elastin and Skin-Neoplasms

We researched articles that used photodynamic therapy (PDT) for skin wound healing in humans.. The systematic review was conducted through scientific articles that investigated the action of PDT on wound healing in humans, published from July 2005 to March 2017, in the data bases PubMed and LILACS.. The main types of wound described in selected articles in this review were chronic ulcer and non-melanoma skin cancer. For accomplishing the PDT, second generation of photosensitizing agents with laser or light emitting diode were used. The studies demonstrated that PDT contribute in several ways to the wound healing process: leading to cellular death; reducing or increasing inflammation; stimulating fibroblasts proliferation and, consequently, of collagen and elastin; raising transforming growth factor beta and metalloproteinases. Based on this, PDT provided good results in wound healing process, acting in several steps and accelerating tissue repair.. PDT improved healing in many wound models in humans, revealing itself as a promising therapeutic modality for stimulating wound healing and remodelling.

Topics: Cell Death; Collagen; Elastin; Fibroblasts; Humans; Metalloproteases; Photochemotherapy; Photosensitizing Agents; Skin Neoplasms; Skin Ulcer; Transforming Growth Factors; Wound Healing

Chemical peeling is a common treatment in cosmetic dermatology. A peel that has been used for many years is trichloroacetic acid. Its adverse effects have for a long time been a major limitation. We present a practical review of the characteristics, mechanisms of action, indications, and complications of superficial chemical peels and of peeling with trichloroacetic acid.

Topics: Acids; Animals; Chemexfoliation; Collagen Type I; Drug Combinations; Elastin; Epidermis; Ethanol; Facial Dermatoses; Humans; Hyperpigmentation; Keratolytic Agents; Lactic Acid; Mice; Pigmentation Disorders; Precancerous Conditions; Resorcinols; Salicylates; Skin Aging; Skin Neoplasms; Trichloroacetic Acid

A review of the medical literature concerning the effect of the menopause and its hormonal treatment on the skin.. An extensive Medline and Pubmed internet search utilizing the key words: collagen, elastin, estrogen, hormone replacement therapy, skin and aging.. The literature review demonstrated a wide array of research ranging from basic science work to clinical implications of the effects of the menopause and its treatment on the skin.. Estrogen loss at menopause has a profound influence on skin. Estrogen treatment in postmenopausal women has been repeatedly shown to increase collagen content, dermal thickness and elasticity, and data on the effect of estrogen on skin water content are also promising. Further, physiologic studies on estrogen and wound healing suggest that hormone replacement therapy (HRT) may play a beneficial role in cutaneous injury repair. Results on the effect of HRT on other physiologic characteristics of skin, such as elastin content, sebaceous secretions, wrinkling and blood flow, are discordant. Given the responsiveness of skin to estrogen, the effects of HRT on aging skin require further examination, and careful molecular studies will likely clarify estrogen's effects at the cellular level.

Topics: Acne Vulgaris; Collagen; Elasticity; Elastin; Estrogen Replacement Therapy; Estrogens; Female; Humans; Menopause; Receptors, Estrogen; Skin; Skin Aging; Skin Neoplasms; Skin Physiological Phenomena; Treatment Outcome; Wound Healing

The recent progress made in understanding the normal biology and biochemistry of the extracellular matrix of human skin has allowed us to identify several different levels at which errors could be introduced into the structure and metabolism of collagen or elastin, the two major fibrillar components of the dermis. Currently, several heritable cutaneous diseases are known to display distinct collagen or elastin abnormalities. This article reviews some of the heritable cutaneous diseases and highlights those entities in which definite information on molecular alterations in collagen or elastin is available.

Topics: Adult; Collagen; Collagen Diseases; Cutis Laxa; Ehlers-Danlos Syndrome; Elastin; Fibroma; Humans; Male; Osteopoikilosis; Osteosclerosis; Pedigree; Skin Diseases; Skin Neoplasms

Topics: Animals; Arteriosclerosis; Chemical Phenomena; Chemistry; Chick Embryo; Copper; Deficiency Diseases; Elastic Tissue; Elastin; Fibroma; Guinea Pigs; Haplorhini; Histocytochemistry; Microscopy; Microscopy, Electron; Pseudoxanthoma Elasticum; Rats; Skin Neoplasms; Staining and Labeling; Swine

The first-ever application of high-frequency ultrasound combined with multiphoton tomography (MPT) and dermoscopy in a clinical trial is reported. 47 patients with different dermatoses such as benign and malign skin cancers, connective tissue diseases, inflammatory skin diseases, and autoimmune bullous skin diseases have been investigated with (i) state-of-the-art and highly sophisticated ultrasound systems for dermatology, (ii) the femtosecond laser multiphoton tomograph and (iii) dermoscopes. Dermoscopy provides two-dimensional color images of the skin surface with a magnification up to 70 x. Depending on the ultrasonic frequencies from 7.5 MHz to 100 MHz, the signal depth varies from about 1 mm to 80 mm. Vertical ultrasound wide-field images provide fast information on depth and volume of the lesion. The 100 MHz ultrasound allows imaging with resolutions down to 16 μm (axial) and 32 μm (lateral). Multiphoton tomography provides 0.36 x 0.36 x 0.001 mm³ horizontal optical sections of a particular region of interest with submicron resolution down to 200 μm tissue depth. The autofluorescence of mitochondrial coenzymes, keratin, melanin, and elastin as well as the network of collagen structures can be imaged. The combination of ultrasound and MPT opens novel synergistic possibilities in diagnostics of skin diseases with a special focus on the early detection of skin cancer as well as the evaluation of treatments.

