Background: It has been reported that COX-2 expression is associated with MMP-2 expression in thyroid and breast cancers, suggesting that MMPs are linked to COX-2-mediated carcinogenesis. Several polymorphisms within the MMP2 promoter region have been reported in cases with oncogenesis and tumor progression, especially in colorectal carcinogenesis. Materials and Methods: This research evaluated risk of association of the SNPs, including genes for COX-2 (AIG transition at +202) and MMP-2 (Crr transition at-1306), with colorectal cancer in 125 patients and 125 healthy controls. Results and Conclusions: Our data confirmed that MMP2 C-1306 T mutations were significantly more common in colon cancer patients than in our control Saudi population; p=O.0121. On the other hand in our study, there was no significant association between genotype distribution ofthe COX2 polymorphism and colorectal cancer; p=0.847. An elevated frequency ofthe mutated genotype in the control group as compared to the patients subjects indeed suggested that this polymorphism could decrease risk in the Saudi population. Our study confirmed that the polymorphisms that could affect the expressions of MMP-2 and COX-2 the colon cancer patients were significantly higher than that in the COX-2 negative group. The frequency of individuals with MMP2 polymorphisms in colon cancer patients was higher than individuals with combination of COX2 and MMP2 polymorphisms. Our study confirmed that individuals who carried the polymorphisms that could affect the expressions ofCOX2 are more susceptible to colon cancer. MMP2 regulatory polymorphisms could be considered as protective; further studies need to confirm the results with more samples and healthy subjects.
Purpose: To investigate clinicopathological features in patients with recurrent colorectal cancer within 1 year and more than 1 year after curative resection. Materials and Methods: We retrospectively evaluated 103 patients with disease recurrence before versus after 1 year of resection. Thirty-two patients (31%) were diagnosed with recurrence less than 1 year after curative resection for colorectal cancer (early recurrence) and 71 (69%) after more than 1 year (non-early recurrence). Results: The early recurrence group displayed a significantly lower overall survival rate for both colon cancer (p=0, 01) and rectal cancer (p<0.001). Inadequate lymph node dissection was a significant predictor for early relapse. There were no statistically significant differences in clinicopathological variables such as age, sex, primary tumor localization, stage, depth of invasion, lymphovascular invasion and perineural invasion between the early and non-early recurrence groups. However, a K-ras mutation subgroup was significantly associated with early recurrence (p<0.001). Conclusions: Poor survival is associated with early recurrence for patients undergoing resection for non-metastatic colorectal cancer, as well as K-ras mutation.
Purpose: To evaluate efficacy of radiofrequency ablation (RFA) in treating colorectal cancer patients with liver metastases. Methods: During January 2010 to April 2012, 56 colorectal cancer patients with liver metastases underwent RFA. CT scans were obtained one month after RFA for all patients to evaluate tumor response. (CR+PR+SD)/n was used to count the disease control rates (DCR). Survival data of 1, 2 and 3 years were obtained from follow up. Results: Patients were followed for 10 to 40 months after RFA (mean time, $25{\pm}10months$). Median survival time was 27 months. The 1, 2, 3 year survival rate were 80.4%, 71.4%, 41%, 1 % respectively. 3-year survival time for patients with CR or PR after RFA was 68.8% and 4.3% respectively, the difference was statistically significant. The number of CR, PR, SD and PD in our study was 13, 23, 11 and 9 respectively. Conclusions: RFA could be an effective method for treating colorectal cancer patients with liver metastases, and prolong survival time, especially for metastatic lesions less than or equal to 3 cm. But this result should be confirmed by randomized controlled studies.
Kara, Oguz;Duman, Berna Bozkurt;Kara, Banu;Erdogan, Seyda;Parsak, Cem Kaan;Sakman, Gurhan
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.
