Hospital General Universitario Gregorio Marañón

About: Hospital General Universitario Gregorio Marañón is a healthcare organization based out in Madrid, Spain. It is known for research contribution in the topics: Population & Transplantation. The organization has 11975 authors who have published 12386 publications receiving 244847 citations.

Prognostic factors for disease-free survival in patients with T3-4 or N+ rectal cancer treated with preoperative chemoradiation therapy, surgery, and intraoperative irradiation.

Abstract: Purpose: Fluoropyrimidine-radiosensitizing agents in conjunction with preoperative radiotherapy have proven to induce tumor and nodal downstaging effects, sphincter preservation promotion, and mid-term favorable survival rates. Intraoperative electron beam radiation therapy may improve pelvic control in patients with locally advanced rectal cancer stages. Potential predictive factors for response and disease-free survival, with intense local multidisciplinary approach, are analyzed. Methods and Materials: One hundred fifteen patients with rectal cancer were treated with oral 5-fluorouracil or Tegafur with preoperative radiotherapy, surgery, and intraoperative electron beam radiation therapy to identify potential pre- and on-treatment characteristics that might be of prognostic value for disease outcome. Univariate and multivariate analyses were performed. Results: Older patients and those treated with Tegafur were more likely to achieve a major histologic response, categorized as persistence of minimal residual microscopic disease foci in the surgical specimen (“mic” response). Factors unfavorably associated with disease-free survival in the multivariate model were male gender and persistence of macroscopic disease in the rectal wall (“mac” response). Accordingly, 3-year disease-free survival rates in the groups of patients with 0, 1, or 2 of these risk factors were 100%, 81%, and 53%, respectively (p < 0.001). Conclusions: Females with an intense pathologic response (pTmic residue) to preoperative chemoradiotherapy have an excellent 3-year disease-free survival. This information might be of interest for stratification of patients in the development of adjuvant treatment trials. © 2006 Elsevier Inc. Rectal cancer, Prognostic factors, Preoperative chemoradiation, Surgery, Intraoperative radiotherapy.

Phase I First-in-Human Dose Escalation Study of the oral SF3B1 modulator H3B-8800 in myeloid neoplasms.

Abstract: We conducted a phase I clinical trial of H3B-8800, an oral small molecule that binds Splicing Factor 3B1 (SF3B1), in patients with MDS, CMML, or AML. Among 84 enrolled patients (42 MDS, 4 CMML and 38 AML), 62 were red blood cell (RBC) transfusion dependent at study entry. Dose escalation cohorts examined two once-daily dosing regimens: schedule I (5 days on/9 days off, range of doses studied 1-40 mg, n = 65) and schedule II (21 days on/7 days off, 7-20 mg, n = 19); 27 patients received treatment for ≥180 days. The most common treatment-related, treatment-emergent adverse events included diarrhea, nausea, fatigue, and vomiting. No complete or partial responses meeting IWG criteria were observed; however, RBC transfusion free intervals >56 days were observed in nine patients who were transfusion dependent at study entry (15%). Of 15 MDS patients with missense SF3B1 mutations, five experienced RBC transfusion independence (TI). Elevated pre-treatment expression of aberrant transcripts of Transmembrane Protein 14C (TMEM14C), an SF3B1 splicing target encoding a mitochondrial porphyrin transporter, was observed in MDS patients experiencing RBC TI. In summary, H3B-8800 treatment was associated with mostly low-grade TAEs and induced RBC TI in a biomarker-defined subset of MDS.

Murine eosinophils and IL-1: alpha IL-1 mRNA detection by in situ hybridization. Production and release of IL-1 from peritoneal eosinophils.

Abstract: The presence of IL-1 mRNA in eosinophils from mice infected with larvae of the parasite Mesocestoides corti was investigated by in situ hybridization technique. S35 labeled cDNA probe for alpha IL-1, hybridized with mRNA in murine eosinophils and macrophages. After 6 h of LPS stimulation eosinophils were able to express mRNA in their cytoplasm. This expression was highly increased by the addition of indomethacine. The IL-1 mRNA expression in murine macrophages was higher than in eosinophils in LPS-stimulated cells. This difference was statistically significant, p less than 0.001. To test if eosinophils may produce and release IL-1 in the culture medium, we isolated these cells in a Percoll gradient. Cell preparations with a purity exceeding 94% were cultured with various stimuli and their supernatants were tested for IL-1 activity. Eosinophils produced 169.65 +/- 73 U/ml when stimulated with LPS (n = 14). A dose-dependent response was obtained when the eosinophils were in the presence of the calcium ionophore A23187. Controls were performed to rule out the contribution of the contaminating population on the thymocyte proliferating activity. They were also used to detect other possible causes of interference in the assay, such as leukotrienes or TNF. IL-1 in supernatants was also detected using a conversion assay such as EL-4 thymoma cells. IL-1 activity was first detected in culture supernatants 18 h later, maximal production being in the first 24 h. In accordance with our hybridization results, an increase in IL-1 activity was obtained when eosinophils were stimulated with LPS and treated with indomethacine. The factor had a molecular mass between 16 to 20 kDa that corresponded to the described for murine IL-1. Inasmuch as IL-1 is an important mediator of inflammatory reactions this IL may enhance the proinflammatory action of eosinophils.