PubMed

Chan, Aegean H; Shulman, Kenneth J; Lee, Bonnie A

2017-04-01

Distinguishing regressed lichen planus-like keratosis (LPLK) from regressed melanoma can be difficult on histopathologic examination, potentially resulting in mismanagement of patients. We aimed to identify histopathologic features by which regressed melanoma can be differentiated from regressed LPLK. Twenty actively inflamed LPLK, 12 LPLK with regression and 15 melanomas with regression were compared and evaluated by hematoxylin and eosin staining as well as Melan-A, microphthalmia transcription factor (MiTF) and cytokeratin (AE1/AE3) immunostaining. (1) A total of 40% of regressed melanomas showed complete or near complete loss of melanocytes within the epidermis with Melan-A and MiTF immunostaining, while 8% of regressed LPLK exhibited this finding. (2) Necrotic keratinocytes were seen in the epidermis in 33% regressed melanomas as opposed to all of the regressed LPLK. (3) A dense infiltrate of melanophages in the papillary dermis was seen in 40% of regressed melanomas, a feature not seen in regressed LPLK. In summary, our findings suggest that a complete or near complete loss of melanocytes within the epidermis strongly favors a regressed melanoma over a regressed LPLK. In addition, necrotic epidermal keratinocytes and the presence of a dense band-like distribution of dermal melanophages can be helpful in differentiating these lesions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Transcriptional regulation of ataxia-telangiectasia and Rad3-related protein by activated p21-activated kinase-1 protects keratinocytes in UV-B-induced premalignant skin lesions.

PubMed

Beesetti, S; Mavuluri, J; Surabhi, R P; Oberyszyn, T M; Tober, K; Pitani, R S; Joseph, L D; Venkatraman, G; Rayala, S K

2017-11-02

Sun-induced skin lesions, in particular actinic keratosis, are generally considered as premalignant skin lesions that can progress into squamous cell carcinoma (SCC) and invasive SCC if left untreated. Therefore, understanding the molecular mechanisms by which the ultraviolet-B (UV-B)-exposed cells are being protected and the signaling pathways that promote the progression of certain premalignant skin lesions to malignant lesions will permit us to prevent or cure skin cancers. In the current study, we found that phospho-p21-activated kinase-1 (Pak1) and Pak1 expression was high in clinical samples of sunlight-induced premalignant skin lesions assessed by immunohistochemistry. Further, we observed that phospho-Pak1 and Pak1 levels are high in UV-B-exposed hairless SKH mouse model skin samples as compared with unexposed skin tissue. Our results from cell line and animal models showed that Pak1 is activated in response to UV-B radiation, and this activated Pak1 translocates from the cytoplasm to the nucleus. Inside the nucleus, Pak1 via C-Fos binds to a specific promoter region of DNA repair kinase ATR (ataxia-telangiectasia and Rad3-related protein) and acts as a transcriptional regulator of ATR. Results from our analysis showed that Pak1 overexpression, knockdown and Pak1 knockout cell line models showed that Pak1 confers protection to keratinocytes from UV-B-induced apoptosis and DNA damage via ATR. To our knowledge, this is the first study that evaluates the functional and clinical significance of a signaling molecule, Pak1, in sun-induced premalignant skin lesions and indicates that increased Pak1 activation and expression could serve as an early warning sign of progression toward non-melanoma skin cancer, if ignored.

Correlation of serum IgE levels and clinical manifestations in patients with actinic prurigo*

PubMed Central

Cuevas-Gonzalez, Juan Carlos; Lievanos-Estrada, Zahide; Vega-Memije, Maria Elisa; Hojyo-Tomoka, Maria Teresa; Dominguez-Soto, Luciano

2016-01-01

BACKGROUND: Actinic prurigo is an idiopathic photodermatosis, the pathophysiology of which has been hypothesized to involve subtype IV type b (Th2) hypersensitive response, whereby IL4, IL5, and IL13 are secreted and mediate the production of B cells, IgE, and IgG4. OBJECTIVES: To examine the association of serum IgE levels and the clinical severity of injuries. METHODS: This case-control study comprised patients with a clinical and histopathological diagnosis of actinic prurigo, as well as clinically healthy subjects, from whom 3cc of peripheral blood was taken for immunoassay. Cases were classified by lesion severity as mild, moderate, and severe. Descriptive statistics were analyzed, and chi-square test was performed. RESULTS: We included 21 actinic prurigo patients and 21 subjects without disease; 11 patients with actinic prurigo had elevated serum IgE levels, and 10 had low serum levels. Six actinic prurigo (AP) patients with elevated serum levels of IgE had moderate injuries, 4 had severe injuries, and 1 had minor injuries. Eight out of 10 patients with normal IgE levels presented with minor injuries in the clinical evaluation. The 21 controls did not have increased serum IgE levels. CONCLUSIONS: Elevated IgE levels are associated with moderate to severe clinical lesions, suggesting that actinic prurigo entails a type IV subtype b hypersensitivity response in which Th2 cells predominate. PMID:26982774

Melanoma or Pseudo melanoma Change in a pigmented lesion after application of topical 5-Fluorouracil

DTIC Science & Technology

2017-10-26

morphologic change in a pigmented lesion following topical field therapy with 5-FU for actinic damage on the trunk. After four weeks of twice daily...morphologic change in a pigmented lesion following topical field therapy with 5-FU for actinic damage on the trunk. After four weeks of twice daily...After four weeks of twice daily application, a previously benign appearing pigmented lesion displayed a change in clinical morphology that

Applying laser speckle images to skin science: skin lesion differentiation by polarization

NASA Astrophysics Data System (ADS)

Lee, Tim K.; Tchvialeva, Lioudmila; Dhadwal, Gurbir; Sotoodian, Bahman; Kalai, Sunil; Zeng, Haishan; Lui, Harvey; McLean, David I.

2011-09-01

Skin cancer is a worldwide health problem. It is the most common cancer in the countries with a large white population; furthermore, the incidence of malignant melanoma, the most dangerous form of skin cancer, has been increasing steadily over the last three decades. There is an urgent need to develop in-vivo, noninvasive diagnostic tools for the disease. This paper attempts to response to the challenge by introducing a simple and fast method based on polarization and laser speckle. The degree of maintaining polarization estimates the fraction of linearly maintaining polarization in the backscattered speckle field. Clinical experiments of 214 skin lesions including malignant melanomas, squamous cell carcinomas, basal cell carcinomas, nevi, and seborrheic keratoses demonstrated that such a parameter can potentially diagnose different skin lesion types. ROC analyses showed that malignant melanoma and seborrheic keratosis could be differentiated by both the blue and red lasers with the area under the curve (AUC) = 0.8 and 0.7, respectively. Also malignant melanoma and squamous cell carcinoma could be separated by the blue laser (AUC = 0.9), while nevus and seborrheic keratosis could be identified using the red laser (AUC = 0.7). These experiments demonstrated that polarization could be a potential in-vivo diagnostic indicator for skin diseases.

Applying laser speckle images to skin science: skin lesion differentiation by polarization

NASA Astrophysics Data System (ADS)

Lee, Tim K.; Tchvialeva, Lioudmila; Dhadwal, Gurbir; Sotoodian, Bahman; Kalai, Sunil; Zeng, Haishan; Lui, Harvey; McLean, David I.

2012-01-01

Skin cancer is a worldwide health problem. It is the most common cancer in the countries with a large white population; furthermore, the incidence of malignant melanoma, the most dangerous form of skin cancer, has been increasing steadily over the last three decades. There is an urgent need to develop in-vivo, noninvasive diagnostic tools for the disease. This paper attempts to response to the challenge by introducing a simple and fast method based on polarization and laser speckle. The degree of maintaining polarization estimates the fraction of linearly maintaining polarization in the backscattered speckle field. Clinical experiments of 214 skin lesions including malignant melanomas, squamous cell carcinomas, basal cell carcinomas, nevi, and seborrheic keratoses demonstrated that such a parameter can potentially diagnose different skin lesion types. ROC analyses showed that malignant melanoma and seborrheic keratosis could be differentiated by both the blue and red lasers with the area under the curve (AUC) = 0.8 and 0.7, respectively. Also malignant melanoma and squamous cell carcinoma could be separated by the blue laser (AUC = 0.9), while nevus and seborrheic keratosis could be identified using the red laser (AUC = 0.7). These experiments demonstrated that polarization could be a potential in-vivo diagnostic indicator for skin diseases.

Actin Interacting Protein1 and Actin Depolymerizing Factor Drive Rapid Actin Dynamics in Physcomitrella patens[W

PubMed Central

Augustine, Robert C.; Pattavina, Kelli A.; Tüzel, Erkan; Vidali, Luis; Bezanilla, Magdalena

2011-01-01

The remodeling of actin networks is required for a variety of cellular processes in eukaryotes. In plants, several actin binding proteins have been implicated in remodeling cortical actin filaments (F-actin). However, the extent to which these proteins support F-actin dynamics in planta has not been tested. Using reverse genetics, complementation analyses, and cell biological approaches, we assessed the in vivo function of two actin turnover proteins: actin interacting protein1 (AIP1) and actin depolymerizing factor (ADF). We report that AIP1 is a single-copy gene in the moss Physcomitrella patens. AIP1 knockout plants are viable but have reduced expansion of tip-growing cells. AIP1 is diffusely cytosolic and functions in a common genetic pathway with ADF to promote tip growth. Specifically, ADF can partially compensate for loss of AIP1, and AIP1 requires ADF for function. Consistent with a role in actin remodeling, AIP1 knockout lines accumulate F-actin bundles, have fewer dynamic ends, and have reduced severing frequency. Importantly, we demonstrate that AIP1 promotes and ADF is essential for cortical F-actin dynamics. PMID:22003077

Clinical clues for differential diagnosis between verruca plana and verruca plana-like seborrheic keratosis.

PubMed

Kim, Won-Jeong; Lee, Won-Ku; Song, Margaret; Kim, Hoon-Soo; Ko, Hyun-Chang; Kim, Byung-Soo; Kim, Moon-Bum

2015-04-01

Sometimes the clinical differentiation between verruca plana (VP) and VP-like seborrheic keratosis (SK) could be challenged. However, there have been no studies on this issue to date. The aim of this study was to elucidate clinical and dermoscopic differences between these two diseases, and also to suggest a diagnostic algorithm of VP and VP-like SK without skin biopsy. The patients who had lesions clinically considered as VP or VP-like SK were the target of our study. We took clinical and dermoscopic photos with informed consent and conducted a questionnaire. All patients had their diagnoses confirmed by biopsy. Thirty-three patients were enrolled in our study. Seventeen patients were finally diagnosed with VP (51.5%) and 16 patients with VP-like SK (48.5%). In clinical findings, VP-like SK showed significantly more scattered distribution than VP (P = 0.039), which exhibited more clustered or grouped distribution (P = 0.039). In dermoscopic findings, brain-like appearance was more commonly observed in VP-like SK (P = 0.003) whereas VP showed more red dots or globular vessels (P = 0.017) and even-colored light brown to yellow patch (P < 0.001). Sex, onset age, the size of each lesion, location, color and shape showed no significant differences between them (P > 0.05). Based on our results, we suggest a diagnostic algorithm using Koebner's phenomenon, dermoscopic findings, distribution of each lesion and biopsy for multiple VP-like lesions in adults, and we think it will be a very useful diagnostic tool in daily clinical dermatological practice. © 2015 Japanese Dermatological Association.

Treatment of Bowen Disease With Photodynamic Therapy and the Advantages of Sequential Topical Imiquimod.

PubMed

Victoria-Martínez, A M; Martínez-Leborans, L; Ortiz-Salvador, J M; Pérez-Ferriols, A

2017-03-01

Photodynamic therapy (PDT) has been shown to be useful and effective in the treatment of actinic keratosis, Bowen disease, and basal cell carcinoma. We present a series of 13 Bowen disease lesions treated using PDT. Complete responses were achieved in 11 (84%) of the lesions after 3 months of treatment; at 18 months, complete responses were seen in 9 (70%) of the lesions. Patients who presented a partial response or recurrence were treated with topical 5% imiquimod and achieved complete responses. The lesions that presented partial response or recurrence were the largest lesions, between 3 and 5cm in diameter. PDT in monotherapy or combined sequentially with imiquimod is an excellent and well-tolerated therapeutic option for Bowen disease. The treatment has few adverse effects and shows satisfactory results, particularly in multiple large lesions in areas of difficult surgical reconstruction or in elderly patients with a high surgical risk. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Control of actin-based motility through localized actin binding

PubMed Central

Banigan, Edward J.; Lee, Kun-Chun; Liu, Andrea J.

2014-01-01

A wide variety of cell biological and biomimetic systems use actin polymerization to drive motility. It has been suggested that an object such as a bacterium can propel itself by self-assembling a high concentration of actin behind it if it is repelled by actin. However, it is also known that it is essential for the moving object to bind actin. Therefore, a key question is how the actin tail can propel an object when it both binds and repels the object. We present a physically consistent Brownian dynamics model for actin-based motility that includes the minimal components of the dendritic nucleation model and allows for both attractive and repulsive interactions between actin and a moveable disk. We find that the concentration gradient of filamentous actin generated by polymerization is sufficient to propel the object, even with moderately strong binding interactions. Additionally, actin binding can act as a biophysical cap, and may directly control motility through modulation of network growth. Overall, this mechanism is robust in that it can drive motility against a load up to a stall pressure that depends on the Young’s modulus of the actin network and can explain several aspects of actin-based motility. PMID:24225232

Selective Blockade of Cytoskeletal Actin Remodeling Reduces Experimental Choroidal Neovascularization

PubMed Central

Caballero, Sergio; Yang, Ru; Chaqour, Brahim

2011-01-01

Purpose. The efficacy of the peptide Ac-EEED on reducing cell adhesion and proliferation in vitro and choroidal neovascularization (CNV) in vivo was examined. Methods. The peptide chimera containing the Ac-EEED sequence was chemically linked to the N terminus of the XMTM delivery peptide from the Erns viral surface protein. Ac-EEED or scrambled control peptide (SCRAM) was added to cultures of vascular smooth muscle cells, pericytes, endothelial cells, and fibroblasts, and adhesion, growth, and matrix production was assessed. Ac-EEED or SCRAM was injected into the vitreous of mice undergoing laser rupture of Bruch's membrane to induce CNV and lesion volume, neovascularization and lesion fibrosis were assessed. Results. Ac-EEED–induced changes in the morphology of the actin cytoskeleton by inhibiting polymerization of G-actin and disrupting the formation of stress fibers. Pretreatment with Ac-EEED resulted in endothelial cells becoming less responsive to the mitogenic and pro-adhesive effects of VEGF. Ac-EEED treatment in fibroblasts reduced TGF-β–induced fibrosis as assessed by decreased levels of connective tissue growth factor, cysteine-rich 61, collagen I (COL1A2), and collagen III (COL3A1). CNV lesion size and fibrosis were reduced in a concentration-dependent manner by up to 60%. Conclusions. In vitro studies showed that Ac-EEED affects a broad range of mechanical properties associated with cytoskeletal actin to reduce growth factor effects. The utilization of Ac-EEED in vivo may offer a novel therapeutic strategy by both suppressed neovessel growth and curtailing fibrosis typically associated with the involutional stage of CNV. PMID:21178140

Evaluation of hypoxia, angiogenesis, and lymphangiogenesis in actinic cheilitis.

PubMed

Barbosa, Natália G; Souza, Lélia B; Nonaka, Cassiano F W; Silveira, Ericka J D

2016-11-01

Actinic cheilitis is a potentially malignant condition caused mainly by chronic sun exposure. Here we aim to evaluate the role of hypoxia, angiogenesis, and lymphatic density in the clinical and morphological progression of a series of cases of actinic cheilitis. Immunohistochemistry was used to evaluate positivity to hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF)-C, and D2-40 in 40 cases of actinic cheilitis of the lower lip. The cases studied exhibited variable degrees of positivity to the markers. The median number of lymphatic vessels was 3.2, 2.4, and 3.0 in lesions showing no epithelial dysplasia (NED) and with mild (MED) and moderate (MOED) epithelial dysplasia, respectively. The median VEGF-C positivity index was 82.44% (NED), 92.74% (MED), and 82.83% (MOED), and the median HIF-1α positivity index was 11.57% (NED), 5.26% (MED), and 13.55% (MOED). No significant differences in lymphatic density or median VEGF-C and HIF-1α positivity indices were observed between histological grades or clinical presentations of actinic cheilitis (P > 0.05). Although representing early events in lip carcinogenesis, the present results suggest that hypoxia, angiogenesis, and lymphangiogenesis do not influence the morphological or clinical progression of actinic cheilitis. © 2016 The International Society of Dermatology.

Apoptosis and apoptotic pathway in actinic prurigo by immunohistochemistry

PubMed Central

Cuevas-González, Juan-Carlos; García-Vázquez, Francisco-Javier; Rodríguez-Lobato, Erika; Farfán-Morales, José-Eduardo

2016-01-01

Background Actinic prurigo (AP) is an idiopathic photodermatosis, this entity requires exposure to UV-B and -A to develop lesions. Apoptosis is a physiological death program that can be initiated by a permanently active mechanism (extrinsic pathway) or irreparable damage (intrinsic pathway). Material and Methods Descriptive study, the sample size comprised 64 paraffin blocks of tissue with a diagnosis of AP. In H&E-stained slides, the diagnosis of AP was corroborated, and 1-µm-thick sections were processed for immunohistochemistry (IHC). A database was constructed with SPSS version 20, Inc., Chicago, IL, USA, and descriptive statistics were analyzed by X2 test and comparison of means. Results A total of 64 cases were processed, of which 40 (62.5%) were cheilitis AP and 24 (37.5%) were AP in the skin. Of the 40 cheilitis samples, 27 were positive for Bcl-2 and caspase 3 (67.5%), p53 was expressed in 30 (75%). Of the skin lesions,p53 and caspase 3 were expressed in 18 of 24 cases (75%), and 13 were positive for Bcl-2 (54%). Conclusions We propose that apoptosis is the last step in the type IV subtype a-b hypersensitivity response-activation of the intrinsic pathway indicates that external factors, such as UV-A and -B are the trigger. Key words:Apoptosis, actinic prurigo, cheilitis actinic prurigo. PMID:26615506

Actinic Cheilitis: A Case Report and a Review of the Literature

PubMed Central

Wood, Neil Hamilton; Khammissa, Razia; Meyerov, Robin; Lemmer, Johan; Feller, Liviu

2011-01-01

In actinic cheilitis, the current view is that the keratinocytes have undergone transformation forming a field of epithelium with the potential for neoplastic transformation. Clinical features include diffuse and poorly demarcated atrophic, erosive or keratotic plaques that may affect some parts of, or the entire vermilion border. Fair-complexioned people, those with albinism and people with eversion of the lip are all subject to actinic cheilitis. Prophylactic measures against all forms of sunlight-induced lesions must include limitation of exposure to the sun during peak sunlight hours, the use of appropriate protective clothing, and the use of a sunscreen cream. In this article, a case of albinism is used to illustrate the nature of actinic cheilitis, its clinical features and its treatment. PMID:21228959

Actin Bodies in Yeast Quiescent Cells: An Immediately Available Actin Reserve?

PubMed Central

Pinson, Benoît; Salin, Bénédicte; Daignan-Fornier, Bertrand

2006-01-01

Most eukaryotic cells spend most of their life in a quiescent state, poised to respond to specific signals to proliferate. In Saccharomyces cerevisiae, entry into and exit from quiescence are dependent only on the availability of nutrients in the environment. The transition from quiescence to proliferation requires not only drastic metabolic changes but also a complete remodeling of various cellular structures. Here, we describe an actin cytoskeleton organization specific of the yeast quiescent state. When cells cease to divide, actin is reorganized into structures that we named “actin bodies.” We show that actin bodies contain F-actin and several actin-binding proteins such as fimbrin and capping protein. Furthermore, by contrast to actin patches or cables, actin bodies are mostly immobile, and we could not detect any actin filament turnover. Finally, we show that upon cells refeeding, actin bodies rapidly disappear and actin cables and patches can be assembled in the absence of de novo protein synthesis. This led us to propose that actin bodies are a reserve of actin that can be immediately mobilized for actin cables and patches formation upon reentry into a proliferation cycle. PMID:16914523

[Screening for cutaneous carcinoma].

PubMed

Beani, J C

1996-09-01

Skin carcinoma is the most frequent of all cancers. The main risk factor is represented by solar exposition and, so, individuals with special risk are xeroderma pigmento sum (enzymatic defect of DNA repair), light phototype person, sun-seekers, outdoor-workers and patients treated with high doses of PUVA. X-rays, mineral oils, tar and arsenic are also known skin carcinogens. HPV can also participate to skin carcinogenis alone or associated with UV particularly in immunosupressed sujets. Subjects with predisposition for skin carcinoma can be pointed out and cautioned. Detection of preepitheliomatous lesions is easy; actinic keratosis are the main signs.

Epidemiology of skin diseases in renal transplant recipients in a tertiary hospital.

PubMed

Chen, Qi Ping; Aw, Derrick C W

2010-12-01

There is no published epidemiological data on skin diseases in kidney transplant recipients in this tropical country, which has multi-ethnic groups with the Chinese as the predominant ethnic group. Skin diseases of 143 renal transplant recipients were studied in a skin clinic of a tertiary institution during annual surveillance visits from June 2006 to March 2009. Our study showed that except the common drug specific skin manifestations, sebaceous hyperplasia (56.6%), seborrheic keratosis (60.8%), melanocytic naevi (76.9%), skin tags (37.1%) and viral (29.4%) and fungal (20.3%) infections were the most prevalent skin diseases among renal transplant recipients living in Singapore. The prevalence of pre-malignant and malignant tumours was very low (11.2% actinic keratosis, 1.4% Bowen's disease, 1.4% squamous cell carcinoma, 0.7% basal cell carcinoma, 0.7% keratoacanthoma). Male predominance was seen in sebaceous hyperplasia (72.4% vs 32.1%), actinic keratosis (17.2% vs 1.8%), viral (36.8% vs 19.6%) and fungal (27.6% vs 8.9%) infections. Our study also showed increased prevalence of sebaceous hyperplasia with increased age but its prevalence was significantly higher than that reported in the age matched general population. The prevalence of seborrheic keratosis, actinic keratosis and viral infection correlated positively with post-transplant duration. Our study provides epidemiological data for the prevalence of skin diseases in renal transplant recipients. It emphasises the importance of dermatologic follow-up for renal transplant patients in order to obtain a diagnosis and manage treatable skin diseases.

Keratosis lichenoides chronica: proposal of a concept.

PubMed

Böer, Almut

2006-06-01

It has been a subject of controversy whether keratosis lichenoides chronica (KLC) is a distinctive inflammatory disease of the skin or whether it represents a manifestation of another well-known disease, such as lichen planus, lupus erythematosus, or lichen simplex chronicus. In search of clear criteria for diagnosis of KLC the entire literature pertinent to the subject was studied and findings clinical and histopathologic as they were telegraphed in them were compared with a patient of my own experience. Review of the literature reveals more than 60 patients in whom the diagnosis of KLC was made. Three categories emerge based on whether the findings presented in a particular article (1) do not permit any diagnosis to be rendered; (2) do allow a diagnosis specific to be made, such as of lichen simplex, lichen planus, or lupus erythematosus; or (3) do not correspond to any disease well defined, such as lichen simplex, lichen planus, lupus erythematosus, but seem to show attributes morphologic, clinically and histopathologically, that are repeatable. Patients diagnosed as having KLC obviously represent a potpourri of different diseases, the most common of them being lichen simplex chronicus, lichen planus, and lupus erythematosus. Fewer than 25 patients reported on, however, presented themselves with lesions very similar to one another clinically, namely, an eruption that involved the face in a manner reminiscent of seborrheic dermatitis and with tiny papules on the trunk and extremities, which assumed linear and reticulate shapes by way of confluence of lesions. Individual papules were infundibulocentric and acrosyringocentric. Findings histopathologic were those of a lichenoid interface dermatitis affiliated with numerous necrotic keratocytes and covered by parakeratosis housing neutrophils in staggered fashion. These patients seem to have an authentic and distinctive condition that is exceedingly rare. In conclusion, the diagnosis of KLC should be made only for

Photodynamic therapy is more effective than imiquimod for actinic keratosis in organ transplant recipients: a randomized intraindividual controlled trial.

PubMed

Togsverd-Bo, K; Halldin, C; Sandberg, C; Gonzalez, H; Wennberg, A M; Sørensen, S S; Wulf, H C; Haedersdal, M

2018-04-01

Actinic keratoses (AKs) in solid organ transplant recipients (OTRs) are difficult-to-treat premalignancies and comparison of topical therapies is therefore warranted. In an intraindividual study to compare the efficacy and safety of field treatment with methyl aminolaevulinate photodynamic therapy (MAL-PDT) and imiquimod (IMIQ) for AKs in OTRs. OTRs (n = 35) with 572 AKs (grade I-III) in two similar areas on the face, scalp, dorsal hands or forearms were included. All patients received one MAL-PDT and one IMIQ session (three applications per week for 4 weeks) in each study area according to randomization. Treatments were repeated after 2 months (IMIQ) and 3 months (PDT) in skin with incomplete AK response. Outcome measures were complete lesion response (CR), skin reactions, laboratory results and treatment preference. The majority of study areas received two treatment sessions (PDT n = 25 patients; IMIQ n = 29 patients). At 3 months after two treatments, skin treated with PDT achieved a higher rate of CR (AK I-III median 78%; range 50-100) compared with IMIQ-treated skin areas (median 61%, range 33-100; P < 0·001). Fewer emergent AKs were seen in PDT-treated skin vs. IMIQ-treated skin (0·7 vs. 1·5 AKs, P = 0·04). Patients developed more intense inflammatory skin reactions following PDT, which resolved more rapidly compared with IMIQ (median 10 days vs. 18 days, P < 0·01). Patient preference (P = 0·47) and cosmesis (P > 0·30) were similar for PDT and IMIQ. Compared with IMIQ, PDT treatment obtained a higher rate of AK clearance at 3-month follow-up and achieved shorter-lasting, but more intense, short-term skin reactions. © 2017 British Association of Dermatologists.

Ingenol Mebutate for Recalcitrant Chronic Actinic Cheilitis.

PubMed

Tzika, Evangelia; Masouyé, Isabelle; Mühlstädt, Michael; Laffitte, Emmanuel

2016-01-01

We present the case of a healthy 76-year-old man with a whitish, hyperkeratotic lesion of the lower lip diagnosed as actinic cheilitis (AC) previously treated with classic red light photodynamic therapy 5 years ago. Initial treatment with 5% imiquimod cream - also with intensified application - failed. After 2 cycles thrice daily, consecutive applications of 150 μg/g ingenol mebutate gel at 3 weeks' interval, the lesions cleared completely. Surprisingly, no pustular or crusting reaction or other side effect occurred contrary to expectation. Remission was stable for 10 months, when recurrence occurred. Ingenol mebutate proved to be a feasible and safe treatment in this otherwise refractory case of AC. © 2016 S. Karger AG, Basel.

Technical advance: identification of plant actin-binding proteins by F-actin affinity chromatography

NASA Technical Reports Server (NTRS)

Hu, S.; Brady, S. R.; Kovar, D. R.; Staiger, C. J.; Clark, G. B.; Roux, S. J.; Muday, G. K.

2000-01-01

Proteins that interact with the actin cytoskeleton often modulate the dynamics or organization of the cytoskeleton or use the cytoskeleton to control their localization. In plants, very few actin-binding proteins have been identified and most are thought to modulate cytoskeleton function. To identify actin-binding proteins that are unique to plants, the development of new biochemical procedures will be critical. Affinity columns using actin monomers (globular actin, G-actin) or actin filaments (filamentous actin, F-actin) have been used to identify actin-binding proteins from a wide variety of organisms. Monomeric actin from zucchini (Cucurbita pepo L.) hypocotyl tissue was purified to electrophoretic homogeneity and shown to be native and competent for polymerization to actin filaments. G-actin, F-actin and bovine serum albumin affinity columns were prepared and used to separate samples enriched in either soluble or membrane-associated actin-binding proteins. Extracts of soluble actin-binding proteins yield distinct patterns when eluted from the G-actin and F-actin columns, respectively, leading to the identification of a putative F-actin-binding protein of approximately 40 kDa. When plasma membrane-associated proteins were applied to these columns, two abundant polypeptides eluted selectively from the F-actin column and cross-reacted with antiserum against pea annexins. Additionally, a protein that binds auxin transport inhibitors, the naphthylphthalamic acid binding protein, which has been previously suggested to associate with the actin cytoskeleton, was eluted in a single peak from the F-actin column. These experiments provide a new approach that may help to identify novel actin-binding proteins from plants.

Technical advance: identification of plant actin-binding proteins by F-actin affinity chromatography.

PubMed

Hu, S; Brady, S R; Kovar, D R; Staiger, C J; Clark, G B; Roux, S J; Muday, G K

2000-10-01

Proteins that interact with the actin cytoskeleton often modulate the dynamics or organization of the cytoskeleton or use the cytoskeleton to control their localization. In plants, very few actin-binding proteins have been identified and most are thought to modulate cytoskeleton function. To identify actin-binding proteins that are unique to plants, the development of new biochemical procedures will be critical. Affinity columns using actin monomers (globular actin, G-actin) or actin filaments (filamentous actin, F-actin) have been used to identify actin-binding proteins from a wide variety of organisms. Monomeric actin from zucchini (Cucurbita pepo L.) hypocotyl tissue was purified to electrophoretic homogeneity and shown to be native and competent for polymerization to actin filaments. G-actin, F-actin and bovine serum albumin affinity columns were prepared and used to separate samples enriched in either soluble or membrane-associated actin-binding proteins. Extracts of soluble actin-binding proteins yield distinct patterns when eluted from the G-actin and F-actin columns, respectively, leading to the identification of a putative F-actin-binding protein of approximately 40 kDa. When plasma membrane-associated proteins were applied to these columns, two abundant polypeptides eluted selectively from the F-actin column and cross-reacted with antiserum against pea annexins. Additionally, a protein that binds auxin transport inhibitors, the naphthylphthalamic acid binding protein, which has been previously suggested to associate with the actin cytoskeleton, was eluted in a single peak from the F-actin column. These experiments provide a new approach that may help to identify novel actin-binding proteins from plants.

