Publications by authors named "Menglin Xu"

23 Publications

  • Page 1 of 1

White and Black Differences in Perceived Access to Health and Community Services and Self-Rated Health in an Age-Friendly Community Assessment.

J Appl Gerontol 2021 Jun 11:7334648211023251. Epub 2021 Jun 11.

Age-Friendly Innovation Center, Columbus, USA.

Objectives: This study sought to identify the race differences in perceived access to health and community services and self-rated health (SRH) among White and Black older adult participants of an age-friendly community assessment.

Methods: Responses ( = 313) to a baseline assessment of Columbus, Ohio, residents aged ≥50 years were analyzed.

Results: Significant differences were found between White and Black older adults regarding SRH, with Black older adults reporting lower SRH. Black older adults reported significantly lower perceived access to 11 out of the 13 health and community services. There were no significant differences by race regarding ratings of Columbus and personal neighborhoods as a place for people to live as they age. Regression analyses found income was a significant predictor of SRH for both White and Black older adults.

Discussion: Opportunities to increase perceived access and knowledge of health and community services for older adults through targeted, equitable interventions are warranted.
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http://dx.doi.org/10.1177/07334648211023251DOI Listing
June 2021

Sensory perceptions of survivors of cancer and their caregivers upon blinded evaluation of produce from two different sources.

Support Care Cancer 2021 Mar 17. Epub 2021 Mar 17.

Medical Dietetics & Health Sciences, School of Health and Rehabilitation Sciences, The Ohio State University College of Medicine, Columbus, OH, USA.

Purpose: Evidence documents the role of modifiable lifestyle behaviors in optimizing physical and mental health outcomes for survivors of cancer. Fruit and vegetable consumption is one such behavior, and understanding survivor sensory perceptions of produce can inform interventions aimed at improving dietary patterns. The objective of this study was to assess the sensory perceptions of survivors of cancer and their caregivers when asked to evaluate garden-harvested and grocery-purchased produce.

Methods: Participants enrolled in a garden-based biobehavioral intervention and their caregivers (n=32) were invited to participate in a sensory evaluation of four produce types: tangerine cherry tomatoes, green cabbage, green beans, and green bell peppers. Samples were coded and distributed in a random fashion, and participants completed validated sensory surveys (preference, liking/acceptability, and discrimination) for each type of produce.

Results: Upon initial blinded evaluation, a significant preference for grocery-purchased produce was noted for green cabbage, green beans, and green bell peppers but not tomatoes (all p<0.05). After self-labeling, however, participants reported a preference for perceived garden-harvested produce (all p≤0.001) even when incorrectly labeled. Liking/acceptability scores were significantly higher among self-labeled garden-harvested versus self-labeled grocery-purchased for all types of produce (all p≤0.001). These data reveal survivors of cancer and their caregivers perceive garden-harvested produce as superior to grocery-purchased, though were unable to accurately identify the two sources based upon sensory factors such as taste, smell, and texture alone when blinded for three of the four types of produce.

Conclusion: Findings indicate future interventions should address perceptions of produce to facilitate improvements in consumption in these vulnerable individuals.
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http://dx.doi.org/10.1007/s00520-021-06090-3DOI Listing
March 2021

AIM2 inhibits colorectal cancer cell proliferation and migration through suppression of Gli1.

Aging (Albany NY) 2020 12 3;13(1):1017-1031. Epub 2020 Dec 3.

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu 241000, China.

