Cellular and extracellular markers of hemangioma

Several cellular and extracellular markers that distinguish the phases of the hemangioma life cycle have been described previously. However, details of the phenotypic changes of; the various cellular elements during hemangioma development have not been fully reported, and the extracellular matrix composition, especially in the vicinity of the proliferating endothelial cells, is poorly described. This study examined the expression of cellular and extracellular molecules and cytokines in the proliferative, involuting, and involuted phases of hemangioma. Paraffin-embedded hemangioma specimens, four from each phase, were examined histochemically and immunohistochemically. Throughout the three phases, vascular endothelial cells stained positive for CD31 and von Willebrand factor, although in the involuted phase, not all vessels in the tissue expressed these endothelial markers. Proliferating cell nuclear antigen was expressed by the majority of endothelial cells and pericytes in the proliferative and early involuting phases, but its expression was negligible in the involuted phase. In addition to finding that the total number of mast cells was highest in the involuting phase, the authors observed that the proportion of chymase-positive mast cells decreased with the progression of hemangioma and that virtually all mast cells expressed the biogenic amine phenotype throughout the hemangioma life cycle. The localization of vascular endothelial growth factor predominantly to the pericytes and endothelial cells during the proliferative phase and of basic fibroblast growth factor to the endothelial cells in both the proliferative and early involuting phases is consistent with previous reports, although the latter growth factorwas also observed in mast cells. Type IV collagen and the beta chain of laminin and perlecan were detected in the basement membranes in all phases. Interestingly, collagen types I, III, and V were present in basal membranes throughout the phases and with increasing density in the stromal areas with involution, although type I collagen was less prominent during the proliferative phase. Short-chain collagen type VIII was localized extracellularly throughout the development of hemangioma but, during the early proliferative phase, it was also detected within mast cells. The expression of specific cytokines and cellular and extracellular markers may help distinguish the different clinical phases of the hemangioima life cycle. These results provide further insight into the biology of hemangioma.     

Mast cells and hemangioma

Hemangioma is a primary tumor of the microvasculature in which angiogenesis is initially excessive, followed by spontaneous regression of the newly formed vessels, with the cellular parenchyma gradually being replaced with fibrofatty tissue. Mast cells, which are highly heterogenous in terms of their morphology, function, and metabolic products, have been implicated in the pathophysiology of hemangioma. Csaba stain shows that mast cells are predominantly of the biogenic amine phenotype throughout the development of hemangioma. The predominance of this phenotype remains unaltered following successful steroid therapy, although their number increases fourfold. Mast cells, all of which stain positive for tryptase, and those that stain positive for chymase as well, have been identified in hemangioma biopsy specimens throughout the three developmental phases. The total number of mast cells is highest during the involuting phase, less in the involuted phase, and least in the proliferative phase. The proportion of mast cells that contain both tryptase and chymase decreases from the proliferative through involuting to the involuted phase. This decreasing proportion of mast cells that contain both tryptase and chymase with ongoing involution parallels that of progressive deposition of the extracellular matrix as indicated by increasing fibrosis and fatty deposition. The short-chain type VIII collagen, thought to play a key role in angiogenesis, has been detected throughout the developmental phases of hemangioma. It has been postulated that this collagen, which is produced early in new vessel development, provides a substratum to facilitate the migration of endothelial cells. It may also facilitate the deposition of other extracellular constituents and influence cell movement and the maintenance of cell phenotypes. The intracellular localization of type VIII collagen in mast cells only in the early proliferative phase suggests that there is an active synthesis by mast cells during this phase. The increasing extracellular localization during hemangioma development may be caused by an increased secretion of protein from intracellular stores. The increased number of mast cells during the involuting phase indicates that these cells may play a role in the regression of hemangioma. This is in contrast to the large body of evidence showing the proangiogenic role of mast cells. The proportion of proliferating mast cells decreases, whereas the proportion of mast cells positive for clusterin/apolipoprotein J increases with ongoing involution of hemangioma. Clusterin/apolipoprotein J expression has been considered as a prominent marker of apoptotic cell loss. The presence of clusterin/apolipoprotein J granules both in the adjacent endothelial cells and in capillary lumens suggests that mast cells may be secreting this apoptotic modulator to promote the regression of hemangioma. Certain effectors produced by mast cells may participate in the development of hemangioma. It has been proposed that one of the functions of mast cells is to release factors leading to the regression of hemangioma. The evidence suggests that although mast cells may have a function in the endothelial proliferation in hemangioma, they also play a crucial role in the regression of this tumor. However, the roles of mast cells in the life cycle of hemangioma are likely to be complex and may involve stimulators of angiogenesis in the proliferative phase but inhibitors in later phases.     

