Cox-2 e sua associação com fatores prognósticos e resposta à quimioterapia primária em pacientes com câncer de mama

OBJETIVO: Avaliar em pacientes com câncer de mama a expressão imunoistoquímica da cox-2 antes da quimioterapia primária com 5-fluorouracil, epirrubicina e ciclofosfamida (FEC) e a associação desta com tamanho inicial do tumor, estado linfonodal, receptores hormonais, expressão da Her-2 e com a resposta clínica e anatomopatológica. MÉTODOS: Estudo retrospectivo com 41 mulheres portadoras do diagnóstico histopatológico de carcinoma ductal de mama. Foram submetidas à quimioterapia primária com esquema FEC (5-fluorouracil, epirrubicina e ciclofosfamida) na dosagem de 500mg/m2, 75mg/m2 e 500 mg/m2, respectivamente. Os critérios de inclusão foram intervalo etário entre 30 e 70 anos, estadiamento II a IIIA, após comprovação da ausência de metástase, tumor primário de mama, único e unilateral, tipo histológico ductal invasivo e ausência de cardiopatia e gestação. Para avaliação da expressão da proteína Her 2 neuutilizaram-se anticorpos monoclonais de coelho. Para visibilizar a expressão da proteína cox-2 utilizaram-se anticorpos policlonais obtidos do soro de cabras. A avaliação da resposta clínica ao tratamento foi realizada por exame físico mensurando-se o maior eixo tumoral por paquímetro. As medidas foram realizadas à admissão e após os ciclos de quimioterapia primária. Após três sessões quimioterápicas com intervalos de 21 dias realizou-se o procedimento cirúrgico. Adotaram-se os critérios do RECIST. Após a operação foi avaliada a resposta anatomopatológica local, sendo considerada completa quando da ausência de neoplasia invasiva e do componente in situ. Na avaliação imumoistoquímica para os receptores de estrogênio utilizaram-se estrogen receptor NCL-ER6F11 e para progesterona, progesterone receptor, NCL-PGR-312 considerando positiva quando da coloração em 10% ou mais das células tumorais. RESULTADOS: A distribuição segundo estadiamento clínico UICC verificaram-se seis no estádio IIA (14,6%), 22 no estádio IIB (53,6%) e 13 estádio IIIA (31,8%). A avaliação clínica inicial do maior eixo tumoral variou de 2,5 a 15 cm e mediana de 5 cm. Foram identificadas 14 pacientes (34,1%) com estado linfonodal negativo e 27 positivo (65,9%). Observou-se que 19 (46,3%) apresentavam-se no menacme e 22 (53,6%) na menopausa. CONCLUSÃO: Houve associação da expressão da cox-2 à fatores de pior prognóstico no câncer de mama como estado linfonodal positivo, receptores hormonais negativos e expressão da Her-2.

Effect of medroxy-progesterone acetate on follicular growth and endometrial cycloxygenase-2 (COX-2) expression during the bovine estrous cycle

The objective of this study was to evaluate the effect of medroxy-progesterone acetate (MAP) with or without estradiol benzoate (EB) on follicular growth during the estrous cycle in cattle. In the first experiment, Hereford cows were synchronized with a synthetic analogue of PGF2 alpha and were treated with two different doses of MAP (250 or 500 mg) with or without EB for 7 days starting on day 8 of the estrous cycle. Follicular growth was inhibited (P<0.05) in all cows except controls and those receiving 250mg MAP without EB. Seventy-five percent of the animals (15/20) showed estrus on days 21 and 22 of the cycle rather than at MAP withdrawal, demonstrating that these treatments did not induce estrus. To determine whether the EB treatment altered endometrial sensitivity to oxytocin and thus the luteolytic cascade, multiparous pre-synchronized cows received 5 mg of EB followed 6 hours later with 50 IU of oxytocin (OT; n=9). Eight hours after EB injection, endometrial fragments were collected from the cows on days 4, 13 and 17 of the estrous cycle and COX-2 gene expression was measured by PCR. EB increased COX-2 mRNA levels only on day 17 of the estrous cycle (P<0.05). In conclusion, MAP alone or associated with EB is able to suppress bovine follicular growth. However, EB in the presence of MAP is not efficient to induce luteolysis in cows when injected on day 8 of the estrous cycle.

