Postlumpectomy loco-regional breast cancer therapy with liposomal therapeutic agents: Retention and distribution in nude rats

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11562-e11562
Author(s):  
S. Li ◽  
B. Goins ◽  
W. T. Phillips ◽  
M. Saenz ◽  
P. Otto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Nodes ◽  
Xenograft Model ◽  
Therapeutic Agents ◽  
Surgical Removal ◽  
Post Mortem ◽  
Surface Charges ◽  
Nude Rats ◽  
Anionic Liposomes

e11562 Background: Post-lumpectomy loco-regional radiation therapy, such as brachytherapy, has been shown to decrease breast cancer recurrence and increase patient survival. Limitations of current brachytherapy are the relatively high radiation absorbed dose delivered to normal breast and the inability to treat potentially involved lymph nodes. Locally administered liposomes are being investigated for delivery of drugs and therapeutic radionuclides. We propose a new post-lumpectomy loco-regional therapy with liposome-carried therapeutic agents. To investigate, radiolabeled liposomes were injected into the surgical cavity of a nude rat model one day following surgical removal of the breast tumor, and in vivo retention and distribution were monitored with nuclear imaging and post- mortem dissection. Methods: Six liposome formulations containing 0.2% molar ratio Rhodamine B-lipid and cationic, neutral, or anionic surface charges were manufactured at diameters of 400 or 100 nm and characterized. Breast cancer xenograft model in female nude rats was set up by inoculating MDA-MB-231 cells into the fat pad of the left breast of each rat. When tumor volumes reached 1.9 cm3 on average, the majority of each tumor was surgically removed, leaving ∼0.05 cm3 tumor tissue in the cavity. Then, each rat (3–4 rats/group) was intracavitarily injected with 0.5 ml of 99mTc-liposomes (4 mCi., 30 mg total lipids/kg body weight). In vivo distribution of 99mTc-activity was measured with planar gamma camera and SPECT imaging at various times. Post-mortem stereo fluorescent images of surgical cavity and the surrounding lymph nodes at 44 h were acquired. Results: All 99mTc-liposome formulations had approximately ≥ 50% retention in the surgical cavity at 44 h after injection. 99mTc-anionic liposomes of 100 nm diameter had an optimal lymph node targeting with ∼6%/g tissue in the surrounding lymph nodes at 44 h. Fluorescence imaging of the liposomes clearly showed their clearance through surrounding lymphatics and retention in lymph nodes. Conclusions: Anionic liposomes of 100 nm diameter are promising carriers for the simultaneous treatment of the surgical cavity and its draining lymph nodes. No significant financial relationships to disclose.

scholarly journals [6]-Gingerol-Derived Semi-Synthetic Compound SSi6 Inhibits Tumor Growth and Metastatic Dissemination in Triple-Negative Breast Cancer Xenograft Models

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2855
Author(s):  
Liany Luna-Dulcey ◽  
James Almada da Silva ◽  
Veronica Jimenez-Renard ◽  
Eduardo Caleiras ◽  
Silvana Mouron ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Nodes ◽  
Primary Tumor ◽  
Cancer Metastasis ◽  
Triple Negative ◽  
Xenograft Model ◽  
Breast Cancer Metastasis ◽  
Synthetic Compound ◽  
Xenograft Models

Breast cancer metastasis is the most common cause of cancer death in women worldwide. Triple-negative breast cancers (TNBC) form a heterogeneous group of tumors that have higher relapse rates and poorer survival compared to other breast cancer subtypes. Thus, this work reports the antitumor and antimetastatic activities of a [6]-gingerol-derived semi-synthetic compound named SSi6 on MDA-MB-231 TNBC cells using xenograft models. SSi6 did not cause toxic effects in vivo as demonstrated by body weight and hematological and histological evaluations. From the orthotopic xenograft model, we demonstrated that SSi6 slows and inhibits the growth of the primary tumor, as well as prevents metastatic spontaneous progression from lymph nodes to the lungs. Moreover, a second xenograft model with resection of the primary tumor showed that SSi6 also blocks the progression of metastases from the lymph nodes to other visceral organs. Taken together, our results demonstrate that SSi6 is a promising compound to be investigated in other preclinical and clinical models to be applied as a complementary therapy for TNBC.

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.

