20 results on '"Chen, Yan"'
Search Results
2. Gut epithelial TSC1/mTOR controls RIPK3-dependent necroptosis in intestinal inflammation and cancer
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Xie, Yadong, Zhao, Yifan, Shi, Lei, Li, Wei, Chen, Kun, Li, Min, Chen, Xia, Zhang, Haiwei, Li, Tiantian, Matsuzawa-Ishimoto, Yu, Yao, Xiaomin, Shao, Dianhui, Ke, Zunfu, Li, Jian, Chen, Yan, Zhang, Xiaoming, Cui, Jun, Cui, Shuzhong, Leng, Qibin, Cadwell, Ken, Li, Xiaoxia, Wei, Hong, Zhang, Haibing, Li, Huabin, and Xiao, Hui
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Dextrans ,Colon cancer ,Inflammation ,Cancer ,Microbiota (Symbiotic organisms) ,Gastrointestinal diseases ,Colitis ,Inflammatory bowel diseases ,Epithelium ,Diseases ,Ubiquitin ,Sulfates ,Colorectal cancer ,Polysaccharides ,Health care industry - Abstract
Although Western diet and dysbiosis are the most prominent environmental factors associated with inflammatory bowel diseases (IBDs), the corresponding host factors and cellular mechanisms remain poorly defined. Here we report that the TSC1/mTOR pathway in the gut epithelium represents a metabolic and innate immune checkpoint for intestinal dysfunction and inflammation. mTOR hyperactivation triggered by Western diet or Tsc1 ablation led to epithelium necroptosis, barrier disruption, and predisposition to dextran sulfate sodium-induced colitis and inflammation-associated colon cancer. Mechanistically, our results uncovered a critical role for TSC1/mTOR in restraining the expression and activation of RIPK3 in the gut epithelium through TRIM11-mediated ubiquitination and autophagy-dependent degradation. Notably, microbiota depletion by antibiotics or gnotobiotics attenuated RIPK3 expression and activation, thereby alleviating epithelial necroptosis and colitis driven by mTOR hyperactivation. mTOR primarily impinged on RIPK3 to potentiate necroptosis induced by TNF and by microbial pathogen-associated molecular patterns (PAMPs), and hyperactive mTOR and aberrant necroptosis were intertwined in human IBDs. Together, our data reveal a previously unsuspected link between the Western diet, microbiota, and necroptosis and identify the mTOR/RIPK3/necroptosis axis as a driving force for intestinal inflammation and cancer., Introduction Inflammatory bowel diseases (IBDs), comprising Crohn's disease and ulcerative colitis, are chronic and relapsing inflammatory disorders manifested in the gastrointestinal (GI) tract (1, 2). Despite a continuous increase in [...]
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- 2020
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3. Colorectal Cancer Diagnostic Algorithm Based on Sub-Patch Weight Color Histogram in Combination of Improved Least Squares Support Vector Machine for Pathological Image
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Yang, Kai, Zhou, Bi, Yi, Fei, Chen, Yan, and Chen, Yingsheng
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- 2019
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4. Pathological Complete Response Following Neoadjuvant Tislelizumab Monotherapy in Treatment-Naive Locally Advanced, MMR-Deficient/MSI-High Ascending Colon Cancer: A Case Report.
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Hei, Yue, Yang, Ruixia, Kong, Shengnan, Zhang, Hongmei, and Chen, Yan
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COLON cancer ,BOWEL obstructions ,COLORECTAL cancer ,NEOADJUVANT chemotherapy ,COMPUTED tomography - Abstract
Although recent trials started the use of neoadjuvant immunotherapy (NIT) in instability-high (MSI-H) or mismatch repair deficient (dMMR) early-stage or locally advanced colorectal cancer (LACRC), little data on the treatment strategy of NIT has been shown, and whether the tirelizumab mono-immune checkpoint inhibitor (ICI) can be used as NIT for patients with LACRC has not been reported as yet. In this study we report on a locally advanced ascending colon cancer case with a history of incomplete intestinal obstruction which achieved a pathologic complete response (pCR) after treated with Tirelizumab as NIT. A 32-year-old man was diagnosed with locally advanced ascending colon cancer with MSI-H and dMMR. An incomplete intestinal obstruction accompanied with hyperpyrexia occurred unexpectedly and was eased by symptomatic treatment. There was no peritonitis or other acute complications. NIT (three cycles of Tirelizumab) was suggested by the MDT board and partial response was achieved according to CT scanning, and pCR was further revealed by postoperative pathology. A ctDNA clearance confirmed the R0 resection and some immunotherapy related predictors were also detected using the NGS method. Our case study contributes to the evidence on the feasibility, efficacy, and safety of f Tirelizumab as a mono ICI for an optional neoadjuvant therapy in patients with MSI-H/dMMR LACRC. [ABSTRACT FROM AUTHOR]
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- 2023
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5. Prognostic Value of Combined Preoperative Carcinoembryonic Antigen and Prognostic Nutritional Index in Patients With Stage II–III Colon Cancer
