The number of detected GEP-NET increased about 5-fold in Germany between 1976 and 2006. At the same time, their anatomic distribution changed, and the survival of GEP-NET patients improved significantly. Second malignancies are common and influence the overall survival of GEP-NET patients. Thus, GEP-NET warrant our attention as well as intensive research on their tumorigenesis.

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(2015) A sensitive WST-8-based bioassay for PEGylated granulocyte colony stimulating factor using the NFS-60 cell line, Pharmaceutical Biology, 53:6, 849-854, DOI: 10.3109/13880209.2014 Context: Granulocyte colony stimulating factor (G-CSF) has been commonly used to treat neutropenia caused by chemotherapy, radiotherapy, and organ transplants. Improved in vitro efficacy of G-CSF has already been observed by conjugating it to polyethylene glycol (PEG).Objective: The in vivo bioassay using tetrazolium dye with the NFS-60 cell line has been recommended for G-CSF but no such monographs are available for PEGylated G-CSF in pharmacopeias. In the present study, the assay recommended for G-CSF was evaluated for its suitability to PEGylated G-CSF. Materials and methods:The generally used MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium]-based assay was compared with a bioassay employing a water-soluble tetrazolium dye, WST-8 [2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium], using NFS-60 cells at a concentration of 7 Â 10 5 cells/ ml against 800 IU/ml of PEGylated G-CSF at 24, 48, 72, and 72 h time points to determine the efficacy of PEGylated G-CSF. Further, the optimized WST-8 dye-based assay was used to test the potency of various commercially available PEGylated G-CSF preparations. Results: The results demonstrated enhanced sensitivity of the WST-8-based assay over the conventional MTS-based assay for determining the potency of PEGylated G-CSF using the NFS-60 cell line. Conclusion: Our study demonstrates the potential application of WST-8-based bioassays for other biotherapeutic proteins of human and veterinary interest.

Equlllbrlum dlstrlbutlon data for three Important systems, water-ethyl acetate-acetic acld-sodium sulfate, water-2-ethylhexanol-acetlc acid-sodlum sulfate, and water-methyl ethyl ketone-acetlc acld-sodium sulfate, at 30 OC are presented. Empirical correlatlons are obtalned to represent these experimental data. Wlth an Increase In the salt concentration, the dlstrlbutlon coefflclent of acetic acid Increases, showing the "saltlng-out" effect. Wlth the solvents ethyl acetate and P-ethylhexanol the saltlng-out coefflclent decreases wlth an Increase In the acetlc acld concentratlon, whlle wlth the solvent methyl ethyl ketone the salting-out coefflclent Increases wlth an Increase In the acetic acld concentratlon. Thls change In salting-out coefflclent wlth acetic acld concentratlon Is explalned on the basls of solvent solublllty, saltlng-out of the solvent, and the solvent afflnlty for the acetlc acld.The distribution data for the water-acetic acid-solvent system are available in the literature for many organic solvents ( 7-3). However, very often, in practice, the aqueous streams contain salts such as sodium sulfate. The effect of salt on the distribution of acetic acid between water and an organic solvent has thus a direct engineering application.Swabb and Mongan (4) have studied the salt effect in the system water-isopropyl ether-acetic acid-sodium sulfate.McAteer et ai. (5) have studied the water-methyl isobutyl ketone-acetic acid-sulfuric acid system. The effect of lithium chloride, sodium chloride, and potassium chloride on the water-acetic acid-benzene system has been studied by Eisen and Joffe (6). the effect of magnesium chloride on the same system has been studied by Desai and Eisen (7). However, data are not available for the salt effect with such useful solvents as ethyl acetate, 2-ethylhexano1, and methyl ethyl ketone. In the present work, therefore, the effect of sodium sulfate on the distribution of acetic acid between water and each of the above-mentioned solvents was studied.The electrostatic theories explain the sat effects on the basis of the ateration in the dielectric constant of the solution. Debye and McAulay (9), Debye (IO), and Butler (11) have derived equations for the activity coefficient of nonelectrolytes in dilute salt solutions. These equations predict that satingout will occur if the dielectric constant of the nonelectrolyte solution is less than that of water, and salting-in if the reverse is true. The theories predict that the logarithm of the activity coefficient of the nonelectrolyte is a linear function of the ionic strength.According to the internal pressure concept proposed byTammann (72) and applied by McDevit and Long (73), the contraction in total volume upon the addition of salt to water can be thought of as a compression of the solvent. This compression makes it more difficult for the introduction of a molecule of nonelectrolyte, and this results in salting-out. An increase in total volume upon the addition of a sat wouM produce the counter effect known as salting-in. Semiqua...