Hemangioma is a benign vascular tumor that can lead to disfigurement and/or life-threatening consequences. Although there are a variety of therapeis, such as surgery, freezing, radiation, and laser, each modality has its own disadvantages. For example, surgery and freezing may cause scarring at the hemangioma site, and radiotherapy is reported to be associated with the occurrence of skin cancer.

Pingyangmycin (PYM), discovered and manufactured in China, is a widely used antitumor antibiotic of which the main component is blemoycin A5. Bleomycin was first reported to have an antiangiogenic effect by Oikawa(1). Subsequently we examined PYM with the chick chorioallantoic membrane (CAM) model to determine whether it can inhibit the chick embryonic CAM neo-vascularization/angiogenesis. Furthermore, we conducted another experiment to confirm PYM’s antiangiogenic effect on Lewis lung carcinoma in C57BL/6 mouse model (unpublished data). Subsequently we employed it to treat hemangioma using topical injection. This communication details our experience of the PYM treatment in 4 children with hemangioma.

Chick embryonic (CAM) assay: The false air sac method established by us earlier was employed. Firstly, 7-day-old Leghorn embryonic eggs were taken out from an incubator where the temperature was kept at 38.5-39°C and the relative humidity was 65-70%. A 1 ´ 2 cm2 window was carefully opened with an electric dentist’s drill. The shell membrane was removed to expose the CAM. In the experimental group, a carrier (0.5 cm in diameter, Whatman filter paper pellet which absorbed 0.5 mg PYM) was put onto the center of CAM. In the control group, the carrier was absorbed at 5 ml 1% methylcellulose. Then the window was sealed with a transparent plastic tape and the embryonic eggs were put into the incubator again. All the above procedures were done under aseptic conditions. Forty eight hours later, the eggs were taken out of the incubator. The CAM microvessels and microcirculation were observed under stereomicroscope and microcirculatory microscope, respectively.

Clinical data: 14 hemangioma patients (age 3 months to 2 years) were evaluated. Eight were male. Most tumors were either strawberry-like or sponge-like, localized to the face, fore-breast and neck. All parents voluntarily agreed to subject their children to PYM injection therapy. Along with PYM injection, 0.1% lidocaine was used to reduce pain and dexamethasone to prevent allergic reaction. PYM dose was 0.2 mg per kilogram body weight, but the maximum used was 3mg per injection. PYM was topically injected into the tumor tissue evenly through one injection dot. The number of injections required depended on the size of the lesion, for instance, if its diameter was less than 1cm, one was enough. The tumor became pale shortly after injection. Photographic records were kept both before and after treatment.

PYM significantly inhibited CAM neovascularization (Table I). Not only did the number of microvessels reduce, but also microcirculation of CAM mainly around the pellet was dramatically affected. The local blood flow slowed down and volume decreased simultaneously. However, the microcirculation far removed from the pellet was almost normal.

Among 14 hemangioma children, 9 tumors disappeared completely after one or two injections of PYM. The other 5 tumors diminished and eventually disappeared after more than three PYM injections.

Table I:Antiangiogenic Effect of PYM on Chick Embryonic CAM

There is considerable evidence that malignant solid tumor growth depends upon angiogenesis, the formation of new blood vessels. More importantly, angiogenesis, as a prerequisite, provides a pathway for cancer cells to spread to distant parts of the body and then form metastasis(2). Therefore, antiangiogenesis therapy is considered to be a promising approach to target cancer(3,4). Although, hemangioma is a benign tumor, it is charac-terized with endothelial cell proliferation. Angiogenesis inhibitor, PYM, has been verified to suppress endothelial cell proliferation and migration (unpublished data), two indispens-able steps of angiogenesis. On the basis of such consideration, PYM was used to treat hemangioma in this clinical trial.

PYM is generally used as a cytotoxic agent and commonly involved in the chemotherapy of esophageal and ovary cancers. In this investigation, the results indicate that topical injection of PYM is an effective means of hemangioma treatment, especially in the surface of the body.

A variety of angiogenic factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor (TGF) can express in relatively high level in hemangioma(5-9). Therefore, angiogenesis antagonists may pro-vide a novel means for hemangioma treat-ment(10,11). White et al. reported that inter-feron alfa-2a can be used to treat infant pulmonary hemangioma and got satisfactory effect(12).

The utility of PYM for treatment of hemangioma needs to be explored in larger clinical trials.

Contributors: WLC designed and finished the study and drafted the paper; he will act as the guarantor for this paper. SGJ participated in some animal experiments and clinical trials.
Funding: This work was supported by a program grant from Shandong Committe of Science and Technology (Grant 961226702).
Competing interests: None stated.

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