Maria Martinez-Iniesta et al. (2008) European Worm Meeting "Identification of response and resistance genes to 5-fluroracil (5-FU) in Caenorhabditis elegans."

Maria Martinez-Iniesta, Xavi Sole, Nuria Baixeras, Alberto Villanueva, Laura Padulles, Ramon Salazar, Victor Moreno, J Ramon Germa, Gabriel Capella

[European Worm Meeting, 2008]

Introduction: Colorectal cancer (CRC) is one of the leading causes of. cancer-related mortality in the Western world. In Spain is the second type. of cancer in incidence and mortality in both sexes and 50% of total. diagnostic cases death. Despite the improvement of diagnostic and treatment. only a few decreases have been observed. About 60% of all patients. diagnosed with CRC will present localized disease, being the surgery the. mainstay therapy. The rest of patients (Duke''s C and D) are diagnosed with. distal metastasis. 5-FU and oxaliplatin based chemotherapy (QT) are the. base of the standard treatment of colorectal cancer patients in both. adjuvant and metastasic setting. Initially, more patients did not respond. to QT treatments and others relapse after a short period of response. In. spite of the clinical relevance of 5-FU, little is known about the. mechanisms of resistance to this drug commonly observed in colorectal. cancer patients. Aim: To identify the genes involved in the mechanism of. resistance to 5-FU in the pluricellular model organisms Caenorhabditis. elegans (C.elegans), and posterior validation of these genes as a markers. of response/sensitivity to 5-FU chemotherapy treatments in tumor series.. Methods and Results: A 5-FU plate toxicity assay has been established. We. are characterizing the ceTS-1 gene, C.elegans homolog of human thymidylate. synthase gene, and temporal and cellular expression patterns during. development are studying in GFP transgenic worms. Different alternative. splicing isoforms are generating in CeTS-1 with unknown biological. implications that we are evaluating. Different phenotypes have been. associated with the worm 5-FU treatment. N2 wild-type worms and cib-1(e300). mutant, harboring a point mutation in Thymidilate Synthase gene (Schnabel. R), were synchronized, and both strains of worms were growth at different. drug concentrations and at different times. Profiles of 5-FU response are. being determined in C.elegans Affymetrix microarrays. To identify response. genes (we expected around 100-150 genes) we are performing a feeding double-. stranded RNA-mediated interference (dsRNAi) screening for response genes.. Conclusions: Identification in C. elegans of genes involved in the. resistance/sensitivity to 5-FU drug and later validation of their. predictive value of response in colorectal cancer series may permit to. dispose of the some genetic markers that finally can improve the CRC. patient treatment.. avillanueva@iconcologia.net

Schulze, Jens et al. (2011) International Worm Meeting "Evolution of embryonic development in nematodes."

Schulze, Jens, Schierenberg, Einhard

[International Worm Meeting, 2011]

Nematodes are well suited for a comparative study of early embryogenesis. Analyzing development of a single model system like Caenorhabditis elegans does not shed any light on the degree of evolutionary modifications within the taxon Nematoda. For better understanding evolution of development among nematodes including the identification of plesiomorphic and apomorphic characters, we compared early embryogenesis of representatives from all 12 nematode clades (phylogeny after Holterman et al., 2006; Mol. Biol. Evol. 23:1792-1800). Our data reveal that embryogenesis is unexpectedly variable with floating transitions that can be interpreted as frozen images of evolutionary change. Particularly, members of clade 1 and 2 differ massively from the standard C. elegans. Nevertheless, some basic developmental similarities appear to be common among all nematodes, e.g. the general existence of at least partial cell lineages and the influence of Polarity Organizing Centers (POCs). These POCs are required for generating a linear sequence of cells along the a-p axis which constitute the ventral midline. Depending on phylogenetic position fewer or more cells of this midline divide into left and right daughters this way establishing bilateral symmetry within individual lineages. Our studies reveal the stepwise emergence of founder cells and dramatic fate shifts during evolution. The comparison between embryogenesis of the basal nematode Tobrilus stefanskii and the tardigrade Hypsibius dujardini (Gabriel et al., 2007; Dev. Biol. 312, 545-59) with respect to the early cell division pattern revealed surprising similarities between these two. This may be considered as embryological support for the Ecdysozoa hypothesis.