scholarly journals Aqueous Extract ofPaeonia suffruticosaInhibits Migration and Metastasis of Renal Cell Carcinoma Cells via Suppressing VEGFR-3 Pathway

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Shih-Chin Wang ◽  
Sai-Wen Tang ◽  
Sio-Hong Lam ◽  
Chung-Chieh Wang ◽  
Yu-Huei Liu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Cell Carcinoma ◽  
Aqueous Extract ◽  
Actin Filament ◽  
Renal Cell ◽  
Chinese Herbs ◽  
Vegf Receptor ◽  
Cytoskeletal Dynamics ◽  
Cell Migration And Proliferation

Renal cell carcinoma (RCC) cells are characterized by strong drug resistance and high metastatic incidence. In this study, the effects of ten kinds of Chinese herbs on RCC cell migration and proliferation were examined. Aqueous extract ofPaeonia suffruticosa(PS-A) exerted strong inhibitory effects on cancer cell migration, mobility, and invasion. The results of mouse xenograft experiments showed that the treatment of PS-A significantly suppressed tumor growth and pulmonary metastasis. We further found that PS-A markedly decreased expression of VEGF receptor-3 (VEGFR-3) and phosphorylation of FAK in RCC cells. Moreover, the activation of Rac-1, a modulator of cytoskeletal dynamics, was remarkably reduced by PS-A. Additionally, PS-A suppressed polymerization of actin filament as demonstrated by confocal microscopy analysis and decreased the ratio of F-actin to G-actin in RCC cells, suggesting that PS-A inhibits RCC cell migration through modulating VEGFR-3/FAK/Rac-1 pathway to disrupt actin filament polymerization. In conclusion, this research elucidates the effects and molecular mechanism for antimigration of PS-A on RCC cells and suggests PS-A to be a therapeutic or adjuvant strategy for the patients with aggressive RCC.

Orai1 and STIM1 are critical for cell migration and proliferation of clear cell renal cell carcinoma

2014 ◽  
Vol 448 (1) ◽  
pp. 76-82 ◽  
Author(s):  
Ji-Hee Kim ◽  
Sayamaa Lkhagvadorj ◽  
Mi-Ra Lee ◽  
Kyu-Hee Hwang ◽  
Hyun Chul Chung ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Cell Migration And Proliferation

scholarly journals Elevated MTA1 induced the migration and invasion of renal cell carcinoma through the NF-κB pathway

BMC Urology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Cai Lv ◽  
Yuan Huang ◽  
Qingqing Lei ◽  
Zhenxiang Liu ◽  
Shixing Shen ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Normal Tissue ◽  
Negative Control ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Interfering Rna ◽  
E Cadherin

Abstract Background The metastasis-associated gene 1 (MTA1) has been extensively reported as a crucial oncogene, and its abnormal expression has been associated with the progression of numerous cancers. However, the role of MTA1 in renal cell carcinoma (RCC) progression and metastasis remains unclear. Herein, we investigated the expression of MTA1 and its role in RCC. Methods 109 matched clear cell RCCs (ccRCCs) and corresponding normal tissue samples were analyzed via immunohistochemistry to test the expression of MTA1. Human A498 cell lines were transfected with pcDNA3.1-Flag (control) or Flag-MTA1 to overexpress MTA1 or with specific interfering RNA (si-MTA1) or specific interfering negative control to knockdown MTA1 expression. Transfected cells were used in wound healing and transwell invasion assay. Quantitative real time polymerase chain reaction was used to assess the effect of MTA1 on MMP2/MMP9 and E-cadherin gene expression. Western blot was used to qualify the phosphorylation of p65. Results Herein, we found a significantly increased expression of MTA1 in 109 ccRCCs, compared to the corresponding normal tissue. In addition, the overexpression of MTA1 in A498 cells facilitated cell migration and invasion, while the down-regulation of MTA1 expression using specific interfering RNA sequences could decrease cell migration and invasion. Furthermore, we showed that MTA1 is up-regulated in ccRCCs, which contributes to the migration and invasion of human kidney cancer cells by mediating the expression of MMP2 and MMP9 through the NF-κB signaling pathway. Similarly, we found that MTA1 could regulate E-cadherin expression in RCCs. Conclusions MTA1 is overexpressed in RCC and is involved in the progression of RCC through NF-κB.

