Holistic Approach in the Treatment of Actinic Keratosis: Benefits and Disadvantages of 5-Fluorouracil, Imiquimod, Diclofenac and Curaderm

Background Actinic keratosis is the most prevalent premalignant skin disorder in the white population. Current guidelines provide no clear recommendations about preferred treatments. Methods The parameters;effectiveness, treatment duration, recurrence, side effects and cost of treatment were investigated for three frequently used topical therapies which were then compared with a most recent developed topical therapy. Published clinical data obtained from the literature was used to compare these parameters for 5-fluorouracil, imiquimod and diclofenac and relate them with the newly developed Curaderm. Results A wide variation in the concentrations of the active anti-keratotic ingredients, application frequency, duration of treatment, recurrence rates and cost of treatment exist between the different topical therapies. The efficacy rates and side effects were less variable. Overall, Curaderm is the most suitable treatment for actinic keratosis. Clinical evidence is presented illustrating the effects of Curaderm on field-directed treatments and solitary treatments of actinic keratoses. Conclusions Current medical guidelines do not provide clear recommendations on which treatment approach for actinic keratosis is preferred. Direct head-to-head comparison between treatments with emphasis on efficacy, safety, treatment duration, compliance, convenience, cosmetic outcome, patient acceptance and cost should be available to the patient, the practising physician, healthcare system and should assist in therapeutic treatment guidelines and policymaking. Given the very favourable profiles of these parameters with Curaderm when compared with other home-based treatments, it should be considered that Curaderm is first-in-line.

Solasodine Glycosides: A Topical Therapy for Actinic Keratosis. A Single-Blind, Randomized, Placebo-Controlled, Parallel Group Study with Curaderm^BEC5

Background: Untreated actinic keratosis can advance to squamous cell carcinoma, which in turn is associated with a risk of metastasis. Current treatments for actinic keratosis have many shortcomings. This communication describes the efficacy and safety of a topical cream therapy, CuradermBEC5, containing solasodine glycosides (0.005%) for actinic keratosis.Methods: Randomly assigned patients with actinic keratosis on the face, trunk or extremities received so-lasodine glycosides cream (CuradermBEC5) or placebo (vehicle) that was self-applied to the lesions and covered with an occlusive dressing (micropore) twice daily for 3 consecutive days. Complete clearance and local reactions were as-sessed at 56 days with follow-up periods of 6 months and 1 year. Results: The rate of complete clearance at day 56 was higher with solasodine glycosides than with placebo (92% vs. 38%, P 0.001). The absolute success rates after 1 year follow-up were 82% for solasodine glycosides and 18% for placebo. No differences in local reactions were obtained when solasodine glycosides and placebo were compared. Local reactions in both groups peaked at days 2 and 3 with local pain as the major event. The pain associated with treatments lasted approximately 10 minutes after application of solasodine glycosides and placebo. Complete reepithelialization occurred two weeks after treatment. Adverse events were generally mild to moderate in intensity and resolved without sequelae. Conclusions: Solasodine glycosides cream applied topically twice daily with a dressing for 3 days is effective for the treatment of actinic keratoses.

Factors influencing response to ingenol mebutate therapy for actinic keratosis of face and scalp

AIM To determine factors independently influencing response to ingenol mebutate therapy and assess efficacy on clinical setting of non-hypertrophic non-hyperkeratotic actinic keratosis (AK).METHODS Consecutive patients affected by non-hypertrophic non-hyperkeratotic AKs of the face or scalp were enrolled to receive ingenol mebutate 0.015% gel on a selected skin area of 25 cm^2 for 3 consecutive days.Local skin reactions were calculated at each follow up visit using a validated composite score.Efficacy was evaluated by the comparison of clinical and dermoscopic pictures before the treatment and at day 57,and classified as complete,partial and poor response.RESULTS A number of 130 patients were enrolled,of which 101(77.7%) were treated on the face,while 29 (22.3%) on the scalp.The great majority of our study population (n = 119,91.5%) reached at least a 75% clearance of AKs and,in particular,58 patients (44.6%) achieved a complete response while 61(46.9%) a partial one.Logistic backward multivariate analysis showed that facial localization,level of local skin reaction (LSR) at day 2,the highest LSR values and level of crusts at day 8 were factors independently associated with the achievement of a complete response.CONCLUSION Ingenol mebutate 0.015% gel,when properly applied,is more effective on the face than on the scalp and efficacy is directly associated to LSR score.

