lewis-x-antigen and Liver-Neoplasms

he colonization of the liver by colorectal cancer (CRC) cells is a complicated process which includes many stages, until macrometastases occur. The entrapment of malignant cells within the hepatic sinusoids and their interactions with resident non-parenchymal cells are considered very important for the whole metastatic sequence. In the sinusoids, cell connection and signalling is mediated by multiple cell adhesion molecules, such as the selectins. The three members of the selectin family, E-, P- and L-selectin, in conjunction with sialylated Lewis ligands and CD44 variants, regulate colorectal cell communication and adhesion with platelets, leucocytes, sinusoidal endothelial cells and stellate cells. Their role in CRC liver metastases has been investigated in animal models and human tissue, in vivo and in vitro, in static and shear flow conditions, and their key-function in several molecular pathways has been displayed. Therefore, trials have already commenced aiming to exploit selectins and their ligands in the treatment of benign and malignant diseases. Multiple pharmacological agents have been developed that are being tested for potential therapeutic applications.

Topics: Carbohydrate Conformation; Carbohydrate Sequence; Colorectal Neoplasms; Hexanes; Humans; Lewis X Antigen; Ligands; Liver Neoplasms; Mannose; Molecular Sequence Data; Molecular Structure; Protein Isoforms; Selectins; Sialyl Lewis X Antigen

This review is concerned with the usefulness and the problem of biomarkers for cancer of digestive organs. Carcinoembryonic antigen (CEA) is a most popular and useful tumor marker for cancer of digestive organs. Squamous cell carcinoma (SCC) antigen and CYFRA have been reported as a useful tumor marker for esophageal cancer. CEA and CA 19-9 are a good prognostic factor in gastric cancer patients. The post-operative increase of serum CEA can be a predictive marker for the patients of colorectal cancer. Development of a radioimmunoassay for highly sensitive detection of tumor markers, they are considered to be useful for monitoring after treatment. But are not useful for the early diagnosis. The diagnosis of hepatocellular carcinoma (HCC) is based mainly on serological markers, such as alpha-fetoprotein and PIVKA-II. The two are useful complementary markers of HCC because they do not correlate with each other. But the problem of the false-positive rate for the patients with chronic hepatitis or liver cirrhosis is still remained. A typical marker of pancreatic and bile duct cancer is carbohydrate antigen, but the sensitivity of these markers is only 50%. Recent molecular biological analysis may be used as effective biomarkers in the diagnosis, prognosis, therapy, and risk assessment of digestive cancer.

Topics: alpha-Fetoproteins; Antigens, CD19; Antigens, Neoplasm; Biomarkers; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Carcinoma, Squamous Cell; Colorectal Neoplasms; Digestive System Neoplasms; Esophageal Neoplasms; Female; Humans; Keratin-19; Keratins; Lewis X Antigen; Liver Neoplasms; Pancreatic Neoplasms; Prognosis; Protein Precursors; Prothrombin; Stomach Neoplasms

Four prognostics factors were investigated for colorectal cancer metastases. 1) There were statistically more venous invasions using Victoria blue elastic staining in patients with liver or lymph node metastasis than in those without metastasis. 2) The immunohistochemical expression rate of c-erbB-2 in liver metastasis cases was 27%, which was significantly higher than 3% in no metastasis cases. 3) Sialyl Lewis x (SLex) is related with cell adhesion. SLex positive rates in vessel invasion cancer cells were 71.4% with metastasis and 31.0% without metastasis. 4) Matrilysin is one of MMPs and it was significantly increased with Dukes stage by fluorescence intensity.

Topics: Colorectal Neoplasms; Humans; Lewis X Antigen; Liver Neoplasms; Lymphatic Metastasis; Matrix Metalloproteinase 7; Metalloendopeptidases; Neoplasm Invasiveness; Neoplasm Metastasis; Prognosis; Receptor, ErbB-2; Veins

Topics: Adenocarcinoma; Animals; Antigens, Neoplasm; Biomarkers, Tumor; Carbohydrate Sequence; Carbohydrates; Cell Adhesion; Colorectal Neoplasms; Humans; Lewis X Antigen; Liver Neoplasms; Mice; Molecular Sequence Data; Neoplasm Metastasis; Prognosis; Retrospective Studies; Splenic Neoplasms; Survival Analysis; Tumor Cells, Cultured

Topics: Arginase; Carcinoma, Hepatocellular; Case-Control Studies; Cell Proliferation; Cells, Cultured; Coculture Techniques; Endoplasmic Reticulum Stress; Fucosyltransferases; Humans; Interferons; Lewis X Antigen; Liver Neoplasms; Lymphocyte Activation; Myeloid-Derived Suppressor Cells; Reactive Oxygen Species; Scavenger Receptors, Class E; Signal Transduction; T-Lymphocytes

