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OtherBASIC SCIENCE INVESTIGATIONS

Troponin I Overexpression Inhibits Tumor Growth, Perfusion, and Vascularization of Morris Hepatoma

Kerstin Schmidt, Johannes Hoffend, Annette Altmann, Fabian Kiessling, Ludwig Strauss, Dirk Koczan, Walter Mier, Michael Eisenhut, Ralf Kinscherf and Uwe Haberkorn
Journal of Nuclear Medicine September 2006, 47 (9) 1506-1514;
Kerstin Schmidt
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Johannes Hoffend
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Annette Altmann
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Fabian Kiessling
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Ludwig Strauss
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Dirk Koczan
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Walter Mier
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Michael Eisenhut
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Ralf Kinscherf
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Uwe Haberkorn
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  • Article
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  • FIGURE 1. 
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    FIGURE 1. 

    Expression of TnI in clones of MH3924A. (A) Northern blot. (B) Western blot. Representative blots are shown. α-Tubulin or β-actin was used as internal control. bp = base pairs.

  • FIGURE 2. 
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    FIGURE 2. 

    Proliferation and apoptosis of HUVECs cocultured with WT-MH3924A or TnI-MH3924A cells. (A) Proliferation. (B) Apoptosis. Values are mean ± SEM. *P < 0.05 vs. WT-MH3924A.

  • FIGURE 3. 
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    FIGURE 3. 

    Tumor growth of WT-MH3924A and TnI-MH3924 tumors until 40 d after inoculation. Values are mean ± SEM. ***P < 0.001; **P < 0.01; *P < 0.05 vs. WT-MH3924A.

  • FIGURE 4. 
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    FIGURE 4. 

    H215O PET. Representative images and time–activity curves measured in WT-MH3924A (A and C) and TnI-MH3924A (B and D) tumor; 2-dimensional acquisition. Results of modeling analysis are shown in Table 2. T = tumor.

  • FIGURE 5. 
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    FIGURE 5. 

    Functional MRI. Representative T2-weighted images of WT-MH3924A (A) and TnI-MH3924A (B) tumor. Corresponding parametric images for A and kep are shown in C and D. Range of signal intensity for kep and A is indicated at bottom.

Tables

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    TABLE 1

    Histochemical Analyses of Morris Hepatomas Transplanted into ACI Rats: Apoptosis, Proliferation, Oxidative Stress, and Inflammatory Cells

    ParameterWT-MH3924ATnI-MH3924AP
    H215O PET
     K1 (mL·mL tissue−1·min−1)0.43 ± 0.040.32 ± 0.050.14
     k2 (1/min)0.73 ± 0.090.25 ± 0.070.002
     DV (mL/mL tissue)0.65 ± 0.111.69 ± 0.400.022
     VB (mL·mL−1)0.02 ± 0.010.016 ± 0.0070.94
     68Ga-Albumin uptake (SUV)0.48 ± 0.140.47 ± 0.090.91
    Functional MR amplitude
     Total0.84 ± 0.110.78 ± 0.120.75
     Center0.42 ± 0.090.49 ± 0.100.63
     Periphery1.12 ± 0.091.01 ± 0.170.58
     Muscle0.30 ± 0.070.37 ± 0.070.41
    Functional MR kep
     Total9.19 ± 0.714.82 ± 0.790.003
     Center3.42 ± 1.893.51 ± 1.220.95
     Periphery12.29 ± 1.075.89 ± 1.340.006
     Muscle2.65 ± 0.223.35 ± 1.040.56
    • Values are expressed as mean ± SD (n = 6).

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    TABLE 2

    H215O PET, 68Ga-DOTA-Albumin PET, and T1-Weighted DCE MRI

    ParameterWT-MH3924ATnI-MH3924AP
    H215O PET
     K1 (mL·mL tissue−1·min−1)0.43 ± 0.040.32 ± 0.050.14
     k2 (1/min)0.73 ± 0.090.25 ± 0.070.002
     DV (mL/mL tissue)0.65 ± 0.111.69 ± 0.400.022
     VB (mL·mL−1)0.02 ± 0.010.016 ± 0.0070.94
     68Ga-Albumin uptake (SUV)0.48 ± 0.140.47 ± 0.090.91
    Functional MR amplitude
     Total0.84 ± 0.110.78 ± 0.120.75
     Center0.42 ± 0.090.49 ± 0.100.63
     Periphery1.12 ± 0.091.01 ± 0.170.58
     Muscle0.30 ± 0.070.37 ± 0.070.41
    Functional MR kep
     Total9.19 ± 0.714.82 ± 0.790.003
     Center3.42 ± 1.893.51 ± 1.220.95
     Periphery12.29 ± 1.075.89 ± 1.340.006
     Muscle2.65 ± 0.223.35 ± 1.040.56
    • Tumor perfusion, blood volume, amplitude, and kep were measured in WT-MH3924A (n = 5) and TnI-MH3924A (n = 6) tumors of ACI rats. Skeletal muscle tissue was used as control in MRI studies. Values are expressed as mean ± SD.

