High preoperative plasma vasohibin-1 concentration predicts better prognosis in patients with non-small cell lung carcinoma.

BACKGROUND AND AIM: Vasohibin-1 (VASH1) is an angiogenesis inhibitor synthesized and secreted by endothelial cells, whose expression is induced by angiogenic stimuli such as vascular endothelial growth factor. We have previously demonstrated that VASH1 is immunohistochemically evident in endothelial cells in the tumor microenvironment of patients with non-small cell lung cancer (NSCLC) and is positively correlated with that of vascular endothelial growth factor in cancer cells. Here, we determined the preoperative plasma concentration of VASH1 in patients with NSCLC and evaluated the association between the preoperative VASH1 levels and certain outcomes. METHODS: We analyzed presurgical plasma VASH1 concentrations in a total of 79 lung cancer patients (51 males and 28 females; 34-83 y of age; 46 adenocarcinomas, 27 squamous cell carcinomas, and 6 other types) who underwent lung resection. The impact of preoperative VASH1 level was analyzed using clinical characteristics and prognosis. RESULTS: Plasma VASH1 concentration ranged from 34.1 to 1190.4 fmol/mL. We divided the patients into 3 groups according to plasma VASH1 level for this assessment: low VASH1 group (n = 26), medium VASH1 group (n = 27), and high VASH1 group (n = 26). The death and recurrence rates of the high, medium, and low VASH1 groups were 5.5, 16.2, and 12.7 per 100 person-years, respectively. Multivariate adjusted hazard ratio of death and recurrence of the high VASH1 group was lower than that of the low VASH1 group (hazard ratio 0.42; 95% CI 0.17-0.99). CONCLUSION: The present analysis suggests that high preoperative plasma VASH1 concentration is associated with better prognosis in patients with NSCLC. We propose preoperative VASH1 level as a biomarker for the prognosis of patients with non-small cell lung carcinoma.

Dedifferentiated chondrosarcoma of the chest wall: reconstruction with polypropylene mesh using a transverse rectus abdominis myocutaneous flap.

We report a case of dedifferentiated chondrosarcoma of the chest wall. After resection, the chest wall defect was reconstructed using polypropylene mesh and a transverse rectus abdominis myocutaneous flap. A 61-year-old woman presented with a 16-year history of a slow-growing mass underneath the right chest wall. After percutaneous biopsy, preoperative cytopathological examination of the large mass revealed dedifferentiated chondrosarcoma. The tumor was resected with a wide margin along with the chest wall including skin, the right seventh to tenth ribs, and part of the diaphragm. The chest wall defect was reconstructed with a polypropylene (Marlex) mesh sheet followed by a left-side transverse rectus abdominis myocutaneous flap.

Endogenous angiogenesis inhibitor vasohibin1 exhibits broad-spectrum antilymphangiogenic activity and suppresses lymph node metastasis.

During cancer progression, the angiogenesis that occurs is involved in tumor growth and hematogenous-distant metastasis, whereas lymphangiogenesis is involved in regional lymph node metastasis. Angiogenesis is counterregulated by various endogenous inhibitors; however, little is known about endogenous inhibitors of lymphangiogenesis. We recently isolated vasohibin1 as an angiogenesis inhibitor intrinsic to the endothelium and further demonstrated its anticancer activity through angiogenesis inhibition. Here, we examined the effect of vasohibin1 on lymphangiogenesis. Vasohibin1 exhibited broad-spectrum antilymphangiogenic activity in the mouse cornea induced by factors including VEGF-A, VEGF-C, FGF2, and PDGF-BB. We then inoculated highly lymph node-metastatic cancer cells into mice and examined the effect of vasohibin1 on lymph node metastasis. Tail-vein injection of adenovirus containing the human vasohibin1 gene inhibited tumor lymphangiogenesis and regional lymph node metastasis. Moreover, local injection of recombinant vasohibin1 inhibited lymph node metastasis. These results suggest vasohibin1 to be the first known intrinsic factor having broad-spectrum antilymphangiogenic activity and indicate that it suppresses lymph node metastasis.

Vasohibin-1 expression in endothelium of tumor blood vessels regulates angiogenesis.

In this study, we characterized the significance of the vascular endothelial growth factor-inducible angiogenesis inhibitor vasohibin-1 to tumors. In pathological sections of non-small cell lung carcinoma, vasohibin-1 was present in the endothelial cells of blood vessels of the tumor stroma, but not in the lymphatics. In cancer cells, the presence of vasohibin-1 was associated with hypoxia-inducible factor 1alpha/vascular endothelial growth factor and fibroblast growth factor-2 expression. We then examined the function of vasohibin-1 in the mouse by subcutaneously inoculating with Lewis lung carcinoma cells. Resultant tumors in vasohibin-1(-/-) mice contained more immature blood vessels and fewer apoptotic tumor cells than tumors in wild-type mice. In wild-type mice that had been inoculated with Lewis lung carcinoma cells, tail vein injection of adenovirus containing the human vasohibin-1 gene inhibited tumor growth and tumor angiogenesis. Moreover, the remaining tumor vessels in adenoviral human vasohibin-1 gene-treated mice were small, round, and mature, surrounded by mural cells. The addition of adenoviral human vasohibin-1 gene to cisplatin treatment improved cisplatin's antitumor activity in mice. These results suggest that endogenous vasohibin-1 is not only involved in tumor angiogenesis, but when sufficient exogenous vasohibin-1 is supplied, it blocks sprouting angiogenesis by tumors, matures the remaining vessels, and enhances the antitumor effect of conventional chemotherapy.

A rare case of a pulmonary granular cell tumor presenting as a coin lesion.

A 38-year-old man was found to show a well-defined oval-shaped homogeneous dense mass (20 x 30 mm) in the left upper lung field on chest X-ray. Left upper divisionectomy was performed under video-assisted thoracic surgery. Histology showed that the tumor cells had abundant eosinophilic granular cytoplasm, and were immunopositive for neuron-specific enolase, CD56, S-100 protein, and chromogranin. The proportion of Ki-67 positive cells was < 1%. An electron-microscopic examination showed many membrane-bound whorls in the cytoplasm. Although this was a very rare case presenting as an asymptomatic coin lesion, the histological features were the same as those demonstrated for granular cell tumor at common sites.