Prevent Hair Loss Research Articles

Abstract P5-14-21: Prospective study of hair recovery after (neo)adjuvant chemotherapy with scalp cooling in Japanese breast cancer patients

Abstract Introduction Scalp cooling during chemotherapy infusion to mitigate hair loss for breast cancer patients is becoming popular in European and North American countries. But there is little prospective data regarding hair recovery after chemotherapy with scalp cooling. We reported on the results of hair loss prevention with scalp cooling during (neo)adjuvant chemotherapy with anthracyclines and/or taxanes for 122 Japanese breast cancer patients at the 2018 San Antonio Breast Cancer Symposium. Now we report on the prospective data of hair recovery of our 122 patients. Patients and Methods One hundred and twenty two Japanese breast cancer female patients who completed planned (neo)adjuvant chemotherapy used Paxman Scalp Cooling System for alopecia prevention and were evaluable for hair loss prevention in our prospective study. The scalp cooling was done 30 minutes prior to and during and 90 minutes after each chemotherapy infusion. We evaluated their hair recovery 1, 4, 7, 10, and 13 months after completion of the chemotherapy. We took photographs of the heads of the patients from 5 directions, namely front, back, both sides, and top and asked the patients about the use of a wig or hat to conceal the hair loss using a questionnaire at the times mentioned above. Primary outcomes were grades of alopecia judged by two investigators (defined as Grade 0: 0% of hair loss, G1: 1~25 %, G2: 26~50%, G3: > 50%)(objective grade) and patients' answers to the questionnaire (defined as Grade 0: not at all, G1: sometimes, G2: almost always)(subjective grade). Among 122 patients 79 completed scalp cooling during the whole planned chemotherapy cycles, but 43 discontinued it mostly after the first cycle due to several reasons. We compared the objective and subjective grades of hair loss between the patients who had completed the scalp cooling (79 patients: Group A) and those who had discontinued it (43 patients: Group B). Results Objective grades 1 month after completion of the chemotherapy were Grade 0 in 6 patients (4.9 %), G1 in 13, G2 in 29, and G3 in 74, and subjective grades at 1 month were Grade 0 in 3 patients (2.5 %), G1 in 13, G2 in 105, and unknown in 1. The changes over time in objective grades were as follows; 4 months: G0 55 (47.0 %), G1 52, G2 9, G3 1, unknown 5, 7 months: G0 99 (85.3 %), G1 15, G2 1, G3 1, unknown 6, 10 months: G0 105 (89.7 %), G1 10, G2 1, G3 1, unknown 5, 13 months: G0 104 (92.0 %), G1 7, G2 1, G3 1, unknown 9. On the other hand, the changes in subjective grades were as follows; 4 months: G0 12 (10.3 %), G1 29, G2 76, unknown 5, 7 months: G0 53 (45.7 %), G1 22, G2 41, unknown 6, 10 months: G0 80 (68.4 %), G1 15, G2 22, unknown 5, 13 months: G0 93 (82.3%), G1 7, G2 13, unknown 9. When we compared Group A with Group B, the rates of objective G0 were statistically significantly higher in Group A than Group B, at 4, 10, and 13 months (4 months: 55.7% vs. 28.9%, P = 0.010, 10 months: 96.1% vs. 78.0%, P = 0.006, 13 months: 97.3% vs. 81.6%, P = 0.011) and the rate of subjective G0 was also statistically significantly higher in Group A than Group B at 7 months (53.2 % vs. 30.8 %, P = 0.022). When we restricted the data to those with objective Grade 3 at 1 month, Group A showed tendency of faster hair recovery in the objective grades than Group B. Conclusion It is concluded that scalp cooling during chemotherapy infusion for Japanese breast cancer patients made their hair recovery faster. Citation Format: Shozo Ohsumi, Sachiko Kiyoto, Yuichiro Miyoshi, Mina Takahashi, Seiki Takashima, Kenjiro Aogi, Sachie Shimizu, Miyuki Doi. Prospective study of hair recovery after (neo)adjuvant chemotherapy with scalp cooling in Japanese breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-21.

Frontal fibrosing alopecia with involvement of the central hair part: distribution of hair loss corresponding to areas of sunscreen application

Frontal fibrosing alopecia (FFA) typically presents with band-like scarring alopecia in the frontal and temporal hairline along with eyebrow loss. Although this type of hair loss is being seen with increased frequency worldwide, the etiology of the condition is unknown. Studies have suggested a potential environmental role with moisturizers and sunscreens being possible triggers. Herein, we present a 42-year-old woman with a biopsy-proven diagnosis of frontal fibrosing alopecia. In addition to the typical pattern, she also had a striking linear patch of hair loss along her central part. This was an area where she regularly applied sunscreen for many years. Although a causative role for sunscreen ingredients in the development of FFA has not been proven, the evidence accumulated thus far, including our suggestive case, substantiates the need for further study. Additionally, increasing awareness of this potential effect leading to appropriate counseling regarding cessation of possible triggers may be critical for the prevention of further hair loss.

