Keloid Therapy Research Articles

A comparative study of the effectiveness and safety of injectable combination therapy of keloid and hypertrophic scars with 5-fluorouracil and betamethasone

therapy for their reliable removal. Standard methods of treatment often give unpredictable results, are accompanied by various complications, and require the use of expensive equipment.
 AIM: To investigate the efficacy and safety of intralesional injection of a combination of 5-fluorouracil (5-FU) and betamethasone for the treatment of keloids and hypertrophic scars.
 MATERIALS AND METHODS: The study involved 26 patients who were divided into two equal groups. Patients in group A received intralesional injections of betamethasone, and those in group B received 5-FU and betamethasone. Three injections were performed with an interval of 3 weeks. The scars were assessed at the beginning of the treatment, on the 3rd and 6th week during the treatment, and 4 and 16 weeks after the end of the treatment. The dynamics of scar condition was evaluated by the average decrease in the scar height and density, changes in subjective sensations, and the presence or absence of complications.
 RESULTS: At 4 weeks after the end of the therapy, the total effectiveness of reducing the initial scar height was significantly higher in group B (10 patients; 76.9%) than in group A (6; 46.1%). In the comparison of long-term results at 16 weeks after treatment, 92.3% of the patients from group B and 53.8% of the patients from group A showed cessation of scar growth, flattening and softening, diminished itching and pain, smoothing of the scar contour, and a decrease in the color of the border between the scar and surrounding tissues.
 CONCLUSIONS: The combination of betamethasone with 5-FU is safer and more effective than monotherapy with betamethasone or 5-FU in the treatment of keloid and hypertrophic scars, with a faster and more pronounced decrease in the height and density of the scar, erythema, and subjective sensations. This mode of therapy is characterized by a low relapse rate with prolonged follow-up. The article is of interest to practicing cosmetologists, dermatologists, and plastic surgeons.

Combination therapy of refractory keloid with ultrapulse fractional carbon dioxide (CO2) laser and topical triamcinolone in Asians‐long‐termprevention of keloid recurrence

Keloid often recur after treatment, and recent studies in keloid management favor the combination therapy of laser-assisted drug delivery over monotherapy. Unfortunately, the previous researches lack long-term follow-up. In this prospective study, 41 individuals with refractory keloids underwent eight treatment sessions at 4 weeks intervals consisting of ultrapulse fractional carbon dioxide laser (UFCL), followed by postoperative application topical triamcinolone acetonide (40 mg/ml). Four follow-up moments were chosen, with follow-up of 24 months. The effects of combination therapy on scar pliability, thickness, relief, vascularization, surface area, pain, and itchiness were examined by means of the Patient and Observer Scar Assessment Scale (POSAS). 38 patients completed the full 24 months of follow-up after the whole treatment. The results reveal a fast and abiding improvement of keloid scars after the combination therapy. The mean keloid POSAS scores showed a decreasing trend in subsequent times. All POSAS components improved significantly between baseline and 24 months after start of therapy (P < .05). Long-term follow-up results demonstrate that combination keloid therapy using UFCL and tropical triamcinolone has overall significant improvement and low recurrence rate with a long-term stable results.

Long non-coding RNA LINC01116 accelerates the progression of keloid formation by regulating miR-203/SMAD5 axis

BackgroundEmerging evidence reveals the importance of long non-coding RNAs (lncRNAs) in the development and progression of keloid formation. However, the roles and molecular mechanism of lncRNA LINC01116 in the progression of keloid formation remain largely unknown. MethodsThe expression levels of LINC01116, microRNA-203 (miR-203) and SMAD family member 5 (SMAD5) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell proliferation, migration and invasion were detected by Cell counting Kit-8 (CCK-8) assay and transwell assay. Flow cytometry and western blot assay were used to examine cell apoptosis and extracellular matrix (ECM) production. The interaction between miR-203 and LINC01116 or SMAD5 was predicted by bioinformatics analysis and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) and RNA pull-down assays. ResultsLINC01116 and SMAD5 were upregulated while miR-203 was downregulated in keloid tissues and keloid fibroblasts. LINC01116 knockdown suppressed the proliferation, migration, invasion, and ECM production but induced apoptosis in keloid fibroblasts through enhancing miR-203 and inhibiting SMAD5. Moreover, SMAD5 was identified as a direct target of miR-203 and miR-203 could directly bind to LINC01116. Besides, LINC01116 regulated SMAD5 expression by targeting miR-203. ConclusionDownregulation of LINC01116 inhibited the progression of keloid formation by regulating miR-203/SMAD5 axis, which might provide a novel target for keloid therapy.

