Adoptive immunotherapy monitored by micro-MRI in experimental colorectal liver metastasis

In this study we used the colon carcinoma DHDK12 cell line and generated single metastasis after subcapsular injection in BDIX rats as an experimental tumor model. The aim of the work was to set up in vitro experimental conditions to prepare immune effector cells and in vivo conditions for monitoring the effects of such cells injected as adoptive immunotherapy. Dendritic cells can process tumor cell antigens, induce a T-cell response and be used ex vivo to prepare activated lymphocytes. Lymphocytes were harvested from mesenteric lymph nodes and cocultured with bone marrow-derived autologous dendritic cells previously loaded with irradiated tumor cells. In vitro, the coculture: 1) induced the proliferation of lymphocytes, 2) expanded a preferential subpopulation of T CD8 lymphocytes, and 3) was in favor of lymphocyte cytotoxic activity against the DHDK12 tumor cell line. Activated lymphocytes were injected in the tumor-bearing rat portal vein. Parameters could be set to monitor tumor volume by micro MRI. This monitoring before and after treatment and immunohistochemical examinations revealed that: 1) micro MRI is an appropriate tool to survey metastasis growth in rat, 2) injected lymphocytes increase lesional infiltration with T CD8 cells even 15 days after treatment, 3) a dose of 50 millions lymphocytes is not sufficient to act on the course of the tumor

Is magnetic resonance imaging texture analysis a useful tool for cell therapy in vivo monitoring?

Assessment of anti-tumor treatment efficiency is usually done by measuring tumor size. Treatment may however induce changes in the tumor other than tumor size. Magnetic Resonance Imaging Texture Analysis (MRI-TA) is presently used to follow activated lymphocyte cell therapy. We used a 7T microimager to acquire high-resolution MR images of an experimental liver metastasis from colon carcinoma in rats treated (n = 4) or not (n = 3) with a cell therapy product. MRI-TA was then performed with Linear Discriminant Analysis and showed: i) a significant variation of tumor texture with tumor growth and ii) a significant modification in the texture of tumors treated with activated lymphocytes compared with untreated tumors. T2-weighted images or volume calculation did not evidence any difference. MRI-TA appears as a promising method for early detection and follow-up of response to cell therapy

A highly stable atomic vector magnetometer based on free spin precession

We present a magnetometer based on optically pumped Cs atoms that measures the magnitude and direction of a 1 $\mu$T magnetic field. Multiple circularly polarized laser beams were used to probe the free spin precession of the Cs atoms. The design was optimized for long-time stability and achieves a scalar resolution better than 300 fT for integration times ranging from 80 ms to 1000 s. The best scalar resolution of less than 80 fT was reached with integration times of 1.6 to 6 s. We were able to measure the magnetic field direction with a resolution better than 10 $\mu$rad for integration times from 10 s up to 2000 s

Dendritic cells are defective in breast cancer patients: a potential role for polyamine in this immunodeficiency

INTRODUCTION: Dendritic cells (DCs) are antigen-presenting cells that are currently employed in cancer clinical trials. However, it is not clear whether their ability to induce tumour-specific immune responses when they are isolated from cancer patients is reduced relative to their ability in vivo. We determined the phenotype and functional activity of DCs from cancer patients and investigated the effect of putrescine, a polyamine molecule that is released in large amounts by cancer cells and has been implicated in metastatic invasion, on DCs. METHODS: The IL-4/GM-CSF (granulocyte–macrophage colony-stimulating factor) procedure for culturing blood monocyte-derived DCs was applied to cells from healthy donors and patients (17 with breast, 7 with colorectal and 10 with renal cell carcinoma). The same peroxide-treated tumour cells (M74 cell line) were used for DC pulsing. We investigated the effects of stimulation of autologous lymphocytes by DCs pulsed with treated tumour cells (DC-Tu), and cytolytic activity of T cells was determined in the same target cells. RESULTS: Certain differences were observed between donors and breast cancer patients. The yield of DCs was dramatically weaker, and expression of MHC class II was lower and the percentage of HLA-DR(-)Lin(- )cells higher in patients. Whatever combination of maturating agents was used, expression of markers of mature DCs was significantly lower in patients. Also, DCs from patients exhibited reduced ability to stimulate cytotoxic T lymphocytes. After DC-Tu stimulation, specific cytolytic activity was enhanced by up to 40% when DCs were from donors but only up to 10% when they were from patients. IFN-γ production was repeatedly found to be enhanced in donors but not in patients. By adding putrescine to DCs from donors, it was possible to enhance the HLA-DR(-)Lin(- )cell percentage and to reduce the final cytolytic activity of lymphocytes after DC-Tu stimulation, mimicking defective DC function. These putrescine-induced deficiencies were reversed by treating DCs with all-trans retinoic acid. CONCLUSION: These data are consistent with blockade of antigen-presenting cells at an early stage of differentiation in patients with breast cancer. Putrescine released in the microenvironmement of DCs could be involved in this blockade. Use of all-trans retinoic acid treatment to reverse this blockade and favour ex vivo expansion of antigen-specific T lymphocytes is of real interest

