Tumor desmoide abdominal / Abdominal desmoid tumor

Los tumores desmoides son infrecuentes, presentan crecimiento localmente agresivo, no suelen dar metástasis pero con frecuencia desarrollan un crecimiento infiltrante que amenaza la vida y puede conducir a una gran morbi-mortalidad. Representan el 0.03% de todos los tumores. En base a la experiencia, los expertos recomiendan la administración de dosis altas de tamoxifeno y sulindac como tratamiento primario para los pacientes con tumores desmoides asociados a poliposis adenomatosa familiar (PAF). Sin embargo, el mejor enfoque después de la intervención quirúrgica para pacientes con tumores desmoides esporádicos, aún no se ha determinado (AU)

Desmoid tumors are infrequent, locally aggressive growth, do not usually metastasize but often develop an infiltrating growth that threatens life and can lead to great morbidity and mortality. They represent 0.03% of all tumors. Based on experience, experts recommend the administration of high doses of tamoxifen and sulindac as a primary treatment for patients with desmoid tumors associated with familial adenomatous polyposis (FAP). However, the best approach after surgical intervention for patients with sporadic desmoid tumors has yet to be determined (AU)

Prevalência de dor crônica e sua associação com a situação sociodemográfica e atividade física no lazer em idosos de Florianópolis, Santa Catarina: estudo de base populacional / Prevalence of chronic pain and its association with the sociodemographic situation and physical activity in leisure of elderly in Florianópolis, Santa Catarina: population-based study

OBJETIVO: Estimar a prevalência de dor crônica e sua associação com a situação socioeconômica, demográfica e atividade física no lazer em idosos. MÉTODOS: Este estudo é parte do inquérito epidemiológico e transversal de base populacional e domiciliar EpiFloripa Idoso 2009-2010 realizado com 1.705 idosos (≥ 60 anos), residentes em Florianópolis, Santa Catarina. A partir da resposta afirmativa de dor crônica, foram investigadas as associações com as variáveis obtidas por meio de entrevista estruturada. Realizou-se a estatística descritiva, incluindo cálculos de proporções e intervalos de confiança 95% (IC95%). Na análise bruta e ajustada, empregou-se regressão de Poisson, estimando-se as razões de prevalência, com intervalos de confiança de 95% e valores p ≤ 0,05. RESULTADOS: Dentre os idosos investigados, 29,3% (IC95% 26,5 - 32,2) relataram dor crônica. Na análise ajustada, observou-se que as variáveis sexo feminino, menor escolaridade e pior situação econômica ficaram associadas significativamente com maior prevalência de dor crônica; ser fisicamente ativo no lazer ficou associado significativamente com menor prevalência do desfecho. CONCLUSÕES: Percebe-se que a dor crônica é um agravo que acomete considerável parcela de idosos, havendo desigualdades sociais na sua frequência e sendo beneficamente afetada pela atividade física no lazer. É necessário que políticas públicas de saúde subsidiem programas multidisciplinares de controle da dor incluindo a prática regular de atividade física, voltada especificamente à promoção da saúde do idoso, evitando assim que a dor crônica comprometa a qualidade de vida desta população. .

OBJECTIVE: To estimate the prevalence of chronic pain and its association with socioeconomic and demographic status, and leisure physical activity in the elderly population. METHODS: This study is part of an epidemiological cross-sectional population-based household survey called EpiFloripa Elderly 2009-2010, which was conducted with 1,705 elderly individuals (≥ 60 years) residents of Florianópolis, Santa Catarina. From the positive response to chronic pain, the associations with the variables were investigated through a structured interview. Descriptive statistics were conducted, including ratio calculation and 95% confidence intervals. In crude and adjusted analysis, Poisson regression was utilized, estimating prevalence ratios, with 95% confidence intervals and ≤ 0.05 p-values. RESULTS: Among the subjects, 29.3% (IC95% 26.5 - 32.2) reported chronic pain. Adjusted analysis showed that being female, having less years of schooling, and being in worse economic situation were significantly associated with a higher prevalence of chronic pain. Being physically active during leisure time was significantly associated with lower prevalence of the outcome. CONCLUSIONS: Therefore, it is clear that chronic pain affects a considerable amount of elderly individuals. Social inequalities are a harmful influence in these individuals' quality of life, inasmuch as those inequalities increase the frequency with which chronic pain afflicts them. At the same time, physical activity during leisure time decreases chronic pain frequency. It is fundamental that public health policies subsidize multidisciplinary pain management programs, which should include health targeted physical activity for the elderly, thus preventing the decrease in quality of life that chronic pain brings to this population. .