Interactions between endothelial and tumor cells via E-selectin and sialyl Lewis x (sLex) have been suggested to play a significant role in the development of metastasis and tumor growth. In this work, we tested whether inhibition of E-selectin expression on the surface of endothelial cells might impair endothelial/tumor cells interactions and tumor growth of hepatocarcinoma cells in vitro and in vivo.. We used HepG2 cells that highly express sLex antigens and HuH7 cells that do not express sLex. Inhibition of E-selectin expression on the surface of endothelial cells was obtained by using cimetidine and amiloride treatment.. Cimetidine and amiloride inhibited, respectively, by 20 and 64 % E-selectin expression by activated endothelial cells and significantly subsequent adhesion of HepG2 cells to activated endothelial cells. Subcutaneous injection of cimetidine or amiloride resulted in a significant inhibition of HepG2 cells tumor growth in nu/nu mice but not of HuH7 cells. Thus, cimetidine and amiloride administration led to an inhibition of 57 and 75 % of HepG2 tumor growth in vivo, respectively. This effect was associated with an inhibition of vasculogenesis as demonstrated by anti-CD31 immunostaining.. Inhibition of E-selectin expression allows an anti-tumoral effect on sLex-expressing HCC tumors in vivo. This suggests that interactions between HCC cells and endothelial cells through sLex antigens and E-selectin might be a target for treatment of HCC. Further studies might evaluate the clinical impact of cimetidine and amiloride in the treatment of HCC patients alone or in combination with other anti-tumoral agents.

Topics: Amiloride; Animals; Carcinoma, Hepatocellular; Cell Proliferation; Cimetidine; E-Selectin; Endothelial Cells; Female; Hep G2 Cells; Humans; Lewis X Antigen; Liver Neoplasms; Mice; Neovascularization, Pathologic; Sialyl Lewis X Antigen

The metastasis of hematogenous cancer cells is associated with abnormal glycosylation such as sialyl lewis antigens. Although the hepatitis B virus X protein (HBx) plays important role in liver disease, the precise function of HBx on aberrant glycosylation for metastasis remains unclear.. The human hepatocellular carcinoma tissues, HBx transgenic mice and HBx-transfected cells were used to check the correlation of expressions between HBx and Sialyl lewis antigen for cancer metastasis. To investigate whether expression levels of glycosyltransferases induced in HBx-transfected cells are specifically associated with sialyl lewis A (SLA) synthesis, which enhances metastasis by interaction of liver cancer cells with endothelial cells, ShRNA and siRNAs targeting specific glycosyltransferases were used.. HBx expression in liver cancer region of HCC is associated with the specific synthesis of SLA. Furthermore, the SLA was specifically induced both in liver tissues from HBx-transgenic mice and in in vitro HBx-transfected cells. HBx increased transcription levels and activities of α2-3 sialyltransferases (ST3Gal III), α1-3/4 fucosyltransferases III and VII (FUT III and VII) genes, which were specific for SLA synthesis, allowing dramatic cell-cell adhesion for metastatic potential. Interestingly, HBx specifically induced expression of N-acetylglucosamine-β1-3 galactosyltransferase V (β1-3GalT 5) gene associated with the initial synthesis of sialyl lewis A, but not β1-4GalT I. The β1-3GalT 5 shRNA suppressed SLA expression by HBx, blocking the adhesion of HBx-transfected cells to the endothelial cells. Moreover, β1-3GalT 5 silencing suppressed lung metastasis of HBx-transfected cells in in vivo lung metastasis system.. HBx targets the specific glycosyltransferases for the SLA synthesis and this process regulates hematogenous cancer cell adhesion to endothelial cells for cancer metastasis.

Topics: Adult; Animals; CA-19-9 Antigen; Carcinoma, Hepatocellular; Cell Line, Tumor; Female; Gene Expression Regulation, Neoplastic; Glycosylation; Glycosyltransferases; Hepatitis B virus; Human Umbilical Vein Endothelial Cells; Humans; Lewis X Antigen; Liver; Liver Neoplasms; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Middle Aged; Neoplasm Metastasis; Oligosaccharides; Sialyl Lewis X Antigen; Trans-Activators; Viral Regulatory and Accessory Proteins

Substantial evidence indicates that inflammation is a critical component of tumor progression. Hepatocellular carcinoma (HCC) is usually derived from inflamed cirrhotic liver with extensive leukocyte infiltration. Neutrophils are the common inflammatory infiltrate in tumors, but their nature and regulation in human cancers remain elusive.. A total of 238 HCC patients were enrolled randomly. Immunohistochemistry and SuperArray Real-Time PCR were used to analyze the distribution and clinical relevance of neutrophils in different microanatomical areas. The regulation and function of neutrophils were assessed by both in vitro and in vivo studies.. Neutrophils were enriched predominantly in peritumoral stroma of HCC tissues and their levels could serve as a powerful predictor for poor survival in HCC patients. Proinflammatory IL-17 is a critical mediator of the recruitment of neutrophils into peritumoral stroma of HCC tissues by epithelial cell-derived CXC chemokines. The accumulated peritumoral neutrophils were the major source of matrix metalloproteinase-9 in HCC tissues; this secreted protein stimulated proangiogenic activity in hepatoma cells. Accordingly, high infiltration of peritumoral neutrophils was positively correlated with angiogenesis progression at tumor-invading edge of HCC patients. Furthermore, we found that selective depletion of neutrophils effectively inhibited tumor angiogenesis and growth, in vivo.. These data provide direct evidence supporting the critical role of neutrophils in human tumor progression and reveal a fine-tuned collaborative action between cancer cells and immune cells in distinct tumor milieu, which reroutes the inflammatory response into a tumor-promoting direction.

