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8.1. Sources of chemicals, reagents and antibodies

AbD Serotec/Bio-Rad AbD Serotec GmbH, Puchheim, Germany

MAC-3: Rat-anti-mouse CD107b antibody, clone: M3/84, catalog no MCA2293A488

Acris, Herford, Germany

CD31 / PECAM1 (C-term): Rabbit polyclonal antibody, catalog no. AP15436PU-M

BioLogo, Kronshagen, Germany

Macrophage Scavenger Receptor, CD204: Mouse monoclonal antibody, clone: SRA-E5, catalog no. CD 204-1

Serum from non-immunized Balb/cJ mice, catalog no. CL8100

BD Biosciences, Heidelberg, Germany

CD45R / B220- biotinylated: Rat monoclonal antibody, biotinylated, clone RA3-6B2, catalog no. 553085

Pax-5: Mouse monoclonal antibody, clone 24, catalog no. 610863

C. Roth GmbH & Co. KG, Karlsruhe, Germany

2-propanol (Isopropyl alcohol, isopropanol), Rotipuran®, catalog no. 6752 Citric acid monohydrate, p.a., catalog no. 3958.1

Ethanol, Rotipuran®, catalog no. 4600.7 Hematoxylin, catalog no. 3816

Hydrochloric acid, Rotipuran®, catalog no. 6331.3

Hydrogen peroxide 30%, Rotipuran® p.a., catalog no. A8070.1 Mayer’s Hematoxylin solution, catalog no. T865

Roticlear®, catalog no. A538.3 Roti®-Histol, catalog no. A6640 Sodium chloride, catalog no. P029 Sodium hydroxide, p.a., catalog no. 6771

Dako, Deutschland GmbH, Hamburg, Germany CD3 (A0452): Rabbit polyclonal antibody, code no. A0452

MAC387: Mouse monoclonal antibody, clone MAC 387, catalog no. M0747

96 Dianova, Hamburg, Germany

Cy2-conjugated goat-anti-rat antibody, catalog no. 112-226-072

European Collection of Cell Cultures (ECACC), Salisbury, GB DH82: canine macrophages / monocyte cell line, 94062922

E. Kremmer, GSF, Research Center for Environmental Health, München, Germany CD44, monoclonal rat antibody, clone 2D10

Life Technologies, Darmstadt, Germany

Cy3-conjugated goat-anti-rabbit antibody, catalog no. A11034

Sigma, Taufkirchen, Germany Bisbenzimide H, catalog no. H33258 Rabbit serum R4505

3,3’-Diaminobenzidin-tetrahydrochloride hydrate (DAB), product no. 32750 Bovine Serum Albumin (BSA), product no. A-3059

Triple Point Biologics, Oregon, USA

RM105-MMP9: Rabbit polyclonal antibody to Gelatinase-B (MMP-9); full length MMP-9 Native protein

RP1-MMP14: Rabbit polyclonal antibody to Membrane-type Matrix Metalloproteinase-1 (MTI-MMP, MMP-14), Hinge region

RP3-TIMP-1: Rabbit polyclonal antibody to TIMP-1 (Tissue Inhibitor of Metalloproteinases), Carboxyterminal region

Thermo Fisher Scientific GmbH, Dreieich, Germany

MMP-2, MAB13405: Mouse monoclonal antibody to Matrix Metalloproteinase-2 (MMP-2) (72kDa Collagenase IV) Ab-1 (Clone CA4001)

University of Veterinary Medicine – Hannover, clinic for small ruminants, Hannover Goat serum

97 Vector Labratories, Inc., Burlingame, USA

Biotinylated goat-anti-mouse immunoglobulin, catalog no. BA 9200 Biotinylated goat-anti-rabbit immunoglobulin, catalog no. BA1000 Vectastain Elite ABC kit, catalog no. PK-6100

8.2. Sources of software, equipment and disposable items Aperio Technologies, Vista, CA, USA

Aperio ImageScope viewer (Version 12)

Carl Zeiss AG, Göttingen, Germany Transmitted-light microscope

Data weighing systems Inc., Elk Grove, USA Precision balance Sartorious portable PT210

Eppendorf AG, Hamburg, Germany Pipette Reference 10 µl

Pipette Reference 20 µl Pipette Reference 100 µl Pipette Reference 1000 µl

Graph Pad Software Inc., San Diego, USA Graph Pad Prism 6 for Windows (Version 6.05)

Gerhard Menzel Glasbearbeitungswerk GmbH Co. KG, Braunschweig, Germany Super Frsot® Plus microscopic slides, catalog no. 041300

Jürgens, Bremen, Germany Magnetic stirrer IKa-Combimag RTC

Kendro Laboratory Products GmbH, Nussloch, Germany Heraeus drying oven UT6

98 Keyence, Japan

KEYENCE Fluorescence Microscope BZ-9000

Leica Mircosystems Nussloch GmbH, Nussloch, Germany Automatic slide stainer, Leica ST 4040

Microtome, Leica RM2035

Medite Medizintechnik, Burgdorf, Germany Automatic cover slipper, Promounter RCM 2000

SAS Institute Inc, Heidelberg, Germany

Statistical Analysis System (SAS) for Windows, Version 9.3

Olympus Optical Co. Europe GmbH, Hamburg, Germany Camera Olympus DP72

Microscope camera Olympus BX-S1

Olympus Soft Imaging Solutions GmbH, Münster, Germany Cell-D 3.2-imaging software

Thermo Electron Ltd., Dreiech, Germany Shandon Coverpaltes®, catalog no. P777.1

W. Knittel Glasbearbeitungs GmbH, Braunschweig, Germany Cover glass (24× 50 mm)

99 8.3. Solutions for immunohistochemistry

3.3’-Diamiobenzidine tetrahydrochlorid solution (DAB) Prepare shortly before use

0.1 g 3.3‘-diaminobenzidine tetra hydrochloride 200 ml phosphate buffered saline (PBS) 200 µl 30% hydrogen peroxide

Phosphate buffered saline (PBS) 40 g sodium chloride

8.97 g sodium hydrogen phosphate 5000 ml distilled water

Adjust pH value at 7.1 with 1 M sodium hydroxide

Citrate buffer, pH 6.0 2.1 g citric acid monohydrate 1000 ml distilled water

Adjust the pH value at 6.0 with 1 M sodium hydroxide

100 8.4. Tables

Tab. 8.4.1: Case number, breed, sex, age and location of the tumor of dogs with spontaneous canine histiocytic sarcomas.

BMD = Bernese mountain dog; m = male; f = female; y = years; E = biopsy sample;

S = case sample

Tab. 8.4.2: Intratumoral inflammatory cell profile in spontaneous canine histiocytic sarcomas. Values depicted represent immunoreactive cells in 10 randomly selected fields in the tumor center and 10 randomly selected fields in the tumor periphery (each 0.1734 mm²) at a 400x magnification.

Case number MAC387 Pax-5 CD3

C P C P C P

E 428-06 A 51 39 0 0 0 41

107 21 0 0 30 65

54 80 0 0 3 4

Case

number Breed Sex Age Tumor location

1 E 6835/07 BMD f 3 y Skin

2 E 1075/07 BMD f 4 y Elbow joint

3 S 1278/05 BMD f 7 y Lymph node

4 E 3700/03 BMD f 8 y Lymph node

5 E 1481/05 BMD m 3 y Skin

6 E 5914/05 BMD m 5 y Skin

7 S 250/06 BMD m 5 y Muscle

8 E 586/06 BMD m 5 y Lung

9 E 1726/04 Rottweiler m 6 y Skin

10 E 2734/04 BMD m 6 y Spleen

11 S 956/07 BMD m 6 y Lung and liver

12 E 4058/07 BMD m 6 y Skin

13 E 2728/04 Rottweiler m 8 y Spleen

14 E 428/06 BMD m 6 y Lymph node

15 E 154/04 BMD m 4 y Knee joint

16 E 4918/05 BMD m 8 y Spleen

101 Tab. 8.4.2: continued

Case number MAC387 Pax-5 CD3

C P C P C P

118 48 0 0 0 16

53 52 0 0 30 7

161 54 0 0 27 0

104 65 0 0 18 0

84 87 0 0 0 0

147 55 0 0 45 5

125 42 0 0 1 0

E 586-06 A 185 80 0 0 18 47

150 77 0 0 11 53

142 117 0 0 19 30

210 79 0 0 27 108

120 80 0 0 35 93

119 193 0 0 40 66

156 95 0 0 44 65

132 122 0 0 35 56

87 76 0 0 2 0

105 81 0 0 13 3

E 154-05 A 108 113 0 8 0 0

87 96 22 0 0 0

115 90 2 19 0 0

138 141 1 0 0 0

108 89 2 3 0 0

124 68 0 3 0 0

64 113 1 0 0 0

65 105 151 2 0 0

58 94 0 0 0 0

165 115 1 17 0 0

E 1075-07 D 20 20 3 114 79 67

24 4 22 39 79 71

17 26 60 215 70 96

11 31 67 0 63 106

22 9 241 0 57 81

31 3 0 40 38 122

37 13 0 0 55 95

36 14 62 67 38 71

20 17 9 0 57 45

6 33 161 18 77 5

E 3700-03 16 9 0 6 28 31

6 5 0 0 36 13

5 9 0 1 22 27

11 5 0 0 27 9

102 Tab. 8.4.2: continued

Case number MAC387 Pax-5 CD3

C P C P C P

E 3700-03 9 4 0 0 30 14

6 6 0 0 13 16

4 7 0 0 15 8

24 3 0 0 9 25

5 8 0 0 7 12

5 11 0 0 8 22

E 4058-07 20 64 0 0 0 0

8 50 0 0 3 0

15 109 0 0 5 0

14 16 0 0 9 3

19 82 0 0 3 1

3 48 0 0 0 3

20 79 0 0 3 0

30 71 0 0 0 0

52 58 0 0 0 0

12 50 0 0 0 0

E 4918-05 54 166 0 0 38 60

77 233 0 0 84 48

45 248 0 0 87 62

75 218 0 0 28 120

84 261 0 0 26 73

76 187 0 0 21 36

70 124 0 0 55 36

118 122 0 0 27 68

21 115 0 0 78 52

20 109 0 0 77 48

E 5914-05 11 11 0 0 19 33

3 6 0 0 31 13

0 10 0 0 18 44

0 10 0 0 38 124

5 9 0 0 55 54

36 9 0 0 25 45

0 28 0 0 39 67

3 30 0 0 32 80

0 11 0 0 64 2

19 15 0 0 34 4

E 6835-07 20 31 0 176 23 76

6 30 6 57 16 48

8 45 2 24 0 67

31 48 54 18 12 88

48 18 2 8 20 63

103 Tab. 8.4.2: continued

Case number MAC387 Pax-5 CD3

C P C P C P

E 6835-07 40 35 8 33 13 81

19 39 10 25 11 55

24 24 8 75 2 56

10 15 5 144 9 146

12 21 7 6 45 82

S 250-06 10 4 0 0 3 12

12 22 0 0 2 23

23 10 0 0 1 20

25 17 0 0 7 33

15 12 0 0 7 33

16 10 0 0 6 40

12 14 0 0 10 27

30 19 0 0 7 70

26 9 0 0 7 11

24 10 0 0 10 17

E 1726-04 8 50 8 373 24 0

10 10 3 42 131 0

14 30 2 248 201 2

14 22 124 54 139 59

13 15 11 54 105 12

27 8 13 350 52 0

10 63 0 41 48 6

14 33 1 434 21 17

8 13 5 74 12 8

8 8 31 150 25 1

E 1481-03 13 15 9 45 111 185

16 6 2 114 82 192

81 8 3 111 69 84

34 15 0 78 67 126

7 2 4 15 81 131

23 1 3 1 119 129

14 4 2 6 112 155

23 3 5 5 110 104

13 6 10 2 94 91

12 5 5 4 120 115

S 1278-05 20 48 0 0 56 20

4 20 0 0 41 20

15 10 0 0 24 33

20 8 0 0 18 17

17 22 0 0 66 44

5 33 0 0 43 85

104 Tab. 8.4.2: continued

Case number MAC387 Pax-5 CD3

C P C P C P

S 1278-05 1 44 0 0 52 40

1 60 0 0 30 76

2 42 0 0 19 73

34 17 0 0 40 89

S 956-07 15 20 40 167 115 162

7 35 57 243 71 137

12 14 136 452 44 311

6 21 135 248 37 424

2 6 82 313 76 320

4 18 86 264 92 150

6 11 121 330 74 243

6 0 1 166 93 350

4 9 110 44 68 263

16 21 105 166 71 220

E 2728-04 89 227 113 162 49 0

57 235 0 154 36 0

53 190 1 76 31 29

43 183 2 103 24 38

88 132 0 179 56 29

82 95 30 292 74 50

75 127 0 9 49 51

78 213 80 27 39 34

57 204 0 387 104 37

51 220 0 286 169 34

E 2734-04 145 68 0 19 23 10

135 87 18 87 23 9

111 77 1 24 11 1

119 170 2 11 24 5

126 121 0 3 56 7

79 100 6 25 15 1

77 42 42 16 16 2

54 43 11 0 7 9

71 55 19 30 11 5

59 28 44 10 5 12

C = tumor center; P = tumor periphery; MAC387 = myeloid/histiocyte antigen as a marker for canine macrophages; PAX-5 = B-lymphocyte marker; CD3 = T-lymphocyte marker; E = biopsy sample; S = case sample

105

Tab. 8.4.3: Immunohistochemical expression of MMP-14, MMP-9, MMP-2 and TIMP-1 in spontaneous canine histiocytic sarcomas depicted as percentage of antigen positive area.

Case

106

107

108

109

110

111

112 inhibitor of matrix metalloproteinase; E = biopsy sample; S = case sample

113

Tab. 8.4.4: CD31 expression in spontaneous canine histiocytic sarcomas. Values are depicted as the number of immunolabeled structures with a definable lumen in 10 randomly selected fields in the tumor center and 10 in the tumor periphery at a 400x magnification

Case

number C P Case

number C P Case

number C P

E 428-06

A 7 35 E 1481-03 9 11 E

1726-04 44 10

18 13 17 4 38 9

11 16 14 6 54 18

5 20 9 10 50 19

15 23 11 14 56 18

45 31 6 9 51 10

38 15 8 12 56 32

11 26 4 10 72 10

9 27 6 18 60 15

21 17 29 13 33 16

mean

value 18 22.3 mean value 11.3 10.7 mean

value 51.4 15.7 E 586-06

A 5 18 E 2728-04 19 8 E

1075-07 D 4 9

10 4 4 5 13 9

6 11 8 2 23 6

2 7 13 3 15 2

5 12 12 15 3 3

2 10 10 1 3 8

5 7 9 3 18 4

6 8 11 3 13 4

7 8 12 0 8 5

8 20 10 0 11 3

mean

value 5.6 10.5 mean value 10.8 4 mean

value 11.1 5.3 E 154-05

A 6 29 E2734-04 7 8

E6835-07 8 18

5 18 5 7 0 21

4 11 1 7 7 11

6 3 3 4 4 7

6 17 3 1 10 9

4 3 6 3 6 10

6 13 4 6 6 2

6 2 4 3 5 2

3 5 5 0 6 11

3 4 5 0 20 7

mean

value 4.9 10.5 mean value 4.3 3.9 mean

value 7.2 9.8

114 Tab. 8.4.4: continued

Case number

C P Case

number

C P Case

number

C P

E3700-03 12 10 E4058-07 52 29 S250-06 1 4

3 0 37 36 0 5

1 0 26 42 0 2

0 1 30 21 0 1

0 2 32 16 2 1

2 3 22 16 0 0

0 0 17 16 0 1

2 0 20 18 0 1

1 0 33 22 1 1

2 0 40 27 0 0

mean

value 2.3 1.6 mean value 30.9 24.3 mean

value 0.4 1.6

E5914-05 26 35 E4918-05 26 17 S956-07 17 31

38 35 25 17 22 20

38 41 21 21 9 19

20 52 17 8 28 21

4 51 11 17 22 8

8 48 16 21 21 17

40 63 16 19 31 14

45 35 15 25 15 12

29 16 12 21 13 9

31 28 23 32 11 14

mean

value 27.9 40.4 mean value 18.2 19.8 mean

value 18.9 16.5

S1278-05 12 6 - - - -

13 6 - - - -

7 7 - - - -

3 2 - - - -

6 2 - - - -

11 0 - - - -

9 0 - - - -

4 1 - - - -

5 3 - - - -

4 0 - - - -

mean

value 7.4 2.7 - - - -

CD31 = Platelet endothelial cell adhesion molecule marker as a marker for microvessel density;

C = tumor center; P = tumor periphery; E = biopsy sample; S = case sample

115

Tab. 8.4.5: Microvessel density (MVD) in spontaneous canine histiocytic sarcomas.

MVD in spontaneous canine histiocytic sarcoma

Case number C P Case number C P

E 428-06 A 103.80 128.60 E 3700-03 13.26 9.22 E 586-06 A 32.29 60.55 E 4058-07 178.20 140.13 E 154-05 A 28.25 60.55 E 4918-05 104.95 114.18 E 1075-07 D 64.01 30.56 E 5914-05 160.89 232.98 E 1726-04 296.42 90.54 E 6835-07 41.52 56.51 E 1481-03 65.16 61.70 S 250-06 2.30 9.22 E 2728-04 62.28 23.06 S 1278-05 42.67 15.57 E2734-04 24.79 22.49 S 956-07 108.99 95.15

MD = microvessel density; C = tumor center; P = tumor periphery; E = biopsy sample; S = case sample; Values are depicted as the number of immunolabeled structures with a definable lumen in 10 randomly selected fields in the tumor center and 10 randomly selected fields in the tumor periphery at a 400x magnification divided by the microscopic field area at 400 magnification (mm²). Field area at 400 magnification = 0.1734 mm² (0.47 mm diameter).

Tab. 8.4.6: Immunohistochemical expression of MMP-2 in subcutaneously xenotransplanted (DH82 cells). Values depicted display the percentage of immunopositive area in 10 randomly selected fields from the tumor center.

DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V28-11 5.57% V78-11 55.46% V118-11 77.25% V310-10 40.94%

V28-11 12.64% V78-11 57.12% V118-11 72.09% V310-10 38.13%

V28-11 6.81% V78-11 51.07% V118-11 61.57% V310-10 28.71%

V28-11 16.77% V78-11 41.32% V118-11 70.65% V310-10 23.41%

V28-11 59.61% V78-11 47.80% V118-11 76.41% V310-10 19.33%

V28-11 32.15% V78-11 34.96% V118-11 55.87% V310-10 25.51%

V28-11 37.29% V78-11 11.19% V118-11 53.25% V310-10 18.69%

V28-11 39.22% V78-11 10.18% V118-11 36.82% V310-10 24.79%

V28-11 12.66% V78-11 12.40% V118-11 7.85% V310-10 27.47%

V28-11 43.57% V78-11 7.27% V118-11 35.54% V310-10 36.71%

V29-11 53.66% V79-11 71.30% V119-11 52.31% V313-10 11.58%

V29-11 12.91% V79-11 2.27% V119-11 63.29% V313-10 16.72%

V29-11 22.07% V79-11 8.54% V119-11 50.40% V313-10 17.02%

V29-11 34.73% V79-11 36.66% V119-11 65.53% V313-10 10.13%

V29-11 20.40% V79-11 1.96% V119-11 47.63% V313-10 6.49%

V29-11 12.21% V79-11 3.01% V119-11 55.07% V313-10 7.82%

V29-11 57.65% V79-11 14.76% V119-11 75.47% V313-10 3.75%

V29-11 43.68% V79-11 4.96% V119-11 56.45% V313-10 2.40%

V29-11 25.73% V79-11 8.23% V119-11 61.84% V313-10 1.77%

V29-11 50.96% V79-11 4.99% V119-11 57.40% V313-10 5.03%

116 Tab. 8.4.6: continued

DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp - - V30-11 6.08% V80-11 58.55% V120-11 44.52% V314-10 14.11%

V30-11 3.08% V80-11 20.53% V120-11 41.94% V314-10 20.41%

V30-11 19.64% V80-11 13.45% V120-11 69.47% V314-10 12.50%

V30-11 73.01% V80-11 20.09% V120-11 62.44% V314-10 18.30%

V30-11 27.54% V80-11 20.05% V120-11 48.06% V314-10 19.38%

V30-11 41.46% V80-11 22.30% V120-11 25.06% V314-10 17.50%

V30-11 23.19% V80-11 3.71% V120-11 21.48% V314-10 8.82%

V30-11 40.15% V80-11 28.40% V120-11 18.97% V314-10 11.60%

V30-11 21.62% V80-11 23.30% V120-11 16.50% V314-10 15.32%

V30-11 13.20% V80-11 30.23% V120-11 32.50% V314-10 10.92%

V31-11 4.09% V81-11 31.35% V121-11 29.48% - - V31-11 1.10% V81-11 9.91% V121-11 11.87% - - V31-11 1.90% V81-11 40.61% V121-11 13.31% - - V31-11 5.20% V81-11 40.08% V121-11 14.00% - - V31-11 7.18% V81-11 32.69% V121-11 12.07% - -

V31-11 38.99% V81-11 41.16% - - - -

V31-11 35.30% V81-11 33.46% - - - -

V31-11 47.52% V81-11 31.50% - - - -

V31-11 6.73% V81-11 22.94% - - - -

V31-11 11.98% V81-11 22.47% - - - -

V32-11 32.82% V82-11 15.81% - - - -

V33-11 38.49% V82-11 21.14% - - - -

V33-11 66.29% V82-11 42.77% - - - -

- - V82-11 53.38% - - - -

- - V82-11 56.89% - - - -

- - V82-11 57.94% - - - -

- - V82-11 61.98% - - - -

- - V82-11 34.51% - - - -

- - V82-11 39.22% - - - -

- - V82-11 65.51% - - - -

- - V83-11 12.31% - - - -

- - V83-11 33.55% - - - -

- - V83-11 26.92% - - - -

- - V83-11 17.82% - - - -

- - V83-11 10.42% - - - -

- - V83-11 8.39% - - - -

- - V83-11 10.00% - - - -

- - V83-11 15.51% - - - -

- - V83-11 14.08% - - - -

117 Tab. 8.4.6: continued

Non-infected DH82

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V10-11 56.18% V60-11 30.09% V99-11 36.57% V1087-09 81.16%