scholarly journals Upregulated circPDK1 Promotes RCC Cell Migration and Invasion by Regulating the miR-377-3P-NOTCH1 Axis in Renal Cell Carcinoma

2020 ◽  
Vol Volume 13 ◽  
pp. 11237-11252
Author(s):  
Zhenlin Huang ◽  
Yinghui Ding ◽  
Lu Zhang ◽  
Siyuan He ◽  
Zhankui Jia ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Migration And Invasion ◽  
Cell Migration And Invasion

scholarly journals The RabGEF ALS2 is a hypoxia inducible target associated with the acquisition of aggressive traits in tumor cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Solange Rivas ◽  
Patricio Silva ◽  
Montserrat Reyes ◽  
Hugo Sepúlveda ◽  
Luis Solano ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Tumor Cell ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Proximal Promoter ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Tumor Cell Migration ◽  
Rab Protein

AbstractTumor hypoxia and the hypoxia inducible factor-1, HIF-1, play critical roles in cancer progression and metastasis. We previously showed that hypoxia activates the endosomal GTPase Rab5, leading to tumor cell migration and invasion, and that these events do not involve changes in Rab protein expression, suggesting the participation of intermediate activators. Here, we identified ALS2, a guanine nucleotide exchange factor that is upregulated in cancer, as responsible for increased Rab5-GTP loading, cell migration and metastasis in hypoxia. Specifically, hypoxia augmented ALS2 mRNA and protein levels, and these events involved HIF-1α-dependent transcription, as shown by RNAi, pharmacological inhibition, chromatin immunoprecipitation and bioinformatics analyses, which identified a functional HIF-1α-binding site in the proximal promoter region of ALS2. Moreover, ALS2 and Rab5 activity were elevated both in a model of endogenous HIF-1α stabilization (renal cell carcinoma) and by following expression of stable non-hydroxylatable HIF-1α. Strikingly, ALS2 upregulation in hypoxia was required for Rab5 activation, tumor cell migration and invasion, as well as experimental metastasis in C57BL/6 mice. Finally, immunohistochemical analyses in patient biopsies with renal cell carcinoma showed that elevated HIF-1α correlates with increased ALS2 expression. Hence, this study identifies ALS2 as a novel hypoxia-inducible gene associated with tumor progression and metastasis.

scholarly journals Tumor suppressive microRNA-138 contributes to cell migration and invasion through its targeting of vimentin in renal cell carcinoma

2012 ◽  
Vol 41 (3) ◽  
pp. 805-817 ◽  
Author(s):  
TAKESHI YAMASAKI ◽  
NAOHIKO SEKI ◽  
YASUTOSHI YAMADA ◽  
HIROFUMI YOSHINO ◽  
HIDEO HIDAKA ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Migration And Invasion ◽  
Cell Migration And Invasion

Overcoming sunitinib-induced resistance by dose escalation in renal cell carcinoma: Evidence in animal models and patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4582-4582 ◽  
Author(s):  
Roberto Pili ◽  
Remi Adelaiye ◽  
Kiersten Marie Miles ◽  
Eric Ciamporcero ◽  
Paula Sotomayor ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Induced Resistance ◽  
Dose Escalation ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Therapeutic Option ◽  
Vegf Receptor ◽  
Cell Renal Cell Carcinoma ◽  
Human Patient

