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Continuous infusion of 5-FU and low-dose CDDP infusion (low-dose FP therapy) is one of the effective combination chemotherapies for advanced and recurrent gastric cancer. Several studies have reported low-dose FP therapy showed high response rates (40-50%) and a low incidence of toxicities. There was a positive correlation between antitumor effect and survival time on neoadjuvant chemotherapy for advanced gastric cancer. It still may be necessary to improve quality of life by changing the regimen of low-dose FP therapy because patients require hospitalization for the therapy.

Biochemical modulation of 5-FU by leucovorin (LV) has been demonstrated to increase the therapeutic effect compared to single agent 5-FU in the treatment of patients (pts) with advanced colorectal cancer. The purpose of this study was to determine the effectiveness of the 5-FU + LV combination as adjuvant therapy following surgery in pts with Dukes' B, C colon cancer. Pts were entered in a stratified clinical trial comparing two different combination chemotherapeutic regimens to single agent 5-FU, given orally as a control. This report summarized the result of treatment in 61 pts who were 5-FU oral alone and 32 pts who were 5-FU (375 mg/m2) and low-dose LV (20 mg/m2) intravenously for 5 days with 5-FU oral intake. 5-FU with LV regimen was associated with an improved survival compared with the single agent 5-FU oral intake (p < 0.05). 5-FU with LV regimen resulted in less recurrence in liver and lung compared with single-agent 5-FU oral intake.

A nation-wide questionnaire survey was undertaken concerning low-dose anticancer therapy of CDDP plus 5-FU, which involves (5-10 mg CDDP/body/day + 300-500 mg/body/day) for 4-6 weeks. Out of 1,525 cases from 130 institutions, 847 cases with evaluable lesions were collected from 79 institutions. The response rate was 56.4% in esophageal cancer, 34.3% in gastric cancer, 35.3% in colorectal cancer, 47.2% in liver cancer and 35.9% in lung cancer, respectively. Adverse effects were found to be fewer and compliance was much better than the conventional therapy. Such figures suggest that the present regimen may be more effective than any so far. Problems for medical administration such as unlicensed CDDP for colorectal cancer were pointed out, which hinder the forthcoming third phase study.

We evaluated the clinical significance of cyclin D1 expression in colorectal adenocarcinoma. One hundred twenty-three specimens resected from patients with colorectal cancers were investigated by staining with a monoclonal antibody against cyclin D1. The possible correlations among cyclin D1 expression, clinicopathologic factors and prognosis were studied. There was no significant association between cyclin D1 expression and various clinicopathological factors. However, disease-free survival was significantly worse in the patients with cyclin D1 strongly positive tumors than in those with cyclin D1 negative tumors. Cyclin D1 overexpression may be useful as a predictor of disease recurrence in patients with colorectal adenocarcinoma.

In this study, the expression of p21 protein was investigated immunohistochemically in 152 patients with gastric cancer. Expression of p21 was detected in 64 tumors (42.1%). There were significant differences among the expression of p21, histologic type, depth of invasion, lymph node metastasis, liver metastasis, and peritoneal metastasis. The deeper the tumor invaded, the more frequent p21 expression increased. Of the 152 patients, lymph node, liver and peritoneal metastasis were found in 86, 13 and 23 patients, respectively. p21 expression was more frequently lost in tumors from patients with metastasis. In relation to prognosis, patients with p21-positive tumors had a significantly better prognosis than those with p21-negative tumors. In conclusion, this study suggested that expression of p21 has a prognostic value in gastric cancer.

The prognosis of pancreatic cancer is extremely poor in digestive cancers even with systemic therapy including surgery. Thus development of a new therapeutic approach is awaited. Recently, new trials of cancer treatments using monoclonal antibodies conjugated with anti-cancer drugs or labeled with isotopes have been reported. Here, we discuss the possible therapeutic application for pancreatic cancer of adriamycin-conjugated and 131I-labeled Nd2, which is produced against pancreatic cancer mucin.

Peritoneal metastasis has been clinically considered to be a terminal stage, so aggressive therapy has not been performed. Recently, the molecular biologic study of cancer metastasis has progressed, so it should be important in the future to examine new therapies based on the mechanism of metastasis. In this paper, the mechanism of peritoneal metastasis, especially adhesion to peritoneum, was investigated using a scirrhous gastric cancer cell line, OCUM-2MD3. The possibility of therapeutic agents for the metastasis based on the mechanism was discussed.