Topics: Adult; Aged; Aged, 80 and over; Coenzymes; Collagen; Elastin; Female; Fluorescence; Humans; Keratins; Lasers; Male; Melanins; Microscopy, Fluorescence, Multiphoton; Middle Aged; Skin; Skin Diseases; Skin Neoplasms; Tomography, Optical; Ultrasonics

Healing wounds and cancers present remarkable cellular and molecular parallels, but the specific roles of the healing phases are largely unknown. We developed a bioinformatics pipeline to identify genes and pathways that define distinct phases across the time-course of healing. Their comparison to cancer transcriptomes revealed that a resolution phase wound signature is associated with increased severity in skin cancer and enriches for extracellular matrix-related pathways. Comparisons of transcriptomes of early- and late-phase wound fibroblasts vs skin cancer-associated fibroblasts (CAFs) identified an "early wound" CAF subtype, which localizes to the inner tumor stroma and expresses collagen-related genes that are controlled by the RUNX2 transcription factor. A "late wound" CAF subtype localizes to the outer tumor stroma and expresses elastin-related genes. Matrix imaging of primary melanoma tissue microarrays validated these matrix signatures and identified collagen- vs elastin-rich niches within the tumor microenvironment, whose spatial organization predicts survival and recurrence. These results identify wound-regulated genes and matrix patterns with prognostic potential in skin cancer.

Topics: Cancer-Associated Fibroblasts; Collagen; Elastin; Fibroblasts; Humans; Skin; Skin Neoplasms; Tumor Microenvironment

