- Email: [email protected]
Sa1950 Derlin-1 Is Overexpressed in Human Colorectal Cancer and Protects Cancer Cells From Apoptosis
AGA Abstracts
Sa1948
Sa1950
Multiplex Helicobacter pylori Serology and Risk of Gastric Cardia and NonCardia Adenocarcinomas Ramin Shakeri, Reza Malekzadeh, Dariush Nasrollahzadeh, Farhad Islami, Masoud Sotoudeh, Angelika Michel, Gwen Murphy, Arash Etemadi, Hossein Poustchi, Tim Waterboer, Michael Pawlita, Paul J. Brennan, Paolo Boffetta, Sanford M. Dawsey, Farin Kamangar, Christian C. Abnet
Derlin-1 Is Overexpressed in Human Colorectal Cancer and Protects Cancer Cells From Apoptosis Zhining Fan Background: Previous studies have been shown that Derlin-1 is involved in human cancers, and it is complicated that Derlin-1 is identified to play an important role in different pathological processes of cancer. However, its expression pattern in human colon cancer and the molecular mechanism of Derlin-1 on colon cancer progression have not been well characterized. In the present study, we investigated the expression level of Derlin-1 in human colon tissues and colon cell lines and its role in human colon cancer. Methods: Specimen of human colon cancer and adjacent normal tissues from the same patients were collected for immunohistochemistry, colon cancer tissue microarrays (TMAs), and Western blot analysis, with antihuman derlin-1 antibody. The expression of derlin-1 in human colon cancer tissues was detected by Quantitative Reverse-Transcriptase Polymerase Chain Reaction (QrtPCR) and Western blot. A shRNA against derlin-1 was transfected into colon cancer cells to inhibit derlin-1 expression. The effects of derlin-1 knockdown on colon cancer cells proliferation and apoptosis were analysed by MTT and flow cytometry analysis. Results: The examination data demonstrated that Derlin-1 is overexpressed in human colon cancer tissues more than the adjacent normal colon tissues, and Derlin-1 overexpression is correlated with colon cancer differentiation, Dukes stage, invasion, lymph node metastasis, and poor overall survival. Knock down of Derlin-1 can trigger colon cancer cells apoptosis, and inhibit colon cancer cells proliferation. Conclusion: Derlin-1 is higher expression in colon cancer tissues than normal colon tissues, and Derlin-1 is closely related to colon cancer progression. Knock down of Derlin-1 can decrease cancer cells proliferation and increase apoptosis, indicated that Derlin-1 may serve as a therapeutic target for human colon cancer. Distribution of Derlin-1 Status in Colon Cancer According to Clinicopathological Characteristics
Background: A recently developed multiplex serology method has been used to identify new virulence factors of Helicobacter pylori. The results of associations with gastric cancer have not been consistent across studies, possibly due to differences in the studied populations and/or the genetic diversity of H. pylori. We aimed to investigate the association between seropositivity to fifteen different H. pylori antigens using the multiplex serology method and the risk of gastric cardia (GCA) and gastric non-cardia (GNCA) adenocarcinomas in northeastern Iran, where the population has both a high prevalence of H. pylori infection and a high incidence of gastric adenocarcinoma. Methods: We included 272 cases of gastric adenocarcinoma (142 GCA, 103 GNCA, and 22 unspecified tumors) and 524 controls who were individually matched to cases for age, sex, and place of residence in this populationbased case-control study. Seropositivity to H. pylori was assessed using both multiplex serology and H. pylori IgG ELISA (BioHit, Finland). Results: H. pylori positivity based on the whole-cell ELISA test and also multiplex serology assay; defined as recognizing antibodies to ≥ 4 antigens; were not significantly associated with any of study groups; and its positivity rate was generally lower in ELISA assay than multiplex serology; GCA cases (79.6% vs. 95.1%), GNCA cases (74.8% vs. 95.2%), and controls (82.4% vs. 94.7%). Of the 15 antibodies in the