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NETSCAPE2.0!GifBuilder 0.4 by Yves Piguet! , 鸺9 濆>Z歵YWvq梬仐x憲IJ睌K匜盪4 o鉀' qb|0ゆN亚笱躧O栌,Ikz秪礧幺|X輜yG5FWIKMOQS'噳媿彂搮+/3湑)-1泝9qTF挭〃煢盷砈惗=M姽7W擟絈幏;K埡芌瓤L镣I唭68:<>嶡怋扗谀菸J略闶P狙樾墚唢d?騚+r唙鰤骔.郂Y 翧榦A !笂$$ Gx蘹xs ;iE$磳0濣[鐽%B|-G謉/\? 涎j掕L擧K*裪O橯鏜饺rbQ琤竧WU歗 舏r缪>u5隦jL╬i蝅[v霫~鳝l蕰ぶ粈煢%虜.闩y颃決柢翍g誜否e%媢X植D獭5嘙谫馪悩鬓燠咸眒bそ裮喔jg楷 6un|圇洱著O% Z蛗{2i猐Q+|k}訝非cm仵绡⑸撆刿衤腠n卷\.趄~}+~邩眚鈧=嚋p颦 p 踺t︰7歸鎭嚍j莸f冣!FYi已 wZ蒯A*痃堁爙瞀\娡湅"偗跚尶閡_5^仌賴CV迏f纲嗢鍃*邆h櫂\嶛]E鈱荺廮&H爼6茍4①%nr興櫾仺^慻褖琢w瀊奚a濻 '剆B鎐媋嘩}`忡╦悮&g螬(|(fJ&dlBS0,-前B 3 @H:*,谈 E琂碖%蔸V玿嘉*l绑([M迸氆类异 ?J懕 蕬8褔{-5l褛1/酡q./駉X鳾紸熔硷*L肞8 0 臌0k<1{|1籏E! , 9濇劲殸歵YWvq梬仐x憲IJ睌K匜盪4 o鉀' qb|0ゆN亚笱躧O栌,Ikz秪礧幺|X輜yG5FWIKMOQS'噳媿彂搮+/3湑)-1泝9qTF挭〃煢盷砈惗=M姽7W擟絈幏;K埡芌瓤L镣I唭68:<>嶡怋扗谀菸J略闶P狙樾墚唢d?騚+r唙鰤骔.郂Y 翧榦A !笂$$ Gx蘹xs ;iE$磳0濣[鐽%B|-G謉/\? 涎j掕L擧K*裪O橯鏜饺rbQ琤竧WU歗 舏r缪>u5隦jL╬i蝅[v霫~鳝l蕰ぶ粈煢%虜.闩y颃決柢翍g誜否e%媢X植D獭5嘙谫馪悩鬓燠咸眒bそ裮喔jg楷 6un|圇洱著O% Z蛗{2i猐Q+|k}訝非cm仵绡⑸撆刿衤腠n卷\.趄~}+~邩眚鈧=嚋p颦 p 踺t︰7歸鎭嚍j莸f冣!FYi已 wZ蒯A*痃堁爙瞀\娡湅"偗跚尶閡_5^仌賴CV迏f纲嗢鍃*邆h櫂\嶛]E鈱荺廮&H爼6茍4①%nr興櫾仺^慻褖琢w瀊奚a濻 '剆B鎐媋嘩}`忡╦悮&g螬(|(fJ&dlBS0,-前B 3 @H:*,谈 E琂碖%蔸V玿嘉*l绑([M迸氆类异 ?J懕 蕬8褔{-5l褛1/酡q./駉X鳾紸熔硷*L肞8 0 臌0k<1{|1籏E! , 09濈>&跔 歵YWvq梬仐x憲IJ睌K匜盪4 o鉀' qb|0ゆN亚笱躧O栌,Ikz秪礧幺|X輜yG5FWIKMOQS'噳媿彂搮+/3湑)-1泝9qTF挭〃煢盷砈惗=M姽7W擟絈幏;K埡芌瓤L镣I唭68:<>嶡怋扗谀菸J略闶P狙樾墚唢d?騚+r唙鰤骔.郂Y 翧榦A !笂$$ Gx蘹xs ;iE$磳0濣[鐽%B|-G謉/\? 涎j掕L擧K*裪O橯鏜饺rbQ琤竧WU歗 舏r缪>u5隦jL╬i蝅[v霫~鳝l蕰ぶ粈煢%虜.闩y颃決柢翍g誜否e%媢X植D獭5嘙谫馪悩鬓燠咸眒bそ裮喔jg楷 6un|圇洱著O% Z蛗{2i猐Q+|k}訝非cm仵绡⑸撆刿衤腠n卷\.趄~}+~邩眚鈧=嚋p颦 p 踺t︰7歸鎭嚍j莸f冣!FYi已 wZ蒯A*痃堁爙瞀\娡湅"偗跚尶閡_5^仌賴CV迏f纲嗢鍃*邆h櫂\嶛]E鈱荺廮&H爼6茍4①%nr興櫾仺^慻褖琢w瀊奚a濻 '剆B鎐媋嘩}`忡╦悮&g螬(|(fJ&dlBS0,-前B 3 @H:*,谈 E琂碖%蔸V玿嘉*l绑([M迸氆类异 ?J懕 蕬8褔{-5l褛1/酡q./駉X鳾紸熔硷*L肞8 0 臌0k<1{|1籏E! , 9澿荆. 歵YWvq梬仐x憲IJ睌K匜盪4 o鉀' qb|0ゆN亚笱躧O栌,Ikz秪礧幺|X輜yG5FWIKMOQS'噳媿彂搮+/3湑)-1泝9qTF挭〃煢盷砈惗=M姽7W擟絈幏;K埡芌瓤L镣I唭68:<>嶡怋扗谀菸J略闶P狙樾墚唢d?騚+r唙鰤骔.郂Y 翧榦A !笂$$ Gx蘹xs ;iE$磳0濣[鐽%B|-G謉/\? 涎j掕L擧K*裪O橯鏜饺rbQ琤竧WU歗 舏r缪>u5隦jL╬i蝅[v霫~鳝l蕰ぶ粈煢%虜.闩y颃決柢翍g誜否e%媢X植D獭5嘙谫馪悩鬓燠咸眒bそ裮喔jg楷 6un|圇洱著O% Z蛗{2i猐Q+|k}訝非cm仵绡⑸撆刿衤腠n卷\.