RESUMEN
Infrequent solitary fibrous tumours of the pleura are associated with hypoglycaemia only in a few percent of the cases; this condition is called Doege-Potter syndrome, named after its first descriptors. Our 63 years old male patient has previously undergone clinical treatment for intrathoracic fluid accumulation on the left side caused by a giant tumour-like mass in the lower left lobe detected by CT scan. In the course of further investigations performed due to increasing load-induced dyspnoea, lung core biopsy verified low grade sarcoma in the tumour. Tumour board suggested surgery. The patient was transferred from the intensive care unit into the operation theater due to increasing dyspnoea and repeated hypoglycaemic periods in rapidly worsening general condition. Pneumonectomy and removal of the tumour was performed on the left side. Histology showed solitary fibrous tumour of the pleura corresponding to Doege-Potter syndrome. The patient was discharged without complications and underwent adjuvant chemotherapy due to pleural dissemination of the tumour observed intraoperatively. One year after surgery the patient underwent surgical removal of a locally recurrent tumour. In spite of repeated chemotherapy local and multiplex contralateral pulmonary progression was observed. Three-year survival was noted from the time of the first surgery. Orv Hetil. 2018; 159(41): 149-153.
Asunto(s)
Sarcoma/patología , Sarcoma/cirugía , Tumor Fibroso Solitario Pleural/patología , Tumor Fibroso Solitario Pleural/cirugía , Progresión de la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Neumonectomía , Síndrome , Resultado del TratamientoRESUMEN
The PC12 rat pheochromocytoma cell line is an in vitro model system widely used for the investigation of intracellular signaling events contributing to neuronal differentiation and cell death. We found earlier that the nitric oxide donor compound sodium nitroprusside (SNP) induced apoptosis of PC12 cells if it was applied in high concentration (400 µM). Yoshioka et al. (J Pharmacol Sci 101:126-134, 2006) reported that cell death evoked by cytotoxic concentrations of SNP could be prevented by a 100 µM SNP pre-treatment in a murine macrophage cell line. The apoptosis caused by toxic-dose SNP treatment (400 µM) could be partially overcome in PC12 cells as well by the low-dose SNP pre-treatment. The partial inhibition of apoptosis was accompanied by reduced phosphorylation of certain proteins (such as stress-activated protein kinases, the p53, and the eIF2α proteins), decreased caspase activation, and less intense internucleosomal DNA fragmentation. The 100 µM SNP pre-treatment reduced the pro-apoptotic potential of certain other stress stimuli (serum withdrawal, cisplatin and tunicamycin treatments) as well, although the underlying biochemical changes were not entirely uniform. On the contrary, the 100 µM SNP pre-treatment was unable to prevent cell death caused by the protein synthesis inhibitor anisomycin. Further clarification of the above-mentioned processes may be important in understanding the mechanisms by which mild nitrosative stress protects cells against certain forms of cellular stress conditions.
Asunto(s)
Donantes de Óxido Nítrico/farmacología , Nitroprusiato/farmacología , Transducción de Señal/efectos de los fármacos , Animales , Caspasa 3 , Muerte Celular/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Citocromos c/metabolismo , Fragmentación del ADN/efectos de los fármacos , Células PC12 , Ratas , Estrés FisiológicoRESUMEN
PC12 rat pheochromocytoma cells are widely used to investigate signaling pathways. The p143p53PC12 cell line expresses a Val143Ala mutant p53 protein that is less capable of binding to the p53 consensus site in DNA than its wild-type counterpart. Nitric oxide (NO), depending on its concentration, is able to activate several signal transduction pathways. We used sodium nitroprusside (SNP), an NO donor compound, to analyze NO-induced cellular stress in order to clarify the mechanism and role of nitrosative stress in pathological processes, including inflammation and cancer. SNP caused cell death when applied at a concentration of 400 µM, p143p53PC12 cells showing higher sensitivity than wild-type PC12 cells. The mechanisms leading to the increased SNP-sensitivity of p143p53PC12 cells were then investigated. The 400-µM SNP treatment caused stress kinase activation, phosphorylation of the eukaryotic initiation factor eIF2α and p53 protein, proteolytic activation of protein kinase R, caspase-9, and caspase-3, p53 stabilization, CHOP induction, cytochrome c release from mitochondria, and a decline in the level of the Bcl-2 protein in both cell lines. All these SNP-induced changes were more robust and/or permanent in cells with the mutant p53 protein. We thus conclude that (1) the main cause of the SNP-induced apoptosis of PC12 cells is the repression of the bcl-2 gene, evoked through p53 stabilization, stress kinase activation, and CHOP induction; (2) the higher SNP sensitivity of p143p53PC12 cells is the consequence of the stronger and earlier activation of the intrinsic apoptotic pathway.