Effects of a New Human Recombinant MnSOD in the Treatment of Photoaging and Actinic Keratosis

Physiological processes, as aerobic metabolism and inflammatory response, generate reactive oxygen species (ROS) that may induce cellular injury when their amount is increased and antioxidant defense mechanisms are overwhelmed. Also, ROS are generated following UV skin irradiation able to deplete the natural antioxidant defenses in the skin. The increase in exposure to UV may lead to photoaging and precancerous skin lesions (actinic keratosis). New antioxidant strategies in the prevention and therapy of skin lesions are urgently needed. In this study, we evaluated the antioxidant efficacy of a recombinant form of human manganese superoxide dismutase able to inhibit reactive oxygen species production in some patients affected by severe photoaging and actinic keratosis.

Actinic keratosis and field cancerization

While actinic keratoses(AKs) have been considered precancerous until recently for being able to turn into squamous cell carcinomas(SCCs), it is now agreed that it would be more appropriate to call them cancerous. Although not all AKs turn into SCC and some of them may even have a spontaneous regression, there is an obvious association between SCC and AK. Approximately 90% of SCs have been reported to develop from AKs and AKs are the preinvasive form of SCCs. The presence of two or more AKs on a photodamaged skin is an indicator of field cancerization and represents an increased risk of invasive SCC. All lesions should be treated since it cannot be foreseen which of the lesions will regress and which will progress to SCC. AK can be a single lesion or it can involve multiple lesions in a field of cancerization; thus, AK treatment is grouped under two headings:(1) Lesion-specific treatment; and (2) Field-targeted treatment. Lesion-specific treatments are practicable in patients with a small number of clinically visible and isolated lesions. These treatments including cryotherapy, surgical excision, shave excision, curettage and laser are based on physical destruction of the visible lesions. Field-targeted treatments are effective in the treatment of visible lesions, subclinical lesions and keratinocyte changes in the areas surrounding the visible lesions. Field targeted treatment options are topical imiquimod cream, 5% 5-fluorouracil cream, ingenol mebutate, diclofenac gel, resimiquimod and photodynamic therapy.

Cryotherapy versus Hydrogen Peroxide in the Treatment of Seborrheic Keratosis

Seborrheic keratosis has a varying degree of pigmentation. In pigmented seborrheic keratosis, the proliferating keratinocytes trigger the activation of neighboring melanocytes by secreting melanocyte-stimulating cytokines. The etiology of seborrheic keratosis is not known. Epidermal growth factors or their receptors have been implicated in the development of seborrheic keratosis. Seborrheic keratoses can safely be left alone, but ugly or easily traumatized ones can be removed with cryotherapy, electrodesiccation, curettage, or shave excision. The present work aims to compare two modalities of treatment for seborrheic keratosis, namely cryotherapy and hydrogen peroxide (30%). Methods: 30 patients with seborrheic keratosis were included in this study. They were divided into two groups, each with 15 patients. The treatment modalities that have been used include cryotherapy and hydrogen peroxide in three different concentrations (30%, 35%, and 40%). Result: The cryotherapy group consisted of 15 patients, 7 males and 8 females. Their ages ranged from 38 to 80 years, with a mean of 56.1 ± 11.4. Clinical and photographic assessments showed complete removal in all 15 patients in this group (100%). As regards the hydrogen peroxide group, this group included 15 patients, distributed among 7 males and 8 females. Their ages ranged from 39 to 90 years, with a mean of 53.9 ± 14.4. Clinical and photographic assessments showed response in only one small superficial lesion in one patient (6.7%) and no response in 14 patients (93.3%). Conclusion: Cryotherapy is an effective, easy, and relatively cheap method for treating seborrheic keratosis.

Discussion on the Treatment of Palmoplantar Keratosis by TCM Soaking and Washing

By combing the mechanism and advantages of traditional Chinese medicine(TCM)soaking and washing and combining TCM syndrome differentiation with western medicine differentiation of diseases,guided by the view that"the principle of external treatment is that of internal treatment",this article discusses the differentiation and treatment ideas of palmoplantar keratosis by TCM soaking and washing,which will provide a reference for clinical treatment.