Mast cell tumours (MCTs) constitute almost 25% of cutaneous neoplasms in dogs. Their biological behaviour is predicted using histopathological grading which is based on several subjective criteria that are vulnerable to intra- and interobserver variability. To improve the prediction of the biological behaviour, several complementary markers have been studied. The integrity of the extracellular matrix (ECM) may play a protective role against tumoral progression, and favour cellular proliferation, angiogenesis, invasion and metastases when altered.. To evaluate the quantification of collagen and elastic fibres as prognostic markers for MCTs.. Thirty-eight random cases of canine cutaneous MCT surgically treated with wide margins were included.. Intratumoral collagen and elastic fibres were identified and quantified on histological sections stained with Masson's trichrome, Picrosirius red and Verhoeff; the results were compared with histopathological grades, mortality due to the disease and postsurgical survival.. Morphometric analysis revealed a significant relationship between histopathological grade and intratumoral collagen index (CoI). In addition, the CoI was considered an independent indicator for mortality and postsurgical survival.. These results support the importance of the CoI in the grading and prognosis of MCTs, suggesting that preservation and/or synthesis of collagen have the potential to become targets for MCT therapeutics.. Les mastocytomes (MCTs) représentent presque 25% des tumeurs cutanées du chien. Leur évolution biologique est prédictible par gévaluation histopathologique basée sur plusieurs critères subjectifs qui sont vulnérables d'un point de vue variabilité intra et inter-observateur. Pour améliorer la prédiction de l’évolution biologique, plusieurs marqueurs complémentaires ont été étudiés. L'intégrité de la matrice extracellulaire (ECM) pourrait jouer un rôle protecteur contre la progression tumorale et son altération pourrait favoriser la prolifération cellulaire, l'angiogenèse, l'invasion et les métastases. HYPOTHÈSES/OBJECTIFS: Evaluer la quantification des fibres de collagène et des fibres élastiques comme facteurs pronostics des MCTs.. Trente huit cas de MCT canins traités par chirurgie avec de larges marges ont été inclus. MATÉRIEL ET MÉTHODE: Le fibres élastiques et de collagène intra-tumorales ont été identifiées et quantifiées sur des sections histopathologiques colorées au trichome de Masson, au rouge Picrosirius et Verhoeff; les résultats étaient comparés avec les grades histopathologiques, la mortalité due à la maladie et au temps de survie post-chirurgical. RÉSULTATS: Une analyse morphométrique a révélé un lien significatif entre le grade histopathologique et l'index de collagène inntratumoral (CoI). En outre, le CoI a été considéré comme un indicateur indépendant pour la mortalité et la survie post-chirurgicale.. Ces résultats soutiennent l'importance du CoI dans le grading et le pronostic des MCTs suggérant que la préservation et/ou la synthèse du collagène a le potentiel de devenir une cible pour le traitement des MCTs.. INTRODUCCIÓN: los mastocitomas (MCTs) constituyen casi el 25% de las neoplasias cutáneas en perros. Su comportamiento biológico se predice utilizando una clasificación histopatológica que se basa en varios criterios subjetivos que son susceptibles de variabilidad intra e interobservador. Para mejorar la predicción del comportamiento biológico, se han estudiado varios marcadores complementarios. La integridad de la matriz extracelular (ECM) puede jugar un papel protector contra la progresión tumoral y favorecer la proliferación celular, la angiogénesis, la invasión y las metástasis cuando se alteran. HIPÓTESIS/OBJETIVOS: Evaluar la cuantificación del colágeno y las fibras elásticas como marcadores de pronóstico para los MCTs. ANIMALES: se incluyeron 38 casos al azar de MCT cutáneo canino tratados quirúrgicamente con amplios márgenes. MÉTODOS Y MATERIALES: el colágeno intratumoral y las fibras elásticas se identificaron y cuantificaron en secciones histológicas teñidas con tricrómico de Masson, rojo de Picrosirius y Verhoeff; Los resultados se compararon con los grados histopatológicos, la mortalidad debida a la enfermedad y la supervivencia postquirúrgica. RESULTADOS: el análisis morfométrico reveló una relación significativa entre el grado histopatológico y el índice de colágeno intratumoral (CoI). Además, el CoI se consideró un indicador independiente de mortalidad y supervivencia postquirúrgica. CONCLUSIONES E IMPORTANCIA CLÍNICA: estos resultados apoyan la importancia del CoI en la clasificación y el pronóstico de los MCTs, lo que sugiere que la preservación y/o la síntesis de colágeno tienen el potencial de convertirse en objetivos para el tratamiento de MCTs.. Mastzelltumore (MCTs) stellen fast 25% der Hautneoplasien bei Hunden dar. Ihr biologisches Verhalten wird mittels histopathologischem „Grading“ vorhergesagt, welches auf verschiedenen subjektiven Kriterien beruht, die empfindlich sind in Bezug auf Intra- und Interobserver Variabilität. Um die Vorhersage des biologischen Verhaltens zu verbessern wurden mehrere komplementäre Marker untersucht. Die Integrität der extrazellulären Matrix (ECM) könnte eine schützende Rolle bei der Tumorprogression spielen und die zelluläre Proliferation, die Angiogenese, Invasion und Metastasen favorisieren, wenn sie geändert wird.. Eine Evaluierung der Quantifizierung von Kollagen und elastischen Fasern als prognostische Marker für MCTs.. Achtunddreißig zufällige Fälle von kutanem MCT bei Hunden, die chirurgisch mit großen Rändern behandelt worden waren, wurden in die Studie aufgenommen.. Es wurden intratumorales Kollagen und elastische Fasern identifiziert und auf histologischen Schnitten, die mit Masson´s Trichrom, Picrosirius und Verhoeff gefärbt worden waren, quantifiziert; die Ergebnisse wurden mit den histopathologischen Graden, der Sterberate aufgrund der Erkrankung und die Überlebensdauer nach der Operation verglichen.. Die morphometrische Analyse zeigte eine signifikante Beziehung zwischen den histopathologischen Graden und dem intratumoralen Kollagenindex (CoI). Zusätzlich wurde der CoI als unabhängiger Indikator für die Sterblichkeit und die Überlebensdauer nach der Operation betrachtet.. Diese Ergebnisse unterstützen die Wichtigkeit von CoI beim „Grading“ und bei der Prognose von MCTs, was darauf hinweist, dass die Erhaltung und/oder die Synthese von Kollagen ein Potential darstellen, Ziele für MCT Therapeutika zu werden.. 背景: 肥満細胞腫(MCT)は、犬における皮膚腫瘍の約25%を占める。MCTの生物学的挙動は、観察者内および観察者間に対するいくつかの不安定な主観的基準に基づく病理組織学的グレーディングによって予測される。生物学的挙動の予測を改善するため、いくつかの相補的マーカーが研究されてきた。細胞外マトリックス(ECM)の健常性は、腫瘍の進行に対して保護的な役割を果たし、そして改変した場合、細胞増殖、血管形成、浸潤および転移に有利に働き得る。 仮説/目的: 本研究の目的は、MCTの予後マーカーとしてコラーゲンおよび弾性繊維の定量化を評価することである。 被験動物: 広範なマージンで外科的に治療された犬の皮膚MCTの無作為症例38例を供した。 材料と方法: 腫瘍内コラーゲンと弾性繊維を、マッソントリクローム染色、ピクロシリウスレッド染色、ヴァーホフ染色で染色した組織切片上で同定し、定量した。そして、その結果を病理組織学的グレード、疾患による死亡率および術後生存率と比較した。 結果: 形態計測解析は、病理組織学的グレードと腫瘍内コラーゲン指数(CoI)との間の有意な関係を明らかにした。さらに、CoIは死亡率および術後生存率に対し独立した指標であると考えられた。 結論および臨床的重要性: 本研究結果は、MCTグレーディングおよび予後におけるCoIの重要性を支持しており、コラーゲンの保持および/または合成がMCT治療の標的になる可能性を示唆している。.. 背景: 肥大细胞瘤(MCTs)占犬皮肤肿瘤的近25%。通过组织病理学分级预测它们的生物学行为,该分类基于几个主观标准,这些标准易受观察者自身和观察者间变化影响。为了提高对生物学行为的预测,研究了几种互补标记。细胞外基质(ECM)的完整性可以起到对肿瘤发展的保护作用,并在改变时有利于细胞增殖、血管生成、侵袭和转移。 假设/目标: 评估胶原和弹性纤维作为MCT预后标志物的量。 动物: 包括38例随机手术治疗的多处犬皮肤MCT的随机病例。 方法和材料: 将组织切片进行Masson三色、Picrosirius红和Verhoeff染色,随后鉴定和定量肿瘤内胶原和弹性纤维; 将结果与组织病理学分级、疾病引起的死亡率和术后生存率进行比较。 结果: 形态学分析显示组织病理学分级与肿瘤内胶原指数(CoI)之间有显著关系。此外,CoI被认为是死亡率和术后生存的独立指标。 结论和临床价值: 这些结果支持CoI在MCT分级和预后中的重要性,提示胶原蛋白的保存和/或合成有可能成为MCT治疗的靶点。.. Os mastocitomas (MCTs) constituem quase 25% das neoplasias cutâneas em cães. O seu comportamento biológico pode ser predito utilizando uma graduação histopatológica baseada em diversos critérios subjetivos que são vulneráveis a variação intra e interobservador. Para melhorar a previsão do comportamento biológico, diversos marcadores complementares têm sido estudados. É possível que a integridade da matriz extracelular (ECM) possua uma função protetora contra a progressão tumoral, e favoreça a proliferação celular, angiogênese, invasão e metástase quando alterada. HIPÓTESE/OBJETIVOS: Avaliar a quantificação de colágeno e fibras elásticas como marcadores de prognóstico para MCTs.. Trinta e oito casos aleatórios de MCTs cutâneos em cães tratados cirurgicamente com margens amplas inclusas. MÉTODOS E MATERIAIS: Colágeno intratumoral e fibras elásticas foram identificadas e quantificadas nos cortes histopatológicos corados com corante tricromo de Masson, Picrosirius vermelho e Verhoeff; os resultados foram comparados com as graduações histopatológicas, mortalidade devido à doença e sobrevida pós-cirúrgica.. A análise morfométrica revelou uma relação significativa entre a graduação histopatológica e o índice de colágeno tumoral (CoI). Além disso, o CoI foi considerado um indicador independente de mortalidade e sobrevida pós-cirúrgica. CONCLUSÕES E IMPORTÂNCIA CLÍNICA: Estes resultados corroboram com a importância do CoI na classificação e no prognóstico de MCTs, sugerindo que a preservação e a síntese de colágeno têm o potencial de se transformarem em alvos para o tratamento de MCTs.

