A supersaturated calcium phosphate solution seems to effectively prevent and treat oral mucositis in haematopoietic stem cell transplanted cancer patients - single centre experience.

PURPOSE: Oral mucositis (OM) is one of the most frequent and bothersome complications of high-dose chemotherapy with subsequent auto- and allogeneic haematopoietic stem cell transplantation (HSCT). We have assessed the effectiveness of supersaturated calcium phosphate rinse (Caphosol ®) and palifermin (Kepivance®) in the prophylaxis of OM caused by HSCT. METHODS: Caphosol® and Kepivance® were prospectively evaluated in OM prophylaxis in 64 patients after HSCT and compared against themselves and an historical control group. RESULTS: Grade 3 and 4 OM was not observed in patients treated with Caphosol® and palifermin. None of those patients needed total parenteral nutrition (TPN), too. In the Caphosol® group 40.9% of the patients did not develop OM, and 70% of patients treated with palifermin were free of any kind of OM symptoms. In the control group OM was observed in all cases. CONCLUSION: Caphosol® seems to decrease the incidence, severity and duration of OM, the demand for opioids and for TPN. It needs to be tested in randomized trials, because its easy administration and cost-effectiveness may render it a valuable addition to the standard care in the treatment of OM.

Excited-state intramolecular proton transfer reaction modulated by low-frequency vibrations: an effect of an electron-donating substituent on the dually fluorescent bis-benzoxazole.

Excited-state intramolecular proton transfer (ESIPT) reaction has been studied in a molecule showing dual fluorescence, the 2,5-bis(2-benzoxazolyl)-4-methoxyphenol (BBMP), and its isotopomers, where the methoxy, and alternatively, the OH group has been deuterated. Attention is focused on the influence of electron donating OCH(3) substituent on fast excited state reaction. Comparison between the resonance-enhanced multiphoton ionization spectrum and the laser-induced excitation of the primary and phototautomeric emissions has been done. The geometry, electron density distribution, vibrational structure as well as the potential energy profiles in the S(0) and S(1) states of four possible rotameric forms of BBMP were calculated with application of the density functional theory (DFT). It allowed identifying the most probable conformer and assessing the role of low-frequency motions for the ESIPT efficiency.

Triple drug combination in the prevention of nausea and vomiting following busulfan plus cyclophosphamide chemotherapy before allogeneic hematopoietic stem cell transplantation.

PURPOSE: A clinical study of triple drug combination (aprepitant+palonosetron+ dexamethasone) was carried out to evaluate its efficacy in preventing both acute and delayed emesis after high-dose chemotherapy (HDC) with busulphan+cyclophosphamide (BuCy) before hematopoietic stem cell transplantation (HSCT). METHODS: The study enrolled 60 patients suffering from various hematological malignancies: 20 in the triple drug antiemetic group and 20 in each of two historical control groups that received dexamethasone plus either ondansetron or palonosetron. The groups were comparable for statistical analysis. The observation period started with the initiation of chemotherapy (0 h) and continued for 24 h after its completion for the acute phase, and during 5 days after finishing chemotherapy for the delayed phase. The response rate of the study drugs was evaluated by a 4-grade scale based on the condition of nausea and vomiting: highly, moderately or slightly effective and not effective. RESULTS: Patients treated with the triple drug combination had significantly higher response rates than those receiving palonosetron or ondansetron (+ dexamethasone) during both the acute and delayed phases: highly effective in early + late phases: 55 vs. 30 vs. 20%; highly effective in early phase: 70 vs. 30 vs. 20%; highly effective in late phase: 55 vs. 55 vs. 30%; highly + moderately effective in early phase: 75 vs. 32 vs. 25%; highly + moderately effective in late phase: 85 vs. 60 vs. 40% for triple drug combination, palonosetron + dexamethasone and ondansetron + dexamethasone, respectively. CONCLUSION: This triple drug combination was more effective than ondansetron or palonosetron (+ dexamethasone) in preventing acute (especially), and delayed nausea and vomiting following BuCy chemotherapy before HSCT.