Mixed porokeratosis with a novel mevalonate kinase gene mutation:A case report

BACKGROUND Porokeratosis is a rare,acquired,or inherited disorder of keratinization.There are numerous clinical types of porokeratosis and they can coexist in one patient and multiple members of an affected family.However,coexistence of disseminated superficial actinic porokeratosis(DSAP)and porokeratosis ptychotropica(Ppt)is rare.CASE SUMMARY A 45-year-old man presented with long-standing skin lesions.Physical examination identified numerous small,brown 2-mm to 4-mm patches on his face and several hyperkeratotic,verrucous plaques on his trunk and extremities.His father and one of his brothers also had similar lesions for years.Skin biopsies indicated a cornoid lamella in the epidermis.We identified c.155G>A mutation in the mevalonate kinase(MVK)gene,which converted a serine residue to asparagine(p.Ser52Asn)and was causative for porokeratosis in this family.A clinicopathologic diagnosis of DSAP and Ppt with a novel MVK gene mutation was made.The hyperkeratotic plaques on the patient’s scrotum were completely removed more than 10 times using a microwave knife.CONCLUSION An unusual case of DSAP coexisting with Ppt harbored a novel MVK gene mutation also present in the patient’s family.

Clinical outcomes and 5-year follow-up results of keratosis pilaris treated by a high concentration of glycolic acid

BACKGROUND Keratosis pilaris is a hereditary abnormal keratosis of the hair follicle orifice.Gray-brown keratotic plugs in the pores and dark red keratotic papules at the openings of hair follicles can be seen,which contain coiled hair and are often accompanied by perifollicular erythema and pigmentation.Glycolic acid can correct the abnormalities of hair follicular duct keratosis and eliminate excessive accumulation of keratinocytes.It also promotes skin metabolism and accelerates the melanin metabolism.The therapeutic effect is related to the glycolic acid concentration.AIM To evaluate the efficacy and safety of a high concentration of glycolic acid in the treatment of keratosis pilaris,and to observe the outcomes at 5-year of follow-up.METHODS Twenty-five participants were recruited and areas with typical keratosis pilaris were selected as testing sites.High concentrations of glycolic acid(50%or 70%)were applied to a circular area(d=8 cm,S=50 cm2)and repeated four times,on days 0,20,40 and 60.Before each treatment and 20 d after the last treatment,on days 0,20,40,60,and 80 and at a 5-year follow-up,The number of follicular keratotic papules were counted and the extent of perifollicular erythema and pigmentation was determined.At the same time,the participants provided subjective evaluations of treatment efficacy and safety.RESULTS Treatment effectiveness was indicated by the percentage of keratotic papules in the test site,on days 20,40,60 and 80,which were 8%,12%,36%,and 60%,respectively.Compared with day 0,each difference was significant(P<0.05).Compared with day 0,differences in melanin content(M)in the skin and skin lightness(L)on days 40,60 and 80,the were statistically significant(P<0.05);skin hemoglobin content(E)on days 60 and 80 was statistically different as compared with before treatment(P<0.05).There were no significant differences in the number of keratotic papules,M,L,and E in 9 participants at the 5-year follow-up compared with before treatment(P>0.05%).CONCLUSION A high concentration of glycolic acid significantly improved skin roughness as well as follicular hyperpigmentation of patients with keratosis pilaris.The treatment was relatively safe,but there was no significant difference at the 5-year follow-up compared to before treatment.

