RESUMEN
We report structurally new type of dimers composed of bent-core molecules connected through their central cores by an alkylene spacer. Various self-assembling structures are discovered when prolonging the terminal alkyl chains in arms. Among diverse mesophases, the antiferroelectric type of switching under an applied electric field is observed.
RESUMEN
BACKGROUND: Our aim was to investigate the prognostic and predictive value of the oncogenic MAPKK-like protein T-cell-originated protein kinase (TOPK) stratified by KRAS and BRAF mutations in patients with sporadic, hereditary and metastatic colorectal cancer (CRC) treated with anti-EGFR therapy. METHODS: Immunohistochemistry (IHC) for TOPK was performed on four study groups. Group 1 included two subgroups of 543 and 501 sporadic CRC patients used to test the reliability of TOPK expression by IHC. In Group 2, representing an additional 222 sporadic CRCs, the prognostic effect of TOPK stratified by KRAS and BRAF was assessed. The prognostic effect of TOPK was further analysed in Group 3, representing 71 hereditary Lynch syndrome-associated CRC patients. In Group 4, the predictive and prognostic value of TOPK was analysed on 45 metastatic patients treated with cetuximab or panitumumab stratified by KRAS and BRAF gene status. RESULTS: In both sporadic CRC subgroups (Group 1), associations of diffuse TOPK expression with clinicopathological features were reproducible. Molecular analysis of sporadic CRCs in Group 2 showed that diffuse TOPK expression was associated with KRAS and BRAF mutations (p<0.001) and with poor outcome in patients with either mutation in univariate and multivariate analysis (P=0.017). In hereditary patients (Group 3), diffuse TOPK was linked to advanced pT stage. In metastatic patients treated with anti-EGFR therapy (Group 4), diffuse TOPK expression was linked to dismal outcome despite objective response to treatment (P=0.01). CONCLUSIONS: TOPK expression is an unfavourable prognostic indicator in sporadic patients with KRAS or BRAF mutations and also in patients with metastatic disease experiencing a response to anti-EGFR therapies. The inhibition of TOPK, which could benefit 30-40% of CRC patients, may represent a new avenue of investigation for targeted therapy.
Asunto(s)
Adenocarcinoma/química , Neoplasias Colorrectales/química , Proteínas Serina-Treonina Quinasas/análisis , Proteínas Proto-Oncogénicas B-raf/genética , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/epidemiología , Adenocarcinoma/genética , Adenocarcinoma/secundario , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Cetuximab , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales Hereditarias sin Poliposis/química , Neoplasias Colorrectales Hereditarias sin Poliposis/epidemiología , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/inmunología , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Genes ras , Humanos , Masculino , Persona de Mediana Edad , Quinasas de Proteína Quinasa Activadas por Mitógenos , Variaciones Dependientes del Observador , Panitumumab , Valor Predictivo de las Pruebas , Pronóstico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Distribución Aleatoria , Reproducibilidad de los Resultados , Transducción de Señal/genéticaRESUMEN
BACKGROUND: Bronchogenic cysts are developmental abnormalities of the primitive foregut which typically occur in the lung. Subdiaphragmatic and, especially, retroperitoneal locations are rare. The histopathological definition consists of the presence of ciliated epithelium together with cartilage or bronchial mucous glands. CASE PRESENTATION: We report on a 49-year-old patient with the incidental finding of a large cystic mass between the diaphragm and the stomach. Imaging studies suggested an adrenal tumour. Surgical resection and postoperative follow-up were uneventful. Histological examination revealed the surprising diagnosis of a bronchogenic cyst. CONCLUSION: Bronchogenic cysts must be considered in the differential diagnosis of retroperitoneal cystic lesions. Regardless of being asymptomatic most of the time, surgical resection is recommended to obtain definitive histological diagnosis and avoid future complications.
Asunto(s)
Quiste Broncogénico/cirugía , Hallazgos Incidentales , Espacio Retroperitoneal , Quiste Broncogénico/diagnóstico , Quiste Broncogénico/patología , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana Edad , Espacio Retroperitoneal/patología , Tomografía Computarizada por Rayos XRESUMEN
In 1821 Napoleon died in exile on the Island of St. Helena. Although the autopsy had suggested stomach cancer as the cause of death, in 1961 an elevated arsenic concentration was found in Napoleon's hair. This finding elicited numerous theories of conspiracy, treachery, and poisoning. Most recent reports even suggested inappropriate medical treatment may have contributed to the exiled Emperor's death. Napoleon's apparent obesity at the time of his demise was interpreted as a strong argument against stomach cancer as the cause of death; however, his weight changes over the course of his life, noticeable from the contemporary iconography, have not been systematically analyzed. To test the hypothesis that Napoleon's weight at death could be compatible with a diagnosis of terminal gastric cancer, we performed several studies to determine: a) Napoleon's weight at death; and b) the changes of his weight during the last 20 years of his life. Our weight modeling was based on the collection of 12 different pairs of trousers worn by Napoleon between 1800 and 1821, the year of his death. Modeling trouser sizes with control data suggested a weight increase from 67 kg to 90 kg by 1820. The trousers worn at the time of death suggested a subsequent weight loss of 11 kg (to 79 kg) during the last year of his life. This weight was confirmed by a second modeling approach based on the subcutaneous fat measurement performed at autopsy (1.5 inches) and a control group of 270 men dying from various causes. This provides a reasonable validation for both weight measurement methods. Napoleon's terminal weight loss of more than 10 kg is suggestive of a severe progressive chronic illness and is highly consistent with a diagnosis of gastric cancer.