Skin microrelief as a diagnostic tool (Conference Presentation)

NASA Astrophysics Data System (ADS)

Tchvialeva, Lioudmila; Phillips, Jamie; Zeng, Haishan; McLean, David; Lui, Harvey; Lee, Tim K.

2017-02-01

Skin surface roughness is an important property for differentiating skin diseases. Recently, roughness has also been identified as a potential diagnostic indicator in the early detection of skin cancer. Objective quantification is usually carried out by creating silicone replicas of the skin and then measuring the replicas. We have developed an alternative in-vivo technique to measure skin roughness based on laser speckle. Laser speckle is the interference pattern produced when coherent light is used to illuminate a rough surface and the backscattered light is imaged. Acquiring speckle contrast measurements from skin phantoms with controllable roughness, we created a calibration curve by linearly interpolating between measured points. This calibration curve accounts for internal scattering and is designed to evaluate skin microrelief whose root-mean-square roughness is in the range of 10-60 micrometers. To validate the effectiveness of our technique, we conducted a study to measure 243 skin lesions including actinic keratosis (8), basal cell carcinoma (24), malignant melanoma (31), nevus (73), squamous cell carcinoma (19), and seborrheic keratosis (79). The average roughness values ranged from 26 to 57 micrometers. Malignant melanoma was ranked as the smoothest and squamous cell carcinoma as the roughest lesion. An ANOVA test confirmed that malignant melanoma has significantly smaller roughness than other lesion types. Our results suggest that skin microrelief can be used to detect malignant melanoma from other skin conditions.

Steady-state nuclear actin levels are determined by export competent actin pool.

PubMed

Skarp, Kari-Pekka; Huet, Guillaume; Vartiainen, Maria K

2013-10-01

A number of studies in the last decade have irrevocably promoted actin into a fully fledged member of the nuclear compartment, where it, among other crucial tasks, facilitates transcription and chromatin remodeling. Changes in nuclear actin levels have been linked to different cellular processes: decreased nuclear actin to quiescence and increased nuclear actin to differentiation. Importin 9 and exportin 6 transport factors are responsible for the continuous nucleocytoplasmic shuttling of actin, but the mechanisms, which result in modulated actin levels, have not been characterized. We find that in cells growing under normal growth conditions, the levels of nuclear actin vary considerably from cell to cell. To understand the basis for this, we have extensively quantified several cellular parameters while at the same time recording the import and export rates of green fluorescent protein (GFP)-tagged actin. Surprisingly, our dataset shows that the ratio of nuclear to cytoplasmic fluorescence intensity, but not nuclear shape, size, cytoplasm size, or their ratio, correlates negatively with both import and export rate of actin. This suggests that high-nuclear actin content is maintained by both diminished import and export. The high nuclear actin containing cells still show high mobility of actin, but it is not export competent, suggesting increased binding of actin to nuclear complexes. Creation of such export incompetent actin pool would ensure enough actin is retained in the nucleus and make it available for the various nuclear functions described for actin. Copyright © 2013 Wiley Periodicals, Inc.

Lights, camera, actin.

PubMed

Rubenstein, Peter A; Wen, Kuo-Kuang

2005-10-01

Actin participates in many important biological processes. Currently, intensive investigation is being carried out in a number of laboratories concerning the function of actin in these processes and the molecular basis of its functions. We present a glimpse into four of these areas: actin-like proteins in bacterial cells, actin in the eukaryotic nucleus, the conformational plasticity of the actin filament, and finally, Arp2/3-dependent regulation of actin filament branching and creation of new filament barbed ends. IUBMB Life, 57: 683-687, 2005.

Treatment Options for Actinic Keratosis

MedlinePlus

... of skin biopsies: Shave biopsy : A sterile razor blade is used to “shave-off” the abnormal-looking ... the surface of the skin with a small blade. Electrodesiccation and curettage : The tumor is cut from ...

Actin-binding proteins sensitively mediate F-actin bundle stiffness

NASA Astrophysics Data System (ADS)

Claessens, Mireille M. A. E.; Bathe, Mark; Frey, Erwin; Bausch, Andreas R.

2006-09-01

Bundles of filamentous actin (F-actin) form primary structural components of a broad range of cytoskeletal processes including filopodia, sensory hair cell bristles and microvilli. Actin-binding proteins (ABPs) allow the cell to tailor the dimensions and mechanical properties of the bundles to suit specific biological functions. Therefore, it is important to obtain quantitative knowledge on the effect of ABPs on the mechanical properties of F-actin bundles. Here we measure the bending stiffness of F-actin bundles crosslinked by three ABPs that are ubiquitous in eukaryotes. We observe distinct regimes of bundle bending stiffness that differ by orders of magnitude depending on ABP type, concentration and bundle size. The behaviour observed experimentally is reproduced quantitatively by a molecular-based mechanical model in which ABP shearing competes with F-actin extension/compression. Our results shed new light on the biomechanical function of ABPs and demonstrate how single-molecule properties determine mesoscopic behaviour. The bending mechanics of F-actin fibre bundles are general and have implications for cytoskeletal mechanics and for the rational design of functional materials.

Clinical and Histopathological Investigation of Seborrheic Keratosis

PubMed Central

Roh, Nam Kyung; Hahn, Hyung Jin; Lee, Yang Won; Choe, Yong Beom

2016-01-01

Background Seborrheic keratosis (SK) is one of the most common epidermal tumors of the skin. However, only a few large-scale clinicohistopathological investigations have been conducted on SK or on the possible correlation between histopathological SK subtype and location. Objective The aim of this study was to analyze the clinical and histopathological features of a relatively large number of cases of diagnosed SK. Methods Two hundred and seventy-one pathology slides of skin tissue from patients with clinically diagnosed SK and 206 cases of biopsy-proven SK were analyzed. The biopsy-proven cases of SK were assessed for histopathological subclassification. The demographic, clinical, and histopathological data of the patients were collected for analysis of associated factors. Results The most frequent histopathological subtype was the acanthotic type, followed by mixed, hyperkeratotic, melanoacanthoma, clonal, irritated, and adenoid types; an unexpectedly high percentage (9.2%) of the melanoacanthoma variant was observed. The adenoid type was more common in sun-exposed sites than in sun-protected sites (p=0.028). Premalignant and malignant entities together represented almost one-quarter (24.2%) of the clinicopathological mismatch cases (i.e., mismatch between the clinical and histopathological diagnoses). Regarding the location of SK development, the frequency of mismatch for the sun-exposed areas was significantly higher than that for sun-protected areas (p=0.043). Conclusion The adenoid type was more common in sun-exposed sites. Biopsy sampling should be performed for lesions situated in sun-exposed areas to exclude other premalignant or malignant diseases. PMID:27081260

Nuclear Functions of Actin

PubMed Central

Visa, Neus; Percipalle, Piergiorgio

2010-01-01

Actin participates in several essential processes in the cell nucleus. Even though the presence of actin in the nucleus was proposed more than 30 years ago, nuclear processes that require actin have been only recently identified. Actin is part of chromatin remodeling complexes; it is associated with the transcription machineries; it becomes incorporated into newly synthesized ribonucleoproteins; and it influences long-range chromatin organization. As in the cytoplasm, nuclear actin works in conjunction with different types of actin-binding proteins that regulate actin function and bridge interactions between actin and other nuclear components. PMID:20452941

Oral mucosal lesions and risk habits among men in an Italian study population.

PubMed

Campisi, G; Margiotta, V

2001-01-01

A randomly selected study population of 118 male subjects (> or = 40 years) living on the Mediterranean island of Pantelleria (southwest of Sicily, Italy) was examined for the presence of oral mucosal lesions, with particular emphasis on the early diagnosis of oral precancerous and cancerous lesions. The study population was interviewed for socioeconomic and behavioural information, and clinically examined using WHO criteria. The prevalence of oral mucosal lesions observed, and data obtained about oral hygiene, tobacco smoking, alcohol drinking and exposure to actinic radiation, were analysed. Alcohol drinking was the most common habit in the study population (73%), followed by tobacco smoking (58.5%, of whom 96% were cigarette smokers). Only 3% showed good oral hygiene and 25% were edentate. Oral lesions were observed in 81.3% of the study group, mainly coated tongue (51.4%), leukoplakia (13.8%), traumatic oral lesions (traumatic ulcers and frictional white lesions) in 9.2%, actinic cheilitis (4.6%), and squamous cell carcinoma in one case (0.9%). Statistically significant associations were found between the prevalence of coated tongue and tobacco smoking (P<0.0001), and between the prevalence of actinic cheilitis and tobacco smoking/alcohol drinking (P<0.05). Analysis of clinical and anamnestic data underlined the effective presence, in the population examined, of the behavioural risk factors for oral precancerous and cancerous lesions, and the lack of cultural motivation towards primary prevention activities, such as the elimination of risk habits.

How actin network dynamics control the onset of actin-based motility

PubMed Central

Kawska, Agnieszka; Carvalho, Kévin; Manzi, John; Boujemaa-Paterski, Rajaa; Blanchoin, Laurent; Martiel, Jean-Louis; Sykes, Cécile

2012-01-01

Cells use their dynamic actin network to control their mechanics and motility. These networks are made of branched actin filaments generated by the Arp2/3 complex. Here we study under which conditions the microscopic organization of branched actin networks builds up a sufficient stress to trigger sustained motility. In our experimental setup, dynamic actin networks or “gels” are grown on a hard bead in a controlled minimal protein system containing actin monomers, profilin, the Arp2/3 complex and capping protein. We vary protein concentrations and follow experimentally and through simulations the shape and mechanical properties of the actin gel growing around beads. Actin gel morphology is controlled by elementary steps including “primer” contact, growth of the network, entanglement, mechanical interaction and force production. We show that varying the biochemical orchestration of these steps can lead to the loss of network cohesion and the lack of effective force production. We propose a predictive phase diagram of actin gel fate as a function of protein concentrations. This work unveils how, in growing actin networks, a tight biochemical and physical coupling smoothens initial primer-caused heterogeneities and governs force buildup and cell motility. PMID:22908255

Resemblance of actin-binding protein/actin gels to covalently crosslinked networks

NASA Astrophysics Data System (ADS)

Janmey, Paul A.; Hvidt, Søren; Lamb, Jennifer; Stossel, Thomas P.

1990-05-01

THE maintainance of the shape of cells is often due to their surface elasticity, which arises mainly from an actin-rich cytoplasmic cortex1,2. On locomotion, phagocytosis or fission, however, these cells become partially fluid-like. The finding of proteins that can bind to actin and control the assembly of, or crosslink, actin filaments, and of intracellular messages that regulate the activities of some of these actin-binding proteins, indicates that such 'gel sol' transformations result from the rearrangement of cortical actin-rich networks3. Alternatively, on the basis of a study of the mechanical properties of mixtures of actin filaments and an Acanthamoeba actin-binding protein, α-actinin, it has been proposed that these transformations can be accounted for by rapid exchange of crosslinks between actin filaments4: the cortical network would be solid when the deformation rate is greater than the rate of crosslink exchange, but would deform or 'creep' when deformation is slow enough to permit crosslinker molecules to rearrange. Here we report, however, that mixtures of actin filaments and actin-binding protein (ABP), an actin crosslinking protein of many higher eukaryotes, form gels Theologically equivalent to covalently crosslinked networks. These gels do not creep in response to applied stress on a time scale compatible with most cell-surface movements. These findings support a more complex and controlled mechanism underlying the dynamic mechanical properties of cortical cytoplasm, and can explain why cells do not collapse under the constant shear forces that often exist in tissues.

[UV-irradiation-induced skin cancer as a new occupational disease].

PubMed

Diepgen, T L; Drexler, H; Elsner, P; Schmitt, J

2015-03-01

With the revision of the German Ordinance on Occupational Diseases, skin cancer due to UV irradiation was amended as a new occupational disease to the list of occupational diseases in Germany. The new occupational disease BK 5103 has the following wording: "Squamous cell carcinoma or multiple actinic keratosis of the skin caused by natural UV irradiation". Actinic keratoses are to be considered as multiple according to this new occupational diseases if they occur as single lesions of more than five annually, or are confluent in an area > 4 cm(2) (field cancerization). It is estimated that more than 2.5 million employees are exposed to natural UV irradiation due to their work (outdoor workers) in Germany and therefore have an increased risk of skin cancer. In this article the medical and technical prerequisites which have to be fulfilled for this new occupational disease in Germany are introduced.

Sebaceous Gland, Hair Shaft, and Epidermal Barrier Abnormalities in Keratosis Pilaris with and without Filaggrin Deficiency

PubMed Central

Gruber, Robert; Sugarman, Jeffrey L.; Crumrine, Debra; Hupe, Melanie; Mauro, Theodora M.; Mauldin, Elizabeth A.; Thyssen, Jacob P.; Brandner, Johanna M.; Hennies, Hans-Christian; Schmuth, Matthias; Elias, Peter M.

2016-01-01

Although keratosis pilaris (KP) is common, its etiopathogenesis remains unknown. KP is associated clinically with ichthyosis vulgaris and atopic dermatitis and molecular genetically with filaggrin-null mutations. In 20 KP patients and 20 matched controls, we assessed the filaggrin and claudin 1 genotypes, the phenotypes by dermatoscopy, and the morphology by light and transmission electron microscopy. Thirty-five percent of KP patients displayed filaggrin mutations, demonstrating that filaggrin mutations only partially account for the KP phenotype. Major histologic and dermatoscopic findings of KP were hyperkeratosis, hypergranulosis, mild T helper cell type 1-dominant lymphocytic inflammation, plugging of follicular orifices, striking absence of sebaceous glands, and hair shaft abnormalities in KP lesions but not in unaffected skin sites. Changes in barrier function and abnormal paracellular permeability were found in both interfollicular and follicular stratum corneum of lesional KP, which correlated ultrastructurally with impaired extracellular lamellar bilayer maturation and organization. All these features were independent of filaggrin genotype. Moreover, ultrastructure of corneodesmosomes and tight junctions appeared normal, immunohistochemistry for claudin 1 showed no reduction in protein amounts, and molecular analysis of claudin 1 was unremarkable. Our findings suggest that absence of sebaceous glands is an early step in KP pathogenesis, resulting in downstream hair shaft and epithelial barrier abnormalities. PMID:25660180

A Case of Lymphomatoid Keratosis

PubMed Central

Choi, Min Jee; Kim, Hei Sung; Kim, Hyung Ok; Song, Kye Yong

2010-01-01

Lymphomatoid keratosis (LK) is considered to be a rare variant of cutaneous lymphoid hyperplasia, with epidermotropism. We herein report a case of LK which developed on the abdomen of an elderly Korean woman. A 60-year-old woman presented with a 10-year history of a pruritic, solitary, brown to black plaque on the abdomen. Histopathologically, the specimen showed hyperkeratosis, parakeratosis, acanthosis and Pautrier's micro-abscess in the epidermis, and a lichenoid infiltration of lymphocytes in the dermis, which expressed both B cell and T cell lineage on the immune-histochemical staining. Based on these clinical and histopathological findings, our case was diagnosed as LK. To our knowledge, this is the first case report of LK in the Korean dermatologic literature. PMID:20548920

F-actin and G-actin binding are uncoupled by mutation of conserved tyrosine residues in maize actin depolymerizing factor (ZmADF)

PubMed Central

Jiang, Chang-Jie; Weeds, Alan G.; Khan, Safina; Hussey, Patrick J.

1997-01-01

Actin depolymerizing factors (ADF) are stimulus responsive actin cytoskeleton modulating proteins. They bind both monomeric actin (G-actin) and filamentous actin (F-actin) and, under certain conditions, F-actin binding is followed by filament severing. In this paper, using mutant maize ADF3 proteins, we demonstrate that the maize ADF3 binding of F-actin can be spatially distinguished from that of G-actin. One mutant, zmadf3–1, in which Tyr-103 and Ala-104 (equivalent to destrin Tyr-117 and Ala-118) have been replaced by phenylalanine and glycine, respectively, binds more weakly to both G-actin and F-actin compared with maize ADF3. A second mutant, zmadf3–2, in which both Tyr-67 and Tyr-70 are replaced by phenylalanine, shows an affinity for G-actin similar to maize ADF3, but F-actin binding is abolished. The two tyrosines, Tyr-67 and Tyr-70, are in the equivalent position to Tyr-82 and Tyr-85 of destrin, respectively. Using the tertiary structure of destrin, yeast cofilin, and Acanthamoeba actophorin, we discuss the implications of removing the aromatic hydroxyls of Tyr-82 and Tyr-85 (i.e., the effect of substituting phenylalanine for tyrosine) and conclude that Tyr-82 plays a critical role in stabilizing the tertiary structure that is essential for F-actin binding. We propose that this tertiary structure is maintained as a result of a hydrogen bond between the hydroxyl of Tyr-82 and the carbonyl of Tyr-117, which is located in the long α-helix; amino acid components of this helix (Leu-111 to Phe-128) have been implicated in G-actin and F-actin binding. The structures of human destrin and yeast cofilin indicate a hydrogen distance of 2.61 and 2.77 Å, respectively, with corresponding bond angles of 99.5° and 113°, close to the optimum for a strong hydrogen bond. PMID:9275236

Intracapsular tonsillectomy for keratosis pharyngeous: A pilot study of postoperative recovery and surgical efficacy.

PubMed

Gaudreau, Philip A; Gessler, Eric M

2017-09-01

Our objective was to perform a pilot study comparing intracapsular radiofrequency ablation tonsillectomy with subcapsular tonsillectomy in adult patients with keratosis pharyngeous. Patients diagnosed with keratosis pharyngeous between December 2010 and February 2013 were randomized to undergo either intracapsular or subcapsular tonsillectomy using radiofrequency ablation. Postoperative pain scores and amount of pain medication taken were recorded for 2 weeks. A 6-month follow-up questionnaire was used to assess efficacy of the procedure. Twenty-two patients completed the initial 2-week questionnaire. Eighteen completed the 6-month follow-up questionnaire. The amount of pain medication consumed on postoperative days 8 (p = 0.0293), 9 (p = 0.0146), and 10 (p = 0.035) was significantly less in the intracapsular group. Risk of recurrence of tonsilloliths was significantly greater at the 6-month follow-up in the intracapsular cohort (p = 0.0291). Based on these findings, in patients undergoing tonsillectomy for keratosis pharyngeous, intracapsular radiofrequency ablation tonsillectomy may result in decreased pain medication consumption compared with subcapsular tonsillectomy. Intracapsular tonsillectomy, however, resulted in a higher rate of recurrence of tonsilloliths. The benefit of decreased pain medication may be offset by the greater likelihood for symptoms to recur. Larger studies are needed to confirm these findings.

Actin turnover maintains actin filament homeostasis during cytokinetic ring contraction

PubMed Central

Palani, Saravanan; Sommese, Ruth; Kamnev, Anton; Hatano, Tomoyuki; Sivaramakrishnan, Sivaraj

2017-01-01

Cytokinesis in many eukaryotes involves a tension-generating actomyosin-based contractile ring. Many components of actomyosin rings turn over during contraction, although the significance of this turnover has remained enigmatic. Here, using Schizosaccharomyces japonicus, we investigate the role of turnover of actin and myosin II in its contraction. Actomyosin ring components self-organize into ∼1-µm-spaced clusters instead of undergoing full-ring contraction in the absence of continuous actin polymerization. This effect is reversed when actin filaments are stabilized. We tested the idea that the function of turnover is to ensure actin filament homeostasis in a synthetic system, in which we abolished turnover by fixing rings in cell ghosts with formaldehyde. We found that these rings contracted fully upon exogenous addition of a vertebrate myosin. We conclude that actin turnover is required to maintain actin filament homeostasis during ring contraction and that the requirement for turnover can be bypassed if homeostasis is achieved artificially. PMID:28655757

p53 AND MDM2 PROTEIN EXPRESSION IN ACTINIC CHEILITIS

PubMed Central

de Freitas, Maria da Conceição Andrade; Ramalho, Luciana Maria Pedreira; Xavier, Flávia Caló Aquino; Moreira, André Luis Gomes; Reis, Sílvia Regina Almeida

2008-01-01

Actinic cheilitis is a potentially malignant lip lesion caused by excessive and prolonged exposure to ultraviolet radiation, which can lead to histomorphological alterations indicative of abnormal cell differentiation. In this pathology, varying degrees of epithelial dysplasia may be found. There are few published studies regarding the p53 and MDM2 proteins in actinic cheilitis. Fifty-eight cases diagnosed with actinic cheilitis were histologically evaluated using Banóczy and Csiba (1976) parameters, and were subjected to immunohistochemical analysis using the streptavidin-biotin method in order to assess p53 and MDM2 protein expression. All studied cases expressed p53 proteins in basal and suprabasal layers. In the basal layer, the nuclei testing positive for p53 were stained intensely, while in the suprabasal layer, cells with slightly stained nuclei were predominant. All cases also tested positive for the MDM2 protein, but with varying degrees of nuclear expression and a predominance of slightly stained cells. A statistically significant correlation between the percentage of p53 and MDM2-positive cells was established, regardless of the degree of epithelial dysplasia. The expression of p53 and MDM2 proteins in actinic cheilitis can be an important indicator in lip carcinogenesis, regardless of the degree of epithelial dysplasia. PMID:19082401

p53 and MDM2 protein expression in actinic cheilitis.

PubMed

de Freitas, Maria da Conceição Andrade; Ramalho, Luciana Maria Pedreira; Xavier, Flávia Caló Aquino; Moreira, André Luis Gomes; Reis, Sílvia Regina Almeida

2008-01-01

Actinic cheilitis is a potentially malignant lip lesion caused by excessive and prolonged exposure to ultraviolet radiation, which can lead to histomorphological alterations indicative of abnormal cell differentiation. In this pathology, varying degrees of epithelial dysplasia may be found. There are few published studies regarding the p53 and MDM2 proteins in actinic cheilitis. Fifty-eight cases diagnosed with actinic cheilitis were histologically evaluated using Banóczy and Csiba (1976) parameters, and were subjected to immunohistochemical analysis using the streptavidin-biotin method in order to assess p53 and MDM2 protein expression. All studied cases expressed p53 proteins in basal and suprabasal layers. In the basal layer, the nuclei testing positive for p53 were stained intensely, while in the suprabasal layer, cells with slightly stained nuclei were predominant. All cases also tested positive for the MDM2 protein, but with varying degrees of nuclear expression and a predominance of slightly stained cells. A statistically significant correlation between the percentage of p53 and MDM2-positive cells was established, regardless of the degree of epithelial dysplasia. The expression of p53 and MDM2 proteins in actinic cheilitis can be an important indicator in lip carcinogenesis, regardless of the degree of epithelial dysplasia.

Synthetic peptides that cause F-actin bundling and block actin depolymerization

DOEpatents

Sederoff, Heike [Raleigh, NC; Huber, Steven C [Savoy, IL; Larabell, Carolyn A [Berkeley, CA

2011-10-18

Synthetic peptides derived from sucrose synthase, and having homology to actin and actin-related proteins, sharing a common motif, useful for causing acting bundling and preventing actin depolymerization. Peptides exhibiting the common motif are described, as well as specific synthetic peptides which caused bundled actin and inhibit actin depolymerization. These peptides can be useful for treating a subject suffering from a disease characterized by cells having neoplastic growth, for anti-cancer therapeutics, delivered to subjects solely, or concomitantly or sequentially with other known cancer therapeutics. These peptides can also be used for stabilizing microfilaments in living cells and inhibiting growth of cells.

Clinical study of noninvasive in vivo melanoma and nonmelanoma skin cancers using multimodal spectral diagnosis

PubMed Central

Lim, Liang; Nichols, Brandon; Migden, Michael R.; Rajaram, Narasimhan; Reichenberg, Jason S.; Markey, Mia K.; Ross, Merrick I.; Tunnell, James W.

2014-01-01

Abstract. The goal of this study was to determine the diagnostic capability of a multimodal spectral diagnosis (SD) for in vivo noninvasive disease diagnosis of melanoma and nonmelanoma skin cancers. We acquired reflectance, fluorescence, and Raman spectra from 137 lesions in 76 patients using custom-built optical fiber-based clinical systems. Biopsies of lesions were classified using standard histopathology as malignant melanoma (MM), nonmelanoma pigmented lesion (PL), basal cell carcinoma (BCC), actinic keratosis (AK), and squamous cell carcinoma (SCC). Spectral data were analyzed using principal component analysis. Using multiple diagnostically relevant principal components, we built leave-one-out logistic regression classifiers. Classification results were compared with histopathology of the lesion. Sensitivity/specificity for classifying MM versus PL (12 versus 17 lesions) was 100%/100%, for SCC and BCC versus AK (57 versus 14 lesions) was 95%/71%, and for AK and SCC and BCC versus normal skin (71 versus 71 lesions) was 90%/85%. The best classification for nonmelanoma skin cancers required multiple modalities; however, the best melanoma classification occurred with Raman spectroscopy alone. The high diagnostic accuracy for classifying both melanoma and nonmelanoma skin cancer lesions demonstrates the potential for SD as a clinical diagnostic device. PMID:25375350

Clinical study of noninvasive in vivo melanoma and nonmelanoma skin cancers using multimodal spectral diagnosis

NASA Astrophysics Data System (ADS)

Lim, Liang; Nichols, Brandon; Migden, Michael R.; Rajaram, Narasimhan; Reichenberg, Jason S.; Markey, Mia K.; Ross, Merrick I.; Tunnell, James W.

2014-11-01

The goal of this study was to determine the diagnostic capability of a multimodal spectral diagnosis (SD) for in vivo noninvasive disease diagnosis of melanoma and nonmelanoma skin cancers. We acquired reflectance, fluorescence, and Raman spectra from 137 lesions in 76 patients using custom-built optical fiber-based clinical systems. Biopsies of lesions were classified using standard histopathology as malignant melanoma (MM), nonmelanoma pigmented lesion (PL), basal cell carcinoma (BCC), actinic keratosis (AK), and squamous cell carcinoma (SCC). Spectral data were analyzed using principal component analysis. Using multiple diagnostically relevant principal components, we built leave-one-out logistic regression classifiers. Classification results were compared with histopathology of the lesion. Sensitivity/specificity for classifying MM versus PL (12 versus 17 lesions) was 100%;/100%;, for SCC and BCC versus AK (57 versus 14 lesions) was 95%;/71%, and for AK and SCC and BCC versus normal skin (71 versus 71 lesions) was 90%/85%. The best classification for nonmelanoma skin cancers required multiple modalities; however, the best melanoma classification occurred with Raman spectroscopy alone. The high diagnostic accuracy for classifying both melanoma and nonmelanoma skin cancer lesions demonstrates the potential for SD as a clinical diagnostic device.

Microscopy basics and the study of actin-actin-binding protein interactions.

PubMed

Thomasson, Maggie S; Macnaughtan, Megan A

2013-12-15

Actin is a multifunctional eukaryotic protein with a globular monomer form that polymerizes into a thin, linear microfilament in cells. Through interactions with various actin-binding proteins (ABPs), actin plays an active role in many cellular processes, such as cell motility and structure. Microscopy techniques are powerful tools for determining the role and mechanism of actin-ABP interactions in these processes. In this article, we describe the basic concepts of fluorescent speckle microscopy, total internal reflection fluorescence microscopy, atomic force microscopy, and cryoelectron microscopy and review recent studies that utilize these techniques to visualize the binding of actin with ABPs. Copyright © 2013 Elsevier Inc. All rights reserved.

Multimodal digital color imaging system for facial skin lesion analysis

NASA Astrophysics Data System (ADS)

Bae, Youngwoo; Lee, Youn-Heum; Jung, Byungjo

2008-02-01

In dermatology, various digital imaging modalities have been used as an important tool to quantitatively evaluate the treatment effect of skin lesions. Cross-polarization color image was used to evaluate skin chromophores (melanin and hemoglobin) information and parallel-polarization image to evaluate skin texture information. In addition, UV-A induced fluorescent image has been widely used to evaluate various skin conditions such as sebum, keratosis, sun damages, and vitiligo. In order to maximize the evaluation efficacy of various skin lesions, it is necessary to integrate various imaging modalities into an imaging system. In this study, we propose a multimodal digital color imaging system, which provides four different digital color images of standard color image, parallel and cross-polarization color image, and UV-A induced fluorescent color image. Herein, we describe the imaging system and present the examples of image analysis. By analyzing the color information and morphological features of facial skin lesions, we are able to comparably and simultaneously evaluate various skin lesions. In conclusion, we are sure that the multimodal color imaging system can be utilized as an important assistant tool in dermatology.

Molecular architecture of the Spire-actin nucleus and its implication for actin filament assembly.

PubMed

Sitar, Tomasz; Gallinger, Julia; Ducka, Anna M; Ikonen, Teemu P; Wohlhoefler, Michael; Schmoller, Kurt M; Bausch, Andreas R; Joel, Peteranne; Trybus, Kathleen M; Noegel, Angelika A; Schleicher, Michael; Huber, Robert; Holak, Tad A

2011-12-06

The Spire protein is a multifunctional regulator of actin assembly. We studied the structures and properties of Spire-actin complexes by X-ray scattering, X-ray crystallography, total internal reflection fluorescence microscopy, and actin polymerization assays. We show that Spire-actin complexes in solution assume a unique, longitudinal-like shape, in which Wiskott-Aldrich syndrome protein homology 2 domains (WH2), in an extended configuration, line up actins along the long axis of the core of the Spire-actin particle. In the complex, the kinase noncatalytic C-lobe domain is positioned at the side of the first N-terminal Spire-actin module. In addition, we find that preformed, isolated Spire-actin complexes are very efficient nucleators of polymerization and afterward dissociate from the growing filament. However, under certain conditions, all Spire constructs--even a single WH2 repeat--sequester actin and disrupt existing filaments. This molecular and structural mechanism of actin polymerization by Spire should apply to other actin-binding proteins that contain WH2 domains in tandem.

Molecular architecture of the Spire–actin nucleus and its implication for actin filament assembly

PubMed Central

Sitar, Tomasz; Gallinger, Julia; Ducka, Anna M.; Ikonen, Teemu P.; Wohlhoefler, Michael; Schmoller, Kurt M.; Bausch, Andreas R.; Joel, Peteranne; Trybus, Kathleen M.; Noegel, Angelika A.; Schleicher, Michael; Huber, Robert; Holak, Tad A.