Effect of pirfenidone and its combination with 5-fluorouracil on keloid fibroblast proliferation and collagen deposition: in vitro study

Background: Keloid is a fibroproliferative disease in which its etiology remains unknown. Various therapy modalities have been improved, but none of them gives a satisfying outcome. Pirfenidone (PFD) is a commonly used drug in pulmonary fibrotic diseases, which has an anti-fibrotic effect. 5-fluorouracil (5-FU) is one of the keloid therapy choices that has long been used. This study aimed to investigate PFD's effect and its combination with 5-FU on fibroblast proliferation and collagen deposition.Methods: This experimental study using post only control group design was conducted by comparing PFD in various doses (0.5, 1.0, 1.5, 2.0, 3.0 mg/ml) and its combination with 5-FU on keloid fibroblast proliferation and collagen deposition. We used MTT (3-[4,5-dimethylthiazol-2-yl}-2,5diphenyl tetrazolium bromide) and Sirius Red assays to measure the fibroblast proliferation and collagen deposition, respectively. The statistical analysis used one-way ANOVA with p-value p&lt;0.05 was considered significant.Results: The combination of PFD 3.0 mg/ml + 5-FU 1.0 mg/ml had more significant effect on inhibiting fibroblast proliferation as well as decreasing collagen deposition compared to 5-FU only (p&lt;0.043). PFD 1.0 mg/ml + 5-FU 1 mg/ml as well as PFD 1.5 mg/ml+ 5-FU 1 mg/ml are more effective in inhibiting fibroblast proliferation and lowering collagen deposition than PFD only with p values of &lt;0.001 and &lt;0.000, respectively.Conclusion: In general, PFD, as well as 5-FU, are effective in inhibiting fibroblast proliferation and decreasing collagen deposition in keloid. However, the combination of both has a better effect compared to PFD or 5-FU monotherapy.

Effects of the circ_101238/miR-138-5p/CDK6 axis on proliferation and apoptosis keloid fibroblasts.

The formation of keloid scars is normally induced by cutaneous injuries, however, the detailed mechanisms underlying keloid formation remain largely unknown. The present study aimed to investigate the effects of circular RNA_101238 (circ_101238) on the proliferation and apoptosis of keloid fibroblasts and to identify the underlying molecular mechanisms of these effects. Reverse transcription-quantitative (RT-q)PCR was performed to determine the expression levels of circ_101238, microRNA (miRNA/miR)-138-5p and cyclin-dependent kinase 6 (CDK6) in keloids and normal skin tissues. Following transfection with short hairpin (sh)-circ_101238, LV-circ_101238, miR-138-5p mimics, miR-138-5p inhibitors and small interfering (si)-CDK6, cell proliferation was assessed using a cell counting kit-8 assay. Furthermore, cell apoptosis was evaluated via flow cytometric analysis, while a dual-luciferase assay was performed to confirm interactions between circ_101238, miR-138-5p and CDK6. The expression levels of the proliferation marker, CDK6 and apoptosis marker, caspase-3 were determined via RT-qPCR and western blot analyses. The results demonstrated that expression levels of circ_101238 and CDK6 were significantly increased in keloid samples, while miR-138-5p expression was reduced in comparison to normal skin. Furthermore, circ_101238 was demonstrated to bind miR-138-5p, which subsequently targeted CDK6. Proliferative activity and CDK6 expression were significantly decreased in keloid fibroblasts following transfection with sh-circ_101238 or miR-138-5p mimics, while cell apoptosis was markedly increased. Furthermore, co-transfection with miR-138-5p mimics reversed the effects caused by overexpression of circ_101238. Treatment of keloid fibroblasts with si-CDK6 counteracted the biological behavior changes induced by miR-138-5p inhibitors. Additionally, transfection with LV-CDK6 reversed the effects caused by miR-138-5p mimics. Taken together, the results of the present study demonstrated that circ_101238 was upregulated in keloid tissues in comparison with normal tissues and that circ_101238 knockdown inhibited cell proliferation, while promoting apoptosis of keloid fibroblasts via the miR-138-5p/CDK6 axis. These results suggest that circ_101238 may serve as a promising therapeutic candidate for keloid therapy and that circ_101238/miR-138-5p/CDK6 signaling has the potential to regulate the growth of keloid fibroblasts.

