The shape of the pelvic inlet may be useful for predicting the operative time.

Heat shock protein 27 (Hsp27) is a chaperone protein of low molecular weight that is produced in response to various stresses and has a cytoprotective function. In the present study we found that there is a strong correlation between sensitivity to 5-fluorouracil (5-FU) and the expression of Hsp27 in colorectal cancer. Apatorsen is an antisense oligonucleotide that targets Hsp27 and has various antitumor effects in some types of cancer, such as bladder and prostate. Although several clinical studies are currently studying apatorsen in many malignancies, to date no promising results have been reported for colorectal cancer. In the present study, we examined the impact of Hsp27 downregulation (via apatorsen) on 5-FU sensitivity in colon cancer both in vitro and in vivo. In vitro, apatorsen significantly decreased the levels of Hsp27 in a dose-dependent manner in human colon cancer SW480 cells. A cell proliferation assay revealed that although apatorsen did not inhibit tumor growth, it resulted in greater 5-FU sensitivity in comparison with treatment with OGX-411 (control). In vivo, intraperitoneal injection of apatorsen decreased the levels of Hsp27 in subcutaneous tumors in a xenograft mouse model using SW480 cells and enhanced 5-FU sensitivity, compared to controls. Although further research is warranted, the present study confirmed that concurrent treatment with Hsp27 knockdown using apatorsen and 5-FU could be a promising therapy for colon cancer.

Background/Aim: In previous work we showed that expression of heat-shock protein 27 (HSP27; encoded by HSPB1) was associated with inherent resistance to . However, the relationship between HSP27 and acquired resistance remains unknown. Materials and Methods: We generated an acquired resistance model (WiDr-R) of a colon cancer cell line by exposing WiDr cells to 5-FU. Cell viability assays under treatment with 5-FU, as well as down-regulation of HSP27 using small interfering HSP27 RNA, were performed. HSP27 mRNA and protein expression was analyzed using real-time polymerase chain reaction and western blotting. Results: 5-FU-acquired resistance induced overexpression of HSP27 mRNA and protein levels in WiDr-R cells. Furthermore, siRNA knockdown of HSP27 in WiDr-R cells reduced 5-FUacquired resistance. Conclusion: These findings demonstrate that HSP27 is associated with 5-FU resistance in human colon cancer cell cells and suggest that HSP27 regulation represents a novel approach to overcoming chemoresistance in colorectal cancer.Colorectal cancer (CRC) is a very common disease worldwide. In advanced cancer, systemic chemotherapy and surgery are key treatment approaches. Currently, systemic chemotherapy for CRC has progressed remarkably. 5-Fluorouracil (5-FU) is a classic and very important cytotoxic anticancer drug; this treatment is commonly combined with other cytotoxic drugs such as oxaliplatin, and irinotecan. Furthermore, a paradigm shift has occurred in the use of molecular target drugs. Administration of vascular endothelial growth factor inhibitors (bevacizumab/ramucirumab) and epidermal growth factor receptor (EGFR) inhibitors (cetuximab/panitumumab) has improved the prognosis of advanced unresectable or recurrent CRC by up to approximately 30 months (1-3).However, resistance to 5-FU-based chemotherapy, which is widely used to treat CRC, remains an insurmountable clinical challenge. Therefore, novel approaches to overcoming 5-FU resistance are required, for which several strategies and drugs have been identified (4-6). Heat-shock proteins, including heat-shock protein 27 (HSP27; encoded by HSPB1), act as molecular chaperones in protein-protein interactions under physiological conditions. Additionally, HSP27 expression is increased in various types of malignant diseases (7-9). Furthermore, a relationship between HSP27 overexpression and drug resistance has been reported (9-11). We have previously suggested that HSP27 is associated with 5-FU resistance in certain human colon cancer cell lines. Cell lines with higher levels of HSP27 expression showed a higher degree of 5-FU resistance compared to those with lower expression levels (12). Additionally, in experiments using cell lines with high HSP27 expression (inherently resistant to 5-FU according to our hypothesis), downregulation of HSP27 using small interfering RNA (siRNA) or short hairpin RNA reduced 5-FU resistance (12, 13). Furthermore, in the same setting, down-regulation of HSP27 using apatorsen, an antisense oligonucleotide that targets HSP27, reduced...

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