Cerebrospinal fluid changes in the excitatory amino acids concentration caused by the standard treatment of acute lymphoblastic leukaemia in children do not correlate with their later cognitive functioning.

The aim of this study was to ascertain whether changes in the concentrations of cerebrospinal fluid excitatory amino acids (EAAs) contribute to neurotoxicity of the standard acute lymphoblastic leukaemia (ALL) treatment protocols. We found a statistically significant increase in glutamate and aspartate in 12 ALL patients during their treatment. Cognitive functioning was examined in all patients at an average of 3.7 years after the disease diagnosis. Importantly, the levels of EAAs during the therapy were not correlated with the results of the cognitive test. This study suggests that standard ALL treatment-induced neurotoxicity may not lead to persistent neurocognitive deficits.

A gastrin transcript expressed in gastrointestinal cancer cells contains an internal ribosome entry site.

As the hormone gastrin promotes gastrointestinal (GI) cancer progression by triggering survival pathways, regulation of gastrin expression at the translational level was explored. Sequence within the 5' untranslated region of a gastrin transcript expressed in GI cancer cells was investigated, then cloned into a bicistronic vector upstream of firefly luciferase and transfected into a series of GI cancer cell lines. Firefly luciferase activity was measured relative to that of a cap-dependent Renilla luciferase. A gastrin transcript that was different from that described in Ensembl was expressed in GI cancer cells. Its transcription appears to be initiated within the region designated as the gene's first intron. In GI cancer cells transfected with the bicistronic construct, firefly luciferase activity increased 8-15-fold compared with the control vector, and there was a further induction of the signal (up to 25-fold) following exposure of the cells to genotoxic stress or hypoxia, suggesting that the sequence acts as an internal ribosome entry site. These data suggest that the gastrin transcript within GI cancer cells contains an internal ribosome entry site that may allow continued expression of gastrin peptides when normal translational mechanisms are inactive, such as in hypoxia, thereby promoting cancer cell survival.

False recognition of emotional stimuli is lateralised in the brain: An fMRI study.

We have investigated whether the left (LH) and right (RH) hemisphere play a different role in eliciting false recognition (FR) and whether their involvement in this memory illusion depends on the emotional content of stimuli. Negative and neutral pictures (taken from IAPS) were presented in the divided-visual field paradigm. Subjects task was to indicate whether the pictures had already been presented or not during the preceding study phase. FR rate was much higher for the RH than the LH presentations. In line, FR resulted in activations mainly in the right prefrontal cortex (PFC) for either RH or LH presentations. Emotional content of stimuli facilitated the formation of false memories and strengthened the involvement of the right PFC in FR induction.

Pre-clinical evaluation of a new orally-active CCK-2R antagonist, Z-360, in gastrointestinal cancer models.

BACKGROUND: Gastrin has a role in gastrointestinal (GI) malignancy. This study provides pre-clinical evaluation of a novel, orally-active gastrin/cholecystokinin-2 receptor (CCK-2R) antagonist, Z-360. METHODS: (125)I gastrin-17 (G17) displacement and G17-stimulated calcium assays were used in classical CCK-2R-transfected cell lines. Akt phosphorylation was assessed by Western blotting. Z-360 efficacy in vivo was evaluated in three human xenograft models, and microvessel density and apoptosis in these models were investigated by immunohistochemistry. RESULTS: Z-360 inhibited (125)I G17 binding to cells expressing CCK-2R, and G17-stimulated signalling. Reduced Akt phosphorylation in an oesophageal cell-line treated with Z-360 was reversed by co-treatment with G17. Z-360 increased survival in a gastric ascites model (p=0.011) and decreased tumour growth in a hepatic metastasis model (81%, p=0.02). In an orthotopic pancreatic model, Z-360 combined with gemcitabine decreased final tumour weight compared to single agents (84%, p=0.002) and there was increased apoptosis and decreased microvessel density in ex vivo tumour tissue. CONCLUSIONS: These results show that the orally-active CCK-2R antagonist, Z-360 has high sub-nM affinity for classical CCK-2R, is well tolerated in vivo and exerts an anti-tumour effect.

