Polymacromonomers consisting of oligostyrene side chains (700 ≤ M n ≤ 5000 g/mol) and of a high molar mass polymethacrylate main chain are shown to exhibit a bottlebrush structure in that the PMA main chain adopts an extremely stiff conformation (i.e., a Kuhn statistical segment length of up to l k = 2000 Å) which is surrounded by the expanded but still flexible polystyrene side chains.

Ca-alginate gels were studied by small-angle X-ray scattering and rheology to determine relations between chemical composition and concentrations of the alginate and the elasticity and structure of the gels. The gels were prepared by in situ release of Ca 2+ from either Ca-EGTA or CaCO3 with total Ca 2+ concentration in the range 5-30 mM. Alginates with low (39%), intermediate (50%), and high (68%) fractions of R-L-GulA originating from the brown algae Ascophyllum nodosum, Laminaria hyperborea leaf, and Laminaria hyperborea stipe, respectively, were employed. Two to three different degrees of polymerization for each chemical composition were used in the experiments. The excess small-angle X-ray scattering for the alginates in solution yielded linear cross-sectional Guinier plots, and the cross-sectional radius of gyration, R g,c, was determined to be 3.1-4.6 Å. The SAXS profiles of the alginate gels depended on the alginate concentration, Ca 2+ concentration, and the alginate composition. The SAXS data suggested that dimerization of chain segments was the principal association mode at low fractional Ca 2+ saturation of guluronic acid of the alginate. Increasing the fractional Ca 2+ saturation of guluronic acid, either by the concentrations or selection of alginate source, yielded coexisting lateral association modes, as manifested in a curvature in the cross-sectional plots. The coexisting junction zone multiplicities occur because of a delicate balance between the block length distribution of the R-L-GulA residues, polymer concentration, and Ca 2+ . These results are quantitative extensions of the "egg-box" model used to describe ionotropic gelation of alginate and hence enhance the understanding of the structure-function relationship of alginate gels.

par Le Bret. On différencie d'abord les régions diluée et semidiluée de ces solutions. On sépare ensuite la région semidiluée en trois régimes, qui sont, par ordre de concentration décroissante, les régimes isotrope, de transition et de réseau. On sépare aussi la région diluée en deux régimes, l'un ordonné et l'autre désordonné. Les régimes isotrope et de réseau ont été décrits par de Gennes, et le régime de transition par Odijk. Les régimes ordonné et désordonné peuvent être distingués selon l'existence de corrélations causées par les répulsions électrostatiques. On utilise la diffusion des rayons X aux petits angles pour confirmer la concentration du passage dilué-semidilué dans des solutions de poly(styrène sulfonate) de sodium. D'autre part, une analyse préliminaire de la distribution des distances confirme la concentration de fusion C*m entre les régimes isotrope et de transition. A présent nous n'avons pas d'information sur le passage entre les régimes de réseau et de transition, ni sur le passage ordonné-désordonné.

Hyaluronan (HA) has been shown to play crucial roles in the tumorigenicity of malignant tumors. Previous studies demonstrated that inhibition of HA suppressed the tumorigenicity of various malignant tumors including breast cancer. 4-methylumbelliferone (MU) has been reported to inhibit HA synthesis in several cell types. However, few studies have focused on the effects of HA inhibition in breast cancer cells by MU, nor the effects on bone metastasis. We hypothesized that MU would suppress the progression of bone metastasis via inhibition of HA synthesis. Here, we investigated the effects of MU on HA expression in MDA-MB-231 breast cancer cell line in addition to their tumorigenicity in vitro and in vivo. HAS2 mRNA expression was downregulated after 6 and 24 hr treatment with MU. Quantitative analysis of HA revealed that MU significantly inhibited the intracellular and cell surface HA. MU significantly inhibited cell growth and induced apoptosis as determined by cell proliferation and TUNEL assays, respectively. Phosphorylation of Akt was suppressed after 12 and 24 hr treatment with MU. MU treatment also inhibited cell motility as well as cell invasiveness. MU also inhibited cell growth and motility in murine fibroblast cell line NIH3T3. In vivo, administration of MU inhibited the expansion of osteolytic lesions on soft X-rays in mouse breast cancer xenograft models. HA accumulation in bone metastatic lesions was perturbed peripherally. These data suggest that MU might be a therapeutic candidate for bone metastasis of breast cancer via suppression of HA synthesis and accumulation.Breast cancer is the most common cancer in women particularly in western countries. 1,2 Approximately 6% of breast cancer patients present to hospital with distant metastasis 2 and about 25% despite neoadjuvant or adjuvant systemic treatment develop distant metastasis. 3 In a retrospective study of patients with metastatic breast cancer, bone was the most common site of metastatic spread and 70% of these patients developed metastases in one or more bones before they died. 4 Bone metastases occasionally result in hypercalcemia, pathologic fractures and spinal cord compression, 5 and substantially reduce patients' quality of life. 6 Hyaluronan (HA) is a high molecular weight linear glycosaminoglycan, the structure of which is composed of repeating disaccharides of D-glucuronic acid and N-acetyl-Dglucosamine. HA is a ubiquitous extracellular and cell surface associated matrix component of connective, epithelial and neural tissues. 7 HA is abundant in surrounding migrating and proliferating cells during morphogenesis and wound healing. 8,9 Increased HA levels are also observed, both in stroma of malignant areas and in a part of tumor parenchyma in some malignant tumors including colorectal, ovarian and breast cancer and liposarcoma. [10][11][12][13][14] Not only the HA accumulation level in the stroma of malignancy 11,15,16 but also the HA level in tumor parenchyma 10,13 has been reported to associate with a poor clinical outcome. In in vitr...