multiplex assay, 10 showed no significant association with all gastric adenocarcinoma, GCA, or GNCA; while CagA and VacA were associated with a significantly increased risk of these cancers in multivariate adjusted models. Conversely, GroEL and NapA were significantly associated with a reduced risk of all gastric adenocarcinoma and GNCA. Conclusion: Our study showed no association between ELISA test positivity and gastric cancer risk, which implies that this method should not be used for risk stratification and referral for H. pylori eradication. Rather, effective risk stratification would require further characterization of H. pylori strain exposure with virulence factors such as CagA and VacA antigens. Our finding regarding lower risk of gastric adenocarcinoma among GroEL and NapA antigen positive subjects deserves additional investigation. Sa1949 Methylated BCAT1 and IKZF1 DNA in Plasma As Novel Biomarkers for Colorectal Cancer Recurrence Erin L. Symonds, Scott Mansfield, Dileep Mangira, David Murray, Rohan T. Baker, Susanne K. Pedersen, Lawrence C. LaPointe, Graeme P. Young Background One million people are diagnosed with colorectal cancer (CRC) annually worldwide. While 66% of cases are suitable for curative surgery, 25-40% will develop metastatic disease subsequent to surgery. Survival rates are poor as recurrence is often detected too late for successful intervention. International guidelines recommend annual diagnostic imaging (e.g. CT and colonoscopy) for 5 years. In addition, biannual or quarterly blood measurements of the tumour marker carcinoembryonic antigen (CEA) are recommended as a means to guide accelerated diagnostic imaging for suspicion of recurrence. Monitoring of CEA levels are controversial due to a documented poor sensitivity for recurrent disease. We have developed a 2-gene blood test for detection of methylated DNA (BCAT1 and IKZF1) leaked from colonic tumours into circulation, with a sensitivity of 66% for CRC (any stage) and a specificity of 94%. We have demonstrated that the methylated genes disappear (73%) or are significantly reduced (20%) following CRC resection. Aims To estimate the correlation of the 2-gene blood test in post-resection CRC cases with recurrent disease as diagnosed by radiological imaging or colonoscopy. A secondary aim is to compare the positivity of the 2-gene blood test with CEA in post-surgery CRC patients with and without recurrence. Methods Blood was collected from CRC patients 6-60 months into their follow-up program (n=59, median age 70y, 70% male) and assayed for methylated BCAT1 and IKZF1 DNA. The primary cancer stages ranged from stage I to IV (n=12, n=19, n=24, n=2) with 2 unstaged. Any blood sample with the presence of methylated BCAT1 and/or IKZF1 DNA was considered positive. A subgroup of patients (n=36) was tested for both CEA and methylated BCAT1 and IKZF1 DNA levels in blood. Follow-up colonoscopic and CT investigations performed after the blood analysis were assessed for CRC recurrence (local or distant). Results The 2-gene blood test was positive in 19 of 59 (32%) patients during their post-resection follow-up period. Investigations identified 8 cases of recurrence, 4 cases suspicious for recurrence, 3 cases suggestive of other cancers (SCC, thyroid and bone) and 4 cases without evidence of recurrence. Of the 40 with a negative 2-gene result, 36 were confirmed as having no recurrence, 2 had recurrence and 2 were suspicious for recurrence. Of the sub-group (n=36) tested with CEA and the 2-gene blood test, 7 were confirmed to have recurrence, all were CEA negative but 6 (86%) were positive by the 2gene blood test (Table). Conclusions In this pilot study, the 2-gene blood test was positive in 75% of the confirmed/suspected CRC recurrence cases and in 10% of cases with no recurrence being evident at that time as assessed by other methods. Further investigations are required to confirm the utility of this blood test for regular surveillance post-resection.
AGA Abstracts
*P < 0.05 was considered statistically significant.
