• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.12
• /
• pp.6397-6401
• /
• 2012

Background: No factor has thus far been identified to predict the efficacy of bevacizumab therapy for colorectal cancer. We here therefore studied PTEN, VEGF, HER2 and p53 by immunohistochemistry as possible prognostic and predictive factors. Materials and Methods: A total of 34 retrospectively collected tumor samples were evaluated, all from patients receiving bevacizumab-based regimens. VEGF-A, PTEN, HER2, p53 were assessed and data was compared with clinicopathologic characteristics of patients and the bevacizumab response rate. Results: In this study, the median age of the 34 metastatic colorectal cancer patients was 55.5 (24-75), twelve (35.3%) being women and 22 (64.7%) men. PTEN, VEGF, HER2, p53 expressions were compared with bevacizumab response and other chacteristics of disease. Statistical significant differences were not found between bevacizumab response rates and different expression levels of VEGF, PTEN, HER2 and p53 (respectively p=0.256, p=0.832, p=0.189, p=0.131). However, a survival difference was noted in the VEGF expression negative group (median OS:55 months; 95%CI, 22-88 months) (p=0.01). There was no statistically significant OS difference in other groups (PTEN p=0.6, HER2 p=0.189, p53 p=0.13). Conclusions: We did not find any predictive factor for BV therapy in our study. VEGF negative expression could be an important prognostic factor in metastatic colorectal carcinoma.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.9
• /
• pp.4033-4037
• /
• 2014

Emerging evidence has shown associations of microRNA-205 (miR-205) with crucial cell processes such as the epithelial-mesenchymal transition (EMT) and aberrant expression with tumorigenesis in many types of human malignancy. This prospective study characterized the contribution of miR-205 to the colorectal cancer (CRC) tumorigenesis. The real-time reverse transcription-polymerase chain reaction was used to examine miR-205 levels prospectively in 36 pairs of samples of CRC tissue and adjacent noncancerous tissue (>2 cm from cancer tissue). In addition, the relationship between miR-205 levels and clinicopathological features was explored. The capability of miR-205 to function as a tumor marker was also examined. miR-205 expression levels did not show significant changes overall. However, miR-205 was significantly downregulated in a group of CRC samples compared with matched noncancerous tissue samples. Moreover, decreased miR-205 correlated significantly with lymphatic metastasis. A receiver operating characteristic (ROC) curve also showed an optimum cut off point of $1.4{\times}10^{-3}$ to distinguish lymphatic metastatic CRCs from non-metastatic CRCs. Interestingly we found lymphatic metastasis in almost 80% of the depressed samples. This study suggested that miR-205 could be reduced in the majority of metastatic CRCs and the risk of CRC metastasis may be predicted by monitoring miR-205 in patient samples collected at the time of the initial diagnosis. Therefore, targeting miR-205 and its potential environmental activators might be a promising therapeutic option to prevent malignant progression toward metastasis.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.16
• /
• pp.6559-6564
• /
• 2014

Objective: To evaluate the efficacy and safety of bevacizumab in the treatment of patients with metastatic colorectal cancer (mCRC). Methods: In a single-center, observational study of 91 Chinese patients with mCRC who received bevacizumab in combination with chemotherapy was conducted. Objective response rates (ORRs), progression-free survival (PFS), overall survival (OS) and adverse events were recorded, and the relationships between various clinical factors and PFS or OS were evaluated by Cox proportional hazards models. Results: Treatment with bevacizumab and chemotherapy was effective and tolerable. Univariate analysis showed that PFS and OS were significantly associated with the Eastern Cooperative Oncology Group performance status (ECOG-PS) score, duration of bevacizumab exposure, and whether chemotherapy was continued after discontinuation of bevacizumab treatment. A multivariate analysis showed that the duration of bevacizumab exposure and whether chemotherapy was continued after discontinuation of bevacizumab were independent prognostic factors for PFS and OS. Conclusion: In Chinese mCRC population, the shorter the duration of exposure to bevacizumab and chemotherapy, the worse the prognosis is.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.8
• /
• pp.4117-4123
• /
• 2016

