Lewis blood group antigens (a and b) in human breast tissues. Loss of Lewis-b in breast cancer cells and correlation with tumor grade.

The Lewis blood group antigens (Lewis-a [Lea] and Lewis-b [Leb]) and their precursors are present on various normal human epithelial cell surfaces. The authors examined 35 benign and malignant human breast lesions using mouse monoclonal antibodies to synthetic Lea and Leb carbohydrate antigens. Normal breast lobular and ductal epithelium and benign breast lesions showed Leb staining but only occasional Lea staining. In invasive ductal carcinomas of breast, of all grades, a loss of Leb antigen staining was found in 80% of the breast cancer cases. This reduced Leb antigen expression increased with the grade of malignancy. Therefore, the loss of Leb blood group antigens on breast cancer cell surfaces may suggest altered fucosylation patterns in malignant cells and reflect the degree of malignancy and/or invasiveness.     

Distribution of blood group antigens A, B, H, Lewisa, and Lewisb in human normal, fetal, and malignant colonic tissue

In humans, most blood group substances (BGS) are expressed throughout the fetal colon but are absent from the distal portion of adult colon. Cancers of the distal colon frequently reexpress BGS thereby suggesting that these antigens behave as oncofetal antigens at this organ site. We used a sensitive immunoperoxidase method with monoclonal antibodies directed against blood groups A, B, O (H), Lewisa and Lewisb to systematically evaluate BGS expression in fetal colon, normal adult colon from immediate autopsies of kidney donors, mucosa adjacent to cancer (transitional mucosa) and colorectal cancer tissues. In normal colon, BG-A, B, H, and Lewisb were expressed in proximal but not distal colon, whereas Lewisa was distributed uniformly throughout the colon. In colon cancer, and fetal colon, the proximal-distal gradient of BG-A, B, H, and Lewisb expression was abolished because of enhanced distal expression of these antigens. In cancer tissues, three patterns of altered BGS expression emerged: (a) incompatible expression of BG-A or BG-B (over 50% of patients); (b) deletion of BGS; and (c) precursor BG-H accumulation (80% of 25 tumors). BGS staining of transitional mucosa closely resembled that of the adjacent tumor except that no examples of BGS deletion were encountered in transitional mucosa. The goblet cell secretory vacuole accounted for most of the BGS expression in normal colon, but cancer cells demonstrated differentiation-dependent antigenic expression such that well-differentiated tumors expressed BGS on cell apical membranes and glandular contents, but poorly differentiated cancers exhibited diffuse cytoplasmic staining. These findings confirm the oncofetal nature of BGS in distal colon cancer, and provide immunohistochemical evidence for a diverse repertoire of altered antigen expression in colon cancer. Further investigation is needed to elucidate the possible genetic and biochemical mechanisms involved.     

Activity of the human blood group ABO, Se, H, Le, and X gene-encoded glycosyltransferases in normal and malignant bladder urothelium

Immunohistochemistry has led to the finding of an expression of ABO-related blood group antigens in normal and malignant bladder urothelium which is different from that found on erythrocytes from the same individual. This includes a loss of blood group ABO expression in malignant urothelium, and the expression of Leb antigens in normal and malignant cells from individuals with Le(a+b-) and Le(a-b-) erythrocytes. To elucidate the mechanism of this blood group antigen expression in urothelium we have analyzed the activity of the specific glycosyltransferases encoded by the ABO, Se, H, Le, and X blood group genes in normal and malignant urothelium. Biopsies of normal urothelium were obtained from 22 individuals and biopsies of urothelial tumors from 20 individuals. The tissue donors were typed for ABO, Lewis, and secretor status on erythrocytes and saliva. The biopsies were disaggregated to single cell suspensions, and the activity of the individual glycosyltransferases was determined as pmol of labeled sugar incorporated by oligosaccharide acceptors per 100,000 cells. The A (alpha-3-N-acetyl-D-galactosaminyl) and B (alpha-3-D-galactosyl) gene-specified transferases showed no activity in malignant cells, whereas all other enzymes examined were expressed in both normal and malignant cells. Secretors and nonsecretors showed the same alpha-2-L-fucosyltransferase activity in both normal and malignant cells, whereas the alpha-3-L-fucosyltransferase was reduced (P less than 0.02) in malignant cells from Lewis positive individuals. The Lewis gene-encoded alpha-4-L-fucosyltransferase showed a similar activity in Lewis positive and negative individuals. These results indicate that the disappearance of A and B blood group antigens in bladder tumors and the expression of Leb antigens in normal and malignant cells from individuals with Le(a+b-) and Le(a-b-) erythrocytes are due to corresponding differences in glycosyltransferases. The results indicate that the ABO, H, Se, and Le genes are subjected to a tissue-dependent differential expression.     

