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Preclinical evaluation of azathioprine plus buthionine sulfoximine in the treatment of human hepatocarcinoma and colon carcinoma

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World Journal of gastroenterology 2011年第34期17卷 3899-3911页

作者： Borja Hernández-Breijo Jorge Monserrat Sara Ramírez-Rubio Eva P Cuevas Diana Vara Inés Díaz-Laviada M Dolores Fernández-Moreno Irene D Román Javier P gisbert luis g guijarro Molecular Hepatic Toxicology Unit Biochemistry and Molecular Biology Department University of Alcalá Networked Biomedical Research Center of Hepatic and Digestive Diseases (CIBEREHD) Medicine Department University of Alcalá Neuroendocrinology of Cannabinoid/Vanilloid System Unit Biochemistry and Molecular Biology Department University of Alcalá gastroenterology Unit Hospital de la Princesa Institute of Health Research Princesa Networked Biomedical Research Center of Hepatic and Digestive Diseases (CIBEREHD)

AIM: To evaluate the efficacy and the safety of azathioprine (AZA) and buthionine sulfoximine (BSO) bylocalized application into Hepg2 tumor in ***: Different hepatoma and colon carcinoma cell lines (Hepg2, HuH7, Chang liver, LoVo, RKO, SW-48, SW-480) were grown in minimal essencial medium supplemented with 10% fetal bovine serum and 1% antibiotic/antimycotic solution and maintained in a humidified 37 ℃ incubator with 5% CO2. These cells were pretreated with BSO for 24 h and then with AZA for different times. We examined the effects of this combination on some proteins and on cellular death. We also studied the eff icacy and the safety of AZA (6 mg/kg per day) and BSO (90 mg/kg per day) in Hepg2 tumor growth in vivo using athymic mice. We measured safety by serological markers such as aminotransferases and creatine ***: The in vitro studies revealed a new mechanism of action for the AZA plus BSO combination in the cancer cells compared with other thiopurines (6-mercaptopurine, 6-methylmercaptopurine, 6-thioguanine and 6-methylthioguanine) in combination with BSO. The cytotoxic effect of AZA plus BSO in Hepg2 cells resulted from necroptosis induction in a mitochondrial-dependent manner. From kinetic studies we suggest that glutathione (gSH) depletion stimulates c-Jun amino-terminal kinase and Bax translocation in Hepg2 cells with subsequent deregulation of mitochondria (cytochrome c release, loss of membrane potential), and proteolysis activation leading to loss of membrane integrity, release of lactate dehydrogenase and DNA degradation. Some of this biochemical and cellular changes could be reversed by N-acetylcysteine (a gSH replenisher). In vivo studies showed that Hepg2 tumor growth was inhibited when AZA was combined with ***: Our studies suggest that a combination of AZA plus BSO could be useful for localizedtreatment of hepatocellular carcinoma as in the currently used transarterial chemoembolization method.

关键词：硫唑嘌呤结肠癌肝癌 Hepg2细胞评价亚砜肿瘤生长临床

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N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis: Randomized,placebo-controlled pilot study

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World Journal of gastroenterology 2008年第18期14卷 2851-2857页

作者： luis g guijarro Jose Mate Javier P gisbert Jose luis Perez-Calle Ignacio Marín-Jimenez Encarna Arriaza Tomás Olleros Mario Delgado Maria S Castillejo David Prieto-Merino Venancio gonzalez Lara Amado Salvador Pea Department of Biochemistry and Molecular Biology CIBERehd Alcalá University Alcalá de Henares Madrid Spain gastroenterology Unit CIBERehd La Princesa University Hospital Autonomous University Madrid Spain gastroenterology Unit Gregorio Maraón University Hospital Complutense University Madrid Spain group Farmasierra SL. Ctra N-Ⅱ Km 26.200 San Sebastián de los Reyes Madrid Spain Laboratory of Immunogenetics Department of Pathology VU University Medical Center Amsterdam The Netherlands

AIM: To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine (NAC) co-administration with mesalamine in ulcerative colitis (UC) patients. METHODS: Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine (2.4 g/d) plus N-acetyl-L-cysteine (0.8 g/d) (group A) or mesalamine plus placebo (group B). Patients were monitored using the Modified Truelove-Witts Severity Index (MTWSI). The primary endpoint was clinical remission (MTWSI ≤ 2) at 4 wk. Secondary endpoints were clinical response (defined as a reduction from baseline in the MTWSI of ≥ 2 points) and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS: Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine (group A) and mesalamine plus placebo (group B) respectively (OR = 1.71; 95% CI: 0.46 to 6.36; P = 0.19; NNT = 7.7). Analysis of variance (ANOVA) of data indicated a significant reduction of MTWSI in group A (P = 0.046) with respect to basal condition without significant changes in the group B (P = 0.735) during treatment. Clinical responses were 66% (group A) vs 44% (group B) after 4 wk of treatment (OR = 2.5; 95% CI: 0.64 to 9.65; P = 0.11; NNT = 4.5). Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups. CONCLUSION: In group A (oral NAC combined with mesalamine) contrarily to group B (mesalamine alone), the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.

关键词：白细胞间介素大肠溃疡 N-乙酰基-L-半胱氨酸治疗方法

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化学与微生物实验室

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现代装饰 2024年第3期 62-69页

作者： Jose luis Esteban Penelas(设计) Yolanda Hernandez Lorente(设计) Maria Esteban Casanas(设计) Antonio guijarro(设计) Marina Rodriguez Sotoca(设计) Kevin Roman Cruz(设计) Yakaterina Savina(设计) Imagen Subliminal(摄影) 舒禹(编译) 不详 Miguel de guzman+Rocio Romero

建筑呈现明显的后工业美学特征,内设有一个微生物和化学分析实验室,功能设施极为复杂,使用中需要极高的功能效率与超先进的图像兼容。设计重新激活地区周围的强大工业景观,通过穿孔立面,过滤环境并生成独特的室内景观。

关键词：微生物实验室工业景观室内景观功能设施美学特征

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Nonnegative curvature and twisted bundles

Nonnegative curvature and twisted bundles

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Nanjing Workshop on geometry and Analysis 2005

作者： luis guijarro

An open and nonnegatively curved manifold is diffeomorphic to a vector bundle over some compact submanifold, known as a soul. It is still unclear in many situations how the metric and the topological structure of the manifold interact. In this talk we will review some of the consequences that the nonnegative curvature condition sets on the manifold, and study how the sphericity of the Euler class of the bundle translates into certain rigidity of the metric.

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