In this study, the expression of retinoblastoma (RB) protein was investigated immunohistochemically in 94 patients with gastric cancer. Overexpression of RB was detected in 48 tumors (51.1%). There was no significant association among the expression of RB, histologic type, lymph node metastasis, and liver metastasis. However, a significant difference was noted with respect to depth of invasion and peritoneal metastases. Among 94 patients, peritoneal metastases were observed in 11 patients. RB expression was detected in only two of these cases with peritoneal metastases, which was significantly less than those without peritoneal metastases. In relation to prognosis, patients with RB-positive tumors had a significantly better prognosis than those with RB-negative tumors. In conclusion, this study suggested that expression of RB has a prognostic value in gastric cancer.

Fifteen cases with very advanced and recurrent gastric carcinoma were treated by 5-FU plus cisplatin. Among them, 6 cases were responder (CR + PR) and 9 cases were nonresponder (NC). In order to select the responder, p53 protein status in the tissue obtained by endoscopical biopsy before chemotherapy was studied. The immunohistochemical method was by the avidin-biotin complex method using anti-p53 protein monoclonal antibody. One CR case showed negative p53 staining and 2 of 5 cases of PR cases exhibited positive p53 staining. The staining of all 9 NC cases was positive. Significantly high p53 protein overexpression in the nonresponder cases was indicated. In conclusion, our result suggested that the immunohistochemical method detecting p53 protein in the biopsy specimen may be useful to predict the effect by chemotherapy.

Tumor cell invasion and metastasis are likely to be complex processes involving a variety of cell surface receptors mediating interactions with a number of extracellular matrix molecules, including fibronectin, laminin, and collagen. We have applied this interaction of receptors for specific adhesive substrates in vitro, using specific monoclonal antibody and biologically active synthetic peptides with human pancreatic carcinoma cell, PANC-1. Tripeptide Arg-Gly-Asp (RGD) inhibited adhesion on PANC-1 cells to fibronectin but less effective in blocking adhesion to laminin and collagen, although anti beta 1-integrin antibody significantly inhibited adhesion of fibronectin but less inhibited to laminin, collagen. Our studies emphasize the importance of synthetic tripeptide RGD in adhesion on PANC-1 to extracellular matrix protein, as well as indicating the specificity of cell surface receptor, beta 1 integrin.

We first investigated the difference in carbohydrate antigens' expression between primary tumors and matched metastatic liver lesions of colorectal carcinomas, using immunohistochemical methods. Regarding the degree of expression, SLA, SLX and SPan-1 antigens were found to be expressed on a larger proportion of tumor cells in liver metastases than in primary tumors. Second, comparing the expression of carbohydrate antigens on highly metastatic colon cancer cell line to the parental line, the expression of SLA on the surface of highly metastatic variant was increased more intensively than the parental line. Finally, we investigated the contribution of carbohydrate antigens to endothelial E-selectin binding in colon and pancreatic cancer cells, and the results indicated that SLA might play a significant role in this binding. These findings suggest that the expression of carbohydrate antigens on the surface of cancer cells obviously contributed to E-selectin binding and also to metastatic potential.

The amplification of c-myc DNA for fresh frozen tissue of 31 gastric adenocarcinomas was examined with dot blot hybridization method. Using the avidin-biotin peroxidase complex method, the expression of c-myc protein was examined immunohistochemically for formalin-fixed paraffin embedded tissue of 51 gastric adenocarcinomas including the same cases for c-myc DNA analysis. c-myc DNA amplification was detected in only 4 cases (12.9%). However, c-myc protein overexpression was recognized in 21 cases (41.2%). Only one of 4 cases showing c-myc DNA amplification indicated overexpression of c-myc protein. There was no statistically significant relation of c-myc protein overexpression with clinicopathological factors (histology, depth of invasion, invasion of the vessels, metastasis, intraabdominal dissemination and histological staging). These results suggest overexpression of c-myc protein could be recognized even in early gastric cancer indicating the relation of this gene product with proliferation of gastric cancer cells, although its role in the progression and metastasis of gastric adenocarcinoma might be minimal.

