| BackgroundHemangioma is the most common benign tumor of infants and young children with the incidence rate from3%to8%. As for the gender, it seems the females are more vulnerable than the male, since the ratio of male to female is ranging from1:3to1:5. The benign tumor can be divided into three periods on the clinical course: theses are. the proliferative phase, the involuting phase and the dissipated phase. Moreover According to the different Clinical Manifestations, the infantile hemangiomas can be classified into the following sub categories:clinical superficial hemangioma (capillary hemangioma), deep hemangioma (cavernous hemangioma), and mixed type hemangioma (capillary, cavernous hemangioma). Although85-90%of infantile hemangioma go disappeared by own, some adverse clinical outcome could occur depending on the size,the location or the growth rate, i.e., the tumor located in the airway may compress the trachea, resulting in breathing difficulties of the children; The big hemangioma is a common cause of cardiac insufficiency for the children; The rapid growing of hemangioma often caused significant pain, skin ulceration and bleeding. Pervious treatments on hemangioma, such as orticosteroid steroid hormones, laser, cryotherapy, vincristine, interferon, had positive effect on the tumor, but they also have some side effects, thus limiting their clinical application.In2008, Leaute-Labreze, the doctor at Bordeaux Children’s Hospital (France), reported that they accidently discovered the shrink of the hemangioma tumor when they treated cardiomyopathy accompanying by severe Hemangioma of a child and another child with the increased cardiac output also accompanying by Hemangioma, using the propranolol. After having the consent from the parents of the sick child, they used Propranolol to treat nine children with maxillofacial hemangioma.24hours after taking the treatment, the color of the tumor becomed lighter and the size also becomed smaller, to some extent. This new treatment method had aroused the interests and concerns from specialists internationally and domestically. However reports regarding the side effects of orally taking Propranolol also appeared. These adverse reaction including decreased heart rate, diarrhea, low blood sugar etc. and so forth Thus it is true that oral Propranolol treatment of infantile Hemangioma can sometimes cause adverse reactions for the sick children, but most of these adverse reactions can be self-improved and recovered without any additional treatment. Moreover, Oral treatment of Propranolol is convenient, noninvasive, and has significant effect, therefore, clinical treatment of oral treatment of Propranolol on the infantile Hemangioma cases has become more and more popular.Propranolol, a non-selective adrenergic beta-receptor blockers, could be competitive to antagonism of neurotransmitters and catecholamine beta-receptor agonism. It usually used as clinical medicine for the treatment of hypertension, supraventricular tachycardia, ischemic heart disease, arrhythmia and other diseases, in pediatrics for the treatment of heart disease or neonatal hyperthyroidism. Propranolol has been used in clinic for over40years. The long clinical usage proved its security and well tolerated. But the mechanism of propranolol in treatment of infantile hemangioma is still unclear. Combined with the function which has known already of propranolol on vascular endothelial cells, vascular tone, angiogenesis, and cell apoptosis, we speculated that the possible mechanisms for oral propranolol treatment of infantile hemangioma:(1), the vasoconstriction role. After Oral propranolol treatment in children with hemangioma for three days, the tumor can be observed with lighter color and softened;(2), the impact of angiogenic factors expression;(3), inhibition the expression of matrix metalloproteinase;(4), the promotion of hemangioma endothelial cell apoptosis.Objects:1, Observing different expressions of VEGF、eNOS、Bcl-2and the difference of microvessel density in the tissues from the patients with hemangiomas at different points of time.2, To explore the possible mechanism of Popranolol treatment of infantile Hemangioma in order to improve Propranolol treatment to reduce the incidence of adverse reactions,3, Understanding the mechanism of the Propranolol treatment of infant Hemangioma may help us to understand the pathogenesis of infantile Hemangioma.Methods:Scetion One:Clinical efficacy of oral propranolol treatment of infantile hemangioma1We collected the data of the inpatients and outpatients with oral propranolol or local injection of PYM treatment of infantile hemangiomas in the Laser and Plastic Surgery Center of Guangzhou Millitary General Hospital from January2006to November2011. Patients were divided into the propranolol group and pingyangmycin (PYM)group.40cases of18males and22females, aged1-14months, with an average age of3months were in the propranolol group. Locations of the tumor:21cases on head and face.9cases on limbs,4cases on chests,3cases at perineal,3cases on neck or back. Size of tumors:the largest one was9cm×6cm, the smallest one was1cm×0.5cm.37cases of18males and19females, aged3-24months, with an average age of5months were in the PYM group,. Locations of tumors:22cases on head and face,5cases on limbs,7cases on chest,1cases at perineum,2cases on the neck or back. Tumor size:the maximum is5cm x3cm, the smallest is0.8cm×0.3cm.2With the use of SPSS13.0, we campared the cure rate after6months’treatment and the side efeects occurred during the treatment.Section Two:The different expressions of VEGF、eNOS、Bcl-2and the difference of microvessel density in the tissues got from the patients with hemangiomas at different points in time.1、We collected data of infantile hemangiomas inpatiens and outpatients treated with oral propranolol treatment in the Laser and Plastic Surgery Center of Guangzhou Millitary General Hospital from December2010to December2011. We take samples of tissue from patients at four points of time:5cases were before the treatment,6cases were at72hours after the treatment,4cases were at3months after the treatment and9cases were at6months after the treatment. The tissue samples were fixed in fomalin immediately and then paraffin-embedded.2、Tissue samples in every group were sectioned. Sections were stained with HE and immunohistochemistry. Expressions of the glucosetransporterprotei n-1(GLUT-1), BCL-2, endothelial nitric oxide synthase (eNOS),CD34and vascula r endothelial growth factor (VEGF) of each specimen were detected. CD34is a commonly used marker of vascular endothelial cells. Detection of CD34was use d to measure the density of blood vessels in the hemangioma tumor tissue. The results of the four fields at high magnification (20×10) observed on each slid e were calculated average. GLUT-1is a marker of tumor blood vessels, The positi ve expression of GLUT-1in the sample tissue insures that sample does come fr-om infantile hemangiomas.3、The slices were obsered with upright fluorescence microscope(model:BX-51,produced in Olympus Ltd.). MOD(mean optical density) of the slices which were marked VEGF,BCL-2and eNOS were measured.Result1、The effcet showed there were no significant difference between the two group(P>0.05). But less side effect occurred in the propranolol group than the pingyangmycin group (P<0.05)2、The expression of eNOS in the before treatment group is significantly higher than the72h after treatment group (P<0.05).And the expression between the3months afetr treatment group and the6months after treatment group showed no any difference(P>0.05).3、The expression of VEGF in the before treatment group is significantly higher than the3months after treatment group (P<0.05). The before treatment group is also higher than the6months after treatment group (P<0.05).And the expression between the before treatment group and the72hours after treatment group showed no any difference(P>0.05).4、As the same as the expression of VEGF,the expression of Bcl-2in the before treatment group is higher than the3months after treatment and the6months group (P<0.05).But there is no difference between the before treatment group and the72h after treatment group(P>0.05).5、The density of microvessel in the before treatment group is higher than in the3months after treatment group and the6months after treatment group (P<0.05).And it showed no difference between the befor treatment group and the72 hours after treatment group(P>0.05).Conclusions1、Orally propranolol is a safe, simple and effective medicine for infantile hemangiomas therapy.2、Oral propranolol treatment of infantile hemangiomas is effective by reducing the synthesis of eNOS.3、In the medium and late stage of infantile hemangiomas, propranolol inhibited angiogenesis by reducing the synthesis of VEGF and promoted apoptosis of capillary endothelial cells by decreasing the expression of Bcl-2. |
PDF Full Text Request