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Sa1952 Unraveling the Mechanisms Involved in Exercise Prevention of Colorectal Cancer: The Role of Skeletal Muscles Mart DeLaCruz, Anuj Chhaparia, Navneet Momi, Ramesh K. Wali, Hemant K. Roy Background: One largely underexplored epidemiological observation has been the striking (~25%) reduction in colorectal cancer (CRC) attributable to exercise (even after controlling for confounders such as obesity and diabetes) (Robsahm et al., Eur J Cancer Prev. 2013). Interventional trials suggest a reduction in colonic epithelial proliferation (McTiernan et al., CEBP 2006). However, the biological mechanisms remain unclear with most groups focused on increased insulin sensitivity. We hypothesized that skeletal muscle may potentially be secreting products that could impact the colon. In order to test this hypothesis we devised a unique co-culture system with skeletal muscle cells and CRC cell line HCT-116. Methods: Human skeletal muscle cell were stimulated with C-pace EP Culture Pacer for 24hrs. PhosphoAcetyl CoA Carboxylase (pACC) protein expression was assessed to confirm contraction. Skeletal muscle media from contracting skeletal muscle cells was concentrated with Amicon Ultra-0.5 centrifugal filter device and used to treat CRC cell line HCT-116 for 24 hrs. Protein was isolated for western blot analysis for assessment of phospho-MEK1/2, PCNA, cyclin D1, and phospho-Rb. Results: Skeletal muscle cell contraction was confirmed altered pACC protein expression. Treatment with contracted skeletal muscle cell concentrate was effective at reducing pMEK1/2 expression by ~30% (p=0.05). Consistent with this finding, proliferation marker PCNA was also reduced (46% reduction, p=0.05). Cell cycle regulators phosphoRb and cyclin D1 were markedly down-regulated with treatment (73% reduction, p=0.007, 86% reduction, p=0.005 respectively), providing some insight on the effects of our treatment on cell proliferation in HCT-116s. Conclusion: We have developed a novel system that may enable, for the first time, mechanistic studies to elucidate the role of skeletal muscle in CRC prevention. Our data indicates a secreted factor(s) from skeletal muscles that plays a role in the anti-proliferative effect that is a hallmark of exercise's anti-neoplastic properties. Studies are ongoing to better characterize and then isolate these proteins. The clinical implications of this work is potentially large including identifying a molecular target that could be mimicked by pharmacological agents. Furthermore, identifying this factor may allow development of assays to optimize the type (i.e. cardiovascular versus strength training) and intensity of exercise for anti-neoplastic activity against CRC and other exercise-modulated malignancies (e.g. breast, prostate, lung etc).
Derlin-1 is overexpressed in human colon cancer tissue by imapoptosismunohistochemistry. Survival analyses of patients with and without Derlin-1 overexpression.{BR}Derlin-1 is overexpressed in human colon cancer tissue by western blotting analysis and real-time qPCR.{BR}Derlin-1 plays a role in the proliferation and apoptosisof colon cancer cell Figure 1. Skeletal Muscle Cell treated HCT-116 Protein Expression. Sa1951 Sa1953
Circulating microRNA-203 Predicts Metastases, Early Recurrence, and Poor Prognosis in Human Gastric Cancer Yuji Toiyama, Hiroki Imaoka, Masato Okigami, Hiromi Yasuda, Susumu Saigusa, Masaki Ohi, Minako Kobayashi, Toshimitsu Araki, Koji Tanaka, Yasuhiro Inoue, Yasuhiko Mohri, Masato Kusunoki
Epigallocatechin-3-Gallate (EGCG) Targets Cancer Stem-Like Cells and Enhances 5-Fluorouracil Chemosensitivity in Chemoresistant Colorectal Cancer Hanh-My T. Tran, Oscar A. Tovar-Carmago, Shusuke Toden, Ajay Goel
Background: Epithelial-mesenchymal transition (EMT) manifests through downregulation of E-cadherin and successive loss of cell-to-cell adhesion, leading to a mesenchymal phenotype [12]. This contributes to accelerated invasiveness, dissemination, and metastasis of epithelial tumor cells in several carcinomas, including gastric cancer (GC). The miR-200 family (miR-200a, miR-200b, miR-200c, miR-141, and miR-429), and miR-203 inhibits the E-cadherin suppressor targets such as ZEB1, ZEB2, and SNAI2, which are important initiators of EMT in various types of cancer. Despite their involvement in metastasis, none of the previous studies has investigated the clinical significance of miR-200 family and miR-203 expression in serum of patients with GC. Aim: The aim of this study was to evaluate serum EMT-associated miRNAs (miR-200 family and miR-203) for metastatic and prognostic noninvasive biomarkers in GC. Methods: In the initial screening, we selected candidate miRNAs associated with metastasis by analyzing expression of the miR-200 family and miR203 in serum samples from 12 patients with Stage I and IV GC. The second phase involved independent validation of candidate miRNAs in serum from 130 patients with GC and 22 controls. Results: In the screening step, miR-203 was significantly suppressed in the serum
