THE RELATIONSHIP OF EPO OVER-EXPRESSION TO VHL MUTATIONS AND Hif1α AND 2α IN SCCRCC

2008 ◽  
Vol 179 (4S) ◽  
pp. 91-91
Author(s):  
Kan Gong ◽  
Kai Zhang ◽  
Ning Zhang ◽  
Qun Yan Na
2015 ◽  
Vol 37 (4) ◽  
pp. 1442-1453 ◽  
Author(s):  
Fei Zhang ◽  
Jing Wang ◽  
Jianjun Chu ◽  
Cheng Yang ◽  
Hui Xiao ◽  
...  

Background/Aims: There have been many studies on the etiology of osteoarthritis (OA) with regard to the function of inflammatory cytokines, the process of cartilage degradation, the function of miR-146a, hypoxia stimulation and autophagy in OA chondrocytes, but there have been no reports on the relationship between miR-146a and autophagy in cartilage, especially under hypoxia. This study aimed to confirm the relationship of miR-146a and autophagy in cartilage under hypoxia. Methods: Chondrocytes were treated by hypoxia gradients, and the main factors including HIF-1α, HIF-2α, miR-146a and Bcl-2 and autophagy markers ULK-1, ATG-5 were detected by quantitative PCR (Q-PCR) and western blotting. The autophagy marker LC-3 was detected by immunofluorescence. The reciprocal effects between miR-146a and Bcl-2 were confirmed by several combinations of shRNAs and adenovirus-gene systems followed by Q-PCR and western blot detection. Results: Hypoxia maintained the chondrocytes phenotype and promoted autophagy and miR-146a expression via HIF-1α, but not HIF-2α, while miR-146a did not reversely affect HIF-1α. The autophagy induced by hypoxia through HIF-1α, miR-146a and Bcl-2. Simply, hypoxia induced HIF-1α, and HIF-1α increased miR-146a, but miR-146a suppressed Bcl-2, an autophagy inhibitor. While Bcl-2 affected neither HIF-1α nor miR-146a. The absence of both HIF-1α and miR-146a or Bcl-2 over-expression inhibited hypoxia-induced autophagy. Conclusion: HIF-1α, miR-146a and Bcl-2 play crucial roles during hypoxia-induced autophagy, Hypoxia, HIF-1α and miR-146a promote chondrocytes autophagy via depressing Bcl-2. We conclude that miR-146a may serve as a novel therapeutic target for protecting cartilage from degeneration in OA.


2020 ◽  
Vol 134 (4) ◽  
pp. 338-343
Author(s):  
C-C Sim ◽  
E U-H Sim

AbstractObjectivesThe conclusive prognostic significance of cyclo-oxygenase-2 has been determined in various cancers but not in nasopharyngeal carcinoma. Therefore, this study aimed to evaluate the relationship of cyclo-oxygenase-2 expression with the survival outcome and treatment response of nasopharyngeal carcinoma patients via a systematic meta-analysis approach.MethodsA meta-analysis was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (‘PRISMA’) checklist. The primary clinical characteristics of patients, and hazard ratios with 95 per cent confidence intervals of overall survival data, were tabulated from eligible studies. The relationship of cyclo-oxygenase-2 expression with survival outcome (expressed as hazard ratio) and treatment response (expressed as odds ratio) in nasopharyngeal carcinoma patients was analysed, and explained with the aid of forest plot charts.Results and conclusionThe pooled hazard ratio for overall survival was 2.02 (95 per cent confidence interval = 1.65–2.47). This indicates that the over-expression of cyclo-oxygenase-2 is significantly associated with the poor survival of nasopharyngeal carcinoma patients. The pooled odds ratio of 0.98 (95 per cent confidence interval = 0.27–3.49) reveals that over-expression of cyclo-oxygenase-2 was not significantly related to the treatment outcome.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3041-3041 ◽  
Author(s):  
Katie Streicher ◽  
Chris Morehouse ◽  
Yinong Sebastian ◽  
Michael Kuziora ◽  
Brandon W. Higgs ◽  
...  

3041 Background: We previously reported that NSCLC pts with high pretreatment tumoral IFNG mRNA signature (sig) expression have improved outcomes (ORR, PFS, OS) to the anti-PD-L1 therapy durvalumab (D). To explore the relationship of other immunotherapy targets with the IFNG sig, we evaluated expression of CD137, PD1, PDL1, CTLA4, GITR, OX40, TLR7, TLR8, CD73, TIM3, NKG2A, IDO1, CD40, LAG3, A2AR, CXCR4, iNOS, ARG1, and STAT3 in D-treated NSCLC. Methods: CP1108/NCT01693562 was a nonrandomized phase 1/2 trial evaluating D (10 mg/kg Q2W) in advanced NSCLC. As of 24OCT16, 304 primarily previously-treated pts were enrolled. RNA sequencing was conducted on available tumor specimens from 98 pts. ORR was evaluated using RECIST v1.1. 19 genes were z-scored, scaled and clustered across pt tumors. Each gene was coded binary using 0 as a cut point. The proportion of tumors with concordant or discordant over-expression between a gene and the IFNG sig was calculated. Results: In 43% of evaluable NSCLC pts, mRNAs for PD-1, IDO1, PD-L1, CD40, CTLA4, LAG3, TIM3, TLR8, NKG2A, and CD137 were co-expressed with IFNG sig (Spearman’s rho > = 0.7). In 34% of evaluable pts, TLR7, OX40, GITR, A2AR, and CXCR4 mRNAs had moderate concordance with IFNG sig (0.5 < rho < 0.7) and in 23% of evaluable pts iNOS, CD73, ARG1, and STAT3 had low concordance (rho < 0.5). Within the cluster of pts including high IFNG sig, a small subset expressed high iNOS and CD73; however, pts with high STAT3 or ARG1 formed a distinct cluster within the low IFNG sig subset. The subset with high IFNG sig had an ORR of 24% compared to only 10% in all other subsets combined. Conclusions: Our findings enrich understanding of the immune microenvironment of NSCLC by identifying three broad categories of tumors: tumors with pre-existing immunity that have high IFNg sig and select other IO pathways with enhanced responses to D; tumors with moderate expression of IO genes in which the local microenvironment is crucial; finally a distinct “cold” subset of tumors with high expression of STAT3 or ARG1 and characterized by low or no expression of IFNG sig and other IO genes. These results may aid in identifying the right pts for anti-PD-L1 and in prioritizing immunotherapy combinations.