Topics: Animals; Biomarkers, Tumor; Collagen; Dogs; Elastic Tissue; Elastin; Female; Histological Techniques; Male; Mast Cells; Prognosis; Skin Neoplasms

Lysyl oxidase-like 2 (LOXL2) is a copper-dependent monoamine oxidase that contributes to the remodelling of the extracellular matrix (ECM) by cross linkage of collagen and elastin fibres and has emerged as a potential therapeutic target in cancer and fibrosis. In the skin, LOXL2 is essential for epidermal cell polarity and differentiation. However, its role in the dermis has not been evaluated. We found that Loxl2 is dispensable for mouse dermal development, maturation and homeostasis, yet affects dermal stiffness. Neither loss of Loxl2 nor increased Loxl2 expression affected dermal architecture following treatment with the phorbol ester TPA. Furthermore, Loxl2 expression did not alter the stroma of DMBA-TPA-induced tumours. We conclude that, although Loxl2 is expressed in both dermis and epidermis, its function appears largely confined to the epidermis.

Topics: Amino Acid Oxidoreductases; Animals; Collagen; Dermis; Elastin; Extracellular Matrix; Humans; Mice; Mice, Knockout; Neoplasm Proteins; Skin Neoplasms; Tetradecanoylphorbol Acetate

Dermatofibrosarcoma protuberans (DFSP) is a locally invasive neoplasia with a pattern of infiltrative growth that leads to extended resections. To avoid unnecessary resections and spare tissues, its treatment requires an adequate assessment of the margins. We present a case where artificial dermis (Matriderm®) was used followed by skin graft for reconstruction. We present a 50-year-old woman with a DFSP in the occipital region. She was referred to us after a first surgery with positive margins. A wide local excision with a 2-cm margin was performed and periosteal tissue was also removed, which led to exposure of the skull. Matriderm was placed on the bone surface and dressings were changed every other day. Meanwhile, margins were evaluated by the complete circumferential and peripheral deep margin assessment (CCPDMA) and were positive for DFSP in the superior margin. After 4 weeks the area was completely covered by granulation tissue and a new resection followed by reconstruction with a skin graft was performed. With regard to the difficulties in the margin assessment in DFSP, we present artificial dermis (Matriderm) as an option for reconstructive surgery in these patients, especially when a skin graft cannot be performed as a first option.

Topics: Collagen; Dermatofibrosarcoma; Elastin; Female; Head and Neck Neoplasms; Humans; Middle Aged; Scalp; Skin Neoplasms; Skin Transplantation; Skin, Artificial

In oncology, dermal equivalent may be indicated to cover losses of substance related to skin tumors or after the removal of skin flaps.. To report our experience of two dermal equivalents, Matriderm 1 mm with a one-stage graft (DE1) and Integra DL with a two-stage graft (DE2) in oncology.. Retrospective, single-center study involving 16 patients.. Sixteen patients received dermal equivalents as an alternative to flaps (7 cases), over tendinous areas (7 cases), and for cosmetic purposes (2 cases). Twelve patients received DE1 and four DE2. Wound healing times with DE1 were 4 weeks less than those with DE2. Three cases of infection were noted with DE2. The use of dermal equivalents as an alternative to skin flaps was effective, and no adhesions were found over the tendinous areas.. The learning curve, the two-stage graft required with DE2, and not using a vacuum-assisted closure system can explain the high infection rate. The use of dermal equivalents is particularly indicated in the treatment of skin defect in oncology. The possibility of a one-stage graft with DE1 and combination with negative pressure therapy is beneficial.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Chondroitin Sulfates; Collagen; Elastin; Head and Neck Neoplasms; Humans; Middle Aged; Otorhinolaryngologic Neoplasms; Plastic Surgery Procedures; Retrospective Studies; Skin Neoplasms; Skin Transplantation; Skin, Artificial; Surgical Flaps; Surgical Wound Infection; Time Factors; Wound Healing; Young Adult

Adnexal skin tumors are rare and mostly not common. Their appearance are atypical and only histologically to save. 2 cases were demonstrated with impressing extension demanding a complex surgical approach.

Topics: Abdominal Wall; Adenocarcinoma, Sebaceous; Aged, 80 and over; Collagen; Elastin; Esthetics; Female; Follow-Up Studies; Humans; Male; Microsurgery; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Pilomatrixoma; Plastic Surgery Procedures; Sebaceous Gland Neoplasms; Skin Neoplasms; Skin Transplantation; Surgical Flaps; Tomography, X-Ray Computed

Topics: Elastin; Humans; Immunohistochemistry; Melanoma; Nevus; Skin Neoplasms

As deep soft tissue defects with exposed bone, cartilage or tendons are not suitable for wound closure with skin mesh grafts, other techniques are needed. We report on six patients, one female and five males, aged between 32 and 89 years, and deep soft tissue defects with exposed tendons, cartilage or bone. The aetiology of these defects was vascular (n = 3), tumour surgery (2), and post-traumatic (1). Wounds were treated with a collagen-elastin matrix applied above the exposed structures. In five patients, the procedure was combined with mesh graft transplantation in the same setting. Follow-up varied between 12 and 40 weeks. Wound healing was uncomplicated in all transplanted patients until first dressing change after 7 days. All but one transplant showed a 100% take rate and the transplant was stable within 10-14 days. A complete wound closure was also achieved without transplantation, but this took 8 weeks. No adverse effects were noted. There was no skin contracture of the skin grafts. Collagen-elastin matrix with split-thickness skin grafts is a useful tool in deep soft tissue. The time to heal can be reduced.