Topics: Carcinoma, Hepatocellular; Disease Progression; Epithelial Cells; Fucosyltransferases; Hepatitis; Humans; Interleukin-17; Lewis X Antigen; Liver Cirrhosis; Liver Neoplasms; Matrix Metalloproteinase 9; Neovascularization, Pathologic; Neutrophils; Predictive Value of Tests; Signal Transduction; Survival Rate; Vascular Endothelial Growth Factor A

Hepatoid adenocarcinoma is a rare neoplasm, which has a striking morphologic similarity to hepatocarcinoma. It has been described in different organs, the most common are stomach, lung, and pancreas. In some cases, it is characterized by high serum levels of α-fetoprotein. This tumor has a pattern similar to the hepatocarcinoma. The typical features are a combination of histopathologic aspects of solid nests and trabecular structures of polygonal atypical cells with eosinophil and granular cytoplasm and immunohistochemical expression of α-fetoprotein and of carcinoembryonic antigen in half of cases. Here, we report the case of an old female patient affected by hepatoid adenocarcinoma of the ureter with ovarian, small intestine, and hepatic involvement. We discuss the clinical aspects, the morphologic features, and the immunoistochemical staining useful for differential diagnosis.

Topics: Adenocarcinoma; Aged, 80 and over; Carcinoma, Hepatocellular; Female; GATA3 Transcription Factor; Humans; Immunohistochemistry; Intestine, Small; Lewis X Antigen; Liver Neoplasms; Membrane Proteins; Ovarian Neoplasms; Ureter

The expressions of three X series Lewis antigens, including Lewis X (Le(x)), sialyl Lewis X (SLe(x)) and sialyl dimeric Lewis X (SDLe(x)) were studied with immuno-histochemical methods in human non-small cell pulmonary cancer (NSCPC) and primary liver cancer (PLC) with different pathological conditions. The Lewis antigens are mainly expressed on the cell surfaces, medially or slightly in the cytoplasm, but not in the cell nuclei of the cancer tissues. The regions adjacent to the cancer tissues do not express any Lewis antigens. The positive rates of these antigens in NSCPC were within the range of 75% to approximately 86%. There was no apparent difference in positive rates between the cases with different differentiation and the presence or absence of metastasis in peripheral lymph nodes, nor among the three antigens, except that the positive rate of SDLe(x) was lower (about 56%) in the cases with well/medium differentiation and without metastasis. However, the expression-intensities (SI indexes) of all three antigens were significantly higher in the samples of poor differentiation and with metastasis as compared to those with well/medium differentiation and without metastasis. The two sialyl Lewis antigens increased more significantly than non-sialylated Le(x). The expressions of these antigens were also observed in the peripheral lymph nodes with metastasis, but not in those without metastasis. The positive rates of Le(x), SLe(x) and SDLe(x) in human primary liver cancer were 83.3%, 88.9% and 77.8%, respectively. In the cases with cancer cell thrombosis (CCT) in portal vein (an index of metastasis), the expressions of all these three antigens were stronger than those in the cases without CCT. SLe(x) was the most abundant and most highly increased Lewis antigen on the surface of NSCPC and PLC, especially in the cases with poor differentiation and metastasis. In the study of the enzymatic basis of the increased Lewis antigens in PLC by using Northern blot, it was found that the level of alpha1,3 FucT-III/VI mRNA in PLC tissues was much higher than that in the adjacent regions, and more significantly higher in the cancer tissues from patients with CCT in portal vein. In contrast, the expression of alpha1,3 FucT-VII was rather low in cancer tissues and not different from the adjacent regions in spite of the presence or absence of CCT. These results reveal that the SLe(x) in PLC is mainly synthesized by alpha1,3 FucT-III/VI (especially VI) and is the most im

Topics: Carcinoma, Non-Small-Cell Lung; Humans; Lewis X Antigen; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Neoplasm Staging

The relationship between the structures of glycans on the surface of H7721 cells, a human hepatocarcinoma cell line, and the cell behaviors was studied by using neuraminidase and alpha-L-fucosidase to remove the terminal sialyl or fucosyl residues of surface glycans respectively. The cell adhesion to fibronectin (Fn), laminin (Ln) and human umbilical vein epithelial cell (HUVEC), as well as cell chemotactic migration and invasion were selected as the parameters of the cell behaviors. It was found that sialyl residue was not essential for the cell adhesion to Fn, but was important in the cell adhesion to Ln and chemotactic cell invasion, and very crucial in the cell adhesion to HUVEC and chemotactic migration. In contrast, fucosyl residue was probably participate in cell adhesion to Fn, Ln and HUVEC, but not important in chemotactic migration and invasion. The cell adhesion to HUVEC, chemotactic migration and invasion were inhibited by the monoclonal antibody of sialyl Lewis X (SLex), but not by the antibody of non-sialyl Lewis X (Lex). This result supports the finding that sialyl residue is more important than fucosyl residue in the contribution to the above-mentioned three cell processes.

