Comparison of mouse mammary gland imaging techniques and applications: Reflectance confocal microscopy, GFP Imaging, and ultrasound

<p>Abstract</p> <p>Background</p> <p>Genetically engineered mouse models of mammary gland cancer enable the <it>in vivo </it>study of molecular mechanisms and signaling during development and cancer pathophysiology. However, traditional whole mount and histological imaging modalities are only applicable to non-viable tissue.</p> <p>Methods</p> <p>We evaluated three techniques that can be quickly applied to living tissue for imaging normal and cancerous mammary gland: reflectance confocal microscopy, green fluorescent protein imaging, and ultrasound imaging.</p> <p>Results</p> <p>In the current study, reflectance confocal imaging offered the highest resolution and was used to optically section mammary ductal structures in the whole mammary gland. Glands remained viable in mammary gland whole organ culture when 1% acetic acid was used as a contrast agent. Our application of using green fluorescent protein expressing transgenic mice in our study allowed for whole mammary gland ductal structures imaging and enabled straightforward serial imaging of mammary gland ducts in whole organ culture to visualize the growth and differentiation process. Ultrasound imaging showed the lowest resolution. However, ultrasound was able to detect mammary preneoplastic lesions 0.2 mm in size and was used to follow cancer growth with serial imaging in living mice.</p> <p>Conclusion</p> <p>In conclusion, each technique enabled serial imaging of living mammary tissue and visualization of growth and development, quickly and with minimal tissue preparation. The use of the higher resolution reflectance confocal and green fluorescent protein imaging techniques and lower resolution ultrasound were complementary.</p

Intratumoral chemotherapy for lung cancer: re-challenge current targeted therapies

Wolfgang Hohenforst-Schmidt,1 Paul Zarogoulidis,2,3 Kaid Darwiche,3 Thomas Vogl,4 Eugene P Goldberg,5 Haidong Huang,6 Michael Simoff,7 Qiang Li,6 Robert Browning,8 J Francis Turner,9 Patrick Le Pivert,10 Dionysios Spyratos,2 Konstantinos Zarogoulidis,2 Seyhan I Celikoglu,11 Firuz Celikoglu,11 Johannes Brachmann11II Medical Clinic, Coburg Hospital, University of Wuerzburg, Coburg, Germany; 2Pulmonary Department-Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 3Department of Interventional Pneumology, Ruhrlandklinik, West German Lung Center, University Hospital, University Duisburg-Essen, Essen, Germany; 4Department of Diagnostic and Interventional Radiology, Goethe University of Frankfurt, Frankfurt, Germany; 5Biomaterials Science and Engineering, Department of Materials Science and Engineering, University of Florida, FL, USA; 6Department of Respiratory Diseases, Changhai Hospital/First Affiliated Hospital of the Second Military Medical University, Shanghai, People&#39;s Republic of China; 7Bronchoscopy and Interventional Pulmonology, Pulmonary and Critical Care Medicine, Henry Ford Hospital, Wayne State University, School of Medicine, MI, USA; 8Pulmonary and Critical Care Medicine, Interventional Pulmonology, National Naval Medical Center, Walter Reed Army Medical Center, Bethesda, USA; 9Pulmonary Medicine, University of Nevada School of Medicine, National Supercomputing Center for Energy and the Environment University of Nevada, Las Vegas, USA; 10Interventional Drug Delivery Systems and Strategies (ID2S2), Medical Cryogenics, Jupiter, FL, USA; 11Pulmonary Department, Cerrahpasa Medical Faculty, University of Istanbul, Istanbul, TurkeyAbstract: Strategies to enhance the already established doublet chemotherapy regimen for lung cancer have been investigated for more than 20 years. Initially, the concept was to administer chemotherapy drugs locally to the tumor site for efficient diffusion through passive transport within the tumor. Recent advances have enhanced the diffusion of pharmaceuticals through active transport by using pharmaceuticals designed to target the genome of tumors. In the present study, five patients with non-small cell lung cancer epidermal growth factor receptor (EGFR) negative stage IIIa&ndash;IV International Union Against Cancer 7 (UICC-7), and with Eastern Cooperative Oncology Group (ECOG) 2 scores were administered platinum-based doublet chemotherapy using combined intratumoral-regional and intravenous route of administration. Cisplatin analogues were injected at 0.5%&ndash;1% concentration within the tumor lesion and proven malignant lymph nodes according to pretreatment histological/cytological results and the concentration of systemic infusion was decreased to 70% of a standard protocol. This combined intravenous plus intratumoral-regional chemotherapy is used as a first line therapy on this short series of patients. To the best of our knowledge this is the first report of direct treatment of involved lymph nodes with cisplatin by endobronchial ultrasound drug delivery with a needle without any adverse effects. The initial overall survival and local response are suggestive of a better efficacy compared to established doublet cisplatin&ndash;based systemic chemotherapy in (higher) standard concentrations alone according to the UICC 7 database expected survival. An extensive search of the literature was performed to gather information of previously published literature of intratumoral chemo-drug administration and formulation for this treatment modality. Our study shows a favorable local response, more than a 50% reduction, for a massive tumor mass after administration of five sessions of intratumoral chemotherapy plus two cycles of low-dose intravenous chemotherapy according to our protocol. These encouraging results (even in very sick ECOG 2 patients with central obstructive non-small cell lung cancer having a worse prognosis and quality of life than a non-small cell lung cancer in ECOG 0 of the same tumor node metastasis [TNM]-stage without central obstruction) for a chemotherapy-only protocol that differs from conventional cisplatin-based doublet chemotherapy by the route, target site, and dose paves the way for broader applications of this technique. Finally, future perspectives of this treatment and pharmaceutical design for intratumoral administration are presented.Keywords: cisplatin, lymph nodes, chemotherapy, intratumoral, lung cance

Constraints on Solar System early evolution by MicrOmega analysis of Ryugu carbonates

International audienc

Space weathering record and pristine state of Ryugu samples from MicrOmega spectral analysis

International audienc

First compositional analysis of Ryugu samples by the MicrOmega hyperspectral microscope

International audienceThe characterization of objects that have best preserved the mineralogical and molecular phases formed in the earliest stages of the Solar System evolution is key to understanding the processes that led to the formation of the planets in their diversity. The Hayabusa2 mission of the Japan Aerospace Exploration Agency has returned for the first time samples collected at the surface of a C-type asteroid, Ryugu1,2. They are now preserved at the Extraterrestrial Samples Curation Center of the Japan Aerospace Exploration Agency at the Institute of Space and Astronautical Science in Sagamihara, Japan, where they are submitted to a first round of purely non-destructive analyses. The MicrOmega hyperspectral microscope developed at the Institut d'Astrophysique Spatiale (Orsay, France), which operates in the near-infrared range (0.99-3.65 µm), is performing their mineralogical and molecular characterization down to the scale of a few tens of micrometres. Strong features at 2.7 µm (indicating their OH-rich content) and at 3.4 µm (diagnostic of the presence of organics) dominate at a global scale, but key distinctive signatures have been identified at a submillimetre scale. In particular, carbonates (a fraction of them enriched in iron) as well as NH-rich compounds have been detected. The occurrence of volatile-rich species, likely originating from the outer Solar System, would support Ryugu having preserved both pristine material and altered phases, which are now available for refined laboratory analyses with the potential to draw new insights into the formation and evolution paths of planetary bodies in our Solar System