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41.
Lilia Suárez María-Belén Vidriales José García-Lara?a Guillermo Sanz María-José Moreno Antonio López Susana Barrena Rafael Martínez Mar Tormo Luis Palomera Esperanza Lavilla Ma Consuelo López-Berges María de Santiago M Encarnación Pérez de Equiza Jesús F San Miguel Alberto Orfao 《Clinical cancer research》2004,10(22):7599-7606
Myelodysplastic syndromes and acute myeloid leukemia (AML) are heterogeneous disorders in which conflicting results in apoptosis and multidrug resistance (MDR) have been reported. We have evaluated by multiparameter flow cytometry the expression of apoptosis- (APO2.7, bcl-2, and bax) and MDR-related proteins [P-glycoprotein (P-gp), multidrug resistance protein (MRP), and lung resistance protein (LRP)] specifically on bone marrow (BM) CD34+ cells, and their major CD32-/dim and CD32+ subsets, in de novo AML (n=90), high-risk myelodysplastic syndrome (n=9), and low-risk myelodysplastic syndrome (n=21) patients at diagnosis, and compared with normal BM CD34+ cells (n=6). CD34+ myeloid cells from AML and high-risk myelodysplastic syndrome patients displayed higher expression of bcl-2 (P <0.0001) and lower reactivity for APO2.7 (P=0.002) compared with low-risk myelodysplastic syndrome and normal controls. Similar results applied to the two predefined CD34+ myeloid cell subsets. No significant differences were found in the expression of P-gp, MRP, and LRP between low-risk myelodysplastic syndrome patients and normal BM, but decreased expression of MRP (P <0.03) in AML and high-risk myelodysplastic syndromes and P-gp (P=0.008) in high-risk myelodysplastic syndromes were detected. Hierarchical clustering analysis showed that low-risk myelodysplastic syndrome patients were clustered next to normal BM samples, whereas high-risk myelodysplastic syndromes were clustered together and mixed with the de novo AML patients. In summary, increased resistance to chemotherapy of CD34+ cells from both AML and high-risk myelodysplastic syndromes would be explained more appropriately in terms of an increased antiapoptotic phenotype rather than a MDR phenotype. In low-risk myelodysplastic syndromes abnormally high apoptotic rates would be restricted to the CD34- cell compartments. 相似文献
42.
Susana B Bravo María E R García-Rendueles Rafael Seoane Vanesa Dosil José Cameselle-Teijeiro Luis López-Lázaro Juan Zalvide Francisco Barreiro Celia M Pombo Clara V Alvarez 《Clinical cancer research》2005,11(21):7664-7673
Undifferentiated (anaplastic) thyroid carcinoma is a highly aggressive human cancer with very poor prognosis. Although there have been a few studies of candidate treatments, the fact that it is an infrequent tumor makes it very difficult to design clinical trials. A strong association has been observed between undifferentiated thyroid carcinoma and TP53 mutations in numerous molecular genetic and expression studies. Plitidepsin (Aplidin, PharmaMar, Madrid, Spain) is a novel anticancer compound obtained from a sea tunicate. This compound has been reported to induce apoptosis independently of TP53 status. We investigated the actions of plitidepsin in human thyroid cancer cells. In initial experiments using primary cultured cells from a differentiated (papillary) carcinoma, we found that 100 nmol/L plitidepsin induced apoptosis, whereas lower doses were cytostatic. Because our aim was to study the effects of plitidepsin at clinically relevant concentrations, subsequent experiments were done with a dosage regimen reflecting plasma concentrations observed in previously reported clinical trials: 100 nmol/L for 4 hours, followed by 10 nmol/L for 20 hours (4(100)/20(10) plitidepsin). This plitidepsin dosage regimen blocked the proliferation of a primary undifferentiated/anaplastic thyroid carcinoma culture obtained in our laboratory and of a commercial cell line (8305C) obtained from an undifferentiated thyroid carcinoma; however, it did not induce apoptosis. The proportion of cells in the G(1) phase of the cell cycle was greatly increased and the proportion in the S/G(2)-M phases greatly reduced, suggesting that plitidepsin blocks G(1)-to-S transition. Levels of the cyclin D1/cyclin-dependent kinase 4/p21 complex proteins were decreased and, in line with this, the levels of unphosphorylated Rb1 increased. The decrease in cell cycle proteins correlated with hypoacetylation of histone H3. Finally, we did experiments to assess how rapidly tumor cells return to their initial pretreatment proliferative behavior after 4(100)/20(10) plitidepsin treatment. Cells from undifferentiated tumors needed more than 3 days to recover logarithmic growth, and after 7 days, cell number was still significantly lower than in control cultures. 4(100)/20(10) plitidepsin inhibited the growth in soft agar. Together, our data show that plitidepsin is able to block in vitro cell cycle progression at concentrations similar to serum concentrations observed in vivo, and that this effect is persistent for several days after plitidepsin removal. Whether plitidepsin will prove to be clinically useful in the treatment of undifferentiated thyroid cancers remains to be established. However, our results raise the possibility that plitidepsin might be effective alone or in combination with radiotherapy and/or other drug treatments. 相似文献
43.
