| 1. |
- Song, Guohe, et al.
(author)
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TIMP1 is a prognostic marker for the progression and metastasis of colon cancer through FAK-PI3K/AKT and MAPK pathway
- 2016
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In: Journal of Experimental & Clinical Cancer Research. - London, United Kingdom : BioMed Central (BMC). - 1756-9966. ; 35:1
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Journal article (peer-reviewed)abstract
- Background: Tissue inhibitor matrix metalloproteinase 1 (TIMP1) plays a vital role in carcinogenesis, yet its precise functional roles and regulation remain unclear. In this study, we aim to investigate its biological function and clinical significance in human colon cancer.Methods: We analyzed the expression of TIMP1 in both public database (Oncomine and TCGA) and 94 cases of primary colon cancer and matched normal colon tissue specimens. The underlying mechanisms of altered TIMP1 expression on cell tumorigenesis, proliferation, and metastasis were explored in vitro and in vivo.Results: TIMP1 was overexpressed in colon tumorous tissues and lymph node metastasis specimens than in normal tissues. The aberrant expression of TIMP1 was significantly associated with the regional lymph node metastasis (p = 0.033), distant metastasis (p = 0.039), vascular invasion (p = 0.024) and the American Joint Committee on Cancer (AJCC) stage (p = 0.026). Cox proportional hazards model showed that TIMP1 was an independent prognostic indicator of disease-free survival (HR = 2.603, 95 % CI: 1.115-6.077, p = 0.027) and overall survival (HR = 2.907, 95 % CI: 1.254-6.737, p = 0.013) for patients with colon cancer. Consistent with this, our findings highlight that suppression of TIMP1 expression decreased proliferation, and metastasis but increased apoptosis by inducing TIMP1 specific regulated FAK-PI3K/AKT and MAPK pathway.Conclusion: TIMP1 might play an important role in promoting tumorigenesis and metastasis of human colon cancer and function as a potential prognostic indicator for colon cancer.
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| 2. |
- Wang, Mo-Jin, et al.
(author)
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The prognostic factors and multiple biomarkers in young patients with colorectal cancer
- 2015
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In: Scientific Reports. - : Nature Publishing Group: Open Access Journals - Option C / Nature Publishing Group. - 2045-2322. ; 5:10645
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Journal article (peer-reviewed)abstract
- The incidence of colorectal cancer (CRC) in young patients (less than= 50 years of age) appears to be increasing. However, their clinicopathological characteristics and survival are controversial. Likewise, the biomarkers are unclear. We used the West China (2008-2013, China), Surveillance, Epidemiology, and End Results program (1973-2011, United States) and Linkoping Cancer (1972-2009, Sweden) databases to analyse clinicopathological characteristics, survival and multiple biomarkers of young CRC patients. A total of 509,934 CRC patients were included from the three databases. The young CRC patients tended to have more distal location tumours, fewer tumour numbers, later stage, more mucinous carcinoma and poorer differentiation. The cancer-specific survival (CSS) of young patients was significantly better. The PRL (HR = 12.341, 95% CI = 1.615-94.276, P = 0.010), RBM3 (HR = 0.093, 95% CI = 0.012-0.712, P = 0.018), Wrap53 (HR = 1.952, 95% CI = 0.452-6.342, P = 0.031), p53 (HR = 5.549, 95% CI = 1.176-26.178, P = 0.045) and DNA status (HR = 17.602, 95% CI = 2.551-121.448, P = 0.001) were associated with CSS of the young patients. In conclusion, this study suggests that young CRC patients present advanced tumours and more malignant pathological features, while they have a better prognosis. The PRL, RBM3, Wrap53, p53 and DNA status are potential prognostic biomarkers for the young CRC patients.
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| 3. |
- Xiao, Chao, et al.
