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1.
Medicine (Baltimore) ; 99(4): e18886, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977896

RESUMO

RATIONALE: Giant keloids often have indications for surgical resection, but postoperative reconstruction of the skin and high recurrence of keloids are a challenge for clinical treatment. This article reports a rare successful treatment of a giant keloid in the anterior chest wall by multistage surgery combined with radiotherapy, which is why this case is meaningful. PATIENT CONCERNS: A 66-year-old woman presented a giant keloid with ulcerations and severe itching on the anterior chest wall. She had a history of keloid disease for more than 10 years, and had been treated by multiple operations, with no success. DIAGNOSES: The patient was diagnosed as keloid based on her history and symptoms. Histopathology findings supported our diagnosis. INTERVENTIONS: We successfully excised the keloid after 5 operations and 2 rounds of electron-beam radiotherapy, which was applied at 24 hours after the 4th and 5th operation. OUTCOMES: There was no sign of recurrence over the follow-up period of 24 months. LESSONS: The combination of multistage surgery and radiotherapy presents as a good choice for the treatment of giant keloids.


Assuntos
Procedimentos Cirúrgicos Dermatológicos/métodos , Queloide/cirurgia , Parede Torácica/cirurgia , Idoso , Feminino , Humanos , Queloide/patologia , Queloide/radioterapia , Período Pós-Operatório , Radioterapia Adjuvante , Pele/patologia , Parede Torácica/patologia
2.
Medicine (Baltimore) ; 98(48): e18094, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770227

RESUMO

RATIONALE: Micro-plasma radio-frequency (MPR) technology has been demonstrated a safe and effective treatment for kinds of scars, but there is no report about the application of the MPR on keloids. In this investigation, we creatively use MPR technology combining with hypofractionated electron-beam radiation to cure keloids. PATIENT CONCERNS AND DIAGNOSES: From February 2013 to December 2016, 22 Asian patients (16 male, 6 female, age 19-46 years, mean age 28.14 ±â€Š7.31 years) with keloids over half a year were enrolled in this study. INTERVENTIONS AND OUTCOMES: All patients received a single MPR technology treatment by roller tip at 80-100 watt, and then hypofractionated electron-beam radiation of 6 MeV were performed twice, within 24 hours and one week after the operation with 9 Gy per time. Improvement were determined by the Vancouver Scar Scales (VSS) according to digital photographs. The results show that the volume of keloids reduced significantly among most patients. Only 3 patients encountered with mild to moderate hyperpigmentation, and none of malignance and worsening or recurrence of scars was observed. LESSONS: MPR technology combined with post-operative hypofractionated electron-beam radiation therapy is an effective method for patients with multiple keloids distributed widely on the body with minimal complications, especially for patients with widely distributed keloids.


Assuntos
Queloide/radioterapia , Terapia por Radiofrequência/métodos , Adulto , Terapia Combinada , Elétrons , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Hipofracionamento da Dose de Radiação , Recidiva , Resultado do Tratamento , Adulto Jovem
3.
Rev. bras. cir. plást ; 34(3): 391-398, jul.-sep. 2019. ilus
Artigo em Inglês, Português | LILACS | ID: biblio-1047162

RESUMO

Introdução: Queloides surgem de resposta excessiva à lesão da derme, resultando em proliferação de fibroblastos, produção exagerada de colágeno e comprometimento da pele sadia adjacente. O diagnóstico é clínico e muitos métodos conservadores e cirúrgicos já foram utilizados para tratamento. Porém, dados da eficácia desses tratamentos são limitados e não há consenso na literatura quanto a melhor técnica a ser empregada, permanecendo uma lacuna que necessita ser preenchida, a fim de que seus usos sejam indicados com maior confiabilidade, em um modelo de medicina baseada em evidências. Métodos: Revisão não sistemática da literatura sobre "queloides" nas bases de dados PubMed, Scielo, MEDLINE, UptoDate e livros-texto das áreas de Dermatologia e Cirurgia Dermatológica. Revisão de Literatura: Foram enumeradas e abordadas as principais informações sobre técnicas cirúrgicas e adjuvantes empregadas para essas lesões, que são: excisão, injeções intralesionais, crioterapia, laserterapia, revestimento com gel de silicone, radioterapia e pressoterapia. Torna-se relevante o levantamento dessas informações, tendo em vista que, além de poder causar dor, prurido e restrição de movimento, o principal motivo da procura de assistência médica para queloide é devido ao aspecto cosmético/estético, e as taxas de reincidência e falha terapêutica ainda são altas, sendo necessário conscientizar o paciente sobre o procedimento e seus efeitos. Conclusão: São muitos os tratamentos disponíveis para o queloide, sejam cirúrgicos ou não, todavia não há consenso sobre uma abordagem universalmente aceita. São necessários mais estudos, com a finalidade de definir a melhor conduta e atingir melhores resultados, visto a qualidade mediana das evidências apresentadas nos estudos.