趄~}+~邩眚鈧=嚋p颦 p 踺t︰7歸鎭嚍j莸f冣!FYi已 wZ蒯A*痃堁爙瞀\娡湅"偗跚尶閡_5^仌賴CV迏f纲嗢鍃*邆h櫂\嶛]E鈱荺廮&H爼6茍4①%nr興櫾仺^慻褖琢w瀊奚a濻 '剆B鎐媋嘩}`忡╦悮&g螬(|(fJ&dlBS0,-前B 3 @H:*,谈 E琂碖%蔸V玿嘉*l绑([M迸氆类异 ?J懕 蕬8褔{-5l褛1/酡q./駉X鳾紸熔硷*L肞8 0 臌0k<1{|1籏E! , 9濁>爮6Z歵YWvq梬仐x憲IJ睌K匜盪4 o鉀' qb|0ゆN亚笱躧O栌,Ikz秪礧幺|X輜yG5FWIKMOQS'噳媿彂搮+/3湑)-1泝9qTF挭〃煢盷砈惗=M姽7W擟絈幏;K埡芌瓤L镣I唭68:<>嶡怋扗谀菸J略闶P狙樾墚唢d?騚+r唙鰤骔.郂Y 翧榦A !笂$$ Gx蘹xs ;iE$磳0濣[鐽%B|-G謉/\? 涎j掕L擧K*裪O橯鏜饺rbQ琤竧WU歗 舏r缪>u5隦jL╬i蝅[v霫~鳝l蕰ぶ粈煢%虜.闩y颃決柢翍g誜否e%媢X植D獭5嘙谫馪悩鬓燠咸眒bそ裮喔jg楷 6un|圇洱著O% Z蛗{2i猐Q+|k}訝非cm仵绡⑸撆刿衤腠n卷\.趄~}+~邩眚鈧=嚋p颦 p 踺t︰7歸鎭嚍j莸f冣!FYi已 wZ蒯A*痃堁爙瞀\娡湅"偗跚尶閡_5^仌賴CV迏f纲嗢鍃*邆h櫂\嶛]E鈱荺廮&H爼6茍4①%nr興櫾仺^慻褖琢w瀊奚a濻 '剆B鎐媋嘩}`忡╦悮&g螬(|(fJ&dlBS0,-前B 3 @H:*,谈 E琂碖%蔸V玿嘉*l绑([M迸氆类异 ?J懕 蕬8褔{-5l褛1/酡q./駉X鳾紸熔硷*L肞8 0 臌0k<1{|1籏E! , 9濃緺>殹歵YWvq梬仐x憲IJ睌K匜盪4 o鉀' qb|0ゆN亚笱躧O栌,Ikz秪礧幺|X輜yG5FWIKMOQS'噳媿彂搮+/3湑)-1泝9qTF挭〃煢盷砈惗=M姽7W擟絈幏;K埡芌瓤L镣I唭68:<>嶡怋扗谀菸J略闶P狙樾墚唢d?騚+r唙鰤骔.郂Y 翧榦A !笂$$ Gx蘹xs ;iE$磳0濣[鐽%B|-G謉/\? 涎j掕L擧K*裪O橯鏜饺rbQ琤竧WU歗 舏r缪>u5隦jL╬i蝅[v霫~鳝l蕰ぶ粈煢%虜.闩y颃決柢翍g誜否e%媢X植D獭5嘙谫馪悩鬓燠咸眒bそ裮喔jg楷 6un|圇洱著O% Z蛗{2i猐Q+|k}訝非cm仵绡⑸撆刿衤腠n卷\.趄~}+~邩眚鈧=嚋p颦 p 踺t︰7歸鎭嚍j莸f冣!FYi已 wZ蒯A*痃堁爙瞀\娡湅"偗跚尶閡_5^仌賴CV迏f纲嗢鍃*邆h櫂\嶛]E鈱荺廮&H爼6茍4①%nr興櫾仺^慻褖琢w瀊奚a濻 '剆B鎐媋嘩}`忡╦悮&g螬(|(fJ&dlBS0,-前B 3 @H:*,谈 E琂碖%蔸V玿嘉*l绑([M迸氆类异 ?J懕 蕬8褔{-5l褛1/酡q./駉X鳾紸熔硷*L肞8 0 臌0k<1{|1籏E! , 凹9 濄>凇歵YWvq梬仐x憲IJ睌K匜盪4 o鉀' qb|0ゆN亚笱躧O栌,Ikz秪礧幺|X輜yG5FWIKMOQS'噳媿彂搮+/3湑)-1泝9qTF挭〃煢盷砈惗=M姽7W擟絈幏;K埡芌瓤L镣I唭68:<>嶡怋扗谀菸J略闶P狙樾墚唢d?騚+r唙鰤骔.郂Y 翧榦A !笂$$ Gx蘹xs ;iE$磳0濣[鐽%B|-G謉/\? 涎j掕L擧K*裪O橯鏜饺rbQ琤竧WU歗 舏r缪>u5隦jL╬i蝅[v霫~鳝l蕰ぶ粈煢%虜.闩y颃決柢翍g誜否e%媢X植D獭5嘙谫馪悩鬓燠咸眒bそ裮喔jg楷 6un|圇洱著O% Z蛗{2i猐Q+|k}訝非cm仵绡⑸撆刿衤腠n卷\.趄~}+~邩眚鈧=嚋p颦 p 踺t︰7歸鎭嚍j莸f冣!FYi已 wZ蒯A*痃堁爙瞀\娡湅"偗跚尶閡_5^仌賴CV迏f纲嗢鍃*邆h櫂\嶛]E鈱荺廮&H爼6茍4①%nr興櫾仺^慻褖琢w瀊奚a濻 '剆B鎐媋嘩}`忡╦悮&g螬(|(fJ&dlBS0,-前B 3 @H:*,谈 E琂碖%蔸V玿嘉*l绑([M迸氆类异 ?J懕 蕬8褔{-5l褛1/酡q./駉X鳾紸熔硷*L肞8 0 臌0k<1{|1籏E!, 屑9 濅尽歵YWvq梬仐x憲IJ睌K匜盪4 o鉀' qb|0ゆN亚笱躧O栌,Ikz秪礧幺|X輜yG5FWIKMOQS'噳媿彂搮+/3湑)-1泝9qTF挭〃煢盷砈惗=M姽7W擟絈幏;K埡芌瓤L镣I唭68:<>嶡怋扗谀菸J略闶P狙樾墚唢d?騚+r唙鰤骔.郂Y 翧榦A !笂$$ Gx蘹xs ;iE$磳0濣[鐽%B|-G謉/\? 