Topics: Antibodies, Monoclonal; Carcinoma, Hepatocellular; Cell Adhesion; Cell Line, Tumor; Cells, Cultured; Chemotaxis; Fibronectins; Humans; Laminin; Lewis X Antigen; Liver Neoplasms; Polysaccharides; Sialyl Lewis X Antigen

Carbohydrate expression of cancer cells is closely related to the metastatic nature of colorectal cancer. In the present study we investigated the relevance of carbohydrate expression profiles of colorectal cancer cells in the primary lesion to metastatic distribution patterns as well as prognosis in 134 cases. Carbohydrate expression was estimated by histochemistry with 17 kinds of lectins and 3 kinds of Lewis-related monoclonal antibodies (MAbs), and correlations between the staining and clinicopathological parameters were examined. The results showed that lymphatic invasion, lymph node metastasis, and peritoneal metastasis correlated with staining with lectins that bind galactose/N-acetylgalactosamine residues (Gal/GalNAc) such as Maclura pomifera (MPA), Arachis hypogaea (PNA), Helix pomatia (HPA), and Vicia villosa (VVA). In contrast, hepatic metastasis correlated with staining with Anguilla anguilla lectin (AAA), anti-LewisX (LEX-2), anti-sialyl Lewisa (NS 19-9), and anti-sialyl-dimeric LewisX (FH-6) MAbs, all of which bind preferentially to fucosylated carbohydrate chains. The five-year survival rate of patients was related to the staining of cancers with MPA, HPA, FH-6 or NS19-9, and MPA- and FH-6 staining were independent prognostic factors. We conclude that carbohydrate expression profiles of cancer cells are relevant to the route of tumor cell dissemination, metastatic pattern as well as prognosis of colorectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Animals; Antibodies, Monoclonal; Antigens, Neoplasm; Carbohydrate Metabolism; Carbohydrate Sequence; Carbohydrates; Colorectal Neoplasms; Female; Humans; Lectins; Lewis X Antigen; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Molecular Sequence Data; Neoplasm Invasiveness; Neoplasm Metastasis; Oligosaccharides; Peritoneal Neoplasms; Prognosis; Prospective Studies; Sialyl Lewis X Antigen; Staining and Labeling

The expressions of Lewis (Le) antigens, alpha-1,3/1,4 fucosyltransferases (alpha-1,3/1,4 FuTs), and metastatic potential after the treatment of 2 differentiation inducers, all- trans retinoic acid (ATRA), 8-bromo-cyclic 3',5'adenosine monophosphate (8-Br-cAMP); and 2 proliferation inducers, epidermal growth factor (EGF) and phobol-12-myristate-13-acetate (PMA), on 7721 human hepatocarcinoma cell line were studied. Cell adhesion to human umbilical vein endothelial cells (HUVEC), cell migration through transwell and invasion through matrigel were selected as the indexes of metastatic potential-related phenotypes. Using fluorescence-labelled antibodies and flow-cytometric analysis, it was found that 7721 cells mainly expressed sialyl Lewis X (SLe(x)) and a less amount of sialyl dimeric Lewis X (SDLe(x)) antigens on the cell surface. Their expressions were down-regulated by ATRA, and up-regulated by EGF. SLe(x)antigen was also decreased and increased by the treatment of 8-Br-cAMP and PMA respectively. With Northern blot to detect the mRNAs of alpha-1,3/1,4 FuTs, the main enzymatic basis for the change in SLe(x)expression was found to be the alteration of the expression of alpha-1,3 FuT-VII. It was evidenced by the observations that alpha-1,3 FuT-VII was the main alpha-1,3/1,4 FuT in 7721 cells, while alpha-1,3/1,4 FuT-III and alpha-1,3 FuT-VI were expressed rather low. The changes in the expressions of SLe(x)antigen and alpha-1,3 FuT-VII resulted in the altered cell adhesion to tumour necrosis factor-alpha stimulated HUVEC, since only the monoclonal antibody of the SLe(x), but not other monoclonal antibodies blocked the adhesion of 7721 cells to HUVEC. The migration and invasion of 7721 cells were also reduced by the treatment of ATRA or 8-Br-cAMP, and elevated by EGF or PMA. The above findings indicate that the metastatic potential of 7721 cells is suppressed by differentiation-inducers and promoted by proliferation-inducers.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Antineoplastic Agents; Carcinoma, Hepatocellular; Cell Adhesion; Cell Differentiation; Cell Division; Cell Movement; Epidermal Growth Factor; Fucosyltransferases; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Liver Neoplasms; Neoplasm Metastasis; Phenotype; Tetradecanoylphorbol Acetate; Tretinoin; Tumor Cells, Cultured

Topics: Animals; Antibodies, Monoclonal; Cell Adhesion; Colorectal Neoplasms; E-Selectin; Endothelium, Vascular; Flow Cytometry; HT29 Cells; Humans; Immunohistochemistry; In Situ Hybridization; Lewis X Antigen; Liver Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Electron; Microscopy, Electron, Scanning; N-Acetylneuraminic Acid; RNA, Messenger; Tumor Cells, Cultured; Umbilical Veins

To improve the survival rate of patients with colon cancer, liver metastases must be eradicated in a clinically occult state. This study was designed to find a predictor for potential liver metastases or micrometastases in colon cancer.. Peripheral blood samples and tumor specimens were obtained from 36 patients with colon cancers. The blood samples were subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, and the expression of sialylated carbohydrates was also investigated in the tumors immunohistochemically.. A carcinoembryonic antigen (CEA)-specific signal in the blood was detected in 9 of 12 (75%) patients with liver metastasis and in 8 of 24 (33%) patients without liver metastasis, respectively (P < 0.05). The positive rates of sialyl Lewis A (sLeA) and sialyl Lewis X (sLeX) were 36.3% and 40% in tumors without liver metastasis vs. 58.3% and 100% with liver metastasis, respectively. Within a year after surgery, liver metastases became clinically evident in three of the four patients without liver metastasis who showed a CEA-positive signal in their blood preoperatively and who had tumors with a strong expression of sLeX.. A combination of both markers may provide prognostic information for liver metastases in colon cancer.