V10-11 28.42% V60-11 17.07% V99-11 45.99% V1087-09 86.47%

V10-11 24.28% V60-11 13.17% V99-11 40.19% V1087-09 92.96%

V10-11 40.69% V60-11 11.98% V99-11 31.24% V1087-09 89.77%

V10-11 44.57% V60-11 9.00% V99-11 30.61% V1087-09 86.14%

V10-11 47.46% V60-11 12.08% V99-11 29.91% V1087-09 95.51%

V10-11 41.90% V60-11 22.89% V99-11 27.06% V1087-09 94.27%

V10-11 46.99% V60-11 12.66% V99-11 5.33% V1087-09 72.48%

V10-11 55.51% V60-11 16.27% V99-11 3.10% V1088-09 6.38%

V10-11 42.81% V60-11 10.16% V99-11 2.20% V1088-09 7.73%

V11-11 11.82% V61-11 24.84% V100-11 47.79% V1088-09 9.71%

V11-11 1.73% V61-11 18.06% V100-11 33.79% V1088-09 3.23%

V11-11 3.10% V61-11 24.92% V100-11 27.79% V1088-09 26.17%

V11-11 3.33% V61-11 24.79% V100-11 24.50% V1088-09 9.92%

V11-11 41.70% V61-11 22.56% V100-11 32.54% V1088-09 16.51%

V11-11 29.88% V61-11 32.76% V100-11 38.34% V1088-09 2.58%

V11-11 86.82% V61-11 30.58% V100-11 39.23% V1088-09 32.01%

V11-11 67.46% V61-11 30.21% V100-11 38.34% V1088-09 9.20%

V11-11 4.74% V61-11 36.05% V100-11 39.74% V1089-09 4.45%

V11-11 19.16% V61-11 17.94% V100-11 34.59% V1089-09 2.39%

V12-11 17.96% V62-11 30.61% V101-11 27.57% V1089-09 1.62%

V12-11 23.22% V62-11 27.38% V101-11 29.97% V1089-09 1.52%

V12-11 43.89% V62-11 28.11% V101-11 22.29% V1089-09 2.57%

V12-11 14.23% V62-11 18.76% V101-11 17.71% V1089-09 1.76%

V12-11 11.30% V62-11 12.81% V101-11 17.63% V1089-09 1.83%

V12-11 23.07% V62-11 22.90% V101-11 13.70% V1089-09 3.64%

V12-11 1.20% V62-11 12.70% V101-11 14.76% V1089-09 13.48%

V12-11 2.08% V62-11 19.61% V101-11 20.63% V1089-09 2.56%

V12-11 2.38% V62-11 21.50% V101-11 15.89% V1090-09 15.34%

V12-11 6.57% V62-11 32.33% V101-11 12.26% V1090-09 27.47%

V13-11 7.27% V63-11 10.39% V102-11 16.69% V1090-09 22.48%

V13-11 60.83% V63-11 19.03% V102-11 17.86% V1090-09 20.22%

V13-11 4.09% V63-11 23.90% V102-11 20.83% V1090-09 25.40%

V13-11 2.89% V63-11 27.51% V102-11 16.45% V1090-09 25.41%

V13-11 3.45% V63-11 4.70% V102-11 19.19% V1090-09 19.64%

V13-11 7.30% V63-11 14.05% V102-11 24.85% V1090-09 26.17%

V13-11 61.10% V63-11 1.65% V102-11 25.66% V1090-09 31.50%

V13-11 43.35% V63-11 5.23% V102-11 25.00% V1090-09 17.81%

V13-11 68.40% V63-11 1.46% V102-11 20.19% V1091-09 3.54%

V13-11 73.25% V63-11 7.67% V102-11 11.69% V1091-09 3.48%

V14-11 13.70% V64-11 18.34% V103-11 5.42% V1091-09 3.29%

118 Tab. 8.4.6: continued

Non-infected DH82

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V14-11 10.96% V64-11 12.92% V103-11 6.80% V1091-09 4.98%

V14-11 8.49% V64-11 22.96% V103-11 4.17% V1091-09 3.93%

V14-11 12.21% V64-11 14.58% V103-11 5.38% V1091-09 4.52%

V14-11 11.11% V64-11 10.59% V103-11 4.69% V1091-09 4.42%

- - V64-11 17.81% V103-11 5.57% V1091-09 4.76%

- - V64-11 4.62% V103-11 2.71% V1091-09 5.76%

- - V64-11 10.64% V103-11 7.07% V1091-09 4.09%

- - V64-11 5.55% V103-11 8.61% - -

- - V64-11 12.19% V103-11 1.37% - -

Tab. 8.4.6: continued

UV-DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V22-11 4.06% V72-11 10.60% V110-11 71.59% V319-11 2.69%

V22-11 21.06% V72-11 8.64% V110-11 58.21% V319-11 9.71%

V22-11 80.19% V72-11 23.04% V110-11 33.66% V319-11 28.15%

V22-11 82.17% V72-11 23.28% V110-11 19.05% V319-11 31.39%

V22-11 46.50% V72-11 16.95% V110-11 25.58% V319-11 31.81%

V22-11 51.31% V72-11 14.98% V110-11 23.52% V320-11 20.52%

V22-11 33.09% V72-11 19.70% V110-11 13.16% V320-11 24.10%

V22-11 25.88% V72-11 15.03% V110-11 11.40% V320-11 16.34%

V22-11 29.09% V72-11 11.60% V110-11 26.15% V320-11 15.78%

V22-11 20.80% V72-11 20.47% V110-11 30.56% V320-11 52.01%

V23-11 1.40% V73-11 20.35% V111-11 33.85% V320-11 30.80%

V23-11 2.10% V73-11 25.14% V111-11 34.11% V320-11 28.16%

V23-11 3.46% V73-11 18.98% V111-11 36.72% V320-11 19.51%

V23-11 3.68% V73-11 14.17% V111-11 37.78% V320-11 33.49%

V23-11 5.71% V73-11 9.45% V111-11 22.78% V320-11 25.72%

V23-11 10.79% V73-11 9.28% V111-11 18.80% V321-11 21.58%

V23-11 3.10% V73-11 25.18% V111-11 30.86% V321-11 501.49%

V23-11 3.84% V73-11 13.71% V111-11 21.71% V321-11 34.60%

V23-11 2.46% V73-11 19.70% V111-11 26.41% V321-11 33.64%

V23-11 2.99% V73-11 8.97% V111-11 41.88% V321-11 40.35%

V24-11 4.92% V74-11 7.94% V112-11 19.13% V321-11 4.38%

V24-11 6.53% V74-11 18.48% V112-11 16.90% V321-11 18.76%

V24-11 5.94% V74-11 11.22% V112-11 10.91% V321-11 17.70%

V24-11 2.11% V74-11 7.49% V112-11 21.78% V321-11 31.46%

V24-11 6.56% V74-11 18.94% V112-11 13.19% V321-11 30.83%

V24-11 1.17% V74-11 5.58% V112-11 26.34% V322-11 18.96%

V24-11 1.74% V74-11 8.79% V112-11 36.15% V322-11 15.94%

119 Tab. 8.4.6: continued

UV-DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V24-11 5.55% V74-11 8.19% V112-11 25.92% V322-11 25.77%

V24-11 5.85% V74-11 6.53% V112-11 24.45% V322-11 35.87%

V24-11 13.11% V74-11 23.36% V112-11 25.92% V322-11 20.37%

V25-11 2.43% V75-11 14.03% V113-11 53.63% V322-11 35.27%

V25-11 1.81% V75-11 27.80% V113-11 57.43% V322-11 18.94%

V25-11 7.05% V75-11 18.22% V113-11 66.50% V322-11 44.52%

V25-11 3.86% V75-11 19.59% V113-11 64.70% V322-11 43.31%

V25-11 1.01% V75-11 24.58% V113-11 63.99% V322-11 36.89%

V25-11 4.43% V75-11 1.92% V114-11 15.30% V323-11 27.68%

V25-11 1.87% V75-11 1.87% V114-11 11.19% V323-11 29.34%

V25-11 4.08% V75-11 17.03% V114-11 22.09% V323-11 52.27%

V25-11 2.77% V75-11 18.85% V114-11 39.69% V323-11 33.60%

V25-11 11.82% V75-11 6.79% V114-11 4.40% V323-11 35.88%

V26-11 2.26% V76-11 1.12% V114-11 10.89% V323-11 41.11%

V26-11 7.83% V76-11 2.08% V114-11 6.82% V323-11 41.04%

V26-11 3.04% V76-11 2.76% V114-11 24.39% V323-11 50.05%

V26-11 9.93% V76-11 6.36% V114-11 36.53% V323-11 28.34%

V26-11 13.95% V76-11 5.59% V114-11 35.81% V323-11 41.34%

V26-11 4.07% V76-11 6.78% V115-11 6.05% V324-11 20.72%

V26-11 3.26% V76-11 3.12% V115-11 4.05% V324-11 19.42%

V26-11 1.94% V76-11 3.60% V115-11 2.52% V324-11 22.35%

V26-11 4.74% V76-11 3.41% V115-11 22.36% V324-11 28.41%

V26-11 4.52% V76-11 22.13% V115-11 45.36% V324-11 29.66%

V27-11 5.73% V77-11 23.94% V115-11 38.90% V324-11 20.06%

V27-11 5.30% V77-11 22.66% V115-11 38.10% V324-11 25.01%

Tab. 8.4.6: continued

UV-DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V27-11 1.60% V77-11 14.20% V115-11 23.59% V324-11 27.92%

V27-11 5.36% V77-11 21.65% V115-11 23.63% V324-11 24.15%

V27-11 31.61% V77-11 10.59% V115-11 25.43% V324-11 20.52%

V27-11 24.44% V77-11 15.10% - - - -

V27-11 13.11% V77-11 14.12% - - - -

V27-11 2.54% V77-11 12.63% - - - -

V27-11 9.14% V77-11 1.59% - - - -

V27-11 4.47% - - - -

MMP = matrix metalloproteinase; CDV = canine distemper virus (Onderstepoort strain);

DH82CDVai = acutely CDV infected xenografts; non-infected DH82 = non-treated xenografts (control group); UV-DH82CDVai = UV-inactivated CDV acutely infected DH82 xenografts (control group);dtp = days after transplantation

120

Tab. 8.4.7: Immunohistochemical expression of MMP-2 in subcutaneously xenotransplanted (DH82 cells). Values depicted display the percentage of immunopositive area in 10 randomly selected fields from the tumor periphery.

DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V28-11 64,86% V78-11 63,52% V118-11 73,36% V310-10 54,93%

V28-11 57,84% V78-11 64,63% V118-11 67,88% V310-10 65,16%

V28-11 68,26% V78-11 64,63% V118-11 76,08% V310-10 71,94%

V28-11 38,95% V78-11 77,22% V118-11 72,58% V310-10 59,97%

V28-11 40,67% V78-11 66,13% V118-11 75,85% V310-10 68,71%

V28-11 47,11% V78-11 71,31% V118-11 72,05% V310-10 63,45%

V28-11 46,19% V78-11 70,53% V118-11 67,68% V310-10 71,13%

V28-11 74,03% V78-11 75,85% V118-11 79,39% V310-10 70,26%

V28-11 67,74% V78-11 68,11% V118-11 84,65% V310-10 54,29%

V28-11 64,94% V78-11 69,69% V118-11 82,97% V310-10 53,94%

V29-11 86,65% V79-11 82,40% V119-11 79,30% V312-10 13,22%

V29-11 82,43% V79-11 60,52% V119-11 78,58% V312-10 13,13%

V29-11 91,89% V79-11 67,88% V119-11 83,05% V312-10 14,80%

V29-11 81,87% V79-11 67,36% V119-11 81,38% V312-10 10,15%

V29-11 68,12% V79-11 77,06% V119-11 74,92% V312-10 13,70%

V29-11 70,12% V79-11 82,00% V119-11 73,00% V312-10 11,64%

V29-11 87,00% V79-11 79,88% V119-11 73,57% V312-10 13,46%

V29-11 82,73% V79-11 79,63% V119-11 74,32% V312-10 9,58%

V29-11 79,24% V79-11 73,65% V119-11 78,48% V312-10 7,69%

V29-11 76,53% V79-11 66,87% V119-11 74,85% V312-10 13,36%

V30-11 83,76% V80-11 82,94% V120-11 56,61% V313-10 13,60%

V30-11 83,76% V80-11 78,53% V120-11 57,66% V313-10 17,74%

V30-11 87,07% V80-11 75,52% V120-11 66,22% V313-10 10,12%

V30-11 75,32% V80-11 68,39% V120-11 75,19% V313-10 25,86%

V30-11 56,96% V80-11 60,85% V120-11 70,63% V313-10 20,09%

V30-11 61,65% V80-11 68,01% V121-11 27,93% V313-10 16,40%

V30-11 70,53% V80-11 73,16% V121-11 20,11% V313-10 19,04%

V30-11 68,28% V80-11 75,18% V121-11 32,32% V313-10 19,58%

V30-11 70,14% V80-11 62,53% V121-11 34,98% V313-10 9,68%

V30-11 88,46% V80-11 66,08% V121-11 23,10% V313-10 19,58%

V31-11 72,98% V81-11 67,06% V121-11 32,02% V314-10 27,36%

V31-11 57,14% V81-11 63,30% V121-11 17,77% V314-10 27,05%

V31-11 71,57% V81-11 65,92% V121-11 28,32% V314-10 20,72%

V31-11 68,81% V81-11 70,30% V121-11 30,11% V314-10 27,20%

V31-11 72,87% V81-11 65,83% V121-11 30,73% V314-10 21,52%

V31-11 69,79% V81-11 77,51% - - V314-10 24,16%

V31-11 73,42% V81-11 78,82% - - V314-10 27,34%

V31-11 57,85% V81-11 63,27% - - V314-10 20,05%

121 Tab. 8.4.7: continued

DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V31-11 70,17% V81-11 56,16% - - V314-10 6,49%

V31-11 66,71% V81-11 82,61% - - - -

V32-11 69,46% V82-11 70,82% - - - -

V32-11 79,57% V82-11 70,71% - - - -

V32-11 56,91% V82-11 54,53% - - - -

V32-11 69,17% V82-11 60,38% - - - -

V32-11 82,97% V82-11 54,35% - - - -

V33-11 83,37% V82-11 53,91% - - - -

V33-11 75,05% V82-11 51,97% - - - -

V33-11 72,68% V82-11 62,24% - - - -

V33-11 81,38% V82-11 47,19% - - - -

V33-11 79,57% V82-11 68,14% - - - -

Tab. 8.4.7: continued

Non-infected DH82

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V10-11 60,10% V60-11 67,43% V99-11 66,71% V1087-09 81,16%

V10-11 83,62% V60-11 58,56% V99-11 70,29% V1087-09 86,47%

V10-11 62,47% V60-11 63,40% V99-11 72,70% V1087-09 92,96%

V10-11 49,75% V60-11 54,40% V99-11 68,87% V1087-09 89,77%

V10-11 75,87% V60-11 52,20% V99-11 65,30% V1087-09 86,14%

V10-11 66,06% V60-11 64,01% V99-11 64,70% V1087-09 95,51%

V10-11 76,65% V60-11 32,93% V99-11 62,16% V1087-09 94,27%

V10-11 77,82% V60-11 41,85% V99-11 57,48% V1087-09 72,48%

V10-11 72,97% V60-11 34,78% V99-11 65,55% V1088-09 87,74%

V10-11 74,69% V60-11 56,20% V99-11 58,21% V1088-09 90,47%

V11-11 83,97% V61-11 32,54% V100-11 50,02% V1088-09 85,73%

V11-11 76,31% V61-11 34,93% V100-11 74,53% V1088-09 87,40%

V11-11 90,33% V61-11 39,79% V100-11 75,59% V1088-09 83,02%

V11-11 82,74% V61-11 36,49% V100-11 64,05% V1088-09 79,17%

V11-11 82,38% V61-11 52,08% V100-11 67,00% V1088-09 84,44%

V11-11 90,88% V61-11 50,40% V100-11 56,73% V1088-09 88,73%

V11-11 96,00% V61-11 46,99% V100-11 61,98% V1088-09 81,97%

V11-11 89,59% V61-11 31,52% V100-11 72,72% V1088-09 81,96%

V11-11 87,75% V61-11 34,25% V100-11 70,05% V1089-09 24,51%

V11-11 86,60% V61-11 30,36% V100-11 60,20% V1089-09 46,81%

V13-11 90,98% V62-11 35,10% V101-11 33,53% V1089-09 38,19%

V13-11 96,03% V62-11 30,87% V101-11 18,79% V1089-09 33,71%

V13-11 83,84% V62-11 53,23% V101-11 59,82% V1089-09 51,16%

122 Tab. 8.4.7: continued

Non-infected DH82

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V13-11 91,57% V62-11 60,83% V101-11 46,79% V1089-09 37,85%

V13-11 94,16% V62-11 66,59% V101-11 46,66% V1089-09 46,50%

V13-11 89,13% V62-11 65,49% V101-11 34,88% V1089-09 28,32%

V13-11 61,74% V62-11 49,32% V101-11 34,75% V1089-09 8,73%

V13-11 65,03% V62-11 49,07% V101-11 33,66% V1089-09 8,38%

V13-11 94,99% V62-11 43,34% V101-11 21,18% V1089-09 47,01%

V13-11 96,06% V62-11 50,80% V101-11 21,01% V1089-09 59,42%

V14-11 46,23% V63-11 21,39% V102-11 21,16% V1089-09 45,64%

V14-11 44,70% V63-11 36,47% V102-11 33,44% V1089-09 72,26%

V14-11 40,49% V63-11 25,99% V102-11 36,41% V1089-09 66,90%

V14-11 36,88% V63-11 23,60% V102-11 43,52% V1089-09 41,64%

V14-11 27,62% V63-11 34,77% V102-11 38,38% V1089-09 69,17%

- - V63-11 35,54% V102-11 37,58% V1089-09 48,14%

- - V63-11 46,09% V102-11 30,92% V1089-09 34,67%

- - V63-11 47,20% V102-11 34,33% V1089-09 41,99%

- - V63-11 52,79% V102-11 21,09% V1091-09 4,70%

- - V63-11 45,43% V102-11 30,75% V1091-09 12,37%

- - V64-11 41,33% V103-11 40,14% V1091-09 12,64%

- - V64-11 40,82% V103-11 35,04% V1091-09 4,43%

- - V64-11 32,36% V103-11 31,11% V1091-09 6,76%

- - V64-11 59,12% V103-11 44,58% V1091-09 8,17%

- - V64-11 69,51% V103-11 38,34% V1091-09 5,51%

- - V64-11 54,18% V103-11 33,96% V1091-09 5,18%

- - V64-11 47,26% V103-11 41,84% V1091-09 13,02%

- - V64-11 29,10% V103-11 46,48% V1091-09 17,53%

- - V64-11 37,36% V103-11 46,87% -

-- - V64-11 25,25% V103-11 20,71% - -

Tab. 8.4.7: continued

UV-DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V22-11 73,78% V72-11 31,63% V111-11 35,99% V319-11 88,95%

V22-11 77,06% V72-11 47,92% V111-11 49,28% V319-11 90,41%

V22-11 80,72% V72-11 55,88% V111-11 43,72% V319-11 79,67%

V22-11 90,68% V72-11 42,64% V111-11 57,34% V319-11 79,91%

V22-11 59,48% V72-11 53,10% V111-11 66,37% V319-11 61,47%

V22-11 91,11% V72-11 53,92% V111-11 68,06% V319-11 70,92%

V22-11 82,85% V72-11 55,61% V111-11 66,06% V319-11 82,12%

V22-11 90,16% V72-11 52,26% V111-11 66,29% V319-11 89,16%

123 Tab. 8.4.7: continued

UV-DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V22-11 80,96% V72-11 61,23% V111-11 59,53% V319-11 67,92%

V22-11 86,04% V72-11 48,17% V111-11 73,24% V319-11 83,19%

V23-11 81,53% V73-11 61,05% V112-11 61,57% V320-11 61,01%

V23-11 84,80% V73-11 68,21% V112-11 56,23% V320-11 79,85%

V23-11 86,56% V73-11 62,13% V112-11 58,47% V320-11 63,83%

V23-11 83,28% V73-11 78,44% V112-11 39,77% V320-11 89,07%

V23-11 84,03% V73-11 80,61% V112-11 54,75% V320-11 87,34%

V23-11 84,32% V73-11 80,61% V112-11 52,12% V320-11 91,67%

V23-11 78,16% V73-11 62,26% V112-11 50,35% V320-11 91,01%

V23-11 69,38% V73-11 53,73% V112-11 58,69% V320-11 89,23%

V23-11 53,85% V73-11 37,84% V112-11 47,09% V320-11 91,17%

V23-11 60,66% V73-11 54,55% V112-11 58,50% V320-11 90,69%

V24-11 51,19% V74-11 44,14% V113-11 58,37% V321-11 52,68%

V24-11 52,07% V74-11 43,17% V113-11 69,90% V321-11 48,13%

V24-11 64,89% V74-11 42,30% V113-11 80,03% V321-11 47,67%

V24-11 44,67% V74-11 43,33% V113-11 69,72% V321-11 48,04%

V24-11 45,77% V74-11 63,81% V113-11 79,75% V321-11 54,62%

V24-11 28,82% V74-11 50,50% V113-11 77,68% V321-11 60,25%

V24-11 49,71% V74-11 32,72% V113-11 63,82% V321-11 65,23%

V24-11 42,61% V74-11 31,72% V113-11 68,58% V321-11 71,11%

V24-11 39,63% V74-11 35,36% V113-11 68,73% V321-11 76,09%

V24-11 38,54% V74-11 39,53% V113-11 65,56% V321-11 68,89%

V25-11 62,39% V75-11 31,48% V114-11 67,64% V322-11 56,14%

V25-11 76,01% V75-11 39,57% V114-11 62,96% V322-11 59,71%

V25-11 47,30% V75-11 50,20% V114-11 70,13% V322-11 60,35%

V25-11 51,43% V75-11 57,68% V114-11 62,27% V322-11 63,61%

V25-11 67,56% V75-11 47,76% V114-11 67,67% V322-11 55,99%

V25-11 66,43% V75-11 40,20% V114-11 76,34% V322-11 52,82%

V25-11 54,14% V75-11 50,99% V114-11 69,90% V322-11 64,88%

V25-11 66,44% V75-11 27,44% V114-11 69,42% V322-11 59,72%

V25-11 69,22% V75-11 35,68% V114-11 55,54% V322-11 63,09%

V25-11 72,11% V75-11 55,63% V114-11 47,54% V322-11 60,60%

V26-11 57,52% V76-11 55,23% V115-11 54,57% V323-11 52,55%

V26-11 51,35% V76-11 54,92% V115-11 67,86% V323-11 37,74%

V26-11 47,27% V76-11 44,35% V115-11 66,66% V323-11 54,02%

V26-11 55,97% V76-11 57,53% V115-11 61,46% V323-11 66,55%

V26-11 54,43% V76-11 59,31% V115-11 42,88% V323-11 71,97%

V26-11 47,50% V76-11 41,69% V115-11 77,80% V323-11 63,42%

V26-11 62,83% V76-11 56,91% V115-11 82,61% V323-11 64,31%

V26-11 65,28% V76-11 67,02% V115-11 76,83% V323-11 68,32%

124 Tab. 8.4.7: continued

UV-DH82CDVai

Animal 44 dtp Animal 54 dtp - - Animal 77 dtp V26-11 33,40% V76-11 58,77% V115-11 66,06% V323-11 79,74%

V26-11 45,69% V76-11 27,77% V115-11 66,25% V323-11 62,89%

V27-11 29,90% V77-11 34,77% - - V324-11 31,12%

V27-11 25,94% V77-11 38,51% - - V324-11 30,57%

V27-11 33,87% V77-11 40,17% - - V324-11 33,00%

V27-11 45,16% V77-11 58,23% - - V324-11 44,09%

V27-11 21,19% V77-11 54,21% - - V324-11 46,54%

V27-11 27,54% V77-11 53,99% - - V324-11 34,33%

V27-11 26,67% V77-11 35,42% - - V324-11 40,14%

V27-11 36,66% V77-11 25,46% - - V324-11 53,55%

V27-11 45,15% V77-11 45,58% - - V324-11 64,11%

V27-11 30,14% V77-11 34,62% - - V324-11 28,67%

MMP = matrix metalloproteinase; CDV = canine distemper virus (Onderstepoort strain);

DH82CDVai = acutely CDV infected xenografts; non-infected DH82 = non-treated xenografts (control group); UV-DH82CDVai = UV-inactivated CDV acutely infected DH82 xenografts (control group);dtp = days after transplantation

Tab. 8.4.8: Immunohistochemical expression of MMP-9 in subcutaneously xenotransplanted (DH82 cells). Values depicted display the percentage of immunopositive area in 10 randomly selected fields from the tumor periphery.

DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V28-11 89.73% V78-11 62.46% V117-11 26.28% V310-11 46.13%

V28-11 86.38% V78-11 75.13% V117-11 41.83% V310-11 56.36%

V28-11 82.22% V78-11 61.37% V117-11 32.23% V310-11 40.99%

V28-11 87.96% V78-11 81.48% V117-11 15.71% V310-11 45.96%

V28-11 71.61% V78-11 79.49% V117-11 39.86% V310-11 40.48%

V28-11 85.72% V78-11 80.05% V117-11 3.12539e V310-11 40.42%

V28-11 86.52% V78-11 69.53% V117-11 42.36% V310-11 49.79%

V28-11 83.09% V78-11 60.37% V117-11 51.93% V310-11 52.16%

V28-11 86.55% V78-11 78.16% V117-11 28.91% V310-11 47.86%

V28-11 89.96% V78-11 54.73% V117-11 27.06% V310-11 53.87%

V29-11 81.29% V79-11 84.36% V118-11 66.28% V312-11 27.43%

V29-11 84.35% V79-11 81.83% V118-11 45.47% V312-11 25.90%

V29-11 77.78% V79-11 44.83% V118-11 48.95% V312-11 31.03%

V29-11 85.47% V79-11 82.38% V118-11 28.47% V312-11 43.80%

V29-11 86.08% V79-11 88.39% V118-11 46.49% V312-11 41.44%

V30-11 90.12% V79-11 85.66% V118-11 40.42% V312-11 43.36%

V30-11 69.82% V79-11 68.91% V118-11 42.78% V312-11 33.10%

125 Tab. 8.4.8: continued

DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V30-11 93.99% V79-11 85.85% V118-11 51.56% V312-11 32.78%

V30-11 71.48% V79-11 65.07% V118-11 52.50% V312-11 32.53%

V30-11 60.79% V79-11 79.14% V118-11 49.33% V312-11 21.22%

V30-11 84.79% V80-11 83.03% V119-11 76.83% V313-11 36.34%

V30-11 83.64% V80-11 82.56% V119-11 52.57% V313-11 49.91%

V30-11 60.28% V80-11 78.68% V119-11 38.52% V313-11 42.99%

V30-11 81.35% V80-11 68.99% V119-11 45.58% V313-11 35.26%

V30-11 82.25% V80-11 69.00% V119-11 40.19% V313-11 59.44%

V30-11 79.69% V80-11 58.19% V119-11 39.73% V313-11 60.59%

V32-11 92.89% V80-11 68.72% V119-11 20.02% V313-11 52.60%

V32-11 83.06% V80-11 61.07% V119-11 54.10% V313-11 49.45%

V32-11 72.68% V80-11 26.60% V119-11 42.43% V313-11 40.61%

V32-11 87.88% V80-11 42.89% V119-11 5.02% V313-11 52.02%

V33-11 85.99% V81-11 48.86% V120-11 56.26% V314-11 33.42%

V33-11 94.68% V81-11 24.15% V120-11 74.91% V314-11 26.68%

- - V81-11 19.27% V120-11 67.66% V314-11 28.03%

- - V81-11 25.65% V120-11 54.89% V314-11 46.59%

- - V81-11 14.48% V120-11 54.95% V314-11 42.31%

- - V81-11 39.53% V121-11 33.30% V314-11 43.19%

- - V81-11 41.61% V121-11 19.41% V314-11 41.26%

- - V81-11 37.02% V121-11 35.88% V314-11 19.39%

- - V81-11 41.56% V121-11 35.69% V314-11 10.76%

- - V81-11 56.19% V121-11 35.82% V314-11 17.65%

- - V82-11 63.19% V121-11 27.73% - -

- - V82-11 47.50% V121-11 27.58% - -

- - V82-11 77.87% V121-11 16.67% - -

- - V82-11 55.83% V121-11 19.54% - -

- - V82-11 55.12% V121-11 2.23% - -

- - V82-11 34.24% - - - -

- - V82-11 62.68% - - - -

- - V82-11 67.73% - - - -

- - V82-11 74.06% - - - -

- - V82-11 64.73% - - - -

- - V83-11 90.07% - - - -

- - Animal 54 dtp - - - -

- - V83-11 84.90% - - - -

- - V83-11 40.90% - - - -

- - V83-11 40.97% - - - -

- - V83-11 65.32% - - - -

- - V83-11 93.74% - - - -

- - V83-11 87.80% - - - -

126 Tab. 8.4.8: continued

DH82CDVai

- - V83-11 72.14% - - - -

- - V83-11 96.57% - - - -

- - V83-11 54.29% - - - -

Non-infected DH82

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V10-11 54.30% V60-11 46.25% V98-11 53.46% V1088-11 16.85%

V10-11 43.68% V60-11 55.79% V98-11 53.42% V1088-11 16.91%

V10-11 49.39% V60-11 68.18% V98-11 50.69% V1088-11 18.28%

V10-11 32.86% V60-11 55.21% V98-11 62.84% V1088-11 10.12%

V10-11 63.53% V60-11 46.93% V98-11 59.37% V1088-11 15.14%

V10-11 56.61% V60-11 74.24% V98-11 12.74% V1088-11 15.83%

V10-11 55.12% V60-11 74.13% V98-11 45.42% V1088-11 13.89%

V10-11 75.06% V60-11 71.43% V98-11 57.43% V1088-11 15.94%

V10-11 83.05% V60-11 73.92% V98-11 53.52% V1088-11 15.22%

V10-11 86.6748 V61-11 74.83% V98-11 38.86% V1088-11 14.62%

V11-11 73.57% V61-11 65.42% V99-11 34.96% V1089-11 63.53%

V11-11 53.78% V61-11 79.00% V99-11 52.46% V1089-11 69.84%

V11-11 67.73% V61-11 55.47% V99-11 78.21% V1089-11 70.11%

V11-11 64.71% V61-11 57.00% V99-11 86.57% V1089-11 70.41%

V11-11 59.83% V61-11 68.03% V99-11 77.23% V1089-11 68.53%

V11-11 59.42% V61-11 59.55% V99-11 73.68% V1089-11 57.06%

V11-11 69.93% V61-11 60.66% V99-11 68.68% V1089-11 50.22%

V11-11 69.38% V61-11 71.27% V99-11 72.96% V1089-11 56.94%

V11-11 59.78% V61-11 41.24% V99-11 61.78% V1089-11 64.34%

V11-11 66.62% V61-11 75.39% V99-11 61.65% V1089-11 59.57%

V13-11 89.36% V62-11 61.79% V100-11 43.56% V1090-11 22.06%

V13-11 89.44% V62-11 57.04% V100-11 54.82% V1090-11 18.62%

V13-11 82.09% V62-11 55.06% V100-11 47.80% V1090-11 22.81%

V13-11 84.04% V62-11 22.12% V100-11 53.02% V1090-11 27.71%

V13-11 89.72% V62-11 31.77% V100-11 60.52% V1090-11 20.07%

V13-11 86.81% V62-11 32.93% V100-11 68.61% V1090-11 24.85%

V13-11 73.77% V62-11 35.93% V100-11 80.57% V1090-11 29.30%

V13-11 66.30% V62-11 51.50% V100-11 79.66% V1090-11 29.94%

V13-11 79.64% V62-11 54.03% V100-11 67.13% V1090-11 24.64%

V13-11 55.42% V62-11 23.97% V100-11 62.80% V1090-11 15.78%

V14-11 28.36% V63-11 63.89% V101-11 55.26% V1091-11 71.36%

V14-11 7.88% V63-11 74.94% V101-11 59.13% V1091-11 77.47%

V14-11 8.70% V63-11 70.86% V101-11 49.40% V1091-11 72.35%

V14-11 5.92% V63-11 67.80% V101-11 52.65% V1091-11 73.27%

V14-11 12.67% V63-11 68.05% V101-11 63.79% V1091-11 53.53%

V14-11 4.84% V63-11 76.73% V101-11 62.37% V1091-11 53.33%

V14-11 7.52% V63-11 45.31% V101-11 62.49% V1091-11 74.04%

127 Tab. 8.4.8: continued

Non-infected DH82

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V14-11 8.48% V63-11 58.48% V101-11 51.30% V1091-11 67.80%

V14-11 20.14% V63-11 71.88% V101-11 36.98% V1091-11 66.69%

V14-11 7.93% V63-11 76.73% V101-11 45.02% V1091-11 80.18%

V15-11 85.73% V64-11 79.10% V102-11 31.30% - - V15-11 72.63% V64-11 88.06% V102-11 11.73% - - V15-11 69.92% V64-11 92.34% V102-11 16.32% - - V15-11 35.75% V64-11 84.93% V102-11 16.70% - - V15-11 43.32% V64-11 88.21% V102-11 16.18% - - V15-11 51.89% V64-11 92.61% V102-11 25.01% - - V15-11 46.13% V64-11 91.24% V102-11 16.93% - - V15-11 64.70% V64-11 89.56% V102-11 1.02% - - V15-11 63.21% V64-11 85.31% V102-11 2.79% - - V15-11 86.53% V64-11 94.85% V102-11 7.10% - -

- - V65-11 44.07% V103-11 61.33% - -

- - V65-11 32.87% V103-11 61.24% - -

- - V65-11 5.42% V103-11 62.63% - -

- - V65-11 3.96% V103-11 66.75% - -

- - V65-11 21.01% V103-11 57.29% - -

- - V65-11 33.55% V103-11 41.55% - -

- - V65-11 27.75% V103-11 41.55% - -

- - V65-11 25.13% V103-11 37.13% - -

- - V65-11 41.41% V103-11 27.98% - -

- - V65-11 57.61% V103-11 60.67% - -

UV-DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V22-11 54.56% V72-10 73.32% V 110-11 80.59% V319-11 38.05%

V22-11 34.90% V72-10 73.77% V 110-11 78.08% V319-11 40.96%

V22-11 38.92% V72-10 68.93% V 110-11 49.55% V319-11 36.25%

V22-11 23.68% V72-10 57.07% V 110-11 43.54% V319-11 19.13%

V22-11 40.19% V72-10 52.68% V 110-11 18.24% V319-11 27.62%

V22-11 27.16% V72-10 32.43% V 110-11 7.11% V319-11 42.82%

V22-11 42.90% V72-10 34.73% V 110-11 32.10% V319-11 9.05%

V22-11 46.13% V72-10 37.52% V 110-11 60.01% V319-11 15.78%

V22-11 45.04% V72-10 21.11% V 110-11 70.94% V319-11 19.59%

V22-11 58.27% V72-10 58.24% V 110-11 81.46% V319-11 39.40%

V23-11 44.13% V73-10 34.38% V 111-11 52.14% V320-11 69.74%

V22-11 71.43% V73-10 34.06% V 111-11 46.51% V320-11 66.97%

V22-11 58.54% V73-10 39.05% V 111-11 69.41% V320-11 11.94%

V23-11 36.65% V73-10 41.31% V 111-11 74.95% V320-11 12.88%

V23-11 29.41% V73-10 45.15% V 111-11 87.32% V320-11 10.53%

V23-11 51.85% V73-10 49.07% V 111-11 92.63% V320-11 13.33%

128 Tab. 8.4.8: continued

UV-DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V23-11 20.85% V73-10 28.81% V 111-11 76.97% V320-11 10.28%

V23-11 39.26% V73-10 12.18% V 111-11 65.99% V320-11 12.16%

V23-11 15.49% V73-10 23.39% V 111-11 91.15% V320-11 26.12%

V23-11 20.91% V73-10 31.35% V 111-11 92.35% V320-11 25.97%

V24-11 60.51% V74-10 26.68% V 112-11 13.80% V321-11 15.78%

V24-11 79.95% V74-10 24.20% V 112-11 17.38% V321-11 45.14%

V24-11 69.93% V74-10 51.60% V 112-11 52.87% V321-11 55.73%

V24-11 63.50% V74-10 56.44% V 112-11 60.72% V321-11 54.18%

V24-11 68.98% V74-10 37.61% V 112-11 41.09% V321-11 70.43%

V24-11 67.52% V74-10 54.85% V 112-11 49.51% V321-11 84.63%

V24-11 68.41% V74-10 39.89% V 112-11 28.91% V321-11 77.00%

V24-11 56.79% V74-10 30.95% V 112-11 25.17% V321-11 63.43%

V24-11 68.34% V74-10 24.22% V 112-11 24.64% V321-11 51.13%

V24-11 30.32% V74-10 32.86% V 112-11 56.06% V321-11 41.75%

V25-11 39.88% V75-10 59.20% V 113-11 57.26% V322-11 60.10%

V25-11 50.52% V75-10 60.33% V 113-11 57.76% V322-11 60.78%

V25-11 52.16% V75-10 77.25% V 113-11 69.14% V322-11 63.68%

V25-11 58.02% V75-10 81.11% V 113-11 79.83% V322-11 65.50%

V25-11 58.08% V75-10 84.23% V 113-11 82.05% V322-11 66.53%

V25-11 70.01% V75-10 85.83% V 113-11 69.68% V322-11 64.19%

V25-11 73.49% V75-10 84.49% V 113-11 61.18% V322-11 44.73%

V25-11 77.49% V75-10 89.90% V 113-11 61.68% V322-11 46.79%

V25-11 64.62% V75-10 76.90% V 113-11 31.19% V322-11 49.48%

V25-11 56.62% V75-10 47.83% V 113-11 20.90% V322-11 54.40%

V26-11 58.52% V76-10 67.28% V 114-11 6.32% V323-11 20.76%

V26-11 25.03% V76-10 68.57% V 114-11 59.87% V323-11 13.94%

V26-11 26.29% V76-10 73.55% V 114-11 8.41% V323-11 15.79%

V26-11 44.90% V76-10 70.44% V 114-11 18.58% V323-11 17.38%

V26-11 55.31% V76-10 66.15% V 114-11 31.16% V323-11 20.07%

V27-11 20.86% V76-10 62.53% V 114-11 62.09% V323-11 17.76%

V27-11 38.39% V76-10 69.50% V 114-11 45.77% V323-11 16.35%

V27-11 45.49% V76-10 63.44% V 114-11 50.83% V323-11 16.15%

V27-11 33.56% V76-10 56.78% V 114-11 38.62% V323-11 18.67%

V27-11 33.49% V76-10 74.48% V 114-11 61.83% V323-11 9.54%

V27-11 36.39% V77-10 53.99% V 115-11 81.36% V324-11 55.29%

V27-11 26.40% V77-10 53.61% V 115-11 72.29% V324-11 66.96%

V27-11 45.15% V77-10 64.74% V 115-11 74.85% V324-11 65.51%

V27-11 32.41% V77-10 71.48% V 115-11 78.33% V324-11 71.76%

V27-11 31.73% V77-10 62.04% V 115-11 73.89% V324-11 74.83%

- - V77-10 63.15% V 115-11 70.19% V324-11 86.35%

- - V77-10 55.51% V 115-11 55.82% V324-11 82.56%

129 Tab. 8.4.8: continued

UV-DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp - - V77-10 45.03% V 115-11 78.99% V324-11 71.67%

- - V77-10 51.09% V 115-11 88.11% V324-11 55.73%

MMP = matrix metalloproteinase; CDV = canine distemper virus (Onderstepoort strain);

DH82CDVai = acutely CDV infected xenografts; non-infected DH82 = non-treated xenografts (control group); UV-DH82CDVai = UV-inactivated CDV acutely infected DH82 xenografts (control group);dtp = days after transplantation

Tab. 8.4.9: Immunohistochemical expression of MMP-9 in subcutaneously xenotransplanted (DH82 cells). Values depicted display the percentage of immunopositive area in 10 randomly selected fields from the tumor center.

DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V28-11 15.79% V78-11 81.80% V117-11 7.17% V310-11 59.51%

V28-11 85.92% V78-11 66.81% V117-11 17.91% V310-11 52.47%

V28-11 19.96% V78-11 69.06% V117-11 35.24% V310-11 57.58%

V28-11 20.52% V78-11 56.82% V117-11 15.34% V310-11 56.87%

V28-11 69.88% V78-11 53.95% V117-11 3.62% V310-11 66.45%

V28-11 43.79% V78-11 70.78% V117-11 11.79% V310-11 62.91%

V28-11 87.35% V78-11 44.17% V117-11 4.13% V310-11 56.93%

V28-11 22.65% V78-11 34.28% V117-11 14.32% V310-11 48.61%

V28-11 38.98% V78-11 77.26% V117-11 22.42% V310-11 42.25%

V28-11 14.99% V78-11 68.75% V117-11 17.95% V310-11 47.66%

V29-11 83.01% V79-11 10.26% V118-11 11.60% V312-11 4.17%

V29-11 11.23% V79-11 11.80% V118-11 29.91% V312-11 5.21%

V29-11 58.13% V79-11 7.84% V118-11 25.97% V312-11 3.50%

V29-11 83.47% V79-11 35.10% V118-11 3.80% V312-11 2.49%

V29-11 55.46% V79-11 17.41% V118-11 2.73% V312-11 4.86%

V31-11 49.20% V79-11 20.65% V118-11 6.45% V312-11 4.86%

V31-11 51.53% V79-11 40.06% V118-11 7.89% V312-11 6.48%

V31-11 33.10% V79-11 28.99% V118-11 9.77% V312-11 4.99%

V31-11 29.33% V79-11 10.81% V118-11 5.25% V312-11 2.19%

V31-11 9.94% V79-11 6.64% V118-11 12.49% V312-11 1.32%

V31-11 21.46% V80-11 49.62% V119-11 15.06% V313-11 48.58%

V31-11 9.26% V80-11 33.46% V119-11 10.92% V313-11 47.64%

V31-11 4.41% V80-11 25.56% V119-11 28.41% V313-11 37.78%

V31-11 8.35% V80-11 17.63% V119-11 13.20% V313-11 40.98%

V31-11 30.07% V80-11 57.73% V119-11 8.69% V313-11 24.23%

V32-11 43.83% V80-11 32.99% V119-11 4.53% V313-11 35.37%

V32-11 57.44% V80-11 40.63% V119-11 16.35% V313-11 45.71%

130 Tab. 8.4.9: continued

DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V32-11 88.71% V80-11 51.50% V119-11 10.24% V313-11 34.86%

V33-11 82.92% V80-11 32.52% V119-11 13.12% V313-11 42.47%

V33-11 38.98% V80-11 29.21% V119-11 19.03% V313-11 36.60%

- - V81-11 5.18% V120-11 36.17% V314-11 19.31%

- - V81-11 6.18% V120-11 43.41% V314-11 19.35%

- - V81-11 8.86% V120-11 43.83% V314-11 21.61%

- - V81-11 6.90% V121-11 4.38% V314-11 26.93%

- - V81-11 9.68% V121-11 3.09% V314-11 34.53%

- - V81-11 10.02% V121-11 2.34% V314-11 37.80%

- - V81-11 8.30% V121-11 2.60% V314-11 12.73%

- - V81-11 3.53% V121-11 3.58% V314-11 22.61%

- - V81-11 6.47% V121-11 5.78% V314-11 13.34%

- - V81-11 6.85% V121-11 18.15% V314-11 10.14%

- - V82-11 26.05% V121-11 6.92% - -

- - V82-11 25.85% V121-11 2.11% - -

- - V82-11 59.03% V121-11 12.12% - -

- - V82-11 58.92% - - - -

- - V82-11 63.82% - - - -

- - V82-11 41.03% - - - -

- - V82-11 36.48% - - - -

- - V82-11 50.87% - - - -

- - V82-11 41.66% - - - -

- - V82-11 30.89% - - - -

- - V82-11 24.63% - - - -

- - V83-11 25.29% - - - -

- - V83-11 37.13% - - - -

- - V83-11 48.28% - - - -

- - V83-11 32.73% - - - -

- - V83-11 24.60% - - - -

- - V83-11 26.00% - - - -

- - V83-11 21.74% - - - -

- - V83-11 29.24% - - - -

- - V83-11 31.17% - - - -

Non-infected DH82

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V10-11 5.70% V60-11 1.32% V98-11 6.83% V1087-11 39.44%

V10-11 30.21% V60-11 20.93% V98-11 14.72% V1087-11 35.53%

V10-11 9.47% V60-11 23.51% V98-11 16.17% V1087-11 38.31%

V10-11 8.25% V60-11 60.57% V98-11 24.37% V1088-11 62.48%

V10-11 11.99% V60-11 54.78% V98-11 28.18% V1088-11 61.55%

V10-11 28.50% V60-11 51.70% V98-11 29.56% V1088-11 47.38%

131 Tab. 8.4.9: continued

Non-infected DH82

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V10-11 8.58% V60-11 8.26% V98-11 43.85% V1088-11 48.15%

V10-11 11.48% V60-11 8.91% V98-11 27.67% V1088-11 44.47%

V10-11 23.81% V60-11 4.00% V98-11 51.69% V1088-11 48.24%

V10-11 21.50% V60-11 6.78% V98-11 34.85% V1088-11 42.69%

V11-11 10.59% V61-11 39.92% V99-11 53.55% V1088-11 51.28%

V11-11 7.71% V61-11 27.30% V99-11 58.14% V1088-11 23.89%

V11-11 6.78% V61-11 39.15% V99-11 52.96% V1088-11 16.95%

V11-11 11.20% V61-11 23.97% V99-11 43.65% V1088-11 19.33%

V11-11 19.03% V61-11 35.02% V99-11 39.54% V1089-11 17.37%

V11-11 25.66% V61-11 31.66% V99-11 35.46% V1089-11 10.91%

V11-11 9.87% V61-11 25.92% V99-11 33.75% V1089-11 11.05%

V11-11 6.25% V61-11 40.22% V99-11 54.95% V1089-11 10.89%

V11-11 21.54% V61-11 42.18% V99-11 31.13% V1089-11 13.65%

V11-11 14.16% V61-11 34.13% V99-11 24.17% V1089-11 14.46%

V13-11 1.95% V62-11 32.92% V100-11 56.19% V1089-11 11.08%

V13-11 25.99% V62-11 45.93% V100-11 67.04% V1089-11 10.83%

V13-11 72.43% V62-11 41.87% V100-11 66.02% V1089-11 4.47%

V13-11 63.77% V62-11 29.88% V100-11 76.02% V1089-11 74.72%

V13-11 70.30% V62-11 11.82% V100-11 47.19% V1090-11 53.99%

V13-11 63.77% V62-11 33.66% V100-11 52.91% V1090-11 60.70%

V13-11 64.56% V62-11 31.07% V100-11 6.84% V1090-11 61.10%

V13-11 72.49% V62-11 13.17% V100-11 55.32% V1090-11 57.60%

V13-11 65.24% V62-11 8.13% V100-11 39.14% V1090-11 55.23%

V13-11 68.00% V62-11 34.04% V100-11 56.15% V1090-11 56.41%

V14-11 4.14% V63-11 42.51% V101-11 35.92% V1090-11 62.68%

V14-11 8.15% V63-11 45.09% V101-11 25.42% V1090-11 61.64%

V14-11 6.93% V63-11 30.82% V101-11 28.37% V1090-11 64.55%

V14-11 9.93% V63-11 33.78% V101-11 28.38% V1090-11 32.49%

V14-11 1.95% V63-11 35.90% V101-11 26.57% V1091-11 30.36%

V14-11 1.96% V63-11 25.11% V101-11 41.32% V1091-11 20.00%

V14-11 1.46% V63-11 25.45% V101-11 58.92% V1091-11 19.47%

V14-11 6.06% V63-11 29.98% V101-11 55.17% V1091-11 22.73%

V14-11 5.31% V63-11 33.22% V101-11 35.16% V1091-11 16.26%

V14-11 4.83% V63-11 32.56% V101-11 26.15% V1091-11 24.64%

V15-11 5.20% V64-11 43.11% V102-11 1.37% V1091-11 43.53%

V15-11 5.50% V64-11 50.32% V102-11 2.76% V1091-11 42.63%

V15-11 11.13% V64-11 55.43% V102-11 3.88% V1091-11 29.38%

V15-11 15.56% V64-11 60.21% V102-11 3.66% - - V15-11 4.18% V64-11 66.95% V102-11 2.70% - - V15-11 7.63% V64-11 67.56% V102-11 4.85% - - V15-11 19.49% V64-11 20.06% V102-11 1.60% - -

132 Tab. 8.4.9: continued

Non-infected DH82

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V15-11 34.38% V64-11 51.76% V102-11 2.61% - - V15-11 66.43% V64-11 36.73% V102-11 2.43% - - V15-11 62.03% V64-11 17.37% V102-11 6.84% - -

- - V65-11 18.13% V103-11 39.87% - -

- - V65-11 13.69% V103-11 42.33% - -

- - V65-11 13.88% V103-11 29.27% - -

- - V65-11 16.87% V103-11 24.15% - -

- - V65-11 1.27% V103-11 24.05% - -

- - V65-11 7.51% V103-11 32.15% - -

- - V65-11 5.37% V103-11 33.41% - -

- - V65-11 2.31% V103-11 38.29% - -

- - V65-11 7.85% V103-11 25.08% - -

- - V65-11 1.43% V103-11 36.84% - -

UV-DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V22-11 8.24% V72-10 5.96% V 110-11 24.06% V319-11 43.32%