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Chen-Yan Long, Shao-Long Lu, Yi Chen, Gang Liu, Chang Zhao, Yan-Song Xu, Hua-Ge Zhong, Ling-Xu Huang, and Zheng Liang
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Oncology ,Prognostic variable ,medicine.medical_specialty ,Multivariate analysis ,RD1-811 ,Colorectal cancer ,nomogram ,03 medical and health sciences ,0302 clinical medicine ,Carcinoembryonic antigen ,Internal medicine ,medicine ,Stage (cooking) ,Original Research ,Tumor marker ,biology ,business.industry ,Cancer ,Nomogram ,medicine.disease ,nutritional status ,colon cancer ,030220 oncology & carcinogenesis ,tumor marker ,biology.protein ,030211 gastroenterology & hepatology ,Surgery ,prognosis ,business - Abstract
Background: Tumor status can affect patient prognosis. Prognostic nutritional index (PNI), as a nutritional indicator, is closely related to the prognosis of cancer. However, few studies have examined the combined prognostic value of CEA and PNI in patients. This study investigated the relationship between CEA/PNI and prognosis of colon cancer patients.Methods: A total of 513 patients with stage II–III colon cancer who underwent curative resection at two medical centers from 2009 to 2019 were included. Clinicopathological factors were assessed and overall survival (OS) was assessed in a cohort of 413 patients. Multivariate analysis was used to identify independent prognostic variables to construct histograms predicting 1-year and 3-year OS. Data from 100 independent patients in the validation group was used to validate the prognostic model.Results: The median OS time was 33.6 months, and mortality was observed in 54 patients. Multivariate analysis revealed that preoperative CEA/PNI, lymph node metastasis, peripheral nerve invasion, operation mode, and postoperative chemotherapy were independent factors for prognosis evaluation and thus were utilized to develop the nomogram. The C-index was 0.788 in the learning set and 0.836 in the validation set. The calibration curves reached favorable consensus among the 1-, 3-year OS prediction and actual observation.Conclusion: The combined use of CEA and PNI is an independent prognostic factor and thus can serve as a basis for a model to predict the prognosis of patients with stage II–III colon cancer.
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- 2021
6. Surgical site infection after intracorporeal anastomosis for left-sided colon cancer: study protocol for a non-inferiority multicenter randomized controlled trial (STARS).
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He, Liang, Li, Meng, Zhang, Jia-xin, Tong, Wei-hua, Chen, Yan, and Wang, Quan
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SURGICAL site infections ,COLON cancer ,SURGICAL anastomosis ,SURGICAL complications ,NOSOCOMIAL infections ,DEEP brain stimulation ,RESEARCH funding ,CLINICAL trials ,COLON tumors ,LONGITUDINAL method ,RESEARCH ,SOCIAL networks ,ARTHRITIS Impact Measurement Scales - Abstract
Background: Surgical site infection (SSI), as one of the most common hospital-acquired infection, is usually associated with increased morbidity, mortality, and health care burden. SSI is a significant perioperative complication after colon cancer surgery, particularly for left-sided colon cancer. This paper describes the background and design of the "Surgical Site Infection after intracorporeal anastomosis for Left-sided Colon Cancer: study protocol for a non-inferiority multicenter Randomized Controlled Trial (STARS)." The STARS trial aims to compare the incidence of SSI after intracorporeal anastomosis and extracorporeal anastomosis after radical resection of colon cancer and to explore the risk factors of SSI.Methods: A total of 354 left colon cancer patients from 8 hospitals in China will be enrolled in this multi-center randomized controlled study. The primary outcome of this study is the incidence of SSI 30 days after left-sided colon cancer surgery. Secondary outcome measures include operation time, blood loss, conversion rate, incidence of perioperative complications, completeness of resection, number of lymph nodes collected and postoperative recovery characteristics, 3-year disease-free survival, and 5-year overall survival. The first patient was enrolled in January 2021.Discussion: To our knowledge, this is the first prospective multicenter study to investigate whether there is a difference in the SSI incidence after intracorporeal and extracorporeal anastomosis for left-sided colon cancer in China. The results may provide more evidence that supports performing total laparoscopic left-sided colon cancer surgery.Trial Registration: The trial has been registered on ClinicalTrials.gov website (ID: NCT04201717). Registered on September 22, 2020. [ABSTRACT FROM AUTHOR]- Published
- 2022
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7. Characteristics of Prognostic Programmed Cell Death–Related Long Noncoding RNAs Associated With Immune Infiltration and Therapeutic Responses to Colon Cancer.
