Abstract: The present invention aims to provide a novel reagent for tumor testing and a novel pharmaceutical composition for tumor prevention. The present invention provides a reagent for tumor detection, which comprises a probe for the FEAT gene or amplification primers for the FEAT gene, or an antibody against the FEAT protein or a fragment of the antibody. Moreover, the present invention also provides a pharmaceutical composition for tumor prevention, which is configured to use the FEAT gene or the FEAT protein as a tumor marker to thereby recognize tumor cells.

Abstract: The present invention provides an induced cancer cell capable of self-replication in vitro which is useful in cancer therapy research and the research for cancer-related drug discovery, processes for production thereof, cancer cells induced by the malignant cells, and applications of these cells. The present invention provides an induced cancer stem cell capable of proliferation (self-replication) in vitro, wherein the induced cancer stem cell has the following two characteristics: (1) expressing the six genes (self-renewal related genes) POU5F1, NANOG, SOX2, ZFP42, LIN28, and TERT selected from a certain group of genes; and (2) having an aberration which is either (a) a mutation in an endogenous tumor suppressor gene or (b) increased expression of an endogenous cancer-related gene.

Abstract: It is intended to provide a tool, a procedure and so on which are useful in developing a therapeutic strategy efficacious in inhibiting or overcoming the resistance against a CD20-directed molecular-targeted drug. Thus, a CD20-negatively converted B-cell malignant lymphocyte cell line is provided. Also, a model animal indicating the pathological conditions of CD20-negatively converted B-cell malignant lymphocyte is provided. Further, a method of screening a substance, which is efficacious against CD20-positive B-cell malignant lymphocyte or CD20-negatively converted B cell malignant lymphocyte, is provided. Furthermore, a drug against CD20-positive B-cell malignant lymphocyte or CD20-negatively converted B-cell malignant lymphocyte, which is characterized by being used together with a CD20-directed molecular-targeted drug, is provided. In one embodiment, a DNA methylase inhibitor or a histone deacetylase inhibitor is employed as the active ingredient.

Abstract: The present application is directed to compositions and methods for inhibiting angiogenesis and treating or preventing unwanted cell proliferation, including tumors, by inhibiting the hedgehog pathway, e.g., with an antagonist of the hedgehog pathway such as those disclosed herein.

Abstract: Use of an animal model of spontaneous metastasis bearing a tumor derived from a cell line RM72 (Accession No. NITE BP-1110) allows simultaneous evaluation of tumorigenesis and spontaneous cancer metastasis. Use of a screening method using the animal model of spontaneous metastasis allows the obtainment of a substance having an anticancer activity and/or an anti-metastatic activity. Use of another screening method for selecting a substance that increases the expression of RECK in a cancer cell allows the obtainment of a substance that can serve as an active ingredient in an anticancer drug.

Abstract: The present invention relates to methods for the diagnostic and the staging of cancer such as liver cancer. The present invention also relates to methods for the treatment of cancer including liver cancer such as hepatocellular carcinoma (HCC).

Abstract: Disruption of mitogen inducible gene 6 (Mig-6) in mice by homologous recombination (KO mice) led to early onset osteoarthritis (OA) as revealed by simultaneous enlargement and deformity of multiple joints, degradation of articular cartilage and the development of bony outgrowths or osteophytes within the joint space. Because of the striking similarity to human OA, Mig-6 KO mice are a useful animal model for studying the mechanism of this disease and for testing new drugs or therapies for treating OA. These KO mice also developed epithelial hyperplasia, adenoma, and adenocarcinoma in organs such as lung, gallbladder, and bile duct. Mig-6 is therefore a tumor suppressor gene and is a candidate gene for the frequent Ip36 genetic alterations found in lung cancer. It can be used as a tumor biomarker as well as a target for cancer therapy.

Abstract: The present invention relates to a genetically modified pig as a model for studying breast cancer, mitochondria related protein folding disorders and/or epidermolysis bullosa simplex. The modified pig model displays one or more phenotypes associated with any of said disorders. Disclosed is also a modified pig comprising a modified endogeneous BRCA1 and/or BRCA2 gene, and/or a modified ornithine transcarbamylase gene, and/or a modified Keratin 14 gene and/or a transcriptional or translational product or part thereof. The invention further relates to methods for producing the modified pig; and methods for evaluating the effect of a therapeutical treatment of breast cancer, mitochondria related protein folding disorders and/or epidermolysis bullosa simplex; methods for screening the efficacy of a pharmaceutical composition; and a method for treatment of a human being suffering from breast cancer, mitochondria related protein folding disorders and/or epidermolysis bullosa simplex are disclosed.