涎j掕L擧K*裪O橯鏜饺rbQ琤竧WU歗 舏r缪>u5隦jL╬i蝅[v霫~鳝l蕰ぶ粈煢%虜.闩y颃決柢翍g誜否e%媢X植D獭5嘙谫馪悩鬓燠咸眒bそ裮喔jg楷 6un|圇洱著O% Z蛗{2i猐Q+|k}訝非cm仵绡⑸撆刿衤腠n卷\.趄~}+~邩眚鈧=嚋p颦 p 踺t︰7歸鎭嚍j莸f冣!FYi已 wZ蒯A*痃堁爙瞀\娡湅"偗跚尶閡_5^仌賴CV迏f纲嗢鍃*邆h櫂\嶛]E鈱荺廮&H爼6茍4①%nr興櫾仺^慻褖琢w瀊奚a濻 '剆B鎐媋嘩}`忡╦悮&g螬(|(fJ&dlBS0,-前B 3 @H:*,谈 E琂碖%蔸V玿嘉*l绑([M迸氆类异 ?J懕 蕬8褔{-5l褛1/酡q./駉X鳾紸熔硷*L肞8 0 臌0k<1{|1籏E;縬鼲IEND瓸`n=X駘皫牣H8>匘塒NG  IHDRX齏壪sRGB pHYs+礗DATx^忑w$W枼 "E挋YUY濤骇努7緳5kfUuwuu2蒨Hp`窘鞯 A0#坧槢<鬓硰>[葜Q牐@G亷>W >镛唬@G亷: v鬆G亷>k t@鳼黩: t(a7: t(蠶喑劅躔w/逹牐@G亷vs牐@G亷>k t@鳼黩: t(a7: t(蠶喑劅躔w/逹牐@G亷vs牐@G亷>k t@鳼黩: t(a7: t(蠶喑劅躔w/逹牐@G亷vs牐@G亷>k t@鳼黩: t(a7: t(蠶喑劅躔w/逹牐@G亷vs牐@G亷>k t@鳼黩: t(a7: t(蠶喑劅躔w/逹牐@G亷vs牐@G亷>k t@鳼黩: t(a7: t(蠶喑劅躔w/逹牐@G亷vs牐@G亷>k t@鳼黩: t(a7: t(蠶喑劅躔w/逹牐@G亷vs牐@G亷>k t@鳼黩: t(a7: t(蠶喑劅躔w/逹牐@G亷vs牐@G亷>k t@鳼黩: t(a7: t(蠶喑劅躔w/逹牐@G亷vs牐@G亷>k t@鳼黩: t(皚qq裃。@G亷: |t8??鐧贩冯锛翸笘#踇庫4聫n杌(蠶牐@GQ`粖m"Mi匃"ZwpG亷: |福u骦囔4qD籫(蠶牐@G伝S牏囗p确uk_禄摵;玻@G亷>D D 苢x觱-RvρqP籫(蠶牐@G7RT唯z9錨幟蜧鳩:wt(蠶牐/L伝D佹橖 &D齾嚩粆G亷: <,n#m[QPj#m鯵猾u(蠶牐纆K伓I岐2W暭k犴皙赹絝甈玂庇?跧亟xG亷~I 軘貇撴Y粙t(蠶牐累Q`#儒莲7眭z4墥5咪头桧'辬嗪: t(蠶(pmㄧF禵;哰n鼀!畢姻 嵃阮: t(pw TLn7恟 邸1砘'bg禁鄒Gv(蠶牐繡Q* 稉隴鋻夡譌苘遒畾F;醈柚観牐@G亷I乲u羦疤U惋攴?蠱莀葸橣rh籯u(蠶牐)p%瞞壹V;|銜Wc)威泑嚌Fx/聉w(蠶牐繻)卸^禔S'仢瘴Y欲j櫺j6劖鼂#=> =7N靘飨献協阠lo]_喆禄巋w\G亷: 6T兵黬抺U 瓒伬~艄v]4葑鑩巾A;:f韄糥]据皏gu(蠶牐繻)搬l7坔W 光唭斑X+%p躲h扜貇竴钆礝荠:愝q: t(p_ 摧~3@誇 涚0檴傢Irn/莅崺WQ饢'4蔓kw|G亷: 軌讍哣膴^XA1 Wm3轾碰:;皻U匐瑠册讨莣豛E07楩;嶐N觅訯牐@G亷oM乲 5^*vQ74B|.#e3鴔>:谷/匾oz﨨#|霊鞱(蠶牐@G佦(P駉C5苄+^踈 <_m].!\範b_漱V佫1朧|%跏a7; t(蠶嘟P嗒/{狝?珌$獲:*@豩: 圊豆B鄲s耎M圳dh勶e媣(蠶喑5i桒Ll 猆-版NギR閎Kg0釫X#萚漮-Vg(垊茽%/衔fцx浸p0m醵8|+雋尌D. 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Mechanism of pharmacologic action&%0%g 3  鹄   餪榓? ?"6?@`NNN?NTG 痱^1 Cell biology mechanisms of antitumor effect&000gf3J   瓞   餪詆? ?"6?@`NNN?NT 疝^2 Biochemistry mechanisms of antitumor effect&000gf36 餒  0師藿h ? 秽33櫃櫶___PPT10i.躷p"<+D='  = @B +0 鹬餹(  鹉   餱`\? ??"6?@`NNN?N| 痧\1 Cell biology mechanism of antitumor effect&/0/g f3J   餵  餤0b? ??"6?