V22-11 12.32% V72-10 20.50% V 110-11 16.69% V319-11 27.73%

V22-11 1.68% V72-10 44.71% V 110-11 48.80% V319-11 19.71%

V22-11 1.94% V72-10 38.93% V 110-11 53.58% V319-11 23.35%

V22-11 34.47% V72-10 38.90% V 110-11 70.42% V319-11 14.61%

V22-11 25.22% V72-10 33.86% V 110-11 43.86% V319-11 8.78%

V22-11 13.49% V72-10 12.25% V 110-11 33.69% V319-11 8.05%

V22-11 1.61% V72-10 6.83% V 110-11 32.13% V319-11 6.84%

V22-11 3.22% V72-10 36.06% V 110-11 34.55% V319-11 10.01%

V22-11 7.05% V72-10 35.83% V 110-11 23.25% V319-11 15.91%

V23-11 6.48% V73-10 39.14% V 111-11 7.52% V320-11 73.78%

V23-11 1.82% V73-10 16.34% V 111-11 53.76% V320-11 46.58%

V23-11 5.54% V73-10 23.23% V 111-11 53.47% V320-11 35.91%

V23-11 10.29% V73-10 13.76% V 111-11 67.38% V320-11 28.11%

V23-11 10.13% V73-10 7.75% V 111-11 53.89% V320-11 38.99%

V23-11 2.40% V73-10 10.98% V 111-11 43.41% V320-11 58.61%

V23-11 1.06% V73-10 9.67% V 111-11 65.28% V320-11 32.56%

V23-11 14.75% V73-10 6.29% V 111-11 11.19% V320-11 20.18%

V23-11 3.99% V73-10 8.81% V 111-11 10.63% V320-11 41.01%

V23-11 2.59% V73-10 7.68% V 111-11 11.66% V320-11 39.64%

V24-11 20.87% V74-10 1.13% V 112-11 23.88% V321-11 27.07%

V24-11 1.63% V74-10 2.45% V 112-11 32.19% V321-11 24.30%

V24-11 5.12% V74-10 9.41% V 112-11 25.76% V321-11 24.26%

V24-11 1.71% V74-10 1.73% V 112-11 43.00% V321-11 15.66%

V24-11 8.21% V74-10 2.19% V 112-11 32.13% V321-11 13.18%

V24-11 7.52% V74-10 5.23% V 112-11 37.10% V321-11 8.84%

133 Tab. 8.4.9: continued

UV-DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V24-11 6.86% V74-10 4.65% V 112-11 26.09% V321-11 5.02%

V24-11 4.81% V74-10 4.58% V 112-11 34.19% V321-11 7.90%

V24-11 8.03% V74-10 9.41% V 112-11 46.24% V321-11 5.52%

V24-11 11.30% V74-10 5.37% V 112-11 36.61% V321-11 2.85%

V25-11 4.88% V75-10 12.98% V 113-11 26.92% V322-11 37.32%

V25-11 5.68% V75-10 9.64% V 113-11 36.09% V322-11 32.22%

V25-11 2.08% V75-10 30.66% V 113-11 36.46% V322-11 55.82%

V25-11 3.64% V75-10 54.70% V 113-11 28.72% V322-11 39.86%

V25-11 1.90% V75-10 11.00% V 113-11 23.54% V322-11 39.85%

V25-11 1.41% V75-10 48.77% V 113-11 34.16% V322-11 39.41%

V25-11 4.42% V75-10 41.97% V 113-11 34.16% V322-11 20.45%

V25-11 7.92% V75-10 7.26% V 113-11 23.03% V322-11 24.10%

V25-11 7.28% V75-10 38.50% V 113-11 29.31% V322-11 28.84%

V25-11 7.93% V75-10 48.51% V 113-11 36.03% V322-11 32.74%

V26-11 5.63% V76-10 38.50% V 114-11 14.66% V323-11 9.48%

V26-11 3.48% V76-10 70.25% V 114-11 12.03% V323-11 7.68%

V26-11 5.91% V76-10 25.45% V 114-11 15.67% V323-11 4.84%

V26-11 21.94% V76-10 62.77% V 114-11 12.49% V323-11 1.64%

V26-11 15.73% V76-10 19.18% V 114-11 11.42% V323-11 6.30%

V27-11 6.83% V76-10 6.45% V 114-11 31.48% V323-11 6.15%

V27-11 3.65% V76-10 5.68% V 114-11 4.93% V323-11 7.93%

V27-11 8.88% V76-10 1.51% V 114-11 19.20% V323-11 4.24%

V27-11 20.37% V76-10 5.94% V 114-11 4.18% V323-11 3.56%

V27-11 16.20% V76-10 7.50% V 114-11 18.44% V323-11 3.24%

V27-11 29.37% V77-10 14.84% V 115-11 50.02% V324-11 51.23%

V27-11 5.31% V77-10 17.97% V 115-11 16.76% V324-11 62.50%

V27-11 2.47% V77-10 14.12% V 115-11 37.24% V324-11 58.90%

V27-11 10.70% V77-10 42.50% V 115-11 37.52% V324-11 70.17%

V27-11 16.53% V77-10 24.21% V 115-11 37.52% V324-11 59.91%

- - V77-10 12.67% V 115-11 34.74% V324-11 59.91%

- - V77-10 40.65% V 115-11 40.30% V324-11 61.25%

- - V77-10 4.06% V 115-11 27.71% V324-11 55.61%

- - V77-10 15.98% V 115-11 25.48% V324-11 59.62%

- - V77-10 17.39% V 115-11 26.41% V324-11 41.41%

MMP = matrix metalloproteinase; CDV = canine distemper virus (Onderstepoort strain);

DH82CDVai = acutely CDV infected xenografts; non-infected DH82 = non-treated xenografts (control group); UV-DH82CDVai = UV-inactivated CDV acutely infected DH82 xenografts (control group);dtp = days after transplantation

134

Tab. 8.4.10: Immunohistochemical expression of MMP-14 in subcutaneously xenotransplanted (DH82 cells). Values depicted display the percentage of immunopositive area in 10 randomly selected fields from the tumor periphery.

DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V28-11 97.02% V78-11 54.97% V117-11 62.03% V310-10 96.63%

V28-11 95.87% V78-11 65.44% V117-11 60.51% V310-10 96.33%

V28-11 86.92% V78-11 70.38% V117-11 23.92% V310-10 95.00%

V28-11 83.75% V78-11 77.68% V117-11 65.92% V310-10 97.56%

V28-11 75.52% V78-11 84.78% V117-11 56.20% V310-10 97.39%

V28-11 86.73% V78-11 66.91% V117-11 26.94% V310-10 96.35%

V28-11 85.07% V78-11 59.08% V117-11 53.99% V310-10 97.35%

V28-11 90.01% V78-11 44.69% V117-11 64.62% V310-10 96.38%

V28-11 87.32% V78-11 43.91% V117-11 29.09% V310-10 97.10%

V28-11 78.43% V78-11 69.11% V117-11 32.08% V310-10 97.91%

V29-11 84.57% V79-11 84.17% V118-11 62.88% V312-10 44.58%

V29-11 91.48% V79-11 83.87% V118-11 85.91% V312-10 69.44%

V29-11 92.03% V79-11 87.57% V118-11 86.80% V312-10 45.88%

V29-11 94.11% V79-11 87.57% V118-11 75.79% V312-10 71.86%

V29-11 84.71% V79-11 89.81% V118-11 81.21% V312-10 64.05%

V29-11 71.00% V79-11 83.32% V118-11 87.19% V312-10 82.80%

V29-11 80.97% V79-11 89.82% V118-11 87.41% V312-10 89.91%

V29-11 77.28% V79-11 85.02% V118-11 93.59% V312-10 91.52%

V29-11 90.19% V79-11 83.32% V118-11 62.89% V312-10 83.53%

V29-11 90.34% V79-11 89.45% V118-11 69.88% V312-10 76.44%

V30-11 76.77% V80-11 75.72% V119-11 40.19% V313-10 94.41%

V30-11 66.93% V80-11 75.51% V119-11 61.26% V313-10 97.57%

V30-11 74.01% V80-11 77.82% V119-11 42.67% V313-10 90.17%

V30-11 74.45% V80-11 65.58% V119-11 69.99% V313-10 99.31%

V30-11 86.05% V80-11 55.96% V119-11 66.32% V313-10 98.11%

V30-11 91.53% V80-11 73.81% V119-11 78.95% V313-10 96.38%

V30-11 82.56% V80-11 77.93% V119-11 62.89% V313-10 95.60%

V30-11 79.21% V80-11 65.63% V119-11 62.02% V313-10 97.60%

V30-11 81.68% V80-11 79.89% V119-11 65.52% V313-10 94.79%

V30-11 86.49% V80-11 65.63% V119-11 57.19% V313-10 91.58%

V31-11 70.65% V81-11 56.66% V120-11 55.37% V314-10 90.93%

V31-11 76.93% V81-11 82.28% V120-11 31.80% V314-10 97.56%

V31-11 77.23% V81-11 84.93% V120-11 51.42% V314-10 86.15%

V31-11 78.37% V81-11 77.19% V120-11 60.12% V314-10 88.21%

V31-11 75.99% V81-11 64.17% V120-11 42.72% V314-10 88.92%

V31-11 64.64% V81-11 62.46% V121-11 77.18% V314-10 80.89%

135 Tab. 8.4.10: continued

Tab. 8.4.10: continued

DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V31-11 60.38% V81-11 61.68% V121-11 82.25% V314-10 76.21%

V31-11 82.08% V81-11 72.53% V121-11 63.54% V314-10 56.33%

V31-11 68.26% V81-11 70.88% V121-11 85.83% V314-10 69.67%

V31-11 78.80% V81-11 70.40% V121-11 81.50% V314-10 68.08%

V32-11 90.59% V82-11 60.74% V121-11 63.96% - - V32-11 98.70% V82-11 57.51% V121-11 46.43% - - V32-11 98.28% V82-11 80.08% V121-11 81.17% - - V32-11 87.50% V82-11 71.57% V121-11 61.66% - -

V32-11 64.21% V82-11 71.29% - - - -

V32-11 94.41% V82-11 78.55% - - - -

V32-11 95.67% V82-11 86.31% - - - -

V32-11 82.88% V82-11 70.29% - - - -

V32-11 97.43% V82-11 86.09% - - - -

V32-11 90.83% V82-11 85.65% - - - -

V33-11 84.73% V83-11 89.71% - - - -

V33-11 98.78% V83-11 88.21% - - - -

V33-11 94.81% V83-11 79.41% - - - -

V33-11 95.84% V83-11 82.44% - - - -

V33-11 92.00% V83-11 79.44% - - - -

- - V83-11 89.13% - - - -

- - V83-11 92.79% - - - -

- - V83-11 92.37% - - - -

- - V83-11 91.02% - - - -

Non-infected DH82

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V10-11 94.91% V61-11 63.85% V98-11 84.43% V1087-09 98.86%

V10-11 89.56% V61-11 77.11% V98-11 92.97% V1087-09 99.03%

V10-11 92.08% V61-11 76.91% V98-11 94.51% V1087-09 97.52%

V10-11 88.11% V61-11 80.11% V98-11 89.47% V1088-09 81.73%

V10-11 90.28% V61-11 60.22% V98-11 95.98% V1088-09 92.55%

V10-11 80.64% V61-11 68.62% V98-11 97.35% V1088-09 81.69%

V10-11 85.00% V61-11 58.43% V98-11 96.13% V1088-09 92.01%

V10-11 84.65% V61-11 59.86% V98-11 89.54% V1088-09 96.06%

V10-11 63.01% V61-11 63.69% V98-11 26.39% V1088-09 84.86%

V10-11 90.88% V61-11 56.75% V98-11 19.14% V1088-09 89.65%

V11-11 93.59% V62-11 89.92% V99-11 92.71% V1088-09 86.33%

V11-11 91.97% V62-11 89.80% V99-11 92.57% V1088-09 82.51%

V11-11 95.30% V62-11 88.14% V99-11 89.40% V1088-09 82.41%

V11-11 93.79% V62-11 90.69% V99-11 89.20% V1089-09 83.61%

136 Tab. 8.4.10: continued

Non-infected DH82

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V11-11 96.37% V62-11 52.92% V99-11 86.12% V1089-09 83.67%

V11-11 98.17% V62-11 75.45% V99-11 88.89% V1089-09 89.98%

V11-11 98.84% V62-11 82.19% V99-11 95.57% V1089-09 91.91%

V11-11 96.02% V62-11 80.16% V99-11 93.99% V1089-09 87.40%

V11-11 96.91% V62-11 84.24% V99-11 95.64% V1089-09 83.89%

V11-11 96.74% V62-11 88.68% V99-11 92.91% V1089-09 86.50%

V12-11 57.66% V63-11 72.84% V100-11 87.68% V1089-09 85.17%

V12-11 54.61% V63-11 88.33% V100-11 87.68% V1089-09 93.50%

V12-11 73.35% V63-11 74.01% V100-11 93.13% V1089-09 91.07%

V12-11 77.14% V63-11 56.28% V100-11 78.33% V1090-09 94.37%

V12-11 59.87% V63-11 50.25% V100-11 75.60% V1090-09 98.47%

V12-11 64.13% V63-11 70.66% V100-11 92.33% V1090-09 94.65%

V12-11 81.94% V63-11 86.00% V100-11 86.52% V1090-09 98.29%

V12-11 44.34% V63-11 86.00% V100-11 91.32% V1090-09 98.86%

V12-11 83.94% V63-11 86.99% V100-11 88.21% V1090-09 97.45%

V12-11 84.32% V63-11 80.41% V100-11 88.41% V1090-09 98.44%

V13-11 92.78% V65-11 68.96% V101-11 59.27% V1090-09 98.47%

V13-11 98.16% V65-11 89.69% V101-11 80.56% V1090-09 90.91%

V13-11 94.24% V65-11 56.18% V101-11 94.20% V1090-09 79.02%

V13-11 96.81% V65-11 70.18% V101-11 89.97% V1091-09 97.97%

V13-11 96.27% V65-11 58.63% V101-11 95.40% V1091-09 98.26%

V13-11 96.27% V65-11 93.52% V101-11 89.16% V1091-09 98.26%

V13-11 91.66% V65-11 87.04% V101-11 91.30% V1091-09 94.54%

V13-11 68.35% V65-11 87.04% V101-11 91.10% V1091-09 96.91%

V13-11 71.07% V65-11 96.02% V101-11 84.07% V1091-09 82.97%

V13-11 57.53% V65-11 86.78% V101-11 89.71% V1091-09 94.90%

V14-11 32.85% - - V102-11 94.04% V1091-09 91.23%

V14-11 56.00% - - V102-11 94.83% V1091-09 86.69%

137 Tab. 8.4.10: continued

Tab. 8.4.10: continued

Non-infected DH82

Animal 44 dtp - - Animal 63 dtp Animal 77 dtp V14-11 55.61% - - V102-11 98.26% V1091-09 93.24%

V14-11 32.97% - - V102-11 95.54% - -

V14-11 69.03% - - V102-11 93.48% - -

V14-11 31.73% - - V102-11 92.71% - -

V14-11 12.68% - - V102-11 90.40% - -

V14-11 38.72% - - V102-11 92.54% - -

V14-11 66.35% - - V102-11 88.87% - -

V14-11 42.25% - - V102-11 92.08% - -

V15-11 69.08% - - V103-11 39.64% - -

V15-11 68.42% - - V103-11 90.68% - -

V15-11 73.34% - - V103-11 91.29% - -

V15-11 79.29% - - V103-11 81.11% - -

V15-11 56.81% - - V103-11 56.70% - -

V15-11 33.71% - - V103-11 50.93% - -

- - - - V103-11 56.90% - -

- - - - V103-11 84.85% - -

- - - - V103-11 64.55% - -

- - - - V103-11 65.29% - -

UV-DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V22-11 88.69% V72-11 79.84% V110-11 99.47% V319-11 39.46%

V22-11 91.07% V72-11 59.17% V110-11 99.97% V319-11 34.08%

V22-11 91.16% V72-11 89.45% V110-11 95.91% V319-11 37.18%

V22-11 91.66% V72-11 84.44% V110-11 99.84% V319-11 53.63%

V22-11 90.10% V72-11 92.82% V110-11 97.96% V319-11 34.96%

V22-11 97.45% V72-11 81.67% V110-11 99.88% V319-11 12.76%

V22-11 94.92% V72-11 90.55% V110-11 97.99% V319-11 16.96%

V22-11 98.51% V72-11 93.58% V110-11 97.92% V319-11 35.46%

V22-11 95.98% V72-11 95.57% V110-11 99.17% V319-11 37.91%

V22-11 94.28% V72-11 60.93% V110-11 97.53% V319-11 18.36%

V23-11 95.44% V73-11 63.25% V111-11 98.80% V320-11 26.73%

V23-11 99.00% V73-11 79.48% V111-11 99.80% V320-11 22.09%

V23-11 98.93% V73-11 90.38% V111-11 99.81% V320-11 40.91%

V23-11 98.00% V73-11 94.57% V111-11 98.27% V320-11 52.59%

V23-11 97.39% V73-11 91.92% V111-11 96.02% V320-11 45.06%

V23-11 94.43% V73-11 87.59% V111-11 96.25% V320-11 61.95%

V23-11 97.36% V73-11 84.13% V111-11 96.67% V320-11 66.83%

138 Tab. 8.4.10: continued

UV-DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V23-11 91.64% V73-11 34.82% V111-11 98.58% V320-11 63.79%

V23-11 93.32% V73-11 42.92% V111-11 96.41% V320-11 43.56%

V23-11 93.59% V73-11 63.36% V111-11 98.49% V320-11 32.88%

V24-11 88.26% V74-11 85.30% V112-11 99.48% V321-11 85.35%

V24-11 97.36% V74-11 85.09% V112-11 99.46% V321-11 83.89%

V24-11 99.00% V74-11 66.21% V112-11 99.65% V321-11 86.35%

V24-11 99.77% V74-11 77.09% V112-11 89.89% V321-11 90.28%

V24-11 99.00% V74-11 74.11% V112-11 93.69% V321-11 86.68%

V24-11 78.27% V74-11 72.32% V112-11 98.27% V321-11 78.00%

V24-11 86.14% V74-11 77.37% V112-11 95.25% V321-11 86.04%

V24-11 57.61% V74-11 86.90% V112-11 99.10% V321-11 89.22%

V24-11 98.05% V74-11 73.38% V112-11 99.37% V321-11 80.07%

V24-11 98.82% V74-11 67.64% V112-11 99.71% V321-11 70.55%

V25-11 68.64% V75-11 83.87% V113-11 99.20% V322-11 42.47%

V25-11 94.12% V75-11 84.91% V113-11 97.71% V322-11 61.71%

V25-11 95.77% V75-11 88.57% V113-11 99.96% V322-11 78.02%

V25-11 97.26% V75-11 86.75% V113-11 99.80% V322-11 66.70%

V25-11 98.97% V75-11 70.88% V113-11 97.62% V322-11 68.11%

V25-11 98.35% V75-11 75.95% V113-11 98.41% V322-11 58.29%

V25-11 92.32% V75-11 75.95% V113-11 98.30% V322-11 67.09%

V25-11 95.37% V75-11 29.28% V113-11 97.99% V322-11 79.51%

V25-11 94.59% V75-11 62.12% V113-11 99.44% V322-11 57.28%

V25-11 63.05% V75-11 74.61% V113-11 98.18% V322-11 26.75%

V26-11 98.36% V76-11 76.09% V114-11 99.67% V323-11 35.48%

V26-11 90.40% V76-11 95.25% V114-11 98.94% V323-11 40.82%

V26-11 89.54% V76-11 94.86% V114-11 99.85% V323-11 59.06%

V26-11 98.56% V76-11 90.07% V114-11 99.90% V323-11 37.93%

V26-11 97.99% V76-11 86.13% V114-11 99.98% V323-11 54.35%

V26-11 97.82% V76-11 70.28% V114-11 99.72% V323-11 47.34%

V26-11 90.87% V76-11 39.79% V114-11 93.61% V323-11 63.64%

V26-11 95.36% V76-11 46.17% V114-11 85.88% V323-11 57.07%

V26-11 87.85% V76-11 51.80% V114-11 98.49% V323-11 57.74%

V26-11 96.62% V76-11 48.82% V114-11 98.85% V323-11 54.55%

V27-11 91.57% V77-11 75.49% V115-11 99.43% V324-11 45.39%

V27-11 83.34% V77-11 76.94% V115-11 99.85% V324-11 59.17%

V27-11 92.74% V77-11 87.47% V115-11 99.56% V324-11 53.20%

V27-11 92.66% V77-11 84.01% V115-11 96.70% V324-11 54.49%

V27-11 98.36% V77-11 88.45% V115-11 99.73% V324-11 73.80%

139 Tab. 8.4.10: continued

MMP = matrix metalloproteinase; CDV = canine distemper virus (Onderstepoort strain);

DH82CDVai = acutely CDV infected xenografts; non-infected DH82 = non-treated xenografts (control group); UV-DH82CDVai = UV-inactivated CDV acutely infected DH82 xenografts (control group);dtp = days after transplantation

Tab. 8.4.11: Immunohistochemical expression of MMP-14 in subcutaneously xenotransplanted (DH82 cells). Values depicted display the percentage of immunopositive area in 10 randomly selected fields from the tumor center.

DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V28-11 8.32% V78-11 69.49% V117-11 43.12% V310-10 90.36%

V28-11 2.45% V78-11 69.00% V117-11 67.30% V310-10 75.98%

V28-11 1.07% V78-11 61.43% V117-11 82.18% V310-10 95.85%

V28-11 13.32% V78-11 57.74% V117-11 57.84% V310-10 96.11%

V28-11 5.13% V78-11 53.98% V117-11 58.50% V310-10 91.81%

V28-11 1.58% V78-11 57.95% V117-11 69.93% V310-10 95.82%

V28-11 2.37% V78-11 54.17% V117-11 71.96% V310-10 96.92%

V28-11 6.52% V78-11 54.13% V117-11 74.37% V310-10 94.37%

V28-11 9.51% V78-11 59.86% V117-11 76.47% V310-10 96.48%

V28-11 1.23% V78-11 59.59% V117-11 36.38% V310-10 96.60%

V29-11 48.22% V79-11 2.32% V118-11 96.28% V312-10 17.02%

V29-11 15.78% V79-11 60.68% V118-11 93.19% V312-10 48.43%

V29-11 25.71% V79-11 44.45% V118-11 84.37% V312-10 73.51%

V30-11 18.60% V79-11 28.94% V118-11 80.88% V312-10 65.91%

V30-11 9.34% V79-11 13.97% V118-11 22.47% V312-10 75.19%

V30-11 7.81% V79-11 1.78% V118-11 83.02% V312-10 57.89%

V30-11 25.45% V79-11 9.23% V118-11 56.59% V312-10 55.68%

V30-11 7.98% V79-11 22.84% V118-11 44.14% V312-10 51.27%

V30-11 7.00% V79-11 9.08% V118-11 92.64% V312-10 35.59%

V30-11 52.79% V79-11 1.47% V118-11 66.90% V312-10 75.50%

V30-11 62.96% V80-11 30.10% V119-11 51.69% V312-10 90.50%

V30-11 81.67% V80-11 40.69% V119-11 84.97% V313-10 90.89%

V30-11 2.34% V80-11 55.52% V119-11 65.38% V313-10 55.17%

V31-11 84.44% V80-11 15.06% V119-11 94.23% V313-10 58.72%

V31-11 32.57% V80-11 5.06% V119-11 71.25% V313-10 86.13%

UV-DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V27-11 93.49% V77-11 83.85% V115-11 98.18% V324-11 72.43%

V27-11 98.16% V77-11 85.21% V115-11 98.18% V324-11 79.86%

V27-11 89.02% V77-11 70.37% V115-11 97.93% V324-11 71.01%

V27-11 98.05% V77-11 28.81% V115-11 84.09% V324-11 74.44%

V27-11 98.86% V77-11 37.24% V115-11 96.98% V324-11 91.58%

140 Tab. 8.4.11: continued

DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V31-11 25.17% V80-11 10.13% V119-11 62.07% V313-10 96.12%

V31-11 93.84% V80-11 10.54% V119-11 71.19% V313-10 89.53%

V31-11 9.71% V80-11 2.74% V119-11 83.48% V313-10 92.38%

V31-11 87.29% V80-11 19.85% V119-11 85.10% V313-10 88.86%

V31-11 1.99% V80-11 4.36% V119-11 86.64% V313-10 80.70%

V31-11 88.01% V82-11 18.37% V120-11 30.44% V313-10 75.96%

V31-11 56.64% V82-11 14.66% V120-11 61.62% V314-10 76.15%

V31-11 71.01% V82-11 12.72% V120-11 74.87% V314-10 71.99%

V32-11 74.65% V82-11 22.06% V120-11 47.51% V314-10 78.59%

V32-11 64.21% V82-11 29.69% V120-11 30.13% V314-10 77.27%

V33-11 84.71% V82-11 65.67% V121-11 7.18% V314-10 77.57%

- - V82-11 60.58% V121-11 69.39% V314-10 82.46%

- - V82-11 49.06% V121-11 66.38% V314-10 86.31%

- - V82-11 44.17% V121-11 29.58% V314-10 60.80%

- - V82-11 36.62% V121-11 39.70% V314-10 63.45%

- - V83-11 16.63% V121-11 55.49% - -

- - V83-11 16.98% V121-11 83.58% - -

- - V83-11 27.65% V121-11 9.58% - -

- - V83-11 33.81% V121-11 10.23% - -

- - V83-11 30.62% V121-11 27.26% - -

- - V83-11 57.79% - - - -

- - V83-11 47.63% - - - -

- - V83-11 41.97% - - - -

- - V83-11 12.32% - - - -

- - V83-11 39.27% - - - -

- - - -

V10-11 78.89% V60-11 16.71% V98-11 32.37% V1087-09 98.86%

V10-11 73.90% V60-11 55.79% V98-11 20.58% V1087-09 99.03%

V10-11 74.93% V60-11 54.88% V98-11 39.36% V1087-09 97.52%

V10-11 5.17% V60-11 64.60% V98-11 66.46% V1088-09 41.56%

V10-11 24.37% V60-11 57.01% V98-11 35.11% V1088-09 67.29%

V10-11 37.76% V60-11 46.77% V98-11 25.25% V1088-09 67.03%

V10-11 23.55% V60-11 43.11% V98-11 40.94% V1088-09 49.96%

V10-11 94.44% V60-11 64.72% V98-11 33.80% V1088-09 4.03%

V10-11 92.88% V60-11 26.54% V98-11 30.33% V1088-09 50.97%

V10-11 73.48% V60-11 30.63% V98-11 34.91% V1088-09 4.04%

V11-11 32.30% V61-11 3.65% V99-11 75.50% V1088-09 3.10%

V11-11 5.64% V61-11 3.83% V99-11 71.31% V1088-09 30.68%

V11-11 20.96% V61-11 15.59% V99-11 79.42% V1088-09 37.40%

V11-11 13.04% V61-11 3.86% V99-11 64.10% V1089-09 28.00%

V11-11 13.39% V61-11 17.35% V99-11 65.95% V1089-09 25.38%

141 Tab. 8.4.11: continued

Non-infected DH82

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V11-11 49.10% V61-11 28.08% V99-11 75.76% V1089-09 25.27%

V11-11 30.07% V61-11 16.15% V99-11 74.52% V1089-09 36.44%

V11-11 9.44% V61-11 22.50% V99-11 78.56% V1089-09 49.93%

V11-11 19.00% V61-11 6.76% V99-11 77.58% V1089-09 54.86%

V11-11 6.56% V61-11 1.64% V99-11 79.05% V1089-09 60.42%

V12-11 8.78% V62-11 0.13% V100-11 86.69% V1089-09 77.61%

V12-11 77.75% V62-11 1.56% V100-11 84.81% V1089-09 81.40%

V12-11 42.02% V62-11 26.87% V100-11 84.39% V1089-09 78.67%

V12-11 2.34% V62-11 58.98% V100-11 79.10% V1090-09 90.50%

V12-11 4.00% V62-11 71.14% V100-11 83.67% V1090-09 90.89%

V12-11 6.22% V62-11 70.26% V100-11 78.56% V1090-09 55.17%

V12-11 33.14% V62-11 80.04% V100-11 78.10% V1090-09 58.72%

V12-11 98.46% V62-11 67.60% V100-11 75.87% V1090-09 86.13%

V12-11 92.95% V62-11 76.00% V100-11 69.69% V1090-09 96.12%

V12-11 61.75% V62-11 4.46% V100-11 78.69% V1090-09 89.53%

V13-11 75.17% V63-11 11.05% V101-11 12.14% V1090-09 92.38%

V13-11 43.09% V63-11 47.80% V101-11 20.17% V1090-09 88.86%

V13-11 9.16% V63-11 41.93% V101-11 60.97% V1090-09 80.70%

V13-11 39.30% V63-11 65.39% V101-11 73.51% V1091-09 57.21%

V13-11 50.11% V63-11 76.02% V101-11 77.18% V1091-09 85.43%

V13-11 71.67% V63-11 42.29% V101-11 76.42% V1091-09 76.78%

V13-11 53.47% V63-11 44.95% V101-11 49.94% V1091-09 82.24%

V13-11 49.48% V63-11 30.31% V101-11 68.21% V1091-09 91.51%

V13-11 18.03% V63-11 38.37% V101-11 58.53% V1091-09 92.59%

V13-11 23.47% V63-11 31.87% V101-11 55.91% V1091-09 92.12%

V14-11 5.93% V64-11 32.15% V102-11 55.81% V1091-09 96.50%

V14-11 7.89% V64-11 38.97% V102-11 70.04% V1091-09 91.28%

V14-11 85.93% V64-11 7.56% V102-11 75.67% V1091-09 81.29%

V14-11 17.68% V64-11 7.01% V102-11 69.95% - - V14-11 97.45% V64-11 8.88% V102-11 64.87% - - V14-11 35.57% V65-11 53.72% V102-11 62.72% - - V14-11 7.32% V65-11 81.77% V102-11 67.22% - - V14-11 14.59% V65-11 96.79% V102-11 73.31% - - V14-11 9.98% V65-11 0.29% V102-11 76.46% - - V14-11 59.07% V65-11 0.61% V102-11 75.89% - - V15-11 98.43% V65-11 0.74% V103-11 14.03% - - V15-11 58.72% V65-11 0.57% V103-11 1.81% - -

142 Tab. 8.4.11: continued

Non-infected DH82

Animal 44 dtp Animal 54 dtp Animal 63 dtp - - V15-11 37.88% V65-11 2.06% V103-11 26.38% - - V15-11 27.01% V65-11 37.37% V103-11 23.39% - - V15-11 46.12% V65-11 5.85% V103-11 8.30% - -

V15-11 11.31% - - V103-11 31.64% - -

V15-11 56.56% - - V103-11 27.57% - -

V15-11 50.32% - - V103-11 65.84% - -

V15-11 77.99% - - V103-11 61.85% - -

V15-11 84.67% - - V103-11 68.49% - -

UV-DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V22-11 25.60% V72-11 66.18% V110-11 97.46% V320-11 24.98%

V22-11 7.74% V72-11 85.37% V110-11 98.80% V320-11 21.65%

V22-11 25.66% V72-11 69.04% V110-11 98.63% V320-11 31.90%

V22-11 64.68% V72-11 83.88% V110-11 98.15% V320-11 27.49%

V22-11 51.59% V72-11 89.59% V110-11 99.15% V320-11 28.42%

V22-11 76.28% V72-11 94.63% V110-11 99.78% V320-11 22.85%

V22-11 4.77% V72-11 68.05% V110-11 99.66% V320-11 35.91%

V22-11 36.62% V72-11 91.22% V110-11 98.95% V320-11 26.04%

V22-11 5.79% V72-11 97.77% V110-11 98.69% V320-11 34.27%

V22-11 37.20% V72-11 8.79% V110-11 98.64% V320-11 36.15%

V23-11 19.66% V73-11 48.14% V111-11 95.92% V321-11 77.23%

V23-11 3.77% V73-11 41.40% V111-11 94.90% V321-11 70.76%

V23-11 17.84% V73-11 22.84% V111-11 94.73% V321-11 63.49%

V23-11 17.84% V73-11 15.86% V111-11 94.65% V321-11 70.28%

V23-11 14.90% V73-11 3.69% V111-11 91.18% V321-11 70.23%

V23-11 16.47% V73-11 2.08% V111-11 89.51% V321-11 65.76%

V23-11 24.76% V73-11 1.29% V111-11 92.62% V321-11 69.28%

V23-11 22.62% V73-11 4.35% V111-11 91.65% V321-11 71.53%

V23-11 24.09% V73-11 4.31% V111-11 87.00% V321-11 67.25%

V23-11 69.92% V73-11 1.10% V111-11 87.47% V321-11 77.66%

V24-11 42.67% V74-11 58.89% V112-11 99.62% V322-11 47.93%

V24-11 23.12% V74-11 62.77% V112-11 99.30% V322-11 31.15%

V24-11 20.15% V74-11 68.36% V112-11 97.48% V322-11 18.52%

V24-11 14.43% V74-11 49.17% V112-11 98.48% V322-11 20.28%

V24-11 12.77% V74-11 59.12% V112-11 98.48% V322-11 19.94%

V24-11 64.76% V74-11 88.33% V112-11 99.17% V322-11 18.88%

V24-11 12.84% V74-11 30.33% V112-11 98.31% V322-11 18.18%

V24-11 25.87% V74-11 27.06% V112-11 96.33% V322-11 12.61%

V24-11 16.30% V74-11 30.54% V112-11 98.25% V322-11 9.61%

V24-11 17.42% V74-11 30.21% V112-11 98.92% V323-11 34.67%

V25-11 24.52% V75-11 8.05% V113-11 98.85% V323-11 19.43%

143 Tab. 8.4.11: continued

UV-DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V25-11 22.25% V75-11 14.47% V113-11 94.98% V323-11 24.84%

V25-11 13.58% V75-11 6.19% V113-11 86.73% V323-11 22.58%

V25-11 6.80% V75-11 22.65% V113-11 82.22% V323-11 24.64%

V25-11 21.75% V75-11 8.59% V113-11 87.09% V323-11 20.87%

V25-11 15.57% V75-11 19.55% V113-11 84.57% V323-11 19.53%

V25-11 31.96% V75-11 6.45% V113-11 80.35% V323-11 24.59%

V25-11 36.05% V75-11 13.98% V113-11 89.98% V323-11 17.08%

V25-11 28.18% V75-11 11.16% V113-11 81.37% V323-11 11.96%

V26-11 50.40% V76-11 38.24% V113-11 80.25% V324-11 10.84%

V26-11 31.55% V76-11 93.49% V114-11 99.72% V324-11 56.30%

V26-11 27.69% V76-11 85.26% V114-11 98.98% V324-11 72.01%

V26-11 51.31% V76-11 91.94% V114-11 99.60% V324-11 65.44%

V26-11 48.26% V76-11 91.37% V114-11 99.57% V324-11 53.70%

V26-11 89.80% V76-11 74.64% V114-11 99.68% V324-11 58.89%

V26-11 48.26% V76-11 19.93% V114-11 99.29% V324-11 47.16%

V26-11 72.89% V76-11 18.30% V114-11 99.29% V324-11 41.86%

V26-11 23.07% V76-11 40.40% V114-11 99.59% V324-11 34.88%

V26-11 22.59% V76-11 24.12% V114-11 99.17% V324-11 36.36%

V27-11 55.34% V77-11 49.55% V115-11 98.75% V324-11 30.91%

V27-11 74.24% V77-11 40.65% V115-11 99.16% - - V27-11 65.86% V77-11 52.46% V115-11 97.85% - - V27-11 61.77% V77-11 19.09% V115-11 98.21% - - V27-11 67.38% V77-11 6.86% V115-11 97.91% - - V27-11 26.77% V77-11 1.49% V115-11 97.46% - - V27-11 57.34% V77-11 3.43% V115-11 99.35% - - V27-11 65.98% V77-11 82.86% V115-11 99.00% - - V27-11 51.99% V77-11 11.82% V115-11 98.93% - - V27-11 72.19% V77-11 2.98% V115-11 98.73% - -

- - V77-11 28.83% V115-11 98.86% - -

MMP = matrix metalloproteinase; CDV = canine distemper virus (Onderstepoort strain);

DH82CDVai = acutely CDV infected xenografts; non-infected DH82 = non-treated xenografts (control group); UV-DH82CDVai = UV-inactivated CDV acutely infected DH82 xenografts (control group);dtp = days after transplantation

144

Tab. 8.4.12: Immunohistochemical expression of TIMP-1 in subcutaneously xenotransplanted (DH82 cells). Values depicted display the percentage of immunopositive area in 10 randomly selected fields from the tumor periphery.

DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V28-11 98.38% V78-11 9.89% V117-11 27.04% V310-10 73..40%

V28-11 98.36% V78-11 18.12% V117-11 32.16% V310-10 82.03%

V28-11 99.54% V78-11 12.12% V117-11 33.90% V310-10 72.58%

V28-11 98.91% V78-11 10.43% V117-11 38.69% V310-10 63.63%

V28-11 99.28% V78-11 25.01% V117-11 38.69% V310-10 21.93%

V28-11 98.80% V78-11 9.17% V117-11 36.19% V310-10 53.44%

V28-11 98.63% V78-11 13.49% V117-11 25.84% V310-10 50.11%

V28-11 87.07% V78-11 16.02% V117-11 44.05% V310-10 71.58%

V28-11 82.21% V78-11 24.54% V117-11 53.58% V310-10 79.52%

V28-11 94.29% V78-11 14.45% V117-11 44.94% V310-10 89.27%

V29-11 96.58% V79-11 37.12% V118-11 59.37% V312-10 50.07%

V29-11 96.59% V79-11 51.07% V118-11 46.13% V312-10 51.07%

V29-11 95.68% V79-11 57.92% V118-11 63.23% V312-10 20.23%

V29-11 94.32% V79-11 72.17% V118-11 66.21% V312-10 47.34%

V29-11 92.32% V79-11 65.48% V118-11 69.85% V312-10 56.20%

V29-11 86.46% V79-11 80.46% V118-11 75.52% V312-10 55.99%

V29-11 87.38% V79-11 67.25% V118-11 74.22% V312-10 65.44%

V29-11 89.83% V79-11 34.29% V118-11 79.89% V312-10 54.38%

V29-11 89.96% V79-11 71.99% V118-11 65.16% V312-10 61.19%

V29-11 96.35% V79-11 26.69% V118-11 51.97% V312-10 52.43%

V30-11 83.52% V80-11 54.27% V119-11 67.08% V313-10 48.03%

V30-11 88.70% V80-11 92.66% V119-11 52.29% V313-10 34.04%

V30-11 85.85% V80-11 89.26% V119-11 40.82% V313-10 23.62%

V30-11 86.85% V80-11 74.84% V119-11 34.91% V313-10 30.05%

V30-11 86.69% V80-11 68.57% V119-11 43.82% V313-10 40.67%

V30-11 83.67% V80-11 81.91% V119-11 80.47% V313-10 39.03%

V30-11 82.54% V80-11 61.75% V119-11 17.49% V313-10 30.12%

V30-11 94.42% V80-11 70.88% V119-11 52.39% V313-10 53.98%

V30-11 81.37% V80-11 64.13% V119-11 53.72% V313-10 38.49%

V30-11 85.38% V80-11 75.25% V119-11 58.01% V313-10 43.61%

V31-11 98.96% V82-11 23.92% V120-11 30.92% V314-10 1.86%

V31-11 94.74% V82-11 30.20% V120-11 29.19% V314-10 25.75%

V31-11 94.49% V82-11 42.09% V120-11 25.23% V314-10 45.63%

V31-11 87.62% V82-11 28.52% V120-11 27.47% V314-10 23.47%

V31-11 89.50% V82-11 45.94% V120-11 49.46% V314-10 35.05%

V31-11 97.26% V82-11 46.64% V120-11 38.40% V314-10 39.46%

V31-11 97.77% V82-11 23.64% V120-11 67.34% V314-10 29.37%

145 Tab. 8.4.12: continued

DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V31-11 97.05% V82-11 32.82% V120-11 29.78% V314-10 40.04%

V31-11 95.63% V82-11 38.81% V120-11 43.85% V314-10 13.60%

V31-11 78.90% V82-11 28.17% V120-11 56.83% V314-10 7.92%

V32-11 93.85% V83-11 100% V121-11 37.17% - - V32-11 95.96% V83-11 100% V121-11 40.65% - - V32-11 88.75% V83-11 100% V121-11 65.20% - - V32-11 97.70% V83-11 100% V121-11 62.07% - - V32-11 96.09% V83-11 100% V121-11 34.35% - - V33-11 88.81% V83-11 100% V121-11 62.74% - - V33-11 90.26% V83-11 100% V121-11 46.84% - - V33-11 94.13% V83-11 100% V121-11 61.47% - - V33-11 91.36% V83-11 100% V121-11 61.02% - - V33-11 95.09% V83-11 100% V121-11 43.46% - - Tab. 8.4.12: continued

Non-infected DH82

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V10-11 98.18% V60-11 80.69% V98-11 95.25% V1087-09 75.16%

V10-11 98.82% V60-11 67.17% V98-11 86.87% V1087-09 58.98%

V10-11 96.04% V60-11 73.88% V98-11 78.56% V1087-09 76.07%

V10-11 89.89% V60-11 44.44% V98-11 87.67% V1087-09 68.58%

V10-11 95.81% V60-11 48.50% V98-11 73.62% V1087-09 83.90%

V10-11 94.84% V60-11 60.30% V98-11 84.34% V1087-09 84.69%

V10-11 96.95% V60-11 63.76% V98-11 45.29% V1087-09 84.32%

V10-11 95.70% V60-11 67.40% V98-11 54.32% V1087-09 64.59%

V10-11 94.66% V60-11 46.89% V98-11 33.72% V1087-09 86.32%

V10-11 96.94% V60-11 67.83% V98-11 71.90% V1087-09 88.34%

V11-11 97.25% V61-11 94.45% V99-11 61.07% V1088-09 91.33%

V11-11 81.02% V61-11 92.34% V99-11 72.94% V1088-09 87.22%

V11-11 98.23% V61-11 94.18% V99-11 73.14% V1088-09 82.46%

V11-11 96.92% V61-11 92.52% V99-11 71.59% V1088-09 57.56%

V11-11 96.87% V61-11 90.92% V99-11 61.47% V1088-09 58.30%

V11-11 92.90% V61-11 55.61% V99-11 39.93% V1088-09 86.38%

V11-11 98.46% V61-11 77.66% V99-11 41.17% V1088-09 72.49%

V11-11 89.63% V61-11 95.28% V99-11 24.36% V1088-09 75.96%

V11-11 99.01% V61-11 66.71% V99-11 16.68% V1088-09 78.85%

V11-11 84.61% V61-11 70.87% V99-11 29.64% V1088-09 94.37%

V12-11 94.62% V62-11 91.09% V100-11 58.19% V1089-09 90.05%

V12-11 97.52% V62-11 64.20% V100-11 54.57% V1089-09 89.90%

V12-11 96.20% V62-11 67.05% V100-11 73.98% V1089-09 84.33%

V12-11 86.60% V62-11 73.61% V100-11 38.59% V1089-09 89.29%

146 Tab. 8.4.12: continued

Non-infected DH82

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V12-11 95.80% V62-11 78.64% V100-11 56.05% V1089-09 79.39%

V12-11 92.91% V62-11 88.56% V100-11 44.06% V1089-09 48.16%

V12-11 93.99% V62-11 90.14% V100-11 22.41% V1089-09 74.58%

V12-11 96.05% V62-11 94.06% V100-11 40.93% V1089-09 41.81%

V12-11 92.36% V62-11 92.12% V100-11 43.20% V1089-09 10.27%

V12-11 94.40% V62-11 80.35% V100-11 45.28% V1089-09 62.23%

V13-11 97.75% V63-11 62.01% V101-11 30.85% V1090-09 82.24%

V13-11 94.62% V63-11 77.11% V101-11 53.28% V1090-09 87.16%

V13-11 99.07% V63-11 71.05% V101-11 60.31% V1090-09 82.41%

V13-11 89.23% V63-11 78.11% V101-11 76.21% V1090-09 74.23%

V13-11 99.49% V63-11 74.93% V101-11 72.04% V1090-09 71.96%

V13-11 99.72% V63-11 61.60% V101-11 84.50% V1090-09 85.08%

V13-11 81.83% V63-11 30.56% V101-11 70.72% V1090-09 87.25%

V13-11 98.64% V63-11 14.25% V101-11 76.22% V1090-09 86.76%

V13-11 97.71% V63-11 35.30% V101-11 32.33% V1090-09 88.74%

V13-11 77.56% V63-11 65.75% V101-11 56.38% V1090-09 85.92%

V14-11 83.76% V64-11 30.32% V102-11 63.46% V1091-09 77.34%

V14-11 81.63% V64-11 37.81% V102-11 50.37% V1091-09 73.51%

V14-11 82.97% V64-11 44.01% V102-11 45.78% V1091-09 40.57%

V14-11 93.67% V64-11 50.37% V102-11 21.24% V1091-09 35.85%

V14-11 96.12% V64-11 46.63% V102-11 23.15% V1091-09 65.14%

V14-11 62.88% V64-11 46.79% V102-11 40.19% V1091-09 63.72%

V14-11 85.78% V64-11 42.39% V102-11 40.72% V1091-09 66.53%

V14-11 46.46% V64-11 35.69% V102-11 46.78% V1091-09 77.16%

V14-11 43.92% V64-11 31.56% V102-11 42.09% V1091-09 62.25%

V14-11 89.16% V64-11 29.40% V102-11 42.16% V1091-09 88.02%

V15-11 66.41% V65-11 76.16% - - - -

V15-11 78.94% V65-11 72.10% - - - -

V15-11 80.62% V65-11 88.28% - - - -

V15-11 87.71% V65-11 87.80% - - - -

V15-11 96.51% V65-11 79.20% - - - -

V15-11 92.14% V65-11 70.12% - - - -

V15-11 92.62% V65-11 41.48% - - - -

V15-11 92.88% V65-11 59.67% - - - -

V15-11 97.46% V65-11 81.77% - - - -

V15-11 98.38% V65-11 89% - - - -

147 Tab. 8.4.12: continued

UV-DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V22-11 93.56% V72-11 60.07% V110-11 61.11% V319-11 99.07%

V22-11 93.97% V72-11 73.96% V110-11 72.09% V319-11 98.73%

V22-11 96.99% V72-11 79.29% V110-11 73.69% V319-11 96.59%

V22-11 93.78% V72-11 81.64% V110-11 54.12% V319-11 92.48%

V22-11 91.48% V72-11 96.74% V110-11 66.41% V319-11 94.01%

V22-11 79.95% V72-11 95.03% V110-11 68.75% V319-11 92.08%

V22-11 66.76% V72-11 99.18% V110-11 52.48% V319-11 91.04%

V22-11 78.18% V72-11 62.17% V110-11 45.80% V319-11 85.65%

V22-11 87.90% V72-11 74.19% V110-11 62.70% V319-11 74.28%

V22-11 93.51% V72-11 88.71% V110-11 61.03% V319-11 84.20%

V23-11 13.80% V73-11 89.03% V111-11 10.86% V320-11 67.58%

V23-11 52.87% V73-11 91.12% V111-11 34.83% V320-11 80.62%

V23-11 21.06% V73-11 89.83% V111-11 56.29% V320-11 44.68%

V23-11 15.67% V73-11 87.27% V111-11 31.26% V320-11 85.41%

V23-11 17.22% V73-11 66.40% V111-11 22.43% V320-11 72.16%

V23-11 4.33% V73-11 72.92% V111-11 21.83% V320-11 77.20%

V23-11 17.75% V73-11 76.80% V111-11 31.76% V320-11 75.69%

V23-11 25.15% V73-11 80.30% V111-11 28.03% V320-11 51.86%

V23-11 4.45% V73-11 67.16% V111-11 37.36% V320-11 81.10%

V23-11 8.65% V73-11 93.86% V111-11 43.27% V320-11 88%

V24-11 77.40% V74-10 38% V112-11 43.66% V321-11 84.09%

V24-11 51.30% V74-10 38.08% V112-11 55.37% V321-11 82.59%

V24-11 65.12% V74-10 67.02% V112-11 56.46% V321-11 89.66%

V24-11 77.18% V74-10 67.55% V112-11 62.93% V321-11 92.59%

V24-11 95.63% V74-10 84.81% V112-11 60.92% V321-11 85.82%

V24-11 90.42% V74-10 79.00% V112-11 54.34% V321-11 69.10%

V24-11 86.17% V74-10 79.07% V112-11 68.77% V321-11 76.59%

V24-11 66.92% V74-10 74.11% V112-11 52.98% V321-11 63.08%

V24-11 82.54% V74-10 71.81% V112-11 30.90% V321-11 50.36%

V24-11 80% V74-10 82.97% V112-11 49.04% V321-11 78.77%

V25-11 84.40% V75-10 81.09% V113-11 35.95% V322-11 73.15%

V25-11 93.46% V75-10 87.90% V113-11 51.02% V322-11 56.37%

V25-11 88.71% V75-10 85.11% V113-11 35.45% V322-11 68.53%

V25-11 78.72% V75-10 92.31% V113-11 23.61% V322-11 42.57%

V25-11 71.51% V75-10 90.77% V113-11 26.04% V322-11 80.26%

V25-11 47.23% V75-10 91.73% V113-11 34.76% V322-11 71.84%

V25-11 42.98% V75-10 98.68% V113-11 44.09% V322-11 76.59%

V25-11 58.31% V75-10 96.17% V113-11 56.12% V322-11 81.27%

V25-11 64.09% V75-10 99.41% V113-11 52.72% V322-11 79.29%

V25-11 49.36% V75-10 98.44% V113-11 52.65% V322-11 78.60%

V26-11 80.45% V76-10 96.97% V114-11 78.81% V323-11 79.18%

148 Tab. 8.4.12: continued

UV-DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V26-11 80.98% V76-10 99.63% V114-11 81.27% V323-11 68.39%

