Retinoids are natural and synthetic vitamin A derivatives that are effective for the prevention and the treatment of non-melanoma skin cancers (NMSC). NMSCs constitute a heterogenous group of non-melanocyte-derived skin cancers that impose substantial burdens on patients and healthcare systems. They include entities such as basal cell carcinoma and cutaneous squamous cell carcinoma (collectively called keratinocyte carcinomas), cutaneous lymphomas and Kaposi’s sarcoma among others. The retinoid signaling pathway plays influential roles in skin physiology and pathology. These compounds regulate diverse biological processes within the skin, including proliferation, differentiation, angiogenesis and immune regulation. Collectively, retinoids can suppress skin carcinogenesis. Both topical and systemic retinoids have been investigated in clinical trials as NMSC prophylactics and treatments. Desirable efficacy and tolerability in clinical trials have prompted health regulatory bodies to approve the use of retinoids for NMSC management. Acceptable off-label uses of these compounds as drugs for skin cancers are also described. This review is a comprehensive outline on the biochemistry of retinoids, their activities in the skin, their effects on cancer cells and their adoption in clinical practice.
Actinic keratosis (AK) is among the most commonly diagnosed skin diseases with potentially life-threatening repercussions if left untreated. Usage of pharmacologic agents represents one of many therapeutic strategies that can be used to help manage these lesions. Ongoing research into these compounds continues to change our clinical understanding as to which agents most benefit particular patient populations. Indeed, factors such as past personal medical history, lesion location and tolerability of therapy only represent a few considerations that clinicians must account for when prescribing appropriate treatment. This review focuses on specific drugs used in either the prevention or treatment of AKs. Nicotinamide, acitretin and topical 5-fluorouracil (5-FU) continue to be used with fidelity in the chemoprevention of actinic keratosis, although some uncertainty persists in regard to which agents should be used in immunocompetent vs. immunodeficient/immunosuppressed patients. Topical 5-FU, including combination formulations with either calcipotriol or salicylic acid, as well as imiquimod, diclofenac and photodynamic light therapy are all accepted treatment strategies employed to target and eliminate AKs. Five percent of 5-FU is regarded as the most effective therapy in the condition, although the literature has conflictingly shown that lower concentrations of the drug might also be as effective. Topical diclofenac (3%) appears to be less efficacious than 5% 5-FU, 3.75–5% imiquimod and photodynamic light therapy despite its favorable side effect profile. Finally, traditional photodynamic light therapy, while painful, appears to be of higher efficacy in comparison to its more tolerable counterpart, daylight phototherapy.
The present study investigates the mediating roles of psychological inflexibility and differential coping strategies on perceived stress and post-traumatic symptoms and growth in the context of COVID-19. Study one recruited 662 participants (54.8% women; Mage = 40.64 years, SD = 13.04) who completed a cross-sectional questionnaire. It was proposed that orientation to the problem, avoidance strategies, psychological inflexibility, and positive attitude were mediators for the positive association between perceived stress and PTSD symptoms. The fit indices for the path model were excellent: CFI = 0.977, TLI = 0.950, RMSEA = 0.057 [90%CI = 0.043–0.081], and SRMS = 0.042. Gender and stressful events encountered had indirect effects on the endogenous variables. In study two, 128 participants (57.8% women; Mage = 42.30, SD = 12.08) were assessed for post-traumatic growth one year later. Psychological inflexibility and orientation acted as mediators between perceived stress and PTSD symptoms. Furthermore, a novel path model was constructed in which psychological inflexibility and orientation to the problem as mediators for perceived stress and PTSD symptoms. The indices for the path model were excellent: CFI = 0.99, TLI = 0.97, RMSEA = 0.055 [90%CI = 0.001–0.144], and SRMS = 0.49. Furthermore, PTSD symptoms, psychological inflexibility, and orientation to the problem predicted post-traumatic growth. Specifically, both orientation to the problem (β = .06 [90%CI: .01;.13]) and psychological inflexibility (β = .14 [90%CI: .08;.26]) had an indirect effect on post-traumatic growth. Overall, these results significantly contribute to the literature as orientation to the problem positively predicted PTSD symptoms and post-traumatic growth one year later while psychological inflexibility predicted PTSD symptoms and less post-traumatic growth one year later. These results underline the importance of assessing both symptomology and psychological growth to determine adaptive coping strategies in specific contexts.
Breast cancer represents the most frequent cancer and the leading cause of cancer death among women. Thus, the prevention and early diagnosis of breast cancer appears to be of primary urgency as well as the development of new treatments able to improve its prognosis. Nerve Growth Factor (NGF) is a neurotrophic factor that plays a key role in the regulation of neuronal functions thought the binding to the Tropomyosin receptor kinase A (TrkA) and the Nerve Growth Factor receptor or Pan-Neurotrophin Receptor 75 (NGFR/p75NTR). Also, its precursor (pro-NGF) can extert biological activity by forming a trimeric complex with NGFR/p75NTR and sortilin or by binding to TrkA receptors with low affinity. Both in vitro and in vivo studies showed that NGF is synthesized and released by breast cancer cells and has mitogen, antiapoptotic and angiogenic effects on these cells through the activation of different signaling cascades that involve TrkA and NGFR/p75NTR receptors. Conversely, pro-NGF signaling has been related to breast cancer invasion and metastasis. Other studies suggested that NGF and its receptors could represent a good diagnostic and prognostic tool, as well as promising therapeutic targets for breast cancer. Here, we comprehensively summarize and systematically review the current experimental evidence on this topic.
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