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Biomedical subjects

D Lotan

Publications and source records attributed to D Lotan.

At least 19 recordsLinked to original sources
PubMed1995

Carcinoembryonic antigen and other glycoconjugates act as ligands for galectin-3 in human colon carcinoma cells.

Galectin-1 and galectin-3, galactoside-binding lectins with molecular weights of M(r) 14,500 and 31,000, respectively, are expressed in normal and malignant cells and have been implicated in regulation of cell growth, adhesion, and metastasis. We analyzed the expression of galectins in 21 cultured human colon carcinoma cell lines by immunoblotting. Galectin-1 was detected in only 7, whereas galectin-3 was found in 20 of the cell lines. KM12 cells, which express only galectin-3, were used to isolate this lectin by affinity chromatography, and the purified lectin was used to identify complementary glycoconjugates by blotting. Galectin-3 was shown to bind to human laminin, carcinoembryonic antigen, and lysosome-associated membrane glycoproteins, which are involved in cell adhesion. Galectin-3 was localized on the KM12 cell surface and colocalized with carcinoembryonic antigen. Several endogenous glycoproteins and cell surface proteins of molecular weights in the range M(r) 58,000 to > 200,000, including carcinoembryonic antigen and lysosome-associated membrane glycoproteins, were identified as galectin-3 ligands by coimmunoprecipitation with and affinity chromatography on immobilized galectin-3. These data demonstrate that galectin-3 interacts with several adhesion molecules and suggest that this lectin may have a role in human colon carcinoma cell adhesion.

Antigens, CD↗
PubMed1995

Enhanced efficacy of combinations of retinoic acid- and retinoid X receptor-selective retinoids and alpha-interferon in inhibition of cervical carcinoma cell proliferation.

Retinoic acid receptors and retinoid X receptors form heterodimers, bind to retinoic acid response elements, and transactivate the transcription of retinoid-responsive genes. Two synthetic retinoids [4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-anthracenyl)benzoic acid (TTAB) and 6-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-2-naphthale n ecarboxylic acid (TTNN)], which preferentially bind retinoic acid receptors, inhibited the proliferation of cervical carcinoma ME180 cells by 50% at 0.2 nM and 0.2 microM, respectively. In contrast, two other retinoids [2-(4-carboxyphenyl)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthalenyl)-1,3-dithiane (SR11203) and 4-(2-methyl-1-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthalenyl)propenyl)benzoic acid (SR11217)], which preferentially bind retinoic X receptors, inhibited growth by only 12 and 18% at 1 microM, respectively. The combination of suboptimal concentrations of TTAB (0.1 nM) or TTNN (10 nM) with each of the retinoic X receptor-selective retinoids at 1 microM showed more than additive effects on cell proliferation, especially with SR11217. Further increases in proliferation inhibition were observed when IFN-alpha (100 units/ml) was added to these retinoid combinations. Activation of transcription of a reporter gene linked 3' to the retinoic acid receptor beta retinoic acid response element in transiently transfected cells also exhibited additive effects when the cells were treated with combinations of TTAB or TTNN with SR11217. This additive activation of transcription may be the reason why the combination of retinoids is more effective than each retinoid alone. The results also suggest that the use of combinations of retinoids and IFN-alpha may lead to enhanced antitumor effects.

Cell Division↗
PubMed1995

Metastatic renal carcinoma in a pediatric recipient of an adult cadaveric donor kidney.

A 15-year old male with chronic renal failure secondary to obstructive uropathy received an adult cadaveric donor kidney. Evaluation for painless macroscopic hematuria occurring 2 years after transplantation disclosed a metastatic renal cell carcinoma, which by the use of restriction fragment length polymorphism analysis was shown to be of the donor's origin. Transplant nephrectomy and cessation of immunosuppressive therapy resulted in complete regression of multiple pulmonary metastases.