Role of pigment epithelium-derived factor in the involution of hemangioma: Autocrine growth inhibition of hemangioma-derived endothelial cells

Hemangioma is a benign tumor derived from abnormal blood vessel growth. Unlike other vascular tumor counterparts, a hemangioma is known to proliferate during its early stage but it is followed by a stage of involution where regression of the tumor occurs. The critical onset leading to the involution of hemangioma is currently not well understood. This study focused on the molecular identities of the involution of hemangioma. We demonstrated that a soluble factor released from the involuting phase of hemangioma-derived endothelial cells (HemECs) and identified pigment epithelium-derived factor (PEDF) as an anti-angiogenic factor that was associated with the growth inhibition of the involuting HemECs. The growth inhibition of the involuting HemECs was reversed by suppression of PEDF in the involuting HemECs. Furthermore, we found that PEDF was more up-regulated in the involuting phase of hemangioma tissues than in the proliferating or the involuted. Taken together, we propose that PEDF accelerates the involution of hemangioma by growth inhibition of HemECs in an autocrine manner. The regulatory mechanism of PEDF expression could be a potential therapeutic target to treat hemangiomas.     

Management of parotid hemangioma in 100 children

Most problematic infantile hemangiomas are successfully treated with pharmacological therapy. However, there are reports that hemangioma of the parotid gland responds poorly to corticosteroid and interferon. To better clarify the management of parotid hemangioma, the authors retrospectively studied the records of 100 consecutive patients, seen between 1975 and 2002. The characteristics of the tumor, including sex ratio, presence at birth, size, side, complications, and involvement of adjacent structures, were recorded. The indications for and response to treatment and the need for surgical procedures were documented and statistically analyzed. The female-to-male ratio was 4.5:1. Forty percent of parotid hemangiomas were on the right side, 36 percent were on the left, and 24 percent were bilateral. Forty-five percent of patients had a premonitory cutaneous lesion at birth. Fifty-nine percent of parotid hemangiomas ulcerated during the early proliferative phase. Eighty-eight percent involved nearby structures (ear, 70 percent; lip, 34 percent; subglottic region, 21 percent; eye, 18 percent; and nose, 3 percent). Seven percent of patients required tracheostomy, and 3 percent had signs of congestive heart failure. Seventy infants received pharmacological treatment. Sixty-seven patients were initially managed with corticosteroids; regression or stabilization was noted in 83 percent of tumors (56 of 67 tumors). Twenty-one patients received interferon: 11 in whom corticosteroid therapy had failed, seven in whom the tumor stabilized with corticosteroid therapy but further regression was needed, and three who had interferon as primary therapy. Ninety-five percent of the lesions that were resistant to corticosteroid subsequently responded to interferon alfa-2a or -2b. The overall response rate to pharmacological therapy was 98 percent. A reconstructive procedure was necessary during the involuting or involuted phase in 66 percent of patients: 92 percent had preauricular excision of redundant skin and/or fibrofatty tissue and 37 percent of patients had auricular revision. In summary, drug therapy was effective in the majority of infants with parotid hemangioma, whether given because the tumor was large, deforming, ulcerated, or involved nearby structures with functional consequences. Infantile hemangioma in the parotid gland responded to pharmacological treatment in a similar manner as hemangioma in other locations.     

