肿瘤相关的皮肤血管损害

肿瘤相关的皮肤血管损害包含副肿瘤性血管损害及皮肤肿瘤直接导致的血管损伤.概述目前肿瘤相关的皮肤血管损害的发病情况、可能的发病机制、分类和临床特点,了解不同皮肤血管损害与肿瘤之间可能存在的关系.在诊治皮肤血管疾患的过程中,对于血管损害慢性持续存在,常规血管炎的治疗抵抗,伴有体重减轻、发热、贫血等全身体征,尤其是老年患者,应及时进行相关肿瘤的筛查.此类疾病的预后多与其对应的肿瘤种类相关,应早期针对病因进行治疗.     

Pigmented purpura and cutaneous vascular occlusion syndromes

Purpura is defined as a visible hemorrhage in the skin or mucosa, which is not evanescent upon pressure. Proper classification allows a better patient approach due to its multiple diagnoses. Purpuras can be categorized by size, morphology, and other characteristics. The course varies according to the etiology, as do the diagnostic approach and treatment. This review discusses pigmented purpuras and some cutaneous vascular occlusion syndromes.     

S-nitrosoglutathione-containing hydrogel accelerates rat cutaneous wound repair

BACKGROUND: Nitric oxide (NO) plays a key role in wound repair and S-nitrosothiols like S-nitrosoglutathione (GSNO) are well known NO donors. METHODS: Animals were separated in two groups and submitted to excisional wounds on the dorsal surface at the first day. GSNO (100 microm)-containing hydrogels were topically applied on the wound bed in the GSNO group, daily, during the first 4 days. Control group was topically treated with hydrogel without GSNO for the same period. Wound contraction and re-epithelialization were measured. Animals were sacrificed 21 days after wounding. Samples of lesion and normal tissue were formalin-fixed, paraffin embedded for histological analysis. RESULTS: Wound contraction, measured 14 and 21 days after wounding, was greater in the GSNO group than in the control group (P<0.05 for both). The re-epithelialized wound area, measured 14 days after wounding, was higher in the GSNO group than in the control group (P<0.05). A higher amount of inflammatory cells was observed in superficial and deep areas of the granulation tissue of the control group compared to the GSNO group. Twenty-one days after wounding, thin red-yellow collagen fibers arranged perpendicularly to the surface were found in the granulation tissue of the control group, whereas in the GSNO-treated group collagen fibers were thicker and arranged parallel to the surface. Increased number of mast cells was observed in the GSNO group compared with that in the control group. Vascularization and myofibroblast distribution were similar in both groups. CONCLUSION: Topical application of GSNO-containing hydrogel during the early phases of rat cutaneous wound repair accelerates wound closure and re-epithelialization and affects granulation tissue organization.     

The horizon for treating cutaneous vascular lesions

Dermatologists encounter a wide range of cutaneous vascular lesions, including infantile hemangiomas, port-wine stain birthmarks, arteriovenous malformations, venous malformations, Kaposi sarcomas, angiosarcomas, and angiofibromas. Current treatment modalities to reduce these lesions include topical and/or intralesional steroids, laser therapy, surgical resection, and endovascular therapy. However, each method has limitations owing to recurrence, comorbidities, toxicity, or lesion location. Photodynamic therapy, antiangiogenic therapy, and evolving methods of sclerotherapy are promising areas of development that may mitigate limitations of current treatments and offer exciting options for patients and their physicians.     

Potential roles of fibronectin in cutaneous wound repair

Fibronectin has many potential roles in wound repair, including chemotactic factor activity for monocytes, fibroblasts, and endothelial cells; opsonin activity and opsonin promoter activity for microorganism and tissue debris; substratum for cell migration and localization; and a scaffold for building extracellular matrix. Although fibronectin has been reported to have intrinsic growth-promoting ability, coisolation of authentic growth factors with fibronectin raises doubts about this observation. Whether the addition of exogenous fibronectin to wounds can augment healing is a question for future studies.     