2011-01-01

The Spire protein is a multifunctional regulator of actin assembly. We studied the structures and properties of Spire–actin complexes by X-ray scattering, X-ray crystallography, total internal reflection fluorescence microscopy, and actin polymerization assays. We show that Spire–actin complexes in solution assume a unique, longitudinal-like shape, in which Wiskott–Aldrich syndrome protein homology 2 domains (WH2), in an extended configuration, line up actins along the long axis of the core of the Spire–actin particle. In the complex, the kinase noncatalytic C-lobe domain is positioned at the side of the first N-terminal Spire–actin module. In addition, we find that preformed, isolated Spire–actin complexes are very efficient nucleators of polymerization and afterward dissociate from the growing filament. However, under certain conditions, all Spire constructs—even a single WH2 repeat—sequester actin and disrupt existing filaments. This molecular and structural mechanism of actin polymerization by Spire should apply to other actin-binding proteins that contain WH2 domains in tandem. PMID:22106272

Photodynamic therapy for actinic cheilitis: a systematic review.

PubMed

Yazdani Abyaneh, Mohammad-Ali; Falto-Aizpurua, Leyre; Griffith, Robert D; Nouri, Keyvan

2015-02-01

Actinic cheilitis (AC) is a premalignant lesion of the lips that can progress to squamous cell carcinoma and metastasize. Actinic cheilitis is difficult to treat because surgical treatments have significant adverse effects whereas less invasive procedures have uncertain efficacy. Photodynamic therapy (PDT) may offer a noninvasive yet effective treatment option for AC. To systematically review the safety and efficacy of PDT for AC. The terms "photodynamic," "actinic," "solar," "cheilitis," and "cheilosis" were used in combinations to search the PubMed database. Studies were considered for inclusion based on eligibility criteria, and specific data were extracted from all studies. The authors identified 15 eligible case series encompassing a total of 242 treated subjects. Among studies that evaluated subjects for complete clinical response, 139 of 223 subjects (62%) showed complete response at final follow-ups ranging from 3 to 30 months. Among studies that evaluated subjects for histological outcome, 57 of 121 subjects (47%) demonstrated histological cure at final follow-ups ranging from 1.5 to 18 months. Cosmetic outcomes were good to excellent in the majority of subjects, and adverse events were well tolerated. Photodynamic therapy is safe and has the potential to clinically and histologically treat AC, with a need for future randomized controlled trials.

Cofilin Changes the Twist of F-Actin: Implications for Actin Filament Dynamics and Cellular Function

PubMed Central

McGough, Amy; Pope, Brian; Chiu, Wah; Weeds, Alan

1997-01-01

Cofilin is an actin depolymerizing protein found widely distributed in animals and plants. We have used electron cryomicroscopy and helical reconstruction to identify its binding site on actin filaments. Cofilin binds filamentous (F)-actin cooperatively by bridging two longitudinally associated actin subunits. The binding site is centered axially at subdomain 2 of the lower actin subunit and radially at the cleft between subdomains 1 and 3 of the upper actin subunit. Our work has revealed a totally unexpected (and unique) property of cofilin, namely, its ability to change filament twist. As a consequence of this change in twist, filaments decorated with cofilin have much shorter ‘actin crossovers' (∼75% of those normally observed in F-actin structures). Although their binding sites are distinct, cofilin and phalloidin do not bind simultaneously to F-actin. This is the first demonstration of a protein that excludes another actin-binding molecule by changing filament twist. Alteration of F-actin structure by cofilin/ADF appears to be a novel mechanism through which the actin cytoskeleton may be regulated or remodeled. PMID:9265645

Actin-interacting Protein 1 Promotes Disassembly of Actin-depolymerizing Factor/Cofilin-bound Actin Filaments in a pH-dependent Manner.

PubMed

Nomura, Kazumi; Hayakawa, Kimihide; Tatsumi, Hitoshi; Ono, Shoichiro

2016-03-04

Actin-interacting protein 1 (AIP1) is a conserved WD repeat protein that promotes disassembly of actin filaments when actin-depolymerizing factor (ADF)/cofilin is present. Although AIP1 is known to be essential for a number of cellular events involving dynamic rearrangement of the actin cytoskeleton, the regulatory mechanism of the function of AIP1 is unknown. In this study, we report that two AIP1 isoforms from the nematode Caenorhabditis elegans, known as UNC-78 and AIPL-1, are pH-sensitive in enhancement of actin filament disassembly. Both AIP1 isoforms only weakly enhance disassembly of ADF/cofilin-bound actin filaments at an acidic pH but show stronger disassembly activity at neutral and basic pH values. However, a severing-defective mutant of UNC-78 shows pH-insensitive binding to ADF/cofilin-decorated actin filaments, suggesting that the process of filament severing or disassembly, but not filament binding, is pH-dependent. His-60 of AIP1 is located near the predicted binding surface for the ADF/cofilin-actin complex, and an H60K mutation of AIP1 partially impairs its pH sensitivity, suggesting that His-60 is involved in the pH sensor for AIP1. These biochemical results suggest that pH-dependent changes in AIP1 activity might be a novel regulatory mechanism of actin filament dynamics. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Torsional Rigidity of Single Actin Filaments and Actin-Actin Bond Breaking Force under Torsion Measured Directly by in vitro Micromanipulation

NASA Astrophysics Data System (ADS)

Tsuda, Yuri; Yasutake, Hironori; Ishijima, Akihiko; Yanagida, Toshio

1996-11-01

Knowledge of the elastic properties of actin filaments is crucial for considering its role in muscle contraction, cellular motile events, and formation of cell shape. The stiffness of actin filaments in the directions of stretching and bending has been determined. In this study, we have directly determined the torsional rigidity and breaking force of single actin filaments by measuring the rotational Brownian motion and tensile strength using optical tweezers and microneedles, respectively. Rotational angular fluctuations of filaments supplied the torsional rigidity as (8.0 ± 1.2) × 10-26 Nm2. This value is similar to that deduced from the longitudinal rigidity, assuming the actin filament to be a homogeneous rod. The breaking force of the actin-actin bond was measured while twisting a filament through various angles using microneedles. The breaking force decreased greatly under twist, e.g., from 600-320 pN when filaments were turned through 90 degrees, independent of the rotational direction. Our results indicate that an actin filament exhibits comparable flexibility in the rotational and longitudinal directions, but breaks more easily under torsional load.

[Keratosis palmoplantaris maculosa seu papulosa (Davies-Colley) simulating multiple cornua cutanea].

PubMed

Schreiber, D; Stücker, M; Hoffmann, K; Bacharach-Buhles, M; Altmeyer, P

1997-08-01

Patient with extensive keratosis palmoplantaris maculosa seu papulosa (Davies-Colley) presented with multiple cutaneous horns. The clinical picture, the histology, the electro microscopic examination, the negative tumor screening and the viral classification in the tissue allowed the differentiation from other palmoplantar keratoses. The patient was treated successfully using a combination of acitretin with physical and chemical measures.

Actinic cheilitis and squamous cell carcinoma of the lip: clinical, histopathological and immunogenetic aspects.

PubMed

Vieira, Renata Aparecida Martinez Antunes Ribeiro; Minicucci, Eliana Maria; Marques, Mariangela Esther Alencar; Marques, Silvio Alencar

2012-01-01

Actinic cheilitis is the main precancerous lesion of the lip. Squamous cell carcinoma of the lip is reported together with oral carcinomas in the Brazilian official statistics. Overall, they account for 40% of the head and neck carcinomas. In general, physicians and dentists know little about what causes oral tumor development and progression. Tumor suppressor genes and cell proliferation regulatory proteins play a role in the progression of actinic cheilitis to squamous cell carcinoma and in its biological behavior. Knowledge on prognostic and diagnostic markers has a positive impact on the follow-up of these patients.

A case report of disappearing pigmented skin lesions associated with pembrolizumab treatment for metastatic melanoma.

PubMed

Wolner, Z J; Marghoob, A A; Pulitzer, M P; Postow, M A; Marchetti, M A

2018-01-01

Pembrolizumab is an immune checkpoint inhibitor that targets the programmed cell death (PD)-1 receptor. Common cutaneous adverse side-effects of PD-1 inhibitors include maculopapular rash, pruritus, vitiligo and lichenoid skin and mucosal reactions. Here we describe a man in his sixties with metastatic melanoma treated with pembrolizumab who subsequently developed fading or disappearance of pigmented skin lesions, lightening of the skin, and poliosis of the eyebrows, eyelashes and scalp and body hair. Compared with baseline high-resolution three-dimensional total-body photography, we observed fading or disappearance of solar lentigines, seborrhoeic keratoses and melanocytic naevi, suggesting that PD-1 inhibitors may affect the evolution of these benign skin lesions. With dermatoscopic follow-up, altered lesions showed either blue-grey peppering/granularity or fading in colour without other identifiable features. No halo lesions or lesions with surrounding inflammation were identified. One changed pigmented lesion that showed blue-grey peppering/granularity on dermoscopy was biopsied and interpreted as a macular seborrhoeic keratosis with melanophages. Further studies are required to elucidate the effects of PD-1 inhibition on benign skin lesions. © 2017 British Association of Dermatologists.

Myopodin is an F-actin bundling protein with multiple independent actin-binding regions.

PubMed

Linnemann, Anja; Vakeel, Padmanabhan; Bezerra, Eduardo; Orfanos, Zacharias; Djinović-Carugo, Kristina; van der Ven, Peter F M; Kirfel, Gregor; Fürst, Dieter O

2013-02-01

The assembly of striated muscle myofibrils is a multistep process in which a variety of proteins is involved. One of the first and most important steps in myofibrillogenesis is the arrangement of thin myofilaments into ordered I-Z-I brushes, requiring the coordinated activity of numerous actin binding proteins. The early expression of myopodin prior to sarcomeric α-actinin, as well as its binding to actin, α-actinin and filamin indicate an important role for this protein in actin cytoskeleton remodelling with the precise function of myopodin in this process yet remaining to be resolved. While myopodin was previously described as a protein capable of cross-linking actin filaments into thick bundles upon transient transfections, it has remained unclear whether myopodin alone is capable of bundling actin, or if additional proteins are involved. We have therefore investigated the in vitro actin binding properties of myopodin. High speed cosedimentation assays with skeletal muscle actin confirmed direct binding of myopodin to F-actin and showed that this interaction is mediated by at least two independent actin binding sites, found in all myopodin isoforms identified to date. Furthermore, low-speed cosedimentation assays revealed that not only full length myopodin, but also the fragment containing only the second binding site, bundles microfilaments in the absence of accessory proteins. Ultrastructural analysis demonstrated that this bundling activity resembled that of α-actinin. Biochemical experiments revealed that bundling was not achieved by myopodin's ability to dimerize, indicating the presence of two individual F-actin binding sites within the second binding segment. Thus full length myopodin contains at least three F-actin binding sites. These data provide further understanding of the mechanisms by which myopodin contributes to actin reorganization during myofibril assembly.

Oral mucosal lesions and their association with sociodemographic, behavioral, and health status factors.

PubMed

Gheno, José Nicolau; Martins, Marco Antonio Trevizani; Munerato, Maria Cristina; Hugo, Fernando Neves; Sant'ana Filho, Manoel; Weissheimer, Camila; Carrard, Vinicius Coelho; Martins, Manoela Domingues

2015-01-01

The aim of this study was to evaluate the frequency of oral mucosal lesions and their associations with sociodemographic, health, and behavioral factors in a southern Brazilian population. Information was collected from participants (n = 801) using a structured questionnaire during an oral cancer screening campaign held at an agribusiness show in southern Brazil in 2009. Data were described using frequency distributions or means and standard deviations. Associations between independent variables and outcomes were assessed using the Chi-squared test. A total of 465 lesions were detected (actinic cheilitis: n = 204, 25.5%; candidiasis: n = 50, 6.2%; fibrous inflammatory hyperplasia: n = 42, 5.2%; ulceration, n = 33, 4.1%; hemangioma: n = 14, 1.7%; leukoplakia: n = 11, 1.4%). Candidiasis, actinic cheilitis, and fibrous inflammatory hyperplasia were associated significantly with literacy. Actinic cheilitis was also associated significantly with sun exposure and hat use, and leukoplakia was associated with smoking. The high frequency of oral mucosal lesions observed highlights the importance of education about risk factors. Additionally, training of health professionals, mainly those from public health services, in the use of preventive and community education strategies is needed.

Nucleation of actin polymerization by gelsolin.

PubMed

Ditsch, A; Wegner, A

1994-08-15

The time-course of assembly of actin with gelsolin was measured by the fluorescence increase of a fluorescent label covalently linked to actin. The actin concentrations ranged from values far below the critical concentration to values above the critical concentration of the pointed ends of actin filaments. If the concentration of actin was in the range of the critical monomer concentration (0.64 microM), the time-course of the concentration of actin assembled with gelsolin revealed a sigmoidal shape. At higher actin concentrations the time-course of association of actin with gelsolin approximated an exponential curve. The measured time-courses of assembly were quantitatively interpreted by kinetic rate equations. A poor fit was obtained if two actin molecules were assumed to bind to gelsolin to form a 1:2 gelsolin-actin complex and subsequently further actin molecules were assumed to polymerize onto the 1:2 gelsolin-actin complex toward the pointed end. A considerably better agreement between calculated and measured time-courses was achieved if additional creation of actin filaments by fast fragmentation of newly formed actin filaments by not yet consumed gelsolin was assumed to occur. This suggests that both polymerization of actin onto gelsolin and fragmentation of actin filaments contribute to formation of new actin filaments by gelsolin. Furthermore it could be demonstrated that below the critical monomer concentration appreciable amounts of actin are incorporated into gelsolin-actin oligomers.

Tumor-Preferential Induction of Immune Responses and Epidermal Cell Death in Actinic Keratoses by Ingenol Mebutate

PubMed Central

Zibert, John R.; Schön, Margarete; Hald, Andreas; Hansen, Maria H.; Litman, Thomas; Schön, Michael P.

2016-01-01

The rapid and strong clinical efficacy of the first-in-class, ingenol mebutate, against actinic keratosis (AK) has resulted in its recent approval. We conducted the first comprehensive analysis of the cellular and molecular mode of action of topical ingenol mebutate 0.05% gel in both AK and uninvolved skin of 26 patients in a phase I, single-center, open-label, within-patient comparison. As early as 1 day after application, ingenol mebutate induced profound epidermal cell death, along with a strong infiltrate of CD4+ and CD8+ T-cells, neutrophils, and macrophages. Endothelial ICAM-1 activation became evident after 2 days. The reaction pattern was significantly more pronounced in AK compared with uninvolved skin, suggesting a tumor-preferential mode of action. Extensive molecular analyses and transcriptomic profiling of mRNAs and microRNAs demonstrated alterations in gene clusters functionally associated with epidermal development, inflammation, innate immunity, and response to wounding. Ingenol mebutate reveals a unique mode of action linking directly to anti-tumoral effects. Trial Registration: ClinicalTrials.gov NCT01387711 PMID:27612149

PI(3,5)P2 controls endosomal branched actin dynamics by regulating cortactin–actin interactions

PubMed Central

Hong, Nan Hyung; Qi, Aidong

2015-01-01

Branched actin critically contributes to membrane trafficking by regulating membrane curvature, dynamics, fission, and transport. However, how actin dynamics are controlled at membranes is poorly understood. Here, we identify the branched actin regulator cortactin as a direct binding partner of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) and demonstrate that their interaction promotes turnover of late endosomal actin. In vitro biochemical studies indicated that cortactin binds PI(3,5)P2 via its actin filament-binding region. Furthermore, PI(3,5)P2 competed with actin filaments for binding to cortactin, thereby antagonizing cortactin activity. These findings suggest that PI(3,5)P2 formation on endosomes may remove cortactin from endosome-associated branched actin. Indeed, inhibition of PI(3,5)P2 production led to cortactin accumulation and actin stabilization on Rab7+ endosomes. Conversely, inhibition of Arp2/3 complex activity greatly reduced cortactin localization to late endosomes. Knockdown of cortactin reversed PI(3,5)P2-inhibitor–induced actin accumulation and stabilization on endosomes. These data suggest a model in which PI(3,5)P2 binding removes cortactin from late endosomal branched actin networks and thereby promotes net actin turnover. PMID:26323691

Actin stress in cell reprogramming

PubMed Central

Guo, Jun; Wang, Yuexiu; Sachs, Frederick; Meng, Fanjie

2014-01-01

Cell mechanics plays a role in stem cell reprogramming and differentiation. To understand this process better, we created a genetically encoded optical probe, named actin–cpstFRET–actin (AcpA), to report forces in actin in living cells in real time. We showed that stemness was associated with increased force in actin. We reprogrammed HEK-293 cells into stem-like cells using no transcription factors but simply by softening the substrate. However, Madin-Darby canine kidney (MDCK) cell reprogramming required, in addition to a soft substrate, Harvey rat sarcoma viral oncogene homolog expression. Replating the stem-like cells on glass led to redifferentiation and reduced force in actin. The actin force probe was a FRET sensor, called cpstFRET (circularly permuted stretch sensitive FRET), flanked by g-actin subunits. The labeled actin expressed efficiently in HEK, MDCK, 3T3, and bovine aortic endothelial cells and in multiple stable cell lines created from those cells. The viability of the cell lines demonstrated that labeled actin did not significantly affect cell physiology. The labeled actin distribution was similar to that observed with GFP-tagged actin. We also examined the stress in the actin cross-linker actinin. Actinin force was not always correlated with actin force, emphasizing the need for addressing protein specificity when discussing forces. Because actin is a primary structural protein in animal cells, understanding its force distribution is central to understanding animal cell physiology and the many linked reactions such as stress-induced gene expression. This new probe permits measuring actin forces in a wide range of experiments on preparations ranging from isolated proteins to transgenic animals. PMID:25422450

Treatment of Actinic Purpura

PubMed Central

2017-01-01

Mature skin is prone to bruising, resulting in a condition known as actinic purpura, characterized by unsightly ecchymosis and purple patches. Similar to other skin conditions, the incidence of actinic purpura increases with advancing age and occurs with equal frequency among men and women. The unsightly appearance of actinic purpura may be a source of emotional distress among the elderly. A new product has been formulated specifically for the treatment of actinic purpura. This product contains retinol, α-hydroxy acids, arnica oil, ceramides, niacinamide, and phytonadione, which effectively treat actinic purpura by improving local circulation, thickening the skin, and repairing the skin barrier. The objective of this paper is to review the beneficial properties of these ingredients and their respective roles in the treatment of actinic purpura. PMID:28979656

Long-term Efficacy of Topical Fluorouracil Cream, 5%, for Treating Actinic Keratosis: A Randomized Clinical Trial.

PubMed

Pomerantz, Hyemin; Hogan, Daniel; Eilers, David; Swetter, Susan M; Chen, Suephy C; Jacob, Sharon E; Warshaw, Erin M; Stricklin, George; Dellavalle, Robert P; Sidhu-Malik, Navjeet; Konnikov, Nellie; Werth, Victoria P; Keri, Jonette; Lew, Robert; Weinstock, Martin A

2015-09-01

Topical fluorouracil was demonstrated to be effective in reducing the number of actinic keratoses (AKs) for up to 6 months, but no randomized trials studied its long-term efficacy. To evaluate the long-term efficacy of a single course of fluorouracil cream, 5%, for AK treatment. The Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) trial was a randomized, double-blinded, placebo-controlled trial with patients from dermatology clinics at 12 VA medical centers recruited from 2009 to 2011 and followed up until 2013. Our study population comprised 932 veterans with 2 or more keratinocyte carcinomas in the 5 years prior to enrollment. The mean follow-up duration was 2.6 years in both treatment and control groups. Participants applied either topical fluorouracil cream, 5% (n = 468), or vehicle control cream (n = 464) to the face and ears twice daily for up to 4 weeks. This study reports on AK counts and treatments, which were secondary outcomes of the VAKCC trial. Actinic keratoses on the face and ears were counted by study dermatologists at enrollment and at study visits every 6 months. The number of spot treatments for AKs on the face and ears at semiannual study visits and in between study visits was recorded. The number of AKs on the face and ears per participant was not different between the fluorouracil and control groups at randomization (11.1 vs 10.6, P > .10). After randomization, the fluorouracil group had fewer AKs compared with the control group at 6 months (3.0 vs 8.1, P < .001) and for the overall study duration (P < .001). The fluorouracil group also had higher complete AK clearance rates (38% vs 17% at 6 months) and fewer spot treatments at 6-month intervals, at study visits, and in between study visits during the trial (P < .01 for all). The fluorouracil group took longer to require the first spot AK treatment (6.2 months) compared with the control group (6.0 months) (hazard ratio, 0.69; 95% CI, 0.60-0.79). The

Actin assembly factors regulate the gelation kinetics and architecture of F-actin networks.

PubMed

Falzone, Tobias T; Oakes, Patrick W; Sees, Jennifer; Kovar, David R; Gardel, Margaret L

2013-04-16

Dynamic regulation of the actin cytoskeleton is required for diverse cellular processes. Proteins regulating the assembly kinetics of the cytoskeletal biopolymer F-actin are known to impact the architecture of actin cytoskeletal networks in vivo, but the underlying mechanisms are not well understood. Here, we demonstrate that changes to actin assembly kinetics with physiologically relevant proteins profilin and formin (mDia1 and Cdc12) have dramatic consequences on the architecture and gelation kinetics of otherwise biochemically identical cross-linked F-actin networks. Reduced F-actin nucleation rates promote the formation of a sparse network of thick bundles, whereas increased nucleation rates result in a denser network of thinner bundles. Changes to F-actin elongation rates also have marked consequences. At low elongation rates, gelation ceases and a solution of rigid bundles is formed. By contrast, rapid filament elongation accelerates dynamic arrest and promotes gelation with minimal F-actin density. These results are consistent with a recently developed model of how kinetic constraints regulate network architecture and underscore how molecular control of polymer assembly is exploited to modulate cytoskeletal architecture and material properties. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

The pros and cons of common actin labeling tools for visualizing actin dynamics during Drosophila oogenesis

PubMed Central

Spracklen, Andrew J.; Fagan, Tiffany N.; Lovander, Kaylee E.; Tootle, Tina L.

2015-01-01

Dynamic remodeling of the actin cytoskeleton is required for both development and tissue homeostasis. While fixed image analysis has provided significant insight into such events, a complete understanding of cytoskeletal dynamics requires live imaging. Numerous tools for the live imaging of actin have been generated by fusing the actin-binding domain from an actin-interacting protein to a fluorescent protein. Here we comparatively assess the utility of three such tools – Utrophin, Lifeact, and F-tractin – for characterizing the actin remodeling events occurring within the germline-derived nurse cells during Drosophila mid-oogenesis or follicle development. Specifically, we used the UAS/GAL4 system to express these tools at different levels and in different cells, and analyzed these tools for effects on fertility, alterations in the actin cytoskeleton, and ability to label filamentous actin (F-actin) structures by both fixed and live imaging. While both Utrophin and Lifeact robustly label F-actin structures within the Drosophila germline, when strongly expressed they cause sterility and severe actin defects including cortical actin breakdown resulting in multi-nucleate nurse cells, early F-actin filament and aggregate formation during stage 9 (S9), and disorganized parallel actin filament bundles during stage 10B (S10B). However, by using a weaker germline GAL4 driver in combination with a higher temperature, Utrophin can label F-actin with minimal defects. Additionally, strong Utrophin expression within the germline causes F-actin formation in the nurse cell nuclei and germinal vesicle during mid-oogenesis. Similarly, Lifeact expression results in nuclear F-actin only within the germinal vesicle. F-tractin expresses at a lower level than the other two labeling tools, but labels cytoplasmic F-actin structures well without causing sterility or striking actin defects. Together these studies reveal how critical it is to evaluate the utility of each actin labeling

The yeast actin cytoskeleton.

PubMed

Mishra, Mithilesh; Huang, Junqi; Balasubramanian, Mohan K

2014-03-01

The actin cytoskeleton is a complex network of dynamic polymers, which plays an important role in various fundamental cellular processes, including maintenance of cell shape, polarity, cell division, cell migration, endocytosis, vesicular trafficking, and mechanosensation. Precise spatiotemporal assembly and disassembly of actin structures is regulated by the coordinated activity of about 100 highly conserved accessory proteins, which nucleate, elongate, cross-link, and sever actin filaments. Both in vivo studies in a wide range of organisms from yeast to metazoans and in vitro studies of purified proteins have helped shape the current understanding of actin dynamics and function. Molecular genetics, genome-wide functional analysis, sophisticated real-time imaging, and ultrastructural studies in concert with biochemical analysis have made yeast an attractive model to understand the actin cytoskeleton, its molecular dynamics, and physiological function. Studies of the yeast actin cytoskeleton have contributed substantially in defining the universal mechanism regulating actin assembly and disassembly in eukaryotes. Here, we review some of the important insights generated by the study of actin cytoskeleton in two important yeast models the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Co-transcriptional nuclear actin dynamics

PubMed Central

Percipalle, Piergiorgio

2013-01-01

Actin is a key player for nuclear structure and function regulating both chromosome organization and gene activity. In the cell nucleus actin interacts with many different proteins. Among these proteins several studies have identified classical nuclear factors involved in chromatin structure and function, transcription and RNA processing as well as proteins that are normally involved in controlling the actin cytoskeleton. These discoveries have raised the possibility that nuclear actin performs its multi task activities through tight interactions with different sets of proteins. This high degree of promiscuity in the spectrum of protein-to-protein interactions correlates well with the conformational plasticity of actin and the ability to undergo regulated changes in its polymerization states. Several of the factors involved in controlling head-to-tail actin polymerization have been shown to be in the nucleus where they seem to regulate gene activity. By focusing on the multiple tasks performed by actin and actin-binding proteins, possible models of how actin dynamics controls the different phases of the RNA polymerase II transcription cycle are being identified. PMID:23138849

Adhesive F-actin Waves: A Novel Integrin-Mediated Adhesion Complex Coupled to Ventral Actin Polymerization

PubMed Central

Case, Lindsay B.; Waterman, Clare M.

2011-01-01

At the leading lamellipodium of migrating cells, protrusion of an Arp2/3-nucleated actin network is coupled to formation of integrin-based adhesions, suggesting that Arp2/3-mediated actin polymerization and integrin-dependent adhesion may be mechanistically linked. Arp2/3 also mediates actin polymerization in structures distinct from the lamellipodium, in “ventral F-actin waves” that propagate as spots and wavefronts along the ventral plasma membrane. Here we show that integrins engage the extracellular matrix downstream of ventral F-actin waves in several mammalian cell lines as well as in primary mouse embryonic fibroblasts. These “adhesive F-actin waves” require a cycle of integrin engagement and disengagement to the extracellular matrix for their formation and propagation, and exhibit morphometry and a hierarchical assembly and disassembly mechanism distinct from other integrin-containing structures. After Arp2/3-mediated actin polymerization, zyxin and VASP are co-recruited to adhesive F-actin waves, followed by paxillin and vinculin, and finally talin and integrin. Adhesive F-actin waves thus represent a previously uncharacterized integrin-based adhesion complex associated with Arp2/3-mediated actin polymerization. PMID:22069459

Filopodia-like Actin Cables Position Nuclei in Association with Perinuclear Actin in Drosophila Nurse Cells

PubMed Central

Huelsmann, Sven; Ylänne, Jari; Brown, Nicholas H.

2013-01-01

Summary Controlling the position of the nucleus is vital for a number of cellular processes from yeast to humans. In Drosophila nurse cells, nuclear positioning is crucial during dumping, when nurse cells contract and expel their contents into the oocyte. We provide evidence that in nurse cells, continuous filopodia-like actin cables, growing from the plasma membrane and extending to the nucleus, achieve nuclear positioning. These actin cables move nuclei away from ring canals. When nurse cells contract, actin cables associate laterally with the nuclei, in some cases inducing nuclear turning so that actin cables become partially wound around the nuclei. Our data suggest that a perinuclear actin meshwork connects actin cables to nuclei via actin-crosslinking proteins such as the filamin Cheerio. We provide a revised model for how actin structures position nuclei in nurse cells, employing evolutionary conserved machinery. PMID:24091012

Nucleus-associated actin in Amoeba proteus.

PubMed

Berdieva, Mariia; Bogolyubov, Dmitry; Podlipaeva, Yuliya; Goodkov, Andrew

2016-10-01

The presence, spatial distribution and forms of intranuclear and nucleus-associated cytoplasmic actin were studied in Amoeba proteus with immunocytochemical approaches. Labeling with different anti-actin antibodies and staining with TRITC-phalloidin and fluorescent deoxyribonuclease I were used. We showed that actin is abundant within the nucleus as well as in the cytoplasm of A. proteus cells. According to DNase I experiments, the predominant form of intranuclear actin is G-actin which is associated with chromatin strands. Besides, unpolymerized actin was shown to participate in organization of a prominent actin layer adjacent to the outer surface of nuclear envelope. No significant amount of F-actin was found in the nucleus. At the same time, the amoeba nucleus is enclosed in a basket-like structure formed by circumnuclear actin filaments and bundles connected with global cytoplasmic actin cytoskeleton. A supposed architectural function of actin filaments was studied by treatment with actin-depolymerizing agent latrunculin A. It disassembled the circumnuclear actin system, but did not affect the intranuclear chromatin structure. The results obtained for amoeba cells support the modern concept that actin is involved in fundamental nuclear processes that have evolved in the cells of multicellular organisms. Copyright © 2016 Elsevier GmbH. All rights reserved.

Actin Assembly Factors Regulate the Gelation Kinetics and Architecture of F-actin Networks

PubMed Central

Falzone, Tobias T.; Oakes, Patrick W.; Sees, Jennifer; Kovar, David R.; Gardel, Margaret L.

2013-01-01

Dynamic regulation of the actin cytoskeleton is required for diverse cellular processes. Proteins regulating the assembly kinetics of the cytoskeletal biopolymer F-actin are known to impact the architecture of actin cytoskeletal networks in vivo, but the underlying mechanisms are not well understood. Here, we demonstrate that changes to actin assembly kinetics with physiologically relevant proteins profilin and formin (mDia1 and Cdc12) have dramatic consequences on the architecture and gelation kinetics of otherwise biochemically identical cross-linked F-actin networks. Reduced F-actin nucleation rates promote the formation of a sparse network of thick bundles, whereas increased nucleation rates result in a denser network of thinner bundles. Changes to F-actin elongation rates also have marked consequences. At low elongation rates, gelation ceases and a solution of rigid bundles is formed. By contrast, rapid filament elongation accelerates dynamic arrest and promotes gelation with minimal F-actin density. These results are consistent with a recently developed model of how kinetic constraints regulate network architecture and underscore how molecular control of polymer assembly is exploited to modulate cytoskeletal architecture and material properties. PMID:23601318

United States Food and Drug Administration Product Label Changes.

