title: Metabonomic studies of pancreatic cancer response to radiotherapy in a mouse xenograft model using magnetic resonance spectroscopy and principal components analysis.
abstract: OBJECTIVE
  To investigate the metabolic profiles of xenograft pancreatic cancer before and after radiotherapy by high-resolution magic angle spinning proton magnetic resonance spectroscopy (HRMAS (1)H NMR) combined with principal components analysis (PCA) and evaluate the radiotherapeutic effect.
  
  
  METHODS
  The nude mouse xenograft model of human pancreatic cancer was established by injecting human pancreatic cancer cell SW1990 subcutaneously into the nude mice. When the tumors volume reached 800 mm(3), the mice received various radiation doses. Two weeks later, tumor tissue sections were prepared for running the NMR measurements. (1)H NMR and PCA were used to determine the changes in the metabolic profiles of tumor tissues after radiotherapy. Metabolic profiles of normal pancreas, pancreatic tumor tissues, and radiation- treated pancreatic tumor tissues were compared.
  
  
  RESULTS
  Compared with (1)H NMR spectra of the normal nude mouse pancreas, the levels of choline, taurine, alanine, isoleucine, leucine, valine, lactate, and glutamic acid of the pancreatic cancer group were increased, whereas an opposite trend for phosphocholine, glycerophosphocholine, and betaine was observed. The ratio of phosphocholine to creatine, and glycerophosphocholine to creatine showed noticeable decrease in the pancreatic cancer group. After further evaluation of the tissue metabolic profile after treatment with three different radiation doses, no significant change in metabolites was observed in the (1)H NMR spectra, while the inhibition of tumor growth was in proportion to the radiation doses. However, PCA results showed that the levels of choline and betaine were decreased with the increased radiation dose, and conversely, the level of acetic acid was dramatically increased.
  
  
  CONCLUSIONS
  The combined methods were demonstrated to have the potential for allowing early diagnosis and assessment of pancreatic cancer response to radiotherapy.
authors.affiliation: Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
authors.forename: Xin-Hong
authors.initials: XH
authors.lastname: He
authors.forename: Wen-Tao
authors.initials: WT
authors.lastname: Li
authors.forename: Ya-Jia
authors.initials: YJ
authors.lastname: Gu
authors.forename: Bao-Feng
authors.initials: BF
authors.lastname: Yang
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Deng
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Yu
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Peng
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D011237:Predictive Value of Tests; D025341:Principal Component Analysis; D013997:Time Factors; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor
keywords: High-resolution magic angle spinning proton magnetic resonance spectroscopy; Pancreatic cancer; Principal components analysis; Radiotherapy