RESUMEN
Published data indicate the involvement of eosinophil granulocytes and eosinophil cationic protein (ECP) in tumor defense. The aim of this study was to analyze serum ECP concentrations in patients with differentiated thyroid cancer (DTC) before, 3 days and 7 days after radioactive iodine (131-I) therapy. Association of ECP concentrations with histological type of tumor, stage of disease and/or levels of selected T-helper 2 (Th2) cytokines was examined. The study population included 17 DTC patients and 10 control subjects. ECP was measured by fluoroimmunoassay (FIA). Th2 (cytokines interleukin 4 (IL-4), interleukin 5 (IL-5), and interleukin 13 (IL-13)) were determined by enzyme-linked immunosorbent assays (ELISA). We found that ECP values in DTC patients before radioactive iodine therapy were approximately two-fold higher than in the controls, but the difference was statistically significant only if the patients with DTC and associated Hashimoto thyroiditis (HT) were included. There was no correlation between the serum concentrations of IL-5 and ECP. Radioactive iodine therapy led to a decrease in serum ECP level which did not follow the decline in serum protein levels. Additional studies are needed to determine the significance of these findings.
Asunto(s)
Regulación hacia Abajo/efectos de la radiación , Proteína Catiónica del Eosinófilo/sangre , Radioisótopos de Yodo/uso terapéutico , Radiofármacos/uso terapéutico , Células Th2/efectos de la radiación , Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/terapia , Adulto , Anciano , Carcinoma Papilar/sangre , Carcinoma Papilar/patología , Carcinoma Papilar/fisiopatología , Carcinoma Papilar/terapia , Carcinoma Papilar Folicular/sangre , Carcinoma Papilar Folicular/patología , Carcinoma Papilar Folicular/fisiopatología , Carcinoma Papilar Folicular/terapia , Diferenciación Celular , Terapia Combinada , Citocinas/sangre , Citocinas/metabolismo , Proteína Catiónica del Eosinófilo/metabolismo , Femenino , Enfermedad de Hashimoto/etiología , Enfermedad de Hashimoto/inmunología , Enfermedad de Hashimoto/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Reproducibilidad de los Resultados , Células Th2/inmunología , Células Th2/metabolismo , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/fisiopatología , Tiroidectomía , Adulto JovenRESUMEN
Coccid-derived natural food colorants contain active ingredients that potentiate inhibition of tissue proteolysis mediated by activation of plasma hyaluronan-binding protein (PHBP). In the present study, we examined the effect of lac color (LC) and cochineal extract (CE), representative coccid-derived colorants containing laccaic acid and carminic acid as active ingredients, in an intracapsular invasion model of experimental thyroid cancers using rats. One week after initiation with N-bis(hydroxypropyl)nitrosamine, male F344/NSIc rats were fed a powdered diet containing 5.0% LC or 3.0% CE during promotion with 0.15% sulfadimethoxine (SDM) in the drinking water for 13 weeks. Capsular invasive carcinomas (CICs) and lung metastases were decreased by LC treatment and accompanied by transcript downregulation on angiogenesis and PHBP-related tissue proteolysis in CICs. In contrast, CE upregulated angiogenesis-related genes in CICs. PHBP was expressed in capsular macrophages and thyroid proliferative lesions with increased intensity in CICs, and LC decreased PHBP-expressing CICs. The size of CICs and their proliferation activity, however, were unchanged compared with those treated with SDM alone. Suppression of cancer by invasion by LC was more evident after an eight-week treatment, exhibiting a profound decrease in tenascin-C-positive early invasive foci and marked reductions in capsular inflammation and fibrosis. These results suggest that LC and CE exerted dissimilar effects on CIC development, the former suppressing the initial step of neoplastic cell invasion into the capsule by targeting PHBP activity of macrophages and neoplastic cells on tissue proteolysis involving inflammatory responses and angiogenesis, and the latter promoting angiogenesis of developed CICs at later stages.