Introduction: Keloids are characterized by an abnormal response to dermal trauma, resulting in fibroblast proliferation, excessive collagen production, and impairment of adjacent healthy tissue. The diagnosis is clinical, and many conservative and surgical methods can be used as treatments. However, data on the efficacy of these treatments are limited, and there is no consensus regarding the best treatment option. This gap needs to be filled by developing comprehensive evidence-based therapies. Methods: A non-systematic literature review of keloid scars was carried out using PubMed, Scielo, MEDLINE, UptoDate, and dermatology and dermatological surgery textbooks. Literature review: The search retrieved relevant information on surgical and adjuvant therapies used for keloids, including excision, intralesional injections, cryotherapy, laser therapy, silicone gel sheeting, radiation therapy, and pressure therapy. These data are crucial because, in addition to complaints of pain, itching, and restriction of movement, the main reason for seeking treatment for keloids is for cosmetic and aesthetic improvement, and the rates of recurrence and treatment failure are high, emphasizing the importance of creating awareness regarding the available procedures and their effectiveness. Conclusion: Many surgical and adjuvant therapies for keloids are available. Nonetheless, there is no consensus on a universally accepted treatment. Therefore, additional high-quality studies are needed to identify the most effective therapeutic approaches to achieve better results.


Assuntos
Humanos , História do Século XXI , Recidiva , Cirurgia Plástica , Terapêutica , Fator 1 de Crescimento de Fibroblastos , Fibroblastos , Procedimentos Cirúrgicos Dermatológicos , Queloide , Cirurgia Plástica/efeitos adversos , Cirurgia Plástica/métodos , Terapêutica/métodos , Ferimentos e Lesões , Ferimentos e Lesões/cirurgia , Ferimentos e Lesões/terapia , Fator 1 de Crescimento de Fibroblastos/análise , Fator 1 de Crescimento de Fibroblastos/efeitos adversos , Cicatriz , Cicatriz/complicações , Procedimentos Cirúrgicos Dermatológicos/métodos , Queloide/cirurgia
4.
Niger J Clin Pract ; 22(8): 1049-1054, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31417046

RESUMO

Background: Keloid is a major complication of wound healing. The clinical spectrum ranges from unaesthetic lesions minimally invading the adjacent skin to large grotesque lesions sometimes associated with contractures. Subjects and Methods: The patients were seen over 2 years in a tertiary hospital setting. The following information was obtained with a proforma: the biodata, etiology of keloid, region affected, symptoms, and treatment prior to presentation. The keloids were examined and the sizes were grouped into small, medium, and large keloids; the severities of symptoms were determined using the visual analog scale. Results: 159 patients with 224 keloids were seen over 2-year period with male-to-female ratio of 1:1.24. The most common causes of keloid were trauma and acne (27.0% and 20.1%, respectively). The trunk had a statistically significant higher number of symptomatic keloid compared with other regions keloids. The larger keloids were more symptomatic compared with the smaller ones, P = 0.000. There were more pruritic keloids than painful ones. About 25% of patients had positive family history in first-degree relative, 16% in second-degree relative, and their keloid are more symptomatic than those without family history. Conclusion: In view of the burden of keloids, early treatment is advised. Unnecessary trauma and extra piercing should be avoided; elective surgeries that are deferrable should be postponed until when necessary.


