Gadolinium retention in the tunica media of arterial walls-a complementary study using elemental bioimaging and immunogold staining.

Gadolinium (Gd) deposition has been found in both animal and human tissues after injections of Gd-based contrast agents (GBCAs). Without the knowledge of which tissues are most affected, it is difficult to determine whether Gd accumulation could lead to any pathological changes. The current study aims at investigating histological sections of three patients who were exposed to GBCAs during their lifetime, and identify areas of Gd accumulation. Tissue sections of three autopsy cases were investigated by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to assess the distribution of Gd, and the deposition within tissue sections was quantified. Additional application of laser ablation-inductively coupled plasma-optical emission spectroscopy (LA-ICP-OES) enabled a sensitive detection of calcium (Ca) in the vessel walls, which is usually impeded in LA-ICP-MS due to the isobaric interference with argon. Complementary LA-ICP-MS and LA-ICP-OES analysis revealed that Gd was co-localized with zinc and Ca, in the area where smooth muscle actin was present. Notably, high levels of Gd were found in the tunica media of arterial walls, which requires further research into potential Gd-related toxicity in this specific location.

Multimodal Imaging of Patients With Gliomas Confirms 11C-MET PET as a Complementary Marker to MRI for Noninvasive Tumor Grading and Intraindividual Follow-Up After Therapy.

The value of combined L-( methyl-[11C]) methionine positron-emitting tomography (MET-PET) and magnetic resonance imaging (MRI) with regard to tumor extent, entity prediction, and therapy effects in clinical routine in patients with suspicion of a brain tumor was investigated. In n = 65 patients with histologically verified brain lesions n = 70 MET-PET and MRI (T1-weighted gadolinium-enhanced [T1w-Gd] and fluid-attenuated inversion recovery or T2-weighted [FLAIR/T2w]) examinations were performed. The computer software "visualization and analysis framework volume rendering engine (Voreen)" was used for analysis of extent and intersection of tumor compartments. Binary logistic regression models were developed to differentiate between World Health Organization (WHO) tumor types/grades. Tumor sizes as defined by thresholding based on tumor-to-background ratios were significantly different as determined by MET-PET (21.6 ± 36.8 cm3), T1w-Gd-MRI (3.9 ± 7.8 cm3), and FLAIR/T2-MRI (64.8 ± 60.4 cm3; P < .001). The MET-PET visualized tumor activity where MRI parameters were negative: PET positive tumor volume without Gd enhancement was 19.8 ± 35.0 cm3 and without changes in FLAIR/T2 10.3 ± 25.7 cm3. FLAIR/T2-MRI visualized greatest tumor extent with differences to MET-PET being greater in posttherapy (64.6 ± 62.7 cm3) than in newly diagnosed patients (20.5 ± 52.6 cm3). The binary logistic regression model differentiated between WHO tumor types (fibrillary astrocytoma II n = 10 from other gliomas n = 16) with an accuracy of 80.8% in patients at primary diagnosis. Combined PET and MRI improve the evaluation of tumor activity, extent, type/grade prediction, and therapy-induced changes in patients with glioma and serve information highly relevant for diagnosis and management.

The tyrosine kinase c-Abl promotes proliferation and is expressed in atypical teratoid and malignant rhabdoid tumors.

BACKGROUND: Atypical teratoid/rhaboid tumors (AT/RTs) and extracranial malignant rhabdoid tumors are highly malignant neoplasms with a dismal prognosis. These tumors predominantly affect infants and targeted, adjuvant treatment approaches would be highly desirable. METHODS: In the current study, the authors investigated the expression and functional role of tyrosine kinases in 2 malignant rhabdoid tumor cell lines (A204 and G401) and in a series of 5 AT/RTs and 18 malignant rhabdoid tumors (13 rhabdoid tumors of the kidney and 5 extrarenal rhabdoid tumors). RESULTS: Both cell lines consistently expressed the tyrosine kinase c-Abl, which promoted proliferation as assessed by small interfering RNA knockdown. Blockage of c-Abl using the tyrosine kinase inhibitor imatinib resulted in reduced cellular growth in both cell lines. Furthermore, c-Abl was expressed in all rhabdoid tumors, whereas expression of platelet-derived growth factor receptor subtypes alpha and beta was infrequent and c-Kit expression was absent. CONCLUSIONS: The current data pointed toward a role for c-Abl in the biology of malignant rhabdoid tumors and provided a rationale for the investigation of tyrosine kinase inhibitors that target c-Abl for the treatment of these aggressive tumors.

Tissue expression of the nuclear progesterone receptor in male non-human primates and men.

In females, progesterone is associated with reproductive functions. In males, its role and the expression of its genomic receptor are not very well understood. In attempts to achieve a hormonal male contraceptive method, gestagens are used to downregulate gonadotropin and sperm production. It is therefore essential to understand the mechanism of action of progesterone at the molecular level in males, especially in primates. This investigation was undertaken: (a) to determine whether the genomic progesterone receptor is expressed in males; and (b) to locate it in various organs that are potential targets of gestagens. Human tissues were obtained at surgery for benign prostatic hyperplasia or prostate cancer and at autopsy. Non-human primate tissues were obtained at autopsy. This study was performed by analyzing the genomic progesterone receptor by immunohistochemistry, Western blot and RT-PCR. The nuclear progesterone receptor was expressed in pituitary and hypothalamus of both monkeys and men. In the testis progesterone receptor expression was found in a few peritubular and interstitial cells, but not in germ cells. In addition, expression was detected in the epididymis, prostate and male mammary gland. Reverse transcriptase (RT)-PCR experiments indicated that progesterone receptor A and B are expressed in all tissues analyzed. These data exclude direct genomic effects of gestagens at the spermatogenic level but indicate that a male contraceptive based on gestagens might have some effects on other tissues, such as the epididymis, prostate and mammary gland.