Bo-Young Oh

siRNA targeting Livin decreases tumor in a xenograft model for colon cancer

AIM To evaluate the effect of silencing Livin gene expression with siRNA to apoptosis and proliferation in a colon cancer cell line. METHODS To investigate the anticancer effect of silencing Livin gene expression, we established an siRNA transfected cell line using the HCT116 colon cancer cell line. After confirming the successful transfection, MTT assay, flow cytometry and annexin V staining were employed to evaluate the antiapoptotic effect. To confirm the in vivo effect of Livin-siRNA, different doses of Livin-siRNA were injected into xenografted tumors in BALB/c nude mice model. RESULTS Livin expression was dramatically decreased after siRNA transfection, especially at 25 μmol/L of siRNA, but this suppression was not dose-dependent. The cell count at 18 h after transfection was significantly reduced as compared with controls (P < 0.01), but tended not to decrease proportionally depending on transfected dose or time. MTT assay revealed that silencing the Livin gene suppressed cellular proliferation at 18 h after transfection (P = 0.04); however, the inhibitory effect disappeared thereafter. Also, there was no significant difference in cellular proliferation depending on siRNA dose. The rate of apoptosis also increased with silencing of the Livin gene. In vivo, the tumor size significantly decreased after Livin-siRNA injection at 20 μmol/L concentration (P = 0.03). There were no significant body weight changes of mice after siRNA injection. Histologic examination revealed no significant toxic reaction in kidney, liver and brain of mice. CONCLUSION siRNA-mediated downregulation of Livin expression can induce apoptosis in colon cancer in vitro and in vivo, which suggests the possibility of new cancer therapeutics using siRNA.

Metastasis to the breast from colonic adenocarcinoma

A 63-year-old woman was referred to a breast surgeon with a breast mass discovered incidentally during follow-up study after colon cancer surgery. Invasive adenocarcinoma was revealed on core needle biopsy. Wide excision of the breast including the tumor was performed. On standard histological examination the tumor showed features of moderately differentiated adenocarcinoma. The immunohistochemistry study revealed positive results for cytokeratin (CK)20 and CDX2, but negative for CK7. These are typical characteristics for colon cancer. Considering her history of subtotal colectomy for sigmoid colon cancer, it is presumable that the mass in the breast was of colonic origin, and it was an extremely rare case of metastasis to the breast from primary colorectal neoplasm. Although the instance is rare, clinicians should keep the possibility of breast metastasis from colorectal cancer in mind for early and correct diagnosis.

Optimal Time of Initiating Adjuvant Chemotherapy After Curative Surgery in Colorectal Cancer Patients

Purpose Adjuvant chemotherapy is routinely recommended for locally advanced colorectal cancer (CRC). There are very few data for the optimal starting date of adjuvant chemotherapy after the surgery. This study aimed to evaluate the effectiveness of earlier adoption of adjuvant chemotherapy after curative surgery for stage III CRC. Methods In this study, 159 patients with stage III CRC, who had undergone a curative resection, were enrolled retrospectively. Patients were categorized into 3 groups representing different timings to initiate the chemotherapy; less than 2 weeks (group 1), 3 to 4 weeks (group 2), and more than 5 weeks (group 3). The overall survival rate (OS) and the relapse-free survival rate (RFS) were analyzed to evaluate the effectiveness of adjuvant chemotherapy. Results The 5-year OSs of the patients were 73.7% in group 1, 67.0% in group 2, and 55.2% in group 3. The 5-year RFSs of the patients were 48.8% in group 1, 64.7% in group 2, and 57.1% in group 3. There were no significant differences in either the OS or the RFS (P = 0.200, P = 0.405). Conclusion Starting chemotherapy earlier than 6 weeks after surgery does not show any significant difference. Thus, although adjuvant chemotherapy should preferably begin within 6 weeks, the starting date should not necessarily be hastened, and the patients general condition should be taken into consideration.

Psychological attitude to self-appraisal of stoma patients: prospective observation of stoma duration effect to self-appraisal

Purpose In recent years, many psychological problems in patients with stomas have been addressed in a number of studies. But there are only a few studies that use objective measures to take into account self-appraisal by patients with permanent or temporary stomas. The aim of this study is to compare the psychological attitude of patients with permanent and temporary stomas and to determine the most appropriate psychological supportive care. Methods Sixty-five patients, who received a stoma between January 2009 and March 2012, were classified into two groups with either permanent or temporary stomas and were observed prospectively. We developed a questionnaire with the aid of a psychiatrist to analyze the grade of psychological attitude of self-appraisal of patients. The questionnaire was categorized into three parts; body image scale, self-esteem scale, and depression scale. Patients responded to the questionnaire 4 weeks after the operation and the answers of each group were compared. Results Out of 65 patients, 42 received temporary stomas and 23 received permanent stomas. There was no significant mean difference between permanent and temporary stoma patients in the body image scale, the self-esteem scale, and the depression scale. However, patients with a permanent stoma tended to have a worse body image and lower self-esteem on some specific items within the questionnaires. Conclusion Patients with stomas have negative attitudes toward themselves and some meaningful differences were found between different types of stoma applied. Surgeons should be concerned about postoperative psychological support for patients with stomas.