Background: Methylation of promoter 2 of the SHP1 gene is epithelial cell specific, with reported potential as a lymph node metastatic marker. Objective: To demonstrate SHP1-P2 methylation-specific quantitative PCR effectiveness in detecting colorectal cancer (CRC) DNA in lymph nodes. Materials and Methods: SHP1-P2 methylation levels were measured in lymph nodes of CRC patients and compared with pathological findings and patient prognosis. Results: Lymph nodes of CRC metastatic patients without microscopically detectable cancer cells had higher SHP1-P2 methylation levels than lymph nodes of controls (p<0.001). In addition, a higher SHP1-P2 methylation level was associated with a shorter duration until adverse disease events, metastasis, recurrence and death (r2 = 0.236 and p value = 0.048). Studying two cohorts of 74 CRC patients without microscopic lymph node metastases showed that only the cohort containing samples with high SHP1-P2 methylation levels had a significant hazard ratio of 3.8 (95%CI = 1.02 to 14.2). Conclusions: SHP1-P2 methylation PCR can detect CRC DNA in lymph nodes even if cancer cells are not visible under a microscope, confirming applicability as a potential universal lymph node metastatic marker.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.3
• /
• pp.1175-1179
• /
• 2016

The results of this study demonstrate the potential prognostic and predictive values of KRAS and BRAF gene mutations in patients with colorectal cancer (CRC). It has been proven that KRAS and BRAF mutations are predictive biomarkers for resistance to anti-EGFR monoclonal antibody treatment in patients with metastatic CRC (mCRC). We demonstrated the distribution of KRAS (codons 12, 13 and 61) and BRAF (codon 600) gene mutations in 50 mCRCs using direct sequencing and compared the results with clinicopathological data. KRAS and BRAF mutations were identified in 15 (30%) and 1 (2%) patients, respectively. We identified KRAS mutations in codon 12, 13 and 61 in 73.3% (11/15), 20% (3/15) and 6.67% (1/15) of the positive patients, respectively. The KRAS mutation frequency was significantly higher in tumors located in the ascending colon (p=0.043). Thus, we found that approximately 1/3 of the patients with mCRC had KRAS mutations and the only clinicopathological factor related to this mutation was tumor location. Future studies with larger patient groups should yield more accurate data regarding the molecular mechanism of CRC and the association between KRAS and BRAF mutations and clinicopathological features.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.4
• /
• pp.1729-1732
• /
• 2016

In the patients with metastatic colorectal cancer (mCRC), RAS testing is the first step to identify those that could benefit from anti-EGFR therapy. This study examined associations between KRAS mutations and clinicopathological and survival data in Iranian patients with mCRC. Between 2008 to2015 in a retrospective study, 83 cases of mCRC were referred to the Clinic of Medical Oncology. The mean follow-up was 45 months that there were 27 deaths. The 3 patients that did not complete follow-up were censored from the study. KRAS and NRAS were analyzed using allele-specific PCR primers and pyrosequencing in exons 2, 3 and 4. Multivariate survival analysis using Cox's regression model was used for affecting of variables on overall survival (OS). The mean age at diagnosis for patients was 57.7 (range, 18 to 80 years) and 61.4% were male. There was no significant different between prognostic factors and KRAS mutation with wild-type. Also, There was no significant different between KRAS mutation and KRAS wild-type for survival, but there was a significant different between KRAS 12 and 13 mutations for survival (HR 0.13, 95% CI 0.03-0.66, P=0.01). In conclusion, the prevalence of KRAS mutations in CRC patients was below 50% but higher than in other studies in Iran. As in many studies, patients with KRAS 12 mutations had better OS thn those with KRAS 13 mutation. In addition to KRAS testing, other biomarkers are needed to determine the best treatment for patients with mCRC.

• Journal of Digestive Cancer Reports
• /
• v.7 no.1
• /
• pp.1-4
• /
• 2019

It is important to choose the appropriate treatment option for patients with colorectal cancer (CRC), because it could affect the prognosis of patients. Chemotherapy is effective in prolonging survival and time to progression in patients with advanced CRC. Adjuvant chemotherapy have been reported to reduce the recurrence rate of colorectal cancer by 30% in patients with stage 3 or high risk of stage 2 CRC. Although palliative chemotherapy does not offer long-term benefits, as life expectancy remains below 12 months in most of those receiving treatment, recent developments in the treatment including target agents and immunotherapy have improved the median overall survival time in patients with metastatic CRC by up to 30 months. Chemotherapy for patients with CRC is classified into neoadjuvant, adjuvant, and palliative therapy according to the status of patients. In this review, I summarized the chemotherapy for patients with CRC, which applying in clinical practice.