@`NNN?N  餒@8___PPT9 餜Cell Cycle-Nonspecific (CCNS) Agents: Alkylating agent, Antibiotics, Platinum antitumor compoundCell Cycle-Specific (CCS) Agents: Methotrexate: S phase Vinca alkaloid: M phaseE1f3!0f3$1f390f3%gfg f兀g烃g f!gfg fg烃3g烃b&  4  @`餒  0師藿h ? 33洙33y___PPT10Y+D='  = @B ++ 0  鹩 @ 餶 (  鸢   餱瑆? ??"6?@`NNN?Nc  疖\2 Biochemistry mechanisms of antitumor effect&/0/gf36 餿   餱? ??"zBH餒@8___PPT9 饊&Affecting biosesynthesis of nucleic acid('1ff'Gf @`0  <t*饉vn___PPT9PH     >\Dihydrofolate Reductase InhibitorMethotrexateh/1!G烃g烃 G烃 g 烃@    8X疰  <3S  饅synthesis of tetrahydrofolate G烃   <錈 W  饹-synthesis of thymidylate, purine nucleotides ..G烃, 鸺  <欹 Z  餚formation of DNA, RNA G烃餜B  s *DC餜B  s *D% 餜B  s *D 餒  0師藿h ? 33洙330 \餞 痨(  養  6棘jp 疖Nb) Pyrimidine AntagonistsFluorouracil ((G烃6   8X痤  <尮 饌deoxythymidylate synthetase G烃$ 鹎  0冀} 餲deoxyuridylic acid G烃 鹫  <dpZ  餴deoxythymidylic acid G烃鸷  養枧 f  餒DNA synthesis G烃餜B  s *D}餜B  s *Dp餜B  s *D c 餒  0師藿h ? 秽33櫃櫶80___PPT10.蠞恥Y30 饹 3(  瘊  6$jK 饠.C) Purine Antagonists G烃$ 鹄  養|}}  餘6-thioinosinic acid G烃瓞  <枵@  餈HGPRT Gf鹞  <] } 餬MercaptopurineG烃餜B  s *D  痼  <(,  饑!purine nucleotide interconversion""G烃$ 餜B  s *D  餒  0師藿h ? 秽33櫃櫶80___PPT10.袧]<0 2*P 鹇(    6t7,? 鸪3d) Ribonucleotide Reductase Inhibitor: Hydroxyurea 44G烃>  鹈  0瓣u  餭cytidylic acid G烃 鹪  <达r  餳deoxycytidylic acid G烃鸫  <滛 j (  餒DNA synthesis G烃餜B  s *D餜B  s *D餜B  s *D% 餒  0師藿h ? 秽33櫃櫶80___PPT10.覞`c燓0 j餬 瘊(  瘙  養 饘8e) DNA Polymerase InhibitorG烃疔  0  饆Cytarabine (ara-C ) G烃$ 疱  <| 饄5'-mononucleotide (AraCMP)  G烃痍  <H PJtp 饉triphosphate (AraCTP)  G烃$ 鹪  6% -t E  餹 DNA polymerase (G烃鸲  < 8  餔DNA synthesis  G烃餜B  s *D  餜B  s *D  餜B  s *Dp  S 餜B  s *Dc   F 餒  0師藿h ? 秽33櫃櫶80___PPT10.諠皜 s0 饌(  鸲  <<F 餔 0C 饈  養-? ?"6?