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1. 现èã·ã°ãã«äŒéçµè·¯
ã[çµè·¯åãäŸ: PI3K/AKT/mTOR] ãå³ç€ºããåºçæºåãæŽã£ã现èã·ã°ãã«äŒéçµè·¯å³ãäœæããŠãã ããã圢質èã®å容äœïŒ[å容äœå]ïŒããå§ãã[äž»èŠäžéäœ] ãéããŠäžæµã®ãšãã§ã¯ã¿ãŒ [転åå åãŸãã¯æ©èœçã¢ãŠãããã] ãžãšã·ã°ãã«äŒæããã©ã£ãŠãã ããããªã³é žåïŒäžžå²ã¿ PïŒããŠãããã³åïŒäžžå²ã¿ UbïŒãç§»è¡ã€ãã³ãã«ã¯ç°ãªãç¢å°ã¹ã¿ã€ã«ã䜿çšããŠãã ãããçœèæ¯ã« 2 è²ã¹ããŒã ïŒã¢ã¯ãã£ãã³ã³ããŒãã³ãã«ã¯ [äž»è²]ãéã¢ã¯ãã£ãã«ã¯ç°è²ïŒãé©çšããŠãã ããããã¹ãŠã®ã¿ã³ãã¯è³ªãæšæº HGNC ã·ã³ãã«ã§ã©ãã«ä»ãããŠãã ãããäºçްèã³ã³ããŒãã¡ã³ãã©ãã«ïŒåœ¢è³ªèã现èè³ªãæ žïŒãå«ããŠãã ãããã
2. ã¿ã³ãã¯è³ªæ§é å³
ã[ã¿ã³ãã¯è³ªå] ã®ãã¡ã€ã³ã¢ãŒããã¯ãã£ã®æš¡åŒå³ãçæããŠãã ãããN æ«ç«¯ãã C æ«ç«¯ãŸã§ã®æ¬¡ã®ãã¡ã€ã³ã瀺ããŠãã ãã: [ããããã®æ®åºç¯å²ä»ãã§ãã¡ã€ã³ããªã¹ããäŸ: PH ãã¡ã€ã³ (aa 1â100)ããããŒãŒãã¡ã€ã³ (aa 150â400)ãèª¿ç¯ C æ«ç«¯ (aa 401â480)]ãæ¢ç¥ã®ç¿»èš³åŸä¿®é£Ÿéšäœã瀺ããŠãã ãã: [æ®åºçªå·] ã§ã®ãªã³é žåã[æ®åºçªå·] ã§ã®ãŠãããã³åãäžè²«ããå¡äŸã§åãã¡ã€ã³ã«è²åãããããããã¯ã䜿çšããŠãã ãããç·åœ¢ã¹ã±ãŒã«ããŒãå«ããŠãã ãããã¹ã¿ã€ã«: ã¬ãã¥ãŒèšäºã®å³ããã«ã«é©ããã¯ãªãŒã³ãªã¢ã«ãããã¯ã€ã©ã¹ããã
3. å®éšã¯ãŒã¯ãã㌠/ ãããã³ã«
ã[ãããã³ã«åãäŸ: ã¯ãããã³å ç«æ²éåŸã®ã·ãŒã±ã³ã·ã³ã° (ChIP-seq)] ã®ã¹ããããã€ã¹ãããã®å®éšã¯ãŒã¯ãããŒå³ãäœæããŠãã ãããæ¬¡ã®é 次ã¹ããããæããŠãã ãã: [é åºéãã«ã¹ãããããªã¹ã]ãåã¹ãããã«é·æ¹åœ¢ã®ããã¯ã¹ãäžåãç¢å°ã§æ¥ç¶ããŠãã ãããåããã¯ã¹å ã«ã倪åã§ã¹ãããåãš 1 è¡ã®æé 泚ãå«ããŠãã ããã[è²] ã䜿çšããŠã¹ããã [çªå·] ã§ã¯ãªãã£ã«ã«ãªå質管çãã§ãã¯ãã€ã³ãããã€ã©ã€ãããŠãã ãããã¯ãªãŒã³ãªçœèæ¯ã«ã©ã€ãã°ã¬ãŒã®ããã¯ã¹å¡ãã€ã¶ããšé»ããã¹ããé©çšããŠãã ãããå³ããŒãžã³ã«æšå®æé泚éã远å ããŠãã ãããã
4. èåš / çµç¹æé¢
