Expression of Glycolipids Bearing Lewis Phenotypes in Tissues and Cultured Cells of Human Gynecological Cancers

Transformation-associated expression of Le^b (Lewis antigen-b) or Le^Y in human colorectal carcinomas has been well described. To examine the expression of glycosphingolipids (GSLs) bearing Lewis-phenotypes in human gynecological carcinoma-derived cells, we determined the concentrations of all GSLs. Although neither Le^b nor Le^Y was present in HEC-108 cells established from the poorly differentiated type of endometrial adenocarcinoma, other cell lines from moderately or well-differentiated types expressed either Le^b or Le^Y, or both, at concentrations of 0.01 to 0.03 μg per mg of dry cells, which comprised 0.3 to 1.3% of the total GSLs. In the cervical and ovarian carcinoma-derived cell lines, Lewis phenotypes tended to be carried by nLc₄Cer, which was accumulated in the cells without sialylation or fucosylation. These results indicated that expression of Le^b- or Le^Y-phenotypes was strongly dependent on the metabolic ability to supply the precursor GSLs. Both Le^b and Le^Y were successfully detected by monoclonal antibody MSN-1, which was a useful probe for the simultaneous detection of Le^b and Le^Y. On application of MSN-1, either Le^b or Le^Y was detected in tissues from patients with well- and moderately differentiated types of endometrial adenocarcinoma at concentrations of 0.01 to 0.04 μg per mg of dry tissues, but not in the tissues of poorly differentiated type. Normal endometria at the follicular and luteal phases also contained the antigens, but the concentrations and the frequency of antigen expression were lower than those in the well- and moderately differentiated types of endometrial adenocarcinoma.     

Clinical experiences with fetal heart rate monitoring of one thousand patients in labor

A series of 1,000 labor patients has been monitored electronically, and their records reviewed. Monitoring provides accurate objective evidence that fetal condition is good and that tolerance for labor is normal. With a normal record, the likelihood is strong that a normal baby will be delivered. Electronic fetal heart rate monitoring is unreliable in the prediction of babies born in poor condition. It does, however, provide an excellent screening test for selection of patients for scalp pH determinations. Electronic monitoring of fetal heart rate provides early evidence of fetal anoxia. It should be carried out in all patients receiving oxytocin during labor to avoid episodes of fetal anoxia. External monitoring methods currently available permit routine monitoring of all patients in labor. Whether monitoring all normal patients will improve fetal health and survival is still an unanswered question.     

The Presence of CA19-9 in Serum and Saliva from Lewis Blood-group Negative Cancer Patients

Eighteen cancer patients showed high levels of CA19-9 in sera, even though the blood-group phenotypes of their red blood cells were Le(a — b —). Seven of these patients (group I) were determined as Le(a — b —) from both red blood cells and saliva consistently, whereas eleven other patients (group II) secreted either Le^a or Le^b antigen in saliva and showed the expression of incompatible Lewis blood-group antigens. GDP-fucose: N -acetyl-glucosaminide a (1 × 4)-L-fucosyltransferase was demonstrated to be present in salivas from both group I and group II. These results suggest that a cancer-associated alteration of Lewis blood-group antigen expression occurs in cancer patients.     

Aminoguanidine downregulates expression of cytokine-induced Fas and inducible nitric oxide synthase but not cytokine-enhanced surface antigens of rat islet cells

Autoimmune beta-cell destruction occurs directly by cell-mediated cytotoxicity or indirectly by cytokines released from infiltrating lymphocytes. Cytokines (IL-1beta/IFN-gamma) modify or induce expression of MHC antigens and ICAM-1 on beta-cells which can lead to an improved binding of T-lymphocytes to beta-cells and finally to an enhanced cell-mediated cytotoxicity. Cytokines also induce Fas-expression and inducible nitric oxide synthase (iNOS) causing generation of nitric oxide (NO) which is toxic for beta-cells. The iNOS inhibitor aminoguanidine (AG) delays diabetes onset, but does not reduce diabetes incidence. We wanted to know whether AG inhibits cytokine-induced expression of Fas, MHC antigens and ICAM-1 on beta-cells of LEW.1W and BB/OK rat islets after culture with IL-1beta/IFN-gamma. NO was completely inhibited by 5.0 mmol/L AG while 0.5 mmol/L had no inhibitory effect. AG downregulated Fas-expression on the surface of beta-cells. Cytokine-induced/enhanced expression of MHC class-II and ICAM-1 was not affected by any AG concentration. AG syngergistically increased cytokine-induced enhancement of MHC class-I antigen density. AG possibly blocks the indirect pathway of beta-cell damage in vivo due to inhibition of Fas and iNOS and improves direct cell-mediated cytotoxicity due to drastic increased MHC class-I expression. Inhibition of only one pathway of beta-cell destruction is not sufficient to prevent diabetes.     

CD4+ CD56+ neoplasia: clinical and biological features with emphasis on cytotoxic drug-induced apoptosis and expression of sialyl Lewis X

CD4+CD56+ neoplasia is a rare malignancy of unclarified origin. So far only 57 cases have been reported. We characterized in detail a case of CD4+ CD56+ malignancy with special emphasis on apoptosis induced by cytotoxic drugs and expression of sialyl Lewis X (CD15s). The disease was diagnosed in a 73-year-old female presenting with skin involvement, generalized lymphadenopathy and bone marrow infiltration. Treatment with cladribine/mitoxantrone induced a short-lasting partial response and the patient died 6 months after diagnosis. The neoplastic cells expressed CD4, CD56, HLA-DR, and CD15s. PCR for the T-cell receptor γchain revealed a polyclonal amplification product. In situ hybridization for Epstein-Barr Virus (EBV) was negative. Cytotoxic granule-associated proteins were not detected, consistent with the observation that the cells did not mediate cytotoxic activity against several target cells. Apoptosis of the tumor cells was inducible by anthracyclines and cladribine but not with gemcitabine. Combinations of cladribine or gemcitabine with anthracyclines however, resulted in synergistic effects on apoptosis. Expression of CD15s on the CD56+ cells was three times higher than on CD56+ cells from healthy controls. The results demonstrate that the features of the present case is in accordance with the diagnosis of CD4+ CD56+ malignancy. This is the first report demonstrating increased CD15s expression on a CD4+ CD56+ neoplasia, possibly explaining the frequent occurrence of the disease in the skin.     

Regulation of differentiation- and proliferation-inducers on Lewis antigens, alpha-fucosyltransferase and metastatic potential in hepatocarcinoma cells

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.