Colorectal cancer (CRC) is the second most frequent cause of direct cancer death worldwide. The study of the molecular state of oncogenes has predictive and prognostic value in metastatic CRC (mCRC). The B-raf proto-oncogene (BRAF) gene mutation represents the 8%-12% of all mutations in mCRC. The BRAF V600E mutation, considered the most common alteration of BRAF, corresponds to a constitutive kinase with a high activating capacity of the RAS/RAF/MEK/ERK pathway after a cascade of successive phosphorylations in the transcription of genes. BRAF V600E mutation is more prevalent in women, elderly, right-sided colon cancer and Caucasian population. Unfortunately, it is considered a poor predictive and prognosis biomarker. Patients with mCRC BRAF V600E mutated (BRAFm) are generally associated with poor response to chemotherapy and short progression-free survival and overall survival. Recently, randomised clinical trials have studied the combination of different chemotherapy regimens with angiogenic inhibitors in mCRC BRAFm. In addition, new anti-BRAF and immunotherapy agents have also been studied in this population, with positive results. The objective of this review is to acknowledge the biology and molecular pathway of BRAF, critically analyse the clinical trials and the therapy options published until today and evaluate the options of treatment according to the patient's clinical presentation.
Objetivo: Determinar el efecto hipoglicemiante de las catáfilas de cebolla (Allium cepa). Material y Métodos: Estudio experimental de tipo aleatorizado. Los extractos fueron obtenidos de catáfilas de muestras provenientes de tres fincas agrícolas -Tacna, Arequipa y Lima-, en alcohol de 70º GL por 7 días, con movimiento del macerado en oscuridad; filtrada y deshidratada en una estufa a no más de 40º C; luego se diluyó 1.4 g de cada muestra con 7.6 ml de agua destilada y 1 ml de twin 80. En el ensayo se utilizó cinco grupos de ratones de la cepa balb C 53 con seis unidades experimentales cada uno. A cuatro de estos grupos se les indujo un estado hiperglicemiante con glucosa administrada por vía intraperitoneal a una dosis de 3 g de glucosa/kg de peso corpóreo. A tres de estos grupos se les administró el extracto correspondiente de muestras de cada finca, mientras que el grupo de control fue utilizado para monitorear el nivel de glicemia alcanzado por el estado hiperglicemiante inducido. El grupo restante (basal) no recibió extracto ni se le indujo estado diabético y sus niveles de glucemia normales sirvieron para la comparación con los resultados de los otros grupos. Se administró 1 ml/100 g de cada extracto a cada grupo respectivo, a una dosis de 0.4 g/100 g de peso corpóreo. Finalmente, se tomaron muestras de glucemia a los 45 y 90 minutos después de la administración de glucosa. Resultados: El grupo control tuvo medias de glucemia de 264 mg/dl y 147,6667 mg/dl a los 45 y 90 minutos mientras que el grupo basal tuvo medias de 115,6666 mg/dl y 101,8333 mg/dl. Los grupos Arequipa, Orgánica (Lima) e Ilabaya (Tacna) presentaron medias de 123,8333, 184 y 202 mg/dl respectivamente a los 45 minutos, mientras que a los 90 minutos las medias fueron de 100,6667, 126,8333 y 107,6667 mg/dl. Conclusión: Los extractos elaborados a base de cascara de cebolla tienen efectos hipoglicemiantes en ratones. El extracto de catafilas arequipeñas demostró posees el mayor efecto hipoglicemiante. Palabras Claves: catáfilas de cebolla, efecto hipoglicemiante.
e21522 Background: The standard treatment for patients with advance EGFR mutated NSCLC are Tirosine Kinasa inhibitors (TKI), we face in our clinical practice a different profile of toxicity; there is limited data of Inflammatory markers in this especial population. The aim of our study is to determine whether neutrophil lymphocyte ratio (NLR), lymphocyte platelet ratio(PLR), RDW-CV and body mass index (BMI) are related to the develop of this toxicity. Methods: We retrospectively analyzed data of patients with EGFRm NSCLC at Aliada Clinic between January 2016 to December 2019. Inflammatory markers were obtained from laboratory tests performed during the first visit as outpatient. The BMI kg/m2 at the start of the treatment was defined as the weight (kg) divided by the height (m) squared. Adverse event (AE) were graded according CTCAE v5.0. Results: A total of 164 patients were diagnosed with advanced NSCLC, of these 50 patients were assessed, 29 women and 21 men. The average age was 58.9 years, median of 59.5 ( 38 to 83; SD: 11.7). The most frequent EGFR mutation was deletion 19 (59.6%) followed by L858R mutation ( 23.1%) . The median BMI was 25.18 (16.2 to 41.3 kg/m2) 46.2% were normal, 36.5% were overweight, and 11.5 % were obese. 80% present any grade of AE. The most frequent AE was skin related: 75% (90 % grade I or II) follow by gastrointestinal: 57.6% (74 % grade I or II). There were no significant differences between NLR according to toxicity grade I-II vs III-IV (media: 3.44 and 4.32; P = 0.46); PLR according toxicity grade I-II vs III-IV (media: 229.41 and 251-50; P = 0.78); and RDW-CV according to toxicity grade I-II vs III-IV (media: 14.17 and 14.4; P = 0.74). Similarly, no significant differences were observed among toxicity profiles in relation to BMI (p = 0.2). Finally, there was no impact of severity of toxicity on progression-free survival (p = 0.64) or overall survival 24,33 months (IC 95% 16,05 – 32,6; p = 0.9). Conclusions: There was no relation between inflammatory markers and the grade of toxicity in patients with EGFRm advance NSCLC receiving TKIs. We suggest increase the population to validate our results.
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