To date, no effective method exists that predicts the response to preoperative chemoradiation (CRT) in locally advanced rectal cancer (LARC). Nevertheless, identification of patients who have a ...higher likelihood of responding to preoperative CRT could be crucial in decreasing treatment morbidity and avoiding expensive and time-consuming treatments. The aim of this study was to identify signatures or molecular markers related to response to pre-operative CRT in LARC. We analyzed the gene expression profiles of 26 pre-treatment biopsies of LARC (10 responders and 16 non-responders) without metastasis using Human WG CodeLink microarray platform. Two hundred and fifty seven genes were differentially over-expressed in the responder patient subgroup. Ingenuity Pathway Analysis revealed a significant ratio of differentially expressed genes related to cancer, cellular growth and proliferation pathways, and c-Myc network. We demonstrated that high Gng4, c-Myc, Pola1, and Rrm1 mRNA expression levels was a significant prognostic factor for response to treatment in LARC patients (p<0.05). Using this gene set, we were able to establish a new model for predicting the response to CRT in rectal cancer with a sensitivity of 60% and 100% specificity. Our results reflect the value of gene expression profiling to gain insight about the molecular pathways involved in the response to treatment of LARC patients. These findings could be clinically relevant and support the use of mRNA levels when aiming to identify patients who respond to CRT therapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We introduce a novel method aimed to obtain the scale factor between in-plane magnetization components, indispensable for vectorial-magneto-optic Kerr effect (v-MOKE) experiments, convenient for ...experimental setups where it is difficult or unfeasible to rotate the electromagnet. Unlike the original method, in our proposal the electromagnet (and all other optical components) are fixed, extending in this way the possibility to implement v-MOKE magnetometry. Two films, FePt 9 and 100 nm thickness, were used as sample probes, presenting in-plane magnetic uniaxial anisotropy and in-plane magnetic isotropy, respectively. All experiments were carried out at room temperature and employing an home-made MOKE system. We also introduce a closed mathematical expression for the scale factor linking both magnetization components in terms of experimental and sample dependent parameters.
•Low-energy ion scattering spectra are generally described by classical models.•New features in the spectrum of Ar colliding with a Cu(111) surface are unexplained.•Simulations based on molecular ...dynamics are able to describe these features.•Surface steps are linked to the new unexplained features.
Low-energy ion scattering (LEIS) is distinguished by its acute surface sensitivity. Depending on the projectile/target system under analysis and the incoming energy of the projectile, it can provide information on the outermost atomic layer of the target surface. Due to the range of energies involved in LEIS, an elemental model based on a two-body classical elastic collision is generally accepted to describe the energy-position of all the peaks appearing in a LEIS spectrum. Here, we show that, under specific experimental conditions for Ar+ ions colliding with a Cu(111) surface, there exist certain peaks in the LEIS spectra that cannot be explained by the binary collision model. We experimentally show also that the appearance of these peaks is strongly dependent on the experimental conditions. We use molecular dynamics simulations to describe and understand the physical processes behind these particular features in the LEIS spectrum. We determine that surface defects such as islands or steps, inherent to any real physical surface, are crucial to the existence of the mentioned singular features in the Ar/Cu LEIS spectrum.
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In this work we take advantage of the large sensitivity and in-depth resolution of Auger electron spectroscopy (AES) to study in a detailed way the growth of C60 over different substrates, namely ...Cu(1 1 1), Si(1 0 0) and graphene. The ability of AES, as compared to more local probes like STM or AFM, to follow the process in a dynamic way, allows us to study the growth of C60 below and over one ML, including the change of C60 over either Si or Cu to the growth of C60 over a C60 film. We found that the growth always proceeds layer by layer. This result shows that differences in diffusion barriers are not as important as one may think following the idea of diffusion by a jumping mechanism. We propose that the sticking coefficient, governed by the adsorption energy, is responsible for the differences observed between Cu and Si. Our results also point to a different charge transfer among fullerene molecules and these surfaces. The same result is suggested in the case of C60 over graphene, but in this case our conclusion comes from the variable temperature experiments.
Preoperative chemoradiation significantly improves oncological outcome in locally advanced rectal cancer. However there is no effective method of predicting tumor response to chemoradiation in these ...patients. Peripheral blood mononuclear cells have emerged recently as pathology markers of cancer and other diseases, making possible their use as therapy predictors. Furthermore, the importance of the immune response in radiosensivity of solid organs led us to hypothesized that microarray gene expression profiling of peripheral blood mononuclear cells could identify patients with response to chemoradiation in rectal cancer. Thirty five 35 patients with locally advanced rectal cancer were recruited initially to perform the study. Peripheral blood samples were obtained before neaodjuvant treatment. RNA was extracted and purified to obtain cDNA and cRNA for hybridization of microarrays included in Human WG CodeLink bioarrays. Quantitative real time PCR was used to validate microarray experiment data. Results were correlated with pathological response, according to Mandard´s criteria and final UICC Stage (patients with tumor regression grade 1-2 and downstaging being defined as responders and patients with grade 3-5 and no downstaging as non-responders). Twenty seven out of 35 patients were finally included in the study. We performed a multiple t-test using Significance Analysis of Microarrays, to find those genes differing significantly in expression, between responders (n = 11) and non-responders (n = 16) to CRT. The differently expressed genes were: BC 035656.1, CIR, PRDM2, CAPG, FALZ, HLA-DPB2, NUPL2, and ZFP36. The measurement of FALZ (p = 0.029) gene expression level determined by qRT-PCR, showed statistically significant differences between the two groups. Gene expression profiling reveals novel genes in peripheral blood samples of mononuclear cells that could predict responders and non-responders to chemoradiation in patients with locally advanced rectal cancer. Moreover, our investigation added further evidence to the importance of mononuclear cells' mediated response in the neoadjuvant treatment of rectal cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We report measurements of AlF3 thin film growth on Cu(1 1 1) at room temperature by means of scanning tunneling microscopy. The growth proceeds by the formation of fractal islands characterized by a ...very corrugated surface. Through uncovered zones and island density we determined a diffusion length of ~25 nm for the adsorbed molecules. Even with this large diffusion length the step-edges do not appear fully decorated. These experimental results are contrasted with simulations based on a limited diffusion aggregation model and Metropolis Monte Carlo. Additionally, the results of the AlF3 sub-monolayer growth on Cu(1 1 1) are compared with our previous results on Cu(1 0 0), finding that both systems show more differences than similarities. Thus, while the growth on Cu(1 0 0) shows fully decorated step-edges, on Cu(1 1 1), they present non-covered zones even at coverages as high as 0.7 monolayers. Supported on MC simulations we suggest that the qualitative difference between both faces is due to different step-edge behaviour.
