The success of tissue engineering applications can potentially be dramatically improved with the addition of adjuncts that increase the proliferation and differentiation of progenitor or stem cells. Platelet-rich plasma (PRP) has recently emerged as a potential biologic tool to treat acute and chronic tendon disorders. The regenerative potential of PRP is based on the release of growth factors that occurs with platelet rupture. Its autologous nature gives it a significant advantage in tissue engineering applications. To test whether PRP may be useful specifically for cartilage regeneration, a cell culture experiment was devised in which mesenchymal stem cells (MSCs) were grown in control media or media enhanced with inactivated, buffered PRP. Proliferation 7 days after PRP treatment was increased: 1.041 versus 0.199 for the control media cells ( p < 0.001). The messenger RNA (mRNA) level of the osteogenic marker RUNX2 was 52.84 versus 26.88 for the control group ( p < 0.005). Likewise the mRNA level of the chondrogenic markers Sox-9 and aggrecan was 29.74 versus 2.29 for the control group ( p < 0.001) and 21.04 versus 1.93 ( p < 0.001), respectively. These results confirm that PRP enhances MSC proliferation and suggest that PRP causes chondrogenic differentiation of MSC in vitro.

BackgroundLiposomal formulations of anthracyclines appear to have favorable toxicity profile when compared with conventional anthracyclines in elderly, high risk cardiac patients and patients with prior use of anthracyclines. Randomized controlled trials have evaluated the efficacy and safety profile of liposomal formulations with conventional anthracyclines. Our aim is to evaluate the adverse effects and quantify the relative safety profile of the liposomal and conventional anthracyclines through meta-analysis of the published randomized trials.MethodsWe conducted a broad search strategy of major electronic databases. We performed a meta- analysis of adverse effects on randomized controlled trials comparing liposomal formulation and conventional anthracyclines on different tumors. The primary outcome was the adverse effects including congestive heart failure (CHF), hematological toxicity, palmar-plantar erythrodysthesias (PPE), alopecia, nausea and vomiting. The odds ratios of the adverse effects were calculated separately and the overall odds ratio of the pooled data was calculated.ResultsWe identified nine randomized controlled trials comparing liposomal formulations and conventional anthracyclines. The study included 2220 patients, of which1112 patients were treated with liposomal formulations and 1108 were treated with conventional anthracyclines. We found that the liposomal formulations have low incidence of CHF(OR 0.34, 95% CI, 0.24–0.47), alopecia (OR 0.0.25, 95% CI, 0.0.10-0.62), neutropenia (OR 0.62, 95% CI, 0.45- 0.85),(OR 0.89, 95% CI, 0.71-1.125), and thrombocytopenia (OR 0.87, 95% CI, 0.61-1.25). The incidence of PPE was similar in both arms (OR 1.08, 95% CI, 0.11- 10.30).ConclusionsLiposomal doxorubicin and pegylated liposomal doxorubicin demonstrated favorable toxicity profiles with better cardiac safety and less myelosuppression, alopecia, nausea and vomiting compared with the conventional anthracyclines. The better therapeutic index of liposomal anthracyclines without compromising the efficacy makes it a favorable choice over conventional anthracyclines in elderly patients, patients with risk factors for cardiac disease and patients with prior use of anthracyclines.

JAK-STAT (Janus associated kinase-signal transducer and activator of transcription) pathway plays a critical role in transduction of extracellular signals from cytokines and growth factors involved in hematopoiesis, immune regulation, fertility, lactation, growth and embryogenesis. JAK family contains four cytoplasmic tyrosine kinases, JAK1-3 and Tyk2. Seven STAT proteins have been identified in human cells, STAT1-6, including STAT5a and STAT5b. Negative regulators of JAK–STAT pathways include tyrosine phosphatases (SHP1 and 2, CD45), protein inhibitors of activated STATs (PIAS), suppressors of cytokine signaling (SOCS) proteins, and cytokine-inducible SH2-containing protein (CIS). Dysregulation of JAK-STAT pathway have been found to be key events in a variety of hematological malignancies. JAK inhibitors are among the first successful agents reaching clinical application. Ruxolitinib (Jakafi), a non-selective inhibitor of JAK1 & 2, has been approved by FDA for patients with intermediate to high risk primary or secondary myelofibrosis. This review will also summarize early data on selective JAK inhibitors, including SAR302503 (TG101348), lestaurtinib (CEP701), CYT387, SB1518 (pacritinib), LY2784544, XL019, BMS-911543, NS-018, and AZD1480.