Topics: Adult; Aged; Aged, 80 and over; Biocompatible Materials; Elastin; Extracellular Matrix; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Leg Ulcer; Male; Severity of Illness Index; Skin Neoplasms; Skin Transplantation; Skin, Artificial; Soft Tissue Injuries; Wound Healing

Twenty to 30% of malignant melanomas are associated with melanocytic nevi; however, sometimes it is difficult to distinguish the melanoma from the nevus by routine histology. We have previously described distinctive patterns of elastic fibers in nevi and in melanomas.. We analyzed elastic fiber patterns using elastin immunostain and elastic van Gieson (EVG) stain in 30 cases of invasive melanomas associated with nevi, 12 control melanocytic nevi and 14 control invasive melanomas.. Elastin immunostain was superior to EVG in showing the elastic fiber patterns. In nevi, the elastic fibers were preserved between nests and often around individual melanocytes. In contrast, melanomas had markedly decreased elastic fibers in the stroma and within the nests of melanocytes. The melanoma pushed down the pre-existing thin elastic fibers of the papillary dermis, forming a compressed layer at its base, which separated the melanoma from the nevus. On sun-damaged skin, the solar elastosis had similar elastin and EVG patterns. In three cases with dense inflammation, the layer of elastic fibers between melanoma and nevus was still present but less evident.. The distinctive patterns of elastic fibers, best shown by the elastin immunostain, were helpful in evaluating melanomas associated with melanocytic nevi.

Topics: Elastin; Humans; Immunohistochemistry; Male; Melanoma; Neoplasm Invasiveness; Nevus; Skin Neoplasms; Sunlight

The heterotrimeric G protein alpha-subunit G(s)alpha links receptors to stimulation of cAMP/protein kinase A signaling, which inhibits skin fibroblast proliferation and collagen synthesis. We now describe the development of fibrous tumors in mice with heterozygous disruption of the Gnas gene, which encodes G(s)alpha and other gene products.. Disruption of Gnas exon 2 on either the maternal or paternal allele (Gnas(E2-/+)) results in fibromas or angiofibromas on the ears, paws and tail beginning at 4 months of age. The tumors were composed of fibroblastic cell proliferation with collagen and elastin deposition and calcification, and seemed to be associated with mechanical skin damage. The presence of calcification was associated with greater amounts of matrix metalloproteinase-2, suggesting an association between calcium deposition and extracellular matrix degradation. Osteoblast-specific markers were absent, consistent with the calcification not being secondary to ossification. Molecular studies showed that the tumors were not associated with deletion of the wild-type allele, making it unlikely that these tumors resulted from homozygous loss of G(s)alpha.. These findings provide in vivo evidence that G(s)alpha pathways inhibit fibroblast and endothelial proliferation and matrix deposition.

Topics: Angiofibroma; Animals; Calcinosis; Chromogranins; Collagen; Elastin; Fibroma; GTP-Binding Protein alpha Subunits, Gs; Mice; Skin Neoplasms

Melanomas containing more elastin are associated with higher stages of the disease. The interaction between elastin-derived peptides and melanoma cells appears to play an important role in the progression of melanomas. The effects of the elastin-derived peptides VGVAPG and VAPG have been investigated on the migration, invasion, adhesion and angiogenesis of human melanoma cells of different invasive potential. Elastin, tropoelastin and VGVAPG peptide were demonstrated at the invasion site of melanoma using histochemistry and immunohistochemistry. Not only the VGVAPG elastin-derived peptide, which exhibits the XGXXPG consensus sequence in its primary structure, but also the shorter VAPG bind directly to 3 cell surface receptors: galectin-3, integrin alpha v beta 3 and elastin-binding protein. Our results suggest that the increased levels of elastin-derived peptides facilitate the invasion of melanoma cells: (i) VGVAPG and VAPG elastin-derived peptides are chemotactic for melanoma cells; (ii) they can increase the migration of melanoma cells and the expression of CXCR-4 and CXCL-12 chemokines; (iii) they enhance the expression of the elastin-degrading MMP-2 and MMP-3; (iv) they increase the attachment of melanoma cells and the expression of different adhesion molecules; (v) they increase the expression of the lymphangiogenic VEGF-C and (vi) the galectin-3 receptor can mediate all these effects. Clinical and therapeutic aspects are also discussed.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carrier Proteins; Cell Adhesion; Cell Adhesion Molecules; Cell Movement; Chemokine CXCL12; Chemotaxis; Disease Progression; Elastin; Flow Cytometry; Galectin 3; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Glycoproteins; Humans; Immunohistochemistry; Matrix Metalloproteinase 2; Matrix Metalloproteinase 3; Melanoma; Neoplasm Invasiveness; Neovascularization, Pathologic; Oligopeptides; Polymerase Chain Reaction; Receptors, CXCR4; Skin Neoplasms; Tropoelastin; Vascular Endothelial Growth Factor C

By studying more than 1,200 patients with cutaneous melanoma and long-term follow-up, I examined the relationship between solar elastosis and age at diagnosis of melanoma, key features of melanoma, and the outcome of overall survival in melanoma. I found that melanomas with elastosis were diagnosed significantly later than those without elastosis (P approximately 0; log-rank test). This result may be because elastosis is positively related to age. However, I also found that melanomas of head and neck areas, which tend to have more elastosis, were diagnosed at later ages than melanomas of other body sites (P = 1.2 x 10-5; log-rank test). Thus, a second explanation for the results favors a protective effect of elastosis on the development of cutaneous melanoma, possibly related to increased levels of vitamin D. I also found that once melanoma develops, cases with elastosis demonstrated no differences in thickness, mitotic rate, ulceration, or overall survival time from cases without elastosis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Elastic Tissue; Elastin; Female; Humans; Male; Melanoma; Middle Aged; Neoplasms, Radiation-Induced; Skin Neoplasms; Sunlight

