ABSTRACT: Gastric cancer has a dramatic prognosis, making it mandatory to analyze the possible benefit from novel drug associations. In this study, we looked at the combined effects of lovastatin, a cholesterol lowering drug, and docetaxel, a potent microtubule-stabilizing agent, in the HGT-1 human gastric cancer cell line. Transcriptional profiling was used to compare the responses to the individual or combined treatments by these compounds, together with death inducing activity.
Project description:A "Cartes d'Identite des Tumeurs" (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net). Affymetrix UU133A gene expression data for a series of 32 cases of systemic Anaplastic Large Cell Lymphoma<br> (ALCL) and 5 ALCL cell lines; used to (1) confirm that tumors expressing Anaplastic Lymphoma Kinase (ALK+ ALCL) and ALK- ALCLs are different entities, (2) identify most significantly differentially expressed genes between ALK+ and ALK- samples, (3) generate a molecular signature of ALK- ALCL, (4) perform unsupervised analysis classifying ALCL in sub-groups related to morphology and clinical variables (e.g. disease stage and enrichment with 'early relapse' patients).<br> <br> Principal Investigator: Dr Georges DELSOL-- Centre de Physiopathologie Toulouse-Purpan CHU-Purpan -- Toulouse -- France -- Email: delsol.g@chu-toulouse.fr <br> Programme "Cartes d'identite des Tumeurs" (CIT) of the "Ligue Nationale Contre le Cancer" (LNCC)<br> Submitter: Fabien PETEL (petelf@ligue-cancer.net)
Project description:In order to investigate the involvement of Hsp27 in splicing, we performed a whole-genome exonic expression profiling of the castration-resistant prostate cancer PC-3 cells treated by Hsp27-siRNA or CTL-siRNA (both in biological duplicates).
Project description:We identified four virulence phenotypes of Rickettsia prowazekii (the deadly agent of epidemic typhus) that are associated with the upregulation of antiapoptotic genes (virulent strain) or the Interferon I pathway (avirulent). Transcriptional and proteomic analyses of R. prowazekii linked surface protein expression and methylation with virulence. By sequencing a virulent strain and using comparative genomics, we found hotspots of mutations in homopolymeric tracts of poly(A) and poly(T) that lead to gene split and inactivation and explain the loss of virulence in the vaccine strain. These areas of instability explains adaptive mutations leading to virulence recovery in the vaccine strain. Transcriptional analysis of two different strains growing in L929 cells. A virulent strain (Rp22) was compared to a avirulent strain (Erus). The experiment was performed with 3 independant biological replicates.
Project description:Statins are among the most frequently prescribed drugs because of their efficacy and low toxicity in treating hypercholesterolemia. Recently, statins have been reported to inhibit the proliferative activity of cancer cells, especially those with *TP53* mutations. Since *TP53* mutations occur in almost all of the ovarian high-grade serous carcinoma, we determined if statins suppressed tumor growth in animal models of ovarian cancer. Two ovarian cancer mouse models were employed. The first one was a genetically engineered model, mogp-TAg, in which the promoter of oviduct glycoprotein-1 was used to drive the expression of SV40 T-antigen in gynecologic tissues. These mice spontaneously develop serous tubal intraepithelial carcinomas (STICs), which are known as ovarian cancer precursor lesions. The second model was a xenograft tumor model in which human ovarian cancer cells were inoculated into immunocompromised mice. Mice in both models were treated with lovastatin, and effects on tumor growth were monitored. The molecular mechanisms underlying the anti-tumor effects of lovastatin were also investigated. Lovastatin significantly reduced the development of STICs in mogp-TAg mice and inhibited ovarian tumor growth in the mouse xenograft model. Knockdown of prenylation enzymes in the mevalonate pathway recapitulated the lovastatin-induced anti-proliferative phenotype. Transcriptome analysis indicated that lovastatin affected the expression of genes associated with DNA replication, Rho/PLC signaling, glycolysis, and cholesterol biosynthesis pathways, suggesting that statins have pleiotropic effects on tumor cells. The above results suggest that repurposing statin drugs for ovarian cancer may provide a promising strategy to prevent and manage this devastating disease. SKOV3 and OVCAR5 cells were treated with either 10uM Lovastatin or DMSO for 48 hours before harvested for gene expression array.
