identification and applications of mgags a group of novel gastric cancer associated antigens
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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,

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identification and applications of mgags a group of novel gastric cancer associated antigens

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,

Fourth Military Medical University, Xi’an, China

gastric cancer
Gastric cancer
  • Cause about 200,000 deaths annually
  • Early detection is not very easy
  • Mass survey is not feasible in China
the nature and immunohistochemical reactivity of mg series monoclonal antibodies
The nature and immunohistochemical reactivity of MG series monoclonal antibodies

Positive immunohistochemical reaction (% of cases)

Ig

subclass

mAb

Gastric

cancer

Colonic

cancer

Esophageal

cancer

Hepatic

cancer

Pancreatic

cancer

IgG1

IgG1

IgG2

IgG1

IgG1

IgG1

IgG1

IgG1

IgG1

IgM

IgG1

IgG1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

MGa-5

MGa-7

MGa-9

MGa-11

MGb-1

MGb-2

MGc-1

MGd-1

MGe-1

MGe-2

MGg-1

MGg-2

28.6

66.7

72.6

36.0

68.8

42.0

50.0

70.0

20.0

46.7

44.8

67.6

16.7

25.0

25.0

0

16.7

0

9.1

0

0

40.9

20.5

32.3

25.0

22.2

30.0

16.7

0

14.3

0

0

0

55.6

0

13.0

slide6

Early detection of gastric cancer from

precancerous lesions of stomach

Retrogress

Disappear

Dysplasia

Malignant transformation

4.0~19.0%

slide7

Follow up study of patients

with dysplasia of gastric mucosa

Dysplasia(90 cases)

Stained by MGa-7

29 cases (+)

61 cases (-)

19 cases

(41 months)

16 cases

(42 months)

No malignant change

but 1 case became

positive in staining

Malignant change

in 6 cases( 4 cases

early gastric cancer)

slide14

Immunofluorescent diagnosis

of cancer cells in malignant ascitic fluid or pleural effusion

Methods

Cases

%

Positive

cases

Immunoflourescent

examination

Conventional cytological

examination

76

76

69

59

90.7

77.6

(P<0.05)

radioimmunoimaging of tumor in vivo
Radioimmunoimaging of tumor in vivo
  • The satisfactory imaging results were obtained in 73.3% of patients with gastric cancer(74/101). Metastatic tumor in liver, pancreas and supraclavicular lymph node could also be detected.
rii of patients with gastric cancer
RII of Patients with Gastric Cancer

Positive rate(%)

87.5(7/8)

75.9(22/29)

44.4(4/9)

50.0(2/4)

0 (0/7)

100(3/3)

131I-McAb

MG7F(ab)2

MG7IgG

MGd1

MGb2

MG11

MG7+MGd1

slide29

RIA

IRMA

EIA

Detection rate of gastric cancer using existing serological diagnostic methods

slide30

Reasons of low dectection rate for gastric cancer

GC antigens

5%

95%

Gastric lumen

Blood circulation

metabolized

slide31

?

IF

EIA

RIA

slide32

Advantages and disadvantages of PCR

  • High sensitivity
  • 25,000 publications
  • Just for detection of nucleic acid
slide34

pXJ 19

MG7 -p XJ 19

pXJ 19

slide35

Sensitivity comparison of IPCR to EIA

KATO III MG7AgP

(x cell/ml) concentration

IPCR 2 x 101 3.8 x 10-14 <0.001

EIA 2 x 105 3.0 x 10-11

slide36

Detection of MGAgs in different

gastric diseases with IPCR

Cases Positive %

Gastric cancer 198 164 82.8

Peptic ulcer 78 6 7.7

Chronic gastritis 118 7 5.9

Donor 236 2 0.8

slide37

Positive results of MGAgs in different cancers with IPCR

Cancer of Cases Positive %

Stomach 198 164 82.8

Colon 90 40 44.4

Esophagus 86 15 17.4

Ovary 45 1 2.2

Lung 66 4 6.1

Liver 84 0 0

Uterus 27 0 0

slide38

Positive results of MGAgs in different histological patterns of gastric cancer

Histological type

Well differentiated

Poorly differentiated

Mucous adenocarcinoma

Mucous cell carcinoma

Cases Positive %

151 122 80.8

80 56 70.0

31 20 64.5

29 16 55.2

slide39

Positive results of MGAgs at different stages of gastric cancers

Stage Cases Positive %

Early 31 12 38.7

Advanced 116 91 78.4

slide40

Comparison of MGAgs to other tumor markers

33.7

27.9

38.4

45.3

81.4

Gastric ca.

