Combining nuclear magnetic resonance spectroscopy and mass spectrometry in biomarker discovery

Biomarkers in Medicine

Volumn 3, Issue 3, 2009, Pages 307-322

  Gowda, G A Nagana ^a   Ijiare, Omkar B ^b   Shanaiah, Narasimhamurthy ^a  

^a PURDUE UNIVERSITY   (United States)

^b NATIONAL RESEARCH COUNCIL CANADA   (Canada)

Author keywords

Cancer; Cholangiocarcinoma; Colon cancer; Gallbladder cancer; Gastric cancer; Gastrointestinal; Hepatobiliary diseases; Hepatocellular carcinoma; Mass spectrometry; Metabolic profiling; Metabolomics; Multivariate statistical analysis; NMR spectroscopy; Pancreatic cancer

Indexed keywords

ARACHIDONIC ACID; CHENODEOXYCHOLIC ACID; DISOPYRAMIDE; GENTAMICIN; GLYCEROPHOSPHORYLCHOLINE; HYDRAZINE; IBUPROFEN; IFOSFAMIDE; LACTIC ACID; MERCURIC CHLORIDE; PARACETAMOL; PHOSPHORYLCHOLINE; PLASMALOGEN; SPHINGOMYELIN; TAURINE; TUMOR MARKER; URSODEOXYCHOLIC ACID;

ANALYTIC METHOD; COLORECTAL CANCER; GASTROINTESTINAL TUMOR; HEPATOBILIARY SYSTEM CANCER; HIGH THROUGHPUT SCREENING; HUMAN; LIVER CANCER; LIVER TOXICITY; LIVER TUMOR; MASS SPECTROMETRY; METABOLOMICS; NEPHROTOXICITY; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PANCREAS CANCER; PANCREAS TUMOR; PRINCIPAL COMPONENT ANALYSIS; REVIEW; SENSITIVITY AND SPECIFICITY; STOMACH CANCER; TUMOR DIFFERENTIATION;

EID: 68049088929     PISSN: 17520363     EISSN: None     Source Type: Journal    
DOI: 10.2217/bmm.09.22     Document Type: Review

References (121)