Reduction of aflatoxin B1 during tortilla production and identification of degradation by-products by direct-injection electrospray mass spectrometry (DIESI-MS) / Reducción de la aflatoxina B1 durante la producción de tortilla y la identificación de los productos de degradación por espectrometría de masas con ionización por electrospray de inyección-directa (DIESI-MS)

Objective. To determine the effect of pH, and exposure time over the inactivation of aflatoxin B1 (AFB1) during the tortilla making process as well as the degradative molecules generated. Materials and methods. Inactivation of AFB1 in maize-dough with alkaline pH and in alkaline methanolic solutions was determined by HPLC. Kinetics of time exposure of AFB1 in methanolic solution and the degradative products were analyzed by direct injection electrospray mass spectometry (DIESI-MS). Results. The alkaline pH of the maize-dough after nixtamalización between 10.2, and 30-40 minutes of resting at room temperature allows the 100% reduction of AFB1. DIESI-MS analysis of the extracts indicated the presence of two degradation molecules from AFB1. Conclusion. The alkaline pH of maize-dough and resting time are the principal factors involved in diminishing AFB1 levels in tortillas. A procedure to the tortilla making process is proposed, which allows the reduction of remnant AFB1, avoiding the accumulative effect over consumers.

Objetivo. Determinar el efecto del pH alcalino de la masa de maíz y el tiempo de exposición sobre la aflatoxina B1 (AFB1) durante la producción de tortillas e identificar los posibles productos de degradación mediante DIESI-MS. Material y métodos. La inactivación de la AFB1 a pH alcalino y diferentes tiempos de exposición en masa nixtamalizada y en soluciones metanólicas fueron determinadas por HPLC. La cinética de degradación de AFB1, y los productos de degradación en soluciones metanólicas se determinaron por DIESI-MS. Resultados. El pH alcalino de la masa y 30 a 40 minutos de reposo redujeron en 100% la AFB1 adicionada. Se identificaron dos moléculas de degradación. Conclusión. Los principales factores involucrados en la disminución de la AFB1 durante la producción de tortillas son la hidrólisis alcalina y el tiempo de reposo. Se propone un procedimiento para la producción de tortilla que reducirá la AFB1 residual evitando el efecto acumulativo en los consumidores.

Synergistic Effect of Sulindac and Simvastatin on Apoptosis in Lung Cancer A549 Cells through AKT-Dependent Downregulation of Survivin / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Non-steroidal anti-inflammatory drugs (NSAIDs) and statins are potential chemopreventive or chemotherapeutic agents. The mechanism underlying the deregulation of survivin by NSAIDs and statins in human non-small cell lung cancer cells has not been elucidated. In this study, we investigated the synergistic interaction of sulindac and simvastatin in lung cancer A549 cells. MATERIALS AND METHODS: Cell viability was measured by an MTT assay, while the expression of apoptotic markers, AKT, and survivin in response to sulindac and simvastatin was examined by Western blotting. DNA fragmentation by apoptosis was analyzed by flow cytometry in A549 cells. Reactive oxygen species (ROS) generation was measured by flow cytometry using H2DCFDA and MitoSOX Red, and the effects of pretreatment with N-acetylcysteine were tested. The effects of AKT on survivin expression in sulindac- and simvastatin-treated cells were assessed. Survivin was knocked down or overexpressed to determine its role in apoptosis induced by sulindac and simvastatin. RESULTS: Sulindac and simvastatin synergistically augmented apoptotic activity and intracellular ROS production in A549 cells. Inhibition of AKT by siRNA or LY294002 inhibited survivin, while AKT overexpression markedly increased survivin expression, even in the presence of sulindac and simvastatin. Moreover, survivin siRNA enhanced sulindac- and simvastatininduced apoptosis. In contrast, survivin upregulation protected against sulindac- and simvastatin-induced apoptosis. CONCLUSION: Combined treatment with sulindac and simvastatin augmented their apoptotic potential in lung cancer cells through AKT signaling-dependent downregulation of survivin. These results indicate that sulindac and simvastatin may be clinically promising therapies for the prevention of lung cancer.

