https://cancerbiologyprogram.med.wayne.edu/pdfs/hallmarks_cancer_article.pdf

Hallmarks of cancer: the next generation.

Global strategy for asthma management and prevention

http://aiocm.org/member/Immunity,%20Inflammation,%20and%20Cancer.pdf

Immunity, Inflammation, and Cancer

p53, the Cellular Gatekeeper for Growth and Division

Apoptosis - the regulated destruction of a cell - is a complicated process. The decision to die cannot be taken lightly, and the activity of many genes influence a cell's likelihood of activating its self-destruction programme. Once the decision is taken, proper execution of the apoptotic programme requires the coordinated activation and execution of multiple subprogrammes. Here I review the basic components of the death machinery, describe how they interact to regulate apoptosis in a coordinated manner, and discuss the main pathways that are used to activate cell death.

The biochemistry of apoptosis

Methods for screening for modulators of autophagy are disclosed. Methods for identifying genes whose expression inhibits autophagy, as well as genes whose expression promotes autophagy, are disclosed. Also disclosed are methods for identifying compounds that stimulate autophagy, as well as compounds that inhibit autophagy. Cell lines that may be used in the methods of identification are also disclosed.

Therapeutic modulation of autophagy

The DNA tumor virus adenovirus infects human cells, recruits them into a proliferative state, and borrows elements of the host cell transcription, translation, and DNA replication machinery to reproduce viral proteins and DNA. In rodent cells which are semipermissive for adenovirus infection, cell growth is deregulated but virus replication is ineffective. As the viral infection does not progress to completion, the deregulation of cell growth control produces transformation. The viral genes required for oncogenic transformation are the E1A and E1B oncogenes.

Regulation of Apoptosis by the Transforming Gene Products of Adenovirus

Significance Autophagy defects are a risk factor for inflammatory bowel diseases (IBDs), but the mechanism remains unknown. We show here that conditional whole-body deletion of Atg5 or Fip200, but not Atg7, is lethal due to loss of ileum stem cells and barrier function likely caused by different kinetics of autophagy loss, which was rescued by slow deletion. Specific autophagy loss in PDGFRα+ mesenchymal cells (PMCs) resulted in loss of Wnt signaling responsible for failed stem cell renewal. We also observed depletion of aspartate and nucleotides throughout the ileum. Our results illustrate that autophagy is required for PMC metabolism and survival necessary to sustain intestinal stem cells and mouse survival, and failure to maintain PMCs through autophagy contributes to IBD.

Autophagy in PDGFRα+ mesenchymal cells is essential for intestinal stem cell survival

Chemotherapy and androgen ablation therapy are only temporarily effective against prostate cancer, and current studies are ongoing to test agents that target proteins responsible for autocrine and paracrine stimulated growth. Given limitations of current laboratory models to test the effect of these agents on cell growth and protein targets, we developed a coculture model that can distinguish paracrine stimulated growth and effects on proteins. We found that LNCaP prostate cancer cells and an immortalized rat prostate cell line transfected to overexpress the antiapoptotic resistance protein Bcl-2 were stimulated to grow (>2-fold increase, p < 0.01) through autocrine effects from additional cells in an upper chamber of our system. Using a proteomic approach with a two-dimensional differential in gel electrophoresis method to increase fidelity, four proteins were found to increase after autocrine induced growth stimulation. These proteins were all identified by mass spectrometry as enzymes in the glycolytic pathway, validating the ability of this system to detect both clonogenic growth and the effect on proteins. These data, therefore, demonstrate a novel coculture model for further study of agents that target proteins in pathways of paracrine or autocrine stimulated cell growth.

/pdf/a-novel-proteomic-coculture-model-of-prostate-cancer-cell-4ljj6esbtp.pdf

A novel proteomic coculture model of prostate cancer cell growth.

Macroautophagy (autophagy hereafter) captures and degrades intracellular proteins and organelles in lysosomes as a quality control mechanism and recycles their components to sustain survival in starvation. Cellular self-cannibalization by autophagy is thought to have a context-dependent role in cancer. Autophagy inactivation is destructive to normal tissues and can promote cancer initiation while some established cancers upregulate autophagy that promotes their survival. We are only beginning to understand the role of autophagy in cancer and the precise mechanisms behind tumour suppression and promotion and the molecular and physiological contexts involved.

/pdf/q-a-targeting-autophagy-in-cancer-a-new-therapeutic-3ogpuu7h5u.pdf

Eileen White

Papers

Therapeutic modulation of autophagy

Regulation of Apoptosis by the Transforming Gene Products of Adenovirus

Autophagy in PDGFRα+ mesenchymal cells is essential for intestinal stem cell survival

A novel proteomic coculture model of prostate cancer cell growth.

Q&A: targeting autophagy in cancer-a new therapeutic?