Adolescent↗
PubMed1994

Concomitant increases in galectin-1 and its glycoconjugate ligands (carcinoembryonic antigen, lamp-1, and lamp-2) in cultured human colon carcinoma cells by sodium butyrate.

Galactoside-binding lectins (galectins) with molecular masses of about 14.5 kilodaltons (galectin-1) and 31 kilodaltons (galectin-3) have been found in a variety of normal and malignant cells and have been implicated in the regulation of cell growth, cell adhesion, and metastasis. The KM12 human colon carcinoma cell line was found to express only galectin-3. Because the levels of both galectins are developmentally regulated and can be modulated during the differentiation of several cultured tumor cell lines, we studied the ability of 11 differentiation-inducing agents to induce galectin-1 expression in the KM12 cells. Treatment of these cells with sodium butyrate, an established differentiation-inducing agent for colon carcinoma cells, resulted in the induction of galectin-1, which was detected by immunoblotting as well as by affinity chromatography. This effect was not seen with any of the 10 other differentiating agents: hexamethylene bisacetamide, dimethyl sulfoxide, dimethyl formamide, herbimycin A, mycophenolic acid, retinoic acid, difluoromethyl ornithine, dibutyryl cAMP, 8-chloro cAMP, and transforming growth factor beta 1. Galectin-1 induction by butyrate was observed in seven other human colon carcinoma cell lines. Further studies with the KM12 cells revealed that butyrate caused cell flattening, suppressed cell proliferation and colony formation in agarose, and increased the level of carcinoembryonic antigen, a marker of human colon carcinoma cell differentiation, within 48 h of treatment. The increase in galectin-1 level was dependent linearly on butyrate concentration (range, 1-4 mM). Galectin-1 mRNA expression was detected by Northern blotting as early as 6 h, and the protein was detected after 24 h of treatment initiation. The level of the constitutively expressed galectin-3 was also increased by butyrate but to a lesser extent than the level of galectin-1. Butyrate-induced galectin-1 was detected on the cell surface by immunoprecipitation from radioiodinated cell surface proteins as well as by indirect immunofluorescence labeling. Affinity-purified human galectin-1 was found to bind to purified polylactosamine-containing glycoproteins and to detergent-solubilized cellular proteins electroblotted onto nitrocellulose membranes. Affinity chromatography of [3H]glucosamine-labeled KM12 cell extracts on immobilized galectin-1 followed by immunoprecipitation from the lactose-eluted material demonstrated that lysosome-associated membrane glycoprotein-1, carcinoembryonic antigen, and nonspecific cross-reacting antigen are the major galectin-1-binding proteins in these cells. These results indicate that galectin-1 expression may be associated with the differentiation of KM12 cells and that several glycoproteins shown to be important in colon carcinoma adhesion and metastasis are capable of functioning as its endogenous ligands.

Animals↗
PubMed1994

Expression of a 31-kDa lactoside-binding lectin in normal human gastric mucosa and in primary and metastatic gastric carcinomas.

The expression of lactoside-binding lectin L-31 was analyzed in normal mucosa and in primary and metastatic gastric carcinomas. Immunoblotting revealed L-31 lectin in extracts of normal and malignant gastric tissues from 26 patients. The L-31 level was higher in tumor than in normal tissue in 9/26 cases, similar in 14/26 cases, and lower in 3/26 cases. Anti-L-31 monoclonal antibodies (MAbs) were used in immunohistochemical analyses to compare lectin expression in specimens of primary gastric carcinomas and adjacent normal mucosa from 39 patients and in specimens of metastases and the corresponding primary gastric carcinomas from 74 patients. The lectin was detected in normal gastric epithelial cells and in all gastric carcinoma specimens, albeit in varying amounts. The L-31 level was significantly higher in the primary tumor than in adjacent normal tissue in 55% of the well-differentiated tubular carcinoma cases and in 50% of stage-III and -IV tumors. L-31 expression in liver metastases from well-differentiated tubular primary gastric carcinomas was higher in 31% of the cases relative to the corresponding primary cancers. Likewise, L-31 expression in metastases from poorly differentiated gastric carcinomas in lymph nodes was higher in 38% of the cases compared to the primary cancers. The higher expression of L-31 in primary cancers and metastases of certain types implicates this lectin in the metastatic phenotype, but the presence of L-31 in a primary cancer is not sufficient to allow the metastatic propensity of the tumor to be predicted.