PubMed

Kircik, Leon; Sung, Julie C; Stein-Gold, Linda; Goldenberg, Gary

2017-02-01

Once a drug has been approved by the United States Food and Drug Administration and is on the market, the Food and Drug Administration communicates new safety information through product label changes. Most of these label changes occur after a spontaneous report to either the drug manufacturing companies or the Food and Drug Administration MedWatch program. As a result, 400 to 500 label changes occur every year. Actinic keratosis treatments exemplify the commonality of label changes throughout the postmarket course of a drug. Diclofenac gel, 5-fluorouracil cream, imiquimod, and ingenol mebutate are examples of actinic keratosis treatments that have all undergone at least one label revision. With the current system of spontaneous reports leading to numerous label changes, each occurrence does not necessarily signify a radical change in the safety of a drug.

Computational Study of the Binding Mechanism of Actin-Depolymerizing Factor 1 with Actin in Arabidopsis thaliana.

PubMed

Du, Juan; Wang, Xue; Dong, Chun-Hai; Yang, Jian Ming; Yao, Xiao Jun

2016-01-01

Actin is a highly conserved protein. It plays important roles in cellular function and exists either in the monomeric (G-actin) or polymeric form (F-actin). Members of the actin-depolymerizing factor (ADF)/cofilin protein family bind to both G-actin and F-actin and play vital roles in actin dynamics by manipulating the rates of filament polymerization and depolymerization. It has been reported that the S6D and R98A/K100A mutants of actin-depolymerizing factor 1 (ADF1) in Arabidopsis thaliana decreased the binding affinity of ADF for the actin monomer. To investigate the binding mechanism and dynamic behavior of the ADF1-actin complex, we constructed a homology model of the AtADF1-actin complex based on the crystal structure of AtADF1 and the twinfilin C-terminal ADF-H domain in a complex with a mouse actin monomer. The model was then refined for subsequent molecular dynamics simulations. Increased binding energy of the mutated system was observed using the Molecular Mechanics Generalized Born Surface Area and Poisson-Boltzmann Surface Area (MM-GB/PBSA) methods. To determine the residues that make decisive contributions to the ADF1 actin-binding affinity, per-residue decomposition and computational alanine scanning analyses were performed, which provided more detailed information on the binding mechanism. Root-mean-square fluctuation and principal component analyses confirmed that the S6D and R98A/K100A mutants induced an increased conformational flexibility. The comprehensive molecular insight gained from this study is of great importance for understanding the binding mechanism of ADF1 and G-actin.

Computational Study of the Binding Mechanism of Actin-Depolymerizing Factor 1 with Actin in Arabidopsis thaliana

PubMed Central

Wang, Xue; Dong, Chun-Hai; Yang, Jian Ming; Yao, Xiao Jun

2016-01-01

Actin is a highly conserved protein. It plays important roles in cellular function and exists either in the monomeric (G-actin) or polymeric form (F-actin). Members of the actin-depolymerizing factor (ADF)/cofilin protein family bind to both G-actin and F-actin and play vital roles in actin dynamics by manipulating the rates of filament polymerization and depolymerization. It has been reported that the S6D and R98A/K100A mutants of actin-depolymerizing factor 1 (ADF1) in Arabidopsis thaliana decreased the binding affinity of ADF for the actin monomer. To investigate the binding mechanism and dynamic behavior of the ADF1–actin complex, we constructed a homology model of the AtADF1–actin complex based on the crystal structure of AtADF1 and the twinfilin C-terminal ADF-H domain in a complex with a mouse actin monomer. The model was then refined for subsequent molecular dynamics simulations. Increased binding energy of the mutated system was observed using the Molecular Mechanics Generalized Born Surface Area and Poisson–Boltzmann Surface Area (MM-GB/PBSA) methods. To determine the residues that make decisive contributions to the ADF1 actin-binding affinity, per-residue decomposition and computational alanine scanning analyses were performed, which provided more detailed information on the binding mechanism. Root-mean-square fluctuation and principal component analyses confirmed that the S6D and R98A/K100A mutants induced an increased conformational flexibility. The comprehensive molecular insight gained from this study is of great importance for understanding the binding mechanism of ADF1 and G-actin. PMID:27414648

A new F-actin structure in fungi: actin ring formation around the cell nucleus of Cryptococcus neoformans.

PubMed

Kopecká, Marie; Kawamoto, Susumu; Yamaguchi, Masashi

2013-04-01

The F-actin cytoskeleton of Cryptococcus neoformans is known to comprise actin cables, cortical patches and cytokinetic ring. Here, we describe a new F-actin structure in fungi, a perinuclear F-actin collar ring around the cell nucleus, by fluorescent microscopic imaging of rhodamine phalloidin-stained F-actin. Perinuclear F-actin rings form in Cryptococcus neoformans treated with the microtubule inhibitor Nocodazole or with the drug solvent dimethyl sulfoxide (DMSO) or grown in yeast extract peptone dextrose (YEPD) medium, but they are absent in cells treated with Latrunculin A. Perinuclear F-actin rings may function as 'funicular cabin' for the cell nucleus, and actin cables as intracellular 'funicular' suspending nucleus in the central position in the cell and moving nucleus along the polarity axis along actin cables.

Unusual benign polypoid and papular neoplasms and tumor-like lesions of the vulva.

PubMed

AbdullGaffar, Badr; Keloth, Tasnim R; Raman, Lakshmiah G; Mahmood, Suaad; Almulla, Amal; AlMarzouqi, Mamoun; Al-Hasani, Salam

2014-04-01

We aimed to investigate the prevalence and spectrum of unusual benign neoplasms and tumor-like lesions presenting as vulvar polyps and papules, to study their clinical, pathologic, hormonal, and developmental features and whether they have important associations with other pathologic lesions or clinical diseases. We conducted a retrospective review study of 115 vulvar specimens over 7 years. Common lesions, for example, fibroepithelial polyps, skin tags, papillomas, abscesses, viral warts and common cysts, were excluded. We found 21 cases (18%) with uncommon benign vulvar lesions. They included 7 epithelial cysts, 3 vascular lesions, 3 glandular neoplasms, 3 endometrioses, 1 caruncle, 1 pilonidal sinus, 1 prolapsed urethra, 1 seborrheic keratosis, and 1 granular cell tumor. The age range was between 1 and 64 years with a mean age of 33 years. Most (86%) were 2.5 cm or less. Many were asymptomatic incidental pathologic findings that can be missed clinically. Nine cases have important clinical associations or coexisting incidental pathologic lesions. Some lesions demonstrated hormone receptors. Some were clinically confused with fibroepithelial polyps, abscesses, warts, melanocytic lesions, and tumors. In conclusion, although the vulva is a small compartment, its developmental and histologic complexity can result in a variety of unusual and rare benign polypoid and papular lesions, some unique to the vulva, which might present diagnostic challenges to the clinicians and pathologists. In addition, many bear controversy regarding their histogenesis and origin of development in the vulva. Copyright © 2014 Elsevier Inc. All rights reserved.

Actin Depolymerizing Factor (ADF/Cofilin) Enhances the Rate of Filament Turnover: Implication in Actin-based Motility

PubMed Central

Carlier, Marie-France; Laurent, Valérie; Santolini, Jérôme; Melki, Ronald; Didry, Dominique; Xia, Gui-Xian; Hong, Yan; Chua, Nam-Hai; Pantaloni, Dominique

1997-01-01

Actin-binding proteins of the actin depolymerizing factor (ADF)/cofilin family are thought to control actin-based motile processes. ADF1 from Arabidopsis thaliana appears to be a good model that is functionally similar to other members of the family. The function of ADF in actin dynamics has been examined using a combination of physical–chemical methods and actin-based motility assays, under physiological ionic conditions and at pH 7.8. ADF binds the ADPbound forms of G- or F-actin with an affinity two orders of magnitude higher than the ATP- or ADP-Pi– bound forms. A major property of ADF is its ability to enhance the in vitro turnover rate (treadmilling) of actin filaments to a value comparable to that observed in vivo in motile lamellipodia. ADF increases the rate of propulsion of Listeria monocytogenes in highly diluted, ADF-limited platelet extracts and shortens the actin tails. These effects are mediated by the participation of ADF in actin filament assembly, which results in a change in the kinetic parameters at the two ends of the actin filament. The kinetic effects of ADF are end specific and cannot be accounted for by filament severing. The main functionally relevant effect is a 25-fold increase in the rate of actin dissociation from the pointed ends, while the rate of dissociation from the barbed ends is unchanged. This large increase in the rate-limiting step of the monomer-polymer cycle at steady state is responsible for the increase in the rate of actin-based motile processes. In conclusion, the function of ADF is not to sequester G-actin. ADF uses ATP hydrolysis in actin assembly to enhance filament dynamics. PMID:9087445

Glutathione depletion triggers actin cytoskeleton changes via actin-binding proteins.

PubMed

Zepeta-Flores, Nahum; Valverde, Mahara; Lopez-Saavedra, Alejandro; Rojas, Emilio

2018-06-04

The importance of glutathione (GSH) in alternative cellular roles to the canonically proposed, were analyzed in a model unable to synthesize GSH. Gene expression analysis shows that the regulation of the actin cytoskeleton pathway is strongly impacted by the absence of GSH. To test this hypothesis, we evaluate the effect of GSH depletion via buthionine sulfoximine (5 and 12.5 mM) in human neuroblastoma MSN cells. In the present study, 70% of GSH reduction did not induce reactive oxygen species, lipoperoxidation, or cytotoxicity, which enabled us to evaluate the effect of glutathione in the absence of oxidative stress. The cells with decreasing GSH levels acquired morphology changes that depended on the actin cytoskeleton and not on tubulin. We evaluated the expression of three actin-binding proteins: thymosin β4, profilin and gelsolin, showing a reduced expression, both at gene and protein levels at 24 hours of treatment; however, this suppression disappears after 48 hours of treatment. These changes were sufficient to trigger the co-localization of the three proteins towards cytoplasmic projections. Our data confirm that a decrease in GSH in the absence of oxidative stress can transiently inhibit the actin binding proteins and that this stimulus is sufficient to induce changes in cellular morphology via the actin cytoskeleton.

Affimer proteins for F-actin: novel affinity reagents that label F-actin in live and fixed cells.

PubMed

Lopata, Anna; Hughes, Ruth; Tiede, Christian; Heissler, Sarah M; Sellers, James R; Knight, Peter J; Tomlinson, Darren; Peckham, Michelle

2018-04-26

Imaging the actin cytoskeleton in cells uses a wide range of approaches. Typically, a fluorescent derivative of the small cyclic peptide phalloidin is used to image F-actin in fixed cells. Lifeact and F-tractin are popular for imaging the cytoskeleton in live cells. Here we characterised novel affinity reagents called Affimers that specifically bind to F-actin in vitro to determine if they are suitable alternatives as eGFP-fusion proteins, to label actin in live cells, or for labeling F-actin in fixed cells. In vitro experiments showed that 3 out of the 4 Affimers (Affimers 6, 14 and 24) tested bind tightly to purified F-actin, and appear to have overlapping binding sites. As eGFP-fusion proteins, the same 3 Affimers label F-actin in live cells. FRAP experiments suggest that eGFP-Affimer 6 behaves most similarly to F-tractin and Lifeact. However, it does not colocalise with mCherry-actin in dynamic ruffles, and may preferentially bind stable actin filaments. All 4 Affimers label F-actin in methanol fixed cells, while only Affimer 14 labels F-actin after paraformaldehyde fixation. eGFP-Affimer 6 has potential for use in selectively imaging the stable actin cytoskeleton in live cells, while all 4 Affimers are strong alternatives to phalloidin for labelling F-actin in fixed cells.

Cytoskeletal actin dynamics shape a ramifying actin network underpinning immunological synapse formation

PubMed Central

Fritzsche, Marco; Fernandes, Ricardo A.; Chang, Veronica T.; Colin-York, Huw; Clausen, Mathias P.; Felce, James H.; Galiani, Silvia; Erlenkämper, Christoph; Santos, Ana M.; Heddleston, John M.; Pedroza-Pacheco, Isabela; Waithe, Dominic; de la Serna, Jorge Bernardino; Lagerholm, B. Christoffer; Liu, Tsung-li; Chew, Teng-Leong; Betzig, Eric; Davis, Simon J.; Eggeling, Christian

2017-01-01

T cell activation and especially trafficking of T cell receptor microclusters during immunological synapse formation are widely thought to rely on cytoskeletal remodeling. However, important details on the involvement of actin in the latter transport processes are missing. Using a suite of advanced optical microscopes to analyze resting and activated T cells, we show that, following contact formation with activating surfaces, these cells sequentially rearrange their cortical actin across the entire cell, creating a previously unreported ramifying actin network above the immunological synapse. This network shows all the characteristics of an inward-growing transportation network and its dynamics correlating with T cell receptor rearrangements. This actin reorganization is accompanied by an increase in the nanoscale actin meshwork size and the dynamic adjustment of the turnover times and filament lengths of two differently sized filamentous actin populations, wherein formin-mediated long actin filaments support a very flat and stiff contact at the immunological synapse interface. The initiation of immunological synapse formation, as highlighted by calcium release, requires markedly little contact with activating surfaces and no cytoskeletal rearrangements. Our work suggests that incipient signaling in T cells initiates global cytoskeletal rearrangements across the whole cell, including a stiffening process for possibly mechanically supporting contact formation at the immunological synapse interface as well as a central ramified transportation network apparently directed at the consolidation of the contact and the delivery of effector functions. PMID:28691087

Mechanism of Actin-Based Motility

NASA Astrophysics Data System (ADS)

Pantaloni, Dominique; Le Clainche, Christophe; Carlier, Marie-France

2001-05-01

Spatially controlled polymerization of actin is at the origin of cell motility and is responsible for the formation of cellular protrusions like lamellipodia. The pathogens Listeria monocytogenes and Shigella flexneri, which undergo actin-based propulsion, are acknowledged models of the leading edge of lamellipodia. Actin-based motility of the bacteria or of functionalized microspheres can be reconstituted in vitro from only five pure proteins. Movement results from the regulated site-directed treadmilling of actin filaments, consistent with observations of actin dynamics in living motile cells and with the biochemical properties of the components of the synthetic motility medium.

Actin filaments as tension sensors.

PubMed

Galkin, Vitold E; Orlova, Albina; Egelman, Edward H

2012-02-07

The field of mechanobiology has witnessed an explosive growth over the past several years as interest has greatly increased in understanding how mechanical forces are transduced by cells and how cells migrate, adhere and generate traction. Actin, a highly abundant and anomalously conserved protein, plays a large role in forming the dynamic cytoskeleton that is so essential for cell form, motility and mechanosensitivity. While the actin filament (F-actin) has been viewed as dynamic in terms of polymerization and depolymerization, new results suggest that F-actin itself may function as a highly dynamic tension sensor. This property may help explain the unusual conservation of actin's sequence, as well as shed further light on actin's essential role in structures from sarcomeres to stress fibers. Copyright © 2012 Elsevier Ltd. All rights reserved.

Photodynamic therapy in actinic cheilitis: clinical and anatomopathological evaluation of 19 patients.

PubMed

Ribeiro, Camila Ferrari; Souza, Fernanda Homem de Mello de; Jordão, Juliana Merheb; Haendchen, Letícia Cortes; Mesquita, Lismary; Schmitt, Juliano Vilaverde; Faucz, Luciana Lisboa

2012-01-01

Actinic cheilitis, a common disease caused by chronic solar exposure and tobacco use, is considered a premalignant lesion with potential to develop into squamous cell carcinoma. Some of the available treatments are invasive, have unaesthetic results and require multiple sessions. To assess the efficacy of a therapy and its cosmetic results. In this uncontrolled clinical trial a single photodynamic therapy (PDT) session using 16% methyl-aminolevulinate was performed on actinic cheilitis of the lower lip. A standardized questionnaire was applied in order to assess the clinical improvement from the patients' point of view and the satisfaction with the treatment. Anatomopathological evaluation was performed before the treatment and two months afterwards. The sample was composed of 19 patients (10 males and 9 females), phototypes I to III, with average age of 62 years. Main adverse effects were: sudden pain, scabs, herpes flare-up, and edema. The average score of pain during the procedure was 5,8+2,9. At the final assessment the patients reported improvement of 80% and satisfaction of 85% (p<0.01). Anatomopathological analysis showed a significant decrease of dysplasia (p=0.03) in spite of its presence in 84% of cases. There was no significant correlation between the level of dysplasia with either the subjective impression of clinical improvement (p=0.82) or with the patients' final satisfaction (p=0.96). PDT is effective in the treatment of actinic cheilitis, but it is associated with a significant level of pain. Due to the persistence of dysplasia, more research needs to be done in order to define the ideal number of sessions for the effective treatment of these lesions.

Interactions between G-actin and myosin subfragment 1: immunochemical probing of the NH2-terminal segment on actin.

PubMed

DasGupta, G; White, J; Cheung, P; Reisler, E

1990-09-11

The role of the N-terminal segment of actin in myosin-induced polymerization of G-actin was studied by using peptide antibodies directed against the first seven N-terminal residues of alpha-skeletal actin. Light scattering, fluorescence, and analytical ultracentrifugation experiments showed that the Fab fragments of these antibodies inhibited the polymerization of G-actin by myosin subfragment 1 (S-1) by inhibiting the binding of these proteins to each other. Fluorescence measurements using actin labeled with pyrenyliodoacetamide revealed that Fab inhibited the initial step in the binding of S-1 to G-actin. It is deduced from these results and from other literature data that the initial contact between G-actin and S-1 involves residues 1-7 on actin and residues 633-642 on the S-1 heavy chain. This interaction appears to be of major importance for the binding of S-1 and G-actin. The presence of additional myosin contact sites on G-actin was indicated by concentration-dependent recovery of S-1 binding to G-actin without displacement of Fab. The reduced Fab inhibition of S-1 binding to polymerizing and polymerized actin is consistent with the tightening of acto-S-1 binding at these sites or the creation of new sites upon formation of F-actin.

Computational model of polarized actin cables and cytokinetic actin ring formation in budding yeast

PubMed Central

Tang, Haosu; Bidone, Tamara C.

2015-01-01

The budding yeast actin cables and contractile ring are important for polarized growth and division, revealing basic aspects of cytoskeletal function. To study these formin-nucleated structures, we built a 3D computational model with actin filaments represented as beads connected by springs. Polymerization by formins at the bud tip and bud neck, crosslinking, severing, and myosin pulling, are included. Parameter values were estimated from prior experiments. The model generates actin cable structures and dynamics similar to those of wild type and formin deletion mutant cells. Simulations with increased polymerization rate result in long, wavy cables. Simulated pulling by type V myosin stretches actin cables. Increasing the affinity of actin filaments for the bud neck together with reduced myosin V pulling promotes the formation of a bundle of antiparallel filaments at the bud neck, which we suggest as a model for the assembly of actin filaments to the contractile ring. PMID:26538307

Role of gelsolin interaction with actin in regulation and creation of actin nuclei in chemotactic peptide activated polymorphonuclear neutrophils.

PubMed Central

Deaton, J D; Guerrero, T; Howard, T H

1992-01-01

In vitro Ca++ activates gelsolin to sever F-actin and form a gelsolin-actin (GA) complex at the+end of F-actin that is not dissociated by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) but is separated by EGTA+PIP/PIP2. The gelsolin blocks the+end on the actin filament, but the-end of the filament can still initiate actin polymerization. In thrombin activated platelets, evidence suggests that severing of F-actin by gelsolin increases GA complex, creates one-end actin nucleus and one cryptic+end actin nucleus per cut, and then dissociates to yield free+ends to nucleate rapid actin assembly. We examined the role of F-actin severing in creation and regulation of nuclei and polymerization in polymorphonuclear neutrophils (PMNs). At 2-s intervals after formyl peptide (FMLP) activation of endotoxin free (ETF) PMNs, change in GA complex was correlated with change in+end actin nuclei,-end actin nuclei, and F-actin content. GA complex was quantitated by electrophoretograms of proteins absorbed by antigelsolin from cells lysed in 10 mM EGTA,+end actin nuclei as cytochalasin (CD) sensitive and-end actin nuclei as CD insensitive increases in G-pyrenyl actin polymerization rates induced by the same PMNs, and F-actin content by NBDphallacidin binding to fixed cells. Thirty three percent of gelsolin was in GA complex in basal ETF PMNs; from 2-6 s, GA complexes dissociate (low = 15% at 10 s) and sequentially+end nuclei and F-actin content and then-end nuclei increase to a maximum at 10 s. At > s GA complex increase toward basal and + end nuclei and F-actin content returned toward basal. These kinetic data show gelsolin regulates availability of + end nuclei and actin polymerization in FMLP. However, absence of an initial increase in GA complex or - end nucleating activity shows FMLP activation does not cause gelsolin to sever F- or to bind G-actin to create cryptic + end nuclei in PMNs; the results suggest the + nucleus formation is gelsolin

Role of gelsolin interaction with actin in regulation and creation of actin nuclei in chemotactic peptide activated polymorphonuclear neutrophils.

PubMed

Deaton, J D; Guerrero, T; Howard, T H

1992-12-01

In vitro Ca++ activates gelsolin to sever F-actin and form a gelsolin-actin (GA) complex at the+end of F-actin that is not dissociated by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) but is separated by EGTA+PIP/PIP2. The gelsolin blocks the+end on the actin filament, but the-end of the filament can still initiate actin polymerization. In thrombin activated platelets, evidence suggests that severing of F-actin by gelsolin increases GA complex, creates one-end actin nucleus and one cryptic+end actin nucleus per cut, and then dissociates to yield free+ends to nucleate rapid actin assembly. We examined the role of F-actin severing in creation and regulation of nuclei and polymerization in polymorphonuclear neutrophils (PMNs). At 2-s intervals after formyl peptide (FMLP) activation of endotoxin free (ETF) PMNs, change in GA complex was correlated with change in+end actin nuclei,-end actin nuclei, and F-actin content. GA complex was quantitated by electrophoretograms of proteins absorbed by antigelsolin from cells lysed in 10 mM EGTA,+end actin nuclei as cytochalasin (CD) sensitive and-end actin nuclei as CD insensitive increases in G-pyrenyl actin polymerization rates induced by the same PMNs, and F-actin content by NBDphallacidin binding to fixed cells. Thirty three percent of gelsolin was in GA complex in basal ETF PMNs; from 2-6 s, GA complexes dissociate (low = 15% at 10 s) and sequentially+end nuclei and F-actin content and then-end nuclei increase to a maximum at 10 s. At > s GA complex increase toward basal and + end nuclei and F-actin content returned toward basal. These kinetic data show gelsolin regulates availability of + end nuclei and actin polymerization in FMLP. However, absence of an initial increase in GA complex or - end nucleating activity shows FMLP activation does not cause gelsolin to sever F- or to bind G-actin to create cryptic + end nuclei in PMNs; the results suggest the + nucleus formation is gelsolin

Arp2/3 complex–dependent actin networks constrain myosin II function in driving retrograde actin flow

PubMed Central

Yang, Qing; Zhang, Xiao-Feng; Pollard, Thomas D.

2012-01-01

The Arp2/3 complex nucleates actin filaments to generate networks at the leading edge of motile cells. Nonmuscle myosin II produces contractile forces involved in driving actin network translocation. We inhibited the Arp2/3 complex and/or myosin II with small molecules to investigate their respective functions in neuronal growth cone actin dynamics. Inhibition of the Arp2/3 complex with CK666 reduced barbed end actin assembly site density at the leading edge, disrupted actin veils, and resulted in veil retraction. Strikingly, retrograde actin flow rates increased with Arp2/3 complex inhibition; however, when myosin II activity was blocked, Arp2/3 complex inhibition now resulted in slowing of retrograde actin flow and veils no longer retracted. Retrograde flow rate increases induced by Arp2/3 complex inhibition were independent of Rho kinase activity. These results provide evidence that, although the Arp2/3 complex and myosin II are spatially segregated, actin networks assembled by the Arp2/3 complex can restrict myosin II–dependent contractility with consequent effects on growth cone motility. PMID:22711700

A Second Las17 Monomeric Actin-Binding Motif Functions in Arp2/3-Dependent Actin Polymerization During Endocytosis

PubMed Central

Feliciano, Daniel; Tolsma, Thomas O.; Farrell, Kristen B.; Aradi, Al; Di Pietro, Santiago M.

2018-01-01

During clathrin-mediated endocytosis (CME), actin assembly provides force to drive vesicle internalization. Members of the Wiskott–Aldrich syndrome protein (WASP) family play a fundamental role stimulating actin assembly. WASP family proteins contain a WH2 motif that binds globular actin (G-actin) and a central-acidic motif that binds the Arp2/3 complex, thus promoting the formation of branched actin filaments. Yeast WASP (Las17) is the strongest of five factors promoting Arp2/3-dependent actin polymerization during CME. It was suggested that this strong activity may be caused by a putative second G-actin-binding motif in Las17. Here, we describe the in vitro and in vivo characterization of such Las17 G-actin-binding motif (LGM) and its dependence on a group of conserved arginine residues. Using the yeast two-hybrid system, GST-pulldown, fluorescence polarization and pyrene-actin polymerization assays, we show that LGM binds G-actin and is necessary for normal Arp2/3-mediated actin polymerization in vitro. Live-cell fluorescence microscopy experiments demonstrate that LGM is required for normal dynamics of actin polymerization during CME. Further, LGM is necessary for normal dynamics of endocytic machinery components that are recruited at early, intermediate and late stages of endocytosis, as well as for optimal endocytosis of native CME cargo. Both in vitro and in vivo experiments show that LGM has relatively lower potency compared to the previously known Las17 G-actin-binding motif, WH2. These results establish a second G-actin-binding motif in Las17 and advance our knowledge on the mechanism of actin assembly during CME. PMID:25615019

United States Food and Drug Administration Product Label Changes

PubMed Central

Sung, Julie C.; Stein-Gold, Linda; Goldenberg, Gary

2017-01-01

Once a drug has been approved by the United States Food and Drug Administration and is on the market, the Food and Drug Administration communicates new safety information through product label changes. Most of these label changes occur after a spontaneous report to either the drug manufacturing companies or the Food and Drug Administration MedWatch program. As a result, 400 to 500 label changes occur every year. Actinic keratosis treatments exemplify the commonality of label changes throughout the postmarket course of a drug. Diclofenac gel, 5-fluorouracil cream, imiquimod, and ingenol mebutate are examples of actinic keratosis treatments that have all undergone at least one label revision. With the current system of spontaneous reports leading to numerous label changes, each occurrence does not necessarily signify a radical change in the safety of a drug. PMID:28367259

United States Food and Drug Administration Product Label Changes

PubMed Central

Sung, Julie C.; Stein-Gold, Linda; Goldenberg, Gary

2016-01-01

Once a drug has been approved by the United States Food and Drug Administration and is on the market, the Food and Drug Administration communicates new safety information through product label changes. Most of these label changes occur after a spontaneous report to either the drug manufacturing companies or the Food and Drug Administration MedWatch program. As a result, 400 to 500 label changes occur every year. Actinic keratosis treatments exemplify the commonality of label changes throughout the postmarket course of a drug. Diclofenac gel, 5-fluorouracil cream, imiquimod, and ingenol mebutate are examples of actinic keratosis treatments that have all undergone at least one label revision. With the current system of spontaneous reports leading to numerous label changes, each occurrence does not necessarily signify a radical change in the safety of a drug. PMID:26962391

Fascin regulates nuclear actin during Drosophila oogenesis

PubMed Central

Kelpsch, Daniel J.; Groen, Christopher M.; Fagan, Tiffany N.; Sudhir, Sweta; Tootle, Tina L.

2016-01-01

Drosophila oogenesis provides a developmental system with which to study nuclear actin. During Stages 5–9, nuclear actin levels are high in the oocyte and exhibit variation within the nurse cells. Cofilin and Profilin, which regulate the nuclear import and export of actin, also localize to the nuclei. Expression of GFP-tagged Actin results in nuclear actin rod formation. These findings indicate that nuclear actin must be tightly regulated during oogenesis. One factor mediating this regulation is Fascin. Overexpression of Fascin enhances nuclear GFP-Actin rod formation, and Fascin colocalizes with the rods. Loss of Fascin reduces, whereas overexpression of Fascin increases, the frequency of nurse cells with high levels of nuclear actin, but neither alters the overall nuclear level of actin within the ovary. These data suggest that Fascin regulates the ability of specific cells to accumulate nuclear actin. Evidence indicates that Fascin positively regulates nuclear actin through Cofilin. Loss of Fascin results in decreased nuclear Cofilin. In addition, Fascin and Cofilin genetically interact, as double heterozygotes exhibit a reduction in the number of nurse cells with high nuclear actin levels. These findings are likely applicable beyond Drosophila follicle development, as the localization and functions of Fascin and the mechanisms regulating nuclear actin are widely conserved. PMID:27535426

In Vivo, Villin Is Required for Ca2+-Dependent F-Actin Disruption in Intestinal Brush Borders

PubMed Central

Ferrary, Evelyne; Cohen-Tannoudji, Michel; Pehau-Arnaudet, Gérard; Lapillonne, Alexandre; Athman, Rafika; Ruiz, Tereza; Boulouha, Lilia; El Marjou, Fatima; Doye, Anne; Fontaine, Jean-Jacques; Antony, Claude; Babinet, Charles; Louvard, Daniel; Jaisser, Frédéric; Robine, Sylvie

1999-01-01

Villin is an actin-binding protein localized in intestinal and kidney brush borders. In vitro, villin has been demonstrated to bundle and sever F-actin in a Ca2+-dependent manner. We generated knockout mice to study the role of villin in vivo. In villin-null mice, no noticeable changes were observed in the ultrastructure of the microvilli or in the localization and expression of the actin-binding and membrane proteins of the intestine. Interestingly, the response to elevated intracellular Ca2+ differed significantly between mutant and normal mice. In wild-type animals, isolated brush borders were disrupted by the addition of Ca2+, whereas Ca2+ had no effect in villin-null isolates. Moreover, increase in intracellular Ca2+ by serosal carbachol or mucosal Ca2+ ionophore A23187 application abolished the F-actin labeling only in the brush border of wild-type animals. This F-actin disruption was also observed in physiological fasting/refeeding experiments. Oral administration of dextran sulfate sodium, an agent that causes colonic epithelial injury, induced large mucosal lesions resulting in a higher death probability in mice lacking villin, 36 ± 9.6%, compared with wild-type mice, 70 ± 8.8%, at day 13. These results suggest that in vivo, villin is not necessary for the bundling of F-actin microfilaments, whereas it is necessary for the reorganization elicited by various signals. We postulate that this property might be involved in cellular plasticity related to cell injury. PMID:10459016

New developments in occupational dermatology.