(author)
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RBBP6 increases radioresistance and serves as a therapeutic target for preoperative radiotherapy in colorectal cancer
- 2018
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In: Cancer Science. - : Blackwell Publishing. - 1347-9032 .- 1349-7006. ; 109:4, s. 1075-1087
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Journal article (peer-reviewed)abstract
- Radiotherapy (RT) can be used as preoperative treatment to downstage initially unresectable locally rectal carcinoma, but the radioresistance and recurrence remain significant problems. Retinoblastoma binding protein 6 (RBBP6) has been implicated in the regulation of cell cycle, apoptosis and chemoresistance both in vitro and in vivo. This study investigated whether the inhibition of RBBP6 expression would improve radiosensitivity in human colorectal cancer cells. After SW620 and HT29 cells were exposed to radiation, the levels of RBBP6 mRNA and protein increased over time in both two cells. Moreover, a significant reduction in clonogenic survival and a decrease in cell viability in parallel with an obvious increase in cell apoptosis were demonstrated in irradiated RBBP6-knockdown cells. Besides, transfection with RBBP6 shRNA improved levels of G2-M phase arrest which blocked the cells in a more radiosensitive period of the cell cycle. These observations indicated that cell cycle and apoptosis mechanisms may be connected with tumor cell survival following radiotherapy. In vivo, tumor growth rate of nude mice in RBBP6-knockdown group was significantly slower than that in other groups. These results indicated that RBBP6 overexpression could resist colorectal cancer cells against radiation by regulating cell cycle and apoptosis pathways, and inhibition of RBBP6 could enhance radiosensitivity of human colorectal cancer.
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| 4. |
- Jin, Zhichao, et al.
(author)
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A retrospective survey of research design and statistical analyses in selected Chinese medical journals in 1998 and 2008
- 2010
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In: PLOS ONE. - : PLOS. - 1932-6203. ; 5:5
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Journal article (peer-reviewed)abstract
- BACKGROUND: High quality clinical research not only requires advanced professional knowledge, but also needs sound study design and correct statistical analyses. The number of clinical research articles published in Chinese medical journals has increased immensely in the past decade, but study design quality and statistical analyses have remained suboptimal. The aim of this investigation was to gather evidence on the quality of study design and statistical analyses in clinical researches conducted in China for the first decade of the new millennium.METHODOLOGY/PRINCIPAL FINDINGS: Ten (10) leading Chinese medical journals were selected and all original articles published in 1998 (N = 1,335) and 2008 (N = 1,578) were thoroughly categorized and reviewed. A well-defined and validated checklist on study design, statistical analyses, results presentation, and interpretation was used for review and evaluation. Main outcomes were the frequencies of different types of study design, error/defect proportion in design and statistical analyses, and implementation of CONSORT in randomized clinical trials. From 1998 to 2008: The error/defect proportion in statistical analyses decreased significantly ( = 12.03, p<0.001), 59.8% (545/1,335) in 1998 compared to 52.2% (664/1,578) in 2008. The overall error/defect proportion of study design also decreased ( = 21.22, p<0.001), 50.9% (680/1,335) compared to 42.40% (669/1,578). In 2008, design with randomized clinical trials remained low in single digit (3.8%, 60/1,578) with two-third showed poor results reporting (defects in 44 papers, 73.3%). Nearly half of the published studies were retrospective in nature, 49.3% (658/1,335) in 1998 compared to 48.2% (761/1,578) in 2008. Decreases in defect proportions were observed in both results presentation ( = 93.26, p<0.001), 92.7% (945/1,019) compared to 78.2% (1023/1,309) and interpretation ( = 27.26, p<0.001), 9.7% (99/1,019) compared to 4.3% (56/1,309), some serious ones persisted.CONCLUSIONS/SIGNIFICANCE: Chinese medical research seems to have made significant progress regarding statistical analyses, but there remains ample room for improvement regarding study designs. Retrospective clinical studies are the most often used design, whereas randomized clinical trials are rare and often show methodological weaknesses. Urgent implementation of the CONSORT statement is imperative.
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| 5. |
- Liao, Qianfang, 1983-, et al.
(author)
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Type-1 and Type-2 effective Takagi-Sugeno fuzzy models for decentralized control of multi-input-multi-output processes
- 2017
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In: Journal of Process Control. - : Elsevier. - 0959-1524 .- 1873-2771. ; 52, s. 26-44
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Journal article (peer-reviewed)abstract
- tEffective model is a novel tool for decentralized controller design to handle the interconnected inter-actions in a multi-input-multi-output (MIMO) process. In this paper, Type-1 and Type-2 effectiveTakagi-Sugeno fuzzy models (ETSM) are investigated. By means of the loop pairing criterion, simple cal-culations are given to build Type-1/Type-2 ETSMs which are used to describe a group of non-interactingequivalent single-input-single-output (SISO) systems to represent an MIMO process, consequently thedecentralized controller design can be converted to multiple independent single-loop controller designs,and enjoy the well-developed linear control algorithms. The main contributions of this paper are: i)Compared to the existing T-S fuzzy model based decentralized control methods using extra terms tocharacterize interactions, ETSM is a simple feasible alternative; ii) Compared to the existing effectivemodel methods using linear transfer functions, ETSM can be carried out without requiring exact mathe-matical process functions, and lays a basis to develop robust controllers since fuzzy system is powerful tohandle uncertainties; iii) Type-1 and Type-2 ETSMs are presented under a unified framework to provideobjective comparisons. A nonlinear MIMO process is used to demonstrate the ETSMs’ superiority overthe effective transfer function (ETF) counterparts as well as the evident advantage of Type-2 ETSMs interms of robustness. A multi-evaporator refrigeration system is employed to validate the practicabilityof the proposed methods.
