scholarly journals Effect of eribulin on angiogenesis and endothelial adhesion molecules.

2021 ◽  
Author(s):  
Andrea Abbona ◽  
Antonella Falletta ◽  
Matteo Paccagnella ◽  
Simonetta Astigiano ◽  
Stefania Martini ◽  
...  

Tumor vasculature is an important component of the tumor microenvironment and deeply affect anticancer immune response. Eribulin is a non taxane inhibitor of the mitotic spindle. However, off-target effect interfering with the tumor vasculature have been reported. The mechanisms responsible of this effect is not clear. We designed an in vitro study to investigate the effect of eribulin on neo-angiogenesis and on the adhesion molecules ICAM-1 and VCAM-1, with or without TGF-beta. We also investigated the effects of paclitaxel and vinorelbine in the same experimental conditions. Eribulin was able to up-regulate the epithelial markers VE-cadherin and CD-31 in the HUVEC and tube formation in HUVEC cultured in Matrigel. The drug effectively arrested tube formation even in presence of TGF-beta. Eribulin counteracted the TGF-beta induced change in cell shape from the endothelial cobblestone-like morphology to an elongated spindle-shaped morphology that is characteristic of EndMT. We also observed that eribulin is able to upregulate ICAM-1 and to counteract its downregulation induced by TGF-beta. In this study, eribulin was able to inhibit the vasculature remodeling and the downregulation of ICAM-1 induced by TGF-beta. These effects might have important therapeutic consequence if the drug will be administered with immunotherapy.

2021 ◽  
Author(s):  
Andrea Abbona ◽  
Matteo Paccagnella ◽  
Simonetta Astigiano ◽  
Stefania Martini ◽  
Nerina Denaro ◽  
...  

Abstract Tumor vasculature is an important component of the tumor microenvironment and deeply affects anticancer immune response. Eribulin is a non-taxane inhibitor of the mitotic spindle. However, off-target effects interfering with the tumor vasculature have been reported. The mechanisms responsible of this effect are still unclear.We designed an in vitro study to investigate the effect of eribulin, with or without TGF-β, on neo-angiogenesis, and on the expression of the adhesion molecules ICAM-1 and VCAM-1. We also investigated the effects of paclitaxel and vinorelbine in the same experimental conditions.Eribulin up-regulated the epithelial markers VE-cadherin and CD-31 in HUVEC and inhibited tube formation in HUVEC cultured in Matrigel. The drug effectively arrested tube formation even in presence of TGF-β and counteracted the TGF-β-induced change in cell shape from the endothelial cobblestone-like morphology to an elongated spindleshaped morphology.We also observed that eribulin was able to upregulate ICAM-1 and to counteract its downregulation induced by TGF-β.Eribulin therefore exerts different off-label effects: increases vascular remodeling, counteracts the endothelial tomesenchymal transition (EndMT) mediated by TGF-β and promotes tumor infiltration by immune cells by increasing expression of ICAM-1 and transcription of CD31 and VE-cadherin.Moreover, eribulin was able to inhibit vasculature remodeling and the induction of EndMT mediated by TGF-β better than vinorelbine and paclitaxel.The effects observed in this study might have important therapeutic consequence if the drug will be administered with immunotherapy.


2004 ◽  
Vol 5 (1) ◽  
pp. 18-30 ◽  
Author(s):  
Carlos A. Muñoz ◽  
Anna Torrado ◽  
Manuel Valiente ◽  
Wu Zhang ◽  
Yiming Li

Abstract The aim of the present study was to determine the ability of a dentifrice containing a mixture of ion-exchange resins (named NMTD), which supplies calcium, fluoride, phosphate, and zinc ions, to promote remineralization and/or inhibit demineralization of dental human enamel in a pH cycling model in vitro. A fluoride toothpaste was used as the control. The enamel specimens were tested for microhardness before and after 10 days and 16 days of the demineralizing and remineralizing treatments. The results of this study showed both dentifrices were effective in limiting in vitro enamel demineralization although the effects were not significantly different from each other. Inclusion of calcium and phosphate ion-exchange resins in the dentifrice containing a fluoride ion-exchange resin maintained a similar net outcome of the conventional dentifrice in the demineralization/ remineralization process under the experimental conditions employed. Citation Torrado A, Valiente M, Zhang W, et. al. Remineralization Potential of a New Toothpaste Formulation: An In-Vitro Study. J Contemp Dent Pract 2004 February;(5)1:018-030.


