Transcriptional and functional profilling of human embryonic stem cell-derived cardiomyocytes

Human embryonic stemcells (hESCs) can serve as a potentially limitless source of cells that may enable regeneration of diseased tissue and organs. Here we investigate the use of human embryonic stemcell-derived cardiomyocytes (hESC-CMs) in promoting recovery from cardiac ischemia reperfusion injury in a mouse model. Using microarrays, we have described the hESC-CM transcriptome within the spectrum of changes that occur between undifferentiated hESCs and fetal heart cells. The hESC-CMs expressed cardiomyocyte genes at levels similar to those found in 20-week fetal heart cells, making this population a good source of potential replacement cells in vivo. Echocardiographic studies showed significant improvement in heart function by 8 weeks after transplantation. Finally, we demonstrate long-term engraftment of hESC-CMs by using molecular imaging to track cellular localization, survival, and proliferation in vivo. Taken together, global gene expression profiling of hESC differentiation enables a systems-based analysis of the biological processes, networks, and genes that drive hESC fate decisions, and studies such as this will serve as the foundation for future clinical applications of stem cell therapies. © 2008 Cao et al.published_or_final_versio

Thoracoscopic detection of occult indeterminate pulmonary nodules using bronchoscopic pleural dye marking

Background: The annual incidence of a small indeterminate pulmonary nodule (IPN) on computed tomography (CT) scan remains high. While traditional paradigms exist, the integration of new technologies into these diagnostic and treatment algorithms can result in alternative, potentially more efficient methods of managing these findings. Methods: We report on an alternative diagnostic and therapeutic strategy for the management of an IPN. This approach combines electromagnetic navigational bronchoscopy (ENB) with an updated approach to placement of a pleural dye marker. This technique lends itself to a minimally invasive wedge resection via either video-assisted thoracoscopic surgery (VATS) or a robotic approach. Results: Subsequent to alterations in the procedure, a cohort of 22 patients with an IPN was reviewed. Navigation was possible in 21 out of 22 patients with one patient excluded based on airway anatomy. The remaining 21 patients underwent ENB with pleural dye marking followed by minimally invasive wedge resection. The median size of the nodules was 13.4 mm (range: 7–29). There were no complications from the ENB procedure. Indigo carmine dye was used in ten patients. Methylene blue was used in the remaining 11 patients. In 81% of cases, the visceral pleural marker was visible at the time of surgery. In one patient, there was diffuse staining of the parietal pleura. In three additional patients, no dye was identified within the hemithorax. In all cases where dye marker was present on the visceral pleural surface, it was in proximity to the IPN and part of the excised specimen. Conclusions: ENB with pleural dye marking can provide a safe and effective method to localize an IPN and can allow for subsequent minimally invasive resection. Depending on the characteristics and location of the nodule, this method may allow more rapid identification intraoperatively

Breast imaging technology: Recent advances in imaging endogenous or transferred gene expression utilizing radionuclide technologies in living subjects - applications to breast cancer

A variety of imaging technologies is being investigated as tools for studying gene expression in living subjects. Two technologies that use radiolabeled isotopes are single photon emission computed tomography (SPECT) and positron emission tomography (PET). A relatively high sensitivity, a full quantitative tomographic capability, and the ability to extend small animal imaging assays directly into human applications characterize radionuclide approaches. Various radiolabeled probes (tracers) can be synthesized to target specific molecules present in breast cancer cells. These include antibodies or ligands to target cell surface receptors, substrates for intracellular enzymes, antisense oligodeoxynucleotide probes for targeting mRNA, probes for targeting intracellular receptors, and probes for genes transferred into the cell. We briefly discuss each of these imaging approaches and focus in detail on imaging reporter genes. In a PET reporter gene system for in vivo reporter gene imaging, the protein products of the reporter genes sequester positron emitting reporter probes. PET subsequently measures the PET reporter gene dependent sequestration of the PET reporter probe in living animals. We describe and review reporter gene approaches using the herpes simplex type 1 virus thymidine kinase and the dopamine type 2 receptor genes. Application of the reporter gene approach to animal models for breast cancer is discussed. Prospects for future applications of the transgene imaging technology in human gene therapy are also discussed. Both SPECT and PET provide unique opportunities to study animal models of breast cancer with direct application to human imaging. Continued development of new technology, probes and assays should help in the better understanding of basic breast cancer biology and in the improved management of breast cancer patients