1. Wishart DS: Metabolomics: the principles and potential applications to transplantation. Am. J. Transplant. 5(12), 2814-2820 (2005).
2. Nicholson JK, Lindon JC: Systems biology: metabonomics. Nature 455(7216), 1054-1056 (2008).
3. Wishart DS, Knox C, Guo AC et al.: HMDB: a knowledgebase for the human metabolome. Nucleic Acids Res. 37(database issue), D603-D610 (2009).
4. Pasikanti KK, Ho PC, Chan EC: Gas chromatography/mass spectrometry in metabolic profiling of biological fluids. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 871(2), 202-211 (2008).
5. Nagana Gowda GA, Zhang S, Gu H, Asiago V, Shanaiah N, Raftery D: Metabolomics-based methods for early disease diagnostics. Expert. Rev. Mol. Diagn. 8(5), 617-633 (2008).
6. Raftery D, Nagana Gowda GA: An approaching new wave of multicomponent biomarker diagnostics? J. Urol. 179(6), 2089-2090 (2008).
7. Holmes E, Wilson ID, Nicholson JK: Metabolic phenotyping in health and disease. Cell 134(5), 714-717 (2008).
8. Beckonert O, Keun HC, Ebbels TM et al.: Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts. Nat. Protoc. 2(11), 2692-2703 (2007).
9. Wu DH, Chen AD, Johnson CS: An improved diffusion-ordered spectroscopy experiment incorporating bipolar-gradient pulses. J. Magn. Reson. Series A 115(2), 260-264 (1995).
10. 13C HMBC-NMR spectroscopy combined with pattern recognition procedures performed on filtered variables. Anal. Chem. 74(10), 2261-2273 (2002).
11. Tang HR, Wang Y, Nicholson JK, Lindon JC: Use of relaxation-edited one-dimensional and two dimensional nuclear magnetic resonance spectroscopy to improve detection of small metabolites in blood plasma. Anal. Biochem. 325(2), 260-272 (2004)
12. Xi Y, de Ropp JS, Viant MR, Woodruff DL, Yu P: Automated screening for metabolites in complex mixtures using 2D COSY NMR spectroscopy. Metabolomics 2(4), 221-233 (2006).
13. Viant MR: Improved methods for the acquisition and interpretation of NMR metabolomic data. Biochem. Biophys. Res. Commun. 310(3), 943-948 (2003).
14. Xi Y, de Ropp JS, Viant MR, Woodruff DL, Yu P: Improved identification of metabolites in complex mixtures using HSQC NMR spectroscopy. Anal. Chim. Acta 614(2), 127-133 (2008).
15. 1H NMR spectroscopy, HPLC-NMR/MS and UPLC-MS. Mol. Biosyst. 5(2), 180-190 (2009).
16. Spraul M, Freund AS, Nast RE, Withers RS, Maas WE, Corcoran O: Advancing NMR sensitivity for LC-NMR-MS using a cryoflow probe: application to the ana lysis of acetaminophen metabolites in urine. Anal. Chem. 75(6), 1536-1541(2003).
17. 1H-NMR for mass-limited, nanoliter-volume samples. Science 270(5244), 1967-1970 (1995).
18. Webb AG: Microcoil nuclear magnetic resonance spectroscopy. J. Pharm. Biomed. Anal. 38(5), 892-903 (2005).
19. 13C NMR. Proc. Natl Acad. Sci. USA 104(28), 11540-11544 (2007).
20. 15N tag for sensitive and high-resolution nuclear magnetic resonance profiling of the carboxyl-containing metabolites. Anal. Chem. (2009) (In Press)
21. Lindon JC, Holmes E, Nicholson JK: Metabonomics techniques and applications to pharmaceutical research and development. Pharm. Res. 23(6), 1075-1088 (2006).
22. Kind T, Tolstikov V, Fiehn O, Weiss RH: A comprehensive urinary metabolomic approach for identifying kidney cancer. Anal. Biochem. 363(2), 185-195 (2007).
23. Wilson ID, Nicholson JK, Castro-Perez J et al.: High resolution 'ultra performance' liquid chromatography coupled to OA-TOF mass spectrometry as a tool for differential metabolic pathway profiling in functional genomic studies. J. Proteome Res. 4(2), 591-598 (2005).
24. van der Greef J, Smilde AK: Symbiosis of chemometrics and metabolomics: past, present, and future. J. Chemometrics 19(5-7), 376-386 (2005).
25. Brown SC, Kruppa G, Dasseux JL: Metabolomics applications of FT-ICR mass spectrometry. Mass Spectrom. Rev. 24(2), 223-231(2005).
26. Granger JH, Bake A, Plumb RS et al.: Ultra performance liquid chromatography-MS(TOF): New separations technology for high throughput metabonomics. Drug Met. Rev. 36(2), 252-252 (2004).