Abstract: The object of the invention is to provide a method for producing tumor cells by carrying out gene transfer into cells derived from normal cells. The invention provides a method for producing tumor cells by transferring cancer-associated genes into immortalized small airway epithelial cells.

Abstract: Rodent therapeutic models are provided containing at least human hepatocytes and at least one of human hematopoietic bone marrow cells and human cord blood. Such rodent therapeutic models can also be immunodeficient and/or contain human intestinal enzymes. These partially humanized rodent therapeutic models can have at least partially humanized bone marrow and a partially humanized liver. These rodent models include mice. The rodent models can be transplanted with one or more tumors, for example, xenotransplantation with a human tumor. Toxicological and efficacy trials of various therapies, for example, anti-cancer therapies, can be performed with these rodent therapeutic models. Oral administration of camptothecin can demonstrate increased toxicity in the humanized mice.

Abstract: An object of the present invention is to provide a method for producing tumor cells from cells derived from normal cells without using hTERT. The present invention provides a method for producing tumor cells by carrying out the following treatments (1) and (2) on normal mammary epithelial cells: (1) elimination of p53 function; and (2) introduction v-Src gene.

Abstract: Methods for screening compounds to treat an oncological disorder regulated through a tumor-inducing pathway are provided. The compounds are administered to non-human animal subjects having a disease model, so that the subjects display pathology symptoms that correspond to the oncological disorder in humans. The subjects carry a regulatable transgene expression, of which is associated with tumor formation, and further carry regulatable genes for suppression of tumor formation. The disease-pathology symptoms are induced using a site-specific recombination system to induce expression of the transgene associated with tumor formation and negatively regulate or eliminate the genes for suppression of the tumor formation. The methods further involve analyzing tumor formation in subjects administered the compound and comparing appearance and amount of tumors in the subjects administered the compound with control subjects not administered the compound.

Abstract: Described herein are compositions and methods for the treatment of cancer, and particularly brain cancer (e.g., glioma) in a mammal. In various embodiments of the invention, a combined therapeutic approach including TK with systemic ganciclovir administration and Flt3L are used in connection with gene therapeutic techniques or direct peptide injection for the aforementioned indications. Kits useful in practicing the inventive method are also disclosed, as are animal models useful for studying brain cancer.

Abstract: Markers useful for the identification, characterization and, optionally, the enrichment or isolation of tumorigenic cells or cell subpopulations are disclosed.

Abstract: The invention relates generally to the field of cancer prognosis and treatment. More particularly, the present invention relates to methods and compositions that utilize a particular panel of gene products (“biomarkers”) and their differential expression patterns (“expression signatures”), wherein the expression patterns correlate with responsiveness, or lack thereof, to chemotherapy treatment. The invention is based on the identification of a specific set of biomarkers that are differentially expressed in chemotherapy-treated tumors and which are useful in predicting the likelihood of a therapeutic response, including residual disease persistence and subsequent tumor recurrence in cancer patients receiving chemotherapy. The gene panel is also useful in designing specific adjuvant modalities with improved therapeutic efficiency. Also disclosed are methods for characterizing tumors according to expression of the biomarkers described herein.

Abstract: Reconstituted human breast tumor models are disclosed. The models, which are incorporated into mice, provide actual tumors that arise spontaneously, thereby mimicking naturally occurring breast cancer. The tumors are genetically human, because they arise from human mammary tissues that develop from human mammary epithelial cells implanted into host mice. Prior to implantation, the mammary epithelial cells are genetically modified to contain either: (a) a recombinant human oncogene and an SV40er; or (b) a recombinant human oncogene, a transgene or shRNA that inhibits the p53 pathway, and a transgene or shRNA that inhibits the Rb pathway.

Abstract: The present application is directed to compositions and methods for inhibiting angiogenesis and treating or preventing unwanted cell proliferation, including tumors, by inhibiting the hedgehog pathway, e.g., with an antagonist of the hedgehog pathway such as those disclosed herein.

Abstract: 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.

Abstract: The present invention relates to animal model systems comprising a chimera between an avian embryo and a mammalian organism. Specifically, chimeric model systems comprising normal, diseased or genetically transformed mammalian cells and tissues transplanted into avian embryos, and uses thereof for in vivo testing of drugs and therapeutic modalities are disclosed.

