We have recently shown that low intensity, intermediate frequency, electric fields inhibit by an anti-microtubule mechanism of action, cancerous cell growth in vitro. Using implanted electrodes, these fields were also shown to inhibit the growth of dermal tumors in mice. The present study extends these findings to additional cell lines [human breast carcinoma; MDA-MB-231, and human non-small-cell lung carcinoma (H1299)] and to animal tumor models (intradermal B16F1 melanoma and intracranial F-98 glioma) using external insulated electrodes. These findings led to the initiation of a pilot clinical trial of the effects of TTFields in 10 patients with recurrent glioblastoma (GBM). Median time to disease progression in these patients was 26.1 weeks and median overall survival was 62.2 weeks. These time to disease progression and OS values are more than double the reported medians of historical control patients. No device-related serious adverse events were seen after >70 months of cumulative treatment in all of the patients. The only device-related side effect seen was a mild to moderate contact dermatitis beneath the field delivering electrodes. We conclude that TTFields are a safe and effective new treatment modality which effectively slows down tumor growth in vitro, in vivo and, as demonstrated here, in human cancer patients.cancer ͉ glioblastoma ͉ tumor treating fields B Because living cells consist of ions, polar or charged molecules, membranes, and organelles, they are responsive to and often generate electric fields and currents. The electric activity of cells plays a key roll in many essential biological processes. The electric fields associated with all of the above phenomena are in the range of 0-10

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Background: The present study explores the efficacy and toxicity of combining a new, non-toxic, cancer treatment modality, termed Tumor Treating Fields (TTFields), with chemotherapeutic treatment in-vitro, in-vivo and in a pilot clinical trial.

T1 and T2 relaxation times and iron concentrations were measured in 24 specimens of gray matter from fresh human and monkey brains at magnetic fields from 0.05 to 1.5 Tesla. Three different effects were found that correlate with iron content: a T1-shortening that falls off somewhat at high fields, a T2-shortening that is field-independent and thus important at low fields, and a contribution to 1/T2 that increases linearly with field strength. This linear field dependence has been seen only in ferritin and other ferric oxyhydroxide particles. Our results are in agreement with in vivo MRI studies and are generally consistent with values for ferritin solution, except for differences such as clustering of ferritin in tissue. A cerebral cavernous hemangioma specimen showed similar T2-shortening, but with a 2.7 times larger magnitude, attributed to larger clusters of hemosiderin in macrophages. The dependence on interecho time 2 tau was measured in three brains; 1/T2 increased significantly for tau up to 32 ms, as expected from the size of the ferritin clusters. These findings support the theory that ferritin iron is the primary determinant of MRI contrast in normal gray matter.

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This study was an initial phase II trial in humans of molecular magnetic resonance (MR) imaging for improved visualization of thrombi in vessel territories potentially responsible for stroke using a new fibrin-specific contrast agent (EP-2104R). Eleven patients with thrombus in the left ventricle (n = 2), left or right atrium (n = 4), thoracic aorta (n = 4) or carotid artery (n = 1) as verified by an index examination (ultrasound, computed tomograpy, or conventional MR) were enrolled. All MR imaging was performed on 1.5 T whole-body MR-system using an inversion-recovery black-blood gradient-echo sequence. The same sequence was performed before and 2-6 h after low-dose intravenous administration of 4 mumol/kg EP-2104R. Two investigators assessed image quality and signal amplification. Furthermore, contrast-to-noise ratios (CNR) between the clot and the blood pool/surrounding soft tissue before and after administration of the contrast agent were compared using Student's t-test. MR imaging and data analysis were successfully completed in 10 patients. No major adverse effects occurred. On enhanced images, thrombi demonstrated high signal amplification, typically at the clot surface, with a significantly increased contrast in comparison to the surrounding blood pool and soft tissue (CNR for clot vs. blood pool, unenhanced and enhanced: 6 +/- 8 and 29 +/- 14; CNR for clot vs. soft tissue, unenhanced and enhanced: 0 +/- 4 and 21 +/- 13; P < 0.01 for both comparisons). EP-2104R allows for molecular MR imaging of thrombi potentially responsible for stroke. High contrast between thrombus and surrounding blood and soft tissues can be achieved with enhanced imaging.

By combining nuclear magnetic relaxometry on 39 ferritin samples with different iron loading with magnetometry, results were obtained that suggest a new interpretation of the core structure and magnetic properties of ferritin. These studies provide evidence that, contrary to most earlier reports, the ferritin core is antiferromagnetic (AFM) even at body temperature and possesses a superparamagnetic (SPM) moment due to incomplete cancellation of antiparallel sublattices, as predicted by Néel's theory. This moment also provides a likely explanation for the anomalous T2 shortening in ferritin solution. However, the number of SPM moments derived from this model is less than the number of ferritin molecules determined chemically, and a similar discrepancy was found by retrospectively fitting previously published magnetometry data. In other words, only a fraction of the ferritin molecules seem to be SPM. The studies also provide evidence for paramagnetic (PM) Curie-Weiss iron ions at the core surface, where the local Néel temperature is lower; these ions are apparently responsible for the weaker T1 shortening. In fact, the conversion of uncompensated AFM lattice ions to PM ions could explain the small number of SPM particles. The apparent Curie Law behavior of ferritin thus appears to be a coincidental result of different temperature dependences of the PM and SPM components.

In acromegaly, LGK is a useful adjunct to primary neurosurgery when treating post-surgical residues because it can limit the duration of medical therapy. It can be used as a primary therapy when neurosurgery is not possible.