institute of digestive diseases ,xijing hospital,
DESCRIPTION
Identification and applications of MGAgs -------a group of novel gastric cancer associated antigens. Daiming Fan,Xueyong Zhang,Xitao Chen, ,Jialu Hu, Zhengxian Mu , Jun Ren, Jie Ding,Kaichun Wu. Institute of Digestive Diseases ,Xijing Hospital, - PowerPoint PPT PresentationTRANSCRIPT
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Identification and applications of MGAgs
-------a group of novel gastric cancer associated antigens
Institute of Digestive Diseases ,Xijing Hospital, Fourth Military Medical University, Xi’an, China
Daiming Fan,Xueyong Zhang,Xitao Chen, ,Jialu Hu, Zhengxian Mu , Jun Ren, Jie Ding,Kaichun Wu
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Gastric cancer
• Cause about 200,000 deaths annually
• Early detection is not very easy
• Mass survey is not feasible in China
• Cause about 200,000 deaths annually
• Early detection is not very easy
• Mass survey is not feasible in China
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Positive immunohistochemical reaction (% of cases)Positive immunohistochemical reaction (% of cases)
The nature and immunohistochemical reactivity of MG series monoclonal
antibodies
The nature and immunohistochemical reactivity of MG series monoclonal
antibodies
MGa-5MGa-7MGa-9MGa-11MGb-1MGb-2MGc-1MGd-1MGe-1MGe-2MGg-1MGg-2
MGa-5MGa-7MGa-9MGa-11MGb-1MGb-2MGc-1MGd-1MGe-1MGe-2MGg-1MGg-2
IgG1IgG1IgG2IgG1IgG1IgG1IgG1IgG1IgG1IgMIgG1IgG1
IgG1IgG1IgG2IgG1IgG1IgG1IgG1IgG1IgG1IgMIgG1IgG1
28.666.772.636.068.842.050.070.020.046.744.867.6
28.666.772.636.068.842.050.070.020.046.744.867.6
16.725.025.0 016.7 0 9.1 0 040.920.532.3
16.725.025.0 016.7 0 9.1 0 040.920.532.3
25.022.230.016.7 014.3 0 0 055.6 013.0
25.022.230.016.7 014.3 0 0 055.6 013.0
000000000000
000000000000
000000000000
000000000000
mAbmAb Igsubclass
Igsubclass Gastric
cancerGastriccancer
Coloniccancer
Coloniccancer
Esophagealcancer
Esophagealcancer
Hepaticcancer
Hepaticcancer
Pancreaticcancer
Pancreaticcancer
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Early detection of gastric cancer from precancerous lesions of stomach
Early detection of gastric cancer from precancerous lesions of stomach
DysplasiaDysplasia
RetrogressRetrogress
Malignant transformationMalignant transformation
DisappearDisappear
4.0~19.0%4.0~19.0%
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Follow up study of patients with dysplasia of gastric mucosa
Follow up study of patients with dysplasia of gastric mucosa
Dysplasia(90 cases)Dysplasia(90 cases)
Stained by MGa-7Stained by MGa-7
29 cases (+)29 cases (+)
Malignant change in 6 cases( 4 cases
early gastric cancer)
Malignant change in 6 cases( 4 cases
early gastric cancer)
16 cases (42 months)16 cases (42 months)
61 cases (-)61 cases (-)
No malignant change but 1 case became positive in staining
No malignant change but 1 case became positive in staining
19 cases (41 months)
19 cases (41 months)
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Immunofluorescent diagnosis of cancer cells in malignant ascitic fluid or
pleural effusion
Immunofluorescent diagnosis of cancer cells in malignant ascitic fluid or
pleural effusionMethodsMethods
Immunoflourescent examinationConventional cytological examination
Immunoflourescent examinationConventional cytological examination
CasesCases
76
76
76
76
Positivecases
Positivecases
69
59
69
59
%%
90.7
77.6
90.7
77.6
(P<0.05)(P<0.05)
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Radioimmunoimaging of tumor in vivo
• The satisfactory imaging results were obtained
in 73.3% of patients with gastric cancer(74/10
1). Metastatic tumor in liver, pancreas and sup
raclavicular lymph node could also be detected.