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| 6. |
- Meng, Mei, et al.
(author)
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Accumulation of total mercury and methylmercury in rice plants collected from different mining areas in China
- 2014
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In: Environmental Pollution. - : Pergamon Press. - 0269-7491 .- 1873-6424. ; 184, s. 179-186
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Journal article (peer-reviewed)abstract
- A total of 155 rice plants were collected from ten mining areas in three provinces of China (Hunan, Guizhou and Guangdong), where most of mercury (Hg) mining takes place in China. During the harvest season, whole rice plants were sampled and divided into root, stalk & leaf, husk and seed (brown rice), together with soil from root zone. Although the degree of Hg contamination varied significantly among different mining areas, rice seed showed the highest ability for methylmercury (MeHg) accumulation. Both concentrations of total mercury (THg) and MeHg in rice plants were significantly correlated with Hg levels in soil, indicating soil is still an important source for both inorganic mercury (IHg) and MeHg in rice plants. The obvious discrepancy between the distribution patterns of THg and MeHg reflected different pathways of IHg and MeHg accumulation. Water soluble Hg may play more important role in MeHg accumulation in rice plants.
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| 7. |
- Meng, Wen-Jian, et al.
(author)
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Expressions of miR-302a, miR-105, and miR-888 Play Critical Roles in Pathogenesis, Radiotherapy, and Prognosis on Rectal Cancer Patients : A Study From Rectal Cancer Patients in a Swedish Rectal Cancer Trial of Preoperative Radiotherapy to Big Database Analyses
- 2020
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In: Frontiers in Oncology. - : Frontiers. - 2234-943X. ; 10
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Journal article (peer-reviewed)abstract
- Differential expressions and functions of various micoRNAs (miRNAs) have been intensively studied in both colon and rectal cancers. However, the importance of miRNAs on radiotherapy (RT) response and clinical outcome in rectal cancer patients remains unclear. In this study, we used real-time polymerase chain reaction to examine the expressions of miR-302a, miR-105, and miR-888 in normal mucosa and cancer tissue from rectal cancer patients with and without preoperative RT. The biological function of miR-302a, miR-105, and miR-888 expression was further analyzed and identified through the public databases: TCGA (The Cancer Genome Atlas) and GEPIA (Gene Expression Profiling Interactive Analysis). The results showed that the expression of miR-105 in rectal cancer was higher than that in normal mucosa in RT (P = 0.042) and non-RT patients (P = 0.003) and was associated with mucinous histological type (P = 0.004), COX-2 (P = 0.042), and p73 expression (P = 0.030). The expression of miR-302a was shown more frequently in cancers with necrosis (P = 0.033) and with WRAP53 expression (P = 0.015), whereas miR-888 expression occurred more frequently in tumors with protein the expression of survivin (P = 0.015), AEG-1 (astrocyte elevated gene-1) (P = 0.003), and SATB1 (special AT-rich sequence binding protein 1) (P = 0.036). Moreover, TargetScan also predicted AEG-1 and SATB1 as putative targets for miR-888. The miRNA-gene network analysis showed that ABI2 was associated with all the three miRNAs, with lower expression and good diagnostic value in rectal cancers. The TCGA database demonstrated the association of miR-105 expression with high carcinoembryonic antigen level (P = 0.048). RT reduced the expressions of miR-302a, miR-105, and miR-888. Prognostic analysis showed that miR-888 expression was independently associated with worse survival of patients without RT [overall survival, P = 0.001; disease-free survival, P = 0.009]. Analysis of biological function revealed that the protein serine/threonine kinase activity and PI3K-AKT signaling pathway were the most significantly enriched functions and pathways, respectively. Our findings suggest that miR-105 is involved in rectal cancer pathogenesis and miR-888 is associated with prognosis. MiR-302a, miR-105, and miR-888 have potential influence on the pathogenesis, RT, and prognosis of rectal cancer.
