Other Cell Lines

Another human colonic cancer cell line is T84, which forms monolayers that are even tighter than those of the Caco-2. It has been described as resembling a colonic crypt cell phenotype. Hence, these cells have been used mainly in studies of epithelial ion secretion and are generally not considered to be adequate for drug transport studies, particularly with respect to carrier-mediated processes [13, 91, 92]. The rat intestinal epithelial cell line IEC-18 has been evaluated as a model to study small intestinal epithelial permeability. This cell line, which forms very leaky monolayers, was proposed to be a better model than the Caco-2 monolayers for evaluating the small intestinal paracellular permeation of hydrophilic molecules [93]. Importantly, the leaky tight junctions of the IEC-18 cells are a result of an undeveloped paracellular barrier lacking the perijunctional actin belt. In addition, the IEC-18 cells have minute expression of transporters [91, 93]. 

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Bryant From what we have done with the genetics, it looks like they are required for larval growth in general. At least two other cell lines have been shown to condition the medium in this way. 

Several companies have expressed the cDNA coding for human factor VIII C in a variety of eukaryotic production systems (human VIII C contains 25 potential glycosylation sites). CHO cells and BHK cell lines have been most commonly used, in addition to other cell lines, such as various mouse carcinoma cell lines. The recombinant factor VIII product generally contains only VIII C (i.e. is devoid of vWF). However, both clinical and preclinical studies have shown that administration of this product to patients suffering from haemophilia A is equally as effective as administering blood-derived factor VIII complex. The recombinant VIII C product appears to bind plasma... 

The compensatory effect of cholesterol observed in D407 cells have also been demonstrated in other cell lines (Cho et al. 1998 Holleran et al. 1998) and may well be a consequence of tamoxifen-induced severe inhibition of lanosterol (to cholesterol)-converting enzymes. In rat liver preparations and CHO cells, sterol A8-isomerase (IC50 0.21-0.15. iM) was the most sensitive... 

Despite the availability of other cell lines, Caco-2 cells remain the most widely used intestinal cell culture model at present. This model has provided valuable information necessary for lead optimization in the drug discovery process. However, it is important to understand that compounds with high permeability in this model are typically well absorbed, whereas compounds with low solubility and low permeability in this model may not necessarily be poorly absorbed in vivo. Although this type of positive selection limits the usefulness in providing a structure-permeability relationship, the Caco-2 model has the most effect in drug discovery when the screen is implemented early and in conjunction with other types of in vitro and in vivo permeability/absorption screens. 

Other cell lines used in permeability studies include the T84 human colonic adenocarcinoma colonic crypt cell model. This line has a reduced carrier expression, secrets mucus, and has very high resistance [31, 32], The IEC cell line is a rat fetal intestinal epithelium cell with higher permeabilities than Caco-2 cells [33], LLC PKi is a pig kidney epithelial cell line with low expression of efflux systems, but expression systems for transport proteins [32], 2/4/A1 cells are a conditionally immortalized rat fetal intestinal epithelium line with crypt cell-like morphology and temperature-sensitive differentiation [34], They form differentiated monolayers with tight junctions, increased brush border enzymes when grown on extracellular matrices with laminin. Transport of drugs with LP in 2/4/A1 monolayers was comparable to that in the human jejunum and up to 300 times faster than that in Caco-2 monolayers. In contrast, the permeability of HP drugs was comparable in both cell lines [34],... 

Several cell lines were screened for their response to three standard chemotherapy drugs fludarabine, vincristine, and Gleevec decreases in the mean optophoretic distance of Bcr-Abl positive cell line K-562 with no effect in the other cell lines demonstrate that the downshift in mean displacement is specific to the presence of the Bcr-Abl oncoprotein fludarabine, however, was ineffective in causing a decrease in the optophoretic displacement of the K-562 cell line, but showed an effect in the other four cell lines mobility values for each cell in the population have been taken and averaged, but data on subsets of the cells can still be extracted and further analyzed. 

In vitro (Caco-2 and other cell lines Ussing chamber) Physicochemical properties In silico (in computro)... 

Other cell lines such as those from melanoma tissue exhibited clusters containing as many as 90 genes with high levels of expression, many of which are involved in melanin metabolism. When cell line expression patterns were found among different tissues of origin, it was also observed that the patterns... 

In the laboratory the immortal cell lines are those derived from cancer. The most famous is the HeLa cancer cells that many of us use as one of the cell lines tested against various anticancer agents. The name HeLa cells is derived from Henrietta Lacks, a black woman, who died from cervical cancer. The cells are so strong that they invade other cell lines, both healthy and other cancer cell lines, giving contaminated or mutated cell lines. HeLa cells have good telomerase levels. If antisense RNA is added to HeLa cells so that the RNA contains the opposite message to the ordinary RNA in the telomerase, the effect is that the telomerase is blocked and the HeLa cells are no longer immortal and die after about 25 replications. 

The availability of biologically active i Sj.iabelled EPO facilitated the detection and study of cell surface receptors. In addition to erythroid precursors, various other cell lines were shown to express EPO receptors, at least when cultured in vitro. Many harboured two classes of receptors a high-affinity and a low-affinity form. Most appeared to express between 1000 and 3000 receptors/cell. Radiotracer experiments illustrated that the EPO receptor is rapidly internalized after ligand binding and the EPO-receptor complex is subsequently degraded within lysosomes. 

Regulation of alkaline phosphatase activity was discussed by Cox and Griffin 65). Steroids such as hydrocortisone or prednisolone (1 (ig/ml of medium) can induce a 3- to 20-fold rise in certain HeLa cell cultures, while other cell lines are induced by 15 mM phenyl phosphate. Recently, it has been shown that fibroblast cell cultures are also stimulated by prednisolone (( ( ). According to one report, Pi may have a control function here a decrease in the level of rat kidney P produced by a low phosphate diet was accompanied by an increase in alkaline phosphatase. Nine other enzymes monitored were unaffected 67). 

In the present study, we examined the pattern of fucolipids and gangliosides in cultured cell lines and alterations produced by a differentiating agent. A human fetal intestinal line (FHS), and four human colonic tumor lines (SKCO-1, HT-29, SW-480 and SW-620) were used. Cells were grown with or without sodium butyrate, (1.0 mM in SKCO-1 and 2.5 mM in all other cell lines) in... 

A novel approach using the sorbent phase directly (with no extraction) in contact with cell lines from rainbow trout liver was developed by Schirmer et al.114 and Bopp et al.115 The cell lines were used to detect EROD activity from specific PAHs. A modified ceramic dosimeter (Toximeter sampler containing Biosilon 160-300 pm diameter polystyrene beads as the sorbent phase) was deployed for extended periods in groundwater known to be contaminated by PAHs. The response obtained using the cell lines incubated with Biosilon beads correlated with the concentrations of PAHs known to have EROD-inducing activity. The system is versatile as other cell lines can be used depending on the toxicological response of interest. 

The cell lines most commonly employed for production of biopharmaceuticals include CHO-K1, BHK-21, and Vero cells, besides various antibody-secreting hybridomas. Other cell lines, such as NSO, HEK-293 and PER.C6, have also been employed for recombinant protein production. 

Some cell lines, such as Namalwa, can grow satisfactorily in medium in which the only protein is albumin. Other cell lines show distinct protein requirements, such as albumin, transferrin, and insulin, or the addition of polypeptide growth factors, isolated from non-serum sources that have shown stimulation of many cell types in culture. Some cells have very fastidious growth requirements and their stability and productivity may be reduced significantly in serum-free media. 

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