RESUMEN
KRAS mutations in patients with metastatic colorectal cancer (CRC) are a negative marker of the effectiveness of anti-EGFR therapy and have prognostic significance. KRAS genotyping was performed in the material from patients with metastatic CRC. KRAS mutations were determined in tumor DNA from archival biopsies of 573 patients using PCR and sequencing. Mutations in the exon 2 of the KRAS gene were detected in 36.3% of cases of CRC, while often in women (41.1%) than in men (31.2%). There were identified eight types of KRAS mutations, the most frequent--replacement of G12D (33.7%), G12V (32.7%) and G13D (12.5%). There were revealed differences in the frequency and spectrum of KRAS mutations in CRC of various locations; in tumors of the rectum dominated mutation G12V (39%). The Russian CRC patients find out a higher frequency of mutations G12V and a lower frequency of mutations G13D, than patients from Europe and it should be taken into account when assessing the response of CRC patients with different mutant KRAS status on chemotherapy and targeted therapy.
Asunto(s)
Sustitución de Aminoácidos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Mutación , Proteínas Proto-Oncogénicas/genética , Proteínas ras/genética , Adulto , Anciano , Ácido Aspártico , Femenino , Glicina , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Proteínas Proto-Oncogénicas p21(ras) , ValinaRESUMEN
Evaluation of tumor markers expression pattern which determines individual progression parameters is one of the major topics in molecular oncopathology research. This work presents research on expression analysis of several Ras-Ral associated signal transduction pathway proteins (Arf6, RalA and BIRC5) in accordance with clinical criteria in non small cell lung cancer patients. Using Western-blot analysis and RT-PCR Arf6, RalA and BIRC5 expression has been analyzed in parallel in 53 non small cell lung cancer samples of different origin. Arf6 protein expression was elevated in 55% non small cell lung cancer tumor samples in comparison with normal tissue. In the group of squamous cell lung cancer Arf6 expression elevation was observed more often. RalA protein expression was decreased in comparison to normal tissue samples in 64% of non small cell lung cancer regardless to morphological structure. Correlation between RalA protein expression decrease and absence of regional metastases was revealed for squamous cell lung cancer. BIRC5 protein expression in tumor samples versus corresponding normal tissue was 1.3 times more often elevated in the squamous cell lung cancer group (in 76% tumor samples). At the same time elevation of BIRC5 expression was fixed only in 63% of adenocarcinoma tumor samples. A statistically significant decrease (p = 0.0158) of RalA protein expression and increase (p = 0.0498) of Arf6 protein expression in comparison with normal tissue was found for T1-2N0M0 and T1-2N1-2M0 groups of squamous cell lung cancer correspondingly.
Asunto(s)
Factores de Ribosilacion-ADP/biosíntesis , Biomarcadores de Tumor/biosíntesis , Carcinoma de Pulmón de Células no Pequeñas/patología , Proteínas Inhibidoras de la Apoptosis/biosíntesis , Neoplasias Pulmonares/patología , Proteínas de Unión al GTP ral/biosíntesis , Factor 6 de Ribosilación del ADP , Factores de Ribosilacion-ADP/genética , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Expresión Génica/genética , Humanos , Proteínas Inhibidoras de la Apoptosis/genética , Neoplasias Pulmonares/metabolismo , Metástasis de la Neoplasia , Estadificación de Neoplasias , Survivin , Proteínas de Unión al GTP ral/genéticaAsunto(s)
Fibroblastos/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pancreáticas/metabolismo , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Factor de Crecimiento de Hepatocito/metabolismo , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Interleucina-6/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/patología , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta2/metabolismo , Células Tumorales CultivadasRESUMEN
Immunohistochemical analysis of the expression and distribution of nm23 protein and biochemical analysis of the main components of plasminogen activation system in tumors were carried out in stomach cancer patients. The data indicate that the expression of nm23 protein in malignant epithelial gastric tumors is heterogeneous, characterized by cytoplasmic and nuclear immunoreactivity. Reduced expression of the marker is more typical of poorly or undifferentiated tumors. The expression of nm23 protein positively correlated with tPA level (r(s)=0.4; p=0.01) and did not correlate with the content of uPA and PAI-1 in tumors. High PAI-1 values in tumors (>0.5 ng/mg protein) significantly correlated with lower 3-year overall survival of stomach cancer patients. These data confirm the role of the studied proteins in invasion and metastases of malignant tumors and suggest a relationship between changes in the expression of nm23 protein and mechanisms of stomach cancer progress.