No abstract

The polymerization of macromonomers (that is, end-functionalized oligomers. Scheme 1) has been a matter of extensive research in order to prepare well-defined comblike polymers. ['] 10-50 for most of the samples, and accordingly, such polymers should form liquid-crystalline phases.Here we report on X-ray scattering measurements of the polymacromonomers in toluene performed at the synchroton source in Tsukuba, Japan. which indeed show the formation of lyotropic phases, probably nematic, in semi-concentrated solution. The investigated polymacromonomer sample had a molar mass of M , = (2.2.10') gmol-' corresponding to a contour length L, = 1400 8,. The polydispersity index determined by gel permeation chromatography (GPC) was M,/M, z 1.5, and the ' the scattering angle) for polyinacromonomer concentrations 0.2 2 c 2 30% (w/w). In the dilute regime c < 0.5 YO the form factor P(4) of a single chain is measured: the intensity is seen to decrease monotonically with increasing 4. However, the qScheme 1. Reaction scheme for the preparation of the macromonomers.However, the homopolymerization of macromonomers did not yield degrees of polymerization significantly exceeding the length of a macromonomer itself, unless copolymerized with conventional small monomers. A major breakthrough was achieved by Tsukahara et al., who in a radical mechanism homopolymerized anionically prepared oligostyrenes with molar masses between lo3 and lo4 gmol-' that were end-functionalized with methacryloyl groups and obtained degrees of polymerization (weight average) P, of up to 1000.[21 Recent structure characterization of such long-chain polymacromonomers revealed that the main chain exhibits an almost rodlike conformation as measured by the Kuhn statistical segment length ofApparently. the extended structure of the polymethacrylate (PMA) main chain is caused by the strong overcrowding of the oligostyrene side chains, which are only separated by a contour distance 1 = 2.5 8, at the polymer backbone.Also, because of the length of the side chains, the diameter or cross-section of this curved cylindrical macromolecule or "bot- Particularly at the highest measured concentration of 31.5 %, the width of the scattering peak narrows drastically. The scattering peaks observed at higher concentrations cannot be explained by single-particle scattering but rather reflect the interparticle structure factor S(4) originating from the intermolecular order of the molecules.On application of Bragg's relation, a mean distance dB between the scattering planes (100) of hexagonal order is obtained from the scattering peak at q,,, [Eq. (a)]. The mean par-ticle distance d2 is then derived from Equation(b). In order to

Background:Hyaluronan (HA) plays crucial roles in the tumourigenicity of many types of malignant tumours. 4-Methylumbelliferone (MU) is an inhibitor of HA synthesis. Several studies have shown its inhibitory effects on malignant tumours; however, none have focused on its effects on osteosarcoma.Methods:We investigated the effects of MU on HA accumulation and tumourigenicity of highly metastatic murine osteosarcoma cells (LM8) that have HA-rich cell-associated matrix, and human osteosarcoma cell lines (MG-63 and HOS).Results:In vitro, MU inhibited HA retention, thereby reducing the formation of functional cell-associated matrices, and also inhibited cell proliferation, migration, and invasion. Akt phosphorylation was suppressed by MU (1.0 m). In vivo, although MU showed only a mild inhibitory effect on the growth of the primary tumour, it markedly inhibited (75% reduction) the development of lung metastasis. Hyaluronan retention in the periphery of the primary tumour was markedly suppressed by MU.Conclusion:These findings suggested that MU suppressed HA retention and cell-associated matrix formation in osteosarcoma cells, resulting in a reduction of tumourigenicity, including lung metastasis. 4-Methylumbelliferone is a promising therapeutic agent targeting both primary tumours and distant metastasis of osteosarcoma, possibly via suppression of HA retention.

The initial stage of fiber structure development in the continuous neck-drawing of amorphous poly(ethylene terephthalate) fibers was analyzed by in-situ wide-angle x-ray diffraction, small-angle x-ray scattering, and temperature measurements. The time error of the measurements (< 600 μs) was obtained by synchrotron x-ray source and laser irradiation heating. A highly ordered fibrillar-shaped two-dimensional (smectic-like) structure was found to be formed less than 1 ms after necking. By analyzing its (001') and (002') diffractions, the length of the structure 60-70 nm were obtained. A three-dimensionally ordered triclinic crystal began to form with the vanishing of the structure around 1 ms after necking. The amount and size of the crystal were almost saturated within several milliseconds of necking, during which time a mainly exothermic heat of crystallization was also observed.