Concurrence of Merkel Cell Carcinoma and Squamous Cell Carcinoma in A Patient with Generalized Actinic Keratosis: A Case Report

Introduction:Merkel cell carcinoma(MCC)is a rare,aggressive cutaneous malignancy,and its pathogenesis might relate to ultraviolet light and Merkel cell polyomavirus infection.MCC in the Chinese population is uncommon.Here,we present a case of MCC that occurred based on widespread actinic keratosis(AK)in a Chinese female.Case report:An 82-year-old woman presented with two rapidly enlarging and rupture lesions on the face for 1 year.Biopsy was suggestive of squamous cell carcinoma(SCC)on the forehead and MCC on the left cheek.The patient had a history of generalized AK for 3 years.The lesion on the left cheek was also revealed as an AK by histopathological examination 1 year ago.Complete surgical resection was performed to remove the two malignancies.Discussion:The co-occurrence of AK,SCC,and MCC in a Chinese woman is unusual.Immunohistopathological examination is vital for correct diagnosis.The three tumors,in this case,may originate from two different precursor cells and are affected by the same carcinogen.Alternatively,they may come from the same pluripotent epidermal stem cells,and chronic exposure to ultraviolet light and Merkel cell polyomavirus lead to the formation of different types of tumors.The coexist of MCC with other cutaneous tumors provided a train of thought for exploring the origin of MCC.Conclusion:We reported a rare co-existence phenomenon of MCC associated with AK and SCC.Hence,long-term follow-up and early treatment are imperative for patients with premalignant lesions,such as widespread AK.

Oculocutaneous Albinism with Squamous Cell Carcinoma, Bowen’s Disease and Actinic Keratosis: A Case Report

IntroductionOculocutaneous albinism (OCA) is an autosomal recessive disorder characterized by defects in melanin synthesis that affect the skin,eyes,ears,and hair to varying degrees.Because of the melanin deficiency,albino patients are at high risk for sun-induced skin cancers.Herein,we report a rare case of an OCA type 4 combined with a progressive carcinogenesis for precancerous (actinic keratosis,AK),in situ (Bowen's disease),and invasive status of squamous cell carcinoma (SCC).

A rare interesting case of seborrheic keratosis of pinna

Seborrheic keratosis is a benign tumour of external ear originating from proliferative epithelial cells. Its most common site ranges from the retroauricular region to the helical rim. Diagnosis is made on the basis of clinical & histopathological examination. Here, we discuss the clinical presentation, differential diagnosis, pathological diagnosis and management of such a case.

Expression of matrix metalloproteinases 9 and 12 in actinic cheilitis

AIM: To investigate the role of matrix-degrading metalloproteinases 9, 12(MMPs), as mediators of functional connective tissue damage in actinic cheilitis.METHODS: Thirty five formalin-fixed, paraffin embedded specimens of actinic cheilitis, and twelve specimens of normal lower lip vermillion, which were obtained by the archives of the Department of Oral Medicine and Maxillofacial Pathology, were examined. From each block, 5 μm thick sections were cut and routinely stained with Hematoxylin and Eosin. Immunohistochemical studies were performed on 4-μm thick sections of formalin-fixed paraffin embedded actinic cheilitis lesions and of normal lower lip vermillion, for MMP-9 and MMP-12 in serial sections of our specimens. Appropriate positive and negative controls were performed to confirm the specificity of the staining reaction. MMP immunohistochemistry was evaluated using a semiquantitative immunoreactive score.RESULTS: Haematoxylin and eosin staining revealedin actinic cheilitis lesions atrophic stratified squamous cell epithelium, or focally and irregularly hyperplastic of variable thickness, in some areas was observed marked keratin production. Varying degrees of epithelial dysplasia were noticed with a wide spectrum of change within the same specimen. Characteristic was the appearance of chronic inflammatory infiltration, and a band of amorphous acellular, basophilic change like solar elastosis(elastin replacement of collagen). In normal lower lip specimens weak and scanty positive expression of MMP-9 and MMP-12 was observed. Anti-MMP-9 antibody showed a weak reaction, in actinic cheilitis lesions, focal in the elastotic material, in chronic inflammatory cells and mostly in macrophages and neutrophils. Strong and in some cases diffused immunohistochemical expression of MMP-12 was detected in actinic cheilitis lesions in the areas of the fragmented, distorted and thickened elastic fibers. MMP-12 was also expressed in chronic inflammatory cells and mostly macrophages. MMP-12 was significantly higher in actinic cheilitis specimens compared with the normal lower lip specimens(P = 0.0029).CONCLUSION: Our results suggest that especially MMP-12 may play an important role in remodeling events occurring in the connective tissue during long-term exposure to sunlight in the actinic cheilitis lesions.