Colorectal cancer (CRC) is a common malignant tumor and is one of the leading causes of cancer-related deaths worldwide. Absent in melanoma 2 (AIM2), as a member of the pyrin-HIN family proteins, plays contentious roles in different types of cancers. In the present work, we provide evidence that AIM2 was commonly downregulated in human CRC and loss of AIM2 significantly correlated with tumor size, depth of invasion, lymph node metastasis (LNM) and TNM (Tumor, Node, Metastases) stage in patients suffering from CRC. AIM2 knockdown promoted CRC cell proliferation, migration and epithelial-mesenchymal transition (EMT) progress, whereas AIM2 overexpression did the opposite. AIM2 inhibited glioma-associated oncogene-1 (Gli1) expression through Smoothened homolog (SMO)-independent pathway and regulated CRC cell proliferation and migration in a Gli1-dependent manner. Moreover, AIM2 could modulate Protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway and the increased Gli1 expression and EMT progress induced by AIM2 depletion was reversed after incubation with AKT inhibitor Ly294002 in CRC cells. In conclusion, our results define AIM2 as a novel regulator of Gli1 in CRC cell growth and metastasis, and suggest that the AIM2/AKT/mTOR/Gli1 signaling axis may serve as a potential target for treatment of CRC.
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http://dx.doi.org/10.18632/aging.202226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835022PMC
December 2020

Increased bleeding risk associated with concurrent vascular endothelial growth factor receptor tyrosine kinase inhibitors and low-molecular-weight heparin.

Cancer 2021 Mar 20;127(6):938-945. Epub 2020 Nov 20.

Division of Medical Oncology, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, Ohio.

Background: Some cancer patients who are diagnosed with thromboembolism may require dual treatment with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) and factor Xa inhibitors (low-molecular-weight heparin [LMWH] or direct oral anticoagulants [DOACs]). However, to the authors' knowledge, the safety of such combinations has not been well characterized.

Methods: Patients with advanced cancer who were treated with concurrent VEGFR TKIs and factor Xa inhibitors between 2010 and 2018 at The Ohio State University Comprehensive Cancer Center were included. Charts were reviewed retrospectively for clinically significant bleeding events occurring during concurrent treatment compared with those occurring during factor Xa inhibitor therapy alone, using each patient as their own control. The Fisher exact test was used to compare distribution of bleeding severities. The Cox proportional hazards model was used to compare bleeding risk between groups.

Results: Among 86 patients, there were 29 clinically significant bleeding events (including 8 major bleeding events) reported during concurrent treatment and 17 events (including 4 major bleeding events) reported during factor Xa inhibitor therapy alone over a median follow-up of 63 days. Concurrent treatment was associated with significantly higher risks of overall bleeding (hazard ratio, 2.45; 95% confidence interval, 1.28-4.69 [P = .007]) and first-onset bleeding (hazard ratio, 2.23; 95% confidence interval, 1.13-4.42 [P = .02]). Analysis of 6-month bleeding risk and the subgroups of patients treated with concurrent TKIs and LMWH versus LMWH alone demonstrated a similar trend. The sample size was inadequate for comparisons between treatment with concurrent TKIs and DOACs versus DOACs alone.

Conclusions: Concurrent treatment with VEGFR TKIs and LMWH was found to be associated with a significantly increased risk of bleeding events when compared with LMWH therapy alone.
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http://dx.doi.org/10.1002/cncr.33337DOI Listing
March 2021

Clinical value and potential association of Rab1A and FoxM1 aberrant expression in colorectal cancer.

Sci Rep 2020 11 19;10(1):20160. Epub 2020 Nov 19.

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, No. 2 Zheshan West Road, Jinghu District, Wuhu, 241000, Anhui Province, China.

Colorectal carcinoma (CRC) is one of the most common malignancies with a dismal 5-year survival rate. Our recent study indicated that Rab1A expression was closely related to GLI1 expression. A previous study shows that aberrant overexpression of GLI1 promotes colorectal cancer metastasis via FoxM1 overexpression. However, the potential correlation between Rab1A and FoxM1 in CRC remains elusive. Immunohistochemistry was performed to investigate the association of the expression of Rab1A and FoxM1 and to determine the prognosis in 135 CRC tissue and adjacent normal tissues. Using Oncomine datasets, we found that Rab1A and FoxM1 mRNA were obviously upregulated in CRC tissues compared to normal tissues. Additionally, the expression of Rab1A and FoxM1 was significantly higher in CRC tissues than that in normal tissues. Rab1A expression was positively correlated with FoxM1 expression in CRC, especially in TNM stage III. In addition, Rab1A and FoxM1 overexpression was found to be significantly correlated with poor prognosis in CRC patients. Besides, both high expression of Rab1A and FoxM1 led to a worse prognosis than anyone low group, and both low expression of Rab1A and FoxM1 had a better prognosis than the anyone low group. Therefore, Rab1A and FoxM1 play crucial roles and could be used as clinical biomarkers in CRC.
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http://dx.doi.org/10.1038/s41598-020-77182-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678875PMC
November 2020