Background: Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide. Targeting autophagic cell death is emerging as a novel strategy in cancer chemotherapy. Aldose reductase (AR) catalyzes the rate limiting step of the polyol pathway of glucose metabolism; besides reducing glucose to sorbitol, AR reduces lipid peroxidation-derived aldehydes and their glutathione conjugates. A complex interplay between autophagic cell death and/or survival may in turn govern tumor metastasis. This exploratory study aimed to investigate the potential role of AR inhibition using a novel inhibitor Fidarestat in the regulation of autophagy in CRC cells. Materials and Methods: For glucose depletion (GD), HT-29 and SW480 CRC cells were rinsed with glucose-free RPMI-1640, followed by incubation in GD medium +/- Fidarestat ($10{\mu}M$). Proteins were extracted by a RIPA-method followed by Western blotting ($35-50{\mu}g$ of protein; n=3). Results: Autophagic regulatory markers, primarily, microtubule associated protein light chain (LC) 3, autophagy-related gene (ATG) 5, ATG 7 and Beclin-1 were expressed in CRC cells; glyceraldehyde-3 phosphate dehydrogenase (GAPDH) was used as an internal reference. LC3 II (14 kDa) expression was relatively high compared to LC3A/B I levels in both CRC cell lines, suggesting occurrence of autophagy. Expression of non-autophagic markers, high mobility group box (HMG)-1 and Bcl-2, was comparatively low. Conclusions: GD +/- ARI induced autophagy in HT-29 and SW-480 cells, thereby implicating Fidarestat as a promising therapeutic agent for colorectal cancer; future studies with more potent ARIs are warranted to fully dissect the molecular regulatory networks for autophagy in colorectal carcinoma.
Background: There is no suggested molecular indicator for the determination of which patients will benefit from anti-angiogenetic treatment in metastatic colorectal cancers. Materials and Methods: In this study, VEGF and $HIF-1{\alpha}$ expression and their clinical significance were studied in tumor tissues of patients with colorectal cancer receiving bevacizumab-based treatment. VEGF and $HIF-1{\alpha}$ were assessed by immunohistochemistry in the primary tumors of 53 metastatic colorectal cancer patients receiving chemotherapy in combination with first line bevacizumab. Results: The clinical benefit rate in the low-VEGF expression group was 38%, while it was 62% in the high expression group. While the median progression-free survival (PFS) was 10 months in the high-VEGF expression group, it was 8 months in the low-VEGF expression group (p = 0.009). The median overall survival (OS) was found to be 26 months vs 15 months. Thus, when VEGF was strongly expressed it was in favor of that group and the difference was statistically significant (p = 0.03). High VEGF expression rate was an independent factor that correlated with OS or PFS (p=0.016 and 0.009, respectively). Conclusions: The data showed that VEGF may have predictive value for determining the treatment of CRC.
Hassan, Muhammad Radzi Abu;Suan, Mohd Azri Mohd;Soelar, Shahrul Aiman;Mohammed, Noor Syahireen;Ismail, Ibtisam;Ahmad, Faizah
Asian Pacific Journal of Cancer Prevention
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v.17
no.7
/
pp.3575-3581
/
2016
Background: Cancer survival analysis is an essential indicator for effective early detection and improvements in cancer treatment. This study was undertaken to document colorectal cancer survival and associated prognostic factors in Malaysians. Materials and Methods: All data were retrieved from the National Cancer Patient Registry-Colorectal Cancer. Only cases with confirmed diagnosis through histology between the year 2008 and 2009 were included. Retrieved data include socio-demographic information, pathological features and treatment received. Survival curves were plotted using the Kaplan-Meier method. Univariate analysis of all variables was then made using the Log-rank test. All significant factors that influenced survival of patients were further analysed in a multivariate analysis using Cox' regression. Results: Total of 1,214 patients were included in the study. The overall 3- and 5-year survival rates were 59.1% and 48.7%, respectively. Patients with localized tumours had better prognosis compared to those with advanced stage cancer. In univariate analysis, staging at diagnosis (p<0.001), primary tumour size (p<0.001), involvement of lymph nodes (p<0.001) and treatment modalities (p=0.001) were found to be predictors of survival. None of the socio-demographic characteristics were found to exert any influence. In Cox regression analysis, staging at diagnosis (p<0.001), primary tumour size (p<0.001), involvement of lymph nodes (p<0.001) and treatment modalities (p<0.001) were determined as independent prognostic factors of survival after adjusted for age, gender and ethnicity. Conclusions: The overall survival rate for colorectal cancer patients in Malaysia is similar to those in other Asian countries, with staging at diagnosis, primary tumor size, involvement of lymph node and treatment modalities having significant effects. More efforts are needed to improve national survival rates in future.