2009 ◽  
Vol 77 (7) ◽  
pp. 3109-3116 ◽  
Author(s):  
Helena Svensson ◽  
Malin Hansson ◽  
Jan Kilhamn ◽  
Steffen Backert ◽  
Marianne Quiding-Järbrink

ABSTRACT Helicobacter pylori is one of the most common bacterial pathogens, infecting up to 50% of the world's population. The host is not able to clear the infection, leading to life-long chronic inflammation with continuous infiltration of lymphocytes and granulocytes. The migration of leukocytes from the blood into inflamed tissue is dependent on adhesion molecules expressed on the vascular endothelium. The aim of this study was to characterize the effect of H. pylori-induced gastritis with regard to the expression of endothelial adhesion molecules in the gastric mucosa and compare this to other types of chronic mucosal inflammations. Our results demonstrate an increased level of expression of the adhesion molecule E-selectin, but not of intracellular adhesion molecule 1, vascular adhesion molecule 1, or vascular adhesion protein 1, in H. pylori-induced gastritis but not in gastritis induced by acetylsalicylic acid or pouchitis. The upregulated E-selectin expression was determined to be localized to the gastric mucosa rather than being a systemic response to the infection. Moreover, the H. pylori type IV secretion system encoded by the cag pathogenicity island (cagPAI) was found to be an important determinant for the upregulation of human endothelial E-selectin expression in vitro, and this process is probably dependent on the CagL protein, mediating binding to α5β1 integrins. Thus, endothelial E-selectin expression induced by H. pylori probably contributes to the large influx of neutrophils and macrophages seen in infected individuals, and our results suggest that this process may be more pronounced in patients infected with cagPAI-positive H. pylori strains and may thereby contribute to tissue damage in these individuals.


Blood ◽  
1994 ◽  
Vol 84 (7) ◽  
pp. 2068-2101 ◽  
Author(s):  
TM Carlos ◽  
JM Harlan

In the 9 years since the last review on leukocyte and endothelial interactions was published in this journal many of the critical structures involved in leukocyte adherence to and migration across endothelium have been elucidated. With the advent of cell and molecular biology approaches, investigations have progressed from the early descriptions by intravital microscopy and histology, to functional and immunologic characterization of adhesion molecules, and now to the development of genetically deficient animals and the first phase I trial of “anti-adhesion” therapy in humans. The molecular cloning and definition of the adhesive functions of the leukocyte integrins, endothelial members of the Ig gene superfamily, and the selectins has already provided sufficient information to construct an operative paradigm of the molecular basis of leukocyte emigration. The regulation of these adhesion molecules by chemoattractants, cytokines, or chemokines, and the interrelationships of adhesion pathways need to be examined in vitro and, particularly, in vivo. Additional studies are required to dissect the contribution of the individual adhesion molecules to leukocyte emigration in various models of inflammation or immune reaction. Certainly, new adhesion structures will be identified, and the current paradigm of leukocyte emigration will be refined. The promise of new insights into the biology and pathology of the inflammatory and immune response, and the potential for new therapies for a wide variety of diseases assures that this will continue to be an exciting area of investigation.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Weijie Liang ◽  
Jie Wu ◽  
Xinguang Qiu

Abstract Background Colorectal cancer (CRC) is a common malignant tumor globally. Meanwhile, LINC01116 has been proposed as risk factor for various tumors, including CRC. But the regulation of LINC01116 in CRC required more validated data. This study aimed to elucidate the potential function of LINC01116 in regulating cell proliferation and angiogenesis of CRC. Methods LINC01116 expression in 80 pairs of CRC tumor and adjacent non-tumor tissues was determined by qRT-PCR. After transfection of pcDNA3.1-LINC01116, sh-LINC01116, sh-TPM1, pcDNA3.1-EZH2 or sh-EZH2 in SW480 and HCT116 cells, the levels of LINC01116, TPM1 and EZH2 were measured by qRT-PCR or Western blot. The cell biological function of CRC cell lines was determined by CCK-8, colony formation assays, tube formation and scratch assays. RNA pull-down and RIP assays were applied to detect the binding of LINC01116 with EZH2 and H3K27me3. Binding of EZH2 to the TPM1 promoter was assessed by ChIP assay. Finally, xenograft models in nude mice were established to validate the results of in vitro experiments. Results LINC01116 was overexpressed in CRC tissues and high expression of LINC01116 was negatively correlated with postoperative survival. In vitro study showed LINC01116 expression could significantly enhance CRC progression, including increasing cell proliferation, migration and angiogenesis. Besides, investigations into the mechanism disclosed that LINC01116 could regulate EZH2 to inactivate TPM1 promoter, thus promoting CRC cell proliferation and angiogenesis. Moreover, consistent results of in vivo experiments were conformed in vitro experiments. Conclusion LINC01116 promotes the proliferation and angiogenesis of CRC cells by recruiting EZH2 to potentiate methylation in the TPM1 promoter region to inhibit the transcription of TPM1.