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| 8. |
- Meng, Wen-Jian, et al.
(author)
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MicroRNA Expression Profile Reveals miR-17-92 and miR-143-145 Cluster in Synchronous Colorectal Cancer
- 2015
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In: Medicine. - : Lippincott Williams & Wilkins. - 0025-7974 .- 1536-5964. ; 94:32
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Journal article (peer-reviewed)abstract
- The expression of abnormal microRNA (miRNA, miR) is a ubiquitous feature of colorectal cancer (CRC). The pathological features and clinical behaviors of synchronous CRC have been comprehensively described; however, the expression profile of miRNA and small nucleolar RNA (snoRNA) in synchronous CRC has not been elucidated. In the present study, the expression profile of miRNA and snoRNA in 5 synchronous CRCs, along with the matched normal colorectal tissue was evaluated by microarray. Function and pathway analyses of putative targets, predicted from miRNA-mRNA interaction, were performed. Moreover, we analyzed clinicopathological and molecular characteristics of 22 patients with synchronous CRC and 579 solitary CRCs in a retrospective cohort study. We found a global dysregulation of miRNAs, including an oncogenic miR-17-92 cluster and oncosuppressive miR-143-145 cluster, and snoRNAs in synchronous CRC. Differential miRNA rather than snoRNA expression was robust enough to distinguish synchronous cancer from normal mucosa. Function analysis of putative targets suggested that miRNA clusters may modulate multiple effectors of oncogenic pathways involved in the pathogenesis of synchronous CRC. A comparison of normal mucosa between synchronous and solitary CRC suggested a differential genetic background of synchronous CRC from solitary CRC during carcinogenesis. Compared with solitary cancer patients, synchronous cases exhibited multiple extra-colonic cancers (P=0.012), coexistence of adenoma (P=0.012), microsatellite instability (P=0.024), and less glucose transporter 1 (P=0.037). Aberrant miRNA expression profiles could potentially be used as a diagnostic tool for synchronous CRC. Our findings represent the first comprehensive miRNA and snoRNA expression signatures for synchronous CRC, implicating that the miRNAs and snoRNAs may present therapeutic targets for synchronous CRC.
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| 9. |
- Middeldorp, Christel M., et al.
(author)
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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
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In: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
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Journal article (peer-reviewed)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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| 10. |
- Wang, Chao-Jie, et al.
(author)
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FBI-1 mRNA in normal mucosa is an independent prognostic factor in colorectal cancer patients
- 2018
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In: International Journal of Clinical and Experimental Pathology. - : e-Century Publishing. - 1936-2625. ; 11:2, s. 642-649
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Journal article (peer-reviewed)abstract
- Although several studies provide evidence that FBI-1 is an important gene regulator in colorectal cancer (CRC), it is noteworthy that, to our knowledge, no analysis of the correlation between FBI-1 expression and prognosis in CRC has been reported. Using real-time RT-PCR, we detected FBI-1 mRNA in 161 CRC patients (primary tumor, along with the corresponding normal mucosa), 36 liver metastases, and analyzed the relationship of its expression with clinicopathological features. Colon cancer cell lines were used to study FBI-1 function. Our study found that FBI-1 was significant up-regulated in tumor tissue (2.621 +/- 0.157) compared with the corresponding normal mucosa (1.620 +/- 0.165, P < 0.0001). FBI-1 in normal mucosa was a prognostic factor (P = 0.039, RR 0.431, 95% CI 0.194-0.958), independent of gender, age, stage, and differentiation. High levels of FBI-1 mRNA were related with good survival. Patients with complications had a higher primary tumor FBI-1 expression than those without complications (3.400 +/- 0.332 vs. 2.516 +/- 0.241, P = 0.032). Suppression of FBI-1 in colon cancer cell lines could repress proliferation of cancer cells. In conclusion, FBI-1 mRNA is overexpressed in CRC, and takes part in the development of CRC. FBI-1 mRNA in normal mucosa is an independent prognostic factor. Our findings give further support to the concept of "field cancerization", and hint that when we study a biomarker, we should not only focus on the tumor tissue but also the corresponding normal mucosa.
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