Clinical Applications of Radio-Frequency Ablation in Liver Metastasis of Colorectal Cancer

Purpose The aim of this study is to evaluate long-term survival and prognostic factors for radio-frequency ablation (RFA) in colorectal liver metastases. Methods We retrospectively reviewed 35 colorectal liver metastases patients who underwent RFA between 2004 and 2008. We analyzed survival after RFA and prognostic factors for survival. Results Of the 35 patients, 23 patients were male and 12 were female. Their mean age was 62.40 ± 12.52 years. Mean overall survival was 38.8 ± 4.6 months, and mean progression free survival was 19.9 ± 3.4 months. Three- and 5-year overall survival rates were 42.7 ± 0.1% and 26.0 ± 0.1%, respectively. Three- and 5-year progression-free survival rates were 19.6 ± 0.1% and 4.9 ± 0.04%, respectively. Overall survival and progression-free survival were significantly improved in male and in patients with carcinoembryonic antigen (CEA) ≤ 100 ng/mL, carbohydrate antigen (CA) 19-9 ≤ 100 ng/mL, absence of extrahepatic disease, and a unilobar hepatic lesion. In addition, progression-free survival was improved in patients with a solitary hepatic lesion. On the multivariate analysis, significant survival factors were the absence of extrahepatic disease and the presence of a unilobar hepatic lesion. Conclusion RFA for colorectal liver metastases is an effective treatment option in male patients and in patients with CEA or CA19-9 ≤ 100, absence of extrahepatic disease, a solitary hepatic lesion, and a unilobar hepatic lesion.

Role of β1-Integrin in Colorectal Cancer: Case-Control Study.

Purpose In the metastatic process, interactions between circulating tumor cells (CTCs) and the extracellular matrix or surrounding cells are required. β1-Integrin may mediate these interactions. The aim of this study was to investigate whether β1-integrin is associated with the detection of CTCs in colorectal cancer. Methods We enrolled 30 patients with colorectal cancer (experimental group) and 30 patients with benign diseases (control group). Blood samples were obtained from each group, carcinoembryonic antigen (CEA) mRNA for CTCs marker and β1-integrin mRNA levels were estimated by using reverse transcription-polymerase chain reaction, and the results were compared between the two groups. In the experimental group, preoperative results were compared with postoperative results for each marker. In addition, we analyzed the correlation between the expressions of β1-integrin and CEA. Results CEA mRNA was detected more frequently in colorectal cancer patients than in control patients (P = 0.008). CEA mRNA was significantly reduced after surgery in the colorectal cancer patients (P = 0.032). β1-Integrin mRNA was detected more in colorectal cancer patients than in the patients with benign diseases (P < 0.001). In colorectal cancer patients, expression of β1-integrin mRNA was detected more for advanced-stage cancer than for early-stage cancer (P = 0.033) and was significantly decreased after surgery (P < 0.001). In addition, expression of β1-integrin mRNA was significantly associated with that of CEA mRNA in colorectal cancer patients (P = 0.001). Conclusion In conclusion, β1-integrin is a potential factor for forming a prognosis following surgical resection in colorectal cancer patients. β1-Integrin may be a candidate for use as a marker for early detection of micrometastatic tumor cells and for monitoring the therapeutic response in colorectal cancer patients.

The availability of computed tomography for pulmonary staging in colorectal cancer

Purpose Chest computed tomography is performed frequently for the preoperative pulmonary staging in colorectal cancers (CRCs) regardless of the result of chest x-ray (CXR) due to its high sensitivities and specificities. The advancement of CT technology detects more indeterminate lung lesions that may require further investigations, referrals and follow-up. The aim of this study was to suggest a guideline for performing chest CT for preoperative pulmonary staging in colorectal cancer. Methods We performed a retrospective analysis of the records of patients who had chest CT preformed without the evidence of metastasis on CXR for preoperative pulmonary staging. Results Of 21 patients with metastatic nodules on chest CT, 23.8% showed pulmonary metastasis on positron emission tomography, 47.6% showed extrapulmonary metastasis on preoperative evaluation and 61.9% showed elevated serum carcinoembryonic antigen level above 10 ng/mL. These results showed significant value compared to patients without metastatic nodules. But, in analyzing patients with or without indeterminate nodules in the three contents listed above, there was no significance. Conclusion In the patients with CRC who show normal CXR and exhibit positivity in PET, preoperative extrapulmonary metastasis and elevated serum CEA level above 10 ng/mL preoperatively, chest CT would be helpful in preoperative staging.