Characterization of an intraperitoneal ovarian cancer xenograft model in nude rats using noninvasive microPET imaging

2007 ◽  
Vol 17 (2) ◽  
pp. 407-417 ◽  
Author(s):  
C. L. Zavaleta ◽  
W. T. Phillips ◽  
Y. C. Bradley ◽  
L. M. McMANUS ◽  
P. A. Jerabek ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Lymph Nodes ◽  
Peritoneal Cavity ◽  
Imaging Modality ◽  
Xenograft Model ◽  
Tumor Model ◽  
Fdg Uptake ◽  
Tumor Bearing ◽  
Nude Rats ◽  
Biodistribution Data

MicroPET is a noninvasive imaging modality that can potentially track tumor development in nude rats using the radiotracer fluorine 18-fluorodeoxyglucose (18F-FDG). Our goal was to determine whether microPET, as opposed to more invasive techniques, could be used to noninvasively monitor the development of ovarian cancer in the peritoneal cavity of nude rats for monitoring treatment response in future studies. Female nude rats were inoculated intraperitoneally with 36 million NIH:OVCAR-3 cells. Imaging was carried out at 2, 4, 6, or 8 weeks postinoculation. Each rat was fasted overnight and intravenously injected with 11.1 MBq (300 μCi) of 18F-FDG in 0.2 mL of saline. Thirty minutes following injection, the rats were placed in the microPET and scanned for 30 min. After imaging, rats were euthanized for ascites and tissue collection for biodistribution and histopathologic correlation. Standard uptake values (SUVs) of 18F-FDG within the peritoneal cavity were also calculated from regions of interest analysis of the microPET images. MicroPET images showed diffuse increased uptake of 18F-FDG throughout the peritoneal cavity of tumor rats (mean SUV = 4.64) compared with control rats (mean SUV = 1.03). Ascites gathered from tumor-bearing rats had increased 18F-FDG uptake as opposed to the peritoneal fluid collected from control rats. Biodistribution data revealed that the percent injected dose per gram (% ID/g) was significantly higher in tumor-bearing rats (6.29%) than in control rats (0.59%) in the peritoneal lymph nodes. Pathology verified that these lymph nodes were more reactive in tumor-bearing rats. By 6 weeks, some rats developed solid masses within the peritoneum, which could be detected on microPET images and confirmed as tumor by histopathology. 18F-FDG uptake in these tumors at necropsy was 2.83% ID/g. These results correlate with previous invasive laparoscopic studies of the same tumor model and demonstrate that microPET using 18F-FDG is a promising noninvasive tool to localize and follow tumor growth in an intraperitoneal ovarian cancer model.

Effect of Auraptene on angiogenesis in Xenograft model of breast cancer

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mohammad Reza Shiran ◽  
Elham Mahmoudian ◽  
Abolghasem Ajami ◽  
Seyed Mostafa Hosseini ◽  
Ayjamal Khojasteh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Animal Model ◽  
Protein Expression ◽  
Western Blot ◽  
Xenograft Model ◽  
Dependent Manner ◽  
Concentration Dependent Manner

Abstract Objectives Angiogenesis is the most important challenge in breast cancer treatment. Recently, scientists become interesting in rare natural products and intensive researches was performed to identify their pharmacological profile. Auraptene shows helpful effects such as cancer chemo-preventive, anti-inflammatory, anti-oxidant, immuno-modulatory. In this regard, we investigated the anti-angiogenesis effect of Auraptene in in-vitro and in-vivo model of breast cancer. Methods In this study, 4T, MDA-MB-231 and HUVEC cell lines were used. The proliferation study was done by MTT assay. For tube formation assay, 250 matrigel, 1 × 104 HUVEC treated with Auraptene, 20 ng/mL EGF, 20 ng/mL bFGF and 20 ng/mL VEGF were used. Gene expression of important gene related to angiogenesis in animal model of breast cancer was investigated by Real-time PCR. Protein expression of VCAM-1 and TNFR-1 gene related to angiogenesis in animal model of breast cancer was investigated by western-blot. Results Auraptene treatment led to reduction in cell viability of MDA-MB-231 in a concentration-dependent manner. Also, we observed change in the number of tubes or branches formed by cells incubated with 40 and 80 μM Auraptene. Auraptene effect the gene expression of important gene related to angiogenesis (VEGF, VEGFR2, COX2, IFNɣ). Moreover, the western blot data exhibited that Auraptene effect the protein expression of VCAM-1 and TNFR-1. Conclusions Overall, this study shows that Auraptene significantly suppressed angiogenesis via down-regulation of VEGF, VEGFR2, VCAM-1, TNFR-1, COX-2 and up-regulation of IFNγ.

scholarly journals Isoform-specific promotion of breast cancer tumorigenicity by TBX3 involves induction of angiogenesis

2019 ◽  
Vol 100 (3) ◽  
pp. 400-413
Author(s):  
Milica Krstic ◽  
Haider M. Hassan ◽  
Bart Kolendowski ◽  
M. Nicole Hague ◽  
Pieter. H. Anborgh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Subtype ◽  
Xenograft Model ◽  
Tumor Formation ◽  
Transcriptional Analysis ◽  
Breast Cancer Cell Lines ◽  
Tumor Vascularity ◽  
Mouse Xenograft Model

