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https://read.qxmd.com/read/30855743/randomized-trial-of-four-treatment-approaches-for-actinic-keratosis
#1
Maud H E Jansen, Janneke P H M Kessels, Patty J Nelemans, Nina Kouloubis, Aimee H M M Arits, Han P A van Pelt, Patricia J F Quaedvlieg, Brigitte A B Essers, Peter M Steijlen, Nicole W J Kelleners-Smeets, Klara Mosterd
BACKGROUND: Actinic keratosis is the most frequent premalignant skin disease in the white population. In current guidelines, no clear recommendations are made about which treatment is preferred. METHODS: We investigated the effectiveness of four frequently used field-directed treatments (for multiple lesions in a continuous area). Patients with a clinical diagnosis of five or more actinic keratosis lesions on the head, involving one continuous area of 25 to 100 cm2 , were enrolled at four Dutch hospitals...
March 7, 2019: New England Journal of Medicine
https://read.qxmd.com/read/30801837/ingenol-mebutate-mediated-reduction-of-p53-positive-keratinocytes-in-skin-cancerization-field-directly-correlates-with-clinical-response-in-patients-with-multiple-actinic-keratoses
#2
Vieri Grandi, Paola di Gennaro, Samuele Torrigiani, Luigi Basco, Irene Lastrucci, Nicola Pimpinelli
BACKGROUND: UV radiation represents the main risk factor for Non Melanoma Skin Cancers (NMSC). Chronic UV exposure induces "p53 patches", i.e. clonal outgrowths of keratinocytes with high nuclear expression of mutated p53, which might progress to actinic keratosis (AK) and ultimately squamous cell carcinomas (SCC). AIMS: Analysis of Ingenol mebutate gel (150 and 500 mcg/g) effects in the reduction of "p53 patches" inside skin cancerization field (CF) in patients with multiple AKs of face/scalp or trunk/extremities, in order to investigate if the expected reduction of p53+ keratinocytes might have a direct role in the long-term AK reduction in treated areas...
February 23, 2019: Journal of the European Academy of Dermatology and Venereology: JEADV
https://read.qxmd.com/read/30766448/mediators-of-inflammation-in-topical-therapy-of-skin-cancers
#3
REVIEW
Vlad Mihai Voiculescu, Cristina Victoria Lisievici, Mihai Lupu, Cristina Vajaitu, Carmen Cristina Draghici, Alexandra Victoria Popa, Iulia Solomon, Teona Ioana Sebe, Maria Magdalena Constantin, Constantin Caruntu
Taking into consideration that the immune system plays a very important role in the development of melanoma and non-melanoma skin cancers, which have a high prevalence in immunosuppressed patients and after prolonged ultraviolet radiation, the interest in developing novel therapies, in particular targeting the inflammation in cancer, has increased in the past years. The latest data suggest that therapies such as imiquimod (IMQ), ingenol mebutate (IM), 5-fluorouracil (5-FU), retinoids, and nonsteroidal anti-inflammatory drugs (NSAIDs) have been used with success in the topical treatment of some cancers...
2019: Mediators of Inflammation
https://read.qxmd.com/read/30710390/efficacy-of-photodynamic-therapy-combined-with-topical-interventions-for-the-treatment-of-actinic-keratosis-a-meta-analysis
#4
M V Heppt, T Steeb, U Leiter, C Berking
BACKGROUND: Photodynamic therapy (PDT) is a highly effective treatment option for patients with actinic keratoses (AK). However, efficacy can be reduced by insufficient illumination or hyperkeratotic nature of lesions. OBJECTIVES: To investigate if PDT combined with a topical intervention is superior to monotherapy in terms of efficacy and tolerability. METHODS: A systematic literature research was conducted in Medline, Embase, and CENTRAL...
February 1, 2019: Journal of the European Academy of Dermatology and Venereology: JEADV
https://read.qxmd.com/read/30706457/a-randomized-open-controlled-trial-of-tretinoin-0-05-cream-vs-low-dose-oral-isotretinoin-for-the-treatment-of-field-cancerization
#5
Mayra Ianhez, Sebastião A Pinto, Helio A Miot, Ediléia Bagatin
BACKGROUND: Sun exposure may lead to actinic keratoses (AKs), field cancerization, and skin cancer. Effective treatment of AKs and field cancerization is important. Oral and topical retinoids can be used for this purpose. To compare clinical, histological, and immunohistochemical effects of oral and topical retinoid for AKs and field cancerization on face and upper limbs of immunocompetent patients, as well as the impact on quality of life, safety, and tolerability. METHODS: This study compared 10 mg/day oral isotretinoin (ISO) to 0...