Safety and Efficacy of Deeply Rooted<sup>®</sup> Nutraceutical for Hair Growth in Women

Hair loss can significantly affect quality of life. Patients seeking treatment for hair loss find that many surgical or medication options involve significant risks or side effects. DEEPLY ROOTED® is a nutritional supplement that combines botanical and natural ingredients with the goal of effectively reducing hair loss and stimulating hair growth—without the side effects of many standard treatments. DEEPLY ROOTED’s active ingredients have both anti-inflammatory and adaptogenic properties, and inhibit dihydrotestosterone without the use of hormones, drugs, or industry by-products. This 3-month prospective study evaluates the effectiveness of DEEPLY ROOTED® for the prevention of hair loss. Healthy female subjects complaining of hair loss were enrolled, and supplied with three months of DEEPLY ROOTED®, without other compensation. The primary endpoint was a significant increase in hair growth. This was measured using anonymously collected patient data to evaluate hair growth and quality, as well as blinded Investigator hair assessment data. Patients who ingested DEEPLY ROOTED® over a three-month period reported noticeable improvement of hair growth (91%), increased hair volume (86%), and improved hair quality (86%). Subjects were noted to exhibit an increase in the number of new hairs, hair thickness and scalp coverage. No significant adverse effects were reported. DEEPLY ROOTED® safely helped over 90% of otherwise healthy women with self-perceived hair thinning to improve hair quality and quantity. The unique combination of botanical and natural ingredients provided a drug-free alternative for the management of hair loss.

Effect of Chrysanthemum zawadskii Extract on Dermal Papilla Cell Proliferation and Hair Growth.

BackgroundChrysanthemum zawadskii (CZ) belongs to the genus Chrysanthemum, also known as ‘Gu-Jeol-Cho’ in Korea. CZ has been used as herbal remedy to manage cough, hypertensive disorders, pharyngitis, bronchitis, gastroenteritis, pneumonia, bladder diseases and common cold. However, its effect on hair growth has not been documented.ObjectiveThe aim of present study was to elucidate the beneficial effects of CZ on hair growth.MethodsProliferation of follicular dermal papilla (DP) cells from human scalp skin was evaluated by MTT assay. The expression of various molecules in DP cells was checked by western blot assay. Effect of CZ extract on the hair growth was evaluated by hair organ culture and C57BL/6 mice model.ResultsCultivation of DP cells with CZ extract increased cellular proliferation, increased expression of phosphorylated protein kinase B (p-Akt), p-ERK, B-cell lymphoma 2, and decreased expression of Bax. Treatment of human hair follicles with CZ extract significantly enhanced hair growth. Additionally, CZ markedly shortened telogen period, increased anagen transformation and stimulated hair growth in the animal study.ConclusionThese results suggest that CZ extract has an effect of promoting hair growth and may therefore be a useful a therapeutic remedy for preventing hair loss.

Formulation and Examination of Organic Oil and Shampoo from Fish Scales

Cosmetics are utilized to upgrade the appearance or scent of the human body. Beautifying agents incorporate skin creams, lotions, powders, aromas, lipsticks, fingernail and toe nail polish, eye and facial cosmetics, permanent waves, and numerous different kinds of items. To make the hair sound and gleaming, there are several manufactured oils and hair shampoos. But when in contrast to the artificial one, natural cosmetics have growing demand in the world market and are an priceless gift of nature, as it is secure and free from facet results like hair fall and damage. As it is safe and free from symptoms like hair fall and harm. As the age increases, people suffer from hair loss and damage due to the less secretion of keratin. As we age, our body’s natural levels of collagen decrease, leading to thinning and shedding of hair. Research shows that collagen may support and increase hair-building proteins (keratin) in the body. This can help strengthen hair strands, promote hair growth and prevent hair loss. Collagen may even help to prevent the appearance of grey hairs by supporting the healthy structure of the hair follicle, where the pigment of hair is produced. Collagen supplements also have been shown to be effective in treating dry, brittle hair, helping to maintain healthy moisture levels in the hair. The present work was aimed to formulate organic oil and shampoo using fish scales and various herbs. The formulated organic oil and shampoo were evaluated for homogeneity, appearance, odour, saponification value, pH etc.

Protective effects of human umbilical cord blood‑derived mesenchymal stem cells against dexamethasone‑induced apoptotic cell death in hair follicles.