Ezrin和Fascin蛋白在血管瘤中异常表达的研究

目的应用免疫组织化学方法检测不同时期血管瘤组织中膜细胞骨架链接蛋白Ezrin和Fascin蛋白的表达,以探讨其在血管瘤发生、发展过程中的作用机制。方法收集武汉大学人民医院病理科2005年9月-2009年12月皮肤毛细血管瘤存档蜡块50例,其中男性25例,女性25例。采用免疫组织化学S-P法检测50例皮肤血管瘤增生期、退化期及正常皮肤组织中Ezrin和Fascin的表达水平,采用HPIAS-1000图文报告管理系统对Ezrin和Fascin的表达进行定量分析,并用SPSS11.5软件对各组免疫组织化学反应阳性颗粒的平均光密度、阳性面积率做单因素方差分析和SNK(q)检验。结果 (1)Ezrin的表达增生期血管瘤血管内皮细胞中可见密集分布的棕黄色颗粒,Ezrin呈高表达,正常皮肤组及退化组血管内皮细胞中可见少量的棕黄色颗粒,Ezrin表达弱。增生期组Ezrin的表达明显高于退化期组和正常皮肤组(P0.05),而后两组比较差异无统计学意义(P0.05)。(2)Fascin的表达增生期血管瘤血管内皮细胞中可见密集分布的棕黄色颗粒,Fascin呈高表达,正常皮肤组及退化组血管内皮细胞细胞中可见少量的棕黄色颗粒,Fascin表达弱。增生期组Fascin的表达明显高于退化期组和正常皮肤组(P0.05),而后两组比较差异无统计学意义(P0.05)。结论Ezrin和Fascin在血管瘤增生期均上调表达,表明Ezrin和Fascin均与血管瘤的发生、发展有密切关系。     

EZH2和CBX7在皮肤血管瘤中的异常表达及意义

目的探讨EZH2和CBX7在血管瘤中的的异常表达及临床意义。方法收集武汉大学人民医院病理科2005年9月一2009年12月皮肤毛细血管瘤存档蜡块50例,其中男性25例,女性25例。采用免疫组织化学S-P法检测50例皮肤血管瘤增生期、退化期及正常皮肤组织中EZH2和CBX7的表达水平,采用图像分析系统对EZH2和CBX7的表达进行定量分析,并用SPSS13．0软件对各组免疫组织化学反应阳性颗粒的平均光密度、阳性面积率做单因素方差分析和SNK（q）检验。结果增生期血管瘤血管内皮细胞中可见密集分布的棕黄色颗粒,EZH2和CBX7呈高表达,退化组及正常皮肤组血管内皮细胞中可见少量的棕黄色颗粒,EZH2和CBX7表达弱。增生期组EZH2和CBX7的表达明显高于退化期组和正常皮肤组（P〈0．05）,而后两组比较差异无统计学意义（P〉0．05）。结论EZH2和CBX7在血管瘤增生期均上调表达,表明EZH2和CBX7均与血管瘤内皮细胞的增殖密切相关。     

Local serum levels of vascular endothelial growth factor in infantile hemangioma: Intriguing mechanism of endothelial growth

The pathogenesis of hemangiomas still remains poorly understood. Dysregulation of angiogenesis has been proposed to play a central role in hemangioma pathogenesis. The aim of our study was to determine the peripheral and local serum levels of VEGF in patients with hemangiomas and vascular malformations. Material and methods: The study group consisted of 52 children with infantile hemangioma (33 with proliferative lesions, 19 with involuting lesions), 14 children with vascular malformations and 36 healthy children. VEGF serum levels were analyzed by an ELISA assay and the values between the groups were compared. Results: The serum peripheral VEGF concentrations in children with proliferative hemangiomas were significantly higher than in patients with involuting hemangiomas, vascular malformations and controls. There was no correlation between the measured cytokine level, hemangioma size, and the age of the patients. The local serum VEGF levels in 29 children with hemangiomas were distinctly lower than in the peripheral blood, both in 20 proliferating hemangiomas (p < 0.0001) and 9 involuting ones (p = 0.007); and the difference between females and males was non-significant (NS p = 0.06). Conclusions: (1) VEGF serum levels vary in the different phases of hemangioma growth and may help to distinguish hemangiomas from vascular malformations; (2) obtained local results may support the intrinsic theory of endothelial cell proliferation in hemangiomas.     