January 31, 2019: International Journal of Dermatology
https://read.qxmd.com/read/30706338/modified-ingenol-semi-synthetic-derivatives-from-euphorbia-tirucalli-induce-cytotoxicity-on-a-large-panel-of-human-cancer-cell-lines
#6
Viviane A O Silva, Marcela N Rosa, Olga Martinho, Amilcar Tanuri, João Paulo Lima, Luiz F Pianowski, Rui M Reis
The latex from Euphorbia tirucalli is used in Brazil as a folk medicine for several diseases, including cancer. Recently, we showed a cytotoxic activity of E. tirucalli euphol in a wide range of cancer cell lines. Moreover, we showed that euphol inhibits proliferation, motility and colony formation in pancreatic cancer cells, induces autophagy and sensitizes glioblastoma cells to temozolomide cytotoxicity. Herein, we report in vitro activity of three semi-synthetic ingenol compounds derived from E. tirucalli, IngA (ingenol-3-trans-cinnamate), IngB (ingenol-3-hexanoate) and IngC (ingenol-3-dodecanoate), against a large panel of human cancer cell lines...
February 1, 2019: Investigational New Drugs
https://read.qxmd.com/read/30636590/natural-cytotoxic-diterpenoids-a-potential-source-of-drug-leads-for-melanoma-therapy
#7
Jose M Prieto, Dâmaris Silveira
Diterpenes present complex structure and due to their unique carbon skeleton and interesting biological activities, have been the focus of continuous studies for the development of new anticancer agents. Phorbol esters have been known for their activity against skin malignancies since ancient times. Taxol was first studied in melanoma cells, and recently ingenol mebutate has been approved for the chemoprevention of melanoma in actinic keratosis patients. Therefore, there is scope for research on this class of compounds...
January 11, 2019: Current Pharmaceutical Design
https://read.qxmd.com/read/30460703/ingenol-mebutate-for-the-treatment-of-anogenital-condylomata-acuminata
#8
J Magdaleno-Tapial, C Valenzuela-Oñate, M Giacaman-von der Weth, B Ferrer-Guillén, M García-Legaz Martínez, Á Martínez-Domenech, P Hernández-Bel
No abstract text is available yet for this article.
November 20, 2018: Clinical and Experimental Dermatology
https://read.qxmd.com/read/30428649/photodynamic-therapy-activated-by-intense-pulsed-light-in-the-treatment-of-actinic-keratosis
#9
Marco Michelini
BACKGROUND: Actinic keratosis (AK), a hyperkeratotic lesion induced by solar exposure, is the precancerous lesion that most frequently develops into squamous cell carcinoma. Cryotherapy, topical fluorouracil 5, topical diclofenac 3% gel and, more recently, ingenol mebutate are used in addition to surgery. However, these treatments have varying degrees of effectiveness and are not always tolerated due to side effects. In recent years, Photodynamic Therapy (PDT), has asserted itself as a new effective and safe method for the treatment of actinic keratoses with almost no side effects...
November 9, 2018: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://read.qxmd.com/read/30323610/clinical-utility-of-ingenol-mebutate-in-the-management-of-actinic-keratosis-perspectives-from-clinical-practice
#10
REVIEW
Nevena Skroza, Nicoletta Bernardini, Ilaria Proietti, Concetta Potenza
Actinic keratoses (AKs) are epidermal cutaneous neoplasia observed predominantly in middle-aged and older subjects with mainly photo type I and photo type II on sun-exposed surfaces as a result of DNA damage. AKs have historically been characterized as being "precancerous"; however, now it is considered by many authors a carcinoma in situ that can persist or progress to invasive squamous cell carcinoma (SCC) with metastatic potential. Despite the advances in the recognition of typical clinic, dermoscopic and histologic patterns, currently it is not yet possible to predict which AKs will progress to SCC...
