AC133+ progenitor cells as gene delivery vehicle and cellular probe in subcutaneous tumor models: a preliminary study

<p>Abstract</p> <p>Background</p> <p>Despite enormous progress in gene therapy for breast cancer, an optimal systemic vehicle for delivering gene products to the target tissue is still lacking. The purpose of this study was to determine whether AC133+ progenitor cells (APC) can be used as both gene delivery vehicles and cellular probes for magnetic resonance imaging (MRI). In this study, we used superparamagentic iron oxide (SPIO)-labeled APCs to carry the human sodium iodide symporter (hNIS) gene to the sites of implanted breast cancer in mouse model. In vivo real time tracking of these cells was performed by MRI and expression of hNIS was determined by Tc-99m pertechnetate (Tc-99m) scan.</p> <p>Results</p> <p>Three million human breast cancer (MDA-MB-231) cells were subcutaneously implanted in the right flank of nude mice. APCs, isolated from fresh human cord blood, were genetically transformed to carry the hNIS gene using adenoviral vectors and magnetically labeled with ferumoxides-protamine sulfate (FePro) complexes. Magnetically labeled genetically transformed cells were administered intravenously in tumor bearing mice when tumors reached 0.5 cm in the largest dimension. MRI and single photon emission computed tomography (SPECT) images were acquired 3 and 7 days after cell injection, with a 7 Tesla animal MRI system and a custom built micro-SPECT using Tc-99m, respectively. Expression of hNIS in accumulated cells was determined by staining with anti-hNIS antibody. APCs were efficiently labeled with ferumoxide-protamine sulfate (FePro) complexes and transduced with hNIS gene. Our study showed not only the accumulation of intravenously administered genetically transformed, magnetically labeled APCs in the implanted breast cancer, but also the expression of hNIS gene at the tumor site. Tc-99m activity ratio (tumor/non-tumor) was significantly different between animals that received non-transduced and transduced cells (P < 0.001).</p> <p>Conclusion</p> <p>This study indicates that genetically transformed, magnetically labeled APCs can be used both as delivery vehicles and cellular probes for detecting <it>in vivo </it>migration and homing of cells. Furthermore, they can potentially be used as a gene carrier system for the treatment of tumor or other diseases.</p

Quantum Correlations in NMR systems

In conventional NMR experiments, the Zeeman energy gaps of the nuclear spin ensembles are much lower than their thermal energies, and accordingly exhibit tiny polarizations. Generally such low-purity quantum states are devoid of quantum entanglement. However, there exist certain nonclassical correlations which can be observed even in such systems. In this chapter, we discuss three such quantum correlations, namely, quantum contextuality, Leggett-Garg temporal correlations, and quantum discord. In each case, we provide a brief theoretical background and then describe some results from NMR experiments.Comment: 21 pages, 7 figure

Evaluating major curriculum change:the effect on student confidence

Aim: The aim of this study was to evaluate the effect of major curriculum change within a UK dental school on final-year student self-rated confidence levels. Methods: Final-year dental students graduating in each year between 2007 and 2012 completed the same course evaluation questionnaire, which assessed their confidence in relation to a range of clinical procedures using a Likert-type scale. This period spanned the introduction of a new curriculum and allowed analysis of differences in self-rated confidence between students graduating from the old (2007 and 2008) and new (2009–2012) curricula, across thirty key procedures. Results: New curriculum students showed significantly higher self-confidence ratings in nineteen of the thirty procedures, compared with those on the old curriculum. For the remaining eleven procedures there was no significant difference between the two curricula. The proportion of students on the outcomes-based curriculum rating themselves as 'confident” was statistically significantly higher in seven out of the thirty procedures, when compared with the traditional curriculum, and unchanged or nonsignificantly increased in the remainder. Discussion and conclusions: The relationship between specific curricular innovations and student confidence is considered, as is the usefulness of self-rated confidence in curriculum evaluation. Curriculum change appeared to have a positive effect on student confidence across a range of procedures

Combination of Vatalanib and a 20-HETE Synthesis Inhibitor Results in Decreased Tumor Growth in an Animal Model of Human Glioma