Low temperature scattering with the R-matrix method: the Morse potential

Experiments are starting to probe collisions and chemical reactions between atoms and molecules at ultra-low temperatures. We have developed a new theoretical procedure for studying these collisions using the R-matrix method. Here this method is tested for the atom -- atom collisions described by a Morse potential. Analytic solutions for continuum states of the Morse potential are derived and compared with numerical results computed using an R-matrix method where the inner region wavefunctions are obtained using a standard nuclear motion algorithm. Results are given for eigenphases and scattering lengths. Excellent agreement is obtained in all cases. Progress in developing a general procedure for treating ultra-low energy reactive and non-reactive collisions is discussed.Comment: 18 pages, 6 figures, 3 tables, conferenc

Parity-violating Electron Deuteron Scattering and the Proton's Neutral Weak Axial Vector Form Factor

We report on a new measurement of the parity-violating asymmetry in quasielastic electron scattering from the deuteron at backward angles at Q2= 0.038 (GeV/c)2. This quantity provides a determination of the neutral weak axial vector form factor of the nucleon, which can potentially receive large electroweak corrections. The measured asymmetry A=-3.51 +/- 0.57(stat) +/- 0.58(sys)ppm is consistent with theoretical predictions. We also report on updated results of the previous experiment at Q2=0.091 (GeV/c)2, which are also consistent with theoretical predictions.Comment: 4 pages, 2 figures, submitted to Phys. Rev. Let

An Improved Search for the Neutron Electric Dipole Moment

A permanent electric dipole moment of fundamental spin-1/2 particles violates both parity (P) and time re- versal (T) symmetry, and hence, also charge-parity (CP) symmetry since there is no sign of CPT-violation. The search for a neutron electric dipole moment (nEDM) probes CP violation within and beyond the Stan- dard Model. The experiment, set up at the Paul Scherrer Institute (PSI), an improved, upgraded version of the apparatus which provided the current best experimental limit, dn < 2.9E-26 ecm (90% C.L.), by the RAL/Sussex/ILL collaboration: Baker et al., Phys. Rev. Lett. 97, 131801 (2006). In the next two years we aim to improve the sensitivity of the apparatus to sigma(dn) = 2.6E-27 ecm corresponding to an upper limit of dn < 5E-27 ecm (95% C.L.), in case for a null result. In parallel the collaboration works on the design of a new apparatus to further increase the sensitivity to sigma(dn) = 2.6E-28 ecm.Comment: APS Division for particles and fields, Conference Proceedings, Two figure

Parity-violating Electron Deuteron Scattering and the Proton's Neutral Weak Axial Vector Form Factor

We report on a new measurement of the parity-violating asymmetry in quasielastic electron scattering from the deuteron at backward angles at Q2= 0.038 (GeV/c)2. This quantity provides a determination of the neutral weak axial vector form factor of the nucleon, which can potentially receive large electroweak corrections. The measured asymmetry A=-3.51 +/- 0.57(stat) +/- 0.58(sys)ppm is consistent with theoretical predictions. We also report on updated results of the previous experiment at Q2=0.091 (GeV/c)2, which are also consistent with theoretical predictions.Comment: 4 pages, 2 figures, submitted to Phys. Rev. Let