Korkokäyrän mallintaminen: tarkastelussa Cox-Ingersoll-Ross -malli

Korot ovat erittäin tärkeässä osassa kaikessa taloudellisessa toiminnassa ja tästä syystä niiden kehitystä seurataan mielenkiinnolla. Yksi keino korkojen kehityksen tutkimiseen on rahoitusmarkkinoilla havaittavan korkokäyrän tarkastelu. Tämän tutkielman tarkoituksena on tarkastella Cox-Ingersoll-Ross-mallin soveltuvuutta korkokäyrän empiriseen mallintamiseen. Tässä tutkielmassa Cox-Ingersoll-Ross-malli estimoidaan pienimmän neliösumman – ja suurimman uskottavuuden –menetelmillä. Tutkimuksen datana käytetään 3 kuukauden euribor-korkojen ja Saksan valtion 3 kuukauden mittaisen joukkolainan päivätason tuottoja kolmelta eri vuoden mittaiselta periodilta. Mallin avulla estimoituja korkokäyriä verrataan samojen periodien lopussa rahoitusmarkkinoilla realisoituneisiin korkokäyriin. Estimoinnin tulosten perusteella Cox-Ingersoll- Ross-malli ei sovi varauksitta korkokäyrän mallintamiseen. Pienimmän neliösumman –menetelmän diagnostisista tarkastuksista käy ilmi, että menetelmä ei ole sopiva mallin estimoimiseen. Suurimman uskottavuuden –estimoinnin avulla estimoidut korkokäyrät eroavat kaikissa paitsi yhdessä tapauksessa melko selvästi realisoituneista korkokäyristä. Tutkielman tuloksissa on selviä yhtymäkohtia aiempien empiristen tutkimusten tuloksiin. Varsinkin mallin odotusarvohakuisuutta (mean reversion) kuvaavan parametrin estimoinnissa ilmenee epävarmuutta, mikä vaikuttaa koko mallin toimintaan. Sama tulos ilmenee myös aiemmista tutkimuksista, osassa jopa kyseenalaistetaan koko ilmiön olemassaolo. Tutkielman tuloksista voidaan päätellä, että yhden muuttujan Cox-Ingersoll-Ross-malli ei varauksitta sovellu korkokäyrän empiriseen mallintamiseen. Todennäköisiä syitä tähän ovat mallin tekemät epärealistiset taustaoletukset sekä se, että tarkasteluperiodien aikana Eurooppa kärsi velkakriisistä, mikä kevensi Euroopan keskuspankin rahapolitiikkaa ja alensi korkotasoa. Tämä seikka vaikuttaa eri periodien tulosten vertailukelpoisuuteen. Tutkielman johtopäätöksenä on, että yhden muuttujan mallien sijaan korkokäyrän mallintamisessa tulisi keskittyä 3 muuttujan malleihin. Tällöin jokaiselle korkokäyrän elementille: taso, kulmakerroin ja konveksisuus saataisiin oma muuttujansa. Tämä helpottaisi myös korkokäyrän volatiliteetin mallintamisessa, mikä osoittautuu ongelmalliseksi vain yhtä muuttujaa käytettäessä.

Cellular and molecular studies of the effects of a selective COX-2 inhibitor celecoxib in the cardiac cell line H9c2 and their correlation with death mechanisms

Cardiovascular disease is one of the leading causes of death worldwide, and evidence indicates a correlation between the inflammatory process and cardiac dysfunction. Selective inhibitors of cyclooxygenase-2 (COX-2) enzyme are not recommended for long-term use because of potentially severe side effects to the heart. Considering this and the frequent prescribing of commercial celecoxib, the present study analyzed cellular and molecular effects of 1 and 10 µM celecoxib in a cell culture model. After a 24-h incubation, celecoxib reduced cell viability in a dose-dependent manner as also demonstrated in MTT assays. Furthermore, reverse transcription-polymerase chain reaction analysis showed that the drug modulated the expression level of genes related to death pathways, and Western blot analyses demonstrated a modulatory effect of the drug on COX-2 protein levels in cardiac cells. In addition, the results demonstrated a downregulation of prostaglandin E2 production by the cardiac cells incubated with celecoxib, in a dose-specific manner. These results are consistent with the decrease in cell viability and the presence of necrotic processes shown by Fourier transform infrared analysis, suggesting a direct correlation of prostanoids in cellular homeostasis and survival.

Possible roles of COX-1 in learning and memory impairment induced by traumatic brain injury in mice

People who suffer from traumatic brain injury (TBI) often experience cognitive deficits in spatial reference and working memory. The possible roles of cyclooxygenase-1 (COX-1) in learning and memory impairment in mice with TBI are far from well known. Adult mice subjected to TBI were treated with the COX-1 selective inhibitor SC560. Performance in the open field and on the beam walk was then used to assess motor and behavioral function 1, 3, 7, 14, and 21 days following injury. Acquisition of spatial learning and memory retention was assessed using the Morris water maze on day 15 post-TBI. The expressions of COX-1, prostaglandin E2 (PGE2), interleukin (IL)-6, brain-derived neurotrophic factor (BDNF), platelet-derived growth factor BB (PDGF-BB), synapsin-I, and synaptophysin were detected in TBI mice. Administration of SC560 improved performance of beam walk tasks as well as spatial learning and memory after TBI. SC560 also reduced expressions of inflammatory markers IL-6 and PGE2, and reversed the expressions of COX-1, BDNF, PDGF-BB, synapsin-I, and synaptophysin in TBI mice. The present findings demonstrated that COX-1 might play an important role in cognitive deficits after TBI and that selective COX-1 inhibition should be further investigated as a potential therapeutic approach for TBI.

[James Middleton] Cox, gouverneur de l'Ohio : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58595

Modèle des 2 temples de Bahai qui seront élevés à Chicago et New York et qui seront des temples de prière pour toutes les religions : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 59709

Boulevard du Dayton News (Ohio), propriété de M. [le sénateur James] Cox [angle de S. Ludlow St. et W. 4th St. à Dayton, Ohio] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 60120

M. et Mme Cox [le candidat à la présidence des États-Unis en 1920 accompagné de son épouse] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 59979

L'Organisation de la famille, selon le vrai modèle signalé par l'histoire de toutes les races et de tous les temps, par M. F. Le Play,... avec trois appendices, par MM. É. Cheysson, F. Le Play et C. Jannet. 2e édition...

Comprend : La Famille-souche du Lavedan