Matrikines and matricryptins: Implications for cutaneous cancers and skin repair

Dermatologists are faced daily with the need to optimize skin repair and excise cutaneous cancers. The extracellular matrix plays a pivotal role in cellular migration, proliferation, and gene regulation during wound healing and progression of melanoma, basal cell carcinoma, and squamous cell carcinoma. Within the last few years, a new class of ligand, the matrikine or matricryptin, has been characterized as subdomains of various ECM proteins capable of signaling to the cell through receptors, such as growth factor receptors. Two classes exist: the "natural" matrikines, which signal directly from the extracellular milieu and "cryptic" matrikines (matricryptins) that require proteolytic processing to reveal the ligand or to release the ligand from its ECM protein. Unlike traditional soluble growth factors, most matrikines possess low binding affinity to their receptors and are often presented in multiple valency that likely increase avidity to receptors. The presentation of these ligands within the ECM can result in unique outcomes. The EGF-like repeats of tenascin-C and laminin-5 signal to EGFR preferentially to upregulate migration during skin repair and tumor progression. Other matrikines in collagen, elastin, decorin, and laminin-1 can promote chemotaxis, mitogenesis, and metastasis in cancers, such as melanoma. Finally, the unique properties of matrikines have been utilized in cancer therapeutics and tissue engineering. Within the next few years, the nature and function of this emerging class of matrikine ligands will have an impact on dermatology, as these proteins are altered in wound repair and skin diseases.     

The pharmacology of isolated cutaneous vascular smooth muscle

Human and dog and rabbit skin blood vessel strips give contractile responses to catecholamines, serotonin, and angiotensin II. Alpha receptors for catecholamine can be demonstrated. Species and organ variations occur in the small vessel tissue response to bradykinin (dog), histamine (rabbit) and acetylcholine (lung). A prostaglandin-contractile activity could be demonstrated on cutaneous vessels. This activity was most marked in dog paw vessels and rarely occurred in human skin. Potentiation of catecholamine by prostaglandin E-, A- and F- contractions could be demonstrated. The prostaglandin receptor was not blocked by alpha or beta blocking agents. The prostaglandin response was related to calcium concentration and was unrelated to exogenous or endogenous cyclic AMP.     

The cutaneous vascular system in chronic skin inflammation

The blood and lymphatic vasculature have an important role in skin homeostasis. Angiogenesis and lymphangiogenesis-the growth of new vessels from existing ones-have received tremendous interest because of their role in promoting cancer spread. However, there is increasing evidence that both vessel types also have a major role in acute and chronic inflammatory disorders. Vessels change their phenotype during inflammation (vascular remodeling). In inflamed skin, vascular remodeling consists of a hyperpermeable, enlarged network of vessels with increased blood flow, and influx of inflammatory cells. During chronic inflammation, the activated endothelium expresses adhesion molecules, cytokines, and other molecules that lead to leukocyte rolling, attachment, and migration into the skin. Recent studies reveal that inhibition of blood vessel activation exerts potent anti-inflammatory properties. Thus, anti-angiogenic drugs might be used to treat inflammatory conditions. In particular, topical application of anti-angiogenic drugs might be ideally suited to circumvent the adverse effects of systemic therapy with angiogenesis inhibitors. Our recent results indicate that stimulation of lymphatic vessel growth and function unexpectedly represents a new approach for treating chronic inflammatory disorders.     

The pulsed dye laser for cutaneous vascular and nonvascular lesions

The pulsed dye laser was originally developed for the treatment of vascular lesions, especially hemangiomas and port-wine stains. The central concept of pulsed-dye laser is to preserving the epidermis by allowing hemoglobin to be more precisely targeted within lesions. More recently, the pulsed dye laser has also been used in the treatment of a wide spectrum of nonvascular lesions. Because of its safety profile, and its selectivity in targeting lesions, therapists can comfortably treat a wide variety of lesions in all age groups and anatomic sites.     

Proteoglycans in So-Called Cellulite

Glycosaminoglycans are a group of polysaccharide chains covalently linked to proteins to form proteoglycan molecules with high water-attracting properties. The ultrastructural localization of glycosaminoglycans in the so-called cellulite skin and in normal subjects was studied. Data show that there is increasing concentration of glycosaminoglycans in the cellulite skin, presumably leading to a rise in the amount of water retained in the skin in this disease.     

