Teratogenic effect of isotretinoin in both fertile females and males (Review).

Isotretinoin is an oral derivate of vitamin A that has been used since 1982 for the treatment of multiple dermatologic conditions such as severe acne, rosacea, scarring alopecia, ichthyosis or non-melanoma skin cancer prophylaxis. The recommended dose is 0.5-1 mg/kg/day for a period of 4-6 months in sebaceous gland pathologies. There are many adverse effects caused by isotretinoin but by far the most important is the teratogenicity induced by this drug which is estimated to have a 20-35% risk to infants that are exposed to isotretinoin in utero and includes numerous congenital defects such as craniofacial defects, cardiovascular and neurological malformations or thymic disorders. Isotretinoin induces apoptosis and cell cycle arrest in human sebocytes, emphasizing these as processes associated with its teratogenic effect. The aim of this review is to analyze the latest literature data regarding the teratogenic effect of isotretinoin for both fertile females and males and its biological effects underlying the occurrence of congenital malformations under the influence of isotretinoin.

Regressive melanoma in a female patient: A case report.

Regressive melanoma is a phenomenon characterized by partial or complete replacement of cutaneous melanoma by fibrotic structures as a result of local host immune response. The dermoscopic features include 'scar-like' depigmentation that can be described as hypopigmented to pigmented macules, pink macules, linear-irregular vessels, globular vessel pattern, hyperpigmented macular remnants, blue gray 'peppered' papular remnants and white transverse bands. Fully regressive melanoma is very rare, and, in majority of cases, the tumor is associated with metastases, so the prognosis is very poor due to this fact. Regressive melanomas are rare since it represents an advance stage of melanoma evolution. Their treatment requires a collaboration between the dermatologist and the oncologist in order to improve the quality of life of the patient and also the survival rate.

Mediators of Inflammation in Topical Therapy of Skin Cancers.

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. Herein, we review the topical treatment targeting the inflammation in skin cancer and the mechanisms involved in these processes. Currently, various associations have shown a superior success rate than monotherapy, such as systemic acitretin and topical IMQ, topical 5-FU with tretinoin cream, or IMQ with checkpoint inhibitor cytotoxic T lymphocyte antigen 4. Novel therapies targeting Toll-like receptor-7 (TLR-7) with higher selectivity than IMQ are also of great interest.

The Central Role of Inflammation Associated with Checkpoint Inhibitor Treatments.

An important function of the immune system is its ability to differentiate between healthy cells in the organism and "foreign" cells, allowing the latest to be attacked and the first ones to be conserved. The most important molecules in this process are considered to be checkpoint inhibitors. This review is focused on the association between cancer and inflammation, underlying the mechanisms of action of monoclonal antibodies that are targeting checkpoint inhibitors: ipilimumab against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and pembrolizumab and nivolumab against programmed cell death protein 1 (PD-1), their indications for treatment, and side effects. Presence of antibodies against checkpoint inhibitors shows promising results in the clinical trials in patients with types of cancer difficult to treat until now such as melanoma, non-small-cell lung cancer (NSCLC), and renal cell carcinoma, offering an increase in the overall survival rate, response rate, and progression-free rate. Resistance is now observed to emerge in patients treated with this therapy, showing the need for more studies in order to design a biomarker that will predict the type of response to immunotherapy.

Gene polymorphisms of TNF-238G/A, TNF-308G/A, IL10-1082G/A, TNFAIP3, and MC4R and comorbidity occurrence in a Romanian population with psoriasis.

Rationale.Psoriasis is a prevalent chronic inflammatory disease with worldwide distribution affecting approximately 2% of the Caucasian population. There have been many population- and family-based studies that agree on the strong genetic component of this disease. Several studies have investigated the relationship between cytokine gene polymorphisms, psoriasis, and the occurrence of comorbidities but their data are conflicting. Objective.This study examines cytokine gene single-nucleotide polymorphisms (SNPs) in the context of psoriasis and metabolic syndrome, with a focus on the occurrence of comorbidities in psoriasis patients. The working hypothesis is that particular SNPs may predispose to an accelerated disease course and more comorbidities in psoriasis patients. Methods:This cross-sectional study was carried out in 2016 in the Dermatology Department of "Elias" University Emergency Hospital, Bucharest and included 82 psoriasis patients. Several clinical and laboratory parameters were recorded, and the presence of metabolic syndrome (MetS) was noted. Using real-time PCR, we tested for the following SNPs: rs361525, rs1800629, rs1800896, rs610604, rs17782313. Results:Disease severity was not significantly influenced by any of the five studied SNPs. Gene polymorphism of rs17782313 was found to influence the occurrence of psoriatic arthritis. In these patients, rs610604 and rs17782313 polymorphisms were associated with the presence of diabetes mellitus. Furthermore, rs17782313 influenced the presence of obesity, heterozygotes being more at risk. Our data suggested that MetS occurred independently of the five studied SNPs. Discussion.The influence of certain cytokine gene polymorphisms on multiple organ systems is justification enough for further analysis of the genetic and molecular mechanisms of metabolic syndrome development in psoriasis patients. Abbreviations:single-nucleotide polymorphisms - SNPs, metabolic syndrome - MetS.