Chugai Seiyaku Kabushiki Kaisha

Jatco Corporation

Hitachi, Ltd.

Nissan Motor Company Limited

Nikon Corporation

Yamaha Hatsudoki Kabushiki Kaisha

Pharmalogicals Research Pte. Ltd.

Ciea International Inc.

University of Miyazaki

Masami Suzuki

Atsuhiko Kato

Koichi Matsubara

Shinta Kobayashi

Yu Jau Chen

Tatsumi Yamazaki

Hisafumi Okabe

Hiroshi Nishida

Tsuyoshi Takahashi

Fumihiro Yamanaka

Takeshi Watanabe

Daisuke Nakamura

Masayuki Tsuchiya

Miho Watanabe

Yoshihiko Okabe

Yoshihito Fukuoka

Hiroki Matsui

Jun Naruse

Tomio Suzuki

Kenji Yoshida

Katsuhiro Matsuo

Goh Endo

Juliana Sim

Osamu Natori

Minoru Tanikawa

Etsuko Fujii

Tomoyuki Igawa

Yoshinori Watanabe

Hiroyuki Tsunoda

Taichi Kuramochi

Atsuhiko Maeda

Tatsuhiko Tachibana

Hirotake Shiraiwa

Go Endo

Yasuko Kinoshita

Haruhisa Tsuchikawa

Masamichi Sugimoto

Yutaka Imaizumi

Shigero Tamba

Kazuki Hirasako

Keii Ueno

Minoru Sato

Katsumi Kawamura

Mineo Takahashi

Kazumi Aiba

Keiko Esaki

Toshinori Kazama

Nobuyuki Okamoto

Mikio Higashi

Masanobu Honda

Hiroaki Kataoka

Muneo Iida

Chie Kato

Masaki Yamazaki

Toshiaki Ito

Etsuko Takeiri

Kazuhiro Numano

Eri Hashimoto

Masanobu Ueda

Masayuki Fujii

Seiji Tada

Jiro Mochida

Jyosei Simizu

Hirotake Takai

Provided is a cancer stem cell mass from which cells incapable of forming cancer are substantially removed and which has a characteristic property of reproducing a layered structure of a cancer tissue; a process for producing the cancer stem cell mass; and use of the cancer stem cell mass. A human cancer tissue was repeatedly grown in a NOG mouse, separated cancer cells from the grown cancer tissue, and tested and compared various cancer cell culture processes. As a result, a cancer stem cell composition which is homogeneous and is substantially free of the coexistence of cells capable of forming cancer and cells incapable of forming cancer in a mixed state can be produced successively by employing an attached culture process using a serum-free stem cell culture medium rather than a generally employed floating culture process.

Cancer stem cell population and method for production thereof

An objective of the present invention is to obtain two types of substantively homogeneous cancer stem cell populations which can be characterized using the cell surface marker Lgr5, and to provide cancer therapeutics using an antibody against a cell membrane molecule specifically expressed in these cancer stem cells by identifying said cell membrane molecule. A further objective is to provide, using an antibody against a cell membrane molecule specifically expressed in cancer stem cells, a reagent for detecting cancer stem cells, and a method for diagnosing and sorting cancer patients. The present inventors discovered that highly pure large intestine cancer stem cells (CSC) can be obtained in a large quantity, and identified the two types of conditions of large intestine CSCs distinguishable through Lgr5 expression. Moreover, the present inventors discovered that an antibody against a cell membrane molecule specifically expressed in said cancer stem cells can damage said cells.

Cancer stem cell-specific molecule

An objective of the present invention is to provide non-human animal models of cancer pathology, which mimic the hierarchical organization, cancer progression process, or biological property of human cancer tissues, and uses thereof. To achieve the objective described above, first, the present inventors transplanted cells of NOG-established cancer lines into NOG mice and morphologically observed the resulting tissue organization. As a result, the non-human animal models were demonstrated to exhibit pathologies (the hierarchical organization, cancer progression process, or biological properties of the cancer cells) similar to that of human cancer. Specifically, the present inventors succeeded in preparing non-human animal models exhibiting pathologies more similar to a human cancer, and cell culture systems using NOG-established cancer cell lines where the in vitro cell morphology is more similar to that of human cancer.

