title: Squamous cell head and neck cancer: evidence of angiogenic regeneration during radiotherapy.
abstract: OBJECTIVE
  Intra-tumoural neoangiogenesis is an essential process for tumour progression. Although intensification of angiogenic pathways during cytotoxic therapy has been reported by a few experimental studies, the role of angiogenesis in response to radiotherapy is unclear. We recently reported an adverse effect of intense angiogenesis in the radiotherapy outcome of squamous cell head and neck cancer (SCHNC). In the present study we investigated the radiotherapy-induced changes in the microvessel density (MVD) and in the expression of the angiogenic factor thymidine phosphorylase (TP) in SCHNC.
  
  
  METHODS
  Twenty-four patients with SCHNC underwent a biopsy of the primary lesion immediately before and after delivery of 20Gy of conventionally fractionated radiotherapy. The MVD and the expression of TP was assessed with immunohistochemistry.
  
  
  RESULTS
  The irradiated samples were composed of cancer cell islets or bands, immersed within avascular degenerated tissue. In tumours that did not reach complete response after the end of radiotherapy, these viable cancer tissue areas had a significantly higher MVD (p=0.006) and increased percentage of cancer cells with nuclear TP expression (p=0.0004) than the MVD and the TP expression noted in specimens before radiotherapy. TP expression in these islets was directly related to the MVD (p=0.004, r=0.56).
  
  
  CONCLUSIONS
  The present study supports the idea that intensified angiogenic growth (angiogenic regeneration) during radiotherapy is associated with failure of radiotherapy.
authors.affiliation: Tumour and Angiogenesis Research Group, Department of Radiotherapy-Oncology, Democritus University of Thrace, Alexandroupolis, Greece. targ@her.forthnet.gr
authors.forename: M I
authors.initials: MI
authors.lastname: Koukourakis
authors.forename: A
authors.initials: A
authors.lastname: Giatromanolaki
authors.forename: E
authors.initials: E
authors.lastname: Sivridis
authors.forename: K
authors.initials: K
authors.lastname: Simopoulos
authors.forename: G
authors.initials: G
authors.lastname: Pissakas
authors.forename: K C
authors.initials: KC
authors.lastname: Gatter
authors.forename: A L
authors.initials: AL
authors.lastname: Harris
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000201:enzymology / Q000532:radiotherapy*; D019583:Dose Fractionation, Radiation; D006258:Head and Neck Neoplasms / Q000098:blood supply* / Q000201:enzymology / Q000532:radiotherapy*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000503:physiopathology* / Q000532:radiotherapy*; D011446:Prospective Studies; D012038:Regeneration / Q000528:radiation effects; D013939:Thymidine Phosphorylase / Q000096:biosynthesis
chemical_list: D013939:Thymidine Phosphorylase