Cancer-associated alterations of blood group antigen expression in human colorectal polyps

Human colorectal carcinoma tissues may exhibit several patterns of altered blood group substance (BGS) expression: reappearance of A, B, H, or Lewisb antigens in distal colon; deletion of BGS in the proximal colon with or without precursor substance accumulation; and incompatible BGS expression in proximal or distal colon. The present study evaluated these cancer-associated alterations in colorectal polyps with different malignant potential. With respect to ABH antigens, hyperplastic polyps (HPs), considered to have no malignant potential, did not exhibit incompatibility and only a few cases demonstrated BGS reappearance or deletion. Adenomatous polyps (APs) however, frequently reexpressed ABH antigens or expressed incompatible BG-A or B in 27% of polyps; one specimen demonstrated BG-B deletion. Precursor expression was not found in HPs but was frequently observed in APs. Reappearance of ABH in distal polyps was significantly correlated with increasing grade of dysplasia, but was not significantly correlated with polyp size or histological type. With respect to Lewis antigen expression, Lewisb reappearance occurred in almost every distal polyp, and Lewisa-Lewisb coexpression was also quite common. Lea deletion was frequently noted, especially in HP, but the significance of this finding is unclear. This study indicates that several antigenic alterations that occur in colorectal cancer tissues also appear in premalignant polyps, and often in early stages of the neoplastic process. The observation that incompatible expression of BG-A or B occurs only in AP and cancer tissues (as well as mucosa adjacent to cancer) but not in fetal colonic mucosa, adult normal colonic mucosa, or HP, suggests that this may be a cancer-specific phenomenon.     

Distribution of blood group antigens A, B, H, and I(Ma) in mucus-producing adenocarcinoma of human lung

The distribution of blood group antigens A, B, and H and their precursor antigen I(Ma) in the mucus of lung cancer patients was studied histochemically. Antigens A, B, and H compatible with the ABO status of the patients were expressed in the mucus of bronchial gland mucous cells and bronchial goblet cells except in a few patients presumed to be nonsecretors , while antigen I(Ma) was not expressed at all in these cells. In contrast, compatible antigens A, B, and H were decreased or not present in cancer cells but antigen I(Ma) accumulated. Accumulation of antigen I(Ma), which resulted from incomplete synthesis of antigens A, B, and H, was a tumor-associated phenomenon in the mucus of the lung and was found in all patients examined. However, the degree of this accumulation varied from patient to patient, and tumor cells showed marked heterogeneity even in an individual case. In addition, accumulation of antigen associated with loss of antigens A and B was demonstrated in cancer cell mucus of patients with a blood group status other than O. Expression of incompatible blood group antigen reactive with anti-A serum (A-like antigen) also was detected in cancer cell mucus of blood group B patients.     

