RESUMO
Thyroid cancer is the most abundant tumor of the endocrine organs. Poorly differentiated thyroid cancer is still difficult to treat. Human cells exposed to long-term real (r-) and simulated (s-) microgravity (µg) revealed morphological alterations and changes in the expression profile of genes involved in several biological processes. The objective of this study was to examine the effects of short-term µg on poorly differentiated follicular thyroid cancer cells (FTC-133 cell line) resulting from 6 min of exposure to µg on a sounding rocket flight. As sounding rocket flights consist of several flight phases with different acceleration forces, rigorous control experiments are mandatory. Hypergravity (hyper-g) experiments were performed at 18g on a centrifuge in simulation of the rocket launch and s-µg was simulated by a random positioning machine (RPM). qPCR analyses of selected genes revealed no remarkable expression changes in controls as well as in hyper-g samples taken at the end of the first minute of launch. Using a centrifuge initiating 18g for 1 min, however, presented moderate gene expression changes, which were significant for COL1A1, VCL, CFL1, PTK2, IL6, CXCL8 and MMP14. We also identified a network of mutual interactions of the investigated genes and proteins by employing in-silico analyses. Lastly, µg-samples indicated that microgravity is a stronger regulator of gene expression than hyper-g.
Assuntos
Hipergravidade , Voo Espacial , Neoplasias da Glândula Tireoide/patologia , Ausência de Peso , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Proteínas de Membrana/metabolismo , Neoplasias da Glândula Tireoide/genéticaRESUMO
Human follicular thyroid cancer cells (FTC-133) were sent to space via a sounding rocket during the TEXUS-53 mission to determine the impact of short-term microgravity on these cells. To enable cell culture and fixation in real microgravity, an automated experiment container (EC) was constructed. In order to ensure safe cell culture, cell-chambers consisting of polycarbonate (PC) material were used. They were highly biocompatible as proved by measuring cell survival using Annexin V flow cytometry. In the follow-up experiment, FTC-133 cells were sent to space via a sounding rocket and were fixed before and after the microgravity (µg) phase with RNAlater. In addition, cells were tested for reactions on hypergravity (hyper-g) as much as 18 g to determine whether worst case acceleration during launch can have an influence on the cells. We investigated genes belonging to biological processes such as cytoskeleton, cell adhesion, tumor growth, angiogenesis and apoptosis. Pathway analyses revealed central functions of VEGFA and EGF. EGF upregulates aspartate beta-hydroxylase (ASPH) which is influencing CASP3. Hyper-g induced a significant up-regulation of TUBB1, VIM, RDX, CAV1, VEGFA and BCL2. FTC-133 cells grown in an automated EC exposed to µg revealed moderate gene expression changes indicating their survival in orbit.
Assuntos
Expressão Gênica , Hipergravidade , Ausência de Peso , Materiais Biocompatíveis/química , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Linhagem Celular Tumoral , Citoesqueleto/genética , Regulação para Baixo , Fator de Crescimento Epidérmico/metabolismo , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Voo Espacial , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Regulação para Cima/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
RATIONALE AND OBJECTIVES: The aim of this study was to assess splenic perfusion in patients with spleen involvement in malignant hematologic diseases and liver cirrhosis and in controls without hepatosplenic disease using volume perfusion computed tomography. MATERIALS AND METHODS: Between October 2009 and December 2011, 14 hematologic patients with known spleen involvement were recruited. An additional 17 consecutive patients without known splenic or liver disease were enrolled as controls, as well as 29 patients with liver cirrhosis and portal hypertension. A 40-second volume perfusion computed tomographic scan of the upper abdomen was performed. Analysis included measurement of splenic volume, blood flow (BF), blood volume (BV), K(trans), and mean transit time (MTT). RESULTS: In lymphoma patients, mean splenic volume and perfusion parameters were as follows: splenic volume, 1125.34 mL; BF, 61.24 mL/100 mL/min; BV, 16.53 mL/100 mL; K(trans), 37.00 mL/100 mL/min; and MTT, 12.42 seconds. All perfusion values of patients with lymphoma and cirrhosis differed significantly, except for BV, compared to controls. For patients with lymphoma, significant correlations were found between splenic volume and BF (r = -0.683, P = .000), splenic volume and BV (r = -0.525, P = .002), and splenic volume and MTT (r = 0.543, P = .001). During treatment, significant correlations between the diameters of nodular lymphoma target lesions, splenic volume, and the perfusion parameters were present for splenic volume (r = 0.601, P = .002), BF (r = -0.777, P = .000) and BV (r = -0.500, P = .011). CONCLUSIONS: Volume perfusion computed tomography represents a novel tool for the assessment of splenic perfusion. Preliminary results in patients with spleen involvement reveal lower perfusion values compared to controls or patients with cirrhosis. Therefore, this technique might provide additional information in clinical routine.