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Chen, Yan, Zhang, Yue, Lu, Jiayi, Liu, Zhongchen, Zhao, Shasha, Zhang, Mengmei, Lu, Mingzhi, Xu, Wen, Sun, Fenyong, Wu, Qi, Zhong, Qi, and Cui, Zhongqi
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LINCRNA ,COLON cancer ,APOPTOSIS ,PROGNOSIS ,PROGNOSTIC models - Abstract
Programmed cell death (PCD) plays an important role in the onset and progression of various cancers. The molecular events surrounding the occurrence of abnormally expressed long noncoding RNAs (lncRNAs) leading to colon cancer (CC) have become a focus. We comprehensively evaluated the roles of PCD-related lncRNAs in the clinical management of CC and their immune responses. Therefore, we screened 41 prognostic PCD-related lncRNAs in The Cancer Genome Atlas database using co-expression analysis and assigned patients to groups according to the results of cluster analysis. The immune response and functions of cluster 2 were substantially suppressed, which might explain the poor prognosis in this group. A prognostic model comprising eight PCD-related lncRNAs was developed, and its effectiveness was verified using an external database. High-and low-risk groups had different epigenetic modifications and changes in immune cell infiltration. Patients in the high-risk group were resistant to immunotherapy and various chemotherapeutic drugs. Studies in vitro and in vivo further confirmed a carcinogenic role of the lncRNA U62317.4. Our findings of the prognostic value of PCD-related lncRNAs revealed their important roles in immune response disorders, thus providing valuable insights into the clinical management and molecular mechanisms of CC. [ABSTRACT FROM AUTHOR]
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- 2022
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8. The Circumferential Resection Margin Is a Prognostic Predictor in Colon Cancer.
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Tang, Xin-Yi, Huang, Meng-Xi, Han, Si-Qi, Chang, Yue, Li, Zhi-Ping, Kao, Xiao-Ming, Chen, Yan-Yan, Liu, Chao, Huang, Ya-Di, Chen, Yi-Tian, Lei, Zeng-Jie, and Chu, Xiao-Yuan
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COLON cancer ,PROPENSITY score matching ,ESOPHAGEAL cancer ,CHI-squared test ,CANCER patients ,RECTAL cancer - Abstract
Objective: This study aimed to investigate the potential value of circumferential resection margin (CRM) in colon cancer prognostics. Summary Background Data: CRM has been extensively studied as an important prognostic factor in rectal and esophageal cancer, but not in colon cancer. Methods: Data from 6,681 CRM-positive patients and 25,908 CRM-negative patients diagnosed with colon cancer in 2010–2015 were obtained from the Surveillance, Epidemiology, and End Results database. Statistical analysis methods utilized included the chi-square test, Kaplan-Meier estimates, Cox proportional, and X-tile software analyses. Results: After propensity score matching, CRM positivity was found to be negatively related with survival (P < 0.001). X-tile software identified 0 and 30 mm as optimal cutoff values (P < 0.001) for prognosis, which was applicable only in stage II–IV patients. A 20 and 33% risk decrease were observed in patients with CRM between 0 and 30 mm [95% confidence interval (CI) = 0.76–0.84], and larger than 30 mm (95% CI = 0.62–0.71), respectively. Chemotherapy strongly benefited prognosis with a hazard ratio of 0.36 (95% CI = 0.34–0.38) for overall survival (OS). Patients with a CRM value of 0–30 mm seemed to benefit most from chemotherapy compared with other groups. CRM and number of regional lymph nodes are independent risk factors, and the latter is a good substitute for CRM in AJCC stage I patients. Conclusion: CRM positivity is a strong unfavorable survival indicator for colon cancer patients. A better outcome is expected with CRM values larger than 30 mm. This cutoff value only applied to stage II–IV patients. For stage I patients, number of regional lymph nodes is a good substitute to predict survival. Chemotherapy was another favorable prognostic factor, especially for patients with a CRM value between 0 and 30 mm. [ABSTRACT FROM AUTHOR]
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- 2020
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9. Decreasing acute toxicity and suppressing colorectal carcinoma using Sorafenib-loaded nanoparticles.
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Li, Ningxi, Chen, Yan, Sun, Huimin, Huang, Tingwenli, Chen, Tianyu, Jiang, Yichun, Yang, Qian, Yan, Xiaoyan, and Wu, Min
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SORAFENIB ,NANOCARRIERS ,DRUG side effects ,COLON cancer ,APOPTOSIS - Abstract
Objective: A polymer-based nanoparticle was constructed to target sorafenib delivery to colorectal carcinoma cells and decrease the side effects of the drug. Methods: Sorafenib-loaded nanoparticles (S-NPs) based on PEG-PLGA were prepared using a double emulsion solvent evaporation method. The properties of S-NPs were evaluated and then their effects on the viability of colorectal cancer cells and normal human cells were assessed. The mechanism of S-NP internalization was explored using cellular uptake assays and in vitro fluorescence confocal imaging. Acute toxicity of sorafenib on its own or within S-NPs was assessed in mice. Results: S-NPs showed high drug loading and entrapment efficiencies, they did not cause extensive hemolysis, and they efficiently inhibited growth of colorectal cancer cell lines and human umbilical vein endothelial cells. S-NPs showed lower acute toxicity than the free drug. Conclusions: Loading sorafenib into nanoparticles can enhance its uptake by colorectal cancer cells and decrease its acute toxicity. [ABSTRACT FROM AUTHOR]
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- 2020
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10. The role of tissue and serum carcinoembryonic antigen in stages I to III of colorectal cancer—A retrospective cohort study.
