scholarly journals Cross-drug resistance to sunitinib induced by doxorubicin in endothelial cells

2014 ◽  
Vol 9 (3) ◽  
pp. 1287-1292 ◽  
Author(s):  
LIMIN HUANG ◽  
CHAOQUAN HU ◽  
MÉLANIE DI BENEDETTO ◽  
RÉMI VARIN ◽  
JIELIN LIU ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Endothelial Cells

The mechanism of human angiosarcoma drug resistance

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9567-9567
Author(s):  
V. Ravi ◽  
D. Henry ◽  
S. Chen ◽  
M. K. Wong
Keyword(s):  
Drug Resistance ◽  
Endothelial Cells ◽  
Cell Migration ◽  
Malignant Neoplasm ◽  
Therapeutic Strategies ◽  
Migration And Invasion ◽  
Development Of Resistance ◽  
Vegf Pathway ◽  
And Function ◽  
Invasion Assays

9567 Background: Angiosarcoma (AS) is a malignant neoplasm of endothelial cells. AS has an extremely poor outcome since it can metastasize widely and rapidly becomes chemoresistant. Understanding the mechanism of this resistance is important not only because of the critical need for new therapeutic strategies in sarcoma, but also since it sheds light on important pathways in endothelial growth that may help understand tumor angiogenesis. Methods/Results: We have established and characterized stable pre-chemotherapy (named B8) and chemotherapy-resistant (named D3) angiosarcoma cell lines from an individual patient with primary (non radiated) breast angiosarcoma prior to initiation of chemotherapy and later after development of resistance to adriamycin, ifosfamide, gemcitabine, docetaxel, paclitaxel, interferon, thalidomide and bevacizumab. D3 cells differ dramatically from B8s in morphology and function. Prechemotherapy B8 cells assume a polygonal morphology reminiscent of native endothelial cells, the D3 cells throw out long processes that span several cell lengths, and do not appear to contact-inhibit. Migration and invasion assays confirm the highly motile nature of these cells. Although it is not surprising that the D3 cells were doxorubicin resistant, we found that unlike the B8 cells, the D3 cells actively transcribe VEGF. In keeping with this, D3 cells are relatively more sensitive to growth inhibition by the anti-VEGF drug bevacizumab than chemonaïve B8 cells. Conclusion: These studies reveal two avenues to target chemoresistant human angiosarcoma; via agents affecting cell migration and those agents that target the VEGF pathway. No significant financial relationships to disclose.

Antiproliferative, antiangiogenesis, and reversal of chemoresistance by specific cathepsin L inhibitors

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14643-e14643
Author(s):  
A. Rebbaa ◽  
E. Dyskin ◽  
E. Dier ◽  
C. Gallati ◽  
C. Honko ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Endothelial Cells ◽  
Tumor Growth ◽  
Anticancer Agents ◽  
Cellular Proliferation ◽  
Cathepsin L ◽  
Neuroblastoma Cell ◽  
Drug Candidate ◽  
Dependent Manner

e14643 Background: Uncontrolled proliferation, enhanced angiogenesis and the development of resistance to therapy are hallmarks of cancer; therefore, the development of approaches to simultaneously target these three processes would be the most desirable. Previous work from our laboratory has demonstrated that NapSul-Ile-Trp-CHO (NSITC), a specific inhibitors of cathepsin L, and its analogs strongly inhibited cancer cell proliferation and suppressed the development of drug resistance in vitro (Zheng X. et al., 2004 Cancer Res. 64:1773–80). In the present study, we sought to investigate the validity of these observations in vivo, and to dissect the underlying mechanism(s). Methods: Nude mice (Strain CD1) bearing xenografts of doxorubicin resistant neuroblastoma cell line SKN-SH/R were challenged with doxorubicin (1.5 mg/Kg) alone, NSITC (20 mg/kg) alone or the combination of both. The effect of NSITC on tumor angiogenesis was also investigated using the Chick Chorioallantoic Membrane (CAM). Putative mechanisms by which NSITC inhibits cellular proliferation, drug resistance and angiogenesis were studied using cancer and endothelial cells maintained in culture. Results: The in vivo data indicated that doxorubicin alone had no effect on tumor growth, however NSITC alone exerted 40% inhibition and the combination of both drugs reduced tumor growth by about 90%. NSITC also caused a 125% inhibition of blood vessel branching in the CAM model (at 1 μg/CAM). Investigation of the underlying mechanisms of its action revealed that at low concentration, NSITC forces cancer cells into senescence, preventing them from developing resistance to classical anticancer agents, and at high concentrations, it induced autophagic cell death. NSITC also strongly inhibited the proliferation and invasion of endothelial cells in a dose dependent manner with more than 90% inhibition at 20 μM. Conclusions: Overall, these findings suggest that NSITC has multi-anticancer functions and thus, may represent a potential drug candidate for the treatment of aggressive malignancies. No significant financial relationships to disclose.

