Abnormal blood vessels formed by human liver cavernous hemangioma endothelial cells in nude mice are suitable for drug evaluation.

Cavernous hemangioma is vascular malformation with developmental aberrations. It was assumed that the abnormality of endothelial cells contributed greatly to the occurrence of cavernous hemangioma. In our previous study, we have found distinct characteristics of endothelial cells derived from human liver cavernous hemangioma (HCHEC). Here, we reported the abnormal vascular vessels formed by primary HCHEC in nude mice and that the drug podophyllotoxin can destroy HCHEC in vitro and in vivo. HCHEC was isolated from a human liver cavernous hemangioma specimen, and the HCHEC generated a red hemangioma-like mass 7 days after subcutaneously co-inoculating HCHEC and human liver cancer cells (Bel-7402) in nude mice. Lentiviral expression of GFP and immunohistochemistry for human CD31 was used to confirm that the HCHEC formed the blood vessels in nude mice. And the pathological features of vascular vessels formed by HCHEC were very similar to clinical cavernous hemangioma. In addition, by MTT assay, the drug podophyllotoxin was found inhibiting HCHEC viability, and by TUNEL and DNA ladder assays, podophyllotoxin was found inducing apoptosis of HCHEC. Moreover, podophyllotoxin was also effective for destroying the abnormal vascular vessels in the hemangioma-like mass in nude mice. In summary, the HCHEC can form abnormal blood vessels in nude mice, and we can evaluate drugs for cavernous hemangioma by using HCHEC in vitro and in vivo.

[Characteristics of endothelial cells derived from human hepatic cavernous hemangioma in vitro].

OBJECTIVE: To investigate the characteristics of endothelial cells derived from human cavernous hemangioma in morphology, phenotypes and functions. METHODS: Endothelial cells were isolated from human hepatic cavernous hemangioma. The morphological, and phenotypical and functional features of these cells were analyzed by transmission electron microscopy, fluorescence-activated cell sorter, RT-PCR, zymography, and confocal microscopy. Human liver sinusoidal endothelial cells (LSEC) were used as control. RESULTS: As compared with the LSEC, abnormally expanded endoplasmic reticulums and similarly arranged cytoplasmic vacuoles were found in the endothelial cells derived from hepatic cavernous hemangioma (HCHEC) by transmission electron microscopy. Flow cytometry showed that expression of alphavbeta3 was significantly increased in the HCHEC. The mRNA of vascular endothelial cell growth factor and angiopoietin 1 were more abundant in HCHEC than that in LSEC. Functional analysis indicated that the HCHEC exhibited strong activated angiogenesis capacity and formed abnormal capillary-like structures. HCHEC produced more pro-matrix metalloproteinase 2 (MMP-2) and the activated MMP-2 form as compared with the LSEC. Confocal microscopy revealed that MMP-2 was concentrated in those cytoplasmic granules of the HCHEC and was consistent with the distribution of the expanded endoplasmic reticulums. CONCLUSION: The endothelial cells derived from human cavernous hemangioma differ from the normal endothelial cells in morphology, phenotypes and functions.

Effect of electro-acupuncture in treating patients with lingual hemangioma.

OBJECTIVE: To explore the clinical effect of electro-acupuncture (EA) in treating patients with lingual hemangioma (LHG). METHODS: EA therapy was applied on 36 patients by directly inserting the platinum needles into LHG through a trocar with plastic insulating cannula to protect the normal tissues and connecting the needles with the electro-chemical therapeutic apparatus of model ZAY-B. Then electricity was given until the tumor body got contracted and rigid. The result was assessed 6 months after EA was started. RESULTS: All patients were treated effectively, namely, the effective rate was 100%, with the therapeutic effect reaching grade I in 29 patients (80.6%), grade II in 7 (19.4%), and all having the function of tongue recovered to normal. CONCLUSION: EA shows special superiorities in treating LHG, proved to bring about less injury and quick recovery and being simple in operation. Especially when applied on huge LHG, it could not only remove the tumor, but also preserve the function of the tongue, so it is a brand-new approach that is likely to be accepted by patients.

Combined electro-acupuncture with liver artery intubation in treatment of massive liver cancer.

OBJECTIVE: To investigate the clinical effectiveness of electro-acupuncture therapy (EAT) in combination with liver artery intubation chemotherapy for massive liver cancer. METHODS: A total of 106 patients were divided into 3 groups. In group A, patients underwent EAT in combination with invasive therapy. In group B, patients received EAT alone. In group C, patients underwent liver artery intubation chemotherapy. In group A and B, subcostal oblique incision was performed to expose liver cancer, and electrodes were inserted into the tumor under direct vision. In group A, liver artery intubation was performed during operation, followed by chemotherapy through the tube. Liver artery intubation chemotherapy was performed only in group C. RESULTS: The effective rate was 73.7% (28/38), 55.6% (20/36) and 28.1% (9/32) in group A, B and C, respectively. CONCLUSIONS: Electro-acupuncture therapy in combination with liver artery intubation chemotherapy achieves best results. It is an effective therapy for massive liver cancer.

[Observation on effect of electro-acupuncture in treating maxillofacial hemangioma].