Immunohistological observation of blood group-related antigens in lung adenocarcinomas using monoclonal antibodies

The immunohistological distribution of blood group (BG)-related antigens including A, B, H type 2, and sialylated Lex in lung adenocarcinomas was examined using monoclonal antibodies. BG-A, B, and H type 2 compatible with the ABO status in tumor cells were expressed in 60% of the cases. Accumulation of H type 2, associated with loss of BG-A and B, was observed in tumor cells of patients with BG status other than 0. Tumor-associated antigens, Lex and sialylated Lex were detected in 36.0% and 72.0%, respectively. Modification of carbohydrate antigens in cancer may be associated with incomplete synthesis; accumulation of precursor antigen; and activated sialylation.     

Histo-Blood Group Antigens in Oral Cancer and Potentially Malignant Disorders

Background: Early detection of oral cancer is of critical importance because survival rates markedly improve when oral lesions are identified at an early stage. Aim of the present study is to investigate the expression of ABO (H) antigens in tissue specimens of oral cancer and potentially malignant disorders and to determine the role of ABO (H) antigens in tumour staging. Materials and Methods: A prospective study was conducted on 60 cases of oral cancer and potentially malignant diseases. Specific red cell adherence test (SRCA-test) was used for studying A, B and O (H) antigens in tissue specimens and iso-antigenicity of epithelium was graded according to degree of adherence of indicator red blood cells. Results: Among OSMF group, grade II adherence was seen in 53.3% cases, grade III in 33.3% cases, grade IV in 13.3% cases. In leukoplakia group, grade II adherence was seen in 26.7% cases, grade III adherence in 53.3% cases, grade IV adherence in 20% cases. Within the leukoplakia group, cases with dysplasia showed decreased adherence, compared with cases without dysplasia. Oral cancer group, negative adherence was seen in 13.3% cases, grade I adherence in 46.7% cases, grade II in 40% cases. In oral cancer group, antigen reactivity was less in poorly and moderately differentiated carcinoma, compared to well differentiated carcinoma. Conclusions: Antigen adherence and degree of loss of ABO (H) antigens in tissue specimens can be used for staging of the tumour.     

Immunohistochemical studies of blood group-related antigens in human superficial esophageal carcinomas

A total of 63 surgically resected esophageal carcinomas (including 49 superficial esophageal carcinomas) and histologically normal tissue adjacent to the superficial carcinoma (nontumorous epithelium) were examined immunohistochemically for the blood group antigens (BGA) A, B, H, Lewisa, Lewisb, Lewisx, and Lewisy. Deletion of an expected A, B or H antigen occurred in 12 (24.5%) of the 49 superficial carcinomas and three (21.4%) of the 14 advanced carcinomas. Incompatible expression of an unexpected A or B antigens occurred in only one case (1.6%) in the carcinoma. In the clinicopathologic study, there was a significant correlation between immunoreactivity of Lewisa and depth of cancer invasion (chi-square test, P less than 0.05). In the superficial carcinoma, there were significant correlations between immunoreactivity of Lewisx and lymph node status (chi-square test, P less than 0.05), immunoreactivity of Lewisy and prognosis (Z test, P less than 0.05), and incompatible expression of Lewisb for tumor against nontumorous epithelium and histologic variation (chi-square test, P less than 0.01). The functional significance of alternations in BGA expression that may be associated with oncogenesis is not clear. However, immunohistochemical determination of BGA may be a more advantageous marker to predict the patient's clinical course in superficial esophageal carcinoma.     

An HLA-A24-restricted cytotoxic T lymphocyte epitope of a tumor-associated protein, survivin.

