scholarly journals Ultrasound-Targeted Microbubble Destruction Enhances Inhibitory Effect of Apatinib on Angiogenesis in Triple Negative Breast Carcinoma Xenografts

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Dengke Hong ◽  
Jiajia Yang ◽  
Jingjing Guo ◽  
Yu Zhang ◽  
Zhikui Chen
Keyword(s):  
Body Weight ◽  
Tumor Growth ◽  
Nude Mice ◽  
Triple Negative ◽  
Good Condition ◽  
Xenograft Model ◽  
Inhibitory Effect ◽  
Blood Parameters ◽  
Model Control ◽  
Growth Inhibiting

Ultrasound-targeted microbubble destruction (UTMD) has been proven as an effective technique to assist drugs to cross the vascular wall and cell membrane. This study was aimed at evaluating the synergistic antiangiogenic and growth-inhibiting effects of apatinib (APA) and UTMD on the triple negative breast cancer (TNBC). The TNBC xenograft model was established in nude mice ( n = 40 ) which were then randomly divided into the APA plus UTMD (APA-U) group, UTMD group, APA group, and model control (M) group ( n = 10 per group). Corresponding treatment was done once daily for 14 consecutive days. The general condition and body weight of tumor-bearing nude mice were monitored. Routine blood test and detection of liver and kidney function were done after treatments. The tumor size and microcirculation were examined by two-dimensional ultrasonography (2DUS) and contrast-enhanced ultrasonography (CEUS), respectively. Then, the tumor tissues were harvested for the detection of vascular endothelial growth factor (VEGF) by immunohistochemistry and for CD31-PAS double staining to assess microvessel density (MVD) and heterogeneous vascular positivity rate. After treatments, the tumor growth and angiogenesis were significantly inhibited in the APA group and the APA-U group, and these effects were more obvious in the APA-U group. The tumor volume, CEUS parameters, VEGF expression, and MVD in the APA-U group were significantly lower than those in the APA group ( P < 0.05 ), while there were no marked differences in the heterogeneous vascular positivity rate, body weight, and blood parameters between the two groups ( P > 0.05 ). In the UTMD group, the tumor growth and angiogenesis were not significantly inhibited, and all the parameters were similar to those in the M group ( P > 0.05 ). During the experiment, all mice survived and generally had good condition. In conclusion, APA combined with UTMD may exert synergistic antiangiogenic and growth-inhibiting effects on the TNBC and not increase the heterogeneous vasculature and the severity of APA-related systemic side effects.

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 Edelfosine nanoemulsions inhibit tumor growth of triple negative breast cancer in zebrafish xenograft model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sofia M. Saraiva ◽  
Carlha Gutiérrez-Lovera ◽  
Jeannette Martínez-Val ◽  
Sainza Lores ◽  
Belén L. Bouzo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Xenograft Model ◽  
Skin Barrier ◽  
Zebrafish Embryos ◽  
Biorelevant Media

AbstractTriple negative breast cancer (TNBC) is known for being very aggressive, heterogeneous and highly metastatic. The standard of care treatment is still chemotherapy, with adjacent toxicity and low efficacy, highlighting the need for alternative and more effective therapeutic strategies. Edelfosine, an alkyl-lysophospholipid, has proved to be a promising therapy for several cancer types, upon delivery in lipid nanoparticles. Therefore, the objective of this work was to explore the potential of edelfosine for the treatment of TNBC. Edelfosine nanoemulsions (ET-NEs) composed by edelfosine, Miglyol 812 and phosphatidylcholine as excipients, due to their good safety profile, presented an average size of about 120 nm and a neutral zeta potential, and were stable in biorelevant media. The ability of ET-NEs to interrupt tumor growth in TNBC was demonstrated both in vitro, using a highly aggressive and invasive TNBC cell line, and in vivo, using zebrafish embryos. Importantly, ET-NEs were able to penetrate through the skin barrier of MDA-MB 231 xenografted zebrafish embryos, into the yolk sac, leading to an effective decrease of highly aggressive and invasive tumoral cells’ proliferation. Altogether the results demonstrate the potential of ET-NEs for the development of new therapeutic approaches for TNBC.