In Vitro Tissue Microarrays for Quick and Efficient Spheroid Characterization.

Three-dimensional (3D) in vitro microphysiological cultures, such as spheroids and organoids, promise increased patient relevance and therapeutic predictivity compared with reductionist cell monolayers. However, high-throughput characterization techniques for 3D models are currently limited to simplistic live/dead assays. By sectioning and staining in vitro microtissues, researchers can examine their structure; detect DNA, RNA, and protein targets; and visualize them at the level of single cells. The morphological examination and immunochemistry staining for in vitro cultures has historically been done in a laborious manner involving testing one set of cultures at a time. We have developed a technology to rapidly screen spheroid phenotype and protein expression by arranging 66 spheroids in a gel array for paraffin embedding, sectioning, and immunohistochemsitry. The process is quick, mostly automatable, and uses 11 times less reagents than conventional techniques. Here we showcase the capabilities of the technique in an array made up of 11 different cell lines stained in conventional hematoxylin and eosin (H&E) staining, as well as immunohistochemistry staining for estrogen (ER), progesterone (PR), and human epidermal growth factor (Her-2) receptors, and TP53. This new methodology can be used in optimizing stem cell-based models of disease and development, for tissue engineering, safety screening, and efficacy screens in cancer research.

Cognitive control over memory - individual differences in memory performance for emotional and neutral material.

It is widely accepted that people differ in memory performance. The ability to control one's memory depends on multiple factors, including the emotional properties of the memorized material. While it was widely demonstrated that emotion can facilitate memory, it is unclear how emotion modifies our ability to suppress memory. One of the reasons for the lack of consensus among researchers is that individual differences in memory performance were largely neglected in previous studies. We used the directed forgetting paradigm in an fMRI study, in which subjects viewed neutral and emotional words, which they were instructed to remember or to forget. Subsequently, subjects' memory of these words was tested. Finally, they assessed the words on scales of valence, arousal, sadness and fear. We found that memory performance depended on instruction as reflected in the engagement of the lateral prefrontal cortex (lateral PFC), irrespective of emotional properties of words. While the lateral PFC engagement did not differ between neutral and emotional conditions, it correlated with behavioural performance when emotional - as opposed to neutral - words were presented. A deeper understanding of the underlying brain mechanisms is likely to require a study of individual differences in cognitive abilities to suppress memory.

Stable DHLA-PEG capped PbS quantum dots: from synthesis to near-infrared biomedical imaging.

The short shelf-life of water-soluble quantum dots (QDs) due to colloidal instability represents a major drawback to their exploitation. This work examines the colloidal stability of PbS nanoparticles capped with dihydrolipoic acid-polyethylene glycol (DHLA-PEG) ligands terminated with functional groups such as -NH2, -COOH, OMe and -N3. and their application for in vivo imaging. We prove a mechanism of colloidal instability and develop a strategy to produce for the first time stable PEG-capped PbS quantum dots with high quantum yield and optical emission in the first and the second near-infrared (NIR) windows of low absorption of biological tissues. The NIR imaging of in vivo biodistribution is demonstrated at wavelengths >1000 nm, with benefits of reduced tissue absorption and light scattering. The stability, biocompatibility and potential for further QD functionalization open up realistic prospects for non-invasive bioimaging applications.

Androgen receptors may act in a paracrine manner to regulate oesophageal adenocarcinoma growth.

