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11. Etiology of Induced Pancreatic Cancer ........................................................................... 72 Effects of Cholecystoduodenostomy and Choledochostomy ..................................................... 72 Effects of Partial Pancreatico-Colostomy .................................................................................. 72 Effects of Ductal Ligation and Excision ..................................................................................... 73 Anatomical Location of Induced Tumors ................................................................................... 73 12. Structural Changes During Pancreatic Carcinogenesis ................................................ 75 Alteration of Acinar Cells ........................................................................................................... 75 Alteration of Centroacinar and Intercalated Cells ...................................................................... 75 Alteration of Islet Cells .............................................................................................................. 81 Alteration of Ductules (intra-lobular and inter-lobular ducts) ..................................................... 81 Alteration of Small Ducts (interlobular, secondary ducts) ......................................................... 91 Alteration of Large Ducts (main ducts) ..................................................................................... 91 Alteration of Common Pancreatic Duct ..................................................................................... 92 Alteration of Common Bile Duct ................................................................................................ 93 13. Morphology of Induced Tumors ...................................................................................... 94 Tumors Arising from Within or Around the Islets ....................................................................... 94 Tumors Arising from Large Ducts ............................................................................................. 98 Tumors Arising from Ductules ................................................................................................... 99 14. Biology of Induced Tumors ............................................................................................ 118 Blood Group Antigen Expression ............................................................................................ 118 Expression of Lectins in Normal and Malignant Hamster Pancreatic Cells .............................. 126 Expression of Growth Factors in Normal and Malignant Pancreatic Cells ............................... 127 15. Molecular Biological Studies ......................................................................................... 128 16. Pancreatic Cell Lines ...................................................................................................... 131 Ductal Cell Culture .................................................................................................................. 131 Pancreatic Islet Cell Culture .................................................................................................... 133 17. Modification of Pancreatic Carcinogenesis .................................................................. 159 Effect of Growth Factors and Regeneration on Pancreatic Carcinogenesis ............................ 159 Effects of Nutrition on Longevity and Carcinogenicity ............................................................. 159 Effects of Pancreatic Secretagogue on Pancreatic Carcinogenesis ........................................ 173 The Effects of Various Conditions and Chemicals in Pancreatic Carcinogenesis .................... 181 The Effects of Cruciferous Vegetables and Polyphenoles in Pancreatic Carcinogenesis ........ 188 The Effect of Amino Acids in Pancreatic Carcinogenesis ........................................................ 190 The Effects of Enzymes in Pancreatic Carcinogenesis ........................................................... 191 18. Diagnostic Studies in Induced Pancreatic Cancer ....................................................... 194 Retro Grade Pancreatography ................................................................................................ 194 Test of Excretory Functions .................................................................................................... 194 Endocrine Abnormalities in the Pancreas................................................................................ 195 Endocrine Hormones in Pancreatic Exocrine Secretion .......................................................... 196 19. Prevention and Therapy of Pancreatic Cancer ............................................................. 202 The Effects of Anti-hyperlipidemic/Anti-diabetic Agents on Hamster Pancreatic Cancer ......... 202 iv
The Effects of Anti-inflammatory Agents on Hamster Pancreatic Cancer ................................ 203 The Effects of Natural Products on Hamster Pancreatic Cancer ............................................. 205 The Effects of Hormones on Hamster Pancreatic Cancer ....................................................... 206 The Effects of Chemotherapeutic Agents on Hamster Pancreatic Cancer ............................... 207 The Effects of Polyamine and Enzyme Inhibitors on Hamster Pancreatic Cancer ................... 208 Molecular Therapy of Hamster Pancreatic Cancer .................................................................. 210 Photodynamic Therapy of Hamster Pancreatic Cancer ........................................................... 211 20. Comparative Data on Pancreatic Cancer in Humans and Syrian Golden Hamster ... 213 21. Conclusions from the Studies on Pancreatic Carcinogenesis .................................... 220 References ............................................................................................................................ 227 v
Page 2 and 3: Proof Copy The Hamster as a Pancrea
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
Page 52 and 53: eached 50%, which was a significant
Page 54 and 55:
CHAPTER 8 Metabolic Studies on Panc
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450 3A family was involved, directl
Page 58 and 59:
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
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BOP by subcutaneous injection (5 mg
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Figure 52. The patterns of hamster
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experiments, SZ-induced diabetes si
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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
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Figure 69. Top: Hyperplastic centro
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Figure 71. Pseudoductular formation
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Figure 73. Ductular complexes showi
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Figure 75. Intra-insular ductular p
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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
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aising the question of the possible
Page 102 and 103:
Classification of pancreatic tumors
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include those lesions which consist
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Figure 92. Intra-ductal papillomas.
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Figure 96. a) Intra-ductal carcinom
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Figure 98. Ductular (tubular), well
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Figure 103.a) Tubular mucinous carc
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Squamous cell carcinoma. Pure squam
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Figure 110. poorly differentiated p
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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,
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DCC, and Rb-1 suppressor genes and
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Figure 142. Karyotype of the normal
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present crucial factors. Progress h
Page 144 and 145:
Figure 145. Human islets in culture
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Figure 147. Human islets in culture
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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
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Figure 156. Tumor growth in the ham
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Figure 160. Mono nucleated and poly
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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
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wt at six and seven weeks of age. T
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synthesis and release of large amou
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pancreatic ductular carcinoma incid
Page 182 and 183:
modifying effect of PH on pancreati
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predominant form of DNA alkylation
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the following 37 weeks. Additional
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tritiated thymidine (unpublished),
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or at the time of cellular regenera
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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
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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
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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
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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
Page 258 and 259:
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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