Effect of sulindac on improving autistic behaviors in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To test the effect of sulindac on autistic behaviors in a rat model and explore the possible mechanisms.</p><p><b>METHODS</b>Autistic rat models were established by a single intraperitoneal injection of sodium valproate (VPA) at 12.5 days of pregnancy. The pregnant rats were treated with oral sulindac at a daily dose of 80 mg/kg until weaning of the newborn rats (23 days after being born), which were divided into control, VPA treatment, sulindac treatment, and VPA+ sulindac treatment groups. The social interaction and neuroethology of the newborn rats were evaluated at 35 days, and the levels of β-catenin and phosphorylated Gsk3β in the brain tissues were investigated by Western blotting.</p><p><b>RESULTS</b>Compared with the control rats, the rats treated with VPA showed lower social interaction, longer moving time in central area, and reduced standing times. Treatment with sulindac alone resulted in no obvious changes in the social interaction or neuroethology of the newborn rats, but sulindac treatment corrected VPA-induced autistic-like behaviors. Sulindac also attenuated VPA-triggered p-Gsk3β downregulation and β-catenin upregulation in the prefrontal lobe, seahorse and cerebellum.</p><p><b>CONCLUSION</b>Sulindac can improve the behaviors of autistic rats possibly by suppressing Wnt signaling pathway.</p>

Computerized Tomography Contrast Induced Nephropathy (CIN) among adult inpatients / Nefropatia induzida por contraste (NIC) em pacientes adultos internados submetidos à tomografia computadorizada por contraste

Introduction: Contrast induced nephropathy (CIN) is one of the complications of the use of intravascular contrast agents, being defined as a reduction of the glomerular filtration rate caused by the iodinated contrast. Most CIN data derive from the cardiovascular literature, which identified as the most consistent risk factors pre-existing chronic renal insufficiency and diabetes mellitus. However, these studies limit their conclusions to a more specific patient population. Computerized tomography as a cause of CIN has been studied less often. Objective: To report on the incidence of computerized tomography contrast induced nephropathy (CIN) in an inpatient population of a tertiary general hospital, identifying potentially avoidable risk factors. Methods: We performed a prospective cohort study with inpatients admitted at a tertiary hospital requiring contrast-induced CT. The primary outcome was the development of CIN, measure by the alteration of serum creatinine or glomerular filtration rate in 48 or 72 hours. Through clinical interview, we verified possible risk factors and preventive measures instituted by the medical team and their association with development of CIN. Results: Of a total of 410 patients, 35 (8.5%) developed CIN. There was a positive correlation between CIN and the presence of diabetes mellitus (OR = 2.15; 95%CI 1.35-4.06; p = 0.02), heart failure (OR = 2.23; 95%CI 1.18-8.8; p = 0.022), and renal failure (OR = 3.36; 95%CI 1.57- 7.17; p = 0.002) Conclusion: Incidence of CIN varies according to the population. Diabetes mellitus, heart failure and renal failure were independent risk factors for the development of CT-associated CIN. Further studies are needed to better understand and treat CT-associated CIN. .

Introdução: Nefropatia induzida por contraste (NIC) é consequência do uso de meios de contraste intravenoso, sendo definida como uma redução da taxa de filtração glomerular. A maioria dos dados de NIC são da literatura cardiovascular, que identificou como fatores de risco insuficiência renal crônica e diabetes. Entretanto, esses estudos limitam suas conclusões a uma população especifica de pacientes. Tomografia Computadorizada contrastada como causa de NIC foi menos estudada. Objetivo: Reportar incidência de NIC numa população de pacientes internados em hospital terciário submetidos à tomografia computadorizada com contraste, identificando possíveis fatores de risco evitáveis. Métodos: Realizamos um estudo de coorte prospectivo com pacientes internados em hospital terciário e que necessitaram de tomografia computadorizada com contraste. O desfecho primário foi desenvolvimento de NIC, verificado por meio da variação da creatinina sérica ou taxa de filtração glomerular em 48 ou 72 horas. Em entrevista clínica, verificamos possíveis fatores de risco, assim como medidas preventivas instituídas pela equipe médica e suas possíveis associações com desenvolvimento de NIC. Resultados: Do total de 410 pacientes, 35 (8,5%) desenvolveram NIC. Houve correlação positiva entre desenvolvimento de NIC e a presença de diabetes mellitus (OR = 2,15; 95%CI 1,35-4,06; p = 0,02), insuficiência cardíaca (OR = 2,23; 95%CI 1,18-8,8; p = 0,022), e insuficiência renal (OR = 3,36; 95%CI 1,57-7,17; p = 0,002). Conclusão: A incidência de NIC varia de acordo com a população. Diabetes, insuficiência cardíaca e insuficiência renal foram fatores de risco independentes para o desenvolvimento de NIC. Mais estudos são ...

Contexto social del debate sobre el control natal en Colombia en las décadas de 1960 y 1970: política, medicina y sociedad / The social context of the birth control debate in Colombia in the 1960s and 1970s: politics, medicine and society

El artículo busca presentar el contexto y aproximación preliminares necesarios para comprender y abordar el debate sobre el control natal en Colombia en las décadas de 1960 y 1970. Recoge las principales posturas en conflicto en dicho período, y los discursos y lógicas que permearon la llegada de los programas de planificación norteamericanos a América Latina como forma de control político de los movimientos revolucionarios.