27. Villas-Boas SG, Mas S, Akesson M, Silas G, Smedsgaard J, Nielsen J: Mass spectrometry in metabolome ana lysis. Mass Spectrom. Rev. 24(5), 613-646 (2005).
28. Zhang X, Wei D, Yap Y, Li L, Guo S, Chene F: Mass spectrometry-based 'omics' technologies in cancer diagnostics. Mass Spectrom. Rev. 26(3), 403-431(2007).
29. Mohler RE, Dombek KM, Hoggard JC, Young ET, Synovec RE: Comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry ana lysis of metabolites in fermenting and respiring yeast cells. Anal. Chem. 78(8), 2700-2709 (2006).
30. O'Hagan S, Dunn WB, Knowles JD et al.: Closed-loop, multiobjective optimization of two-dimensional gas chromatography/mass spectrometry for serum metabolomics. Anal. Chem. 79(2), 464-476(2007).
31. Zhang Z, Shah B: Characterization of variable regions of monoclonal antibodies by top-down mass spectrometry. Anal. Chem. 79(15), 5723-5729 (2007).
32. Ojanperä S, Pelander A, Pelzing M, Krebs I, Vuori E, Ojanperä I: Isotopic pattern and accurate mass determination in urine drug screening by liquid chromatography/time-of-flight mass spectrometry. Rapid Commun. Mass Spectrom. 20(7), 1161-1167 (2006).
33. Lenz EM, Wilson ID: Analytical strategies in metabonomics. J. Proteome Res. 6(2), 443-458 (2007).
34. Takáts Z, Wiseman JM, Gologan B, Cooks RG: Mass spectrometry sampling under ambient conditions with desorption electrospray ionization. Science 306(5695), 471-473 (2004).
35. Chen H, Venter A, Cooks RG: Extractive electrospray ionization for direct ana lysis of undiluted urine, milk and other complex mixtures without sample preparation. Chem. Commun. 19, 2042-2044 (2006).
36. Cody RB, Laramee JA, Durst HD: Versatile new ion source for the ana lysis of materials in open air under ambient conditions. Anal. Chem. 77(8), 2297-2302 (2005).
37. Goodacre R, Broadhurst D, Smilde AK et al.: Proposed minimum reporting standards for data ana lysis in metabolomics. Metabolomics 3(3), 231-241(2007).
38. Lee KR, Lin X, Park DC, Eslava S: Megavariate data ana lysis of mass spectrometric proteomics data using latent variable projection method. Proteomics 3(9), 1680-1686 (2003).
39. Beckonert O, Bollard ME, Ebbels TMD et al.: NMR-based metabonomic toxicity classification: hierarchical cluster ana lysis and k-nearest-neighbour approaches. Anal. Chim. Acta 490(1), 3-15(2003).
40. Somorjai RL, Dolenko B, Demko A et al.: Mapping high-dimensional data onto a relative distance plane - an exact method for visualizing and characterizing high-dimensional patterns. J. Biomed. Inform. 37(5), 366-379 (2004).
41. Mahadevan S, Shah SL, Marrie TJ, Slupsky CM: Analysis of metabolomic data using support vector machines. Anal. Chem. 80(19), 7562-7570 (2008).
42. Wold H: Partial least squares. In: Encyclopedia of Statistical Sciences (Volume 6). Kotz S, Johnson NL (Eds). Wiley, NY, USA, 581-591 (1985).
43. Barker M, Rayens W: Partial least squares for discrimination. J. Chemometrics 17(3), 166-173 (2003).
44. Trygg J, Holmes E, Lundstedt T: Chemometrics in metabonomics. J. Proteome Res. 6(2), 469-479 (2007).
45. 1H NMR spectra. Acta. Chim. Sinica 65(2), 152-158 (2007).
46. Trygg J, Wold S: Orthogonal projections to latent structures (O-PLS). J. Chemometrics 16(3), 119-128 (2003).
47. Rantalainen M, Cloarec O, Beckonert O et al.: Statistically integrated metabonomic-proteomic studies on a human prostate cancer xenograft model in mice. J. Proteome Res. 5(10), 2642-2655(2006).
48. Werner E, Heilier JF, Ducruix C, Ezan E, Junot C, Tabet JC: Mass spectrometry for the identi?cation of the discriminating signals from metabolomics: current status and future trends. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 871(2), 143-163 (2008).
49. Blow N: Metabolomics: Biochemistry's new look. Nature 455(7213), 697-700 (2008).
50. Wishart DS, Lewis MJ, Morrissey JA et al.: The human cerebrospinal fluid metabolome. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 871(2), 164-173 (2008).
