Sulfur, after calcium and phosphorus, is the most abundant mineral element found in our body. It is available to us in our diets, derived almost exclusively from proteins, and yet only 2 of the 20 amino acids normally present in proteins contains sulfur. One of these amino acids, methionine, cannot be synthesized by our bodies and therefore has to be supplied by the diet. Cysteine, another sulfur containing amino acid, and a large number of key metabolic intermediates essential for life, are synthesized by us, but the process requires a steady supply of sulfur.

Background: Demineralized bone matrix is an osteoinductive and osteoconductive material that is often used in orthopaedic surgery to induce bone formation. Autologous platelet-rich plasma, which contains proliferative and chemoattractant growth factors, has been used as a demineralized bone matrix adjuvant with mixed results. One variable during clinical use appears to be whether the platelet-rich plasma is activated with thrombin or is implanted in a liquid form with intact platelets. The objective of the present study was to determine if platelet-rich plasma can increase the osteoinductivity of demineralized bone matrix when used without thrombin activation. Methods: The bioactivity of the demineralized bone matrix was evaluated in vitro by determining alkaline phosphatase production by C2C12 myoblast cells. The effect of thrombin activation on platelet-rich plasma was studied in vitro by evaluating osteosarcoma and bone marrow stromal cells for cell number and transforming growth factor-β1 activation. Demineralized bone matrices supplemented with platelet-rich plasma, with or without thrombin activation, were implanted intramuscularly in athymic rats and were examined at fourteen, twenty-eight, and fifty-six days. Histological samples were analyzed for osteogenesis and chondrogenesis. Osteogenesis was further characterized on the basis of alkaline phosphatase activity. Results: In vitro, thrombin triggered an immediate release of growth factors from the platelet-rich plasma, and the platelet-rich plasma increased the number of both osteosarcoma and stromal cells in a dose-dependent manner. Thrombin activation of the platelet-rich plasma eliminated such stimulatory effects. In vivo, the platelet-rich plasma stimulated chondrogenesis on Day 14 and osteogenesis on Days 28 and 56, whereas thrombin-activated platelet-rich plasma acted as an inhibitor of such events. In addition, inflammatory cells were detected in demineralized bone matrix samples that were mixed with thrombin-activated platelet-rich plasma. These cells were not present in matrix mixed with platelet-rich plasma alone. Conclusions: Platelet-rich plasma significantly increased in vivo demineralized bone matrix osteoinductivity only when used without thrombin activation. Clinical Relevance: Platelet-rich plasma has the potential to increase the osteoinductivity of demineralized bone matrix in clinical applications. On the other hand, its activation by thrombin immediately prior to implantation significantly inhibits this activity.

The heterogeneous and dynamic tumor microenvironment has significant impact on cancer cell proliferation, invasion, drug response, and is probably associated with entering dormancy and recurrence. However, these complex settings are hard to recapitulate in vitro. In this study, we mimic different restriction forces that tumor cells are exposed to using a physiologically relevant 3D model with tunable mechanical stiffness. Breast cancer MDA-MB-231, colon cancer HCT-116 and pancreatic cancer CFPAC cells embedded in the stiffer gels exhibit a changed morphology and cluster formation, prolonged doubling time, and a slower metabolism rate, recapitulating the pathway from competency to dormancy. Altering environmental restriction allows them to re-enter and exit dormant conditions and change their sensitivities to drugs such as paclitaxol and gemcitabine. Cells surviving drug treatments can still regain competent growth and form tumors in vivo. We have successfully developed an in vitro 3D model to mimic the effects of matrix restriction on tumor cells and this high throughput model can be used to study tumor cellular functions and their drug responses in their different states. This all in one platform may aid effective drug development.

We summarize the risk factors that may significantly contribute to racial disparities in pancreatic cancer, which is now the third leading cause of cancer deaths and projected to be second around 2030 in 12 years. For decades, the incidence rate of pancreatic cancer among Blacks has been 30% to 70% higher than other racial groups in the United States and the 5-year survival rate is approximately 5%. Diabetes and obesity have been identified as potentially predisposing factors to pancreatic cancer and both are more common among Blacks. Smoking continues to be one of the most important risk factors for pancreatic cancer and smoking rates are higher among Blacks compared to other racial groups. The overall risk of pancreatic cancer due to changes in DNA is thought to be the same for most racial groups; however, DNA methylation levels have been observed to be significantly different between Blacks and Whites. This finding may underlie the racial disparities in pancreatic cancer. Identification and prevention of these factors may be effective strategies to reduce the high incidence and mortality rates for pancreatic cancer among Blacks.