Antibodies, Monoclonal↗
PubMed1994

Expression of galectins on microvessel endothelial cells and their involvement in tumour cell adhesion.

Lactoside-binding lectins (galectins) with molecular weights of about 14.5 kDa (galectin-1) and 29-35 kDa (galectin-3) bind preferentially to polylactosaminoglycan-containing glycoconjugates and have been found on the surface of tumour cells and implicated in cell-cell and cell-extracellular matrix adhesion and metastasis. We have demonstrated by immunoblotting that both galectin-1 and galectin-3 are present in extracts of endothelial cells cultured from bovine aorta, rat lung, mouse lung and mouse brain microvessels, whereas mouse hepatic sinusoidal endothelial cells expressed primarily galectin-1. These galectins were also localized by indirect immunofluorescent labelling on the surface of the different endothelial cells in culture and by immunohistochemical staining in human tissues in vivo. Anti-galectin-1 antibodies inhibited the adhesion of liver-preferring murine RAW117-H10 large-cell lymphoma cells to hepatic sinusoidal endothelial cells or lung microvessel endothelial cells in vitro. The data indicate that galectin-1 is expressed on the extracellular surface of endothelial cells and can mediate in part the adhesion of RAW117-H10 cells to liver microvessel endothelial cells.

Animals↗
PubMed1994

Changes in body composition of children with chronic renal failure during growth hormone treatment.

Growth hormone (GH) has different known metabolic effects, among which are lipolysis and anabolic action. We have studied the changes in body composition of children with chronic renal failure (CRF) after 1 year of daily treatment with GH. Body fat percentage and fat body mass (FBM) were derived from four site skinfold measurements; lean body mass (LBM) from total body potassium (TBK) and mid-arm muscle circumference (MAMC); bone mineral density (BMD) was measured by dual photon absorptiometry. GH treatment had a positive effect on weight, height and MAMC, but no effect on LBM (as reflected by TBK), FBM and BMD. Z-scores were derived in order to compare subjects with a normal population. While no significant change in z-score was noticed for weight, height, MAMC, FBM and BMD, TBK decreased during treatment. We conclude that GH therapy does not ultimately increase LBM in CRF patients compared with other GH-treated groups.

Body Composition↗
PubMed1994

The impact of fetal screening on indications for cystourethrography in infants.

To evaluate cystourethrography in the era of fetal screening, we evaluated retrospectively the clinical and imaging findings of all children up to the age of 1 year who underwent a cystourethrogram in a 5-year period (1987-1992). There were 292 children, 64 neonates (< 1 month, 51 boys, 13 girls) and 228 infants (1 month-1 year, 111 boys, 117 girls). Hydronephrosis detected prenatally and confirmed after birth by US was the indication for cystourethrography in 88 children (72 boys, 16 girls). This 4.5 to 1, male to female ratio is very unusual compared to children with urinary tract infection, the great majority of whom are girls. The findings based on imaging studies in these 88 children with hydronephrosis included 31 with vesicoureteral reflux (VUR) (in 4 this was secondary), 23 with obstruction at the ureteropelvic junction (UPJ), 13 with multicystic dysplastic kidney, 2 with obstruction at the ureterovesical junction, 1 with ectopic ureterocele and 1 with posterior urethral valves, both the latter without reflux. Eleven children had normal postnatal studies and six children were lost to follow-up. Urinary tract infection (UTI) was the indication in 163 children (62 boys, 101 girls). Forty-one children were examined for other causes. Although most cases of hydronephrosis were detected on fetal screening, UTI was still the most common indication for cystourethrography and some significant abnormalities were found in these symptomatic children.