Alopecia is a common and distressing condition, and developing new therapeutic agents to prevent hair loss is important. Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) have been studied intensively in regenerative medicine. However, the therapeutic potential of these cells against hair loss and hair organ damage remains unclear, and the effects of hUCB-MSC transplantation on hair loss require evaluation. The current study aimed to investigate the effects of hUCB-MSCs on hair regression in vivo and restoration of anagen conduction on hair growth in vitro. The effects of hUCB-MSCs were explored in mouse catagen induction models using a topical treatment of 0.1% dexamethasone to induce hair regression. Dexamethasone was also used to simulate a stress environment in vitro. The results demonstrated that hUCB-MSCs significantly prevented hair regression induced by dexamethasone topical stimulation in vivo. Additionally, hUCB-MSCs significantly increased the proliferation of human dermal papilla cells (hDPCs) and HaCaT cells, which are key constituent cells of the hair follicle. Stimulation of vascular endothelial growth factor secretion and decreased expression of DKK-1 by hUCB-MSCs were also observed in hDPCs. Restoration of cell viability by hUCB-MSCs suggested that these cells exerted a protective effect on glucocorticoid stress-associated hair loss. In addition, anti-apoptotic effects and regulation of the autophagic flux recovery were observed in HaCaT cells. The results of the present study indicated that hUCB-MSCs may have the capacity to protect hair follicular dermal papilla cells and keratinocytes, thus preventing hair loss. Additionally, the protective effects of hUCB-MSCs may be resistant to dysregulation of autophagy under harmful stress.

Hair growth-promoting effect of recombinant human sonic hedgehog proteins

BackgroundHair loss, known as alopecia, causes psychological stress and influences social interactions. At present, treatment for hair loss is somewhat limited, transient, and unpredictable. Based on the critical role of sonic hedgehog (Shh) in hair follicle development, Shh itself would be a good therapeutic candidate for the prevention of hair loss as well as promotion of hair growth.MethodsTo investigate its potential use for hair treatment, we overexpressed Shh protein in E.coli by making silent mutations in 12 amino acids from N-terminus of Shh and purified it with Ni-affinity chromatography.ResultsPurified Shh proteins were able to activate Gli-responsive luciferase reporter gene in a dose-dependent manner and induce the alkaline phosphatase (AP) activity in the presence of bone morphogenic protein 4 (BMP-4). In addition, we confirmed that the treatment of recombinant Shh proteins to human dermal papilla (hDP) cells significantly increased the expressions of Shh-responsive genes as well as hair growth-related genes. Finally, we found that the administration of Shh proteins into the dorsal skin of the mouse could promote the hair density and length.ConclusionExogenous Shh proteins induced hair-related gene expression by stimulating both Shh signaling pathway and Wnt/β-catenin pathway in DP cells, and might therefore be a potential hair promoting agent.

Safety of Lower Scalp Cooling Temperature to Prevent Hair Loss From Chemotherapy in Breast Cancer Patients

Safety of Lower Scalp Cooling Temperature to Prevent Hair Loss From Chemotherapy in Breast Cancer Patients

Hair Growth Promotion by Extracts of Inula Helenium and Caesalpinia Sappan Bark in Patients with Androgenetic Alopecia: A Pre-clinical Study Using Phototrichogram Analysis

Inula helenium (IH) is known to possess antifungal, anti-bacterial, anti-helminthic, and anti-proliferation activities. Caesalpinia Sappan (CS) is known to reduce inflammation and improve blood circulation. Based on their folkloric use, these plants are expected to be promising candidates for promoting hair growth and preventing hair loss. Moreover, these plants are rich sources of certain phytochemicals, which have been reported to promote hair growth. In this clinical trial, we investigate the efficacy of a scalp shampoo formulated by mixing extracts of IH and CS in preventing hair loss and promoting hair growth in patients with androgenetic alopecia. Using a phototrichogram (Folliscope 2.8, LeadM, Korea), we compared the hair density and total hair counts in patients receiving the scalp shampoo at baseline, and at 8, 16, and 24 weeks after use of the shampoo. We found a statistically significant increase in the total hair count in the test group (n = 23) after 16 and 24 weeks of using the scalp shampoo (2.17 n/cm2 ± 5.72, p < 0.05; and 4.30 n/cm2 ± 6.37, p < 0.01, respectively) as compared to the control subjects. Based on the results of this clinical study, we conclude that the IH and CS extract complex is a promising remedy for preventing hair loss and promoting hair growth.

