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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...
August 13, 2018: Antimicrobial Agents and Chemotherapy
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...
August 3, 2018: Expert Opinion on Drug Metabolism & Toxicology
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...
August 1, 2018: International Journal of Dermatology
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
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...
July 19, 2018: European Journal of Medicinal Chemistry
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
Sean R Christensen
Cutaneous squamous cell carcinoma (SCC) is among the most common cancers in humans, and many patients with SCC will develop multiple tumors within their lifetime. The field cancerization concept, originally proposed over 60 years ago, hypothesized that multiple primary cancers may arise simultaneously and coexist with subclinical precursor lesions within a defined field. Genetic sequencing of SCC and precursor lesions has identified what may be the earliest clonal proliferations in SCC development and confirmed that field cancerization in the skin is mediated by ultraviolet radiation...
2018: F1000Research
Joanna Dong, Gary Goldenberg
Cutaneous field cancerization arises due to UV-induced carcinogenesis of a "field" of subclinically transformed skin and actinic keratoses (AKs) with a tendency to progress and recur. Commonly used treatment methods for multiple AKs include imiquimod, fluorouracil, ingenol mebutate, and photodynamic therapy; however, new options in field-directed therapy with superior efficacy, cosmesis, and convenience may appeal to patients. Ablative and nonablative lasers may fulfill these advantages and have been investigated as monotherapies and combination therapies for field cancerization...
May 2018: Cutis; Cutaneous Medicine for the Practitioner
Stephan A Braun, Martin Barsch, Peter A Gerber
Therapeutic options of anogenital warts (AGW) at the urethral meatus are limited and often require effortful and time-consuming procedures under general anesthesia. Here, we present two cases of AGW at the urethral meatus, which we have successfully treated with low-dose topical ingenol mebutate-gel.
May 3, 2018: Sexually Transmitted Diseases
Silvia S Iannazzone, Vito Ingordo
Surgical excision is the first-choice treatment for basal cell carcinoma (BCC). Other treatments with topical agents such as 5-fluorouracil or imiquimod have also been suggested for use in superficial BCC (sBCC). Ingenol mebutate (IM) is a novel agent employed in the treatment of superficial actinic keratoses. The drug has been also successfully used in the treatment of sBCC. A case of large nodular BCC (nBCC) of the face in a 100-year-old inoperable woman is described. IM 0.015% gel was applied once daily for three consecutive days...
April 2018: Dermatology Practical & Conceptual
Georgios Gaitanis, Dora Gougopoulou, Eleni Kapsali, Ioannis D Bassukas
Hydroxycarbamide (HC) is the first-line treatment for certain myeloproliferative neoplasms, such as polycythemia vera and essential thrombocytosis (ET). In a subset of these patients long-term treatment with HC can result in the development of confluent actinic keratoses (AK) followed by invasive keratinocytic carcinomas ("squamous dysplasia"), preferentially on sun-exposed skin. Discontinuation or dose reduction of HC may result in partial improvement. A 59-year-old farmer after 14 years on HC (2 gr/d) and acetylsalicylic acid (100 mg/d) for ET, was referred for numerous, hyperkeratotic AK on face, scalp, and hands that could not be controlled with repeated ( N = 15) cryosurgery sessions in the previous 3 years...
2018: Case Reports in Dermatological Medicine
M Ehret, C Velter, M Tebacher, C Bruant-Rodier, B Cribier
INTRODUCTION: Ingenol mebutate is an actinic keratosis treatment, which has a dual action mechanism. It allows a rapid cellular death and a severe inflammation. OBSERVATION: We report the case of a 75 years old patient with a rapidly growing tumor 5 weeks after application of ingenol mebutate on typical actinic keratosis. Histological analysis after surgical excision showed an invasive squamous cell carcinoma (SCC); with aggressiveness signs: perineural infiltration and vascular permeation...
May 17, 2018: Annales de Dermatologie et de Vénéréologie
Roberto Maglie, Vieri Grandi, Vincenza Maio, Alessandro Pileri
No abstract text is available yet for this article.
June 2018: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
E Benati, R Pampena, C Bombonato, S Borsari, M Lombardi, C Longo
Actinic cheilitis (AC) can precede the development of squamous cell carcinoma (SCC) of the lip, a location with higher risk of invasiveness and metastasis. Herein, we reported the use of ingenol mebutate (IngMeb) 0.015% gel on three consecutive days to treat three patients suffering from AC. All the three patients achieved complete clearance of AC with rapid clinical effect, favorable safety profile, good patient's compliance related to short time of applications, and few local skin reactions. So IngMeb is an attractive new therapy for AC...