We investigated the variable adhesiveness of pancreatic cancer cells by glycosylation inhibitor to elucidate the role of carbohydrate antigens in cell-cell and cell to extracellular matrix adhesion. Various carbohydrate antigens were strongly expressed on pancreatic cancer cell (SW1990) by ELISA, and these expression correlated to its in vitro invasiveness and in vivo metastatic potential. Cellular adhesion to Matrigel, laminin and collagen type IV and homotypic cellular aggregation in SW1990 were enhanced by reducing O-linked glycosylation with its inhibitor (Bzl-GalNAc), and these effect were reversed by additional purified mucins. These results suggested that O-linked glycoproteins on SW1990 cell surface may inhibit its adhesiveness to the substratum and aggregation properties by hindering surface receptors, and this variability of adhesiveness induced by altered glycosylation may have an another important role in highly metastatic potential of well glycosylated cancer cells.

Quantification of nuclear DNA content in cancer is considered a prognostic factor, and several investigators have demonstrated that aneuploid tumors are more aggressive than diploid tumors. In this report, we investigated the relationship between metastatic capacity and nuclear DNA content using gastric and colon cancer cell lines. We established a highly peritoneal metastatic cell line (2M-D3) from a gastric cancer cell line (2M) and a highly liver metastatic cell line (LM-H3) from colon cancer cell line (LM) in our laboratory. Both the highly metastatic cell lines have more capacity for growth and metastasis, but lower nuclear DNA content and chromosome numbers than these parental cell lines. The results indicated that metastatic capacity was inversely proportional to nuclear DNA content. We cannot provide a satisfactory explanation for this inverse correlation between metastatic capacity and nuclear DNA content, but it is supposed that each cancer cell may have suitable and stable nuclear DNA content in metastasis.

The clinical significance of AgNOR and microvessel quantitation as prognostic indicators in Stage I breast cancer were examined. This study included 99 patients with Stage I breast cancer, with a median follow-up period of 119 months. AgNOR was stained by Crocker's method and microvessels were identified by immunohistochemical staining for Factor VIII-related antigen in formalin-fixed, paraffin-embedded primary tumors. AgNOR score related with tumor size. Microvessel count was related to estrogen receptor status. When patients were classified into two groups by the mean AgNOR score, higher scores had a tendency to be correlated with shorter overall survival. And when classified by microvessel count, higher counts were significantly associated with shorter overall, survival (p < 0.01). The microvessel count might be a useful predictor and the AgNOR score could be used to corroborate predictions for identifying patients at high risk for relapse and death in Stage I breast cancer.

In this study, the expression of thymidine phophorylase (dThdPase) was investigated immunohistochemically in 73 patients with gastric cancer. dThd Pase was mainly distributed at the apical portion, or cytoplasm of cancer cells and its expression was detected in 52 tumors (71.2%). There were no significant association among the expression of dThdPase, histologic type, depth of invasion, and lymph node metastasis. However, a significant difference was noted with respect to liver metastases. Among 73 patients, liver metastases were observed in 11 patients. dThdPase expression was detected in all of these cases with liver metastases, which was significantly more common than those without such metastases. In relation to the prognosis, patients with dThdPase-positive tumors had a significantly worse prognosis than those with dThdPase-negative tumors. In conclusion, the expression of dThdPase may be useful as a predictor of malignant potential in gastric cancer.

We report on the establishment and characterization of a scirrhous gastric cancer cell line, designated OCUM-2M, derived from a 49-year-old Japanese female. OCUM-2M was derived from a primary tumor of stomach taken by total gastrectomy. The cell line grew singly or in clusters in the cultured medium. The cell line continued to multiply for more than one year. Doubling time was 37.3 hours, chromosomal mode was 70. The DNA ploidy pattern was aneuploid and DNA index was 1.59. It produced several tumor-associated antigens such as CEA, CA19-9, SLX and SPan-1. The cell line was transplantable in athymic BALB/c nude mice, and histological findings of the xenografted tumor showed poorly differentiated adenocarcinoma. The growth of OCUM-2M was stimulated following the addition of EGF, b-FGF and KGF, and decreased following the addition of TGF-beta 1. This cell line is useful in vitro and in vivo systems for studies of the biology of scirrhous gastric carcinoma.

We established new human breast cancer cell line, OCUB-1 derived from the pleural effusion of 53-year old female with recurrent breast cancer. Two sub-cell lines were also established with cloning technique from OCUB-1. Investigating the differences of characteristics between OCUB-1M and 1F, OCUB-1M shows a monolayered growing and OCUB-1F grows in floating. OCUB-1M and 1F revealed Modo 84 and 41 by chromosomal analysis and flow cytometric analysis showed OCUB-1M had twice amount of DNAs as -1F. OCUB-1M revealed higher expression of E-cadherin and laminin receptor against-1F, and activity of 92kDa type IV collagenase could be seen only in OCUB-1M. Estorogen and progesteron receptor were negative in either OCUB-1M and -1F, and no production of tumor markers in the spent media (CEA, CA19-9, CA15-3 and NCC-ST439) was detected in both cells. Both cells could be hetero-transplanted in nude mice, but they showed different histology.