Ectodysplasin-A2 induces apoptosis in cultured human hair follicle cells and promotes regression of hair follicles in mice

Ectodysplasin is a ligand of the TNF family that plays a key role in ectodermal differentiation. EDA-A1 and EDA-A2 are two isoforms of ectodysplasin that differ only by the insertion of two amino acids and bind to two different receptors, ectodysplasin A receptor (EDAR) and ectodysplasin A2 receptor (EDA2R), respectively. Mutations of EDA-A1 and its receptor EDAR have been associated with hypohidrotic ecodermal dysplasia (HED). However, the role of EDA-A2 and the expression pattern of EDA2R in human hair follicles and in the mouse hair growth cycle have not been reported. In this study, we first investigated the expression of EDA2R in human hair follicles and in cultured follicular cells. EDA2R was strongly expressed in outer root sheath (ORS) cells and weakly expressed in dermal papilla (DP) cells. EDA-A2 induced the apoptosis of both ORS cells and DP cells via the activation of cleaved caspase-3. In addition, EDA2R was highly expressed in the late anagen phase compared with other phases in the hair growth cycle. Moreover, EDA-A2 induced apoptosis in cultured human hair follicle cells and in the mouse hair growth cycle, causing the premature onset of the catagen phase. Collectively, our results suggest that EDA-A2/EDA2R signaling could inhibit hair growth, and an inhibitor of EDA-A2/EDA2R signaling may be a promising agent for the treatment and prevention of hair loss.

Preparation and characterization of herbal shampoo from goat milk and natural extract

Shampoo is one of the cosmetic type product using surfactants as the main compound which when used under the specified conditions will remove surface grease, dirt, and skin debris from the hairs without adversely affecting the user. Currently shampoo is not only used to cleanse dirt on the hair and scalp but also to hair growth and prevent hair loss. To achieve this goal, the shampoo industries used a variety of additives chemicals that can potentially risk for user. In this study, we tried to make two types of herbal shampoo using natural leafs extract. The formula of shampoo 1, consist of goat milk, celery leaf extract, banana knot extract, and pegagan leaf extract while shampoo 2 using goat milk, noni extract, mangkokan leaf extract and spinach extract. Both of that shampoo preparations were analyzed the physical appearance and physicochemical. The results showed that the physical performance both herbal shampoo were light brown in color, transparent and good odor while the physicochemical characteristics of herbal shampoo formula 1 comprise pH, solid content, surface tension and foam ability were 5.25; 29.17%; 51.17 dyne/cm and 9.50 mL, while herbal shampoo formula 2 has a pH of 5.5; solid content of 29.67%; surface tension of 44.63 dyne/cm and foam ability of 15.0 mL. Formulated herbal shampoo shows physicochemical properties comparable to the commercial shampoo.

1770P - Randomised controlled trial of scalp cooling (SC) for the prevention of chemotherapy induced alopecia (CIA)

