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Lorena Martin-Morales Sara Manzano Maria Rodrigo-Faus Adrian Vicente-Barrueco Victor Lorca Gonzalo Núñez-Moreno Paloma Bragado Almudena Porras Trinidad Caldes Pilar Garre Alvaro Gutierrez-Uzquiza 《International journal of cancer. Journal international du cancer》2023,152(2):283-297
Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future. 相似文献
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A. Armentia S. Martín-Armentia A. Moral D. Montejo B. Martin-Armentia R. Sastre S. Fernández A. Corell D. Fernandez 《Allergologia et immunopathologia》2019,47(4):350-356
Introduction and objectivesBiological aerosols play a vital role in the interactions between the atmosphere, biosphere, climate and public health and fungal spores are a component with allergic importance.We constructed a database in Castile & Leon (Spain) and carry out molecular-level component-resolved diagnosis to complete the air quality study carried out since 2006 by our aerobiological network (RACYL) to aid clinical diagnosis and treatment.MethodsWe reviewed a database of 19,774 patients (adults and children) with allergic respiratory disease treated in our unit during the last 12 years. We also made a component-resolved diagnosis of the molecules involved in the pathology in a randomly selected population of 150 patients.ResultsThe dimeric glycoprotein Alt a1 from Alternaria is the most prevalent and most useful allergen in the diagnosis of patients with allergy to fungi in our area (94.4%), followed by enolase Alt a 6 (Alternaria), ribonuclease Asp f 1 of Aspergillus and mannitol dehydrogenase from Cla h 8 (Cladosporium).ConclusionsOur results have helped determine which spore molecules are most-closely associated with allergies. Molecular analysis will be useful to determine more accurate and useful immunotherapy in these patients. 相似文献
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Outcomes at 3 years of a prospective pilot study of Campath-1H and sirolimus immunosuppression for renal transplantation 总被引:2,自引:0,他引:2
Rolf N. Barth Christina A. Janus Christine A. Lillesand Nancy A. Radke John D. Pirsch Bryan N. Becker Luis A. Fernandez L. Thomas Chin Yolanda T. Becker Jon S. Odorico Anthony M. D''Alessandro Hans W. Sollinger Stuart J. Knechtle 《Transplant international》2006,19(11):885-892
Campath-1H (alemtuzumab) induction was used for renal transplantation in combination with sirolimus as immunosuppression. We previously reported a high (28%) rate of early rejection with this regimen, and now report 3-year outcomes. Twenty-nine patients were recipients of either deceased donor or non-HLA (Human Leukocyte Antigen) identical living donor primary renal allografts. Clinical parameters including infection, malignancy, kidney function, and kidney histology were followed prospectively for 3 years. Three-year cumulative graft and patient survival were 96% and 100%, respectively. Twenty patients were maintained on steroid-free immunosuppressive regimens, and 15 patients were maintained on monotherapy for immunosuppression (12 on sirolimus). No serious infectious complications were observed and two patients developed basal cell skin cancer. The 3-year results of our initial pilot study demonstrate good graft (96%) and patient (100%) outcomes. Campath-1H induction has yielded a high proportion of patients maintained on immunosuppressive monotherapy (57%) without serious infectious- and no malignancy-related complications. The reported regimen yielded novel insights into both Campath-1H and sirolimus therapy in renal transplantation. Because of the higher incidence of early rejection, we recommend a modified strategy of immunosuppression including a brief course of a calcineurin inhibitor. 相似文献
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Oral allergy syndrome induced by spinach 总被引:1,自引:1,他引:0
I. Sanchez F. Rodriguez J. L. Garcia-Abujeta L. Fernandez D. Quiñones D. Martin-Gil 《Allergy》1997,52(12):1245-1246
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We report a case of vasoactive-agent-induced priapism successfully treated in the emergency department with 10 mg of metaraminol injected into the corpora cavernosa. 相似文献
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Andrew E. Springer Kayan Lewis Steven H. Kelder Maria E. Fernandez Cristina S. Barroso Deanna M. Hoelscher 《Journal of immigrant and minority health / Center for Minority Public Health》2010,12(5):769-780
Research on physical activity (PA) by level of acculturation in Hispanic children is limited and findings have been mixed.
We examined PA participation by primary language used with parents in a representative sample of 4th, 8th, and 11th grade
Texas public school students. Mixed-effects regression models were conducted using cross-sectional data from the 2004–2005
School Physical Activity and Nutrition Study (n = 22,049). Self-reported PA was compared among three language-ethnic groups: Spanish-Hispanic (SH) (referent); English-Hispanic
(EH); and English-Other (EO). EH and/or EO girls were generally between 1.25 and 2.58 [OR] times more likely to participate in PA across grade levels,
with the largest differences found for school sports in 8th grade girls. EH and EO 8th grade boys were 1.71 (CI: 1.40, 2.10)
and 2.06 (CI: 1.68, 2.51) times, respectively, more likely to participate in school sports. Findings indicate important disparities
in Spanish-speaking Hispanic children’s PA participation. 相似文献