National Institute of Advanced Industrial Science and Technology

Chugai Seiyaku Kabushiki Kaisha

Other

Chanel Parfums Beaute

Kaul-tech Co., Ltd.

Renu Wadhwa

Sunil Kaul

Takashi Sugihara

Akiko Ohide

Youji Mitsui

Atsushi Inoue

Christian Mahe

Nobuhiro Ando

Kazunari Taira

Maki Shiota

Roger R Reddel

It is an object of the present invention to provide a method for preparing a water extract of ashwagandha, which comprises increasing the amounts of withanone and withaferin A contained as active ingredients in the water extract of ashwagandha leaves. In addition, it is another object of the present invention to more economically and simply provide a pharmaceutical composition comprising ashwagandha leaves. The present invention relates to a method for preparing a water extract of ashwagandha leaves, which comprises extracting ashwagandha leaves with water in the presence of cyclodextrin, and a method for enhancing the anticancer activity of the water extract of ashwagandha leaves. The present invention also relates to a pharmaceutical composition for treating or preventing cancer, comprising the water extract of ashwagandha leaves. The present invention further relates to a pharmaceutical composition comprising dry powders of ashwagandha leaves and cyclodextrin.

Method for preparing water extract of ashwagandha leaves which has enhanced anti-cancer activity utilizing cyclodextrin, and pharmaceutical composition containing ashwagandha leaves

A method to identify target genes or proteins for regulating melanogenesis or pigmentation and to screen for compounds for manipulation of melanogenesis or pigmentation, the method of screening for candidate compounds for regulating melanogenesis or pigmentation, includes bringing test compounds into contact with cells capable of expressing mortalin and/or Hsp60 in vitro, and selecting, from among the test compounds, a compound that changes the expression level of mortalin and/or Hsp60.

Method of screening for candidate compounds for regulating melanogenesis or pigmentation

The amino acid sequences of paratope regions involved in internalizing function of an anti-mortalin antibody into tumor cells were determined for the L-chain and H-chain variable regions of cellular internalizing anti-mortalin antibodies and non-internalizing anti-mortalin antibodies. Cancer-cell-specific drug delivery is provided by using the mortalin-binding activity of a single-chain antibody (scFv) wherein L-chain and H-chain variable regions both having the paratope region are linked together via a peptide linker. Also, the sequence of 6 amino acids of an epitope to be recognized by an anti-mortalin antibody having the internalizing function was determined. With the use of an expression vector comprising a nucleic acid that encodes the epitope, an agent for accelerating internalization of a mortalin antibody, a drug bound thereto, and the like into cancer cells is provided.

Paratope and epitope of anti-mortalin antibody

The present invention provides anti-mortalin peptide antibodies having stronger anticancer effects than known anti-mortalin antibodies, hybridomas producing such antibodies, and anticancer agents using such antibodies. Specifically, a hybridoma C-26 strain (FERM P-21875) and a hybridoma C-69 strain (FERM P-21876) producing anti-mortalin monoclonal antibodies having the function of being internalized by cancer cells and specificity to mortalin antigens, and having the good function of suppressing the cancer cell proliferation in vivo were obtained from hybridoma clones obtained using as an immunogen cocktail of the 2 types of peptide containing 'LFGRAP' and 'KAMQDAEVSKSDIGEVI' epitopes for an anti-mortalin antibody having the function of being internalized by cancer cells. Thus, anticancer agents containing the monoclonal antibodies as active ingredients could also be provided. Moreover, the epitope sequences recognized by these monoclonal antibodies were confirmed to be &#x201c;EVILVG&#x201d; and &#x201c;DLFGR.&#x201d;

Hybridomas producing monoclonal anti-mortalin peptide antibodies

A full-length cDNA encoding novel proteins involved in the control of cell proliferation (human Gros1-L and S) was successfully isolated from the human testis cDNA libraries. A full-length cDNA encoding the mouse homologues of the human Gros1 (mouse Gros1-L and S) was also isolated. The colony forming activity of cells exogenously expressing Gros1-L was significantly reduced, while that of cells expressing Gros1 antisense RNA was significantly increased.

Tumor suppressor gene

The present invention relates to cancer therapies using an antibody that binds to mortalin 2 and a functional nucleic acid. Mortalin expression was found to be upregulated in immortalized cells and tumor tissues. Immortalized human cells highly expressing mortalin showed anchorage-independent growth. When the K antibody, which is a specific anti-mortalin antibody, was injected into a tumor of a nude mouse, tumor growth was suppressed or the tumor shrank compared with the case of a control. In accordance with the present invention, the use of a specific anti-mortalin antibody (K antibody) for tumor therapies and the use of such antibody as a carrier molecule for transportation of immunotoxicin and the like into cells are provided. It has been shown that mortalin can be a target for cancer therapies. In accordance with the present invention, a novel and effective anticancer agent is provided. In addition, an anti-mortalin antibody that is internalized by cells is developed. Thus, various applications using such antibody are provided.

Use of anti-mortalin 2 antibody and functional nucleic acid for cancer therapies

A gene expressed specifically in the testis has been unexpectedly isolated in the course of studies of the expression of a gene encoding an unknown protein that triggers cell death. The isolated gene was a novel gene sequence that had no significant homologue in the database. This gene was also found to be involved in the regulation of differentiation in the testis and to encode a protein, Tesmin, which may regulate the differentiation of spermatogeneous cells into primary spermatocytes. Tesmin proteins are described herein, as are antibodies that bind to such proteins.

Antibodies to a testis-specific differentiation-regulatory factor

A gene expressed specifically in the testis has been unexpectedly isolated in the course of studies of the expression of a gene encoding an unknown protein that triggers cell death. The isolated gene was a novel gene sequence that had no significant homologue in the database. This gene was also found to be involved in the regulation of differentiation in the testis.

Testis-specific differentiation-regulatory factor

A gene was unexpectedly isolated in an attempt to isolate a gene specifically expressed in immortalized cells via antibody screening using an antibody raised against a protein occurring specifically in immortalized cells. The gene thus isolated shares no sequence homology with the entries deposited in the database and was strongly expressed in skeletal muscles and undifferentiated cells. The protein encoded by this gene inhibits the differentiation of myoblasts into myotubes. It also inhibits the transactivation function of p53, a transcription factor involved in tumor suppression.

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Ibaraki, Japan

Renu Wadhwa