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Article: [Progress in research on mRNA therapeutics for the treatment of genetic diseases].

Shi, Wenjun / Cheng, Xianshuo / Luo, Pei / Ma, Jilong / Dong, Jian

Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics

2024 Volume 41, Issue 3, Page(s) 368–376

Abstract: In recent years, mRNA drugs have shown a great potential for the treatment of genetic diseases and attracted the attention of many researchers. This article has reviewed the advance in the research of mRNA drugs for the treatment of genetic diseases over ...

Abstract	In recent years, mRNA drugs have shown a great potential for the treatment of genetic diseases and attracted the attention of many researchers. This article has reviewed the advance in the research of mRNA drugs for the treatment of genetic diseases over the past 30 years, including their mechanisms of action and structure design, with a focus on their advantages as alternative therapies such as high specificity, low dosage, and sustained expression. Meanwhile, challenges for the effective delivery and storage methods for the mRNA drugs are discussed, with an aim to provide guidance for subsequent researches.
MeSH term(s)	Humans ; RNA, Messenger/genetics
Chemical Substances	RNA, Messenger
Language	Chinese
Publishing date	2024-03-06
Publishing country	China
Document type	English Abstract ; Journal Article
ISSN	1003-9406
ISSN	1003-9406
DOI	10.3760/cma.j.cn511374-20230203-00051
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Article ; Online: Which Drugs are More Effective in Preventing Familial Adenomatous Polyposis Progression Based on Network Meta-Analysis?

Luo, Pei / Shi, Wenjun / Cheng, Xianshuo / Yang, Jun / Pei, Gen / Dong, Jian

Current pharmaceutical design

2024

Abstract: Background: Familial adenomatous polyposis (FAP) is an inherited disorder. At present, an increasing number of medications are being employed to treat FAP; however, only a few have been assessed for their efficacy and safety. Therefore, this study aimed ...

Abstract	Background: Familial adenomatous polyposis (FAP) is an inherited disorder. At present, an increasing number of medications are being employed to treat FAP; however, only a few have been assessed for their efficacy and safety. Therefore, this study aimed to conduct a network meta-analysis to compare the therapeutic outcomes and adverse drug reactions of all FAP-associated medications. Method: Six relevant databases were searched to identify pertinent randomized controlled trials (RCTs), and information on the dosage and frequency of various drugs was extracted. Additionally, data on changes in polyp counts and dimensions, as well as treatment-related adverse reactions for different medications were collected. The Bayesian method was employed to directly or indirectly compare the impact of different treatment regimens on changes in polyp numbers and diameters, and the safety of the drugs was investigated. Results: CXB at 16 mg/kg/day significantly reduced polyp numbers. Celecoxib at 8 mg/kg/day and sulindac (150 mg twice daily) plus erlotinib (75 mg/day) were effective for tolerant FAP patients. Additionally, EPAFFA 2 g daily and sulindac (150 mg twice daily) plus erlotinib (75 mg/day) emerged as the most effective for reducing polyp size. Conclusion: The most effective treatment for reducing the number of colorectal polyps is celecoxib 16 mg/kg/day. On the other hand, a daily dosage of 2 g EPA-FFA demonstrates the best results in terms of decreasing colorectal polyp diameter.
Language	English
Publishing date	2024-05-02
Publishing country	United Arab Emirates
Document type	Meta-Analysis
ZDB-ID	1304236-1
ISSN	1873-4286 ; 1381-6128
ISSN (online)	1873-4286
ISSN	1381-6128
DOI	10.2174/0113816128289465240422074745
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Article ; Online: Molecular mechanism of colorectal cancer and screening of molecular markers based on bioinformatics analysis

Zhao Jikun / Kuang Dadong / Cheng Xianshuo / Geng Jiwei / Huang Yong / Zhao Haojie / Yang Zhibin

Open Life Sciences, Vol 18, Iss 1, Pp 1-

2023 Volume 10

Abstract: Genomics and bioinformatics methods were used to screen genes and molecular markers correlated with colorectal cancer incidence and progression, and their biological functions were analyzed. Differentially expressed genes were obtained using the GEO2R ... ...

