Sunday, July 10, 2011

Week 4 --- Joyce

Besides the colorectal cancer surgeries, I watched the surgery of rectal hemingioma in a 46 years old male this week. Although vascular malformations have been found in every organ, hemangioma of the colon and rectum are rare. Hemangiomas are hamartomatous vascular growths that can be found throughout the gastrointestinal tract and they may be of the capillary or cavernous type. The surgeon team led by Dr. Lee took out the rectal hemingioma by minimally invasive surgery and the segmental resection of the rectosigmoid colon and a submucosal tumor was fulfilled with blood clots and engorged vascular structures could be found. Another case is the intestinal polyposis syndrome which belongs to the broad categories of familial adenomatous polyposis and most likely to develop into colorectal cancer if no properly prevention and treatment were performed. Intestinal polyposis syndrome is caused by adenomatous polyposis (APC) gene mutation. APC is a tumor suppressor gene whose lost-function mutation leads to WNT pathway over-activation and consequently neoplasia or adenomas in GI tract. Usually intestinal polyps are destroyed by cautery instead of cutting the colon segment in disease locations to avoid the unnecessary tissue damage.
Regarding research project, I designed the human centresome loci whose sequence is special to human and used to “straintyping” the human cells from mouse tissues. The human centersome region amplified well in the liver, lung, thymus as well as intra-abdomen metastatic tumors. Another exciting progress is in the two metastatic tumors from patient samples, one already past the immortalization point and grow out in vitro stem cell medium. So far only one paper reported they developed a primary colorectal cancer line generating lymph node metastasis from subcutaneous xenografts. While their metastasis is only limited in lymph nodes and did not metastasized to those fetal organs like liver and spleens which are the common locations clinical colorectal cancers invade. Therefore our lines are the first cases which can metastasize to internal fetal organs through subcutaneous injection. Although the orthotropic mouse models of colorectal metastasis into other organs from intra-intestinal injection are pretty mature, it is hard to image the metastasis process through deep abdomen and also hard to evaluate the therapeutic effects in the orthotopic tumor models. The subcutaneously metastasizing models could be used for imaging as well as treatment evaluation by tumor sizes. In the other hand, the lines could be gene profiling by entire exon sequencing for the potential mutants account for internal metastasis.
Another research direction also goes well in that we use the currently developed primary lines for drug screening. And we found some components can chemosensitize the KRAS mutant lines.

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