Journal Article

MDA-MB-231-luc2, IVIS, Breast Cancer, Bioware

In recent years, oncolytic adenoviruses have shown some promise as a novel class of antitumor agents. However, their utility in targeting bone metastases is relatively less studied. We have examined whether the systemic therapy of oncolytic adenoviruses expressing the soluble form of transforming growth factor-beta (TGFbeta) receptor II fused with human immunoglobulin G1 can be developed for the treatment of established breast cancer bone metastases. MDA-MB-231-luc2 human breast cancer cells were injected in the left heart ventricle of nude mice to establish bone metastasis. Mice with hind limb tumors were administered (on days 8 and 11) oncolytic adenoviruses-Ad.sTbetaRFc or mhTERTAd.sTbetaRFc. Skeletal tumor growth was monitored weekly by bioluminescence imaging (BLI) and radiography. At the termination time on day 28, hind limb bones were analyzed for tumor burden, synchrotron micro-computed tomography, and osteoclast activation. Intravenous delivery of Ad.sTbetaRFc and mhTERTAd.sTbetaRFc induced significant inhibition of tumor growth, reduction of tumor burden, osteoclast activation, and increased animals' survival. Oncolytic adenoviruses were safer than dl309, a wild-type virus. A slight elevation of liver enzyme activity was observed after Ad.sTbetaRFc administration; this subsided with time. Based on these studies, we believe that Ad.sTbetaRFc and mhTERTAd.sTbetaRFc can be developed as a safe and effective approach for the treatment of established bone metastasis.

Journal Article

HCT-116-luc2, IVIS, Bioware, HCT116-luc2

Non-thermal plasma (NTP) is generated by ionizing neutral gas molecules/atoms leading to a highly reactive gas at ambient temperature containing excited molecules, reactive species and generating transient electric fields. Given its potential to interact with tissue or cells without a significant temperature increase, NTP appears as a promising approach for the treatment of various diseases including cancer. The aim of our study was to evaluate the interest of NTP both in vitro and in vivo. To this end, we evaluated the antitumor activity of NTP in vitro on two human cancer cell lines (glioblastoma U87MG and colorectal carcinoma HCT-116). Our data showed that NTP generated a large amount of reactive oxygen species (ROS), leading to the formation of DNA damages. This resulted in a multiphase cell cycle arrest and a subsequent apoptosis induction. In addition, in vivo experiments on U87MG bearing mice showed that NTP induced a reduction of bioluminescence and tumor volume as compared to nontreated mice. An induction of apoptosis was also observed together with an accumulation of cells in S phase of the cell cycle suggesting an arrest of tumor proliferation. In conclusion, we demonstrated here that the potential of NTP to generate ROS renders this strategy particularly promising in the context of tumor treatment.

Journal Article

MDA-MB-231-D3H1, MDA-MB-231-luc-D3H1, IVIS, Bioware, Breast Cancer

STUDY DESIGN: In vivo experiments to develop a rat spine single metastasis model by using human breast cancer cells. OBJECTIVE: To study the survival and tumorigenesis of the human breast cancer cells after transplantation to vertebral body (VB) by intraosseous injection as a model for therapeutic studies of spine metastatic tumor. SUMMARY OF BACKGROUND DATA: VBs are the most common bones involved in the metastases of breast cancer. To develop experimental therapeutics requires an appropriate animal model. Moreover, it is also important to establish accurate and sensitive detection methods for the evaluation. METHODS: MDA-MB-231 human breast cancer cells were injected into 3-week-old female athymic rats. The tumorigenesis was assayed with quantitative in vivo bioluminescence (IVIS), microcomputed tomography (micro-CT), quantitative CT (qCT), micro position emission tomography (micro-PET), and histologic studies. RESULTS: A spine single metastasis model of human breast cancer was successfully developed in rats. The IVIS signal intensity from the cancer cells increased after 2 weeks. Signal from the tumor in spine can be detected by micro-PET at day 1. The signal intensity decreased after 1 week and then recovered and continually increased afterwards. Bone destruction was demonstrated in the qCT and micro-CT images. However, both qCT and micro-CT found that the bone density in the cancer cell-injected VB increased before the appearance of osteolysis. The growth of tumor and the reaction of bone in the VB were observed simultaneously by histology. CONCLUSION: A spine single metastasis model was developed by injection of human breast cancer cells into the VB of athymic rats. This is the first report of quantitative evaluation with micro-PET in a spine metastasis model. In addition, the detection of osteogenesis after the introduction of MDA-MB-231 cells in vivo is a novel observation.

