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Query: KEGG:D02003 (NBT)
 1,323 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A system has been developed for the culture of cells that provides conditions favoring the formation of tissues comparable to conditions existing in nature. The culture chamber is a lens-shaped pouch composed of two thin-walled, reinforced, waffled collagen membranes facing each other. The chamber is immersed in medium in a closed transparent container and incubated on a rocker. On histologic study, after days to weeks in culture, human mammary cancer cell lines BT-20, MCF-7, MDA-231, MDA-468, and T47D grow in the chamber as distinctive structured epithelial tissue. Dog kidney cell line MDCK grows as a papillary adenocarcinoma and rat bladder cancer line NBT-II as an epidermoid carcinoma; cells from clinical effusion tumors produce distinct tissue. Changes in histologic phenotype may be driven by molecular changes at the level of the genome. Resulting alteration of the biochemical functions essential for the integrity of specific durable tissue organization should alter or reset the pattern of tissue organization and of biological behavior, including malignancy and response to cytotoxic chemicals. Lenticular pouch culture promises to be an effective tool for exploring the molecular changes associated with histogenesis and malignancy.
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PMID:Human mammary cancer cell lines and other epithelial cells cultured as organoid tissue in lenticular pouches of reinforced collagen membranes. 946 83

The physiologically active metabolite of the vitamin D seco-steroid hormone, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is a major regulator of mineral homeostasis. Recent evidence also suggests its role in regulating proliferation and differentiation of cells, including cancer cells. Therapeutic application of 1,25(OH)2D3 to hyperproliferative disease, such as cancer, is thwarted by its hypercalcemic activity. To overcome this problem, analogs of 1,25(OH)2D3 have been produced which retain growth regulating properties and exhibit decreased hypercalcemic activity. In the present study, the efficacy of the vitamin D2 analog, 1,24(S)-dihydroxyvitamin D2 (1,24(S)-(OH)2D2) in the inhibition of cancer cell proliferation and in inducing differentiation of cancer cells was compared to that of 1,25(OH)2D3. By the [3H]-thymidine incorporation procedure, 1,24(S)-(OH)2D2 is as equipotent as 1,25(OH)2D3 in inhibiting the proliferation of five different cell lines, ROS 17/2.8, the rat osteosarcoma cell line, MCF-7, the human breast cancer cell line, HD-11, the chick bone marrow v myc transformed cell line, HT-29, the human colon cancer cell line and HL-60, the human leukemia cell line. The inhibitory action was dose and time-dependent. The NBT reduction method indicated that 1,24(S)-(OH)2D2 induces the differentiation of the human leukemia cell (HL-60) to the same extent as 1,25(OH)2D3. Notwithstanding the vast similarity between 1,24(S)-(OH)2D2 and 1,25(OH)2D3 with regard to the above activities, they differ in their effects on calcium regulation. In conclusion, the present results encourage the use of 1,24(S)-(OH)2D2 for the treatment of cancer disease in vivo.
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PMID:The novel analog 1,24(S)-dihydroxyvitamin D2 is as equipotent as 1,25-dihydroxyvitamin D3 in growth regulation of cancer cell lines. 967 3

Induction of hematopoietic differentiation in human promyelocytic leukemia cells (HL-60) by new synthetic drugs or natural products has recently been recognized as a new strategy in the identification and testing of potential cancer chemopreventive and/or chemotherapeutic agents. 2-(Allythio) pyrazine (2-AP) is a pyrazine derivative of allysulfide, which has been suggested to be a potential cancer chemopreventive agent in previous in vivo and in vitro experiments. In the present study, we have investigated the inducing effect of granulocytic differentiation in HL-60 cells by 2-AP. Treatment of HL-60 cells with various concentrations of 2-AP (1-100 microM) for 7 days showed the induction of granulocytic differentiation following both morphological examination and NBT (nitroblue tetrazolium) testing (up to 40 and 52%, respectively). The expressions of bcl-2 and c-myc were down-regulated during granulocytic differentiation of HL-60 cells (up to 40%). The immunoblots for G1 cyclins in the G1-S phase transition (cyclin D1 and E) showed a progressive decrease of their expressions in both concentration- and time-dependent manners (up to 30 and 50%, respectively). These results suggest that 2-AP could induce the differentiation of HL-60 cells and might have potent cancer chemoprevention and/or chemotherapy roles in human leukemias.
Cancer Lett 1999 Sep 20
PMID:Induction of granulocytic differentiation in acute promyelocytic leukemia cells (HL-60) by 2-(allylthio) pyrazine. 1050 71