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Tong, Guojun, Xu, Wei, Zhang, Guiyang, Liu, Jian, Zheng, Zhaozheng, Chen, Yan, Niu, Pingping, and Xu, Xuting
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CARCINOEMBRYONIC antigen ,COLON cancer ,CANCER invasiveness ,TUMORS ,POSTOPERATIVE care ,COHORT analysis ,PROGNOSIS - Abstract
Purpose: Tissue carcinoembryonic antigen (t‐CEA) and serum carcinoembryonic antigen (s‐CEA) expression profiles are the most useful tumor markers for the diagnosis and evaluation of colorectal cancer (CRC) worldwide; however, their roles in CRC progression remain controversial. This study aimed to compare the prognostic values of both s‐CEA and t‐CEA in CRC. Methods: A total of 517 patients from January 2006 to December 2010 with stages I‐III CRC were retrospectively examined, with 5‐year postoperative follow‐up and death as end‐points. T‐CEA expression, s‐CEA expression, and clinical pathological parameters were inputted into the SPSS 21.0 software. The Kaplan‐Meier method was used to analyze the 5‐year disease‐free survival (DFS) rate of patients in different tumor node metastasis (TNM) stages based on t‐CEA and s‐CEA expression. Results: Tumor differentiation and the number of positive lymph node harvests were significantly different among the t‐CEA groups (P < 0.001, P = 0.002); however, clinicopathological features showed no significant difference. The groups with high s‐CEA and t‐CEA expression had a significantly poorer prognosis than those with low s‐CEA (P = 0.021) and t‐CEA (P < 0.01) expression, respectively. The multivariate analysis demonstrated that t‐CEA was an independent prognostic factor in CRC (P < 0.001), but s‐CEA was not (P = 0.339). The 5‐year disease‐free survival rates among the t‐CEA groups were significantly different in stages I, II, and III of CRC (P = 0.001, P < 0.001, P < 0.001), whereas in the s‐CEA groups, this difference was observed only in stage III (P = 0.014). Conclusion: This study shows that postoperative t‐CEA expression is an independent factor associated with poorer CRC prognosis and has a higher prognostic value than that of preoperative s‐CEA expression. Tissue carcinoembryonic antigen (t‐CEA)expression and serum carcinoembryonic antigen (s‐CEA) expression of colorectal carcinoma (CRC) are the most useful tumor markers for the diagnosis and evaluation of prognosis, but the role remains controversial. The objective of this study was to compare the prognostic value of CEA both in serum and tumor tissue in CRC. [ABSTRACT FROM AUTHOR]
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- 2018
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11. Severe Intestinal Inflammation in the Small Intestine of Mice Induced by Controllable Deletion of Claudin-7.
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Li, Wen-Jing, Xu, Chang, Wang, Kun, Li, Teng-Yan, Wang, Xiao-Nan, Yang, Hui, Xing, Tiaosi, Li, Wen-Xia, Chen, Yan-Hua, Gao, Hong, and Ding, Lei
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ENTERITIS ,CLAUDINS ,LABORATORY mice ,TUMOR suppressor genes ,TIGHT junctions ,COLON cancer ,HYPERPLASIA ,ADENOMA ,ANIMAL experimentation ,BIOLOGICAL models ,CELL membranes ,COMPARATIVE studies ,IMMUNOHISTOCHEMISTRY ,SMALL intestine ,INTESTINAL tumors ,RESEARCH methodology ,MEDICAL cooperation ,MEMBRANE proteins ,MICE ,GENETIC mutation ,RESEARCH ,RESEARCH funding ,SCANNING electron microscopy ,TAMOXIFEN ,WESTERN immunoblotting ,PHENOTYPES ,EVALUATION research - Abstract
Background: As a potential tumor suppressor gene, Claudin-7 (Cldn7), which is a component of tight junctions, may play an important role in colorectal cancer occurrence and development.Aims: To generate a knockout mouse model of inducible conditional Cldn7 in the intestine and analyze the phenotype of the mice after induction with tamoxifen.Methods: We constructed Cldn7-flox transgenic mice and crossed them with Villin-CreERT2 mice. The Cldn7 inducible conditional knockout mice appeared normal and were well developed at birth. We induced Cldn7 gene deletion by injecting different dosages of tamoxifen into the mice and then conducted a further phenotypic analysis.Results: After induction for 5 days in succession at a dose of 200 µl tamoxifen in sunflower oil at 10 mg/ml per mouse every time, the mice appeared dehydrated, had a lower temperature, and displayed inactivity or death. The results of hematoxylin-eosin staining showed that the intestines of the Cldn7 inducible conditional knockout mice had severe intestinal defects that included epithelial cell sloughing, necrosis, inflammation and hyperplasia. Owing to the death of ICKO mice, we adjusted the dose of tamoxifen to a dose of 100 µl in sunflower oil at 10 mg/ml per mouse (aged more than 8 weeks old) every 4 days. And we could induce atypical hyperplasia and adenoma in the intestine. Immunofluorescent staining indicated that the intestinal epithelial structure was destroyed. Electron microscopy experimental analysis indicated that the intercellular gap along the basolateral membrane of Cldn7 inducible conditional knockout mice in the intestine was increased and that contact between the cells and matrix was loosened.Conclusions: We generated a model of intestinal Cldn7 inducible conditional knockout mice. Intestinal Cldn7 deletion induced by tamoxifen initiated inflammation and hyperplasia in mice. [ABSTRACT FROM AUTHOR]- Published
- 2018
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12. Lower Expression of SPRY4 Predicts a Poor Prognosis and Regulates Cell Proliferation in Colorectal Cancer.