Treatment of keloids with a single dose of low-energy superficial X-ray radiation to prevent recurrence after surgical excision: An in vitro and in vivo study

Although keloids have been empirically treated with steroids and radiation, evidence-based radiation parameters for keloid therapy are lacking. To determine evidence-based radiation parameters for blocking keloid fibroblast proliferation invitro and apply them to patients. The effects of various radiation parameters and steroids on cell proliferation, cell death, and collagen production in keloid explants and fibroblasts were evaluated with standard assays. Effective radiation parameters were then tested on patients. No differences were observed between the effects of 50 and 320 kV radiation or between single and fractionated radiation doses on keloid fibroblasts. A 3 Gy, 50 kV dose inhibited keloid fibroblast proliferation in culture, whereas 9Gy completely blocked their outgrowth from explants by inducing multiple cell death pathways and reducing collagen levels. Thirteen of 14 keloids treated with a single 8 Gy, 50 kV dose of radiation did not recur, although 4 patients with 6 keloids were lost to follow-up. Seventy-five percent of patients received steroids for pruritus, whereas approximately 25% of patients were lost to follow-up. A single 8 Gy dose of superficial 50 kV radiation delivered an average of 34days after keloid excision maybe sufficient to minimize recurrence, including in individuals resistant to steroids. Higher radiation energies, doses, or fractions may be unnecessary for keloid therapy.

TM4SF1 involves in miR-1-3p/miR-214-5p-mediated inhibition of the migration and proliferation in keloid by regulating AKT/ERK signaling

AimsTransmembrane 4 L six family member 1 (TM4SF1) is a small plasma membrane glycoprotein that is highly expressed in cancers. However, the role of TM4SF1 that plays in keloids remains unknown. We investigated the expression, function and the microRNA (miRNA) regulatory network of TM4SF1 in keloids. Main methodsSmall interfering RNAs and lentivirus were used to alter the expression of TM4SF1 in fibroblasts. Dual-luciferase reporter assays were applied to determine the miRNA targets. Immunohistochemistry, western blotting, qRT-PCR, wound healing assays, Transwell assays, cell count kit-8 assays and flow cytometry were also employed in this study. Key findingsTM4SF1 was frequently upregulated in human keloid fibroblasts (HKFs) compared with human normal skin fibroblasts (HSFs). The downregulation of TM4SF1 significantly inhibited proliferation and migration, and induced apoptosis in HKFs. Furthermore, si-TM4SF1 inhibited the AKT/ERK signaling. Meanwhile, the upregulation of TM4SF1 promoted proliferation, migration and the activation of AKT/ERK signaling in human foreskin fibroblasts (HFF-1). Moreover, TM4SF1 can be regulated by miRNAs, which have been validated to play important roles in keloids by posttranscriptional regulation of gene expression. After screening, we found miR-1-3p and miR-214-5p targeted TM4SF1, inhibited TM4SF1 expression, cell proliferation, migration, and induced apoptosis in HKFs. And the level of miR-1-3p and miR-214-5p were found lower in HKFs than in HSFs. SignificanceOur study demonstrates a novel regulatory mechanism by which miR-1-3p, miR-214-5p, and TM4SF1 are involved in proliferation, cell motility, and apoptosis, suggesting that they may be potential targets in therapies for keloids.

Auricular keloid management in Asian skin: Clinical outcome of intralesional excision and postoperative triamcinolone acetonide intralesional injection.