BACKGROUND: Due to the hypervascular nature of glioblastoma (GBM), antiangiogenic treatments, such as vatalanib, have been added as an adjuvant to control angiogenesis and tumor growth. However, evidence of progressive tumor growth and resistance to antiangiogenic treatment has been observed. To counter the unwanted effect of vatalanib on GBM growth, we have added a new agent known as N-hydroxy-N\u27-(4-butyl-2 methylphenyl)formamidine (HET0016), which is a selective inhibitor of 20-hydroxyeicosatetraenoic acid (20-HETE) synthesis. The aims of the studies were to determine 1) whether the addition of HET0016 can attenuate the unwanted effect of vatalanib on tumor growth and 2) whether the treatment schedule would have a crucial impact on controlling GBM. METHODS: U251 human glioma cells (4×10(5)) were implanted orthotopically. Two different treatment schedules were investigated. Treatment starting on day 8 (8-21 days treatment) of the tumor implantation was to mimic treatment following detection of tumor, where tumor would have hypoxic microenvironment and well-developed neovascularization. Drug treatment starting on the same day of tumor implantation (0-21 days treatment) was to mimic cases following radiation therapy or surgery. There were four different treatment groups: vehicle, vatalanib (oral treatment 50 mg/kg/d), HET0016 (intraperitoneal treatment 10 mg/kg/d), and combined (vatalanib and HET0016). Following scheduled treatments, all animals underwent magnetic resonance imaging on day 22, followed by euthanasia. Brain specimens were equally divided for immunohistochemistry and protein array analysis. RESULTS: Our results demonstrated a trend that HET0016, alone or in combination with vatalanib, is capable of controlling the tumor growth compared with that of vatalanib alone, indicating attenuation of the unwanted effect of vatalanib. When both vatalanib and HET0016 were administered together on the day of the tumor implantation (0-21 days treatment), tumor volume, tumor blood volume, permeability, extravascular and extracellular space volume, tumor cell proliferation, and cell migration were decreased compared with that of the vehicle-treated group. CONCLUSION: HET0016 is capable of controlling tumor growth and migration, but these effects are dependent on the timing of drug administration. The addition of HET0016 to vatalanib may attenuate the unwanted effect of vatalanib

MRI to assess chemoprevention in transgenic adenocarcinoma of mouse prostate (TRAMP)

<p>Abstract</p> <p>Background</p> <p>The current method to determine the efficacy of chemoprevention in TRAMP mouse model of carcinoma of prostate (CaP) is by extracting and weighing the prostate at different time points or by immunohistochemistry analysis. Non-invasive determination of volumes of prostate glands and seminal vesicles before, during and after treatment would be valuable in investigating the efficacy of newer chemopreventive agents in CaP. The purpose of this study was to determine whether <it>in vivo </it>magnetic resonance imaging (MRI) using a 3 tesla clinical MRI system can be used to follow the effect of chemoprevention in TRAMP model of mouse CaP.</p> <p>Methods</p> <p>Mice were randomized into control and treated groups. The animals in treated group received 10 µmol/kg of CDDO, 5 days a week for 20 weeks. Animals underwent <it>in vivo </it>MRI of prostate gland and seminal vesicles by a clinical 3 Tesla MRI system just before (at 5 weeks), during and at the end of treatment, at 25 weeks. T1-weighted and fat saturation (FATSAT) multiecho fast spin echo T2- weighted images (T2WI) were acquired. Volume of the prostate glands and seminal vesicles was determined from MR images. T2 signal intensity changes in the seminal vesicles were determined by subtracting higher echo time (TE) from lower TE T2WI. Following treatments all animals were sacrificed, prostate and seminal vesicles collected, and the tissues prepared for histological staining. All data were expressed as mean ± 1 standard deviation. Two-way or multivariate analysis of variance followed by post-hoc test was applied to determine the significant differences. A p-value of <0.05 was considered significant.</p> <p>Results</p> <p>Histological analysis indicated tumor in 100% of control mice, whereas 10% of the treated mice showed tumor in prostate gland. Both MRI and measured prostate weights showed higher volume/weight in control mouse group. MRI showed significantly higher volume of seminal vesicles in control animals and T2 signal intensity changes in seminal vesicles of control mice indicating higher number of tumor foci, which was also proven by histology.</p> <p>Conclusions</p> <p><it>In vivo </it>MRI is helpful in determining the efficacy of chemoprevention of prostate cancer in TRAMP mice.</p