The article seeks to present the necessary context and a preliminary approach to understanding and addressing the birth control debate in Colombia in the 1960s and 1970s. It covers the main conflicting positions during that period and the discourses and logics permeating the arrival of North American family planning programs to Latin America as a form of political control of revolutionary movements.

Effect of Super-Oxidized Water, Sodium Hypochlorite and EDTA on Dentin Microhardness

The present study aimed to evaluate the influence of the following irrigating solutions on the microhardness of root canal dentin: 2% sodium hypochlorite (2NaOCl), 5% sodium hypochlorite (5NaOCl), super-oxidized water (400 ppm Sterilox - Sx) and 17% EDTA (E). Eighty roots from bovine incisors were randomly divided into 8 groups (n=10): 2NaOCl, 5NaOCl, Sx, and 2NaOCl + E, 5NaOCl + E, Sx + E (associated with E as final irrigant for 5 min), E solely and distilled water (dH2O) as the negative control. Root canal preparation was performed by hand instruments, using one of the irrigation protocols for 30 min. Then, 5 mm of the cervical root third were cut out from each sample and subjected to the Vickers microhardness test, at two points, one at approximately 500-1000 µm from the root canal lumen (distance 1), and the other at approximately 500-1000 µm from the external root surface (distance 2). Data were analyzed by Wilcoxon and Kruskal-Wallis tests at 5% significance level. Microhardness values at distance 1 were significantly lower than those at distance 2 for all groups, except 5NaOCl and 5NaOCl + E groups (p>0.05). EDTA showed the lowest microhardness values. However, no statistically significant difference was detected among groups at distance 1 and EDTA was significantly different only from Sx at distance 2. In conclusion, all tested solutions showed lower microhardness at the most superficial root canal dentin layer compared to the one found near the external root surface, except 5NaOCl and 5NaOCl + E; EDTA promoted lower microhardness values in comparison to Sterilox at this site.

O presente estudo teve como objetivo avaliar a influência das seguintes soluções irrigadoras na microdureza da dentina do canal radicular: hipoclorito de sódio a 2% (NaOCl2), hipoclorito de sódio a 5% (NaOCl5), água superoxidada (Sterilox(r) 400 ppm - Sx) e EDTA a 17% (E). Oitenta raízes de incisivos bovinos foram divididas aleatoriamente em 8 grupos (n=10): NaOCl2, NaOCl5, Sx e NaOCl2 + E, NaOCl5 + E, Sx + E (associados ao E como irrigante final por 5 min), E isolado e água destilada (H2Od), como controle negativo. O preparo dos canais radiculares foi realizado com instrumentos manuais, usando um dos protocolos de irrigação por 30 min. A seguir, 5 mm do terço cervical de cada amostra foram cortados perpendicularmente e submetidos ao teste de microdureza de Vickers, em dois pontos, um aproximadamente 500-1000 µm da luz do canal radicular (distância 1), e o outro aproximadamente 500-1000 µm da superfície externa da raiz (distância 2). Os dados foram analisados pelos testes de Wilcoxon e Kruskal-Wallis com um nível de significância de 5%. Os valores de microdureza na distância 1 foram significativamente menores do que na distância 2 para todos os grupos, exceto NaOCl5 e NaOCl5 +E (p>0,05). O EDTA mostrou os menores valores de microdureza. No entanto, não foi detectada diferença estatisticamente significativa entre os grupos na distância 1 e o EDTA foi significativamente diferente apenas do Sx na distância 2. Pode-se concluir que todas as soluções testadas mostraram menor microdureza na camada de dentina mais superficial do canal radicular em comparação aos valores encontrados próximo à superfície radicular externa, exceto NaOCl5 e NaOCl5 + E; o EDTA promoveu menor microdureza em comparação ao Sterilox(r) neste ponto.

Use of medicinal plants by black women: ethnography study in a low-income community / Uso de las plantas medicinales por las mujeres negras: estudio etnográfico en una comunidad de bajos ingresos / Uso de plantas medicinais por mulheres negras: estudo etnográfico em uma comunidade de baixa renda

Objective To explore beliefs, values and practices related to the use of medicinal plants among low-income black families. Method The research method was ethnography and the participant observation process was done in a low-income community in the peripheral area of the City of São Paulo. Twenty black women were interviewed. Results Two cultural sub-themes, I do use medicines that I learned to make with my mother and with religious practitioners to care for diseases and Home medicines are to treat problems that are not serious, and the cultural theme I do use home medicines to treat simple diseases because I always have them at my disposal, they are free and I don’t need a medical prescription represent beliefs, values, and practices related to the use of medicinal plants among low-income black families. Conclusion The development of such practices, which can hide ethnic and social vulnerability, reveals the resilience of low-income black women in the process of confronting problems during the health-illness process. .

