Interspecific chimeras. Transplantation of neural crest between mouse and chick embryos.
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Biomedical subjects
Publications and source records attributed to V Herlea.
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Monitoring the migrations of cells during embryonic development requires a system in which cells can be identified in situ during locomotion. One promising system involves the generation of chimeras by transplanting mouse cells into chick embryos in ovo to exploit the wealth of mouse genetic variants. The success of this technique relies on the ability to detect individual mouse cells in a chick environment with high specificity. The murine B2 family of short interspersed elements is present in the mouse genome at copy numbers in excess of 10(5), whereas this sequence is absent in the chick genome based on hybridization techniques. This differential of five orders of magnitude produces signals in mouse cells that are easily identified, even in an environment that is predominantly chick. Thus, the B2 repeat probe is highly effective for the purpose of identifying mouse cells in mouse-chick chimeras.
Microsatellite instability (MSI) characterizes the hereditary nonpolyposis colorectal cancer syndrome but is also found in sporadic tumors. Frameshifts in microsatellites found in the coding regions (CDRs) of the TGFbeta1-RII, IGFIIR, hMSH3, hMSH6, and BAX genes indicate that MSI is involved in tumorigenesis by targeting genes that are directly implicated in the tumorigenic process. To identify additional genes targeted for MSI, we performed an analysis of the GenBank database that revealed 21 microsatellite repeats located in the CDR of 18 genes (12% of the analyzed sequences) whose function could be potentially associated with the tumorigenic process. Mutational studies of 57 sporadic gastrointestinal tumor DNAs revealed the presence of length variations in three of them: (a) BLM; (b) CBL; and (c) HOXA1. In the BLM gene, we found a frameshift mutation in a polyadenine repeat, whereas in the CBL proto-oncogene, an expansion of a trinucleotide repeat was detected with no translation shift. These alterations were present in 18 and 9%, respectively, of the genetically unstable sporadic gastrointestinal tumors analyzed, but in none of the cancers without the mutator phenotype. These changes were present in the DNA from the tumor but not in that from normal cells of the same patient. The HOXA1 retraction of a trinucleotide repeat was as frequent in both types of cancers and was also found in some normal paired tissues, therefore behaving as a neutral polymorphism. Our data extend the spectrum of unstable microsatellites located in gene CDRs and suggest that BLM and possibly CBL are involved in gastrointestinal tumorigenesis. Based on its proposed function, the BLM gene could represent a link between MSI and chromosomal instability pathways, because MSI targeting of the BLM gene could generate hypermutability and/or chromosomal instability.
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One documented case of Wilms' tumor in an adult patient is presented. The patient is diagnosed clinically with renal tumor, probably renal carcinoma. Wilms' tumor is extremely difficult to diagnose preoperatively in an adult patient. The pathologic hallmarks of this neoplasm are distinctive and it is histologically similar to the childhood tumor. The therapeutic guidelines and surgical principles governing childhood Wilms' tumor should be applied to adult Wilms' tumor. This patient is still alive after 15 months.
Five cases of iterative liver resections are presented, out of a total of 150 hepatectomies performed between 1.01.1995-1.01.1998. The resections were carried out for recurrent adenoma (one case), cholangiocarcinoma (two cases), hepatocellular carcinoma (one case), colo-rectal cancer metastasis (one case). Only cases with at least one major hepatic resection were included. Re-resections were more difficult than the primary resection due, first of all, to the modified vascular anatomy. Intraoperative ultrasound permitted localization of intrahepatic recurrences. Iterative liver resection appears to be the best therapeutical choice for patients with recurrent liver tumors.