Abstract: The invention provides compositions and methods for detecting and/or modulating TOX3 gene expression and/or biological activity. Such compositions and methods find utility in the detection and/or treatment of certain subsets of cancers, e.g. breast cancer. In particular, the inventive compositions and methods are drawn to production and use of anti-TOX3 antibodies and TOX3 nucleic acids for both detection and modulation of TOX3. The invention also provides for pharmaceutical compositions and methods for the modulation of TOX3 in a subject in need thereof. Further aspects of the invention relate to transgenic mice that either over-express or inducibly express TOX3.

Abstract: The invention concerns materials and methods relating to the use of OMD (osteomodulin) and\or PRELP (Proline/arginine-rich end leucine-rich repeat protein) expression, particularly under-expression, to discriminate cancer and non-cancer cells in a variety of cancers. The invention further provides methods and materials based on OMD and\or PRELP for use in therapy e.g. to suppress cancer initiation or development.

Abstract: We have established and studied a colony of mice with a unique trait of host resistance to both ascites and solid cancers induced by transplantable cells. One dramatic manifestation of this trait is age-dependent spontaneous regression of advanced cancers. This powerful resistance segregates as a single-locus dominant trait, is independent of tumor burden and is effective against cell lines from multiple types of cancer. During spontaneous regression or immediately following exposure, cancer cells provoke a massive infiltration of host leukocytes which form aggregates and rosettes with tumor cells. The cytolytic destruction of cancer cells by innate leukocytes is rapid and specific without apparent damage to normal cells. The mice are healthy, cancer-free and have a normal life span. These observations suggest a previously unrecognized mechanism of immune surveillance that may have potential for therapy or prevention of cancer.

Abstract: Provided is a mosaic mouse model for use in determining the potency of an shRNA in vivo for reducing survival of cancer cells of chemotherapy-resistant leukemia. The syngeneic mouse recipient is transplanted with tet-on competent leukemia cells carrying a bicistronic nucleic acid construct comprising a promoter operably linked to a fusion gene associated with chemotherapy-resistant leukemia, and a sequence encoding a reverse tet-transactivator protein, such that both coding sequences are co-expressed from the promoter. Also provided are methods of treating soft tissue cancers.

Abstract: Methods for culturing cancer cells in vitro using a three-dimensional scaffold, scaffolds that include the cultured cancer cells, and methods for using the cultured cancer cells and the scaffolds that include the cultured cancer cells in anticancer therapeutic drug development.

Abstract: The present invention relates in a first aspect to a cell model containing chondrocytes whereby said chondrocytes contain a first heterologous nucleic acid sequence operably linked with a mb1 promoter sequence. In another aspect, the present invention relates to a cell model, in particular, to a transgenic animal model whose genome comprises a first heterologous nucleic acid sequence encoding a recombinase and/or restriction enzyme operably linked to a chondrocyte specific promoter, and a second heterologous nucleic acid sequence encoding a target peptide of interest wherein the second nucleic acid sequence further comprises recombination sequences or restriction site for the enzyme encoded by the first heterologous nucleic acid sequence. In addition, methods for screening foreign agent or methods for testing the efficacy and/or efficiency of an agent are provided.

Abstract: The present invention describes Photolabile Compounds methods for use of the compounds. The Photolabile Compounds have a photoreleasable ligand, which can be biologically active, and which is photoreleased from the compound upon exposure to light. In some embodiments, the Photolabile Compounds comprise a light antenna, such as a labeling molecule or an active derivative thereof. In one embodiment, the light is visible light, which is not detrimental to the viability of biological samples, such as cells and tissues, in which the released organic molecule is bioactive and can have a therapeutic effect. In another embodiment, the photoreleasable ligand can be a labeling molecule, such as a fluorescent molecule.

Abstract: The present application relates to a composition including gut flora-derived extracellular vesicles, and to an animal disease model using same. In addition, the present application relates to a method for using the gut flora-derived extracellular vesicles to efficiently search for a candidate drug which may prevent or treat diseases that occur due to gut flora-derived extracellular vesicles, and to a vaccine which can efficiently prevent or treat infections caused by gut flora or diseases that occur due to gut flora-derived extracellular vesicles. Further, the development of diagnostic technology to discover, using the gut flora-derived extracellular vesicles of the present application, the etiology of diseases that occur due to gut flora-derived extracellular vesicles, can be achieved.

Abstract: Developed here is a mitotic network comprising a signature of up to 54 genes, and including also sub-sets of genes within the signature, which can identify members by requiring higher correlation values for a signature gene. The present mitotic network provides for methods for prognosis and diagnosis of various cancers. The mitotic network is conserved across cancers exhibiting aberrant mitotic activity and several genes in the network act as therapeutic targets. Development of other inhibitors of mitosis can apply expression values of the genes in the mitotic network from patient tissue to select patients during clinical validation of the new drugs.