Bidirectional Association Between Daily Physical Activity and Postconcussion Symptoms Among Youth.

JAMA Netw Open 2020 11 2;3(11):e2027486. Epub 2020 Nov 2.

Department of Psychology, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.

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http://dx.doi.org/10.1001/jamanetworkopen.2020.27486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672517PMC
November 2020

Yes-Associated Protein Contributes to Cell Proliferation and Migration of Gastric Cancer via Activation of Gli1.

Onco Targets Ther 2020 27;13:10867-10876. Epub 2020 Oct 27.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu 241000, People's Republic of China.

Objective: In the present study, we aimed to explore the potential oncogenic property and the internal mechanism of yes-associated protein (YAP) in gastric cancer (GC).

Materials And Methods: YAP protein levels were evaluated in human GC tissues and paired normal tissues using immunohistochemistry (IHC). The role of YAP in regulating GC cell proliferation and migration was verified by genetic manipulation in vitro. Western blot analysis was used to determine the molecular signaling to explain the mechanism of the observed YAP effects in GC.

Results: Nuclear YAP protein expression was upregulated in GC tissues, and high nuclear YAP level was significantly correlated with lymph node metastasis (LNM) and tumor node metastasis (TNM) stage in patients suffered from GC. YAP knockdown inhibited GC cell proliferation, migration and epithelial-mesenchymal transition (EMT) progress in vitro, whereas YAP elevation did the opposite. YAP regulated glioma-associated oncogene-1 (Gli1) expression independent of smoothened homolog (SMO). YAP modulated protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway in GC cells.

Conclusion: YAP enhanced GC cell proliferation and migration potentially via its regulation of Gli1 expression through the non-classical Hedgehog pathway, indicating suppression of YAP/Gli1 signaling axis may highlight a new entry point for combination therapy of GC.
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http://dx.doi.org/10.2147/OTT.S266449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603417PMC
October 2020

Mental health-related quality of life is associated with diet quality among survivors of breast cancer.

Support Care Cancer 2021 Apr 25;29(4):2021-2028. Epub 2020 Aug 25.

Division of Medical Dietetics and Health Sciences, School of Health and Rehabilitation Sciences, College of Medicine, The Ohio State University, 306 Atwell Hall 453 W. 10th Ave., Columbus, OH, 43210, USA.

Objective: This study sought to understand the association of mental health-related quality of life (MHRQoL) and nutritional status (food security status and malnutrition risk), with diet quality among female survivors of breast cancer.

Method: This pilot cross-sectional study utilized self-report survey data from the RAND-36, the USDA 2-item food insecurity screen, the Malnutrition Screening Tool (MST), and the Diet History Questionnaire II (DHQII)/Health Eating Index 2015 (HEI). Participants self-selected participation after being identified through an academic medical center cancer registry and contact through mailed recruitment letters and flyers posted in oncology clinics. Emotional well-being and social functioning composite scores of the RAND-36 were used to characterize MHRQoL. Correlational and regression analyses were performed to assess the association of diet quality, nutritional status, and MHRQoL.

Results: The majority of participants (n = 90) were non-Hispanic white (90%), average age of 71.3 ± 8.1 years, and an average body mass index (BMI) of 28.2 ± 6.6. Four of the 90 participants (4.4%) scored at risk for food insecurity. Linear regression indicated that social functioning composite scores were positively associated with HEI scores (β = 0.11, SE = 0.53, p = 0.03). Controlling for demographic characteristics, education level (β = 5.25, SE = 2.25, p = 0.02) was positively associated with HEI scores.