Assuntos
Queloide/patologia , Dor/etiologia , Adulto , Demografia , Feminino , Humanos , Queloide/epidemiologia , Masculino , Nigéria/epidemiologia , Dor/epidemiologia , Escala Visual Analógica , Cicatrização
5.
Pan Afr Med J ; 33: 62, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31448024

RESUMO

Keloid is a benign fibroblastic tumor which is most often secondary to a scar, but it can occur spontaneously in a subject with black skin. We report the case of a 19-year old patient, electrician, presenting with giant right retroauricular mass evolving over two years. For some time, the patient has experienced a feeling of heaviness on the pavilion of the right ear. The lesion had manifested as a hard, pruritic, non-painful patch gradually increasing in size. The patient had received several topical and antiseptics treatments without any effect. He had a history of traumatic injury in the right retroauricular sulcus. A month after, pruritic hypertrophic scar occurred. Physical examination showed voluminous hard, fixed, retroauricular tumor (10 × 6 cm) with normal skin color, non-painful on movement (A). Its base was sessile. The remainder of the physical examination was normal. Ultrasound showed little vascularized skin tumor of the right retroauricular sulcus with more or less sharp margins, measuring 9 x 5 cm. Two diagnoses were suspected: post-traumatic keloid (most likely) and Darier Ferrand dermatofibrosarcoma. Biopsy was performed and histological examination showed keloid. The patient underwent intramarginal excision (B). The surgical specimens weighed 75 grams (C). The postoperative course was simple with disappearance of the feeling of heaviness.


Assuntos
Orelha/patologia , Queloide/diagnóstico , Ferimentos e Lesões/complicações , Biópsia , Dermatofibrossarcoma/diagnóstico , Diagnóstico Diferencial , Humanos , Queloide/etiologia , Queloide/cirurgia , Masculino , Neoplasias Cutâneas/diagnóstico , Adulto Jovem
6.
Biomed Res Int ; 2019: 4693528, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428636

RESUMO

Background: Keloids are hard nodules or plaques formed by excessive proliferation of connective tissue. Radiotherapy, widely used in various benign and malignant skin diseases, is an effective treatment for keloids. This work evaluates Intrabeam photon radiotherapy in the management of keloids. Methods: Fourteen patients who have undergone Intrabeam radiotherapy for a total of 15 sites of keloids were followed up. Twelve cases were first onset and the other two had recurrent diseases. Thirteen patients underwent surgical resection of keloids before radiotherapy. One relapsing patient received only 2 rounds of radiation therapy as she could not be reoperated. Radiotherapy was divided into 2 sessions on days 0 and 3 after surgery. The dose was 4 or 5 Gy each time for 3 min 14 s to 12 min 1 s. In addition, we compared our data to the recurrence of keloids in fourteen patients who had previously been exposed to electron beam using conventional accelerators. Results: We analyzed the treatment for adverse reactions and recurrence. In the Intrabeam group, one patient developed superficial skin ulcers a month after treatment. No one experienced wound rupture, bleeding, infection, skin contractures, or obvious hyperpigmentation. None of the fourteen cases showed any recurrence so far after on median 22.5 months of follow-up. Five patients in the electron beam group relapsed 3 to 10 months after treatment. Conclusion: Here, Intrabeam photon radiotherapy was shown to be an effective treatment for keloid scars and it is therefore recommended for management of this disease.


Assuntos
Queloide/radioterapia , Terapia por Raios X/instrumentação , Terapia por Raios X/métodos , Adulto , Feminino , Seguimentos , Humanos , Queloide/patologia , Masculino , Pessoa de Meia-Idade
7.
Life Sci ; 234: 116779, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31430452

RESUMO

Emerging evidence has revealed that microRNAs (miRNAs) play critical roles in keloid pathogenesis. However, potential molecular mechanism of keloid formation remains unclear. In the present study, our findings showed that miR-152-3p mRNA expression level was notably up-regulated in keloid tissues and keloid fibroblasts compared with that of normal skin tissues and normal skin fibroblasts, respectively. Furthermore, miR-152-3p inhibition remarkably suppressed cell proliferation, which was increased by miR-152-3p overexpression. Cell invasion was also significantly decreased by miR-152-3p inhibition, whereas was increased by miR-152-3p overexpression. The mRNA and protein expression levels of extracellular matrix components including type I collagen, type III collagen and fibronectin were decreased by miR-152-3p inhibition, but were increased by miR-152-3p overexpression. In addition, results of dual-luciferase reporter assay indicated that FOXF1 is a direct target of miR-152-3p. FOXF1 overexpression significantly inhibits cell proliferation, invasion, and extracellular matrix in keloid fibroblasts, and the suppressive effects of miR-152-3p mimic on these functions were notably partly reversed by FOXF1 overexpression. Taken together, these findings indicated that miR-152-3p regulates cell proliferation, invasion and extracellular matrix expression through targeting FOXF1 in keloid fibroblasts, suggesting that miR-152-3p is a novel and promising molecular target for keloid treatment.


