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Proof Copy The Hamster as a Pancreatic Cancer Model By: Parviz M. Pour, M.D. Eppley/University of Nebraska Cancer Center Omaha, NE Published by: The Pancreapedia: Exocrine Pancreas Knowledge Base In partnership with the University of Michigan Library Ann Arbor, MI 48109 and The American Pancreatic Association ISBN XXXXXXXXXXXXX Published under Creative Commons License 3.0
Table of Contents Foreword .................................................................................................................................. vi 1. Introduction ........................................................................................................................... 1 2. Pancreatic Cancer Models ................................................................................................... 2 Rat .............................................................................................................................................. 2 Inbred or Outbred Mice ............................................................................................................... 3 Immunodeficient Mice ................................................................................................................. 3 Transgenic Mice ........................................................................................................................ .4 Other Models .............................................................................................................................. 5 3. Hamsters in Toxicological Research ................................................................................... 6 Spontaneous Diseases of Syrian Golden Hamsters .................................................................... 7 4. The Pancreas of the Syrian Golden Hamster .................................................................... 10 Organogenesis of the Hamster Pancreas ................................................................................. 13 Cellular and Sub-cellular Anatomy of the Pancreas .................................................................. 14 Heterotopic Pancreas ............................................................................................................... 25 Comparative Anatomic-Histological Pancreatic Data ................................................................ 26 5. Physiology of the Hamster Exocrine Pancreas ................................................................ 27 Basic Secretory Function .......................................................................................................... 27 Secretagogue Stimulation ......................................................................................................... 27 Pattern of Pancreatic Secretions in Aging Hamsters ................................................................. 28 6. Spontaneous Diseases of the Hamster Pancreas ............................................................ 30 Comparative Spontaneous Pancreatic Diseases ...................................................................... 34 7. Pancreatic Carcinogens ..................................................................................................... 35 Effect of Genetic Factors in Response to Pancreatic Carcinogenic Nitrosamines ..................... 43 Rapid Method for Pancreatic Cancer Induction ......................................................................... 43 Other Methods for Pancreatic Cancer Induction........................................................................ 44 Trans Placental Effect of Pancreatic Carcinogens .................................................................... 44 8. Metabolic Studies on Pancreatic Carcinogens ................................................................. 46 Theory of the Importance of Cyclic Structure of the Carcinogen in the Pancreatotropic Effect .. 51 9. Drug-Metabolizing Enzymes in the Pancreas ................................................................... 54 10. The Role of Islets in Pancreatic Carcinogenesis ............................................................ 57 Effect of Intact Islets ................................................................................................................. 57 Effects of Diabetogenic Chemicals............................................................................................ 57 Effects of Nicotinamide ............................................................................................................. 63 Effects of Exogenous Insulin ..................................................................................................... 64 Effects of Islet Cell Neogenesis ................................................................................................ 65 Effects of Cell Proliferation ........................................................................................................ 66 Effects of Islet Transplantation .................................................................................................. 67 iii
Page 4 and 5: 11. Etiology of Induced Pancreatic
Page 6 and 7: This book is dedicated to the late
Page 8 and 9: with his researchers and provided h
Page 10 and 11: The first experimental pancreatic t
Page 12 and 13: immunodeficiency) mice, which have
Page 14 and 15: CHAPTER 3 Hamsters in Toxicological
Page 16 and 17: Figure 1. Comparative data on the a
Page 18 and 19: CHAPTER 4 The Pancreas of the Syria
Page 20 and 21: This designation, although arbitrar
Page 22 and 23: through the common duct into the gu
Page 24 and 25: shape with an almost transparent cy
Page 26 and 27: of the ducts (i.e., the wider the l
Page 28 and 29: Figure 20. Pancreatic islets of Syr
Page 30 and 31: Figure 23. Two cilia in a normal ha
Page 32 and 33: Figure 27. An islet with mostly typ
Page 34 and 35: enclosed in the lymphoreticular tis
Page 36 and 37: females showed no significant diffe
Page 38 and 39: CHAPTER 6 Spontaneous Diseases of t
Page 40 and 41: incidence) and almost regularly inv
Page 42 and 43: Figure 37. Patterns of islet cell t
Page 44 and 45: Figure 39. The molecular structure
Page 46 and 47: mg/kg body wt resulted in pancreati
Page 48 and 49: Lesions were also found in the peri
Page 50 and 51: high protein diet. These findings w
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eached 50%, which was a significant
Page 54 and 55:
CHAPTER 8 Metabolic Studies on Panc
Page 56 and 57:
450 3A family was involved, directl
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The ability of MOP to damage pancre
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(along with traces of BHP, but no u
Page 62 and 63:
CHAPTER 9 Drug-Metabolizing Enzymes
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Accordingly, in the rat and possibl
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carcinoma in Group 2 relate to the
Page 68 and 69:
BOP by subcutaneous injection (5 mg
Page 70 and 71:
Figure 52. The patterns of hamster
Page 72 and 73:
experiments, SZ-induced diabetes si
Page 74 and 75:
Figure 55. Presence of endocrine ce
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Figure 56. Homologous islets transp
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The normoglycemia in SZ-treated ham
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CHAPTER 11 Etiology of Induced Panc
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Among 75 adenocarcinomas, 14 (19%)
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egularly show hypertrophy and hyper
Page 86 and 87:
Figure 69. Top: Hyperplastic centro
Page 88 and 89:
Figure 71. Pseudoductular formation
Page 90 and 91:
Figure 73. Ductular complexes showi
Page 92 and 93:
Figure 75. Intra-insular ductular p
Page 94 and 95:
Figure 77. a) A cystic ductule with
Page 96 and 97:
Figure 79. Islet cell neogenesis. T
Page 98 and 99:
Figure 81. Alteration of large and
Page 100 and 101:
aising the question of the possible
Page 102 and 103:
Classification of pancreatic tumors
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include those lesions which consist
Page 106 and 107:
Figure 92. Intra-ductal papillomas.