Asunto(s)
Sustitución de Aminoácidos , Apoptosis , Óxido Nítrico/metabolismo , Estrés Fisiológico , Proteína p53 Supresora de Tumor/metabolismo , Animales , Caspasa 3/genética , Caspasa 3/metabolismo , Caspasa 9/genética , Caspasa 9/metabolismo , Citocromos c/genética , Citocromos c/metabolismo , Factor 2 Eucariótico de Iniciación/genética , Factor 2 Eucariótico de Iniciación/metabolismo , Mitocondrias/genética , Mitocondrias/metabolismo , Mitocondrias/patología , Mutación Missense , Óxido Nítrico/genética , Donantes de Óxido Nítrico/farmacología , Nitroprusiato/farmacología , Células PC12 , Fosforilación/efectos de los fármacos , Fosforilación/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Toxic concentrations of the second messenger nitric oxide cause cellular stress leading to cell death. Ras proteins, possible targets of nitric oxide-induced nitrosylation, may act as mediators in nitrosative stress. To analyze the possible involvement of Ras proteins in nitric oxide cytotoxicity, a PC12 rat phaeochromocytoma cell line expressing a dominant negative Ras mutant protein was used in this study. Cytotoxic concentrations of the nitric oxide donor sodium nitroprusside activated several proapoptotic mechanisms, including stimulation of the stress kinase pathways mediated by c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), inhibition of the translation initiation factor eIF2α, induction and phosphorylation of the p53 protein, and inhibited Akt-mediated antiapoptotic signaling, independent of Ras function. Simultaneously, Ras-dependent stimulation of the prosurvival ERK pathway was also observed, followed by an increased activation of the caspase-9/caspase-3 cascade in cells with impaired Ras function. It is concluded that nitric oxide stimulation of multiple signaling pathways contributes to the cell death program, whereas concomitant activation of the Ras/ERK pathway provides a certain degree of protection.
Asunto(s)
Supervivencia Celular , Nitroprusiato/farmacología , Proteínas ras/metabolismo , Animales , Apoptosis , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Línea Celular Tumoral , Núcleo Celular/metabolismo , Fragmentación del ADN , Activación Enzimática , Genes Dominantes , MAP Quinasa Quinasa 4/metabolismo , Proteínas Mutantes/metabolismo , Óxido Nítrico/metabolismo , Células PC12 , Ratas , Transducción de Señal , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Nitric oxide (NO) is a mediator of a diverse array of inter- and intracellular signal transduction processes. The aim of the present study was to analyze its possible role as a second messenger in the process of neuronal differentiation of PC12 pheochromocytoma cells. Upon NGF treatment wildtype PC12 cells stop dividing and develop neurites. In contrast, a PC12 subclone (designated M-M17-26) expressing a dominant-negative mutant Ras protein keeps proliferating and fails to grow neurites after NGF treatment. Sodium nitroprusside (SNP), an NO donor, was found to induce the p53 protein and to inhibit proliferation of both PC12 and M-M17-26 cells, but failed to induce neuronal differentiation in these cell lines. Key signaling pathways (the ERK and Akt pathways) were also not affected by SNP treatment, and the phosphorylation of CREB transcription factor was only slightly stimulated. It is thus concluded from the results presented in this paper that NO is unable to activate signaling proteins acting downstream or independent of Ras that are required for neuronal differentiation.