Abstract 17055: Novel Dual mTOR Inhibitor/AMPK Activator Mitigates Doxorubicin Cardiotoxicity and Potentiates Its Chemotherapeutic Efficacy Against Triple Negative Breast Cancer

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Anindita Das ◽  
Sahak Hovsepian ◽  
Sayantanee Das ◽  
Arun Samidurai ◽  
Adolfo G Mauro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Weight ◽  
Tumor Growth ◽  
Triple Negative Breast Cancer ◽  
Mtor Inhibitor ◽  
Triple Negative ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Chemotherapeutic Efficacy

Background: Doxorubicin (DOX) is a first-line anticancer drug for the treatment of triple negative breast cancer (TNBC). However, its dose-dependent delayed and progressive cardiotoxicity limits its therapeutic application. NovoMedix (NM922) is a novel dual mTOR inhibitor/AMPK activator that was shown to attenuate adverse cardiac remodeling and fibrosis in a pressure-overload mouse model of heart failure. We investigated whether combination therapy with DOX and NM922 exhibits synergistic chemotherapeutic effect while mitigating DOX cardiotoxicity. Methods & Results: Tumors were generated in athymic female BALB/cAnNCr-nu/nu mice by implanting MDA-MB-231 cells into the rear right flank. Mice with tumors (volume≈200mm 3 ) were randomized into 6 groups and treated as follows: 1) Control (n=10); 2) DOX (3 mg/kg; i.p. twice weekly, total 15 mg/kg; n=10); 3) NM922 (25 mg/kg/d; p.o. n=5); 4) DOX+NM922 (25 mg/kg/d; p.o. n=15); 5) NM922 (100 mg/kg/d; p.o. n=5); 6) DOX+NM922 (100 mg/kg/d; p.o. n=15). Tumor size, body weight and cardiac function were assessed throughout the study. DOX alone, and to a significant extent when in combination with NM922 (25 mg/kg) reduced tumor growth compared to control. NM922 (100 mg/kg) with/without DOX significantly reduced tumor growth as compared to DOX alone (Fig A). DOX caused reduction in body weight and survival of tumor-bearing mice. NM922 did not prevent DOX-induced cachexia, but significantly improved survival in DOX-treated mice (Fig B). DOX treatment caused a significant decline in left ventricular ejection fraction compared to control over 3 weeks, which was ameliorated with NM922 (100 mg/kg) co-treatment (Fig C&D). Conclusion: Our results suggest that NM922 may potentiate the chemotherapeutic efficacy of DOX in TNBC, while mitigating its cardiotoxicity. Moreover, these findings advocate the potential efficacy of utilizing lower DOX dosages when combined with NM922, which would have significant clinical implications.

scholarly journals Chemokine Expression Is Involved in the Vascular Neogenesis of Ewing Sarcoma: A Preliminary Analysis of the Early Stages of Angiogenesis in a Xenograft Model

2018 ◽  
Vol 22 (1) ◽  
pp. 30-39
Author(s):  
Francisco Giner ◽  
José A López-Guerrero ◽  
Antonio Fernández-Serra ◽  
Isidro Machado ◽  
Empar Mayordomo-Aranda ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Tumor Cells ◽  
Nude Mice ◽  
Ewing Sarcoma ◽  
Xenograft Model ◽  
Bone Cancer ◽  
Mouse Serum ◽  
Early Stages ◽  
Peritumoral Stroma ◽  
Ligand Expression

Background Ewing sarcoma (EWS) is the second most common bone cancer in pediatric patients. Angiogenesis is a major factor for tumor growth and metastasis. Our aim was to carry out a histological, immunohistochemical, and molecular characterization of the neovascularization established between xenotransplanted tumors and the host during the initial phases of growth in nude mice in three angiogenesis experiments (ES2, ES3, and ES4). Methods The original human EWS were implanted subcutaneously on the backs of three nude mice. Tumor pieces 3 mm–4 mm in size from early passages of Nu432, Nu495, and Nu471 were also implanted subcutaneously on the backs of three sets (ES2, ES3, and ES4) of athymic Balb-c nude mice (n = 14 each). The animals were sacrificed at 24, 48, and 96 hours and at 7, 14, 21, and 28 days after implantation to perform histological, immunohistochemical, and molecular studies (neovascularization experiments). Results We observed histological, ultrastructural, and immunohistochemical changes in the xenografted tumor at different times after implantation. Chemokine ligand expression peaked twice, once during the first 48 hours and again in the second week. We observed that tumor cells in contact with murine peritumoral stroma presented higher expression of chemokine ligands as well as more tumor cells around the capillary vessels. Mouse serum vascular endothelial growth factor levels peaked twice, once in the first hours and then in the second week after tumor implantation. Conclusion Chemokines and other angiogenic factors may be relevant in the angiogenic mechanism during tumor growth. This model provides information on the early stages of the angiogenic process and could be a useful tool in researching anti-angiogenic drugs for new therapeutic strategies in EWS.