Conclusion: Diet quality and MHRQoL were associated among breast cancer survivors, with education level also being associated with diet quality. These results can be used to aid targeted nutrition counseling and mental health interventions to address the nutritional vulnerabilities among female breast cancer survivors, particularly among older cancer survivors.
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http://dx.doi.org/10.1007/s00520-020-05698-1DOI Listing
April 2021

ENO1 Acts as a Prognostic Biomarker Candidate and Promotes Tumor Growth and Migration Ability Through the Regulation of Rab1A in Colorectal Cancer.

Cancer Manag Res 2019 26;11:9969-9978. Epub 2019 Nov 26.

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu 241000, People's Republic of China.

Background: Colorectal carcinoma (CRC) is one of the most common malignancies with a dismal 5-year survival rate. The glycolytic enzyme α-enolase () is overexpressed in multiple cancers and is involved in tumor cell proliferation and metastasis. However, its clinical significance, biological role, and underlying molecular mechanisms in CRC are still unclear. The aim of the present study was to investigate the potential role of in the initiation and development of CRC.

Patients And Methods: The in situ expression of ENO1 in CRC and adjacent normal tissues was examined by immunohistochemistry. The effects of on the in vitro proliferation and migration of CRC cell lines were investigated by MTT, colony formation, and Transwell assays. Finally, the in vivo tumorigenic capacity of ENO1 was assessed in a mouse model.

Results: ENO1 was overexpressed in CRC tissues and significantly correlated with the clinicopathological parameters. Furthermore, Rab1A was also overexpressed in CRC tissues and was positively correlated to that of ENO1. The high expression levels of both ENO1 and Rab1A led to significantly worse prognosis of CRC patients compared to either alone. Furthermore, knockdown of ENO1 significantly inhibited CRC cells proliferation and migration in vitro and reduced xenograft growth in vivo via the concomitant downregulation of Rab1A.

Conclusion: The ENO1/Rab1A signaling axis is involved in CRC progression and is a potential biomarker for the treatment of CRC.
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http://dx.doi.org/10.2147/CMAR.S226429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6884970PMC
November 2019

Pooled analysis of prognostic value and clinical significance of Rab1A expression in human solid tumors.

Medicine (Baltimore) 2019 Dec;98(50):e18370

Department of gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou.

Background: This study aims to assess the relationship between Rab1A expression and clinicopathological parameters and prognosis of patients with human solid cancer by summarizing the studies included.

Methods: PubMed, EMBASE, The Cochrane Library, and other sources were searched for relative studies. The risk ratios (RRs) and confidence interval (CI) were used to assess association between Rab1A expression and clinical parameters and prognosis in solid cancer patients.

Results: Eight studies were included in the final analysis with 800 patients. The results revealed that expression of Rab1A was significantly related with differentiation (RR = 0.883, 95%CI = 0.782-0.997, P = .044), lymph node metastasis (RR = 0.835, 95%CI = 0.753-0.926, P = .001), tumor-lymph node-metastasis (TNM) stage (RR = 1.190, 95%CI = 1.071-1.322, P < .001) and tumor size (RR = 0.818, 95%CI = 0.730-0.915, P < .001). What is more, no significant difference was seen in 1-year survival between high and low expression of Rab1A in multiple malignancies (RR = 0.855, 95%CI = 0.697-1.050, P = .136). However, increased Rab1A revealed poorer prognosis with 2-year survival (RR = 0.760, 95%CI = 0.701-0.824, P < .001), 3-year survival (RR = 0.669, 95%CI = 0.604-0.742, P < .001), 4-year survival (RR = 0.622, 95%CI = 0.554-0.698, P < .001) and 5-year survival (RR = 0.525, 95%CI = 0.458-0.698, P < .001). Expression of Rab1A was increased obviously in solid cancer tissues compared with the adjacent normal tissue (RR = 4.78, 95%CI 4.05-5.63, P = .015).