Tiaml和Rac1在皮肤血管瘤组织中的表达及意义

目的 探讨Tiaml和Rac1在人皮肤血管瘤组织中的表达及其临床意义.方法 收集武汉大学人民医院病理科2008年-2011年皮肤毛细血管瘤存档蜡块40例,其中男性15例,女性25例.采用免疫组织化学S-P法检测40例皮肤血管瘤增生期、退化期及正常皮肤组织Tiaml和Rac1表达水平,采用HPIAS-1000图文报告管理系统对Tiaml和Rac1的表达进行定量分析,并用SPSS11.5软件对各组免疫组织化学反应阳性颗粒的平均光密度、阳性面积率做单因素方差分析和SNK（q）检验.结果 （1）增生期血管瘤血管内皮细胞中可见密集分布的棕黄色颗粒,Tiaml呈高表达,正常皮肤组及退化组血管内皮细胞中可见少量的棕黄色颗粒,Tiaml呈低表达.增生期组Tiaml的表达明显高于退化期组和正常皮肤组（P〈0.05）,而后两组比较差异无统计学意义（P〉0.05）.（2）增生期血管瘤血管内皮细胞中可见密集分布的棕黄色颗粒,Rac1呈高表达,正常皮肤组及退化组血管内皮细胞中可见少量的棕黄色颗粒,Rac1呈低表达.增生期组Rac1的表达明显高于退化期组和正常皮肤组（P〈0.05）,而后两组比较差异无统计学意义（P〉0.05）.结论 Tiaml和Rac1在血管瘤增生期均呈高表达,表明Tiaml和Rac1在血管瘤的发生和发展中起了重要作用.     

皮肤血管瘤组织中WT-1、Bcl-2、P53的表达及意义

目的研究肾母细胞瘤基因（WT-1）、Bcl-2和P53在增生期、退化期血管瘤及正常组织中的表达,探讨其意义及相互关联。方法采用免疫组化SP法检测人皮肤血管瘤组织中WT1、Bcl-2和P53在增生期、退化期及正常皮肤组织中血管内皮细胞中的表达水平,利用计算机成像分析技术检测不同时期皮肤血管瘤与正常皮肤组织WT1、Bcl-2和P53的平均光密度及其阳性面积率。结果1.WT-1在退化期血管瘤中有较强表达,而在增生期血管瘤和正常皮肤组织中表达微弱或不表达（P〈0.05）。2.Bcl-2在增生期血管瘤的表达明显高于退化期血管瘤和正常皮肤组织（P〈0.01）;Bcl-2在退化期血管瘤的表达与正常皮肤组织相比,差异无显著性（P〉0.05）。3.p53基因在增生期血管瘤组织中表达水平高于退化期,差异有极显著性意义（P〈0.01）,退化期血管瘤p53基因表达水平与正常皮肤组织相比,差异无显著性意义（P〉0.05）。结论1.WT-1可能通过促进内皮细胞凋亡而抑制血管瘤的增生;2.Bcl-2可能是通过抑制内皮细胞的凋亡,使其增殖和凋亡失衡;3.P53可能促进了血管瘤增生期内皮细胞的增殖,使血管内皮细胞大量生成。     

