no / Hair loss can be a psychologically devastating adverse effect of chemotherapy, but satisfactory management strategies for chemotherapy-induced alopecia remain elusive. In this Review we focus on the complex pathobiology of this side-effect. We discuss the clinical features and current management approaches, then draw upon evidence from mouse models and human hair-follicle organ-culture studies to explore the main pathobiology principles and explain why chemotherapy-induced alopecia is so challenging to manage. P53-dependent apoptosis of hair-matrix keratinocytes and chemotherapy-induced hair-cycle abnormalities, driven by the dystrophic anagen or dystrophic catagen pathway, play important parts in the degree of hair-follicle damage, alopecia phenotype, and hair-regrowth pattern. Additionally, the degree of hair-follicle stem-cell damage determines whether chemotherapy-induced alopecia is reversible. We highlight the need for carefully designed preclinical research models to generate novel, clinically relevant pointers to how this condition may be overcome.

Yes / Background: Multiple biomarkers have been associated with hair loss in women, but studies showed inconsistent results. Objective: We investigated the association between markers of cardiovascular disease risk (e.g., serum lipid levels and hypertension) and aging (e.g., 25-hydroxyvitamin D and insulin-like growth factor) with hair loss in a population of middle-aged women. Methods: In a random subgroup of 323 middle-aged women (mean age: 61.5 years) from the Leiden Longevity Study, hair loss was graded by three assessors using the Sinclair scale; women with a mean score higher than 1.5 were classified as cases with hair loss. Results: Every standard deviation increase in HDL cholesterol was associated with a 0.65 times lower risk (95% confidence interval [CI]: 0.46–0.91) of hair loss; for IGF-1 the risk was 0.68 times lower (95% CI: 0.48–0.97) per standard deviation increase, independent of the other studied variables. Women with both IGF-1 and HDL cholesterol levels below the median of the study population had a 3.47 times higher risk (95% CI: 1.30–9.25) of having hair loss. Limitations: The observational setting limits causal inference of the findings. Conclusion: Low HDL cholesterol and IGF-1 were associated with a higher risk of hair loss in women. / This study was funded by the Innovation Oriented Research Program on Genomics (SenterNovem; IGE01014 and IGE5007), the Centre for Medical Systems Biology (CMSB), the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research (05040202 and 050-060-810, NCHA), Unilever PLC and the European Union-funded Network of Excellence Lifespan (FP6 036894).

Estudo qualitativo, cujo objetivo foi compreender o significado da alopecia, decorrente de quimioterapia, para mulheres submetidas a esse tipo de tratamento para o câncer ginecológico ou mamário, e teve como referencial teórico o Interacionismo Simbólico. Os dados foram obtidos por meio de entrevistas e prontuários de 15 mulheres que apresentaram alopecia como evento adverso ao tratamento quimioterápico, e frequentavam um serviço especializado em reabilitação pós-mastectomia ou um ambulatório ou enfermaria de oncologia de um hospital universitário do interior de São Paulo. Foram identificadas duas unidades temáticas pela Análise de Conteúdo: 1) o significado da alopecia para as mulheres que a apresentam, na relação consigo próprias; e 2) na relação com os outros e com o mundo. Na relação consigo próprias, a alopecia significou necessidade de lidar com alterações emocionais e da autoestima, necessidade de disfarce, dificuldade de lidar com a alopecia, de se olhar no espelho e de falar sobre o assunto, sendo que a mulher descobriu formas de lidar com os problemas ocasionados pela queda de cabelo, embora este tenha sido um problema que muitas vezes trouxe sofrimento maior do que o câncer em si. Já na relação com os outros e com o mundo, a alopecia foi tida como um estigma relacionado ao câncer e seus tratamentos, trouxe mudanças nos hábitos e rotinas, além de interferir na sexualidade. Assim, puderam ser identificadas instituições que ofereceram apoio às mulheres. Compreender o significado pleno da experiência de alopecia na vida cotidiana dessas mulheres é fundamental para poder proporcionar-lhes apoio durante o curso da doença, e para auxiliá-las no desenvolvimento de estratégias para lidar com as mudanças que ocorrem durante o tratamento do câncer. / Qualitative study aimed to understand the meaning of hair loss because chemotherapy for women undergoing this type of treatment for breast or gynecological cancer, and had the theoretical Symbolic Interaction. Data were collected through interviews and medical records of15 women who had hair loss as an adverse event to chemotherapy, and attended a specialized rehabilitation postmastectomy or a clinic or oncology ward of a university hospital in São Paulo. Two thematic units were identified by Content Analysis: 1) the meaning of hair loss for women, in relation to themselves, and 2) the relationship with others and with the world. In relation to themselves, hair loss meant the necessity to deal with emotional and self-esteem, the necessity to disguise, difficulty to deal with alopecia, to look in the mirror and talk about it, although the woman discovered ways of dealing with the problems caused by hair loss, this has been a problem that often caused more suffering than the cancer. In the relation with others and with the world, the hair loss was seen as a stigma related to cancer and its treatments, caused changes in habits and routines, as well as interfere with sexuality. Therefore could be identified institutions which offered support for women. Understand the full meaning of the experience of hair loss in women\'s daily life is crucial to be able to provide them support during the course of the disease, and to assist them in developing strategies to deal with the changes that occur during cancer treatment

