普萘洛尔治疗婴幼儿血管瘤中后期耐药的研究及预测

Infantile hemangioma (IH) is the most common benign tumor of infancy. Propranolol has been the first-line treatment for problematic IHs. Although the efficiency of propranolol is very high in the early stage, there are still about 20.8% patients who nearly fail to respond to propranolol in the midanaphase treatment. We call such phenomenon—midanaphase propranolol-resistance. Elucidating this phenomenon and solving this problem are the difficulties and keystones of current treatment for IHs. We have been committing to the screen of biomarks in serum, and have found that hemodynamics in resistant lesions are different from non-resistant. This research aims at proposing the concept of midanaphase propranolol-resistance through a prospective clinical research with a large of samples and subsequent summary. Then, the roles of hemodynamic in the regression and resistance of IHs after propranolol treatment are explored. Finally, peculiar long non-coding RNAs in the serum of propranolol-resistant patients are been screened, which can provide theoretic foundation for diagnosing midanaphase propranolol-resistant patients before treatment and developing more targeted therapies. The above mentioned elucidation and solution not only can further confirm the regression mechanism of IHs after propranolol treatment, but also cover the shortages of propranolol and diagnose midanaphase propranolol-resistant patients before treatment in order to achieve the goal of precision medicine for IHs.

婴幼儿血管瘤是婴幼儿最为常见的良性肿瘤，口服普萘洛尔已成为治疗严重血管瘤的首选。虽然普萘洛尔前期有效率极高，但约有20.8%的患儿在治疗中后期效果甚微甚至无效，我们将这种现象称之为中后期耐药，对其进行解释和解决是目前血管瘤治疗的重点和难点。本课题组长期从事血管瘤血清标志物的筛查，并在前期研究中发现耐药病灶血流动力学与非耐药病灶有所不同。本研究希望通过大样本、前瞻性研究对耐药现象进行归纳总结，提出中后期耐药概念，进而探究血流动力学在普萘洛尔促进血管瘤消退过程及耐药现象中扮演的角色，最后通过血清标志物的筛查寻找耐药患儿血清特异表达的长链非编码RNA，以期为今后临床早期发现耐药患儿及开发专门针对耐药患儿的治疗奠定理论基础。对中后期耐药现象进行解释和解决，不仅能进一步证实普萘洛尔促进血管瘤消退的机制，更能弥补普萘洛尔临床应用的缺点，有望在治疗前发现中后期耐药患儿，为最终实现精准医疗的目标奠定基础。

婴幼儿血管瘤是婴幼儿最为常见的良性肿瘤，口服普萘洛尔已成为治疗严重血管瘤的首选。虽然普萘洛尔前期有效率极高，但有部分患儿在治疗中后期效果甚微甚至无效，我们将这种现象称之为中后期耐药，对其进行解释和解决是目前血管瘤治疗的重点和难点。本研究希望通过大样本、前瞻性研究对普萘洛尔治疗婴幼儿血管瘤过程中的中后期耐药现象进行归纳总结，提出中后期耐药概念，进而探究血流动力学在普萘洛尔促进血管瘤消退过程及耐药现象中扮演的角色，最后通过血清标志物的筛查寻找耐药患儿血清特异表达的长链非编码RNA，以期为今后临床早期发现耐药患儿及开发专门针对耐药患儿的治疗奠定理论基础。我们通过大样本的前瞻性研究发现约有37.2%的血管瘤患儿出现中后期耐药，在普萘洛尔治疗血管瘤过程中病灶存在明显的血流动力学变化。对普萘洛尔治疗婴幼儿血管瘤中后期耐药现象进行解释和解决，不仅能进一步证实普萘洛尔促进血管瘤消退的机制，更能弥补普萘洛尔临床应用的缺点，有望在治疗前发现中后期耐药患儿，为最终实现精准医疗的目标奠定基础。