Peripheral T-cell lymphomas (PTCLs) are aggressive tumors in which the current therapy based on multiagent chemotherapy is not successful. Since cytochrome P450 3A subfamily (CYP3A) enzymes are ...involved in the inactivation of chemotherapy drugs, we hypothesized that CYP3A and P-glycoprotein (MDR1) expression in these lymphomas could result in a poor clinical response. We measured tumoral CYP3A and MDR1 mRNA content in 44 T-cell lymphomas, finding a large variation in CYP3A expression. Multiplex polymerase chain reaction (PCR) analysis and fluorescence in situ hybridization (FISH) analysis showed genomic gains affecting CYP3A and MDR1 genes in T-cell lines and primary tumors, suggesting that this could be the mechanism underlying the tumoral expression variation. To test whether the tumoral expression of CYP3A and/or MDR1 could influence PTCL treatment outcome, their expression levels were compared with the clinical response and survival of the patients, finding that a high tumoral expression of CYP3A4 was significantly associated with a lower complete remission rate. This was further investigated with cell lines stably expressing CYP3A4 that exhibited an increased resistance to doxorubicin and etoposide. In conclusion, a high CYP3A4 tumoral expression could be useful to predict poor response to the standard PTCL chemotherapy; in these cases alternative chemotherapy combinations or doses should be explored.
Background: it is well known that moderate or vigorous physical exercise produces an increase in free radicals. Aim: the aims of this study were to observe changes in malondialdehyde and antioxidant ...vitamins after a maximum incremental test, and to relate malondialdehyde and antioxidant vitamin values to performance parameters. Methods: eighty-four male athletes participated in this study. Participants performed a maximum incremental test until exhaustion on a treadmill. Malondialdehyde in plasma and antioxidant vitamins in plasma and erythrocytes were determined before and after the test. Results: in plasma, there was a decrease in malondialdehyde after the test. In erythrocytes, results showed increases in vitamin C and decreases in vitamin E after the test. Maximal oxygen uptake values were associated positively with vitamin C and negatively with malondialdehyde levels before the test. On the other hand, maximal oxygen uptake, total test time, and total test distance were positively related to the malondialdehyde values obtained after the test. Conclusions: a maximum incremental test did not produce any changes in plasma vitamins in athletes. However, it increased the levels of vitamin C in erythrocytes and decreased malondialdehyde values in plasma and vitamin E in erythrocytes. The levels of malondialdehyde, vitamin C and vitamin E were related to performance parameters. These results may be linked to the adaptation of antioxidant systems due to regular training.
The aim of the present study was to determine changes in serum concentrations of trace elements Cooper (Cu), Chromiun (Cr), Manganesum (Mn), Nickel (Ni) and Selenium (Se) in high-level sportsmen.
...Eighty professional athletes of different metabolic modalities, were recruited before the start of their training period. Thirty one sedentary participants of the same geographic area constituted the control group. Cu, Cr, Mn, Ni and Se analysis was performed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS).
Higher concentrations of Cr (
< 0.001), Mn (
< 0.085), and Ni (
< 0.001) were found in sportsmen in comparison to controls, inversely, Se values were lower (
< 0.001) among sportsmen. When sportsmen were classified by metabolic modalities, it was found that aerobic-anaerobic group had higher (
< 0.01) Cu concentrations than controls and the other sportsmen. The highest Cr values were found in aerobic participants. For Mn, the major levels were found in aerobic and aerobic-anaerobic groups as well (
< 0.001). The lowest Se levels were found among anaerobic sportsmen (
< 0.001).
This research showed that daily, continuum physical training induced alterations in serum essential minerals concentrations, as well as that these changes can be dependent of the exercise modality practiced.
Nodal peripheral T-cell lymphomas (PTCLs) constitute a heterogeneous group of neoplasms, suggesting the existence of molecular differences contributing to their histologic and clinical variability. ...Initial expression profiling studies of T-cell lymphomas have been inconclusive in yielding clinically relevant insights. We applied DNA microarrays to gain insight into the molecular signatures associated with prognosis.
We analyzed the expression profiles of 35 nodal PTCLs (23 PTCLs unspecified and 12 angioimmunoblastic) using two different microarray platforms, the cDNA microarray developed at the Spanish National Cancer Centre and an oligonucleotide microarray.
We identified five clusters of genes, the expression of which varied significantly among the samples. Genes in these clusters seemed to be functionally related to different cellular processes such as proliferation, inflammatory response, and T-cell or B-cell lineages. Regardless of the microarray platform used, overexpression of genes in the proliferation signature was associated significantly with shorter survival of patients. This proliferation signature included genes commonly associated with the cell cycle, such as CCNA, CCNB, TOP2A, and PCNA. Moreover the PTCL proliferation signature showed a statistically significant inverse correlation with clusters of the inflammatory response (P < .0001), as well as with the percentage of CD68(+) cells.
Our findings indicate that proliferation could be an important factor in evaluating nodal PTCL outcome and may help to define a more aggressive phenotype.
Mesenchymal stem cells have potential applications in inflammatory bowel disease due to their immunomodulatory properties. Our aim was to evaluate the feasibility, safety and efficacy of endoscopic ...administration of adipose-derived mesenchymal stem cells (ASCs) in a colitis model in rats.
Colitis was induced in rats by rectal trinitrobenzenesulfonic acid (TNBS). After 24 h ASCs (10
cells) or saline vehicle were endoscopically injected into the distal colon. Rats were followed for 11 days. Daily weight, endoscopic score at days 1 and 11, macroscopic appearance at necropsy, colon length and mRNA expression of Foxp3 and IL-10 in mesenteric lymph nodes (MLN) were analyzed.