Background: In colorectal cancer (CRC), 40-60% of patients develop metastasis. The epithelial-mesenchymal transition (EMT) is a pivotal and intricate process that increases the metastatic potential of CRC. The aim of this study was to investigate the effect of Korean Red Ginseng extract (RGE) on colorectal metastasis through inhibition of EMT and the metastatic abilities of CRC cells. Methods: To investigate the effect of RGE on the metastatic phenotypes of CRC cells, CT26 and HT29 cells were evaluated by using an adhesion assay, a wound-healing assay, an invasion assay, zymography, and real-time reverse transcription-polymerase chain reaction. Western-blot analysis was conducted to elucidate the molecular mechanisms of RGE, which showed an inhibitory effect on the transforming growth factor-${\beta}1$ ($TGF-{\beta}1$)-induced EMT in HT29 cells. Additionally, the antimetastatic effect of RGE was evaluated in a mouse model of lung metastasis injected with CT26 cells. Results: RGE decreased the adhesion and migration ability of the CT26 cells and TGF-${\beta}1$-treated HT29 cells. The invasion ability was also reduced by RGE treatment through the inhibition of matrix metalloproteinase-9 expression and activity. Moreover, RGE suppressed the TGF-${\beta}1$-induced EMT via TGF-${\beta}1$/Smad-signaling-mediated Snail/E-cadherin expression in HT29 cells and lung tissue in CT26 tumor-bearing mice. Conclusion: Our results demonstrated that RGE inhibited colorectal lung metastasis through a reduction in metastatic phenotypes, such as migration, invasion, and the EMT of CRC cells.
Kim, Tae Yeon;Cho, Jong Ho;Choi, Yong Soo;Kim, Hong Kwan;Kim, Jhin Gook;Shim, Young Mog
Journal of Chest Surgery
/
v.55
no.1
/
pp.37-43
/
2022
Background: The surgical strategy for single-stage resection of primary colorectal cancer (CRC) and synchronous pulmonary metastases remains a matter of debate. Methods: Perioperative data of patients who underwent single-stage resection of primary CRC and synchronous pulmonary metastases were compared to those of patients who underwent 2-stage resections. The demographic data, number of metastases, type of pulmonary and colorectal resections, operation time, blood loss, postoperative complications, morbidities, mortality, medical costs, and length of hospital stay were analyzed. Results: Twenty-two patients underwent single-stage resection of primary CRC and pulmonary metastases, while 27 patients underwent 2-stage resection. Tumor size and the number of pulmonary metastases were not significantly different between the 2 groups. The extent of pulmonary metastasectomy and abdominal procedures were similar in both groups, as was the thoracic surgical approach (video-assisted thoracic surgery vs. thoracotomy). However, open laparotomy was performed more frequently in the 2-stage group than in the single-stage group (p=0.045), which also had a longer total anesthetic time (p=0.013). The operation time, medical costs, estimated blood loss, complication rates, and severity were similar in both groups, but the length of hospital stay was shorter in the single-stage group (p<0.001). Conclusion: Single-stage colorectal and pulmonary resection shortened the overall hospital stay, with no significant changes in operation time, medical costs, hospital mortality, and morbidity. Therefore, single-stage resection could be a good surgical strategy in selected patients.
Kim, Myung-Se;Kim, Sung-Kyu;Kim, Jae-Hwang;Kwan, Koing-Bo;Kim, Heung-Dae
Radiation Oncology Journal
/
v.9
no.2
/
pp.265-270
/
1991
Colorectal cancer is the second most frequent malignant tumor in the United States and fourth most frequent tumor in Korea. Surgery has been used as a primary treatment modality but reported overall survivals after curative resection were from $20\%\;to\;50\%$. Local recurrence is the most common failure in the treatment of locally advanced colorectal cancer. Once recurrence has developed, surgery has rarely the role and the five year survival of locally advanced rectal cancer is less than $5\%$, in spite of massive combination therapy. Intraoperative radiotherapy (IORT) with or without external beam irradiation has been advocated for reducing local recurrence and improving survival. The recent report of local failure by this modality was only $5\%$, this indicated that significant improvement of local control could be achieved. We performed 6 cases of IORT for locally advanced colorectal cancer which is the first experience in Korea. Patient's eligibility, treatment applicator, electron energy, dose distribution on the surface and depth within the treatment field and detailed skills are discussed. We hope that our IORT protocol can reduce local failure and increase the long term survival significantly.
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