PubMed · 15300616
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W Michael McDonnell, Jason A Dominitz. 2004. CT colonoscopy.. https://doi.org/10.1053/j.gastro.2004.06.045
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To review the preventive approaches for recurrence after curative resection of hepatic metastases from colorectal carcinoma, we have summarized all available publications reporting randomized control trials (RCTs) covered in PubMed. The treatment approaches presented above include adjuvant intrahepatic arterial infusion chemotherapy, systemic chemotherapy, neoadjuvant chemotherapy, and immunotherapy. Although no standard treatment has been established, several approaches present promising results, which are both effective and tolerable in post-hepatectomy patients. Intrahepatic arterial infusion chemotherapy should be regarded as effective and tolerable and it increases overall survival (OS) and disease-free survival (DFS) of patients, while 5-fluorouracil-based systemic chemotherapy has not shown any significant survival benefit. Fortunately chemotherapy combined with hepatic arterial infusion and intravenous infusion has shown OS and DFS benefit in many researches. Few neoadjuvant RCT studies have been conducted to evaluate its effect on prolonging survivals although many retrospective studies and case reports are published in which unresectable colorectal liver metastases are downstaged and made resectable with neoadjuvant chemotherapy. Liver resection supplemented with immunotherapy is associated with optimal results; however, it is also questioned by others. In conclusion, several adjuvant approaches have been studied for their efficacy on recurrence after hepatectomy for liver metastases from colorectal cancer (CRC), but multi-centric RCT is still needed for further evaluation on their efficacy and systemic or local toxicities. In addition, new adjuvant treatment should be investigated to provide more effective and tolerable methods for the patients with resectable hepatic metastases from CRC.
The OZF (ZNF146) protein is a 33 kDa Kruppel protein, composed solely of 10 zinc finger motifs. It is overexpressed in the majority of pancreatic cancers and in more than 80% of colorectal cancers. We found an interaction between OZF and the telomeric hRap1 protein with a yeast two-hybrid screen. hRap1 (TERF2IP) is an ortholog of the yeast telomeric protein, scRap1 originally identified as a regulator of telomere length. In HeLa cells, it interacts with TRF2, a telomere repeat binding factor whose inactivation causes a dysregulation of telomere length and structure. Immunoprecipitation with anti-hRap1 antibodies in conditions that allow the purification of proteins associated with hRap1, demonstrated that OZF binds to hRap1 in HeLa cells. Using deletion mutants, we mapped the interacting domain of each protein. The three zinc fingers at the C-terminus of OZF interact with a region of hRap1 located downstream of the coil domain. It involves a stretch of at least 25 amino acids at the C-terminus of hRap1 that interact with TRF2. This suggests that OZF overexpression in tumours may alter the balance between hRap1 and other telomeric proteins and therefore that OZF function may be linked to telomere regulation.
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