PubMed

Diepgen, Thomas L

2016-09-01

Occupational skin diseases according to BK No. 5101 - "severe or recurrent skin diseases which have forced the person to discontinue all occupational activities that caused or could cause the development, worsening, or recurrence of the disease" - is the most commonly reported notifiable occupational diseases in Germany. Following the optimization of measures of primary, secondary, and tertiary prevention, today most individuals affected are able to continue their profession. With the revision of the German ordinance on occupational diseases (BKV) in January 2015, skin cancer caused by UV irradiation was added to the list of occupational diseases. The new occupational disease (BK) 5103 is defined as "squamous cell carcinoma or multiple actinic keratoses of the skin caused by natural UV irradiation". In this context, "multiple" signifies the occurrence of either more than five individual actinic keratosis lesions over the course of 12 months or the presence of field cancerization of > 4 cm(2) . In the following review, important aspects of this new occupational disease will be highlighted and discussed. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Geometrical Determinants of Neuronal Actin Waves.

PubMed

Tomba, Caterina; Braïni, Céline; Bugnicourt, Ghislain; Cohen, Floriane; Friedrich, Benjamin M; Gov, Nir S; Villard, Catherine

2017-01-01

Hippocampal neurons produce in their early stages of growth propagative, actin-rich dynamical structures called actin waves. The directional motion of actin waves from the soma to the tip of neuronal extensions has been associated with net forward growth, and ultimately with the specification of neurites into axon and dendrites. Here, geometrical cues are used to control actin wave dynamics by constraining neurons on adhesive stripes of various widths. A key observable, the average time between the production of consecutive actin waves, or mean inter-wave interval (IWI), was identified. It scales with the neurite width, and more precisely with the width of the proximal segment close to the soma. In addition, the IWI is independent of the total number of neurites. These two results suggest a mechanistic model of actin wave production, by which the material conveyed by actin waves is assembled in the soma until it reaches the threshold leading to the initiation and propagation of a new actin wave. Based on these observations, we formulate a predictive theoretical description of actin wave-driven neuronal growth and polarization, which consistently accounts for different sets of experiments.

Geometrical Determinants of Neuronal Actin Waves

PubMed Central

Tomba, Caterina; Braïni, Céline; Bugnicourt, Ghislain; Cohen, Floriane; Friedrich, Benjamin M.; Gov, Nir S.; Villard, Catherine

2017-01-01

Hippocampal neurons produce in their early stages of growth propagative, actin-rich dynamical structures called actin waves. The directional motion of actin waves from the soma to the tip of neuronal extensions has been associated with net forward growth, and ultimately with the specification of neurites into axon and dendrites. Here, geometrical cues are used to control actin wave dynamics by constraining neurons on adhesive stripes of various widths. A key observable, the average time between the production of consecutive actin waves, or mean inter-wave interval (IWI), was identified. It scales with the neurite width, and more precisely with the width of the proximal segment close to the soma. In addition, the IWI is independent of the total number of neurites. These two results suggest a mechanistic model of actin wave production, by which the material conveyed by actin waves is assembled in the soma until it reaches the threshold leading to the initiation and propagation of a new actin wave. Based on these observations, we formulate a predictive theoretical description of actin wave-driven neuronal growth and polarization, which consistently accounts for different sets of experiments. PMID:28424590

Prevalence of actinic cheilitis in a population of agricultural sugarcane workers.

PubMed

Miranda, Ana M O; Soares, Léo G; Ferrari, Thiago M; Silva, Denise G; Falabella, Márcio E V; Tinoco, Eduardo M B

2012-01-01

Actinic cheilitis (AC) is a pre-malignant inflammatory reaction of the lips caused by continuous exposure to solar rays. The aim of this study was to assess the prevalence of AC in a population of sugarcane workers in Brazil. 1,539 individuals who were exposed to the sun during working hours and 150 individuals who were not exposed were screened for clinical signs of AC. The sample was classified according to years of exposure to the sun, ethnicity, gender smoking and severity of the lesion. A 9.16% (n= 141) prevalence of AC was observed among the population which had been exposed to the sun. The prevalence of AC lesions was significantly higher among individuals who had been exposed to the sun for more than 10 years than among those who had been exposed for less than 10 years, and among Caucasians and males than non-Caucasians and females. It was concluded that the severity of the lesions was associated with time of exposure to the sun.

Bacterial Actins.

PubMed

Izoré, Thierry; van den Ent, Fusinita

2017-01-01

A diverse set of protein polymers, structurally related to actin filaments contributes to the organization of bacterial cells as cytomotive or cytoskeletal filaments. This chapter describes actin homologs encoded by bacterial chromosomes. MamK filaments, unique to magnetotactic bacteria, help establishing magnetic biological compasses by interacting with magnetosomes. Magnetosomes are intracellular membrane invaginations containing biomineralized crystals of iron oxide that are positioned by MamK along the long-axis of the cell. FtsA is widespread across bacteria and it is one of the earliest components of the divisome to arrive at midcell, where it anchors the cell division machinery to the membrane. FtsA binds directly to FtsZ filaments and to the membrane through its C-terminus. FtsA shows altered domain architecture when compared to the canonical actin fold. FtsA's subdomain 1C replaces subdomain 1B of other members of the actin family and is located on the opposite side of the molecule. Nevertheless, when FtsA assembles into protofilaments, the protofilament structure is preserved, as subdomain 1C replaces subdomain IB of the following subunit in a canonical actin filament. MreB has an essential role in shape-maintenance of most rod-shaped bacteria. Unusually, MreB filaments assemble from two protofilaments in a flat and antiparallel arrangement. This non-polar architecture implies that both MreB filament ends are structurally identical. MreB filaments bind directly to membranes where they interact with both cytosolic and membrane proteins, thereby forming a key component of the elongasome. MreB filaments in cells are short and dynamic, moving around the long axis of rod-shaped cells, sensing curvature of the membrane and being implicated in peptidoglycan synthesis.

Surface-induced polymerization of actin.

PubMed Central

Renault, A; Lenne, P F; Zakri, C; Aradian, A; Vénien-Bryan, C; Amblard, F

1999-01-01

Living cells contain a very large amount of membrane surface area, which potentially influences the direction, the kinetics, and the localization of biochemical reactions. This paper quantitatively evaluates the possibility that a lipid monolayer can adsorb actin from a nonpolymerizing solution, induce its polymerization, and form a 2D network of individual actin filaments, in conditions that forbid bulk polymerization. G- and F-actin solutions were studied beneath saturated Langmuir monolayers containing phosphatidylcholine (PC, neutral) and stearylamine (SA, a positively charged surfactant) at PC:SA = 3:1 molar ratio. Ellipsometry, tensiometry, shear elastic measurements, electron microscopy, and dark-field light microscopy were used to characterize the adsorption kinetics and the interfacial polymerization of actin. In all cases studied, actin follows a monoexponential reaction-limited adsorption with similar time constants (approximately 10(3) s). At a longer time scale the shear elasticity of the monomeric actin adsorbate increases only in the presence of lipids, to a 2D shear elastic modulus of mu approximately 30 mN/m, indicating the formation of a structure coupled to the monolayer. Electron microscopy shows the formation of a 2D network of actin filaments at the PC:SA surface, and several arguments strongly suggest that this network is indeed causing the observed elasticity. Adsorption of F-actin to PC:SA leads more quickly to a slightly more rigid interface with a modulus of mu approximately 50 mN/m. PMID:10049338

Mesoscopic model of actin-based propulsion.

PubMed

Zhu, Jie; Mogilner, Alex

2012-01-01

Two theoretical models dominate current understanding of actin-based propulsion: microscopic polymerization ratchet model predicts that growing and writhing actin filaments generate forces and movements, while macroscopic elastic propulsion model suggests that deformation and stress of growing actin gel are responsible for the propulsion. We examine both experimentally and computationally the 2D movement of ellipsoidal beads propelled by actin tails and show that neither of the two models can explain the observed bistability of the orientation of the beads. To explain the data, we develop a 2D hybrid mesoscopic model by reconciling these two models such that individual actin filaments undergoing nucleation, elongation, attachment, detachment and capping are embedded into the boundary of a node-spring viscoelastic network representing the macroscopic actin gel. Stochastic simulations of this 'in silico' actin network show that the combined effects of the macroscopic elastic deformation and microscopic ratchets can explain the observed bistable orientation of the actin-propelled ellipsoidal beads. To test the theory further, we analyze observed distribution of the curvatures of the trajectories and show that the hybrid model's predictions fit the data. Finally, we demonstrate that the model can explain both concave-up and concave-down force-velocity relations for growing actin networks depending on the characteristic time scale and network recoil. To summarize, we propose that both microscopic polymerization ratchets and macroscopic stresses of the deformable actin network are responsible for the force and movement generation.

Polycation induced actin bundles.

PubMed

Muhlrad, Andras; Grintsevich, Elena E; Reisler, Emil

2011-04-01

Three polycations, polylysine, the polyamine spermine and the polycationic protein lysozyme were used to study the formation, structure, ionic strength sensitivity and dissociation of polycation-induced actin bundles. Bundles form fast, simultaneously with the polymerization of MgATP-G-actins, upon the addition of polycations to solutions of actins at low ionic strength conditions. This indicates that nuclei and/or nascent filaments bundle due to attractive, electrostatic effect of polycations and the neutralization of repulsive interactions of negative charges on actin. The attractive forces between the filaments are strong, as shown by the low (in nanomolar range) critical concentration of their bundling at low ionic strength. These bundles are sensitive to ionic strength and disassemble partially in 100 mM NaCl, but both the dissociation and ionic strength sensitivity can be countered by higher polycation concentrations. Cys374 residues of actin monomers residing on neighboring filaments in the bundles can be cross-linked by the short span (5.4Å) MTS-1 (1,1-methanedyl bismethanethiosulfonate) cross-linker, which indicates a tight packing of filaments in the bundles. The interfilament cross-links, which connect monomers located on oppositely oriented filaments, prevent disassembly of bundles at high ionic strength. Cofilin and the polysaccharide polyanion heparin disassemble lysozyme induced actin bundles more effectively than the polylysine-induced bundles. The actin-lysozyme bundles are pathologically significant as both proteins are found in the pulmonary airways of cystic fibrosis patients. Their bundles contribute to the formation of viscous mucus, which is the main cause of breathing difficulties and eventual death in this disorder. Copyright © 2011 Elsevier B.V. All rights reserved.

Dermoscopic Clues for Diagnosing Melanomas That Resemble Seborrheic Keratosis

PubMed Central

Segura, Sonia; Aguilera, Paula; Scalvenzi, Massimiliano; Longo, Caterina; Barreiro, Alicia; Broganelli, Paolo; Cavicchini, Stefano; Llambrich, Alex; Zaballos, Pedro; Thomas, Luc; Malvehy, Josep; Puig, Susana; Zalaudek, Iris

2017-01-01

Importance Melanomas that clinically mimic seborrheic keratosis (SK) can delay diagnosis and adequate treatment. However, little is known about the value of dermoscopy in recognizing these difficult-to-diagnose melanomas. Objective To describe the dermoscopic features of SK-like melanomas to understand their clinical morphology. Design, Setting, and Participants This observational retrospective study used 134 clinical and dermoscopic images of histopathologically proven melanomas in 134 patients treated in 9 skin cancer centers in Spain, France, Italy, and Austria. Without knowledge that the definite diagnosis for all the lesions was melanoma, 2 dermoscopy-trained observers evaluated the clinical descriptions and 48 dermoscopic features (including all melanocytic and nonmelanocytic criteria) of all 134 images and classified each dermoscopically as SK or not SK. The total dermoscopy score and the 7-point checklist score were assessed. Images of the lesions and patient data were collected from July 15, 2013, through July 31, 2014. Main Outcomes and Measures Frequencies of specific morphologic patterns of (clinically and dermoscopically) SK-like melanomas, patient demographics, and interobserver agreement of criteria were evaluated. Results Of the 134 cases collected from 72 men and 61 women, all of whom were white and who had a mean (SD) age of 55.6 (17.5) years, 110 (82.1%) revealed dermoscopic features suggestive of melanoma, including pigment network (74 [55.2%]), blue-white veil (72 [53.7%]), globules and dots (68 [50.7%]), pseudopods or streaks (47 [35.1%]), and blue-black sign (43 [32.3%]). The remaining 24 cases (17.9%) were considered likely SKs, even by dermoscopy. Overall, lesions showed a scaly and hyperkeratotic surface (45 [33.6%]), yellowish keratin (42 [31.3%]), comedo-like openings (41 [30.5%]), and milia-like cysts (30 [22.4%]). The entire sample achieved a mean (SD) total dermoscopy score of 4.7 (1.6) and a 7-point checklist score of 4.4 (2

Actinic Prurigo Cheilitis: A Clinicopathologic Review of 75 Cases.

PubMed

Plaza, Jose A; Toussaint, Sonia; Prieto, Victor G; Mercadillo, Patricia; Diez de Medina, Juan C; Lourenco, Silvia; Batdorf, Bjorn; Sangueza, Martin

2016-06-01

Actinic prurigo (AP) is a chronic idiopathic photodermatosis that primarily affects American Indians in the United States and Mestizos in Latin American countries. Clinically, the onset of the disease is usually in the first decade of life but may appear initially in adult life, and it is characterized by symmetric involvement of sun-exposed areas of the skin, particularly areas of the face, resulting in polymorphic erythematous papules, macules, and plaques in different stages of evolution. Lower lip involvement includes swelling, scaling, fissures, hyperpigmentation, and ulcerations of the vermilion border. and in some cases could represent the only manifestation of the disease. The histopathologic features of AP have been studied; however, there is a controversy regarding whether AP cheilitis has distinct histopathologic features that could allow accurate separation from other specific and nonspecific forms of cheilitis. The diagnosis can be challenging, mainly when lip lesions are the only manifestation of the disease. In this study, the authors investigate the clinicopathologic features of 75 cases of AP cheilitis to provide further criteria for its diagnosis and classification. All 75 patients presented with lip lesions. Thirty-three cases were diagnosed as AP cheilitis with cutaneous lesions and 42 cases were diagnosed as AP cheilitis without cutaneous lesions (only lip lesions). Histologically, of the 33 cases with AP cheilitis with cutaneous lesions, 17 (52%) cases showed follicular cheilitis, and of the 42 cases that had only lip lesions, 18 (43%) cases showed follicular cheilitis. Histologically, AP cheilitis can present as follicular cheilitis; thus, supporting the diagnosis. Also, our findings confirm that lip lesions can present as the only manifestation of the disease, showing typical histological and clinical features. This form of cheilitis has not being well described in the dermatologic and dermatopathologic literature.

Nuclear positioning by actin cables and perinuclear actin

PubMed Central

Huelsmann, Sven; Brown, Nicholas H

2014-01-01

Nuclear positioning is an important process during development and homeostasis. Depending on the affected tissue, mislocalized nuclei can alter cellular processes such as polarization, differentiation, or migration and lead ultimately to diseases. Many cells actively control the position of their nucleus using their cytoskeleton and motor proteins. We have recently shown that during Drosophila oogenesis, nurse cells employ cytoplasmic actin cables in association with perinuclear actin to position their nucleus. Here, we briefly summarize our work and discuss why nuclear positioning in nurse cells is specialized but the molecular mechanisms are likely to be more generally used. PMID:24905988

Non-Straub type actin from molluscan catch muscle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shelud'ko, Nikolay S., E-mail: sheludko@stl.ru; Girich, Ulyana V.; Lazarev, Stanislav S.

We have developed a method of obtaining natural actin from smooth muscles of the bivalves on the example of the Crenomytilus grayanus catch muscle. The muscles were previously rigorized to prevent a loss of thin filaments during homogenization and washings. Thin filaments were isolated with a low ionic strength solution in the presence of ATP and sodium pyrophosphate. Surface proteins of thin filaments-tropomyosin, troponin, calponin and some minor actin-binding proteins-were dissociated from actin filaments by increasing the ionic strength to 0.6 M KCL. Natural fibrillar actin obtained in that way depolymerizes easily in low ionic strength solutions commonly used for themore » extraction of Straub-type actin from acetone powder. Purification of natural actin was carried out by the polymerization–depolymerization cycle. The content of inactivated actin remaining in the supernatant is much less than at a similar purification of Straub-type actin. A comparative investigation was performed between the natural mussel actin and the Straub-type rabbit skeletal actin in terms of the key properties of actin: polymerization, activation of Mg-ATPase activity of myosin, and the electron-microscopic structure of actin polymers. -- Highlights: •We developed method of repolymerizable invertebrate smooth muscle actin obtaining. •Our method does not involve use of denaturating agents, which could modify proteins. •Viscosity and polymerization rate of actin, gained that way, is similar to Straub one. •Electron microscopy showed that repolymerized mussel actin is similar to Straub one. •Repolymerized mussel actin has greater ATPase activating capacity, than Straub actin.« less

The nuclear F-actin interactome of Xenopus oocytes reveals an actin-bundling kinesin that is essential for meiotic cytokinesis

PubMed Central

Samwer, Matthias; Dehne, Heinz-Jürgen; Spira, Felix; Kollmar, Martin; Gerlich, Daniel W; Urlaub, Henning; Görlich, Dirk

2013-01-01

Nuclei of Xenopus laevis oocytes grow 100 000-fold larger in volume than a typical somatic nucleus and require an unusual intranuclear F-actin scaffold for mechanical stability. We now developed a method for mapping F-actin interactomes and identified a comprehensive set of F-actin binders from the oocyte nuclei. Unexpectedly, the most prominent interactor was a novel kinesin termed NabKin (Nuclear and meiotic actin-bundling Kinesin). NabKin not only binds microtubules but also F-actin structures, such as the intranuclear actin bundles in prophase and the contractile actomyosin ring during cytokinesis. The interaction between NabKin and F-actin is negatively regulated by Importin-β and is responsive to spatial information provided by RanGTP. Disconnecting NabKin from F-actin during meiosis caused cytokinesis failure and egg polyploidy. We also found actin-bundling activity in Nabkin's somatic paralogue KIF14, which was previously shown to be essential for somatic cell division. Our data are consistent with the notion that NabKin/KIF14 directly link microtubules with F-actin and that such link is essential for cytokinesis. PMID:23727888

Immunohistochemical localization of human papilloma virus in conjunctival neoplasias: A retrospective study

PubMed Central

Sharma, Anjana; Panda, Anita

2007-01-01

Background: The extent of association of human papilloma virus (HPV) in human conjunctival neoplasias has been debated in studies originating from different parts of the world, but no substantial evidence has been generated on Indian subjects. This prompted us to carry out a retrospective study on conjunctival neoplasias diagnosed over the past 12 years. Materials and Methods: Histopathological and immunohistochemical analysis of 65 specimens of ocular neoplasias and 30 normal controls diagnosed between 1991 and 2002 at a tertiary eye care hospital, was undertaken. Formalin-fixed, paraffin-embedded tissues were reviewed for confirming histopathological diagnosis, presence of koilocytosis and changes related to actinic keratosis. Immunohistochemical analysis was done using HPV-specific monoclonal antibodies. Clinicopathological correlation and the association of HPV antigen with the histopathological features were performed. Results: Out of the 65 cases analyzed, 35 were papillomas and 30 were ocular surface squamous neoplasias (OSSN). The mean age was 48 years with a male preponderance. Histologically, koilocytosis was observed in 17.1% of papillomas and 36.6% of OSSN. Actinic keratosis was present in 33% of OSSN. Immunohistochemically 17.1% conjunctival papillomas stained positive for HPV antigen, all cases of OSSN were negative for HPV. There was no correlation between koilocytosis or actinic keratosis and the detection of HPV antigen. Conclusions: The association between HPV and conjunctival neoplasias is variable in different geographical areas and also depends on the methods of detection used. This study warrants the need for applying more advanced techniques at a molecular level to determine the possible etiology of HPV in conjunctival neoplasias among Asian-Indians. PMID:17699945

Cytologic features of hyperplastic epidermis.

PubMed

Eng, A M; Worobec, S

1977-10-01

The cytologic features of hyperplastic epidermis in common lesions such as verruca, seborrheic keratosis, condyloma accuminatum, fibroepithelial polyp, corn, radiodermatitis, prurigo nodularis, epidermal nevus, dermatofibroma, tricholemmona, inverted follicular keratosis and pseudoepitheliomatous hyperplasia were studied. Common, as well as distinguishing cytologic points are recognized.

Electrostatic interactions between the Bni1p formin FH2 domain and actin influence actin filament nucleation

DOE PAGES

Baker, Joseph L.; Courtemanche, Naomi; Parton, Daniel L.; ...

2014-12-04

Formins catalyze nucleation and growth of actin filaments. In this paper, we study the structure and interactions of actin with the FH2 domain of budding yeast formin Bni1p. We built an all-atom model of the formin dimer on an Oda actin filament 7-mer and studied structural relaxation and interprotein interactions by molecular dynamics simulations. These simulations produced a refined model for the FH2 dimer associated with the barbed end of the filament and showed electrostatic interactions between the formin knob and actin target-binding cleft. Mutations of two formin residues contributing to these interactions (R1423N, K1467L, or both) reduced the interactionmore » energies between the proteins, and in coarse-grained simulations, the formin lost more interprotein contacts with an actin dimer than with an actin 7-mer. Finally, biochemical experiments confirmed a strong influence of these mutations on Bni1p-mediated actin filament nucleation, but not elongation, suggesting that different interactions contribute to these two functions of formins.« less

Plasma levels of F-actin and F:G-actin ratio as potential new biomarkers in patients with septic shock.

PubMed

Belsky, Justin B; Morris, Daniel C; Bouchebl, Ralph; Filbin, Michael R; Bobbitt, Kevin R; Jaehne, Anja K; Rivers, Emanuel P

2016-01-01

To compare plasma levels of F-actin, G-actin and thymosin beta 4 (TB4) in humans with septic shock, noninfectious systemic inflammatory response syndrome (SIRS) and healthy controls. F-actin was significantly elevated in septic shock as compared with noninfectious SIRS and healthy controls. G-actin levels were greatest in the noninfectious SIRS group but significantly elevated in septic shock as compared with healthy controls. TB4 was not detectable in the septic shock or noninfectious SIRS group above the assay's lowest detection range (78 ng/ml). F-actin is significantly elevated in patients with septic shock as compared with noninfectious SIRS. F-actin and the F:G-actin ratio are potential biomarkers for the diagnosis of septic shock.

A systems-biology approach to yeast actin cables.

PubMed

Drake, Tyler; Yusuf, Eddy; Vavylonis, Dimitrios

2012-01-01

We focus on actin cables in yeast as a model system for understanding cytoskeletal organization and the workings of actin itself. In particular, we highlight quantitative approaches on the kinetics of actin-cable assembly and methods of measuring their morphology by image analysis. Actin cables described by these studies can span greater lengths than a thousand end-to-end actin-monomers. Because of this difference in length scales, control of the actin-cable system constitutes a junction between short-range interactions - among actin-monomers and nucleating, polymerization-facilitating, side-binding, severing, and cross-linking proteins - and the emergence of cell-scale physical form as embodied by the actin cables themselves.

Stochastic Severing of Actin Filaments by Actin Depolymerizing Factor/Cofilin Controls the Emergence of a Steady Dynamical Regime

PubMed Central

Roland, Jeremy; Berro, Julien; Michelot, Alphée; Blanchoin, Laurent; Martiel, Jean-Louis

2008-01-01

Actin dynamics (i.e., polymerization/depolymerization) powers a large number of cellular processes. However, a great deal remains to be learned to explain the rapid actin filament turnover observed in vivo. Here, we developed a minimal kinetic model that describes key details of actin filament dynamics in the presence of actin depolymerizing factor (ADF)/cofilin. We limited the molecular mechanism to 1), the spontaneous growth of filaments by polymerization of actin monomers, 2), the ageing of actin subunits in filaments, 3), the cooperative binding of ADF/cofilin to actin filament subunits, and 4), filament severing by ADF/cofilin. First, from numerical simulations and mathematical analysis, we found that the average filament length, 〈L〉, is controlled by the concentration of actin monomers (power law: 5/6) and ADF/cofilin (power law: −2/3). We also showed that the average subunit residence time inside the filament, 〈T〉, depends on the actin monomer (power law: −1/6) and ADF/cofilin (power law: −2/3) concentrations. In addition, filament length fluctuations are ∼20% of the average filament length. Moreover, ADF/cofilin fragmentation while modulating filament length keeps filaments in a high molar ratio of ATP- or ADP-Pi versus ADP-bound subunits. This latter property has a protective effect against a too high severing activity of ADF/cofilin. We propose that the activity of ADF/cofilin in vivo is under the control of an affinity gradient that builds up dynamically along growing actin filaments. Our analysis shows that ADF/cofilin regulation maintains actin filaments in a highly dynamical state compatible with the cytoskeleton dynamics observed in vivo. PMID:18065447

Geometrical and Mechanical Properties Control Actin Filament Organization

PubMed Central

Ennomani, Hajer; Théry, Manuel; Nedelec, Francois; Blanchoin, Laurent

2015-01-01

The different actin structures governing eukaryotic cell shape and movement are not only determined by the properties of the actin filaments and associated proteins, but also by geometrical constraints. We recently demonstrated that limiting nucleation to specific regions was sufficient to obtain actin networks with different organization. To further investigate how spatially constrained actin nucleation determines the emergent actin organization, we performed detailed simulations of the actin filament system using Cytosim. We first calibrated the steric interaction between filaments, by matching, in simulations and experiments, the bundled actin organization observed with a rectangular bar of nucleating factor. We then studied the overall organization of actin filaments generated by more complex pattern geometries used experimentally. We found that the fraction of parallel versus antiparallel bundles is determined by the mechanical properties of actin filament or bundles and the efficiency of nucleation. Thus nucleation geometry, actin filaments local interactions, bundle rigidity, and nucleation efficiency are the key parameters controlling the emergent actin architecture. We finally simulated more complex nucleation patterns and performed the corresponding experiments to confirm the predictive capabilities of the model. PMID:26016478

Boolean gates on actin filaments

NASA Astrophysics Data System (ADS)

Siccardi, Stefano; Tuszynski, Jack A.; Adamatzky, Andrew

2016-01-01

Actin is a globular protein which forms long polar filaments in the eukaryotic cytoskeleton. Actin networks play a key role in cell mechanics and cell motility. They have also been implicated in information transmission and processing, memory and learning in neuronal cells. The actin filaments have been shown to support propagation of voltage pulses. Here we apply a coupled nonlinear transmission line model of actin filaments to study interactions between voltage pulses. To represent digital information we assign a logical TRUTH value to the presence of a voltage pulse in a given location of the actin filament, and FALSE to the pulse's absence, so that information flows along the filament with pulse transmission. When two pulses, representing Boolean values of input variables, interact, then they can facilitate or inhibit further propagation of each other. We explore this phenomenon to construct Boolean logical gates and a one-bit half-adder with interacting voltage pulses. We discuss implications of these findings on cellular process and technological applications.

Actin filaments-A target for redox regulation.

PubMed

Wilson, Carlos; Terman, Jonathan R; González-Billault, Christian; Ahmed, Giasuddin

2016-10-01

Actin and its ability to polymerize into dynamic filaments is critical for the form and function of cells throughout the body. While multiple proteins have been characterized as affecting actin dynamics through noncovalent means, actin and its protein regulators are also susceptible to covalent modifications of their amino acid residues. In this regard, oxidation-reduction (Redox) intermediates have emerged as key modulators of the actin cytoskeleton with multiple different effects on cellular form and function. Here, we review work implicating Redox intermediates in post-translationally altering actin and discuss what is known regarding how these alterations affect the properties of actin. We also focus on two of the best characterized enzymatic sources of these Redox intermediates-the NADPH oxidase NOX and the flavoprotein monooxygenase MICAL-and detail how they have both been identified as altering actin, but share little similarity and employ different means to regulate actin dynamics. Finally, we discuss the role of these enzymes and redox signaling in regulating the actin cytoskeleton in vivo and highlight their importance for neuronal form and function in health and disease. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Actin dynamics in Amoeba proteus motility.

PubMed

Pomorski, P; Krzemiński, P; Wasik, A; Wierzbicka, K; Barańska, J; Kłopocka, W

2007-01-01

We studied the distribution of the endogenous Arp2/3 complex in Amoeba proteus and visualised the ratio of filamentous (F-actin) to total actin in living cells. The presented results show that in the highly motile Amoeba proteus, Arp2/3 complex-dependent actin polymerisation is involved in the formation of the branching network of the contractile layer, adhesive structures, and perinuclear cytoskeleton. The aggregation of the Arp2/3 complex in the cortical network, with the exception of the uroid and advancing fronts, and the spatial orientation of microfilaments at the leading edge suggest that actin polymerisation in this area is not sufficient to provide the driving force for membrane displacement. The examined proteins were enriched in the pinocytotic pseudopodia and the perinuclear cytoskeleton in pinocytotic amoebae. In migrating amoebae, the course of changes in F-actin concentration corresponded with the distribution of tension in the cell cortex. The maximum level of F-actin in migrating amoebae was observed in the middle-posterior region and in the front of retracting pseudopodia. Arp2/3 complex-dependent actin polymerisation did not seem to influence F-actin concentration. The strongly condensed state of the microfilament system could be attributed to strong isometric contraction of the cortical layer accompanied by its retraction from distal cell regions. Isotonic contraction was limited to the uroid.