Conclusion: This study revealed Rab1A expression links closely with tumor size, differentiation, lymph node metastasis, TNM stage and poor prognosis of human solid cancer patients. It may act as a biomarker of prognosis and a novel therapeutic target in solid cancer.
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http://dx.doi.org/10.1097/MD.0000000000018370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6922505PMC
December 2019

Expression analysis and implication of Rab1A in gastrointestinal relevant tumor.

Sci Rep 2019 09 16;9(1):13384. Epub 2019 Sep 16.

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, 241000, P.R. China.

Gastrointestinal cancers have become increasingly prevalent worldwide. Previous studies have reported an oncogenic function of Rab1A in colorectal cancer and hepatocellular carcinomas via the mTOR pathway. However, the exact role of Rab1A in gastrointestinal cancers remains elusive. We detected significantly higher expression of Rab1A in the gastrointestinal tumor tissues compared to that in other cancer types following an in silico analysis of TGCA and GTEX databases. Furthermore, Rab1A was overexpressed in the gastrointestinal tumor tissues compared to the para-tumor tissues. Although Rab1A expression levels were not associated with the tumor-lymph node-metastasis (TNM) stage, Rab1A overexpression in the tumor tissues of a gastric cancer (GC) cohort was strongly correlated with poor prognosis in the patients. In addition, Rab1A knockdown significantly inhibited the in vitro proliferation and migration abilities of GC cells, as well as the growth of GC xenografts in vivo. Furthermore, a positive correlation was observed between Rab1A expression levels and that of different upstream/downstream mTOR targets. Taken together, Rab1A regulates the PI3K-AKT-mTORC1 pathway through the mTORC1 complex consisting of mTORC1, Rheb and Rab1A, and is a promising therapeutic target in GC.
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http://dx.doi.org/10.1038/s41598-019-49786-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746845PMC
September 2019

Imaging aquatic animal cells and associated pathogens by atomic force microscopy in air.

Biotechnol Lett 2019 Oct 13;41(10):1105-1110. Epub 2019 Aug 13.

Key Laboratory of Maricultural Organism Disease Control, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, No. 106 Nanjing Road, Qingdao, 266071, China.

Atomic force microscopy (AFM) is a sophisticated imaging tool with nanoscale resolution that is widely used in structural biology, cell biology, and material science, among other fields. However, to date it has rarely been applied to the study of aquatic animals, especially on one of the main cultured species, shrimp. One reason for this is that no shrimp cell line established until now, primary cell is fragile and difficult to be studied under AFM. In this study, we used AFM to image three different types of biological material from shrimp (Litopenaeus vannamei) in air, including hemocytes and two associated pathogens. Without obvious deformations when the cells were imaged in air and in the case for the haemocytes and the cells were fixed as well. The result suggests hydrophobic glass coverslips are a suitable substrate for adhesion of these samples. The method described here can be applied to the preparation of other fragile biological samples from aquatic animals for high-resolution analyses of host-pathogen interactions and other basic physiological processes.
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http://dx.doi.org/10.1007/s10529-019-02720-3DOI Listing
October 2019

Influence of gene modification in biological behaviors and responses of mouse lung telocytes to inflammation.

J Transl Med 2019 05 15;17(1):158. Epub 2019 May 15.

Zhongshan Hospital Institute of Clinical Science, Shanghai Institute of Clinical Bioinformatics, Shanghai Engineering Research for AI Technology for Cardiopulmonary Diseases, Shanghai, China.

Background: Telocytes play key roles in maintenance of organ/tissue function and prevention of organ injury. However, there are great challenges to investigate telocytes functions using primary telocytes, due to the difficulties of isolation, identification, and stability. The present study aims at constructing continuous cell strain of mouse lung telocyte cell line with stable characters by gene modification and investigating biological behaviors and responses of gene-modified telocytes to inflammation.

