Abstract: The present invention regards mutant forms of Bik that comprise anti-cell proliferation and/or pro-apoptotic activities. In particular embodiments, the Bik polypeptides comprise a substitution at Thr33 and Ser35 and, in some embodiments, phosphorylation at these sites is inhibited. In more particular embodiments, these forms are useful for cancer therapy, particularly when administered in combination with liposomes. In embodiments wherein a mutant Bik polynucleotide is administered for cancer therapy, the polynucleotide may be regulated in a tissue-specific manner.

Abstract: Methods of determining prognosis in a subject with a hyperproliferative disease, including determining expression and/or function of 14-3-3 zeta in the subject, are disclosed. Also disclosed are methods of making a pharmaceutical agent that modulates apoptosis, including the steps of obtaining one or more candidate, testing the one or more candidate substances to determine their ability to modulate the expression and/or function of 14-3-3 zeta, selecting a candidate substance determined to modulate the expression and/or function of 14-3-3 zeta, and making a pharmaceutical composition that includes the selected candidate substance. In addition, methods of treating a subject with a hyperproliferative disease, including making a pharmaceutical agent by the methods set forth herein, and administering the pharmaceutical agent to a subject, are disclosed. The hyperproliferative disease can be cancer, such as breast cancer.

Abstract: The present invention regards cancer-specific control sequences that direct expression of a polynucleotide encoding a therapeutic gene product for treatment of the cancer. Specifically, the invention encompasses breast cancer-, prostate cancer-, and pancreatic cancer-specific control sequences. Two breast cancer-specific sequences utilize specific regions of topoisomerase II? and transferrin receptor promoters, particularly in combination with an enhancer. The prostate cancer-specific and pancreatic cancer-specific control sequences utilize composites of tissue-specific control sequences, a two-step transcription amplification sequence, and a post-transcriptional control sequence. In more particular embodiments, these polynucleotides are administered in combination with liposomes.

Abstract: Methods of determining prognosis in a subject with a hyperproliferative disease, including determining expression and/or function of 14-3-3 zeta in the subject, are disclosed. Also disclosed are methods of making a pharmaceutical agent that modulates apoptosis, including the steps of obtaining one or more candidate, testing the one or more candidate substances to determine their ability to modulate the expression and/or function of 14-3-3 zeta, selecting a candidate substance determined to modulate the expression and/or function of 14-3-3 zeta, and making a pharmaceutical composition that includes the selected candidate substance. In addition, methods of treating a subject with a hyperproliferative disease, including making a pharmaceutical agent by the methods set forth herein, and administering the pharmaceutical agent to a subject, are disclosed. The hyperproliferative disease can be cancer, such as breast cancer.

Abstract: The present invention is directed to compositions comprising an angiogenesis inhibitor coupled to a therapeutic or diagnostic agent. In a specific embodiment, the composition is a fusion gene or fusion gene product encoding the angiogenesis inhibitor coupled to a therapeutic or diagnostic agent. In a particular embodiment, the composition is used for methods to treat angiogenesis-related diseases, such as cancer.

Abstract: The present invention relates to methods for the inhibition, of the gene product of the neu oncogene, p185neu tyrosine kinase. Over-expression of the neu oncogene leads to chemoresistance. The methods disclosed involve the novel use of E1A and/or LT in combination with chemotherapeutic drugs to treat carcinoma. Furthermore, E1A surprisingly potentiates the antineoplastic effects of the chemotherapeutic agents. The inventors propose that E1A sensitizes cancer cells such that they become amenable to treatment by chemotherapeutic drugs.

Abstract: The present invention regards cancer-specific control sequences that direct expression of a polynucleotide encoding a therapeutic gene product for treatment of the cancer. Specifically, the invention encompasses breast cancer-, prostate cancer-, and pancreatic cancer-specific control sequences. Two breast cancer-specific sequences utilize specific regions of topoisomerase II? and transferrin receptor promoters, particularly in combination with an enhancer. The prostate cancer-specific and pancreatic cancer-specific control sequences utilize composites of tissue-specific control sequences, a two-step transcription amplification sequence, and a post-transcriptional control sequence. In more particular embodiments, these polynucleotides are administered in combination with liposomes.

Abstract: The present invention regards IFIX proteins, polypeptides, peptides, and the polynucleotides that encode them. In particular embodiments, the IFIX proteins, polypeptides, and/or peptides comprise tumor suppressive, anti-cell proliferative pro-apoptotic and/or cell cycle arrest-inducing activities. In more particular embodiments, these forms are useful for cancer therapy, particularly when administered in combination with liposomes.

Abstract: Methods of determining prognosis in a subject with a hyperproliferative disease, including determining expression and/or function of 14-3-3 zeta in the subject, are disclosed. Also disclosed are methods of making a pharmaceutical agent that modulates apoptosis, including the steps of obtaining one or more candidate, testing the one or more candidate substances to determine their ability to modulate the expression and/or function of 14-3-3 zeta, selecting a candidate substance determined to modulate the expression and/or function of 14-3-3 zeta, and making a pharmaceutical composition that includes the selected candidate substance. In addition, methods of treating a subject with a hyperproliferative disease, including making a pharmaceutical agent by the methods set forth herein, and administering the pharmaceutical agent to a subject, are disclosed. The hyperproliferative disease can be cancer, such as breast cancer.

