Glioma cells promote angiogenesis through the release of exosomes containing long non-coding RNA POU3F3.

OBJECTIVE: Angiogenesis is a key event in the progression of gliomas, and emerging evidence suggests that exosomes are signaling extracellular organelles that modulate the tumor microenvironment and promote angiogenesis and tumor progression. This study aimed to explore the mechanism by which glioma-derived exosomes affect angiogenesis. MATERIALS AND METHODS: qRT-PCR was used to determine the expression level of linc-POU3F3 in glioma tissue as well as glioma cell lines. Ultrafiltration combined with a purification method was used to isolate exosomes derived from A172 cells (A172-Exo) and linc-POU3F3 shRNA-treated A172 cells (shA172-Exo). Transmission electron microscopy, Western blot and tunable resistive pulse sensing (TRPS) were used to identify exosomes. In vitro migration, proliferation, and tube formation experiments, as well as in vivo CAM assays, were used to analyze the pro-angiogenesis ability of exosomes. qRT-PCR and Western blot were used to identify expression levels of angiogenesis-related genes and proteins in human brain microvascular endothelial cells (HBMECs) after being cultured with exosomes. RESULTS: The levels of linc-POU3F3 were upregulated in glioma tissue and significantly correlated with the advanced tumor stage. A172 cells exhibited the highest expression level. A172-Exo was similar to shA172-Exo (50-100 nm in diameter) and expressed Alix, Tsg101 and CD9, while the expression level of linc-POU3F3 in A172-Exo was significantly higher than that in shA172-Exo. HBMECs rapidly internalized A172-Exo and shA172-Exo, and the linc-POU3F3 expression level in HBMECs treated with A172-Exo was significantly higher than the level in HBMECs treated with shA172-Exo. A172-Exo exhibited better function in promoting HBMECs migration, proliferation, tubular-like structure formation in vitro and arteriole formation in vivo. The gene and protein expression level of bFGF, bFGFR, VEGFA, and Angio in HBMECs treated with A172-Exo was much higher than that of HBMECs treated with shA172-Exo. CONCLUSIONS: These results indicated that gliomas can induce angiogenesis by secreting exosomes enriched in linc-POU3F3. Exosomes and lncRNA-POU3F3 may, therefore, function as a putative therapeutic target in glioma.

1991 outlook: progress will require partnerships, improved productivity--roundtable discussion.

To address the myriad problems and challenges in the next year, the operative word will be partnership. That's according to members of Modern Healthcare's editorial advisory board in their discussion of the healthcare industry in 1991. The experts see the need for hospitals, physicians and the business community to team up to control costs, solve staffing woes and take initial steps toward healthcare reform.

Economic credentialing--why it must be stopped.

In this article, the author describes how hospitals are using economic factors in the credentialing process, points out the flaws in this practice, and discusses some of the relevant case law. The author concludes by explaining why economic credentialing should be discontinued and urges physicians to reject it.

Preserving what we cannot replace: authority commensurate with responsibility.

Today's physicians are faced with conflicting pressures. As hospitals attempt to base staff privileges on the physician's ability to operate with economic restraint, physicians must struggle to maintain the medical staff autonomy vital to the provision of quality patient care. Dr. Lang urges medical staff unity against corporate influence over medical practice, and proposes a separate management organization for medical staffs, with separate funding for medical staff activities.

Inherent powers of the hospital medical staff.

The medical staff is a self-governing, legally separate entity representing the collective professional responsibility of its members in the management and administration of medical care within the hospital. This article explores the essentials of medical staff self-governance: the development and adoption of medical staff bylaws, which may not be unilaterally amended by the governing board; the selection and removal of medical staff officers; the establishment and enforcement of standards for medical staff membership; the establishment of patient care standards; and access to independent legal counsel.

Enhancement of clearances by activated charcoal in an in vitro model of peritoneal dialysis.

The use of sorbents in dialysate to increase solute clearances in continuous ambulatory peritoneal dialysis (CAPD) was investigated. With in vitro simulations of CAPD, the kinetics of irreversible binding of creatinine to activated charcoal were assessed. Cellulose dialyzer fibers were submerged in two liters of dialysate for 3-8 hour exchanges. Perfusate was pumped single pass through the fibers. Commercial dialysates with 1.5% and 4.25% dextrose as an osmotic agent were controls. Experimental exchanges contained either large or small particles of activated charcoal. Unencapsulated and collodion encapsulated large particles were also studied. From the perfusate side, creatinine, clearance and mass transfer were determined; dialysate/perfusate ratios (D/P) of free creatinine concentrations were assessed. We found that incorporation of small unencapsulated particles of activated charcoal would double both clearance and mass transfer of creatinine. It also maintained D/P values less than 0.6 even up to 8 hours. Small particles absorbed more than 10 times more creatinine per gram than large particles. Significant differences between encapsulated and unencapsulated large particles were not found. In summary, activated charcoal might double creatinine removal per exchange in CAPD. Animal studies of collodion encapsulated small particles and other sorbent-enzyme systems in CAPD dialysate solutions seem warranted.