Structure and Diffusive Properties of Water in Polymer Hydrogels.

To investigate the diffusive properties of water in hydrogels, ab initio molecular orbital and molecular dynamics calculations of poly-N,N-dimethylacrylamide-water systems were performed. The results show that the mean diffusion coefficient of water drastically decreases in the middle dehydration stage. In this stage, the mobilities of water are restrained because part of the water forms hydrogen bonds to bind polymer chains due to a glass transition. In addition to the three well-known types of water (i.e., bound, intermediate, and free water) around hydrophilic polymers in hydrogels, our results suggest that the intermediate water can be further classified into two types: first and second intermediate water. The bound and first intermediate water acts as a cross-linker between polymer chains, even if the polymer does not form intra- or intermolecular bonds itself. The diffusive properties of water might have important implications for the interpretation of properties of polymer hydrogels.

Tetrasilane-bridged bicyclo[4.1.0]heptasil-1(6)-ene.

Tetrasilane-bridged bicyclo[4.1.0]heptasil-1(6)-ene 1 was synthesized by the reduction of 1,1,2,2-tetrachlorocyclohexasilane 2 in 12% yield as red-orange crystals. The structure and properties of 1 were studied by spectroscopy, X-ray crystallography, and theoretical calculations. The linkage of the cyclotrisilene moiety with two tetrasilane chains with tert-butyl groups remarkably affects its structure and (29)Si NMR spectrum.

[A case of primary unknown cancer responding to CDGP/S-1].

A 77-year-old woman visited our hospital with the chief complaint of left supraclavicular lymph node redness and swelling. Needle biopsy revealed metastatic, epithelial, undifferentiated carcinoma. However, the primary tumor remained unknown despite further thorough examinations, FDG-PET showed abnormal FDG accumulation at the lymph nodes of para-aortic and left external iliac artery area in addition to left supraclavicular lymph node. However, CT and MRI showed no lymph node swelling in the peritoneal cavity. Nedaplatin (CDGP) combined with S-1 therapy was carried out for this primary unknown cancer with lymph node metastases. Three months after CDGP/S-1 therapy was begun, the swollen left supraclavicular lymph node was obviously reduced by 42.5%. Moreover, abnormal FDG accumulation at left supraclavicular and para-aortic lymph nodes dramatically decreased and that at the left external iliac artery area disappeared. The anti-tumor effect was evaluated as a partial response by use of Response Evaluation Criteria in Solid Tumors (RECIST). Standard treatment for primary unknown cancer was not established, because it includes various carcinomas. Here we report a case of primary unknown cancer successfully treated with CDGP/S-1. This combined therapy was considered to be one of the promising strategies for a primary unknown cancer.

A novel synthetic drug, LB-18, closely related to lembehyne-A derived from a marine sponge, induces caspase-independent cell death to human neuroblastoma cells.

Neuroblastoma is a common solid tumor of children that arises from the sympathetic nervous system. Much work has consequently focused on the possibility of inducing marked cell death in neuroblastoma, and the new effective drugs are required. We have newly synthesized LB-18, closely related to lembehyne A (LB-A), a polyacetylene derived from a kind of marine sponge. LB-A has been shown to induce p21/WAF1 and causes G1 phase arrest in mouse neuroblastoma Neuro2A cells; however, we show here that LB-18 causes cell death in human neuroblastoma KP-N-TK cells in a dose-dependent manner. TUNEL assay and flow cytometric analysis showed that the cell death caused by LB-18 was associated with the DNA damage but the pan-caspase inhibitor, zVAD-fmk, could not prevent the cell death. Western blot analysis and cleavage of the caspase-3 or -7 substrate assay showed that LB-18 could not activate caspases 3, 7, 8 and 9. These results suggest that LB-18 causes caspase-independent cell death in human neuroblastoma cells. In the future, LB-18 may be useful for cancer therapeutics, especially for neuroblastoma.

Lysocellin, a metabolite of the novel drug 'alopestatin', induces G1 arrest and prevents cytotoxicity induced by etoposide.

We report here that lysocellin, a polyether antibiotic from a streptomycete, induces G1 phase arrest in human osteosarcoma MG63 cells. Lysocellin up-regulates p21WAF1/Cip1 and down-regulates cyclin D1 at the mRNA level. In addition, cyclin D1 is down-regulated by the proteasome-dependent signal pathway in MG63 cells. In drug combination studies, we found that lysocellin treatment weakened the cytotoxic activity of etoposide in MG63 cells using a colony-formation assay. To study the in vivo efficacy of lysocellin, we isolated a novel compound related to lysocellin from the same streptomycete, and found that the novel drug is converted to lysocellin in vivo and decreases etoposide-induced alopecia in a neonatal rat model. We raise the possibility that this novel drug, named 'alopestatin', may be a promising agent against alopecia.

A new cancer diagnostic system based on a CDK profiling technology.

A series of molecular pathological investigations of the molecules that stimulate the cyclin dependent kinases (CDK1, 2, 4, and 6) have led to enormous accumulation of knowledge of the clinical significance of these molecules for cancer diagnosis. However, the molecules have yet to be applied to clinical cancer diagnosis, as there is no available technology for application of the knowledge in a clinical setting. We hypothesized that the direct measurement of CDK activities and expressions (CDK profiling) might produce clinically relevant values for the diagnosis. This study investigated the clinical relevance of CDK profiling in gastrointestinal carcinoma tissues by using originally developed expression and activity analysis methods. We have established novel methods and an apparatus for analyzing the expression and activities of the CDK molecules in lysate of tumor tissue in a clinical setting, and examined 30 surgically dissected gastrointestinal carcinomas and corresponding normal mucosal specimens. We demonstrate here that remarkably elevated CDK2 activity is evident in more than 70% of carcinoma tissues. Moreover, a G1-CDK activity profiling accurately mirrored the differences in proliferation between tumor and normal colonic tissues. Our results suggest that CDK profiling is a potent molecular-clinical approach to complement the conventional pathological diagnosis, and to further assist in the individualized medications.