Star cluster formation and feedback in different environments of a Milky Way-like galaxy

This is the author accepted manuscriptData availability: The data underlying this paper will be shared on reasonable request to the corresponding author.It remains unclear how galactic environment affects star formation and stellar cluster properties. This is difficult to address in Milky Way-mass galaxy simulations because of limited resolution and less accurate feedback compared to cloud-scale models. We carry out zoom-in simulations to re-simulate 100–300 pc regions of a Milky Way-like galaxy using smoothed particle hydrodynamics, including finer resolution (0.4 M⊙ per particle), cluster-sink particles, ray-traced photoionization from O stars, H2/CO chemistry, and ISM heating/cooling. We select ∼106 M⊙ cloud complexes from a galactic bar, inner spiral arm, outer arm, and inter-arm region (in order of galactocentric radius), retaining the original galactic potentials. The surface densities of star formation rate and neutral gas follow ΣSFR ∝ Σ 1.3 gas, with the bar lying higher up the relation than the other regions. However, the inter-arm region forms stars 2–3x less efficiently than the arm models at the same Σgas. The bar produces the most massive cluster, the inner arm the second, and the inter-arm the third. Almost all clusters in the bar and inner arm are small (radii < 5 pc), while 30-50 per cent of clusters in the outer arm and inter-arm have larger radii more like associations. Bar and inner arm clusters rotate at least twice as fast, on average, than clusters in the outer arm and inter-arm regions. The degree of spatial clustering also decreases from bar to inter-arm. Our results indicate that young massive clusters, potentially progenitors of globular clusters, may preferentially form near the bar/inner arm compared to outer arm/inter-arm regions.European Commissio

Sonographic Evaluation of Effect of Smoking and Fatty Meals on Gallbladder

Background: It is well established that fatty food causes gallbladder contraction by releasing cholecystokinin (CCK). Smoking also causes contraction of gallbladder. There are a limited number of studies evaluating the effect of smoking and fatty meals on gallbladder motility by ultrasonography.Objective: The aim of this study is to see the effect of smoking on gallbladder contraction in comparison with fatty meals.Materials and Methods: This cross sectional study was conducted on thirty young adult male volunteers having age between 18−40 years in the department of Radiology and Imaging of Bangabandhu Sheikh Mujib Medical University. Unbiased gallbladder volume measurement of each volunteer was taken on two separate days before and after taking fatty food and as well as before and after smoking at 5,15, 30 and 60 minutes interval. All information were meticulously recorded in structured data collection sheet and analyzed statistically. Then mean gallbladder volume changes against time were presented graphically for two groups using the pre and post smoking values.Results: The result shows that smoking has contractile effect on gallbladder like fatty food. The mean comparison of net change of gallbladder volume before and after smoking and before and after fatty food intake in both smoker and non-smoker groups has been statistically significant (p&lt;0.05).Conclusion: Fatty food and smoking should be strictly prohibited before ultrasonography of hepatobiliary system for better evaluation.J Enam Med Col 2018; 8(1): 29-34</jats:p

Optimization of growth media components for polyhydroxyalkanoate (PHA) production from organic acids by Ralstonia eutropha

We employed systematic mixture analysis to determine optimal levels of acetate, propionate, and butyrate for cell growth and polyhydroxyalkanoate (PHA) production by Ralstonia eutropha H16. Butyrate was the preferred acid for robust cell growth and high PHA production. The 3-hydroxyvalerate content in the resulting PHA depended on the proportion of propionate initially present in the growth medium. The proportion of acetate dramatically affected the final pH of the growth medium. A model was constructed using our data that predicts the effects of these acids, individually and in combination, on cell dry weight (CDW), PHA content (%CDW), PHA production, 3HV in the polymer, and final culture pH. Cell growth and PHA production improved approximately 1.5-fold over initial conditions when the proportion of butyrate was increased. Optimization of the phosphate buffer content in medium containing higher amounts of butyrate improved cell growth and PHA production more than 4-fold. The validated organic acid mixture analysis model can be used to optimize R. eutropha culture conditions, in order to meet targets for PHA production and/or polymer HV content. By modifying the growth medium made from treated industrial waste, such as palm oil mill effluent, more PHA can be produced.Malaysia. Ministry of Science, Technology and Innovation (MOSTI