Background: Green tea has been used as a traditional medicine for treating cardiovascular disease, weight loss, and cancer prevention in Asian countries for centuries. Emerging evidence suggests epigallocatechin-3-gallate (EGCG), the most abundant and active catechin present in green tea, appears to have potent anti-tumorigenic properties. Resistance to cytotoxic chemotherapy is a major cause of mortality in colorectal cancer (CRC) patients. A small subset of cancer cells, termed "cancer stem cells" (CSC), are believed to be the major contributors of chemoresistance and tumor recurrence. Recently EGCG has been shown to suppress CSC growth and proliferation in various cancers, but whether EGCG can specifically target CSCs and can subsequently sensitize chemoresistant cells to various treatments in CRC remains unknown. Aim: We aimed to investigate the chemosensitizing effects of EGCG in 5-Fluorouracil (5FU)-resistant CRC cells and spheroid-derived CSCs, as well as interrogate the molecular mechanisms responsible for chemopreventive effects of EGCG. Methods: We established 5FU-resistant (5FUR) cell lines through continuous and dose-escalating treatment of these CRC cells with the chemotherapeutic drug over 9-12
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AGA Abstracts
AGA Abstracts
of patients with Stage IV compared with Stage I GC (p < 0.05). In contrast, no significant differences were observed in serum miR-200a and miR-429 expression between GC patients with Stage I and IV. Expression levels of the remaining miRNAs, (miR-200b, miR-200c, and miR-141) could not be determined in serum in our study. On the basis of these observations, we subsequently focused on validating and further exploring the clinical significance of miR-203 for noninvasive biomarkers. Validation analysis revealed that expression levels of serum miR-203 in GC patients were significantly lower than in normal controls (p < 0.0001) and expression levels of miR-203 decreased in accordance with tumor TNM stage progression (p < 0.0001). Serum miR-203 expression was significantly lower in GC patients with higher T stage, vessel invasion, and lymph node, peritoneal, and distant metastases. Kaplan-Meier analysis showed that GC patients with low miR-203 expression had significantly poorer OS and DFS than those with high miR-203 expression (p < 0.0001 and p = 0.021, respectively). Multivariate analysis revealed that low serum miR-203 expression was an independent predictive marker for lymph node, peritoneal, and distant metastases, and poor prognosis in GC, respectively. Conclusion: We demonstrated novel evidence of serum miR-203 expression as a robust noninvasive biomarker for prognosis and predictive metastasis in patients with GC.
Sa1948
Sa1950
Multiplex Helicobacter pylori Serology and Risk of Gastric Cardia and NonCardia Adenocarcinomas Ramin Shakeri, Reza Malekzadeh, Dariush Nasrollahzadeh, Farhad Islami, Masoud Sotoudeh, Angelika Michel, Gwen Murphy, Arash Etemadi, Hossein Poustchi, Tim Waterboer, Michael Pawlita, Paul J. Brennan, Paolo Boffetta, Sanford M. Dawsey, Farin Kamangar, Christian C. Abnet
Derlin-1 Is Overexpressed in Human Colorectal Cancer and Protects Cancer Cells From Apoptosis Zhining Fan Background: Previous studies have been shown that Derlin-1 is involved in human cancers, and it is complicated that Derlin-1 is identified to play an important role in different pathological processes of cancer. However, its expression pattern in human colon cancer and the molecular mechanism of Derlin-1 on colon cancer progression have not been well characterized. In the present study, we investigated the expression level of Derlin-1 in human colon tissues and colon cell lines and its role in human colon cancer. Methods: Specimen of human colon cancer and adjacent normal tissues from the same patients were collected for immunohistochemistry, colon cancer tissue microarrays (TMAs), and Western blot analysis, with antihuman derlin-1 antibody. The expression of derlin-1 in human colon cancer tissues was detected by Quantitative Reverse-Transcriptase Polymerase Chain Reaction (QrtPCR) and Western blot. A shRNA against derlin-1 was transfected into colon cancer cells to inhibit derlin-1 expression. The effects of derlin-1 knockdown on colon cancer cells proliferation and apoptosis were analysed by MTT and flow cytometry analysis. Results: The examination data demonstrated that Derlin-1 is overexpressed in human colon cancer tissues more than the adjacent normal colon tissues, and Derlin-1 overexpression is correlated with colon cancer differentiation, Dukes stage, invasion, lymph node metastasis, and poor overall survival. Knock down of Derlin-1 can trigger colon cancer cells apoptosis, and inhibit colon cancer cells proliferation. Conclusion: Derlin-1 is higher expression in colon cancer tissues than normal colon tissues, and Derlin-1 is closely related to colon cancer progression. Knock down of Derlin-1 can decrease cancer cells proliferation and increase apoptosis, indicated that Derlin-1 may serve as a therapeutic target for human colon cancer. Distribution of Derlin-1 Status in Colon Cancer According to Clinicopathological Characteristics