BackgroundThe only randomized trial of SC to prevent the distressing chemo-toxicity, CIA did not evaluate its effect on hair regrowth (HR) and was conducted in a predominantly taxane (T) treated population. We conducted a randomized trial of SC in a setting of anthracycline (A) and taxane chemotherapy and assessed its effect on CIA and HR. MethodsNon-metastatic breast cancer women undergoing (neo)adjuvant chemotherapy were randomized to receive SC using Paxman scalp cooling system during every cycle of chemotherapy, or no SC. The primary end point was successful hair preservation (HP) assessed clinically and by review of 5 photographs, using the CTCAE version 4.0 scale (defined as grade 0 = no, grade1=< 50% hair loss, not requiring a wig) after the 4 cycles or 12 weeks of chemotherapy. Secondary endpoints were HR at 6 and 12 weeks after completion of chemotherapy, adverse events and comparative quality of life scores. ResultsBetween December 2016 and July 2018, 51 patients, with median age 38 (21-58) years, were randomized to SC (34) or control arm (17) in a 2:1 ratio. 25/51 (49%) patients received A followed by T and two arms were balanced with respect to this factor. Modified intension to treat population (32) comprised of women who received at least one cycle of chemotherapy. HP rate was significantly higher in SC arm (18/32, 56.3%) compared to control arm (0/17, 0%; difference 56.3%, 95% CI 31%-73%, P=0.000004). HR was higher in SC arm compared to control at 6 weeks (89% vs 12%; difference 77%, 95% CI 49%-88%, p<0.001) and 12 weeks (100% vs 59%; difference 41%, 95% CI 8%-64%, p=0.0003). HP after 4 cycles was higher in patients receiving T versus those receiving A (77% vs 33%, p=0.0307). Patient reported hair loss at primary endpoint evaluation landmark was significantly lower in SC versus control arm (45% vs 82%, p=0.016) with compulsive head cover use of 47 % in SC vs 100% in controls (p=0.0001). Of 33 patients who started on SC, 23(69%) patients experienced grade 1-2 cold related adverse effects in SC arm with no grade 3-4 events. ConclusionsWomen with breast cancer receiving A or T chemotherapy were significantly more likely to have <50% hair loss after chemotherapy, had superior hair regrowth and improved patient reported outcomes, if scalp cooling was used. Clinical trial identificationCTRI/2017/02/007896. Legal entity responsible for the studyJyoti Bajpai. FundingOrbis Paxman Hair Loss Prevention System. DisclosureJ. Bajpai: Research grant / Funding (institution), No Personal Financial disclosures to declare: Eli Lilly; Advisory / Consultancy, Research grant / Funding (institution), No Personal Financial disclosures to declare: Novartis; Research grant / Funding (institution), No Personal Financial disclosures to declare: Roche; Research grant / Funding (institution), No Personal Financial disclosures to declare: Samsung Bioepis Co. Ltd; Research grant / Funding (institution), No Personal Financial disclosures to declare: Sun Pharma; Leadership role, No Personal Financial disclosures to declare: Immuno-oncology Society of India(I-OSI); Leadership role, No Personal Financial disclosures to declare: Indian Society of Medical and Paediatric Oncology (ISMPO) ; Leadership role, No Personal Financial disclosures to declare: Indian cooperative Oncology network (ICON); Leadership role, No Personal Financial disclosures to declare: Teenage and Young Cancer Association (TYA). S. Gupta: Advisory / Consultancy, Research grant / Funding (institution), No Personal Financial disclosures to declare: Roche; Advisory / Consultancy, Research grant / Funding (institution), No Personal Financial disclosures to declare: Sanofi; Research grant / Funding (institution), No Personal Financial disclosures to declare: Johnson & Johnson; Research grant / Funding (institution), No Personal Financial disclosures to declare: Amgen; Research grant / Funding (institution), No Personal Financial disclosures to declare: Celltrion; Advisory / Consultancy, Research grant / Funding (institution), No Personal Financial disclosures to declare: Oncosten; Research grant / Funding (institution), No Personal Financial disclosures to declare: Novartis; Research grant / Funding (institution), No Personal Financial disclosures to declare: Intas; Research grant / Funding (institution), No Personal Financial disclosures to declare: Eisai; Research grant / Funding (institution), No Personal Financial disclosures to declare: Biocon; Advisory / Consultancy, No Personal Financial disclosures to declare: DRL; Advisory / Consultancy, No Personal Financial disclosures to declare: Biocon; Advisory / Consultancy, No Personal Financial disclosures to declare: Pfizer; Advisory / Consultancy, No Personal Financial disclosures to declare: Core diagnostics. All other authors have declared no conflicts of interest.

FORMULATION AND EVALUATION OF HERBAL GEL CONTAINING Allium cepa EXTRACT

Herbal medicines widely improved for primary health care because of better cultural acceptability and better compatibility with human body and lesser side effects. The aim of present study was to formulate and evaluate of herbal gel containing Allium cepa extract. Topical gel formulation was designed by using Allium cepa extract and carbopol 934 as a gelling agent and different excipients. The herbaceous plant Allium cepa (onion). It has great health significance and is consumed for nutritional and health benefits for last centuries. It contains flavonoids compound. Plant extract used for prevention of hair loss. Raw onion eaten in salad form this is play very important role in health benefits. Gel was prepared by incorporating extract of Allium cepa in gel at a particular step in order to prepare non greasy formulation. Gel Formulation F3 Batch was optimized in the concentration 1.5% of Carbopol 934. Different gel formulations were evaluated for their physical appearance; pH, Spreadability, Homogeneity in-vitro diffusion ,Viscosity and Drug Excipients comparability study are carried out.

Efficacy of Scalp Cooling in Preventing and Recovering From Chemotherapy-Induced Alopecia in Breast Cancer Patients: The HOPE Study.

Purpose: This study aimed to assess the efficacy of scalp-cooling devices in preventing chemotherapy-induced alopecia in Japanese breast cancer patients and investigate whether a scalp-cooling device improves hair volume recovery over a 12 weeks period after completing chemotherapy.Methods: This multicenter controlled trial included women with breast cancer undergoing chemotherapy in Japan between February 2016 and March 2018. The primary endpoint was the proportion of patients with no alopecia at the end of chemotherapy. The secondary endpoint included hair volume at 12 weeks after completing chemotherapy.Results: A total of 48 patients were enrolled; of them, 34 and 14 were sequentially allocated to the scalp-cooling group using the Paxman Hair Loss Prevention System and the control group, respectively. There was no significant difference in average age between the scalp-cooling and the control groups (50.0 ± 9.6 vs. 49.0 ± 9.0 years). More than 50% of patients in each group had stage II breast cancer (scalp-cooling group: 53.1%; control group: 64.3%), more than 90% received adjuvant chemotherapy (scalp-cooling group: 96.9%; control group: 92.9%), and more than 60% were treated with a docetaxel/cyclophosphamide regimen (scalp-cooling group: 75.0%; control group: 64.3%). There were more patients judged to have no alopecia at the end of chemotherapy in the scalp-cooling group than in the control group (26.7% [8/30] vs. 0% [0/13]; P = 0.011). The proportion of patients with alopecia who experienced an increase in hair volume of ≥50% within 12 weeks duration after chemotherapy was 85.7% (24/28) in the scalp-cooling group and 50.0% (6/12) in the control group. No patient developed serious adverse events related to the scalp-cooling device.Conclusions: The use of a scalp-cooling device prevented alopecia with acceptable safety for Japanese patients. In addition, scalp cooling resulted in faster recovery of hair volume after chemotherapy, even in patients for whom scalp cooling failed to prevent chemotherapy-induced alopecia.

