Resistance formation is one of the major hurdles in cancer therapy. Metronomic anti-angiogenic treatment of xenografted prostate cancer tumors in SCID mice with cyclophosphamide (CPA) results in the appearance of resistant tumors. To investigate the complex molecular changes occurring during resistance formation, we performed a comprehensive gene expression analysis of the resistant tumors in vivo. We observed a multitude of differentially expressed genes, e.g., PASD1, ANXA3, NTS or PLAT, when comparing resistant to in vivo passaged tumor samples. Furthermore, tumor cells from in vivo and in vitro conditions showed a significant difference in target gene expression. We assigned the differentially expressed genes to functional pathways like axon guidance, steroid biosynthesis and complement and coagulation cascades. Most of the genes were involved in anti-coagulation, indicating its possible importance. Upregulation of anti-coagulatory ANXA3 and PLAT and downregulation of PLAT inhibitor SERPINA were validated by qPCR. In contrast, coagulation factor F3 was upregulated, accompanied by the expression of an altered gene product. These findings give insights into the resistance mechanisms of metronomical CPA treatment suggesting an important role of anti-coagulation in resistance formation.
A Comprehensive Gene Expression Analysis of Resistance Formation upon Metronomic Cyclophosphamide Therapy.
Specimen part, Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Escherichia coli infection induces distinct local and systemic transcriptome responses in the mammary gland.
Specimen part, Time
View SamplesGastric cancer is still one of the most common causes of cancer-related death worldwide, which is mainly attributable to late diagnosis and poor treatment options. Infection with H. pylori, different environmental factors and genetic alterations are known to influence the risk of developing gastric tumors. However, the molecular mechanisms involved in gastric carcinogenesis are still not fully understood, making it difficult to design targeted therapeutic approaches.
The stem cell factor SOX2 regulates the tumorigenic potential in human gastric cancer cells.
Specimen part, Cell line, Treatment, Time
View SamplesGLP-1 agonists are potent glucose-lowering agents, however, their effect on adolescent organisms needs to be clarified
Effects of the glucagon-like peptide-1 receptor agonist liraglutide in juvenile transgenic pigs modeling a pre-diabetic condition.
Age, Specimen part, Treatment
View SamplesDuchenne muscular dystrophy (DMD) is caused by mutations in the X-linked dystrophin (DMD) gene. The absence of dystrophin protein leads to progressive muscle weakness and wasting, disability and death. To establish a tailored large animal model of DMD, we deleted DMD exon 52 in male pig cells by gene targeting and generated offspring by nuclear transfer. DMD pigs exhibit absence of dystrophin in skeletal muscles, increased serum creatine kinase levels, progressive dystrophic changes of skeletal muscles, impaired mobility, muscle weakness, and a maximum life span of 3 months due to respiratory impairment. To address the accelerated development of muscular dystrophy in DMD pigs as compared to human patients, we performed a genome-wide transcriptome study of M. biceps femoris samples from 2-day-old and 3-month-old DMD and age-matched wild-type pigs. The transcriptome changes in 3-month-old DMD pigs were in good accordance with the findings of gene expression profiles in human DMD, reflecting the processes of degeneration, regeneration, inflammation, fibrosis, and impaired metabolic activity. The transcriptome profile of 2-day-old DMD pigs pointed towards increased protein and DNA catabolism, reduced extracellular matrix formation and cell proliferation and showed similarities with transcriptome changes induced by exercise injury in muscle. Our transcriptome studies provide new insights into congenital changes associated with dystrophin deficiency and secondary complications arising during postnatal development. Thus the DMD pig is a useful model to determine the hierarchy of physiological derangements in dystrophin-deficient muscle.
Dystrophin-deficient pigs provide new insights into the hierarchy of physiological derangements of dystrophic muscle.
Age, Specimen part
View SamplesTo validate the suitability of two commonly used colorectal cancer cell lines, DLD1 and SW480, as model systems to study colorectal carcinogenesis, we treated these cell lines with -catenin siRNA and identified -catenin target genes using DNA microarrays. The list of identified target genes was compared to previously published -catenin target genes found in the PubMed and the GEO databases.
Comprehensive analysis of β-catenin target genes in colorectal carcinoma cell lines with deregulated Wnt/β-catenin signaling.
Cell line, Treatment
View SamplesTwo pancreatic cancer cell lines with different metastatic and growth potential were compared under hypoxic conditions and under normal atmospheric oxygen pressure. The FG cell lines shows very few metastases and slow growth in mouse xenograft models. L3.6pl, derived from FG by cycles re-implantation of metastatic cells obtained after orthotopic tumor growth in nude mice, shows high motility, aggressive growth and very high metastatic potential
Hypoxia-independent gene expression mediated by SOX9 promotes aggressive pancreatic tumor biology.
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View SamplesBy comparison of the transcriptome profiles of infected and healthy udder tissue we analyse gene expression in the late stage of infection with E. coli 1303.
Actions and interactions of progesterone and estrogen on transcriptome profiles of the bovine endometrium.
Specimen part
View SamplesBy comparison of the transcriptome profiles of udder quarters neighboring to infected quarters and healthy udder tissue we analyse gene expression in the late stage of infection with E. coli 1303.
Escherichia coli infection induces distinct local and systemic transcriptome responses in the mammary gland.
Specimen part, Time
View SamplesBy comparison of the transcriptome profiles of infected and healthy udder tissue we analyse gene expression in the late stage of infection with E. coli 1303.
Escherichia coli infection induces distinct local and systemic transcriptome responses in the mammary gland.
Specimen part, Time
View Samples