Background: A recently developed multiplex serology method has been used to identify new virulence factors of Helicobacter pylori. The results of associations with gastric cancer have not been consistent across studies, possibly due to differences in the studied populations and/or the genetic diversity of H. pylori. We aimed to investigate the association between seropositivity to fifteen different H. pylori antigens using the multiplex serology method and the risk of gastric cardia (GCA) and gastric non-cardia (GNCA) adenocarcinomas in northeastern Iran, where the population has both a high prevalence of H. pylori infection and a high incidence of gastric adenocarcinoma. Methods: We included 272 cases of gastric adenocarcinoma (142 GCA, 103 GNCA, and 22 unspecified tumors) and 524 controls who were individually matched to cases for age, sex, and place of residence in this populationbased case-control study. Seropositivity to H. pylori was assessed using both multiplex serology and H. pylori IgG ELISA (BioHit, Finland). Results: H. pylori positivity based on the whole-cell ELISA test and also multiplex serology assay; defined as recognizing antibodies to ≥ 4 antigens; were not significantly associated with any of study groups; and its positivity rate was generally lower in ELISA assay than multiplex serology; GCA cases (79.6% vs. 95.1%), GNCA cases (74.8% vs. 95.2%), and controls (82.4% vs. 94.7%). Of the 15 antibodies in the multiplex assay, 10 showed no significant association with all gastric adenocarcinoma, GCA, or GNCA; while CagA and VacA were associated with a significantly increased risk of these cancers in multivariate adjusted models. Conversely, GroEL and NapA were significantly associated with a reduced risk of all gastric adenocarcinoma and GNCA. Conclusion: Our study showed no association between ELISA test positivity and gastric cancer risk, which implies that this method should not be used for risk stratification and referral for H. pylori eradication. Rather, effective risk stratification would require further characterization of H. pylori strain exposure with virulence factors such as CagA and VacA antigens. Our finding regarding lower risk of gastric adenocarcinoma among GroEL and NapA antigen positive subjects deserves additional investigation. Sa1949 Methylated BCAT1 and IKZF1 DNA in Plasma As Novel Biomarkers for Colorectal Cancer Recurrence Erin L. Symonds, Scott Mansfield, Dileep Mangira, David Murray, Rohan T. Baker, Susanne K. Pedersen, Lawrence C. LaPointe, Graeme P. Young Background One million people are diagnosed with colorectal cancer (CRC) annually worldwide. While 66% of cases are suitable for curative surgery, 25-40% will develop metastatic disease subsequent to surgery. Survival rates are poor as recurrence is often detected too late for successful intervention. International guidelines recommend annual diagnostic imaging (e.g. CT and colonoscopy) for 5 years. In addition, biannual or quarterly blood measurements of the tumour marker carcinoembryonic antigen (CEA) are recommended as a means to guide accelerated diagnostic imaging for suspicion of recurrence. Monitoring of CEA levels are controversial due to a documented poor sensitivity for recurrent disease. We have developed a 2-gene blood test for detection of methylated DNA (BCAT1 and IKZF1) leaked from colonic tumours into circulation, with a sensitivity of 66% for CRC (any stage) and a specificity of 94%. We have demonstrated that the methylated genes disappear (73%) or are significantly reduced (20%) following CRC resection. Aims To estimate the correlation of the 2-gene blood test in post-resection CRC cases with recurrent disease as diagnosed by radiological imaging or colonoscopy. A secondary aim is to compare the positivity of the 2-gene blood test with CEA in post-surgery CRC patients with and without recurrence. Methods Blood was collected from CRC patients 6-60 months into their follow-up program (n=59, median age 70y, 70% male) and assayed for methylated BCAT1 and IKZF1 DNA. The primary cancer stages ranged from stage I to IV (n=12, n=19, n=24, n=2) with 2 unstaged. Any blood sample with the presence of methylated BCAT1 and/or IKZF1 DNA was considered positive. A subgroup of patients (n=36) was tested for both CEA and methylated BCAT1 and IKZF1 DNA levels in blood. Follow-up colonoscopic and CT investigations performed after the blood analysis were assessed for CRC recurrence (local or distant). Results The 2-gene blood test was positive in 19 of 59 (32%) patients during their post-resection follow-up period. Investigations identified 8 cases of recurrence, 4 cases suspicious for recurrence, 3 cases suggestive of other cancers (SCC, thyroid and bone) and 4 cases without evidence of recurrence. Of the 40 with a negative 2-gene result, 36 were confirmed as having no recurrence, 2 had recurrence and 2 were suspicious for recurrence. Of the sub-group (n=36) tested with CEA and the 2-gene blood test, 7 were confirmed to have recurrence, all were CEA negative but 6 (86%) were positive by the 2gene blood test (Table). Conclusions In this pilot study, the 2-gene blood test was positive in 75% of the confirmed/suspected CRC recurrence cases and in 10% of cases with no recurrence being evident at that time as assessed by other methods. Further investigations are required to confirm the utility of this blood test for regular surveillance post-resection.