Effect of FSH supplementation on the GnRH antagonist suppressed growth of PC-3 cell xenografts in nude mice.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. e630-e630
Author(s):  
Olayiwola Oduwole ◽  
Phil Rawson ◽  
Nafis Rahman ◽  
Wolfgang Koechling ◽  
Ilpo Huhtaniemi
Keyword(s):  
Prostate Cancer ◽  
Tumor Growth ◽  
Nude Mice ◽  
Gnrh Agonist ◽  
Gnrh Antagonist ◽  
Inhibitory Effect ◽  
Prostate Cancer Treatment ◽  
Beneficial Effects ◽  
Hormone Ablation ◽  
Agonist And Antagonist

e630 Background: One of the fundamental differences between GnRH agonist and antagonist treatment is the permanent suppression of FSH by antagonist, while a rebound in FSH secretion has been documented upon agonist treatments. To assess the potential beneficial effects of permanent FSH suppression in the hormone ablation treatment of prostate cancer we studied the effect of the GnRH antagonist degarelix in the absence and presence of FSH supplementation on the growth of PC-3 human prostate cancer cell xenografts in nude mice. Methods: Intact (n = 20) and gonadectomized (n = 20) nude male mice were inoculated with 2 x 106PC-3 cells. Half of each group received degarelix treatment at 10 mg/kg body weight s.c. In a second experiment (n = 10/group), degarelix treatment was supplemented with recombinant human FSH at10 IU/kg/day using i.p. ALZET osmotic minipumps. Tumor growth in both experiments was monitored for 4 weeks by external inspection and caliper measurement, after which the mice were sacrificed. Results: The first experiment demonstrated that degarelix treatment significantly reduced tumor growth by 33% and 35%, respectively, in intact and gonadectomized mice as compared to non-treated controls (p<0.0001 for each). In the second experiment, FSH reversed the inhibitory effect of degarelix in intact mice. Conclusions: These results demonstrated that the suppression of PC-3 xenograft growth by GnRH antagonist treatment was completely inhibited by concomitant FSH treatment. The findings prove experimentally the principle that combined FSH and LH suppression by GnRH antagonist could offer an advantage over the isolated LH suppression by GnRH agonist upon prostate cancer treatment. [Table: see text]

scholarly journals Chinese Formula Ganji Fang Inhibits Tumor Growth Through Regulating Cell Mitosis by Reducing ARPP-19 Expression in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Chunlei Zhang ◽  
Kaiyue Tang ◽  
Lili Yang ◽  
Yang Liu ◽  
Yifan Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Survival Time ◽  
Nude Mice ◽  
Tumor Volume ◽  
Xenograft Model ◽  
The Body ◽  
Proliferation Index ◽  
Mouse Xenograft Model ◽  
Liver And Kidney

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies with high rate of mortality worldwide. Rare effective treatment is available for HCC patients especially at advanced stage. Ganji Fang (GJF), one formula of traditional Chinese medicine (TCM), has shown therapeutic effect on HCC in clinical application. This study aims at evaluating the anti-HCC effect and safety of GJF treatment, as well as exploring the potential underlying molecular mechanism by using HCC mouse model. Methods: HepG2 cells were subcutaneously injected into the upper flank of male BALB/c nude mice to establish the HCC Xenograft model. Mice were randomly assigned to three groups, treated respectively with high (GJF-H group) or low dose (GJF-L group) of GJF or vehicle (Control group) via gavage. The tumor volume was detected dynamically. Four weeks later, the weight and proliferation activity of tumors were measured. Western blot and immunohistochemistry were used to detect the expression of cAMP-regulated phosphoprotein 19 (ARPP-19) and the regulated molecules. H&E staining of tissue section of liver and kidney was used to assess the toxicity of the formula. Foe investigation of survival time, SMMC 7721 cells were injected subcutaneously to the BALB/c-nude mice. The tumor-bearing mice were allocated into two groups (Control and GJF-H) and treated as above description. The death number of mice was recorded and the survival time was analyzed.Results: Compared with control, the body weight and activity of GJF-treated mice were improved obviously. No toxic change was observed in tissues of liver and kidney. The tumor volume and weight was significantly down-regulated by GJF dose-dependently. The mice with GJF treatment showed the tendency of prolonging survival time. The proliferation index and PCNA expression in the tumor of GJF group were lower than in control. Furthermore, GJF down-regulated levels of ARPP-19 and phospho-(Ser) CDKs substrates, up-regulated level of inactivated cyclin division cycle 2 (Cdc2). Conclusion: GJF can effectively inhibit tumor growth of HCC and improve the general condition of the nude mouse xenograft model. The mechanism of inhibiting tumor growth is partially related to down-regulating ARPP-19 to inhibit mitosis and cell proliferation of HCC.

scholarly journals Inhibitory effect of KDR-specific monoclonal antibody on tumor growth in nude mice bearing human gastric cancer

2011 ◽  
Vol 19 (28) ◽  
pp. 2925
Author(s):  
Gui-Mei Kong ◽  
Xiao-Rong Zhang ◽  
Ke-Yan Wu ◽  
Fei-Yan Zhao ◽  
Hai-Hang Zhu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Monoclonal Antibody ◽  
Tumor Growth ◽  
Nude Mice ◽  
Inhibitory Effect ◽  
Human Gastric Cancer ◽  
Specific Monoclonal Antibody
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