The present invention provides methods and compositions that use a polypeptide that includes a methyl-CpG-binding domain to capture and isolate methylated DNA from a sample.

In accordance with the invention, a novel gene translocation, (4p15, 6q22), in human non-small cell lung carcinoma (NSCLC) that results in a fusion proteins combining part of Sodium-dependent Phosphate Transporter Isoform NaPi-3b protein (SLC34A2) with Proto-oncogene Tyrosine Protein Kinase ROS Precursor (ROS) kinase has now been identified. The SLC34A2-ROS fusion protein is anticipated to drive the proliferation and survival of a subgroup of NSCLC tumors. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ROS kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of the new fusion protein enables new methods for determining the presence of these mutant ROS kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.

Provided herein are methods for treating cancer in a patient who has been determined to have positive expression of CD200 receptor (CD200R1) and one or more biomarkers (i.e., ICOS, TIGIT, TNFRSF9, HAVCR2, PDCD1, FCGR2A, FCGR1A, CD163, and/or CD14) by administering to the patient a CD200 inhibitor. Also provided are methods for monitoring responsiveness of a patient having cancer to treatment with a CD200 inhibitor, the method comprising: determining expression levels of CD200R1 and one or more biomarkers (i.e., ICOS, TIGIT, TNFRSF9, HAVCR2, PDCD1, FCGR2A, FCGR1A, CD163, and/or CD14) in a biological sample from the patient, wherein increased expression levels of CD200R1 and the one or more biomarkers, as compared to expression levels in a biological sample of the same type obtained from the subject prior to treatment with the CD200 inhibitor, indicates that the subject is responsive to treatment with the CD200 inhibitor.

Disclosed are compounds having formula (1): ##STR00001##
or a pharmaceutically acceptable salt, ester, amide, solvate, or stereoisomer thereof, wherein L, Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4, Y.sup.5, Z.sup.1, Z.sup.2, Z.sup.3, Z.sup.4, Z.sup.5, Z.sup.6 are each as defined in the specification; compositions thereof; uses thereof; and methods of use thereof.

The present invention relates to a method of screening for a cancer therapeutic agent using Cyclin B1, Cyclin-dependent kinase 1 (CDK1), and retinoic acid receptor responder 1 (RARRES1), and a composition for diagnosing cancer or predicting a prognosis using the same. As a result of having conducted intensive studies to discover molecular mechanisms for diagnosing cancer and predicting a prognosis, the inventors of the present invention confirmed that in cancer-derived samples, according to the degree of mutual binding between RARRES1 and CDK1 or Cyclin B1, the mitosis of cancer cells was arrested, the formation of CDK1-Cyclin B1 complexes was suppressed, and the degradation of these proteins was promoted, and thus RARRES1 was a crucial factor in the diagnosis of cancer, prognosis prediction, and the treatment of cancer. In addition, through these findings, it is anticipated that RARRES1 may be widely used in screening for a cancer therapeutic agent exhibiting a decrease in the degree of binding between CDK1 and Cyclin B1, an increase in the degree of binding between the RARRES1 gene and CDK1 or Cyclin B1, and a decrease in an amount or activity of the CDK1 protein or the Cyclin B1 protein, and in the development of drugs. In addition, the present invention relates to a targeting vector including a portion of the Rarres1 gene and sequences used in producing a conditional knockout animal model, an animal cell for producing a tumorigenic animal model, which is produced using the targeting vector, a tumorigenic Rarres1.sup.−/− animal model produced using the animal cell, a method of producing the animal model, and a method of screening for a cancer therapeutic agent by using the method. Thus, as a result of having conducted intensive studies to discover molecular mechanisms for diagnosing cancer and predicting a prognosis, the inventors of the present invention confirmed that a Rarres1.sup.−/− animal model was prone to spontaneous tumors and exhibited increased phosphorylation of CDK1 and Cyclin B1 and a high activity of a CDK1-Cyclin B1 complex, and thus it was confirmed that the tumor cell cycle progression was unusually rapid due to a decrease in protein degradation ability. In particular, it was confirmed that stem cell proliferation was increased, and chromosomes were unstable upon induction of mitotic defects and mitosis, from which it was confirmed that RARRES1 is a crucial factor in diagnosing cancer, predicting a prognosis, and treating cancer. Moreover, it is anticipated that the Rarres1.sup.−/− animal model can be variously used for screening for a cancer therapeutic agent and developing a drug, through the relationship between RARRES1

The present invention relates to utilizing terminal erythroid differentiation (TED) as a biomarker for prognosis and as a therapeutic target in myeloid malignancies, in particular myelodyplastic syndromes. The present invention relates to identifying patients with myelodysplastic syndromes at risk for poor survival/outcomes who would benefit from aggressive treatment, by characterizing their TED profile using protein and gene expression markers and combinations thereof.

Methods are provided for treating a hematologic cancer comprising administering an anticancer agent to a subject identified as having an increased mobilization of a subpopulation of lymphocytes from a malignancy following administration of an irreversible Btk inhibitor. Methods also are provided for identification of subjects for treatment and the analysis of cells mobilized from a hematologic malignancy following administration of an irreversible Btk inhibitor.

This invention relates to agents that bind human Siglecs having inhibitory activity in immune cells, and that neutralize the inhibitory activity of such Siglec. Such agents can be used for the treatment of cancers or infectious disease.

Sarcomas are rare malignant tumors arising from the mesenchymal tissues at all body sites. The inventors show that in a mouse model of p16/p19 deficiency prone to tumor development, the absence of the mouse pantetheinase Vnn1 enhances the frequency of aggressive fibrosarcomas. They also show that reintroduction of a catalytically active form of the Vnn1 pantetheinase limits tumor growth in vivo. Interestingly, VNN1 expression in human sarcomas is associated with reduced aggressiveness and lower risk of metastatic relapse in patients. In conclusion, Vnn1 represents a novel marker of sarcoma and may modulate tumor aggressiveness by sustaining myofibroblast cell differentiation, thereby limiting evolution towards undifferentiated tumors. The present invention relates to the use of Vnn1 as a biomarker and a therapeutic target in sarcomas.

It is therefore the objective of the present invention to provide minigastrin derivates which further improve the accumulation in CCK-2 receptor positive tumours by simultaneously very low accumulation in other organs, e.g. the kidneys. This objective is achieved according to the present invention by a minigastrin derivate having the formula: X-Z-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH.sub.2 (Y), wherein at least one of the connecting or terminal amide bonds between, before or after the amino acids of the sequence Z, Ala, Tyr, Gly, Trp, Met, Asp, Phe and NH.sub.2 or Y (C-terminal) is replaced by a 1,4-disubstituted or a 1,5-disubstituted 1,2,3-triazole, while X stands for a chemical group attached to the peptide for the purpose of diagnostic and/or therapeutic intervention at CCK-2 receptor relevant diseases, Y stands for C-terminal modifications of the peptide, such as amide, primary and secondary amides, free carboxylic acids and carboxylic ester derivatives including but not limited to amides and esters derived from linear or branched alkyl-,alkenyl-, alkynyl- aromatic-, and heterocyclic alcohols, and Z stands for a linker or DGlu* wherein DGlu* stands for a chain of DGlu having 1 to 6 repetitions (-DGlu-to-DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-). These minigastrin derivates have a high specific internalization, excellent IC.sub.50 values and sufficient plasma stability.