Methods: Mouse primary lung telocytes were isolated and identified using immune-labeling markers and immunoelectron microscopy. Primary telocytes were transformed with Simian vacuolating virus 40 small and large T antigen (SV40). Biological characters, behaviors morphology, and proliferation of those gene-modified telocytes were defined and monitored dynamically for 50 generations, as compared with primary lung telocytes. Cell cycle of mouse primary lung telocytes or gene-modified telocytes was detected by flow cytometry.

Results: Gene modified telocytes of generations 5, 10, 30 and 50 were observed with telopodes and also showed CD34 and ckit positive. Multiple cellular morphology were also observed on telocyte cell-line under monitor of celliq and enhanced cell proliferation were showed. SV40 transduction was also reduced apoptosis and increased the ratio of S and G2 phases in telocyte cell-line.

Conclusion: We successfully constructed mouse lung telocyte cell-line which maintained the biological properties and behaviors as primary telocytes and could responses to inflammation induced by LPS. Thus, gene-modified lung telocytes, Telocyte Line, would provide a cell tool for researchers exploring the roles and applications of telocytes involved in physiological and pathological states in future.
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http://dx.doi.org/10.1186/s12967-019-1870-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521571PMC
May 2019

Prognosis, Significance and Positive Correlation of Rab1A and p-S6K/Gli1 Expression in Gastric Cancer.

Anticancer Agents Med Chem 2019 ;19(11):1359-1367

Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215006, China.

Background: Gastric Cancer (GC) is a frequently common malignancy. Recent studies have reported Rab1A as an activator of mTORC1, and the mTOR1 pathway is involved in regulating Gli1 expression in several cancers. Only a few studies have been performed to explore the relationship between Rab1A and p-S6K/Gli1in GC.

Methods: Immunohistochemistry (IHC) was performed to explore the association of Rab1A/p-S6K/Gli1 expression and prognosis in 117 GC tissue samples and adjacent normal tissues.

Results: Our results indicated that Rab1A/p-S6K/Gli1 was significantly overexpressed in GC tissues. High expression of Rab1A was closely related to the tumor size and the depth of tumor invasion. In addition, Rab1A expression was closely related with p-S6K/Gli1 expression in GC, and high level of Rab1A/p-S6K/Gli1 caused worse prognosis of GC patients. The univariate and multivariate analysis indicated that the expression of Rab1A was an independent prognostic factor. Moreover, both high Rab1A and p-S6K expression led to a worse prognosis when compared to a single positive expression as well as both high Rab1A/Gli1 expression also led to a worse prognosis than the single positive expression of Rab1A/Gli1. Strikingly, the overexpression of p-S6K also led to a worse prognosis in Rab1A positive patients, as did Gli1.

Conclusion: Our results indicate that Rab1A/mTOR/S6K/Gli1 axis played a crucial role in GC, which may provide a novel field on targeted therapy of GC, especially for mTORC1-targeted therapy-resistant cancers.
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http://dx.doi.org/10.2174/1871520619666190416110851DOI Listing
March 2020

Rab1A promotes proliferation and migration abilities via regulation of the HER2/AKT-independent mTOR/S6K1 pathway in colorectal cancer.

Oncol Rep 2019 May 15;41(5):2717-2728. Epub 2019 Mar 15.

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui 241000, P.R. China.