Amparo Rodríguez Sánchez María J. Chueca Guindulain María Alija Merillas Susana Ares Segura José Carlos Moreno Navarro María Dolores Rodríguez Arnao 《Anales de pediatría (Barcelona, Spain : 2003)》2019,90(4):250.e1-250.e8
The screening program of congenital hypothyroidism (CH) is probably one of the best achievements in paediatrics. Thyroid hormones are essential for brain development and brain maturation that continue through the neonatal period. Hypothyroidism that begins in the first months of life causes irreversible damage to the central nervous system, and is one of the most frequent and preventable causes of mental retardation. As children with congenital hypothyroidism are born with a normal appearance, analytical studies are required to immediately start the appropriate therapy.This article analyses the aims, diagnostic procedures, tests required, aetiology, and differential diagnosis in this disorder. Especially relevant is to perform frequent monitoring to ensure dose adjustments of L-Thyroxine therapy, avoiding infra- or supra-dosing that negatively affects neurosensory functions. Re-evaluation of the aetiology permanent vs transient hypothyroidism is always recommended after 3 years of chronological age.The relevance of this screening program should be widely discussed in paediatrics. The main objective is to avoid cerebral damage in these patients, and has been highly successful and economically beneficial.Other aspects are required to optimise patient outcomes, to perform all the controls according to the recommendations and to include, in the near future, the diagnosis of central hypothyroidism. Implementation of this program is necessary to progress in accordance with current scientific knowledge. 相似文献
44.
Karen D. Wright MD MS Mihaela M. Onciu MD Elaine Coustan‐Smith MS Dario Campana MD PhD Susana C. Raimondi PhD Hiroto Inaba MD PhD Raul Ribeiro MD Ching‐Hon Pui MD John T. Sandlund MD 《Pediatric blood & cancer》2013,60(7):E38-E41
Dendritic cell leukemia (DCL) or hematodermic tumor is an uncommon subtype of acute leukemia. In contrast to adult cases, children tend to have a less aggressive course. The diagnosis of DCL should be considered when its characteristic morphologic features are present and leukemic cells co‐express CD4 and CD56. Cases of DCL among pediatric patients have been reported to respond to therapeutic regimens for acute lymphoblastic leukemia, but details regarding the specifics of therapy are lacking. Pediatr Blood Cancer 2013; 60: E38–E41. © 2013 Wiley Periodicals, Inc. 相似文献
45.