Stimulation of Hair Growth by Small Molecules that Activate Autophagy

Hair plays important roles, ranging from the conservation of body heat to the preservation of psychological well-being. Hair loss or alopecia affects millions worldwide, but methods that can be used to regrow hair are lacking. We report that quiescent (telogen) hair follicles can be stimulated to initiate anagen and hair growth by small molecules that activate autophagy, including the metabolites α-ketoglutarate (α-KG) and α-ketobutyrate (α-KB), and the prescription drugs rapamycin and metformin, which impinge on mTOR and AMPK signaling. Stimulation of hair growth by these agents is blocked by specific autophagy inhibitors, suggesting a mechanistic link between autophagy and hair regeneration. Consistently, increased autophagy is detected upon anagen entry during the natural hair follicle cycle, and oral α-KB prevents hair loss in aged mice. Our finding that anagen can be pharmacologically activated in telogen skin when natural anagen-inducing signal(s) are absent has implications for the treatment of hair loss patients.

Bacillus/Trapa japonica Fruit Extract Ferment Filtrate enhances human hair follicle dermal papilla cell proliferation via the Akt/ERK/GSK-3\u03b2 signaling pathway

BackgroundDespite advances in medical treatments, the proportion of the population suffering from alopecia is increasing, creating a need for new treatments to control hair loss and prevent balding. Treatments based on plant-derived compounds could potentially prevent hair loss. Human hair follicle dermal papilla (HDP) cells, a type of specialized fibroblast in the hair bulb, play an essential role in controlling hair growth and in conditions such as androgenic alopecia. We examined the effect of Bacillus/Trapa japonica fruit ferment filtrate extracts (TJFs) on HDP cells to determine whether activation of the Akt/ERK/GSK-3β signaling pathway improved HDP cell proliferation.MethodsWe prepared TJFs using various methods. The extract properties were analyzed using WST-1, Lowry, and cell migration assays as well as immunofluorescence staining. We also determined the cell cycle stage and performed western blotting and an in ovo chick chorioallantoic membrane assay. Last, we constructed an organotypic three-dimensional cell culture model for immunohistochemical use.ResultsOur study confirmed that the TJFs contained numerous peptides and five unknown fractions. The TJFs stimulated HDP cell proliferation and migration via the Akt/ERK/GSK-3β signaling pathway. To verify that the Akt/ERK/GSK-3β pathway affected HDP cell proliferation, we treated HDP cells with LY294002 (an Akt inhibitor), BIO (a GSK-3β inhibitor), and PD98059 (an ERK inhibitor). The TJFs also induced cell cycle progression, inhibited type І 5α-reductase, decreased apoptosis, and enhanced angiogenesis (vascular expansion). In addition to these signaling pathways, proteins including insulin-like growth factor-1 and keratinocyte growth factor, stimulating hair growth, were detected in the three-dimensional cell culture model.ConclusionsOur results confirmed that TJFs enhance HDP cell proliferation via the Akt/ERK/GSK-3β signaling pathway, suggesting a potential treatment for alopecia.

The effect of scalp cooling on CIA-related quality of life in breast cancer patients: a systematic review.