The DNA ploidy pattern and the expression of proliferating cell nuclear antigen (PCNA) were investigated in 72 gastric carcinoma patients to determine the possible correlation between proliferation kinetics and biological behavior. The diploid pattern was more often observed in cases with mucosal invasion (m cancer) than other cases (sm or advanced cancer). The PCNA labelling index in cases with mucosal invasion was significantly lower than in other cases. The sm cancer was more often observed in patients with high PCNA labelling index (> or = 30%) and aneuploid pattern, while m cancer was more common in patients with low PCNA labelling (< 20%) index and diploid pattern. As a result of this study, we conclude that proliferating kinetics of m cancer may differ from that for sm or advanced cancer. Furthermore, DNA ploidy pattern and PCNA labelling index may be useful as a parameter of depth of invasion.

An attempt was made to investigate the status of cell proliferation in the remnant stomach, using endoscopically biopsied specimens, with cell cycle analysis by flow cytometry (FCM) and ornithine decarboxylase (ODC) activity determination. Fifty-three partially gastrectomized patients (male 33, female 20) were examined. Their mean age was 60.5, and 22 underwent Billroth I (BI), and 30 Billroth II (B II) operation. The mean time elapsing from the initial operation was 4.0 years. Almost all specimens showed DNA diploidy by FCM. The S phase cell percentage was higher in the stomal area, especially in the B II group. Significantly higher ODC activity was recognized in the stomal mucosa especially in the B II group. A significant positive relationship was noted between postoperative duration and ODC activity in the B II group. These results suggest activated cell proliferation in the stomal area of the remnant stomach. Especially in the B II group, cell proliferation increased with time after initial operation. This activated cell proliferation may play some role in the carcinogenesis of the remnant stomach.

We investigated the effect of hyperthermia against pancreatic cancer cell in various aspects including of cytokinetics. The hyperthermia above 43 degrees C was thought to have strong effect for the studies on surviving cell number and morphological change of Capan-2 and RWP-1 cells after heating treatment. The cell inoculated to the nude mice subcutaneously after heating treatment at 43 degrees C was recognized the tumor forming at 3 weeks later, however, the growth speed was slower than that of control to which untreated Capan-2 cells were inoculated. As the case of 44 degrees C, the tumor forming was not recognized at all. The cytokinetics was measured by flow cytometric bromodeoxyuridine (BrdUrd)/DNA analysis. Up to 43 degrees C in accordance with increase in the heating temperature, the accumulation in G2M phase increased, and the amount of BrdUrd incorporated 5 phase decreased. At the temperature above 44 degrees C, BrdUrd was hardly incorporated into S phase cells and the cell cycle was almost stopped. These results suggested the usefulness of hyperthermia and strong effect of heating treatment above 44 degrees C against pancreatic cancer cell.

Molecular size of SPan-1 antigen and co-expression between SPan-1 epitope and Lewis phenotype determinants (LPD) on the same molecule in sera from patients with pancreatic, gastric and colon cancer and in culture medium from cancer cell line were studied. Column chromatography study on culture medium and sera showed that SPan-1 immunoreactivity was found in the void volume region as single major peak, or followed by one or two minor peak in the included volume. All of 4 pancreatic cancer cell lines showed molecular size heterogeneity. Co-expression between SPan-1 epitope and LPD on the same molecule was recognized in sera from cancer patients with Lewis a or Lewis b positive, but not in patients with Lewis a-, b-. Molecular carrying SPan-1 epitope had more frequently SPan-1 epitope than LPD in sera from cancer patients. These findings suggest that molecular size heterogeneity of SPan-1 antigen was more often in pancreatic cancer cells and overexpression of SPan-1 epitope on the same molecule seems to be specific for cancer.