BACKGROUND: The role of androgen receptors (ARs) in tumorigenesis, including transcription of fibroblast growth factors (FGFs), is established in prostate cancer. This study examined the role of ARs and FGFs in oesophageal adenocarcinoma (EAC), where tumour incidence in males is higher. METHODS: AR gene expression was analysed using quantitative RT-PCR; AR, fibroblast growth factor receptor-1 (FGFR-1) and fibroblast growth factor-8 isoform b (FGF-8b) protein by immunohistochemistry; and serum steroid levels (testosterone, progesterone, luteinising hormone and follicle stimulating hormone (FSH)) by immunoassay. A human oesophageal adenocarcinoma cell line was grown subcutaneously in nude mice. RESULTS: AR gene expression was of significantly higher levels than oesophageal adenocarcinomas (n=21, p=0.002) and in the squamous carcinoma line (OE21) compared with the adenocarcinoma lines (OE33 and OE19). Median serum testosterone levels in oesophageal carcinoma patients were higher than in age-matched controls (p=0.01) and reduced postoperatively, in patients undergoing curative resection (p=0.006). No significant differences were observed in hormones except FSH, where preoperative levels were significantly higher in the EAC group. AR protein was expressed in normal oesophageal squamous epithelial cells and also in the stroma of 18/23 EAC samples. FGFR-1 protein was expressed in malignant epithelium of 23/23 tumour samples. OE19 xenografts grew faster in male versus female mice (tumour weight at day 21, 1.14 g and 0.28 g, respectively, p=0.005) and had elevated FGF receptor expression. CONCLUSIONS: AR expressed in the stroma of oesophageal adenocarcinomas may induce paracrine effects following stimulation by androgens (including tumour-derived), possibly via FGFs, including FGF-8b.

Data on the number and frequency of scientific literature citations for established medulloblastoma cell lines.

This article collates information about the number of scientific articles mentioning each of the established medulloblastoma cell lines, derived through a systematic search of Web of Science, Scopus and Google Scholar in 2016. The data for each cell line have been presented as raw number of citations, percentage share of the total citations for each search engine and as an average percentage between the three search engines. In order to correct for the time since each cell line has been in use, the raw citation data have also been divided by the number of years since the derivation of each cell line. This is a supporting article for a review of in vitro models of medulloblastoma published in "in vitro models of medulloblastoma: choosing the right tool for the job" (D.P. Ivanov, D.A. Walker, B. Coyle, A.M. Grabowska, 2016) [1].

Taurine chloramine, a product of activated neutrophils, inhibits in vitro the generation of nitric oxide and other macrophage inflammatory mediators.

Taurine (Tau) is an exceptionally abundant free amino acid in the cytosol of inflammatory cells and especially in neutrophils. Taurine protects cells from self-destruction during processes that generate oxidants. The major function of Tau in leukocytes is to trap chlorinated oxidants (HOCl). Taurine reacts with HOCl to produce the long-lived compound taurine chloramine (TauCl). Previously, we have shown that other products of the neutrophil chlorinating system are able to modify functions of macrophages. In this study, we investigated in vitro the influence of TauCl on the generation of inflammatory mediators by activated macrophages. We have found that TauCl inhibited the generation of nitric oxide, prostaglandin E2, tumor necrosis factor alpha, and interleukin-6, but TauCl slightly enhanced the release of IL-1 alpha. The formation of nitrites by interferon-gamma-activated macrophages was inhibited by TauCl in a dose-dependent manner. Taurine chloramine also reduced the level of inducible nitric oxide synthase (iNOS) mRNA in macrophages, in a similar concentration-dependent manner. Although our experiments do not exclude a direct effect of TauCl on enzymatic activity of iNOS, the inhibition of iNOS expression seems to be the major mechanism responsible for suppression of NO formation. Finally, we discuss the biological role of TauCl in vivo. We suggest that at the site of inflammation TauCl works as a specific signaling molecule of activated neutrophils that coordinates the generation of inflammatory mediators in macrophages.

Lateral differences in the detection of stereoscopic depth.

The experiment investigated the hemifield differences in stereoscopic depth perception. Random dot stereograms (Julesz figures) producing the experience of a square appearing in front or behind the fixation plane were used as stimuli. The patterns in depth were exposed either in the left or in the right side of the stereograms for 30 msec. Three different magnitudes of depth were used. The results showed a higher amount of correct detections of depth in the left visual field than in the right visual field. The effects of direction and magnitude of depth were also significant. The hypothesis referring the observed results to the right hemisphere superiority in stereoscopic depth perception is discussed.