V26-11 91.33% V76-10 99.81% V114-11 61.69% V323-11 70.03%

V26-11 91.14% V76-10 99.69% V114-11 64.42% V323-11 70%

V26-11 96.65% V76-10 99.84% V114-11 61.13% V323-11 64.06%

V26-11 97.41% V76-10 98.67% V114-11 76.24% V323-11 86.14%

V26-11 92.23% V76-10 99.80% V114-11 72.88% V323-11 76.15%

V26-11 90.89% V76-10 98.78% V114-11 78.59% V323-11 52.44%

V26-11 98.07% V76-10 93.72% V114-11 72.32% V323-11 70.34%

V26-11 95.86% V76-10 99.47% V114-11 70.00% V323-11 61.68%

V27-11 87.69% V77-11 98.86% V115-11 77.92% V324-11 84.63%

V27-11 94.42% V77-11 99.50% V115-11 79.68% V324-11 84.61%

V27-11 94.47% V77-11 99.64% V115-11 72.17% V324-11 88.46%

V27-11 92.31% V77-11 99.30% V115-11 69.60% V324-11 67.61%

V27-11 93.37% V77-11 96.31% V115-11 76.91% V324-11 62.08%

V27-11 95.05% V77-11 96.79% V115-11 84.07% V324-11 50.31%

V27-11 90.77% V77-11 98.73% V115-11 80.26% V324-11 78.26%

V27-11 83.84% V77-11 99.50% V115-11 85.73% V324-11 67.01%

V27-11 76.21% V77-11 98.83% V115-11 82.04% V324-11 59.22%

V27-11 73.58% V77-11 99.83% V115-11 69.56% V324-11 66.44%

TIMP = tissue inhibitor of matrix metalloproteinase; CDV = canine distemper virus (Onderstepoort strain); DH82CDVai = acutely CDV infected xenografts; non-infected DH82 = non-treated xenografts (control group); UV-DH82CDVai = UV-inactivated CDV acutely infected DH82 xenografts (control group);dtp = days after transplantation

149

Tab. 8.4.13: Immunohistochemical expression of TIMP-1 in subcutaneously xenotransplanted (DH82 cells). Values depicted display the percentage of immunopositive area in 10 randomly selected fields from the tumor center.

DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V28-11 8.98% V78-11 31.11% V117-11 7.30% V310-10 29.63%

V28-11 4.43% V78-11 32.74% V117-11 6.99% V310-10 30.63%

V28-11 5.30% V78-11 17.63% V117-11 4.11% V310-10 20.20%

V28-11 10.42% V78-11 9.79% V117-11 9.35% V310-10 49.35%

V28-11 6% V78-11 24% V117-11 8.62% V310-10 65.70%

V28-11 5.88% V78-11 36.27% V117-11 3.99% V310-10 68.32%

V28-11 18.73% V78-11 28.60% V117-11 6.84% V310-10 69.39%

V29-11 27.97% V78-11 38.31% V117-11 5.50% V310-10 1.40%

V29-11 7.42% V78-11 23.84% V117-11 18.24% V310-10 17.83%

V29-11 7.54% V78-11 32.78% V117-11 7.08% V310-10 60.42%

V29-11 13.58% V79-11 1.54% V118-11 42.59% V312-10 18.07%

V29-11 14.04% V79-11 7.82% V118-11 39.11% V312-10 6.90%

V29-11 7.30% V79-11 11.92% V118-11 19.02% V312-10 6.90%

V29-11 2.46% V79-11 1.38% V118-11 6.34% V312-10 6.90%

V29-11 33.07% V79-11 4.80% V118-11 14.36% V312-10 13.07%

V29-11 14.83% V79-11 61.26% V118-11 2.86% V312-10 5.79%

V30-11 2.84% V79-11 10.40% V118-11 7.32% V312-10 21.40%

V30-11 6.69% V79-11 10.31% V118-11 2.10% V312-10 14.51%

V30-11 3.70% V79-11 1.86% V118-11 7.06% V312-10 18.01%

V30-11 11.01% V79-11 7.99% V118-11 14.10% V312-10 3.94%

V30-11 6.65% V80-11 39.67% V119-11 2.04% V313-10 43.53%

V30-11 7.76% V80-11 66.39% V119-11 2.53% V313-10 22.28%

V30-11 1.43% V80-11 63.08% V119-11 14.80% V313-10 5.21%

V30-11 2.60% V80-11 10.88% V119-11 2.13% V313-10 13.07%

V30-11 3.05% V80-11 1.70% V119-11 13.95% V313-10 11.63%

V30-11 7.52% V80-11 3.88% V119-11 42.32% V313-10 9.22%

V31-11 54.94% V80-11 8.60% V119-11 26.88% V313-10 3.96%

V32-11 89.66% V80-11 2.82% V119-11 19.68% V313-10 12.56%

V32-11 52.17% V80-11 3.68% V119-11 13.25% V313-10 15.40%

- - V80-11 11.12% V119-11 46.06% V313-10 13.95%

- - V81-11 10.37% V120-11 14.79% V314-10 0.03%

- - V81-11 8.83% V120-11 15.46% V314-10 1.31%

- - V81-11 47.43% V120-11 26.62% V314-10 30%

- - V81-11 42.59% V120-11 25.92% V314-10 29.98%

- - V81-11 56.35% V121-11 1.76% V314-10 13.81%

- - V81-11 72.09% V121-11 7.64% V314-10 17.91%

- - V81-11 31.25% V121-11 16.15% V314-10 52.79%

- - V81-11 9.08% V121-11 8.32% V314-10 37.53%

- - V81-11 15.38% V121-11 5.35% V314-10 33.56%

150 Tab. 8.4.13: continued

DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp - - V81-11 18.19% V121-11 25.18% V314-10 53.15%

- - - - V121-11 12.11% - -

- - - - V121-11 16.65% - -

- - - - V121-11 36.68% - -

- - - - V121-11 43.52% - -

Non-infected DH82

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V10-11 78.88% V60-11 22.94% V98-11 7.50% V1087-11 48.78%

V10-11 74.87% V60-11 2.73% V98-11 9.22% V1087-11 64.04%

V10-11 60.81% V60-11 40.07% V98-11 46.29% V1087-11 46.95%

V10-11 65.24% V60-11 5.72% V98-11 71.10% V1087-11 51.21%

V10-11 65.75% V60-11 25.94% V98-11 43.56% V1087-11 30.53%

V10-11 65.62% V60-11 11.96% V98-11 61% V1088-11 3.37%

V10-11 68.24% V60-11 6.71% V98-11 28.09% V1088-11 6.69%

V10-11 70.23% V60-11 26.79% V98-11 52.91% V1088-11 10.53%

V10-11 77.33% V60-11 6.15% V98-11 75.92% V1088-11 4.75%

V10-11 91.14% V60-11 16.76% V98-11 21.04% V1088-11 4.36%

V11-11 36.78% V61-11 19.48% V99-11 21.46% V1088-11 11.37%

V11-11 13.73% V61-11 7.49% V99-11 13.23% V1088-11 14.84%

V11-11 16.78% V61-11 28.03% V99-11 35.87% V1088-11 6.42%

V11-11 8.71% V61-11 50.35% V99-11 51.31% V1088-11 17.20%

V11-11 33.20% V61-11 60.75% V99-11 42.73% V1088-11 27.02%

V11-11 68.00% V61-11 55.31% V99-11 38.93% V1089-11 11.42%

V11-11 89.86% V61-11 47.46% V99-11 13.02% V1089-11 18.26%

V11-11 20.66% V61-11 14.00% V99-11 14.22% V1089-11 17.42%

V11-11 8.28% V61-11 82.48% V99-11 7.63% V1089-11 14.96%

V11-11 13.36% V61-11 59.90% V99-11 21.82% V1089-11 40.71%

V12-11 19.94% V62-11 44.47% V100-11 29.40% V1089-11 23.58%

V12-11 33.79% V62-11 6.94% V100-11 27.24% V1089-11 38.62%

V12-11 30.58% V62-11 3.33% V100-11 29.23% V1089-11 7.90%

V12-11 15.75% V62-11 56.21% V100-11 34.00% V1089-11 12.16%

V12-11 6.51% V62-11 58.44% V100-11 17.30% V1089-11 33.47%

V12-11 5.75% V62-11 66.22% V100-11 21.54% V1090-11 29.51%

V12-11 3.69% V62-11 60.48% V100-11 54.36% V1090-11 58.91%

V12-11 4.16% V62-11 62.34% V100-11 55.13% V1090-11 17.83%

V12-11 10.35% V62-11 66.07% V100-11 64.58% V1090-11 60.00%

V12-11 14.67% V62-11 3.48% V100-11 46.63% V1090-11 49.08%

V13-11 14.94% V63-11 4.08% V101-11 43.43% V1090-11 31.40%

151 Tab. 8.4.13: continued

Non-infected DH82

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V13-11 6.11% V63-11 7.25% V101-11 29.96% V1090-11 30.10%

V13-11 83.20% V63-11 1.85% V101-11 19.71% V1090-11 66.98%

V13-11 68.59% V63-11 37.28% V101-11 31.77% V1090-11 57.98%

V13-11 11.87% V63-11 40.68% V101-11 25.34% V1090-11 38.93%

V13-11 19.49% V63-11 33.73% V101-11 34.16% V1090-11 8.47%

V13-11 8.51% V63-11 9.82% V101-11 29.15% V1091-11 3.78%

V13-11 15.94% V63-11 16.73% V101-11 23.61% V1091-11 7.81%

V13-11 36.44% V63-11 8.86% V101-11 31.31% V1091-11 8.01%

V13-11 77.94% V63-11 36.48% V101-11 30.05% V1091-11 1.88%

V14-11 7.36% V64-11 5.79% V102-11 10.92% V1091-11 7.68%

V14-11 1.62% V64-11 10.59% V102-11 19.42% V1091-11 2.24%

V14-11 5.04% V64-11 7.42% V102-11 27.44% V1091-11 66.10%

V14-11 1.38% V64-11 5.55% V102-11 25.81% V1091-11 63.18%

V14-11 8.79% V64-11 3.98% V102-11 33.45% V1091-11 48.61%

V14-11 4.84% V64-11 8.26% V102-11 33.40% - - V14-11 3.99% V64-11 2.11% V102-11 35.35% - - V14-11 6.68% V64-11 6.34% V102-11 19.90% - - V14-11 9.75% V64-11 3.44% V102-11 10.92% - - V14-11 7.51% V64-11 27.93% V102-11 17.51% - -

V15-11 12.53% V65-11 45.74% - - - -

V15-11 2.46% V65-11 58.24% - - - -

V15-11 1.03% V65-11 72.02% - - - -

V15-11 2.82% V65-11 68.94% - - - -

V15-11 1.87% V65-11 4.42% - - - -

V15-11 2.59% V65-11 6.02% - - - -

V15-11 3.81% V65-11 29.65% - - - -

V15-11 4.75% V65-11 4.78% - - - -

V15-11 10.59% V65-11 26.40% - - - -

V15-11 22.10% V65-11 55.93% - - - -

UV-DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V22-11 5.78% V72-10 16.82% V110-11 20.78% V319-11 24.89%

V22-11 16.24% V72-10 27.35% V110-11 20.52% V319-11 13.12%

V22-11 5.87% V72-10 71.81% V110-11 21.14% V319-11 12.49%

V22-11 69.75% V72-10 20.39% V110-11 13.89% V319-11 16.96%

V22-11 69.04% V72-10 56.51% V110-11 24.22% V319-11 15.61%

V22-11 26.88% V72-10 35.54% V110-11 25.26% V319-11 11.81%

V22-11 24.23% V72-10 46.05% V110-11 10.14% V319-11 3.48%

V22-11 8.11% V72-10 45.78% V110-11 15.66% V319-11 6.91%

V22-11 27.94% V72-10 45.90% V110-11 20.39% V319-11 6.01%

V22-11 42.07% V72-10 46.42% V110-11 5.33% V319-11 18.37%

152 Tab. 8.4.13: continued

UV-DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V23-11 18.46% V73-10 44.08% V111-11 5.96% V320-11 41.82%

V23-11 7.35% V73-10 45.77% V111-11 8.59% V320-11 20.07%

V23-11 1.25% V73-10 35.45% V111-11 2.54% V320-11 8.13%

V23-11 1% V73-10 44.45% V111-11 8.49% V320-11 3.04%

V23-11 6.37% V73-10 43.10% V111-11 14.02% V320-11 3.41%

V23-11 12.73% V73-10 68.13% V111-11 7.02% V320-11 3.28%

V23-11 6.82% V73-10 63.15% V111-11 6.62% V320-11 2.19%

V23-11 5.65% V73-10 69.86% V111-11 8.76% V320-11 3.78%

V23-11 5.44% V73-10 86.62% V111-11 8.25% V320-11 1.65%

V24-11 4.28% V74-10 12.29% V112-11 16.52% V321-11 8.30%

V23-11 5.06% V73-10 76.89% V111-11 7.85% V320-11 2.46%

V24-11 1.43% V74-10 6.51% V112-11 10.09% V321-11 10.70%

V24-11 3.70% V74-10 25.03% V112-11 16.45% V321-11 10.22%

V24-11 9.78% V74-10 10.87% V112-11 29.19% V321-11 9.51%

V24-11 4.98% V74-10 10.99% V112-11 25.18% V321-11 4.86%

V24-11 6.65% V74-10 15.23% V112-11 4.43% V321-11 19.46%

V24-11 4.60% V74-10 22.05% V112-11 20.45% V321-11 16.67%

V24-11 5.86% V74-10 40.14% V112-11 36.01% V321-11 21.94%

V24-11 19.38% V74-10 6.06% V112-11 32.59% V321-11 11.28%

V24-11 8.28% V74-10 34.54% V112-11 21.79% V321-11 29.38%

V25-11 0.74% V75-10 3.55% V113-11 12.20% V322-11 8.30%

V25-11 1.50% V75-10 0.42% V113-11 28.83% V322-11 3.86%

V25-11 2.08% V75-10 23.46% V113-11 45.68% V322-11 6.45%

V25-11 2.39% V75-10 8.59% V113-11 32.01% V322-11 1.55%

V25-11 3.74% V75-10 6.02% V113-11 63.55% V322-11 2.85%

V25-11 2.01% V75-10 10.76% V113-11 54.53% V322-11 17.63%

V25-11 2.35% V75-10 16.15% V113-11 60.62% V322-11 18.60%

V25-11 1.44% V75-10 46.27% V113-11 56.13% V322-11 11.51%

V25-11 3.61% V75-10 33.54% V113-11 14.88% V322-11 3.79%

V25-11 0.56% V75-10 11.27% V113-11 14.51% V322-11 9.28%

V26-11 31.49% V76-10 6.36% V114-11 61.02% V323-11 55.12%

V26-11 57.64% V76-10 2.52% V114-11 58.44% V323-11 71.30%

V26-11 64.33% V76-10 9.11% V114-11 61.31% V323-11 36.51%

V26-11 45.47% V76-10 4.47% V114-11 33.57% V323-11 71.44%

V26-11 46.45% V76-10 4.17% V114-11 67.46% V323-11 34.38%

V26-11 46.55% V76-10 4.70% V114-11 53.95% V323-11 67.51%

V26-11 49.21% V76-10 86.39% V114-11 52.34% V323-11 70.76%

V26-11 29.67% V76-10 33.15% V114-11 63.89% V323-11 70.28%

V26-11 44.84% V76-10 48.07% V114-11 52.51% V323-11 54.76%

V26-11 58.70% V76-10 88.59% V114-11 39.68% V323-11 42.22%

V27-11 16.51% V77-10 57.74% V115-11 47.33% V324-11 26.30%

153 Tab. 8.4.13: continued

UV-DH82CDVai

Animal 44 dtp Animal 54 dtp Animal 63 dtp Animal 77 dtp V27-11 25.66% V77-10 14.92% V115-11 42.65% V324-11 47.73%

V27-11 43.88% V77-10 23.38% V115-11 49.73% V324-11 44.78%

V27-11 25.77% V77-10 53.42% V115-11 41.82% V324-11 47.67%

V27-11 13.13% V77-10 42.16% V115-11 37.09% V324-11 52.74%

V27-11 21.78% V77-10 27.61% V115-11 42.09% V324-11 50.49%

V27-11 21.78% V77-10 68.30% V115-11 55.92% V324-11 41.34%

V27-11 25.72% V77-10 66.64% V115-11 40.33% V324-11 33.59%

V27-11 8.36% V77-10 37.16% V115-11 57.72% V324-11 23.36%

V27-11 7.01% V77-10 74.68% V115-11 67.10% V324-11 54.81%

TIMP = tissue inhibitor of matrix metalloproteinase; CDV = canine distemper virus (Onderstepoort strain); DH82CDVai = acutely CDV infected xenografts; non-infected DH82 = non-treated xenografts (control group); UV-DH82CDVai = UV-inactivated CDV acutely infected DH82 xenografts (control group);dtp = days after transplantation

154

Tab. 8.4.14: Immunohistochemical expression of MMP-2 in persistently infected subcutaneously xenotransplanted (DH82 cells). Values depicted display the percentage of immunopositive area in 10 randomly selected fields from the whole tumor.

DH82CDVpi

Animal 7 dtp Animal 14 dtp Animal 21 dtp Animal 35 dtp V1101-11 96.93% V1113-10 19.57% V1150-10 9.93% V1196-10 38.01%

V1101-11 84.17% V1113-10 23.27% V1150-10 9.82% V1196-10 27.13%

V1101-11 71.84% V1113-10 39.00% V1150-10 10.22% V1196-10 25.69%

V1101-11 81.45% V1113-10 18.03% V1150-10 3.12% V1196-10 19.71%

V1101-11 81.14% V1113-10 58.37% V1150-10 17.59% - - V1101-11 82.56% V1113-10 73.20% V1150-10 56.53% - - V1101-11 60.32% V1113-10 52.06% V1150-10 35.56% - - V1101-11 58.59% V1113-10 54.58% V1150-10 44.04% - - V1102-11 34.33% V1113-10 46.73% V1150-10 16.69% - - V1102-11 49.48% V1113-10 26.08% V1150-10 27.46% - - V1102-11 56.39% V1114-10 60.74% V1152-10 4.44% - - V1102-11 50.03% V1114-10 27.81% V1152-10 15.61% - - V1102-11 62.47% V1114-10 13.78% V1152-10 58.09% - - V1102-11 61.22% V1114-10 64.55% V1152-10 11.09% - - V1102-11 66.55% V1114-10 58.70% V1152-10 5.23% - - V1102-11 62.60% V1114-10 27.44% V1152-10 23.08% - - V1103-11 10.73% V1114-10 19.48% V1152-10 48.75% - - V1103-11 10.07% V1114-10 58.94% V1152-10 3.30% - - V1103-11 12.11% V1114-10 40.78% V1152-10 25.41% - - V1103-11 16.81% V1114-10 14.48% V1152-10 11.94% - - V1103-11 22.39% V1115-10 29.79% V1154-10 4.01% - - V1103-11 26.18% V1115-10 17.03% V1154-10 7.83% - - V1104-11 19.30% V1115-10 29.43% V1154-10 7.03% - - V1104-11 25.68% V1115-10 40.14% V1154-10 5.25% - - V1104-11 29.06% V1115-10 20.51% V1154-10 4.79% - - V1104-11 39.07% V1115-10 34.18% V1155-10 3.27% - - V1104-11 24.69% V1115-10 48.58% V1155-10 3.27% - - V1104-11 34.20% V1115-10 28.83% V1155-10 8.40% - - V1104-11 34.58% V1115-10 17.40% V1155-10 3.54% - - V1104-11 39.29% V1115-10 22.92% V1155-10 2.59% - - V1104-11 17.87% V1116-10 23.33% V1155-10 5.64% - - V1105-11 7.10% V1116-10 18.45% V1155-10 1.99% - - V1105-11 25.63% V1116-10 30.84% V1155-10 2.47% - - V1105-11 20.74% V1116-10 28.69% V1155-10 6.67% - -

V1105-11 18.00% V1116-10 30.02% - - - -

V1105-11 18.83% V1116-10 29.66% - - - -

V1106-11 15.52% V1116-10 37.77% - - - -

V1106-11 29.34% V1116-10 8.23% - - - -

V1106-11 32.03% V1116-10 4.76% - - - -

155 Tab. 8.4.14: continued

DH82CDVpi

Animal 7 dtp Animal 14 dtp Animal 21 dtp - -

V1106-11 14.95% V1116-10 10.21% - - - -

- - V1117-10 2.44% - - - -

- - V1117-10 2.42% - - - -

- - V1117-10 1.69% - - - -

- - V1117-10 1.71% - - - -

- - V1117-10 1.53% - - - -

- - V1117-10 1.90% - - - -

- - V1117-10 3.33% - - - -

- - V1117-10 12.32% - - - -

- - V1118-10 4.69% - - - -

- - V1118-10 7.57% - - - -

- - V1118-10 7.51% - - - -

- - Animal 14 dtp - - - -

- - V1118-10 5.30% - - - -

- - V1118-10 3.21% - - - -

- - V1118-10 7.10% - - - -

- - V1118-10 9.22% - - - -

- - V1118-10 3.66% - - - -

- - V1118-10 3.80% - - - -

- - V1118-10 3.63% - - - -

Non-infected DH82

Animal 7 dtp Animal 14 dtp Animal 21 dtp Animal 35 dtp V1095-10 49.62% V1107-10 33.52% V1145-10 27.08% V1189-10 56.22%

V1095-10 37.19% V1107-10 23.33% V1145-10 6.99% V1189-10 40.21%

V1095-10 33.15% V1107-10 27.90% V1145-10 21.19% V1189-10 25.28%

V1095-10 18.25% V1107-10 22.02% V1145-10 14.75% V1189-10 38.65%

V1095-10 33.77% V1107-10 18.65% V1145-10 11.20% V1189-10 23.75%

V1095-10 43.31% V1107-10 24.08% V1145-10 9.29% V1189-10 20.19%

V1095-10 36.98% V1107-10 36.88% V1145-10 10.69% V1189-10 20.09%

V1095-10 34.08% V1107-10 41.43% V1145-10 15.68% V1189-10 27.99%

V1095-10 38.85% V1107-10 38.85% V1145-10 25.09% V1189-10 26.02%

V1095-10 40.86% V1107-10 30.75% V1145-10 7.57% V1189-10 13.21%

V1096-10 28.35% V1108-10 31.84% V1146-10 25.09% V1190-10 32.17%

V1096-10 29.29% V1108-10 27.31% V1146-10 14.27% V1190-10 25.57%

V1096-10 37.50% V1108-10 27.21% V1146-10 0.04% V1190-10 25.80%

V1096-10 14.43% V1108-10 28.75% V1146-10 17.16% V1190-10 22.56%

V1096-10 40.46% V1108-10 27.02% V1146-10 22.56% V1190-10 21.84%

V1096-10 41.07% V1108-10 21.96% V1146-10 17.13% V1190-10 22.47%

V1096-10 40.78% V1108-10 31.45% V1146-10 20.49% V1190-10 26.33%

156 Tab. 8.4.14: continued

Non-infected DH82

Animal 7 dtp Animal 14 dtp Animal 21 dtp Animal 35 dtp V1096-10 46.29% V1108-10 26.50% V1146-10 32.66% V1190-10 18.22%