Assuntos
Matriz Extracelular/patologia , Fibroblastos/patologia , Fatores de Transcrição Forkhead/genética , Queloide/patologia , MicroRNAs/genética , Regiões 3' não Traduzidas , Adolescente , Adulto , Movimento Celular , Proliferação de Células , Células Cultivadas , Matriz Extracelular/genética , Fibroblastos/citologia , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Humanos , Queloide/genética , Regulação para Cima , Adulto Jovem
8.
Int J Mol Sci ; 20(17)2019 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-31450620

RESUMO

Overabundance of extracellular matrix resulting from hyperproliferation of keloid fibroblasts (KFs) and dysregulation of apoptosis represents the main pathophysiology underlying keloids. High-mobility group box 1 (HMGB1) plays important roles in the regulation of cellular death. Suppression of HMGB1 inhibits autophagy while increasing apoptosis. Suppression of HMGB1 with glycyrrhizin has therapeutic benefits in fibrotic diseases. In this study, we explored the possible involvement of autophagy and HMGB1 as a cell death regulator in keloid pathogenesis. We have highlighted the potential utility of glycyrrhizin as an antifibrotic agent via regulation of the aberrant balance between autophagy and apoptosis in keloids. Higher HMGB1 expression and enhanced autophagy were observed in keloids. The proliferation of KFs was decreased following glycyrrhizin treatment. While apoptosis was enhanced in keloids after glycyrrhizin treatment, autophagy was significantly reduced. The expressions of ERK1/2, Akt, and NF-κB, were enhanced in HMGB1-teated fibroblasts, but decreased following glycyrrhizin treatment. The expression of extracellular matrix (ECM) components was reduced in glycyrrhizin-treated keloids. TGF-ß, Smad2/3, ERK1/2, and HMGB1 were decreased in glycyrrhizin-treated keloids. Treatment with the autophagy inhibitor 3-MA resulted in a decrease of autophagy markers and collagen in the TGF-ß-treated fibroblasts. The results indicated that autophagy plays an important role in the pathogenesis of keloids. Because glycyrrhizin appears to reduce ECM and downregulate autophagy in keloids, its potential use for treatment of keloids is indicated.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Ácido Glicirrízico/farmacologia , Proteína HMGB1/antagonistas & inibidores , Queloide/metabolismo , Biomarcadores , Sobrevivência Celular/genética , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/ultraestrutura , Fibrose/etiologia , Fibrose/metabolismo , Expressão Gênica , Humanos , Imuno-Histoquímica
9.
Laryngorhinootologie ; 98(8): 536-544, 2019 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-31387131

RESUMO

The overproduction of altered collagen fibers and the overexpression of Tumor Growth Factor-ß must be blocked in order to interrupt the growth process within a keloid scar. This can barely be achieved with the classical therapeutic methods. The results of keloid treatment are difficult to predict and the recurrence rate is usually over 50 %. In addition, some of the procedures used (e. g. irradiation) may induce additional health risks. Intralesional cryosurgery offers a therapeutic alternative that has been evaluated since more than a decade. Our own experience in more than one thousand keloid treatments allows a critical evaluation of the classification in those keloid types, which are recommended to be treated with the technique and those, which may not respond.


Assuntos
Criocirurgia , Queloide , Humanos , Injeções Intralesionais , Seleção de Pacientes , Recidiva
10.
Kobe J Med Sci ; 65(1): E10-E18, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31341152