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Zhou, Xiaoling, Xie, Sheng, Yuan, Chunluan, Jiang, Li, Huang, Xiaoyan, Li, Liumei, Chen, Yan, Luo, Lichuan, Zhang, Jianxuan, Wang, Daogang, Liu, Lijian, Shi, Wei, Han, Liang, Tang, Nong, and Ji, Yunxi
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COLON cancer ,CELL proliferation ,CELL growth ,CELLULAR signal transduction ,CANCER invasiveness - Abstract
Background/Aims: Colorectal cancer (CRC) is the third most common type of cancer worldwide. Sprouty proteins are modulators of mitogeninduced signal transduction processes and therefore can influence the process of cancerogenesis. The encoded protein of Sprouty homolog 4 (SPRY4) is associated with various human cancers. However, its biological role and clinical significance in CRC development and progression are unknown. Methods: The aim of this study was to evaluate the expression and biological role of SPRY4 in colorectal cancer. qRT-PCR was performed to investigate the expression of SPRY4 in tumor tissues and corresponding non tumor colorectal tissues from 70 patients. The effect of SPRY4 on proliferation was evaluated by MTT and colony formation assays. CRC cells transfected with SPRY4 were injected into nude mice to study the effect of SPRY4 on tumorigenesis in vivo. Results: The lower expression of SPRY4 was remarkably correlated with deep tumor invasion and advanced TNM stage. Multivariate analyses revealed that SPRY4 expression served as an independent predictor for overall survival. Using 5-aza treatment, we also observed that SPRY4 expression can be affected by DNA methylation. Further experiments revealed that overexpressed SPRY4 significantly inhibited CRC cell proliferation both in vitro and in vivo. Conclusion: Our study demonstrated that SPRY4 is involved in the development and progression of colorectal cancer by regulating cell proliferation and shows that SPRY4 may be a potential diagnostic and prognostic target in patients with colorectal cancer. [ABSTRACT FROM AUTHOR]
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- 2016
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13. Relationships Between p16 Gene Promoter Methylation and Clinicopathologic Features of Colorectal Cancer: A Meta-Analysis of 27 Cohort Studies.
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Chen, Yan-Zhi, Liu, Dan, Zhao, Yu-Xia, Wang, He-Tong, Gao, Ya, and Chen, Ying
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METHYLATION , *COLON cancer , *PATHOLOGY , *BIOMARKERS , *LYMPH nodes - Abstract
Many existing studies have demonstrated that p16 promoter methylation might be correlated with the clinicopathologic features of colorectal cancer (CRC), but individually published results are inconclusive. This meta-analysis aimed to derive a more precise estimation of the relationships between p16 promoter methylation and the clinicopathologic features of CRC. We searched the CISCOM, CINAHL, Web of Science, PubMed, Google Scholar, EBSCO, Cochrane Library, and CBM databases from inception through August 1, 2013. Meta-analysis was performed using the STATA 12.0 software. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated under fixed- or random-effects models. Twenty-seven clinical cohort studies were included with a total of 3311 CRC patients. Our meta-analysis results revealed that p16 promoter methylation was associated with pathological characteristics of CRC (tumor, nodes, metastasis stage: OR=1.55, 95% CI: 1.14-2.13, p=0.006; lymph node metastasis: OR=2.40, 95% CI: 1.37-4.19, p=0.002; histologic grade: OR=2.72, 95% CI: 1.63-4.54, p<0.001; Dukes stage: OR=2.06, 95% CI: 1.57-2.71, p=0.002; tumor size: OR=1.99, 95% CI: 1.03-3.85, p=0.041; location: OR=2.49, 95% CI: 1.95-3.18, p<0.001, respectively). Subgroup analysis by ethnicity suggested that there were also significant correlations between p16 gene promoter methylation and pathological characteristics of CRC among both Caucasian and Asian populations (all p<0.05). Our meta-analysis suggests that promoter methylation of the p16 gene may be strongly correlated with the clinicopathologic features of CRC. Thus, p16 gene promoter methylation may be a potential biomarker for CRC. [ABSTRACT FROM AUTHOR]
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- 2014
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14. PAQR3 Plays a Suppressive Role in the Tumorigenesis of Colorectal Cancers.