Method for searching and screening for target of anti-cancer agent using non-human animal model having NOG established cancer cell line transplanted therein

The purpose of the present invention is to provide: a cancer stem cell mass from which cells incapable of forming cancer are substantially removed and which has a characteristic property of reproducing a layered structure of a cancer tissue; a process for producing the cancer stem cell mass; and use of the cancer stem cell mass. For achieving the purpose, the present inventors grew a human cancer tissue repeatedly in a NOG mouse, separated cancer cells from the grown cancer tissue, and made a comparison of various cancer cell culture processes with each other. As a result, a cancer stem cell composition which is homogeneous and is substantially free of the coexistence of cells capable of forming cancer and cells incapable of forming cancer in a mixed state can be produced successively by employing an attached culture process using a serum-free stem cell culture medium rather than a generally employed floating culture process, and consequently the present invention has been accomplished.

An objective of the present invention is to provide: a cancer stem cell isolated using a cell marker; a substantively homogeneous cancer stem cell population including said cancer stem cell; and a method of preparing said cancer stem cell population. Another objective of the present invention is to provide: a method for separating cancer stem cells with a high proliferative potential and those with a low proliferative potential; a method for inducing cancer stem cells to have a different proliferative potential; and cancer stem cells separated or induced by these separation or induction methods. A further objective of the present invention is to provide: a method of screening for pharmaceuticals using said cancer stem cell or cancer stem cell population; a method for detecting the presence of said cancer stem cell or cancer stem cell population and for identifying or quantifying the same. The present inventors discovered that highly pure colon cancer stem cells (CSC) can be obtained in a large quantity, and identified two types of states of colon CSCs distinguishable through Lgr5 expression.

Cancer stem cell isolation

The inventors successfully produced anti-Epiregulin antibodies showing cross-species reactivity between cynomolgus monkey (non-human animals) and human, anti-Epiregulin antibodies with suppressed chemical degradation, anti-Epiregulin antibodies with lowered isoelectric point, anti-Epiregulin antibodies with increased thermal denaturation midpoint temperature, and anti-Epiregulin antibodies with reduced amount of aggregate by performing appropriate amino acid residue substitutions in the variable-region sequences of the humanized EP27 antibody which inhibits growth of cancer cells by exhibiting cytotoxic activity and neutralizing activity against human Epiregulin-expressing cancer cells.

Humanized anti-epiregulin antibody, and cancer therapeutic agent comprising said antibody as active ingredient

A neutral determination device is provided with an inhibitor switch and a controller. The inhibitor switch outputs an inhibitor switch signal that indicates a vehicle running range of a vehicle. The controller is programmed to execute a neutral determination process upon determining the vehicle running range exists based on the inhibitor switch signal and a rotational speed control is being performed on a motor that is configured to output a force that drives the vehicle. The controller is programmed to determine existence of a neutral state of a control valve that is configured to selectively supply a control hydraulic pressure to a hydraulic pressure chamber of the clutch upon determining that a motor torque during the rotational speed control is smaller than an estimated motor torque based on a target transmission torque capacity of a clutch that selectively connects and disconnects the motor to and from a drive wheel.

Neutral determination device and vehicle control apparatus

A control device of an automatic transmission that controls the automatic transmission including a friction engagement element capable of continuously changing a transmission torque includes: a first heat load estimation unit configured to estimate a heat load state in the friction engagement element based on an indication value of the transmission torque; and an estimation stop unit configured to stop the estimation of the heat load state based on a state where the indication value of the transmission torque differs from an actual value of the transmission torque actually transmitted by the friction engagement element.