(86)

29

24

33

39

70

Benign diseases

(83)

10

6

6

7

7

Marker

CEA

CA50

CA19-9

TAG-72

MG7 Ag-IPCR

12.0

7.2

7.2

8.4

8.4

slide43

抗癌药

1u

1000u

100u

10u

MDR

10万种药

slide44

Total ratios 58%

MDR1 10%

MRP 12%

LRP 10%

GST-pi 36%

Non-detected

42%

42% 58%

多个已知耐药相关分子在胃癌中的表达

slide45

MDR cells

Sensitive cells

Anticancer drug

In vitro selection

polyA+ RNAs

proteins

SSH/DD-PCR

2-D gel electrophoresis

30 proteins

83 genes

slide46

pH 10 - 3 IEF 

pH 10 - 3 IEF 

SDS --PAGE

SGC7901/VCR

SGC7901

Protein spectrums displayed by 2-D gel

slide47

11

11

12

11

12

19

19

19

SGC7901 SGC7901/VCR

slide48

3 specifically expressed in MDR cells

6 up-regulated in MDR cells

30 proteins

19 down-regulated in MDR cells

2 specifically expressed in sensitive cells

slide52

Fourteen molecules have been proved to play certain roles in tumor MDR:

  • MGr1-Ag
  • prion protein
  • Ribosomal protein S13
  • Ribosomal protein L23
  • zinc ribbon protein ZNRD1
  • calcyclin binding protein
  • tumor susceptibility gene 101
  • mitotic arrest deficient 2
  • Occludin
  • phosphotriose isomerase
  • Ribosomal protein L6
  • putative magnesium transporter
  • novel gene PTD001
  • novel gene V62
slide53

INTERNATIONAL PUBLICATIONS

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 2007

Exp Oncol. 28(4):258-62 2006

J Exp Clin Cancer Res.25(4):601-606 2006

Hybridoma (Larchmt). 25(6):378-381 2006

Neoplasia. 8(12):995-1002 2006

FASEB J. 20(11):1886-1888 2006

Hepatology. 43(3):415-424 2006

Oncogene. 25(7):1008-1017 2006

J Mol Med. 84(9):764-773 2006

Cancer Letter. 242(1):20-27 2006

Hybridoma. 25(2):91-4 2006

Cancer Letter. 243(2):246-254 2006

Int J Cancer. 118(12):2965-2972 2006

EXCLI Journal. 5:79-92 2006

J Histochem Cytochem.54(12):1437-44 2006

Expert Rev Vaccines. 5(2):223-31 2006

Biochem Cell Biol. 84(2):135-41 2006

Tumour Biol. 27(2):84-91 2006

EXCLI Journal. 5:42-45 2006

BBRC. 345(3):1092-1098 2006

Hybridoma. 25(5):278-82 2006

Cancer Biol Ther. 5(8):950-956 2006

EXCLI Journal. 5:25-32 2006

Life Sciences. 78(12):1277-86 2006

Gene Ther. 13(4):313-320 2006

Tumour Biol. 27(1):27-35 2006

BBRC. 341(4):964-972 2006

Cancer Biol Ther. 5(3):261-6 2006

Clin Exp Immunol. 144(2):319-325 2006

J Histochem Cytochem.54(4):417-426 2006

Biochem Cell Biol. 84(2):199-206 2006

Cell Biol Int. 30(11):920-3 2006

slide55

Thank you !

Institute of Digestive Disease Xijing Hospital FMMU

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