Abstract: Provided is a substance capable of effectively suppressing cancer metastasis or a pharmaceutical composition that effectively acts on an inflammatory disease. The pharmaceutical composition is a pharmaceutical composition containing, as an active ingredient, an antibody or an antibody fragment thereof having antigen-binding activity for an S100A8/A9 heterodimer, and blocks interaction between S100A8/A9 and a group of receptors therefor, to thereby strongly suppress cancer metastasis both in vitro and in vivo, or alleviate inflammation. That is, the anti-S100A8/A9 antibody or the antibody fragment thereof can strongly suppress cancer metastasis or alleviate inflammation, by virtue of its blocking action on the interaction between S100A8/A9 and the group of receptors therefor.

Abstract: Provided is a substance capable of effectively suppressing cancer metastasis or a pharmaceutical composition that effectively acts on an inflammatory disease. The pharmaceutical composition is a pharmaceutical composition containing, as an active ingredient, an antibody or an antibody fragment thereof having antigen-binding activity for an S100A8/A9 heterodimer, and blocks interaction between S100A8/A9 and a group of receptors therefor, to thereby strongly suppress cancer metastasis both in vitro and in vivo, or alleviate inflammation. That is, the anti-S100A8/A9 antibody or the antibody fragment thereof can strongly suppress cancer metastasis or alleviate inflammation, by virtue of its blocking action on the interaction between S100A8/A9 and the group of receptors therefor.

Abstract: The present invention provides an inflammatory pulmonary disease agent capable of effectively preventing and/or treating an inflammatory pulmonary disease, and specifically relates to a prophylactic and/or therapeutic agent for an inflammatory pulmonary disease containing, as an active ingredient, an antibody or an antibody fragment having antigen-binding activity for an S100A8/A9 heterodimer. The inflammatory pulmonary disease can be effectively prevented and/or treated by blocking interaction between S100A8/A9 and a group of receptors therefor. Specifically, the inflammatory pulmonary disease can be effectively prevented and/or treated by: blocking interaction between S100A8/A9 and RAGE, which is a receptor therefor, to suppress: the expression of NF-?B, which is a transcription factor present downstream of RAGE and induces the expression of various inflammatory cytokines; the proliferation of activated fibroblasts; and the differentiation of activated fibroblasts into myofibroblasts.

Abstract: One purpose of the present invention aims to provide a novel drug delivery means for targeting neovascularity. Another purpose of the invention is to provide a novel drug delivery means for targeting hyperpermeable vasculature. Still another purpose of the invention is to provide a method and a detection reagent for treatment or diagnosis of various diseases including malignant tumors. The present conjugate of a drug and an anti-HMGB1 antibody or an antigen-binding fragment thereof is administered to a subject and incorporated into proangiogenic or hyperpermeable vascular endothelial cells to deliver the drug to the cells. In addition, the conjugate is used to provide a method and a detection reagent for treatment or diagnosis of various diseases including malignant tumors.

Abstract: It is an object of the present invention to provide an agent for enhancing phagocytosis ability, specifically an agent for enhancing phagocytosis ability that functions as a therapeutic agent or therapeutic adjunct for various bacterial infectious diseases, viral infectious diseases, fungal infectious diseases, parasitic infectious diseases, and mixed infectious diseases thereof by enhancing phagocytosis ability of neutrophils. The above-mentioned object is achieved by an agent for enhancing phagocytosis ability including HRG as an active ingredient. The inventors of the present invention have focused attention on the function of HRG on regulation of neutrophil activities, and as the result of extensive investigations, have newly found that HRG effectively enhances phagocytosis ability against a pathogen or foreign matter derived from bacteria, viruses, fungi, parasites, and the like among the neutrophil activities.

Abstract: Provided is a substance capable of effectively suppressing cancer metastasis or a pharmaceutical composition that effectively acts on an inflammatory disease. The pharmaceutical composition is a pharmaceutical composition containing, as an active ingredient, an antibody or an antibody fragment thereof having antigen-binding activity for an S100A8/A9 heterodimer, and blocks interaction between S100A8/A9 and a group of receptors therefor, to thereby strongly suppress cancer metastasis both in vitro and in vivo, or alleviate inflammation. That is, the anti-S100A8/A9 antibody or the antibody fragment thereof can strongly suppress cancer metastasis or alleviate inflammation, by virtue of its blocking action on the interaction between S100A8/A9 and the group of receptors therefor.

