scholarly journals Inhibition of tumor growth and angiogenesis by a lysophosphatidic acid antagonist in an engineered three-dimensional lung cancer xenograft model

Cancer ◽  
2010 ◽  
Vol 116 (7) ◽  
pp. 1739-1750 ◽  
Author(s):  
Xiaoyu Xu ◽  
Glenn D. Prestwich
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Lysophosphatidic Acid ◽  
Three Dimensional ◽  
Xenograft Model ◽  
Acid Antagonist ◽  
Inhibition Of Tumor Growth

scholarly journals LOXL1 Is Regulated by Integrin α11 and Promotes Non-Small Cell Lung Cancer Tumorigenicity

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 705 ◽  
Author(s):  
Cédric Zeltz ◽  
Elena Pasko ◽  
Thomas R. Cox ◽  
Roya Navab ◽  
Ming-Sound Tsao
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Xenograft Model ◽  
Tumor Stroma ◽  
Small Cell ◽  
Matrix Remodeling ◽  
Small Cell Lung

Integrin α11, a stromal collagen receptor, promotes tumor growth and metastasis of non-small cell lung cancer (NSCLC) and is associated with the regulation of collagen stiffness in the tumor stroma. We have previously reported that lysyl oxidase like-1 (LOXL1), a matrix cross-linking enzyme, is down-regulated in integrin α11-deficient mice. In the present study, we investigated the relationship between LOXL1 and integrin α11, and the role of LOXL1 in NSCLC tumorigenicity. Our results show that the expression of LOXL1 and integrin α11 was correlated in three lung adenocarcinoma patient datasets and that integrin α11 indeed regulated LOXL1 expression in stromal cells. Using cancer-associated fibroblast (CAF) with either a knockdown or overexpression of LOXL1, we demonstrated a role for LOXL1 in collagen matrix remodeling and collagen fiber alignment in vitro and in vivo in a NSCLC xenograft model. As a consequence of collagen reorganization in NSCLC tumor stroma, we showed that LOXL1 supported tumor growth and progression. Our findings demonstrate that stromal LOXL1, under regulation of integrin α11, is a determinant factor of NSCLC tumorigenesis and may be an interesting target in this disease.

scholarly journals Tumor growth affects the metabonomic phenotypes of multiple mouse non-involved organs in an A549 lung cancer xenograft model

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Shan Xu ◽  
Yuan Tian ◽  
Yili Hu ◽  
Nijia Zhang ◽  
Sheng Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Xenograft Model ◽  
A549 Lung

Effect of anamorelin/ONO-7643, a selective ghrelin receptor agonist, on tumor growth in a lung cancer mouse xenograft model.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19577-e19577
Author(s):  
Robert Northrup ◽  
Ken Kuroda ◽  
Elizabeth Manning Duus ◽  
Sheri Routt Barnes ◽  
Tim Wiley ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Body Weight ◽  
Tumor Growth ◽  
Food Consumption ◽  
Nude Mice ◽  
Receptor Agonist ◽  
Xenograft Model ◽  
Ghrelin Receptor ◽  
Mouse Xenograft Model ◽  
Ghrelin Receptor Agonist

e19577 Background: Anamorelin/ONO-7643 is an orally-active ghrelin receptor agonist in development for non-small cell lung cancer (NSCLC)-related cachexia/anorexia. It displays both anabolic and orexigenic properties via its ghrelin and growth hormone (GH) secretagogue activity. However, increasing GH and insulin-like growth factor-1 (IGF-1) in cancer patients raises potential concerns of stimulating tumor growth. In this study, we investigated the effect of ghrelin and Anamorelin/ONO-7643 on tumor growth in a NSCLC xenograft model. Methods: On Day 1 (D1), 21 days after implanting A549 tumors, female nude mice were sorted into six groups (n=15/group) and administered ghrelin (2 mg/kg i.p.), Anamorelin/ONO-7643 (3, 10, or 30 mg/kg p.o.) or vehicles (saline i.p. or de-ionized water p.o.) for 28 days, starting on D3. Tumor growth, body weight, and food consumption were monitored. Mice used to assess plasma levels of murine GH (mGH) and IGF-1 (mIGF-1) were sorted into three groups (n=21/group) and treated for 28 days with ghrelin, the high dose of Anamorelin/ONO-7643 or vehicle (de-ionized water p.o.). Results: After 28 days of treatment, there was no difference in median tumor volumes (D30 values: 1008, 936, 1080, 666 and 847 mm3 for vehicle, ghrelin and Anamorelin/ONO-7643 at 3, 10 and 30 mg/kg, respectively). Ghrelin significantly increased mGH compared to controls, while Anamorelin/ONO-7643 modestly increased mGH. Peak mIGF-1 levels were slightly higher in animals given ghrelin or Anamorelin/ONO-7643 compared to vehicle, although not significantly. Anamorelin/ONO-7643 at 10 and 30 mg/kg/day showed a statistically significant (p<0.01) increase in body weight from D1 to D30 compared to control animals, with no change in food consumption. Ghrelin treatment had no effect on body weight or food consumption. Conclusions: Anamorelin/ONO-7643 or ghrelin treatment for 28 days had no effect on tumor growth in A549 tumor-bearing nude mice, despite increased mGH and a trend of increased mIGF-1. Anamorelin/ONO-7643 also significantly increased body weight at 10 and 30 mg/kg/day. These results support using ghrelin receptor agonist-based treatments in managing NSCLC-related cachexia/anorexia.

