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Molecular Docking of 4-Tert-buthyl-bis-(2,6-thiomorpholin-4-ylmethyl)-1-phenol (LQM319) on Fas Receptor (CD95)

Journal of Cancer Therapy 2013年第1期4卷 176-181页

作者： Oscar Zuniga Victor HVazquez Ana Maria Velazquez Victor HAbrego Sandra Diaz-Barriga Arceo patricia ramirez Roberto Diaz Enrique Angeles Laboratorio de Toxicologia y Genetica Departamento de C.BiologicasFacultad de Estudios Superiores CuautitlanUniversidad Nacional Autonoma de MexicoCuautitlan IzcalliMexico Laboratorio de Quimica Medicinal Departamento de Ciencias Quimicas Facultad de Estudios Superiores Cuautitlan Universidad Nacional Autonoma de MexicoCuautitlan IzcalliMrxico.

The balance between cell proliferation and cell growth characterizes tissue homeostasis on one side and cell death on the other side. Fas receptor-mediated apoptosis is a control mechanism for tissue homeostasis, and avoiding this death pathway predisposes to many human diseases, including cancer. Current therapies for this disease are invasive and do not have the desired effect in the control of the disease. In this context, the search for new drugs that contribute to a better treatment is gaining more relevance. 4-tert-butyl-bis-(2,6-thiomorpholin-4-ylmethyl)-1-phenol (LQM319) [1,2] is a drug currently in preclinical stage, and we have shown that it has a hypertensive effect, similar to captopril, in a hypertensive rat model. Different studies have shown that some chemicals that are used as antihypertensive agents have an antineoplastic effect against certain types of cancer, as is the case of hydralazine [3], and captopril [4], among others [5]. On the other hand, it has been reported that morpholine derivatives may activate Fas (CD95)-mediated apoptosis. The aim of the present study was to show the interaction between CD95 (receptor) and thiomorpholine derivatives (ligand) using molecular modeling and docking studies, and to elucidate the possible action mechanism of 4-tert-butyl-bis-(2,6-thiomorpholin-4-ylmethyl)-1-phenol.

关键词： Fas Receptor (CD95) Fas Ligand (FasL) Docking

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Identification of ompL1 and lipL32 Genes to Diagnosis of Pathogenic Leptospiraspp. Isolated from Cattle

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Open Journal of Veterinary Medicine 2014年第5期4卷 102-112页

作者： Hernández-Rodríguez patricia Gomez ramirez Arlen Baquero Mónica Quintero Gladys Faculty of Agricultural Sciences Veterinary Medicine Program Universidad de la Salle Bogotá Colombia Health Research Center—CISVI Bogotá Colombia Molecular Biology and Immunogenetics Research Group—BIOMIGEN Bogotá Colombia

Diagnosis of leptospirosis in Colombia is based on clinical history and serological testing. However, disease symptoms are nonspecific and there is no uniform criteria regarding the qualifications considered positive. Therefore, it is important to identify and characterize genes associated with pathogenicity in native strains for the development of new diagnostic tests and vaccine production. The aim of this study was to identify the ompL1 and lipL32 genes in Leptospira strains isolated from urine samples of cattle. Sixteen strains were obtained from urine samples and, DNA was isolated to perform two Polymerase Chain Reaction (PCR) tests which identified lipL32 and ompL1 genes. As positive control, a reference strain of L. interrogans was used. L. biflexa and Escherichia coli strains were used as a negative control. In 100% of the samples were identified amplicons of 960 bp and 423 bp corresponding to ompL1 and lipL32 genes respectively. Thus, the pathogenic property and conservation of genes in the isolated strains were confirmed. This study is presented as a contribution to the diagnosis of leptospirosis to use these genes as molecular markers of infection. The results of this study might provide clues for future clinical, epidemiological and molecular research leading to implement new diagnostic strategies and to expand knowledge of the pathophysiology of a disease of public health impact on human and animal.

关键词： Leptospirosis PCR ompL1 lipL32

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Clinical-pathological and molecular characterization of long-term survivors with advanced non-small cell lung cancer

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Cancer Biology & Medicine 2020年第2期17卷 444-457页

作者： Juan Moreno-Rubio Santiago Ponce Rosa Alvarez Maria Eugenia Olmedo Sandra Falagan Xabier Mielgo Fatima Navarro patricia Cruz Luis Cabezon-Gutierrez Carlos Aguado Gonzalo Colmenarejo Marta Munoz-Fernandez de Leglaria Ana Belen Enguita Maria Cebollero Amparo Benito Isabel Alemany Carolina del Castillo Ricardo Ramos Ana ramirez de Molina Enrique Casado Maria Sereno Ana ramirez de Molina1 Enrique Casado5Maria Sereno5 XIMDEA Food InstituteCEI UAM+CSICMadrid 28702Spain 12 de Octubre University Hospital Madrid 28041Spain Gregorio Maranon University Hospital Madrid 28009Spain Ramon y Cajal University Hospital Madrid 28034Spain Infanta Sofia University Hospital San Sebastian De Los ReyesMadrid 28702Spain Fundacion Alcorcon University Hospital AlcorconMadrid 28922Spain Prlncipe de Asturias University Hospital Alcala De HenaresMadrid 28805Spain La Paz University Hospital Madrid 28046Spain University Hospital of Torrejon Torrejon De ArdozMadrid 28850Spain Clinico San Carlos University Hospital Madrid 28040Spain Parque Cientifico de Madrid Foundation Madrid 28049Spain

Objective:Long-term survivors(LS)of non-small cell lung cancer(NSCLC)without driver alterations,displaying an overall survival(OS)of more than 3 years,comprise around 10%of cases in several series treated with *** are classical prognosis factors for these cases[stage,Eastern Cooperative Oncology Group(ECOG),etc.],but more data are required in the *** this multi-center study,we focused on LS of advanced NSCLC with OS above 36 months to perform a clinical-pathological and molecular ***:In the first step,we conducted a clinical-pathological characterization of the ***,we carried out a genetic analysis by comparing LS to a sample of short-term survivors(SS)(with an OS less than 9 months).We initially used whole-genome RNA-seq to identify differentiating profiles of LS and SS,and later confirmed these with reverse transcription-polymerase chain reaction(RT-PCR)for the rest of the ***:A total of 94 patients were included,who were mainly men,former smokers,having adenocarcinoma(AC)-type NSCLC with an ECOG of *** obtained an initial differential transcriptome expression,displaying 5 over-and 33 under-expressed genes involved in different pathways:namely,the secretin receptor,surfactant protein,trefoil factor 1(T FF1),serpin,Ca-channels,and Tolllike receptor(TLRs)***,RT-PCR analysis of 40(20 LS/20 SS)samples confirmed that four genes(surfactant proteins and SFTP)were significantly down-regulated in SS compared to LS by using an analysis of covariance(ANCOVA)model:SFTPA1(P=0.023),SFTPA2(P=0.027),SFTPB{P=0.02),and SFT PC(P=0.047).Conclusions:We present a sequential genetic analysis of a sample of NSCLCLS with no driver alterations,obtaining a differential RNA-seq/RT-PCR profile showing an abnormal expression of SF genes.

关键词： Long-term survivors non-small cell lung cancer surfactant proteins

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