Abstract: Provided is a gene expression cassette for stably and highly producing a protein of interest. The gene expression cassette has a structure in which a DNA construct (X) containing a gene of interest and a poly A addition sequence is sandwiched between a promoter (P) and an enhancer (P?), the gene expression cassette further including transposon sequences (T) upstream of the promoter (P) and downstream of the enhancer (P?). Further, in the gene expression cassette, when a nuclear matrix binding sequence (M) is appropriately arranged upstream of a replication initiation sequence (S) in combination with the transposon sequence (T), the protein of interest can be more effectively produced stably and in a large amount. For example, HRG, PD-1, EMMPRIN, NPTN?, EMB, RAGE, MCAM, ALCAM, ErbB2, and an antibody can each be produced stably and in a large amount.

Abstract: The present invention provides a neutrophil activation regulator comprising a histidine-rich glycoprotein (HRG) for the treatment of systemic inflammatory response syndrome (SIRS), diseases caused by neutrophil activation and/or inflammatory diseases accompanied by neutrophil activation in a subject in need thereof. Further, the present invention provides methods for predicting the severity of systemic inflammatory response syndrome (SIRS), diseases caused by neutrophil activation and/or inflammatory diseases accompanied by neutrophil activation in a subject in need thereof, and methods for predicting the survival of a subject with systemic inflammatory response syndrome (SIRS), diseases caused by neutrophil activation and/or inflammatory diseases accompanied by neutrophil activation, that comprise determining the blood level of histidine-rich glycoprotein in the subject.

Abstract: The present invention provides a therapeutic agent, a treatment method and an inspection method for diseases caused by activation of neutrophils. More specifically, the invention relates to a neutrophil activation regulator which comprising a histidine-rich glycoprotein (HRG) as an active ingredient, and provides a therapeutic agent for diseases caused by neutrophil activation comprising the neutrophil activation regulator, a treatment method for diseases caused by neutrophil activation, and further an inspection method for diseases caused by neutrophil activation. The present invention is based on the neutrophil activation regulator including the HRG as an active ingredient. The present invention extends to the depressant agent for neutrophil-vascular endothelial cell interaction including the HRG of the present invention as an active ingredient, the treatment method for diseases caused by neutrophil activation and/or inflammatory diseases accompanied by neutrophil activation.

Abstract: An object of the present invention is to provide a method for increasing the expression of foreign genes, in particular, using a promoter, an enhancer, and the like, and an expression cassette containing a promoter, an enhancer, and the like, by which gene expression can be increased. The purpose is achieved with the use of the gene expression cassette comprising a DNA construct containing a gene to be expressed and a poly A addition sequence that are located downstream of a 1st promoter, and further comprising an enhancer or a 2nd promoter ligated downstream of the DNA construct.

Abstract: This invention provides an inducer of apoptosis in cancer cells comprising a fragment of the REIC/Dkk-3 gene and a cancer therapeutic agent comprising the same. This invention also provides a polynucleotide fragment encoding the REIC/Dkk-3 protein (a) or (b), which encodes a polypeptide having apoptosis activity: (a) a polynucleotide encoding a polypeptide comprising an amino acid sequence of amino acid 1 to any of amino acids 39 to 78 of the amino acid sequence of the REIC/Dkk-3 protein as shown in SEQ ID NO: 2; or (b) a polynucleotide encoding a polypeptide comprising an amino acid sequence derived from the amino acid sequence of amino acid 1 to any of amino acids 39 to 78 of the amino acid sequence of the REIC/Dkk-3 protein as shown in SEQ ID NO: 2 by substitution, deletion, or addition of 1 or several amino acids and having apoptosis activity.

Abstract: The present invention provides a neutrophil activation regulator comprising a histidine-rich glycoprotein (HRG) for the treatment of systemic inflammatory response syndrome (SIRS), diseases caused by neutrophil activation and/or inflammatory diseases accompanied by neutrophil activation in a subject in need thereof. Further, the present invention provides methods for predicting the severity of systemic inflammatory response syndrome (SIRS), diseases caused by neutrophil activation and/or inflammatory diseases accompanied by neutrophil activation in a subject in need thereof, and methods for predicting the survival of a subject with systemic inflammatory response syndrome (SIRS), diseases caused by neutrophil activation and/or inflammatory diseases accompanied by neutrophil activation, that comprise determining the blood level of histidine-rich glycoprotein in the subject.

Abstract: An objective of the present invention is to provide an adenovirus vector expressing a REIC/Dkk-3 protein at a high level and containing a DNA construct for expression of REIC/Dkk-3 DNA, wherein the DNA construct is prepared by ligating, from the 5? terminal side, (i) a CMV promoter, (ii) REIC/Dkk-3 DNA, (iii) a polyA addition sequence, and (iv) enhancers prepared by linking an hTERT (Telomerase Reverse Transcriptase) enhancer, an SV40 enhancer, and a CMV enhancer in this order.

