The purposes of this research were to glycosylate lysozyme with dextran under Maillard reaction conditions and assess the antimicrobial characteristics of the lysozyme-dextran conjugate in a culture medium and cheese curd. Solutions containing lysozyme and dextran were incubated at 60 degrees C and at 79% relative humidity. Gel permeation chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis were used to follow the glycosylation process. Under optimum conditions 3.7 mol of dextran were coupled to 1 mol of lysozyme. Lytic activity of the conjugate against the cell wall of Micrococcus luteus was about 62% of that of native lysozyme. Evaluation of the lysozyme-dextran conjugate against test microorganisms (Staphylococcus aureus and Escherichia coli) in culture media indicated a progressive increase in antimicrobial activity, with an increase in enzyme-conjugate concentration. The lysozyme-dextran conjugate was also effective against E. coli in a natural food system, as it reduced the bacterial count by 3 log in cheese curd after 40 days of storage. Unlike E. coli, the antimicrobial action of lysozyme against S. aureus was not improved by conjugation with dextran in both in vitro and in vivo tests. Antimicrobial activity of the lysozyme-dextran conjugate against gram-negative bacteria is probably related to the remaining lytic activity as well as the excellent surfactant properties of the lysozyme-dextran conjugate. These results might increase the applicability of lysozyme as a natural antimicrobial ingredient in different food products.

1995-12-01·Cancer research

Labeling of polypeptides with technetium-99m using a dextran spacer.

Article

作者: Marquez, M ; Nilsson, S ; Westlin, J E ; Holmberg, A

Radioimmunoscintigraphy and other forms of scintigraphy are becoming increasingly important as tools in detection and evaluation of cancer diseases. Several radionuclides can be considered as radiolabel; however, 99mTc may be the most suitable because of easy availability and near ideal physical properties. This study describes how dextran is coupled to a monoclonal anticytokeratin antibody, epidermal growth factor, and somatostatin through stable amine bonds. The dextran moiety could then be labeled with 40-62 MBq of 99mTc. The labeling efficiency was 60-94%, determined by gel filtration or TLC. The specific binding could be considerably preserved after the dextranation, the antibody retained > 90% of its activity, epidermal growth factor bound with > 90% specificity to receptor-expressing tumor cells, and somatostatin showed approximately 40% specific binding to rat adrenal homogenates. Because somatostatin only has a transient half-like in vivo, the in vivo plasma half-life of somatostatin-dextran was tested in normal female Sprague-Dawley rats. The result showed a strong enhancement of the plasma half-life that was dependent on two compartments, 4 and 8 h.

Oncology Reports3区 · 医学

Incubation with somatostatin, 5-aza decitabine and trichostatin up-regulates somatostatin receptor expression in prostate cancer cells

3区 · 医学

Article

作者: Liu, Zhaoxu ; Marquez, Marcela ; Nilsson, Sten ; Holmberg, Anders R.

Somatostatin (SMS), binds to its specific receptors (SSTRs) and transduces growth inhibitory, anti-secretory and apoptotic signals. Several human cancers express SSTRs, including prostate cancer, and therefore SMS is of interest for anti-cancer therapy. DNA methylation and histone modifications are involved in normal cell development, gene imprinting and human carcinogenesis. Reversing DNA methylation is an attractive therapeutic possibility, since epigenetic modifications change gene expression without changing the gene function. DNA methylation inhibitors such as 5-aza-2'-deoxycytidine (5'-aza, decitabine) have been used to treat several types of haematological malignancies. Histone deacetylase inhibitors such as trichostatin (TSA), are a new class of 'targeted anti-cancer agents'. TSA and decitabine can induce growth arrest, apoptosis or terminal differentiation in a variety of solid and haematological cancers in advanced disease patients. In the present study, the LNCaP cell line (prostate cancer) was incubated with SMS or Somadex (an SMS polymer conjugate) for three days, 1 nM per day, and the untreated cells were the negative control. For DNA demethylation, cells were grown in the presence of 2.5 microM 5-aza for 120 h, and re-fed with 5-aza-containing fresh medium at day 3. The total incubation time with 5-aza was 120 h. TSA at 1.0 microM was added into the cultured cells for 24 h. The combined treatment of 5-aza and TSA was performed by incubating the cells with 5-aza for 120 h followed by a 24-h exposure to TSA. Using cDNA obtained from these cell lines, the difference in the expression level of SSTR mRNA transcripts before and after 5-aza and TSA treatments was analyzed by RT-PCR. An increased induction of mRNA expression of the five SSTR subtypes was observed in the LNCaP cells when incubated with SMS/Somadex (dose-dependent). The inhibition of DNA methylation and histone acetylation resulted in the up-regulation of SSTR5 mRNA expression. The results demonstrate a positive feedback loop between SMS and its receptors. This regulation pathway may enhance the anti-tumor activity of somatostatin. To benefit from this effect in a clinical setting, the dose, dose frequency and pan affinity of the SMS derivative are important factors. The epigenetic manipulation with DNA methylation or histone deacetylase inhibitors, combined with SMS, may offer a novel alternative for the treatment of advanced prostate cancer.

100 项与 SomaDex 相关的药物交易

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