Abstracts of National PhD Students Days 2018 (NPSD’2018) 1st Edition, May 4-5, 2018, Université Ibn Zohr Agadir Maroc, Ouarzazate, Morocco

Abstracts of National PhD Students Days 2018 (NPSD’2018) 1st Edition, May 4-5, 2018, Université Ibn Zohr Agadir Maroc, Ouarzazate, Morocc

Estudo da suplementaçao crônica com óleo de peixe associada á administraçao de naproxeno, clenbuterol e insulina sobre a caquexia e crescimento tumoral em ratos

Orientador : Luiz Claudio FernandesDissertaçao (mestrado) - Universidade Federal do Paraná, Setor de Ciencias BiológicasResumo: Caquexia, associada ou não à anorexia, é uma síndrome frequentemente presente em indivíduos com câncer, caracterizada por intenso catabolismo periférico, levando à debilidade do organismo e prejudicando ou mesmo impossibilitando intervenções terapêuticas mais agressivas contra o câncer. Os mecanismos que induzem o estabelecimento da caquexia ainda não estão totalmente claros, mas as alterações metabólicas provocadas pela presença do tumor e resposta imunológica inadequada por parte do hospedeiro parecem estar envolvidos. Este estudo investigou o efeito da suplementação com óleo de peixe ao longo da vida, associada ou não à intervenções farmacológicas, sobre o crescimento tumoral e caquexia. Ratas Wistar foram suplementadas com óleo de peixe (poliinsaturado) ou óleo de côco (saturado), dose de 1g/Kg de peso corpóreo, desde o desmame (21 dias) até a fase adulta, incluindo períodos de gravidez e amamentação. A prole masculina gerada por estas ratas foi submetida ao mesmo protocolo. Ao completarem 90 dias, estes ratos foram inoculados com suspensão de células do tumor de Walker 256 (2 x 10 7 céls/mL), e ratos controle foram inoculados com solução salina. Quatro dias depois, iniciou-se tratamento com naproxeno, naproxeno + clenbuterol, ou naproxeno + clenbuterol + insulina. Quatorze dias após a inoculação, os animais foram sacrificados. Tumor, coração e baço foram removidos e pesados. Fígado, músculo sóleo e a porção branca do músculo gastrocnêmio foram retirados para mensuração do conteúdo de glicogênio. O sangue foi coletado para análises bioquímicas. Os grupos portadores de tumor sem suplementação e suplementado com óleo de côco não apresentaram diferença estatística entre si em nenhum dos parâmetros analisados. Entretanto, estes dois grupos tiveram pesos tumorais e concentrações séricas de lactato e triacilgliceróis significativamente maiores (p<0,05), e quantidade de glicogênio, concentrações séricas de colesterol-HDL, insulina, glicose significativamente menores (p<0,05) quando comparados aos demais grupos. Nenhuma suplementação ou tratamento provocou alterações nas concentrações séricas de colesterol e lipídios totais, e no peso do coração quando comparados aos grupos sem tumor. Quanto ao peso do baço, todos os grupos portadores de tumor apresentaram valores maiores quando comparados aos grupos sem tumor, porém não apresentaram diferença estatística quando comparados entre si. A suplementação com óleo de peixe e o tratamento com naproxeno, naproxeno + Clenbuterol, e naproxeno + Clenbuterol + insulina, apresentaram resultados semelhantes entre si e quando comparados aos grupos sem tumor. Nossos resultados sugerem que os ácidos graxos poliinsaturados w-3, presentes no óleo de peixe, e os fármacos utilizados, interferem no crescimento tumoral, reduzindo-o, e revertem o quadro caquético, sem provocar efeitos colaterais indesejáveis, melhorando a qualidade de vida dos pacientes e possibilitando intervenções mais agressivas contra o câncer.Abstract: Cachexia is a syndrome characterized by anorexia and intense peripheral catabolism, frequently observed in cancer patients. This syndrome hinder and, sometimes, make impossible aggressive therapeutic interventions, such as chemotherapy. The mechanisms that induce appearance of the cachexia are not fully clear yet, although metabolic alterations tumor-induced and inadequate immune response of host certainly are involved. This research investigate the effect of fish oil supplementation, along the life, associated or not with pharmacologic approaches, on the tumor growth and cachexia. Females Wistar rats were supplemented with either fish oil (polyunsaturated) or coconut oil (saturated), since wean until adult phase. The generated male offspring were submitted to the same protocol. When these rats were 90 days-old, they and others non-supplemented used as control, were inoculated with a suspension of Walker 256 tumor cells (2 x 10 7 cells/mL). After 4 days, initiated the pharmacologic approaches with naproxen, naproxen +clenbuterol, or naproxen + clenbuterol + insulin. In 14th day after inoculation, the rats were sacrificed. Tumor, heart and spleen were excised and weighed. Liver, soleus muscle and white portion of gastrocnemius muscle were removed to glycogen content measurement. Blood were collected to biochemistry analysis. The non-supplemented and coconut oil supplemented tumor-bearing rats didn't show statistic difference among themselves in any analyzed measurements; however, these two groups presented tumor weights and lactate and triacylglycerol blood levels significantly higher (p<0,05), and hepatic and muscle glycogen content and cholesterol- HDL, insulin and glucose blood levels significantly lower (p<0,05) as compared to all others groups. Neither supplementation nor treatment promoted alterations in total lipids and cholesterol blood levels and heart weight as compared to non-tumor groups. All tumor-bearing groups presented spleen weight significantly higher (p<0,05) as compared to non-tumor groups, however, didn't present statistic difference as compared among themselves. The fish oil supplementation and the treatment with naproxen, naproxen + clenbuterol, or naproxen + clenbuterol + insulin, showed similar results among themselves and as compared to the non-tumor rats in all analyzed ix measurements, except spleen weight, cited above. Our results suggest that polyunsaturated fatty acids w-3, present in fish oil, and the pharmacos used reduce tumor growth, revert cachexia and don't promote side effects undesirable, improving the patients' life quality and making possible more aggressive interventions against cancer

