ABSTRACT
The fluorescence in situ (FISH) belongs to the most often used molecular cytogenetic techniques, applied in many areas of diagnosis and research. The analysis of FISH images relies on localization and counting the red and green spots in order to determine HER2 status of the breast cancer samples. The algorithm of spot localization presented in the paper is based on 3-D shape analysis of the image objects. The subsequent regions of the image are matched to the reference pattern and the results of this matching influence localization of spots. The paper compares different shapes of the reference pattern and their efficiency in spot localization. The numerical experiments have been performed on the basis of 12 cases (patients), each represented by three images. Few thousands of cells have been analysed. The quantitative analyses comparing different versions of algorithm are presented and compared to the expert results. The best version of the procedure provides the absolute relative difference to the expert results smaller than 3%. These results confirm high efficiency of the proposed approach to the spot identification. The proposed method of FISH image analysis improves the efficiency of detecting fluorescent signals in FISH images. The evaluation results are encouraging for further testing of the developed automatic system directed to application in medical practice.
Subject(s)
Algorithms , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Image Processing, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , In Situ Hybridization, Fluorescence/methods , Humans , Receptor, ErbB-2/analysis , Receptor, ErbB-2/geneticsABSTRACT
BACKGROUND: The aim of this study was to search for predictive and prognostic factors in patients with metastatic renal cell carcinoma (mRCC) treated with everolimus among the components of PI3K/AKT/mTOR pathway. PATIENTS AND METHODS: In a prospective, one-arm, phase II study, patients with mRCC received everolimus (10 mg/day) using a 30-day cycle. A prospectively planned evaluation of potential biomarkers of PI3K/AKT/mTOR pathway. RESULTS: The median age of the 58 patients enrolled into the study was 60 years (range 41-78 years). In multivariate analysis, it was found that the adverse independent predictors for everolimus therapy were histological grade G1/2 {hazard ratio (HR): 2.68 [95% confidence interval (CI) 1.29-5.58, P = 0.0082]}, increased lactate dehydrogenase (LDH) level before treatment [HR: 2.55 (95% CI 1.30-4.99, P = 0.0064)] and the PIK3CA gene variant rs6443624 (HR: AC + AA versus CC = 2.08, 95% CI 1 11-3.89, P = 0.0254). In multivariate analysis, it was observed that the adverse independent prognostic factors were: elevated corrected calcium level [HR: 4.17 (95% CI 1.66-10.51; P = 0.0024)] and the PIK3CA gene variant rs6443624 [HR: AC + AA versus CC = 1.97 (95% CI 1.02-3.79; P = 0.0421)]. CONCLUSIONS: The PI3KCA gene polymorphism, LDH, and histologic grade can predict the effects of everolimus treatment. The corrected calcium level and the PIK3CA gene variant rs6443624 may be independent prognostic factors. Further investigation is needed to confirm and validate these findings prospectively in other RCC trials.
Subject(s)
Carcinoma, Papillary/genetics , Carcinoma, Renal Cell/genetics , Everolimus/therapeutic use , Kidney Neoplasms/genetics , Phosphatidylinositol 3-Kinases/genetics , TOR Serine-Threonine Kinases/genetics , Adult , Aged , Carcinoma, Papillary/drug therapy , Carcinoma, Papillary/mortality , Carcinoma, Papillary/secondary , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/secondary , Class I Phosphatidylinositol 3-Kinases , Female , Follow-Up Studies , Genotype , Humans , Kidney Neoplasms/drug therapy , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Male , Middle Aged , Mutation/genetics , Neoplasm Grading , Phosphoinositide-3 Kinase Inhibitors , Polymerase Chain Reaction , Prognosis , Prospective Studies , Protein Kinase Inhibitors/therapeutic use , Survival Rate , TOR Serine-Threonine Kinases/antagonists & inhibitorsABSTRACT
Este articulo desarrolla la segunda parte de las conclusiones del trabajo de investigación El Trabajo interdisciplinario en la asistencia pediátrica de alta complejidad, realizada entre los años 2004-2005. La metodología implementada fue la de estudio de un caso con un carácter exploratorio y desriptivo. Se realizó con un diseño holístico donde se conjugaron diferentes técnicas cualitativas para lograr una validación convergente de fuentes primarias (entrevistas, observaciones, grupos focales) y secundarias de información (archivos institucionales y bibliografía sobre administración sanitaria). El objetivo general fue contribuir al diseño de modelos de organización hospitalaria que favorezcan la interdisciplina. Para ello se estudiaron dos grupos de profesionales, aquellos que intercambian asistemáticamente y los que lo hacen de modo sistemático. Ambos parten de un diagnóstico semejante sobre los problemas para el intercambio, pero el grupo que trabaja interdisciplinariamente en programas ha encontrado modos de resolverlos o intenta hacerlo. La investigación identificó como facilitadores de la interdisciplina determinadas condiciones institucionales, perfil de los profesionales y modalidades de vínculo. El análisis del material permitió caracterizar los diversos aportes del trabajo conjunto con respecto a los pacientes, a los profesionales, al hospital y al conocimiento científico y posibilitó construir indicadores de la existencia de trabajo interdisciplinario. Se concluyó que el mandato institucional es indispensable pero no es suficiente para la concreción de un trabajo interdisciplinario. Este proceso se construye a partir de los dasafíos que plantea la complejidad de la práctica, de la experiencia del compartir de la confrontación de distintos modelos posibles de trabajo