Female↗
PubMed1994

Early neonatal renal venous thrombosis: long-term outcome.

Renal venous thrombosis was diagnosed in the first week of life in 6 of 30,101 live infant births born at the Chaim Sheba Medical Center in Israel from 1984 to 1989. The thrombosis was unilateral in 5 neonates and bilateral in 1. Predisposing maternal risk factors included 2 cases of maternal diabetes and 1 case of maternal hypertension with associated intrauterine growth retardation. Perinatal risk factors included 2 cases of prematurity with severe hyaline membrane disease, 1 infant who was small for gestational age and another with asphyxia. Follow-up for 1-5 years following the acute event revealed normal growth and development in all infants. None of the patients was hypertensive and all had normal renal glomerular and tubular functions. Renal imaging and scan studies revealed loss of perfusion in 4 atrophic kidneys and diminished perfusion in the remaining 2. In conclusion, although renal venous thrombosis in neonates is associated with low mortality, long-term dysfunction in the affected kidney is common.

Causality↗
PubMed1992

Effect of growth hormone therapy on IGF-I, bone GLA-protein and bone mineral content in short children with and without chronic renal failure.

Chronic renal failure (CRF) in the young is complicated by, among other conditions, growth retardation, hyperparathyroidism and uremic osteodystrophy. Many children with CRF are now being treated with growth hormone (GH). Since GH has a direct mitogenic effect on osteoblasts in culture, we studied the effects of GH therapy on osteoblastic activity, such as serum alkaline phosphatase (AP), bone GLA-protein (BGP) and bone mass density (BMD) in poorly growing children with and without CRF. Fifteen (4 girls, 11 boys) healthy children with short stature (SS) and 10 (3 girls, 7 boys) children with end-stage renal failure (CRF) 4.5-12.4 years of age were treated with daily subcutaneous injections of GH in a dose of 0.1-0.125 IU/kg/day for 1 year. IGF-I, BGP and BMD of the spine were determined before and after the year of treatment. During GH therapy, a similar increase in height velocity and IGF-I were noted in SS and CRF groups: 3.8 +/- 0.77 to 8.38 +/- 1.25 (p < 0.001) vs. 4.0 +/- 0.6 to 7.14 +/- 1.3 cm/year (p < 0.001) and 7.8 +/- 2.6 to 21.8 +/- 7.5 (p < 0.01) vs. 7.9 +/- 1.3 to 21.5 +/- 5.6 nmol/l (p < 0.01), respectively. AP increased from 205 +/- 27 to 274 +/- 50 IU/l (p < 0.01) in the SS group but not in CRF patients (223 +/- 58 pre- 218 +/- 51 IU/l post-GH therapy).(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗
PubMed1990

Increased fucosylation of high-molecular-weight glycoproteins accompanies retinoic-acid-induced differentiation of F-9 embryonal carcinoma cells.

Retinoic acid (RA) treatment of F-9 embryonal carcinoma cells resulted in cell flattening and increased production of laminin B1 chain, both indicating differentiation to endoderm-like cells. In addition, RA caused a time- and dose-dependent decrease in growth rate in monolayer culture and a dose-dependent decrease in the ability of the cells to form colonies in soft agarose. Differentiation was accompanied by an increase in the fucosylation of specific high-molecular-weight cellular and cell-surface glycoproteins. The fucosylation of glycoproteins of Mr 175,000 (gp175), 250,000 (gp250), and 400,000 (gp400) increased as early as 24 hr after the addition of 5 x 10(-6) M RA to the culture medium. These changes preceded both growth inhibition and the induction of laminin B1 expression, which were detected 48 to 72 hr after addition of RA. The increased fucosylation of these glycoproteins showed a distinct dose-response relationship. Both gp175 and gp250 showed the greatest increase in fucosylation at 10(-5) M, which was also the dose at which RA induced laminin maximally, while the fucosylation of gp400 was greatest at 10(-8) M RA and declined at higher concentrations. The overall synthesis of large fucosylated glycopeptides decreased in RA-treated cells, in spite of the increases in the fucosylation of specific cellular glycoproteins. RA-induced differentiation of F-9 cells was also accompanied by a time- and dose-dependent increase in fucosyltransferase activity. Although the functions of these glycoproteins are not currently known, the early increase in their fucosylation can be considered as a marker of differentiation in this system.