To date an increasing number of T-cell epitopes derived from various tumor-associated antigens have been reported, and they proved to play significant roles for tumor rejection both in vivo and in vitro. Survivin was originally identified as a member of the inhibitor of apoptosis protein family. Expression of this gene is developmentally regulated. Although survivin is expressed during normal fetal development, the expression is barely detected in terminally differentiated adult tissues except for testis, thymus, and placenta. In contrast, it is abundantly expressed in a wide variety of malignant tissues. We examined the expression of survivin and the two splicing variants survivin-2B and survivin-DeltaEx3 in various cancer cells, immortalized cells, and normal adult tissues. It was demonstrated that two splicing variants were detected in various types of cancer cells as well as survivin, and their expression was more restricted to cancer cells as compared with survivin expression. To identify HLA-A24-restricted T-cell epitopes from survivin and the variant proteins, three peptides were selected from amino acid sequence of these proteins, based on the HLA-A24-binding motif. Peptide binding assay to HLA-A24 revealed that only one peptide designated as survivin-2B80-88 (AYACNTSTL) was capable of binding to HLA-A24. By stimulating peripheral blood lymphocytes with the peptide-pulsed antigen-presenting cells, CTLs were successfully induced in vitro from five of five HLA-A24-positive cancer patients. The CTLs showed significant cytotoxicity against HLA-A24-positive survivin-2B-positive cancer cells. These data suggest that survivin-2B80-88 may be a potent T-cell epitope eliciting CTL response against a splicing variant survivin-2B, which is specifically expressed in many kinds of cancer cells.     

Expression of histo-blood-group-A/B-gene-defined glycosyltransferases in normal and malignant epithelia: correlation with A/B-carbohydrate expression.

Malignant transformation of oral and bladder epithelia is often associated with loss of histo-blood-group-A- and -B-carbohydrate antigens, whereas these antigens, which are absent in normal adult distal colon (but present in fetal colon) reappear in malignant distal colon. In order to gain insight into the genetic basis of the biosynthetic regulation for these changes, we have correlated the expression of the A- and B-carbohydrate antigens with that of the A/B-gene-defined glycosyltransferases in colon, bladder and oral carcinomas by immunohistology. A newly developed anti-A/B-transferase monoclonal antibody (MAb) was used to demonstrate the in situ localization of transferase expression at the individual cell level with correlation to carbohydrate antigen expression, and gave the essential information that the transferase is derived from the ABO gene complex. The reappearance of A- and B-carbohydrate antigens in carcinomas of the distal colon was found to be unrelated to the expression of the A/B-transferase proteins, which were expressed throughout normal adult colon in accordance with previous enzymatic studies. In contrast, the loss of A- and B-carbohydrate antigens in malignant bladder and oral epithelia was accompanied by concordant loss of enzymes.     

Cell surface antigens of human trophoblast and choriocarcinoma defined by monoclonal antibodies

Six distinct cell surface antigens of human trophoblast and choriocarcinoma were defined with MAbs. The distribution of the antigens was determined by MHA assays on 150 tumor cell lines and normal cell cultures and by immunofluorescence tests with a wide range of normal adult and fetal tissues and a tumor panel. Antigen LK26 is expressed on all cultured choriocarcinoma, teratocarcinoma and renal cancer lines but is absent from most cell lines derived from other tumor types and from cultures of normal kidney epithelium and fibroblasts. LK26 expression in normal tissues is restricted to the trophoblast. No other adult or fetal tissue was found to express the antigen, but choriocarcinoma and teratocarcinoma tissues were LK26+. SV19 is expressed on cultured choriocarcinomas and teratocarcinomas and on subsets of breast and colon cancer lines, but not on 120 additional cultures tested. In tissues, SV19 is detected in normal placenta, mammary gland and colon epithelium as well as in tumors of breast, colon and lung. Two antibodies, AbSV63 and AbK8, react with PLAP and AbSV63 also reacts with the intestinal form of the enzyme. AbLK24 defines a heat-stable determinant present on choriocarcinoma and breast cancer cell lines but absent from most other cultured cells. It is expressed on a small range of normal and malignant epithelial tissues, including normal trophoblast, normal breast epithelium and urothelium and tumors derived from these tissues. One antigen, K66, showed a wide distribution on cultured epithelial cells but was not found in any normal or malignant tissue. Finally, S4, a previously described marker of normal and malignant kidney epithelial cells, was also expressed on the choriocarcinoma cell lines. Four of the antigens are glycoproteins that could be immunoprecipitated from radiolabelled extracts of choriocarcinoma cells: LK26 (Mr 35,000), SV19 (Mr 40,000), PLAP (Mr 68,000) and S4 (Mr 160,000). The highly restricted distribution of LK26, SV19, S4, and PLAP in normal tissues and their expression in tumors make these antigens potential diagnostic markers of gestational choriocarcinoma and germ-cell tumors and, possibly, targets for immunotherapy.     