AGA Abstracts
*P < 0.05 was considered statistically significant.
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Sa1952 Unraveling the Mechanisms Involved in Exercise Prevention of Colorectal Cancer: The Role of Skeletal Muscles Mart DeLaCruz, Anuj Chhaparia, Navneet Momi, Ramesh K. Wali, Hemant K. Roy Background: One largely underexplored epidemiological observation has been the striking (~25%) reduction in colorectal cancer (CRC) attributable to exercise (even after controlling for confounders such as obesity and diabetes) (Robsahm et al., Eur J Cancer Prev. 2013). Interventional trials suggest a reduction in colonic epithelial proliferation (McTiernan et al., CEBP 2006). However, the biological mechanisms remain unclear with most groups focused on increased insulin sensitivity. We hypothesized that skeletal muscle may potentially be secreting products that could impact the colon. In order to test this hypothesis we devised a unique co-culture system with skeletal muscle cells and CRC cell line HCT-116. Methods: Human skeletal muscle cell were stimulated with C-pace EP Culture Pacer for 24hrs. PhosphoAcetyl CoA Carboxylase (pACC) protein expression was assessed to confirm contraction. Skeletal muscle media from contracting skeletal muscle cells was concentrated with Amicon Ultra-0.5 centrifugal filter device and used to treat CRC cell line HCT-116 for 24 hrs. Protein was isolated for western blot analysis for assessment of phospho-MEK1/2, PCNA, cyclin D1, and phospho-Rb. Results: Skeletal muscle cell contraction was confirmed altered pACC protein expression. Treatment with contracted skeletal muscle cell concentrate was effective at reducing pMEK1/2 expression by ~30% (p=0.05). Consistent with this finding, proliferation marker PCNA was also reduced (46% reduction, p=0.05). Cell cycle regulators phosphoRb and cyclin D1 were markedly down-regulated with treatment (73% reduction, p=0.007, 86% reduction, p=0.005 respectively), providing some insight on the effects of our treatment on cell proliferation in HCT-116s. Conclusion: We have developed a novel system that may enable, for the first time, mechanistic studies to elucidate the role of skeletal muscle in CRC prevention. Our data indicates a secreted factor(s) from skeletal muscles that plays a role in the anti-proliferative effect that is a hallmark of exercise's anti-neoplastic properties. Studies are ongoing to better characterize and then isolate these proteins. The clinical implications of this work is potentially large including identifying a molecular target that could be mimicked by pharmacological agents. Furthermore, identifying this factor may allow development of assays to optimize the type (i.e. cardiovascular versus strength training) and intensity of exercise for anti-neoplastic activity against CRC and other exercise-modulated malignancies (e.g. breast, prostate, lung etc).