Autofluorescence of seborrheic keratosis (warts) and of tissue surrounding malignant tumors

NASA Astrophysics Data System (ADS)

Lohmann, Wolfgang; Schill, Wolf-Bernhard; Bohle, Rainer M.; Dreyer, Thomas

1997-12-01

Autofluorescence measurements on human tissue have revealed a decrease in intensity in malignant tumors and an increase in the healthy region adjacent to the tumor. This latter event might serve as a protective wall against the invasive tumor cells. The composition of this wall is still unknown. Antioxidants such as NADH might be involved. In the case of seborrheic keratosis (wart), the intensity is increased in the pigmented spots. Care must be taken, therefore, when warts are attached to malignant tumors. The resulting value is, then, not indicative for the condition of the system.

Oral mucosal lesions in older people: relation to salivary secretion, systemic diseases and medications.

PubMed

Lynge Pedersen, A M; Nauntofte, B; Smidt, D; Torpet, L A

2015-09-01

To determine the prevalence of oral mucosal lesions in a sample of older Danish people and to investigate their associations with age, gender, systemic diseases, medications, xerostomia and salivary secretion. A total of 668 community-dwelling individuals aged 65-95 years underwent a clinical examination, measurements of unstimulated and stimulated whole and labial salivary flow rates and an interview regarding xerostomia, general health, medication, tobacco and alcohol habits. Seventy-five per cent of all participants and 70% of the non-medicated ones had one or more oral mucosal lesions. The most prevalent lesions were lingual varicosities (28.3%), denture stomatitis (12.7%), candidiasis (11.8%), fissured tongue (9.1%) and frictional keratosis (8.4%). Lesions were generally associated with smoking and xerostomia. Varicosities were more common in participants with systemic diseases and medication intake, particularly with cardiovascular diseases and agents. Fissured tongue and atrophic tongue were associated with female gender, xerostomia and low unstimulated whole and labial salivary secretion. Oral candidiasis was associated with older age; being male; current smoker; having >3 diseases, intake of medications and low salivary flow rates; and identified in relation to denture stomatitis, fissured tongue and atrophic tongue and median rhomboid glossitis. Oral mucosal lesions are prevalent in older Danish people and generally associated with changes in both local and systemic factors. Tongue lesions in particular appeared as indicators that may identify patients with specific need of oral intervention. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A Systems-Biology Approach to Yeast Actin Cables

PubMed Central

Drake, Tyler; Yusuf, Eddy; Vavylonis, Dimitrios

2011-01-01

We focus on actin cables in yeast as a model system for understanding cytoskeletal organization and the workings of actin itself. In particular, we highlight quantitative approaches on the kinetics of actin cable assembly and methods of measuring their morphology by image analysis. Actin cables described by these studies can span greater lengths than a thousand end-to-end actin monomers. Because of this difference in length scales, control of the actin-cable system constitutes a junction between short-range interactions—among actin monomers and nucleating, polymerization-facilitating, side-binding, severing, and cross-linking proteins—and the emergence of cell-scale physical form as embodied by the actin cables themselves. PMID:22161338

Allele-specific Effects of Human Deafness γ-Actin Mutations (DFNA20/26) on the Actin/Cofilin Interaction*

PubMed Central

Bryan, Keith E.; Rubenstein, Peter A.

2009-01-01

Auditory hair cell function requires proper assembly and regulation of the nonmuscle gamma isoactin-rich cytoskeleton, and six point mutations in this isoactin cause a type of delayed onset autosomal dominant nonsyndromic progressive hearing loss, DFNA20/26. The molecular basis underlying this actin-dependent hearing loss is unknown. To address this problem, the mutations have been introduced into yeast actin, and their effects on actin function were assessed in vivo and in vitro. Because we previously showed that polymerization was unaffected in five of the six mutants, we have focused on proteins that regulate actin, in particular cofilin, which severs F-actin and sequesters actin monomers. The mutations do not affect the interaction of cofilin with G-actin. However, T89I and V370A mutant F-actins are much more susceptible to cofilin disassembly than WT filaments in vitro. Conversely, P332A filaments demonstrate enhanced resistance. Wild type actin solutions containing T89I, K118M, or P332A mutant actins at mole fractions similar to those found in the hair cell respond in vitro toward cofilin in a manner proportional to the level of the mutant present. Finally, depression of cofilin action in vivo by elimination of the cofilin-activating protein, Aip1p, rescues the inability to grow on glycerol caused by K118M, T278I, P332A, and V370A. These results suggest that a filament instability caused by these mutations can be balanced by decreasing a system in vivo that promotes increased filament turnover. Such mutant-dependent filament destabilization could easily result in hair cell malfunction leading to the late-onset hearing loss observed in these patients. PMID:19419963

F-Actin Dynamics in Neurospora crassa ▿ †

PubMed Central

Berepiki, Adokiye; Lichius, Alexander; Shoji, Jun-Ya; Tilsner, Jens; Read, Nick D.

2010-01-01

This study demonstrates the utility of Lifeact for the investigation of actin dynamics in Neurospora crassa and also represents the first report of simultaneous live-cell imaging of the actin and microtubule cytoskeletons in filamentous fungi. Lifeact is a 17-amino-acid peptide derived from the nonessential Saccharomyces cerevisiae actin-binding protein Abp140p. Fused to green fluorescent protein (GFP) or red fluorescent protein (TagRFP), Lifeact allowed live-cell imaging of actin patches, cables, and rings in N. crassa without interfering with cellular functions. Actin cables and patches localized to sites of active growth during the establishment and maintenance of cell polarity in germ tubes and conidial anastomosis tubes (CATs). Recurrent phases of formation and retrograde movement of complex arrays of actin cables were observed at growing tips of germ tubes and CATs. Two populations of actin patches exhibiting slow and fast movement were distinguished, and rapid (1.2 μm/s) saltatory transport of patches along cables was observed. Actin cables accumulated and subsequently condensed into actin rings associated with septum formation. F-actin organization was markedly different in the tip regions of mature hyphae and in germ tubes. Only mature hyphae displayed a subapical collar of actin patches and a concentration of F-actin within the core of the Spitzenkörper. Coexpression of Lifeact-TagRFP and β-tubulin–GFP revealed distinct but interrelated localization patterns of F-actin and microtubules during the initiation and maintenance of tip growth. PMID:20139238

Control of the actin cytoskeleton in root hair development.

PubMed

Pei, Weike; Du, Fei; Zhang, Yi; He, Tian; Ren, Haiyun

2012-05-01

The development of root hair includes four stages: bulge site selection, bulge formation, tip growth, and maturation. The actin cytoskeleton is involved in all of these stages and is organized into distinct arrangements in the different stages. In addition to the actin configuration, actin isoforms also play distinct roles in the different stages. The actin cytoskeleton is regulated by actin-binding proteins, such as formin, Arp2/3 complex, profilin, actin depolymerizing factor, and villin. Some upstream signals, i.e. calcium, phospholipids, and small GTPase regulate the activity of these actin-binding proteins to produce the proper actin configuration. We constructed a working model on how the actin cytoskeleton is controlled by actin-binding proteins and upstream signaling in root hair development based on the current literature: at the tip of hairs, actin polymerization appears to be facilitated by Arp2/3 complex that is activated by small GTPase, and profilin that is regulated by phosphatidylinositol 4,5-bisphosphate. Meanwhile, actin depolymerization and turnover are likely mediated by villin and actin depolymerizing factor, which are stimulated by calcium. At the shank, actin cables are produced by formin and villin. Under the complicated interaction, the actin cytoskeleton is controlled spatially and temporally during root hair development. © 2012 Elsevier Ireland Ltd. All rights reserved.

Disrupting actin-myosin-actin connectivity in airway smooth muscle as a treatment for asthma?

PubMed

Lavoie, Tera L; Dowell, Maria L; Lakser, Oren J; Gerthoffer, William T; Fredberg, Jeffrey J; Seow, Chun Y; Mitchell, Richard W; Solway, Julian

2009-05-01

Breathing is known to functionally antagonize bronchoconstriction caused by airway muscle contraction. During breathing, tidal lung inflation generates force fluctuations that are transmitted to the contracted airway muscle. In vitro, experimental application of force fluctuations to contracted airway smooth muscle strips causes them to relengthen. Such force fluctuation-induced relengthening (FFIR) likely represents the mechanism by which breathing antagonizes bronchoconstriction. Thus, understanding the mechanisms that regulate FFIR of contracted airway muscle could suggest novel therapeutic interventions to increase FFIR, and so to enhance the beneficial effects of breathing in suppressing bronchoconstriction. Here we propose that the connectivity between actin filaments in contracting airway myocytes is a key determinant of FFIR, and suggest that disrupting actin-myosin-actin connectivity by interfering with actin polymerization or with myosin polymerization merits further evaluation as a potential novel approach for preventing prolonged bronchoconstriction in asthma.

Structure of the Rigor Actin-Tropomyosin-Myosin Complex

PubMed Central

Behrmann, Elmar; Müller, Mirco; Penczek, Pawel A.; Mannherz, Hans Georg; Manstein, Dietmar J.; Raunser, Stefan

2014-01-01

The interaction of myosin with actin filaments is the central feature of muscle contraction and cargo movement along actin filaments of the cytoskeleton. Myosin converts the chemical energy stored in ATP into force and movement along actin filaments. Myosin binding to actin induces conformational changes that are coupled to the nucleotide-binding pocket and amplified by a specialized region of the motor domain for efficient force generation. Tropomyosin plays a key role in regulating the productive interaction between myosins and actin. Here, we report the 8 Å resolution structure of the actin-tropomyosin-myosin complex determined by cryo electron microscopy. The pseudo-atomic model of the complex obtained from fitting crystal structures into the map defines the large actin-myosin-tropomyosin interface and the molecular interactions between the proteins in detail and allows us to propose a structural model for tropomyosin dependent myosin binding to actin and actin-induced nucleotide release from myosin. PMID:22817895

Daylight-mediated photodynamic therapy in Spain: advantages and disadvantages.

PubMed

Pérez-Pérez, L; García-Gavín, J; Gilaberte, Y

2014-09-01

Photodynamic therapy (PDT) is an option for the treatment of actinic keratosis, Bowen disease, and certain types of basal cell carcinoma. It is also used to treat various other types of skin condition, including inflammatory and infectious disorders. The main disadvantages of PDT are the time it takes to administer (both for the patient and for health professionals) and the pain associated with treatment. Daylight-mediated PDT has recently been reported to be an alternative to the conventional approach. Several studies have shown it to be similar in efficacy to and better tolerated than classic PDT for the treatment of mild to moderate actinic keratosis. Nevertheless, most of these studies are from northern Europe, and no data have been reported from southern Europe. The present article reviews the main studies published to date, presents the treatment protocol, and summarizes our experience with a group of treated patients. Copyright © 2013 Elsevier España, S.L.U. y AEDV. All rights reserved.

Actin Age Orchestrates Myosin-5 and Myosin-6 Runlengths

PubMed Central

Zimmermann, Dennis; Santos, Alicja; Kovar, David R.; Rock, Ronald S.

2015-01-01

Summary Unlike a static and immobile skeleton, the actin cytoskeleton is a highly dynamic network of filamentous actin (F-actin) polymers that continuously turn over. In addition to generating mechanical forces and sensing mechanical deformation, dynamic F-actin networks serve as cellular tracks for myosin motor traffic. However, much of our mechanistic understanding of processive myosins comes from in vitro studies where motility was studied on pre-assembled and artificially stabilized, static F-actin tracks. In this work, we examine the role of actin dynamics in single-molecule myosin motility using assembling F-actin and the two highly processive motors, myosin-5 and myosin-6. These two myosins have distinct functions in the cell and travel in opposite directions along actin filaments [1–3]. Myosin-5 walks towards the barbed ends of F-actin, traveling to sites of actin polymerization at the cell periphery [4]. Myosin-6 walks towards the pointed end of F-actin [5], traveling towards the cell center along older segments of the actin filament. We find that myosin-5 takes 1.3 to 1.5-fold longer runs on ADP•Pi (young) F-actin, while myosin-6 takes 1.7 to 3.6-fold longer runs along ADP (old) F-actin. These results suggest that conformational differences between ADP•Pi and ADP F-actin tailor these myosins to walk farther toward their preferred actin filament end. Taken together, these experiments define a new mechanism by which myosin traffic may sort to different F-actin networks depending on filament age. PMID:26190073

Actin expression in some Platyhelminthe species.

PubMed

Fagotti, A; Panara, F; Di Rosa, I; Simoncelli, F; Gabbiani, G; Pascolini, R

1994-10-01

Actin expression in some Platyhelminthe species was demonstrated by western-blotting and immunocytochemical analysis using two distinct anti-actin antibodies: the anti-total actin that reacts against all actin isoforms of higher vertebrates and the anti-alpha SM-1 that recognizes the alpha-smooth muscle (alpha SM) isotype of endothermic vertebrates (Skalli et al., 1986). Western-blotting experiments showed that all species tested, including some free-living Platyhelminthes (Tricladida and Rhabdocoela) and the parasitic Fasciola hepatica, were stained by anti-total actin antibody while only Dugesidae and Dendrocoelidae showed a positive immunoreactivity against anti-alpha SM-1. These results were confirmed by cytochemical immunolocalization using both avidin biotin conjugated peroxidase reaction on paraffin sections, and immunogold staining on Lowicryl 4KM embedded specimens. Our findings may contribute to the understanding of Platyhelminthes phylogeny.

Bulkiness or aromatic nature of tyrosine-143 of actin is important for the weak binding between F-actin and myosin-ADP-phosphate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gomibuchi, Yuki; Uyeda, Taro Q.P.; Wakabayashi, Takeyuki, E-mail: tw007@nasu.bio.teikyo-u.ac.jp

2013-11-29

Highlights: •The effect of mutation of Tyr143 that becomes more exposed on assembly was examined. •Mutation of tyrosine-143 of Dictyostelium actin changed actin polymerizability. •The bulkiness or aromatic nature of Tyr143 is important for the weak binding. •The weak interaction between myosin and actin strengthened by Tyr143Trp mutation. -- Abstract: Actin filaments (F-actin) interact with myosin and activate its ATPase to support force generation. By comparing crystal structures of G-actin and the quasi-atomic model of F-actin based on high-resolution cryo-electron microscopy, the tyrosine-143 was found to be exposed more than 60 Å{sup 2} to the solvent in F-actin. Because tyrosine-143more » flanks the hydrophobic cleft near the hydrophobic helix that binds to myosin, the mutant actins, of which the tyrosine-143 was replaced with tryptophan, phenylalanine, or isoleucine, were generated using the Dictyostelium expression system. It polymerized significantly poorly when induced by NaCl, but almost normally by KCl. In the presence of phalloidin and KCl, the extents of the polymerization of all the mutant actins were comparable to that of the wild-type actin so that the actin-activated myosin ATPase activity could be reliably compared. The affinity of skeletal heavy meromyosin to F-actin and the maximum ATPase activity (V{sub max}) were estimated by a double reciprocal plot. The Tyr143Trp-actin showed the higher affinity (smaller K{sub app}) than that of the wild-type actin, with the V{sub max} being almost unchanged. The K{sub app} and V{sub max} of the Tyr143Phe-actin were similar to those of the wild-type actin. However, the activation by Tyr143Ile-actin was much smaller than the wild-type actin and the accurate determination of K{sub app} was difficult. Comparison of the myosin ATPase activated by the various mutant actins at the same concentration of F-actin showed that the extent of activation correlates well with the solvent-accessible surface areas

Actin growth profile in clathrin-mediated endocytosis

NASA Astrophysics Data System (ADS)

Tweten, D. J.; Bayly, P. V.; Carlsson, A. E.

2017-05-01

Clathrin-mediated endocytosis in yeast is driven by a protein patch containing close to 100 different types of proteins. Among the proteins are 5000 -10 000 copies of polymerized actin, and successful endocytosis requires growth of the actin network. Since it is not known exactly how actin network growth drives endocytosis, we calculate the spatial distribution of actin growth required to generate the force that drives the process. First, we establish the force distribution that must be supplied by actin growth, by combining membrane-bending profiles obtained via electron microscopy with established theories of membrane mechanics. Next, we determine the profile of actin growth, using a continuum mechanics approach and an iterative procedure starting with an actin growth profile obtained from a linear analysis. The profile has fairly constant growth outside a central hole of radius 45-50 nm, but very little growth in this hole. This growth profile can reproduce the required forces if the actin shear modulus exceeds 80 kPa, and the growing filaments can exert very large polymerization forces. The growth profile prediction could be tested via electron-microscopy or super-resolution experiments in which the turgor pressure is suddenly turned off.

Interactions of histatin-3 and histatin-5 with actin.

PubMed

Blotnick, Edna; Sol, Asaf; Bachrach, Gilad; Muhlrad, Andras

2017-03-06

Histatins are histidine rich polypeptides produced in the parotid and submandibular gland and secreted into the saliva. Histatin-3 and -5 are the most important polycationic histatins. They possess antimicrobial activity against fungi such as Candida albicans. Histatin-5 has a higher antifungal activity than histatin-3 while histatin-3 is mostly involved in wound healing in the oral cavity. We found that these histatins, like other polycationic peptides and proteins, such as LL-37, lysozyme and histones, interact with extracellular actin. Histatin-3 and -5 polymerize globular actin (G-actin) to filamentous actin (F-actin) and bundle F-actin filaments. Both actin polymerization and bundling by histatins is pH sensitive due to the high histidine content of histatins. In spite of the equal number of net positive charges and histidine residues in histatin-3 and -5, less histatin-3 is needed than histatin-5 for polymerization and bundling of actin. The efficiency of actin polymerization and bundling by histatins greatly increases with decreasing pH. Histatin-3 and -5 induced actin bundles are dissociated by 100 and 50 mM NaCl, respectively. The relatively low NaCl concentration required to dissociate histatin-induced bundles implies that the actin-histatin filaments bind to each other mainly by electrostatic forces. The binding of histatin-3 to F-actin is stronger than that of histatin-5 showing that hydrophobic forces have also some role in histatin-3- actin interaction. Histatins affect the fluorescence of probes attached to the D-loop of G-actin indicating histatin induced changes in actin structure. Transglutaminase cross-links histatins to actin. Competition and limited proteolysis experiments indicate that the main histatin cross-linking site on actin is glutamine-49 on the D-loop of actin. Both histatin-3 and -5 interacts with actin, however, histatin 3 binds stronger to actin and affects actin structure at lower concentration than histatin-5 due to the extra 8

A dynamic formin-dependent deep F-actin network in axons

PubMed Central

Ganguly, Archan; Tang, Yong; Wang, Lina; Ladt, Kelsey; Loi, Jonathan; Dargent, Bénédicte; Leterrier, Christophe

2015-01-01

Although actin at neuronal growth cones is well-studied, much less is known about actin organization and dynamics along axon shafts and presynaptic boutons. Using probes that selectively label filamentous-actin (F-actin), we found focal “actin hotspots” along axons—spaced ∼3–4 µm apart—where actin undergoes continuous assembly/disassembly. These foci are a nidus for vigorous actin polymerization, generating long filaments spurting bidirectionally along axons—a phenomenon we call “actin trails.” Super-resolution microscopy reveals intra-axonal deep actin filaments in addition to the subplasmalemmal “actin rings” described recently. F-actin hotspots colocalize with stationary axonal endosomes, and blocking vesicle transport diminishes the actin trails, suggesting mechanistic links between vesicles and F-actin kinetics. Actin trails are formin—but not Arp2/3—dependent and help enrich actin at presynaptic boutons. Finally, formin inhibition dramatically disrupts synaptic recycling. Collectively, available data suggest a two-tier F-actin organization in axons, with stable “actin rings” providing mechanical support to the plasma membrane and dynamic "actin trails" generating a flexible cytoskeletal network with putative physiological roles. PMID:26216902

[Chronic ulceration of the hand in a mechanic: epidermoid carcinoma should be suspected].

PubMed

Naciri, Ilhame; Hassam, Baderddine

2017-01-01

Cutaneous squamous cell carcinoma is a malignant tumor developed from the epidermis or the squamous mucosa. It may occur de novo or, most often, on precancerous lesions, including actinic keratoses. This tumor can sometimes be secondary to physical or chemical hazardous conditions encountered during the professional activity. We here report the case of a 40-year old mechanic presenting with ulceration of the dorsal side of his right wrist, evolving over 6 months. The lesion had first appeared as a small keratosic lesion that had transformed into an erosion and then into an ulceration increasing rapidly in size. The patient had no initial trauma and he had no particular previous history except the handling of chemicals (fuels, mineral oil, paint) without gloves for about the last 30 years. Physical examination showed a large sized ulcero-budding tumor (5 × 6 cm) on the dorsal side of his right wrist (A), associated with diffuse multiple actinic keratosis lesions on his two forearms and on the back of his hands (B). The patient also had two painless hard mobile adenopathies measuring 1.5 cm in diameter, on the ipsilateral epitrochlear and axillary regions. The remainder of the clinical examination was normal. Viral hepatitis serology test, treponemal test and retrovirus (HIV) test were negative. Histological examination of a biopsy sample confirmed the diagnosis of well differentiated and infiltrating squamous cell carcinoma. The biopsy of the axillary adenopathy objectified ganglionic metastasis with capsular break-in and extension to the periganglionar tissue. The remainder of the staging was without abnormalities. The patient underwent wide resection of the lesion with lymph node dissection followed by radiation therapy. Patient's evolution was marked by early local recurrence (two months later) requiring reoperation. The postoperative course was uneventful.

Three’s company: The fission yeast actin cytoskeleton

PubMed Central

Kovar, David R.; Sirotkin, Vladimir; Lord, Matthew

2010-01-01

How the actin cytoskeleton assembles into different structures to drive diverse cellular processes is a fundamental cell biological question. In addition to orchestrating the appropriate combination of regulators and actin-binding proteins, different actin-based structures must insulate themselves from one another to maintain specificity within a crowded cytoplasm. Actin specification is particularly vexing in complex eukaryotes where a multitude of protein isoforms and actin structures operate within the same cell. Fission yeast Schizosaccharomyces pombe possesses a single actin isoform that functions in three distinct structures throughout the cell cycle. In this review, we explore recent studies in fission yeast that help unravel how different actin structures operate in cells. PMID:21145239

Microtopographic Inspection and Fractal Analysis of Skin Neoplasia

NASA Astrophysics Data System (ADS)

Costa, Manuel F. M.; Hipolito, Alberto Valencia; Gutierrez, Gustavo Fidel; Chanona, Jorge; Gallegos, Eva Ramón

2008-04-01

Early detection of skin cancer is fundamental to a successful treatment. Changes in the shape, including the relief, of skin lesions are an indicator of a possible malignity. Optical microtopographic inspection of skin lesions can be used to identify diagnostic patterns of benign and malign skin' lesions. Statistical parameters like the mean roughness (Ra) may allow the discrimination between different types of lesions and degree of malignity. Fractal analysis of bi-dimensional and 3D images of skin lesions can validate or complement that assessment by calculation of its fractal dimensions (FD). On the study herein reported the microtopographic inspection of the skin lesions were performed using the optical triangulation based microtopographer developed at the Physics Department of the University of Minho, MICROTOP.03.MFC. The patients that participated in this research work were men and women older than 15 years with the clinical and histopathology diagnoses of: melanoma, basocellular carcinoma, epidermoide carcinoma, actinic keratosis, keratoacantosis and benign nevus. Latex impressions of the lesions were taken and microtopographically analyzed. Characteristic information for each type of studied lesion was obtained. For melanoma it was observed that on the average these tumors present an increased roughness of around 67 percent compared to the roughness of the healthy skin. This feature allows the distinction from other tumors as basocellular carcinoma (were the roughness increase was in the average of 49 percent) and benign lesions as the epidermoide cyst (37 percent) or the seborrhea keratosis (4 percent). Tumor size and roughness are directly proportional to the grade of malignality. The characterization of the fractal geometry of 2D (histological slides) and 3D images of skin lesions was performed by obtaining its FD evaluated by means of the Box counting method. Results obtained showed that the average fractal dimension of histological slide images (FDh

The nature of the globular- to fibrous-actin transition.

PubMed

Oda, Toshiro; Iwasa, Mitsusada; Aihara, Tomoki; Maéda, Yuichiro; Narita, Akihiro

2009-01-22

Actin plays crucial parts in cell motility through a dynamic process driven by polymerization and depolymerization, that is, the globular (G) to fibrous (F) actin transition. Although our knowledge about the actin-based cellular functions and the molecules that regulate the G- to F-actin transition is growing, the structural aspects of the transition remain enigmatic. We created a model of F-actin using X-ray fibre diffraction intensities obtained from well oriented sols of rabbit skeletal muscle F-actin to 3.3 A in the radial direction and 5.6 A along the equator. Here we show that the G- to F-actin conformational transition is a simple relative rotation of the two major domains by about 20 degrees. As a result of the domain rotation, the actin molecule in the filament is flat. The flat form is essential for the formation of stable, helical F-actin. Our F-actin structure model provides the basis for understanding actin polymerization as well as its molecular interactions with actin-binding proteins.

Pattern of galectins expression in actinic cheilitis with different risks of malignant transformation.

PubMed

Lopes, Maria Luiza Diniz de Sousa; Nonaka, Cassiano Francisco Weege; Queiroz, Lélia Maria Guedes; de Souza, Lélia Batista; Miguel, Márcia Cristina da Costa; da Silveira, Éricka Janine Dantas

2016-09-01

Actinic cheilitis (AC) is a chronic inflammatory lesion that in some situations can turn into squamous cell carcinoma of the lip. The molecular mechanisms involved in this process are not yet completely understood. This study aimed to investigate the expression pattern of galectins in actinic cheilitis according to the histopathological grading. Immunoexpression of galectin-1, galectin-3, galectin-7, and galectin-9 was semiquantitatively analyzed in 65 cases of actinic cheilitis graded as low risk (n = 40) or high risk (n = 25) of malignant transformation. Association between the location of the galectins in the cellular compartments and histopathological grading was analyzed. Galectin-1 was mainly observed in the cell cytoplasm, and was elevated (score 3) in 60% of cases, regardless of the histopathological grade (P > 0.05). Galectin-3 expression was higher in high-risk group than in the low-risk group (P < 0.05), with a predominant expression in the cytoplasm and nucleus of low-risk (67.5%), and only in the cytoplasm of high-risk cases (60%) (P < 0.05). Galectin-7 expression did not show significant differences between low-risk and high-risk groups (P > 0.05). With respect to galectin-9, 89.2% of cases were positive, showing decrease in median of scores as there was an increase in histological grade (P < 0.001), with predominant expression in the nucleus and cytoplasm. This study is the first indication of galectins involvement in the pathogenesis and morphologic progression of actinic cheilitis, particularly galectin-3 and galectin-9. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Recruitment Kinetics of Tropomyosin Tpm3.1 to Actin Filament Bundles in the Cytoskeleton Is Independent of Actin Filament Kinetics.

PubMed

Appaduray, Mark A; Masedunskas, Andrius; Bryce, Nicole S; Lucas, Christine A; Warren, Sean C; Timpson, Paul; Stear, Jeffrey H; Gunning, Peter W; Hardeman, Edna C

2016-01-01

The actin cytoskeleton is a dynamic network of filaments that is involved in virtually every cellular process. Most actin filaments in metazoa exist as a co-polymer of actin and tropomyosin (Tpm) and the function of an actin filament is primarily defined by the specific Tpm isoform associated with it. However, there is little information on the interdependence of these co-polymers during filament assembly and disassembly. We addressed this by investigating the recovery kinetics of fluorescently tagged isoform Tpm3.1 into actin filament bundles using FRAP analysis in cell culture and in vivo in rats using intracellular intravital microscopy, in the presence or absence of the actin-targeting drug jasplakinolide. The mobile fraction of Tpm3.1 is between 50% and 70% depending on whether the tag is at the C- or N-terminus and whether the analysis is in vivo or in cultured cells. We find that the continuous dynamic exchange of Tpm3.1 is not significantly impacted by jasplakinolide, unlike tagged actin. We conclude that tagged Tpm3.1 may be able to undergo exchange in actin filament bundles largely independent of the assembly and turnover of actin.

Liquid behavior of cross-linked actin bundles.

PubMed

Weirich, Kimberly L; Banerjee, Shiladitya; Dasbiswas, Kinjal; Witten, Thomas A; Vaikuntanathan, Suriyanarayanan; Gardel, Margaret L

2017-02-28

The actin cytoskeleton is a critical regulator of cytoplasmic architecture and mechanics, essential in a myriad of physiological processes. Here we demonstrate a liquid phase of actin filaments in the presence of the physiological cross-linker, filamin. Filamin condenses short actin filaments into spindle-shaped droplets, or tactoids, with shape dynamics consistent with a continuum model of anisotropic liquids. We find that cross-linker density controls the droplet shape and deformation timescales, consistent with a variable interfacial tension and viscosity. Near the liquid-solid transition, cross-linked actin bundles show behaviors reminiscent of fluid threads, including capillary instabilities and contraction. These data reveal a liquid droplet phase of actin, demixed from the surrounding solution and dominated by interfacial tension. These results suggest a mechanism to control organization, morphology, and dynamics of the actin cytoskeleton.

Molecular cloning of actin genes in Trichomonas vaginalis and phylogeny inferred from actin sequences.

PubMed

Bricheux, G; Brugerolle, G

1997-08-01

The parasitic protozoan Trichomonas vaginalis is known to contain the ubiquitous and highly conserved protein actin. A genomic library and a cDNA library have been screened to identify and clone the actin gene(s) of T. vaginalis. The nucleotide sequence of one gene and its flanking regions have been determined. The open reading frame encodes a protein of 376 amino acids. The sequence is not interrupted by any introns and the promoter could be represented by a 10 bp motif close to a consensus motif also found upstream of most sequenced T. vaginalis genes. The five different clones isolated from the cDNA library have similar sequences and encode three actin proteins differing only by one or two amino acids. A phylogenetic analysis of 31 actin sequences by distance matrix and parsimony methods, using centractin as outgroup, gives congruent trees with Parabasala branching above Diplomonadida.

Tropomyosin inhibits ADF/cofilin-dependent actin filament dynamics.