Various options such as surgical excision, steroid injection, cryotherapy, pressure dressing, and radiation therapy are available for the treatment of auricular keloids. In particular, auricular keloid therapy using surgical excision is important because recurrence rates are low compared with keloids occurring in other parts of the body. We aimed to evaluate the clinical outcomes of intralesional excision followed by postoperative triamcinolone acetonide intralesional injection (TA ILI) as auricular keloid treatments. We conducted a surgery records and chart review of patients who underwent auricular keloid treatment with intralesional excision and TA ILI. Reduction in height and volume was assessed by two blinded dermatologists. We also analyzed the recurrence rate over a 2-year period and evaluated patient satisfaction using an 11-point questionnaire (0-10). Eighteen Korean patients (2 males and 16 females) with a mean age of 26.5years and a total of 20 lesions were evaluated. Lesion types by descending frequency were lobular (n=10, 50%), anterior/posterior button (n=3, 15%), wrap-around (n=3, 15%), dumbbell (n=2, 10%), and sessile (n=2, 10%). The total recurrence rate was 5% (1/20) within the 24-month follow-up period. Significant reduction (> 50%) in height and volume was achieved in 95% of patients. No serious or persistent adverse events were reported during the follow-up period. We confirmed that TA ILI after intralesional excision can be effective for auricular keloid management. A low recurrence rate similar to that of postoperative radiation therapy was obtained with an effective surgical procedure and minimal postoperative treatment.

Ethanolic Extract of Nerium indicum Mill. Decreases Transforming Growth Factor Beta-1 and Vascular Endothelial Growth Factor Expressions in Keloid Fibroblasts

BACKGROUND: Keloid is a benign fibroproliferative dermis tumor characterized by an increase in growth factors which induce fibroblast proliferation, excessive migration, and synthesis of collagen. Nerium indicum Mill. extract had been studied as a keloid therapy agent. 5α-oleandrin contained in N. indicum has antikeloid activity by inhibiting keloid fibroblast proliferation, fibroblast migration, collagen deposition, and transforming growth factor beta-1 (TGF-β1) synthesis.&#x0D; OBJECTIVE: This study aimed to determine the effect of administration of N. indicum extract on TGF-β1 and vascular endothelial growth factor (VEGF) expression in keloid fibroblast.&#x0D; METHODS: This research was a quasi-experimental research with a post-test only control group design. The research subjects were fibroblast cells passage IV-VII isolated from patients’ keloid tissue with explant techniques. Treatment groups received N. indicum extract with a serial concentration of 2 μg/ml, 1 μg/ml, and 0.5 μg/ml, and control group received medium only. The supernatant was obtained after 72 h incubation period. Examination of TGF-β1 and VEGF expressions was performed using ELISA procedure.&#x0D; RESULT: The expression of TGF-β1 in the treatment groups of the extract N. indicum (2 μg/ml, 1 μg/ml, and 0.5 μg/ml) was significantly lower than a control group of keloid fibroblasts (p &lt; 0.05), according to increased concentration. VEGF expression in the treatment groups of N. indicum extract was lower compared to the control group of keloid fibroblasts. A significant decrease in keloid fibroblast VEGF levels occurred at extract concentrations of 2 μg/ml and 1 μg/ml (p &lt; 0.05).&#x0D; CONCLUSION: N. indicum extract could decrease TGF-β1 and VEGF expressions compared to control medium in keloid fibroblast cultures.

Outcome of combined surgical and intralesional steroids injection therapy for management of ear keloid

Background: Ear keloid is one of the challenging problems that affect people of different races with substantial aesthetic outcomes. Various types of treatment modalities, including intralesional corticosteroid injection are advocated to lower recurrence following excision.&#x0D; Objectives: To investigate the efficacy of a combined excision and postoperative intralesional triamcinolone acetonide (TA) injection for treating ear keloid patients.&#x0D; Methodology: This was a descriptive study done to observe the outcome of combined approach of surgical and intra-lesional steroids injection therapy for ear keloids. Age, sex, site, size, duration, recurrence, and aesthetic outcome were evaluated.&#x0D; Results: A total of 18 patients representing 19 ear keloids, with one case having bilateral and 3 pediatric cases were included from February 2018 to January 2019.The mean age was 22 years with female to male ratio of 5:1, site were left sided 9 (50%), right 8 (44%) and 1(6%) bilateral. About 10 (53%) cases were at helix, and 9(47%) at ear lobule. Mean length of ear keloid was 1.53 cm with range of 0.5-3cm and mean breath 1.39cm with the range of 0.5-2.5 cm. The mean duration of ear keloid was 9.47 months. 2 (11%) cases showed a history of recurrence. Injection triamcinolone acetonide hypersensitivity was noted by 1 (5.3%) patient. Evaluation for all patients with aesthetic outcome was mean ± standard deviation (4.38±1.025).&#x0D; Conclusion: Management of ear keloid using the combination of surgical excision and intra-lesional steroids injection therapy can be a good alternative option with low recurrence rate.

