Periostin antisense oligonucleotide suppresses bleomycin-induced formation of a lung premetastatic niche for melanoma.

Metastasis is the leading cause of cancer death. A tumor-supportive microenvironment, or premetastatic niche, at potential secondary tumor sites plays an important role in metastasis, especially in tumor cell colonization. Although a fibrotic milieu is known to promote tumorigenesis and metastasis, the underlying molecular contributors to this effect have remained unclear.

Periostin antisense oligonucleotide prevents adhesion formation after surgery in mice.

To study the role of periostin in adhesion formation, the effect of periostin antisense oligonucleotide (PAO) on adhesion formation was evaluated in mice. Under anesthesia, the serous membrane of the cecum was abraded, and the adhesion score and mRNA levels of periostin and its related factors were determined after surgery. Saline, 40 mg/kg of negative sense oligonucleotide (NSO), or 40 mg/kg of PAO were injected into the abdomen after surgery, and the adhesion score and mRNA levels were evaluated 14 days later.

Stoichiometry-focused (18)F-labeling of alkyne-substituted oligodeoxynucleotides using azido([(18)F]fluoromethyl)benzenes by Cu-catalyzed Huisgen reaction.

A novel method for (18)F-radiolabeling of oligodeoxynucleotides (ODNs) by a Cu-catalyzed Huisgen reaction has been developed by using the lowest possible amount of the precursor biomolecule for the realization of stoichiometry-oriented PET (positron emission tomography) chemistry. Under the optimized cyclization conditions of p- or m-azido([(18)F]fluoromethyl)benzene and alkyne-substituted ODN (20nmol) at 40°C for 15min in the presence of CuSO(4), TBTA [tris((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)amine], and sodium ascorbate (2:1:2), the synthesis of (18)F-labeled ODNs with sufficiently high radioactivities of 2.1-2.

Predicting the phenotypic response of resource-competing communities to environmental change.

We formulated responses in functional traits by competitive communities to continual environmental changes, and examined the association of the trait dynamics with species richness and interspecific competition. As an aggregate measure for community properties we employed the mean community trait value as the species traits averaged over an entire community with weighting by relative species abundances. For three particular types of community, in which there was competition for abiotic resources, competition for biotic resources, or species packing on an environmental gradient, we analytically proved that the responses of the mean community trait to environmental change were determined by the total trait range in the community but were weakly associated with the strength of competition and the number of species.

Increase in nuclease resistance and incorporation of NF-kappaB decoy oligodeoxynucleotides by modification of the 3'-terminus.

Background: For the development of molecular therapy based on oligodeoxynucleotides (ODN), ODN have to be stable against nucleases and be specific to the target transcription factor. To decrease non-specific binding and degradation from the 3'-terminus of ODN, we designed partially annealed ODN by binding the extremities of two single strands, resulting in a ribbon-shaped ODN, so called ribbon-type decoy ODN (R-ODN).

Methods: We evaluated the efficiency in the process of enzymatic ligation of R-ODN, the binding activity to nuclear factor-kappaB (NF-kappaB), and the stability against Exonuclease III and nucleases present in serum.

Functional and physical interactions between ERCC1 and MSH2 complexes for resistance to cis-diamminedichloroplatinum(II) in mammalian cells.

Bulky DNA lesions are mainly repaired by nucleotide excision repair (NER), in which the interaction of ERCC1 with XPA protein recruits the ERCC1-XPF complex, which acts as a structure-specific endonuclease in the repair process. However, additional functions besides NER have been suggested for the ERCC1-XPF complex, because ERCC1- or XPF-deficient rodent cells are significantly more sensitive to DNA interstrand cross-linking (ICL) agents such as cis-diamminedichloroplatinum(II) (CDDP) than any other NER-deficient cells and because ERCC1-deficient mice suffer a more severe phenotype than XPA-deficient mice. By using RNA interference we show here that suppression of ERCC1 expression increases the sensitivity of xeroderma pigmentosum group A (XPA)-deficient human cells to CDDP but not to UV.

Additive roles of XPA and MSH2 genes in UVB-induced skin tumorigenesis in mice.

We have made xeroderma pigmentosum group A gene (XPA)-knockout mice (XPA(-/-) mice). The XPA(-/-) mice had no detectable activity for nucleotide excision repair (NER) and showed a high incidence of UVB-induced skin tumorigenesis. We have also found that cell lines derived from skin cancers in UVB-irradiated XPA(-/-) mice become tolerant to UV-irradiation and showed abnormal UV-induced cell cycle checkpoints and decreased mismatch repair (MMR) activity.