VEGF and VEGFR family members are expressed by neoplastic cells of NF1-associated tumors and may play an oncogenic role in malignant peripheral nerve sheath tumor growth through an autocrine loop.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder. The role of angiogenesis and VEGF pathway in the pathogenesis of neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs) remains poorly understood. We assessed the expression of VEGF and VEGFR family members in cohorts of plexiform neurofibromas (pNF), MPNSTs and MPNST cell lines at transcript [pNF, n = 49; MPNST, n = 34] and protein levels [pNF, n = 21; MPNST, n = 9]. VEGF and VEGFR members were variably expressed in cell lines. VEGFA (p = 3.10-5), VEGFR1 (p = 0.08), and VEGFR2 (p = 2.10-4) mRNAs were overexpressed in MPNSTs in comparison with pNFs. Both VEGFA and VEGFR1 proteins were expressed by spindle tumor cells of pNFs and MPNSTs. VEGFA was expressed more in MPNSTs than in pNFs (p = 9.10-6) and a trend for VEGFR1 overexpression was observed (p = 0.06). VEGFR2 was not found at the protein level. The microvascular density was significantly reduced in MPNSTs as compared to pNFs (p = 0.0025), with no differences regarding the expression of the activated phosphorylated forms of ERK (P-ERK [p = 0.63]) and AKT (P-AKT [p = 0.41]) in endothelial cells, suggesting that VEGF-dependant angiogenesis may not be critical for MPNST oncogenesis. Altogether, these results indicate that the VEGF-VEGFR pathway may play a role in the development of pNFs and MPNSTs, independently of angiogenesis. Whether or not it drives an oncogenic autocrine/paracrine loop in neoplastic cells, participating in an increased activation of signaling pathways downstream of tyrosine kinase receptors, including VEGFRs, is a tempting hypothesis. Nevertheless, the specific targeting of angiogenesis in MPNSTs may not be sufficient to slow down tumor growth.

Solar urticaria successfully treated with intravenous immunoglobulins.

BACKGROUND: Idiopathic solar urticaria (SU) is a rare type of physical urticaria, occurring immediately after exposure to visible or ultraviolet (UV) light. Treatment is based on sun avoidance and on high doses of antihistamines, but is sometimes inefficient. METHODS: We report on a 41-year-old patient with severe SU who was successfully treated with a single course of 2 g/kg of intravenous immunoglobulins (IVIG). RESULTS: A dramatic improvement in UVA and UVB tolerance was rapidly observed, with an increase of up to 10 times the UVA minimal urticarial dose on day 3. The treatment with terfenadine was continued. Healing of photosensitivity was persistent since 100 days after the single course of IVIG, no urticarian reaction was provoked with polychromatic irradiation rising above 8.3 J/cm(2) or after UVA doses rising above 15 J/cm(2). CONCLUSION: Use of IVIG in severe SU can be discussed when high-dose antihistamines are inefficient and quality of life is affected.