Author(s):  
Janina Golob Deeb ◽  
Anja Frantar ◽  
George R. Deeb ◽  
Caroline K. Carrico ◽  
Ksenija Rener-Sitar

The aim of this randomized in vitro study was to compare the time and accuracy of implant site preparation and implant placement using a trephine drill versus a conventional drilling technique under dynamic navigation. A total of 42 implants were placed in simulation jaw models with the two drilling techniques by two operators with previous experience with dynamic navigation. The timing of each implant placement was recorded, and horizontal, vertical, and angulation discrepancies between the planned and placed implants were compared. There was no significant difference in time or accuracy between the trephine and conventional drilling techniques. Implant site preparation with a single trephine drill using dynamic navigation was as accurate under in vitro experimental conditions as a conventional drilling sequence.


2005 ◽  
Vol 100 (4) ◽  
pp. 1007-1013 ◽  
Author(s):  
Zhu Biao ◽  
Xue Zhanggang ◽  
Jiang Hao ◽  
Miao Changhong ◽  
Cang Jing

Author(s):  
Riccardo Vismara ◽  
Dario Comparolo ◽  
Andrea Mangini ◽  
Carlo Antona ◽  
Gianfranco B. Fiore

The in vitro approach to the study of the hemodynamics of heart valves allows easier-to-control and well repeatable experimental conditions, if compared with studies on animal models. A deep, detailed insight into specific issues is possible, despite the unavoidable simplification of the physiological complexity.


2011 ◽  
Vol 05 (03) ◽  
pp. 310-317 ◽  
Author(s):  
Simona Tecco ◽  
Donato Di Iorio ◽  
Riccardo Nucera ◽  
Beatrice Di Bisceglie ◽  
Giancarlo Cordasco ◽  
...  

ABSTRACTObjectives: This in vitro study evaluated the friction (F) generated by aligned stainless steel (SS) conventional brackets, self-ligating Damon MX© brackets (SDS Ormco, Glendora, California, USA), Time3© brackets (American Orthodontics, Sheboygan, Wisconsin, USA), Vision LP© brackets (American Orthodontics), and low-friction Slide© ligatures (Leone, Firenze, Italy) coupled with various SS, nickel-titanium (NiTi), and beta-titanium (TMA) archwires. Methods: All brackets had a 0.022-inch slot, and the orthodontic archwires were 0.014-inch, 0.016-inch, 0.014×0.025-inch, 0.018×0.025-inch, and 0.019×0.025-inch NiTi; 0.017×0.025-inch TMA; and 0.019×0.025-inch SS. Each bracket-archwire combination was tested 10 times. In the test, 10 brackets of the same group were mounted in alignment on a metal bar. The archwires moved through all the 10 brackets at a crosshead speed of 0.5 mm/min (each run lasted approximately 5 min). The differences among 5 groups of brackets were analyzed through the Kruskal-Wallis test, and a Mann-Whitney test was calculated as post hoc analysis. The P value was set at 0.05. Results: Coupled with 0.014-inch NiTi and 0.016-inch NiTi, Victory Series© brackets generated the greatest F, while Damon MX© and Vision LP© brackets generated the lowest (P<.05); no significant differences were observed between Time3© brackets and Slide© ligatures. Coupled with all the rectangular archwires, Victory Series© brackets, Slide© ligatures, and Vision LP© self-ligating brackets generated significantly lower F than did Time3© and Damon MX© self-ligating brackets (P<.05). Conclusions: These findings suggest that self-ligating brackets are a family of brackets that, in vitro, can generate different levels of F when coupled with thin or thick, rectangular, or round archwires. Clinical conclusions based on our results are not possible due to the limitations of the experimental conditions. (Eur J Dent 2011;5:310-317)


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