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    TABLE 3

    Changes in Gene Expression in Genetically Modified TnI-Expressing Hepatomas

    GeneTumor ratioCell ratio
    Angiogenesis associated
     Mast cell protease 1059.820.73
     Vascular chymase11.460.55
     Mast cell protease 8 precursor9.681.27
     Mast cell protease 35.290.68
     VEGF-D3.313.2
     FGF2.740.44
    Apoptosis associated
     Leukocyte common antigen receptor (LAR)6.871.22
     Leukocyte common antigen-related protein2.560.45
     ICE-like cysteine protease (Lice)2.550.6
     A2b-adenosine receptor2.490.81
    Signal transduction and stress
     Glutathione S-transferase8.471.81
     Prolactin6.891
     2′,5′-Oligoadenylate synthetase6.680.48
     Menkes protein6.490.42
     C kinase substrate calmodulin-binding protein5.70.99
     High-affinity IgE receptor (Fc-ε-R-I)5.662.78
     cAMP-regulated phosphoprotein5.032.63
     PPAR-γ4.241.15
     Cholecystokinin-A receptor3.491.72
     Liver microsomal retinol dehydrogenase type I3.190.69
     Nicotinic acetylcholine receptor α-33.161.08
     Extracellular calcium-sensing receptor3.140.53
     Megalin3.060.8
      γ-Crystallin D type3.030.75
     Glycolipid-anchored form of acetylcholinesterase2.881.14
     CCA32.851.22
     Regeneration-associated serpin protein-1 (rasp-1)2.760.9
     Cytochrome P-450b2.760.82
     Retinol dehydrogenase type II2.511.33
     Prepro-complement C32.470.19
     Calcium-activated potassium channel β-subunit2.41.85
     Guanylin2.330.79
     cAMP protein kinase regulatory subunit2.330.45
     Hsp70-32.31.08
     GABA-B receptor gb22.290.83
     Na+,K+-ATPase (EC 3.6.1.3) α2 subunit2.260.64
     Anaphylatoxin C3a receptor2.232.34
     Granzyme-like protein III2.220.64
     GABA-A receptor δ-subunit2.211.5
     T-cell receptor α-chain2.170.65
     Insulin receptor (IRS-1)2.020.48
    • VEGF-D = vascular endothelial growth factor-D; FGF = fibroblast growth factor; ICE = interleukin 1β converting enzyme; cAMP = cyclic adenosine monophosphate; PPAR-γ = peroxisome proliferator-activated receptor γ; CCA3 = confluent 3Y1 cell-associated 3; Hsp70-3 = heat shock protein 70-3; GABA-B = γ-aminobutyric acid receptor B; GABA-A = γ-aminobutyric acid receptor A.

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Journal of Nuclear Medicine: 47 (9)
Journal of Nuclear Medicine
Vol. 47, Issue 9
September 2006
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Troponin I Overexpression Inhibits Tumor Growth, Perfusion, and Vascularization of Morris Hepatoma
Kerstin Schmidt, Johannes Hoffend, Annette Altmann, Fabian Kiessling, Ludwig Strauss, Dirk Koczan, Walter Mier, Michael Eisenhut, Ralf Kinscherf, Uwe Haberkorn
Journal of Nuclear Medicine Sep 2006, 47 (9) 1506-1514;

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Troponin I Overexpression Inhibits Tumor Growth, Perfusion, and Vascularization of Morris Hepatoma
Kerstin Schmidt, Johannes Hoffend, Annette Altmann, Fabian Kiessling, Ludwig Strauss, Dirk Koczan, Walter Mier, Michael Eisenhut, Ralf Kinscherf, Uwe Haberkorn
Journal of Nuclear Medicine Sep 2006, 47 (9) 1506-1514;
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