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Molecular Imaging of the Extracellular Matrix and Lymphatic Phenomena in Tumors
Published in Martin G. Pomper, Juri G. Gelovani, Benjamin Tsui, Kathleen Gabrielson, Richard Wahl, S. Sam Gambhir, Jeff Bulte, Raymond Gibson, William C. Eckelman, Molecular Imaging in Oncology, 2008
Arvind P. Pathak, Zaver M. Bhujwalla
Despite major advances in intravital microscopy and optical imaging techniques, dynamic, noninvasive, in vivo investigations of the tumor-host tissue interface remain a challenge. Recent progress in MRI techniques and the synthesis of novel MRI contrast agents will help bridge the resolution gap between macroscopic lymphangiography approaches and intravital multiphoton microscopy. With MRI visualization of the tumor-host tissue interface in its entirety, including the lymphatics and extravascular transport through the ECM, can be achieved at relatively high spatial resolutions (100–250 µm) in vivo. This type of complete coverage of the entire tumor is not possible with the optical techniques currently available, especially for imaging deep-seated lymphatic-convective transport in tumor tissues that may be optically opaque.
Positively-Charged Liposomes for Targeting Tumor Vasculature
Published in Mansoor M. Amiji, Nanotechnology for Cancer Therapy, 2006
Intravital microscopy has been used to investigate the interactions of PCLs with tumor vessels in vivo.31 When PCLs were intravenously injected into tumor bearing (LS174T-human colon adenocarcinoma) mice, analysis of spatial distribution of liposomes 24 h post-injection revealed significant vascular targeting in tumors (~27.5% coverage) compared to vessels in normal tissues (~3.6% coverage).31 Moreover, the extent of vascular areas targeted did not vary as a function of tumor type or anatomical location.31 Several lines of evidence suggest that PEG coating does not inhibit cationic liposomes from binding to negatively charged surfaces. In addition to experimental data supporting this hypothesis, the values of zeta potential (electric potential across a double membrane surface) confirm that a sufficient electrostatic membrane potential still exists in the presence of PEG.31,52,83
Lung Microcirculation
Published in John H. Barker, Gary L. Anderson, Michael D. Menger, Clinically Applied Microcirculation Research, 2019
Andrew M. Roberts, Dick W. Slaaf
Although there are limitations due to accessibility and movement of the tissue, intravital microscopy has been adapted for observation of microvessels and alveoli at the surface of the lungs in a variety of preparations. The method of ventilation is an important consideration as it relates to the control of blood gases, pulmonary and systemic pressures, as well as enabling microscopy at sufficient magnification. With current video imaging techniques, it is possible to measure vessel dimensions in conjunction with relevant hemodynamic variables. Models have been developed to determine the distribution of pressure and flow, and it is possible to examine transit time and permeability across microvascular networks. This has improved the ability to characterize the lung microcirculation and its responses during different physiological and pathophysiological conditions and enables a direct quantitative approach. A significant advantage of this technique is that blood flow can be observed in the region of gas exchange. On the other hand, since it is only possible to examine vessels that are close to the pleural surface, some branches, larger vessels, and microcirculation of deeper regions are excluded from observation. However, although vessels close to the pleural surface may not be representative of the entire lung, they appear to reflect general microvascular and physiological relationships.15,33 Thus, intravital microscopy offers a method to directly observe how various stimuli and substances affect specific elements of the lung microcirculation and to study mechanisms of various diseases, abnormal function, and possible therapeutic interventions.
Dual role of E-cadherin in cancer cells
Published in Tissue Barriers, 2022
Svetlana N. Rubtsova, Irina Y. Zhitnyak, Natalya A. Gloushankova
In many cases, cancer cells invade the surrounding stroma not individually but as cohesive clusters in which the cells are linked together by E-cadherin-based AJs (Figure 3a). Cells moving as a group often exhibit more persistent migration than single cells.142,143 Collective invasion of tumor cells into collagen matrix was first observed ex vivo in explants of primary tumors, e.g. oral squamous cell carcinoma and breast ductal carcinoma.144 In human pancreatic, colorectal, lung and breast carcinomas, histopathological analysis showed that groups of invading cells at the cancer-host interface positively stained for E-cadherin.145–147 Collective invasion of cancer cells was also detected using intravital microscopy in various experimental models.148,149
Engineering polymeric nanocapsules for an efficient drainage and biodistribution in the lymphatic system
Published in Journal of Drug Targeting, 2019
Ana Sara Cordeiro, José Crecente-Campo, Belén L. Bouzo, Santiago F. González, María de la Fuente, María José Alonso
Two-photon intravital microscopy (2P-IVM) is an innovative imaging technology that allows the observation of biological interactions at subcellular level, in real time, and with high resolution [47,48]. This technique is particularly interesting for the tracking of nanosystems in biological microenvironments [49,50] because it relies on a near-infrared laser source to excite fluorophores using two low-energy photons at the same time, thus minimising the risk of tissue damage. As a consequence, 2P-IVM allows deeper penetration into the tissue (up to several hundred microns), with reduced photobleaching and phototoxicity [50]. In this work, we used 2P-IVM for the comparative analysis of the lymphatic biodistribution and lymph node accumulation of NCs with different particle sizes and polymeric shells. We also used flow cytometry analysis to provide quantitative data on the distribution of the formulations to the lymphatics and their accumulation in the different lymph nodes studied.
By word of mouse: using animal models in venous thrombosis research
Published in Platelets, 2020
Several imaging methods have recently been utilized in the context of mouse models of DVT and have proven to be relevant complementary tools to study the development of thrombus. Moreover, imaging techniques have a clear advantage over terminal procedures required for ex vivo assessments. Intravital microscopy allows real-time visualization of cellular processes by using fluorescent dyes and antibodies in vivo using wide-field video or confocal microscopy. Particularly, in the IVC stenosis model, intravital microscopy was used to study cell–cell and cell–vessel wall interactions during the initial phase of venous thrombus formation [15,16,39,41].