April 24, 2018: Dermatologic Therapy
David J-Y D Bon, Ondřej Kováč, Vendula Ferugová, František Zálešák, Jiří Pospíšil
Herein we report the efficient one- and two-carbon homologation of 1° and 2° alcohols to their corresponding homologated esters via the Mitsunobu reaction using β-carbonyl benzothiazole (BT) sulfone intermediates. The one-carbon homologation approach uses standard Mitsunobu C-S bond formation, oxidation and subsequent alkylation, while the two-carbon homologation uses a less common C-C bond forming Mitsunobu reaction. In this latter case, the use of β-BT sulfone bearing esters lowers the p Ka sufficiently enough for the substrate to be used as a carbon-based nucleophile and deliver the homologated β-BT sulfone ester, and this superfluous sulfone group can then be cleaved...
May 4, 2018: Journal of Organic Chemistry
C Wyatt Shields, John P White, Erica G Osta, Jerishma Patel, Shashank Rajkumar, Nickolas Kirby, Jean-Philippe Therrien, Stefan Zauscher
Retinol, a derivative of vitamin A, is a ubiquitous compound used to treat acne, reduce wrinkles and protect against conditions like psoriasis and ichthyosis. While retinol is used as the primary active ingredient (AI) in many skin care formulations, its efficacy is often limited by an extreme sensitivity to degrade and toxicity at high concentrations. While microencapsulation is an appealing method to help overcome these issues, few microencapsulation strategies have made a major translational impact due to challenges with complexity, cost, limited protection of the AI and poor control of the release of the AI...
May 28, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Nathan Jetter, Neha Chandan, Stephanie Wang, Maria Tsoukas
Actinic keratoses (AKs) are atypical, precancerous proliferations of keratinocytes that develop because of chronic exposure to ultraviolet (UV) radiation. Treatment of AK can be lesion-directed or field-directed. Field cancerization theory postulates that the skin surrounding AK is also at increased risk for possible malignant transformation since it has been exposed to the same chronic UV light. Field-directed therapies thus have the potential to address subclinical damage, reduce AK recurrence rates, and potentially reduce the risk of squamous cell carcinoma (SCC) development...
August 2018: American Journal of Clinical Dermatology
Bruna De Felice, Francesco Manfellotto, Corrado Garbi, Margherita Santoriello, Massimo Nacca
Keloids are benign skin tumors that develop in individuals who have a positive family history of keloid disorders. Keloids are characterized by a deregulated wound‑healing process, atypical fibroblasts with extreme deposition of extracellular matrix components, particularly collagen, increased cell proliferation and associated failure of apoptosis. Recently ingenol‑mebutate has been used as a novel agent with anti‑proliferative activity on human keloids as an alternative treatment option in patients, once conventional therapies have failed...
May 2018: Molecular Medicine Reports
Romana Čeović, Mikela Petković, Zrinka Bukvić Mokos, Krešimir Kostović
Nonmelanoma skin cancer (NMSC) is the most common cancer, with the median age at NMSC diagnosis is 71 years. Treatment options for NMSC include surgical therapy, which is usually the first-choice treatment, and nonsurgical modalities. Therapeutic modalities depend on tumor localization, histologic type, and biologic behavior, as well as patient comorbidities, age, and life expectancy. Nonsurgical treatments include cryotherapy, local therapies (imiquimod, 5-fluorouracil, ingenol mebutate, and diclofenac), photodynamic therapy, radiotherapy, and hedgehog inhibitors...
March 2018: Clinics in Dermatology
Kinnosuke Yahiro, Sayaka Nagasawa, Kimitoshi Ichimura, Hiroki Takeuchi, Kohei Ogura, Hiroyasu Tsutsuki, Takeshi Shimizu, Sunao Iyoda, Makoto Ohnishi, Hirotaro Iwase, Joel Moss, Masatoshi Noda
Shiga toxigenic Escherichia coli (STEC) are responsible for a worldwide foodborne disease, which is characterized by severe bloody diarrhea and hemolytic uremic syndrome (HUS). Subtilase cytotoxin (SubAB) is a novel AB5 toxin, which is produced by Locus for Enterocyte Effacement (LEE)-negative STEC. Cleavage of the BiP protein by SubAB induces endoplasmic reticulum (ER) stress, followed by induction of cytotoxicity in vitro or lethal severe hemorrhagic inflammation in mice. Here we found that steroids and diacylglycerol (DAG) analogues (e...
December 2018: Cell Death Discovery
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