Early gastric cancer in the region of the fundic gland was found to occur predominantly in women. Many lesions of this type were identified in the posterior wall of the middle portion of the stomach. Histologically, the lesions were classified as poorly differentiated carcinomas in all cases of early cancer. In 9 patients with cancer of linitis plastica type having IIc lesions located in the region of the fundic gland, the tumor focus was also in posterior wall of the middle portion of the stomach. Giant folds were present diffusely in all other portions of the gastric mucosa in these latter cases. These cases also had diffuse infiltration of cancer cells into the submucosa, muscle layer and extraserosal regions. Histologically, the lesions were classified in all cases of linitis plastica type as poorly differentiated carcinomas including signet ring cells. Acid mucopolysaccharides (AMPS) and sialic acid were histochemically detected in the interstitial tissues of early gastric carcinomas and linitis plastica type gastric cancers. The AMPS digestion rates were higher for early cancer tissue. The present results support the hypothesis that early gastric cancer in the region of the fundic gland may occur in conditions favoring tumor growth and may develop into cancer of linitis plastica type.

For an extracorporeal circulation, either a unidirectional pump or a one-way valve is required. Most of the one-way valves developed so far for a cardiac valve operation have excellent rheological features. But, they are too expensive to be thrown away after a short usage in a disposable bypass circuit. Though a ball valve is simple to make and not expensive, the spherical float inside the valve causes a turbulence in the down stream. This turbulence in the blood stream will become a cause of hematological side effects during the extracorporeal circulation. To prevent this turbulence, we designed a cone shape float with a hemispherical head and a tapered tail. The valve chamber was also changed to a similar shape with a diameter 4 mm larger than that of the float. Three small notch-like spacers were made near the head of the float to prevent wedging of the float into the cone shape region of the valve chamber. Water passed through the valve with a laminar flow without much resistance. Regurgitation at the valve by reversing pressure was insignificant. But, the valve sometimes fell into dysfunction suddenly. Observation with a videocamera revealed that the float often began a long axis rotation and tail swung in the flow. Then the valve suddenly fell in to dysfunction due to the oblique fixation of the float in the valve chamber. A gentle knock of the valve could resume the valve function. However, the cone shaped valve will not be suitable for an extracorporeal life support system where any hazard must be avoided.

We studied clinical significance of serum SPan-1 antigen, which is human pancreatic cancer associated antigen, in hepatobiliary and pancreatic diseases employing newly developed kit. The sensitivity of serum SPan-1 antigen levels for pancreatic cancer, gallbladder carcinoma, hepatocellular carcinoma, bile duct cancer were 90.9%, 77.8%, 60.7%, 60.0% respectively. No correlation was found between serum SPan-1 antigen levels and total bilirubin levels. SPan-1 positivity in patients with hepatic disease including hepatocellular carcinoma was rather high, but there were few cases more than 100 U/ml. The mechanism of the elevated level was supposed to be release of the antigen from bile-duct epithelium, and this must be taken into consideration at diagnosis referred to serum SPan-1 antigen level.

Basic evaluation of SPan-1 assay (SPan-1 RIA. BEAD) and clinical significance of serum SPan-1 levels for the diagnosis of pancreatic cancer were studied. This assay was reproducible, reliable and simple to perform. It required minimal samples (duplicate 50 microliters) and may be done within 4 hrs. Normal subjects (N = 1182) had serum SPan-1 antigen levels which ranged 0 to 42.8 units/ml with a mean of 7.5 units/ml and above 40 units/ml was considered to be positive. SPan-1 antigen levels in cultured medium of four out of five pancreatic cancer cell lines showed more than 1000 units/ml by this assay. While over 90% of pancreatic cancer patients had elevated levels of serum SPan-1 antigen, only 0-17% of patients with other malignant and non malignant gastrointestinal diseases such as pancreatitis (chronic or acute), gastric cancer or colon cancer had above normal levels. Furthermore, levels of serum SPan-1 antigen correlated well with treatment and recurrence of disease in patients with pancreatic and gastric cancer. These results suggest that determination of serum SPan-1 antigen levels by this assay kit is useful for the diagnosis and monitoring of pancreatic cancer.

Seventy-six cases of primary cancer of the breast were studied by clinicopathological examination and immunohistological examination using monoclonal antibodies. They were composed of 40 cases positive for estrogen receptor (ER) and 36 cases negative for ER, the ER-positive rate being 52.6%. ER was detected more frequently in the postmenopausal group than in the premenopausal group, though the ER-positive rate was not significantly different between the two groups. The disease was advanced with a large tumor (greater than t3) and high-grade lymph node metastasis in ER-negative cases compared with ER-positive cases. The carbohydrate antigens specific to SPan-1, CA 19-9 and SLEX were found in 34.2%, 39.5% and 68.4% of the cases studied, respectively. These antigens were detected more often, if not significantly, in cases with a large mass and high-grade metastasis than in those with a small mass and without metastasis or with low-grade metastasis. The SPan-1-positive rate was significantly higher in ER-negative cases graded t1 or t2 than in ER-positive cases falling under the same category of tumor size. Significant differences were also noticed between the ER-negative and ER-positive groups with respect to CA 19-9-positive rate (t2 category) and SLEX-positive rate (t3 category). Similar data were obtained when our cases were classified by the degree of lymph node metastasis. In consequence, the present observations suggested that the expression of carbohydrate antigens in primary breast cancer and disease progress might be correlated with ER status.