Animals↗
PubMed1990

Retinoic acid inhibition of human melanoma cell invasion through a reconstituted basement membrane and its relation to decreases in the expression of proteolytic enzymes and motility factor receptor.

Treatment of four A375 human melanoma sublines (A375, A375P, A375P-5, A375M), exhibiting distinct metastatic potentials in vivo, with beta-all-trans-retinoic acid in vitro caused a dose- and time-dependent inhibition of the ability of these cells to penetrate Matrigel-coated filters using a reconstituted basement membrane invasion assay. The possible mechanisms of action responsible for the antiinvasive effect were further investigated, and the data showed that compared with untreated cells the retinoic acid-treated cells: (a) secreted lower levels of collagenolytic enzymes, as demonstrated by a decreased ability of the cells to degrade [3H]proline-labeled type IV collagen substrate and by a reduction in the activity of a secreted Mr 64,000 collagenolytic enzyme detected in type IV collagen-containing polyacrylamide gels; (b) expressed lower levels of the human type IV collagenase mRNA (except in the A375P cells), as detected by Northern blot analysis; (c) exhibited decreased levels of tissue plasminogen activator activity, as demonstrated by a chromogenic assay; (d) were 10-40% less adhesive to a reconstituted basement membrane matrix, as determined by a 60-min Na2(51)CrO4-labeled cell attachment assay; (e) exhibited an increase in the high affinity metastasis-associated cell surface laminin receptor, as determined by flow cytometry after binding of fluorescently labeled laminin receptor antibody; and (f) expressed decreased amounts of gp78, a cell surface receptor for motility factor, demonstrated by immunoblotting and immunofluorescence. Collectively, these data suggest that retinoic acid inhibits tumor cell invasion through a basement membrane-like matrix by suppressing matrix degradation and by altering cell surface receptors.

Basement Membrane↗
PubMed1990

Inhibition of growth and squamous-cell differentiation markers in cultured human head and neck squamous carcinoma cells by beta-all-trans retinoic acid.

Vitamin A and some of its metabolites such as beta-all-trans retinoic acid (RA) have been implicated in the regulation of differentiation of normal and malignant epithelial cells in vivo and in vitro. In the present study the effects of RA on the growth and differentiation of 7 cell lines derived from human head and neck squamous-cell carcinomas (HNSCCs) were examined. RA (greater than 0.01 microM) inhibited the proliferation in monolayer culture of 6 of 7 HNSCC cell lines. One cell line (UMSCC-35) was very sensitive, 5 (UMSCC-10A, -19, -30, -22B and HNSCC 1483) were moderately sensitive, and 1 (HNSCC 183) was insensitive. Three of the cell lines (UMSCC-22B, -30, and HNSCC 1483) were capable of forming colonies in semisolid medium--a capability that was suppressed by RA. The HNSCC cell lines expressed various levels of the squamous-cell differentiation markers type I (particulate, epidermal) transglutaminase (TGase) and cholesterol sulfate (CS). RA treatment (I microM, 6 days) decreased TGase activity by more than 50% in 3 (UMSCC-10A, -22B and 1483) of the 7 cell lines, and the effect on UMSCC-22B was dose-dependent. Type II TGase (soluble, tissue type) activity was detected in 3 cell lines, and after RA treatment its activity increased in HNSCC 1483 and 183 cells and decreased in UMSCC-19. Following RA treatment, CS levels decreased by 20, 25, 70, 76, 89 and 91% in cell lines UMSCC-30, -10A, 183, UMSCC-35, -22B, and HNSCC 1483, respectively. The suppression by RA of CS accumulation in the 1483 cells was dose-dependent. Cholesterol sulfotransferase activity, which is responsible for CS synthesis, was suppressed by 40-97% after RA treatment of UMSCC-19, -22B, and HNSCC 1483. Our results demonstrate that RA inhibits the growth and decreases the level of 2 squamous differentiation markers in HNSCC cells.