Topics: Colonic Neoplasms; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Lewis X Antigen; Liver Neoplasms; Oligosaccharides; Predictive Value of Tests; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm; Sialyl Lewis X Antigen

Peritoneal dissemination and hepatic metastasis commonly occur after patients with pancreatic cancer have undergone surgery. It is thought that specific adhesion molecules play corresponding roles in cancer metastasis.. We conducted in vitro and in vivo studies to assess the role of adhesion molecules in these processes, using SW1990 cells derived from human pancreatic cancer.. SW1990 cells pronouncedly expressed sialyl Lewis(a) (s-Le[a]) and sialyl Lewis(x) antigens (s-Le[x]), CD44H, and beta1 integrin. Also, SW1990 cells showed a strong binding activity to IL-1beta activated human umbilical vein endothelial cells, cultured murine endothelial cells (F-2 cells), and human peritoneal mesothelial cells. Invasive ability of SW1990 cells to F-2 cells was also observed. The adhesion leading to implantation of cancer cells to endothelial cells were inhibited by treatment with the antibodies against s-Le(a) and against beta1 integrin, respectively. Treatments with the antibodies against s-Le(a) and beta1 integrin each inhibited the development of liver metastasis in nude mice with SW1990 cells. The adhesion of SW1990 cells to peritoneal mesothelial cells was markedly inhibited by antibodies each against CD44 or beta1 integrin, but was completely blocked by using a combination of these two antibodies. These antibodies inhibited the dissemination of SW1990 cells in the peritoneal cavity of nude mice and prolonged their survival.. These findings suggest that s-Le(a) and integrin mediate the process from adhesion to implantation of SW1990 cells to endothelial cells, and CD44 and integrin play important roles in the initial attachment of SW1990 cells to mesothelial cells. It is thus speculated that compounds that interfere with the function of cell adhesion molecules may decrease the incidence of pancreatic cancer metastasis.

Topics: Animals; Antibodies; Cell Adhesion Molecules; E-Selectin; Humans; Hyaluronan Receptors; Integrin beta1; Interleukin-1; Lewis X Antigen; Liver Neoplasms; Male; Mice; Mice, Nude; Neoplasm Transplantation; Pancreatic Neoplasms; Peritoneal Neoplasms; Tumor Cells, Cultured

Activation of telomerase and stabilization of telomeres are considered necessary for immortalization of tumor cells. Telomerase activity was analyzed in 69 hepatocellular carcinomas and adjacent chronic liver disease tissues. The telomerase activity level was examined in relation to clinicopathologic features.. Telomerase activity was determined by a telomeric repeat amplification protocol. Immature and mature leukocytes were removed from homogenized tissue of adjacent livers using anti-CD45 and anti-CD15 monoclonal antibody-coated magnetic beads.. Telomerase activity was detected in hepatocellular carcinomas and leukocytes, but not in liver cells from adjacent chronic liver disease tissues after the separation of leukocytes. All hepatocellular carcinomas displayed telomerase activity, and the activity level correlated with the degree of differentiation (P=0.021) and patient survival (P=0.039).. These results indicate that activation of telomerase may be required as a critical step in hepatocarcinogenesis and tumor development, and detection of telomerase activity with removal of contaminating leukocytes may be useful in the characterization or prognostication of hepatocellular carcinoma.

Topics: Adult; Aged; Antibodies, Monoclonal; Carcinoma, Hepatocellular; Female; Hepatitis, Chronic; Humans; Leukocyte Common Antigens; Leukocytes; Lewis X Antigen; Liver; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Prognosis; Survival Rate; Telomerase; Tumor Cells, Cultured

TEC-01 monoclonal antibody recognizes the oligosaccharide structure Galbeta1-->4[Fucalpha1-->3] GlcNAc (Le(X) hapten). To determine its fine specificity, reactivity of TEC-01 antibody with Le(X) glycosphingolipids, isolated from human liver metastasis of adenocarcinoma, and Le(X) neoglycolipid were analysed. Immunostaining of Le(X) glycosphingolipids, fractionated by thin-layer chromatography, showed that TEC-01 reacted with difucosyl and trifucosyl Le(X) glycosphingolipids but not with Le(X) pentasaccharide ceramide. Interestingly, TEC-01 also reacted with Le(X) neoglycolipid prepared by reductive amination from Le(X) pentasaccharide, lacto-N-fucopentaose III, and L-1,2-dipalmitoyl-sn-glycerophosphoethanolamine. The combined data suggest that TEC-01 recognizes Le(X) hapten in glycolipids with longer oligosaccharide chain moiety.