Various mechanisms of epithelial cell plasticity in morphogenesis have been studied at the genetic and molecular levels. Several control genes have been identified including genes encoding transcription factors and growth factor receptors. These mechanisms may be reactivated during the progression of carcinomas. One of the mechanisms underlying epithelial plasticity is the epithelial-mesenchymal transition. This process has been extensively studied using the NBT-II bladder carcinoma cell line. Cells of this line undergo a reversible transition following exposure to several growth factors including FGF-1, EGF, TGFalpha and SF/HGF, which activate tyrosine kinase surface receptors. Two separate transduction pathways have been identified. The transient activation of c-Src is involved in cytoskeleton remodeling whereas the Ras pathway controls the transcription of genes such as the transcription factor Slug which is involved in the internalization of desmosomes. These two pathways cooperate to induce the morphological transition, scattering and locomotion of fibroblast-like cells. Growth/scatter factor-producing NBT-II cells are more invasive than cells that do not contain this factor, in orthotopic confrontation assay. In vivo, these cells are very tumorigenic and may confer a more malignant phenotype on parental cells via a community effect. The role of several growth factors and their receptors has been investigated in human bladder carcinomas. A subset of these tumors with poor outcomes produce low levels of FGFR2-IIIb. The synthesis of this receptor de novo in bladder cell lines reduces proliferation in vitro and tumor growth in nude mice. FGFR2-IIIb functions as a tumor suppressor, consistent with the differentiation-inducing capacities of FGF receptors in the suprabasal cells of the skin. FGFR2-IIIb signaling may be involved in the maintenance of E-cadherin, the prototype epithelial adhesion molecule, which is only downregulated in a fraction of tumors with low FGFR2-IIIb synthesis. Human bladder tumors may also activate autocrine loops such as that for EGFR and their ligands, as already demonstrated for murine bladder tumors. Therefore, our results suggest that multifunctional growth factors and their receptors are involved in cell proliferation and epithelial cell plasticity, acting either as positive or negative regulators of tumor progression. The effect on the morphological transition is also clearly relevant to the mechanism governing dissemination and the formation of micrometastatic tumor cells. The extrapolation of these discoveries to human carcinomas should provide markers facilitating the more accurate prediction of the biological behavior of a given tumor and identify clinically and pathologically significant parameters. The identification of critical changes in the growth factor pathways involved in tumor progression will not only provide insight into the genetic and molecular basis of this process, but should also identify targets for new therapies.
Cancer Metastasis Rev 1999
PMID:Epithelial cell plasticity in development and tumor progression. 1050 44

The homophilic cell adhesion molecule CEACAM1 (C-CAM, BGP, CD66a) occurs as two coexpressed isoforms, CEACAM1-L and CEACAM1-S, in epithelia, endothelia, and leukocytes. CEACAM1-L can inhibit tumor growth; this effect is influenced by CEACAM1-S. To characterize the growth regulatory properties of CEACAM1, we analyzed the expression patterns of the isoforms, and here we demonstrate that both the expression levels and the S:L isoform ratios differ in proliferating and quiescent rat epithelial cells. Quiescent prostate NbE cells expressed more CEACAM1 than quiescent bladder NBT-II cells, a pattern that correlated with the expression levels in the parental tissues. In contrast, both the expression levels and the isoform ratios were strikingly similar in proliferating NbE and NBT-II cells, showing that a particular CEACAM1 expression pattern is compatible with cell proliferation. However, in confluent cells, CEACAM1 seemed to exert inhibitory effects on cell proliferation. Addition of anti-CEACAM1 antibodies to quiescent, confluent cells caused decreased expression of the cyclin-dependent kinase inhibitor, p27Klp1, stimulated growth factor-dependent DNA synthesis, and altered the S:L isoform ratio toward the ratio characteristic of proliferating cells. Taken together, our data suggest that CEACAM1 contributes to contact inhibition of cell proliferation in confluent cells but allows proliferation when expressed at different isoform ratios.
Cancer Res 2000 Mar 01
PMID:The tumor growth-inhibiting cell adhesion molecule CEACAM1 (C-CAM) is differently expressed in proliferating and quiescent epithelial cells and regulates cell proliferation. 1072 82