RESUMO

BACKGROUND: Keloids are characterized by an overabundance of collagen deposition due to elevated activity and proliferation of fibroblasts, which lead to hypoxic conditions. Adaptation to these conditions is regulated by the transcription factor hypoxia inducible factor-1α (HIF-1α). Cytoglobin (Cygb), a reactive oxygen species scavenger, is a target gene of HIF-1α. In our previous study, we showed that Cygb expression in keloid tissue was correlated with HIF-1α expression. However, whether HIF-1α regulates Cygb expression and the proliferation of keloid fibroblasts remained unclear. Therefore, this study aimed to determine the role of HIF-1α in Cygb expression and fibroblast proliferation of keloids. METHODS: This was an in vitro study using a primary culture of keloid fibroblasts in which ibuprofen was used to inhibit HIF-1α expression. The expression of HIF-1α and Cygb mRNA were analyzed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) methods, and their protein levels were analyzed using an enzyme-linked immunosorbent assay (ELISA). Fibroblast proliferation was analyzed using a Trypan blue exclusion assay. RESULTS: Inhibition of HIF-1α by ibuprofen decreased Cygb mRNA expression but not in all the samples, followed by a decrease in the protein level of Cygb. There was a positive correlation between the HIF-1α protein and Cygb mRNA, probably due to the regulation of Cygb by HIF-1α at the mRNA level, but not the protein level. The proliferation of keloid fibroblasts was significantly decreased and positively correlated with the HIF-1α protein. CONCLUSION: HIF-1α regulates Cygb expression and fibroblast proliferation in keloids.


Assuntos
Citoglobina/genética , Fibroblastos/fisiologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , Queloide/metabolismo , Proliferação de Células , Células Cultivadas , Regulação da Expressão Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/análise , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Ibuprofeno/farmacologia , RNA Mensageiro/análise
11.
Plast Reconstr Surg ; 144(2): 372-384, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31348346

RESUMO

BACKGROUND: We investigated expression of prorenin receptor, angiotensin-converting enzyme, angiotensin II receptor 1, and angiotensin II receptor 2 by the embryonic stem cell-like population on the endothelium of the microvessels and perivascular cells within keloid-associated lymphoid tissues. METHODS: Immunohistochemical staining for prorenin receptor, angiotensin-converting enzyme, angiotensin II receptor 1, and angiotensin II receptor 2 was performed on 11 formalin-fixed, paraffin-embedded sections of keloid tissue samples. Immunofluorescence staining was performed on three keloid tissue samples by co-staining with OCT4, CD34, ERG, and tryptase. Real-time quantitative polymerase chain reaction was performed on five keloid tissue samples and four keloid-derived primary cell lines. Western blotting was performed on the four keloid-derived primary cell lines for mRNA and protein expression of these proteins, respectively. RESULTS: Immunohistochemical and immunofluorescence staining showed expression of prorenin receptor, angiotensin-converting enzyme, angiotensin II receptor 1, and angiotensin II receptor 2 in all 11 keloid tissue samples. Prorenin receptor and angiotensin II receptor 1 were expressed on the endothelium and the pericyte layer of the microvessels and perivascular cells, angiotensin II receptor 2 was localized to the endothelium of the microvessels and the tryptase-positive perivascular cells, and angiotensin-converting enzyme was localized to the endothelium of the microvessel, within the keloid-associated lymphoid tissues. Real-time quantitative polymerase chain reaction showed transcripts of prorenin receptor, angiotensin-converting enzyme, and angiotensin II receptor 1 in the keloid tissue samples and keloid-derived primary cell lines, whereas angiotensin II receptor 2 was detected in keloid tissue samples only. Western blotting confirmed the presence of prorenin receptor, angiotensin-converting enzyme, and angiotensin II receptor 1 in the keloid-derived primary cell lines. CONCLUSION: Prorenin receptor, angiotensin-converting enzyme, angiotensin II receptor 1, and angiotensin II receptor 2 were expressed by the embryonic stem cell-like population within the keloid-associated lymphoid tissues, suggesting that this primitive population may be a potential therapeutic target by modulation of the renin-angiotensin system.


Assuntos
Células-Tronco Embrionárias/metabolismo , Queloide/metabolismo , Sistema Renina-Angiotensina/fisiologia , Adolescente , Adulto , Antígenos CD34/metabolismo , Linhagem Celular , Criança , Pré-Escolar , Feminino , Imunofluorescência , Humanos , Queloide/patologia , Masculino , Pessoa de Meia-Idade , Fator 3 de Transcrição de Octâmero/metabolismo , Peptidil Dipeptidase A/metabolismo , RNA Mensageiro/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 2 de Angiotensina/metabolismo , Receptores de Superfície Celular/metabolismo , Regulador Transcricional ERG/metabolismo , Adulto Jovem
12.
Cell Mol Biol (Noisy-le-grand) ; 65(5): 43-48, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31304905

