Cancer-Related Alopecia: From Etiologies to Global Management.

Alopecia represents a multifaceted challenge with distinct etiologies and consequences. Transposed to the world of oncology, different types of alopecia and molecular pathways have been characterized, allowing a better understanding of the underlying mechanisms. In patients with cancer, alopecia can be iatrogenic (i.e., due to conventional chemotherapies, endocrine therapies, targeted therapies, immunotherapies, radiotherapy and surgery) or a direct consequence of the disease itself (e.g., malnutrition, scalp metastases and paraneoplastic syndromes). Identification of the actual incriminated mechanism(s) is therefore essential in order to deliver appropriate supportive care, whether preventive or curative. On the preventive side, the last few years have seen the advent of the automated cooling cap, a prophylactic approach supported by several randomized clinical trials. On the curative side, although the treatments currently available are limited, several promising therapeutic approaches are under development. Appropriate alopecia management is essential, particularly regarding its psychological repercussions with significant consequences on the quality of life of patients and their family and with a potential impact on treatment compliance.

[Alopecia and cancers: From basics to clinical practice]. / Alopécie et cancers : de la physiopathologie à la pratique clinique.

Alopecia, although long considered an unavoidable consequence of cancer therapy, currently presents a multifaceted challenge. The knowledge of the physiology of the hair and consequently of the pathophysiology of alopecia has led to show that there is not one but several types of alopecia. Transposed to the world of oncology, different types of alopecia and subsequently molecular pathways have been characterized, allowing a better understanding of the underlying mechanisms. Thus, in patients with cancer, alopecia can be iatrogenic (chemotherapies, endocrine therapies, targeted therapies, immunotherapies, radiotherapy, surgery) or directly the consequence of the disease itself (malnutrition, scalp metastases, paraneoplastic syndromes). Knowledge of the incriminated mechanism(s) could thus make it possible to deploy an appropriate care component, whether on the preventive or curative sides or in terms of supportive care. These are particularly essential regarding the psychological repercussions caused by alopecia, with significant consequences on the quality of life of patients and with a potential impact on treatment compliance. On the preventive side, the last few years have seen the advent of the automated scalp cooling therapy, supported by several randomized clinical trials. On the curative side, several therapeutic proposals are currently deployed or under development in order to provide relevant treatments.

Sensitive scalp is associated with excessive sebum and perturbed microbiome.

BACKGROUND: Sensitive scalp, one of the most frequent complaints among sensitive skin syndrome, has been described as abnormal and unpleasant sensory reactions of the scalp to environmental stimulus. However, the symptoms are usually objective and hard to diagnose. OBJECTIVE: This study aimed to reveal the biophysical properties and etiology of sensitive scalp. METHODS: Sixty-two healthy female subjects were enrolled and divided into nonsensitive scalp (NS) and sensitive scalp (SS) groups according to questionnaires. Noninvasive instruments were used to measure biophysical properties. Ultra-performance liquid chromatography-tandem mass spectrometry and gas chromatography mass spectrometry were introduced to quantify skin lipids profiles, and 16S rRNA sequencing was used to detect the composition of bacteria. RESULTS: Sensitive scalp showed elevated pH level, more irritated skin, and more fluorescence of porphyrins. Increased sebum production was found in SS group at occiput, among which free fatty acids, cholesteryl ester, and squalene were significantly in higher amount compared with NS. SS also had significantly higher percentage of Propionibacterium, and lower bacterial diversity. CONCLUSIONS: Taken together, sensitive scalp showed disrupted barrier function, abnormal sebum amount and composition, as well as perturbed microbiome, which might be the direct cause. Products targeting these features could be helpful for the treatment of sensitive scalp.

Evaluation of the severity and triggering factors of sensitive scalp in Chinese females.