Abstract	Genomics and bioinformatics methods were used to screen genes and molecular markers correlated with colorectal cancer incidence and progression, and their biological functions were analyzed. Differentially expressed genes were obtained using the GEO2R program following colorectal cancer chip data GSE44076 retrieval from the Gene Expression Omnibus gene expression comprehensive database. An online database (David) that combines annotation, visualization, and gene discovery was utilized for investigating genes. Pathway and protein analyses were performed via resources from the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Visual analysis of the KEGG pathway was carried out according to ClueGO and CluePedia to establish the PPI network of gene interaction between pathways; the genes with the highest connectivity were screened by the molecular complex detection analysis method as Hub genes in this study; gene expression was verified by GEPIA online analysis tool, and Kaplan–Meier survival curve was drawn for prognosis analysis. By analyzing GSE44076 microarray data, 86 genes were selected, and colorectal cancer tissues’ upregulation was observed in 27 genes and downregulation in 59 ones. GO assessment revealed that the differentially expressed genes were basically correlated with retinol dehydrogenase activity, carbon dehydrogenase activity, collagen-containing extracellular matrix, anchored component of memory, and cellular hormone metabolic process. Moreover, the KEGG assessment revealed that the differential genes contained various signal pathways such as retinol metabolism, chemical carotenogenesis, and nitrogen metabolism. Through further analysis of the PPI protein network, 4 clusters were obtained, and 16 Hub genes were screened out by combining the degree of each gene. Through the analysis of each gene on the prognosis of colon cancer through the GEPIA online analysis website, it was found that the expression levels of AQP8, CXCL8, and ZG16 genes were remarkably associated with ...
Keywords	bioinformatics ; colorectal cancer ; pathogenesis ; molecular marker screening ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	De Gruyter
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Molecular mechanism of colorectal cancer and screening of molecular markers based on bioinformatics analysis.

Zhao, Jikun / Kuang, Dadong / Cheng, Xianshuo / Geng, Jiwei / Huang, Yong / Zhao, Haojie / Yang, Zhibin

Open life sciences

2023 Volume 18, Issue 1, Page(s) 20220687

Abstract	Genomics and bioinformatics methods were used to screen genes and molecular markers correlated with colorectal cancer incidence and progression, and their biological functions were analyzed. Differentially expressed genes were obtained using the GEO2R program following colorectal cancer chip data GSE44076 retrieval from the Gene Expression Omnibus gene expression comprehensive database. An online database (David) that combines annotation, visualization, and gene discovery was utilized for investigating genes. Pathway and protein analyses were performed via resources from the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Visual analysis of the KEGG pathway was carried out according to ClueGO and CluePedia to establish the PPI network of gene interaction between pathways; the genes with the highest connectivity were screened by the molecular complex detection analysis method as Hub genes in this study; gene expression was verified by GEPIA online analysis tool, and Kaplan-Meier survival curve was drawn for prognosis analysis. By analyzing GSE44076 microarray data, 86 genes were selected, and colorectal cancer tissues' upregulation was observed in 27 genes and downregulation in 59 ones. GO assessment revealed that the differentially expressed genes were basically correlated with retinol dehydrogenase activity, carbon dehydrogenase activity, collagen-containing extracellular matrix, anchored component of memory, and cellular hormone metabolic process. Moreover, the KEGG assessment revealed that the differential genes contained various signal pathways such as retinol metabolism, chemical carotenogenesis, and nitrogen metabolism. Through further analysis of the PPI protein network, 4 clusters were obtained, and 16 Hub genes were screened out by combining the degree of each gene. Through the analysis of each gene on the prognosis of colon cancer through the GEPIA online analysis website, it was found that the expression levels of AQP8, CXCL8, and ZG16 genes were remarkably associated with colon cancer prognosis (
Language	English
Publishing date	2023-11-10
Publishing country	Poland
Document type	Journal Article
ZDB-ID	2817958-4
ISSN	2391-5412 ; 2391-5412
ISSN (online)	2391-5412
ISSN	2391-5412
DOI	10.1515/biol-2022-0687
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Article ; Online: miR-4323 targets hepatoma-derived growth factor (HDGF) to suppress colorectal cancer cell proliferation.

