Differential gene expression of bone marrow-derived CD34+ cells is associated with survival of patients suffering from myelodysplastic syndrome

One feature of the molecular pathology of myelodysplastic syndromes (MDS) is aberrant gene expression. Such aberrations may be related to patient survival, and may indicate to novel diagnostic and therapeutic targets. Therefore, we aimed at identifying aberrant gene expression that is associated with MDS and patient survival. Bone marrow-derived CD34+ hematopoietic progenitor cells from six healthy persons and 16 patients with MDS were analyzed on cDNA macroarrays comprising 1,185 genes. Thereafter, our patients were followed-up for 54 months. We found differential expression of genes that were hitherto unrecognized in the context of MDS. Differential expression of 10 genes was confirmed by quantitative real-time RT-PCR. Hierarchical cluster analysis facilitated the separation of CD34+ cells of normal donors from patients with MDS. More importantly, it also distinguished MDS-patients with short and long survival. Scrutinizing our cDNA macroarray data for genes that are associated with short survival, we found, among others, increased expression of six different genes that encode the proteasome subunits. On the other hand, the most differentially down-regulated gene was IEX-1, which encodes an anti-apoptotic protein. We confirmed its decreased expression on RNA and protein level in an independent validation set of patient samples. The presented data broadens our notion about the molecular pathology of MDS and may lend itself to better identify patients with short survival. Furthermore, our findings may help to define new molecular targets for drug development and therapeutic approaches for patients with poor prognosis.     

The potential role of SPECT/CT in the preoperative detection of sentinel lymph nodes in breast cancer

Regional lymph node status is the most important prognostic factor in breast cancer. Sentinel lymph node biopsy is the standard method of axillary staging in early breast cancer patients with clinically negative nodes. Preoperative lymphoscintigraphy might support refining biopsy findings by determining the number and location of sentinel lymph nodes. In aged or overweight patients, in the presence of atypical or extra-axillary lymphatic drainage, non-visualized lymph nodes, or sentinel lymph nodes close to the isotope injection site, detection could be aided by a new, hybrid imaging tool: the single-photon emission computed tomography combined with computed tomography (3D SPECT/CT). For the first time in Hungarian language, authors overview the literature: all 14 English-language articles on the implementation of 3D SPECT/CT in sentinel lymph node detection in breast cancer are included. It is concluded that 3D SPECT/CT increases the success rate and quality of preoperative sentinel node identification, and is capable of providing a more accurate staging of breast cancer patients in routine clinical practice.     

Special considerations in breast cancer treatment of an augmented breast

Breast augmentation surgery involving the use of implants has been one of the most popular plastic surgical procedures for decades. As the multi-million female population who received breast implants ages, the risk of cancer is increasing rapidly, therefore the incidence of malignant disease in association with breast implants will increase as well. Although there is no relationship between tumor development and implants, these cases require special considerations in diagnostics, therapy and follow-up methods. Appropriate multidisciplinary treatment of tumors in augmented breasts corresponding with modern oncoplastic principles can only be accomplished based on adequate oncological, breast and plastic surgical knowledge. Supposing a possible increase of this condition in Hungary, too, authors provide a wide review of the literature on the special oncological and esthetic considerations, for the first time in Hungarian language.     

Acute infarct selective MRI contrast agent

To determine the infarct affinity of a low molecular weight contrast agent, Gd(ABE-DTTA), during the subacute phase of myocardial infarct (MI). Dogs (n = 7) were examined, using a closed-chest, reperfused MI model. MI was generated by occluding for 180 min the Left Anterior Descending (LAD) coronary artery with an angioplasty balloon. DE-MRI images with Gd(ABE-DTTA) were obtained on days 4, 14, and 28 after MI. Control DE-MRI by Gd(DTPA) was carried out on day 27. T2-TSE images were acquired on day 3, 13 and 27. Triphenyltetrazolium chloride (TTC) histomorphometry validated postmortem the existence of infarct. Gd(ABE-DTTA) highlighted the infarct on day 4, but not at all on day 14 or on day 28, following MI. On day 4, the mean ± SD signal intensity (SI) of infarcted myocardium in the presence of Gd(ABE-DTTA) significantly differed from that of healthy myocardium (45 ± 6.0 vs. 10 ± 5.0, P < 0.05), but it did not on day 14 (11 ± 9.4 vs. 10 ± 5.7, P = NS), nor on day 28 (7 ± 1.5 vs. 7 ± 2.4, P = NS). The mean ± SD signal intensity enhancement (SIE) induced by Gd(ABE-DTTA) was 386 ± 165% on day 4, significantly different from mean SIE on day 14 (9 ± 20%), and from mean SIE on day 28 (12 ± 18%), following MI (P < 0.05). The last two mean values did not differ significantly (P = NS) from each other. As control, Gd(DTPA) was used and it did highlight the infarct on day 27, inducing a mean SIE value of 312 ± 40%. The mean SIE on day 3, 13, or 27 did not vary significantly (P = NS) on the T2-TSE images (114 ± 41%, 123 ± 41%, and 150 ± 79%, respectively). Post mortem, the existence of infarcts was confirmed by TTC staining. The infarct affinity of Gd(ABE-DTTA) vanishes in the subacute phase of scar healing, allowing its use for infarct age differentiation early on, immediately following the acute phase.     