Colorectal carcinoma (CRC) is one of the most common malignancies worldwide and the second leading cause of cancer‑related deaths in the US. Recently, Rab1A has been reported to be an activator of mTORC1 and p‑S6K1, which is downstream of mTORC1. However, the association between Rab1A and p‑S6K1 in CRC remains elusive. In the present study, we first demonstrated that Rab1A was overexpressed in CRC tissues and Rab1A overexpression was positively related to lymph node invasion, degree of differentiation, venous invasion and tumor‑node‑metastasis (TNM) stage. In both TNM stage I‑II and III‑IV patients, Rab1A‑positive patients had a shorter survival time than Rab1A‑negative patients. Furthermore, in univariate and multivariate analyses, only Rab1A expression was verified as an independent prognostic factor for survival in CRC patients. The level of p‑S6K1 was markedly high in CRC tissues and Rab1A expression level had a positive association with p‑S6K1 level. In addition, high levels of both Rab1A and p‑S6K1 were associated with a poorer prognosis compared with low expression of either Rab1A or p‑S6K1 level. Moreover, high levels of both Rab1A and p‑S6K1 were associated with a poorer prognosis than patients with high levels of either Rab1A or p‑S6K1 alone. Finally, knockdown of Rab1A expression inhibited migration and proliferation of SW480 and HCT116 cell lines by targeting regulation of p‑S6K1. Thus, our findings indicate that Rab1A plays an important role in CRC and may provide a therapeutic target for CRC, particularly for mTORC1‑targeted therapy‑resistant cancers.
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http://dx.doi.org/10.3892/or.2019.7071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448090PMC
May 2019

Selection of AECOPD-specific immunomodulatory biomarkers by integrating genomics and proteomics with clinical informatics.

Cell Biol Toxicol 2018 04 4;34(2):109-123. Epub 2017 Aug 4.

Zhongshan Hospital Institute of Clinical Science, Shanghai Institute of Clinical Bioinformatics, Shanghai Medical College, Fudan University, Shanghai, China.

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) as a serious event has high mortality and medical costs. Systemic inflammation and immune response are the major factors influencing the outcome and quality of patient with AECOPD. On basis of identification and validation of AECOPD-specific inflammatory biomarkers, the present study aimed to identify AECOPD-specific immunomodulatory mediators by evaluating dynamic genomic and proteomic profiles of peripheral blood mononuclear cells (PBMCs) and plasma in patients with AECOPD on day 1, 3, and 10 after the hospital admission, to compare with healthy controls or patients with stable COPD. We found that genes and proteins of C1QC and C1RL were co-differentially up-expressed in patients with COPD or AECOPD, while haptoglobin (HP), ORM1, SERPING1, and C3 were identified as a panel of AECOPD-specific immunomodulatory mediators. We also found that inflammatory stimuli could up-regulate osteopontin (OPN)-associated HP expression through the PI3K signal pathway in A549 cells. Block of autocrine production of OPN by gene inhibition could reduce HP production from inflammation-induced lung epithelial cells. The complex network of AECOPD- or COPD-specific immunomodulatory mediators will benefit the development of precision or personalized medicine strategies for prevention and treatment of AECOPD.
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http://dx.doi.org/10.1007/s10565-017-9405-xDOI Listing
April 2018

Critical roles of mucin-1 in sensitivity of lung cancer cells to tumor necrosis factor-alpha and dexamethasone.

Cell Biol Toxicol 2017 08 3;33(4):361-371. Epub 2017 May 3.

Department of Respiratory Medicine, The First Hospital of Wenzhou Medical University, Wenzhou, China.

Lung cancer is the leading cause of death from cancer. Mucins are glycoproteins with high molecular weight, responsible for cell growth, differentiation, and signaling, and were proposed to be correlated with gene heterogeneity of lung cancer. Here, we report aberrant expression of mucin genes and tumor necrosis factor receptors in lung adenocarcinoma tissues compared with normal tissues in GEO datasets. Mucin-1 (MUC1) gene was selected and considered as the target gene; furthermore, the expression pattern of adenocarcinomic cells (A549, H1650, or H1299 cells) was validated under the stimulation with tumor necrosis factor-alpha (TNFα) or dexamethasone (DEX), separately. MUC1 gene interference was done to A549 cells to show its role in sensitivity of lung cancer cells to TNFα and DEX. Results of our experiments indicate that MUC1 may regulate the influence of inflammatory mediators in effects of glucocorticoids (GCs), as a regulatory target to improve therapeutics. It shows the potential effect of MUC1 and GCs in lung adenocarcinoma (LADC), which may help in LADC treatment in the future.
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http://dx.doi.org/10.1007/s10565-017-9393-xDOI Listing
August 2017

A global view of regulatory networks in lung cancer: An approach to understand homogeneity and heterogeneity.