Pathogenesis and Treatment of Keloids

Keloids are chronic inflammatory fibrous tumors that cause excessive production of such extracellular macromolecules as collagen, due to the overexpression of various growth factors and cytokines. The etiology of keloids is unknown. They cause pain and itching, which together with the red mass leads to physical and mental stress in patients. No definitive treatment for keloids has been established, although various treatment methods have been reported, and the current consensus is that the recurrence of keloids cannot be completely suppressed. Elucidation is awaited of the pathologic mechanism of keloid development and identification of signal transduction pathways that will help establish a molecular targeted therapy for keloids.

Photodynamic therapy for keloids and hypertrophic scars: a review.

Purpose:Keloid is a poorly understood disease that is unique to humans. Hypertrophic scars are similar to keloids and may transform into keloids over time. The standard treatments for these scars are limited by inconsistent efficacy and long treatment/follow-up times. Therefore, a new treatment that is effective for all abnormal scar cases is needed. One option may be photodynamic therapy (PDT). This review assesses the current evidence regarding the safety and efficacy of PDT for keloids and hypertrophic scars.Methods:PubMed, Medline and Web of Science were searched from 1900 onwards for the following terms: ‘keloid and photodynamic therapy (PDT)’; ‘hypertrophic scar and photodynamic therapy (PDT)’; and ‘scar and photodynamic therapy (PDT)’. Articles were included if they reported using topical PDT to treat keloids or hypertrophic scars, the patient(s) had one or more keloids and/or hypertrophic scars, and the effect of PDT on these abnormal scars was described.Results:In total, 538 articles were identified. Thirteen fulfilled all inclusion criteria. Eight were laboratory studies on keloid/hypertrophic scar explants, fibroblasts or tissue-engineered skin models and five were clinical studies/case reports. The clinical results of PDT on keloids and hypertrophic scars are encouraging.Conclusion:PDT appears to play a promising role in keloid and hypertrophic scar therapy but additional clinical studies, particularly randomised clinical trials, are needed.

Analysis Distribution of 32P Radioisotope in Silicone Patch Using Autoradiography Scanner

Silicone patch has active ingredient of radioisotope Phosphorus-32 (32P) in the form of chromic phosphate (Cr32PO4). Radioisotope 32P is a β− (beta) emitter radionuclide with an energy of 1.71 MeV, having a half-life (T½) 14.3 days. A silicone patch with radioactive content of the radioisotope 32P has been used for keloid therapy. Radioisotope 32P as an active substance releases beta emitter continuously which causes the death of fibroblast and inhibits cell proliferation from keloid. In order to provide more optimal results, the distribution of chromic phosphate in silicone patches should be spread evenly. In this case, it provides a good therapeutic effect because of the energy of beta emitter is being released uniform. A chromic phosphate can be made from chromic acid reduction (redox) and phosphoric acid-containing radioisotope 32P by reducing Chrom VI to Chrom III using sodium sulfite (Na2SO3) reducing agent. In this study, we will determine the distribution of radioisotope 32P in silicone patches using an autoradiography scanner. Data from enumeration results were calculated statistically to obtain a relative standard deviation (RSD). The result shows that silicone patch sample has RSD of 0.036% with an average value of 14009482.6 ± 5041.4DLU (digital light unit) for lane and column size (10 x 14).