OBJECTIVE: To investigate the clinical effect of electro-acupuncture (EA) in treating maxillofacial hemangioma (MFH). METHODS: The platinum needles (electrode) were inserted into the MFH under location and guidance with B-ultrasonography or CT, with the number of needles used according to the size of the MFH to make the distance between needles about 1.5 cm, and the peri-lesional health tissue was protected with plastic insulating tube. The electrodes, which were divided as cathode and anode, were linked with the EA apparatus for EA treatment, the often applied voltage was 5.0-7.0 V, current 60-80 mA and quantity about 100 coulombs/cm of MFH's diameter. B-ultrasonography was used for monitoring during EA, and the treatment would be finished when B-ultrasonography showed disappearance of blood flow. RESULTS: Evaluation according to the WHO's standard for therapeutic efficacy evaluation of tumor showed that after treatment, 345 patients (85.2%) were completely remitted (CR), 39(9.6%) partially remitted (PR), 12(3.0%) improved pathologically, and 9 (2.2%) ineffective, the effective rate (CR + PR) was 94.8%. CONCLUSION: EA, as an creative technique for treatment of MFH, has made breakthrough achievement in clinical practice with high efficacy. It also has the superiorities of simple, less injury, quick recovery, with no scar left and easy to be spread, therefore, it provides an effective method for curing MFH.

[Replacement of artificial tracheal prosthesis by two-stage procedure with memory-alloy mesh].

OBJECTIVE: To design an artificial trachea which can totally heal with the native trachea. METHODS: Using memory-alloy mesh as the skeleton to construct an artificial trachea by two-stage operation. After 2-year animal experiment we successfully performed the operation in a patient with recurrent carcinoid of the trachea, radically resected the tumor and primarily reconstructed the trachea. RESULTS: The inner side of this "sandwich" artificial tracheal prosthesis was coated with skin and outside the memory-alloy mesh was muscle and vessel pedicle with good blood supply. The upper and lower anastomosis completely healed with recipient's trachea with a full recovery of trachea. Six-month follow-up showed that the patients resumed their normal life. CONCLUSION: The artificial trachea completely healed with the native trachea and became a part of the human trachea. The inner side of artificial trachea is coated with intact native skin tissue with ample blood supply, totally alive without rejection. Therefore, the pedicled artificial tracheal prosthesis is an real artificial trachea.

Effect of electrochemotherapy in treating patients with venous malformations.

OBJECTIVE: To evaluate the efficacy and safety of electrochemotherapy in treating venous malformations. METHODS: Electrochemotherapy was applied to 665 patients with venous malformations of limbs and trunk, and 505 cases were followed up for half to 6 years. In this study, 228 male and 277 female patients were involved. Diagnosis was made by clinical manifestations and magnetic resonance imaging. The platinum electrodes were inserted into tumor through a trocar with plastic insulating cannula percutaneously and connected with the electrochemical therapeutic apparatus in anodes and cathodes separately. Then electricity was given. The treating voltage is 6-12 V and volume 100-180 mA, the total electricity used is in general 80-100 coulombs per 1.0 square centimeter of tumors' area. The treating time was usually from several dozen minutes to over 2 h depending on the size of the tumor. The severe cases which needed to be treated once again usually were operated after 6 months. RESULTS: The primary efficacy end point was defined as an improvement of patients' symptoms and a reduction in size of tumor 6 months after treatment. Effects were divided into 4 grades, and the efficacy rate decreased from grade 1 to grade 4. The efficacy turned out that 30.1% (152/505) of patients was classified as grade 1; 46.3% (234/505) as grade 2; 19.0% (96/505) as grade 3 and 4.6% (23/505) as grade 4. CONCLUSIONS: Electrochemotherapy shows special superiorities in treating venous malformations. It might bring a confirmed clinical efficacy with the advantages of less injury, quick recovery, simple operation and less complications.

Morphologic, phenotypic and functional characteristics of endothelial cells derived from human hepatic cavernous hemangioma.

BACKGROUNDS/AIMS: The pathogenesis of cavernous hemangiomas is largely unknown, and it is speculated that abnormal vasculogenesis and angiogenesis may be involved. In this study, the characteristics of cavernous hemangioma endothelial cells (CHECs) derived from the human liver were analyzed in terms of morphology, phenotype and function and compared with human liver sinusoidal endothelial cells (LSECs). METHODS AND RESULTS: By transmission electron microscopy, abnormally expanded endoplasmic reticulum (ER) and similarly arranged cytoplasmic vacuoles were only found in CHECs. Phenotypic analysis showed that the expression of alphavbeta3 was significantly increased in CHECs. mRNA expression of vascular endothelial growth factor A, and angiopoietins 1 and 2 was significantly increased in CHECs compared to LSECs. The functional analysis indicated that CHECs released more vascular endothelial growth factor A, produced significantly more pro-matrix metalloproteinase 2 (pro-MMP2) and activated MMP2, and exhibited higher procoagulant and fibrinolytic activities compared with LSECs. Confocal microscopy revealed that MMP2 was concentrated in some cytoplasmic granules of CHECs and was consistent with the distribution of expanded ER. CHECs exhibited more activated angiogenesis capacity and formed abnormal capillary-like structures in vitro. CONCLUSION: These results suggested that endothelial cells (ECs) derived from human cavernous hemangiomas differ from normal ECs in morphology, phenotype and function.