Xia, Cuifeng / Li, Qiang / Cheng, Xianshuo / Wu, Tao / Gao, Pin

Pathology, research and practice

2021 Volume 225, Page(s) 153544

Abstract: MicroRNAs (miRNAs) are regulators of cancer progression via directly binding to the 3' untranslated region (3'UTR) of target genes to control the activity of signaling network. Recent studies have revealed the function of several miRNAs in colorectal ... ...

Abstract	MicroRNAs (miRNAs) are regulators of cancer progression via directly binding to the 3' untranslated region (3'UTR) of target genes to control the activity of signaling network. Recent studies have revealed the function of several miRNAs in colorectal cancer, however, there are still numerous miRNAs which have not been studied yet. Herein, we showed that miR-4323 was a downregulated miRNA according to previous microarray data. The downregulation of miR-4323 was further confirmed in colorectal tumors via RT-qPCR. miR-4323 overexpression decreased cell proliferation rate via induction of cell apoptosis in colorectal cancer cells. Mechanistically, miR-4323 decreased β-catenin and its downstream genes including c-Myc and MMP9 in colorectal cancer cells, indicating the inactivation of Wnt signaling. HDGF, an anti-apoptotic protein, was predicted by several software as a potential target of miR-4323. HDGF was experimentally verified as a target gene of miR-4323 using dual luciferase reporter assay. Ectopic expression of HDGF attenuated the effect of miR-4323 on cell proliferation and apoptosis in cells. Altogether, the data demonstrate a critical role of miR-4323 in the regulation of colorectal cancer.
MeSH term(s)	Apoptosis/genetics ; Cell Line, Tumor ; Cell Proliferation/genetics ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Intercellular Signaling Peptides and Proteins/genetics ; Intercellular Signaling Peptides and Proteins/metabolism ; MicroRNAs/genetics ; MicroRNAs/metabolism
Chemical Substances	Intercellular Signaling Peptides and Proteins ; MIRN-4323 microRNA, human ; MicroRNAs ; hepatoma-derived growth factor
Language	English
Publishing date	2021-07-09
Publishing country	Germany
Document type	Journal Article
ZDB-ID	391889-0
ISSN	1618-0631 ; 0344-0338
ISSN (online)	1618-0631
ISSN	0344-0338
DOI	10.1016/j.prp.2021.153544
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Article ; Online: Insulin-like growth factor 2 mRNA-binding protein 2-stabilized long non-coding RNA Taurine up-regulated gene 1 (TUG1) promotes cisplatin-resistance of colorectal cancer via modulating autophagy.

Xia, Cuifeng / Li, Qiang / Cheng, Xianshuo / Wu, Tao / Gao, Pin / Gu, Yongfang

Bioengineered

2022 Volume 13, Issue 2, Page(s) 2450–2469

Abstract: Long non-coding RNAs (lncRNAs) have been demonstrated to influence the chemoresistance of colorectal cancer (CRC). Therefore, the study is designed to investigate the regulatory function and mechanism of Taurine up-regulated gene 1 (TUG1) in the ... ...