The dermal papillae of the hair follicle control its growth, differentiation and apoptosis via a range of growth factors. These secreted growth factors are known to differ between those of non-balding scalp and those of balding scalp and can even differ in response to a common stimuli – androgen. In balding scalp androgen stimulates the secretion of negative growth factors, while in non-balding scalp androgen is found to exert little or no effect. Dermal papilla cells (DPCs) can be cultured in vitro, however those from balding scalp have been found to undergo premature senescence compared to those from non-balding scalp. A major cause of premature senescence is oxidative stress – the gradual accumulation of reactive oxygen species within the cell causing deleterious loss of function. Reactive oxygen species are known to be mediated in response to androgens and growth factors and in turn may affect growth factor signalling within the cell. Using low oxygen cell culture as a means of reducing oxidative stress, balding and non-balding DPCs were grown and characterised. It was confirmed that low oxygen culture could increase proliferation, delay senescence and reduce reactive oxygen species with both DPC types and that balding DPCs showed a higher sensitivity to oxidative stress. It was also found that secretions of growth factors by the balding DPCs in response to different oxygen conditions differed greatly to that of the occipital DPCs. Androgen, but not TGF-β was found to modulate DPC production of catalase, an antioxidant, under low oxygen conditions and this caused a reduction in reactive oxygen species in the balding DPCs. Balding DPCs also demonstrated an upregulation of the antioxidant total glutathione, however had a reduced fraction of the active reduced form of the molecule. In addition, it was shown for the first time 3 that under cell culture conditions balding DPCs express TGF-β receptors and it was shown that proliferation and migration of the balding DPCs could be affected by addition of exogenous TGF-β, highlighting a potential role for TGF-β as an autocrine growth factor in the balding dermal papilla.