2018: Therapeutics and Clinical Risk Management
https://read.qxmd.com/read/30266096/ingenol-mebutate-induces-a-tumor-cell-directed-inflammatory-response-and-antimicrobial-peptides-thereby-promoting-rapid-tumor-destruction-and-wound-healing
#11
Stephan Alexander Braun, Julia Baran, Holger Schrumpf, Bettina Alexandra Buhren, Edwin Bölke, Bernhard Homey, Peter Arne Gerber
BACKGROUND: Ingenol mebutat (IM)-gel is effective for the topical treatment of epithelial tumors, including actinic keratoses (AKs) or anogenital warts (AGW). AK patients treated with IM develop intensified inflammatory reactions on sights of prior clinical visible or palpable AKs as compared to the surrounding actinically damaged skin, suggesting the induction of a tumor cell-directed inflammation. AGW patients treated with IM develop even stronger inflammatory reactions with large erosions, suggesting a directed inflammatory response against HPV-infected keratinocytes...
September 28, 2018: European Journal of Medical Research
https://read.qxmd.com/read/30260493/effect-of-ingenol-mebutate-on-actinic-keratosis-in-a-korean-population-a-prospective-clinical-dermoscopic-and-histopathological-study-from-a-single-center
#12
Jong Sic Kim, Yu Ri Woo, Miri Kim, Hyun Jeong Park
Actinic keratosis (AK) is an in situ squamous cell carcinoma which is mostly found on sun-damaged skin, and it is prevalent among Caucasians. However, there is a lack of research on evaluating the treatment efficacy of ingenol mebutate (IM) on AK in Asians. This study was intended to analyze the treatment outcomes of IM on AK in Korean patients with regards to clinical, dermoscopic and histopathological aspects. A prospective study on 46 Korean patients who were diagnosed with AK and treated with IM was conducted...
November 2018: Journal of Dermatology
https://read.qxmd.com/read/30258187/identification-of-small-molecule-ion-channel-modulators-in-c-elegans-channelopathy-models
#13
Qiang Jiang, Kai Li, Wen-Jing Lu, Shuang Li, Xin Chen, Xi-Juan Liu, Jie Yuan, Qiurong Ding, Feng Lan, Shi-Qing Cai
Ion channels are important therapeutic targets, but the discovery of ion channel drugs remains challenging due to a lack of assays that allow high-throughput screening in the physiological context. Here we report C. elegans phenotype-based methods for screening ion channel drugs. Expression of modified human ether-a-go-go-related gene (hERG) potassium channels in C. elegans results in egg-laying and locomotive defects, which offer indicators for screening small-molecule channel modulators. Screening in worms expressing hERGA561V , which carries a trafficking-defective mutation A561V known to associate with long-QT syndrome, identifies two functional correctors Prostratin and ingenol-3,20-dibenzoate...
September 26, 2018: Nature Communications
https://read.qxmd.com/read/30246021/efficacy-of-ingenol-mebutate-in-the-treatment-of-actinic-keratoses-a-pre-and-posttreatment-dermoscopic-comparative-analysis
#14
Mattia Carbotti, Rosa Coppola, Salvatore Zanframundo, Valeria Devirgiliis, Vincenzo Panasiti
Actinic keratosis (AK) is a common skin lesion in adults which usually occurs on chronically photoexposed areas and considered as a precancerous lesion or a superficial squamous-cell carcinoma. Many classifications have been proposed and its diagnosis is generally clinical but, sometimes, its wide variety of presentations can make diagnosis difficult, even among expert observers. The malignant potential of AKs imposes an early diagnosis and treatment in order to reduce morbidity and mortality, and, for the characterization of photodamaged skin, noninvasive diagnostic techniques, such as dermoscopy, have proved to be useful, while multiple therapeutic strategies, lesion-directed versus field-directed therapies, are available for the treatment of AKs...
2018: BioMed Research International
https://read.qxmd.com/read/30104276/synthetic-ingenols-maximize-protein-kinase-c-induced-hiv-1-latency-reversal
#15
Adam M Spivak, Racheal A Nell, Mark Petersen, Laura Martins, Paul Sebahar, Ryan E Looper, Vicente Planelles
Antiretroviral therapy (ART) does not cure HIV-1 infection due to the persistence of proviruses in long-lived resting T cells. Strategies targeting these latently infected cells will be necessary to eradicate HIV-1 in infected individuals. Protein kinase C (PKC) activation is an effective mechanism to reactivate latent proviruses and allows for recognition and clearance of infected cells by the immune system. Several ingenol compounds, naturally occurring PKC agonists, have been described to have potent latency reversal activity...