scholarly journals HIF-1α of Bone Marrow Endothelial Cells Implies Relapse and Drug Resistance in Patients with Multiple Myeloma and May Act as a Therapeutic Target

2013 ◽  
Vol 20 (4) ◽  
pp. 847-858 ◽  
Author(s):  
Roberto Ria ◽  
Ivana Catacchio ◽  
Simona Berardi ◽  
Annunziata De Luisi ◽  
Antonella Caivano ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Drug Resistance ◽  
Endothelial Cells ◽  
Therapeutic Target

scholarly journals miRNA-1246 in Extracellular Vesicles Secreted from Metastatic Tumor Induces Drug Resistance in Tumor Endothelial Cells

2020 ◽  
Author(s):  
Chisaho Torii ◽  
Nako Maishi ◽  
Taisuke Kawamoto ◽  
Masahiro Morimoto ◽  
Kosuke Akiyama ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Endothelial Cells ◽  
Induced Resistance ◽  
Extracellular Vesicles ◽  
Metastatic Tumor ◽  
Metastatic Tumors ◽  
Glycoprotein P ◽  
Tumor Endothelial Cells

Abstract Background: Tumor endothelial cells (TECs) reportedly exhibit altered phenotypes. We have demonstrated that TECs acquire drug resistance with the upregulation of p-glycoprotein (p-gp, ABCB1), contrary to traditional assumptions. Furthermore, p-gp expression was higher in TECs of highly metastatic tumors than in those of low metastatic tumors. However, the detailed mechanism of differential p-gp expression in TECs remains unclear. Methods: miRNA was identified in highly metastatic tumor extracellular vesicles (EVs) and the roles of miRNA in endothelial cell resistance were analyzed in vitro and in vivo. Results: In the present study, we found that treatment of highly metastatic tumor-conditioned medium induced resistance to 5-fluorouracil (5-FU) with interleukin-6 (IL-6) upregulation in endothelial cells (ECs). Among the soluble factors secreted from highly metastatic tumors, we focused on extracellular vesicles (EVs) and determined that miR-1246 was contained at a higher level in highly metastatic tumor EVs than in low metastatic tumor EVs. Furthermore, miR-1246 was transported via the EVs into ECs and induced IL-6 expression. Upregulated IL-6 induced resistance to 5-FU with STAT3 and Akt activation in ECs in an autocrine manner. Conclusions: These results suggested that highly metastatic tumors induce drug resistance in ECs by transporting miR-1246 through EVs.

scholarly journals Tumour endothelial cells acquire drug resistance in a tumour microenvironment

2013 ◽  
Vol 153 (3) ◽  
pp. 243-249 ◽  
Author(s):  
K. Hida ◽  
K. Akiyama ◽  
N. Ohga ◽  
N. Maishi ◽  
Y. Hida
Keyword(s):  
Drug Resistance ◽  
Endothelial Cells ◽  
Tumour Microenvironment ◽  
Acquire Drug Resistance

scholarly journals Overexpression of Multiple Drug Resistance Genes in Endothelial Cells from Patients with Refractory Epilepsy

Epilepsia ◽  
2001 ◽  
Vol 42 (12) ◽  
pp. 1501-1506 ◽  
Author(s):  
Stephen M. Dombrowski ◽  
Shailesh Y. Desai ◽  
Matteo Marroni ◽  
Luca Cucullo ◽  
Kris Goodrich ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Endothelial Cells ◽  
Resistance Genes ◽  
Refractory Epilepsy ◽  
Multiple Drug Resistance ◽  
Multiple Drug
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