miR‐155 expression and correlation with clinical outcome in pediatric AML: A report from Children's Oncology Group
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PURPOSE: The mouse eye is a widely used model for retinal disease and has potential to become a model for myopia. Studies of retinal disease will benefit from imaging the fundus in vivo. Experimental models of myopia often rely on manipulation of the visual experience. In both cases, knowledge of the optical quality of the eye, and in particular, the retinal image quality degradation imposed by the ocular aberrations is essential. In this study, we measured the ocular aberrations in the wild type mouse. METHODS: Twelve eyes from six four-week old black C57BL/6 wild type mice were studied. Measurements were done on awake animals, one being also measured under anesthesia for comparative purposes. Ocular aberrations were measured using a custom-built Hartmann-Shack system (using 680-nm illumination). Wave aberrations are reported up to fourth order Zernike polynomials. Spherical equivalent and astigmatism were obtained from the 2nd order Zernike terms. Modulation Transfer Functions (MTF) were estimated for the best focus, and through-focus, to estimate depth-of-focus. All reported data were for 1.5-mm pupils. RESULTS: Hartmann-Shack refractions were consistently hyperopic (10.12+/-1.41 D, mean and standard deviation) and astigmatism was present in many of the eyes (3.64+/-3.70 D, on average). Spherical aberration was positive in all eyes (0.15+/-0.07 microm) and coma terms RMS were significantly high compared to other Zernike terms (0.10+/-0.03 microm). MTFs estimated from wave aberrations show a modulation of 0.4 at 2c/deg, for best focus (and 0.15 without cancelling the measured defocus). For that spatial frequency, depth-of-focus estimated from through-focus modulation data using the Rayleigh criterion was 6D. Aberrations in the eye of one anesthetized mouse were higher than in the same eye of the awake animal. CONCLUSIONS: Hyperopic refractions in the mouse eye are consistent with previous retinoscopic data. The optics of the mouse eye is far from being diffraction-limited at 1.5-mm pupil, with significant amounts of spherical aberration and coma. However, estimates of MTFs from wave aberrations are higher than previously reported using a double-pass technique, resulting in smaller depth-of-field predictions. Despite the large degradation imposed by the aberrations these are lower than the amount of aberrations typically corrected by available correction techniques (i.e., adaptive optics). On the other hand, aberrations do not seem to be the limiting factor in the mouse spatial resolution. While the mouse optics are much more degraded than in other experimental models of myopia, its tolerance to large amounts of defocus does not seem to be determined entirely by the ocular aberrations. 相似文献
48.
49.
Alexis Sentís Irina Kislaya Nathalie Nicolay Hinta Meijerink Jostein Starrfelt Ivn Martínez-Baz Jesús Castilla Katrine Finderup Nielsen Christian Holm Hansen Hanne-Dorthe Emborg Anthony Nardone Tarik Derrough Marta Valenciano Baltazar Nunes Susana Monge the VEBIS-Lot working group VEBIS-Lot working group Ausenda Machado Carlos Dias Itziar Casado Cristina Burgui Amparo Larrauri Clara Mazagatos 《Euro surveillance : bulletin européen sur les maladies transmissibles = European communicable disease bulletin》2022,27(30)
By employing a common protocol and data from electronic health registries in Denmark, Navarre (Spain), Norway and Portugal, we estimated vaccine effectiveness (VE) against hospitalisation due to COVID-19 in individuals aged ≥ 65 years old, without previous documented infection, between October 2021 and March 2022. VE was higher in 65–79-year-olds compared with ≥ 80-year-olds and in those who received a booster compared with those who were primary vaccinated. VE remained high (ca 80%) between ≥ 12 and < 24 weeks after the first booster administration, and after Omicron became dominant. 相似文献
50.
Bartomeu Casabella Abril Marta Trenchs Rodríguez Sara Delgado Girón Susana Muñoz Gómez Fernando González García M. Dolores García Ortega 《Atencion primaria / Sociedad Espa?ola de Medicina de Familia y Comunitaria》2012,44(2):97-106
ObjectiveTest effectiveness and acceptability of interventions short essay-type training in health emergency management (EM).DesignCombined case series and controlled study before and after training sessions.LocationHealth Center (HC).ParticipantsTeam on duty, two monitors-facilitators, and a mannequin.Main measuresVariables: response times, staff performance, resource usage and opinion. Structure: scenarios and key messages. Instrument development: 1. Initial/final questionnaire and events. 2. Essential/non-essential times; 3. Post-test opinion questionnaire. Performance of six consecutive 15 min tests fortnightly (including corrections) and poll after each test. A month later, repeat in random order and under similar conditions. Analysis: repeated measures.ResultsA total of 93 (2/3) workers completed the initial survey, and 74 the final, with 46 participants (25 doctors, 7 nurses, 21 non-health completed 95 direct interventions. Matching participants > 80% between series. A reduction was seen in the “detection of collapse to first defibrillation” interval (10 to 4 min). EM events improved 2-3 fold and “sense of security during a real EM” increased from 23% to 71% among participants. The vast majority of participants said “useful corrections made by the facilitator.” The proportions of those who “would like to see tests introduced” and those who said “re-training was needed in EM” were moderately increased (67.4% vs 85% in health care workers). The “would like to attempt basic life support” was unchanged.ConclusionDespite being reduced in number and duration, this model of intervention has shown positive trends in terms of use and acceptability for implementation in the HC. 相似文献