Project description:In neuroblastoma (NB), the presence of segmental chromosome alterations (SCA) is associated with a higher risk of relapse, even when occurring together with numerical chromosome alterations (NCA). Furthermore, recent evidence shows that SCAs play a role in tumor progression. In order to analyze the role of SCAs in infants with NB, we have performed an extensive retrospective array-CGH analysis of tumours from infants enrolled in the European INES 99.1, 99.2 and 99.3 trials. Tumour samples from 221/300 enrolled patients could be analyzed. SCAs were observed in 11%, 20% and 59% of infants enrolled in trial 99.1 (localised unresectable NB), 99.2 (INSS stage 4s) and 99.3 (INSS stage 4), respectively (p<0.001), and were associated with the presence of bone metastasis (p<0.003). Progression-free survival was poorer in patients whose tumours harbored at least one SCA, in the whole population as well as in trials 99.1 and 99.2. In multivariate analysis, taking into account single genetic alterations, the protocol arm and genomic profile, the SCA genomic profile was the strongest predictor of poor outcome. Although overall survival was excellent, patients with stage 4s disease and a SCA genomic profile had a higher risk of relapse also in the absence of clinical symptoms at diagnosis and required a higher treatment burden for salvage. In conclusion, in infants with NB, a SCA genomic profile is useful to identify patients who will require upfront treatment even in the absence of other clinical indication for therapy, whereas an NCA genomic profile can identify a patient subpopulation in whom treatment reduction can be considered safe. Each of the 218 tumoral genomic DNAs was hybridized against non-tumoral DNA reference on BAC/PAC array or commercial supports in order to determine an overall genomic profile. The reference DNA was obtained from the blood of a single normal individual.
Project description:At implantation the endometrium undergoes dramatic modifications necessary for its physical interactions with the trophoblast as well as the development of the conceptus. We aim to identify endometrial factors and pathways essential for a successful implantation in the caruncular [C] and the intercaruncular [IC] areas in cattle. Using a bovine oligo-array, expression profiles were established at day 20 of the estrous cycle or pregnancy (implantation) showing 446 and 1295 differentially expressed genes (DEG) in [C] and [IC] areas respectively. The impact of the conceptus was higher on the immune response function in [C] but more prominent on the regulation of metabolism function in [IC]. Keywords: Fluorescence Microarray 18 intercaruncular samples, 18 caruncular Samples. Comparisons of cycle (d20) and pregnancy (d20).
Project description:Implantation is crucial for placental development whose quality will directly impact fetal growth and pregnancy success with possible consequences on post-natal health. We postulated that early perturbations of the conceptus-maternal environment communication may alter the endometrium physiology that could account for the final reproductive outcome. Using cattle as an animal model, we compared gene expression profiles of the endometrial caruncular and intercaruncular areas at implantation in three types of pregnancies, namely artificial insemination (AI), in vitro fertilization with embryo transfer (IVF-ET) or somatic cell nuclear transfer (SCNT). Less than 35% of the differentially regulated genes were found to be common between AI, IVF-ET, and SCNT conditions. Compared to AI, numerous biological functions and several canonical pathways and genes were found to be significantly affected in IVF-ET or SCNT, with a major impact on metabolism and immune function in SCNT. Our data show that endometrium can fine-tune its physiology and could be considered as a biological sensor in response to pregnancy manipulations. Determining the limits of the endometrial plasticity should bring new insights on the contribution of the maternal compartment to the issue of pregnancy. Keywords: Fluorescence Microarray 30 samples
Project description:Implantation is crucial for placental development which directly impacts fetal growth and pregnancy success with possible consequences on post-natal health. We postulated that early perturbations of the conceptus-maternal environment communication may alter the endometrium physiology that could account for the final reproductive outcome. Using cattle as an animal model, we compared gene expression profiles of the endometrial caruncular and intercaruncular areas during the critical period of implantation in three types of pregnancies: artificial insemination (AI), in vitro fertilization with embryo transfer (IVF-ET) or somatic cell nuclear transfer (SCNT). Less than 35% of the differentially expressed genes were found to be common between AI, IVF-ET, and SCNT conditions. Compared to AI, numerous biological functions and several canonical pathways and genes were found to be significantly affected in IVF-ET or SCNT, with a major impact on metabolism and immune function in SCNT. Our data show that the endometrium can fine-tune its physiology and could be considered as a biological sensor in response to pregnancy manipulations. Determining the limits of the endometrial plasticity should bring new insights on the contribution of the maternal compartment to the pregnancy outlet. Keywords: Fluorescence Microarray - Dye switch loop design 44 samples
Project description:This SuperSeries is composed of the following subset Series: GSE14047: Comparison between caruncles and intercaruncles in AI, IVF-ET and SCNT pregnancies GSE14050: AI versus IVF-ET & AI versus SCNT Refer to individual Series
Project description:At implantation the endometrium undergoes dramatic modifications necessary for its physical interactions with the trophoblast as well as the development of the conceptus. We aim to identify endometrial factors and pathways essential for a successful implantation in the caruncular [C] and the intercaruncular [IC] areas in cattle. The [C versus IC] direct comparison revealed 1177 and 453 DEG in cyclic and pregnant animals respectively, with a major impact of the conceptus on metabolism and cell adhesion. Keywords: Microarray fluorescence 10 Samples comparing caruncle and intercaruncle in pregnant cows, 10 Samples comparing caruncle and intercaruncle in cyclic cows.