51. 1H NMR spectroscopy in conjunction with multivariate data ana lysis. J. Proteome Res. 6(7), 2605-2614 (2007).
52. Chan EC, Koh PK, Mal M et al.: Metabolic profiling of human colorectal cancer using high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy and gas chromatography mass spectrometry (GC/MS). J. Proteome Res. 8(1), 352-361 (2009).
53. Yang C, Richardson AD, Smith JW, Osterman A: Comparative metabolomics of breast cancer. Pac. Symp. Biocomput. 181-192 (2007).
54. Chen H, Pan Z, Talaty N, Raftery D, Cooks RG: Combining desorption electrospray ionization mass spectrometry and nuclear magnetic resonance for differential metabolomics without sample preparation. Rapid Commun. Mass Spectrom. 20(10), 1577-1584 (2006).
55. Pan Z, Gu H, Talaty N et al.: Principal component ana lysis of urine metabolites detected by NMR and DESI-MS in patients with inborn errors of metabolism. Anal. Bioanal. Chem. 387(2), 539-549 (2007).
56. 1H NMR and HPLC-MS-based metabonomic study of urine from obese (fa/fa) Zucker and normal Wistar-derived rats. J. Pharm. Biomed. Anal. 38(3), 465-471 (2005).
57. 1H NMR and HPLC-TOF MS. Mol. Biosyst. 1(2), 166-175 (205).
58. Gu H, Chen H, Pan Z et al.: Monitoring diet effects via biofluids and their implications for metabolomics studies. Anal. Chem. 79(1), 89-97 (2007).
59. 1H NMR and UPLC-MS(E) statistical heterospectroscopy: characterization of drug metabolites (xenometabolome) in epidemiological studies. Anal. Chem. 80(18), 6835-6844 (2008).
60. Sidelmann UG, Bjørnsdottir I, Shockcor JP, Hansen SH, Lindon JC, Nicholson JK: Directly coupled HPLC-NMR and HPLC-MS approaches for the rapid characterisation of drug metabolites in urine: application to the human metabolism of naproxen. J. Pharm. Biomed. Anal. 24(4), 569-579 (2001).
61. 31P magnetic resonance spectroscopy and mass spectrometry. Cancer Chemother. Pharmacol. 56(4), 409-414 (2005).
62. Shockcor JP, Unger SE, Wilson ID, Foxall PJ, Nicholson JK, Lindon JC: Combined HPLC, NMR spectroscopy, and ion-trap mass spectrometry with application to the detection and characterization of xenobiotic and endogenous metabolites in human urine. Anal. Chem. 68(24), 4431-4435 (1996).
63. Sun J, Schnackenberg LK, Holland RD et al.: Metabonomics evaluation of urine from rats given acute and chronic doses of acetaminophen using NMR and UPLC/MS. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 871(2), 328-340 (2008).
64. 1H-NMR spectroscopy and liquid chromatography-mass spectrometry applied to the investigation of metabolic changes caused by gentamicin-induced nephrotoxicity in the rat. Biomarkers 10(2-3), 173-187 (2005).
65. Crockford DJ, Holmes E, Lindon JC et al.: Statistical heterospectroscopy, an approach to the integrated ana lysis of NMR and UPLC-MS data sets: application in metabonomic toxicology studies. Anal. Chem. 78(2), 363-371 (2006).
66. 1H NMR and HPLC-TOF/MS: time dependent changes in the urinary profile of endogenous metabolites as a result of nephrotoxicity. Analyst 129(6), 535-541 (2004).
67. Xue R, Lin Z, Deng C et al.: A serum metabolomic investigation on hepatocellular carcinoma patients by chemical derivatization followed by gas chromatography/mass spectrometry. Rapid Commun. Mass Spectrom. 22(19), 3061-3068 (2008).
68. Xue R, Dong L, Zhang S et al.: Investigation of volatile biomarkers in liver cancer blood using solid-phase microextraction and gas chromatography/mass spectrometry. Rapid Commun. Mass Spectrom. 22(8), 1181-1186 (2008).
69. Wang Y, Wang T, Shi X et al.: Analysis of acetylcholine, choline and butyrobetaine in human liver tissues by hydrophilic interaction liquid chromatography-tandem mass spectrometry. J. Pharm. Biomed. Anal. 47(4-5), 870-875 (2008).
70. Mendoza ME, Monte MJ, El-Mir MY, Badia MD, Marin JJ: Changes in the pattern of bile acids in the nuclei of rat liver cells during hepatocarcinogenesis. Clin. Sci. 102(2), 143-150 (2002).