V1096-10 37.68% V1108-10 30.72% V1146-10 19.50% V1190-10 25.56%

V1096-10 39.61% V1108-10 28.42% V1146-10 15.79% V1190-10 21.55%

V1097-10 47.94% V1109-10 19.52% V1147-10 45.69% V1191-10 46.60%

V1097-10 23.33% V1109-10 21.51% V1147-10 37.94% V1191-10 44.38%

V1097-10 48.04% V1109-10 22.49% V1147-10 45.07% V1191-10 34.04%

V1097-10 40.41% V1109-10 21.45% V1147-10 33.81% V1191-10 44.52%

V1097-10 56.85% V1109-10 17.55% V1147-10 33.01% V1191-10 36.91%

V1097-10 63.29% V1109-10 22.96% V1147-10 34.53% V1191-10 28.06%

V1097-10 42.55% V1109-10 14.06% V1147-10 46.43% V1191-10 31.37%

V1097-10 56.83% V1109-10 16.45% V1147-10 42.70% V1191-10 29.28%

V1097-10 25.58% V1109-10 28.68% V1147-10 38.84% V1191-10 24.51%

V1097-10 45.64% V1109-10 15.08% V1147-10 46.29% V1191-10 14.24%

V1098-10 60.11% V1110-10 33.62% V1148-10 49.55% V1192-10 20.18%

V1098-10 67.33% V1110-10 34.42% V1148-10 65.78% V1192-10 20.01%

V1098-10 65.98% V1110-10 33.28% V1148-10 76.03% V1192-10 25.77%

V1098-10 57.32% V1110-10 28.07% V1148-10 50.00% V1192-10 21.71%

V1098-10 60.33% V1110-10 35.50% V1148-10 28.95% V1192-10 21.66%

V1098-10 51.66% V1110-10 29.57% V1148-10 45.76% V1192-10 24.01%

V1098-10 44.30% V1110-10 19.17% V1148-10 58.26% V1192-10 20.84%

V1098-10 68.70% V1110-10 31.54% V1148-10 67.98% V1192-10 19.47%

V1098-10 53.05% V1110-10 43.73% V1148-10 50.66% V1192-10 23.42%

V1098-10 58.07% V1110-10 26.74% V1148-10 64.81% V1192-10 11.97%

V1099-10 38.68% V1112-10 18.00% V1149-10 29.03% V1193-10 27.98%

V1099-10 39.16% V1112-10 20.10% V1149-10 60.02% V1193-10 29.28%

V1099-10 30.07% V1112-10 13.40% V1149-10 45.88% V1193-10 24.43%

V1099-10 28.63% V1112-10 24.72% V1149-10 52.09% V1193-10 12.99%

V1099-10 24.58% V1112-10 33.92% V1149-10 37.95% V1193-10 24.43%

V1099-10 29.28% V1112-10 24.32% V1149-10 33.90% V1193-10 23.39%

V1099-10 36.19% V1112-10 36.49% V1149-10 55.09% V1193-10 14.90%

V1099-10 28.32% V1112-10 32.89% V1149-10 34.17% V1193-10 11.58%

V1099-10 36.56% V1112-10 41.43% V1149-10 47.97% V1193-10 2.49%

V1099-10 34.85% V1112-10 36.38% V1149-10 43.55% V1193-10 1.72%

V1100-10 27.11% - - - -

V1100-10 15.67% - - - -

V1100-10 31.06% - - - -

V1100-10 31.06% - - - -

V1100-10 27.02% - - - -

V1100-10 27.37% - - - -

V1100-10 35.63% - - - -

V1100-10 37.58% - - - -

157 Tab. 8.4.14: continued

Non-infected DH82

Animal 7 dtp Animal 14 dtp Animal 21 dtp Animal 35 dtp

V1100-10 29.43% - - - -

V1100-10 15.28% - - - -

MMP = matrix metalloproteinase; CDV = canine distemper virus (Onderstepoort strain);

DH82CDVai = persistently CDV infected xenografts; non-infected DH82 = non-treated xenografts (control group); dtp = days after transplantation

Tab. 8.4.15: Immunohistochemical expression of MMP-9 in persistently infected subcutaneously xenotransplanted (DH82 cells). Values depicted display the percentage of immunopositive area in 10 randomly selected fields from the whole tumor.

DH82CDVpi

Animal 7 dtp Animal 14 dtp Animal 21 dtp Animal 35 dtp V1101-10 92.50% V1113-10 56.02% V1152-10 41.80% V1200-10 13.56%

V1101-10 96.91% V1113-10 52.29% V1152-10 13.46% V1200-10 11.11%

V1101-10 92.48% V1113-10 53.63% V1152-10 25.92% V1200-10 13.39%

V1101-10 93.40% V1113-10 52.28% V1152-10 35.72% - - V1101-10 87.72% V1113-10 58.71% V1152-10 27.20% - - V1101-10 97.39% V1113-10 80.16% V1152-10 36.26% - - V1101-10 86.70% V1113-10 58.46% V1152-10 29.37% - - V1101-10 87% V1113-10 57% V1152-10 26.57% - - V1101-10 88.74% V1113-10 54.36% V1152-10 20.66% - - V1101-10 87.33% V1113-10 36.79% V1152-10 9.88% - - V1102-10 43.70% V1114-10 53.03% V1154-10 37.63% - - V1102-10 45.34% V1114-10 76.31% V1154-10 46.39% - - V1102-10 33.64% V1114-10 63.79% V1154-10 43.20% - - V1102-10 48.32% V1114-10 68.62% V1155-10 25.48% - - V1102-10 59.34% V1114-10 60.99% V1155-10 15.64% - - V1102-10 52.50% V1114-10 67.93% V1155-10 9.47% - - V1102-10 63.13% V1114-10 73.47% V1155-10 22.53% - - V1102-10 31.77% V1114-10 76.05% V1155-10 17.39% - -

V1102-10 37.43% V1114-10 69.57% - - - -

V1102-10 34.31% V1114-10 60.99% - - - -

V1103-10 82.96% V1115-10 33.01% - - - -

V1103-10 87.99% V1115-10 42.27% - - - -

V1103-10 88.06% V1115-10 38.15% - - - -

V1103-10 87.33% V1115-10 60.36% - - - -

V1103-10 73.08% V1115-10 70.09% - - - -

V1103-10 88.63% V1115-10 66% - - - -

V1103-10 87% V1115-10 66.52% - - - -

V1103-10 87.98% V1115-10 56.68% - - - -

158 Tab. 8.4.15: continued

DH82CDVpi

Animal 7 dtp Animal 14 dtp - - - -

V1103-10 88.80% V1115-10 31.87% - - - -

V1103-10 93.78% V1116-10 41.07% - - - -

V1104-10 51.73% V1116-10 52.76% - - - -

V1104-10 58.72% V1116-10 47.95% - - - -

V1104-10 75.45% V1116-10 34.84% - - - -

V1104-10 74.06% V1116-10 50.49% - - - -

V1104-10 49.42% V1116-10 35.49% - - - -

V1104-10 56.11% V1116-10 28.61% - - - -

V1104-10 53.08% V1116-10 21.30% - - - -

V1104-10 48.94% V1116-10 15.13% - - - -

V1104-10 41.38% V1116-10 16.33% - - - -

V1104-10 61.37% V1117-10 69.53% - - - -

V1105-10 42.07% V1117-10 77.41% - - - -

V1105-10 32.10% V1117-10 49.60% - - - -

V1105-10 36.32% V1117-10 35.98% - - - -

V1105-10 37.95% V1118-10 29.36% - - - -

V1105-10 29.86% V1118-10 38.21% - - - -

V1105-10 42.31% - - - -

V1105-10 46.25% - - - -

V1105-10 51.59% - - - -

V1105-10 48.66% - - - -

V1105-10 38.13% - - - -

V1106-10 25.27% - - - -

V1106-10 28.55% - - - -

V1106-10 27.33% - - - -

V1106-10 29.37% - - - -

V1106-10 34.27% - - - -

V1106-10 37.50% - - - -

V1106-10 40.11% - - - -

V1106-10 38.60% - - - -

V1106-10 36.44% - - - -

V1106-10 35.24% - - - -

Non-infected DH82

Animal 7 dtp Animal 14 dtp Animal 21 dtp Animal 35 dtp V1095-10 20.68% V1107-10 52.16% V1145-10 31.15% V1189-10 7.72%

V1095-10 19.21% V1107-10 54.65% V1145-10 49.05% V1189-10 2.20%

V1095-10 17.60% V1107-10 40.16% V1145-10 69.65% V1189-10 26.56%

V1095-10 27.38% V1107-10 24.61% V1145-10 37.39% V1189-10 38.29%

V1095-10 42.23% V1107-10 38.47% V1145-10 28.40% V1189-10 7.22%

V1096-10 13.06% V1107-10 56.83% V1145-10 75.83% V1189-10 58.26%

V1096-10 11.30% V1107-10 63.05% V1145-10 61.05% V1189-10 48.43%

159

V1096-10 24.79% V1107-10 56.83% V1145-10 72.85% V1189-10 29.01%

V1096-10 10.76% V1107-10 55.92% V1145-10 67.63% V1189-10 31.95%

V1096-10 14.09% V1107-10 54.90% V1145-10 78.83% V1189-10 66.07%

V1097-10 29.69% V1108-10 36.46% V1146-10 41.10% V1190-10 77.52%

V1097-10 27.14% V1108-10 36.29% V1146-10 18.78% V1190-10 89.03%

V1097-10 29.48% V1108-10 16.05% V1146-10 11.12% V1190-10 78.59%

V1097-10 28.59% V1108-10 19.53% V1146-10 3.90% V1190-10 79.73%

V1097-10 30.44% V1108-10 26.30% V1146-10 1.87% V1190-10 75.97%

V1098-10 34.76% V1108-10 17.17% V1146-10 66.23% V1190-10 35.06%

V1098-10 48.85% V1108-10 52.37% V1146-10 46.86% V1190-10 17.86%

V1098-10 29.44% V1108-10 36.97% V1146-10 53.31% V1190-10 32.61%

V1098-10 50.17% V1108-10 35.44% V1146-10 59.65% V1190-10 19.02%

V1098-10 36.09% V1108-10 54.25% V1147-10 60.69% V1190-10 36.53%

V1099-10 21.92% V1108-10 50.37% V1147-10 44.70% V1191-10 84.21%

V1099-10 12.83% V1109-10 77.31% V1147-10 61.65% V1191-10 80.30%

V1099-10 16.24% V1109-10 68.75% V1147-10 67.45% V1191-10 66.18%

V1099-10 17.84% V1110-10 34.31% V1147-10 61.10% V1191-10 52.56%

V1099-10 18.01% V1110-10 35.23% V1147-10 76.49% V1191-10 76.91%

V1100-10 6.78% V1110-10 21.93% V1147-10 58.90% V1191-10 7.77%

V1100-10 8.66% V1110-10 22.65% V1147-10 69.29% V1191-10 7.75%

V1100-10 14.68% V1110-10 21.85% V1147-10 71.87% V1191-10 16.67%

V1100-10 16.33% V1111-10 17.23% V1147-10 76.36% V1191-10 34.29%

V1100-10 17.64% V1111-10 9.89% V1147-10 77.25% V1191-10 42.09%

V1095-10 52.06% V1111-10 21.93% V1148-10 25.34% V1192-10 3.68%

V1095-10 36.29% V1111-10 22.18% V1148-10 15.82% V1192-10 1.99%

V1095-10 44.48% V1111-10 11.31% V1148-10 14.82% V1192-10 1.13%

V1095-10 52.69% - - V1148-10 18.20% V1192-10 6.03%

V1095-10 50.85% - - V1148-10 31.56% V1192-10 8.83%

V1096-10 37.01% - - V1148-10 53.36% V1192-10 57.62%

V1096-10 36.37% - - V1148-10 31.67% V1192-10 36.51%

V1096-10 33.08% - - V1148-10 23.26% V1192-10 72.53%

V1096-10 28.77% - - V1148-10 45.35% V1192-10 57.12%

V1096-10 26.98% - - V1148-10 61.37% V1192-10 4.54%

V1097-10 67.65% - - V1149-10 53.24% V1193-10 87.65%

V1097-10 71.95% - - V1149-10 68.39% V1193-10 77.70%

V1097-10 54.58% - - V1149-10 57.88% V1193-10 77.70%

V1097-10 67.88% - - V1149-10 71.00% V1193-10 76.95%

V1097-10 49.82% - - V1149-10 68.16% V1193-10 63.92%

V1098-10 64.14% - - V1149-10 84.40% V1193-10 3.38%

V1098-10 53.01% - - V1149-10 79.34% V1193-10 3.38%

V1098-10 51.72% - - V1149-10 66.28% V1193-10 3.38%

V1098-10 57.43% - - V1149-10 61.06% V1193-10 3.38%

V1098-10 48.33% - - V1149-10 80.05% V1193-10 3.38%

V1099-10 39.96% - - - -

160 Tab. 8.4.15: continued

Non-infected DH82

Animal 7 dtp - - Animal 21 dtp Animal 35 dtp

V1099-10 40.31% - - - -

V1099-10 50.24% - - - -

V1099-10 63.14% - - - -

V1099-10 60.50% - - - -

V1100-10 43.68% - - - -

V1100-10 49.08% - - - -

V1100-10 45.32% - - - -

V1100-10 40.89% - - - -

V1100-10 36.50% - - - -

MMP = matrix metalloproteinase; CDV = canine distemper virus (Onderstepoort strain);

DH82CDVai = persistently CDV infected xenografts; non-infected DH82 = non-treated xenografts (control group); dtp = days after transplantation

Tab. 8.4.16: Immunohistochemical expression of MMP-14 in persistently infected subcutaneously xenotransplanted (DH82 cells). Values depicted display the percentage of immunopositive area in 10 randomly selected fields from the whole tumor.

DH82CDVpi

Animal 7 dtp Animal 14 dtp Animal 21 dtp Animal 35 dtp V1101-10 89.92% V1113-10 56.45% V1150-10 71.62% V1196-10 64.19%

V1101-10 97.07% V1113-10 87.15% V1150-10 80.49% V1196-10 56.55%

V1101-10 94.05% V1113-10 76.80% V1150-10 72.36% V1196-10 64.98%

V1101-10 93.46% V1113-10 71.10% V1150-10 66.42% V1196-10 71.97%

V1101-10 93.16% V1113-10 77.17% V1150-10 62.44% - - V1101-10 91.78% V1113-10 61.10% V1150-10 34.35% - - V1101-10 93.49% V1113-10 46.67% V1150-10 43.37% - - V1101-10 78.03% V1113-10 39.42% V1150-10 50.45% - - V1101-10 87.97% V1113-10 37.88% V1150-10 51.21% - - V1101-10 90.94% V1113-10 33.29% V1150-10 60.78% - - V1102-10 47.27% V1114-10 96.66% V1152-10 83.96% - - V1102-10 62.34% V1114-10 93.77% V1152-10 89.29% - - V1102-10 65.61% V1114-10 93.93% V1152-10 87.32% - - V1102-10 36.83% V1114-10 95.82% V1152-10 62.80% - - V1102-10 42.40% V1114-10 97.26% V1152-10 73.41% - - V1102-10 56.41% V1114-10 79.76% V1152-10 71.02% - - V1102-10 54.85% V1114-10 91.01% V1152-10 72.09% - - V1102-10 58.95% V1114-10 86.28% V1152-10 73.75% - - V1102-10 49.59% V1114-10 89.72% V1154-10 71.21% - - V1102-10 65.20% V1114-10 73.97% V1154-10 92.91% - - V1103-10 74.83% V1115-10 52.71% V1154-10 75.56% - - V1103-10 80.89% V1115-10 74.63% V1155-10 15.00% - - V1103-10 77.87% V1115-10 78.11% V1155-10 40.91% - -

161 Tab. 8.4.16: continued

DH82CDVpi

Animal 7 dtp Animal 14 dtp - - - -

V1103-10 86.17% V1115-10 50.52% V1155-10 15.93% - - V1103-10 73.38% V1115-10 46.05% V1155-10 29.37% - - V1103-10 81.20% V1115-10 49.24% V1155-10 34.47% - -

V1103-10 66.67% V1115-10 64.08% - - - -

V1103-10 65.74% V1115-10 53.89% - - - -

V1103-10 67.39% V1115-10 34.96% - - - -

V1103-10 67.06% V1115-10 42.87% - - - -

V1104-10 83.67% V1116-10 36.26% - - - -

V1104-10 78.16% V1116-10 36.51% - - - -

V1104-10 92.43% V1116-10 56.93% - - - -

V1104-10 92.43% V1116-10 59.14% - - - -

V1104-10 80.90% V1116-10 72.52% - - - -

V1104-10 93.13% V1116-10 54.63% - - - -

V1104-10 93.13% V1117-10 23.20% - - - -

V1104-10 74.45% V1117-10 38.72% - - - -

V1104-10 82.69% V1117-10 36.77% - - - -

V1104-10 76.85% V1117-10 26.44% - - - -

V1105-10 74.83% V1117-10 37.67% - - - -

V1105-10 80.89% V1118-10 78.34% - - - -

V1105-10 77.87% V1118-10 78.15% - - - -

V1105-10 86.17% V1118-10 75.12% - - - -

V1105-10 73.38% V1118-10 68.94% - - - -

V1105-10 81.20% V1118-10 54.97% - - - -

V1105-10 66.67% - - - -

V1105-10 65.74% - - - -

V1105-10 67.39% - - - -

V1105-10 67.06% - - - -

V1106-10 36.68% - - - -

V1106-10 83.85% - - - -

V1106-10 53.06% - - - -

V1106-10 83.02% - - - -

V1106-10 69.06% - - - -

V1106-10 42.50% - - - -

Non-infected DH82

Animal 7 dtp Animal 14 dtp Animal 21 dtp Animal 35 dtp V1095-10 87.43% V1107-10 93.70% V11145- 10 94.71% V1189-10 80.16%

V1095-10 86.19% V1107-10 95.08% V11145- 10 97.39% V1189-10 81.22%

V1095-10 82.76% V1107-10 97.48% V11145- 10 96.62% V1189-10 88.16%

V1095-10 92.45% V1107-10 86.61% V11145- 10 95.89% V1189-10 88.86%

V1095-10 84.60% V1107-10 96.40% V11145- 10 85.42% V1189-10 24.08%

V1095-10 92.85% V1107-10 98.31% V11145- 10 91.38% V1189-10 84.30%

V1095-10 95.19% V1107-10 93.37% V11145- 10 94.80% V1189-10 85.64%

162 Tab. 8.4.16: continued

Non-infected DH82

Animal 7 dtp Animal 14 dtp Animal 21 dtp Animal 35 dtp

V1097-10 99.33% V1111-10 95.99% V11147- 10 82.53% V1191-10 91.83%

V1097-10 99.30% V1111-10 95.99% V11147- 10 84.48% V1191-10 80.55%

V1097-10 82.86% V1111-10 91.12% V11147- 10 92.59% V1191-10 87.89%

V1097-10 99.55% V1112-10 87.47% V11147- 10 88.04% V1191-10 87.46%

V1098-10 94.38% V1112-10 93.16% V11147- 10 87.83% V1191-10 76.91%

V1098-10 98.92% V1112-10 90.38% V11148- 10 90.01% V1192-10 24.75%

V1098-10 98.30% V1112-10 88.87% V11148- 10 98.29% V1192-10 23.90%

V1098-10 97.70% V1112-10 95.41% V11148- 10 76.11% V1192-10 15.01%

V1098-10 95.70% V1112-10 96.69% V11148- 10 96.29% V1192-10 28.37%

V1098-10 95.67% V1112-10 95.02% V11148- 10 93.46% V1192-10 12.53%

V1098-10 97.49% - - V11148- 10 82.19% V1192-10 76.78%

V1099-10 89.40% - - V11148- 10 86.22% V1192-10 79.40%

V1099-10 86.85% - - V11148- 10 86.31% V1192-10 67.96%

V1099-10 81.73% - - V11148- 10 90.01% V1192-10 74.12%

V1099-10 83.41% - - V11148- 10 86.68% V1192-10 76.59%

V1099-10 92.12% - - V11149- 10 93.69% V1193-10 80.59%

V1099-10 95.22% - - V11149- 10 88.72% V1193-10 80.35%

V1099-10 84.16% - - V11149- 10 81.90% V1193-10 79.98%

V1099-10 84.93% - - V11149- 10 76.31% V1193-10 80.66%

V1099-10 93.43% - - V11149- 10 90.56% V1193-10 88.75%

V1099-10 74.32% - - - - V1193-10 93.62%

V1100-10 89.03% - - - - V1193-10 82.92%

V1100-10 89.72% - - - - V1193-10 5.65%

V1100-10 80.88% - - - - V1193-10 16.04%

V1100-10 81.99% - - - - V1193-10 74.51%

V1100-10 89.22% - - - -

V1095-10 91.78% V1107-10 79.61% V11145- 10 64.06% V1189-10 66.19%

V1095-10 93.30% V1107-10 97.95% V11145- 10 91.68% V1189-10 90.63%

V1096-10 85.49% V1107-10 95.78% V11145- 10 91.50% V1189-10 90.44%

V1096-10 92.39% V1108-10 83.63% V11146- 10 90.15% V1190-10 84.37%

V1096-10 96.25% V1108-10 91.70% V11146- 10 93.55% V1190-10 64.93%

V1096-10 97.67% V1108-10 90.69% V11146- 10 87.85% V1190-10 81.19%

V1096-10 93.04% V1108-10 92.09% V11146- 10 91.20% V1190-10 59.29%

V1096-10 93.12% V1108-10 96.58% V11146- 10 79.91% V1190-10 62.24%

V1096-10 93.27% V1109-10 87.08% V11146- 10 5.32% V1190-10 97.33%

V1096-10 92.17% V1109-10 79.23% V11146- 10 95.08% V1190-10 95.77%

V1096-10 93.18% V1110-10 88.85% V11146- 10 93.79% V1190-10 95.03%

V1096-10 93.75% V1110-10 88.43% V11146- 10 66.56% V1190-10 97.07%

V1097-10 98.61% V1110-10 90.60% V11146- 10 72.78% V1190-10 97.73%

V1097-10 97.17% V1110-10 85.37% V11147- 10 91.04% V1191-10 86.72%

V1097-10 97.77% V1111-10 97.11% V11147- 10 93.46% V1191-10 96.39%

V1097-10 98.06% V1111-10 94.02% V11147- 10 89.48% V1191-10 95.05%

V1097-10 99.35% V1111-10 97.43% V11147- 10 94.97% V1191-10 83.24%

V1097-10 99.17% V1111-10 96.98% V11147- 10 83.19% V1191-10 95.79%

163 Tab. 8.4.16: continued

Non-infected DH82

Animal 7 dtp - - - -

V1100-10 89.18% - - - -

V1100-10 87.90% - - - -

V1100-10 88.48% - - - -

V1100-10 84.81% - - - -

V1100-10 82.66% - - - -

MMP = matrix metalloproteinase; CDV = canine distemper virus (Onderstepoort strain);

DH82CDVai = persistently CDV infected xenografts; non-infected DH82 = non-treated xenografts (control group); dtp = days after transplantation

Tab. 8.4.17: Immunohistochemical expression of TIMP-1 in persistently infected subcutaneously xenotransplanted (DH82 cells). Values depicted display the percentage of immunopositive area in 10 randomly selected fields from the whole tumor.