ã[èåšãŸãã¯çµç¹ãäŸ: 现èã¬ãã«ã§ã®ããè ç®è³ª] ã®ã©ãã«ä»ãæé¢å³ãå³ç€ºããŠãã ãããæ¬¡ã®çްèå±€ãšæ§é ã瀺ããŠãã ãã: [å±€/æ§é ããªã¹ã]ãèªç¶äž»çŸ©çãªã«ã©ãŒãã¬ããïŒ[ç®è/çµç¹ããŒã³]ïŒã䜿çšããŠãã ãããã¯ãªãŒã³ãªãµã³ã»ãªããã©ã³ãã®è§£ååŠã©ãã«ãæã€ãªãŒããŒã©ã€ã³ããã€ã©ã¹ãå¢çã®å€ã«é 眮ããŠãã ããã[寞æ³] ã瀺ãã¹ã±ãŒã«ããŒã远å ããŠãã ãããã¹ã¿ã€ã«ã¯å»åŠãžã£ãŒãã«ãæç§æžã«é©ãããã® â ç§åŠçã«æ£ç¢ºã§ãã¹ã¿ã€ã«åãããŠããªããã® â ã§ããã¹ãã§ããã
5. ååŠåå¿æ©æ§
ã[åå¿åãäŸ: ã»ãªã³ãããã¢ãŒãŒè§Šåªã®ããããçµåå æ°Žåè§£] ã®ã¹ããããã€ã¹ãããã®ææ©åå¿æ©æ§ãæããŠãã ããããã¹ãŠã®äžéäœã瀺ããŠãã ãã: [äžéäœããªã¹ã]ãé»åç§»åã«ã¯æšæºçãªæ²ç·ç¢å°è¡šèšã䜿çšããŠãã ãããæ±æ žãæ±é»åãè±é¢åºçš®ãã©ãã«ä»ãããŠãã ãããé·ç§»ç¶æ ã§éšåé»è·ïŒÎŽ+ ãš ÎŽâïŒã衚瀺ããŠãã ãããã¹ããããåäžã®æ°Žå¹³ã·ãŒã±ã³ã¹ã§å·Šããå³ã«é 眮ããŠãã ãããçœèæ¯ã«é»ãæ§é ã䜿çšããŠãã ãããåæ§é ã®äžã«ååç©ã©ãã«ãåç¢å°ã®äžã«åå¿æ¡ä»¶ã©ãã«ïŒpHãæž©åºŠïŒãå«ããŠãã ãããã
6. ããç²åè¬ç©ééã·ã¹ãã
ã[æ²»çå¿çšãäŸ: è现èãžã® siRNA éé] ã®ããã® [ããç²åã®ã¿ã€ããäŸ: è質ããç²å] è¬ç©ééã·ã¹ãã ã®ç§åŠã€ã©ã¹ããäœæããŠãã ãããæ¬¡ã瀺ãããç²åæé¢ãæããŠãã ãã: å€åŽ PEG ã³ãããè質äºéå±€ã·ã§ã«ã[ã«ãŒãŽ] ãå«ãæ°Žæ§ã³ã¢ãééã·ãŒã±ã³ã¹ã 4 ããã«ã§ç€ºããŠãã ãã: (1) å šèº«åŸªç°ã(2) æšç现èã§ã®å容äœåªä»ãšã³ããµã€ããŒã·ã¹ã(3) ãšã³ããœãŒã è±åºã(4) 现èå ã«ãŒãŽæŸåºãäžè²«ããé è²ã䜿çšããŠãã ãã: ç²åã«ã¯ [è²]ãçç©åŠçèã«ã¯ [è²]ããã¹ãŠã®ã³ã³ããŒãã³ããã©ãã«ä»ãããŠãã ãããæåã®ããã«ã«ç²åãµã€ãºã¹ã±ãŒã«ïŒã[çŽåŸ] nmïŒãå«ããŠãã ãããã
7. éºäŒåçºçŸã«ã¹ã±ãŒã
ã[ã·ã°ãã«äŒéã³ã³ããã¹ããäŸ: ãã¯ããã¡ãŒãžã®ã€ã³ã¿ãŒãã§ãã³-γ åºæ¿] ã®çްèå€ã·ã°ãã«ããã¿ã³ãã¯è³ªåºåãŸã§ã®éºäŒåçºçŸã«ã¹ã±ãŒããå³ç€ºããŠãã ãããé æ¬¡ã¹ãããã瀺ããŠãã ãã: ãªã¬ã³ãçµå â åå®¹äœæŽ»æ§å â JAK ãããŒãŒãªã³é žå â STAT 転åå åäºéäœå â æ žèŒžå ¥ â [æšçéºäŒå座] ã§ã®ããã¢ãŒã¿ãŒçµå â mRNA 転å â 现è質翻蚳 â æ©èœçã¿ã³ãã¯è³ªã现èå€ç©ºéïŒäžïŒãã现è質ïŒäžïŒãŸã§åçŽã«é 眮ããŠãã ãããæ žã€ãã³ããåºåãããã«ç Žç·ããã¯ã¹ã䜿çšããŠãã ãããã·ã°ãã«é²è¡ã瀺ãããã«éãããªã¬ã³ãžãžã®ã°ã©ããŒã·ã§ã³ãé©çšããŠãã ããããã¹ãŠã®ååãã¬ãŒã€ãŒãã©ãã«ä»ãããŠãã ãããã