Exponential Stabilization of an Overhead Crane Model

Abstract A problem of exponential stabilization of an overhead crane model represented by a PDE is considered. For any r &gt; 0, the exponential stability at the desired decay rate r is solved in semigroup setting by a collocated-type stabiliser of a target system combined with a term involving the solution of an appropriate PDE. This work is based on paper

The effect of growth on the correlation between the spinal and rib cage deformity: implications on idiopathic scoliosis pathogenesis

<p>Abstract</p> <p>Background</p> <p>Numerous studies have attempted to quantify the correlation between the surface deformity and the Cobb angle without considering growth as an important factor that may influence this correlation. In our series, we noticed that in some younger referred children from the school-screening program there is a discrepancy between the thoracic scoliometer readings and the morphology of their spine. Namely there is a rib hump but no spinal curve and consequently no Cobb angle reading in radiographs, discrepancy which fades away in older children. Based on this observation, we hypothesized that in scoliotics the correlation between the rib cage deformity and this of the spine is weak in younger children and vice versa.</p> <p>Methods</p> <p>Eighty three girls referred on the basis of their hump reading on the scoliometer, with a mean age of 13.4 years old (range 7–18), were included in the study. The spinal deformity was assessed by measuring the thoracic Cobb angle from the postero-anterior spinal radiographs. The rib cage deformity was quantified by measuring the rib-index at the apex of the thoracic curve from the lateral spinal radiographs. The rib-index is defined as the ratio between the distance of the posterior margin of the vertebral body and the most extended point of the most projecting rib contour, divided by the distance between the posterior margin of the same vertebral body and the most protruding point of the least projecting rib contour. Statistical analysis included linear regression models with and without the effect of the variable age. We divided our sample in two subgroups, namely the younger (7–13 years old) and the older (14–18 years old) than the mean age participants. A univariate linear regression analysis was performed for each age group in order to assess the effect of age on Cobb angle and rib index correlation.</p> <p>Results</p> <p>Twenty five per cent of patients with an ATI more than or equal 7 degrees had a spinal curve under 10 degrees or had a straight spine. Linear regressions between the dependent variable "Thoracic Cobb angle" with the independent variable "rib-index" without the effect of the variable "age" is not statistical significant. After sample split, the linear relationship is statistically significant in the age group 14–18 years old (p < 0.03).</p> <p>Conclusion</p> <p>Growth has a significant effect in the correlation between the thoracic and the spinal deformity in girls with idiopathic scoliosis. Therefore it should be taken into consideration when trying to assess the spinal deformity from surface measurements. The findings of the present study implicate the role of the thorax, as it shows that the rib cage deformity precedes the spinal deformity in the pathogenesis of idiopathic scoliosis.</p