Page 108 and 109:
Figure 96. a) Intra-ductal carcinom
Page 110 and 111:
Figure 98. Ductular (tubular), well
Page 112 and 113:
Figure 103.a) Tubular mucinous carc
Page 114 and 115:
Squamous cell carcinoma. Pure squam
Page 116 and 117:
Figure 110. poorly differentiated p
Page 118 and 119:
Figure 114. Giant cell carcinomas o
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Mixed Cell Carcinomas. As in humans
Page 122 and 123:
These findings ubiquitously point t
Page 124 and 125:
Figure 125. Top: Under SEM tumors p
Page 126 and 127:
14a. Blood group antigen expression
Page 128 and 129:
Table 2. Expression of Human Tumor
Page 130 and 131:
There seemed to be differences betw
Page 132 and 133:
Figure 137. Gold-labeled anti-A ant
Page 134 and 135:
Table 3. Lectin-binding patterns in
Page 136 and 137:
As part of our comparative studies,
Page 138 and 139:
DCC, and Rb-1 suppressor genes and
Page 140 and 141:
Figure 142. Karyotype of the normal
Page 142 and 143:
present crucial factors. Progress h
Page 144 and 145:
Figure 145. Human islets in culture
Page 146 and 147:
Figure 147. Human islets in culture
Page 148 and 149:
Figure 150. Chromosomal pattern of
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Carbonic anhydrase was demonstrated
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Figure 154. a) KL5N cells grew in r
Page 154 and 155:
Figure 156. Tumor growth in the ham
Page 156 and 157:
Figure 160. Mono nucleated and poly
Page 158 and 159:
formed a large encapsulated mass wi
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1 cm in the first and the second ge
Page 162 and 163:
Consequently, it must be concluded
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e transferred from the M3:5 medium,
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decrease in the HI° histone was fo
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easonably controlled environment of
Page 170 and 171:
Consumption of HF diets after eight
Page 172 and 173:
saturated fat on pancreatic carcino
Page 174 and 175:
suggested that the enhancement of P
Page 176 and 177:
wt at six and seven weeks of age. T
Page 178 and 179:
synthesis and release of large amou
Page 180 and 181:
pancreatic ductular carcinoma incid
Page 182 and 183:
modifying effect of PH on pancreati
Page 184 and 185:
predominant form of DNA alkylation
Page 186 and 187:
the following 37 weeks. Additional
Page 188 and 189:
tritiated thymidine (unpublished),
Page 190 and 191:
or at the time of cellular regenera
Page 192 and 193:
hamsters receiving the 2% BHA suppl
Page 194 and 195:
the inhibition of pancreatic cancer
Page 196 and 197:
diet in comparison with hamsters fe
Page 198 and 199:
diet supplemented with 2% (group 1)
Page 200 and 201:
single subcutaneous injection of BO
Page 202 and 203:
Figure 168. Pancreatography by retr
Page 204 and 205:
Although we have identified insulin
Page 206 and 207:
Figure 169. Perivascular iendocrine
Page 208 and 209:
ducts and in the micro carcinoma (F
Page 210 and 211:
CHAPTER 19 Prevention and Therapy o
Page 212 and 213:
proMMP-2 is highly activated in PC
Page 214 and 215:
plus adenocarcinomas were significa
Page 216 and 217:
and the combination of 5-fluorourac
Page 218 and 219:
duct carcinogenesis. OPB-3206 may b
Page 220 and 221:
thus receive the highest photodynam
Page 222 and 223:
The same applies to hyperplastic an
Page 224 and 225:
Figure 177. Serial sectioning of a
Page 226 and 227:
atypical-to-malignant and were remo
Page 228 and 229:
CHAPTER 21 Conclusions from the Stu
Page 230 and 231:
While these precursor cells may be
Page 232 and 233:
transform the cultured human islet
Page 234 and 235:
Figure 181. After massive degenerat
Page 236 and 237:
27. Caygill CP, Hill MJ, Hall CN, K
Page 238 and 239:
68. Nakase A, Koizumi T, Fujita N,
Page 240 and 241:
116. Pour PM, Kazakoff K, Dulaney K
Page 242 and 243:
162. Pour P, Althoff J, Nagel D. In
Page 244 and 245:
203. Lawson T, Kolar C. Mutation of
Page 246 and 247:
246. Rettie AE, Korzekwa KR, Kunze
Page 248 and 249:
289. Bell RH, Jr., McCullough PJ, P
Page 250 and 251:
335. Pour PM, Uchida E, Burnett DA,
Page 252 and 253:
375. Resau JH, Hudson EA, Jones RT.
Page 254 and 255:
419. Schreiber AB, Winkler ME, Dery
Page 256 and 257:
463. Fitzgerlad P, Sharkey F, Fogh
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507. Herrington MK, Permert J, Kaza
Page 260 and 261:
548. Permert J, Ihse I, Jorfeldt L,
Page 262 and 263:
586. Nishikawa A, Furukawa F, Kasah
Page 264:
627. Rao MS, Scarpelli DG, Reddy JK
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