Basosquamous Cell Carcinoma of the Lower Lip Arising from Actinic Cheilitis: Case Report and up Date

Background: Basosquamous carcinoma (BSC) is a rare non-melanoma skin cancer, considered to be a subtype of basal cell carcinoma (BCC). BSC often produces distant metastases with a higher risk of recurrence than that of BCC which is not commonly found in the lip. Case Report: A 57-year-old white female patient presented an ulcer on her lower lip that had an ongoing development for over six months. Physical examination, photo documentation, videoroscopy, scraped cytology, toluidine blue test, and biopsy of the ulcer were carried out. Results: Upon physical examination we observed an actinic cheilitis associated with the ulcer. Videoroscopy revealed the presence of fissures and erosion that had not been seen by oroscopy. Toluidine blue test was only positive for the region of the ulcer. Cytological analysis revealed rare nests compatible with carcinoma. Histopathology of the biopsy revealed a carcinoma with nests lined by basal cells associated with areas of squamous differentiation. The patient was then referred to surgery for the removal of the BCC. Analysis of the specimen showed free surgical margins and the immunohistochemical panel did not confirm the initial diagnosis of BCC, indicating a subtype of BSC. After surgery, the patient has been followed by periodic consultations. She is well and without further complications. Coments: BSC is considered to be an aggressive and rare tumor affecting mainly upper face and primarily affects men over 60 years of age. Since our patient is a woman presenting the lesion in the lower lip, this highlights the unusual and interesting presentation of this case report.

Application of topical gentamicin ointment in the treatment of Nagashima-type palmoplantar keratosis in children with a nonsense mutation

Importance:Nagashima-type palmoplantar keratosis(NPPK)is a hereditary dermatosis mostly caused by a nonsense mutation in SERPINB7.Despite the increasing interest in readthrough gentamicin treatment of NPPK,clinical evidence for this treatment is limited.Objective:This study aimed to provide further evidence for the use of topical gentamicin in the treatment of NPPK in children with nonsense mutations.Methods:We designed a bilaterally controlled study of topical gentamicin ointment.Children diagnosed with NPPK carrying nonsense mutations were enrolled in this study.A 0.1%gentamicin ointment was applied to one hand and an emollient to the other for 3 months.A bilateral comparison of the visual analog scale scores for clinical manifestations and safety was performed.Results:Ten children with NPPK were included in this study.In comparison with the emollient side,the topical gentamicin side showed significant improvements in hyperkeratosis,erythema,maceration,and desquamation after 1 and 3 months of treatment(P<0.05).However,hyperhidrosis and odor did not improve significantly.No adverse events were observed during the systemic safety monitoring examinations.Interpretation:Topical gentamicin ointment showed good safety in the treatment of NPPK with nonsense mutations,indicating that it is a promising therapeutic choice in children with NPPK.