Objetivo Explorar las creencias, valores y prácticas sobre el uso de las plantas medicinales entre las familias negras de bajos ingresos. Método El método de investigación fue la etnografía y el proceso de observación participante fue desarrollado en una comunidad de bajos ingresos en las afueras de la Ciudad de São Paulo. Se entrevistó a veinte mujeres negras. Resultados Dos subtemas culturales Uso remedios que aprendí a hacer con mi madre y con los religiosos para cuidar de enfermedades y Remedios caseros se utilizan para resolver problemas que no son graves y el tema cultural Uso remedio casero para resolver enfermedades simples porque tengo todo lo que necesito, es gratuito y no necesita una receta médica simbolizam las prácticas de las mujeres. Conclusión Estas prácticas, que pueden estar enmascarando vulnerabilidades étnicas y sociales, ponen de manifiesto la resiliencia de las mujeres negras de bajos ingresos en el confrontamiento de los problemas del proceso salud-enfermedad. .

Objetivo Explorar crenças, valores e práticas relativas ao uso das plantas medicinais entre famílias negras de baixa renda. Método Pesquisa etnográfica cujo processo de observação participante foi desenvolvido em uma comunidade de baixa renda da periferia da Cidade de São Paulo. Vinte mulheres negras foram entrevistadas. Resultados Dois subtemas culturais, Uso remédios que aprendi a fazer com minha mãe e com os religiosos para cuidar das doenças e Remédios caseiros servem para resolver problemas que não são graves, e o tema cultural Uso remédio caseiro para resolver doenças simples, pois tenho sempre que preciso, é de graça e não precisa de receita médica representam as crenças, valores e práticas relativos ao uso das plantas medicinais entre famílias negras de baixa renda. Conclusão O desenvolvimento dessas práticas, que pode estar mascarando vulnerabilidades étnicas e sociais, revela a resiliência das mulheres negras de baixa renda no enfrentamento dos problemas que encontram no processo saúde-enfermidade. .

Regression of Colonic Adenomas After Treatment With Sulindac in Familial Adenomatous Polyposis: A Case With a 2-Year Follow-up Without a Prophylactic Colectomy

Familial adenomatous polyposis (FAP) is an autosomal dominant disorder characterized by hundreds of colorectal adenomatous polyps that progress to colorectal cancer. Management of patients with FAP is with a total colectomy. Chemopreventive strategies have been studied in FAP patients in an effort to delay the development of adenomas in the upper and the lower gastrointestinal tract and to prevent recurrence of adenomas in the retained rectum of patients after prophylactic surgery. Sulindac, a nonsteroidal anti-inflammatory drug, causes regression of colorectal adenomas in the retained rectal segment of FAP patients. However, evidence regarding long-term use of this therapy and its effect on the intact colon has been insufficient. We report a case in which the long-term use of sulindac was effective in reducing the size and the number of colonic polyps in patients with FAP without a prophylactic colectomy and polypectomy; we also present a review of the literature.

A Novel Germline Mutation in Exon 15 of the APC Gene in Attenuated Familial Adenomatous Polyposis: A Report of Two Cases

Attenuated familial adenomatous polyposis (AFAP) is a variant of familial adenomatous polyposis with fewer than one hundred colorectal polyps and a later age of onset of the cancer. Here, we report two cases of AFAP within family members. Each patient demonstrated the same novel germ line mutation in exon 15 of the adenomatous polyposis coli (APC) gene and was successfully managed with sulindac after refusal to perform colectomy: a 23-year-old man with incidentally diagnosed gastric adenoma and fundic gland polyps underwent colonoscopy, and fewer than 100 colorectal polyps were found; a 48-year-old woman who happened to be the mother of the 23-year-old man also showed fewer than 100 colorectal polyps on colonoscopy. Genetic analysis revealed a novel frameshift mutation in exon 15 of the APC gene. The deletion of adenine-guanine with the insertion of thymine in c.3833-3834 resulted in the formation of stop codon 1,287 in both patients. The patients were treated with sulindac due to their refusal to undergo colectomy. The annual follow-up upper endoscopy and colonoscopy in the following 2 years revealed significant regression of the colorectal polyps in both patients.