Abstract: The present invention provides a therapeutic agent, a treatment method and an inspection method for diseases caused by activation of neutrophils. More specifically, the invention relates to a neutrophil activation regulator which comprising a histidine-rich glycoprotein (HRG) as an active ingredient, and provides a therapeutic agent for diseases caused by neutrophil activation comprising the neutrophil activation regulator, a treatment method for diseases caused by neutrophil activation, and further an inspection method for diseases caused by neutrophil activation. The present invention is based on the neutrophil activation regulator including the HRG as an active ingredient. The present invention extends to the depressant agent for neutrophil-vascular endothelial cell interaction including the HRG of the present invention as an active ingredient, the treatment method for diseases caused by neutrophil activation and/or inflammatory diseases accompanied by neutrophil activation.

Abstract: An objective of the present invention is to provide an adenovirus vector expressing a REIC/Dkk-3 protein at a high level and containing a DNA construct for expression of REIC/Dkk-3 DNA, wherein the DNA construct is prepared by ligating, from the 5? terminal side, (i) a CMV promoter, (ii) REIC/Dkk-3 DNA, (iii) a polyA addition sequence, and (iv) enhancers prepared by linking an hTERT (Telomerase Reverse Transcriptase) enhancer, an SV40 enhancer, and a CMV enhancer in this order.

Abstract: A method for potentiating the antitumor immunity in an animal by administering REIC/Dkk-3, or a therapeutic agent for malignant mesothelioma containing REIC/Dkk-3, or a vector containing the DNA as an active ingredient; wherein the DNA consists of the nucleotide sequence shown in SEQ ID NO: 1; or (b) a DNA hybridizing under stringent conditions to the DNA consisting of a nucleotide sequence complementary to the nucleotide sequence shown in SEQ ID NO: 1 and encoding a protein having apoptosis-inducing activity and interleukin (IL-7) production-accelerating activity in cells.

Abstract: According to the present invention, an apoptosis-inducing agent for prostate cancer comprising REIC/Dkk-3 DNA or an REIC/Dkk-3 protein, and a therapeutic agent for prostate cancer and an agent for inhibiting prostate cancer metastasis that comprise such apoptosis-inducing agent are provided.

Abstract: This invention provides an inducer of apoptosis in cancer cells comprising a fragment of the REIC/Dkk-3 gene and a cancer therapeutic agent comprising the same. This invention also provides a polynucleotide fragment encoding the REIC/Dkk-3 protein (a) or (b), which encodes a polypeptide having apoptosis activity: (a) a polynucleotide encoding a polypeptide comprising an amino acid sequence of amino acid 1 to any of amino acids 39 to 78 of the amino acid sequence of the REIC/Dkk-3 protein as shown in SEQ ID NO: 2; or (b) a polynucleotide encoding a polypeptide comprising an amino acid sequence derived from the amino acid sequence of amino acid 1 to any of amino acids 39 to 78 of the amino acid sequence of the REIC/Dkk-3 protein as shown in SEQ ID NO: 2 by substitution, deletion, or addition of 1 or several amino acids and having apoptosis activity.

Abstract: This invention provides an inducer of apoptosis in cancer cells comprising a fragment of the REIC/Dkk-3 gene and a cancer therapeutic agent comprising the same. This invention also provides a polynucleotide fragment encoding the REIC/Dkk-3 protein (a) or (b), which encodes a polypeptide having apoptosis activity: (a) a polynucleotide encoding a polypeptide comprising an amino acid sequence of amino acid 1 to any of amino acids 39 to 78 of the amino acid sequence of the REIC/Dkk-3 protein as shown in SEQ ID NO: 2; or (b) a polynucleotide encoding a polypeptide comprising an amino acid sequence derived from the amino acid sequence of amino acid 1 to any of amino acids 39 to 78 of the amino acid sequence of the REIC/Dkk-3 protein as shown in SEQ ID NO: 2 by substitution, deletion, or addition of 1 or several amino acids and having apoptosis activity.

Abstract: The invention provides a screening method for chronic inflammation inhibitors or cancer metastasis inhibitors wherein, when a candidate substance as a chronic inflammation inhibitor or cancer metastasis inhibitor significantly inhibits binding between EMMPRIN and S100A9 or S100A8/A9, the candidate substance is evaluated as significantly suppressing chronic inflammation or cancer metastasis.