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Wang, Xiao, Li, Xuebing, Fan, Fengjuan, Jiao, Shi, Wang, Lingdi, Zhu, Lu, Pan, Yi, Wu, Guohao, Ling, Zhi-Qiang, Fang, Jing, and Chen, Yan
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PROGESTATIONAL hormones ,CARCINOGENESIS ,COLON cancer ,RAS proteins ,GENETIC mutation ,ADENOMATOUS polyposis coli - Abstract
PAQR3 is a member of the progestin and adipoQ receptor (PAQR) family and was recently characterized as a spatial regulator that negatively modulates Ras/Raf/MEK/ERK signaling cascade. However, little is known about the physiological functions of PAQR3 in the tumorigenesis of colorectal cancers. The function of PAQR3 in colorectal cancer development in mice was analyzed by crossing Paqr3-depleted mice with ApcMin/+ mice that have a germline mutation of the gene-encoding tumor suppressor adenomatous polyposis coli (APC). The survival time and tumor area in the small intestine of the ApcMin/+ mice was significantly aggravated by Paqr3 deletion. The cell proliferation rate, anchorage-independent growth, EGF-stimulated ERK phosphorylation and EGF-induced nuclear accumulation of β-catenin were inhibited by PAQR3 overexpression and enhanced by PAQR3 knockdown in SW-480 colorectal cancer cells. In humans, the expression level of PAQR3 was significantly decreased in colorectal cancer samples in comparison with adjacent normal tissues. In addition, the expression level of PAQR3 was inversely associated with tumor grade in the colorectal cancer samples. Collectively, our data reveal for the first time that PAQR3 has a tumor suppressor activity in the development of colorectal cancers. [ABSTRACT FROM AUTHOR]
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- 2012
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15. A predicted protein, KIAA0247, is a cell cycle modulator in colorectal cancer cells under 5-FU treatment.
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Chi-Jung Huang, Shung-Haur Yang, Shih-Ming Huang, Chih-Ming Lin, Chih-Cheng Chien, Yan-Chu Chen, Chia-Long Lee, Hao-Han Wu, Chun-Chao Chang, Huang, Chi-Jung, Yang, Shung-Haur, Huang, Shih-Ming, Lin, Chih-Ming, Chien, Chih-Cheng, Chen, Yan-Chu, Lee, Chia-Long, Wu, Hao-Han, and Chang, Chun-Chao
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COLON cancer ,CANCER cells ,PROTEINS ,CANCER-related mortality ,CANCER treatment - Abstract
Background: Colorectal cancer (CRC) is the predominant gastrointestinal malignancy and the leading cause of cancer death. The identification of genes related to CRC is important for the development of successful therapies and earlier diagnosis.Methods: Molecular analysis of feces was evaluated as a potential method for CRC detection. Expression of a predicted protein with unknown function, KIAA0247, was found in feces evaluated using specific quantitative real-time polymerase chain reaction. Its cellular function was then analyzed using immunofluorescent staining and the changes in the cell cycle in response to 5-fluorouracil (5-FU) were assessed.Results: Gastrointestinal tissues and peripheral blood lymphocytes ubiquitously expressed KIAA0247. 56 CRC patients fell into two group categories according to fecal KIAA0247 mRNA expression levels. The group with higher fecal KIAA0247 (n=22; ≥0.4897) had a significantly greater five-year overall survival rate than the group with lower fecal KIAA0247 (n = 30; <0.4897) (66.0 ± 11.6%; p=0.035, log-rank test). Fecal expression of KIAA0247 inversely related to CRC tumor size (Kendall's tau-b=-0.202; p=0.047). Immunofluorescent staining revealed that the cytoplasm of CRC cells evenly expresses KIAA0247 without 5-FU treatment, and KIAA0247 accumulates in the nucleus after 40 μM 5-FU treatment. In HCT116 p53(-/-) cells, which lack p53 cell cycle control, the proportion of cells in the G2/M phase was larger (13%) in KIAA0247-silent cells than in the respective shLuc control (10%) and KIAA0247-overexpressing cells (7%) after the addition of low dose (40 μM) 5-FU. Expression of three cyclin genes (cyclin A2, cyclin B1, and cyclin B2) also downregulated in the cells overexpressing KIAA0247.Conclusions: This is the first description of a linkage between KIAA0247 and CRC. The study's data demonstrate overexpression of KIAA0247 associates with 5-FU therapeutic benefits, and also identify the clinical significance of fecal KIAA0247 in CRC. [ABSTRACT FROM AUTHOR]- Published
- 2011
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16. Polymer-based nanoparticles for chemo/gene-therapy: Evaluation its therapeutic efficacy and toxicity against colorectal carcinoma.