@`NNN?NtI 餒@8___PPT9  饈DNA Cross-linkage agent: alkylating agents Platinum antitumor compound: Cisplatin Antibiotics: Bleomycin Topoismerase inhibitor: camptothecins (1G烃        8X馃  餪d(? ?"6?@`NNN?N餒@8___PPT9 饋'Affecting structure and function of DNA((1f(Gf @`餒  0師藿h ? f觋ff櫶___PPT10i.p塾+D='  = @B +E0 \餞痨(    餤楨? ??"6?@`NNN?N,"餒@8___PPT9 痣CAffecting transcription process and interrupting synthesis of RNA>%1f0fDGf0    % @`皓  <PH- 餷d\___PPT9>6    鹕Anthracyclin DactinomycinR1烃 G烃g烃 G烃$  8X餒  0師藿h ? f觋ff櫶___PPT10i.P+D='  = @B +] 0 t餷 (  餿  餤hX? ??"6?@`NNN?NY 瓞<d. Interfering with the formation and function of proteins ><0f1f=Gf @`穑  養蘓? ?"6?@`NNN?Nms餒@8___PPT9  穑'Microtubule inhibitors: Vinca alkaloid ((1烃(G烃  @`鹱  <糲5  餶tubulin polymerization G烃痍 <e   饉extension of microtubules &G烃 鹌 <8o w  餤 termination of mitotic division !!G烃餜B s *D2餜B s *D% 餜B s *D 餒  0師藿h ? f觋ff櫶___PPT10i.愐3#+D='  = @B ++0 饟 +(  痂  <靹j fp 饇$b) Agent influence amino acid supply&%0烃%G烃 @`鹜  <l  餫 Asparaginase Gf 鹫  <魦 % 餴 L-asparagine G烃 鸷  養◤` % 餒aspartic acid G烃餜B  s *D 餜B  s *DC 疔  <L Y 餺 protein synthesis &G烃餒  0師藿h ? 秽33櫃櫶80___PPT10.贊睯0 皎(  鹂   餱H? ??"6?@`NNN?Ne餒@8___PPT9 饹Affecting hormone homeostasis(1fGf    @`皓  養X? ?"6?@`NNN?N: 饜___PPT9bZ      餫S Estrogens and antiestrogen Androgens and antiandrogen Progestogens glucocorticoid |T1 G烃g烃G烃 g 烃*G烃X    @`餒  0師藿h ? f觋ff櫶80___PPT10.爔?/0 D< 鹛(  $   餱然? ??"6?@`NNN?N  餚1. Resistance&0gf3鹫  餤d? ??"6?@`NNN?NV 餒@8___PPT9  鸾?Inherently resistant Acquired resistance Multidrug Resistance*@1ff@gf+   @`饗   餱樕? ??"6?@`NNN?N7/ 鸱1SectionII Problems associated with chemotherapy H20 g3(g3 (餒  0師藿h ? 33洙33y___PPT10Y+D='  = @B +80 馉8(  疖  養<w 餵Multidrug Resistance gf  餏  0凑/  疰Tumor cells may become generally resistant to a variety of cytotoxic drugs on the basis of decreased uptake or retention of the drugs "G烃; C鹞  <汹 :5  餬P-glycoprotein 6gf3gf餒  0師藿h ? 