title: Does preoperative chemo-radiotherapy enhance the expression of vascular endothelial growth factor in patients with rectal cancer?
abstract: To assess whether preoperative chemo-radiotherapy enhances the expression of vascular endothelial growth factor (VEGF) in patients with colorectal cancer, we investigated in vivo and in vitro the interactions between chemo-radiotherapy and the expression of VEGF, and their possible impact on distant metastasis. Cellular cytotoxicity in the colon cancer cell lines, LoVo, SW480 and Caco2, was determined using a WST-8 colorimetric assay after cells were exposed to 5-fluorouracil combined with radiation. In addition, the VEGF levels in cultured cells were measured by ELISA. Preoperative serum samples and tumor specimens were prospectively collected from 32 rectal cancer patients who received preoperative chemo-radiotherapy. Both local and circulating VEGF expression levels were measured perioperatively by ELISA, and assessed in relation to the clinicopathological findings. Perioperative circulating VEGF levels from irradiated patients were also compared with a non-irradiated control group. There were significant increases in local VEGF levels, both in vivo and in vitro, after chemo-radiotherapy, especially in viable cancer cells. The circulating VEGF levels in the irradiated patients were significantly lower after surgery compared with those in the control group. Although preoperative chemo-radiotherapy enhanced tumor-specific VEGF expression, especially in individual cancer cells both in vitro and in vivo, it did not necessarily enhance systemic VEGF expression, possibly because of tumor volume reduction induced by the chemo-radiotherapy.
authors.affiliation: Division of Reparative Medicine, Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie 514-8507, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Inoue
authors.forename: Eiki
authors.initials: E
authors.lastname: Ojima
authors.forename: Hideki
authors.initials: H
authors.lastname: Watanabe
authors.forename: Junichiro
authors.initials: J
authors.lastname: Hiro
authors.forename: Yuji
authors.initials: Y
authors.lastname: Toiyama
authors.forename: Minako
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Chikao
authors.initials: C
authors.lastname: Miki
authors.forename: Masato
authors.initials: M
authors.lastname: Kusunoki
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011300:Preoperative Care; D011829:Radiation Dosage; D012004:Rectal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000097:blood
chemical_list: D000964:Antimetabolites, Antineoplastic; D042461:Vascular Endothelial Growth Factor A; D005472:Fluorouracil