• Journal of Chest Surgery
• /
• v.39 no.11 s.268
• /
• pp.838-843
• /
• 2006

Background: The lung is the most common site of metastatic colorectal cancer comprising 10% of all curative resection of colorectal cancer. The reported 5 year survival rate varies among institutions. The purpose of the present study was to present the retrospective analysis of colorectal metastatic lung cancer surgery at our institution. Material and Method: A total of 61 patients undergoing surgery for metastatic colorectal lung cancer between July 1996 and December 2003 were included in the present study. The stage of the primary colorectal cancer, site of pulmonary metastasis, method of lung resection, the number and size of the metastatic nodules, the recurrence rate, and survival were assessed. Result: The 3 and 5 year survival rates were 66% and 41%, respectively. No significant risk factors were identified among the studied variables by either univariate or multivariate analysis. The mean disease free survival rate was 17 months. The most common recurrent site was lung, and among these patients, 3 underwent a second operation and two are still alive. Conclusion: The results of the above data suggest that pulmonary resection of metastatic lung cancer in select patients after curative resection of colon cancer may be a good therapeutic option with the potential for excellent results.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.14
• /
• pp.5941-5944
• /
• 2014

Purpose: To highlight the potential factors that could predict the response rate of patients with metastatic colorectal cancer (mCRC) treated with pemetrexed combined chemotherapy after first- or second-line chemotherapy using the FOLFOX regimen. Materials and Methods: Between January 2007 and July 2014, 54 patients diagnosed and pathologically-confirmed with advanced colorectal cancer in Jiangsu Cancer Hospital and Research Institute, were enrolled. They received pemetrexed at a dose of $500mg/m^2$ by 10 minute infusion on day 1, repeated every 3 weeks. Doses were modified depending on nadir counts of blood cells. Combined chemotherapeutic agents included irinotecan, lobaplatin, carboplatin, oxaliplatin, gemcitabine, cis-platinum or bevacizumab. Multiple variables (age, sex, hemoglobin, platinum drugs combined, metastasis sites, LDH, ALP, CEA>40 ug/ml) reported earlier were selected. We used logistic regression analysis to evaluate relationships between these and tumor response. Results: On multivariable analysis, we found that age was significant in predicting the responsiveness to pemetrexed (p<0.05) combined with oxaliplatin. We did not find any other factors which were significantly associated with the response rate to chemotherapy with pemetrexed and irinotecan. Conclusions: By multivariate analysis, we found that age had significant impact on the responsiveness of pemetrexed when combined with oxaliplatin. Additional research based on genomic properties of host and tumors are needed to clarify markers for better selection of patients who could benefit from pemetrexed combined chemotherapy.

• Journal of Yeungnam Medical Science
• /
• v.34 no.2
• /
• pp.216-221
• /
• 2017

Background: This study was conducted to investigate preoperative carcinoembryonic antigen (CEA) as a prognostic factor in colorectal cancer. Methods: Between January 2000 and July 2011, 1298 patients with primary adenocarcinoma colorectal cancer without metastasis, who underwent curative resection were retrospectively identified. The patients were divided into two groups according to serum CEA level at primary diagnosis: a high CEA (HCEA) group (serum CEA ${\geq}6ng/mL$) and a normal CEA (NCEA) group (serum CEA <6 ng/mL). A 1:1 propensity score matching analysis was applied to reduce bias. Finally, 364 patients were enrolled in this study. Matched variables were age, gender, preoperative chemoradiotherapy, tumor site, cell differentiation and pathologic stage. Results: The clinicopathological characteristics of the two groups did not differ significantly difference. The systemic metastasis rate was 16.5% (30/182) and 25.3% (46/182) in the NCEA and HCEA groups, respectively (p=0.039). There were no significant differences in local recurrence or metastatic sites between groups. The 5-year disease-free survival (DFS) rate of the HCEA group was worse than that of the NCEA group; however, there was no significant difference in overall survival between the two groups. Conclusion: Elevated preoperative CEA was related to frequent systemic recurrence and low DFS. Therefore, elevated preoperative CEA could be considered a prognostic factor for worse clinical outcomes in patients with colorectal cancer.