The role of RNase 7 in innate cutaneous defense against Pseudomonas aeruginosa

The ribonuclease RNase 7 is a major skin‐derived human antimicrobial protein expressed in keratinocytes. Here we show that the gram‐negative pathogen Pseudomonas aeruginosa secretes factor(s) that induced RNase 7 gene and protein expression in human primary keratinocytes. The metalloprotease inhibitor marimastat, the epidermal growth factor receptor (EGFR) inhibitor AG1478 and the EGFR blocking antibody cetuximab significantly attenuated this induction, indicating an important role of the EGFR for the P. aeruginosa‐mediated RNase 7 induction. In line with this, siRNA‐mediated downregulation of ADAM17, a metalloprotease known to proteolytically mediate the release of soluble EGFR ligands, decreased the P. aeruginosa‐mediated RNase 7 induction in keratinocytes. The impact of the EGFR was also demonstrated in a human 3D skin equivalent where blockade of the EGFR diminished induction of RNase 7 by P. aeruginosa. Blockade of Toll‐like receptor 5 (TLR5), a pattern recognition receptor (PRR) known to be activated by P. aeruginosa, only moderately reduced the P. aeruginosa‐mediated RNase 7 induction in keratinocytes. The functional relevance of RNase 7 to participate in cutaneous defense against P. aeruginosa was demonstrated by antibodies that neutralized the antimicrobial activity of RNase 7. These antibodies significantly inhibited the capacity of human stratum corneum skin extracts to control growth of P. aeruginosa. Taken together, our results indicate that P. aeruginosa induces the expression of RNase 7 in keratinocytes in an EGFR‐dependent manner. Enhanced release of RNase 7 contributes to control cutaneous growth of P. aeruginosa.     

皮肤血管增生性疾病分类(上篇)

血管增生性疾病的分类非常复杂,根据其临床和组织病理学特点可将其分为以下主要的类别:血管错构瘤,血管畸形,血管扩张,血管增生,良性血管肿瘤,恶性血管肿瘤和血管周细胞瘤.该文分两部分介绍常见皮肤血管增生性疾病的临床及组织病理特点,上篇包括血管错构瘤,血管畸形,血管扩张.     

4-Methylpyrazole and the cutaneous vascular sensitivity to alcohol in Orientals

Twelve healthy subjects of Oriental ancestry were challenged with topical applications of lower aliphatic alcohols and aldehydes after topical pretreatment consisting of 4-methylpyrazole in hydrophilic ointment on the volar aspect of one forearm and hydrophilic ointment alone on the contralateral volar forearm. Cutaneous blood flow was monitored by laser Doppler velocimetry. Pretreatment with 4-methylpyrazole, a specific inhibitor of alcohol dehydrogenase, led to a significant decrease in the cutaneous vascular response to the alcohols as a group, but did not lead to changes in the cutaneous vascular response to the aldehydes as a group. Among the individual alcohols, pretreatment with 4-methylpyrazole reduced the response significantly to all concentrations of 1-propanol and 1-butanol. The means of the vascular response to the different concentrations of ethanol decreased, but not significantly. Additionally, 4-methylpyrazole did not have an independent effect on cutaneous blood flow. These results are consistent with the view that the cutaneous vascular reaction to primary alcohols applied topically to the skin of Orientals is provoked, in large part, by the corresponding aldehyde.     

Circulating vascular endothelial growth factor in cutaneous malignant melanoma

BACKGROUND: Angiogenesis has been reported as a parameter of potential prognostic value in solid tumours, as it may facilitate tumour growth and metastasis. One of the most important growth factors involved in angiogenesis is vascular endothelial growth factor (VEGF). OBJECTIVES: To determine the predictive value of circulating VEGF levels in a cohort of patients with melanoma. METHODS: In a prospective cohort study, 324 patients with cutaneous melanoma at different clinical stages were investigated over 2 years (2002-04). VEGF was measured in plasma using enzyme-linked immunosorbent assay. Two hundred and eight patients were able to be followed up for progression of their disease and for blood sample collection (mean +/- SD follow-up 13.4 +/- 0.8 months). Data were compared with the extent of the disease and the clinical course. RESULTS: A significant increase in plasma VEGF levels was found in patients with melanoma compared with healthy controls, with statistically significant differences between patients in stages I, II and III vs. those in stage IV, but not between patients in stages I, II and III. When considering the 237 patients in stages I and II, no statistical correlation was found between plasma VEGF levels and tumour thickness. Baseline plasma VEGF levels were not significantly higher in patients who relapsed compared with nonprogressing patients. Among the 35 patients (two stage I, eight stage II and 25 stage III) who experienced a progression during follow-up, an increase in plasma VEGF level to > 100 pg mL(-1) was found in 20 (sensitivity 57.1%), while 38 of the 173 remaining nonprogressing patients demonstrated an increase in VEGF level, indicating a specificity of 78%. In addition, an increase in plasma VEGF level was found in 58 patients during follow-up, of whom 20 showed evidence of progression, indicating a positive predictive value of 34.5%. However, among the 150 remaining patients who did not demonstrate any increase in plasma VEGF level during follow-up, only 15 experienced a progression, indicating a negative predictive value of 90%. CONCLUSIONS: Our data confirm that blood VEGF levels are significantly increased in patients with melanoma and, more interestingly, that the absence of plasma VEGF level increase during follow-up appears to be associated with remission.