8. é¡åŸ®é¡æ¯èŒããã«
ã[å®éšæ¡ä»¶ãäŸ: å¯Ÿç §ãåŠçœ® AãåŠçœ® BãåŠçœ® C] ã瀺ã [N] ããã«ã®ãã«ãããã«ç§åŠæ¯èŒå³ãäœæããŠãã ãããåããã«ã¯æ¬¡ã®ãã£ã³ãã«ã§ [é¡åŸ®é¡ã¿ã€ããäŸ: å ±çŠç¹èå ] ãã£ãŒã«ããã·ãã¥ã¬ãŒããã¹ãã§ã: [ãã£ã³ãã« 1 è²]ã[ãã£ã³ãã« 2 è²]ãããŒãžã次ãå«ããŠãã ãã: åããã«ã®å³äžã« 10 µm ã¹ã±ãŒã«ããŒ; æ¡ä»¶å šäœã§äžè²«ããæãã/ã³ã³ãã©ã¹ã; å·Šäžé ã«çœããã¹ãã§ããã«ã©ãã«ïŒAãBãCãDïŒãåããã«ã®äžã«äž»èŠãªè¡šçŸåç¹åŸŽã瀺ãåäžè¡ã®æ³šéã远å ããŠãã ãããã¹ã¿ã€ã«: èå ããã«ã«ã¯é»èæ¯ãã¯ãªãŒã³ãªã¢ã«ãããã¯ã¬ã€ã¢ãŠããã
9. èšåºè©Šéšãã¶ã€ã³ãããŒãã£ãŒã
ã[æ£è éå£] ã«ããã [ä»å ¥] ãç ç©¶ãã [詊éšã¿ã€ããäŸ: 第 III çžç¡äœçºåæ¯èŒè©Šéš] ã®ããã® CONSORT ã¹ã¿ã€ã«ã®èšåºè©ŠéšãããŒãã£ãŒãããã¶ã€ã³ããŠãã ãããæ¬¡ã瀺ããŠãã ãã: ç»é²ããã³é©æ Œæ§ã¹ã¯ãªãŒãã³ã° (n = [æ°]); å²ãåœãŠæ¯çã§ã®ç¡äœçºå; ã¢ãŒã ã©ãã«ãšçšéãæã€ [æ°] ä»å ¥ã¢ãŒã ; [é±/æ] ã®ãã©ããŒã¢ããæç¹; äžæ¬¡ããã³äºæ¬¡ãšã³ããã€ã³ãè©äŸ¡; åæ®µéã§ã®è±èœ/ãã©ããŒã¢ããè±èœãæšæºçãªãããŒãã£ãŒãããã¯ã¹ïŒããã»ã¹ã«ã¯é·æ¹åœ¢ã決å®ã«ã¯ãã€ã€ã¢ã³ãïŒã䜿çšããŠãã ãããä»å ¥ã¢ãŒã ã« [è²] ã®ã·ã§ãŒãã£ã³ã°ã§ã¯ãªãŒã³ãªçœèæ¯ãé©çšããŠãã ãããåããŒãã«ãã¬ãŒã¹ãã«ã㌠n å€ãå«ããŠãã ãããã
10. çæ ç³»çžäºäœçšå³
ã[çæ ç³»ãŸãã¯çŸ€éãäŸ: ãµã³ãŽç€æ é€ç¶²] ã®ããã®ç§åŠçæ ç³»çžäºäœçšå³ãäœæããŠãã ããã[N] ã®äž»èŠçš®ãŸãã¯æ©èœçŸ€ã瀺ããŠãã ãã: [çš®ããªã¹ã]ãæ é€çžäºäœçšãæ¹åç¢å°ã§è¡šçŸããŠãã ããïŒç¢å°ã¯æ¶è²»è ãæãïŒãçžäºäœçšã¿ã€ããåºå¥ããŠãã ãã: æé£ïŒå®ç·ïŒãçžå©å ±çïŒç Žç·ïŒãç«¶äºïŒäºéé ç·ïŒãããŒãã®ãµã€ãºããã€ãªãã¹ [ãŸãã¯æ é€ã¬ãã«] ã«æ¯äŸãããŠãã ãããäžæ¬¡çç£è ïŒç·ïŒããé ç¹æé£è ïŒèµ€ïŒãžã®äžè²«ããçš®ã®é è²ã䜿çšããŠãã ãããæ é€ã¬ãã«ãåæ ããããããŒããåçŽã«é 眮ããŠãã ãããå¡äŸãå«ããŠãã ãããã¹ã¿ã€ã«: çœèæ¯ã®ã¯ãªãŒã³ãªã¢ã«ãããã¯ã€ã©ã¹ããã
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