title: Suppression of reactive oxygen species develops lymph node metastasis in colorectal cancer.
abstract: OBJECTIVE
  Recent evidence indicates that reactive oxygen species (ROS) can induce a wide type of cellular responses from proliferation to senescence and cell death. ROS may not be an absolute carcinogenic factor or cancer suppressor. The aim of this study was to assess the biological paradox of ROS in colorectal cancer cells.
  
  
  METHODS
  Blood specimens were obtained from the drainage vein of the tumor during operation in 135 patients with colorectal cancer. Serum ROS levels were measured using the derivatives of reactive oxygen metabolites (d-ROM) test.
  
  
  RESULTS
  Serum ROS levels increased significantly in tumor size larger than 40mm (p<0.01). On the other hand, serum ROS levels decreased significantly in patients with lymph node metastasis (p<0.01). Multiple linear regression models showed a significant association of serum ROS levels with serum carcinoembryonic antigen (CEA) levels (p<0.01) and lymph node metastasis (p=0.026).
  
  
  CONCLUSIONS
  In colorectal cancer cells, the increase of intracellular ROS is first associated with cell growth and invasion. However, a further increase inhibits cancer cell proliferation, whereas any decrease in ROS concentration needs to stimulate lymph node metastasis. Thus, a precise understanding how ROS are generated and involved in lymph node metastasis will help us to design better therapeutic strategies.
authors.affiliation: Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan. tainokuma-gi@umin.net
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Inokuma
authors.forename: Masashi
authors.initials: M
authors.lastname: Haraguchi
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Fujita
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Torashima
authors.forename: Susumu
authors.initials: S
authors.lastname: Eguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanematsu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002272:Carcinoembryonic Antigen / Q000097:blood; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000097:blood* / Q000556:secondary* / Q000628:therapy; D015536:Down-Regulation; D005260:Female; D006801:Humans; D016014:Linear Models; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D018384:Oxidative Stress; D011379:Prognosis; D017382:Reactive Oxygen Species / Q000097:blood*; D015398:Signal Transduction; D013997:Time Factors; D047368:Tumor Burden
chemical_list: D002272:Carcinoembryonic Antigen; D017382:Reactive Oxygen Species