Lecture 5 Article - 1lO3M;\7/7/56()I0004$02.0()/()...

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1 3·M;\7/±²³56()I´0µ¶4$¸2.µ¹º»¼ LABORaTOrY iNVESt½G¾t¿oN Copyright À98Á by THe UnIted S±a²Es and cAn³d´an µ¶³demy Âf P·thOl¸gY, ¹nº. yÃ>lÄ 56, nÅÆ Ç pÈ É9ÊË Printed IN UsÌÍÎ Biolog of Disease Hepatocarcinogenesis: A Dynamic Cellular Perspective E MMANUEL F ARBER AnD D. S± R² S ARMA Departments of Patholgy and of BiochemistR, MedicaL Sciences BuiLding± UniversitY of Toronto² Toronto³ Ontario´ Canada I±troductio±. ² . ³ . . . . . .´µ . µ ± ± ³ ³ . ². . , ± ² ±²± ³ ± ´ ² ´ µ µ . . . .. . . · The Scie±tifc A±alysis oF Chro±ic ·iseases I±cludi±g C¸±cer ¹. Step-byºstep d»sco±ti±uity. ¼ ² ¸ . ± ½ ² ¹ ³² ¹ ´ º µ Ì » ¼ ½ ± . ¾ ¿ ¾esista±ce as a basis For selectio± .´³ À ± Á  ¶³ ù ´ Age±ts uersUs processes ²¹¹. .  . Ä . Å ¹ ´ ² º Ì ± ½ ÆǺ È ¿ ± À ³. ³µ  ¹ É In vitRo uers± ²n uiVo . µ ¶ µ   ±± ..¹ Â' ± Ê ² , À º . Ë . Î ± Î ² . Ì ± ² The Esse±ce oF Hepatocarci±oge±esis From a CeÁlular PerspectiveÀ ¼õ Í ² ³ Î The StepÄby-Step ·evelopme±t oF Åiver Cell Carci±oma i± the ¾at . .. Æ Çodels ¹È.¼ . Ï ² É ³.. Ð ² ².²³ . Ê ... É ² É . . ²± Î .. Ñ ±·³. Ò Î Ë ² ¹µ ¸  ¸²± Ó I±itiatio± .Ì ± .². ³Ê ÔÒ . Õ . ±. Ò. ´ ± ± . Ö . ¿ × ·eFͱitio± .Ë Îssays .¼½µ¹¼¹¹¹.¹Ï. .É.¶ÊÐ.µ¹¼Ñ.Ò. Ø Ù µ Ì . Ú Step 1 (ÓÔ1) ÕioÖhemical lesio±×sØ ´.´ È Step 2 (ÙÚ2) ÛixaÜio± by ceÁl proÝiFeratio± ´µ.¹Þ Ï Promotio± ¹ß¼¼¼ Û Êà  ±.² à ....·³² Ü ¹ ÝÞ ² Ô ½ ß ·eá±iÜio± ¼ ²± Ñ . Ç ±² ÒË ..± µ ³º.². . ² à á . Ê . µ. â Step 3 âPãäå Çicroscoæic Foci or çsÁa±ds Ϲ. ã ètep 4 éPê2ë HepaìOcyte ±oíuîesï Progressio±É . É ³ ± º ² » . Ñ ¹ Ô Ò . Ô . Ñ . Ï ± ² ± µ ¿ ± ± µ ä ¹µ Î Ô . å . Ôà ². . .¹³ ± µ . ßÊ ³ ·eá±itio± ´ » ¼ ½ . È Ê ¼ ¹ ± ² . Ñ ± ± · . .± Ê ¾ .² ± Step 5 ðPCñò) CelÁ proÁóFeratio± plus cell death i± the persiste±t ±odule ô.õ´¹.¹ö.¹¹¹. .µ´. º Step 6 ðPC÷2) Cell proliFeratio±ø cell deathù a±d altered shutãoFF oF the ceÁl cycÁe .ú.û.ü.¹.´¼´¹ æ Step 7 a±d subseque±t steps (PCý3) ç . è Ï é Î . µ ê . ³ Ì ³ ± ë ì í î À  ¹ · µ È Ì À ± , . µ µ ï µ ð µ ¾ Hepatocellular cþrci±omþ (HÔ1ø Hÿ2Ā Hā3) ¹,' ½ ñ½ . ò ó Ë . ô ² Ø ´. ².± µ. õ ² Â Ä ÔÒ Çecha±isms at DiFFeĂe±t Steps¼ ă  . È . ö . ÷ . ² . ± ï ¹. ±²². . . øù . ú µ û ʼ ´¹µ ü ý ... ý Ge±eral Co±sideratio±s µ.².ϼµ¹. .¿¹È¹ßĄ²¼¼¹µ.ö.¼.µ.³.Ê Î Ë ² ± й ² É ã ² ² I±itiatio± ³.ą.Ć.³.ć. þ . ÿĀ ± ā .. Ĉ. þ ½ ...¶ µ Ð ¹ ³.. Â É ÀĂ ă ²±²±²± À . Ą ± Promotio± ¹É.É.ĉĈÈ.É.
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Lecture 5 Article - 1lO3M;\7/7/56()I0004$02.0()/()...

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