防风提取物对IgE致敏肥大细胞的改善作用及机制研究

[目的]探究防风(Saposhnikovia divaricata,SD)提取物对大鼠嗜碱性白血病细胞RBL-2H3脱颗粒的影响及作用机制。[方法]采用噻唑蓝(methylthialazole tetrazolium,MTT)比色法检测,根据5、25、50、100、200、400μg·mL^(-1)SD提取物对RBL-2H3细胞活性的影响,确定后续实验浓度。以免疫球蛋白E(immunoglobulinE,IgE)诱导建立RBL-2H3细胞脱颗粒模型。设立空白对照组、模型组、低剂量SD提取物组(5μg·mL^(-1))、中剂量SD提取物组(25μg·mL^(-1))、高剂量SD提取物组(50μg·mL^(-1))和地塞米松(dexamethasone,DXMS)组(100μg·mL^(-1)),干预30 min。MTT法检测低、中、高剂量SD提取物对RBL-2H3细胞脱颗粒模型活性的影响。甲苯胺蓝染色观察脱颗粒细胞形态,计算细胞脱颗粒率。免疫荧光染色测定细胞F-肌动蛋白(F-actin)表达。酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测细胞β-氨基己糖苷酶、组胺、白细胞介素-4(interleukin-4,IL-4)、白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、干扰素-γ(interferon-γ,IFN-γ)水平。免疫印迹法检测细胞磷脂酰肌醇-3-羟基激酶(phosphoinositide-3 kinase,PI3K)、磷酸化-PI3K(phosphorylation-PI3K,p-PI3K)、蛋白激酶B(protein kinase B,AKT)、磷酸化-AKT(phosphorylation-AKT,p-AKT)、p38丝裂原活化蛋白激酶(p38 mitogen activited protein kinaseelisa,p38MAPK)、磷酸化-p38MAPK(phosphorylation-p38MAPK,p-p38MAPK)、核因子-κB(nuclear factor-κB,NF-κB)、磷酸化-NF-κB(phosphorylation-NF-κB,p-NF-κB)、细胞外调节激酶(extracellular regulated kinases,ERK)、磷酸化-ERK(phosphorylation-ERK,p-ERK)蛋白表达。[结果]低、中、高剂量防风提取物(5、25、50μg·mL^(-1))对RBL-2H3细胞活性无显著影响(P>0.05)。与空白对照组比较,模型组甲苯胺蓝染色细胞数量减少、形态变圆,细胞脱颗粒率显著上升,F-actin表达下降,β-氨基己糖苷酶、组胺、IL-4、IL-6、TNF-α水平升高,IFN-γ水平降低,p-PI3K/PI3K、p-AKT/AKT、p-p38MAPK/p38MAPK、p-NF-κB/NF-κB、p-ERK/ERK表达升高(P<0.01)。与模型组比较,低、中、高剂量SD提取物组和DXMS组细胞F-actin表达增加,β-氨基己糖苷酶、组胺、IL-4、IL-6、TNF-α释放显著下降(P<0.05,P<0.01),IFN-γ释放显著增加(P<0.01),p-PI3K/PI3K、p-AKT/AKT、p-p38MAPK/p38MAPK、p-NF-κB/NF-κB、p-ERK/ERK表达降低(P<0.05,P<0.01);中、高剂量SD提取物组和DXMS组细胞数量增加,形态多呈梭形,细胞脱颗粒率显著下降(P<0.01)。与低剂量SD提取物组比较,高剂量SD提取物组和DXMS组细胞脱颗粒率下降(P<0.01)、F-actin表达增加(P<0.05)、p-p38MAPK/p38MAPK表达降低(P<0.01)。[结论]SD提取物可抑制IgE致敏的RBL-2H3细胞脱颗粒,降低炎性介质水平,其作用机制可能与抑制PI3K/AKT、p38MAPK/NF-κB、ERK蛋白磷酸化有关。

The Value of Excipients and the Required Understanding of the Biological System in Product Development: An Impactful Example of Curaderm, a Topical Skin Cancer Treatment

The incidences of nonmelanoma skin cancer are increasing worldwide, and the ongoing war on its treatment necessitates the development of effective and non-invasive methods. Through basic and clinical research, non-invasive treatments like Curaderm have been developed, leading to improved quality of life for patients. Excipients, previously considered inactive ingredients, play a crucial role in enhancing the performance of topical formulations. The development of Curaderm emphasizes the importance of understanding the interactions between active ingredients, excipients, and the biological system to create effective and affordable pharmaceutical formulations. The systematic approach taken in the development of Curaderm, starting from the observation of the anticancer activity of natural solasodine glycosides and progressing through toxicological and efficacy studies in cell culture, animals, and humans, has provided insights into the pharmacokinetics and pharmacodynamics of solasodine glycosides. It is crucial to determine these pharmacological parameters within the skin’s biological system for maximal effectiveness and cost-effectiveness of a skin cancer treatment. Curaderm, as a topical treatment for nonmelanoma skin cancer, offers benefits beyond those obtained from other topical treatments, providing hope for improved quality of life for patients.

