The present invention relates to a lateral flow test device capable of detecting the presence or absence of unfolded p53 in a liquid sample, such as a blood sample. Also provided are methods of using such a device for quantitative or qualitative measurement of U-p53 in a liquid sample. Detection of the presence of this analyte in the sample identifies if the subject has a risk to develop Alzheimer's Disease, and also is useful to confirm a diagnosis of Alzheimer's disease.

The present invention relates to a method, in particular an in vitro method, for identifying an improved anti-senescence compound based on detecting the binding of said compound in the presence of at least one phosphory lated amino acid in the transcription activation domain (TAD) domain of mammalian protein p53. The present invention further relates to a method, in particular an in vitro method, for monitoring an anti-senescence treatment or prophylaxis in a mammalian subject in need thereof, based on detecting the amount of phosphorylation of amino acids in the TAD and/or C-terminal region of the mammalian p53 protein in a biological sample obtained from said subject and/or detecting the amount and/or co-localization with phosphorylated p53 of the promyelocytic leukemia protein (PML) bodies in a biological sample obtained from said subject. Furthermore, the present invention relates to a kit for performing the above methods as well as respective uses thereof. Finally, improved anti-senescence compounds or pharmaceutical compositions are provided.

Disclosed are fragments of p53 peptide (P1) and their use in the diagnosis and/or prognosis of Alzheimer's disease (AD) in a biological sample. The invention provides a method based on mass spectrometry analysis for the diagnosis of Alzheimer's disease at the pre-clinical and prodromal stages of the disease and for the prognosis of cognitive decline in a subject, by quantitating the levels of one or more p53 peptide fragments in a biological sample of a subject.

The present disclosure discloses a class of nitrogen-containing fused heterocyclic compounds of N-sulfonamide and the use thereof. The nitrogen-containing fused heterocyclic compounds of N-sulfonamide of the present disclosure are compounds of formula I, isotope-labeled compounds thereof, solvates thereof, pharmaceutically acceptable salts thereof, solvates of the pharmaceutically acceptable salts thereof. Such compounds can promote the binding of p53 Y220C mutant with DNA and possess better inhibitory activity against the proliferation of cancer cells.

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Disclosed are isolated or purified T cell receptors (TCRs) having antigenic specificity for human p53.sup.R175H or human p53.sup.Y220C. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

A method of collecting data for diagnosing cancer, determining an onset risk, determining a malignancy grade, and/or predicting a prognosis of cancer according to the present disclosure includes the steps of bringing a sample derived from a subject into contact with tumor-associated antigens to cause an antigen-antibody reaction; measuring an amount of anti-p53 antibody, in the sample, that specifically binds to any of the tumor-associated antigens; and comparing the measured amount of the anti-p53 antibody with a predetermined reference level of the anti-p53 antibody against the tumor-associated antigens. The tumor-associated antigens include one or more p53 isoform variants consisting of amino acid sequences having a mutation in an amino acid sequence of any one of SEQ ID NOs: 1 to 3, and the mutation includes any one of an N-terminal deletion mutation, a C-terminal deletion mutation, and both the N-terminal deletion and the C-terminal deletion mutation.

The present disclosure discloses a class of nitrogen-containing fused heterocyclic compounds of N-sulfonamide and the use thereof. The nitrogen-containing fused heterocyclic compounds of N-sulfonamide of the present disclosure are compounds of formula I, isotope-labeled compounds thereof, solvates thereof, pharmaceutically acceptable salts thereof, solvates of the pharmaceutically acceptable salts thereof. Such compounds can promote the binding of p53 Y220C mutant with DNA and possess better inhibitory activity against the proliferation of cancer cells. ##STR00001##