Mesenchymal Stem Cells (MSCs) migrate specifically to tumors in vivo, and coupled with their capacity to bypass immune surveillance, are attractive vehicles for tumor-targeted delivery of therapeutic agents. This study aimed to introduce MSC-mediated expression of the sodium iodide symporter (NIS) for imaging and therapy of breast cancer. Tumor bearing animals received an intravenous or intratumoral injection of NIS expressing MSCs (MSC-NIS), followed by 99mTcO4- imaging 3-14Days (D) later using a BazookaSPECT γ-camera. Tissue was harvested for analysis of hNIS expression by RQPCR. Therapy animals received an intraperitoneal injection of 131I or saline 14D following injection of MSC-NIS, and tumor volume was monitored for 8 weeks. BazookaSPECT imaging following injection of MSC-NIS revealed an image of animal intestines and chest area at D3, with a weak tumor image also visible. By D14, the tumor was visible with a significant reduction in radionuclide accumulation in non-target tissue observed. hNIS gene expression was detected in the intestines, heart, lungs and tumor at early timepoints but later depleted in non-target tissues and persisted at the tumor site. Based on imaging/biodistribution data, animals received a therapeutic dose of 131I 14D following MSC-NIS injection. This resulted in a significant reduction in tumor growth (Mean ± SEM, 236 ± 62mm3 versus 665 ± 204 mm3 in controls). The ability to noninvasively track MSC migration and transgene expression in real time prior to therapy is a major advantage to this strategy. This promising data supports the feasibility of this approach as a novel therapy for breast cancer.

Iodinated water-soluble compounds have been widely recommended as the most suitable contrast media for diagnosis of gastrointestinal perforations. However, the authors present 6 cases in which mucosal tears and transmural perforations of the upper gastrointestinal tract were either unrecognizable or inadequately shown during initial evaluation with methylglucamine diatrizoate. Re-examination with barium sulfate demonstrated the precise location and extent of the perforations. Reasons for the higher diagnostic yield of barium studies are explained on the basis of experimental and clinical observations.

Objective To study the relationship between lymphovascular space involvement (LVSI) in stage 1a or 1b well-differentiated endometrial cancer and survival.Design Retrospective study consisting of a search of an oncology database to identify women with endometrial cancer between January 1990 and December 2004.Setting Tertiary referral centre, Dublin, Ireland.Sample Women who had well-differentiated stage 1a or 1b endometrial cancer.Methods During the period 1990-2004, 226 patients with endometrial cancer were treated in the National Maternity Hospital, Dublin. We looked at all patients who had welldifferentiated endometrioid adenocarcinoma of the endometrium with invasion of <50% thickness of the myometrium. Forty-one patients fulfilled these inclusion criteria. The presence or absence of LSVI was determined by review of haematoxylin and eosin sections. Patients were followed for 5 years or till death if earlier.Mortality was calculated. Statistical analysis was performed using Fisher's exact test. An odds ratio and 95% confidence interval was calculated using fixed effect Mantel-Haenszel model.Main outcome measures Death from recurrence of endometrial cancer.Results Of the 41 patients, five (12%) were found to have (LVSI). Of the five patients with LVSI, three (60%) patients died of recurrence. All patients with recurrence died of disease and none of the patients without LVSI died (0 of 36). Overall, the survival rate was 92.7%. The presence of LVSI was a highly significant predictor of recurrence (P < 0.001). ConclusionIn patients with early stage well-differentiated adenocarcinoma of the endometrium, the presence of LVSI is associated with a high risk of death.

In vivo imaging is a platform technology with the power to put function in its natural structural context. With the drive to translate stem cell therapies into pre-clinical and clinical trials, early selection of the right imaging techniques is paramount to success. There are many instances in regenerative medicine where the biological, biochemical, and biomechanical mechanisms behind the proposed function of stem cell therapies can be elucidated by appropriate imaging. Imaging techniques can be divided according to whether labels are used and as to whether the imaging can be done in vivo. In vivo human imaging places additional restrictions on the imaging tools that can be used. Microscopies and nanoscopies, especially those requiring fluorescent markers, have made an extraordinary impact on discovery at the molecular and cellular level, but due to their very limited ability to focus in the scattering tissues encountered for in vivo applications they are largely confined to superficial imaging applications in research laboratories. Nanoscopy, which has tremendous benefits in resolution, is limited to the near-field (e.g. near-field scanning optical microscope (NSNOM)) or to very high light intensity (e.g. stimulated emission depletion (STED)) or to slow stochastic events (photo-activated localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM)). In all cases, nanoscopy is limited to very superficial applications. Imaging depth may be increased using multiphoton or coherence gating tricks. Scattering dominates the limitation on imaging depth in most tissues and this can be mitigated by the application of optical clearing techniques that can impose mild (e.g. topical application of glycerol) or severe (e.g. CLARITY) changes to the tissue to be imaged. Progression of therapies through to clinical trials requires some thought as to the imaging and sensing modalities that should be used. Smoother progression is facilitated by the use of comparable imaging modalities throughout the discovery and trial phases, giving label-free techniques an advantage wherever they can be used, although this is seldom considered in the early stages. In this paper, we will explore the techniques that have found success in aiding discovery in stem cell therapies and try to predict the likely technologies best suited to translation and future directions.