title: [Anti-angiogenesis effect of metronomic chemotherapy in multiple myeloma patients].
abstract: OBJECTIVE
  To investigate effects of low-dose cyclophosphamide and prednisone (CP) metronomic chemotherapy on microvessel density of bone marrow, serum vascular endothelial growth factor (VEGF) and platelet derived growth factor BB (PDGF-BB)in multiple myeloma (MM) patients.
  
  
  METHODS
  54 refractory or relapsed MM patients were treated with CP metronomic chemotherapy consisted of oral cyclophosphamide (CTX, 50 mg/d) and prednisone (Pred, 15 mg/d). Bone marrow and peripheral blood of each patient were collected before and 2, 4, 6 months after treatment. Among the 37 assessable patients, 30 cases were responsive with the response rate of 81.08%. Another 17 cases were follow-uped less than 6 months or failure to obtain serum samples or lost to follow-up. Microvessel density of bone marrow was measured by immunohistochemistry and serum VEGF/PDGF-BB expression was analyzed by ELISA in the 37 assessable patients.
  
  
  RESULTS
  2, 4, 6 months following CP metronomic chemotherapy, microvessel densities of bone marrow in the responders were 33.1 ± 4.8/HP, 24.8 ± 3.7/HP, 19.7 ± 2.1/HP respectively; the expressions of VEGF were (394 ± 57) ng/L, (268 ± 32) ng/L and (217 ± 20) ng/L respectively; the expressions of PDGF-BB were (304 ± 31) ng/L, (274 ± 31) ng/L and (196 ± 22) ng/L respectively. After CP metronomic chemotherapy, there were significantly lower of microvessel density, VEGF and PDGF-BB levels than pretreatment \[MVD 48.5 ± 5.9/HP, VEGF (517 ± 60) ng/L, PDGF-BB (484 ± 60) ng/L\]in the responders (P < 0.01). While in the non-responders, after treated by CP metronomic chemotherapy for 2 months, microvessel density, the expression of VEGF and the expression of PDGF-BB were 32.5 ± 4.7/HP, 512 ± 39 ng/L and (452 ± 39) ng/L respectively. There were no significant changes of MVD, VEGF and PDGF-BB levels compared with pretreatment \[MVD 33.2 ± 5.6/HP,VEGF (498 ± 55) ng/L, PDGF-BB (488 ± 44) ng/L\] (P > 0.05).
  
  
  CONCLUSIONS
  Our findings suggested that continuous low-dose CP metronomic chemotherapy could decrease microvessel density of bone marrow in MM patients. Furthermore, it down-regulated expression of serum VEGF and PDGF-BB to exert its anti-angiogenesis in MM.
authors.affiliation: Shanghai Zhabei District Central Hospital, Shanghai 200070, China.
authors.forename: Lie-ping
authors.initials: LP
authors.lastname: Guo
authors.forename: Fan
authors.initials: F
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Yi-zi
authors.initials: YZ
authors.lastname: Zhang
authors.forename: Hao-tian
authors.initials: HT
authors.lastname: Shi
authors.forename: Chen-hui
authors.initials: CH
authors.lastname: Lin
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Hou
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077214:Becaplermin; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D055806:Microvessels / Q000187:drug effects; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000098:blood supply* / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage; D020574:Proto-Oncogene Proteins c-sis / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D020533:Angiogenesis Inhibitors; D020574:Proto-Oncogene Proteins c-sis; D042461:Vascular Endothelial Growth Factor A; D000077214:Becaplermin; D003520:Cyclophosphamide; D011241:Prednisone