Topical doxycycline monohydrate hydrogel 1% targeting proteases/PAR2 pathway is a novel therapeutic for atopic dermatitis
EXPERIMENTAL DERMATOLOGY
Authors: Bohannon, Mary; Liu, Mingjin; Nadeau, Peter; Talton, Judy; Gibson, Daniel; Datta, Susmita; Schultz, Gregory; Talton, James; De Benedetto, Anna
Abstract
Atopic Dermatitis (AD) is characterized by skin barrier disruption and an aberrant immune response. Doxycycline is tetracycline antibiotics broadly used systemically to treat inflammatory dermatologic conditions. Several studies have shown doxycycline has anti-inflammatory and pro-healing properties, mainly by blocking tissue proteolytic activity. It is our hypothesis that daily application of a novel doxycycline topical formulation in AD subjects will reduce severity of the disease, by blocking cutaneous proteases activity and restoring skin barrier function and inflammation. To test this hypothesis, we performed a proof of concept, open-label clinical study. Subjects enrolled in the study (n = 15) applied NanoDOX(R)Hydrogel 1% daily for 4 weeks on a chosen eczematous area. Investigational drug was well tolerated, and no local or systemic adverse events due to investigational drug were reported. Notably, a significant clinical improvement was observed based on a modified Eczema Area & Severity Index (EASI) score of the treated area from start of treatment to 14 and 28 days post-treatment (P < .001). A significant improvement of pruritus was also observed (P = .02). This proof of concept clinical trial is first to explore the impact of a non-systemic doxycycline treatment on AD patients. Our results provide evidence to investigate novel AD treatment strategies targeting cutaneous proteases activity.
Human Kallikrein 5 An Interesting Novel Biomarker in Ovarian Cancer Patients That Elicits Humoral Response
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
Authors: Bandiera, Elisabetta; Zanotti, Laura; Bignotti, Eliana; Romani, Chiara; Tassi, Renata; Todeschini, Paola; Tognon, Germana; Ragnoli, Monica; Santin, Alessandro Davide; Gion, Massimo; Pecorelli, Sergio; Ravaggi, Antonella
Abstract
Introduction: Kallikrein-related peptidases are secreted serine proteases that exert stimulatory or inhibitory effects oil tumor progression. A recent Study demonstrated that kallikrein-related peptidase 5 (KLK5) concentration is elevated in serum of patients with ovarian carcinoma. At the moment, the presence of KLK5 in other ovarian pathological lesions is not clearly determined. Moreover, the possibility of a spontaneous humoral immune response to KLK5 has not been studied yet. Methods: In this Study, we examined KLK5 levels and antibody (IgG and IgM) response to KLK5 in the serum of 50 healthy women, 50 patients with benign pelvic masses, 17 patients with ovarian borderline tumors, and 50 patients with ovarian carcinomas, Using 3 enzyme-linked immunosorbent assay tests available in-house. Results: At 95% specificity oil healthy controls, 52% of patients with ovarian carcinoma showed high serum KLK5 (sKLK5) levels, whereas patients with benign pathological lesions or borderline tumors showed almost undetectable sKLK5 levels. Moreover, sKLK5 levels were positively associated to International Federation of Gynaecologists and Obstetricians stage Suggesting a possible role of sKLK5 in ovarian cancer progression. Our results about humoral response showed elevated levels of KLK5-specific antibodies in 20% of patients with benign masses, 26% of patients with borderline tumors, and 36% of patients with ovarian carcinomas when compared with healthy controls. Interestingly, KLK5 antibodies were also found in patients with undetectable sKLK5 levels. Conclusions: In conclusion, Our results showed that KLK5 is a potential new biomarker to be used in combination with other biomarkers for ovarian cancer detection. Moreover, file existence of KLK5 antibodies Suggests that KLK5 might represent a possible target for immune-based therapies.