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Biomedical subjects

D Lotan

Publications and source records attributed to D Lotan.

At least 19 recordsLinked to original sources
PubMed1999

Induction of differentiation and apoptosis in the prostate cancer cell line LNCaP by sodium butyrate and galectin-1.

Galectin-1 has been implicated in the process of vertebrate developmental regulation. Sodium butyrate is an established differentiation-inducing agent and has been shown to increase galectin-1 expression in colon carcinoma cells. We studied the roles of butyrate and galectin-1 in the induction of differentiation and apoptosis in the prostate cancer cell line LNCaP. Treatment of LNCaP cells with butyrate resulted in induction of galectin-1 expression in a time- and dose-dependent manner. Treatment with butyrate also resulted in inhibition of proliferation, morphologic changes consistent with a differentiated phenotype, and induction of apoptosis. Prostate specific antigen expression was transiently reduced. To determine which of these effects might be secondary to the induction of galectin-1, LNCaP cells were transfected with a galectin-1 expression vector. The transfected cells displayed growth inhibition and an increased rate of apoptosis. PSA expression was not affected. We conclude that galectin-1 may be responsible for many of the phenotypic changes resulting from butyrate treatment and may function downstream in the pathway of butyrate-induced differentiation. We also found PSA to be somewhat inconsistent as an indicator of differentiation of LNCaP cells, likely due to other factors influencing its expression.

Apoptosis↗
PubMed1999

Differential expression of endogenous galectin-1 and galectin-3 in human prostate cancer cell lines and effects of overexpressing galectin-1 on cell phenotype.

We have analyzed the expression of galectin-1 and galectin-3 in four human prostate carcinoma cell lines. Northern analysis and immunoblotting experiments showed that three cell lines express both galectins. However, only galectin-1 was detected on the surface of these cells. The LNCaP line expressed neither galectin. LNCaP was transfected with galectin-1 and four clones were isolated, all of which expressed galectin-1 on the cell surface. Kinetics of binding to extracellular matrix proteins appeared to be accelerated in the transfected lines, but overall binding was not enhanced. When the same experiments were performed in the presence of EDTA to eliminate the effects of integrins, binding of a galectin-1 clone to laminin and fibronectin was increased relative to the control cell line. We propose that galectins may contribute to the adhesive properties of some prostate cancer cells.

Antigens, Differentiation↗
PubMed1998

Modulation of galectin-1 content in human head and neck squamous carcinoma cells by sodium butyrate.

Galectin-1 and galectin-3 are beta-galactoside-binding proteins thought to be important for cellular interactions, growth regulation and differentiation. Alterations in cellular content of galectins have been associated with differentiation, transformation and malignant progression. We examined the modulation of galectin-1 and galectin-3 expression in head and neck squamous cell carcinoma (HNSCC) cell lines by treatment with sodium butyrate, a known differentiation-modulating agent, and identified potential mechanisms of butyrate regulation of galectin-1 levels in one of the cell lines. Sodium butyrate effected an increase in galectin-1 protein concentration in 5 of 8 cell lines. One cell line, MDA-886LN, showed a marked time- and dose-dependent increase from barely detectable amounts with butyrate treatment. Concurrently with increased galectin-1 expression, butyrate treatment promoted morphologic changes, induced growth inhibition and inhibited soft agar colony formation in MDA-886LN cells. Butyrate-treated MDA-886LN cells demonstrated increased galectin-1 mRNA content, suggesting a role for butyrate in transcriptional regulation of galectin-1 expression. Treatment with other inhibitors of histone deacetylase also induced an increase in galectin-1 expression. Together, our results indicate that butyrate treatment can modulate galectin-1 content in MDA-886LN HNSCC cells as well as induce morphologic changes and growth inhibition. This action may involve a combination of transcriptional regulation and inhibition of histone deacetylation.

Animals↗
PubMed1998

Congenital aorto-caval fistula in the newborn: a case report.

