The mechanisms by which polyamines accelerate tumor spread

Increased polyamine concentrations in the blood and urine of cancer patients reflect the enhanced levels of polyamine synthesis in cancer tissues arising from increased activity of enzymes responsible for polyamine synthesis. In addition to their de novo polyamine synthesis, cells can take up polyamines from extracellular sources, such as cancer tissues, food, and intestinal microbiota. Because polyamines are indispensable for cell growth, increased polyamine availability enhances cell growth. However, the malignant potential of cancer is determined by its capability to invade to surrounding tissues and metastasize to distant organs. The mechanisms by which increased polyamine levels enhance the malignant potential of cancer cells and decrease anti-tumor immunity are reviewed. Cancer cells with a greater capability to synthesize polyamines are associated with increased production of proteinases, such as serine proteinase, matrix metalloproteinases, cathepsins, and plasminogen activator, which can degrade surrounding tissues. Although cancer tissues produce vascular growth factors, their deregulated growth induces hypoxia, which in turn enhances polyamine uptake by cancer cells to further augment cell migration and suppress CD44 expression. Increased polyamine uptake by immune cells also results in reduced cytokine production needed for anti-tumor activities and decreases expression of adhesion molecules involved in anti-tumor immunity, such as CD11a and CD56. Immune cells in an environment with increased polyamine levels lose anti-tumor immune functions, such as lymphokine activated killer activities. Recent investigations revealed that increased polyamine availability enhances the capability of cancer cells to invade and metastasize to new tissues while diminishing immune cells' anti-tumor immune functions

Electrospinning Applications in Bioengineering: Fabrication of Bio-Engineered Skeletal Muscle

The objective of this study is to develop a skeletal muscle prosthetic composed entirely of natural or otherwise bioresorbable materials that recapitulates the structure and function of intact muscle. in our fabrication strategy we begin by electrospinning (see Mathews et al., this volume) a hollow, cylindrical fascial sheath composed of poly-glycolic acid (PGA), poly-lactic acid (PLA), Type I collagen microfibers or a blend of these materials (figure 1). The resulting fascial sheath is a highly porous fabric composed of interwoven fibers that range from less than 1 micron to 2-5 microns in diameter (patents pending). Next, we isolate neonatal rat skeletal myoblasts by enzymatic dissociation. The dissociated tissue is subjected to an interval of differential adhesion to enrich the preparation in skeletal muscle myoblasts. The final cell pellet of myoblasts is then suspended at high density in Type I collagen. This suspension is polymerized at 37°C for 10-15 minutes and used to fill a fascial sheaths (patents pending).</jats:p