With aging and cancer there is increased expression or activity of matrix metalloproteinases (MMPs) that degrade and remodel the structural extracellular matrix (ECM). In addition, exposure of skin to ultraviolet (UV) radiation (photoaging) leads to loss of cell viability, membrane damage, and deposition of excessive elastotic material. Lutein has antioxidant, anti-inflammatory, photoprotective, and anti-carcinogenic properties. The goal of this research was to investigate lutein's anti-aging and anti-carcinogenic effects via the regulation of the extracellular matrix remodeling. To this purpose, the effects of lutein on the expression of MMPs and their inhibitors (TIMPs, tissue inhibitors of metalloproteinases) in dermal fibroblasts (intrinsic aging) and melanoma cells were examined. Further, for lutein's photoprotective effects, the regulation of cell viability, membrane integrity, and elastin expression in the non-irradiated, and UVA or UVB radiation exposed fibroblasts were analyzed. Lutein significantly inhibited MMP-1 expression, transcriptionally, and MMP-2 protein levels in dermal fibroblasts, without altering TIMPs expression. It significantly inhibited MMP-1 expression in melanoma cells while stimulating TIMP-2. Lutein did not alter fibroblast or melanoma cell viability or membrane integrity. In ultraviolet radiation exposed fibroblasts, lutein improved cell viability, membrane integrity and inhibited elastin expression, though more significantly in the UVB exposed fibroblasts. In summary, the mechanism to lutein's anti-aging and anti-carcinogenic effects include the inhibition of MMP to TIMP ratio in dermal fibroblasts and melanoma cells, and the inhibition of cell loss, membrane damage and elastin expression in ultraviolet radiation exposed fibroblasts.

Topics: Cell Membrane; Cell Survival; Dermis; Elastin; Extracellular Matrix; Fibroblasts; Humans; In Vitro Techniques; Lutein; Matrix Metalloproteinase 1; Matrix Metalloproteinase 2; Melanoma; Promoter Regions, Genetic; Skin Aging; Skin Neoplasms; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Tumor Cells, Cultured; Ultraviolet Rays

In a previous work, we reported the influence of elastin fragments (EFs) on matrix metalloproteinases-2 and -14 expression and activation in melanoma cells in vitro. We hypothesized that EFs might also modulate expression of other mediators involved during melanoma progression. Therefore we investigated the contribution of EFs on IL-1beta expression, a cytokine playing a key role in melanoma cells activation. Our results evidenced that high tumorigenic melanoma cells (M3Da cells) treated with EFs led to IL-1beta mRNA and protein upregulation. The effects of EFs on M3Da cells were found to be mediated by receptor (spliced galactosidase) occupancy, as being suppressed by lactose and reproduced by cell stimulation with the VGVAPG peptide. Binding of EFs to their receptor induced a rapid activation of extracellular signal-regulated kinase 1/2; and p38 mitogen-activated protein kinase pathways. However, these pathways were not associated with IL-1beta mRNA upregulation by EFs. Concomitantly, we demonstrated that EFs stimulation induced NF-kappaB nuclear translocation and DNA binding on IL-1beta promoter region whereas inhibition of NF-kappaB with the specific chemical inhibitor SN-50 or by overexpression of IkappaB, the endogenous inhibitor of NF-kappaB pathway, totally abolished EFs-mediated IL-1beta mRNA overexpression. These results demonstrate that EFs induce NF-kappaB activation, leading to IL-1beta upregulation in invasive melanoma cells.

Topics: Base Sequence; Elastin; Gene Expression Regulation, Neoplastic; Humans; Interleukin-1; MAP Kinase Signaling System; Melanoma; NF-kappa B p50 Subunit; Peptide Fragments; Promoter Regions, Genetic; Receptors, Interleukin-1; Skin Neoplasms; Transcription Factor RelA; Tumor Cells, Cultured; Up-Regulation

Annular elastolytic giant cell granuloma (AEGCG) is characterized by non-palisading granuloma and elastophagocytic giant cells. Granulomas consist of structured masses of macrophages, dendritic cells, and T lymphocytes which play an essential role in granuloma formation. Two lineage systems of dendritic cells and macrophages originated from peripheral blood monocytes have been established in vitro. To know how elastin fragments are involved in the granuloma formation in AEGCG, we tested in vitro whether elastin fragments potentially induce monocyte-derived macrophages or dendritic cells to form granuloma and multinucleated giant cells. Immunohistochemical studies of the lesional skins of AEGCG (n = 5) revealed that the 67-kDa elastin receptor was specifically expressed in the epithelioid or multinucleated giant cells. Proliferation of factor XIIIa(+) cells and CD68(+) cells was also seen in the lesional skins of AEGCG. Factor XIIIa(+) dendritic cells or CD68(+) macrophages were established by the treatment of granulocyte/macrophage-colony stimulating factor (GM-CSF)/interleukin-4 or M-CSF, respectively. Further treatments of these dendritic cells or macrophages with elastin peptide resulted in the formation of granuloma or multinucleated giant cells which were immunoreactive with anti-67-kDa elastin receptor antibody. These findings suggest that elastic tissue induces factor XIIIa(+) cells and CD68(+) macrophages to form granuloma or multinucleated giant cells and plays an essential role in the formation of granuloma in AEGCG.

Topics: Aged; Aged, 80 and over; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biopsy; Cells, Cultured; Dendritic Cells; Elastin; Factor XIIIa; Female; Granuloma, Giant Cell; HLA-DR Antigens; Humans; In Vitro Techniques; Macrophages; Male; Middle Aged; Monocytes; Receptors, Cell Surface; Skin Neoplasms

Type I collagen mediates melanoma cells invasion through upregulation of matrix metalloproteinases-1 and -2 (MMP-1 and -2) expression and activation. We investigated here the contribution of elastin-derived peptides (ED), degradation products of elastin, the main component of elastic fibers in melanoma cells invasion and MMP-1 and -2 expression. Our results evidenced fragmentation of elastin at the invasive front of melanoma, particularly in the most invasive tumors where those fibers nearly totally vanished. By electron microscopy, elastolysis was found to occur mainly at the periphery of melanoma cells, where close contact between elastic fibers and cells could be noticed. Therefore, we showed in vitro that plating melanoma cells high tumorigenic potential on ED-coated dishes, selectively enhanced MMP-2, as membrane-type MMP-1 (MT1-MMP) production and activation. Nevertheless, pro-MMP-2 activation was not observed owing to the parallel increase in tissue inhibitor of metalloproteinase (TIMP)-2 expression. The effects of ED on melanoma cells were found to be mediated by splicing form of beta-galactosidase (S-Gal) occupancy, as being suppressed by lactose. Supplementing collagen lattices with ED led to consistent activation of MMP-2 that can be attributed to TIMP-2 downregulation. Upregulation of MMP-2 activation by ED led to enhanced melanoma cells invasion through S-Gal occupancy. Immunohistochemistry studies, confirmed that S-Gal expression was more prominent at the melanoma invasion site associated with a strong expression of MMP-2 and MT1-MMP. We hypothesize that ED following interactions with S-Gal elastin receptor can favor melanoma cells invasion through a three-dimensional type I collagen matrix by upregulating MMP-2 activation.

