title: Histological advantages of the tumor graft: a murine model involving transplantation of human pancreatic cancer tissue fragments.
abstract: OBJECTIVE
  Experimental data based on cell line-derived xenograft models (cell xenograft) seldom reproduce the clinical situation, and therefore we demonstrated here the superiority of a murine model involving transplantation of human pancreatic cancer tissue fragments (tumor graft), focusing on the histological features and drug delivery characteristics.
  
  
  METHODS
  Tumor pieces from 10 pancreatic cancer patients were transplanted into SCID (severe combined immunodeficient) mice. Histological characteristics of tumor grafts, including morphology, desmoplastic reaction, and vascularization, were compared with those of cell xenografts. Drug delivery was evaluated by quantifying the concentrations of injected drug, and the results were compared with its histological features.
  
  
  RESULTS
  Eight of the 10 transplanted tumors successfully engrafted. Histological comparisons between tumor grafts and cell xenografts revealed the following: the amount of stroma was more (22.9% ± 11.8% vs 10.8% ± 5.4%; P < 0.05), vessel-cancer cell distance was longer (35.3 ± 39.0 vs 3.9 ± 3.1 μm; P < 0.001), and microvessel density was lower (6.8 ± 1.9 vs 10.8 ± 2.1 vessels/0.4 mm(2); P < 0.05) in tumor grafts. Drug concentrations in tumor grafts were lower than those in cell xenografts (3.3 ± 1.2 vs 6.0±0.2 μg/mL; P = 0.003), and the differences were correlated with the histological differences.
  
  
  CONCLUSIONS
  Pancreatic tumor grafts better reproduce the histological nature of clinical cancer and thus provide a more realistic model that is applicable for pharmacokinetic studies.
authors.affiliation: From the Department of Surgery, Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Akashi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Oda
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ohara
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Miyamoto
authors.forename: Shinji
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Enomoto
authors.forename: Keiichi
authors.initials: K
authors.lastname: Yamada
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Fukunaga
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ohkochi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D064593:Heterografts / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D010179:Pancreas / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D016035:Pancreas Transplantation / Q000379:methods*; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D014183:Transplantation, Heterologous; D047368:Tumor Burden
chemical_list: D000903:Antibiotics, Antineoplastic; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D004317:Doxorubicin