• The satisfactory imaging results were obtained
in 73.3% of patients with gastric cancer(74/10
1). Metastatic tumor in liver, pancreas and sup
raclavicular lymph node could also be detected.
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RII of Patients with Gastric CancerRII of Patients with Gastric Cancer
131I-McAb
MG7F(ab)2
MG7IgG
MGd1
MGb2
MG11
MG7+MGd1
131I-McAb
MG7F(ab)2
MG7IgG
MGd1
MGb2
MG11
MG7+MGd1
Positive rate(%)
87.5(7/8)
75.9(22/29)
44.4(4/9)
50.0(2/4)
0 (0/7)
100(3/3)
Positive rate(%)
87.5(7/8)
75.9(22/29)
44.4(4/9)
50.0(2/4)
0 (0/7)
100(3/3)
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Detection of MGAgs for serological diagnosis of gastric cancer by
immuno-PCR
Detection of MGAgs for serological diagnosis of gastric cancer by
immuno-PCR
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0%
20%
40%
60%
80%
100%
0%
20%
40%
60%
80%
100%
EIAEIAEIAEIA RIARIARIARIA IRMAIRMAIRMAIRMA
Detection rate of gastric cancer using existing serological diagnostic methodsDetection rate of gastric cancer using
existing serological diagnostic methods
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GC antigensGC antigensGC antigensGC antigens
Gastric lumenGastric lumenGastric lumenGastric lumen Blood circulationBlood circulationBlood circulationBlood circulation
metabolizedmetabolized metabolizedmetabolized
Reasons of low dectection rate for gastric cancer
Reasons of low dectection rate for gastric cancer
95%95%95%95% 5%5%5%5%
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????
IFIFIFIF EIAEIAEIAEIA RIARIARIARIA
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• High sensitivityHigh sensitivity
• 25,000 publications25,000 publications
• Just for detection of nucleic acidJust for detection of nucleic acid
• High sensitivityHigh sensitivity
• 25,000 publications25,000 publications
• Just for detection of nucleic acidJust for detection of nucleic acid
Advantages and disadvantages of PCR
Advantages and disadvantages of PCR
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Immuno-PCR
Immuno-PCR
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pXJ 19 pXJ 19MG7 -p XJ 19
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KATO III MGKATO III MG77AgAg PP
(x cell/ml) concentration(x cell/ml) concentration
IPCRIPCR 2 x 10 2 x 101 1 3.8 x 103.8 x 10 -- 14 14 <0.001<0.001
EIA EIA 2 x 102 x 105 5 3.0 x 103.0 x 10 -- 11 11
KATO III MGKATO III MG77AgAg PP
(x cell/ml) concentration(x cell/ml) concentration
IPCRIPCR 2 x 10 2 x 101 1 3.8 x 103.8 x 10 -- 14 14 <0.001<0.001
EIA EIA 2 x 102 x 105 5 3.0 x 103.0 x 10 -- 11 11
Sensitivity comparison of IPCR to EIA
Sensitivity comparison of IPCR to EIA
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Detection of MGAgs in different gastric diseases with IPCR
Cases Positive Cases Positive %%
Gastric cancer 198 164 Gastric cancer 198 164 82.882.8
Peptic ulcer 78 6 7.7Peptic ulcer 78 6 7.7
Chronic gastritis 118 Chronic gastritis 118 7 5.9 7 5.9
Donor 236 Donor 236 2 0.8 2 0.8
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Positive results of MGAgs in different cancers with IPCR
Cancer of Cases Positive Cancer of Cases Positive % % Stomach 198 164 Stomach 198 164 82.882.8Colon 90 Colon 90 40 44.4 40 44.4Esophagus Esophagus 86 15 17.4 86 15 17.4Ovary Ovary 45 45 1 2.2 1 2.2Lung Lung 66 4 6.1 66 4 6.1 Liver Liver 84 0 0 84 0 0Uterus Uterus 27 0 27 0 00