Carcinoma, Squamous Cell↗
PubMed1989

Modulation of galactoside-binding lectins in tumor cells by differentiation-inducing agents.

The effects of the differentiation-inducing agents N6, O2'-dibutyryl cyclic AMP, beta-all-trans retinoic acid, dimethylsulfoxide and butyrate on the levels of galactoside-binding proteins (lectins) in cultured human and murine tumor cells were examined by immunoblotting. Differentiation was associated with decreased levels of a 34-kDa lectin in the K-1735P and B16-F1 melanoma cells and decreased levels of a 14.5-kDa lectin in S20 neuroblastoma, MDA-MB 175 breast carcinoma, HL-60 and THP-1 leukemia cells. The level of a 14.5-kDa lectin increased during differentiation of F-9 embryonal and KM12P colon carcinoma cells. These results indicate that tumor cell differentiation along specific pathways is accompanied by distinct modulation of lectin expression. These changes may recapitulate the normal developmental regulation of lectin expression.

Animals↗
PubMed1989

Inhibition by retinoic acid of type IV collagenolysis and invasion through reconstituted basement membrane by metastatic rat mammary adenocarcinoma cells.

The activity of type IV collagenase, which enables tumor cells to degrade collagen type IV found in the subendothelial basement membrane, has been correlated with the metastatic potential in several tumor types, including the rat 13762NF mammary adenocarcinoma cell line and its clones. In this study, we examined whether all-trans-retinoic acid (all-trans-RA) and other retinoids, which exhibit antitumor activity in vitro and in vivo, affect the collagenolytic activity of metastatic rat 13762NF mammary adenocarcinoma cells. Cells of the highly metastatic lung-colonizing clone MTF7.T35.3, derived from the 13762NF cell line, were treated for 3 days with 0.1, 1, or 10 microM all-trans-RA, harvested, and seeded on [3H]proline-labeled extracellular matrix deposited by cultured rat lung endothelial cells or on a film of purified [3H]proline-labeled type IV collagen. The amount of radioactivity released into the medium during the subsequent 24 to 72 h was measured, and it was found that all-trans-RA treatment inhibited degradation of extracellular matrix and type IV collagen by 50 to 60%. This effect was observed whether the cells had been treated with all-trans-RA in serum-free medium or in medium supplemented with heat-inactivated or acid-treated fetal bovine serum. The growth of the cells was not inhibited under these conditions, except after treatment with 10 microM all-trans-RA in serum-free medium. The reduction in collagenolytic activity was observed in viable cells as well as in conditioned medium. A 24-h exposure of cells to all-trans-RA was sufficient to cause a 30% decrease in the collagenolytic activity, and this inhibitory effect was reversible. The direct addition of all-trans-RA to conditioned medium had no effect on secreted collagenase activity. The apparent molecular weights of the collagenolytic enzymes were determined by electrophoresis of cell extracts and concentrated conditioned medium in type IV collagen-embedded polyacrylamide gels followed by renaturation and activation of the enzymes within the gels. Two major type IV collagenolytic metalloproteinases exhibiting molecular weights of 64,000 and 88,000, respectively, were detected by this method. These two enzymes were also found to have specificity for gelatin. The Mr 64,000 enzyme could be extracted from viable cells (presumably from the cell membrane) by 2% 1-butanol. Treatment with all-trans-RA decreased the level of these enzymes in the cellular, cell membrane, and conditioned medium compartments.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