71. Khan SA, Cox IJ, Hamilton G, Thomas HC, Taylor-Robinson SD: In vivo and in vitro nuclear magnetic resonance spectroscopy as a tool for investigating hepatobiliary disease: a review of H and P MRS applications. Liver Int. 25(2), 273-281 (2005).
72. Cox IJ, Sharif A, Cobbold JF, Thomas HC, Taylor-Robinson SD: Current and future applications of in vitro magnetic resonance spectroscopy in hepatobiliary disease. World J. Gastroenterol. 12(30), 4773-4783 (2006).
73. Soper R, Himmelreich U, Painter D et al.: Pathology of hepatocellular carcinoma and its precursors using proton magnetic resonance spectroscopy and a statistical classification strategy. Pathology 34(5), 417-422 (2002).
74. Griffitts J, Tesiram YA, Reid GE, Saunders D, Floyd RA, Towner RA: In vivo magnetic resonance spectroscopy (MRS) assessment of altered fatty acyl unsaturation in liver tumor formation of a TGFα/c-myc transgenic mouse model. J. Lipid Res. 50(4), 611-622 (2009).
75. Nishijima T, Nishina M, Fujiwara K: Measurement of lactate levels in serum and bile using proton nuclear magnetic resonance in patients with hepatobiliary diseases: its utility in detection of malignancies. Jpn. J. Clin. Oncol. 27(1), 13-17 (1997).
76. 1H-NMR spectroscopy as a route for assessing liver cancer. Lipids 44(1), 27-35 (2009).
77. 1H NMR spectroscopy. Lipids 41(6), 577-589 (2006).
78. 1H NMR spectroscopy. Lipids 41(6), 591-603 (2006).
79. 1H NMR spectroscopy. Magn. Reson. Med. 53(6), 1441-1446 (2005).
80. Srivastava M, Jadegoud Y, Nagana Gowda GA, Sharma A, Kapoor VK, Khetrapal CL: An accurate method for cholesterol analysis in bile. Anal. Letts. 38, 2135-2141 (2005).
81. 13C NMR characterization and stereochemical assignments of bile acids in aqueous media. Lipids 40(10), 1031-1041 (2005).
82. 1H NMR spectroscopy at 800 MHz. Lipids (2009) (Epub ahead of print)
83. Khan SA, Cox IJ, Thillainayagam AV, Bansi DS, Thomas HC, Taylor-Robinson SD: Proton and phosphorus-31 nuclear magnetic resonance spectroscopy of human bile in hepatopancreaticobiliary cancer. Eur. J. Gastroenterol. Hepatol. 17(7), 733-738 (2005).
84. Cox IJ, Bell JD, Peden CJ et al.: In vivo and in vitro 31P magnetic resonance spectroscopy of focal hepatic malignancies. NMR Biomed. 5(3), 114-120 (1992).
85. Cox IJ, Menon DK, Sargentoni J et al.: Phosphorus-31 magnetic resonance spectroscopy of the human liver using chemical shift imaging techniques. J. Hepatol. 14(2-3), 265-275 (1992).
86. Francis IR, Chenevert TL, Gubin B et al.: Malignant hepatic tumors: P-31 MR spectroscopy with one-dimensional chemical shift imaging. Radiology 180(2), 341-344 (1991).
87. Glazer GM, Smith SR, Chenevert TL et al.: Image localized 31P magnetic resonance spectroscopy of the human liver. NMR Biomed. 1(4), 184-189 (1989).
88. Albiin N, Smith IC, Arnelo U et al.: Detection of cholangiocarcinoma with magnetic resonance spectroscopy of bile in patients with and without primary sclerosing cholangitis. Acta Radiol. 49(8), 855-862 (2008).
89. Somashekar BS, Ijare OB, Nagana Gowda GA et al.: Analysis of bile and gallbladder tissue by NMR: A route for diagnosis of gallbladder cancer. Proc. Intl Soc. Mag. Reson. Med. 15, 127 (2007)
90. Srivastava M, Sharma A, Kapoor VK, Nagana Gowda GA: Stones from cancerous and benign gallbladders are different: a proton nuclear magnetic resonance spectroscopy study. Hepatol. Res. 38(10), 997-1005 (2008).
91. 1H MRS study. NMR Biomed. (Epub ahead of print) (2009).
92. 1H NMR spectroscopy for the prediction of therapeutic outcome in patients with fulminant hepatic failure. NMR Biomed. 19(5), 521-526 (2006).
93. 1H NMR spectroscopy. NMR Biomed. 19(1), 90-100 (2006).
94. 31P NMR studies indicate reduced bile constituents in patients with biliary obstruction and infection. NMR Biomed. 22(2), 220-228 (2009).
95. Beger RD , Schnackenberg LK, Holland RD, Li D, Dragan Y: Metabonomic models of human pancreatic cancer using 1D proton NMR spectra of lipids in plasma. Metabolomics 2(3), 125-134 (2006).