皮肤镜及反射式共聚焦显微镜在日光性角化病辅助诊断、治疗中的应用

日光性角化病(actinic keratosis, AK)作为一种常见的皮肤癌前病变,早期准确诊断、个体化治疗尤为重要。皮肤组织病理学检查在皮损整体评估和重复取样方面有一定局限性,皮肤镜及反射式共聚焦显微镜(reflectance confocal microscopy, RCM)作为无创诊断工具具有实时、在体、动态观察等优势,在AK的辅助诊断、疗效评估和随访方面具有较大的潜力。本文主要介绍皮肤镜和反射式共聚焦显微镜在AK的辅助诊断、治疗和随访AK方面的应用。

铁死亡诱导剂RAS合成致死分子3抑制病理性瘢痕成纤维细胞的纤维化

背景:病理性瘢痕主要表现为异常的细胞外基质积累和过度的成纤维细胞增殖,成纤维细胞过度增殖就会产生大量以胶原纤维为主的细胞外基质。因此深入探讨成纤维细胞纤维化在病理性瘢痕形成中的作用,将为揭示病理性瘢痕的机制和生物学治疗提供新思路。目的:探讨铁死亡诱导剂RAS合成致死分子3(RAS-selective lethal small molecule 3,RSL3)对人病理性瘢痕成纤维细胞纤维化的影响。方法:收集10例宁夏医科大学总医院烧伤整形美容科提供的病理性瘢痕组织和同一个体正常皮肤组织,提取人病理性瘢痕成纤维细胞和人正常皮肤成纤维细胞用于后续实验;苏木精-伊红染色观察病理性瘢痕组织和正常皮肤组织的形态;倒置显微镜观察病理性瘢痕成纤维细胞和正常皮肤成纤维细胞的外观形态;免疫荧光实验验证所提取的细胞是否为成纤维细胞;用不同浓度的RSL3(1,3,5,7,9,11,13μmol/L)干预细胞,CCK-8法检测RSL3作用于成纤维细胞的半数抑制浓度(IC_(50));设置对照组(不做处理)和RSL3干预组(用7μmol/L的RSL3干预细胞24 h),qRT-PCR和Western blot检测谷胱甘肽过氧化物酶4、Ⅰ型胶原蛋白、Ⅲ型胶原蛋白和α-平滑肌肌动蛋白的mRNA和蛋白的表达;检测细胞丙二醛浓度;划痕试验检测细胞划痕后24 h剩余划痕面积,并计算剩余划痕面积百分比。结果与结论:①与正常皮肤组相比,病理性瘢痕组的谷胱甘肽过氧化物酶4高表达(mRNA:t=3.252,P<0.01;蛋白:t=5.075,P<0.01);②与正常皮肤成纤维细胞组相比,病理性瘢痕成纤维细胞组的谷胱甘肽过氧化物酶4高表达(mRNA:t=10.32,P<0.01;蛋白:t=26.22,P<0.01);③与对照组相比,RSL3干预组谷胱甘肽过氧化物酶4表达减少(mRNA:t=2.798,P<0.05;蛋白:t=4.643,P<0.01),丙二醛浓度上升(t=2.917,P<0.05),Ⅰ型胶原蛋白(mRNA:t=15.84,P<0.01;蛋白:t=4.610,P<0.01)、Ⅲ型胶原蛋白(mRNA:t=28.86,P<0.01;蛋白:t=7.713,P<0.01)和α-平滑肌肌动蛋白(mRNA:t=2.671,P<0.05;蛋白:t=7.417,P<0.01)的表达减少,迁移能力减弱(t=14.06,P<0.01);④提示RSL3通过抑制谷胱甘肽过氧化物酶4的表达,进而抑制病理性瘢痕成纤维细胞的纤维化和迁移能力。

Gold Standard for Skin Cancer Treatment: Surgery (Mohs) or Microscopic Molecular-Cellular Therapy (Curaderm)?

Non-melanoma skin cancers or keratinocyte cancers such as basal cell carcinoma and squamous cell carcinoma make up approximately 80% and 20% respectively, of skin cancers with the 6 million people that are treated annually in the United States. 1 in 5 Americans and 2 in 3 Australians develop skin cancer by the age of 70 years and in Australia it is the most expensive, amassing $1.5 billion, to treat cancers. Non-melanoma skin cancers are often self-detected and are usually removed by various means in doctors’ surgeries. Mohs micrographic surgery is acclaimed to be the gold standard for the treatment of skin cancer. However, a novel microscopic molecular-cellular non-invasive topical therapy described in this article, challenges the status of Mohs procedure for being the acclaimed gold standard.