日本恶性血液病分子遗传学的发展(英文)课件

書式設定,書式設定,第 2,第 3,第 4,第 5,書式設定,書式設定,第 2,第 3,第 4,第 5,*,“The molecular genetic development of hematologic malignancy in Japan”,Kiyohiko Hatake,M.D.,Ph.D.,Department of Medical Oncology and Hematology,Cancer Institute Hospital,Ariake,Koto,Tokyo,Japan,ASCO-COSA-CSCO-ESMO-JCOG International Symposium,CSCO Annual Meeting 2008,Shanghai,China,“The molecular genetic develop,Disclosure of COI,Research funding,Chugai/Roche,Kirin,BMS,Kyowa,Yakult,Weyth,Novartis,Pfizer,Taiho,Jansen,Otsuka,Bayer,Employment or leadership position,:none,Stock ownership,Takeda,Astellas,Daiichi-Sankyo,Donation,Pfizer,Kirin,Chugai/Roche,Yakult,Novartis,Jansen,Taiho,Honoraria:,none,Consultant or advisort role:,none,Expert Testimony:none,000000000,Disclosure of COIResearch fund,Todays talk,Clinical practice of NHL,Registration system for WHO classification of NHL,Standard chemotherapy in NHL and HL,RCHOP in DLBCL,Resistance to rituximab,Live-cell confocal fluorescence microscopy,CDC,ADCC,Relationship CDC and response to rituximab and prognosis,Mutation of CD20 and CDC,Todays talkClinical practice,Clinical practice of Non-Hodgkins Lymphoma(B-cell lymphoma)in CIH,Old,but an important prognostic marker sIL-2R,and CD5 in RCHOP treatment,Clinical practice of Non-Hodgk,DLBCL:treatment result by CHOPRituximab,CHOP n=83:76%,R-CHOP,n=92:97%,P=0.0002 0.05,%:3-year PFS,Days from treatment,Over-all survival rate,DLBCL:treatment result by CH,87 cases treated by CHOP and 141 cases treated by RCHOP,Were analized in DLBCL.,87 cases treated by CHOP and 1,RCHOP was superior to CHOP in both,RCHOP was superior to CHOP in,日本恶性血液病分子遗传学的发展(英文)课件,日本恶性血液病分子遗传学的发展(英文)课件,日本恶性血液病分子遗传学的发展(英文)课件,RCHOP is superior to CHOP,and sIL-2R is still good marker,For prognosis.,RCHOP is superior to CHOP,and,Mechanisms of action of rituximab,proliferation,block,ADCC,CDC,apoptosis,NK,M,PMN,FcR,C1q,C2-C9,CD20,CD20+lymphoma,rituximab,Mechanisms of action of rituxi,Research methodology,Prediction of response and prognosis,Establishment of clinically applicable bio-imaging,Cancer cells from,the patients,Ultra super speedy,Sensitivity test,Live-cell bio-imaging,Confocal fluoresence,Research methodologyPrediction,Prediction of response to rituximab by imaging,Response to rituximab in lymphoma cells from the patients,Probably,ineffective,Probably,effective,10min,10min,Prediction of response to ritu,The principle of imaging-based CDC susceptibility assay,The principle of imaging-based,Diagnostic details of patients evaluated for CDC susceptibility,Diagnostic details of patients,Correlation between CDC and clinical response,DLBCL,FL,chemotherapy,with rituximab,chemotherapy,w/o rituximab,P=0.0023,P=0.00067,Correlation between CDC and cl,Reproducible ADCC assay,KHYG-1,LTR,Fcgr3a,(158V),LTR,LTR,Fcgr3a,(158F),LTR,IRES,IRES,ZsGreen,ZsGreen,KHYG-1/mock,-ZsGreen,KHYG-1/158V,-ZsGreen,KHYG-1/158F,-ZsGrreen,NK leukemia cell line,CD3-,CD5-,CD7+,CD16-,CD56+,TCR-,ZsGreen,rituximab,PI,Reproducible ADCC assayKHYG-1L,ADCC assay,KHYG-1/mock,KHYG-1/158V,KHYG-1/158F,LDH release assay,Target:Ramos,E/T:1,Co-culture:4hr,51,Cr release assay,Target:Ramos,E/T:1,Co-culture:4hr,ADCC assayKHYG-1/mockKHYG-1/15,Effect of serum on ADCC activity,Serum(-),Serum(+),Rituximab(-),Rituximab(+),Ramos vs KHYG-1/FcRIIIa(158V)in heat-inactivate serum,Effect of serum on ADCC activi,Effects of IgG on ADCC activity,Daudi vs.KHYG-1/FcRIIIa,Rituximab:0.1g/mL,Co-culture:for 4hr,Daudi vs.KHYG-1/FcRIIIa,Rituximab:0.1g/mL,Co-culture:for 4hr,IgG(12mg/mL),Effects of IgG on ADCC activit,Effect of complement on ADCC activity,Daudi vs.KHYG-1/FcRIIIa,Rituximab:0-100g/mL,Co-culture:for 4hr,serum/heat-inactivated serum:50%(v/v),Effect of complement on ADCC a,Summary,Depletion of peripheral B cells,complement,Consumption of C,Serum IgG,CDC,ADCC,C2-C9,rituximab,C1q,NK,M,PMN,CD20,FcR,SummaryDepletion of peripheral,Mutations of C-terminal region of CD20,molecule predict CD20 expression and,time to progression after rituximab,in non-Hodgkins lymphoma,Yasuhito Terui,Yuji Mishima,Natsuhiko Sugimura,Kiyotsugu Kojima,Takuma Sakurai,Yuko Mishima,Ryoko Kuniyoshi,Akiko Rokudai,Masahiro Yokoyama,Kengo Takeuchi,Chie Watanabe,Shunji Takahashi,Yoshinori Ito,and Kiyohiko Hatake,Department of Medical Oncology and Hematology,Cancer Institute Hospital,Japanese Foundation for Cancer Research;,Division of Clinical Chemotherapy,Cancer Chemotherapy Center,Japanese Foundation for Cancer Research;,Olympus Bio-imaging Laboratory,Cancer Chemotherapy Center,Japanese Foundation for Cancer Research;,Department of Pathology,Cancer Institute Hospital,Japanese Foundation for Cancer Research,Tokyo;,Nutritional Science Laboratory,Morinaga Milk Co.,Kanagawa,Japan.,Terui Y et al.,abstracts in ASH 2006 and ASCO 2007,Mutations of C-terminal region,Methods,Since June 2002 to November 2004,retrospective analysis was performed in CIH(evaluable 50 cases of NHL),2.We performed flow cytometry(CD20 antigen)in each fresh lymphoma cells from the patients,3.Mutation analysis of CD20,Methods,Structure