Non-contrast-enhanced magnetic resonance angiography: a reliable clinical tool for evaluating transplant renal artery stenosis

Purpose

To evaluate image quality of non-contrast-enhanced magnetic resonance angiography (MRA) and compare transplant renal artery stenosis (TRAS) seen by non-contrast-enhanced MRA with digital subtraction angiography (DSA) as the gold standard.

Materials and methods

330 patients receiving 369 non-contrast-enhanced MRA examinations from July 2014 to June 2017 were included. Thirty patients received at least two MRA examinations. Image quality was independently assessed by two radiologists. Inter-observer agreement was analyzed. Transplant renal artery anatomy and complications were evaluated and compared with DSA. If possible, accuracy was calculated on a per-artery basis.

Results

Good or excellent image quality was found in 95.4 % (352/369) of examinations with good inter-observer agreement (K=0.760). Twenty-two patients with DSA had 28 non-contrast-enhanced MRA examinations within a 2-month period. Of these, 19 patients had TRAS, two patients had pseudoaneurysms, and one patient had a normal transplant renal artery but an occluded external iliac artery. Non-contrast-enhanced MRA correctly detected 19 TRAS and nine normal arteries, giving 96.6 % accuracy on a per-artery basis.

Conclusions

Non-contrast-enhanced MRA demonstrates a good depiction of the transplanted renal artery and shows good correlation with DSA in cases where there was TRAS.

Key Points

? Good or excellent image quality was found in 95.4 % of examinations. ? Non-contrast-enhanced MRA can clearly map transplant renal artery anatomy. ? Non-contrast-enhanced MRA is a reliable tool to detect TRAS.

     

PHARMACOLOGICAL BIOCOMPATIBILITY BETWEEN INTRAVESICAL PREPARATIONS OF BCG AND INTERFERON-ALPHA 2B

Purpose

To determine if BCG and interferon alpha-2B are mutually compatible as mixed intravesical agents for clinical bladder cancer therapy.

Materials and Methods

Mutual compatibility was assessed by measuring IFN-alpha's effect on BCG metabolic activity, growth rate, and clumping tendency and conversely by observing BCG's effect on IFN-alpha's anti-viral activity. Optical density at 600 nm. (OD600) was used to estimate the number of colony forming units of BCG in suspension during 3 hours measurements of clumping and 8 days measurements of BCG proliferation. BCG viability was evaluated using a substrate marker, MTT, which correlates with BCG density and metabolic activity. The anti-viral activity of IFN-alpha was determined in a cytopathic protection bioassay using the encephalomyocarditis virus/FS-4 cell system.

Results

Continuous shaking of reconstituted BCG for 3 hours at 37C resulted in a marginal (11.3%) drop in OD600 which was minimally altered by inclusion of IFN-alpha at 2 million units (MU)/ml. (12.7% drop). Metabolic activity and growth rate of BCG alone or BCG with IFN-alpha were essentially identical. IFN-alpha's antiviral activity was not affected by incubation with BCG.

Conclusions

The inclusion of IFN-alpha into the usual BCG formulation for intravesical administration has no apparent effect on BCG's viability or tendency to form clumps in suspension. Similarly, the physical mixing of IFN-alpha with BCG does not impair its biological activity. Thus, both agents are pharmacologically compatible for future clinical studies involving combination intravesical therapy.     

Comparing bird and human soaring strategies

Gliding saves much energy, and to make large distances using only this form of flight represents a great challenge for both birds and people. The solution is to make use of the so-called thermals, which are localized, warmer regions in the atmosphere moving upwards with a speed exceeding the descent rate of bird and plane. Whereas birds use this technique mainly for foraging, humans do it as a sporting activity. Thermalling involves efficient optimization including the skilful localization of thermals, trying to guess the most favorable route, estimating the best descending rate, etc. In this study, we address the question whether there are any analogies between the solutions birds and humans find to handle the above task. High-resolution track logs were taken from thermalling falcons and paraglider pilots to determine the essential parameters of the flight patterns. We find that there are relevant common features in the ways birds and humans use thermals. In particular, falcons seem to reproduce the MacCready formula widely used by gliders to calculate the best slope to take before an upcoming thermal.