Dataset Information

Role of increased vascular permeability in chemotherapy-induced alopecia: In vivo imaging of the hair follicular microenvironment in mice.

ABSTRACT: Chemotherapy-induced alopecia is one of the most difficult adverse events of cancer treatment for patients. However, it is still unknown why anticancer drugs cause hair loss. We aimed to clarify the mechanism of chemotherapy-induced alopecia in mice using an in vivo imaging technique with a two-photon microscope, which enables observation of the deep reaction in the living body in real time. In this study, ICR mice were injected intraperitoneally with cyclophosphamide (120 µg/g). Changes in the hair bulb morphology, subcutaneous vessel permeability, and vessel density were evaluated by two-photon microscopy and conventional methods. In order to determine whether there is a causal relationship between vascular permeability and hair loss, we combined cyclophosphamide (50 µg/g) with subcutaneous histamine. Using two?photon microscopy and conventional examination, we confirmed that the hair bulbs became smaller, blood vessels around the hair follicle decreased, and vascular permeability increased at 24 hours after cyclophosphamide injection [corrected]. Apoptosis occurred in vascular endothelial cells around the hair follicle. Additionally, hair loss was exacerbated by temporarily enhancing vascular permeability with histamine. In conclusion, cyclophosphamide caused a decrease in vascular density and an increase in vascular permeability, therefore increased vascular permeability might be one of the causes of chemotherapy-induced alopecia.

SUBMITTER: Sagawa N

PROVIDER: S-EPMC7293075 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Role of increased vascular permeability in chemotherapy-induced alopecia: In vivo imaging of the hair follicular microenvironment in mice.

Sagawa Noriko N Oshima Yusuke Y Hiratsuka Takahiro T Kono Yohei Y Etoh Tsuyoshi T Inomata Masafumi M

Cancer science 20200501 6

Chemotherapy-induced alopecia is one of the most difficult adverse events of cancer treatment for patients. However, it is still unknown why anticancer drugs cause hair loss. We aimed to clarify the mechanism of chemotherapy-induced alopecia in mice using an in vivo imaging technique with a two-photon microscope, which enables observation of the deep reaction in the living body in real time. In this study, ICR mice were injected intraperitoneally with cyclophosphamide (120 µg/g). Changes in the ...[more]

PMID: 32227405

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Project description:The growth and development of hair follicles is influenced by a number of different growth factors and cytokines, particularly members of the fibroblast growth factor (FGF) family. Keratinocyte growth factor (KGF or FGF-7) is a recently identified 28-kd member of the FGF family that induces proliferation of a wide variety of epithelial cells, including keratinocytes within the epidermis and dermal adnexa. Because KGF induces marked proliferation of keratinocytes, and both KGF and KGF receptor (KGFR) mRNA are expressed at high levels in skin, we sought to localize KGF and KGFR in skin by in situ hybridization. KGFR mRNA was relatively strongly expressed by keratinocytes in the basilar epidermis as well as throughout developing hair follicles of rat embryos and neonates. KGF mRNA was expressed at lower levels than was KGFR but could be localized to follicular dermal papillae in rat embryos and neonates. These results prompted us to investigate the effects of KGF on hair follicles in two distinct murine models of alopecia. In the first model, recombinant KGF (rKGF) induced dose-dependent hair growth over most of the body in nu/nu athymic nude mice when administered intraperitoneally or subcutaneously over 17 to 18 days. When administered subcutaneously, rKGF induced the most extensive hair growth at the sites of injection. Histologically, rKGF induced marked follicular and sebaceous gland hypertrophy, a normalization of the nu/nu follicular keratinization defect, and an increase in follicular keratinocyte proliferation as assessed by bromodeoxyuridine labeling. In the second model, a neonatal rat model of cytosine arabinoside chemotherapy-induced alopecia in which interleukin-1, epidermal growth factor, and acidic FGF have all demonstrated some degree of alopecia cytoprotection, rKGF induced a dose-dependent cytoprotective effect, abrogating as much as 50% of the alopecia in this model when administered beginning 1 day before the onset of chemotherapy. Taken together, these data suggest that KGF is an important endogenous mediator of normal hair follicle growth, development, and differentiation.

Project description:ImportanceClinical estimation of hair density has an important role in assessing and tracking the severity and progression of alopecia, yet to the authors' knowledge, no automation currently exists for this process. While some algorithms have been developed to assess alopecia presence on a binary level, their scope has been limited by focusing on a re-creation of the Severity of Alopecia Tool (SALT) score for alopecia areata (AA). Yet hair density loss is common to all alopecia forms, and an evaluation of that loss is used in established scoring systems for androgenetic alopecia (AGA), central centrifugal cicatricial alopecia (CCCA), and many more.ObjectiveTo develop and validate a new model, HairComb, to automatically compute the percentage hair loss from images regardless of alopecia subtype.Design, setting, and participantsIn this research study to create a new algorithmic quantification system for all hair loss, computational imaging analysis and algorithm design using retrospective image data collection were performed. This was a multicenter study, where images were collected at the Children's Hospital of Philadelphia, University of Pennsylvania (Penn), and via a Penn Dermatology web interface. Images were collected from 2015 to 2021, and they were analyzed from 2019 to 2021.Main outcomes and measuresScoring systems correlation analysis was measured by linear and logarithmic regressions. Algorithm performance was evaluated using image segmentation accuracy, density probability regression error, and average percentage hair loss error for labeled images, and Pearson correlation for manual scores.ResultsThere were 404 participants aged 2 years and older that were used for designing and validating HairComb. Scoring systems correlation analysis was performed for 250 participants (70.4% female; mean age, 35.3 years): 75 AGA, 66 AA, 50 CCCA, 27 other alopecia diagnoses (frontal fibrosing alopecia, lichen planopilaris, telogen effluvium, etc), and 32 unaffected scalps without alopecia. Scoring systems showed strong correlations with underlying percentage hair loss, with coefficient of determination R2 values of 0.793 and 0.804 with respect to log of percentage hair loss. Using HairComb, 92% accuracy, 5% regression error, 7% hair loss difference, and predicted scores with errors comparable to annotators were achieved.Conclusions and relevanceIn this research study,it is shown that an algorithm quantitating percentage hair loss may be applied to all forms of alopecia. A generalizable automated assessment of hair loss would provide a way to standardize measurements of hair loss across a range of conditions.

Dataset Information

Role of increased vascular permeability in chemotherapy-induced alopecia: In vivo imaging of the hair follicular microenvironment in mice.

Publications

Role of increased vascular permeability in chemotherapy-induced alopecia: In vivo imaging of the hair follicular microenvironment in mice.

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