The authors report a rare case of congenital fistula between the distal aspect of the descending aorta and the inferior vena cava. The clinical features of this aortocaval fistula is being described as well as the preoperative diagnostic workup, the intraoperative findings, and the complicated postoperative course and treatment.

Angiography↗
PubMed1998

Excessive dietary protein and suboptimal caloric intake have a negative effect on the growth of children with chronic renal disease before and during growth hormone therapy.

Although diet and nutrition are an integral part of the management of individuals with chronic renal failure (CRF), little has been written on the effect of nutrition on the growth response to growth hormone (GH) in CRF. We studied the GH axis and nutritional status of 31 prepubertal children aged 8.7 +/- 0.5 years with a height standard deviation score (SDS) of -3.2 +/- 0.2 (mean +/- SEM) with CRF. Sixteen CRF patients on hemodialysis and 15 on peritoneal dialysis were studied. Forty-four age-matched normal short children without GH deficiency served as controls. Spontaneous 12-hour GH and stimulated GH values were significantly higher and GH binding protein (GHBP) was significantly lower in the CRF patients than in the normal short children. Both before the initiation of GH therapy and after the first year of treatment, the growth velocity (SDS) was inversely correlated with dietary protein intake and positively correlated with caloric intake. GH was administered at a dosage of 28 and 21 IU/m2/wk to the CRF group and the normal short children, respectively, divided into seven daily doses. The growth response of the normal short children was significantly greater than that of the CRF patients. GH therapy induced a smaller increment in GHBP and IGF-I in the CRF patients versus the normal short children (8.8 +/- 2.2 and 10.2 +/- 2.7 v 24.8 +/- 1.3 and 27.6 +/- 2.5 nmol/L, respectively, P < .01). The 1-year growth velocity of the CRF children was most closely correlated with dietary protein and caloric intake. The nutritional status of CRF patients is concluded to be a major factor in growth both before and during GH therapy.

Alkaline Phosphatase↗
PubMed1998

Genetic polymorphisms of the renin-angiotensin system and the outcome of focal segmental glomerulosclerosis in children.

BACKGROUND: The clinical course of primary focal segmental glomerulosclerosis (FSGS) in children is variable, with some patients having a much more rapidly progressing course than others. The purpose of our study was to compare the frequency of three polymorphisms of the renin-angiotensin system (RAS) in children with FSGS with that in healthy controls of matching ethnic groups, and to determine whether the clinical outcome of FSGS was associated with different RAS genotypes. METHODS: Three RAS genotypes were examined in 47 Jewish and Arab children with biopsy-proven primary FSGS and in a large control group: the ACE insertion/deletion polymorphism in intron 16, the M235T mutation in the angiotensinogen gene, and the A1166C in the angiotensin II type 1 receptor gene (AT1R). RESULTS: Arab patients showed a greater tendency towards progressive renal disease than their Jewish counterparts (12 of 21 vs. 9 of 26, P = 0.05) and were less likely to achieve remission (3 of 21 vs. 11 of 26, P < 0.04), despite similar clinical presentation, medical management and follow-up. The RAS allele prevalence was similar among patients and controls of matching ethnic backgrounds, and no difference in allele frequency was found between Arabs and Jews. Homozygotes for the ACE insertion genotype (II) were significantly less likely to have progressive renal disease than patients with the other genotypes (ID and DD; 0 of 6 vs. 21 of 41; P < 0.022). The other RAS polymorphisms were not associated with variations in the clinical course of childhood FSGS. CONCLUSIONS: Homozygosity for the ACE insertion allele may have a protective effect in children with FSGS and can serve as a positive prognostic indicator at diagnosis. The D allele may exert a detrimental dominant effect on outcome. Neither the ACE gene polymorphism nor the other RAS polymorphisms studied are associated with disease prevalence. The AT1R and angiotensinogen gene polymorphisms are not associated with progression of renal disease in FSGS. Ethnic differences in the clinical course of the disease are not linked to these polymorphisms.