A, B, H antigen expression in transitional cell carcinomas of the urinary bladder

The prognostic value of A, B, H blood group antigen determination in superficial bladder cancer is unclear. Recent immunohistochemical studies employing monoclonal antibodies and Ulex Europaeus Agglutinin I (UEA-I) (Vector) have shown that A, B, H detectability and distribution in non-neoplastic urothelium are influenced by methodologic factors and, most importantly, by the secretor status. The authors investigated the A, B, H antigen in 93 tumors of the urinary bladder (78 secretors, 15 nonsecretors) and semiquantified the alterations from the expected normal expression on a scale from 0 to 3. Four O saliva nonsecretors as expected showed no staining and were excluded. Eighty tumors showed abnormal A, B, H expression and in 37 of these, A, B, H antigens were not detected. Tumors of A and O individuals showed statistically different reactivities, probably related to differences in the specificity of the employed A- and H-reagents. A, B, H expression was influenced by stage and grade (P less than 0.05, P less than 0.10) and was correlated to the clinical course of A but not O patients. These results, suggesting that alterations in the A, B, H expression occur early in the neoplastic development and follow the synthetic pathways in an opposite direction, emphasize that reagents recognizing blood group precursor substances, common to all individuals irrespective of the ABO and saliva secretor types, may increase the prognostic accuracy of blood group antigen determination in bladder cancer.     

Mouse monoclonal antibody to embryonic antigen: development, cross-reactivity with rodent and human tumors, and preliminary polypeptide characterization

Hybridomas producing IgM and IgG monoclonal antibodies (MoAb) to embryonic or fetal antigens (EA) were obtained in a completely syngeneic system. Lethally irradiated, 13-day-gestation, C57BL/6N mouse fetal cells or KCI extracts of these fetal cells obtained from primaparous donors were used as immunogens in several regimens to induce splenocytes in C57BL/6N mice that were utilized to form the hybridomas following fusion with a mouse myeloma line. Successful growth and cloning of the IgM-producing hybridomas required supplementation with factor(s) produced in the growth medium of the macrophage cell line RAW 264.7. An enzyme-linked immunosorbent assay (ELISA) was employed to screen the primary fusion hybridomas for antibody directed against fetal cell or adult cell determinants with the use of freshly explanted tissues. Glutaraldehyde-fixed fetal cells as well as crude fetal cell membranes were used as EA+ target cells (i.e., cell lines known to activate T-lymphocyte-mediated tumor resistance) in a solid-phase ELISA to perform quantitative ELISA adsorption tests of the MoAb. The anti-EA monoclonal IgM and the IgG detected common, embryo-specific antigen(s) on mouse, hamster, and human fetuses. Term fetal cells and adult normal tissues of the mouse, hamster, and human did not express cross-reactive determinants for the MoAb by absorption analysis and/or by direct binding in ELISA. EA expression as oncofetal antigens could also be detected with the monoclones on several rodent tumor cell lines tested as well as on a variety of human carcinomas but not on a spectrum of normal human tissues with the use of indirect ELISA absorption and affinity gel and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses. Fluorescence analysis with the monoclones demonstrated specific reactivity with the surface of EA+ tumor cells in the FACS IV flow cytometer. The responsible antigen was carried on a 44- and a 200-kilodalton polypeptide.     