Abstract	Long non-coding RNAs (lncRNAs) have been demonstrated to influence the chemoresistance of colorectal cancer (CRC). Therefore, the study is designed to investigate the regulatory function and mechanism of Taurine up-regulated gene 1 (TUG1) in the cisplatin resistance of CRC. qRT-PCR checked the expressions of TUG1, Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), and miR-195-5p in CRC tissues and cells. The TUG1 or miR-195-5p overexpression model was engineered in CRC cells, followed by treatment with DDP or the autophagy inhibitor (Chloroquine, CQ). CCK8 (Cell Counting Kit-8) and the colony formation experiment monitored cell proliferation. Flow cytometry examined apoptosis, Transwell tracked migration and invasion, and Western blot ascertained the protein profiles of autophagy proteins (LC3I/LC3II and Beclin1) and the HDGF/DDX5/β-catenin pathway. Dual-luciferase gene reporter assay and RNA immunoprecipitation confirmed the binding correlation between TUG1 and miR-195-5p and between miR-195-5p and HDGF. Furthermore,
MeSH term(s)	Autophagy/drug effects ; Cisplatin/pharmacology ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; Drug Resistance, Neoplasm/drug effects ; HT29 Cells ; Humans ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; RNA, Neoplasm/genetics ; RNA, Neoplasm/metabolism ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Signal Transduction/drug effects ; Signal Transduction/genetics
Chemical Substances	IGF2BP2 protein, human ; Neoplasm Proteins ; RNA, Long Noncoding ; RNA, Neoplasm ; RNA-Binding Proteins ; TUG1 long noncoding RNA, human ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2022-01-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2737830-5
ISSN	2165-5987 ; 2165-5979
ISSN (online)	2165-5987
ISSN	2165-5979
DOI	10.1080/21655979.2021.2012918
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Article ; Online: mir-145-5p is a suppressor of colorectal cancer at early stage, while promotes colorectal cancer metastasis at late stage through regulating AKT signaling evoked EMT-mediated anoikis.

Cheng, Xianshuo / Shen, Tao / Liu, Ping / Fang, Shaojun / Yang, Zhibin / Li, Yunfeng / Dong, Jian

BMC cancer

2022 Volume 22, Issue 1, Page(s) 1151

Abstract: Background: miR-145-5P is generally considered as a tumor suppressor at early stage of colorectal cancer, but up-regulation occurs in the progressive and later stages which is associated with metastasis, indicating miR-145-5p may play dual role in ... ...

Abstract	Background: miR-145-5P is generally considered as a tumor suppressor at early stage of colorectal cancer, but up-regulation occurs in the progressive and later stages which is associated with metastasis, indicating miR-145-5p may play dual role in colorectal cancer (CRC). To explore the detailed mechanism of miR-145-5p in carcinogenic is of importance. Methods: The expression pattern of miR-145-5p in CRC patients was downloaded from TCGA database, and the probable mechanism involved in the carcinogenic effect of miR-145-5p was predicted by bioinformatics analysis. Then, interference of miR-145-5p on SW480 and SW620 cells was conducted, and the influences on tumor cell viability, invasion ability, epithelial-mesenchymal transition (EMT), anoikis, and relative protein expression were examined respectively. Results: A total of 522 CRC patients' data indicated that miR-145-5p expression was significantly higher in metastatic CRC than that in non-metastatic CRC, and higher expression of miR-145-5p was correlate with worse prognosis. Overexpression of miR-145-5P-5p enhanced the proliferation and invasion ability of SW620, but inhibited them in SW480. EMT was induced in SW620 after miR-145-5p overexpression and mesenchymal-epithelial transition (MET) was induced in SW480, resulted in the decreased apoptotic rate in SW620 and elevated apoptotic rate in SW480 respectively. Western blot results showed that AKT signaling pathway was involved in the miR-145-5p evoked EMT-mediated anoikis process in SW620 and SW480 cells. Conclusion: miR-145-5p is a tumor suppressor at early stage of CRC, and an oncogene at advanced stage of CRC. AKT signaling evoked EMT-mediated anoikis might be the pathway by which miR-145-5P regulates CRC cell invasion and metastasis.
MeSH term(s)	Humans ; Epithelial-Mesenchymal Transition/genetics ; Anoikis/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Gene Expression Regulation, Neoplastic ; Colorectal Neoplasms/pathology ; Signal Transduction ; Cell Proliferation/genetics ; Cell Movement/genetics ; Cell Line, Tumor
Chemical Substances	Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; MicroRNAs ; MIRN145 microRNA, human
Language	English
Publishing date	2022-11-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2041352-X
ISSN	1471-2407 ; 1471-2407
ISSN (online)	1471-2407
ISSN	1471-2407
DOI	10.1186/s12885-022-10182-6
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Article ; Online: Multi-Omics Characteristics of Ferroptosis Associated with Colon Adenocarcinoma Typing and Survival.