96. 1H MRS studies of three models of pancreatic cancer. Cancer Res. 57(8), 1452-1459 (1997).
97. 1H nuclear magnetic resonance and principal components ana lysis. Cancer Sci. 98(11), 1678-1682 (2007).
98. Cho SG, Lee DH, Lee KY et al.: Differentiation of chronic focal pancreatitis from pancreatic carcinoma by in vivo proton magnetic resonance spectroscopy. J. Comput. Assist. Tomogr. 29(2), 163-169 (2005).
99. 1H NMR and HPLC. Int. J. Pancreatol. 13(3), 175-185 (1993).
100. 1H MRS of bile in the differential diagnosis of cholangiocarcinoma and pancreatic cancer. Proc. Intl Soc. Mag. Reson. Med. 15, 3736 (2008).
101. Mal M, Koh PK, Cheah PY, Chan EC: Development and validation of a gas chromatography/mass spectrometry method for the metabolic profiling of human colon tissue. Rapid Commun. Mass Spectrom. 23(4), 487-494 (2008).
102. Denkert C, Budczies J, Weichert W et al.: Metabolite profiling of human colon carcinoma - deregulation of TCA cycle and amino acid turnover. Mol. Cancer 7, 72 (2008).
103. 1H MRS: correlation with histopathology. Magn. Reson. Med. 30(5), 525-533 (1993).
104. 1H NMR spectra of colon tumors, normal mucosa and their perchloric acid extracts: decreased levels of myo-inositol in tumours can be detected in intact biopsies. NMR Biomed. 9(1), 33-45 (1996).
105. 1H NMR spectroscopy of colon tumors and normal mucosal biopsies; elevated taurine levels and reduced polyethyleneglycol absorption in tumors may have diagnostic significance. NMR Biomed. 6(2), 111-118 (1993).
106. 31P magnetic resonance spectroscopy. Int. J. Colorectal Dis. 6(2), 121-126 (1996).
107. 31P magnetic resonance spectroscopy of human colon cancer. Cancer Res. 50(3), 527-532 (1990).
108. 31P nuclear magnetic resonance phospholipid and phosphatic metabolite profiles. Cancer 76(10), 1715-1723 (1995).
109. 31P magnetic resonance spectroscopy. Magn. Reson. Med. 26(1), 132-140 (1992).
110. Hakomori S, Nudelman E, Levery SB, Kannagi R: Novel fucolipids accumulating in human adenocarcinoma. I. Glycolipids with di- or trifucosylated type 2 chain. J. Biol. Chem. 259(7), 4672-4680 (1984).
111. 1H COSY spectra of plasma membrane fragments shed from human malignant colorectal cells. Magn. Reson. Med. 20(2), 306-311 (1991).
112. Monleón D, Morales JM, Barrasa A, López JA, Vázquez C, Celda B: Metabolite pro?ling of fecal water extracts from human colorectal cancer. NMR Biomed. 22(3), 342-348 (2009).
113. 1H magnetic resonance spectroscopy of fecal extracts. NMR Biomed. (Epub ahead of print) (2009).
114. Tadano T, Kanoh M, Kondoh H et al.: Kinetic ana lysis of bile acids in the feces of colorectal cancer patients by gas chromatography-mass spectrometry (GC-MS). Rinsho Byori. 55(5), 417-427 (2007).
115. Tadano T, Kanoh M, Matsumoto M, Sakamoto K, Kamano T: Studies of serum and feces bile acids determination by gas chromatography-mass spectrometry. Rinsho Byori. 54(2), 103-110 (2006).
116. 1H magnetic resonance spectroscopy of colon tissue. Anticancer Res. 16(3B), 1553-1558 (1996).
117. Brière KM, Kuesel AC, Bird RP, Smith IC: 1H MR visible lipids in colon tissue from normal and carcinogen-treated rats. NMR Biomed. 8(1), 33-40 (1995).
118. 1H magnetic resonance spectroscopy evidence that aberrant crypt foci are preneoplastic lesions in the colon. Anticancer Res. 19(3A), 1699-1703 (1999).
119. Calabrese C, Pisi A, Di Febo G et al.: Biochemical alterations from normal mucosa to gastric cancer by ex vivo magnetic resonance spectroscopy. Cancer Epidemiol. Biomarkers Prev. 17(6), 1386-1395 (2008).
120. Buszewski B, Ulanowska A, Ligor T, Jackowski M, Klodzinska E, Szeliga J: Identification of volatile organic compounds secreted from cancer tissues and bacterial cultures. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 868(1-2), 88-94 (2008).
121. Bennett A, Civier A, Hensby CN, Melhuish PB, Stamford IF: Measurement of arachidonate and its metabolites extracted from human normal and malignant gastrointestinal tissues. Gut 28(3), 315-318 (1987).