p27, cyclin E,and CDK2 expression in normal and cancerous endometrium

The objective was to investigate the immunohistochemical expression of p27, cyclin E, and CDK2 in normal and cancerous endometrium. Expression of p27 in premenopausal normal endometrium was significantly higher than that in postmenopausal normal endometrium (p=0.019). A significantly lower amount of p27 staining was observed in endometrial cancer tissues from premenopausal women than in normal premenopausal endometrium (p=0.015). Cyclin E expression in premenopausal normal endometrium was significantly higher than that in postmenopausal normal endometrium (p=0.003). A significantly higher amount of cyclin E staining was observed in endometrial cancer tissues from postmenopausal women than in normal postmenopausal endometrium (p=0.017). Regarding menopausal status, no significant difference in CDK2 staining was observed between cancerous and normal endometrium. There was a positive significant correlation between cyclin E and CDK2 expression levels in endometrial cancers (p<0.05). Western blot analysis confirmed elevated p27 protein levels in samples with positive p27 immunostaining. Considerable levels of p27 mRNA were detected in all normal and cancerous samples examined by semi-quantitative PCR. No significant relationship was found between telomerase activity and its association with p27 and cyclin E expression in endometrial cancers. These findings suggested that the decreased expression of p27 caused by post-translational mechanism might play an important role in endometrial cancer development in premenopausal women. In addition, increased cyclin E expression may play an important role in endometrial cancer development in postmenopausal women.     

Detection of ABO(H) blood group antigens: a study in tissue culture

The association between malignant transformation and the loss of ABO(H) blood group antigens was documented by several authors. Most of the work was done on paraffin sections, though a small portion was performed on fresh frozen tissues. We suggest that the specific red cell adherance (SRCA) test can be applied to tissues cultivated in tissue culture for determination of malignant transformation. This study supports this assumption.     

Expression of LeY and extended LeY blood group-related antigens in human malignant, premalignant, and nonmalignant colonic tissues

The LeY determinant, a difucosylated type 2 blood group-related antigen, is a positional isomer of the Leb blood group antigen and a fucosylated derivative of the LeX antigen. The LeX antigen behaves like an oncodevelopmental tumor-associated antigen in human colon cancer, and extended polyfucosyl LeX antigens are more specific for colon cancer tissues than are simple, monofucosyl LeX antigens. The present investigation compared the expression of simple and extended LeY antigens in a variety of malignant and nonmalignant human colonic tissues to gain insight into the normal distribution and cancer-associated expression of these antigens. Monoclonal antibody AH-6, which recognizes the LeY epitope irrespective of its carrier carbohydrate chain, stained the majority of specimens regardless of malignant potential or location within the colon. In contrast, CC-1 and CC-2 monoclonal antibodies, which recognize extended LeY structures, and KH-1, which is specific to trifucosyl LeY, preferentially stained malignant colonic tissues and rarely stained normal colonic mucosae. Mucosa immediately adjacent to cancer usually stained with AH-6 but not with KH-1, CC-1, or CC-2. Extended or trifucosyl LeY antigen expression was limited exclusively to premalignant (adenomatous) polyps and was invariably absent from nonpremalignant (hyperplastic) polyps. Moreover, among adenomatous polyps, extended LeY antigen expression tended to correlate with three parameters of malignant potential: larger polyp size; villous histology, and severe dysplasia. AH-6 failed to distinguish between hyperplastic and adenomatous polyps. In second-trimester fetal colonic mucosa, AH-6 bound to both proximal and distal segments whereas KH-1, CC-1, and CC-2 bound only to proximal segments. We conclude that in human colon, the LeY hapten is an oncodevelopmental cancer-associated antigen and extended LeY antigens are highly specific markers for malignancy and premalignancy.     