Paleobiology ◽  
1980 ◽  
Vol 6 (02) ◽  
pp. 146-160 ◽  
Author(s):  
William A. Oliver

The Mesozoic-Cenozoic coral Order Scleractinia has been suggested to have originated or evolved (1) by direct descent from the Paleozoic Order Rugosa or (2) by the development of a skeleton in members of one of the anemone groups that probably have existed throughout Phanerozoic time. In spite of much work on the subject, advocates of the direct descent hypothesis have failed to find convincing evidence of this relationship. Critical points are:(1) Rugosan septal insertion is serial; Scleractinian insertion is cyclic; no intermediate stages have been demonstrated. Apparent intermediates are Scleractinia having bilateral cyclic insertion or teratological Rugosa.(2) There is convincing evidence that the skeletons of many Rugosa were calcitic and none are known to be or to have been aragonitic. In contrast, the skeletons of all living Scleractinia are aragonitic and there is evidence that fossil Scleractinia were aragonitic also. The mineralogic difference is almost certainly due to intrinsic biologic factors.(3) No early Triassic corals of either group are known. This fact is not compelling (by itself) but is important in connection with points 1 and 2, because, given direct descent, both changes took place during this only stage in the history of the two groups in which there are no known corals.


Author(s):  
D. F. Blake ◽  
L. F. Allard ◽  
D. R. Peacor

Echinodermata is a phylum of marine invertebrates which has been extant since Cambrian time (c.a. 500 m.y. before the present). Modern examples of echinoderms include sea urchins, sea stars, and sea lilies (crinoids). The endoskeletons of echinoderms are composed of plates or ossicles (Fig. 1) which are with few exceptions, porous, single crystals of high-magnesian calcite. Despite their single crystal nature, fracture surfaces do not exhibit the near-perfect {10.4} cleavage characteristic of inorganic calcite. This paradoxical mix of biogenic and inorganic features has prompted much recent work on echinoderm skeletal crystallography. Furthermore, fossil echinoderm hard parts comprise a volumetrically significant portion of some marine limestones sequences. The ultrastructural and microchemical characterization of modern skeletal material should lend insight into: 1). The nature of the biogenic processes involved, for example, the relationship of Mg heterogeneity to morphological and structural features in modern echinoderm material, and 2). The nature of the diagenetic changes undergone by their ancient, fossilized counterparts. In this study, high resolution TEM (HRTEM), high voltage TEM (HVTEM), and STEM microanalysis are used to characterize tha ultrastructural and microchemical composition of skeletal elements of the modern crinoid Neocrinus blakei.


Author(s):  
Leon Dmochowski

Electron microscopy has proved to be an invaluable discipline in studies on the relationship of viruses to the origin of leukemia, sarcoma, and other types of tumors in animals and man. The successful cell-free transmission of leukemia and sarcoma in mice, rats, hamsters, and cats, interpreted as due to a virus or viruses, was proved to be due to a virus on the basis of electron microscope studies. These studies demonstrated that all the types of neoplasia in animals of the species examined are produced by a virus of certain characteristic morphological properties similar, if not identical, in the mode of development in all types of neoplasia in animals, as shown in Fig. 1.


Author(s):  
J.R. Pfeiffer ◽  
J.C. Seagrave ◽  
C. Wofsy ◽  
J.M. Oliver

In RBL-2H3 rat leukemic mast cells, crosslinking IgE-receptor complexes with anti-IgE antibody leads to degranulation. Receptor crosslinking also stimulates the redistribution of receptors on the cell surface, a process that can be observed by labeling the anti-IgE with 15 nm protein A-gold particles as described in Stump et al. (1989), followed by back-scattered electron imaging (BEI) in the scanning electron microscope. We report that anti-IgE binding stimulates the redistribution of IgE-receptor complexes at 37“C from a dispersed topography (singlets and doublets; S/D) to distributions dominated sequentially by short chains, small clusters and large aggregates of crosslinked receptors. These patterns can be observed (Figure 1), quantified (Figure 2) and analyzed statistically. Cells incubated with 1 μg/ml anti-IgE, a concentration that stimulates maximum net secretion, redistribute receptors as far as chains and small clusters during a 15 min incubation period. At 3 and 10 μg/ml anti-IgE, net secretion is reduced and the majority of receptors redistribute rapidly into clusters and large aggregates.


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