Identification of Potential Vaccine and Drug Target Candidates by Expressed Sequence Tag Analysis and Immunoscreening of Onchocerca volvulus Larval cDNA Libraries

The search for appropriate vaccine candidates and drug targets against onchocerciasis has so far been confronted with several limitations due to the unavailability of biological material, appropriate molecular resources, and knowledge of the parasite biology. To identify targets for vaccine or chemotherapy development we have undertaken two approaches. First, cDNA expression libraries were constructed from life cycle stages that are critical for establishment of Onchocerca volvulus infection, the third-stage larvae (L3) and the molting L3. A gene discovery effort was then initiated by random expressed sequence tag analysis of 5,506 cDNA clones. Cluster analyses showed that many of the transcripts were up-regulated and/or stage specific in either one or both of the cDNA libraries when compared to the microfilariae, L2, and both adult stages of the parasite. Homology searches against the GenBank database facilitated the identification of several genes of interest, such as proteinases, proteinase inhibitors, antioxidant or detoxification enzymes, and neurotransmitter receptors, as well as structural and housekeeping genes. Other O. volvulus genes showed homology only to predicted genes from the free-living nematode Caenorhabditis elegans or were entirely novel. Some of the novel proteins contain potential secretory leaders. Secondly, by immunoscreening the molting L3 cDNA library with a pool of human sera from putatively immune individuals, we identified six novel immunogenic proteins that otherwise would not have been identified as potential vaccinogens using the gene discovery effort. This study lays a solid foundation for a better understanding of the biology of O. volvulus as well as for the identification of novel targets for filaricidal agents and/or vaccines against onchocerciasis based on immunological and rational hypothesis-driven research

Large bowel cancer in the setting of inflammatory bowel disease: Features and management with a focus on rectal cancer

Background: Inflammatory bowel diseases (IBDs) are a well-known risk factor for the development of colorectal cancer (CRC). This risk relates to different aspects of the disease, such as the duration, activity, and extension, and tends to increase in the presence of associated conditions, such as family history of CRC or some extra-intestinal manifestations. Rectal cancer (RC) in IBD has been poorly investigated. Methods: We reviewed the scientific literature for data on the features and management of RC in the setting of IBD. Here, we provide a practical insight into the diagnosis and management of the condition. Results: Several genetic and environmental factors promote the development of CRC, including alterations of intestinal microflora and mutations in the genes responsible for the cell cycle and for DNA mismatch repair. Dysplasia is the main evidence of a clear conversion of normal epithelium to cancer. Dysplasia is often multifocal, in contrast to sporadic CRC, which explains the tendency toward the development of synchronous and metachronous CRC in patients with IBD. Other conditions that need attention are strictures, for which the threshold for surgery must be low. Treatment of RC in patients with IBD follows the same oncologic criteria as non-IBD-related RC, but patients are often diagnosed at more advanced stages, suggesting that this is frequently overlooked. This is ultimately associated with poorer outcomes in IBD patients. Conclusion: There is a pressing need for more data on IBD-related RC. Implementing knowledge will result in optimization of survival for these patients