Expression of Lewisa, Lewisb, X, and Y blood group antigens in human colonic tumors and normal tissue and in human tumor-derived cell lines

Serological and immunopathological analysis of the expression of Lea, Leb, X, and Y blood group antigens on cell lines and tissues was performed using a panel of mouse monoclonal antibodies. The distribution of the antigens was determined on 155 malignant tumor cell lines of various types and 10 short term cultures of normal fibroblasts and kidney cells. Among colon cancers, all four blood group antigens were expressed on the majority of cell lines. On lung, breast, bladder, and ovarian cancer cell lines, X and Y antigens were the main specificities found, whereas few of the renal and hematopoietic tumor cell lines demonstrated any of the four blood group antigens. No blood group antigens could be detected on astrocytoma or melanoma cell lines. The expression of the antigens was also analyzed on frozen sections of colon carcinoma and adjacent normal colon tissue from 42 patients using the immunoperoxidase method. Lea and X were detected throughout the normal colon and on most colonic tumors. In poorly differentiated colon cancer and in metastatic cancer, decrease of Lea antigen was observed. Leb and Y expression was observed in only 20-45% of normal tissue samples but in almost all colonic carcinoma tissues. A selected number of tumor and normal specimens from patients whose secretor status was known were examined in more detail. Both the staining of the tissues and the reactivity of blood group glycolipids from the same specimens were determined. These studies confirmed the above findings and demonstrated the unexpected ability of tumors of nonsecretors to express Leb and/or Y antigens. In such individuals, in whom the expression of Leb and Y antigens in normal tissues is absent or minimal, these antigens provide possible targets for immunodiagnosis and therapy.     

Nonimmune and immune surveillance. I. Growth of tumors and normal fetal tissues grafted into newborn mice.

Growth of various fetal tissues and transplantable tumors in syngeneic newborn and adult mice [BALB/c, DBA/2, and (CBA X C57BL/6J)F1] was compared. Fetal skin, a mixture of all fetal tissues, and tumors were transplanted. The tumors arose spontaneously [hepatomas, mammary gland adenocarcinoma (MGAC)] or resulted from malignant conversion of ectopic transplants either of fetal tissues (urinary bladder carcinoma, adenocarcinoma of small intestine, stomach sarcoma) or of adult animal tissues (ovarian carcinoma) in the syngeneic system. The growth of fetal skin transplants and teratomas, which developed after transplantation of minced tissue from 18- to 20-day and 12- to 14-day fetuses, was considerably inferior in newborn syngeneic recipients, as compared with similar transplants in adults. Inhibition of tumor growth observed in newborn animals was manifested in prolongation of latent period before tumor node appearance and in slowing of growth rate of developed tumors. One of six tumors studied (MGAC) grew at the same rate in newborn and adult recipients. It was suggested that a special type of cellular and/or humoral mechanisms controlling tumor growth exists in newborns. The activity of such factors was conceivably based on fetal tumor antigens as targets. We assumed that weakly antigenic and strongly antigenic tumors behaved differently in respect to nonimmune and immune surveillance mechanisms.     

Monoclonal antibodies against human gastric cancer

Spleen cells from Balb/c mice immunized with five human gastric cancer cell lines in sequence were fused with murine myeloma cell line SP2/0, and hybridomas 3F4, 3G9 and 3H11, secreting monoclonal antibodiees (MoAbs) against gastric cancer, were obtained through selective culture and screening. These MoAbs have both good selectivity and a high positive rate of reaction for gastric cancer, reaching 5/5 and 84.8% to 93.5% for gastric cancer cells and tissues respectively. The reaction of MoAbs with normal cells and tissues was neglible. The corresponding antigens of the MoAbs were sensitive to digestion by trypsin and pronase and resistant to treatment with sodium periodate, indicating their nature as proteins. The antigen 3G9 could be visualized with Western blotting as two bands with molecular weights of 100KD and 70KD, however no band was found for antigens 3F4 and 3H11. There was a high expression of antigens in the majority of gastric cancer cells and tissues independent of histopathological type of gastric cancer. A low expression of antigens was seen with other tumors and fetal gastrointestinal tissues. These could be considered as gastric cancer-associated antigens or oncofetal antigens with a quite extensive distribution.