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Chen, Yan, Li, NingXi, Xu, Bei, Wu, Min, Yan, XiaoYan, Zhong, LiJun, Cai, Hong, Wang, Ting, Wang, QiuJu, Long, FangYi, Jiang, Gang, and Xiao, HongTao
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PIGMENT epithelium-derived factor , *SORAFENIB , *ACUTE toxicity testing , *NANOPARTICLES , *CARCINOMA , *COLON cancer - Abstract
A newly developed based on PEG-PLGA co-delivery nanoparticles for chemo-gene combined therapy to suppress colorectal carcinoma • The design for a combination therapy for sorafenib and PEDF in a nano-formulation aimed to increase anti-tumor effect on CRC was the first time. • Sora@PEDF-NPs showed better inhibition effect on CRC compared with single loaded nanoparticles in vitro and in vivo. • Sora@PEDF-NPs could decrease the acute toxicity comparing with free Sora on Bal b/c mice. • The PEDF would not increase the toxicity of Sora@PEDF-NPs verified by acute toxicity analysis. Combination treatment through simultaneous delivery of anticancer drugs and gene with nano-formulation has been demonstrated to be an elegant and efficient approach for colorectal cancer therapy. Recently, sorafenib being studied in combination therapy in colorectal cancer (CRC) attracted attention of researchers. On the basis of our previous study, pigment epithelium-derived factor (PEDF) loaded nanoparticles showed good effect on CRC in vitro and in vivo. Herein, we designed a combination therapy for sorafenib (Sora), a multi-kinase inhibitor and PEDF, a powerful antiangiogenic gene, in a nano-formulation aimed to increase anti-tumor effect on CRC for the first time. Sora and PEDF were simultaneously encapsulated in PEG-PLGA based nanoparticles by a modified double-emulsion solvent evaporation method. The obtained co-encapsulated nanoparticles (Sora@PEDF-NPs) showed high entrapment efficiency of both Sora and PEDF — and exhibited a uniform spherical morphology. The release profiles of Sora and PEDF were in a sustained manner. The most effective tumor growth inhibition in the C26 cells and C26-bearing mice was observed in the Sora@PEDF-NPs in comparison with none-drug nanoparticles, free Sora, mono-drug nanoparticles (Sora-NPs and PEDF-NPs) and the mixture of Sora-NPs and equivalent PEDF-NPs (Mix-NPs). More importantly, Sora@PEDF-NPs showed lower toxicity than free Sora in mice according to the acute toxicity test. The serologic biochemical analysis and mice body weight during therapeutic period revealed that Sora@PEDF-NPs had no obvious toxicity. All the data demonstrated that the simultaneously loaded nanoparticles with multi-kinase inhibitor and anti-angiogenic gene might be one of the most potential formulations in the treatment of colorectal carcinoma in clinic and worthy of further investigation. [ABSTRACT FROM AUTHOR]
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- 2019
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17. Effect of CLN3 silencing by RNA interference on the proliferation and apoptosis of human colorectal cancer cells.
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Zhu, Xinguo, Huang, Zhilong, Chen, Yan, Zhou, Jian, Hu, Shuiqing, Zhi, Qiaoming, Song, Shiduo, Wang, Yanan, Wan, Daiwei, Gu, Wen, Zhou, Hao, Zhang, Bo, Cao, Wei, and He, Songbing
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GENE silencing , *RNA interference , *CELL proliferation , *APOPTOSIS , *COLON cancer , *CANCER cells , *GENE expression - Abstract
Abstract: Apoptosis constitutes a system for the removal of aged, or damaged cells, which is regulated by the interplay of pro-apoptotic and antiapoptotic proteins. Previous study has shown that Juvenile Batten disease protein, CLN3, is antiapoptotic gene in NT2 neuronal precursor cells and a few types of cancers. However, in colorectal cancer, whether CLN3 also play its antiapoptotic role and the effect of targeted controlling CLN3 on the biological behavior of human colorectal cancer cell is unknown. We employed the sequence-specific siRNA silencing the CLN3 gene and investigated its effects on growth and apoptosis of colorectal cancer HCT116 cells, which has highest elevation of CLN3 expression among four colorectal cancer cell lines. After CLN3 specific siRNA transfection, mRNA and protein expression levels of CLN3 in HCT116 cells were noticeably decreased. Moreover, CLN3-siRNA inhibited the proliferation of colorectal cancer cells, promoted their apoptosis and induced G0/G1 cell cycle arrest. Our current study demonstrated that CLN3 was expressed in colorectal cancer cells at a high frequency. Moreover, CLN3 down-regulation with RNA interference can inhibit proliferation, apoptosis, and cell cycle progression of colorectal cancer cells. Our study represented a potential new approach to understanding the role of CLN3 in cancer and provides a potential novel strategy colorectal cancer therapy. [Copyright &y& Elsevier]
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- 2014
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18. VMP1 related autophagy and apoptosis in colorectal cancer cells: VMP1 regulates cell death.
