Vitreous inflammatory factors and serous retinal detachment in central retinal vein occlusion: a case control series

<p>Abstract</p> <p>Background</p> <p>This study investigated whether the vitreous fluid levels of soluble vascular endothelial growth factor receptor-2 (sVEGFR-2), pigment epithelium-derived factor (PEDF), and soluble intercellular adhesion molecule 1 (sICAM-1) were associated with the occurrence of serous retinal detachment (SRD) in patients with central retinal vein occlusion (CRVO).</p> <p>Methods</p> <p>We recruited 33 patients with CRVO and macular edema, as well as 18 controls with nonischemic ocular diseases. Eighteen of the 33 patients with CRVO showed SRD on optical coherence tomography of the macula (defined as subretinal accumulation of fluid with low reflectivity), while the other 15 patients only had cystoid macular edema (CME, defined as hyporeflective intraretinal cavities). Retinal ischemia was evaluated by measuring the area of capillary non-perfusion using fluorescein angiography and the public domain Scion Image program, while central macular thickness (CMT) was examined by optical coherence tomography. Vitreous fluid samples were obtained during pars plana vitrectomy and levels of the target molecules were measured by enzyme-linked immunosorbent assay.</p> <p>Results</p> <p>Ischemia was significantly more common in the SRD group (17/18 patients) than in the CME group (5/15 patients) (<it>P </it>< 0.001). The vitreous fluid level of sICAM-1 increased significantly across the three groups from the control group (4.98 ± 1.73 ng/ml) to the CME group (15.4 ± 10.1 ng/ml) and the SRD group (27.1 ± 17.7 ng/ml) (<it>p_trend</it>< 0.001). The vitreous fluid level of sVEGFR-2 also showed a significant increase across the three groups (1083 ± 541 pg/ml, 1181 ± 522 pg/ml, and 1535 ± 617 pg/ml, respectively, <it>p_trend</it>= 0.019). On the other hand, the vitreous fluid level of PEDF showed a significant decrease across the three groups (56.4 ± 40.0 ng/ml, 24.3 ± 17.3 ng/ml, and 16.4 ± 12.6 ng/ml, respectively, <it>p_trend</it>< 0.001).</p> <p>Conclusions</p> <p>Higher levels of inflammatory factors (sICAM-1 and sVEGFR-2) and lower levels of anti-inflammatory PEDF were observed in macular edema patients with SRD, suggesting that inflammation plays a key role in determining the severity of CRVO.</p

Biomarker discovery for practice of precision medicine in hypopharyngeal cancer: a theranostic study on response prediction of the key therapeutic agents

Background: Hypopharyngeal cancer is a relatively rare malignancy with poor prognosis. Current chemotherapeutic algorithm is still far from personalized medicine, and the identification of the truly active therapeutic biomarkers and/or targets is eagerly awaited.Methods: Venturing to focus on the conventional key chemotherapeutic drugs, we identified the most correlative genes (and/or proteins) with cellular sensitivity to docetaxel (TXT), cisplatin (CDDP) and 5-fluorouracil (5-FU) in the expression levels, through 3 steps approach: genome-wide screening, confirmation study on the quantified expression levels, and knock-down and transfection analyses of the candidates. The probable action pathways of selected genes were examined by Ingenuity Pathway Analysis using a large-scale database, The Cancer Genome Atlas.Results: The first genome-wide screening study derived 16 highly correlative genes with cellular drug sensitivity in 15 cell lines (|R| > 0.8, P 0.5, P Conclusion: We newly propose 4 molecules -AGR2, PDE4D,NINJ2 and CDC25B) as the powerful exploratory markers for prediction of cellular response to 3 key chemotherapeutic drugs in hypopharyngeal cancers and also suggest their potentials to be the therapeutic targets, which could contribute to the development of precision medicine of the essential chemotherapy in hypopharyngeal patients.</p

Visual acuity and foveal thickness after vitrectomy for macular edema associated with branch retinal vein occlusion: a case series

Abstract Background The mechanism by which vitrectomy improves macular edema in patients with branch retinal vein occlusion remains unclear, although intraocular levels of vascular endothelial growth factor have been suggested to influence the visual prognosis and macular edema. Methods A series of 54 consecutive patients (54 eyes) with branch retinal vein occlusion was studied prospectively. All patients underwent pars plana vitrectomy for treatment of macular edema. Best corrected visual acuity and retinal thickness (examined by optical coherence tomography) were assessed before and after surgery. The level of vascular endothelial growth factor in vitreous fluid harvested at operation was determined. Patients were followed for at least 6 months postoperatively. Results Both the visual acuity and the retinal thickness showed significant improvement at 6 months postoperatively (P = 0.0002 and P Conclusions These results suggest that the vitreous level of vascular endothelial growth factor might influence the visual prognosis and the response of macular edema to vitrectomy in patients with branch retinal vein occlusion.</p

Interferon-alpha-induced mTOR activation is an anti-hepatitis C virus signal via the phosphatidylinositol 3-kinase-Akt-independent pathway.

OBJECT: The interferon-induced Jak-STAT signal alone is not sufficient to explain all the biological effects of IFN. The PI3-K pathways have emerged as a critical additional component of IFN-induced signaling. This study attempted to clarify that relationship between IFN-induced PI3-K-Akt-mTOR activity and anti-viral action. RESULT: When the human normal hepatocyte derived cell line was treated with rapamycin (rapa) before accretion of IFN-alpha, tyrosine phosphorylation of STAT-1 was diminished. Pretreatment of rapa had an inhibitory effect on the IFN-alpha-induced expression of PKR and p48 in a dose dependent manner. Rapa inhibited the IFN-alpha inducible IFN-stimulated regulatory element luciferase activity in a dose-dependent manner. However, wortmannin, LY294002 and Akt inhibitor did not influence IFN-alpha inducible luciferase activity. To examine the effect of PI3-K-Akt-mTOR on the anti-HCV action of IFN-alpha, the full-length HCV replication system, OR6 cells were used. The pretreatment of rapa attenuated its anti-HCV replication effect in comparison to IFN-alpha alone, whereas the pretreatment with PI3-K inhibitors, wortmannin and LY294002 and Akt inhibitor did not influence IFN-induced anti-HCV replication. CONCLUSION: IFN-induced mTOR activity, independent of PI3K and Akt, is the critical factor for its anti-HCV activity. Jak independent mTOR activity involved STAT-1 phosphorylation and nuclear location, and then PKR is expressed in hepatocytes