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B Schwartz

Publications and source records attributed to B Schwartz.

461 records · Page 26Linked to original sources
PubMedDate not supplied

Transforming growth factor-beta in intestinal epithelial differentiation and neoplasia (review).

Transforming growth factor beta (TGF-beta is a multifunctional regulator of cell growth. It has become increasingly clear that TGF-beta action depends on the responsive cell types. Thus TGF-beta stimulates proliferation of mesenchymal cells and, in contrast, inhibits the growth of a large variety of epithelial cells. Recent studies, albeit controversial, support the notion that a gradient in mRNA transcripts encoding TGF-beta is maintained along the crypt-villus continuum of the small intestine in close correlation with the stage of differentiation of the enterocyte. Exogenous TGF-beta has been shown to inhibit the proliferation of a non-transformed rat jejunal crypt cell line. Additional salient findings have indicated that colon carcinoma cell lines recalcitrant to the restraining action of TGF-beta on proliferation are poorly differentiated, and that moderately differentiated colon tumor lines do retain, at least partly, their responsiveness to TGF-beta. To the best of our knowledge, no evidence is available pertaining to a contributory role of TGF-beta in the signalling mechanisms regulating growth and differentiation of normal colonic epithelial cells. In addition, we are ignorant of whether the interesting findings related to a functional relationship between TGF-beta and colon carcinoma cells lines (vide supra) are applicable to colonic preneoplastic and tumor cells in their natural habitat. In this review, we dwell on the available facts and missing observations, and present conceivable hypotheses pertaining to a putative role of TGF-beta in colon differentiation and neoplasia.

Cell Differentiation↗
PubMedDate not supplied

Expression of human interferon alpha H, an interferon with two potential asparagine-linked glycosylation sites.

Of the large number of human alpha interferon genes identified, only one, Hu-IFN-alpha H, contains potential asparagine-linked glycosylation sites. With the use of a new vector that permits convenient expression, site-specific mutation, and DNA sequencing, Hu-IFN-alpha H was expressed in Escherichia coli. The bacterial product which is not glycosylated is fully active demonstrating that the carbohydrate on this species is not required for antiviral activity.

Asparagine↗
PubMedDate not supplied

Phosphotyrosine, p62 c-myc and p21 c-Ha-ras proteins in colonic epithelium of normal and dimethylhydrazine-treated rats: an immunohistochemical analysis.

In the present study we used monoclonal antibodies to investigate the expression of phosphotyrosine, c-myc and c-Ha-ras proteins along the crypt continuum of normal and transformed rat colon tissue. Colon cancer was induced by administration of dimethylhydrazine. Particular attention was focused on the immunohistochemical pattern of murine colon mucosa during preneoplastic stages so as to permit the identification of putative changes in the expression/location of the oncoproteins prior to frank neoplasia. The immunohistochemical analysis of tyrosinephosphorylated proteins in the normal rat indicated that positive staining was mostly restricted to the lower colonic crypt zones. The carcinogenetic insult altered the magnitude and positional profile of phosphotyrosine along the colon crypt axis during the preneoplastic period. An intense positive reaction was observed in the upper crypt regions. Four weeks following the last DHM administration, viz. before tumor appearance, positive staining was evident in invasive adenocarcinoma tissue. In contrast to phosphotyrosine, the feeble c-myc immunohistochemical staining of normal rat colonic did not exhibit a focal topology. However, following DMH administration and prior to frank neoplasia, a substantial increase in the staining intensity for c-myc was noted, confined mostly to the supranuclear region of luminal cells. Invasive adenocarcinomas displayed intense cytoplasmic c-myc immunoreactivity. p21 c-Ha-ras expression and location along the colon crypt axis showed a different pattern when compared to p62 c-myc and phosphotyrosine. The p21 c-Ha-ras protein was prominently expressed in surface epithelium of normal and DMH-treated rats. Midcrypt colonocytes exhibited moderate p21 ras staining; in contrast, proliferating colonic cells resident in the lower crypt regions were consistently negative. These results suggest that c-Ha-ras gene product plays an important contributory role in determining the differentiated phenotype of the colonic cell.

1,2-Dimethylhydrazine↗
PubMedDate not supplied

Human HT-29 colon carcinoma cells: mucin production and tumorigenicity in relation to growth phases.