Long non-coding RNA HOXA11-AS accelerates the progression of keloid formation via miR-124-3p/TGFβR1 axis

ABSTRACT Emerging evidence reveals the importance of long non-coding RNAs (lncRNAs) in the development and progression of keloid formation, whereas the underlying mechanisms are not well understood. In the present study, we investigated the biological effects and molecular mechanisms of lncRNA HOXA11-AS in keloid formation. First, the expression levels of HOXA11-AS, miR-124-3p, and transforming growth factor β receptor type I (TGFβR1) were measured in both keloid tissues and human keloid fibroblasts (HKFs) using qRT-PCR and western blot analysis, respectively. Next, we adopted both gain- and loss-of-function strategies to explore the significance of HOXA11-AS. TUNEL, flow cytometry, DNA ladder, and tube formation assays were performed to measure cell apoptosis and angiogenesis, respectively. Besides, the potential binding relationship between HOXA11-AS and miR-124-3p, as well as miR-124-3p and TGFβR1 was identified using bioinformatic screening and verified by luciferase reporter assay. Furthermore, we explored the importance of miR-124-3p in HOXA11-AS-induced phenotypes and regulations on TGFβ signaling or PI3K/Akt signaling. We found that HOXA11-AS and TGFβR1 were significantly up-regulated, while miR-124-3p was down-regulated both in keloid tissues or fibroblasts than in normal skin tissues or fibroblasts. Functionally, high expression of HOXA11-AS essentially inhibited cell apoptosis and promoted fibroblast-induced angiogenesis. Mechanistically, miR-124-3p was identified as a downstream effector to be involved in HOXA11-AS-mediated phenotypes through directly targeting TGFβR1, thus modulating PI3K/Akt signaling pathway. Taken together, our findings revealed that HOXA11-AS inhibits cell apoptosis and promotes angiogenesis through miR-124-3p/TGFβR1 axis, contributing to the progression of keloid formation, which might provide a novel target for keloid therapy.

In Vitro and Ex Vivo Models for Functional Testing of Therapeutic Anti-scarring Drug Targets in Keloids.

Significance: Keloids are benign fibro-proliferative raised dermal lesions that spread beyond the original borders of the wound, continue to grow, rarely regress, and are the most common in pigmented individuals after an abnormal wound healing response. The current treatment failure and respective challenges involved highlighting the underlying issue that the etiopathogenesis of keloids is still not well understood. Disease models are required to better understand the disease pathogenesis. It is not possible to establish keloids in animals because of the uniqueness of this disease to human skin. To address this challenge, along these lines, non-animal reproducible models are vital in investigating molecular mechanisms of keloid pathogenesis and therapeutics development. Recent Advances: Various non-animal models have been developed to better understand the molecular mechanisms involved in keloid scarring and aid in identifying and evaluating the therapeutic potential of novel drug candidates. In this scenario, the current review aims at describing in vitro monocultures, co-cultures, organotypic cultures, and ex vivo whole skin keloid tissue organ culture models. Critical Issues and Future Directions: Current treatment options for keloids are far from securing a cure or preventing disease recurrence. Identifying universally accepted effective therapy for keloids has been hampered by the absence of appropriate disease model systems. Animal models do not accurately mimic the disease, thus non-animal model systems are pivotal in keloid research. The use of these models is essential not only for a better understanding of disease biology but also for identifying and evaluating novel drug targets.

Z-plasty and Postoperative Radiotherapy for Upper-arm Keloids: An Analysis of 38 Patients.

Background:Therapies for upper arm keloids include surgical excision followed by postoperative radiotherapy, silicone tape stabilization, and steroid plaster. However, a universally accepted therapeutic strategy for upper-arm keloids is lacking.Methods:All consecutive patients with single upper-arm keloids who underwent keloid excision followed by tension-reducing suturing, multiple z-plasties, and postoperative radiotherapy in 2013–2016 in the keloid/scar specialist clinic at the Department of Plastic, Reconstructive and Aesthetic Surgery of Nippon Medical School, were included in this case series study. Only keloids that arose from the small injury produced during Bacillus Calmette–Guérin vaccination were selected. The postsurgical radiotherapy regimen was 18 Gy administered in 3 fractions over 3 days. Radiotherapy was followed by tension-reducing wound self-management with silicone tape and, if needed, steroid plaster. The primary study objective was keloid recurrence during the 24-month follow-up period. Recurrence was defined as the growth of stiff red lesions in even small areas of the scar that was refractory to at least 2 months of steroid plaster therapy.Results:In total, 38 patients with 38 lesions were enrolled. Two lesions (5.3%) recurred. Both recurrences were successfully treated by concomitant steroid plaster and steroid injection. The recurrence patients were significantly more likely than the nonrecurrence patients to have multiple keloids. The 2 groups did not differ in terms of original keloid size.Conclusions:Upper-arm keloids can be successfully treated by customized plans that involve appropriate surgical modalities (including multiple z-plasties), postoperative radiotherapy (18 Gy/3 fractions/3 d), and postoperative wound/scar self-management with silicone tape and steroid plaster.