Topics: Cell Division; Collagen Type I; Elastic Tissue; Elastin; Galactosides; Humans; Immunohistochemistry; Matrix Metalloproteinase 2; Matrix Metalloproteinases, Membrane-Associated; Melanoma; Metalloendopeptidases; Microscopy, Electron; Peptide Fragments; Retrospective Studies; Skin Neoplasms; Tissue Inhibitor of Metalloproteinase-2; Umbelliferones; Up-Regulation

Malignant melanomas, which produce a large number of substances active in connective tissue modulation, must contend with the dermis to grow and propagate. We studied the morphologic interactions between tumorigenic malignant melanomas and dermal elastin. Formalin-fixed and paraffin-embedded tissues of 108 tumorigenic malignant melanomas were stained for elastic tissue with the Verhoeff-van Gieson method. Various aspects of the relationship between malignant melanoma and dermal elastin were analyzed in relation to the histologic and clinical data using univariate and multivariate analyses. Tumor thickness, mitotic rate, and the presence of elastin remnants within the tumors were found to be independent negative prognostic factors, the latter with borderline significance. Tumors with more remnants of elastin were associated with higher stage of disease and lymph node and distant metastases. Tumor infiltration between the elastic fibers in the tumor depth was associated with high Clark level, greater tumor thickness, high stage of disease, and lymph node metastases. At least partial preservation of elastic fibers in the tumor depth was a relatively good prognostic factor whereas complete absence of elastin was an adverse factor. Focal or multifocal absence of elastin in the midst of the tumors or in their depth was usually associated with lymphocytic infiltrates. We suggest that tumors with remnants of elastic fibers and/or invasion between elastic fibers in their depth may be fast growing and highly invasive. The absence of elastin within tumors and at their advancing edge may be related to the elaboration of elastin-degrading substances by melanoma cells or various inflammatory cells. Our findings indicate that the relationship between malignant melanomas and dermal connective tissue components, specifically elastin, may have prognostic significance.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Dermis; Elastin; Female; Follow-Up Studies; Humans; Male; Melanoma; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; Skin Neoplasms; Stromal Cells

Fibroepithelial polyps are common cutaneous lesions with an unknown etiology. We attempted to demonstrate that fibroepithelial polyps develop secondary to a focal loss of elastic tissue. Forty-five fibroepithelial polyps were examined. All were stained with Verhoeff-van Gieson stain for elastic tissue and examined. All but one specimen had a normal amount of elastin and none revealed abnormally shaped elastic fibers. Abnormal or decreased elastic tissue is not the cause of fibroepithelial polyps.

Topics: Elastic Tissue; Elastin; Humans; Polyps; Skin Neoplasms; Staining and Labeling

Buschke-Ollendorff syndrome (BOS; McKusick 16670) is an autosomal dominant connective-tissue disorder characterized by uneven osseous formation in bone (osteopoikilosis) and fibrous skin papules (dermatofibrosis lenticularis disseminata). We describe two patients in whom BOS occurred in an autosomal dominant inheritance pattern. The connective tissue of the skin lesions showed both collagen and elastin abnormalities by electron microscopy. Cultured fibroblasts from both patients produced 2-8 times more tropoelastin than normal skin fibroblasts in the presence of 10% calf serum. Involved skin fibroblasts of one patient produced up to eight times normal levels, whereas apparently uninvolved skin was also elevated more than threefold. In a second patient, whose involvement was nearly complete, elastin production was high in involved areas and less so in completely involved skin. Transforming growth factor-beta 1 (TGF beta 1), a powerful stimulus for elastin production, brought about similar relative increases in normal and BOS strains. Basic fibroblast growth factor, an antagonist of TGF beta 1-stimulated elastin production, was able to reduce elastin production in basal and TGF beta 1 stimulated BOS strains. Elastin mRNA levels were elevated in all patient strains, suggesting that Buschke-Ollendorff syndrome may result, at least in part, from abnormal regulation of extracellular matrix metabolism that leads to increased steady-state levels of elastin mRNA and elastin accumulation in the dermis.

Topics: Blotting, Southern; Cells, Cultured; Connective Tissue Diseases; Elastin; Female; Fibroblast Growth Factor 2; Fibroblasts; Humans; Male; Microscopy, Electron; Middle Aged; Nevus; Osteopoikilosis; Pedigree; Phenotype; RNA, Messenger; Skin; Skin Neoplasms; Syndrome; Transforming Growth Factor beta

An unusual case of isolated exophytic elastic tissue nevi in the scrotal region of a 64-year-old man is described. The histological and ultrastructural findings were those of abundant abnormal elastic fibers and increased reticulin in the dermis. This hamartomatous lesion possesses clinical and histological features previously undescribed in connective tissue nevi.

Topics: Elastic Tissue; Elastin; Hamartoma; Histocytochemistry; Humans; Male; Microscopy, Electron; Middle Aged; Neoplasms, Connective Tissue; Nevus; Reticulin; Scrotum; Skin; Skin Neoplasms

On the occasion of a case report on histiocytoma associated with elastofibroma-like parts on the shoulder, the extreme rarity of elastofibroma was doubted. This thesis was confirmed by post-mortem reports from Turku and Prague as well as by clinical experiences from Japan. Its possible relationship to other subcutaneous tumors rich in collagen and elastin was mentioned, and the abundant production of elastin was discussed as a variation of a one-sided metabolic mistake of the cells producing parenchyma. The symmetric or multiple, but principally the extracutaneous localization of elastofibromas may also direct our attention to developing factors other than traumatic ones, especially those being hereditary or ethnical.