Asunto(s)
Diferenciación Celular , Neuronas/metabolismo , Óxido Nítrico , Transducción de Señal , Proteínas ras , Animales , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Factor de Crecimiento Nervioso/farmacología , Neuronas/efectos de los fármacos , Óxido Nítrico/metabolismo , Óxido Nítrico/farmacología , Donantes de Óxido Nítrico/metabolismo , Donantes de Óxido Nítrico/farmacología , Nitroprusiato/farmacología , Células PC12 , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Transducción de Señal/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismo , Proteínas ras/genética , Proteínas ras/metabolismoRESUMEN
Obstructive sleep apnea syndrome is a common disorder in adults associated with several cardiovascular diseases and impaired quality of life. Chronic obstructive pulmonary disease is also a common clinical condition in middle-aged adults. The combination of these two conditions can eventuate a severe combined sleep-related breathing disorder. It is important to recognize coexisting sleep apnea in patients with chronic obstructive pulmonary disease in time and to treat it appropriately.
Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Apnea Obstructiva del Sueño/complicaciones , Adulto , Fatiga/etiología , Reflujo Gastroesofágico/etiología , Cefalea/etiología , Humanos , Trastornos de la Memoria/etiología , Persona de Mediana Edad , Polisomnografía , Respiración con Presión Positiva , Enfermedad Pulmonar Obstructiva Crónica/terapia , Calidad de Vida , Apnea Obstructiva del Sueño/terapia , SíndromeRESUMEN
INTRODUCTION: The presence of organ metastases is a major factor for unfavorable prognosis in lung adenocarcinoma (LADC). However, the influence of primary tumor location on metastatic sites and sequence has not been extensively analyzed. METHODS: We performed a multicenter cohort study, evaluating clinicopathological data of 1126 Caucasian LADC patients, focusing on the distinct location of primary tumors and metastatic sites during disease progression. RESULTS: Metastases to the lung (p < 0.001), pleura (p < 0.001) and adrenal glands (p < 0.001) occurred earlier during disease progression and central primary tumors were associated with early metastases (OR 1.43, p = 0.02). In secondary exploratory analysis we found that bone metastases were more frequent in patients with central tumors (OR 1.86, p = 0.017), whereas lung metastases in those with peripheral tumors (OR 1.35, p = 0.015). Central primary LADCs were associated with decreased median overall survival (vs. peripheral tumors, 10.2 vs. 22 months) both in univariate (HR 2.075, p = 0.001) and in multivariate (HR 1.558, p < 0.001) analyses and independent from stage and T factor. By subsequent analysis, we found that bone metastases tend to appear together with adrenal and liver metastases, and adrenal with skin, and pleural with pericardial metastases more frequently than expected if metastatic events occurred independently. CONCLUSION: This comprehensive large cohort analysis demonstrates metastatic site- and sequence-specific variations in patients with LADC. Central LADC is associated with early metastatic disease, bone involvement and, consequently, decreased survival.
Asunto(s)
Adenocarcinoma/patología , Neoplasias de las Glándulas Suprarrenales/secundario , Neoplasias Óseas/secundario , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/patología , Neoplasias Cutáneas/secundario , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , PronósticoRESUMEN
PURPOSE: To assess the within- and between-examiner reliability of corneal endothelial cell density (ECD) measurements with 2 noncontact specular microscopes: a video-based system (SeaEagle) and a photographic system (Noncon Robo). METHODS: In 57 eyes of 57 subjects, 47 healthy subjects and 10 patients with corneal disease, ECD was measured in the center and at 4 paracentral areas with the video-based system (SeaEagle) and in the center with a photographic system (Noncon Robo). For the between-examiner reliability, a second examiner measured the central ECD with the SeaEagle device in 12 healthy subjects. The video-based system was also used to evaluate the agreement between the automated and the manually corrected (semiautomated) modes of repeated measurements. RESULTS: For central ECD in all eyes, the test-retest reliability assessed by the intraclass correlation coefficient was 0.77, 0.99, and 0.91 for the automated SeaEagle, semiautomated SeaEagle, and Noncon Robo, respectively. Correlation was poor to good between the 3 measurement methods (range, 0.61-0.84). For between-examiner reliability, the upper (lower) limits of agreement were 200 (-384) and 149 (-92) cell/mm for the automated and semiautomated SeaEagle, respectively. CONCLUSIONS: The best reliability of repeated measurements was found for the semiautomated SeaEagle. However, the semiautomated method showed significantly higher ECD values than the Noncon Robo, and this difference was highly dependent on ECD. Thus, we suggest that these methods should not be used interchangeably. The fully automated mode may need a further refinement of the cell detection algorithm.