Abstract: A myeloid-specific c-fms-rtTA/(TetO)7-CMV-MMP12 bitransgenic mouse model was created. Induction of MMP12 abnormally elevated frequencies and numbers of common myeloid progenitor (CMP) and granulocyte/macrophage progenitor (GMP) populations, and decreased the frequency and number of the megakaryocyte/erythrocyte progenitor (MEP) population in bone marrow. CD11b+/Gr-1+ immature cell population increased in multiple organs. An immunosuppressive function on T cell proliferation and function by CD11b+/Gr-1+ immature cells was seen in vitro and in vivo from MMP12 over-expression. MMP12 stimulated (Lin?) progenitor cells to differentiate into CD11b+/Gr-1+ immature cells showing immunosuppression on T cell proliferation and function in vitro. Regulatory T cells were increased. In the lung, concentration of interleukin (IL)-6 was increased, which activated oncogenic signal transducer and increased expression of Stat3 downstream genes in epithelial tumor progenitor cells.

Abstract: Transgenic mammals, cells derived from the animals, and methods of using these to monitor the endoplasmic reticulum (ER) stress response are provided. In some embodiments, the methods allow for monitoring the ER stress response in real time. Some of the methods allow non-invasive in vivo visualization of ER stress response. Also provided are methods of screening molecules and/or treatment conditions for the ability to modulate the ER stress response, methods of treating diseases characterized by ER stress response activity, and methods of detecting the toxicity or therapeutic ratio of molecules that modulate the ER stress response.

Abstract: A transgenic mouse expressing JSRV Env transgene that is operably linked to a surfactant protein C promoter (SPCp) is disclosed. The transgenic mouse is prone to developing a lung tumor and serves as an animal model for human lung carcinoma.

Abstract: A method is described to identify secreted proteins identified with stages of malignancy of cancer. The proteins are initially identified by trapping them with a fluorescent protein containing vector that can insert in any gene. The secreted proteins are initially identified by their fluorescence. Secreted proteins identifying tumors with specific degrees of malignancy are isolated to determine if they can serve as markers of cancer progression.

Abstract: The invention provides mutant or transgenic animals and cells derived from the mutant or transgenic animals, and particularly a transgenic mouse, that is useful, among other things, for the study, prognosis and diagnosis of hematological malignancies, including T-cell acute lymphoblastic leukemia (T-ALL). Methods are provided for using the mouse model or mutant animal cells to assist in the discovery and identification of genes that may promote lymphomagenesis, to prognose and diagnose disease, and to screen for potential therapeutic agents or drugs.

Abstract: The disclosure relates to an endothelin receptor antagonist for use in the prevention or treatment of brain metastases in combination with a cytotoxic chemotherapy agent, radiotherapy or both. The endothelin receptor antagonist may for example be bosentan, macitentan or a mixture of bosentan and macitentan.

Abstract: The present invention describes stem cells and progenitor cells derived from hemangiomas, including testing of angiogenic inhibitors using these cells. The invention as described is useful in providing a process to culture and propagate hemangioma stem cells and generate xenograft models to develop treatments for infantile hemangiomas and other types of vascular lesions.

Abstract: The present invention relates to a non-human transgenic animal whose genome comprises a stably integrated transgenic nucleotide sequence encoding Lysine-specific Demethylase 1 (LSD1) operably linked to a promoter. The invention further concerns methods for generating the non-human animal and its use as a cancer model.

Abstract: The present invention concerns the V617F variant of the protein-tyrosine kinase JAK2, said variant being responsible for Vaquez Polyglobulia. The invention also relates to a first intention diagnostic method for erythrocytosis and thrombocytosis allowing their association with myeloproliferative disorders, or to the detection of the JAK2 V617F variant in myeloproliferative disorders allowing their reclassification in a new nosological group.

Abstract: An in vivo assay for assessing the metastatic potential of cancer cells has been developed. This is a functional assay that also allows for screening of compounds that are selective for metastatic cancer. Metastatic cancer is established in animals by intravenous injection of metastatic cancer cells before treatments are tested. This assay has been used to identify benzimidazoles for the treatment of metastatic prostate cancers. The benzimidazole(s) can be formulated for enteral or parenteral administration. In one embodiment, the compositions are formulated for parenteral administration. Compositions containing a benzimidazole exhibit greater cytotoxicity against cell lines prone to metastasis than against cells lines that are less prone to metastasis in vitro. The benzimidazoles described herein were effective at treating metastatic prostate cancer in bone.