Estudo qualitativo, cujo objetivo foi compreender o significado da alopecia, decorrente de quimioterapia, para mulheres submetidas a esse tipo de tratamento para o câncer ginecológico ou mamário, e teve como referencial teórico o Interacionismo Simbólico. Os dados foram obtidos por meio de entrevistas e prontuários de 15 mulheres que apresentaram alopecia como evento adverso ao tratamento quimioterápico, e frequentavam um serviço especializado em reabilitação pós-mastectomia ou um ambulatório ou enfermaria de oncologia de um hospital universitário do interior de São Paulo. Foram identificadas duas unidades temáticas pela Análise de Conteúdo: 1) o significado da alopecia para as mulheres que a apresentam, na relação consigo próprias; e 2) na relação com os outros e com o mundo. Na relação consigo próprias, a alopecia significou necessidade de lidar com alterações emocionais e da autoestima, necessidade de disfarce, dificuldade de lidar com a alopecia, de se olhar no espelho e de falar sobre o assunto, sendo que a mulher descobriu formas de lidar com os problemas ocasionados pela queda de cabelo, embora este tenha sido um problema que muitas vezes trouxe sofrimento maior do que o câncer em si. Já na relação com os outros e com o mundo, a alopecia foi tida como um estigma relacionado ao câncer e seus tratamentos, trouxe mudanças nos hábitos e rotinas, além de interferir na sexualidade. Assim, puderam ser identificadas instituições que ofereceram apoio às mulheres. Compreender o significado pleno da experiência de alopecia na vida cotidiana dessas mulheres é fundamental para poder proporcionar-lhes apoio durante o curso da doença, e para auxiliá-las no desenvolvimento de estratégias para lidar com as mudanças que ocorrem durante o tratamento do câncer. / Qualitative study aimed to understand the meaning of hair loss because chemotherapy for women undergoing this type of treatment for breast or gynecological cancer, and had the theoretical Symbolic Interaction. Data were collected through interviews and medical records of15 women who had hair loss as an adverse event to chemotherapy, and attended a specialized rehabilitation postmastectomy or a clinic or oncology ward of a university hospital in São Paulo. Two thematic units were identified by Content Analysis: 1) the meaning of hair loss for women, in relation to themselves, and 2) the relationship with others and with the world. In relation to themselves, hair loss meant the necessity to deal with emotional and self-esteem, the necessity to disguise, difficulty to deal with alopecia, to look in the mirror and talk about it, although the woman discovered ways of dealing with the problems caused by hair loss, this has been a problem that often caused more suffering than the cancer. In the relation with others and with the world, the hair loss was seen as a stigma related to cancer and its treatments, caused changes in habits and routines, as well as interfere with sexuality. Therefore could be identified institutions which offered support for women. Understand the full meaning of the experience of hair loss in women\'s daily life is crucial to be able to provide them support during the course of the disease, and to assist them in developing strategies to deal with the changes that occur during cancer treatment

Every year an avorage of 40 000 Swedes fall ill with different forms of cancer. Chemotheraphy has an effect on the tumour cells as well as the healthy cells in the body, this causes many side effects which can be very problematic for the patient. The study was carried out in order to indicate the care measures that are taken to deal with the side effects i. e stomatit, loss of hair and sickness/vomiting, that are connected with chemotheraphy so that the outpatients will experience a quality of life. The method used was a qualitative interview with six nurses from the South if Sweden, all of whom are working with chemotheraphy patients. The results showed that the nurses thought that quality of life was individual, in their care work the patients needs and valuations were used as a starting point. Aside form the specific care measures for respective side-effects they put an emphasis on talking and giving information to patients. In addition, they indicated the relationship they had with their patients. Accordi ng to them a good relation to the patient is a prerequisite of good care work.

no / Alopecia areata is an immunologically mediated disease characterized by extreme variability not only in the time of initial onset of hair loss but in the duration, extent and pattern of hair loss during any given episode of active loss. These variables, as well as the unpredictable nature of spontaneous regrowth and lack of a uniform response to various therapies, has made clinical trials in alopecia areata difficult to plan and implement. In fact, there are currently no drugs FDA-approved specifically for the indication of alopecia areata. To help facilitate well-controlled clinical trials for alopecia areata, this National Alopecia Areata Foundation (NAAF) sponsored subgroup of investigators/clinicians experienced in clinical trials and/or in the clinical care of patients with alopecia areata has outlined some general principles and potential endpoints for clinical studies in alopecia areata. These guidelines build on the Alopecia Areata Investigational Assessment Guidelines published in 1991 which established baseline clinical staging and background information important to gather on any alopecia areata patient involved in clinical research.