PubMed

Ono, Shoichiro; Ono, Kanako

2002-03-18

Tropomyosin binds to actin filaments and is implicated in stabilization of actin cytoskeleton. We examined biochemical and cell biological properties of Caenorhabditis elegans tropomyosin (CeTM) and obtained evidence that CeTM is antagonistic to ADF/cofilin-dependent actin filament dynamics. We purified CeTM, actin, and UNC-60B (a muscle-specific ADF/cofilin isoform), all of which are derived from C. elegans, and showed that CeTM and UNC-60B bound to F-actin in a mutually exclusive manner. CeTM inhibited UNC-60B-induced actin depolymerization and enhancement of actin polymerization. Within isolated native thin filaments, actin and CeTM were detected as major components, whereas UNC-60B was present at a trace amount. Purified UNC-60B was unable to interact with the native thin filaments unless CeTM and other associated proteins were removed by high-salt extraction. Purified CeTM was sufficient to restore the resistance of the salt-extracted filaments from UNC-60B. In muscle cells, CeTM and UNC-60B were localized in different patterns. Suppression of CeTM by RNA interference resulted in disorganized actin filaments and paralyzed worms in wild-type background. However, in an ADF/cofilin mutant background, suppression of CeTM did not worsen actin organization and worm motility. These results suggest that tropomyosin is a physiological inhibitor of ADF/cofilin-dependent actin dynamics.

The ultrastructural features of the premalignant oral lesions.

PubMed

Olinici, Doiniţa; Cotrutz, Carmen Elena; Mihali, Ciprian Valentin; Grecu, Vasile Bogdan; Botez, Emanuela Ana; Stoica, Laura; Onofrei, Pavel; Condurache, Oana; Dimitriu, Daniela Cristina

2018-01-01

Premalignant oral lesions are among the most important risk factors for the development of oral squamocellular carcinoma. Recent population studies indicate a significant rise in the prevalence of leukoplakia, erythroplakia/erythroleukoplakia, actinic cheilitis, submucous fibrosis and erosive lichen planus. Since standard histopathological examination has numerous limitations regarding the accurate appreciation of potential malignant transformation, the present study aims to aid these evaluations using the transmission electron microscopy (TEM) technique, which emphasizes ultrastructural changes pertaining to this pathology. Oral mucosa fragments collected from 43 patients that were clinically and histopathologically diagnosed with leukoplakia, erosive actinic cheilitis and erosive lichen planus have been processed through the classic technique for the examination using TEM and were examined using a Philips CM100 transmission electron microscope. The electron microscopy study has confirmed the histopathological diagnosis of the tissue samples examined using photonic microscopy and has furthermore revealed a series of ultrastructural details that on the one hand indicate the tendency for malignant transformation, and on the other reveal characteristic features of tumor development. All the details furnished by TEM complete the overall picture of morphological changes, specific to these lesions, indicating the importance of using these techniques in establishing both a correct diagnosis and prognosis.

Bioinformatics study of the mangrove actin genes

NASA Astrophysics Data System (ADS)

Basyuni, M.; Wasilah, M.; Sumardi

2017-01-01

This study describes the bioinformatics methods to analyze eight actin genes from mangrove plants on DDBJ/EMBL/GenBank as well as predicted the structure, composition, subcellular localization, similarity, and phylogenetic. The physical and chemical properties of eight mangroves showed variation among the genes. The percentage of the secondary structure of eight mangrove actin genes followed the order of a helix > random coil > extended chain structure for BgActl, KcActl, RsActl, and A. corniculatum Act. In contrast to this observation, the remaining actin genes were random coil > extended chain structure > a helix. This study, therefore, shown the prediction of secondary structure was performed for necessary structural information. The values of chloroplast or signal peptide or mitochondrial target were too small, indicated that no chloroplast or mitochondrial transit peptide or signal peptide of secretion pathway in mangrove actin genes. These results suggested the importance of understanding the diversity and functional of properties of the different amino acids in mangrove actin genes. To clarify the relationship among the mangrove actin gene, a phylogenetic tree was constructed. Three groups of mangrove actin genes were formed, the first group contains B. gymnorrhiza BgAct and R. stylosa RsActl. The second cluster which consists of 5 actin genes the largest group, and the last branch consist of one gene, B. sexagula Act. The present study, therefore, supported the previous results that plant actin genes form distinct clusters in the tree.

Kinetics of Binding of Caldesmon to Actin*

PubMed Central

Chalovich, Joseph M.; Chen, Yi-der; Dudek, Ronald; Luo, Hai

2005-01-01

The time course of interaction of caldesmon with actin may be monitored by fluorescence changes that occur upon the binding of 12-(N-methyl-N-(7-nitrobenz-2-oxa-l,3-diazol-4-yl))-labeled caldesmon to actin or to acrylodan actin. The concentration dependence of the observed rate of caldesmon-actin binding was analyzed to a first approximation as a single-step reaction using a Monte Carlo simulation. The derived association and dissociation rates were 107 m−1 s−1 and 18.2 s−1, respectively. Smooth muscle tropomyosin enhances the binding of caldesmon to actin, and this was found to be due to a reduction in the rate of dissociation to 6.3 s −1. There is no evidence from this study for a different mechanism of binding in the presence of tropomyosin. The fluorescence changes that occurred with the binding of 12-(N-methyl-N-(7-nitrobenz-2-oxa-l,3-diazol-4-yl))-labeled caldesmon to actin or actin-tropomyosin were reversed by the addition of myosin subfragment 1 as predicted by a competitive binding mechanism. PMID:7730374

Are non-muscle actin isoforms functionally equivalent?

PubMed

Simiczyjew, Aleksandra; Pietraszek-Gremplewicz, Katarzyna; Mazur, Antonina Joanna; Nowak, Dorota

2017-11-01

Actin is highly conserved and it is the most widespread protein in eukaryotic cells. One of the most important features of actin, which allows it to have many different functions, is its ability to polymerize and interact with many other proteins. Actins are the major constituent of the actin cytoskeleton, which is an important system that is involved in various aspects of cell function, including cell motility, structure, integrity, regulation of signal transduction and transcription. Six mammal actin isoforms are highly conserved and share common functions. Two of them, β and γ non-muscle actin isoforms, which differ only by four amino acids located at the N-terminus of the polypeptide chain, are required for survival and proper cell functioning. We also summarized data about actbl2, which is suggested to be a newly discovered isoactin. Here, we review the current knowledge about tissue-specific expression of the non-muscle actin isoforms and possible functional differences between them. We also discuss molecular tools, which in recent years have allowed for a better understanding of the role of these proteins in cell functioning.

Low-dose 5-fluorouracil in combination with salicylic acid for the treatment of actinic keratoses on the hands and/or forearms - results of a non-interventional study.

PubMed

Reinhold, U; Hadshiew, I; Melzer, A; Prechtl, A

2017-03-01

As an in situ carcinoma, actinic keratoses should be treated early. Previous studies on the efficacy of a low-dose 0.5% 5-fluorouracil solution in combination with 10% salicylic acid (low-dose 5-FU/SA) are mostly related to lesions appearing on the head and face. In contrast, actinic keratoses (AK) lesions of the upper extremities are considered to be difficult to treat. The efficacy of low-dose 5-FU/SA in the treatment of actinic keratoses on the hands and/or forearms was studied for the first time in this non-interventional study (NIS) under practical conditions in a large patient population. In addition to the clinical course during therapy and a follow-up period, the length of application and adherence were documented. As part of this NIS, 649 patients with AK were treated at 207 centres with low-dose 5-FU/SA. The data of the study were recorded at baseline, optionally during an intermediate examination, at the end of therapy and during a final assessment. The average number of AK lesions decreased during the entire observation period by 92%. Side-effects were documented only rarely in the form of local skin reactions (2%). The attending physicians assessed the efficacy, tolerability and safety of the therapy as being predominantly very good or good (in each case ≥90%). AK lesions on the hands and/or forearms were effectively treated with low-dose 5-FU/SA under routine conditions in dermatological practice and the treatment was well tolerated. © 2016 European Academy of Dermatology and Venereology.

Demonstration of prominent actin filaments in the root columella

NASA Technical Reports Server (NTRS)

Collings, D. A.; Zsuppan, G.; Allen, N. S.; Blancaflor, E. B.; Brown, C. S. (Principal Investigator)

2001-01-01

The distribution of actin filaments within the gravity-sensing columella cells of plant roots remains poorly understood, with studies over numerous years providing inconsistent descriptions of actin organization in these cells. This uncertainty in actin organization, and thus in actin's role in graviperception and gravisignaling, has led us to investigate actin arrangements in the columella cells of Zea mays L., Medicago truncatula Gaertn., Linum usitatissiilium L. and Nicotianla benthamiana Domin. Actin organization was examined using a combination of optimized immunofluorescence techniques, and an improved fluorochrome-conjugated phalloidin labeling method reliant on 3-maleimidobenzoyl-N-hydroxy-succinimide ester (MBS) cross-linking combined with glycerol permeabilization. Confocal microscopy of root sections labeled with anti-actin antibodies revealed patterns suggestive of actin throughout the columella region. These patterns included short and fragmented actin bundles, fluorescent rings around amyloplasts and intense fluorescence originating from the nucleus. Additionally, confocal microscopy of MBS-stabilized and Alexa Fluor-phalloidin-labeled root sections revealed a previously undetected state of actin organization in the columella. Discrete actin structures surrounded the amyloplasts and prominent actin cables radiated from the nuclear surface toward the cell periphery. Furthermore, the cortex of the columella cells contained fine actin bundles (or single filaments) that had a predominant transverse orientation. We also used confocal microscopy of plant roots expressing endoplasmic reticulum (ER)-targeted green fluorescent protein to demonstrate rapid ER movements within the columella cells, suggesting that the imaged actin network is functional. The successful identification of discrete actin structures in the root columella cells forms the perception and signaling.

Actin cable dynamics in budding yeast

PubMed Central

Yang, Hyeong-Cheol; Pon, Liza A.

2002-01-01

Actin cables, bundles of actin filaments that align along the long axis of budding yeast, are crucial for establishment of cell polarity. We fused green fluorescent protein (GFP) to actin binding protein 140 (Abp140p) and visualized actin cable dynamics in living yeast. We detected two populations of actin cables: (i) bud-associated cables, which extend from the bud along the mother-bud axis, and (ii) randomly oriented cables, which are relatively short. Time-lapse imaging of Abp140p–GFP revealed an apparent increase in the length of bud-associated actin cables. Analysis of movement of Abp140p–GFP fiduciary marks on bud-associated cables and fluorescence loss in photobleaching experiments revealed that this apparent elongation occurs by assembly of new material at the end of the cable within the bud and movement of the opposite end of the cable toward the tip of the mother cell distal to the bud. The rate of extension of the tip of an elongating actin cable is 0.29 ± 0.08 μm/s. Latrunculin A (Lat-A) treatment completely blocked this process. We also observed movement of randomly oriented cables around the cortex of cells at a rate of 0.59 ± 0.14 μm/s. Mild treatment with Lat-A did not affect the velocity of movement of randomly oriented cables. However, Lat-A treatment did increase the number of randomly oriented, motile cables per cell. Our observations suggest that establishment of bud-associated actin cables during the cell cycle is accomplished not by realignment of existing cables but by assembly of new cables within the bud or bud neck, followed by elongation. PMID:11805329

Utilization of 5-aminolevulinic acid in the photodynamic therapy of tumors: biochemical and photobiological aspects

NASA Astrophysics Data System (ADS)

Pottier, Roy H.; Kennedy, James C.

1994-03-01

Inherent in both plants and animals is the natural porphyrin, Protoporphyrin IX (Pp). Although Pp does not appear to have any intrinsic biological activity, it is a potent natural photosensitizer. When activated with ultraviolet or visible light, this photosensitizer can induce significant photodynamic effects on tissues, cells, subcellular elements, and macromolecules via the production of singlet oxygen. The biosynthesis of endogenous Pp is under strict enzymatic control. It is possible to bypass a rate controlling step and induce large, transient concentrations of Pp by the addition of exogenous 5-aminolevulinic acid (ALA). ALA may be administered systemically or topically. Much larger amounts of Pp are produced in certain types of tumor tissue than in adjacent normal tissue. Topically applied ALA can be used to treat a variety of skin lesions, including actinic keratosis, basal cell carcinomas and psoriasis.

From Cytoskeleton to Gene Expression: Actin in the Nucleus.

PubMed

Viita, Tiina; Vartiainen, Maria K

2017-01-01

Although most people still associate actin mainly with the cytoskeleton, several lines of evidence, with the earliest studies dating back to decades ago, have emphasized the importance of actin also inside the cell nucleus. Actin has been linked to many gene expression processes from gene activation to chromatin remodeling, but also to maintenance of genomic integrity and intranuclear movement of chromosomes and chromosomal loci. Recent advances in visualizing different forms and dynamic properties of nuclear actin have clearly advanced our understanding of the basic concepts by which actin operates in the nucleus. In this chapter we address the different breakthroughs in nuclear actin studies, as well as discuss the regulation nuclear actin and the importance of nuclear actin dynamics in relation to its different nuclear functions. Our aim is to highlight the fact that actin should be considered as an essential component of the cell nucleus, and its nuclear actions should be taken into account also in experiments on cytoplasmic actin networks.

A Continuum Model of Actin Waves in Dictyostelium discoideum

PubMed Central

Khamviwath, Varunyu; Hu, Jifeng; Othmer, Hans G.

2013-01-01

Actin waves are complex dynamical patterns of the dendritic network of filamentous actin in eukaryotes. We developed a model of actin waves in PTEN-deficient Dictyostelium discoideum by deriving an approximation of the dynamics of discrete actin filaments and combining it with a signaling pathway that controls filament branching. This signaling pathway, together with the actin network, contains a positive feedback loop that drives the actin waves. Our model predicts the structure, composition, and dynamics of waves that are consistent with existing experimental evidence, as well as the biochemical dependence on various protein partners. Simulation suggests that actin waves are initiated when local actin network activity, caused by an independent process, exceeds a certain threshold. Moreover, diffusion of proteins that form a positive feedback loop with the actin network alone is sufficient for propagation of actin waves at the observed speed of . Decay of the wave back can be caused by scarcity of network components, and the shape of actin waves is highly dependent on the filament disassembly rate. The model allows retraction of actin waves and captures formation of new wave fronts in broken waves. Our results demonstrate that a delicate balance between a positive feedback, filament disassembly, and local availability of network components is essential for the complex dynamics of actin waves. PMID:23741312

Actin filaments – a target for redox regulation

PubMed Central

Wilson, Carlos; Terman, Jonathan R.; González-Billault, Christian; Ahmed, Giasuddin

2016-01-01

Actin and its ability to polymerize into dynamic filaments is critical for the form and function of cells throughout the body. While multiple proteins have been characterized as affecting actin dynamics through non-covalent means, actin and its protein regulators are also susceptible to covalent modifications of their amino acid residues. In this regard, oxidation-reduction (Redox) intermediates have emerged as key modulators of the actin cytoskeleton with multiple different effects on cellular form and function. Here, we review work implicating Redox intermediates in post-translationally altering actin and discuss what is known regarding how these alterations affect the properties of actin. We also focus on two of the best characterized enzymatic sources of these Redox intermediates – the NADPH oxidase NOX and the flavoprotein monooxygenase MICAL – and detail how they have both been identified as altering actin, but share little similarity and employ different means to regulate actin dynamics. Finally, we discuss the role of these enzymes and redox signaling in regulating the actin cytoskeleton in vivo and highlight their importance for neuronal form and function in health and disease. PMID:27309342

Quantitative Kinetic Study of the Actin-Bundling Protein L-Plastin and of Its Impact on Actin Turn-Over

PubMed Central

Al Tanoury, Ziad; Schaffner-Reckinger, Elisabeth; Halavatyi, Aliaksandr; Hoffmann, Céline; Moes, Michèle; Hadzic, Ermin; Catillon, Marie; Yatskou, Mikalai; Friederich, Evelyne

2010-01-01

Background Initially detected in leukocytes and cancer cells derived from solid tissues, L-plastin/fimbrin belongs to a large family of actin crosslinkers and is considered as a marker for many cancers. Phosphorylation of L-plastin on residue Ser5 increases its F-actin binding activity and is required for L-plastin-mediated cell invasion. Methodology/Principal Findings To study the kinetics of L-plastin and the impact of L-plastin Ser5 phosphorylation on L-plastin dynamics and actin turn-over in live cells, simian Vero cells were transfected with GFP-coupled WT-L-plastin, Ser5 substitution variants (S5/A, S5/E) or actin and analyzed by fluorescence recovery after photobleaching (FRAP). FRAP data were explored by mathematical modeling to estimate steady-state reaction parameters. We demonstrate that in Vero cell focal adhesions L-plastin undergoes rapid cycles of association/dissociation following a two-binding-state model. Phosphorylation of L-plastin increased its association rates by two-fold, whereas dissociation rates were unaffected. Importantly, L-plastin affected actin turn-over by decreasing the actin dissociation rate by four-fold, increasing thereby the amount of F-actin in the focal adhesions, all these effects being promoted by Ser5 phosphorylation. In MCF-7 breast carcinoma cells, phorbol 12-myristate 13-acetate (PMA) treatment induced L-plastin translocation to de novo actin polymerization sites in ruffling membranes and spike-like structures and highly increased its Ser5 phosphorylation. Both inhibition studies and siRNA knock-down of PKC isozymes pointed to the involvement of the novel PKC-δ isozyme in the PMA-elicited signaling pathway leading to L-plastin Ser5 phosphorylation. Furthermore, the L-plastin contribution to actin dynamics regulation was substantiated by its association with a protein complex comprising cortactin, which is known to be involved in this process. Conclusions/Significance Altogether these findings quantitatively

Implementation and analysis of relief patterns of the surface of benign and malignant lesions of the skin by microtopography

NASA Astrophysics Data System (ADS)

López Pacheco, María del Carmen; Filipe Pereira da Cunha Martins-Costa, Manuel; Pérez Zapata, Aura Judith; Domínguez Cherit, Judith; Ramón Gallegos, Eva

2005-12-01

The objective of this study was to be able to distinguish between healthy skin tissue and malignant ones, furthermore determining a unique pattern of roughness for each skin lesion by microtopographic analysis of the skin surface of Mexican patients during the period from April to October 2002. The standard technique used in this study for the diagnosis of skin cancer and the comparison of the results was the haematoxylin eosin histopathological technique. Latex impressions were taken from skin lesions as well as from the healthy skin of each patient to serve as control samples. These impressions were analysed by the MICROTOP.03.MFC microtopographic system inspection. It was observed that when the tumour becomes rougher, more malign will be the lesion. On average, the melanoma present an increase of roughness of 67% compared to healthy skin, obtaining a roughness relation of 1:2.54. The percentage decreases to 49% (49%, 1:60) in the case of basal cell carcinoma and to 40% in pre-malignant lesions such as melanocytic nevus (40%, 1:150). In benign lesions such as the seborrhoea keratosis only a small increase in roughness was noted (4%, 1:0.72). Microtopographic inspection of the skin surface can be considered as a complementary diagnostic technique for skin cancer.

Erbium laser resurfacing for actinic cheilitis.

PubMed

Cohen, Joel L

2013-11-01

Actinic cheilitis is a precancerous condition characterized by grayish-whitish area(s) of discoloration on the mucosal lip, often blunting the demarcation between mucosa and cutaneous lip. Actinic cheilitis is considered to be an early part of the spectrum of squamous cell carcinoma. Squamous cell carcinoma specifically of the lip has a high rate of recurrence and metastasis through the oral cavity leading to a poor overall survival. Risk factors for the development of actinic cheilitis include chronic solar irradiation, increasing age, male gender, light skin complexion, immunosuppression, and possibly tobacco and alcohol consumption. Treatment options include topical pharmacotherapy (eg, fluorouracil, imiquimod) or procedural interventions (eg, cryotherapy, electrosurgery, surgical vermillionectomy, laser resurfacing), each with their known advantages and disadvantages. There is little consensus as to which treatment options offer the most clinical utility given the paucity of comparative clinical data. In my practice, laser resurfacing has become an important tool for the treatment of actinic cheilitis owing to its ease of use and overall safety, tolerability, and cosmetic acceptability. Herein the use of erbium laser resurfacing is described for three actinic cheilitis presentations for which I find it particularly useful: clinically prominent actinic cheilitis, biopsy-proven actinic cheilitis, and treatment of the entire lip following complete tumor excision of squamous cell carcinoma. All patients were treated with a 2940-nm erbium laser (Sciton Profile Contour Tunable Resurfacing Laser [TRL], Sciton, Inc., Palo Alto, CA).

Xenopus egg cytoplasm with intact actin.

PubMed

Field, Christine M; Nguyen, Phuong A; Ishihara, Keisuke; Groen, Aaron C; Mitchison, Timothy J

2014-01-01

We report optimized methods for preparing Xenopus egg extracts without cytochalasin D, that we term "actin-intact egg extract." These are undiluted egg cytoplasm that contains abundant organelles, and glycogen which supplies energy, and represents the least perturbed cell-free cytoplasm preparation we know of. We used this system to probe cell cycle regulation of actin and myosin-II dynamics (Field et al., 2011), and to reconstitute the large, interphase asters that organize early Xenopus embryos (Mitchison et al., 2012; Wühr, Tan, Parker, Detrich, & Mitchison, 2010). Actin-intact Xenopus egg extracts are useful for analysis of actin dynamics, and interaction of actin with other cytoplasmic systems, in a cell-free system that closely mimics egg physiology, and more generally for probing the biochemistry and biophysics of the egg, zygote, and early embryo. Detailed protocols are provided along with assays used to check cell cycle state and tips for handling and storing undiluted egg extracts. © 2014 Elsevier Inc. All rights reserved.

Capillary pericytes express α-smooth muscle actin, which requires prevention of filamentous-actin depolymerization for detection.

PubMed

Alarcon-Martinez, Luis; Yilmaz-Ozcan, Sinem; Yemisci, Muge; Schallek, Jesse; Kılıç, Kıvılcım; Can, Alp; Di Polo, Adriana; Dalkara, Turgay

2018-03-21

Recent evidence suggests that capillary pericytes are contractile and play a crucial role in the regulation of microcirculation. However, failure to detect components of the contractile apparatus in capillary pericytes, most notably α-smooth muscle actin (α-SMA), has questioned these findings. Using strategies that allow rapid filamentous-actin (F-actin) fixation (i.e. snap freeze fixation with methanol at -20°C) or prevent F-actin depolymerization (i.e. with F-actin stabilizing agents), we demonstrate that pericytes on mouse retinal capillaries, including those in intermediate and deeper plexus, express α-SMA. Junctional pericytes were more frequently α-SMA-positive relative to pericytes on linear capillary segments. Intravitreal administration of short interfering RNA (α-SMA-siRNA) suppressed α-SMA expression preferentially in high order branch capillary pericytes, confirming the existence of a smaller pool of α-SMA in distal capillary pericytes that is quickly lost by depolymerization. We conclude that capillary pericytes do express α-SMA, which rapidly depolymerizes during tissue fixation thus evading detection by immunolabeling. © 2018, Alarcon-Martinez et al.

Characterization of actin filament deformation in response to actively driven microspheres propagated through entangled actin networks

NASA Astrophysics Data System (ADS)

Falzone, Tobias; Blair, Savanna; Robertson-Anderson, Rae

2014-03-01

The semi-flexible biopolymer actin is a ubiquitous component of nearly all biological organisms, playing an important role in many biological processes such as cell structure and motility, cancer invasion and metastasis, muscle contraction, and cell signaling. Concentrated actin networks possess unique viscoelastic properties that have been the subject of much theoretical and experimental work. However, much is still unknown regarding the correlation of the applied stress on the network to the induced filament strain at the molecular level. Here, we use dual optical traps alongside fluorescence microscopy to carry out active microrheology measurements that link mechanical stress to structural response at the micron scale. Specifically, we actively drive microspheres through entangled actin networks while simultaneously measuring the force the surrounding filaments exert on the sphere and visualizing the deformation and subsequent relaxation of fluorescent labeled filaments within the network. These measurements, which provide much needed insight into the link between stress and strain in actin networks, are critical for clarifying our theoretical understanding of the complex viscoelastic behavior exhibited in actin networks.

Resistance of Actin to Cleavage during Apoptosis

NASA Astrophysics Data System (ADS)

Song, Qizhong; Wei, Tie; Lees-Miller, Susan; Alnemri, Emad; Watters, Dianne; Lavin, Martin F.

1997-01-01

A small number of cellular proteins present in the nucleus, cytosol, and membrane fraction are specifically cleaved by the interleukin-1β -converting enzyme (ICE)-like family of proteases during apoptosis. Previous results have demonstrated that one of these, the cytoskeletal protein actin, is degraded in rat PC12 pheochromocytoma cells upon serum withdrawal. Extracts from etoposide-treated U937 cells are also capable of cleaving actin. It was assumed that cleavage of actin represented a general phenomenon, and a mechanism coordinating proteolytic, endonucleolytic, and morphological aspects of apoptosis was proposed. We demonstrate here that actin is resistant to degradation in several different human cells induced to undergo apoptosis in response to a variety of stimuli, including Fas ligation, serum withdrawal, cytotoxic T-cell killing, and DNA damage. On the other hand, cell-free extracts from these cells and the ICE-like protease CPP32 were capable of cleaving actin in vitro. We conclude that while actin contains cleavage sites for ICE-like proteases, it is not degraded in vivo in human cells either because of lack of access of these proteases to actin or due to the presence of other factors that prevent degradation.

Live-cell imaging of G-actin dynamics using sequential FDAP

PubMed Central

Kiuchi, Tai; Nagai, Tomoaki; Ohashi, Kazumasa; Watanabe, Naoki; Mizuno, Kensaku

2011-01-01

Various microscopic techniques have been developed to understand the mechanisms that spatiotemporally control actin filament dynamics in live cells. Kinetic data on the processes of actin assembly and disassembly on F-actin have been accumulated. However, the kinetics of cytoplasmic G-actin, a key determinant for actin polymerization, has remained unclear because of a lack of appropriate methods to measure the G-actin concentration quantitatively. We have developed two new microscopic techniques based on the fluorescence decay after photoactivation (FDAP) time-lapse imaging of photoswitchable Dronpa-labeled actin. These techniques, sequential FDAP (s-FDAP) and multipoint FDAP, were used to measure the time-dependent changes in and spatial distribution of the G-actin concentration in live cells. Use of s-FDAP provided data on changes in the G-actin concentration with high temporal resolution; these data were useful for the model analysis of actin assembly processes in live cells. The s-FDAP analysis also provided evidence that the cytoplasmic G-actin concentration substantially decreases after cell stimulation and that the extent of stimulus-induced actin assembly and cell size extension are linearly correlated with the G-actin concentration before cell stimulation. The advantages of using s-FDAP and multipoint FDAP to measure spatiotemporal G-actin dynamics and the roles of G-actin concentration and ADF/cofilin in stimulus-induced actin assembly and lamellipodium extension in live cells are discussed. PMID:22754616

Mechanics model for actin-based motility

NASA Astrophysics Data System (ADS)

Lin, Yuan

2009-02-01

We present here a mechanics model for the force generation by actin polymerization. The possible adhesions between the actin filaments and the load surface, as well as the nucleation and capping of filament tips, are included in this model on top of the well-known elastic Brownian ratchet formulation. A closed form solution is provided from which the force-velocity relationship, summarizing the mechanics of polymerization, can be drawn. Model predictions on the velocity of moving beads driven by actin polymerization are consistent with experiment observations. This model also seems capable of explaining the enhanced actin-based motility of Listeria monocytogenes and beads by the presence of Vasodilator-stimulated phosphoprotein, as observed in recent experiments.

Mechanics model for actin-based motility.

PubMed

Lin, Yuan

2009-02-01

We present here a mechanics model for the force generation by actin polymerization. The possible adhesions between the actin filaments and the load surface, as well as the nucleation and capping of filament tips, are included in this model on top of the well-known elastic Brownian ratchet formulation. A closed form solution is provided from which the force-velocity relationship, summarizing the mechanics of polymerization, can be drawn. Model predictions on the velocity of moving beads driven by actin polymerization are consistent with experiment observations. This model also seems capable of explaining the enhanced actin-based motility of Listeria monocytogenes and beads by the presence of Vasodilator-stimulated phosphoprotein, as observed in recent experiments.

Diverse roles of actin in C. elegans early embryogenesis

PubMed Central

Velarde, Nathalie; Gunsalus, Kristin C; Piano, Fabio

2007-01-01

Background The actin cytoskeleton plays critical roles in early development in Caenorhabditis elegans. To further understand the complex roles of actin in early embryogenesis we use RNAi and in vivo imaging of filamentous actin (F-actin) dynamics. Results Using RNAi, we found processes that are differentially sensitive to levels of actin during early embryogenesis. Mild actin depletion shows defects in cortical ruffling, pseudocleavage, and establishment of polarity, while more severe depletion shows defects in polar body extrusion, cytokinesis, chromosome segregation, and eventually, egg production. These defects indicate that actin is required for proper oocyte development, fertilization, and a wide range of important events during early embryogenesis, including proper chromosome segregation. In vivo visualization of the cortical actin cytoskeleton shows dynamics that parallel but are distinct from the previously described myosin dynamics. Two distinct types of actin organization are observed at the cortex. During asymmetric polarization to the anterior, or the establishment phase (Phase I), actin forms a meshwork of microfilaments and focal accumulations throughout the cortex, while during the anterior maintenance phase (Phase II) it undergoes a morphological transition to asymmetrically localized puncta. The proper asymmetric redistribution is dependent on the PAR proteins, while both asymmetric redistribution and morphological transitions are dependent upon PFN-1 and NMY-2. Just before cytokinesis, actin disappears from most of the cortex and is only found around the presumptive cytokinetic furrow. Finally, we describe dynamic actin-enriched comets in the early embryo. Conclusion During early C. elegans embryogenesis actin plays more roles and its organization is more dynamic than previously described. Morphological transitions of F-actin, from meshwork to puncta, as well as asymmetric redistribution, are regulated by the PAR proteins. Results from this study

Electrostatics Control Actin Filament Nucleation and Elongation Kinetics*

PubMed Central

Crevenna, Alvaro H.; Naredi-Rainer, Nikolaus; Schönichen, André; Dzubiella, Joachim; Barber, Diane L.; Lamb, Don C.; Wedlich-Söldner, Roland

2013-01-01

The actin cytoskeleton is a central mediator of cellular morphogenesis, and rapid actin reorganization drives essential processes such as cell migration and cell division. Whereas several actin-binding proteins are known to be regulated by changes in intracellular pH, detailed information regarding the effect of pH on the actin dynamics itself is still lacking. Here, we combine bulk assays, total internal reflection fluorescence microscopy, fluorescence fluctuation spectroscopy techniques, and theory to comprehensively characterize the effect of pH on actin polymerization. We show that both nucleation and elongation are strongly enhanced at acidic pH, with a maximum close to the pI of actin. Monomer association rates are similarly affected by pH at both ends, although dissociation rates are differentially affected. This indicates that electrostatics control the diffusional encounter but not the dissociation rate, which is critical for the establishment of actin filament asymmetry. A generic model of protein-protein interaction, including electrostatics, explains the observed pH sensitivity as a consequence of charge repulsion. The observed pH effect on actin in vitro agrees with measurements of Listeria propulsion in pH-controlled cells. pH regulation should therefore be considered as a modulator of actin dynamics in a cellular environment. PMID:23486468

Myosin Vs organize actin cables in fission yeast

PubMed Central

Lo Presti, Libera; Chang, Fred; Martin, Sophie G.