Clinical Challenge and Call for Research on Keloid Disorder: Meeting Report from The 3rd International Keloid Research Foundation Symposium, Beijing 2019

Clinical Challenge and Call for Research on Keloid Disorder: Meeting Report from The 3rd International Keloid Research Foundation Symposium, Beijing 2019

CUDC‑907 reverses pathological phenotype of keloid fibroblasts in vitro and in vivo via dual inhibition of PI3K/Akt/mTOR signaling and HDAC2.

Keloids are benign skin tumors with a high recurrence rate following surgical excision. Abnormal intracellular signaling is one of the key mechanisms involved in its pathogenesis. Over-activated phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway and overproduction of histone deacetylases 2 (HDAC2) have also been observed in keloid fibroblasts (KFs). The present study aimed to explore the possibility of reversing the KF pathological phenotype using CUDC-907, a dual inhibitor of PI3K/Akt/mTOR pathway and HDACs. KFs and keloid xenografts were treated with CUDC-907 to examine its inhibitory effects on the pathological activities of KFs in vitro and in vivo. CUDC-907 inhibited cell proliferation, migration, invasion and extracellular matrix deposition of in vitro cultured KFs and also suppressed collagen accumulation and disrupted the capillaries of keloid explants ex vivo and in vivo. A mechanistic study of CUDC-907 revealed the initiation of cell cycle arrest at G2/M phase along with the enhanced expression of cyclin-dependent kinase inhibitor 1 and decreased expression of cyclin B in cells treated with CUDC-907. CUDC-907 not only inhibited AKT and mTOR phosphorylation and promoted the acetylation of histone H3, but also significantly inhibited the phosphorylation levels of Smad2/3 and Erk. These preclinical data demonstrating its anti-keloid effects suggest that CUDC-907 may represent a candidate drug for systemic keloid therapy.

Possible Mechanisms and Prospects of Stem Cell Therapy for Keloids

Possible Mechanisms and Prospects of Stem Cell Therapy for Keloids

Pediatric earlobe keloids: Outcomes and patterns of recurrence

PurposeKeloids occur as a result of abnormal wound healing and as many as 70% of keloids and hypertrophic scars affect the pediatric population. Earlobe keloids, similar to lesions elsewhere in the body, remain a challenging problem given the high rates of recurrence and lack of consensus regarding treatment strategy. This study aims to evaluate the outcomes and patterns of recurrences following treatment of earlobe keloids in a large cohort of pediatric patients to facilitate identification of the optimal treatment strategy. MethodsAll pediatric patients who underwent surgical therapy for earlobe keloids over a 10-year period (2004–2015) were identified and demographic, clinical and outcomes data were collected. A follow-up phone survey was administered to assess rates of long-term recurrence and overall satisfaction with the treatment strategy. Data analysis was performed using Student's t-test and Fisher's exact as appropriate. ResultsA total of 94 patients with 135 keloids were identified. Mean age was 14 years with slight preponderance of females (52%) and a majority (75%) of the patients were African American (AA). Mean keloid size was 2.4 cm (0.25–11 cm) with ear piercing being the most common inciting etiology. Excision with steroid injection (59%) was the most frequent treatment approach followed by excision alone (25%). During a median follow up of 2 years, keloid recurrence occurred in 27 (28.7%) patients, 19 (70.4%) underwent additional therapy with 10 (52.6%) re-recurrences noted. Median time to recurrence was 23 months, with a slightly higher recurrence rate in AA patients (32%; p = 0.26) and in those age < 10 years (50%; p = 0.11). ConclusionThis represents the largest series of earlobe keloids treatment in children. Our data suggest that recurrence rates are unaffected by the age at excision and race of the patient. Moreover, adjuncts to excisional therapy such as steroid injection, compression therapy and radiation also did not appear to influence recurrence. Given the pattern of recurrences studies with longer term follow-up are needed to assess the efficacy of treatment strategies. Type of studyCase series. Level of evidenceIV