Topics: Collagen; Diagnosis, Differential; Elastin; Female; Fibroma; Histiocytoma, Benign Fibrous; Humans; Middle Aged; Shoulder; Skin; Skin Neoplasms

Topics: Collagen; Connective Tissue; Elastin; Extracellular Matrix; Gene Expression Regulation; Humans; Microscopy, Electron; Nervous System Neoplasms; Neurofibromatosis 1; Procollagen; Proteoglycans; Schwann Cells; Skin; Skin Neoplasms

Elastin from both elastofibroma and control skin samples was analyzed by means of pancreatic elastase digestion and subsequent biochemical studies, such as for elastin content and amino acid composition. Elastin of elastofibroma was more resistant to elastase digestion than that of controls. Elastin content was increased almost twice (wet weight) or three times (dry weight) in elastofibroma. The amino acid composition had the characteristics of elastin; however, the cross-linking amino acids such as desmosine, isodesmosine, and lysinonorleucine were increased in elastofibroma when compared with controls. An electron microscopic study showed that the interspersed cells had prominent intermediate filaments without any periodicity, pinocytotic vesicles, rough endoplasmic reticulum, and other organelles. These cells were considered to be fibroblasts not myofibroblasts. Therefore, it could be supposed that fibroblasts newly form an elastin that has a slightly different amino acid composition from that of controls.

Topics: Aged; Amino Acids; Desmosine; Dipeptides; Elastin; Female; Fibroma; Humans; Isodesmosine; Microscopy, Electron; Pancreas; Pancreatic Elastase; Shoulder; Skin Neoplasms

A patient with dermatofibrosis lenticularis disseminata (Buschke-Ollendorff syndrome) was found to have a distinctive abnormality of the cutaneous elastic tissue. This abnormality, studied by histochemical and ultrastructural techniques, was characterized by the presence of hyalinized, thick fibers that entrapped normal bundles of collagen. Histochemically, these fibers stained like elastin but showed certain tinctorial characteristics of pre-elastin. Ultrastructurally, this elastin-like substance was composed of large clumps of electron-dense material with a fine fibrillar coating. The changes were sufficiently distinctive to be diagnosed by light microscopy.

Topics: Collagen; Elastic Tissue; Elastin; Female; Fibroma; Humans; Microscopy, Electron; Middle Aged; Osteopoikilosis; Skin; Skin Neoplasms; Syndrome

The Buschke-Ollendorff syndrome is an association of cutaneous lesions, dermatofibrosis lenticularis disseminata, with osteopoikilosis. This condition is inherited in an autosomal dominant pattern. In order to clarify the biochemical nature of the skin lesions, we have examined 12 patients with the Buschke-Ollendorf syndrome, representing 2 unrelated kindreds. Histologically, the lesions were characterized by excessive amounts of unusually broad, interlacing elastic fibers in the dermis. Digestion of skin secretions with pancreatic elastase completely removed these fibers. Electron microscopy of the dermis further revealed markedly branched elastic fibers without fragmentation. The accumulation of elastin in the skin was also demonstrated by measurements of desmosine employing a radioimmunoassay. The desmosine content of the skin lesions increased 3- to 7-fold when compared to the skin either from healthy controls or from uninvolved skin adjacent to a lesion. The results indicate that the skin lesions of the Buschke-Ollendorff syndrome are connective tissue nevi of the elastin type. Cell cultures from these patients may provide a convenient model to study the control mechanisms involved in elastin metabolism.

Topics: Desmosine; Elastic Tissue; Elastin; Fibroma; Humans; Osteopoikilosis; Osteosclerosis; Skin; Skin Neoplasms; Syndrome

Connective tissue nevi of the skin are hamartomatous lesions consisting predominantly of one of the components of the extracellular matrix, namely, collagen, elastin, or glycosaminoglycans. On the basis of clinical, histopathologic, and genetic considerations, the connective tissue nevi can be classified into defined categories. Association with extracutaneous features allows further delineation of these disease entities and aids in establishing an accurate diagnosis.

Topics: Adolescent; Adult; Collagen; Connective Tissue; Elastin; Female; Glycosaminoglycans; Hamartoma; Humans; Male; Nevus, Pigmented; Skin Neoplasms

After a short compilation of the descriptions of the elastic globes offered in the literature, the results of 446 tissue specimens of five different dermatoses (lichen planus, erythematodes chronicus discoides, tuberculosis cutis luposa, basal cell carcinoma, and nervus cell nevi). An increased appearance of elastic globes was found in erythematodes chronicus discoides and tuberculosis cutis luposa, compared with the other dermatoses. Elastic globes were not limited to special areas of the body, but there were topographical preferences. Elastic globes are common in the aged. The histopathology is descripted.

Topics: Adult; Age Factors; Aged; Carcinoma, Basal Cell; Child, Preschool; Elastic Tissue; Elastin; Extremities; Face; Female; Hair; Head; Humans; Lichen Planus; Lupus Erythematosus, Discoid; Lupus Vulgaris; Male; Middle Aged; Nevus; Skin; Skin Neoplasms

Topics: Carcinoma, Basal Cell; Connective Tissue; Elastic Tissue; Elastin; Glycosaminoglycans; Humans; Microscopy, Electron; Skin; Skin Diseases; Skin Neoplasms; Tuberculosis, Cutaneous

Topics: Aged; Cell Transformation, Neoplastic; Connective Tissue; Elastic Tissue; Elastin; Fibroblasts; Humans; Microscopy, Electron; Middle Aged; Photosensitivity Disorders; Protein Biosynthesis; Proteins; Radiation Effects; Skin Diseases; Skin Neoplasms; Ultraviolet Rays

Topics: Aging; Amino Acids; Carcinoma, Squamous Cell; Collagen; Elastin; Geriatrics; Histology; Humans; Keratosis; Keratosis, Actinic; Radiation Effects; Skin; Skin Aging; Skin Diseases; Skin Neoplasms; Sunlight; Ultraviolet Rays