Recently, we reported the selective accumulation of hypericin in transitional cell carcinoma cells following intravesical instillation of hypericin in humans. This observation infers that hypericin, a potent photosensitizer, could be used as a selective PDT (photodynamic therapy) tool against superficial bladder cancer. The aim of the present study was to investigate in vitro whether hypericin exhibits specific affinity for TCC transitional cell carcinoma) bladder cells and to assess its photocytotoxic effect. Three human TCC cell lines (J-82, T-24 and RT-4), a chemically induced rat TCC cell line (NBT-II), but also non-bladder carcinoma cells (HeLa, A431, MCF-7 and MCF-***ADR) and normal cells (HEL229, RPE and PHK), were used in this comparative study. Flow cytometric analysis of cells treated with different hypericin-containing vehicles for various incubation times (2 hours or 24 hours) indicated that short exposure of the cells (2 hours) to hypericin in the absence of serum results in the highest intracellular accumulation of the compound. As expected, prolonging the incubation time increased both the cellular accumulation and photocytoxicity of hypericia. With the exception of the RT-4 and MCF-7 cells (which were less sensitive to hypericin), all the other carcinoma cell lines examined showed equal sensitivity to the photoactivated hypericia, independently of their histological origin (bladder or non-bladder). Moreover, normal cells exhibited the same pattern of hypericin photosensitivity as shown by the cancer cells, indicating that, in cultured cells, hypericin cellular uptake and subsequent photokilling is not selective. This suggests that in vivo factors other than the cancer cells themselves are responsible for the specific accumulation of hypericin in urothelial carcinoma lesions.
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PMID:Photodynamic activity of hypericin in human urinary bladder carcinoma cells. 1095 29

Many anti-inflammatory agents are known to significantly enhance the terminal differentiation of some cancer cells such as leukemia cells. In this study, the effect of yomogin, a eudesmane sesquiterpene lactone isolated from Artemisia princeps with anti-inflammatory activity, was investigated in human promyelocytic leukemia HL-60 cells. Yomogin by itself induced small increases in cell differentiation, with less than 19 % of the cells attaining a differentiated phenotype. Importantly, yomogin synergistically enhanced differentiation of HL-60 cells in a dose-dependent manner when combined with either 5 nM 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2) D(3)] or 50 nM all- trans retinoic acid (all- trans RA). Cytofluorometric analysis and morphologic studies indicated that the combinations of yomogin and 1,25-(OH)(2) D(3) stimulated differentiation to monocytes whereas the combinations of yomogin and all- trans RA stimulated differentiation to granulocytes. These results suggest that yomogin may be useful in combination with 1,25-(OH)(2) D(3) or all- trans-RA in the differentiation therapy for myeloid leukemias. Abbreviations. 1,25-(OH)(2) D(3) :1,25-dihydroxyvitamin D(3) FITC:fluorescein isothiocyanate NBT:nitroblue tetrazolium RA:retinoic acid PE:phytoerythrin
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PMID:Synergistic induction of 1,25-dihydroxyvitamin D(3)- and all-trans-retinoic acid-induced differentiation of HL-60 leukemia cells by yomogin, a sesquiterpene lactone from Artemisia princeps. 1239 50