Chen, Xiao-Qiong / Lian, Ke / Chen, Zi-Wei / Zhang, Xuan / Li, Ting / Wu, Tao / Shen, Tao / Cai, Xin-Yi / Cheng, Xian-Shuo / Xiao, Fu-Hui / Li, Yun-Feng

Frontiers in bioscience (Landmark edition)

2024 Volume 29, Issue 1, Page(s) 13

Abstract: Background: Ferroptosis, an iron-dependent form of cell death, plays a crucial role in the progression of various cancers, including colon adenocarcinoma (COAD). However, the multi-omics signatures relevant to ferroptosis regulation in COAD diagnosis ... ...

Abstract	Background: Ferroptosis, an iron-dependent form of cell death, plays a crucial role in the progression of various cancers, including colon adenocarcinoma (COAD). However, the multi-omics signatures relevant to ferroptosis regulation in COAD diagnosis remain to be elucidated. Methods: The transcriptomic, miRNAomic, and methylomic profiles of COAD patients were acquired from the Cancer Genome Atlas (TCGA). Ferroptosis activity in these patients was determined, represented by a ferroptosis score (FS), using single-sample gene set enrichment analysis (ssGSEA) based on the expression of ferroptosis-related genes. Results: Results showed that the COAD patients with high-FS displayed favorable survival outcomes and heightened drug sensitivity. They also exhibited an up-regulation of genes involved in immune-related pathways (e.g., tumor necrosis factor signaling pathway), suggesting a correlation between immunity and ferroptosis in COAD progression. Furthermore, three survival prediction models were established based on 10 CpGs, 12 long non-coding RNAs (lncRNAs), and 14 microRNAs (miRNAs), respectively. These models demonstrated high accuracy in predicting COAD survival, achieving areas under the curve (AUC) >0.7. The variables used in the three models also showed strong correlations at different omics levels and were effective at discriminating between high-FS and low-FS COAD patients (AUC >0.7). Conclusions: This study identified different DNA methylation (DNAm), lncRNA, and miRNA characteristics between COAD patients with high and low ferroptosis activity. Furthermore, ferroptosis-related multi-omics signatures were established for COAD prognosis and classification. These insights present new opportunities for improving the efficacy of COAD therapy.
MeSH term(s)	Humans ; Colonic Neoplasms/genetics ; Adenocarcinoma/genetics ; Ferroptosis/genetics ; Multiomics ; MicroRNAs/genetics ; RNA, Long Noncoding
Chemical Substances	MicroRNAs ; RNA, Long Noncoding
Language	English
Publishing date	2024-02-19
Publishing country	Singapore
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2704569-9
ISSN	2768-6698 ; 2768-6698
ISSN (online)	2768-6698
ISSN	2768-6698
DOI	10.31083/j.fbl2901013
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Article: The Combination Therapy of Fluorouracil and Oxaliplatin Suppress the Progression of Colon Cancer Through miR-183-5p/SOCS3 Axis and Downregulating PD-L1.

Tu, Changling / Wang, Yufeng / Cheng, Xianshuo / Zhu, Ying / Yuan, Wenli / Dong, Jian

Cancer management and research

2021 Volume 13, Page(s) 1999–2008

Abstract: Purpose: The purpose of this study was to investigate the mechanism of combination of fluorouracil (FU) and oxaliplatin (OXA) on the progression of colon cancer via miR-183-5p/SOCS3 axis and regulating PD-L1.: Methods: HCT116 cells were treated with ... ...