Desmoplastic small round cell tumor: impact of 18F-FDG PET induced treatment strategy in a patient with long-term outcome

The desmoplastic small round cell tumor (DSRCT) is an uncommon and highly aggressive cancer. The role of 18F-FDG PET in management of DSRCT is little reported. We report a case of metastasized abdominal DSRCT detected in a 43-year old patient whose diagnostic and therapeutic approaches were influenced by 18F-FDG PET-CT. The patient is still alive ten years after diagnosis. 18F-FDG PET-CT seems to be a useful method for assessing therapeutic efficiency and detecting early recurrences even in rare malignancies such as DSRCT

Assessment of tumor redox status through (S)-4-(3-[18F]fluoropropyl)-L-glutamic acid positron emission tomography imaging of system xc- activity

The cell's endogenous antioxidant system is vital to maintenance of redox homeostasis. Despite its central role in normal and pathophysiology, no non-invasive tools exist to measure this system in patients. The cystine/glutamate antiporter system xc- maintains the balance between intracellular reactive oxygen species and antioxidant production through the provision of cystine, a key precursor in glutathione biosynthesis. Here we show that tumor cell retention of a system xc--specific positron emission tomography radiotracer, (S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG), decreases in proportion to levels of oxidative stress following treatment with a range of redox-active compounds. The decrease in [18F]FSPG retention correlated with a depletion of intracellular cystine resulting from increased de novo glutathione biosynthesis, shown through [U-13C6, U-15N2]cystine isotopic tracing. In vivo, treatment with the chemotherapeutic doxorubicin decreased [18F]FSPG tumor uptake in a mouse model of ovarian cancer, coinciding with markers of oxidative stress but preceding tumor shrinkage and decreased glucose utilization. Having already been used in pilot clinical trials, [18F]FSPG PET could be rapidly translated to the clinic as an early redox indicator of tumor response to treatment

Does the availability of positron emission tomography modify diagnostic strategies for solitary pulmonary nodules? An observational study in France

International audienceBACKGROUND: Previous studies showed that at the individual level, positron emission tomography (PET) has some benefits for patients and physicians in terms of cancer management and staging. We aimed to describe the benefits of (PET) in the management of solitary pulmonary nodules (SPNs) in a population level, in terms of the number of diagnostic and invasive tests performed, time to diagnosis and factors determining PET utilization. METHODS: In an observational study, we examined reports of computed tomography (CT) performed and mentioning "spherical lesion", "nodule" or synonymous terms. We found 11,515 reports in a before-PET period, 2002-2003, and 20,075 in an after-PET period, 2004-2005. Patients were followed through their physician, who was responsible for diagnostic management. RESULTS: We had complete data for 112 patients (73.7%) with new cases of SPN in the before-PET period and 250 (81.4%) in the after-PET period. Patients did not differ in mean age (64.9 vs. 64.8 years). The before-PET patients underwent a mean of 4 tests as compared with 3 tests for the after-PET patients (p = 0.08). Patients in the before-PET period had to wait 41.4 days, on average, before receiving a diagnosis as compared with 24.0 days, on average, for patients in the after-PET period who did not undergo PET (p < 0.001). In the after-PET period, 11% of patients underwent PET during the diagnostic process. A spiculated nodule was more likely to determine prescription for PET (p < 0.001). Multivariate analysis revealed that patients in both periods underwent fewer tests when PET was prescribed by general practitioners (p < 0.001) and if the nodule was not spiculated (p < 0.001). The proportion of unnecessary invasive approaches prescribed (47% vs. 49%) did not differ between the groups. CONCLUSION: In our study, 1 year after the availability of PET, the technology was not the first choice for diagnostic management of SPN. Even though we observed a tendency for reduced number of tests and mean time to diagnosis with PET, these phenomena did not fully relate to PET availability in health communities. In addition, the availability of PET in the management of SPN diagnosis did not reduce the overall rate of unnecessary invasive approaches