Abstract: The present invention relates to a prostate cancer cell line CNCM deposit number I-4126, the use thereof for preparing resistant prostate cancer cell lines, the resistant prostate cancer cell lines, and the use of these prostate cancer cell lines for screening compounds of interest.

Abstract: The invention relates to a method of selectively expanding human leukemic cells in a non-adult NOD/SCID/IL2rgnull mouse by transplanting a substance containing a leukemic stem cell derived from a human acute myelogenous leukemia patient to the mouse. In addition, the invention relates to screening for a medicament capable of eradicating leukemic stem cell (LSC), consideration of treatment methods suitable for individual patients, identification of a differentially expressed gene and the like, using a mouse with expanded human leukemic cells.

Abstract: Mechanisms regulating cell proliferation stop and differentiation initiation during the development stage of mammalian embryo, and the proteins involved therein, are presented. Differentiation regulators, methods of regulating differentiation, transgenic organisms with loss of expression of the differentiation regulator, and methods of preparing the transgenic organisms, are provided.

Abstract: DCAMKL-1 has been identified as a biomarker for stem cells, as well as cancer stem cells. Methods of detecting the presence of at least one stem cell, methods of isolating stem cells, and methods of inhibiting growth of cancer cells utilizing DCAMKL-1 are disclosed herein.

Abstract: The present invention relates to antagonists/inhibitors of NR2F6 (nuclear orphan receptor receptor Ear2) for the treatment of a disease related to an insufficient immune response. Furthermore, pharmaceutical compositions comprising said antagonists/inhibitors of NR2F6 and a pharmaceutical carrier are comprised. In a further aspect, the present invention provides for a method for identifying immunoaugmenting agents comprising contacting a cell, tissue or a non-human animal comprising a reporter construct for NR2F6-inhibition with a candidate molecule, measuring the reporter signal and selecting a candidate molecule which alters the reporter signal. Furthermore, the present invention relates to the non-human transgenic animals or cells or tissue derived therefrom useful in the provided methods for identifying immunoaugmenting agents.

Abstract: A method for separating tumor cells with lymphotropic metastatic potential from those without lymphotropic metastatic potential in a human carcinoma. Cells of the carcinoma are transplanted in each of a plurality of fresh athymic mice. At least one of the athymic mice which does not develop a palpable tumor at the transplant site is treated to suppress the T-cell independent innate anti-tumor activity of natural killer cells therein. Tumor-forming cells at the transplant site of the treated athymic animal are harvested to obtain a cell line of cells with lymphotropic metastatic potential, which is also tested for the expression of T-lymphocyte associated molecules. Such cells are intimately associated with low or diminished angiogenicity and immunogenicity. The traditional scientific criteria for human cancer cells is re-defined, and therapeutic targets for human cancer cells is re-focused.

Abstract: The present invention provides a rodent animal for studying the molecular mechanisms and physiological processes associated with uncontrolled cell growth, e.g. cancer, and with a modified FGFR4.

Abstract: Methods for restoring a desired pattern of DNA methylation, inducing re-expression of methylation-silenced tumor suppressor genes (TSGs), and/or inhibiting tumorigenicity both in vitro and in vivo in a subject in need thereof by administering an effective amount of one or more miR-29s sufficient to target one or more of DNMT3A and DNMT3B are disclosed.

Abstract: A transgenic animal model for evaluating growth, survival and/or metastasis of xenotransplanted normal or tumor cells or tissue is disclosed, in which a human growth factor, hHGF stimulates growth in vivo of human cells or tissue. A strain of Tg mice on the C3H background that is immunocompromised as a result of a homozygous scid gene has been bred which express a nucleic acid encoding hHGF/SE The ectopically expressed hHGF/SF ligand significantly enhances growth of human tumor cell lines and explanted tumor cells or tissue that express the Met receptor for hHGF. Such animals also have an enlarged normal livers and greater than normal liver regenerative capacity. Any Met-expressing hHGF-dependent human cells, including hepatocytes and various stem cells can survive and grow in such animals.

Abstract: The present invention relates to a method of developing a Tumor Model System. The invention deals with a tumor model system with adhesion deprived cells. This observation provides a new method for primary detection of transformation of adhesion-deprived cells and tumorigenicity. The adhesion-deprived cells are capable of metastasizing at distant sites and the model system includes both the tumor formation and metastasis.

Abstract: The present invention provides methods of detecting cancer using biomarkers.

Abstract: The present invention provides a human triple-negative breast cancer cell line designated DKAT. The DKAT cell line has a marker profile of high expression of Snail-1 and Snail-2 (Slug); and a p53 mutation in exon 8 at codon 273 (CGT>CAT). The present invention further provides methods of using the DKAT cell line.