scholarly journals Development and Characterization of Patient-Derived Xenografts from Non-Small Cell Lung Cancer Brain Metastases

2020 ◽  
Author(s):  
Andrew M. Baschnagel ◽  
Saakshi Kaushik ◽  
Arda Durmaz ◽  
Steve Goldstein ◽  
Irene M. Ong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Tumor Growth ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Xenograft Model ◽  
Small Cell ◽  
Growth Delay ◽  
Small Cell Lung

AbstractIntroductionThe purpose of this study was to establish and characterize a direct-from patient-derived xenograft (PDX) model of non-small cell lung cancer (NSCLC) brain metastases.MethodsSurgically obtained tissue was implanted subcutaneously and as orthotopic intracranial implants into immunodeficient mice. Histology and DNA loci were compared between original tumor and subsequent PDX passages. Tumors underwent RNA and DNA sequencing and relevant therapeutic targets were identified. Tumor growth rates were assessed following treatment with radiation, MEK inhibitor selumetinib, or MET inhibitor savolitinib. Cell lines were established.ResultsNine NSCLC brain metastases PDXs were established. Morphologically, strong retention of cytoarchitectural features was observed between original patient tumor and subcutaneous and intracranial tumors. Short tandem repeat analysis demonstrated strong concordance between patient tumors and subsequent PDX passages. Transcriptome and mutation analysis revealed high correlation between matched patient and PDX samples. Significant growth inhibition occurred with radiation, with selumetinib in tumors harboring KRAS G12C mutations and with savolitinib in a tumor with MET exon 14 skipping mutation. The combination of radiation and savolitinib resulted in significant tumor growth delay compared to radiation or savolitinib alone our MET exon 14 skipping mutation PDX. Early passage cell strains showed high consistency between patient and PDX tumors.ConclusionWe have established a robust human xenograft model system for investigating NSCLC brain metastases. These PDXs and cell lines show strong phenotypic and molecular correlation with the original patient tumors and provide a valuable resource for testing preclinical therapeutics.

scholarly journals Novel aminochromone derivative inhibits tumor growth on xenograft model of lung cancer in mice

2018 ◽  
Vol 9 (4) ◽  
pp. 130 ◽  
Author(s):  
DmitryS Blinov ◽  
EkaterinaV Blinova ◽  
MarinaO Dudina ◽  
IrinaR Suslova ◽  
ElenaA Samishina ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Xenograft Model

Inhibition of tumor growth in a murine xenograft model by thalidomide

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20083-20083
Author(s):  
L. Horn ◽  
M. Hermes ◽  
J. Schwock ◽  
M. Brulport ◽  
J. G. Hengstler
Keyword(s):  
Cervical Cancer ◽  
Tumor Growth ◽  
Tumor Volume ◽  
Xenograft Model ◽  
Cancer Cell Line ◽  
Cervical Cancer Cell Line ◽  
Tumor Diameter ◽  
Murine Xenograft Model ◽  
Inhibition Of Tumor Growth ◽  
The Mean

20083 Background: Limitations in the treatment of recurrent disease in cervical carcinoma are for radiation therapy large tumor size and pelvic side wall involvement and for exenteration procedurde previous radiation therapy, bulky disease, and others. Alternative approaches including chemotherapy, chemo-radiation, radiation plus hyperthermia and others are accompanied by a failure rate of 50 to 80%. Recent research has shown that the antineoplastic effect of thalidomide (TD) is due to the inhibition of neo-angiogenesis, a decrease of TNF-a, blocking of nuclear factor κβ-kinase activity, stimulation of the IL-2 and downregulation of cell adhesion molecules. Here, we have studied the effect of TD on a cervical cancer cell line in a murine xenograft model. Methods: We injected 7 × 106 HELA cells s.c. into the dorsal skin of 6–8 week-old male nude mice (cd nu−/nu−; Charles River, Sulzfeld, Germany). The tumor diameter was measured with a caliber rule. The maximum and minimum diameters of the tumor were determined. Tumor volume (V) was calculated by the formula: V = a × b × b/2, where a represents the minimum and b the maximum tumor diameter. As soon as tumors reached a volume of 0.25 cm3 the mice were randomized into a treatment (n = 9) and a control group (n = 9). The mice in the treatment group received 14 daily injections of 300 mg/kg (i.p.) thalidomide for 14 days. Animals were housed under specific pathogen-free conditions. The experiments have been approved by the local animal welfare committee. Results: Thalidomide caused a clear delay in tumor growth. Already 7 days after onset of thalidomide therapy the mean tumor volume was smaller in the treated (0.24 ± 0.03 cm3) compared to the control mice (0.73 ± 0.15 cm3; mean ± standard error; p < 0.01). After 14 days of thalidomide treatment the mean tumor volumes were 0.37 ± 0.05 and 1.05 ± 0.19 cm3 in the treated and in the control mice, respectively (p < 0.01). However, after the end of the 14 days treatment period a new onset of tumor growth was observed. In conclusion, thalidomide delayed tumor growth but did not cause tumor remission. Conclusions: TD is effective in inhibition of tumor growth of a cervical cancer cell line in a mouse xenograft model and might be an alternative drug in patients with recurrent cervical carcinoma without any options for established standard therapy. No significant financial relationships to disclose.

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