Endoscopic injection was successful in all the animals. No significant adverse events or mortality due to the procedure occurred. Weight evolution was significantly better in the ASC group, recovering initial weight by day 11 (- 0.8% ± 10.1%, mean ± SD), whereas the vehicle group remained in weight loss (- 6.7% ± 9.2%, p = 0.024). The endoscopic score improved in the ASC group by 47.1% ± 5.3% vs. 21.8% ± 6.6% in the vehicle group (p < 0.01). Stenosis was less frequent in the ASC group (4.8% vs. 41.2%, p < 0.01). Colon length significantly recovered in the ASC group versus the vehicle group (222.6 ± 17.3 mm vs. 193.6 ± 17.9 mm, p < 0.001). The endoscopic score significantly correlated with weight change, macroscopic necropsy score and colon length. Foxp3 and IL-10 mRNA levels in MLN recovered with ASC treatment.
ASC submucosal endoscopic injection is feasible, safe and ameliorates TNBS-induced colitis in rats, especially stenosis.
Currently, there is no efficient therapy for patients with peripheral T cell lymphoma (PTCL). The Proviral Integration site of Moloney murine leukemia virus (PIM) kinases are important mediators of ...cell survival. We aimed to determine the therapeutic value of PIM kinases because they are overexpressed in PTCL patients, T cell lines and primary tumoral T cells. PIM kinases were inhibited genetically (using small interfering and short hairpin RNAs) and pharmacologically (mainly with the pan-PIM inhibitor (PIMi) ETP-39010) in a panel of 8 PTCL cell lines. Effects on cell viability, apoptosis, cell cycle, key proteins and gene expression were evaluated. Individual inhibition of each of the PIM genes did not affect PTCL cell survival, partially because of a compensatory mechanism among the three PIM genes. In contrast, pharmacological inhibition of all PIM kinases strongly induced apoptosis in all PTCL cell lines, without cell cycle arrest, in part through the induction of DNA damage. Therefore, pan-PIMi synergized with Cisplatin. Importantly, pharmacological inhibition of PIM reduced primary tumoral T cell viability without affecting normal T cells ex vivo. Since anaplastic large cell lymphoma (ALK+ ALCL) cell lines were the most sensitive to the pan-PIMi, we tested the simultaneous inhibition of ALK and PIM kinases and found a strong synergistic effect in ALK+ ALCL cell lines. Our findings suggest that PIM kinase inhibition could be of therapeutic value in a subset of PTCL, especially when combined with ALK inhibitors, and might be clinically beneficial in ALK+ ALCL.
The aim of the present study was to determine changes in the serum concentrations of trace elements Cobalt (Co), Molybdenum (Mo) and Zinc (Zn) among high-level sportsmen.
Eighty professional athletes ...of different metabolic modalities (aerobic, anaerobic and aerobic-anaerobic), were recruited before the beginning of their training seasons. Thirty-one sedentary participants of the same geographic area constituted the control group. Co, Mo and Zn analysis was performed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS).
Serum concentration of Mo (p < 0.001) was higher among sportsmen compared to the control group values. Separated by modalities, the concentrations of Co in the aerobic-anaerobic athletes were lower (p < 0.01) than in the control group as well as than in the other athletes. The highest Mo concentration was found in anaerobic sportsmen (p < 0.001), followed by aerobic-anaerobic (p < 0.001) being both statistically higher in comparison with the control group. In relation to Zn, it was observed that aerobic-anaerobic (p < 0.001) and anaerobic (p < 0.001) sportsmen showed higher concentrations than the control participants. However, aerobic sportsmen showed lower concentrations (p < 0.01) than controls.
This data manifest that long-term, daily physical training may induce variations in serum concentrations of several essential elements among sportsmen in comparison to untrained men and that these changes seems to be related to the sports modality practiced.
The selective hydrogenation in the liquid phase of 1-butyne and 1,3-butadiene in the presence of n-butenes over a commercial Pd/Al2O3 egg-shell catalyst has been studied. Although hydrogenation of ...the n-butenes and their isomerization are normally undesirable, kinetics of these reactions should also be evaluated in order to carry out the process at efficient operating conditions. Here, the effect of temperature, in the range 25–65 °C, on the specific rate coefficients of 1,3-butadiene hydrogenation reactions and 1-butene, cis-2-butene, and trans-2-butene hydrogenation and isomerization reactions was evaluated from measurements in a batch reactor system. Further experiments were conducted for the evaluation of selectivity between 1-butyne and 1,3-butadiene hydrogenations at 44 °C. The present results and previous kinetic characterization allow evaluating the most relevant parameters of a set of kinetic expressions for the 10 overall reactions that govern the system transformation.
The aim of this study was to observe the concentrations of trace metals boron, lithium, rubidium, antimony, tin and strontium in the serum of athletes from different modalities and sedentary subjects ...and the possible influence that different energy sports training modalities can have on their concentration.
Eighty professional athletes and 31 sedentary males participated in the present survey. All of them were living in Cáceres (Spain). Serum boron, lithium, rubidium, antimony, tin and strontium analysis was performed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS).
The results show higher concentrations in athletes on tin (
< 0.01), rubidium and antimony (
< 0.001) than the control group. In the case of tin, this item had the highest concentrations only in aerobic sports modalities. Regarding rubidium and antimony, the highest concentrations are found in athletes with lower oxygen consumption (aerobic-anaerobic) (
< 0.001), followed by anaerobic group (
< 0.001).
Our research shows that, probably due to increased water and air intake, especially, trace elements rubidium, antimony and tin reveal major differences in serum concentration of athletes in relation to sedentary subjects. On the other hand, physical training does not change the serum concentration of Boron, Lithium and strontium.
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