Asunto(s)
Compuestos Azo/uso terapéutico , Carcinoma Papilar Folicular/tratamiento farmacológico , Carcinoma Papilar Folicular/fisiopatología , Receptores de Hialuranos/sangre , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/fisiopatología , Animales , Carcinoma Papilar Folicular/inducido químicamente , Proliferación Celular , Modelos Animales de Enfermedad , Masculino , Naftalenosulfonatos , Fosfohidrolasa PTEN/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Endogámicas F344 , Transducción de Señal/fisiología , Sulfadimetoxina/efectos adversos , Hormonas Tiroideas/sangre , Neoplasias de la Tiroides/inducido químicamenteRESUMEN
The family of serine/threonine kinases B/Akt (hereafter Akt) represents a central node in signalling pathways downstream of growth factors, cytokines, and other cellular stimuli. In mammalian cells the Akt family comprises three highly homologous members -known as Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma- that regulate several processes including cell proliferation and survival, growth and response to nutrient availability, migration, tissue invasion and angiogenesis. Aberrant activation of Akt is involved in a variety of human cancers including those arising in the thyroid gland. Here, we review the contribution of Akt-dependent pathway in the proliferation of normal thyrocytes, the different pathogenic mechanisms underlying aberrant Akt signalling in thyroid malignancies as well as the relative roles of Akt substrates that most likely contribute to the onset and/or progression of thyroid cancer. Finally, we discuss the current therapeutic strategies targeting the components of the PI3K/Akt pathway in the context of thyroid malignancy.
Asunto(s)
Carcinoma/fisiopatología , Proteínas Proto-Oncogénicas c-akt/fisiología , Neoplasias de la Tiroides/fisiopatología , Apoptosis/fisiología , Carcinoma Papilar Folicular/fisiopatología , Proliferación Celular/efectos de los fármacos , Humanos , Fosfohidrolasa PTEN/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/efectos de los fármacos , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Proteínas Tirosina Quinasas Receptoras/metabolismo , Transducción de Señal/fisiología , Serina-Treonina Quinasas TOR/fisiología , Neoplasias de la Tiroides/tratamiento farmacológico , Proteínas ras/metabolismoAsunto(s)
Carcinoma Papilar Folicular , Neoplasias de la Tiroides , Carcinoma Papilar Folicular/clasificación , Carcinoma Papilar Folicular/patología , Carcinoma Papilar Folicular/fisiopatología , Humanos , Neoplasias de la Tiroides/clasificación , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/fisiopatologíaRESUMEN
Transcription factors play an essential role in regulating both cell proliferation and programmed cell death. Proliferation and apoptosis-related transcription factor immunoexpression patterns were concomitantly investigated in tissue sections of normal thyroid, goiters, follicular adenomas and well-differentiated papillary and follicular carcinomas using antibodies against prothymosin alpha, E2F-1, p53, Bcl2, and Bax proteins. Proliferation and apoptotic indices were determined by Ki-67 immunoreactivity and the terminal deoxynucleotidyl transferase-mediated deoxy uridine triphosphate nick-end labeling technique, respectively. Prothymosin alpha and E2F-1 immunoexpression levels were found to be significantly elevated in well-differentiated carcinomas compared to adenomas, goiters and normal tissues (P < 0.05). Both proteins were directly correlated with the proliferation index (P < 0.05). E2F-1 was additionally correlated with the apoptotic index (P < 0.05). The majority of cases were negative for p53 staining. Positive Bcl2 immunostaining was detected in all thyroid histotypes. None of the normal tissues showed Bax immunoreactivity, while positive accumulation differed significantly between hyperplastic and neoplastic histotypes. Direct correlations were observed between prothymosin alpha and Bcl2 as well as between E2F-1 and Bax immunoexpression (P < 0.05). These data demonstrate that prothymosin alpha and E2F-1 are strongly involved in the proliferation processes of thyroid neoplasias. Furthermore, prothymosin alpha may promote cell survival through the Bcl2 anti-apoptotic pathway, while E2F-1-induced apoptosis via p53-independent pathways may be associated with transcriptional activation of bax pro-apoptotic gene.