RESUMO

The formation of keloid is associated with accumulation of extracellular matrix (ECM) formed mainly of collagen and fibronectin. Persistent deregulated IL-6 synthesis causes the development of various diseases. This study aim to investigate interleukin 6 (IL-6) serum level and gene polymorphism in a sample of Egyptian patients having keloid. This study was carried out on 90 subjects; 60 patients with keloid, and 30 age and sex matched apparently healthy control. All subjects underwent full history taking, clinical examinations, weight and length measuring to calculate BMI, dermatological examination, analysis of IL6-572 gene polymorphism using REFLP- PCR and IL-6 serum level using ELISA.IL-6 serum levels were significantly higher in keloid patients than control group (75.54±39.18) vs (19.17±6.06), (p <0.001). The higher serum levels of IL-6 were associated with GG genotype (104.84±19.12) followed by CG (57.64±35.38) genotype (P<0.001). GG genotype was significantly higher in keloid patients and increased the risk for keloid development by nearly14 folds (p<0.001, OR (95%CI) =13.81).  CG genotype was significantly observed in keloid patients and increased the risk for keloid development by about 4 times (p=0.010, OR (95%CI) =4.27). G Allele significantly increased the risk for keloid development by about 5 folds (P <0.001 OR =5.11). In conclusion, there was a great association between IL-6 572 gene polymorphism and its serum level in patients with keloid specifically who have family history.


Assuntos
Predisposição Genética para Doença , Interleucina-6/sangue , Interleucina-6/genética , Queloide/sangue , Queloide/genética , Adolescente , Adulto , Estudos de Casos e Controles , Egito , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Regiões Promotoras Genéticas , Adulto Jovem
13.
Life Sci ; 232: 116637, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31288014

RESUMO

Keloid is characterized by overactive fibroblasts. Forkhead box M1 (FOXM1) is transcription factor that plays important roles in the progression of fibrosis. However, the role of FOXM1 in keloid has not been elucidated. In the present study, we examined the expression levels of FOXM1 in clinical keloid tissue specimens and primary keloid fibroblasts (KFs). The results showed that FOXM1 levels were significantly increased in both keloid tissues and KFs. To further investigate the biological functions of FOXM1, FOXM1 was knocked down in KFs by transfection with small interfering RNA targeting FOXM1 (si-FOXM1). Knockdown of FOXM1 inhibited transforming growth factor-ß1 (TGF-ß1)-induced cell proliferation and migration of KFs. Besides, the increased expressions of collagen (coll I), connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA) in TGF-ß1-induced KFs were suppressed by si-FOXM1 transfection. Furthermore, TGF-ß1-induced increase in p-Smad2 and p-Smad3 expressions was attenuated by FOXM1 knockdown. These data indicated that knockdown of FOXM1 inhibited TGF-ß1-induced KFs activation and extracellular matrix (ECM) accumulation, which was attributed to the inhibition of TGF-ß1/Smad pathway.


Assuntos
Proteína Forkhead Box M1/deficiência , Queloide/metabolismo , Actinas/metabolismo , Adolescente , Adulto , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Colágeno/metabolismo , Colágeno Tipo I/metabolismo , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Feminino , Fibroblastos/metabolismo , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Técnicas de Silenciamento de Genes/métodos , Humanos , Queloide/genética , Masculino , Fosforilação , RNA Interferente Pequeno/genética , Transdução de Sinais , Proteína Smad2/antagonistas & inibidores , Proteína Smad2/metabolismo , Proteína Smad3/antagonistas & inibidores , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Fator de Crescimento Transformador beta1/metabolismo
14.
Wounds ; 31(7): 179-183, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31184592

RESUMO

BACKGROUND: Keloids cause cosmetic problems, pain, and pruritus. Different modes of therapy are limited by their efficacy and side effects. High-mobility group box 1 protein (HMGB1) may play a role in keloid pathogenesis; therefore, the therapeutic potential of box A1, an antireceptor of advanced glycation end products antibody, and other inhibitors of HMGB1 may play a role in the treatment of keloids. OBJECTIVE: This study evaluates the role of HMGB1 in patients with keloids by comparing their serum level with healthy controls. MATERIALS AND METHODS: Forty patients with keloids and 40 controls were enrolled in this study. Detailed history and clinical evaluation were performed. A 3-mL sample of whole blood was obtained from both patient groups and centrifuged immediately. The resultant supernatant serum was frozen at -20°C for the detection and quantification of HMGB1 using enzyme-linked immunosorbent assay. RESULTS: There was a statistically significant elevation in the mean value of HMGB1 in keloid cases (74.38 ± 40.16) compared with the mean value of the controls (52.00 ± 5.41; P = .001). Mean value of HMGB1 was positively correlated with keloid severity. CONCLUSIONS: High-mobility group box 1 was found to be elevated in patients with keloids compared with their controls, suggesting its role in excessive scarring and the role of its antagonists in therapy.


