Hannan R.D.,Peter MacCallum Cancer Center |
Hannan R.D.,University of Melbourne |
Hannan R.D.,Monash University |
Hannan R.D.,University of Queensland |
And 4 more authors.
Expert Opinion on Therapeutic Targets | Year: 2013
The nucleoli are the site of the production of ribosomes, the protein synthetic apparatus of the cell. The presence of enlarged nucleoli, reflecting increased ribosomal gene transcription, has long been used by pathologists as an indicator of aggressive tumors. However, over the last 10 years a growing body of evidence has revealed that the nucleolus contains a dynamic cohort of over 4500 proteins, the majority of which have no function in ribosome production. The activity of some of these proteins is modulated by their regulated sequestration and release from the nucleolus. In particular, the nucleolus plays a central role in sensing cellular stress to modulate the abundance of the critical tumor suppressor protein p53. The finding that p53 activity is dysregulated in up to 50% of all human cancers highlights the importance of the nucleolar stress response in limiting malignant transformation. The development of drugs to selectively inhibit transcription of the ribosomal RNA genes in the nucleolus has paved the way for a new therapeutic approach to hijack nucleolar stress to selectively and non-genotoxically activate p53 in tumor cells. Here, we describe the potential application of this exciting new class of drugs for the treatment of human cancer. © Informa UK, Ltd. Source
Cornerstone Pharmaceuticals Inc. | Date: 2013-12-19
Therapeutically-effective amounts of novel analogs or derivatives of alkyl fatty, acids, such as but not limited to lipoic acid, and pharmaceutical formulations comprising such analogs or derivatives and pharmaceutically-acceptable carriers therefor, are useful for the treatment, prevention, imaging, and/or diagnosis of medical disorders.
Cornerstone Pharmaceuticals Inc. | Date: 2014-06-25
Lipoic acid derivatives and pharmaceutical formulations containing lipoic acid derivatives are useful in the treatment and prevention of disease characterized by disease cells that are sensitive to lipoic acid derivatives.
Cornerstone Pharmaceuticals Inc. | Date: 2014-03-27
Lee K.C.,Cornerstone Pharmaceuticals Inc. |
Lee K.C.,Quinnipiac University |
Maturo C.,Cornerstone Pharmaceuticals Inc. |
Rodriguez R.,Cornerstone Pharmaceuticals Inc. |
And 2 more authors.
Journal of Nanoscience and Nanotechnology | Year: 2011
Paclitaxel is an important anticancer drug and is currently used to treat a variety of cancers, including ovarian carcinomas, breast cancer, non-small cell lung cancer, and AIDS-related Kaposi's sarcoma. The objectives of the studies were to assess and compare the safety and efficacy of EmPAC™ (a newly developed nanoemulsion formulation of paclitaxel) versus Taxol® (the injectable formulation of paclitaxel involving the use of polyethylated or polyoxyl castor oil currently used in the clinic). The objectives were also to investigate the mechanism for the improved safety and efficacy of EmPAC over Taxol. These results showed that EmPAC had better anti-tumor efficacy than Taxol, according to in vitrocell culture studies and studies in animal tumor models. EmPAC had improved anti-tumor efficacy even in tumor cell lines that are known to be multi-drug resistant. Part of the mechanism of action for the improved efficacy may be related to EmPAC inducing greater cellular uptake of paclitaxel into tumor cells than Taxol did, according to the in vitro cell culture radioactive-labeled studies and in vitro cell culture antibody studies. It may also partly be because EmPAC delivered more paclitaxel to the tumor mass than Taxol, while the delivery of paclitaxel to other tissues (e.g., blood, muscle, liver, spleen, kidney and lung) were similar between the two formulations of paclitaxel, according to studies in animals with tumor xenograft. EmPAC also had better safety than Taxol according to toxicology studies in rabbits. This may be because EmPAC does not contain the toxic ingredients used in formulating Taxol (such as polyethylated or polyoxyl castor oil). These results support the clinical development of the nanoemulsion formulation of paclitaxel. © 2011 American Scientific Publishers. Source