Genotoxicity of the cyclo-oxygenase-inhibitor sulindac sulfide in the filamentous fungus Aspergillus nidulans

Sulindac sulfide is a non-steroidal anti-inflammatory drug (NSAID) with chemopreventive effect on human cancer cells. Due to the involvement of the somatic recombination in the carcinogenic process, sulindac sulfide's recombinogenic potential was evaluated by the Homozygotization Index (HI) in the filamentous fungus Aspergillus nidulans. The drug's recombinogenic potential was evaluated by its capacity to induce homozygosis of recessive genes from heterozygous diploid cells. Sulindac sulfide at 175 and 350 æM concentrations induced mitotic recombination in A. nidulans diploid cells, with HI values for genetic markers higher than 2.0, and significantly different from control HI values. The recombinogenic effect of NSAID was related to the induction of DNA strand breaks and cell cycle alterations. Sulindac sulfide's carcinogenic potential was also discussed.

Sulfeto de sulindaco é um antiinflamatório não-esteroidal com efeitos quimiopreventivos em cânceres humanos. O presente estudo teve como objetivo avaliar o potencial recombinagênico do sulfeto de sulindaco em células diplóides de Aspergillus nidulans. O efeito recombinagênico da droga foi demonstrado através da homozigotização de genes recessivos, previamente presentes em heterozigose. Os valores de HI (índice de Homozigotização) para diferentes marcadores genéticos apresentaram-se maiores do que 2,0 e significativamente diferentes dos valores obtidos em sulfeto de sulindaco ausência da droga (controle). O potencial recombinagênico do sulfeto de sulindaco foi associado à indução de quebras na molécula do DNA e a alterações no ciclo celular. O potencial carcinogênico do sulfeto de sulindaco foi discutido no presente trabalho.

Sulindac Prevents Esophageal Adenocarcinomas Induced by Gastroduodenal Reflux in Rats

PURPOSE: It is known that cyclooxygenase (COX)-2 expression is increased in Barrett's esophagus and esophageal adenocarcinomas. We studied COX-2 expression and the effect sulindac has on the genesis of Barrett's esophagus and adenocarcinoma in rats undergoing esophagogastroduodenal anastomosis (EGDA). MATERIALS AND METHODS: Fifty-one rats were divided into a control group (n=27), a 500ppm sulindac-treated group (n=15) and 1000 ppm sulindac-treated group (n=9). Randomly selected rats were killed by diethyl ether inhalation at 20 and 40 weeks after surgery. RESULTS: At 40 weeks, rats treated with 1000 ppm sulindac showed narrower esophageal diameter and milder inflammation than the control rats. At 40 weeks, the incidence of Barrett's esophagus was similar between control and sulindac-treated groups, but the incidence of adenocarcinoma was significantly lower in the 1000ppm sulindac-treated group than either the control or 500 ppm sulindac-treated groups. COX-2 was significantly increased in the lower esophagus of control rats killed at 40 weeks. Cyclin D1 expression was negligible in the sulindac- treated group compared with the control group. CONCLUSION: We suggest that the chemopreventive effect of sulindac is related to decreased COX-2 and cyclin D1 expression, which may be influenced by reduced inflammation.

Inhibition of gastric cancer cells growth in vitro by sulindac / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effect of sulindac on proliferation and apoptosis of human gastric cancer BGC-823 cells and its antineoplastic mechanisms.</p><p><b>METHODS</b>Human gastric cancer BGC-823 cells were incubated with sulindac at various concentrations and for different times. Morphological changes of BGC-823 cells were observed under an inversion microscope. MTT colorimetric assay was used to examine the effect of sulindac on the proliferation of BGC-823 cells. Flow cytometry was used to determine the cell cycle distribution and apoptosis. Transmission electron microscopy was performed to examine cell apoptosis morphology. Immunohistochemical staining was used to detect the expressions of COX-2, bcl-2 and ki-67 in the cells.</p><p><b>RESULTS</b>sulindac induced morphologic alterations in BGC-823 cells, inhibited cell proliferation, increased the proportion of cells in G0/G1 phase and decreased the proportion of cells in S phase, induced apoptosis of BGC-823 cells, and decreased expressions of COX-2, bcl-2, ki-67 in the cells. All the effects were in a time- and dose-dependent manner (P < 0.05). Some characteristic morphologic features of apoptosis were revealed by transmission electron microscopy.</p><p><b>CONCLUSION</b>sulindac may inhibit the growth of gastric cancer BGC-823 cells in vitro and the anti-tumor mechanism may be related to changes in cell cycle distribution, induction of apoptosis and inhibition of expression of COX-2, bcl-2, and ki-67.</p>