BACKGROUND: Sensitive scalp which has been recently proposed and assessed by several questionnaires is one of the most cosmetic concerns in sensitive skin syndrome by consumers. OBJECTIVE: This study is to investigate the prevalence and factors related to the scalp sensitivity in China. METHODS: Two well-known questionnaires including four-grade self-assessment and 3S, and a new questionnaire we proposed (10Q), were used to evaluate the severity and symptoms of sensitive scalp. RESULTS: The proportions of sensitive scalp according to self-assessment and 3S were 35.77% and 57.45%, respectively. Distributions of severity and tendency of proportion along ages were significantly different between the two methods. The 10Q questionnaire which we designed could discriminate different grade of severity of sensitive scalp with superior reliability. Moreover, triggering factors which have significant impacts on the symptoms of sensitive scalp were elucidated by logistic regression analysis, including air dryness, exercises, humidity, heat, and sun. CONCLUSION: Questionnaires with more dimensions and details such as 10Q and 3S should be used for the diagnosis, prognosis, and treatment monitoring on sensitive scalp in Chinese female.

The topical corticosteroid classification called into question: towards a new approach.

Vasoconstrictor assay described in 1962 was an interesting assessment of potency of topical corticosteroids at the beginning of these new therapies, however knowledge and technology have evolved and the classification should follow. A topical corticosteroids with a strong vasoconstrictor effect, as determined by vasoconstrictor assay, has not necessary a strong anti-inflammatory effect. Therefore a specific classification adapted to the therapeutic target is needed to be more efficient and thus reduce side effects and corticophobia.

Effects of topical corticosteroids on cell proliferation, cell cycle progression and apoptosis: in vitro comparison on HaCaT.

Topical-corticosteroids are mainly used for the treatment of inflammatory or hyperproliferative skin diseases. The in vivo assay to rank topical-corticosteroids potency, based on the skin blanching, is not adapted to compare their anti-proliferative efficacy. We have compared the antiproliferative effect of six topical-corticosteroids on a model of hyperproliferant keratinocytes (HaCaT). Betamethasone-dipropionate; clobetasol-propionate; betamethasone-valerate; desonide; hydrocortisone-butyrate and hydrocortisone-base, at different concentrations (10(-8)-10(-4)M) have been compared. HaCaT proliferation has been evaluated by MTT-assay and the mechanism of the death was evaluated by annexin V/propidium iodide staining and cell cycle phases analysis. Topical corticosteroids reduced cell growth in a dose-dependent manner. At 10(-4)M, betamethasone dipropionate was the most antiproliferative compound while hydrocortisone-butyrate was the less. Hydrocortisone-base which is usually considered as the less potent topical-corticosteroids showed a clear cytotoxic effect. Betamethasone-dipropionate and betamethasone-valerate induced more apoptosis than necrosis whereas the reverse has been observed for other topical-corticosteroids. All topical-corticosteroids, except clobetasol-propionate, arrested cell cycle mainly in G2-phase. Clobetasol-propionate arrested cell cycle in S-phase population. At 10(-8)M, topical-corticosteroids induced HaCaT proliferation. In terms of antiproliferative effect at 10(-4)M, we propose to rank topical corticosteroids as follow: betamethasone-dipropionate>desonide≥betamethasone-valerate=hydrocortisone-base=clobetasol-propionate>hydrocortisone-butyrate. This classification differs from the current ranking, based on the vasoconstrictive effect, but is more adapted for hyperproliferative disease treatment.

N-palmitoylethanolamine and N-acetylethanolamine are effective in asteatotic eczema: results of a randomized, double-blind, controlled study in 60 patients.