秽33櫃櫶80___PPT10.銤p蛼0 a餣p T瘃(  T9 T 餤$? ??"6?@`NNN?NM7  餼(1) short term toxicity(0ffgf @`饞 T  餪滊 ??W 餤RJ___PPT9,$   馉 Common adverse effects:21烃g烃  8X鸬 T  餪 m ??+ 饎|t___PPT9VN 饳} Bone Marrow Toxicity: hormone, Bleomycin, asparaginase (b) Gastrointestinal Tract Toxicity (c) Hair Follicle Toxicity1g0Gff&Gffgff G ffgffGff6%  A8X! T  餱 m? ??"6?@`NNN?NV 餗 2. Toxicity& 0 gf3餒 T 0師藿h ? 33洙33r0 饝X)(  X鹋 X  餱m? ??"6?@`NNN?N<7 \餒@8___PPT9  稹 Uncommon adverse effects: (1烃g烃$  8X$ X  餱m? ??"6?@`NNN?N,}. 餚(a) Pulmonary toxicity: Bleomycin (b) Hepatotoxicity L-Asparaginase 0Cyclophosphamide (c) Renal toxicityCyclophosphamide (d) NeurotoxicityVincristine0Cisplatin (e) Allergic responseL-Asparaginase0Bleomycin0Paclitaxel :0ff1ffGff          8X餒 X 0師藿h ? 33洙33y___PPT10Y+D='  = @B +0 瓞\餌(  \8 \ 餤9m? ??"6?@`NNN?N%  餻(2) Long term toxicity(0fg f @`鹛 \  餱>m? ??"6?@`NNN?N"*H 餒@8___PPT9  皎: Treatment-induced tumors Infertility and deformability<91烃1烃;g烃8X餒 \ 0師藿h ? 33洙33 0 黏<(  館 6A?Z馂  饁览爬WGn$H!f櫶jJ?Thank you媅SOm 餒  0師藿h ? 秽33櫃櫶___PPT10i.渟 埠 +D='  = @B +m  0  饇 `  (  穰    餏\Jm0e槻0e槻     ? 咥嚵椓@  臕屏5%狭怂 8c8c     ?A)BCD|Ec " ?@ × チ` 芰 嗔  侤ABC DEEFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `abN 匛喤5%徟 溑 犈N 臙婆5%吓 芘 嗯N F 5%   !"?N@ABC DEFFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `ab{ / m 饃   c $窲mT  m 餦   C &Aline12"v<餔  C "A b059T餒   0師藿h ? 秽33櫃櫶___PPT10i.u炃 x+D='  = @B +  0 饦p$0(  $餔 $ C "A b059T穰 $  餏m0e槻0e槻     ? 咥嚵椓@  臕屏5%狭怂 8c8c     ?A)BCD|E||c " ?@ × チ` 芰 嗔  侤ABC DEEFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `abN 匛喤5%徟 溑 犈N 臙婆5%吓 芘 嗯N F 5%   !"?N@ABC DEFFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `ab T/  m 餒 $ 0師藿h ? 