A Case of Graft Intolerance Syndrome Treated by Percutaneous Renal Artery Embolization / 대한신장학회잡지

In patients with renal transplant failure's the graft can be left in situ when there are no additional complications. Graft intolerance occurs in some failed renal grafts when the immunological treatment is completely withdrawn. We experienced a case of graft intolerance syndrome in a patient with renal graft failure treated by percutaneous renal artery embolization. A 31 year -old man was admitted at nephrology department because of fever and hematuria without other infection focus. He was diagnosed as graft intolerance syndrome and treated by percutaneous embolization of the failed renal allograft. The embolization was successful. He suffered from post-emboization syndrome and treated by sulindac. We report this case with a review of relevant literatures and conclud that percutaneous renal artery embolizaion is a simple, safe and effective technique for the treatment of nonfunctioning renal allograft with clinical intolerance. Surgical nephrectomy should be reserved as a second level of treatment when allograft embolization has been ineffective owing to reappearance of manifestations of clinical intolerance.

Combination Treatment with Arsenic Trioxide and Sulindac Induces Apoptosis of NCI-H157 Human Lung Carcinoma Cells via ROS Generation with Mitochondrial Dysfunction / 결핵및호흡기질환

BACKGROUND: Arsenic trioxide (As2O3) has been used to treat acute promyelocytic leukemia, and it induces apoptosis in a variety of solid tumor cell lines including non-small cell lung cancer cells. However, nonsteroidal anti- inflammatory drugs (NSAID) can enhance tumor response to chemotherapeutic drugs or radiation. It was previously demonstrated that a combination treatment with As2O3 and sulindac induces the apoptosis of NCI-H157 human lung carcinoma cells by activating the caspase cascade. This study aimed to determine if a combination treatment augmented its apoptotic potential through other pathways except for the activation of the caspase cascade. MATERIAL AND METHODS: The NCI-H157 cells were treated with As2O3, sulindac and antioxidants such as glutathione (GSH) and N-acetylcysteine (NAC). The cell viability was measured by a MTT assay, and the level of intracellular hydrogen peroxide (H2O2) generation was monitored fluorimetrically using a scopoletin-horse radish peroxidase (HRP) assay. Western blotting and mitochondrial membrane potential transition analysis were performed in order to define the mechanical basis of apoptosis. RESULTS: The viability of the cells was decreased by a combination treatment of As2O3 and sulindac, and the cells were protected using antioxidants in a dose-dependent manner. The increased H2O2 generation by the combination treatment was inhibited by antioxidants. The combination treatment induced changes in the mitochondrial tran-smembrane potential as well as the expression of the Bcl-2 family proteins, and increased cytochrome c release into the cytosol. However, the antioxidants inhibited the effects of the combination treatment. CONCLUSION: Combination treatment with As2O3 and sulindac induces apoptosis in NCI-H157 human lung carcinoma cells via ROS generation with a mitochondrial dysfunction.

Inducing Apoptosis of NCI-H157 Human Lung Carcinoma Cells via Activation of Caspase Cascade by Combination Treatment with Arsenic Trioxide and Sulindac / 결핵

Arsenic trioxide(As2O3) was introduced into the treatment of refractory or relapsed acute promyelocytic leukemia. Some investigators have reported that arsenic trioxide had induced apoptosis in a variety of solid human tumor cell lines, including non-small cell lung cancer. Non-steroidal anti-inflammatory drugs(NSAIDs) are powerful chemopreventive agents for gastrointestinal cancers and the growth of established tumors are reduced by inducing apoptosis. It's also reported that NSAIDs enhanced tumor response to chemotherapeutic drugs or radiation. In this study, we aimed to determine whether combination of arsenic trioxide with sulindac augmented its apoptotic potential in NCI-H157 human lung cancer cells. The human lung cancer cell line NCI-H157 was treated with arsenic trioxide and sulindac. Cell viability was measured by the MTT assay. Apoptosis was measured by nuclear staining and flow cytometric analysis. The catalytic activity of the caspase families were measured by the fluorogenic cleavage of biosubstrates. The western blotting were also performed to define the mechanical basis of apoptosis. Combination treatment of arsenic trioxide and sulindac decreased the viability of NCI-H157 human lung cancer cells in a dose-dependent manner. The catalytic activity of caspase-3, 8 and 9 proteases were increased after combination treatment. Consistently PARP was cleaved from 116kDa to 85kDa fragments, and the expression of ICAD was decreased by time-dependent manner. Also combination treatment increased the expression of Fas and Fas/L. Combination therapy of arsenic trioxide with sulindac augments cell death and induces apoptosis via the activation of caspase cascade in NCI-H157 human lung carcinoma cells.