Topics: Adenocarcinoma; Animals; Antibodies, Monoclonal; Antibody Specificity; Carbohydrate Sequence; Glycosphingolipids; Haptens; Humans; Lewis X Antigen; Liver Neoplasms; Mice; Molecular Sequence Data; Oligosaccharides

Histologic features of recurrent Hodgkin's disease (HD) after conventional therapy are well known, but few studies describe HD after bone marrow transplantation (BMT). Histologic material from 63 patients who underwent BMT performed to treat recurrent nodular sclerosing HD (NSHD) between 1985 and 1994 was examined; 13 of the 63 patients had histologically proved recurrent disease after BMT. Histologic material and clinical findings from the original diagnostic biopsy specimen and pre-BMT and post-BMT specimens were available from our study population of eight patients (five male, three female; age range, 16 to 38 years; median age, 27.5 years). Seven patients had recurrent NSHD after BMT; sites of recurrence included lymph nodes only (four patients), and lymph nodes and lung, lung and liver, and lung only (one patient each). In one patient, a high-grade non-Hodgkin's B-cell lymphoma developed in the large intestine 5 years after BMT. In another, disease progressed from grade 1 in the original biopsy specimen to grade 2 in both the pre-BMT and post-BMT recurrent HD biopsy specimens. Post-BMT biopsy specimens of recurrent HD with lung involvement revealed a substantial increase in sclerosis and fibroblastic features. Paraffin immunoperoxidase studies in seven patients demonstrated substantial change in phenotype of Reed-Stemberg cell variants in only one post-BMT recurrent HD specimen, which showed a +2 reaction with CD30 (Ki-1). No substantial differences in the reactive component were noted between the original biopsy specimen and pre-BMT and post-BMT specimens of recurrent disease. In summary, histologic findings of post-BMT recurrent NSHD do not differ significantly from those of the original diagnostic biopsy or pre-BMT recurrent HD specimens. The lung is the most common site of extranodal post-BMT recurrence. In one patient, high-grade non-Hodgkin's B-cell lymphoma developed after BMT performed to treat recurrent HD.

Topics: Adolescent; Adult; Bone Marrow Transplantation; Female; Hodgkin Disease; Humans; Immunoenzyme Techniques; Ki-1 Antigen; Lewis X Antigen; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Male; Mediastinal Neoplasms; Mucin-1; Necrosis; Recurrence; Sclerosis

Patients with mucinous colon cancers often have a poor prognosis. The aim of this study was to determine whether metastatic potential depends on specific alterations in mucin-associated carbohydrate structures.. A quantitative scoring system was used to examine the expression of mucin-associated carbohydrates in paired human primary colon cancers and metastases and in cecal tumors and liver metastases from an animal model of metastasis. Adhesion of metastatic cells to basement membrane and endothelial ligands was examined.. Metastases expressed a decrease in mucin core structures Tn and T, a reciprocal increase in sialyl T and sialyl Tn, and an increase in peripheral sialyl Le(x) compared with the primary tumors from which they arose. Altered expression of sialylated mucin structures resulted from selective metastasis of cells that produce sialomucins. Antibodies to sialylated epitopes or desialylation inhibited adhesion of metastatic cells to basement membranes. Neutralizing antibody to endothelial-associated E-selectin (a ligand for sialyl Le(x)) inhibited adhesion of metastatic cells to cytokine-activated hepatic endothelial cells, and inhibition of sialomucin with antisense to the MUC2 gene inhibited adhesion to E-selectin.. Increased sialylation of mucin-associated carbohydrates is characteristic of colon cancer cells that are most likely to metastasize. Sialylated carbohydrate structures on mucin play a role in adhesive interactions involving both basement membrane and endothelial-associated ligands.

Topics: Adenocarcinoma; Animals; Antibodies, Monoclonal; Base Sequence; Basement Membrane; Cell Adhesion; Colonic Neoplasms; Disease Models, Animal; E-Selectin; Endothelium; Humans; Immunohistochemistry; Lewis X Antigen; Liver Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Molecular Sequence Data; Mucins; Neoplasm Metastasis; Neoplasm Transplantation; Sialoglycoproteins; Sialomucins

Liver metastasis from colorectal carcinoma is an important problem in surgical treatment and profoundly affects the prognosis of patients. If it were possible to identify characteristic features in the primary lesion strongly related to liver metastasis, these could be used as prognostic markers for liver metastasis. To search for such features, the primary lesions of patients with colorectal carcinoma with liver metastasis were investigated.. Three groups of colorectal carcinoma were examined: Group A with synchronous liver metastases; Group B with only lymph node metastases without recurrence for 5 years; and Group C with recurrence of liver metastases. Groups A and B included 24 cases and Group C, 20. We focused on cancer cell morphology at the invasive front and expression of sialyl Lewis X (sialyl Lex) in the primary cancer.. At the invasive front in Group A it was frequently found that polygonal, not columnar, cancer cells with a single or solitary trabecular form with indistinct polarity, showed an infiltrative growth pattern. This type of morphology was termed "focal dedifferentiation" and graded four levels. Eleven of 24 cases (46%) had severe focal dedifferentiation in Group A, 1 of 24 (4%) in Group B, and 6 of 20 (30%) in Group C. Sialyl Lex staining was positive in 12 of 24 cases (50%) in Group A, in 3 of 24 cases (13%) in Group B, and in 7 of 20 cases (35%) in Group C in the primary carcinoma. In respect to the staining of (sialyl Lex) at focal dedifferentiation, it was positive in 17 of 24 cases (71%) in Group A, in 4 of 24 cases (17%) in Group B and in 11 of 20 cases (55%) in Group C. Focal dedifferentiation and sialyl Lex staining in the primary cancer showed a significant difference between Groups A and B. Sialyl Lex staining at focal dedifferentiation showed a significant difference between Groups A and B and Groups B and C. Other adhesion related molecules, sialyl LeA and CEA, showed no difference among Groups A, B, and C.. Both focal dedifferentiation and expression of sialyl Lex antigen in the primary lesion are considered good markers for assessing the metastatic proclivity of colorectal cancer.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma; Colonic Neoplasms; Female; Gene Expression Regulation, Neoplastic; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Oligosaccharides; Prognosis; Rectal Neoplasms; Sialyl Lewis X Antigen