Abstract	Purpose: The purpose of this study was to investigate the mechanism of combination of fluorouracil (FU) and oxaliplatin (OXA) on the progression of colon cancer via miR-183-5p/SOCS3 axis and regulating PD-L1. Methods: HCT116 cells were treated with 4 μM OXA and 10.5 μM FU, or exogenous regulation of the expression of miR-183-5p, SOCS3 and PD-L1 in HCT116 cells. CCK-8 assay was employed to detect cell viability of HCT116 cells. Flow cytometry was performed to assess the apoptosis and cell cycle. The expression level of SOCS3, PD-L1, chemokines (CCL1, CCL4 and CCL7) and immune escapes related proteins (EGFR, STARD1 and STARD3) in HCT116 cells were assessed by Western blotting. In addition, dual-luciferase reporter gene was carried out to verify the targeted relationship between miR-183-5p with SOCS3. Results: Our study demonstrated that the combination of OXA and FU remarkably suppressed proliferation, promoted apoptosis and arrest cells in G0/G1 phrase of HCT116 cells, and observably downregulated the expression of PD-L1, CCL1, CCL4, CCL7, EGFR, STARD1 and STARD3. Meanwhile, the combination of OXA and FU significantly downregulated miR-183-5p expression. Knockdown of miR-183-5p also repressed the proliferation, promoted apoptosis and arrest cells in G0/G1 phrase of HCT116 cells, and downregulated the expression of PD-L1, CCL1, CCL4, CCL7, EGFR, STARD1 and STARD3. In addition, our study proved that miR-183-5p upregulated PD-L1 by targeting downregulated SOCS3 expression. Finally, we demonstrated that the combination therapy of OXA and FU inhibited the proliferation, promote apoptosis and arrest cells in G0/G1 phrase by downregulating PD-L1 via miR-183-5p/SOCS3 axis. Conclusion: The combination therapy of OXA and FU could suppress the malignant biological behavior, and the mechanism was realized by inhibiting PD-L1 through miR-183-5p/SOCS3 axis.
Language	English
Publishing date	2021-02-25
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2508013-1
ISSN	1179-1322
ISSN	1179-1322
DOI	10.2147/CMAR.S281925
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Article: Association Between Serum Carcinoembryonic Antigen Levels at Different Perioperative Time Points and Colorectal Cancer Outcomes.

Li, Zhenhui / Zhang, Dafu / Pang, Xiaolin / Yan, Shan / Lei, Ming / Cheng, Xianshuo / Song, Qian / Cai, Le / Wang, Zhuozhong / You, Dingyun

Frontiers in oncology

2021 Volume 11, Page(s) 722883

Abstract: Background: Whether elevated postoperative serum carcinoembryonic antigen (CEA) levels are prognostic in patients with stage II colorectal cancer (CRC) remains controversial.: Patients and methods: Primary and sensitivity analysis populations were ... ...

Abstract	Background: Whether elevated postoperative serum carcinoembryonic antigen (CEA) levels are prognostic in patients with stage II colorectal cancer (CRC) remains controversial. Patients and methods: Primary and sensitivity analysis populations were obtained from a retrospective, multicenter longitudinal cohort including consecutive patients without neoadjuvant treatment undergoing curative resection for stage I-III CRC. Serum CEA levels before (CEA Results: Primary and sensitivity analysis populations included 710 [415 men; age, 54.8 (11.6) years] and 1556 patients [941 men; age, 56.2 (11.8) years], respectively. Recurrence hazard ratios (HRs) in the elevated CEA Conclusions: Elevated postoperative CEA levels are prognostic in patients with stage II CRC, with 2-3 months after surgery being the optimal timing for CEA measurement.
Language	English
Publishing date	2021-10-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2021.722883
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