Altered miRNA and gene expression in acute myeloid leukemia with complex karyotype identify networks of prognostic relevance.

Recently, the p53-miR-34a network has been identified to have an important role in tumorigenesis. As in acute myeloid leukemia with complex karyotype (CK-AML) TP53 alterations are the most common known molecular lesion, we further analyzed the p53-miR-34a axis in a large cohort of CK-AML with known TP53 status (TP53(altered), n=57; TP53(unaltered), n=31; altered indicates loss and/or mutation of TP53). Profiling microRNA (miRNA) expression delineated TP53 alteration-associated miRNA profiles, and identified miR-34a and miR-100 as the most significantly down- and upregulated miRNA, respectively. Moreover, we found a distinct miR-34a expression-linked gene expression profile enriched for genes belonging to p53-associated pathways, and implicated in cell cycle progression or apoptosis. Clinically, low miR-34a expression and TP53 alterations predicted for chemotherapy resistance and inferior outcome. Notably, in TP53(unaltered) CK-AML, high miR-34a expression predicted for inferior overall survival (OS), whereas in TP53(biallelic altered) CK-AML, high miR-34a expression pointed to better OS. Thus, detailed molecular profiling links impaired p53 to decreased miR-34a expression, but also identifies p53-independent miR-34a induction mechanisms as shown in TP53(biallelic altered) cell lines treated with 15-deoxy-Δ(12,14)-prostaglandin. An improved understanding of this mechanism might provide novel therapeutic options to restore miR-34a function and thereby induce cell cycle arrest and apoptosis in TP53(altered) CK-AML.

[Preoperative wire localisation of breast lesions by tissue harmonic imaging (THI) sonography]. / Tissue Harmonic Imaging (THI) zur präoperativen sonographischen Markierung von Mammaherden.

PURPOSE: To obtain a fast and reliable preoperative wire localisation of occult lesions in dense breast tissue by tissue harmonic imaging (THI) sonography when localisation by mammography is not reliable enough. MATERIAL AND METHODS: In addition to biplane mammography for breast screening or for follow-up examination after breast-saving therapy, ultrasound was performed by two independent radiologists in 350 patients with mastopathic or fibrotic breast tissue. Using a multifrequency probe (5 - 10 MHz), lesions were documented by conventional B-mode and by THI in similar projections. In 25 lesions not precisely identified in mammography sonographically guided puncture with wire localisation was performed. RESULTS: In 22 of 350 patients 25 circumscribed suspicious lesions with an average diameter of 8 mm were identified, regarded suspicious by ultrasound but not by mammography. Nineteen of 25 lesions found by M-Mode and THI, an additional 6 only by THI. Guided puncture and wire localisation was achieved in 10 minutes on the average. In B-mode, the course of needle and wire was reliably seen in 16 of 25 cases, in THI in all cases. After surgical removal of tissue, histopathology revealed a ductal or lobular carcinoma in 19 cases, metastasis in three cases and benign complicated cysts with fibrotic tissue in the remaining three cases. CONCLUSION: THI is superior to B-mode ultrasound in differentiating suspicious lesions in dense glandular breast tissue. If tumor signs in mammography are not reliable enough or if a precise localisation is not possible, sonographically guided puncture by THI can give reliable results and, furthermore, is faster and more comfortable for the patient than localisation by mammography.

1H MR spectroscopy in patients with metastatic brain tumors: a multicenter study.

In a cooperative study involving six clinical MR centers, localized 1H MR spectroscopy was used to characterize untreated metastatic brain tumors (40 cases, 45 lesions). Cubic volumes (3.4 or 8 cm3) filled for more than 50% by metastatic brain tissue were examined by single-voxel double spin echo MRS, by using chemical shift selective imaging (CHESS) pulses for water suppression and TE = 135 ms. Choline (Cho), creatine (Cr) and N-acetyl aspartate (NAA) levels in brain metastases of mammary carcinoma (n = 13), lung cancer (n = 11) and melanoma (n = 10) were similar. Metastasis NAA/Cho signal intensity ratio varied between 0.00 and 1.17, compared with 2.68 +/- 0.56 (SD) in lobus occipitalis and 1.94 +/- 0.63 in corpus nuclei caudati region (P < 0.0001, both). 1H MR spectroscopy, although not suited to recognize the primary tumor of metastases, could serve as a clinical test for excluding (metastatic) tumor as cause of solitary focal brain disorders that are hard to diagnose with current imaging methods.

[The extension of MR diagnosis in dissecting aortic aneurysms by means of FLASH and snapshot-FLASH sequences]. / Erweiterung der MR-Diagnostik bei dissezierenden Aortenaneurysmen mittels FLASH- und Snapshot-FLASH-Sequenzen.

