Increasing numbers of alterations have been found in protooncogenes (e.g., ras, mir), as well as tumor suppressor genes (e.g., p53, Rb) in various types of tumors. The multiple mutations cannot be explained by the spontaneous mutation rate. It has been suggested that mutator phenotypes leading to the accumulation of these mutations may be required in the early stages of tumorigenesis. To test t...

Colorectal cancer is the second leading cause of mortality from cancer in the United States. Death from colorectal cancer usually results from metastatic disease to the liver. Complete surgical resection is the only potentially curative treatment option for metastatic colorectal cancer to the liver, with a five-year survival rate of approximately 30%-40%. The addition of adjuvant systemic or he...

BACKGROUND The Cub and Sushi Multiple Domains 1 (CSMD1) gene, located on the short arm of chromosome 8, codes for a type I transmembrane protein whose function is currently unknown. CSMD1 expression is frequently lost in many epithelial cancers. Our goal was to characterize the relationships between CSMD1 somatic mutations, allele imbalance, DNA methylation, and the clinical characteristics in ...

A potent modifying locus of intestinal tumorigenesis in the mouse was recently identified as secretory phospholipase A2 (sPLA2). The human homologue of sPLA2 maps to chromosome 1p35, a region frequently lost in human tumors. To evaluate the possibility that sPLA2 was a tumor suppressor gene that was the target of the 1p loss events, we identified polymorphisms within the human sPLA2 gene. Using...

Analysis of tumor markers focuses on expression in primary tumors with the assumption that this is representative of metastatic tumor, against which treatment is targeted. Few studies have compared the expression of such markers in primary and secondary tumors. In this study, several key genes involved in cell cycle regulation were investigated in colorectal tumors and corresponding lymph node ...

The major cause of death in colorectal cancer is related to liver metastasis. Although the metastatic process has been well studied, many aspects of the molecular genetic basis of metastasis remain unclear. Elucidation of the molecular nature of liver metastasis is urgent to improve the outcome of colorectal cancer. We analyzed the chronological gene expression profiles of 104 colorectal sample...

OBJECTIVE Mutation status of the KRAS gene in tumors has been shown to be a predictive biomarker of response to anti-epidermal growth factor receptor antibody therapy in patients with metastatic colorectal cancer. This retrospective analysis examined the association between efficacy and safety of the fully human anti-epidermal growth factor receptor antibody panitumumab and KRAS mutation status...

Alterations of the length of simple repetitive genomic sequences (microsatellite instability, MSI) characterize a distinct mechanism of colorectal carcinogenesis. Such MSI has been found to be associated with hereditary nonpolyposis colorectal cancer (HNPCC) that involves mutation of the human mismatch repair genes hMSH2 and hMLH1 as well as many sporadic cancers of most tissue types. Although ...

Fisetin (3,7,3',4'-tetrahydroxyflavone), which belongs to the flavonoid group of polyphenols and is found in a wide range of plants, has been reported to exhibit a number of biological activities in human cancer cells, including antioxidant, anti-inflammatory, antiangiogenic, anti-invasive and antiproliferative effects. Although previous in vitro studies have shown that fisetin treatment increa...

CDC4/FBXW7 is part of a ubiquitin ligase complex which targets molecules such as cyclin E, c-myc, and c-jun for destruction. CDC4 mutations occur in several cancer types and are best described in colorectal tumors. Knockout of CDC4 in vitro in colorectal cancer cells causes changes suggestive of chromosomal instability (CIN). In p53(+/-) mice, radiation-induced lymphomas show deletion or mutati...