The present study focused on the effect of a series of extracts and two 5,6,7-trioxygenated coumarins isolated from Pterocaulon polystachyum on the proliferation and differentiation of human promonocytic U-937 cells. The petroleum ether extract was the only extract that significantly reduced cell proliferation and induced cell differentiation. Treatment with pure 5-methoxy-6,7-methylenedioxycoumarin (C1) and 5-(3-methyl-2-butenyloxy)-6,7-methylenedioxycoumarin (C2), present in the petroleum ether extract, showed a time and concentration-dependent inhibition on cell proliferation. In addition, the coumarin derivatives were also able to induce CD88 functionality and NBT reduction, markers of monocytic cell differentiation. These results suggest that C1 and C2 might have a potential therapeutic role in the management of leukemia.
Cancer Lett 2004 Jul 16
PMID:Induction of cell differentiation in human leukemia U-937 cells by 5-oxygenated-6,7-methylenedioxycoumarins from Pterocaulon polystachyum. 1518 33

Fibroblast growth factor (FGF)-1 and -2 have potent biological activities implicated in malignant tumor development. Their autocrine and nonautocrine activity in tumor progression of carcinoma was investigated in the NBT-II cell system. Cells were manipulated to either produce and be autocrine for FGF-1 or -2 or to only produce but not respond to these factors. The autocrine cells are highly invasive and tumorigenic and the determination of specific targets of FGF/fibroblast growth factor receptor (FGFR) signaling was assessed. In vitro studies showed that nonautocrine cells behave like epithelial parental cells, whereas autocrine cells have a mesenchymal phenotype correlated with the overexpression of urokinase plasminogen activator receptor (uPAR), the internalization of E-cadherin, and the redistribution of beta-catenin from the cell surface to the cytoplasm and nucleus. uPAR was defined as an early target, whereas E-cadherin and the leukocyte common antigen-related protein-tyrosine phosphatase (LAR-PTP) were later targets of FGF signaling, with FGFR1 activation more efficient than FGFR2 at modulating these targets. Behavior of autocrine cells was consistent with a decrease of tumor-suppressive activities of both E-cadherin and LAR-PTP. These molecular analyses show that the potential of these two growth factors in tumor progression is highly dependent on specific FGFR signaling and highlights its importance as a target for antitumor therapy.
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PMID:Targets of fibroblast growth factor 1 (FGF-1) and FGF-2 signaling involved in the invasive and tumorigenic behavior of carcinoma cells. 1528 42

Pycnogenol, rich of many phytochemicals of medical value, is a commercialized nutrient supplement extracted from the bark of European coastal pine. In this study, we investigated the anti-tumor effects of Pycnogenol on HL-60, U937 and K562 human leukemia cell lines. We found that Pycnogenol inhibited cell proliferation dose- and time-dependently, and the IC(50)s of Pycnogenol on HL-60, U937 and K562 cells were 150, 40 and 100 microg/ml, respectively. When HL-60 cells were incubated with low concentrations of Pycnogenol (50, 100 and 125 microg/ml) for 24 h, a prominent G0/G1 arrest was observed, followed by gradual accumulation of sub-G0/G1 nuclei. At 48 h of treatment, 50-70% of HL-60 cells differentiated, as evidenced by morphological changes, NBT reduction, induction of NSE activity, and increases of cell surface expression of CD11b. However, results from Annexin V/PI staining, DAPI staining and DNA fragmentation assay indicated that Pycnogenol induced HL-60, U937 and K562 cell apoptosis at their respective IC(50)s after 24 h of treatments. Pretreatment of z-DEVD-fmk, a caspase-3 specific inhibitor, not only decreased caspase-3 activity but also reduced the percentage of apoptotic cells induced by Pycnogenol. This indicated that caspase-3 activation was involved in Pycnogenol induced-apoptosis. In conclusion, Pycnogenol induced differentiation and apoptosis in leukemia cells. Our data suggest that Pycnogenol could serve as a potent cancer chemopreventive or chemotherapeutic agent for human leukemia.
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PMID:Pycnogenol induces differentiation and apoptosis in human promyeloid leukemia HL-60 cells. 1586 10


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