Journal Article

LL/2-luc-M38, LL/2-luc, Lewis Lung Carcinoma, IVIS, Adenocarcinoma/drug therapy/genetics/*immunology/metabolism/pathology; Administration, Intranasal; Adult; Aged; Animals; Antibodies, Neutralizing/administration & dosage/*therapeutic use; Antigens, CD/immunology; Female; Forkhead Transcription Factors/genetics/*immunology/metabolism; Gene Expression Regulation, Neoplastic/drug effects/*immunology; Humans; Immunologic Surveillance; Interferon-gamma/biosynthesis/immunology; Interleukin-17/immunology/metabolism; Interleukin-23/immunology/metabolism; Lung/drug effects/*immunology/metabolism/pathology; Lung Neoplasms/drug therapy/genetics/*immunology/metabolism/pathology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; T-Box Domain Proteins/deficiency/*genetics/immunology; T-Lymphocytes, Regulatory/immunology

Lung cancer is the leading cause of cancer deaths worldwide. The cytokine interleukin-17A supports tumour vascularization and growth, however, its role in lung cancer is unknown. Here we show, in the lungs of patients with lung adenocarcinoma, an increase in interleukin-17A that is inversely correlated with the expression of T-bet and correlated with the T regulatory cell transcription factor Foxp3. Local targeting of interleukin-17A in experimental lung adenocarcinoma results in a reduction in tumour load, local expansion of interferon-gamma-producing CD4(+) T cells and a reduction in lung CD4(+)CD25(+)Foxp3(+) regulatory T cells. T-bet((-/-)) mice have a significantly higher tumour load compared with wild-type mice. This is associated with the local upregulation of interleukin-23 and induction of interleukin-17A/interleukin-17R-expressing T cells infiltrating the tumour. Local anti-interleukin-17A antibody treatment partially improves the survival of T-bet((-/-)) mice. These results suggest that local anti-interleukin-17A antibody therapy could be considered for the treatment of lung tumours.

Journal Article

Xen31, Xen 31, MRSA, S. aureus, IVIS, Bioluminescence, Biofilms/drug effects/*radiation effects; Ciprofloxacin/*pharmacology; Culture Media; High-Energy Shock Waves; Humans; *Laser Therapy, Low-Level; Methicillin-Resistant Staphylococcus aureus/*growth &; development/physiology/*radiation effects; Microbial Sensitivity Tests; Reference Values; Sensitivity and Specificity; Spectroscopy, Near-Infrared; Staphylococcal Infections/drug therapy

OBJECTIVE: The aim of the study was to study the efficacy of 2 different lasers in vitro, in disrupting biofilm and killing planktonic pathogenic bacteria. MATERIALS AND METHODS: Biofilms of a stable bioluminescent of Staphylococcus aureus Xen 31 were grown in a 96-well microtiter plate for 3 days. The study included 7 arms: (a) control; (b) ciprofloxacin (3 mg/L, the established minimum inhibitory concentration [MIC]) alone; (c) shock wave (SW) laser alone; (d) near-infrared (NIR) laser alone; (e) SW laser and ciprofloxacin; (f) SW and NIR lasers; (g) SW, NIR lasers, and ciprofloxacin. The results were evaluated with an in vivo imaging system (IVIS) biophotonic system (for live bacteria) and optical density (OD) for total bacteria. RESULTS: Without antibiotics, there was a 43% reduction in OD (P < .05) caused by the combination of SW and NIR suggesting that biofilm had been disrupted. There was an 88% reduction (P < .05) in live biofilm. Ciprofloxacin alone resulted in a decrease of 28% of total live cells (biofilm remaining attached) and 58% of biofilm cells (both P > .05). Ciprofloxacin in combination with SW and SW + NIR lasers caused a decrease of more than 60% in total live biomass and more than 80% of biofilm cells, which was significantly greater than ciprofloxacin alone (P < .05). CONCLUSIONS: We have demonstrated an effective nonpharmacologic treatment method for methicillin-resistant Staphylococcus aureus (MRSA) biofilm disruption and killing using 2 different lasers. The preferred treatment sequence is a SW laser disruption of biofilm followed by NIR laser illumination. Treatment optimization of biofilm is possible with the addition of ciprofloxacin in concentrations consistent with planktonic MIC.