• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1729-1732
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• 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
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• v.7 no.1
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• pp.1-4
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• 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.

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

• Journal of Digestive Cancer Research
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• v.10 no.2
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• pp.65-73
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• 2022

A breakthrough in immunotherapy has changed the outlook for metastatic colorectal cancer (mCRC) treatment as the immune surveillance evasion mechanism of tumor cells has been continuously elucidated. Immune checkpoint inhibitors (ICI), such as pembrolizumab, nivolumab, and ipilimumab, which block immune checkpoint receptors or ligands have been approved for the treatment of mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) mCRC based on numerous clinical studies. However, 50% of dMMR/MSI-H mCRC and most mismatch repair proficient/microsatellite stable mCRC remained unresponsive to current immunotherapy. Clinical trials on combination therapy that adds various treatments, such as target agents, chemotherapy, or radiation therapy to ICI, have been actively conducted to overcome this immunotherapy limitation. Further studies on safety and efficacy are needed although several trials presented promising data. Additionally, dMMR/MSI-H, tumor mutation burden, and programmed cell death ligand-1 expression have been studied as biomarkers for predicting the treatment response to immunotherapy, but the discovery and validation of more sensitively predictable biomarkers remained necessary. Thus, this study aimed to review recent studies on immunotherapy in mCRC, summarize the efficacy and limitation of immunotherapy, and describe the biomarkers that predict treatment response.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.4033-4037
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• 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
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• v.17 no.3
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• pp.1175-1179
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• 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.

• Investigative Magnetic Resonance Imaging
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• v.17 no.1
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• pp.8-18
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• 2013

Purpose : The purpose of this study was to find and categorize the various magnetic resonance imaging (MRI) findings of spinal metastases that correlate with the type of primary cancer. Materials and Methods: We retrospectively reviewed gadolinium-enhanced magnetic resonance images of 30 patients with 169 spinal metastatic lesions from lung cancer (n = 56), breast cancer (n = 29), colorectal cancer (n = 20), hepatocellular carcinoma (HCC) (n = 17), and stomach cancer (n = 47). The size, location, extent of invasion, signal intensity, margin, enhancement pattern, and osteoblastic or osteolytic characteristics of each metastatic tumor were analyzed. Results: The metastatic lesions from HCC were larger than those from the other primary tumors (P < 0.05) except for colorectal cancer (P = 0.268). Well-defined metastatic tumor margins were more frequently seen in lung cancer and breast cancer (P < 0.01). All but HCC showed a tendency to invade the vertebral body rather than the posterior elements (P < 0.02). Colorectal cancer and HCC showed a tendency toward extraosseous invasion without statistical significance. HCC showed a characteristic enhancement pattern of 'worms-in-a-bag'. Rim enhancement with a sclerotic center was only seen in spinal metastases from stomach cancer. Conclusion: Despite many overlapping imaging features, spinal metastases of various primary tumors display some characteristic MRI findings that can help identify the primary cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2473-2481
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• 2015

Colon cancer is one of the leading causes of cancer-associated death worldwide. The prognosis for advanced colorectal cancers remains dismal, mainly due to the propensity for metastatic progression. Accordingly, there is a need for effective anti-metastasis therapeutic agents. Since a great body of research has indicated anticancer effects for curcumin, we investigated the effects of dendrosomal curcumin (DNC) on cellular migration and adhesion of human SW480 cells and possible molecular mechanisms involved. Different methods were applied in this study including MTT, Scratch and adhesion assays as well as real-time PCR and transwell chamber assays. Based on the results obtained, DNC inhibits metastasis by decreasing Hef 1, Zeb 1 and Claudin 1 mRNA levels and can reduce SW480 cell proliferation with $IC_{50}$values of 15.9, 11.6 and $7.64{\mu}M$ at 24, 48 and 72h post-treatment. Thus it might be considered as a safe formulation for therapeutic purpose in colorectal cancer cases.

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

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.2019-2022
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• 2013

Purpose: To investigate the safety and efficacy of pemetrexed combined with chemotherapy as second or third line in patients with stage IV colorectal cancer (CRC). Patients and Methods: This trial was conducted to evaluate the effectiveness and safety of pemetrexed given to patients with recurrent or metastatic colorectal carcinoma who previously received 5-FU-based chemotherapy. All patients were required to have a histological diagnosis of colorectal adenocarcinoma with measurable metastatic disease and prior chemotherapy. Patients received pemetrexed at a dose of 500 $mg/m^2$ by 10 minute infusion on day 1, repeated every 21 days. Doses were modified depending on nadir counts. Combined chemotherapy included Oxaliplatin, Irinotecan and cis-platinum. Results: Thirty patients were enrolled and twenty-nine were evaluable for response. One patient did not have repeat radiological testing to determine response because he went off study after only one cycle of treatment for economic reasons. For 29 evaluable patients, 1 partial response, 6 stable disease and 22 progressive disease were recorded. Response rate was 3.45% (1/29). All responses occurred in patients receiving a starting dose of pemetrexed 500 $mg/m^2$. Median time to progression for all eligible patients was 2.5 months. The most common toxicities experienced were mild to moderate fever, hepatic damage, myelosuppression, nausea, vomiting, constipation, abdominal pain, diarrhea, and skin rash. Conclusion: Pemetrexed at 500 $mg/m^2$ given every three weeks combined with chemotherapy is associated with moderate response and good tolerability in patients with stage IV CRC.