Assuntos
Proteína HMGB1/metabolismo , Queloide/sangue , Queloide/patologia , Adulto , Biomarcadores/sangue , Biópsia por Agulha , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Curva ROC , Valores de Referência , Papel (figurativo) , Índice de Gravidade de Doença , Estatísticas não Paramétricas
15.
Rev Med Suisse ; 15(655): 1213-1216, 2019 Jun 12.
Artigo em Francês | MEDLINE | ID: mdl-31194295

RESUMO

Keloids are debilitating skin lesions that develop often as a result of minor skin lesions. Unlike hypertrophic scars, their main clinical feature is the tendency to extend beyond the initial limits of the wound. They can be responsible for pain and itching and may appear several months after the trauma. Their pathophysiology remains unknown but various mechanisms seem to be involved. Their management includes invasive and non-invasive approaches. At present, there is no satisfactory method or consensus on their management. Since the risk of recurrence after treatment is particularly high, a combination of different methods is proposed. In this article, we present the therapeutic strategy used in our institution concerning these problematic lesions.


Assuntos
Cicatriz Hipertrófica , Queloide , Humanos , Queloide/terapia , Prurido , Recidiva
16.
Mol Med Rep ; 20(2): 1429-1435, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173246

RESUMO

Pathological scarring is a result of the hypertrophy of scar tissue during tissue repair following trauma. The aim of the present study was to assess the effect of ubiquitin­specific protease 4 (USP4) silencing on pathological scarring, and to evaluate the mechanistic basis for the effect. An MTT assay was used to assess cell viability. Immunoprecipitation (IP) was used to determine ubiquitination levels of the TGF­ß receptor (TßR)I and Smad7. Tumor formation was assessed by injecting keloid fibroblasts. Hematoxylin and eosin staining was used to detect pathological changes in tumor tissue. Reverse transcription quantitative polymerase chain reaction and western blot analysis assays were used to evaluate the expression levels of TßRI and Smad7. Compared with the untreated control animals, cell viability and the expression of TßRI and Smad7 increased significantly in animals treated with TGF­ß. Short hairpin RNA for USP4 (shUSP4) decreased the cell viability of negative control cells, TGF­ß­induced cellular proliferation, and the expression of TßRI and Smad7. IP experiments indicated that the ubiquitination level of TßRI was decreased following USP4 silencing. There was no remarkable difference in the structure of scar tissue among the various animal groups at 14 days following treatment, while the necrotic area of the scar tissue in the shUSP4 and vialinin A (USP inhibitor)­treated animals increased significantly at the 28th and 42nd day compared with the control animals. At days 14, 28 and 42, the expression levels of TßRI and Smad7 in the shUSP4 and vialinin A­treated animals were significantly decreased compared with the control animals (P<0.05). In summary, interference with or inhibition of USP4 prevented the activity of the TGF­ß/Smad pathway signaling and inhibited the formation of pathological scars.


Assuntos
Cicatriz/genética , Queloide/genética , Receptor do Fator de Crescimento Transformador beta Tipo I/genética , Proteína Smad7/genética , Fator de Crescimento Transformador beta/genética , Proteases Específicas de Ubiquitina/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cicatriz/metabolismo , Cicatriz/patologia , Cicatriz/prevenção & controle , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibroblastos/transplante , Regulação da Expressão Gênica , Humanos , Queloide/metabolismo , Queloide/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Transdução de Sinais , Proteína Smad7/metabolismo , Compostos de Terfenil/farmacologia , Fator de Crescimento Transformador beta/metabolismo , Transplante Heterólogo , Proteases Específicas de Ubiquitina/antagonistas & inibidores , Proteases Específicas de Ubiquitina/metabolismo
17.
Facial Plast Surg ; 35(3): 260-266, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31189199