Abstract TBX3 is a member of the highly conserved family of T-box transcription factors involved in embryogenesis, organogenesis and tumor progression. While the functional role of TBX3 in tumorigenesis has been widely studied, less is known about the specific functions of the different isoforms (TBX3iso1 and TBX3iso2) which differ in their DNA-binding domain. We therefore sought to investigate the functional consequence of this highly conserved splice event as it relates to TBX3-induced tumorigenesis. By utilizing a nude mouse xenograft model, we have identified differential tumorigenic potential between TBX3 isoforms, with TBX3iso1 overexpression more commonly associated with invasive carcinoma and high tumor vascularity. Transcriptional analysis of signaling pathways altered by TBX3iso1 and TBX3iso2 overexpression revealed significant differences in angiogenesis-related genes. Importantly, osteopontin (OPN), a cancer-associated secreted phosphoprotein, was significantly up-regulated with TBX3iso1 (but not TBX3iso2) overexpression. This pattern was observed across three non/weakly-tumorigenic breast cancer cell lines (21PT, 21NT, and MCF7). Up-regulation of OPN in TBX3iso1 overexpressing cells was associated with induction of hyaluronan synthase 2 (HAS2) expression and increased retention of hyaluronan in pericellular matrices. These transcriptional changes were accompanied by the ability to induce endothelial cell vascular channel formation by conditioned media in vitro, which could be inhibited through addition of an OPN neutralizing antibody. Within the TCGA breast cancer cohort, we identified an 8.1-fold higher TBX3iso1 to TBX3iso2 transcript ratio in tumors relative to control, and this ratio was positively associated with high-tumor grade and an aggressive molecular subtype. Collectively, the described changes involving TBX3iso1-dependent promotion of angiogenesis may thus serve as an adaptive mechanism within breast cancer cells, potentially explaining differences in tumor formation rates between TBX3 isoforms in vivo. This study is the first of its kind to report significant functional differences between the two TBX3 isoforms, both in vitro and in vivo.

scholarly journals Paclitaxel induces lymphatic endothelial cells autophagy to promote metastasis

2019 ◽  
Vol 10 (12) ◽  
Author(s):  
Audrey Zamora ◽  
Melinda Alves ◽  
Charlotte Chollet ◽  
Nicole Therville ◽  
Tiffany Fougeray ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Nodes ◽  
Lymphatic System ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Sentinel Lymph Nodes ◽  
Cancer Drug ◽  
Lymphatic Endothelium ◽  
Primary Tumors

AbstractCytotoxic therapy for breast cancer inhibits the growth of primary tumors, but promotes metastasis to the sentinel lymph nodes through the lymphatic system. However, the effect of first-line chemotherapy on the lymphatic endothelium has been poorly investigated. In this study, we determined that paclitaxel, the anti-cancer drug approved for the treatment of metastatic or locally advanced breast cancer, induces lymphatic endothelial cell (LEC) autophagy to increase metastases. While paclitaxel treatment was largely efficacious in inhibiting LEC adhesion, it had no effect on cell survival. Paclitaxel inhibited LEC migration and branch point formation by inducing an autophagy mechanism independent of Akt phosphorylation. In vivo, paclitaxel mediated a higher permeability of lymphatic endothelium to tumor cells and this effect was reversed by chloroquine, an autophagy-lysosome inhibitor. Despite a strong effect on reducing tumor size, paclitaxel significantly increased metastasis to the sentinel lymph nodes. This effect was restricted to a lymphatic dissemination, as chemotherapy did not affect the blood endothelium. Taken together, our findings suggest that the lymphatic system resists to chemotherapy through an autophagy mechanism to promote malignant progression and metastatic lesions. This study paves the way for new combinative therapies aimed at reducing the number of metastases.

scholarly journals Ginsenoside Rg3: Potential Molecular Targets and Therapeutic Indication in Metastatic Breast Cancer

Medicines ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. 17 ◽  
Author(s):  
Maryam Nakhjavani ◽  
Jennifer E Hardingham ◽  
Helen M Palethorpe ◽  
Yoko Tomita ◽  
Eric Smith ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Metastatic Breast ◽  
Therapeutic Agents ◽  
Ginsenoside Rg3 ◽  
Cancer Models ◽  
Anti Cancer ◽  
Ginseng Plant

Breast cancer is still one of the most prevalent cancers and a leading cause of cancer death worldwide. The key challenge with cancer treatment is the choice of the best therapeutic agents with the least possible toxicities on the patient. Recently, attention has been drawn to herbal compounds, in particular ginsenosides, extracted from the root of the Ginseng plant. In various studies, significant anti-cancer properties of ginsenosides have been reported in different cancers. The mode of action of ginsenoside Rg3 (Rg3) in in vitro and in vivo breast cancer models and its value as an anti-cancer treatment for breast cancer will be reviewed.

Treatment of breast cancer with lymph nodes by volumetric arc therapy (VMAT): Pretreatment and in vivo dosimetry

2015 ◽  
Vol 31 ◽  
pp. e30
Author(s):  
D. Nguyen ◽  
G. Largeron ◽  
F. Josserand-Pietri ◽  
C. Sporea ◽  
M. Khodri
Keyword(s):  
Breast Cancer ◽  
Lymph Nodes ◽  
In Vivo Dosimetry ◽  
Volumetric Arc Therapy ◽  
Arc Therapy
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