With the use of MRI, the lateral pelvic lymph node involvement can be predicted with high accuracy, allowing preoperative identification of patients who need radiotherapy or extensive surgery to escape recurrence.
Purpose: The aim of this study is to identify gene expression signatures that accompany dedifferentiation at the cancer invasion front in colorectal cancer. Experimental Design: Two types of colorectal cancer were selected. Both types were welldifferentiated adenocarcinomas at the superficial lesion. One type showed a dedifferentiated phenotype at the invasion front (typeA, 13 samples); the other showed almost no dedifferentiated cancer cells at the invasion front (type B, 12 samples). Laser microdissection was combined with a cDNA microarray analysis to investigate the superficial lesions and the invasion front in colorectal cancers. Results: Eighty-three genes were differentially expressed between types A and B in the superficial lesions, and the samples of superficial lesions were divided correctly into two clusters by these genes. Interestingly, the samples of the invasion front were also divided into the two same clusters by these genes. The text mining method selected 10 genes involved in potential mechanisms causing dedifferentiation of cancer cells at the invasion front. The potential mechanisms include the networks of transforming growth factor-h,Wnt, and Hedgehog signals. The expression levels of 10 genes were calculated by quantitative reverse transcription-PCR and 8 genes were confirmed to be significantly differentially expressed between two types (P < 0.05). The gene expression profiles of 8 genes divided 12 test cases into two clusters with one misclassification. Conclusions: The molecular mechanisms constructed with 8 genes from three networks of transforming growth factor-h, Wnt, and Hedgehog signals were found to correlate with dedifferentiation at the invasion front of colorectal cancer.
There are increasing reports showing the clinical significance of the p53 polymorphism status in terms of the response to chemotherapy. We investigated whether p53 polymorphism and mutation were associated with in vitro sensitivity to 5-fluorouracil (5-FU) in patients with colorectal cancer. Chemosensitivity to 5-FU was evaluated by the collagen gel droplet embedded culture drug sensitivity test. 5-FU sensitivity of tumor cells without inactive p53 mutation in the arginine/arginine (Arg/Arg) variant was significantly higher than that of tumor cells with or without inactive p53 mutation in other variants (p 5 0.022), whereas the 5-FU sensitivity of tumor cells with inactive p53 mutation in the Arg/Arg variant was significantly lower than that of tumor cells with or without inactive p53 mutation in other variants (p 5 0.002). In the Arg/Arg variant, apoptotic cells induced by 5-FU treatment in patients without inactive p53 mutation were more markedly increased than those in patients with inactive p53 mutation (p 5 0.037). Bax and Bcl-2 protein expressions in tumor tissue treated with 5-FU were associated with both 5-FU sensitivity and the apoptotic cell count. Our data show that the Arg/Arg genotype without inactive p53 mutation could be predictive of a more favorable response and the Arg/Arg genotype with inactive p53 mutation a less favorable response to chemotherapy using 5-FU in CRC. The combination of the p53 codon 72 polymorphism and p53 mutation status is a potential predictive marker of sensitivity to 5-FU in CRC.The p53 tumor suppressor gene encodes a nuclear protein that induces growth arrest or apoptosis in response to cellular stress. 1 Apoptosis is a fundamental mechanism by which DNA-damaging anticancer agents cause cytotoxicity. 2 p53 has a major function in transducing stress to the apoptotic machinery of cells, consistent with the importance of the p53 status as a determinant of the cellular response to DNA-damaging drugs. 3,4 The presence of an intact p53 function confers tumor sensitivity to DNA-damaging agents such as cisplatin. 5 However, p53 is mutated in at least 50% of human cancers. 6 The mutation site is widely distributed in DNA-binding domain including the amino acid part that is called hot spot as codons 175, 245, 248, 249, 273 and 282. In a recent analyses with a large number of patients, type of mutation (inactive TP53 mutations) and adjuvant treatment were identified as important factors in determining the prognostic significance of p53 mutation in colorectal cancer (CRC). 7,8 Another recent study has quantitated the functional activity of different p53 mutation with respect to their ability to transactivate target genes. There were 3 subtypes: mutants with no activity, mutants with significantly reduced but some residual activity and mutants with activity comparable with that of wild-type p53. 9 The most common p53 mutation in human tumors show a clear loss of transactivation activity. 10 We can designate p53 hot spot mutation as inactive p53 mutation. Inactive p53 mutation is impo...
This study demonstrated diabetes mellitus to be independently associated with perineal wound complications, and when the patients have diabetes mellitus, especially with a longer comorbid duration and longer operation time, the clinical path should be changed to reduce perineal wound complications.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.