DH82CDVpi

Animal 7 dtp Animal 14 dtp Animal 21 dtp Animal 35 dtp V1101-10 90.35% V1113-10 92.75% V1150-10 28.10% V1196-10 47.25%

V1101-10 91.26% V1113-10 83.38% V1150-10 47.02% V1196-10 55..82%

V1101-10 90.27% V1113-10 89.15% V1150-10 73.92% V1196-10 73.92%

V1101-10 90.24% V1113-10 57.06% V1150-10 51.74% - - V1101-10 93.29% V1113-10 86.70% V1150-10 30.89% - - V1101-10 98.46% V1113-10 78.26% V1150-10 43.96% - - V1101-10 88.65% V1113-10 84.99% V1150-10 73.14% - - V1101-10 89.75% V1114-10 70.70% V1150-10 46.28% - - V1101-10 98.04% V1114-10 60.07% V1150-10 46.45% - - V1101-10 93.57% V1114-10 75.88% V1150-10 45.89% - - V1102-10 91.33% V1114-10 83.54% V1152-10 38.88% - - V1102-10 84.04% V1114-10 84.82% V1152-10 47.47% - - V1102-10 86.90% V1114-10 80.30% V1152-10 38.34% - - V1102-10 88.92% V1114-10 73.01% V1152-10 33.81% - - V1102-10 82.35% V1114-10 63.01% V1152-10 76.26% - - V1102-10 71.34% V1114-10 60.56% V1152-10 59.55% - - V1102-10 67.18% V1115-10 42.88% V1152-10 53.71% - - V1102-10 57.09% V1115-10 36.15% V1152-10 70.88% - - V1102-10 56.63% V1115-10 42.79% V1152-10 76.84% - - V1102-10 69.18% V1115-10 76.60% V1153-10 79.91% - - V1103-10 32.69% V1115-10 79.57% V1153-10 93.22% - - V1103-10 53.99% V1117-10 71.01% V1153-10 92.90% - - V1103-10 47.15% V1117-10 84.26% V1155-10 59.52% - - V1103-10 47.33% V1117-10 73.23% V1155-10 24.58% - - V1103-10 58.61% V1118-10 68.72% V1155-10 24.27% - -

164 Tab. 8.4.17: continued

DH82CDVpi

Animal 7 dtp Animal 14 dtp Animal 21 dtp - -

V1103-10 63.61% V1118-10 69.85% V1155-10 44.45% - - V1103-10 37.01% V1118-10 65.85% V1155-10 38.07% - - V1103-10 42.47% V1118-10 43.24% V1155-10 50.08% - -

V1103-10 33.13% - - V1155-10 27.03% - -

V1103-10 28.39% - - V1155-10 24.69% - -

V1104-10 86.76% - - V1155-10 59.51% - -

V1104-10 75.23% - - V1155-10 43.47% - -

V1104-10 67.60% - - V1155-10 46.74% - -

V1104-10 70.36% - - - -

V1104-10 81.37% - - - -

V1104-10 53.28% - - - -

V1104-10 70.99% - - - -

V1104-10 51.80% - - - -

V1104-10 51.32% - - - -

V1104-10 69.60% - - - -

V1105-10 39.92% - - - -

V1105-10 42.63% - - - -

V1105-10 26.73% - - - -

V1105-10 31.59% - - - -

V1105-10 20.06% - - - -

V1105-10 33.24% - - - -

V1105-10 37.48% - - - -

V1105-10 28.03% - - - -

V1105-10 24.01% - - - -

V1105-10 24.18% - - - -

V1106-10 32.39% - - - -

V1106-10 14.50% - - - -

V1106-10 26.06% - - - -

V1106-10 22.28% - - - -

V1106-10 15.84% - - - -

V1106-10 56.18% - - - -

V1106-10 65.53% - - - -

V1106-10 59.17% - - - -

V1106-10 62.35% - - - -

V1106-10 49.35% - - - -

Non-infected DH82

Animal 7 dtp Animal 14 dtp Animal 21 dtp Animal 35 dtp V1195-10 57.70% V1107-10 82.75% V1145-10 84.29% V1189-10 3.65%

V1195-10 40.31% V1107-10 75.55% V1145-10 11.92% V1189-10 7.76%

V1195-10 40.76% V1107-10 71.17% V1145-10 92.48% V1189-10 4.45%

V1195-10 32% V1107-10 60.37% V1145-10 94.03% V1189-10 10.88%

165 Tab. 8.4.17: continued

Non-infected DH82

Animal 7 dtp Animal 14 dtp Animal 21 dtp Animal 35 dtp V1195-10 62.74% V1107-10 70.69% V1145-10 51.56% V1189-10 28.41%

V1195-10 72.65% V1107-10 94.50% V1145-10 30.92% V1189-10 41.16%

V1195-10 66.68% V1107-10 85.85% V1145-10 54.72% V1189-10 37.25%

V1195-10 57.43% V1107-10 85.53% V1145-10 40.68% V1189-10 34.21%

V1195-10 58.90% V1107-10 75.51% V1145-10 59.20% V1189-10 28.36%

V1195-10 67.18% V1107-10 73.99% V1145-10 41.67% V1189-10 11.80%

V1195-10 77.67% V1107-10 91.59% V1145-10 92.03% V1189-10 71.59%

V1195-10 76.07% V1107-10 89.03% V1145-10 90.23% V1189-10 56.61%

V1195-10 74.34% V1107-10 81.52% V1145-10 94.94% V1189-10 50.15%

V1195-10 66.10% V1107-10 85.38% V1145-10 93.31% V1189-10 67.45%

V1195-10 69.65% V1107-10 83.68% V1145-10 94.43% V1189-10 65.48%

V1196-10 77.59% V1108-10 53.04% V1145-10 83.04% V1189-10 66.28%

V1196-10 70.95% V1108-10 58.95% V1145-10 90.11% V1189-10 67.97%

V1196-10 72.74% V1108-10 53.61% V1145-10 90.16% V1189-10 67.52%

V1196-10 68.60% V1108-10 50.34% V1145-10 92.74% V1189-10 71.40%

V1196-10 63.87% V1108-10 51.04% V1145-10 94.84% V1189-10 88.15%

V1196-10 83.79% V1108-10 60.98% V1146-10 1.80% V1190-10 81.71%

V1196-10 81.15% V1108-10 63.83% V1146-10 0.60% V1190-10 87.14%

V1196-10 77.26% V1108-10 71.28% V1146-10 7.50% V1190-10 89%

V1196-10 77.19% V1108-10 68.40% V1146-10 8.65% V1190-10 83.35%

V1196-10 83.34% V1108-10 47.47% V1146-10 42.05% V1190-10 91.20%

V1196-10 72.68% V1109-10 28.53% V1146-10 25.52% V1190-10 87.47%

V1196-10 87.36% V1109-10 17.64% V1146-10 35.58% V1190-10 74.02%

V1196-10 80.73% V1109-10 15.26% V1146-10 82.61% V1190-10 95.84%

V1197-10 70.56% V1109-10 9.69% V1146-10 86.19% V1190-10 65.01%

V1197-10 54.09% V1109-10 24.28% V1146-10 78.63% V1190-10 51.26%

V1197-10 66.92% V1109-10 32.32% V1146-10 79.20% V1190-10 9.21%

V1197-10 63.22% V1109-10 49.33% V1146-10 77.43% V1190-10 22.61%

V1197-10 74.73% V1109-10 40.60% V1146-10 88.49% V1190-10 74.53%

V1197-10 80.20% V1111-10 46.74% V1146-10 82% V1190-10 4.39%

V1197-10 77.19% V1111-10 35.80% V1146-10 70.98% V1190-10 16.14%

V1197-10 73.35% V1111-10 15.25% V1146-10 76.05% V1190-10 13.20%

V1197-10 79.89% V1111-10 31.40% V1146-10 70.50% V1190-10 1.35%

V1197-10 86.48% V1111-10 25.87% V1146-10 76.89% V1190-10 5.10%

V1197-10 82.48% V1111-10 26.98% V1147-10 83.18% V1191-10 71.73%

V1197-10 88.03% V1111-10 19.82% V1147-10 81% V1191-10 73.31%

V1197-10 92.31% V1111-10 23.65% V1147-10 76.82% V1191-10 60.63%

V1197-10 87.72% V1111-10 34.72% V1147-10 73.40% V1191-10 39.97%

V1197-10 86.89% V1111-10 27.10% V1147-10 56.31% V1191-10 25.93%

V1198-10 77.66% V1112-10 70.97% V1147-10 74.27% V1191-10 15.69%

V1198-10 66% V1112-10 60.92% V1147-10 83.96% V1191-10 37.83%

166 Tab. 8.4.17: continued

Non-infected DH82

Animal 7 dtp Animal 14 dtp Animal 21 dtp Animal 35 dtp V1198-10 74.52% V1112-10 61.50% V1147-10 59.69% V1191-10 47.81%

V1198-10 67.64% V1112-10 70.61% V1147-10 83.84% V1191-10 36.06%

V1198-10 81.24% V1112-10 45.37% V1147-10 66.62% V1191-10 36.25%

V1198-10 83.65% V1112-10 53.47% V1148-10 21.61% V1191-10 6.50%

V1198-10 85.49% V1112-10 51.42% V1148-10 50.59% V1191-10 4.79%

V1198-10 88.44% V1112-10 53.12% V1148-10 71.88% V1191-10 3.19%

V1198-10 83.36% V1112-10 33.92% V1148-10 23.58% V1191-10 41.35%

V1198-10 71.63% V1112-10 63.28% V1148-10 31.65% V1191-10 0.03%

V1199-10 82.85% V1112-10 55.98% V1149-10 31.07% V1191-10 2.49%

V1199-10 79.48% V1112-10 59.01% V1149-10 14.24% V1191-10 0.02%

V1199-10 75.39% V1112-10 64.67% V1149-10 26.84% V1191-10 7%

V1199-10 72.82% V1112-10 59.94% V1149-10 34.22% V1191-10 0.52%

V1199-10 57.68% V1112-10 62.17% V1149-10 37.34% V1191-10 5.84%

V1199-10 44.15% V1112-10 56.06% V1149-10 84.44% V1192-10 39.18%

V1199-10 54.89% V1112-10 48.91% V1149-10 74.19% V1192-10 27.97%

V1199-10 63.16% V1112-10 52.46% V1149-10 49.35% V1192-10 51.79%

V1199-10 68.37% V1112-10 54.94% V1149-10 59.38% V1192-10 63.56%

V1199-10 73.46% - - V1149-10 52.36% V1192-10 45.58%

V1199-10 86.30% - - - - V1192-10 81.57%

V1199-10 89.17% - - - - V1192-10 75.34%

V1199-10 85.43% - - - - V1192-10 77.10%

V1199-10 87.18% - - - - V1192-10 64.03%

V1199-10 91.83% - - - - V1192-10 82.21%

V1199-10 87.14% - - - - V1192-10 9.25%

V1199-10 86.39% - - - - V1192-10 1.14%

V1199-10 69% - - - - V1192-10 0.07%

V1199-10 71.38% - - - - V1192-10 0.58%

V1199-10 71.10% - - - - V1192-10 32.05%

V1100-10 14.85% - - - - V1192-10 2.88%

V1100-10 21.26% - - - - V1192-10 5.92%

V1100-10 17.43% - - - - V1192-10 14.81%

V1100-10 13.57% - - - - V1192-10 34.11%

V1100-10 27.53% - - - - V1192-10 14..47%

V1100-10 38.82% - - - - V1193-10 82.11%

V1100-10 49.69% - - - - V1193-10 73.58%

V1100-10 60.70% - - - - V1193-10 56.97%

V1100-10 67.48% - - - - V1193-10 60.20%

V1100-10 62.27% - - - - V1193-10 70.47%

- - - V1193-10 76.93%

- - - V1193-10 73.21%

- - - V1193-10 55.28%

167 Tab. 8.4.17: continued

Non-infected DH82

Animal 7 dtp - - - - Animal 35 dtp

- - - V1193-10 60.51%

- - - V1193-10 80.76%

- - - V1193-10 63.00%

- - - V1193-10 0.01%

- - - V1193-10 0.51%

- - - V1193-10 17.60%

- - - V1193-10 47.16%

- - - Animal 35 dtp

- - - V1193-10 49.78%

- - - V1193-10 21.84%

- - - V1193-10 1.94%

- - - V1193-10 1.56%

- - - V1193-10 2.53%

TIMP = tissue inhibitor of matrix metalloproteinase; CDV = canine distemper virus (Onderstepoort strain); DH82CDVai = persistently CDV infected xenografts; non-infected DH82

= non-treated xenografts (control group); dtp = days after transplantation

Tab. 8.4.18: CD31 expression in subcutaneously xenotransplanted DH82 cells (control group). Values are depicted as the number of immunolabeled structures with a definable lumen in 10 randomly selected fields in the tumor center and 10 randomly selected fields in the tumor periphery at a 400x magnification.

Animal C P Animal C P

V10-11 (n.1) 4 10 V60-11 (n.2) 8 12

3 2 9 17

0 1 7 10

0 2 3 13

3 4 4 15

0 4 5 10

2 1 8 10

2 2 10 5

0 2 5 9

1 1 9 10

Mean 1.5 2.9 Mean 6.8 11.1

V11-11 (n.1) 2 1 V61-11 (n.2) 11 5

0 2 12 6

0 2 13 5

0 0 12 1

1 0 7 11

0 0 9 5

3 1 4 3

168 Tab. 8.4.18: continued

Animal C P Animal C P

1 4 1 5

1 0 0 1

1 1 1 3

Mean 0.9 1.1 Mean 7 4.5

V12-11 (n.1) 2 0 V62-11 (n.2) 2 6

1 0 2 4

0 2 3 6

0 0 7 8

1 0 2 2

1 1 13 2

2 2 8 3

0 0 4 4

0 0 3 1

Mean 0.7 0.6 Mean 4.7 4.1

V13-11 (n.1) 1 0 V63-11 (n.2) 1 2

2 0 3 4

4 0 2 5

2 0 3 4

2 1 3 6

2 2 1 6

3 1 1 6

2 1 2 6

1 0 3 6

0 0 3 3

Mean 1.9 0.5 Mean 2.2 4.8

V14-11 (n.1) 3 1 V64-11 (n.2) 11 2

1 1 4 4

1 2 6 6

0 2 11 6

1 2 6 2

4 1 7 5

1 1 3 10

0 2 7 3

1 2 8 3

V14-11 (n.1) 0 1 V64-11 (n.2) 3 5

Mean 1.2 1.5 Mean 6.6 4.6

V15-11 (n.1) 1 2 V65-11 (n.2) 0 3

4 2 1 3

1 2 2 3

1 5 0 5

0 0 1 2

1 3 3 4

169 Tab. 8.4.18: continued

Animal C P Animal C P

V15-11 (n.1) 1 3 V65-11 (n.2) 3 7

Mean 1.2 1.5 Mean 6.6 4.6

V15-11 (n.1) 1 2 V65-11 (n.2) 0 3

2 0 7 4

1 2 4 3

2 2 3 1

Mean 1.4 2.1 Mean 2.4 3.5

V98-11 (n.3) 6 17 V1088-11 (n4) 32 29

14 20 18 16

18 10 8 21

13 20 14 22

23 21 21 22

10 20 11 18

10 10 20 21

15 6 19 13

8 12 15 8

17 12 19 20

Mean 13.4 14.8 Mean 17.7 19

V99-11 (n.3) 14 13 V1089-11 (n.4) 15 40

6 22 12 25

12 11 13 16

14 22 12 10

14 16 11 14

11 13 7 14

19 21 14 12

18 14 7 7

10 14 10 18

10 6 10 5

Mean 12.8 15.2 Mean 11.1 16.1

V100-11 (n.3) 20 12 V1090-11 (n.4) 9 25

22 13 8 13

10 20 1 3

17 25 8 6

13 10 2 12

9 8 19 23

15 25 9 13

18 16 5 11

14 11 5 4

Mean 15.4 15.1 Mean 7.1 12

170 Tab. 8.4.18: continued

Animal C P Animal C P

V101-11 (n.3) 17 13 V1091-11 (n.4) 12 31

9 22 14 20

4 21 7 8

6 11 8 20

4 7 14 22

7 6 5 9

13 7 4 7

10 13 5 3

17 7 9 8

15 11 6 6

Mean 10.2 11.8 Mean 8.4 13.4

V102-11 (n.3) 11 6 - - -

20 17 - - -

19 8 - - -

22 17 - - -

27 12 - - -

13 13 - - -

11 17 - - -

19 12 - - -

15 14 - - -

19 10 - - -

Mean 17.6 12.6

V103-11 (n.3) 16 24 - - -

35 18 - - -

30 20 - - -

12 23 - - -

14 19 - - -

10 13 - - -

17 13 - - -

9 5 - - -

8 11 - - -

14 11 - - -

Mean 16.5 15.7 - - -

CD3 = Platelet endothelial cell adhesion molecule marker for microvessel density; C = tumor center; P = tumor periphery; n.1 = 44 days after transplantation (dtp); n.2 = 54 dtp; n.3 = 63 dtp;

n.4 = 77 dtp

171

Tab. 8.4.19: Microvessel density (MVD) in subcutaneously xenotransplanted DH82 cells (control group).

Animal C P Animal C P

V10-11 (n.1) 8.65 16.72 V98-11 (n.3) 77.27 85.35 V11-11 (n.1) 5.19 6.34 V99-11 (n.3) 70.35 87.65 V12-11 (n.1) 4.03 3.46 V100-11 (n.3) 88.81 87.08 V13-11 (n.1) 10.95 2.88 V101-11 (n.3) 58.82 68.05 V14-11 (n.1) 6.92 8.65 V102-11 (n.3) 101.49 72.66 V15-11 (n.1) 8.07 12.11 V103-11 (n.3) 95.15 90.54 V60-11 (n.2) 39.21 64.01 V1088-11 (n.4) 102.07 109.57 V61-11 (n.2) 40.36 25.95 V1089-11 (n.4) 64.01 92.84 V62-11 (n.2) 27.10 23.64 V1090-11 (n.4) 40.94 69.20

V64-11 (n.2) 38.06 26.52 - - -

V65-11 (n.2) 13.84 20.18 - - -

MVD = microvessel density; C = tumor center; P = tumor periphery; n.1 = 44 days after transplantation (dtp); n.2 = 54 dtp; n.3 = 63 dtp; n.4 = 77 dtp; Values are depicted as the number of immunolabeled structures with a definable lumen in 10 randomly selected fields in the tumor center and 10 randomly selected fields in the tumor periphery at a 400x magnification divided by the microscopic field area at 400 magnification (mm²). Field area at 400 magnification = 0.1734 mm² (0.47 mm diamter)

Tab. 8.4.20: Intratumoral macrophages profile in subcutaneously xenotransplanted DH82 cells (control group).

MAC3

Animal C P Animal C P

V10-11 (#1.1.1) 18.3 7.8 V98-11 (#1.3.1) 78.2 53.5 V12-11 (#1.1.3) 1.2 0.3 V99-11 (#1.3.2) 84 57 V13-11 (#1.1.4) 23.6 23.4 V100-11 (#1.3.3) 51 50.8 V14-11 (#1.1.5) 4.8 3.5 V101-11 (#1.3.4) 1 32.7 V15-11 (#1.1.6) 4.9 3.7 V102-11 (#1.3.5) 25.6 28.4 V60-11 (#1.2.1) 25.7 29.6 V103-11 (#1.3.6) 21.5 47.4 V63-11 (#1.2.4) 11.5 33.6 V1088-11 (#1.4.2) 20 26 V62-11 (#1.2.6) 104.7 45.8 V1090-11 (#1.4.5) 33.5 29

- - - V1091-11 (#1.4.6) 46.2 35.7

MAC3 = monoclonal antibodies for murine macrophage; C = tumor center; P = tumor periphery;

n.1 = 44 days after transplantation (dtp); n.2 = 54 dtp; n.3 = 63 dtp; n.4 = 77 dtp; Values depicted are mean values of immunoreactive cells in 10 randomly selected fields in the tumor center and 10 randomly selected fields in the tumor periphery (each 0.1734 mm²) at a 400x magnification

172

Tab. 8.4.21: p-values of pairwise comparisons between inflammatory cell types in spontaneous canine histiocytic sarcomas (two way ANOVA)

Inflammatory cell Whole tumor area Localization C P MAC387 & CD3 0.7318 MAC387 & CD3 0.9975 0.9900

CD3 & Pax-5 0.0005 CD3 & Pax-5 0.0249 0.1856 MAC387 & Pax-5 <.0001 MAC387 & Pax-5 0.0062 0.0440 Two way ANOVA = significant (p ≤ 0.05); MAC387 = antibody against canine macrophages;

CD3 = antibody against T-lymphocytes; Pax-5 = antibody against B-lymphocytes; C = tumor center; P = tumor periphery

Tab. 8.4.22: p-values of pairwise comparisons of macrophage distribution between tumor center and periphery in a murine xenotransplantation model of histiocytic sarcoma (non-treated control group of acutely infected xenografts; Wilcoxon signed rank test)

Localization MAC3

C vs. P 0.5710

Wilcoxon signed rank test = significant (p ≤ 0.05); MAC3 = antibody against murine macrophage; C = tumor center; Pp = tumor periphery

Tab. 8.4.23: p-values of pairwise comparisons between MMP-14, MMP-2, MMP-9 and TIMP-1 in spontaneous histiocytic sarcomas (Wilcoxon signed rank test)

Localization MMP-14 MMP-9 MMP-2 TIMP-1 C vs. P 0.0023 <.0001 <.0001 <.0001

Wilcoxon signed rank test = significant (p ≤ 0.05); C = tumor center; P = tumor periphery; MMP

= matrix metalloproteinase; TIMP = tissue inhibitor of matrix metalloproteinase

Tab. 8.4.24: p-values of pairwise comparisons between MMP-14, MMP-2, MMP-9 and TIMP-1 (effect of localization) in spontaneous histiocytic sarcomas (Wilcoxon signed rank test)

Localization MMP-14 MMP-9 MMP-2 TIMP-1 C vs. P 0.0023 <.0001 <.0001 <.0001

Wilcoxon signed rank test = significant (p ≤ 0.05); C = tumor center; P = tumor periphery;

MMP = matrix metalloproteinase; TIMP = tissue inhibitor of matrix metalloproteinase

173

Tab. 8.4.25: p-values of pairwise comparisons between MMP-14, MMP-2, MMP-9 and TIMP-1 (effect of time point) in xenotransplanted histiocytic sarcomas – non-treated control group (Wilcoxon signed rank test)

Time point MMP-14 MMP-9 MMP-2 TIMP-1

C P C P C P C P

n.1 and n.2 0.9118 1.0000 0.9976 1.0000 0.9270 <.0001 1.0000 <.0001 n.1 and n.3 0.0081 0.1947 0.6920 0.9995 0.9999 <.0001 1.0000 <.0001 n.1 and n.4 <.0001 0.0007 0.1204 0.2779 1.0000 0.0002 1.0000 0.0076 n.2 and n.3 <.0001 0.9899 1.0000 0.5787 1.0000 1.0000 1.0000 0.253 n.2 and n.4 <.0001 0.1294 0.9886 0.0075 1.0000 0.9976 1.0000 0.9755 n.3 and n.4 0.9783 0.9978 1.0000 0.9972 1.0000 1.0000 1.0000 0.0002 Wilcoxon signed rank test = significant (p ≤ 0.05); C = tumor center; P = tumor periphery; n.1 = 44 days after transplantation (dtp); n.2 = 54 dtp; n.3 = 63 dtp; n.4 = 77 dtp; MMP = matrix metalloproteinase; TIMP = tissue inhibitor of matrix metalloproteinase

Tab. 8.4.26: p-values of pairwise comparisons of MMP-14, MMP-2, MMP-9 and TIMP-1 between spontaneous histiocytic sarcomas and xenotransplanted histiocytic sarcoma (non-treated control group of acutely infected xenografts; Wilcoxon signed rank test)

Time point MMP-14 MMP-9 MMP-2 TIMP-1

C P C P C P C P

CHS and

XDH82 0.2708 <.0001 <.0001 <.0001 <.0001 <.0001 <.0001 <.0001 Wilcoxon signed rank test = significant (p ≤ 0.05); C = tumor center; P = tumor periphery; CHS

= spontaneous histiocytic sarcoma; XDH82: xenotransplantation model of histiocytic sarcoma;

MMP = matrix metalloproteinase; TIMP = tissue inhibitor of matrix metalloproteinase

MMP = matrix metalloproteinase; TIMP = tissue inhibitor of matrix metalloproteinase