Abstract: Disclosed herein is a method for maintenance therapy of a PARP inhibitor in treating a subject with gastric cancer (GC) comprising administering to the subject a therapeutic or maintenance effective amount of a PARP inhibitor, wherein the subject had previously received chemotherapy.

Abstract: The transcription factor and tumor suppressor protein p53 is inactivated in many human cancers. Approximately forty percent of cancers carry large amounts of mutated full-length p53 protein with one of over 900 reported single amino acid changes in the p53 core domain that recognizes p53 DNA binding sites. The ability to restore function to these inactive p53 proteins would dramatically improve cancer therapy. Alternative open reading frames that are more easily engineered encode a wild-type p53. The alternative open reading frames are optimized for codon usage and expression of p53 proteins in E. coli, yeast and mammalian cells. The alternative open reading frames may additionally contain mutations that are naturally found in human cancers, substitutions that correspond to polymorphic p53 alleles, or mutations in residues that can be post-translationally modified.

Abstract: The transcription factor and tumor suppressor protein p53 is inactivated in many human cancers. Approximately forty percent of cancers carry large amounts of mutated full-length p53 protein with one of over 900 reported single amino acid changes in the p53 core domain that recognizes p53 DNA binding sites. The ability to restore function to these inactive p53 proteins would dramatically improve cancer therapy. Alternative open reading frames that are more easily engineered encode a wild-type p53. The alternative open reading frames are optimized for codon usage and expression of p53 proteins in E. coli, yeast and mammalian cells. The alternative open reading frames may additionally contain mutations that are naturally found in human cancers, substitutions that correspond to polymorphic p53 alleles, or mutations in residues that can be post-translationally modified.

Abstract: Yeast strains carrying a human wild-type TP53 are employed to select for mutations. The types of mutations can be analyzed genetically as recessive or dominant-negative. The mutational spectrum of dominant-negative TP53 mutants selected in yeast correlates tightly with TP53 mutations found in human cancers. Thus the use of such yeast assays is validated for studying the effects of various agents on human TP53, one of the most important and ubiquitous of human cancer genes. Assays, kits, and constructs are provide which use yeast as a genetic system for making and studying human TP53 mutations. Such assays can be used to develop therapeutic agents, to study putative carcinogens, and to identify other cellular components which interact with p53 and abrogate its activity.

Abstract: Intragenic suppressor mutations of common p53 mutations are able to function in cis and/or trans. These mutations are useful for identifying small molecule drugs which function in a similar fashion. In addition, the mutations themselves may be useful therapeutically, especially if they function in trans. Methods for rapidly obtaining this type of mutant employ a yeast selection system. Cells having both the negative mutation and intragenic suppressor are useful for studying the interactions of the two, in particular in determining the structure of the homotetramers and heterotetramers.

Abstract: Intragenic suppressor mutations of common p53 mutations are able to function in cis and/or trans. These mutations are useful for identifying small molecule drugs which function in a similar fashion. In addition, the mutations themselves may be useful therapeutically, especially if they function in trans. Methods for rapidly obtaining this type of mutant employ a yeast selection system. Cells having both the negative mutation and intragenic suppressor are useful for studying the interactions of the two, in particular in determining the structure of the homotetramers and heterotetramers.

Abstract: Intragenic suppressor mutations of common p53 mutations are able to function in cis and/or trans. These mutations are useful for identifying small molecule drugs which function in a similar fashion. In addition, the mutations themselves may be useful therapeutically, especially if they function in trans. Methods for rapidly obtaining this type of mutant employ a yeast selection system. Cells having both the negative mutation and intragenic suppressor are useful for studying the interactions of the two, in particular in determining the structure of the homotetramers and heterotetramers.

Abstract: Yeast strains carrying a human wild-type TP53 are employed to select for mutations. The types of mutations can be analyzed genetically as recessive or dominant-negative. The mutational spectrum of dominant-negative TP53 mutants selected in yeast correlates tightly with TP53 mutations found in human cancers. Thus the use of such yeast assays is validated for studying the effects of various agents on human TP53, one of the most important and ubiquitous of human cancer genes. Assays, kits, and constructs are provide which use yeast as a genetic system for making and studying human TP53 mutations. Such assays can be used to develop therapeutic agents, to study putative carcinogens, and to identify other cellular components which interact with p53 and abrogate its activity.