Macrophages have key roles in tumor development and invasion in several human cancers, but little is known about their pathogenic role in cutaneous T-cell lymphoma (CTCL). Herein, we used PCR arrays to profile the expression of inflammatory cytokines in 12 patients with mycosis fungoides (MF), the most common variant of CTCL. Compared with normal controls, MF skin displayed increased mRNA levels of macrophage-related cytokines. Moreover, we detected CD163, a reliable marker of tumor-associated macrophages, in the tumor microenvironment of MF biopsies. To demonstrate that macrophages had a role in CTCL tumorigenesis, we xenografted human CTCL tumor cells in immunocompromised mice and compared tumor development using clodronate-containing liposomes to deplete macrophages in mice. Mice treated with clodronate-containing liposomes show markedly less tumor growth compared with mice treated with phosphate-buffered saline-containing liposomes (P<0.001). We also noted a strong correlation between macrophage depletion and decreased expression of vascular marker, CD31, and lymphatic marker, podoplanin, suggesting a role for macrophages in angiogenesis. In vitro, clodronate-containing liposomes killed activated murine M2 macrophages, but not Hut78 cells, demonstrating selective ability to induce apoptosis in macrophages. Our data indicate that macrophages have a critical role in the progression of Hut78 cell tumor formation in skin, thus providing a new therapeutic strategy for CTCL.

Although some research in the past has examined how physical limitations in strength or flexibility affect a golfer's performance, the performance outcome most measured was driving distance. Currently, there are no data that have examined the relationship between selected strength and flexibility variables and golf swing faults. The purpose of this study was to examine the relationship between Titleist Performance Institute (TPI) level 1 movement screen variables and 14 common golf swing faults. Thirty-six male and female golfers (mean age, 25.4 ± 9.9 years; height, 175.9 ± 16.2 cm; mass, 76.2 ± 14.6 kg; handicap, 14.2 ± 10.4) participated. Twelve physical tests of strength, flexibility, and balance were assessed using the TPI level 1 golf fitness screening tool. Golfers then hit 4 golf shots (with a 5-iron) while being videoed, and those were then analyzed for 14 different golf swing faults (using V1Pro software). Three significant associations between a physical limitation and a particular golf swing fault were found: toe touch and early hip extension (p = 0.015), bridge on right side with both early hip extension (p = 0.050), and loss of posture (p = 0.028). In addition, an odds ratio showed that when a golfer could not overhead deep squat or single leg balance on left side, they were 2-3 times more likely to exhibit a early hip extension, loss of posture, or slide during the golf swing, as compared with those who could perform a correct overhead deep squat. Based on our findings, it is important for the golf fitness professional to particularly address a golfer's core strength, balance, and hamstring flexibility to help avoid common golf swing faults, which affect a golfer's ball striking ability and ultimately their performance.

BackgroundChimeric antigen receptor (CAR) T-cell therapy is highly effective for treating acute lymphoblastic leukemia and non-Hodgkin’s lymphoma with high rate complete responses. However, the broad clinical application of CAR T-cell therapy has been challenging, largely due to the lack of widespread ability to produce and high cost of CAR T-cell products using traditional methods of production. Automated cell processing in a closed system has emerged as a potential method to increase the feasibility of producing CAR T cells locally at academic centers due to its minimal reliance on experienced labor, thereby making the process less expensive and more consistent than traditional methods of production.MethodIn this study, we describe the successful production of clinical grade CD19 CAR T cells using the Miltenyi CliniMACS Prodigy Automated Cell Processor at University of Colorado Anschutz Medical Campus in a rapid manner with a high frequent CD19 CAR expression.ResultsThe final CAR T-cell product is highly active, low in immune suppression, and absent in exhaustion. Full panel cytokine assays also showed elevated production of Th1 cytokines upon IL-2 stimulation when specifically killing CD19+ target cells.ConclusionThese results demonstrate the feasibility of producing CAR T cells locally in a university hospital setting using automated cell processor for future clinical applications.

The Devonian Duvernay Formation in northwest central Alberta, Canada, has become a hot play in the past few years due to its richness in liquid and gaseous hydrocarbon resources. The oil and gas generation in this shale formation made it the source rock for many oil and gas fields in its vicinity. We attempt to showcase the characterization of Duvernay Formation using 3D multicomponent seismic data and integrating it with the available well log and other relevant data. This has been done by deriving rock-physics parameters (Young’s modulus and Poisson’s ratio) through deterministic simultaneous and joint impedance inversion, with appropriate quantitative interpretation. In particular, we determine the brittleness of the Duvernay interval, which helps us determine the sweet spots therein. The scope of this characterization exercise was extended to explore the induced seismicity observed in the area (i.e., earthquakes of magnitude [Formula: see text]) that is perceived to be associated with hydraulic fracture stimulation of the Duvernay. This has been a cause of media coverage lately. We attempt to integrate our results with the induced seismicity data available in the public domain and elaborate on our learning experience gained so far.

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