Abstract Surgical intervention causes oxidative stress leading to an adaptive responses by the body. To evaluate changes in the defense capacity of antioxidant enzymes, we determined the activity of ...glutathione reductase (GR) levels among liver transplant recipients with due to hepatitis C virus cirrhosis. The study was performed in 22 patients (16 males and 6 females) of average ages 52.63 ± 5.49 years for males and 59.67 ± 5.65 years for females. Blood samples for glutathione reductase activity were drawn on admission before as well as at 1, 6, and 12 h and 1, 2, 3, 5 and 7 days after the liver transplantation. Perioperative glutathione reductase levels were significant ( P = .014) over the period using Bonferroni tests. GR activity reached a maximum (15.6112 ± 6.56035 nmol/mg protein) at 3 days after liver transplantation (T3d) ( P = .001). The increased GR activity values detected perioperatively indicated scavenging of reactive oxygen species generated after liver transplantation of hepatitis C virus cirrhosis patients.
Abstract Background We describe an observational, retrospective study that included patients who underwent a liver transplantation (LT) for hepatocellular carcinoma (HCC) in our center between 2004 ...and 2012. Methods Clinical variables were recorded for donors and recipients as diagnosis and treatment, immunosuppressive therapy, toxicity, graft dysfunction, recurrence, and exitus. Fifty-eight patients were analyzed. The mean age was 57 ± 8 years. The viral etiology of HCC was 50% (n = 29), alcoholic 26% (n = 15), and others, 24% (n = 14). Regarding initial immunosuppressive strategy (IS), 51 patients (87.9%) were treated with standard regimen with corticosteroids (CS) and tacrolimus (TA), compared with 7 patients with impaired renal function (12.1%) who underwent a delayed therapy with calcineurin inhibitors (CNI) + mycophenolate mophetil (MMF) + CS. Concomitant use of anti-CD25 monoclonal antibodies was less than 10%. Regarding maintenance, 43 patients (74.1%) were treated with MMF + CNI versus 15 treated only with TA (25.9%). Results Recurrence of HCC was approximately 12%: 7 patients (2 hepatic only, 5 also extra-hepatic). Exitus was established in 19 patients (32.75%); only 3 patients (5.17%) were attributable to HCC. Bivariate studies were conducted according to the initial IS (standard regimen versus delayed therapy) and maintenance therapy (MMF + TA versus TA alone), with no differences in any of them in recurrence, treatment toxicity, graft rejection, and dysfunction. Conclusions In our experience with the IS, we found no differences in the development of recurrent disease, treatment toxicity, development of graft dysfunction, or rejection. We believe that individualized immunosuppressive therapy in these patients is safe and effective.
Social environments have an important effect on a range of ecological processes, and form a crucial component of selection. However, little is known of the link between personality, social behaviour ...and population structure. We combine a well‐understood personality trait with large‐scale social networks in wild songbirds, and show that personality underpins multiple aspects of social organisation. First, we demonstrate a relationship between network centrality and personality with ‘proactive’ (fast‐exploring) individuals associating weakly with greater numbers of conspecifics and moving between flocks. Second, temporal stability of associations relates to personality: ‘reactive’ (slow‐exploring) birds form synergistically stable relationships. Finally, we show that personality influences social structure, with males non‐randomly distributed across groups. These results provide strong evidence that songbirds follow alternative social strategies related to personality. This has implications not only for the causes of social network structure but also for the strength and direction of selection on personality in natural populations.
Abstract Because of a shortage of organs, non–heart-beating donors have been proposed to be a possible source of grafts for orthotopic liver transplantation. Herein, we have presented a blood group ...A+ patient with primary biliary cirrhosis, who underwent orthotopic liver transplantation from a non–heart-beating blood group A− donor. On day 5 after transplantation the patient displayed a low hemoglobin levels as well as an increased total bilirubin with progressive encephalopathy, hypotension, and oligoanuria on day 11. The patient responded to steroid treatment. We assume the main cause of organ dysfunction was a passenger lymphocyte syndrome (ABO-Rh incompatibility). Biliary complications were detected at a 6-month follow-up visit by increased hepatic enzymes. We thus concluded that it is useful to take Rh group into account.
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