Cholesterol Lowering in Cancer Prevention and Therapy

The accumulation of cholesterol in cancer cells and tumor tissues promotes cell growth, proliferation, and migration as well as tumor progression. Cholesterol synthesis is catalyzed by a series of enzymatic reactions. Regulation of these key enzymes can control cholesterol synthesis and modulate cellular cholesterol levels in the cells. Meanwhile, controlling cholesterol transportation, absorption, and depletion could also significantly reduce cellular cholesterol levels. The current evidence supports that cholesterol lowering agents, beyond the expected cholesterol-lowering properties, also display an important anticancer activity in reducing cancer cell growth, proliferation and migration, and inducing apoptosis in a variety of cancer cells. Understanding the mechanisms of cholesterol metabolism and cholesterol lowering could potentially benefit cancer patients in cancer prevention and treatment

Critical Transition in Tissue Homeostasis Accompanies Murine Lung Senescence

BACKGROUND: Respiratory dysfunction is a major contributor to morbidity and mortality in aged populations. The susceptibility to pulmonary insults is attributed to "low pulmonary reserve", ostensibly reflecting a combination of age-related musculoskeletal, immunologic and intrinsic pulmonary dysfunction. METHODS/PRINCIPAL FINDINGS: Using a murine model of the aging lung, senescent DBA/2 mice, we correlated a longitudinal survey of airspace size and injury measures with a transcriptome from the aging lung at 2, 4, 8, 12, 16 and 20 months of age. Morphometric analysis demonstrated a nonlinear pattern of airspace caliber enlargement with a critical transition occurring between 8 and 12 months of age marked by an initial increase in oxidative stress, cell death and elastase activation which is soon followed by inflammatory cell infiltration, immune complex deposition and the onset of airspace enlargement. The temporally correlative transcriptome showed exuberant induction of immunoglobulin genes coincident with airspace enlargement. Immunohistochemistry, ELISA analysis and flow cytometry demonstrated increased immunoglobulin deposition in the lung associated with a contemporaneous increase in activated B-cells expressing high levels of TLR4 (toll receptor 4) and CD86 and macrophages during midlife. These midlife changes culminate in progressive airspace enlargement during late life stages. CONCLUSION/SIGNIFICANCE: Our findings establish that a tissue-specific aging program is evident during a presenescent interval which involves early oxidative stress, cell death and elastase activation, followed by B lymphocyte and macrophage expansion/activation. This sequence heralds the progression to overt airspace enlargement in the aged lung. These signature events, during middle age, indicate that early stages of the aging immune system may have important correlates in the maintenance of tissue morphology. We further show that time-course analyses of aging models, when informed by structural surveys, can reveal nonintuitive signatures of organ-specific aging pathology

Cholesterol Lowering Therapies and Drugs

Using natural products and developing pharmaceutical drugs are emerging topics to reduce blood cholesterol levels for preventing heart disease and stroke. Covering recent progresses in cholesterol-lowering drugs and therapy, this book describes the natural and pharmaceutical products that are in clinical uses to lower cholesterol and lipids and compares these drugs in responses to different diseases such as homozygous familial hypercholesterolemia, atherosclerosis, cardiovascular disease, and cancer. The relationship between ethnicity and cholesterol-lowering drug responses is also reviewed. Each chapter is a building block for the book, but each individual chapter is also a complete subject package for the readers. Researchers from basic and clinic science interested in lipid and cholesterol metabolism, regulation, and lowering will find this book very useful. Features: - Up-to-date information of the molecular mechanisms of cholesterol lowering, the drugs from natural and pharmaceutical products, and their associated therapeutic strategies in human diseases. - Discussion of the pathogenesis of several human diseases, which are associated with high cholesterol levels and evaluation of the results of different cholesterol-lowering drug treatment in these diseases. - Discussion of the combinations of cancer chemotherapy and cholesterol lowering in potential cancer treatment and cancer prevention by cholesterol-lowering drugs. - Critical analysis of the effect of ethnicity on responses to cholesterol-lowering drug therapy leading to rational dose adjustment of cholesterol-lowering drugs for different people use

Lipid Metabolism, Apoptosis and Cancer Therapy

Lipid metabolism is regulated by multiple signaling pathways, and generates a variety of bioactive lipid molecules. These bioactive lipid molecules known as signaling molecules, such as fatty acid, eicosanoids, diacylglycerol, phosphatidic acid, lysophophatidic acid, ceramide, sphingosine, sphingosine-1-phosphate, phosphatidylinositol-3 phosphate, and cholesterol, are involved in the activation or regulation of different signaling pathways. Lipid metabolism participates in the regulation of many cellular processes such as cell growth, proliferation, differentiation, survival, apoptosis, inflammation, motility, membrane homeostasis, chemotherapy response, and drug resistance. Bioactive lipid molecules promote apoptosis via the intrinsic pathway by modulating mitochondrial membrane permeability and activating different enzymes including caspases. In this review, we discuss recent data in the fields of lipid metabolism, lipid-mediated apoptosis, and cancer therapy. In conclusion, understanding the underlying molecular mechanism of lipid metabolism and the function of different lipid molecules could provide the basis for cancer cell death rationale, discover novel and potential targets, and develop new anticancer drugs for cancer therapy

Annealing Response of a Cold-Rolled Binary Al–10Mg Alloy

The effect of annealing temperature on microstructure and mechanical properties of a cold-rolled Al–10Mg alloy has been investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), electron backscatter diffraction (EBSD) and tensile testing. The results showed that supersaturated Mg precipitated along grain boundaries and deformation bands during annealing treatment and precipitation size and the concentration of solid solution Mg atoms increased with the rising of annealing temperature. When annealed at low temperature, accumulation and annihilation of dislocations were the primary way of recovery; as temperature increased to 300 °C, recrystallized grains were formed around the large size β phase through particle-stimulated nucleation. A high ultimate strength (550 MPa) and a middle ductility (14%) were obtained when the Al–10Mg alloy was annealed at 200 °C for 1 h. The abnormal decrease of elongation when the Al–10Mg alloy was annealed at 250–300 °C was due to the formation of a continuous network distribution of large size β phase particles along grain boundaries