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Positive results of MGAgs in different histological patterns of gastric cancer
Histological typeHistological type
Well differentiatedWell differentiated
Poorly differentiatedPoorly differentiated
Mucous adenocarcinomaMucous adenocarcinoma
Mucous cell carcinomaMucous cell carcinoma
Cases Positive %Cases Positive %
151 122 80.8 151 122 80.8
80 56 70.080 56 70.0
31 20 64.531 20 64.5
29 16 29 16 55.2 55.2
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Positive results of MGAgs at different stages of gastric cancers
Stage Cases Positive %Stage Cases Positive %
Early 31 12 38.7Early 31 12 38.7
Advanced 116 91 78.4Advanced 116 91 78.4
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Comparison of MGAgs to other tumor markers
MarkerMarker
CEA CEA
CA50 CA50
CA19-9 CA19-9
TAG-72 TAG-72
MGMG77 Ag-IPCR Ag-IPCR
%%
12.0 12.0
7.27.2
7.27.2
8.48.4
8.4 8.4
Benign diseases Benign diseases (83)(83)
10 10
6 6
6 6
7 7
7 7
% %
33.7 33.7
27.9 27.9
38.4 38.4
45.3 45.3
81.481.4
Gastric ca. Gastric ca.
(86) (86)
29 29
24 24
33 33
39 39
70 70
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10u
100u
1000u1u
10 万种药
MDR
抗癌药
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多个已知耐药相关分子在胃癌中的表达
MDR1 10%
MRP 12%
LRP 10%
GST-pi 36%
Non-detected
42%
Total ratios 58%
42% 58%
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Sensitive cells
MDR cells
polyA+ RNAs proteins
SSH/DD-PCR 2-D gel electrophoresis
83 genes 30 proteins
Anticancer drug
In vitro selection
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SGC7901 SGC7901/VCR
pH 10 - 3 IEF
SD
S --P
AG
E
pH 10 - 3 IEF
Protein spectrums displayed by 2-D gel
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SGC7901 SGC7901/VCR
11 11
19 19
12 1211
19
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30 proteins
3 specifically expressed in MDR cells
6 up-regulated in MDR cells
19 down-regulated in MDR cells
2 specifically expressed in sensitive cells
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新耐药分子 MGr1-Ag 的发现
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Accession number
AF503367
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MGr1
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Fourteen molecules have been proved to play certain roles in tumor MDR:
8. mitotic arrest deficient 2
9. Occludin
10.phosphotriose isomerase
11.Ribosomal protein L6
12.putative magnesium transporter
13.novel gene PTD001
14.novel gene V62
1. MGr1-Ag
2. prion protein
3. Ribosomal protein S13
4. Ribosomal protein L23
5. zinc ribbon protein ZNRD1
6. calcyclin binding protein
7. tumor susceptibility gene 101
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Cancer Letter. 246:129-138 2007
Tissue Antigens. 69(2):170-175 2007
Dig Liver Dis. 39(2):167-172 2007
J Mol Med. 85(2):169-180 2007Exp Oncol. 28(4):258-62 2006J Exp Clin Cancer Res.25(4):601-606 2006Hybridoma (Larchmt). 25(6):378-381
2006
Neoplasia. 8(12):995-1002 2006FASEB J. 20(11):1886-1888 2006Hepatology. 43(3):415-424 2006Oncogene. 25(7):1008-1017 2006 J Mol Med. 84(9):764-773 2006Cancer Letter. 242(1):20-27 2006Hybridoma. 25(2):91-4 2006Cancer Letter. 243(2):246-254 2006Int J Cancer. 118(12):2965-2972 2006EXCLI Journal. 5:79-92 2006J Histochem Cytochem.54(12):1437-44 2006
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