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Kang J.-H.,Japan National Cardiovascular Center Research Institute | Mori T.,Center for Future Chemistry | Niidome T.,Center for Future Chemistry | Takayama K.,Research Institute for Diseases of the Chest | And 4 more authors.
Anticancer Research

Background: Recently, we reported on the existence of activated protein kinase Cα (PKCα) in blood and the possibility for its use in cancer diagnosis. Materials and Methods: In the present study, serum samples collected from patients with different lung cancer types (small-cell cancer, adenocarcinoma, and anaplastic cancer) were phosphorylated with a PKCα-specific peptide substrate and the phosphorylation ratio was detected by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. Results: When 13 patient serum samples were phosphorylated with peptide substrates, phosphorylated peaks were obtained in eight samples. However, no peak associated with the phosphorylated peptide was observed using serum samples obtained from 10 healthy persons. Moreover, broadly used cancer biomarkers (progastrin-releasing peptide, carcinoembryonic antigen, and cytokeratin-19 fragment) were identified in eight samples among the 13 samples studied. Conclusion: These results suggest that serum activated PKCα is a reliable biomarker, applicable to lung cancer diagnosis. © 2013 Anticancer Research. Source

Hamasaki A.,Kyushu University | Hamasaki A.,Japan Science and Technology Agency | Ishida T.,Kyushu University | Ishida T.,Japan Science and Technology Agency | And 3 more authors.
Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry

Gold nanoparticles are drawing great attention because of its interesting properties. Although a bulk gold is chemically inert, a nano-sized particles shows completely different characteristics. Therefore, applications of gold nanoparticles for organic transformations are wide-spreading in recent years. We have developed several organic reactions employing metal oxide supported gold nanoparticles. In these reactions, the catalysis are assumed not only by gold nanoparticles but an active species formed from oxide support depending on the reaction conditions. This phenomenon expands the capability of metal oxide supported gold nanoparticles since the catalysis can be modulated by employing a proper metal oxide support. Source

Kang J.-H.,Kyushu University | Kang J.-H.,Japan National Cardiovascular Center Research Institute | Mori T.,Kyushu University | Kitazaki H.,Kyushu University | And 5 more authors.
Cancer Biomarkers

BACKGROUND: Several serum biomarkers such as antigens, soluble proteins, metabolites, and genes have been identified for the diagnosis of cancers and for monitoring the recurrence after cancer treatment. METHODS: In the present study, a protein kinase C (PKC) α-specific peptide substrate was phosphorylated with serum samples collected from cancer-bearing mice (U87, A431, HepG2, and A549) and the phosphorylation ratio was detected by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). RESULTS: The phosphorylation ratio for peptide substrates significantly increased in the serum of cancer-bearing mice compared with the ratio found in control mice. The addition of a PKCα inhibitor induced a concentration-dependent decrease in phosphorylation ratios, but the non-PKCα inhibitors, rottlerin and H-89, did not significantly effect phosphorylation ratios. CONCLUSIONS: These results suggest that serum activated PKCα is a good biomarker applicable to cancer diagnosis. © 2013 - IOS Press and the authors. All rights reserved. Source

Tanaka H.,Kyushu University | Mori T.,Kyushu University | Niidome T.,Kyushu University | Katayama Y.,Kyushu University | Katayama Y.,International Research Center for Molecular Systems
Bioorganic and Medicinal Chemistry

To provide colloidally stable polyplexes formed between pDNA and cationic polymers, cationic polymers have been modified with hydrophilic polymers to form a hydrophilic shell. Block copolymers of cationic and hydrophilic polymers and cationic polymers grafted with hydrophilic polymers are representative designs of such polymers. Here, we report a new design of cationic polymers and oligocationic peptide-grafted polymers. We synthesized 15 kinds of graft copolymers by varying the number of cationic charges of the peptides and their grafting density. We found that graft copolymers with less cationic peptides and less grafting density formed colloidally stable polyplexes. Interestingly, the less cationic graft copolymers bind to excess amounts of pDNA. We also found that the graft copolymers showed selectivity toward reactive enzymes affording the reaction of pDNA with nucleases, while suppressing both the replication of DNA by DNA polymerase and gene expression. The suppression of the replication and expression is considered to result from the high capacity of the graft copolymers for binding with pDNA. The polynucleotides produced by DNA polymerase or RNA polymerase would be captured by the graft copolymers to impede these enzymatic reactions. © 2011 Elsevier Ltd. All rights reserved. Source

Tsuchiya A.,Kyushu University | Naritomi Y.,Kyushu University | Kushio S.,Kyushu University | Kang J.-H.,Japan National Cardiovascular Center Research Institute | And 8 more authors.
Journal of Biomedical Materials Research - Part A

We have reported a disease-cell specific gene expression system that is responsive to intracellular signaling proteins (e.g., protein kinases and proteases) hyperactivated in diseased cells. For this system, cationic peptide-grafted polymers were synthesized for polyplex formation with genes. Here, we modified poly(ethylene glycol) (PEG) to a protein kinase A (PKA)-responsive polymer to improve polyplex stability. PEG modification neutralized the surface charge of the polyplex and successfully increased polyplex stability at physiological conditions. However, PEG modification (PEG contents, 0.6 and 3.3 mol %) showed almost negligible effects on the reactivity of grafted peptides to PKA and the promotion of gene expression responding to PKA activity. Excessive modification of PEG (PEG contents, 6.8 mol %) inhibited polyplex formation. These results indicate that moderate modification of PEG to the enzyme-responsive polymer improves polyplex stability without inhibiting the reaction with enzymes. © 2012 WILEY PERIODICALS, INC. Source

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