BACKGROUND: Asteatotic eczema (AE) is characterized by itchy, dry, rough, and scaling skin. The treatments for AE are mainly emollients, usually containing urea, lactic acid, or a lactate salt. N-palmitoylethanolamine (PEA) and N-acetylethanolamine (AEA) are both endogenous lipids used as novel therapeutic tools in the treatment of many skin diseases. The purpose of this study was to compare a PEA/AEA emollient with a traditional emollient in the treatment of AE. METHODS: A monocentric, randomized, double-blind, comparative trial was conducted in 60 AE patients to evaluate and compare the efficacy of the two emollients. The level of skin dryness among the subjects ranged from mild to moderate. The subjects' skin barrier function and the current perception threshold were tested for 28 days by clinical scoring and bioengineering technology. RESULTS: The results showed that, although some aspects were improved in both groups, the group using the emollient containing PEA/AEA presented a better skin surface change in capacitance. However, the most impressive finding was the ability of the PEA/AEA emollient to increase the 5 Hz current perception threshold to a normal level after 7 days, with a significant difference between values at baseline and after 14 days. A current perception threshold of 5 Hz was positively and significantly correlated with skin surface hydration and negatively correlated with transepidermal water loss in the PEA/AEA emollient group. CONCLUSION: Compared with traditional emollients, regular application of a topical PEA/AEA emollient could improve both passive and active skin functions simultaneously.

Efficacy of micronutrient supplementation on skin aging and seasonal variation: a randomized, placebo-controlled, double-blind study.

BACKGROUND: Several studies have confirmed dramatic changes in skin surface parameters during the winter months. Although there are many studies supporting the positive effects of topical treatment, there are no published studies demonstrating the effects of oral supplementation in the prevention of negative skin changes during winter. The purpose of this study was to evaluate the efficacy of an oral micronutrient supplement in preventing the negative effects of winter weather on skin quality using noninvasive biometrologic instruments. METHODS: This study included 80 healthy female volunteers aged 35-55 years with phototype II-IV skin. Randomization was balanced. Two tablets of a micronutrient supplement (Perfectil® Platinum) or placebo were administered once daily for 4 months. The volunteers were examined at baseline, after 4 months, and 6 weeks after termination of treatment (month 5.5). The evaluation included skin microrelief by Visioscan® as the main outcome, and the secondary outcomes were results on standard macrophotography, skin tension by Reviscometer®, skin high-frequency ultrasound, and self-assessment. RESULTS: For all pseudoroughness and microrelief indicators, there was a significant increase from baseline to month 4 in the placebo group (P<0.05) but no change in the active group. Descriptive statistics for the mean minimum, mean maximum, and minimum to maximum ratio on the nonexposed study zone showed a significant and dramatic difference between baseline and month 4 and between baseline and month 5.5 (P<0.05) in the active group, indicating decreasing anisotropy of the skin. High-frequency ultrasound on the exposed study zone revealed that skin thickness was significantly decreased in the placebo group during winter but was stable in the treated group (P<0.01). The photography scaling and self-assessment questionnaire revealed no significant changes in either group. CONCLUSION: These results indicate that the skin is prone to seasonal changes during winter, particularly in exposed areas. The data also indicate that oral supplementation can be a safe treatment, with no serious side effects, and may prevent or even eliminate the negative effects of winter on the skin.

Crystallization and preliminary X-ray crystallographic study of the wild type and two mutants of the CP1 hydrolytic domain from Aquifex aeolicus leucyl-tRNA synthetase.

The editing or hydrolytic CP1 domain of leucyl-tRNA synthetase (LeuRS) hydrolyses several misactivated amino acids. The CP1 domain of Aquifex aeolicus LeuRS was expressed, purified and crystallized by the hanging-drop vapour-diffusion method using ammonium sulfate as precipitant. Crystals belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 38.8, b = 98.4, c = 116.7 A. Crystals diffract to beyond 1.8 A resolution and contain two monomers in the asymmetric unit. Two CP1 mutants in which a conserved threonine residue essential for the fidelity of the hydrolytic pathway is mutated to alanine or glutamic acid have also been expressed and crystallized. Crystals of the two CP1 mutants are isomorphs of the wild type and diffract to beyond 1.9 A resolution. All structures were solved by molecular-replacement techniques.