Bmi-1和EZH2基因在皮肤血管瘤组织中的表达及意义

目的探讨Bmi-1和EZH2基因在血管瘤组织中的表达及其意义。方法收集武汉大学人民医院病理科2008年-2011年皮肤毛细血管瘤存档蜡块40例,其中男性15例,女性25例。采用免疫组织化学S～P法检测40例皮肤血管瘤增生期、退化期及正常皮肤组织Bmi-1和EZH2基因表达水平,采用HPIAS-1000图文报告管理系统对Bmi-l和EZH2基因的表达进行定量分析,并用SPSSll．5软件对各组免疫组织化学反应阳性颗粒的平均光密度、阳性面积率做单因素方差分析和SNK（q）检验。结果（1）Bmi-1的表达增生期血管瘤血管内皮细胞中可见密集分布的棕黄色颗粒,Bmi-1呈高表达,正常皮肤组及退化组血管内皮细胞中可见少量的棕黄色颗粒,Bmi-1呈低表达。增生期组Bmi-1的表达明显高于退化期组和正常皮肤组（P〈0．05）,而后两组比较差异无统计学意义（P〉0．05）。（2）EZH2的表达增生期血管瘤血管内皮细胞中可见密集分布的棕黄色颗粒,EZH2呈高表达,正常皮肤组及退化组血管内皮细胞中可见少量的棕黄色颗粒,EZH2呈低表达。增生期组EZH2的表达明显高于退化期组和正常皮肤组（P〈o．05）,而后两组比较差异无统计学意义（P〉0．05）。结论Bmi-1和EZH2基因在血管瘤增生期均呈高表达,表明Bmi-1和EZH2基因均参与了血管瘤的发生和发展。     

A possible mechanism of spontaneous involution of infantile hemangioma

Infantile hemangiomas are common vascular tumours which exhibit a rapid proliferating phase followed by spontaneously involuting for a long time. The formation and development mechanisms are not clear yet. Recent studies show that hemangioma-derived stem cells have multipotential differentiation abilities, including endothelial and mesenchymal differentiation. In addition, mesenchymal stem cell has the capability of inducing endothelial cell apoptosis, differentiating into adipocytes and triggering the involution of hemangiomas. Thus we hypothesize that mesenchymal stem cell may be the source of spontaneously regression of hemangiomas. Further investigations may be needed to develop potential therapeutic implications of mesenchymal stem cell in treating hemangiomas.     

Circular excision of hemangioma and purse-string closure: the smallest possible scar

Localized cutaneous infantile hemangioma acts like a tissue expander. This rapidly growing tumor can destroy elastic fibers or cause ulceration resulting in telangiectases, cutaneous laxity, scarring, and fibrofatty residuum. Although surgeons may dispute indications and timing, most would agree that the scar of resection should be minimized. For this reason, circular excision and purse-string closure is particularly applicable for hemangioma at any stage of its evolution. The purposes of this study were to: (1) analyze the results of circular excision/purse-string closure in all three phases of the life cycle of hemangioma; (2) quantify dimensional changes after resection; and (3) compare the scars after theoretical single-stage lenticular excision with those after staged circular excision/purse-string closure. The authors retrospectively analyzed their experience in 25 children with localized hemangioma who underwent circular excision/purse-string closure from 1997 to 2000. Each hemangioma was measured preoperatively and the scars were measured at most recent follow-up (minimum, 6 months). Preoperative and postoperative dimensions were analyzed using SPSS statistical software. The study included 22 girls and three boys, with an average time to follow-up evaluation of 13.1 months. Twenty-one lesions were in the face and scalp, and five were in the extremity. Five tumors were resected in the proliferative phase (either because of ulceration, bleeding, or visual complications) and 21 were excised in the involuting or involuted phase. Six patients had a second-stage procedure: three had another circular excision and three had later lenticular excision. After single circular excision/purse-string closure, the mean long-axial diameter (length) decreased by 45 percent, the mean short-axial width (width) decreased by 73 percent, and the mean scar area was only 15 percent of the original area. All these differences were statistically significant (p = 0.001). The average width/length ratio decreased by 50 percent, indicating a tendency for scars to linearize. There was no difference in linearization for the three phases of hemangioma (p > 0.05); extremity scars became more linear that those on the face (p = 0.01). The authors devised a formula for scar length after lenticular excision/linear closure, assuming a conventional excisional ratio of 3:1 for a circular lesion. Using this equation, the authors predicted that mean scar length after circular excision, followed by lenticular excision, would be 72 percent shorter than the calculated scar that would result from conventional lenticular excision. In three patients who underwent this two-stage approach, the resultant scar was 69 percent shorter. Circular excision of hemangioma and purse-string closure reduces both the longitudinal and transverse dimensions and converts a large circular lesion into a small ellipsoid scar. If subsequent revision to a linear scar is desirable, its length will be the same or slightly less than the diameter of the original lesion. No other excision and closure technique results in a smaller scar. Another advantage of this method is minimal distortion of surrounding structures.     

