Intramedullary metastases due to non microcytic lung carcinoma Maciá Escalante, Sonia; Martínez Ortiz, María José; Guillén Ponce, Carmen ...
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico,
06/2006, Letnik:
8, Številka:
6
Report
Objective
Large somatotrophic adenomas depict poor response to somatostatin receptor ligands (SRLs). Debulking has shown to enhance SRLs effect in some but not all cases and tumour volume reduction ...has been proposed as the main predictor of response. No biological studies have been performed so far in this matter. We aimed to identify molecular markers of response to SRLs after surgical debulking in GH‐secreting adenomas.
Design
We performed a multicenter retrospective study.
Patients
24 patients bearing large GH‐producing tumours.
Measurements
Clinical data and SRLs response both before and after surgical debulking were collected, and 21 molecular biomarkers of SRLs response were studied in tumour samples by gene expression.
Results
From the 21 molecular markers studied, only two of them predicted enhanced SRLs response after surgery. Tumours with improved response to SRLs after surgical debulking showed lower levels of Ki‐67 (MKI67, FC = 0.17 and P = .008) and higher levels of RAR‐related orphan receptor C (RORC) (FC = 3.1 and P ˂ .001). When a cut‐off of no detectable expression was used for Ki‐67, the model provided a sensitivity of 100% and a specificity of 52.6% with an area under the curve of 65.8%. Using a cut‐off of 2 units of relative expression of RORC, the prediction model showed 100% of sensitivity and specificity.
Conclusions
High levels of RORC and low levels of Ki‐67 identify improved SRLs response after surgical debulking in large somatotropic adenomas. To determine their expression would facilitate medical treatment decision‐making after surgery.
Growth-hormone (GH)-secreting pituitary-tumors (GHomas) are the most common acromegaly cause. At diagnosis, most of them are macroadenomas, and up to 56% display cavernous sinus invasion. Biomarkers ...assessment associated with tumor-growth and invasion are important to optimize their management.
To identify clinical/hormonal/molecular-biomarkers associated with tumor-size and invasiveness in GHomas, and to analyze the influence of pre-treatment with somatostatin-analogs or dopamine-agonists in key molecular biomarkers expression.
Clinical/analytical/radiological-variables were evaluated in 192 patients from the REMAH-study (ambispective multicenter post-surgery study of the Spanish Society of Endocrinology and Nutrition). Expression of somatostatin/ghrelin/dopamine-systems components, and key pituitary/proliferation-markers were evaluated in GHomas after the first surgery. Univariate/multivariate regression studies were performed to identify association between variables.
80% of patients harbor macroadenomas (63.8% with extrasellar-growth). Associations between larger and more invasive GHomas with younger age, visual-abnormalities, higher IGF1-levels, extrasellar/suprasellar-growth and/or cavernous-sinus invasion were found. Higher GH1 and lower PRL/POMC/CGA/AVPR1B/DRD2T/DRD2L expression levels (p<0.05) were associated to tumor invasiveness. LASSO´s penalized regression identified combinations of clinical and molecular features with AUCs between 0.67-0.82. Preoperative therapy with dopamine-agonist or somatostatin-analogs did not alter the expression of any of the markers analyzed except for DRD1/AVPR1B (up-regulated with dopamine-agonist), and FSHB/CRHR1 (down-regulated with somatostatin-analogs).
A specific combination of clinical/analytical/molecular variables was found to be associated with tumor invasiveness and growth capacity in GHomas. Pre-treatment with first-line drugs for acromegaly did not significantly modify the expression of the most relevant biomarkers in our association model. These findings provide valuable insights for risk stratification and personalized management of GHomas.
Se presenta el proyecto denominado Identificación archivística de tipos y series documentales a partir de imágenes digitalizadas de documentos microfilmados que integran los llamados Archivos ...Berrutti, el cual surge de las actividades de investigación en el área de archivología realizadas en la Facultad de Información y Comunicación de la Universidad de la República de Uruguay. Constituye un componente de la línea de investigación Recursos de Investigación Digital, en tanto presenta interés en la tipología de los recursos de información digitales. El objetivo es proponer pautas desde la investigación archivística para el tratamiento de identificación, representación descriptiva y evaluación de las imágenes digitalizadas de documentos microfilmados que integran los Archivos Berrutti del Ministerio de Defensa Nacional del Uruguay. La metodología definida presenta un enfoque cualitativo de tipo exploratorio y descriptivo apropiado para cumplir con los objetivos planteados. Los resultados de la investigación pretenden brindar un abordaje archivístico con el desarrollo de funciones específicas sobre una agrupación documental con características especiales.
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