秽33櫃櫶___PPT10i.u炃 x+D='  = @B +0 p瓠(  p餢 p C    p S #  0   鸠CBoth normal cells and tumor cells go through a growth cycle (Figure 38.4). However, normal and neoplastic tissue may differ in the number of cells that are in the various stages of the cycle. Chemotherapeutic agents that are effective only in replicating cells, that is those cell- "at are cycling, are said to be cell-cycle specific (see Figure, +), whereas other agents are cell-cycle nonspecific. The nonspe- cific drugs such as the alkylating agents, although generally more toxic in cycling cells, are also useful against tumors with a low percentage of replicating cells. P_ , 餒 p 0藿h師 ? 秽33櫃櫶80___PPT10.u@〢0 1)t鹆(  t餢 t C   ) t S X* 0   鹈!Bifunctional alkylating agents,such as the nitrogen mustards, may form covalent bonds with each of two adjacent guanine residues. Such interstrand cross-linkages will inhibit DNA replication and transcription. Intrastrand cross-links also may be produced between DNA and a nearby protein. $"+PZ   d @ E餒 t 0藿h師 ? 秽33櫃櫶80___PPT10.u豦10 饞x*(  x餢 x C   饞 x S 琀  0   ,Chemotherapy may result in the destruction of actively proliferating hematopoietic precursor cells. White blood cell and platelet counts may in turn be decreased, resulting in an increased incidence of life-threatening infections and hemorrhage.Maximum toxicity usually is observed 10 to 14 days after initiation of drug treatment, with recovery by 21 to 28 days. The nausea and vomiting frequently observed after anticancer drug administration are actually thought to be caused by a stimulation of the vomiting center or chemoreceptor trigger zone in the central nervous system (CNS) rather than by a direct gastrointestinal effect. Most anticancer drugs damage hair follicles and produce partial or complete alopecia. Hair usually regrows normally after completion of chemotherapy.The duration of the side effects varies widely. For example, alopecia is transient, but the cardiac, pulmonary, and bladder toxicities are irreversible.  >E 餒 x 0藿h師 ? 秽33櫃櫶80___PPT10.u030  |稷(  |餢 | C     | S 腛  0   黏Since most antineoplastic agents are mutagens, neoplasms (for example, acute nonlymphocytic leukemia) may arise 10 or more years after the original cancer was cured. Treatment-induced neoplasms are especially a prob- lem after therapy with alkylating agents   ]   餒 | 0藿h師 ? 秽33櫃櫶80___PPT10. up邟50 @(  餢  C     S \u  0   !Many patients undergoing chemotherapy fail to respond to treatment from the outset; their cancers are resistant to the available agents. Some neoplastic cells, for example, melanoma, are inherently resistant to most anticancer drugs. Other tumor types may be selected for or acquire resistance to the cytotoxic effects of the medication, particularly after prolonged administration of low drug doses. The development of drug resistance is minimized by short-term, intensive, intermittent therapy with combinations of drugs. Drug combinations are also effective against a broader range of resistant cell lines in the tumor population. A variety of mechanisms are responsible for drug resistance; each is considered separately under the particular drug. Tumor cells may become generally resistant to a variety of cytotoxic drugs on the basis of decreased uptake or retention of the drugs. This form of resistance is termed multidrug, resistance,Stepwise selection of an amplified gene that codes for a transmembrane protein (P-glycoprotein for "permeabil- ity" glycoprotein, is responsible for multidrug resistance (MDR). The resistance is due to ATP-dependent pumping of the drug out of the cell, associated with the presence of P-glyco-protein. 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