We investigated both DNA histogram and the expression of carbohydrate antigens concerning to 168 patients with gastric cancer. Gastric cancer with type II DNA ploidy pattern showed a high incidence of vascular invasion and liver metastasis in the DNA analysis. Furthermore, ten patients with Stage II died of recurrence of gastric cancer within 2 years, of these nine patients showed type II or III DNA ploidy pattern. Then, gastric cancer with type II or III DNA ploidy pattern showed a high incidence of the expression of carbohydrate antigens, where they tended to distribute to cytoplasm and stroma. In conclusion, an analysis of nuclear DNA content appeared useful to predict prognosis in gastric cancer, in which type II DNA ploidy pattern showed the highest degree of malignancy, and both the expression of carbohydrate antigens and their localization possibly fill the role of parameter of the degree of malignancy.

Serum levels of SPan-1 were determined in patients with various gastrointestinal cancers including pancreatic cancer and benign disorders, as well as from healthy subjects, by using a newly developed SPan-1 antigen immunoradiometric assay (SPan-1 RIABEAD, Dainabott). In addition, usefulness of diagnosis for pancreatic cancer by determination of Serum SPan-1 antigen was compared with that of other tumor markers such as CA 19-9, DU-PAN 2, CA 50, CEA and elastase 1 in the same patients. Serum SPan-1 antigen levels in healthy controls ranged from 0 to 156 U/ml with a mean of 7.7 U/ml (+/- 15.0, 2 S.D). Thirty U/ml of serum SPan-1 antigen levels was set as the cut-off value, and 98.9% of healthy controls were within this cut-off value (30 U/ml). Serum SPan-1 antigen levels in pancreatic cancer were distributed from 0-353, 900 U/ml with a mean of 14,466 U/ml (+/- 16.616 SD). Sensitivity of SPan-1 antigen in pancreatic cancer was 81.9%, which was the highest among gastrointestinal cancers, and eight of nine pancreatic cancer patients with stage II showed above normal limits (30 U/ml). Although serum SPan-1 antigen levels in biliary tract cancer and liver cirrhosis showed a high percentage (70.3%, 56.8%), the mean values of SPan-1 antigen levels in these groups were 477 U/ml and 62.8 U/ml, respectively, which was lower than that of pancreatic cancer. False positive ratio of SPan-1 antigen in benign pancreatic disease was lower than that of CA 19-9. Also, comparative studies of SPan-1 antigen and various tumor markers between pancreatic cancer and benign gastrointestinal diseases revealed that SPan-1 antigen showed the highest sensitivity and accuracy in diagnosis for pancreatic cancer among other tumor markers. From these results, measurement of SPan-1 antigen appeared to be the most useful marker in the diagnosis of pancreatic cancer.

A new series of monoclonal antibodies (Span 1-7) was produced by immunizing mice with SW 1990 human pancreatic cancer cells. Span 1-4 antibodies (Ab) reacted with 4-5 of 8 pancreatic cancer cell lines tested and with 5-6 of 9 colon cancer cell lines and some lung cancer cell lines. Span 1-4 antigens (Ag) were detected not only on cell surface but also in cultured spent medium of SW 1990 cells by ELISA. They were also found in the fractions of a cesium chloride gradient of SW 1990 xenograft homogenates which have the highest molecular weight, density and carbohydrate content. Their immunoreactivity is dependent upon sialic acid because prior digestion with neuraminidase abolished their immunoreactivity. Span 5,6,7 Ab reacted with only 3 of 8 pancreatic cancer cell lines tested and did not reacted with any other cell lines such as colon cancer, lung cancer and melanoma. The epitopes which were recognized by Span 5,6,7 Ab did not contain sialic acid. These results suggest that Span 1-4 Ab has potential application in the detection of gastrointestinal cancers and that Span 5,7 may be useful to detect the origin which is unknown by using immunohistochemistry method for metastatic lesions.