JNK interacting protein 1 (JIP-1) protects LNCaP prostate cancer cells from growth arrest and apoptosis mediated by 12-0-tetradecanoylphorbol-13-acetate (TPA)

12-0-tetradecanoylphorbol-13-acetate (TPA) stimulates protein kinase C (PKC) which mediates apoptosis in androgen-sensitive LNCaP human prostate cancer cells. The downstream signals of PKC that mediate TPA-induced apoptosis in LNCaP cells are unclear. In this study, we found that TPA activates the c-Jun NH2-terminal kinase (JNK)/c-Jun/AP-1 pathway. To explore the possible role that the JNK/c-Jun/AP-1 signal pathway has on TPA-induced apoptosis in LNCaP cells, we stably transfected the scaffold protein, JNK interacting protein 1 (JIP-1), which binds to JNK inhibiting its ability to phosphorylate c-Jun. TPA (10(-9)-10(-7) mol l(-1)) caused phosphorylation of JNK in both wild-type and JIP-1-transfected (LNCaP-JIP-1) cells. It resulted in phosphorylation and upregulation of expression of c-Jun protein in the wild-type LNCaP cells, but not in the JIP-1-transfected LNCaP cells. In addition, upregulation of AP-1 reporter activity by TPA (10(-9) mol l(-1)) occurred in LNCaP cells but was abrogated in LNCaP-JIP-1 cells. Thus, TPA stimulated c-Jun through JNK, and JIP-1 effectively blocked JNK. TPA (10(-12)-10(-8) mol l(-1)) treatment of LNCaP cells caused their growth inhibition, cell cycle arrest, upregulation of p53 and p21waf1, and induction of apoptosis. All of these effects were significantly attenuated when LNCaP-JIP-1 cells were similarly treated with TPA. A previous study showed that c-Jun/AP-1 blocked androgen receptor (AR) signaling by inhibiting AR binding to AR response elements (AREs) of target genes including prostate-specific antigen (PSA). Therefore, we hypothesised that TPA would not be able to disrupt the AR signal pathway in LNCaP-JIP-1 cells. Contrary to expectation, TPA (10(-9)-10(-8) mol l(-1)) inhibited DHT-induced AREs reporter activity and decreased levels of PSA in the LNCaP-JIP-1 cells. Taken together, TPA, probably by stimulation of PKC, phosphorylates JNK, which phosphorylates and increases expression of c-Jun leading to AP-1 activity. Growth control of prostate cancer cells can be mediated through the JNK/c-Jun pathway, but androgen responsiveness of these cells can be independent of this pathway, suggesting that androgen independence in progressive prostate cancer may not occur through activation of this pathway

Transcriptional repression of the human collagenase-1 (MMP-1) gene in MDA231 breast cancer cells by all-trans-retinoic acid requires distal regions of the promoter

In the present study, we investigated the mechanisms controlling constitutive transcription of collagenase-1 and its repression by all-trans-retinoic acid (RA) in the highly invasive metastatic and oestrogen-receptor-negative breast cancer cell line MDA231. A combination of in vivo and in vitro experiments that include DNAase I hypersensitivity assays, transient transfection of collagenase-1 promoter constructs, and electrophoretic mobility shift assays implicate several PEA3 sites, binding sites for Ets-related transcription factors, in the constitutive expression of the human collagenase-1 promoter. Transient transfection of promoter constructs linked to the luciferase reporter, along with gel retardation assays, revealed that repression of collagenase-1 transcription by RA is not dependent on the proximal AP-1 site, but, rather, requires sequences located in distal regions of the promoter. Transcriptional analyses and electrophoretic mobility shift assays suggest that the PEA3 site located at –3108 bp facilitates, at least in part, the transcriptional repression of the human collagenase-1 gene in MDA231 cells. We conclude that collagenase-1 repression in MDA231 cells occurs by a novel regulatory pathway that does not depend on the proximal AP-1 site at –73 bp, but does depend on distal regions in the collagenase-1 promoter. © 1999 Cancer Research Campaig