2012-01-01

Myosin V motors are believed to contribute to cell polarization by carrying cargoes along actin tracks. In Schizosaccharomyces pombe, Myosin Vs transport secretory vesicles along actin cables, which are dynamic actin bundles assembled by the formin For3 at cell poles. How these flexible structures are able to extend longitudinally in the cell through the dense cytoplasm is unknown. Here we show that in myosin V (myo52 myo51) null cells, actin cables are curled, bundled, and fail to extend into the cell interior. They also exhibit reduced retrograde flow, suggesting that formin-mediated actin assembly is impaired. Myo52 may contribute to actin cable organization by delivering actin regulators to cell poles, as myoV∆ defects are partially suppressed by diverting cargoes toward cell tips onto microtubules with a kinesin 7–Myo52 tail chimera. In addition, Myo52 motor activity may pull on cables to provide the tension necessary for their extension and efficient assembly, as artificially tethering actin cables to the nuclear envelope via a Myo52 motor domain restores actin cable extension and retrograde flow in myoV mutants. Together these in vivo data reveal elements of a self-organizing system in which the motors shape their own tracks by transporting cargoes and exerting physical pulling forces. PMID:23051734

Myosin Vs organize actin cables in fission yeast.

PubMed

Lo Presti, Libera; Chang, Fred; Martin, Sophie G

2012-12-01

Myosin V motors are believed to contribute to cell polarization by carrying cargoes along actin tracks. In Schizosaccharomyces pombe, Myosin Vs transport secretory vesicles along actin cables, which are dynamic actin bundles assembled by the formin For3 at cell poles. How these flexible structures are able to extend longitudinally in the cell through the dense cytoplasm is unknown. Here we show that in myosin V (myo52 myo51) null cells, actin cables are curled, bundled, and fail to extend into the cell interior. They also exhibit reduced retrograde flow, suggesting that formin-mediated actin assembly is impaired. Myo52 may contribute to actin cable organization by delivering actin regulators to cell poles, as myoV defects are partially suppressed by diverting cargoes toward cell tips onto microtubules with a kinesin 7-Myo52 tail chimera. In addition, Myo52 motor activity may pull on cables to provide the tension necessary for their extension and efficient assembly, as artificially tethering actin cables to the nuclear envelope via a Myo52 motor domain restores actin cable extension and retrograde flow in myoV mutants. Together these in vivo data reveal elements of a self-organizing system in which the motors shape their own tracks by transporting cargoes and exerting physical pulling forces.

Actin filament curvature biases branching direction

NASA Astrophysics Data System (ADS)

Wang, Evan; Risca, Viviana; Chaudhuri, Ovijit; Chia, Jia-Jun; Geissler, Phillip; Fletcher, Daniel

2012-02-01

Actin filaments are key components of the cellular machinery, vital for a wide range of processes ranging from cell motility to endocytosis. Actin filaments can branch, and essential in this process is a protein complex known as the Arp2/3 complex, which nucleate new ``daughter'' filaments from pre-existing ``mother'' filaments by attaching itself to the mother filament. Though much progress has been made in understanding the Arp2/3-actin junction, some very interesting questions remain. In particular, F-actin is a dynamic polymer that undergoes a wide range of fluctuations. Prior studies of the Arp2/3-actin junction provides a very static notion of Arp2/3 binding. The question we ask is how differently does the Arp2/3 complex interact with a straight filament compared to a bent filament? In this study, we used Monte Carlo simulations of a surface-tethered worm-like chain to explore possible mechanisms underlying the experimental observation that there exists preferential branch formation by the Arp2/3 complex on the convex face of a curved filament. We show that a fluctuation gating model in which Arp2/3 binding to the actin filament is dependent upon a rare high-local-curvature shape fluctuation of the filament is consistent with the experimental data.

In vivo determination of optical properties and fluorophore characteristics of non-melanoma skin cancer

NASA Astrophysics Data System (ADS)

Rajaram, Narasimhan; Kovacic, Dianne; Migden, Michael F.; Reichenberg, Jason S.; Nguyen, Tri H.; Tunnell, James W.

2009-02-01

Diffuse optical spectroscopy (DOS) and laser-induced fluorescence (LIF) techniques have widely been used as noninvasive tools for early cancer detection in several organs including the cervix, oral cavity and gastrointestinal tract. Using a combined DOS/LIF approach, one can simultaneously measure the morphology and biochemical composition of tissue and use these features to diagnose malignancy. We report for the first time to our knowledge both the optical properties and native fluorophore characteristics of non-melanoma skin cancer in the UV-visible range. We collected in vivo diffuse reflectance and intrinsic fluorescence measurements from 44 skin lesions on 37 patients. The skin sites were further categorized into three groups of non-melanoma skin cancer according to histopathology: 1) pre-cancerous actinic keratosis 2) malignant squamous cell carcinoma (SCC) and 3) basal cell carcinoma (BCC). We used a custom-built probe-based clinical system that collects both white light reflectance and laser-induced fluorescence in the wavelength range of 350-700 nm. We extracted the blood volume fraction, oxygen saturation, blood vessel size, tissue microarchitecture and melanin content from diffuse reflectance measurements. In addition, we determined the native fluorophore contributions of NADH, collagen and FAD from laser-induced fluorescence for all groups. The scattering from tissue decreased with progression from clinically normal to precancerous actinic keratosis to malignant SCC. A similar trend was observed for clinically normal skin and malignant BCC. Statistically significant differences were observed in the collagen contributions, which were lower in malignant SCC and BCC as compared to normal skin. Our data demonstrates that the mean optical properties and fluorophore contributions of normal, benign and malignant nonmelanoma cancers are significantly different from each other and can potentially be used as biomarkers for the early detection of skin cancer.

Distinct Functional Interactions between Actin Isoforms and Nonsarcomeric Myosins

PubMed Central

Müller, Mirco; Diensthuber, Ralph P.; Chizhov, Igor; Claus, Peter; Heissler, Sarah M.; Preller, Matthias; Taft, Manuel H.; Manstein, Dietmar J.

2013-01-01

Despite their near sequence identity, actin isoforms cannot completely replace each other in vivo and show marked differences in their tissue-specific and subcellular localization. Little is known about isoform-specific differences in their interactions with myosin motors and other actin-binding proteins. Mammalian cytoplasmic β- and γ-actin interact with nonsarcomeric conventional myosins such as the members of the nonmuscle myosin-2 family and myosin-7A. These interactions support a wide range of cellular processes including cytokinesis, maintenance of cell polarity, cell adhesion, migration, and mechano-electrical transduction. To elucidate differences in the ability of isoactins to bind and stimulate the enzymatic activity of individual myosin isoforms, we characterized the interactions of human skeletal muscle α-actin, cytoplasmic β-actin, and cytoplasmic γ-actin with human myosin-7A and nonmuscle myosins-2A, -2B and -2C1. In the case of nonmuscle myosins-2A and -2B, the interaction with either cytoplasmic actin isoform results in 4-fold greater stimulation of myosin ATPase activity than was observed in the presence of α-skeletal muscle actin. Nonmuscle myosin-2C1 is most potently activated by β-actin and myosin-7A by γ-actin. Our results indicate that β- and γ-actin isoforms contribute to the modulation of nonmuscle myosin-2 and myosin-7A activity and thereby to the spatial and temporal regulation of cytoskeletal dynamics. FRET-based analyses show efficient copolymerization abilities for the actin isoforms in vitro. Experiments with hybrid actin filaments show that the extent of actomyosin coupling efficiency can be regulated by the isoform composition of actin filaments. PMID:23923011

Melanoma Is Skin Deep: A 3D Reconstruction Technique for Computerized Dermoscopic Skin Lesion Classification

PubMed Central

Satheesha, T. Y.; Prasad, M. N. Giri; Dhruve, Kashyap D.

2017-01-01

Melanoma mortality rates are the highest amongst skin cancer patients. Melanoma is life threating when it grows beyond the dermis of the skin. Hence, depth is an important factor to diagnose melanoma. This paper introduces a non-invasive computerized dermoscopy system that considers the estimated depth of skin lesions for diagnosis. A 3-D skin lesion reconstruction technique using the estimated depth obtained from regular dermoscopic images is presented. On basis of the 3-D reconstruction, depth and 3-D shape features are extracted. In addition to 3-D features, regular color, texture, and 2-D shape features are also extracted. Feature extraction is critical to achieve accurate results. Apart from melanoma, in-situ melanoma the proposed system is designed to diagnose basal cell carcinoma, blue nevus, dermatofibroma, haemangioma, seborrhoeic keratosis, and normal mole lesions. For experimental evaluations, the PH2, ISIC: Melanoma Project, and ATLAS dermoscopy data sets is considered. Different feature set combinations is considered and performance is evaluated. Significant performance improvement is reported the post inclusion of estimated depth and 3-D features. The good classification scores of sensitivity = 96%, specificity = 97% on PH2 data set and sensitivity = 98%, specificity = 99% on the ATLAS data set is achieved. Experiments conducted to estimate tumor depth from 3-D lesion reconstruction is presented. Experimental results achieved prove that the proposed computerized dermoscopy system is efficient and can be used to diagnose varied skin lesion dermoscopy images. PMID:28512610

Non-ablative fractional resurfacing in combination with topical tretinoin cream as a field treatment modality for multiple actinic keratosis: a pilot study and a review of other field treatment modalities.

PubMed

Prens, Sebastiaan P; de Vries, Karin; Neumann, H A Martino; Prens, Errol P

2013-06-01

Actinic keratoses (AK) are premalignant lesions occurring mainly in sun-damaged skin. Current topical treatment options for AK and photo-damaged skin such as liquid nitrogen and electrosurgery are not suitable for field treatment. Otherwise, therapies suitable for field treatment bring along considerable patient discomfort. Non-ablative fractional resurfacing has emerged as a logical treatment option especially for field treatment of AK. To evaluate the clinical efficacy of fractional laser therapy for clearing AK and improving skin quality. To compare patient friendliness of the "fractional" therapy with those reported for other field treatment modalities. Ten patients with Fitzpatrick skin type I to III with multiple AK and extensive sun-damaged skin, received 5-10 sessions with a 4-week interval using a 1550 nm Erbium-Glass Fractionated laser (Sellas, Korea). Four weeks and 24 weeks after the last treatment the clinical results were evaluated by an independent physician. The mean degree of improvement, in terms of reduction in the number of AK and improvement of skin texture, was 54% on a 4 point PGA scale, and persisted for approximately 6 months. The biggest advantage of fractional laser treatment, besides the eradication of AK and a clear rejuvenation effect, is the absence of "downtime". Fractional non-ablative resurfacing induces significant reduction in the number of AK and improves the skin quality. Also all patients preferred fractional laser therapy above other AK treatment modalities.

The Dynamic Actin Cytoskeleton in Smooth Muscle.

PubMed

Tang, Dale D

2018-01-01

Smooth muscle contraction requires both myosin activation and actin cytoskeletal remodeling. Actin cytoskeletal reorganization facilitates smooth muscle contraction by promoting force transmission between the contractile unit and the extracellular matrix (ECM), and by enhancing intercellular mechanical transduction. Myosin may be viewed to serve as an "engine" for smooth muscle contraction whereas the actin cytoskeleton may function as a "transmission system" in smooth muscle. The actin cytoskeleton in smooth muscle also undergoes restructuring upon activation with growth factors or the ECM, which controls smooth muscle cell proliferation and migration. Abnormal smooth muscle contraction, cell proliferation, and motility contribute to the development of vascular and pulmonary diseases. A number of actin-regulatory proteins including protein kinases have been discovered to orchestrate actin dynamics in smooth muscle. In particular, Abelson tyrosine kinase (c-Abl) is an important molecule that controls actin dynamics, contraction, growth, and motility in smooth muscle. Moreover, c-Abl coordinates the regulation of blood pressure and contributes to the pathogenesis of airway hyperresponsiveness and vascular/airway remodeling in vivo. Thus, c-Abl may be a novel pharmacological target for the development of new therapy to treat smooth muscle diseases such as hypertension and asthma. © 2018 Elsevier Inc. All rights reserved.

The Bacterial Actin MamK

PubMed Central

Ozyamak, Ertan; Kollman, Justin; Agard, David A.; Komeili, Arash

2013-01-01

It is now recognized that actin-like proteins are widespread in bacteria and, in contrast to eukaryotic actins, are highly diverse in sequence and function. The bacterial actin, MamK, represents a clade, primarily found in magnetotactic bacteria, that is involved in the proper organization of subcellular organelles, termed magnetosomes. We have previously shown that MamK from Magnetospirillum magneticum AMB-1 (AMB-1) forms dynamic filaments in vivo. To gain further insights into the molecular mechanisms that underlie MamK dynamics and function, we have now studied the in vitro properties of MamK. We demonstrate that MamK is an ATPase that, in the presence of ATP, assembles rapidly into filaments that disassemble once ATP is depleted. The mutation of a conserved active site residue (E143A) abolishes ATPase activity of MamK but not its ability to form filaments. Filament disassembly depends on both ATPase activity and potassium levels, the latter of which results in the organization of MamK filaments into bundles. These data are consistent with observations indicating that accessory factors are required to promote filament disassembly and for spatial organization of filaments in vivo. We also used cryo-electron microscopy to obtain a high resolution structure of MamK filaments. MamK adopts a two-stranded helical filament architecture, but unlike eukaryotic actin and other actin-like filaments, subunits in MamK strands are unstaggered giving rise to a unique filament architecture. Beyond extending our knowledge of the properties and function of MamK in magnetotactic bacteria, this study emphasizes the functional and structural diversity of bacterial actins in general. PMID:23204522

Probing actin polymerization by intermolecular cross-linking.

PubMed

Millonig, R; Salvo, H; Aebi, U

1988-03-01

We have used N,N'-1,4-phenylenebismaleimide, a bifunctional sulfhydryl cross-linking reagent, to probe the oligomeric state of actin during the early stages of its polymerization into filaments. We document that one of the first steps in the polymerization of globular monomeric actin (G-actin) under a wide variety of ionic conditions is the dimerization of a significant fraction of the G-actin monomer pool. As polymerization proceeds, the yield of this initial dimer ("lower" dimer with an apparent molecular mass of 86 kD by SDS-PAGE [LD]) is attenuated, while an actin filament dimer ("upper" dimer with an apparent molecular mass of 115 kD by SDS-PAGE [UD] as characterized [Elzinga, M., and J. J. Phelan. 1984. Proc. Natl. Acad. Sci. USA. 81:6599-6602]) is formed. This shift from LD to UD occurs concomitant with formation of filaments as assayed by N-(1-pyrenyl)iodoacetamide fluorescence enhancement and electron microscopy. Isolated cross-linked LD does not form filaments, while isolated cross-linked UD will assemble into filaments indistinguishable from those polymerized from unmodified G-actin under typical filament-forming conditions. The presence of cross-linked LD does not effect the kinetics of polymerization of actin monomer, whereas cross-linked UD shortens the "lag phase" of the polymerization reaction in a concentration-dependent fashion. Several converging lines of evidence suggest that, although accounting for a significant oligomeric species formed during early polymerization, the LD is incompatible with the helical symmetry defining the mature actin filament; however, it could represent the interfilament dimer found in paracrystalline arrays or filament bundles. Furthermore, the LD is compatible with the unit cell structure and symmetry common to various types of crystalline actin arrays (Aebi, U., W. E. Fowler, G. Isenberg, T. D. Pollard, and P. R. Smith. 1981. J. Cell Biol. 91:340-351) and might represent the major structural state in which a mutant

Eukaryotic chaperonin containing T-complex polypeptide 1 interacts with filamentous actin and reduces the initial rate of actin polymerization in vitro

PubMed Central

Grantham, Julie; Ruddock, Lloyd W.; Roobol, Anne; Carden, Martin J.

2002-01-01

We have previously observed that subunits of the chaperonin required for actin production (type-II chaperonin containing T-complex polypeptide 1 [CCT]) localize at sites of microfilament assembly. In this article we extend this observation by showing that substantially substoichiometric CCT reduces the initial rate of pyrene-labeled actin polymerization in vitro where eubacterial chaperonin GroEL had no such effect. CCT subunits bound selectively to F-actin in cosedimentation assays, and CCT reduced elongation rates from both purified actin filament “seeds” and the short and stabilized, minus-end blocked filaments in erythrocyte membrane cytoskeletons. These observations suggest CCT might remain involved in biogenesis of the actin cytoskeleton, by acting at filament (+) ends, beyond its already well-established role in producing new actin monomers. PMID:12482199

Formin' actin in the nucleus.

PubMed

Baarlink, Christian; Grosse, Robert

2014-01-01

Many if not most proteins can, under certain conditions, change cellular compartments, such as, for example, shuttling from the cytoplasm to the nucleus. Thus, many proteins may exert functions in various and very different subcellular locations, depending on the signaling context. A large amount of actin regulatory proteins has been detected in the mammalian cell nucleus, although their potential roles are much debated and are just beginning to emerge. Recently, members of the formin family of actin nucleators were also reported to dynamically localize to the nuclear environment. Here we discuss our findings that specific diaphanous-related formins can promote nuclear actin assembly in a signal-dependent manner.

Liquid droplets of cross-linked actin filaments

NASA Astrophysics Data System (ADS)

Weirich, Kimberly; Banerjee, Shiladitya; Dasbiswas, Kinjal; Vaikuntanathan, Suriyanarayan; Gardel, Margaret

Soft materials constructed from biomolecules self-assemble into a myriad of structures that work in concert to support cell physiology. One critical soft material is the actin cytoskeleton, a viscoelastic gel composed of cross-linked actin filaments. Although actin networks are primarily known for their elastic properties, which are crucial to regulating cell mechanics, the viscous behavior has been theorized to enable shape changes and flows. We experimentally demonstrate a fluid phase of cross-linked actin, where cross-linker condenses dilute short actin filaments into spindle-shaped droplets, or tactoids. Tactoids have shape dynamics consistent with a continuum model of liquid crystal droplets. The cross-linker, which acts as a long range attractive interaction, analogous to molecular cohesion, controls the tactoid shape and dynamics, which reports on the liquid's interfacial tension and viscosity. We investigate how the cross-linker properties and filament length influence the liquid properties. These results demonstrate a novel mechanism to control organization of the actin cytoskeleton and provide insight into design principles for complex, macromolecular liquid phases.

Sarcomeric Pattern Formation by Actin Cluster Coalescence

PubMed Central

Friedrich, Benjamin M.; Fischer-Friedrich, Elisabeth; Gov, Nir S.; Safran, Samuel A.

2012-01-01

Contractile function of striated muscle cells depends crucially on the almost crystalline order of actin and myosin filaments in myofibrils, but the physical mechanisms that lead to myofibril assembly remains ill-defined. Passive diffusive sorting of actin filaments into sarcomeric order is kinetically impossible, suggesting a pivotal role of active processes in sarcomeric pattern formation. Using a one-dimensional computational model of an initially unstriated actin bundle, we show that actin filament treadmilling in the presence of processive plus-end crosslinking provides a simple and robust mechanism for the polarity sorting of actin filaments as well as for the correct localization of myosin filaments. We propose that the coalescence of crosslinked actin clusters could be key for sarcomeric pattern formation. In our simulations, sarcomere spacing is set by filament length prompting tight length control already at early stages of pattern formation. The proposed mechanism could be generic and apply both to premyofibrils and nascent myofibrils in developing muscle cells as well as possibly to striated stress-fibers in non-muscle cells. PMID:22685394

Drosophila Spire is an actin nucleation factor.

PubMed

Quinlan, Margot E; Heuser, John E; Kerkhoff, Eugen; Mullins, R Dyche

2005-01-27

The actin cytoskeleton is essential for many cellular functions including shape determination, intracellular transport and locomotion. Previous work has identified two factors--the Arp2/3 complex and the formin family of proteins--that nucleate new actin filaments via different mechanisms. Here we show that the Drosophila protein Spire represents a third class of actin nucleation factor. In vitro, Spire nucleates new filaments at a rate that is similar to that of the formin family of proteins but slower than in the activated Arp2/3 complex, and it remains associated with the slow-growing pointed end of the new filament. Spire contains a cluster of four WASP homology 2 (WH2) domains, each of which binds an actin monomer. Maximal nucleation activity requires all four WH2 domains along with an additional actin-binding motif, conserved among Spire proteins. Spire itself is conserved among metazoans and, together with the formin Cappuccino, is required for axis specification in oocytes and embryos, suggesting that multiple actin nucleation factors collaborate to construct essential cytoskeletal structures.

Measurement and Analysis of in vitro Actin Polymerization

PubMed Central

Doolittle, Lynda K.; Rosen, Michael K.; Padrick, Shae B.

2014-01-01

Summary The polymerization of actin underlies force generation in numerous cellular processes. While actin polymerization can occur spontaneously, cells maintain control over this important process by preventing actin filament nucleation and then allowing stimulated polymerization and elongation by several regulated factors. Actin polymerization, regulated nucleation and controlled elongation activities can be reconstituted in vitro, and used to probe the signaling cascades cells use to control when and where actin polymerization occurs. Introducing a pyrene fluorophore allows detection of filament formation by an increase in pyrene fluorescence. This method has been used for many years and continues to be broadly used, owing to its simplicity and flexibility. Here we describe how to perform and analyze these in vitro actin polymerization assays, with an emphasis on extracting useful descriptive parameters from kinetic data. PMID:23868594

Hypertrophic Stimulation Increases β-actin Dynamics in Adult Feline Cardiomyocytes

PubMed Central

Balasubramanian, Sundaravadivel; Mani, Santhosh K.; Kasiganesan, Harinath; Baicu, Catalin C.; Kuppuswamy, Dhandapani

2010-01-01

The myocardium responds to hemodynamic stress through cellular growth and organ hypertrophy. The impact of cytoskeletal elements on this process, however, is not fully understood. While α-actin in cardiomyocytes governs muscle contraction in combination with the myosin motor, the exact role of β-actin has not been established. We hypothesized that in adult cardiomyocytes, as in non-myocytes, β-actin can facilitate cytoskeletal rearrangement within cytoskeletal structures such as Z-discs. Using a feline right ventricular pressure overload (RVPO) model, we measured the level and distribution of β-actin in normal and pressure overloaded myocardium. Resulting data demonstrated enriched levels of β-actin and enhanced translocation to the Triton-insoluble cytoskeletal and membrane skeletal complexes. In addition, RVPO in vivo and in vitro hypertrophic stimulation with endothelin (ET) or insulin in isolated adult cardiomyocytes enhanced the content of polymerized fraction (F-actin) of β-actin. To determine the localization and dynamics of β-actin, we adenovirally expressed GFP-tagged β-actin in isolated adult cardiomyocytes. The ectopically expressed β-actin-GFP localized to the Z-discs, costameres, and cell termini. Fluorescence recovery after photobleaching (FRAP) measurements of β-actin dynamics revealed that β-actin at the Z-discs is constantly being exchanged with β-actin from cytoplasmic pools and that this exchange is faster upon hypertrophic stimulation with ET or insulin. In addition, in electrically stimulated isolated adult cardiomyocytes, while β-actin overexpression improved cardiomyocyte contractility, immunoneutralization of β-actin resulted in a reduced contractility suggesting that β-actin could be important for the contractile function of adult cardiomyocytes. These studies demonstrate the presence and dynamics of β-actin in the adult cardiomyocyte and reinforce its usefulness in measuring cardiac cytoskeletal rearrangement during

Hypertrophic stimulation increases beta-actin dynamics in adult feline cardiomyocytes.

PubMed

Balasubramanian, Sundaravadivel; Mani, Santhosh K; Kasiganesan, Harinath; Baicu, Catalin C; Kuppuswamy, Dhandapani

2010-07-12

The myocardium responds to hemodynamic stress through cellular growth and organ hypertrophy. The impact of cytoskeletal elements on this process, however, is not fully understood. While alpha-actin in cardiomyocytes governs muscle contraction in combination with the myosin motor, the exact role of beta-actin has not been established. We hypothesized that in adult cardiomyocytes, as in non-myocytes, beta-actin can facilitate cytoskeletal rearrangement within cytoskeletal structures such as Z-discs. Using a feline right ventricular pressure overload (RVPO) model, we measured the level and distribution of beta-actin in normal and pressure overloaded myocardium. Resulting data demonstrated enriched levels of beta-actin and enhanced translocation to the Triton-insoluble cytoskeletal and membrane skeletal complexes. In addition, RVPO in vivo and in vitro hypertrophic stimulation with endothelin (ET) or insulin in isolated adult cardiomyocytes enhanced the content of polymerized fraction (F-actin) of beta-actin. To determine the localization and dynamics of beta-actin, we adenovirally expressed GFP-tagged beta-actin in isolated adult cardiomyocytes. The ectopically expressed beta-actin-GFP localized to the Z-discs, costameres, and cell termini. Fluorescence recovery after photobleaching (FRAP) measurements of beta-actin dynamics revealed that beta-actin at the Z-discs is constantly being exchanged with beta-actin from cytoplasmic pools and that this exchange is faster upon hypertrophic stimulation with ET or insulin. In addition, in electrically stimulated isolated adult cardiomyocytes, while beta-actin overexpression improved cardiomyocyte contractility, immunoneutralization of beta-actin resulted in a reduced contractility suggesting that beta-actin could be important for the contractile function of adult cardiomyocytes. These studies demonstrate the presence and dynamics of beta-actin in the adult cardiomyocyte and reinforce its usefulness in measuring cardiac

[Cytoskeletal actin and its associated proteins. Some examples in Protista].

PubMed

Guillén, N; Carlier, M F; Brugerolle, G; Tardieux, I; Ausseil, J

1998-06-01

Many processes, cell motility being an example, require cells to remodel the actin cytoskeleton in response to both intracellular and extracellular signals. Reorganization of the actin cytoskeleton involves the rapid disassembly and reassembly of actin filaments, a phenomenon regulated by the action of particular actin-binding proteins. In recent years, an interest in studying actin regulation in unicellular organisms has arisen. Parasitic protozoan are among these organisms and studies of the cytoskeleton functions of these protozoan are relevant related to either cell biology or pathogenicity. To discuss recent data in this field, a symposium concerning "Actin and actin-binding proteins in protists" was held on May 8-11 in Paris, France, during the XXXV meeting of the French Society of Protistology. As a brief summary of the symposium we report here findings concerning the in vitro actin dynamic assembly, as well as the characterization of several actin-binding proteins from the parasitic protozoan Entamoeba histolytica, Trichomonas vaginalis and Plasmodium knowlesi. In addition, localization of actin in non-pathogen protists such as Prorocentrum micans and Crypthecodinium cohnii is also presented. The data show that some actin-binding proteins facilitate organization of filaments into higher order structures as pseudopods, while others have regulatory functions, indicating very particular roles for actin-binding proteins. One of the proteins discussed during the symposium, the actin depolymerizing factor ADF, was shown to enhance the treadmilling rate of actin filaments. In vitro, ADF binds to the ADP-bound forms of G-actin and F-actin, thereby participating in and changing the rate of actin assembly. Biochemical approaches allowed the identification of a protein complex formed by HSP/C70-cap32-34 which might also be involved in depolymerization of F-actin in P. knowlesi. Molecular and cellular approaches were used to identify proteins such as ABP-120 and myosin

Actin Turnover-Mediated Gravity Response in Maize Root Apices

PubMed Central

Mancuso, Stefano; Barlow, Peter W; Volkmann, Dieter

2006-01-01

The dynamic actin cytoskeleton has been proposed to be linked to gravity sensing in plants but the mechanistic understanding of these processes remains unknown. We have performed detailed pharmacological analyses of the role of the dynamic actin cytoskeleton in gravibending of maize (Zea mays) root apices. Depolymerization of actin filaments with two drugs having different mode of their actions, cytochalasin D and latrunculin B, stimulated root gravibending. By contrast, drug-induced stimulation of actin polymerization and inhibition of actin turnover, using two different agents phalloidin and jasplakinolide, compromised the root gravibending. Importantly, all these actin drugs inhibited root growth to similar extents suggesting that high actin turnover is essential for the gravity-related growth responses rather than for the general growth process. Both latrunculin B and cytochalasin D treatments inhibited root growth but restored gravibending of the decapped root apices, indicating that there is a strong potential for effective actin-mediated gravity sensing outside the cap. This elusive gravity sensing outside the root cap is dependent not only on the high rate of actin turnover but also on weakening of myosin activities, as general inhibition of myosin ATPases induced stimulation of gravibending of the decapped root apices. Collectively, these data provide evidence for the actin turnover-mediated gravity sensing outside the root cap. PMID:19521476

Nuclear positioning by actin cables and perinuclear actin: Special and general?

PubMed

Huelsmann, Sven; Brown, Nicholas H

2014-01-01

Nuclear positioning is an important process during development and homeostasis. Depending on the affected tissue, mislocalized nuclei can alter cellular processes such as polarization, differentiation, or migration and lead ultimately to diseases. Many cells actively control the position of their nucleus using their cytoskeleton and motor proteins. We have recently shown that during Drosophila oogenesis, nurse cells employ cytoplasmic actin cables in association with perinuclear actin to position their nucleus. Here, we briefly summarize our work and discuss why nuclear positioning in nurse cells is specialized but the molecular mechanisms are likely to be more generally used.

IFT88 influences chondrocyte actin organization and biomechanics.

PubMed