The main aim of this study was to determine whether changes in mucin production/secretion during the growth phases of a human adenocarcinoma cell line, HT-29, are associated with a different tumorigenic potential. HT-29 cells cultured in DMEM supplemented with 10% FCS were harvested in the exponential and post-confluent phases of growth. Metabolic labeling of the cells was performed using [3H]-glucosamine. Following a 24 hr-incubation period, radioactivity was measured in 1 ml-aliquots of cell cytosol and culture medium. Concurrently, mucin synthesis was assessed by size exclusion chromatography of [3H]-glucosamine-labeled glycoprotein in a Sepharose CL-4B column. Clonigenic assay in soft agar of pre- and post-confluent HT-29 cells was determined by scoring viable colonies according to size and number using phase-contrast microscopy. To assess in vivo tumorigenicity, pre-and post-confluent HT-29 cells (4 x 10(6)) in 0.2 ml DMEM were inoculated into nude mice. Tumor size and volume were recorded for 31 days. H-29 cells grew as multilayers of unpolarized, undifferentiated cells. Colony forming efficiency was similar at all growth stages. A significant increase in mucin synthesis was noted in HT-29 cells harvested in the exponential phase of growth compared to the stationary phase (148.3 +/- 41.9 versus 49.1 +/- 5.0, mean +/- SE, dpm/4 x 10(3) cells, p < 0.05). Mucin secretion was not significantly changed. Tumorigenicity in nude mice was consistently higher when the cells were injected in the exponential phase of growth. On day 31 after cell inoculation the average tumor volume/site was 332.7 mm3 in mice injected with HT-29 cells in log phase compared to 142.7 mm3 (p < 0.01) in animals which received post-confluent cells. Tumor weights were 0.36 g and 0.22 g respectively (p < 0.05). The present results indicate a definitive correlation between growth phases of HT-29 cells and mucin synthesis: mucin production was significantly higher in exponentially growing cells. The cloning efficiency in soft agar, a marker of in vitro tumorigenicity, was similar in HT-29 cells irrespective of the growth stage. A main finding of the present study was the increased in vivo tumorigenicity of colon cancer cells inoculated into athymic mice in the log phase of growth compared to cells harvested at post-confluence. These results are consistent with the view that mucin plays an important contributory role in determining tumorigenicity.

Animals↗
PubMedDate not supplied

A role of transforming growth factor-beta 1 in the control of corneal neovascularization.

Transforming growth factor beta 1 (TGF-beta 1) has been implicated in both the stimulation of angiogenesis in vivo and in the inhibition of endothelial cell proliferation in vitro systems. In this study we present evidence showing that under certain experimental conditions TGF-beta 1 may inhibit neovascularization in vivo. TGF-beta 1 was incorporated into ethylene vinyl acetate copolymer (Elvax 40) matrixes which provide a valuable vehicle for the controlled and sustained delivery of bioactive peptides. The biological effectiveness of TGF-beta 1 sequestered in polymer matrices was assessed by measuring the inhibition of [3H]-thymidine incorporation into the DNA of cultured mink lung epithelial cells. Neovascularization was induced in both corneas of albino rabbits by one deep-seated limbal silk suture. Elvax 40 matrixes loaded with TGF-beta 1 (release rate, 1.66 ng/24 h) were implanted in rabbit corneal stroma. "Empty" polymers in the contralateral eye served as controls. Aliquots of aqueous fluid were withdrawn, and the presence activity of phagocytic cells was assessed by the production of superoxide anion (O2) which was measured by the superoxide dismutase-inhibitable reduction of ferricytochrome C. Polymer-enclosed TGF-beta 1 implanted in rabbit corneas significantly suppressed angiogenesis (2.65 +/- 0.4 mm compared to 3.05 +/- 0.3 mm in contralateral controls p < 0.05). Superoxide production in 100 microliters aliquots of aqueous fluid was 0.95 +/- 0.18 and 0.6 +/- 0.18 nmol O2/10 min in control eyes and in the eyes bearing sequestered TGF-beta 1, respectively (p < 0.02). These results indicate that under the experimental conditions selected in this study, TGF-beta 1 significantly suppressed in vivo angiogenesis.

Animals↗