Hair disorders cause significant distress. The main, but limited, treatment for hair loss is minoxidil, an ATP-­sensitive potassium (KATP) channel opener whose mechanism of stimulation is unclear. The regulatory component of KATP channels has three forms: SUR1, SUR2A and SUR2B which all respond to different molecules. Minoxidil only opens SUR2B channels, though SUR1 and SUR2B are present in human hair follicles. To expand our understanding, the red deer hair follicle model was used initially. Deer follicles expressed the same KATP channel genes as human follicles when growing (anagen), but no channels were detected in resting follicles. This reinforces the importance of KATP channels in active hair growth and the usefulness of the deer model. To assess whether SUR1 KATP channels are actually involved in human hair growth, the effects of a selective SUR1 channel opener, NNC55-­9216, on scalp follicle growth in organ culture was examined. NNC55-­9216 stimulated anagen; its effect was augmented by minoxidil. This creates the potential for more effective pharmaceuticals to treat hair loss via SUR1 channels, either alone or in combination with minoxidil. The dermal papilla plays a crucial regulatory role in hair follicle activity determining the type of hair produced. Minoxidil had no effect on dermal papilla cell proliferation, but altered the profile of proteins produced when assessed by proteomics. Further research into the roles of KATP channels and greater understanding of the significance of these protein changes should enhance our knowledge of hair biology and help the development of new, improved therapies for hair pathologies.

Lack of hair due to alopecia or skin grafting procedures causes significant distress due to hair's role in social and sexual communication. Only limited pharmacological agents are currently available to stimulate hair growth; their development is hampered by inappropriate model systems. Most research involves large terminal scalp follicles rather than the clinical targets of tiny vellus or intermediate follicles. The overall aim of this thesis was to develop a novel model system based on intermediate hair follicles. Initially, intermediate follicles from female pre-auricular skin were characterised and compared to matched terminal follicles. Intermediate follicles were smaller, less pigmented, shorter and possessed a more 'tubular' bulb morphology than their more 'bulbous' terminal counterparts. Significant correlations were demonstrated between various hair follicle measurements and corresponding dermal papilla diameters. Isolated terminal follicles grew significantly more than intermediate hair follicles in organ culture for 9 days. Testosterone (10nM), the major regulator of human hair growth, increased only intermediate follicle growth; the anti-androgen, cyproterone acetate (1¿M), prevented this stimulation, unlike the 5¿-reductase type 2 inhibitor finasteride (40ng/ml). Immunohistochemistry demonstrated androgen receptor and 5¿-reductase type 2 proteins in both follicle types, while quantitative real-time PCR and gene microarray analysis detected their increased gene expression in intermediate follicles. Thus, smaller intermediate follicles showed major morphological and gene expression differences to terminal follicles in vivo and retained significant, biologically-relevant differences in vitro in organ culture including androgen-responsiveness. Therefore, intermediate hair follicles offer a novel, exciting, more clinically relevant, albeit technically difficult, model for future investigations into hair growth.

Lack of hair due to alopecia or skin grafting procedures causes significant distress due to hair's role in social and sexual communication. Only limited pharmacological agents are currently available to stimulate hair growth; their development is hampered by inappropriate model systems. Most research involves large terminal scalp follicles rather than the clinical targets of tiny vellus or intermediate follicles. The overall aim of this thesis was to develop a novel model system based on intermediate hair follicles. Initially, intermediate follicles from female pre-auricular skin were characterised and compared to matched terminal follicles. Intermediate follicles were smaller, less pigmented, shorter and possessed a more 'tubular' bulb morphology than their more 'bulbous' terminal counterparts. Significant correlations were demonstrated between various hair follicle measurements and corresponding dermal papilla diameters. Isolated terminal follicles grew significantly more than intermediate hair follicles in organ culture for 9 days. Testosterone (10nM), the major regulator of human hair growth, increased only intermediate follicle growth; the anti-androgen, cyproterone acetate (1μM), prevented this stimulation, unlike the 5α-reductase type 2 inhibitor finasteride (40ng/ml). Immunohistochemistry demonstrated androgen receptor and 5α-reductase type 2 proteins in both follicle types, while quantitative real-time PCR and gene microarray analysis detected their increased gene expression in intermediate follicles. Thus, smaller intermediate follicles showed major morphological and gene expression differences to terminal follicles in vivo and retained significant, biologically-relevant differences in vitro in organ culture including androgen-responsiveness. Therefore, intermediate hair follicles offer a novel, exciting, more clinically relevant, albeit technically difficult, model for future investigations into hair growth.