Chemotherapy-induced alopecia (CIA) remains a distressing adverse event of cancer treatment but may be prevented by scalp cooling. The effectiveness of scalp cooling, however, is dependent on the chemotherapy regimen with successful hair preservation (i.e., < 50% hair loss) in 41-59% of women on taxane-based therapies in comparison to 16-36% on anthracycline-based therapies. Despite the potential utility, use of scalp cooling has shown a more equivocal impact on quality of life (QoL). In this review, we aim to evaluate the use of scalp cooling for CIA and quantitative QoL measures. A systematic review of PubMed, Embase, Web of Science, and Cochrane databases for clinical studies on scalp cooling to prevent CIA published before October 29, 2018 was performed. Clinical studies with 5 or more patients that reported on a quantitative QoL measure were included and graded according to a modified five-point scale from the Oxford Centre for Evidence-Based Medicine. Studies meeting inclusion criteria included 4 randomized clinical trials (RCT), 8 cohort studies, and 1 cross-sectional study with 1282 unique patients. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30: 46%) and Breast Cancer Module (QLQ-BR23: 46%) represented the most commonly used QoL assessments. Overall, 4 (31%) of the 13 studies concluded that scalp cooling was associated with significant improvements in QoL measures; 8 (62%) determined that there was either non-significant or no improvements; and 1 (7.7%) provided a mixed conclusion. Although 2 (50%) RCT demonstrated that scalp cooling can effectively prevent CIA depending on the chemotherapy regimen, these studies did not show that successful hair preservation was associated with improved QoL measures. This review demonstrates that scalp cooling is not consistently associated with significant QoL improvements as assessed by EORTC QLQ-C30 and -BR23. Representing a critical limitation, more than one-third of the studies did not subcategorize QoL outcomes for successfully or unsuccessfully scalp-cooled patients but rather reported on QoL measures for all scalp-cooled patients in general. Failure to prevent hair loss in patients undergoing an expensive and potentially uncomfortable treatment likely contributes to decreased well-being, impacting the overall distribution of QoL measures in scalp cooling patients compared to controls. Future studies should incorporate validated QoL instruments specific to hair disease and classify QoL outcomes for scalp-cooled patients based on the degree of hair preservation.

Abstract P1-17-04: Long-term safety follow-up of patients with early stage breast cancer treated with scalp cooling on the Dignitana scalp cooling trial

Abstract Background Scalp cooling has demonstrated efficacy in preventing hair loss in women with early stage breast cancer receiving neo/adjuvant chemotherapy. Data from 2 prospective trials (Rugo et al, and Nangia et al, JAMA 2017) led to FDA clearance of 2 automated scalp-cooling devices to prevent chemotherapy induced alopecia (CIA). Although scalp metastases from breast cancer are rare, historical concerns about scalp cooling included a theoretical increase in risk of recurrence in scalp due to reduced delivery of chemotherapy to the scalp. Methods We conducted a multicenter prospective trial evaluating the efficacy and safety of the DigniCap in women with stage I-II breast cancer receiving neo/adjuvant chemotherapy excluding sequential or combination anthracycline/taxanes with concurrent matched controls. The primary endpoint was unblinded patient self-assessment of 5 photographs using the Dean scale to estimate hair loss 4 weeks following the last dose of chemotherapy, with success defined as a Dean score of 0-2 (≤ 50% hair loss); additional endpoints included quality of life (QOL) and both short and long-term safety. Results 106 patients using the scalp cooling device and 16 concurrent controls were enrolled. As previously reported, the use of scalp cooling was associated with less alopecia and improvement in several measures of QOL (Rugo et al, JAMA 2017). 91 patients have follow-up (FU) out to 3 years; 73 with estrogen receptor (ER) positive and 18 with ER negative disease. 5 DigniCap patients have developed recurrent breast cancer in breast (n=1), liver (n=1), bone, liver and breast (n=1), bone, liver, lung, and nodes (1), and bone, breast, GI tract and bladder (n=1). Of 12 control patients with available FU, 1 developed metastases to liver. 2 patients have died of metastatic disease, one in the DigniCap arm and one in the control arm. No new safety signals have been detected. Conclusion Scalp cooling using the DigniCap system in patients with early stage breast cancer receiving taxane based neo/adjuvant chemotherapy is safe and effective. No scalp metastases have been reported 3 years following completion of study treatment. 4 year FU data will be presented. The study was funded by The Lazlo Tauber Family Foundation (UCSF), the Anne Moore Breast Cancer Research Fund (Weil Cornell), and the Friedman Family Foundation (Mount Sinai Beth Israel), as well as partially by Dignitana. Citation Format: Rugo HS, Klein P, Melin SA, Hurvitz SA, Melisko ME, Moore A, D'Agostino, Jr. RB, Deluca A, Cigler T. Long-term safety follow-up of patients with early stage breast cancer treated with scalp cooling on the Dignitana scalp cooling trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-17-04.