Interhemispheric transmission of information and functional asymmetry of the human brain.

The study investigated directional differences in interhemispheric transmission time using the VEPs method. Specifically we were interested in whether there exists an asymmetry in the transmission of information to and from the hemisphere specialized in its processing. Two type of stimuli, specific for the left and right hemisphere, were presented in the left and right visual fields. The latency differences between visual evoked potential components registered in the hemispheres ipsilateral and contralateral to the stimulated hemifield were compared. Interhemispheric transmission time was shorter when the information was transferred from the hemisphere non-specialized for its processing to the specialized one than in the opposite direction. The results suggest the existence of a physiological mechanism that ensures fast transmission of information to that hemisphere which is more efficient in its processing.

Impaired grating discrimination following right hemisphere damage.

We investigated the effect of unilateral brain lesions on visual discrimination of low-, middle- and high-frequency gratings. The performance of patients with right hemisphere lesions was significantly impaired compared with that of both controls and patients with left hemisphere lesions. This impairment was largely limited to patients with right posterior hemispheric lesions and was present with all spatial frequencies. These findings run counter to the hypothesis that high and low spatial frequencies are preferentially processed by different hemispheres.

Visual-spatial-frequency model of cerebral asymmetry: a critical survey of behavioral and electrophysiological studies.

In this article, the authors present a review of research on the role of the 2 hemispheres in processing spatial frequencies. J. Sergent (1982a) postulated that the hemispheres differ in their sensitivity to frequency characteristics of the sensory outputs on which cognitive processes are performed. Specifically, she proposed that the right hemisphere displays greater efficiency than the left hemisphere in processing low-spatial-frequency content of a visual image, whereas the left hemisphere is better equipped than the right to deal with high frequencies. The authors present an extensive review of behavioral and electrophysiological studies whose researchers tried to verify Sergent's hypothesis and offer its reformulation, taking into account the findings that have accumulated in the last 10 years.

MHC expression in nonlymphoid tissues of the developing embryo: strongest class I or class II expression in separate populations of potential antigen-presenting cells in the skin, lung, gut, and inter-organ connective tissue.

We define expression of major histocompatibility complex (MHC) antigens in the nonlymphoid tissues of the developing rat. Antibodies to class I heavy and light chains (b2-m), and to class II MHC proteins were used. Strongest MHC expression was by individual cells in the skin, lung, gut, and inter-organ connective tissue. The class I+ and class II+ cells were distinct populations, differing in morphology, distribution, and expression of macrophage-associated antigens. A nonimmunologic role for MHC proteins in development has been proposed. Yet the distributions and antigenic profiles lead us to emphasize immunologic functions that may be served by the early presence of MHC+ cells outside the forming lymphoid organs. Potential contributions to establishment of extrathymic or maternal/fetal tolerance are discussed. Localization of strongest MHC expression to individual connective tissue cells of the developing organs, rather than parenchymal cells, is of clinical relevance to transplantation of fetal tissue.

Isolation of human extravillous trophoblast cells by attachment to laminin-coated magnetic beads.

An isolation method has been developed based on laminin-coated magnetic beads which yields human trophoblast with a high degree of purity. Immunostaining with a panel of monoclonal antibodies indicates that these trophoblast cells are mainly of the extravillous variety. The mechanism for selection may be due to the expression of surface laminin receptors by these cells. This procedure, therefore, can provide appropriate cellular targets for in vitro assays against potential uterine effectors in studies on the local trophoblast-decidual interaction.

Interferon-gamma enhances mRNA and surface expression of class I antigen on human extravillous trophoblast.

Human trophoblast cells with immunocytochemical characteristics of the extravillous population have been isolated from 1st trimester placentae. Treatment of these cells with IFN-gamma increases the expression of Class I antigens at both the cell surface and mRNA level. A similar increase in Class I antigens is also found in JEG-3 choriocarcinoma cells after treatment with IFN-gamma. The possibility that aberrant production of IFN-gamma may upset the fetal-maternal equilibrium in vivo is discussed.