COSMC Is Overexpressed in Proliferating Infantile Hemangioma and Enhances Endothelial Cell Growth via VEGFR2

Infantile hemangiomas are localized lesions comprised primarily of aberrant endothelial cells. COSMC plays a crucial role in blood vessel formation and is characterized as a molecular chaperone of T-synthase which catalyzes the synthesis of T antigen (Galβ1,3GalNAc). T antigen expression is associated with tumor malignancy in many cancers. However, roles of COSMC in infantile hemangioma are still unclear. In this study, immunohistochemistry showed that COSMC was upregulated in proliferating hemangiomas compared with involuted hemangiomas. Higher levels of T antigen expression were also observed in the proliferating hemangioma. Overexpression of COSMC significantly enhanced cell growth and phosphorylation of AKT and ERK in human umbilical vein endothelial cells (HUVECs). Conversely, knockdown of COSMC with siRNA inhibited endothelial cell growth. Mechanistic investigation showed that O-glycans were present on VEGFR2 and these structures were modulated by COSMC. Furthermore, VEGFR2 degradation was delayed by COSMC overexpression and facilitated by COSMC knockdown. We also showed that COSMC was able to regulate VEGF-triggered phosphorylation of VEGFR2. Our results suggest that COSMC is a novel regulator for VEGFR2 signaling in endothelial cells and dysregulation of COSMC expression may contribute to the pathogenesis of hemangioma.     

Knockdown of VEGFR2 Inhibits Proliferation and Induces Apoptosis in Hemangioma-Derived Endothelial Cells

Angiogenesis is a process of development and growth of new capillary blood vessels from pre-existing vessels. Angiogenic growth factors play important roles in the development and maintenance of some malignancies, of which vascular endothelial growth factor (VEGF)/VEGFR2 interactions are involved in proliferation, migration, and survival of many cancer cells. The aim of this study was to investigate the function of VEGFR2 in human hemangiomas (HAs). Using immunohistochemistry assay, we examined the expression levels of VEGF, VEGFR2, Ki-67, glucose transporter-1 (Glut-1), phosphorylated protein kinase B (p-AKT) and p-ERK in different phases of human HAs. Positive expression of VEGF, VEGFR2, Ki-67, Glut-1, p-AKT and p-ERK was significantly increased in proliferating phase HAs, while decreased in involuting phase HAs (P=0.001; P=0.003). In contrast, cell apoptotic indexes were decreased in proliferating phase HAs, but increased in involuting phase HAs (P<0.01). Furthermore, we used small hairpin RNA (shRNA)-mediated VEGFR2 knockdown in primary HA-derived endothelial cells (HemECs) to understand the role of VEGF/VEGFR2 signaling. Knockdown of VEGFR2 by Lv-shVEGFR2 inhibited cell viability and induced apoptosis in primary HemECs companied with decreased expression of p-AKT, p-ERK, p-p38MAPK and Ki-67 and increased expression of caspase-3 (CAS-3); Overexpression of VEGFR2 promoted cell viability and blocked apoptosis in Lv-VEGFR2-transfected HemECs. Taken together, our findings demonstrate that, increased expression of VEGFR2 is involved in the development of primary HemECs possibly through regulation of the AKT and ERK pathways, suggesting that VEGFR2 may be a potential therapeutic target for HAs.Key words: vascular endothelial growth factor receptor 2, hemangioma, proliferation, apoptosis     

Overexpression of catalase or Bcl-2 alters glucose and energy metabolism concomitant with dexamethasone resistance