- Author
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Qian, Qinyi, Zhou, Hao, Chen, Yan, Shen, Chenglong, He, Songbing, Zhao, Hua, Wang, Liang, Wan, Daiwei, and Gu, Wen
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APOPTOSIS , *AUTOPHAGY , *COLON cancer , *CANCER cells , *GENETIC regulation , *MEMBRANE proteins - Abstract
Highlights: [•] This research confirmed VMP1 as a regulator of autophagy in colorectal cancer cell lines. [•] We proved the pro-survival role of VMP1-mediated autophagy in colorectal cancer cell lines. [•] We found the interaction between VMP1 and BECLIN1 also existing in colorectal cancer cell lines. [ABSTRACT FROM AUTHOR]
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- 2014
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19. Preclinical imaging evaluation of a bispecific antibody targeting hPD1/CTLA4 using humanized mice.
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Hou, Xingguo, Liu, Song, Zeng, Ziqing, Wang, Zilei, Ding, Jin, Chen, Yan, Gao, Xiangyu, Wang, Jianghua, Xiao, Guanxi, Li, Baiyong, Zhu, Hua, and Yang, Zhi
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BISPECIFIC antibodies , *IODINE isotopes , *MICE , *COLON cancer , *T cells - Abstract
The lack of an efficient way to screen patients who are responsive to immunotherapy challenges PD1/CTLA4-targeting cancer treatment. Immunotherapeutic efficacy cannot be clearly determined by peripheral blood analyses, tissue gene markers or CT/MR value. Here, we used a radionuclide and imaging techniques to investigate the novel dual targeted antibody cadonilimab (AK104) in PD1/CTLA4-positive cells in vivo. First, humanized PD1/CTLA4 mice were purchased from Biocytogen Pharmaceuticals (Beijing) Co., Ltd. to express hPD1/CTLA4 in T-cells. Then, mouse colon cancer MC38-hPD-L1 cell xenografts were established in humanized mice. A bispecific antibody targeting PD1/CTLA4 (AK104) was labeled with radio-nuclide iodine isotopes. Immuno-PET/CT imaging was performed using a bispecific monoclonal antibody (mAb) probe 124I-AK104, developed in-house, to locate PD1+/CTLA4+ tumor-infiltrating T cells and monitor their distribution in mice to evaluate the therapeutic effect. The 124I-AK104 dual-antibody was successfully constructed with ideal radiochemical characteristics, in vitro stability and specificity. The results of immuno-PET showed that 124I-AK104 revealed strong hPD1/CTLA4-positive responses with high specificity in humanized mice. High uptake of 124I-AK104 was observed not only at the tumor site but also in the spleen. Compared with PD1- or CTLA4-targeting mAb imaging, 124I-AK104 imaging had excellent standard uptake values at the tumor site and higher tumor to nontumor (T/NT) ratios. The results demonstrated the potential of translating 124I-AK104 into a method for screening patients who benefit from immunotherapy and the efficacy, as well as the feasibility, of this method was verified by immuno-PET imaging of humanized mice. [Display omitted] • An antibody-PET probe targeting PD1/CTLA4 was radiolabeled. • High affinity to PD1/CTLA4 in vitro and in vivo. • This tracer can noninvasively demonstrate the presence of PD1/CTLA4-positive infiltrating T cells at the tumor site in humanized mice using an imaging method. [ABSTRACT FROM AUTHOR]
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- 2024
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20. Prognostic Value of Combined Preoperative Carcinoembryonic Antigen and Prognostic Nutritional Index in Patients With Stage II–III Colon Cancer
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Yan-song Xu, Gang Liu, Chang Zhao, Shao-long Lu, Chen-yan Long, Hua-ge Zhong, Yi Chen, Ling-xu Huang, and Zheng Liang
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colon cancer ,tumor marker ,nutritional status ,prognosis ,nomogram ,Surgery ,RD1-811 - Abstract
Background: Tumor status can affect patient prognosis. Prognostic nutritional index (PNI), as a nutritional indicator, is closely related to the prognosis of cancer. However, few studies have examined the combined prognostic value of CEA and PNI in patients. This study investigated the relationship between CEA/PNI and prognosis of colon cancer patients.Methods: A total of 513 patients with stage II–III colon cancer who underwent curative resection at two medical centers from 2009 to 2019 were included. Clinicopathological factors were assessed and overall survival (OS) was assessed in a cohort of 413 patients. Multivariate analysis was used to identify independent prognostic variables to construct histograms predicting 1-year and 3-year OS. Data from 100 independent patients in the validation group was used to validate the prognostic model.Results: The median OS time was 33.6 months, and mortality was observed in 54 patients. Multivariate analysis revealed that preoperative CEA/PNI, lymph node metastasis, peripheral nerve invasion, operation mode, and postoperative chemotherapy were independent factors for prognosis evaluation and thus were utilized to develop the nomogram. The C-index was 0.788 in the learning set and 0.836 in the validation set. The calibration curves reached favorable consensus among the 1-, 3-year OS prediction and actual observation.Conclusion: The combined use of CEA and PNI is an independent prognostic factor and thus can serve as a basis for a model to predict the prognosis of patients with stage II–III colon cancer.
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- 2021
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