RESUMO

Despite the ubiquitous nature of scar tissue, there is not a single, reliable strategy to prevent or treat excessive scarring. The difficulty in arriving at a universally accepted form of management is multifaceted: there is an incomplete understanding of the complex pathophysiology of scar formation; a lack of common metrics hampers the accurate description of scar quality and characteristics; model systems do not exist for proper investigation in the controlled environment of a laboratory; and there is only limited data from prospective, randomized controlled clinical trials. Accordingly, the management of cutaneous scars is typically based upon the experience from practitioners rather than from evidence-based data. This article will review the pathophysiology of excessive scar formation, define the most common scars-hypertrophic scars and keloids-and discuss the evidence to support the current nonsurgical therapies in use to both prevent and treat excessive scars.


Assuntos
Cicatriz Hipertrófica , Queloide , Humanos , Estudos Prospectivos
18.
Artigo em Inglês | MEDLINE | ID: mdl-31233167

RESUMO

INTRODUCTION: The rabbit ear hypertrophic scar model is a preferred animal model of excessive scarring for investigating the scarring process and novel treatment modalities. In this model, surgical removal of perichondrium can be challenging, and it is often insufficient or damages the underlying cartilage. It is hypothesized that cryosurgery would offer a more efficient alternative to conventional surgery. The objective of this study was to compare structural changes in scar tissues in two groups of the hypertrophic scar model: cryosurgery compared to standard conventional surgery. METHODS: We introduced a novel technique to remove perichondrium using cryosurgery. Hypertrophic scars obtained with conventional surgery and cryosurgery were studied in a left-right comparison method. Comparative parameters included the histological structure of the scars and structural changes in the cartilage just beneath the scarring. RESULTS: Cryosurgery produced similar scars in comparison to conventional surgery. Although statistically not significant (p = 0.16), the histological findings of cartilage damage were lower in the cryosurgery group (six out of 21) compared to the established model (10 out of 20). CONCLUSION: This study suggests that cryotherapy can be used for removal of perichondrium.


Assuntos
Cicatriz Hipertrófica/cirurgia , Criocirurgia/métodos , Queloide/cirurgia , Animais , Cicatriz Hipertrófica/patologia , Modelos Animais de Doenças , Queloide/patologia , Coelhos , Cicatrização
19.
Plast Reconstr Surg ; 144(1): 58e-67e, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31246819

RESUMO

BACKGROUND: Fibroproliferative disorders result in excessive scar formation, are associated with high morbidity, and cost billions of dollars every year. Of these, keloid disease presents a particularly challenging clinical problem because the cutaneous scars progress beyond the original site of injury. Altered mechanotransduction has been implicated in keloid development, but the mechanisms governing scar progression into the surrounding tissue remain unknown. The role of mechanotransduction in keloids is further complicated by the differential mechanical properties of keloids and the surrounding skin. METHODS: The authors used human mechanical testing, finite element modeling, and immunohistologic analyses of human specimens to clarify the complex interplay of mechanical stress, strain, and stiffness in keloid scar progression. RESULTS: Changes in human position (i.e., standing, sitting, and supine) are correlated to dynamic changes in local stress/strain distribution, particularly in regions with a predilection for keloids. Keloids are composed of stiff tissue, which displays a fibrotic phenotype with relatively low proliferation. In contrast, the soft skin surrounding keloids is exposed to high mechanical strain that correlates with increased expression of the caveolin-1/rho signaling via rho kinase mechanotransduction pathway and elevated inflammation and proliferation, which may lead to keloid progression. CONCLUSIONS: The authors conclude that changes in human position are strongly correlated with mechanical loading of the predilection sites, which leads to increased mechanical strain in the peripheral tissue surrounding keloids. Furthermore, increased mechanical strain in the peripheral tissue, which is the site of keloid progression, was correlated with aberrant expression of caveolin-1/ROCK signaling pathway. These findings suggest a novel mechanism for keloid progression.


Assuntos
Caveolina 1/fisiologia , Queloide , Mecanotransdução Celular/fisiologia , Transdução de Sinais/fisiologia , Estresse Mecânico , Quinases Associadas a rho/fisiologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Análise de Elementos Finitos , Humanos , Queloide/metabolismo , Queloide/fisiopatologia , Masculino , Pessoa de Meia-Idade , Postura/fisiologia , Adulto Jovem
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