Glucocorticoids induce apoptosis in lymphocytes by causing the release of cytochrome c into the cytosol; however, the events in the signaling phase between translocation of the steroid-receptor complex to the nucleus and the release of cytochrome c have not been elucidated. Previously, we found that, in response to steroid treatment, WEHI7.2 mouse thymic lymphoma cells overexpressing catalase (CAT38) show delayed apoptosis (delayed cytochrome c release) compared to the parental cells, while Bcl-2 overexpressing cells (Hb12) are protected from steroid-induced apoptosis. In lymphocytes, glucocorticoid treatment decreases glucose uptake. Both glucose deprivation and the attendant ATP drop are known inducers of apoptosis. Therefore, we used (31)P and (1)H NMR spectroscopy to compare metabolic profiles of WEHI7.2, CAT38 and Hb12 cells in the presence and absence of dexamethasone to determine: (1) whether glucocorticoid effects on glucose metabolism contribute to the mechanism of steroid-induced apoptosis; and (2) whether catalase or Bcl-2 overexpression altered metabolism thereby providing a mechanism of steroid resistance. Loss of mitochondrial hexokinase activity was correlated to the induction of apoptosis in WEHI7.2 and CAT38 cells. CAT38 and Hb12 cells have an altered basal metabolism which includes increases in hexokinase activity, lactate production when subcultured into new medium, use of mitochondria for ATP production and potentially increased glutaminolysis. These data suggest that: (1) glucocorticoid effects on glucose metabolism may contribute to the mechanism of steroid-induced lymphocyte apoptosis; and (2) the altered metabolism seen in catalase and Bcl-2 overexpressing cells may contribute to both the steroid resistance and increased tumorigenicity of these variants.     

Strawberry hemangioma of infancy: early definitive treatment with an argon laser.

This report documents the successful treatment of a hemangioma (strawberry hemangioma) at 5 weeks of age with the argon laser. The natural course of strawberry hemangioma of infancy is well known. It begins as a very small spot and develops very rapidly within the first few weeks of life. Many grow to a very large size and produce significant morbidity. It is logical to assume that if these were ablated early, the life cycle could be aborted. The patient of this case study developed two spots that appeared to be typical evolving hemangiomas. One was treated and disappeared. The other was not treated and evolved into a typical strawberry hemangioma that eventually involuted. This would indicate that early treatment holds some promise.     

c-Myc在人皮肤血管瘤不同时期的表达及意义

目的探讨c-myc在血管瘤发生、发展及退化过程中的表达状况及意义.方法采用免疫组织化学(S-P法),检测人血管瘤增生期、退化期及正常皮肤组织血管内皮细胞c-myc的表达水平,利用计算机图像分析技术检测不同时期血管瘤和正常皮肤组织c-myc染色的阳性面积率和平均光密度.结果增生期血管瘤内皮细胞c-myc表达水平明显高于退化期及正常皮肤组织,差异有显著性意义(P<0.01);退化期与正常皮肤组织血管内皮细胞c-myc表达水平差异无显著性意义(P>0.05).结论 c-myc通过促进血管内皮细胞增殖在血管瘤的发生和发展过程中起重要作用.     

Proteomic analysis of mitochondria from infantile hemangioma endothelial cells treated with sodium morrhuate and its liposomal formulation

Hemangioma is the most common benign tumor of infancy. The aim of this study is to evaluate the biological effects of sodium morrhuate (SM) and its liposomal formulation on infantile hemangioma endothelial cells (IHECs). Morphological analysis revealed that exposure to liposomal sodium morrhuate (LSM) preferentially caused apoptotic death in IHECs, manifested as shrunken configuration and formation of apoptotic bodies. In contrast, necrotic death was prominent in IHECs treated with an equal concentration of SM. By means of proteomic analysis and confirmation experiments, we revealed that the apoptosis‐inducing effects of LSM were associated with an upregulation of a set of genes involved in mitochondrial death pathway, including apoptosis‐inducing factor, cytochrome c1, caspase‐8, and lamin B1. In conclusion, our data highlight the proapoptotic activity of LSM in IHECs through the mitochondrial apoptotic pathway and may provide a promising avenue to treat hemangiomas of infancy. © 2012 Wiley Periodicals, Inc. J Biochem Mol Toxicol 26:374–380, 2012; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21436