Derlin-1 is overexpressed in human colon cancer tissue by imapoptosismunohistochemistry. Survival analyses of patients with and without Derlin-1 overexpression.{BR}Derlin-1 is overexpressed in human colon cancer tissue by western blotting analysis and real-time qPCR.{BR}Derlin-1 plays a role in the proliferation and apoptosisof colon cancer cell Figure 1. Skeletal Muscle Cell treated HCT-116 Protein Expression. Sa1951 Sa1953
Circulating microRNA-203 Predicts Metastases, Early Recurrence, and Poor Prognosis in Human Gastric Cancer Yuji Toiyama, Hiroki Imaoka, Masato Okigami, Hiromi Yasuda, Susumu Saigusa, Masaki Ohi, Minako Kobayashi, Toshimitsu Araki, Koji Tanaka, Yasuhiro Inoue, Yasuhiko Mohri, Masato Kusunoki
Epigallocatechin-3-Gallate (EGCG) Targets Cancer Stem-Like Cells and Enhances 5-Fluorouracil Chemosensitivity in Chemoresistant Colorectal Cancer Hanh-My T. Tran, Oscar A. Tovar-Carmago, Shusuke Toden, Ajay Goel
Background: Epithelial-mesenchymal transition (EMT) manifests through downregulation of E-cadherin and successive loss of cell-to-cell adhesion, leading to a mesenchymal phenotype [12]. This contributes to accelerated invasiveness, dissemination, and metastasis of epithelial tumor cells in several carcinomas, including gastric cancer (GC). The miR-200 family (miR-200a, miR-200b, miR-200c, miR-141, and miR-429), and miR-203 inhibits the E-cadherin suppressor targets such as ZEB1, ZEB2, and SNAI2, which are important initiators of EMT in various types of cancer. Despite their involvement in metastasis, none of the previous studies has investigated the clinical significance of miR-200 family and miR-203 expression in serum of patients with GC. Aim: The aim of this study was to evaluate serum EMT-associated miRNAs (miR-200 family and miR-203) for metastatic and prognostic noninvasive biomarkers in GC. Methods: In the initial screening, we selected candidate miRNAs associated with metastasis by analyzing expression of the miR-200 family and miR203 in serum samples from 12 patients with Stage I and IV GC. The second phase involved independent validation of candidate miRNAs in serum from 130 patients with GC and 22 controls. Results: In the screening step, miR-203 was significantly suppressed in the serum
Background: Green tea has been used as a traditional medicine for treating cardiovascular disease, weight loss, and cancer prevention in Asian countries for centuries. Emerging evidence suggests epigallocatechin-3-gallate (EGCG), the most abundant and active catechin present in green tea, appears to have potent anti-tumorigenic properties. Resistance to cytotoxic chemotherapy is a major cause of mortality in colorectal cancer (CRC) patients. A small subset of cancer cells, termed "cancer stem cells" (CSC), are believed to be the major contributors of chemoresistance and tumor recurrence. Recently EGCG has been shown to suppress CSC growth and proliferation in various cancers, but whether EGCG can specifically target CSCs and can subsequently sensitize chemoresistant cells to various treatments in CRC remains unknown. Aim: We aimed to investigate the chemosensitizing effects of EGCG in 5-Fluorouracil (5FU)-resistant CRC cells and spheroid-derived CSCs, as well as interrogate the molecular mechanisms responsible for chemopreventive effects of EGCG. Methods: We established 5FU-resistant (5FUR) cell lines through continuous and dose-escalating treatment of these CRC cells with the chemotherapeutic drug over 9-12
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AGA Abstracts
AGA Abstracts
of patients with Stage IV compared with Stage I GC (p < 0.05). In contrast, no significant differences were observed in serum miR-200a and miR-429 expression between GC patients with Stage I and IV. Expression levels of the remaining miRNAs, (miR-200b, miR-200c, and miR-141) could not be determined in serum in our study. On the basis of these observations, we subsequently focused on validating and further exploring the clinical significance of miR-203 for noninvasive biomarkers. Validation analysis revealed that expression levels of serum miR-203 in GC patients were significantly lower than in normal controls (p < 0.0001) and expression levels of miR-203 decreased in accordance with tumor TNM stage progression (p < 0.0001). Serum miR-203 expression was significantly lower in GC patients with higher T stage, vessel invasion, and lymph node, peritoneal, and distant metastases. Kaplan-Meier analysis showed that GC patients with low miR-203 expression had significantly poorer OS and DFS than those with high miR-203 expression (p < 0.0001 and p = 0.021, respectively). Multivariate analysis revealed that low serum miR-203 expression was an independent predictive marker for lymph node, peritoneal, and distant metastases, and poor prognosis in GC, respectively. Conclusion: We demonstrated novel evidence of serum miR-203 expression as a robust noninvasive biomarker for prognosis and predictive metastasis in patients with GC.