Adolescent↗
PubMed1998

A parallel association between differentiation and induction of galectin-1, and inhibition of galectin-3 by retinoic acid in mouse embryonal carcinoma F9 cells.

Soluble endogenous lactoside-binding lectins, galectins, have been implicated in cell adhesion, growth, differentiation, neoplastic transformation, and metastasis. Two major classes of these lectins, galectin-1 and galectin-3, are developmentally regulated. To explore the mechanisms by which the expression of the galectins is regulated and to examine their association with the differentiation processes induced by all-trans retinoic acid (RA), dibutyryl cyclic AMP (Bt2cAMP) and their combination, we used the murine embryonal carcinoma (EC) cell line F9 and its RA-resistant mutant, RA-3-10. RA induced endodermal differentiation and a concurrent induction of galectin-1 and its complementary glycoconjugates (laminin and lysosomal-associated membrane protein, LAMP) in the F9 wild-type (wt) line, but failed to induce differentiation and had no effects on or even reduced the expression of galectin-1, laminin, and LAMP in the RA-3-10 line. On the other hand, RA inhibited expression of galectin-3 in the wild-type line but had no effect on the RA-3-10 line. The galectin-1 gene is at least partially regulated at the transcriptional level. These results demonstrate a parallel association between differentiation and induction of galectin-1, and inhibition of galectin-3 in F9 cells by RA. The study suggests that a regulated expression of galectins and their complementary glycoconjugates is involved in the differentiation pathway induced by RA in F9 cells.

Animals↗
PubMed1998

Higher potency of N-(4-hydroxyphenyl)retinamide than all-trans-retinoic acid in induction of apoptosis in non-small cell lung cancer cell lines.

Most human non-small cell lung cancer (NSCLC) cell lines are refractory to all-trans-retinoic acid (ATRA). Recently, N-(4-hydroxyphenyl)retinamide (4HPR) was found to induce apoptosis in various tumor cells. In this study, we compared and contrasted the effects of 4HPR and ATRA on the growth and apoptosis of 10 NSCLC cell lines and normal human bronchial epithelial (NHBE) cells. All of the cancer cell lines and the NHBE cells were sensitive to 10 microM 4HPR, and their numbers decreased to <20% of the controls after a 5-day treatment, whereas ATRA decreased cell numbers to about 50% of the controls in three cell lines and was less effective in the rest of the tumor cell lines. ATRA inhibited the growth of the NHBE cells by 70-80%. 4HPR induced apoptosis in most of the cells, including the ATRA-resistant ones, as evidenced by a DNA fragmentation assay. No correlation was found between growth inhibition by 4HPR and the expression of retinoic acid receptor beta (determined by Northern blotting and PCR), p53, or Bcl-2 proteins (analyzed by Western blotting). These results demonstrate that 4HPR is more potent than ATRA in inducing apoptosis in NSCLC cells and suggest that further clinical trials for prevention and therapy of NSCLC using 4HPR are warranted.

Antineoplastic Agents↗
PubMed1996

Implication of retinoic acid receptor gamma in squamous differentiation and response to retinoic acid in head and neck SqCC/Y1 squamous carcinoma cells.

Nuclear retinoic acid receptors are considered to be the mediators of most of the effects of retinoic acid (RA) on gene expression. To explore the role of RA receptor gamma (RARgamma) in the growth and differentiation of SqCC/Y1 head and neck squamous carcinoma cells, they were transfected with RARgamma sense and antisense expression vectors and stable clones in which RARgamma expression was either increased or blocked were isolated. The growth inhibitory effect of RA in monolayer culture was enhanced in the sense transfectants and decreased in the antisense ones. The ability to form colonies in semisolid medium was abolished by RA in the sense transfectants, while the antisense transfected clones exhibited heterogeneous responses. The expression the squamous differentiation markers cytokeratin K1 transglutaminase type I, and involucrin was increased in the absence of exogenous retinoid in a sense transfected clone and decreased in an antisense transfected clone. RA suppressed squamous differentiation in both types of transfectant. The expression of epidermal growth factor receptor (EGFR) was higher in the antisense and lower in the sense transfectant than in the parental cells and RA decreased EGFR mRNA level in the parental and the sense transfectant but not in the antisense transfectant. In addition activator protein-1 (AP-1) binding activity was decreased by the RA treatment in the sense clones, but not in the antisense ones. These results suggest that RARgamma mediates the effects of RA on the cell growth both in monolayer culture and in semisolid medium possibly through AP-1 suppression.