4582 Background: Sunitinib is considered a first-line therapeutic option for patients with advanced clear cell renal cell carcinoma (ccRCC). However, despite the clinical efficacy, eventually tumors develop resistance and progress. Thus, we have tested the hypothesis whether sunitinib dose-escalation could overcome initial drug resistance. Methods: Human patient-derived ccRCC xenografts were implanted in SCID mice and were randomly assigned into two groups (sunitinib and vehicle). Mice were treated with sunitinib 5 days/week with a dose-escalation schema starting from 40 mg/kg to 60 mg/kg and 80 mg/kg. Tumor volumes and body weights were assessed weekly. Tumor tissues and blood were collected prior to dose increments. In selected patients treated with 50 mg sunitinib and presenting minimal toxicities, dose was escalated to 62.5 and 75 mg at the time of tumor progression. Results: Our preclinical results show that patient-derived tumors (RP-01 and RP-02), although initially responsive to sunitinib 40 mg/kg, eventually became resistant to treatment. Following dose increase to 60 mg/kg, we observed again tumor response but eventually the tumors became resistant. A similar effect was noticed when we further escalated sunitinib to 80 mg/kg. Immunohistochemistry analysis shows decreased tumor vascularization during response to sunitinib, but then hypervascularization at the time of resistance. Associated increase in expression of the methyltransferase EZH2, the histone marks H3K27me3, H3k4me2 and H3K9me2 in tumors resistant to sunitinib was observed. Analysis of sunitinib and VEGF/VEFGR2 blood and tumor levels will be reported. In parallel, our clinical experience shows that intra-patient sunitinib dose-escalation was safe and clinical benefit was observed. Details on tumor responses and toxicities will be reported. Conclusions: Overall, our results suggest that sunitinib-induced resistance may be overcome in part by increasing the dose of the VEGF receptor tyrosine kinase inhibitor in mouse models and ccRCC patients, and highlights the potential role of epigenetic changes associated with sunitinib resistance.

U.S. regional practice patterns in metastatic renal cell carcinoma (mRCC) patients: A real-world retrospective analysis.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 505-505 ◽  
Author(s):  
Sumanta Kumar Pal ◽  
Magdaliz Gorritz ◽  
Steven A. Sherman ◽  
Zhimei Liu
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Treatment Patterns ◽  
Vegf Receptor ◽  
Wide Range ◽  
Common Sequence ◽  
Treatment Sequences

505 Background: The treatment landscape for metastatic renal cell carcinoma (mRCC) has changed in recent years, with several targeted therapies becoming available for 1st and 2nd line use. The rapidly evolving treatment landscape has left physicians with an abundance of choices for the treatment of mRCC patients. This study aimed to understand whether this has resulted in varying treatment patterns across US regions in 1st and 2nd line targeted therapy for mRCC. Methods: RCC patients who initiated 1st line targeted therapy with a vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFr) or mammalian target of rapamycin (mTOR) inhibitor between January 1, 2004 and June 30, 2011 were identified in the MarketScan database. First-line therapy was defined as the first claim in the database for a targeted therapy. One drug claim was sufficient to establish a line of therapy and a new line was defined as switching to another agent. Treatment patterns in the 1st and 2nd line settings were assessed in patients who initiated 2ndtherapy line after FDA approval of everolimus (Ev) (March 30, 2009) and stratified by geographic region. Results: Of the 6,524 patients included in the study, 1,298 (36%) received a 2nd line targeted therapy after March 30, 2009. Although all possible permutations of treatment sequences were observed, overall, sunitinib (Su) and temsirolimus (Te) combined made up 80% to 83% of the 1st line regimens across regions. The most common sequence was Su->Ev, observed in 18% of patients in the North Central US to 31% in the Northeast; Su->Te was the next most common sequence in all regions. Among patients who received 1st line temsirolimus, the majority initiated 2ndline on either bevacizumab (Be) (7%-12%) or Su (6%-10%) across regions. Conclusions: The most common treatment sequences across all regions were Su->Ev and Su->Te. Although a consistent pattern of sequential therapy emerged across regions, a wide range of on- and off-label strategies was observed outside of the predominant pattern of care. Furthermore, very few patients in this study received additional targeted therapy after 1st line. Further research is needed to identify factors influencing these treatment strategies.

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