Malignant transformation of cells is associated with the change in their carbohydrate antigens. Sialyl-Lewisx (SLEX) is a necroinflammation-associated carbohydrate antigen (NICA) of liver cells, because it is newly expressed in chronic inflammatory liver diseases. The authors addressed whether this type of carbohydrate antigen shows cancer-associated changes.. Expression of SLEX and its related structures was studied immunohistochemically using the well characterized monoclonal antibodies in 13 small and 6 advanced hepatocellular carcinomas (HCC).. SLEX was negative in 7 small HCC, which were well differentiated histologically. Both negative and positive cells were observed in 6 other small HCC. When positive, SLEX was expressed membranously or cytoplasmically. The membrane positive HCC cells were well differentiated. Cytoplasmic expression was observed in the less differentiated cells. The SLEX-negative cells were associated with any degree of differentiation. In six advanced HCC, the expression of SLEX could also be correlated with their histologic differentiation. HCC expressed sialyl-type 2 chain N-acetyllactosamine (2-NAcLc), but not 2-NAcLc, Lewisx, and Lewisy.. SLEX, a NICA, showed HCC-associated changes that were dependent on the levels of HCC cell differentiation. Suppression and reactivation of alpha 1-3fucosyl-transferase was a possible enzymatic basis for the observed changes.

Topics: Adult; Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cell Membrane; Cytoplasm; Female; Gene Expression Regulation, Neoplastic; Humans; Immunoglobulin M; Lewis X Antigen; Liver; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged

The immunohistochemical expression of sialylated and non-sialylated forms of both Le(x) and Le(a) were studied in 87 carcinomas and 42 normal mucosal specimens of colon and rectum, as well as in 32 metastatic lymph nodes and 9 hepatic lesions, using an indirect immunoperoxidase staining. Their antigens were expressed in normal mucosa with the following frequencies: Le(a), 95.2% (40/42); sialyl Le(a), 88.1% (37/42); Le(x), 95.2% (40/42); and sialyl Le(x), 17.0% (7/42), whereas in carcinomas, the respective rate of frequency were: 78.2% (68/87); 78.2% (68/87); 90.8% (79/87); and 93.1% (81/87). Sialyl Le(x) antigen showed the highest tumor specificity compared to other antigens. In three normal mucosal specimens and four carcinomas with Le(a-b-) phenotype, the expression of type 1 antigens (Le(a) and sialyl Le(a)) was not consistent, whereas type 2 antigens (Le(x) and sialyl Le(x)) were consistently observed in carcinomas. The staining of type 1 antigens and Le(x) was decreased in metastatic lesions compared with primary carcinomas, whereas sialyl Le(x) antigen had the same positive-staining rate in both. Metastatic carcinoma expressed the sialylated form more predominantly than the non-sialylated form in type 2 antigens whereas the opposite result was observed in type 1 antigens. These results suggested that: (a) sialyl Le(x), defined by monoclonal antibody CSLEX1, may be useful as a tumor-associated antigen in colorectal carcinoma, and (b) the alteration of Lewis-related carbohydrate antigens in cancer cell membranes, including sialylation and/or aberrant glycosylation, may be related to metastatic behavior.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Antibodies, Monoclonal; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Colorectal Neoplasms; Glycosylation; Humans; Immunohistochemistry; Lewis Blood Group Antigens; Lewis X Antigen; Liver Neoplasms; Lymphatic Metastasis

Expression of the CD15 antigen, which is one of the adhesion molecules, was studied immunohistochemically to investigate the mechanism of intrahepatic metastasis in 56 hepatocellular carcinomas (HCC). Twenty-nine percent (16 of 56) of the HCC expressed CD15. No noncancerous hepatocytes expressed CD15. CD15-positive HCC had histologic intrahepatic metastasis more often than did CD15-negative HCC; the difference was statistically significant (P < 0.02). The survival rate of patients with CD15-negative HCC was better than that of patients with CD15-positive HCC, although the difference was not statistically significant. The authors speculate that there is a relationship between the expression of CD15 and intrahepatic metastasis in HCC.

Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cell Membrane; Female; Gene Expression; Hepatectomy; Humans; Lewis X Antigen; Liver Neoplasms; Male; Middle Aged; Staining and Labeling; Survival Rate

A comparative immunohistochemical study was performed to analyse the expression of cancer-associated carbohydrate antigens by primary and metastatic lesions of colon cancer. We used monoclonal antibodies which reacted with Lea, Lex and Tn as well as their sialylated derivatives. Twenty-one primary lesions in patients without metastasis and 26 primary and metastatic lesions in patients with liver metastasis were studied. Sialyl Lea was expressed by 57% of the primary lesions of patients without metastasis, 65% of the primary lesions of patients with metastasis and 73% of their liver metastases. Sialyl Lex was expressed by 60% of the primary lesions of patients with and without metastasis as well as by approximately 80% of the liver metastases. Sialyl Lea and sialyl Lex showed strong expressions in the liver metastases, significantly greater than in the primary lesions. The findings indicate the increased expressions of sialyl Lea and sialyl Lex to be correlated with liver metastasis of colorectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; CA-19-9 Antigen; Colonic Neoplasms; Female; Gangliosides; Gene Expression Regulation, Neoplastic; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Liver Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Rectal Neoplasms

Phenotypic expression of sialylated Lewis(x) antigen by means of the monoclonal antiserum SNH3 was studied in 87 livers, which included normal and steatotic livers and livers with chronic persistent and chronic active hepatitis, alcoholic hepatitis, allograft rejection, focal nodular hyperplasia, hepatocellular carcinoma, cholangiocarcinoma, metastatic carcinoma, cirrhosis of various causes (autoimmune, alcoholic, viral, drug induced, Wilson's disease, and primary biliary cirrhosis). The biotin-streptavidin-peroxidase method was used on formaldehyde-fixed, paraffin-embedded sections. Sialylated Lewis(x) antigen was not demonstrated in normal livers. Hepatocellular expression in a diffuse or perinodular honeycomb pattern was seen in cirrhosis, irrespective of cause. Sialylated Lewis(x) antigen was also observed in hepatocytes around metastatic carcinoma in the absence of inflammation, cirrhosis, or regeneration. Some bile ductules, most likely ductular hepatocytes, but not bile ducts, expressed sialylated Lewis(x) antigen. Sialylated Lewis(x) antigen was seen diffusely in fibrolamellar hepatocellular carcinoma, focally in other hepatocellular carcinomas, and either focally or diffusely in cholangiocarcinomas.

Topics: Chronic Disease; Fatty Liver; Humans; Hyperplasia; Lewis X Antigen; Liver; Liver Cirrhosis; Liver Diseases; Liver Neoplasms

The clinical usefulness as a tumor-associated antigen of the new monoclonal antibody CSLEX1, which reacts with the sialylated LewisX antigen, has been evaluated serologically in 141 patients with a gastric cancer. The serum sialylated LewisX was measured by fluorescent EIA. The percent positive figure of these gastric cancer patients was 17.0% (24/141), which indicates a significant increase when compared with that of the controls. The percent-positive values, according to the clinical stage, were 9.2%, 9.1%, 15.6%, and 36.4% for stages I, II, III, and IV, respectively. The degree of liver metastasis and peritoneal dissemination of the cancer correlated with the percent-positive values of the antigen. This suggests that sialylated LewisX is useful as a tumor-associated antigen.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Female; Glycolipids; Humans; Lewis X Antigen; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Peritoneal Neoplasms; Predictive Value of Tests; Stomach Neoplasms

We collected a total of 78 tissue specimens, including primary colorectal carcinoma, normal colonic mucosa, and liver metastases of colon carcinoma, to examine whether the extracts of these tissues inhibited the binding of a monoclonal antibody FH6, specific for sialyl-dimeric LeX antigen. The results of inhibition assays demonstrated that: (a) contents of FH6-reactive molecules were greater in carcinoma tissues than in normal colonic mucosa; (b) metastatic foci in livers contained more FH6-reactive molecules than primary tumors; (c) primary tumors from Dukes' stage B1 patients contained less FH6-reactive molecules than primary tumors from Dukes' stage D patients. The inhibitory activity of these tumor tissue extracts against the binding of a monoclonal antibody FH6 to cultured colon carcinoma cells was eliminated by prior treatment of the extracts with sialidase, confirming that the FH6-reactive materials were sialyl-dimeric LeX antigen. Electrophoretic separation of tumor tissue extracts on 3% polyacrylamide gels followed by direct staining with monoclonal antibody FH6 revealed that very high molecular weight glycoproteins, presumably mucins, contained sialyl-dimeric LeX antigen.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Binding, Competitive; Colorectal Neoplasms; Electrophoresis, Polyacrylamide Gel; Glycolipids; Humans; Indicators and Reagents; Intestinal Mucosa; Lewis X Antigen; Liver Neoplasms; Neuraminidase

The mouse embryonal carcinoma cell line F9 differentiates into parietal endoderm cells after a 3-day exposure to retinoic acid and dibutyryl cyclic AMP. Using the experimental metastases assay, we investigated the organ colonization properties of RA-treated and -untreated populations of F9 cells. The results show that untreated F9 cells colonize the liver with a high degree of specificity while the treated populations colonize the lungs. Cells derived from a lung colony colonized only the liver unless they were treated with RA. However, removal of the inducer from culture of differentiated cells did not cause reversal of the lung colonization potential. Our observations also indicate that it is unlikely that lung colonization is due to cell aggregation or to interaction between differentiated and undifferentiated cells. Taken together, these results suggest that RA induces the observed changes of organ colonization properties of F9 cells.

Topics: Animals; Bucladesine; Cell Line; Fucose; Glycolipids; Glycosylation; Lewis X Antigen; Liver Neoplasms; Lung Neoplasms; Mice; Neoplasm Metastasis; Teratoma; Tretinoin