Abstract P4-16-13: Prospective study of scalp cooling for hair loss prevention in Japanese breast cancer women receiving (neo)adjuvant chemotherapy

Abstract Introduction Recently scalp cooling during chemotherapy infusion has been reported to be quite effective to mitigate chemotherapy-induced alopecia. But data in Asian patients are quite limited. Patients and methods Japanese breast cancer female patients who planned to receive (neo)adjuvant chemotherapy were offered to participate in this prospective study of scalp cooling with Paxman Scalp Cooling System for alopecia prevention. The scalp cooling was done 30 minutes prior to and during and 90 minutes after each chemotherapy infusion. Photographs of the head of the participants were taken from 5 directions, namely front, back, both sides, and top, on the day of chemotherapy infusion and 1 month after the last infusion. Two investigators consisting of a physician and a nurse judged the grade of alopecia by looking at the photographs according to the WHO classification. The primary outcomes were the rates of patients with Grade 3 alopecia (defined as hair loss of &amp;gt; 50%) and the rates of patients who used a wig or hat to conceal the hair loss one month after the last infusion of chemotherapy. This paper reports on the former outcome mainly. They were asked to answer a brief questionnaire regarding headache, fatigue, chill etc. shortly after each cooling. They could use the cooling cap for free on the first cycle of chemotherapy. But they were required to purchase it (about 1,130 US$) for the scalp cooling of the following cycles. Results One hundred forty three patients participated in the study and actually used the cooling cap at least once. The mean and median age of them are 50.6 and 50, respectively (28 - 76). One hundred twenty nine patients completed the planned chemotherapy of 4 to 8 cycles (89 Pts 4 cycles, 1 Pt 6 cycles, 39 Pts 8 cycles). Among them (7 patients were not evaluable), 74 patients (60.7 %) had Grade 3 alopecia 1 month after chemotherapy. In 80 patients who used the scalp cooling system throughout the planned chemotherapy (1 patient was not evaluable), 36 patients (45.6 %) experienced Grade 3 alopecia. On the other hand, among 49 patients who discontinued the cooling mostly after the 1st cycle (6 were not evaluable), 38 (88.3 %) had Grade 3 alopecia. When we restrict them to 33 (5 were not evaluable) who decided to discontinue the cooling by day10 of the first cycle of chemotherapy to exclude the patients who discontinued it because of less effect on alopecia prevention than they expected, 25 (89.3 %) experienced Grade 3 alopecia. Comparing the results of those who completed the cooling and patients who decided to discontinue it by day10 of the first cycle, the rates of Grade 3 alopecia (45.6 % vs. 89.3 %) were statistically significantly different in favor of the former (P = 0.0001). Most patients complained of some headache, chill, and pain of the jaw. Conclusion Scalp cooling with Paxman Scalp Cooling System during chemotherapy infusion in Asian women seems as effective for hair loss mitigation as in Caucasian women. Citation Format: Ohsumi S, Kiyoto S, Takahashi M, Hara F, Takashima S, Aogi K, Matsuda M, Yamamura N, Matsuda A, Yamauchi T, Doi M. Prospective study of scalp cooling for hair loss prevention in Japanese breast cancer women receiving (neo)adjuvant chemotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-16-13.

RE-ORGA, a Korean Herb Extract, Can Prevent Hair Loss Induced by Dihydrotestosterone in Human Dermal Papilla Cells.

BackgroundAndrogenic alopecia (AGA) is the most common type of hair loss. It is likely inherited genetically and is promoted by dihydrotestosterone. 5α-reductase has been proven a good target through finasteride use. However, the pathogenesis of AGA cannot be fully explained based only on dihydrotestosterone levels.ObjectiveTo identify similar hairloss inhibition activity of RE-ORGA with mode of action other than finasteride.MethodsWe prepared RE-ORGA from Korean herb mixtures. We performed MTT assays for cytotoxicity, Cell Counting Kit-8 assays for cell proliferation, and western blot to identify expression levels of 5α-reductase and Bax. RNA-sequencing was performed for the expression patterns of genes in dihydrotestosterone-activated pathways. Anti-inflammatory activity was also assessed by the expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin 6.ResultsREORGA could promote the proliferation of human dermal papilla cells and showed low cytotoxicity. It also inhibited the expression of 5α-reductases and Bax in the cells. RNA-sequencing results verified that the mRNA expressions of SRD5A1, Bax, transforming growth factor-beta 1 (TGF-β1), and TGF-β1 induced transcript 1 (TGFβ1I1) were decreased, whereas expression of protein tyrosine kinase 2 beta (PTK2β) was more elevated. REORGA also showed anti-inflammatory activity through decreased mRNA levels of TNF-α.ConclusionTranscriptionally, up-regulation of PTK2β and concomitant down-regulation of TGFβ1I1 imply that RE-ORGA can modulate androgen receptor sensitivity, decreasing the expression of 5α-reductase type II and Bax together with TGF-β1 transcripts; RE-ORGA also showed partial anti-inflammatory activity. Overall, RE-ORGA is expected to alleviate hair loss by regulating 5α-reductase activity and the receptor's androgen sensitivity.