Using a combination of T1 weighted snapshot-flash sequences and intravenous contrast bolus it was possible to demonstrate intraluminal signal differences in a period of seconds. 5 confirmed aortic lesions were studied; 2 old aortic dissections (with differentiation between the true and false lumen), 1 acute aortic dissection and a partially thrombosed thoracic aortic aneurysm were demonstrated. The advantage of this technique lies in its simplicity and reproducibility. Difficulties in interpreting the intraluminal phases arising from spin echo and flash techniques are made easier by interpreting the available signals from this method.

[MRT of orofacial tumors--initial clinical experiences with turbo-flash intensity studies]. / MRT von orofazialen Tumoren--erste klinische Erfahrungen mit Turbo-FLASH-Anflutungsstudien.

We examined 36 patients with carcinomas of the tongue and the floor of the mouth. In 11 cases, a clear definition of the tumor extent was not possible using T2 w. spin echo sequences and T1 w. spin echo and gradient echo sequences after injection of contrast material. This delineation was attained with Turbo-FLASH intensity-vs-time studies (Gad-DTPA). The time of acquisition of each measurement was about 1 sec. At the end of injection of Gad-DTPA, 30 measurements with a delay of 1 sec between two measurements were performed. Using this technique, a marginal zone at the boundary of the tumor of very high signal intensity was visible within first minute after Gadolinium injection. This method is not required in the case of clearly hypointense (majority of the tumors) or hyperintense (minority) lesions on T1 w. Gadolinium-enhanced SE or GE images.

[Significance of reprocessed 3D gradient echo sequences in spinal MRT for surgical interventions in syringomyelia]. / Bedeutung der nachverarbeiteten 3D-Gradienten-Echosequenzen bei spinaler MRT für operative Massnahmen bei Syringomyelie.

Taking a patient with advanced syringomyelia as an example, the article presents a method in which reprocessed 3D-gradient echo sequences from spinal MRI allow centred reconstructions which show all sections of the syrinx, even where the spinal column is curved. This method played an essential role in satisfactorily determining the position of the syrinx for a median myelotomy which, according to clinical criteria, brought about an effective reduction in pressure from the syrinx.

[Imaging the spinal cord in scoliosis in magnetic resonance tomography using the 3D Fourier procedure]. / Darstellung des Myelons bei Skoliosen in der MR-Tomographie mit dem 3D-Fourier-Verfahren.

Recent progress in MR-imaging allows to acquire an entire volume using 3D-Fourier-processing, resulting in an isotope spatial resolution with a voxel-size of about one cubic millimeter. Acquisition time for a matrix of 256 x 256 x 128 amounts to less than 15 minutes, if gradient-echo-sequences are applied (FLASH/FISP). The information contained in such a huge number of data is retrieved with the aid of a special rapid data processing system. Using 3D-Fourier analyses, Spinal cord is imaged very clearly even in cases of extreme kyphoscoliosis. The cord is demonstrated by arbitrary, even curved one Millimeter slices. In addition to that the acquisition of data takes only 15 minutes, which is definitely more rapid than 2D-Fourier. Details can be figured out in a very high precision. This allows to distinguish details such as vessels, small masses and nerve roots. Furthermore the signal-to-noise-ratio of 3D-sequences is higher than in multi-slice-technique. A decisive advantage is the possibility to compute curved planes in post processing of the 3D-data-sets.

[Further development of the diagnostic possibilities of MR tomography. Combination of 3D sequences with a rapid image processing system]. / Weiterentwicklung der diagnostischen Möglichkeiten in der MR-Tomographie: Kombination von 3D-Sequenzen mit schnellem Bildverarbeitungssystem.

Using 3-D Fourier analysis, it is possible during MR tomography to provide isotropic data of large volumes, ie. uniform spatial resolution with a voxel size of 1 mm3. If one uses a gradient echo sequence with a picture matrix of 256 X 256 X 128 voxels, then examination time is less than 15 minutes. The information contained in this enormous amount of data can be evaluated by means of rapid image analysis. The advantages of this method have been demonstrated by three examples from the head and the spine.

[Comparison of MR examinations of the heart with first-pass radionuclide ventriculography]. / Vergleich von MR-Untersuchungen des Herzens mit der First-pass-Radionuklidventrikulographie.

72 patients with various heart diseases were studied by the use of magnetic resonance tomography and first-pass radionuclide angiocardiography. Both methods were compared in the RAO projection to determine the regional correspondence of morphological and functional alterations. The study proved that severe structural and functional disorders are usually combined (global correspondence for all patients 75%). Regionally, however, discrepancies between function and tissue-structure can be observed particularly in patients with anterior wall infarcts at the upper segments. Patchy signal patterns were found to correlate regionally with significant dysfunction particularly during the rapid filling phase.