Control device of automatic transmission and method of controlling automatic transmission

A control apparatus of a hybrid vehicle provided with an engine, a motor, an automatic transmission performing a shift by engaging/disengaging a plurality of engagement elements, a first clutch arranged between the engine and the motor for transmitting/cutting a driving force between the engine and the motor and a second clutch arranged between the motor and driving wheels for transmitting/cutting a driving force from the motor to the driving wheels, has a slip control section that controls the second clutch to a slip state during the shift of the automatic transmission. In a case of a successive shift in which a current shift and a succeeding shift are successively performed, the slip control section gradually increases an engagement pressure of the second clutch when changing the slip state of the second clutch to a fully engaged state after the current shift is completed and before the succeeding shift is completed.

Control apparatus for hybrid vehicle

A control device of a hybrid vehicle includes an engine, a motor/generator, a first clutch, an automatic transmission, a second clutch, and startup/shifting simultaneous processing section. When engine speed increase control for increasing the engine speed by the motor/generator in order to start up the engine during travel and downshifting control of the automatic transmission are processed in parallel, the startup/shifting simultaneous processing section uses the motor torque of the motor/generator to increase the increase of input speed by the downshifting control to a target input speed while engine speed increase control is being performed by the motor/generator.

Hybrid vehicle control device

A hybrid vehicle control device is provided with an engine, a motor/generator, a first clutch, an automatic transmission, a second clutch, and a controller having a simultaneous process selection control section. The simultaneous process selection control section performs engine startup control and downshift control in parallel in cases where the torque outputtable by the motor subsequent to downshifting during overlap of an engine startup request and a downshift request is equal to or greater than the engine startup torque, or performs engine startup control first then downshift control in cases where the torque outputtable by the motor subsequent to downshifting is less than the engine startup torque.

The present invention relates to an in-vitro immunoassay method for detecting the presence of liver cancer cells in a subject. In the method of the present invention, antigen retrieval treatment based on heat-induced epitope retrieval method and antigen retrieval treatment based on protease-induced epitope retrieval method can be combined in the detection of glypican 3 antigen expression in liver cancer tissues to thereby detect the difference in the expression level or expression pattern of the glypican 3 antigen by immunohistochemical staining method. This enables samples, which has been determined by the conventional HIER method as highly expressing glypican 3, to be graded according to the expression level of glypican 3.

Method for detection of liver cancer cell using anti-glypican-3 antibody

A control system for controlling an automatic transmission that is capable of establishing a given speed stage by engaging a given frictional element. The control system comprises an actual time lag measuring section that measures an actual time lag from the time when a speed change instruction for the given speed stage is issued to the time when a gear ratio of the automatic transmission starts to change for the purpose of establishing the given speed stage, a torque detecting section that detects a torque from an engine, a time lag map that provides a suitable time lag in accordance with the detected torque from the engine, a learning correction section that corrects, by learning control, an instruction value for the hydraulic pressure led to the frictional element in a manner to cause the actual time lag to have the same value as the suitable time lag; and a time lag map correcting section that corrects the suitable time lag in accordance with an operation condition of an associated motor vehicle.

Control system of automatic transmission

A speed change control device of an automatic transmission comprises a first control section that, upon detecting a speed change instruction for a speed change from a first given speed to a second given speed, carries out the speed change by reducing an engaging pressure of a releasing side frictional element that has established the first given speed and increasing an engaging pressure of an engaging side frictional element that would establish the second given speed; a second control section that carries out a correction processing to increase the engaging pressure of the releasing side frictional element when a throttle open degree is increased during the speed change carried out by the first control section; and a third control section that inhibits the correction processing of the second control section when the engaging pressure of the releasing side frictional element is lower than a given value.

Speed change control device of automatic transmission

Growing community of inventors

Shizuoka, Japan

Masami Suzuki