Base Sequence↗
PubMed1996

Differential induction of apoptosis by all-trans-retinoic acid and N-(4-hydroxyphenyl)retinamide in human head and neck squamous cell carcinoma cell lines.

Retinoids have been shown to act as cytostatic agents against a variety of tumor cell types, including squamous carcinoma cells. Recently it was reported that certain retinoids can induce apoptosis as well. Because we are investigating the potential of retinoids in chemoprevention and therapy for head and neck premalignant and malignant lesions, we compared the effects of all-trans-retinoic acid (ATRA) and N-(4-hydroxyphenyl)retinamide (4HPR) on seven human head and neck squamous cell carcinoma cell lines (17A, 17B, 22A, 22B, 38, SqCC/Y1, and 1483). Six of the seven cell lines showed dramatic morphological changes after treatment with 10 micrometer 4HPR, whereas no such changes were induced by 10 micrometer ATRA. To determine whether these retinoids can induce apoptosis, we analyzed both detached and attached cells after 2, 5, and 7 days of treatment for evidence of DNA fragmentation by DNA electrophoresis on agarose gels. In five of the seven cell lines, a DNA ladder was observed after treatment with 10 micrometer 4HPR for 5 or 7 days, whereas treatment with ATRA resulted in a less pronounced effect. In 17B cells, a clear DNA ladder was observed as early as 2 days after treatment with 4HPR; however, neither ATRA nor 9-cis-retinoic acid was as effective. In addition, morphological changes associated with apoptotic cell death, such as chromatin condensation and nuclear segmentation, were observed by propidium iodide staining and by electron microscopic analysis after 4HPR treatment. These results demonstrate that 4HPR causes apoptosis in several head and neck squamous cell carcinoma cell lines and that it is more potent in this effect than ATRA.

Antineoplastic Agents↗
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

Inhibition of proliferation and induction of apoptosis in cervical carcinoma cells by retinoids: implications for chemoprevention.

The effects of retinoids including all-trans-retinoic acid (ATRA), 13-CIS-RETINOIC ACID (13CRA), and N-(4-hydroxyphenyl)retinamide (4-HPR) on several cervical carcinoma cell lines in culture were investigated as a prelude to investigating the mechanisms underlying the chemopreventive potential of retinoids in cervical cancer. We found that when used at a concentration of 1 microM, 13CRA and ATRA inhibited the proliferation of three cell lines (ME-180 [HPV 68], SiHa [HPV 18], and HT-3 [HPV-]) by about 80% after a seven-day treatment. Three other cell lines (MS-751 [HPV 18], HeLa [HPV 18], C-33A [HPV-]) were moderately inhibited (30-48%), and two (C-4 II [HPV 18], CaSki [HPV 16]) responded poorly (< 25% inhibition). 4-HPR failed to inhibit the growth of any of these cell lines when used at 1 microM; however, when used at 5 or 10 microM, it induced apoptosis as evidenced by DNA fragmentation in several of the cell lines and was more potent in this effect than 10 microM ATRA. Retinoids that induce apoptosis in malignant cells may be able to exert similar effects on premalignant cells. Such retinoids would be expected to exhibit greater potency as chemopreventive agents than retinoids that exert only cytostatic effects.

Anticarcinogenic Agents↗
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↗