Growth Inhibition and Apoptosis Induction of Sulindac on Human Lung Cancer Cells / 결핵

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAID) are useful in chemoprevention of colorectal cancers. Continuous NSAID administation causes 40% to 50% reduction in relative risk for colorectal cancer. Sulindac possesses an antiproliferative effect and induces apoptosis and tumor regression on colon cancer and other types of cancers. We intended to analyze the effects of sulindac in three non-small cell lung cancer cell lines. MATERIALS AND METHODS: The human lung cancer cell lines, A549, NCI-H157 and NCI-H460 were used for this study. Viability was tested by MTT assay, and cell death rate was measured by lactate dehydrogenase(LDH) release. Apoptosis was estimated by flow cytometric analysis and nuclear staining. RESULTS: Sulindac was able to decrease the viability of non-small cell lung cancer cells in a dose- and time- dependent manner. In a parallel effect of sulindac on cell death rate, LDH release was increased in sulindac-treated lung cancer cells. Sulindac significantly increased apoptosis characterized by an increase of sub-G0/G1 fraction and morphological change of nuclei. The rate of apoptotic cells after sulindac treatment in lung cancer cells increased in a time- and dose- dependent manner in flow cytometric analysis. Apoptotic cells were defined as nuclear shrinkage, chromatin condensation and nuclear fragmentation of cells. CONCLUSION: Sulindac decreases viability and induces the apoptosis of lung cancer cells. Further studies will be needed to elucidate the potential mechanism of sulindac-induced apoptosis in lung cancer cells.

Sulindac-induced Apoptosis without Oligonucleosomal DNA Fragmentation in HT-29 Cells: Its Special References to Mitochondrial Pathway

PURPOSE: This study was undertaken to reveal the molecular mechanism underlying sulindac-induced apoptosis in the human colon cancer cell line HT-29 (mutant p53). METHODS: Apoptosis was determined by using Hoechst 33342 staining, and translocation of proteins was established by using immunofluorescence, immunoelectron microscopy, and Western blotting after ultra- fractionation. RESULTS: This type of apoptosis was associated with decreased mitochondrial membrane potential, a translocation of the apoptosis-inducing factor (AIF) to the nucleus, and morphological evidence of nuclear condensation. However, DNA electrophoresis did not elucidate the ladder pattern of DNA fragments. Instead, a pulse-field gel electrophoresis showed that sulindac led to disintegration of nuclear DNA into-high- molecular-weight DNA fragments of about 100~300 kbp. CONCLUSIONS: Our findings indicate that sulindac induces large-scale DNA fragmentation, suggesting a predominantly AIF-mediated cell-death process, through translocation of the AIF to the nucleus in HT-29 cells.

Effect of Lactacystin on the Sulindac-Induced Apoptosis Mechanisms in HT-29 Cells

PURPOSE: One of possible mechanisms of the antineoplastic effect by nonsteroidal anti-inflammatory drugs (NSAIDs) is an induction of apoptosis. The NSAIDs-induced apoptosis appears to be caspase- and mitochondria-dependent. The ubiquitin-proteasome system, which is a fundamental non- lysosomal tool that cells use to process or degrade a variety of short-lived proteins, is known to be involved in apoptosis and to be located upstream of mitochondrial changes and caspase activation. The present study was conducted to explore the potential role of proteasome pathway in NSAIDs-induced apoptosis. METHODS: We employed sulindac as a NSAID, and the lactacystin as a proteasome inhibitor to investigate the extent of the apoptosis in colon cancer cell line, HT-29 cells. The proteasome activity and the amount of apoptosis were quantified after cells were treated with 1 mM sulindac, 1micrometer lactacystin or both. RESULTS: Sulindac treatment caused apoptosis of the HT-29 cells in a time-dependent manner with resultant changes in nuclear morphology. Western blots also showed caspase-3 activation and PARP cleavage after sulindac treatment. Not only single treatment with lactacystin decreased proteasome activity, but co-treatment with sulindac enhanced decrease in proteasome activity further (P<0.01). Treatment with lactacystin only did not induce apoptosis. However, lactacystin augmented the induction of sulindac-induced apoptosis (P<0.01). This synergistic effect was also proven by Western blot analyses, where co-treatment augmented the caspase-3 activation and PARP degradation. CONCLUSIONS: The combination treatment of sulindac with a proteasome inhibitor lactacystin is suggested to be a very effective strategy for the induction of cancer cell apoptosis. Elucidation of the mechanism underlying the regression of colon cancers by combination of sulindac and lactacystin seems to be an immediate challenge in the near future.