November 2018: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/30074409/pharmacokinetic-and-pharmacodynamic-evaluation-of-ingenol-mebutate-for-the-treatment-of-actinic-keratosis
#16
REVIEW
Eggert Stockfleth, Mike Bastian
Actinic keratosis (AK) is a common skin condition that results from exposure to chronic ultraviolet (UV) radiation. AK is characterized by visible, scaly lesions; sub-clinical lesions may also be present within a field of UV-exposed skin. These lesions exist on a disease continuum with squamous cell carcinoma. Field therapies, such as ingenol mebutate, aim to treat the visible and sub-clinical lesions within an area of sun-damaged skin. Areas covered: According to the SmPC, ingenol mebutate has a proposed dual mechanism of action that induces cell death necrosis with the production of a local pro-inflammatory response and stimulation of apoptosis...
September 2018: Expert Opinion on Drug Metabolism & Toxicology
https://read.qxmd.com/read/30066970/sequential-treatment-of-actinic-keratosis-with-cryotherapy-and-ingenol-mebutate-reflectance-confocal-microscopy-monitoring-of-efficacy-and-local-skin-reaction
#17
Paola Pasquali, Gonzalo Segurado-Miravalles, Salvador González
BACKGROUND: Sequential treatment of actinic keratosis (AK) and cancerization field with cryotherapy and ingenol mebutate (IM) is widely used in clinical practice, however, the order of application of sequential treatment has not been examined yet. OBJECTIVE: To compare different sequential treatments of IM and cryotherapy in AK and to monitor cure rates and local skin reactions (LSR) through reflectance confocal microscopy (RCM). METHODS: Patients with AK were treated with IM and cryotherapy...
October 2018: International Journal of Dermatology
https://read.qxmd.com/read/30066759/ingenol-mebutate-in-the-treatment-of-actinic-keratoses-clearance-rate-and-adverse-effects
#18
Maria Isabel Ramos Saraiva, Larissa Karine Leite Portocarrero, Marcella Amaral Horta Barbosa Vieira, Bethania Cabral Cavalli Swiczar, Andrezza Telles Westin
BACKGROUND: Actinic keratoses are benign intraepithelial skin neoplasms that develop in photoexposed areas and can progress to invasive carcinoma. They are seen frequently in dermatological practice, occurring in 5.1% of consultations. Ingenol mebutate (IM) was recently approved in Brazil as a topical therapy for field cancerization in actinic keratosis. OBJECTIVE: To evaluate the clearance rate and adverse events in the treatment of actinic keratoses with ingenol mebutate...
July 2018: Anais Brasileiros de Dermatologia
https://read.qxmd.com/read/30031972/identification-structural-modification-and-dichotomous-effects-on-human-immunodeficiency-virus-type-1-hiv-1-replication-of-ingenane-esters-from-euphorbia-kansui
#19
Qingbo Liu, Wei Li, Li Huang, Yoshihisa Asada, Susan L Morris-Natschke, Chin-Ho Chen, Kuo-Hsiung Lee, Kazuo Koike
Euphorbia kansui showed potent anti-HIV-1 activity during screening of a library composed of plant extracts from Euphorbiaceae and Thymelaeaceae families. Bioassay-guided isolation led to identification of ingenane esters as the active compounds. Further chemical modification resulted in 3-(2-naphthoyl)ingenol (23), which exhibited the most potent anti-HIV-1 activity. Compound 23 also acted as an HIV-1-latency-reversing agent on activation of HIV-1 replication in a latently infected U1 cell model and a T cell latent HIV-1 model JLat-A2...
August 5, 2018: European Journal of Medicinal Chemistry
https://read.qxmd.com/read/29920789/physician-patient-communication-and-patient-reported-outcomes-in-the-actinic-keratosis-treatment-adherence-initiative-ak-train-a-multicenter-prospective-real-life-study-of-treatment-satisfaction-quality-of-life-and-adherence-to-topical-field-directed-therapy
#20
L Neri, K Peris, C Longo, S Calvieri, P Frascione, A Parodi, L Eibenschuz, U Bottoni, G Pellacani
BACKGROUND: Patients with multiple actinic keratoses (AKs) should be treated with field-directed therapy. Such treatments challenge patients' adherence due to out-of-pocket costs, length of treatment and severity of local skin reactions (LSRs). Effective physician-patient communication (PPC) may buffer therapy-related distress, thus improving quality of life, treatment satisfaction and adherence. OBJECTIVES: We evaluated the interplay between PPC, LSR intensity (safety) and lesion clearance rates (effectiveness) on treatment satisfaction, quality of life and treatment adherence among patients with multiple AKs receiving topical field-directed therapies...
June 19, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
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