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


Institute of digestive diseases xijing hospital

Early detection of gastric cancer from monoclonal antibodies

precancerous lesions of stomach

Retrogress

Disappear

Dysplasia

Malignant transformation

4.0~19.0%


Institute of digestive diseases xijing hospital

Follow up study of patients monoclonal antibodies

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)


Institute of digestive diseases xijing hospital

Immunofluorescent diagnosis monoclonal antibodies

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 monoclonal antibodiesin 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 monoclonal antibodies

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



Institute of digestive diseases xijing hospital

RIA cancer by immuno-PCR

IRMA

EIA

Detection rate of gastric cancer using existing serological diagnostic methods


Institute of digestive diseases xijing hospital

Reasons of low dectection rate for gastric cancer cancer by immuno-PCR

GC antigens

5%

95%

Gastric lumen

Blood circulation

metabolized


Institute of digestive diseases xijing hospital

? cancer by immuno-PCR

IF

EIA

RIA


Institute of digestive diseases xijing hospital

Advantages and disadvantages of PCR cancer by immuno-PCR

  • High sensitivity

  • 25,000 publications

  • Just for detection of nucleic acid


Institute of digestive diseases xijing hospital

Immuno-PCR cancer by immuno-PCR


Institute of digestive diseases xijing hospital

pXJ 19 cancer by immuno-PCR

MG7 -p XJ 19

pXJ 19


Institute of digestive diseases xijing hospital

Sensitivity comparison of IPCR to EIA cancer by immuno-PCR

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


Institute of digestive diseases xijing hospital

Detection of MGAgs in different cancer by immuno-PCR

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


Institute of digestive diseases xijing hospital

Positive results of MGAgs in different cancers with IPCR cancer by immuno-PCR

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


Institute of digestive diseases xijing hospital

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


Institute of digestive diseases xijing hospital

Positive results of MGAgs at different stages of gastric cancers

Stage Cases Positive %

Early 31 12 38.7

Advanced 116 91 78.4


Institute of digestive diseases xijing hospital

Comparison of MGAgs to other tumor markers cancers

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


Institute of digestive diseases xijing hospital

抗癌药 cancers

1u

1000u

100u

10u

MDR

10万种药


Institute of digestive diseases xijing hospital

Total ratios 58% cancers

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


Institute of digestive diseases xijing hospital

MDR cells cancers

Sensitive cells

Anticancer drug

In vitro selection

polyA+ RNAs

proteins

SSH/DD-PCR

2-D gel electrophoresis

30 proteins

83 genes


Institute of digestive diseases xijing hospital

pH 10 - 3 IEF cancers

pH 10 - 3 IEF 

SDS --PAGE

SGC7901/VCR

SGC7901

Protein spectrums displayed by 2-D gel


Institute of digestive diseases xijing hospital

11 cancers

11

12

11

12

19

19

19

SGC7901 SGC7901/VCR


Institute of digestive diseases xijing hospital

3 specifically expressed in MDR cells cancers

6 up-regulated in MDR cells

30 proteins

19 down-regulated in MDR cells

2 specifically expressed in sensitive cells


Institute of digestive diseases xijing hospital

新耐药分子 cancersMGr1-Ag的发现


Institute of digestive diseases xijing hospital

Accession number cancers

AF503367


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MGr1 cancers


Institute of digestive diseases xijing hospital

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


Institute of digestive diseases xijing hospital

INTERNATIONAL PUBLICATIONS tumor MDR:

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


Institute of digestive diseases xijing hospital

Thank you ! tumor MDR:

Institute of Digestive Disease Xijing Hospital FMMU