Abstract: The present invention regards mutant forms of Bik that comprise anti-cell proliferation and/or pro-apoptotic activities. In particular embodiments, the Bik polypeptides comprise a substitution at Thr33 and Ser35 and, in some embodiments, phosphorylation at these sites is inhibited. In more particular embodiments, these forms are useful for cancer therapy, particularly when administered in combination with liposomes. In embodiments wherein a mutant Bik polynucleotide is administered for cancer therapy, the polynucleotide may be regulated in a tissue-specific manner.

Abstract: The invention relates to methods of determining a relative probability of survival for a subject with squamous cell carcinoma by obtaining a biological sample from a subject with squamous cell carcinoma; detecting a level of maspin gene expression in the biological sample; and comparing the level with a threshold level of maspin gene expression. A level of maspin gene expression in the biological sample above the threshold level indicates a relatively high probability of survival, or a level of maspin gene expression in the biological sample below the threshold level indicates a relatively low probability of survival.

Abstract: The present invention relates to methods for the inhibition, of the gene product of the neu oncogene, p185neu tyrosine kinase. Over-expression of the neu oncogene leads to chemoresistance. The methods disclosed involve the novel use of E1A and/or LT in combination with chemotherapeutic drugs to treat carcinoma. Furthermore, E1A surprisingly potentiates the antineoplastic effects of the chemotherapeutic agents. The inventors propose that E1A sensitizes cancer cells such that they become amenable to treatment by chemotherapeutic drugs.

Abstract: The present invention provides methods and compositions for the suppression of oncogenic transformation, tumorigenesis and metastasis. The present invention discloses functional domains of E1A responsible for the suppression of transformation, and provides mini-E1A constructs that can be used for tumor suppression. The invention also discloses methods for the novel use of mini-E1A in combination with chemotherapeutic drugs and/or tyrosine kinase inhibitors.

Abstract: The present invention is directed to compositions comprising an angiogenesis inhibitor coupled to a therapeutic or diagnostic agent. In a specific embodiment, the composition is a fusion gene or fusion gene product encoding the angiogenesis inhibitor coupled to a therapeutic or diagnostic agent. In a particular embodiment, the composition is used for methods to treat angiogenesis-related diseases, such as cancer.

Abstract: The present invention is directed to methods and compositions for cancer therapy, particularly cancers resulting from a defective Wnt/&bgr;-catenin signaling pathway. In specific embodiments, a T-cell factor (Tcf)-responsive promoter regulating expression of a therapeutic gene is administered to an individual having the cancer. In a specific embodiment, the Tcf-responsive promoter comprises a minimal CMV promoter and is present on an adenovirus vector. The promoter regulates expression of a therapeutic gene.

Abstract: The present invention is directed to the pro-apoptotic bok gene product that provides antitumor activity, particularly through induction of apoptosis. In some embodiments of the present invention, Bok is utilized for ovarian cancer, among others, and the composition can be delivered by either viral or non-viral delivery methods.

Abstract: Methods and compositions regarding the prevention of ER-positive cancer and the treatment of ER-positive HER-2/neu-negative breast cancer are disclosed. Compositions exhibiting both tyrosine kinase inhibitor activity and anti-estrogen receptor activity are useful in the cancer treatment.

Abstract: The present invention relates generally to the fields of cancer therapy and gene therapy. More particularly, it demonstrates that PEA3, as exemplified by mPEA3 and hPEA3, is a tumor suppressor and may be used to treat various forms of cancer, for example neu- or ras-mediated cancers.

Abstract: Disclosed are methods and compositions regarding separate mutant forms of p21Cip1/WAF1 that are associated with control of cell growth. Substitution of Thr145 with another amino acid, such as Ala, results in failure to be phosphorylated at that site and leads to retention of the polypeptide in the nucleus, resulting in preferentially suppressing growth of transformed cells. Alternatively, substitution of Thr145 with another amino acid, such as Asp, results in cytoplasmic translocation of the polypeptide and results in enhancing cellular survival.

Abstract: Cyclin D1 is one of the targets of &bgr;-catenin in breast cancer cells. Transactivation of &bgr;-catenin correlated significantly with cyclin D1 expression both in eight breast cell lines in vitro and in 123 patient samples. More importantly, high &bgr;-catenin activity significantly correlated with poor prognosis of the patients and is a strong and independent prognostic factor in breast cancer (p<0.001). Moreover, by multivariate analyses, the inventors found that activated &bgr;-catenin is a strong prognostic factor which provided additional and independent predictive information on patients survival rate even when other prognostic factors, including lymph node metastasis, tumor size, estrogen receptor and progesterone receptor status, were taken into account (p<0.001). This invention demonstrates that &bgr;-catenin is involved in breast cancer formation and/or progression and may serve as a target for breast cancer therapy.