Semin Cancer Biol 2017 02 25;42:31-38. Epub 2016 Nov 25.

Department of Pulmonary Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China. Electronic address:

A number of new biotechnologies are used to identify potential biomarkers for the early detection of lung cancer, enabling a personalized therapy to be developed in response. The combinatorial cross-regulation of hundreds of biological function-specific transcription factors (TFs) is defined as the understanding of regulatory networks of molecules within the cell. Here we integrated global databases with 537 patients with lung adenocarcinoma (ADC), 140 with lung squamous carcinoma (SCC), 9 with lung large-cell carcinoma (LCC), 56 with small-cell lung cancer (SCLC), and 590 without cancer with the understanding of TF functions. The present review aims at the homogeneity or heterogeneity of gene expression profiles among subtypes of lung cancer. About 5, 136, 52, or 16 up-regulated or 19, 24, 122, or 97down-regulated type-special TF genes were identified in ADC, SCC, LCC or SCLC, respectively. DNA-binding and transcription regulator activity associated genes play a dominant role in the differentiation of subtypes in lung cancer. Subtype-specific TF gene regulatory networks with elements should be an alternative for diagnostic and therapeutic targets for early identification of lung cancer and can provide insightful clues to etiology and pathogenesis.
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http://dx.doi.org/10.1016/j.semcancer.2016.11.004DOI Listing
February 2017

New strategies for targeting drug combinations to overcome mutation-driven drug resistance.

Semin Cancer Biol 2017 02 10;42:44-51. Epub 2016 Nov 10.

Zhongshan Hospital Institute of Clinical Science, Fudan University, Shanghai Institute of Clinical Bioinformatics, Biomedical Research Center, Shanghai, China. Electronic address:

Targeted therapies are suggested as an effective alternative for patients with cancer that harbor mutations, but treatment outcomes are frequently limited by primary or acquired drug resistance. The present review describes potential mechanisms of primary or acquired drug resistances to provide a resource for considering how to be overcome. We focus on strategies of targeted drug combinations to minimize the development of drug resistance within the context how resistance develops. Strategies benefit from the combined use of "omics" technologies, i.e., high-throughput functional genomics data, pharmacogenomics, or genome-wide CRISPR-Cas9 screening, to analyze and design targeted drug combinations for mutation-driven drug resistance. We also introduce new insights towards pathway-centric combined therapies as an alternative to overcome the heterogeneity and benefit patient prognoses.
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http://dx.doi.org/10.1016/j.semcancer.2016.11.002DOI Listing
February 2017

Bifactor Structure for the Categorical Chinese Rosenberg Self-Esteem Scale.

Span J Psychol 2016 Oct 11;19:E67. Epub 2016 Oct 11.

University of Macau(China).

Recently, the bifactor model was suggested for the latent structure of the Rosenberg Self-Esteem Scale (RSES). The present paper investigates (i) the differences among bifactor, bifactor negative and other models; (ii) the effects of treating data as both categorical vs continuous; (iii) whether a problematic item in the Chinese RSES should be removed; and (iv) whether the final scoring would be affected. With a sample of 1.734 grade 4-6 school pupils in Hong Kong, we used BIC differences in addition to the usual model fit indices, and found that there was strong evidence for using the bifactor model (RMSEA = .052, 90% CI [.043, .062], CFI = .992, TLI = .984 for 9-item RSES categorical). Little difference is found between treating data as categorical or continuous for fit indices, but the factor loading patterns are better in categorical case. Keeping a problematic item has little effect on fit indices, but would lead to unexpected negative loading. The ranking of loadings within positive and negative items across different conditions are the same, which has important effects on scoring. Loadings in the method effects in the bifactor models are all positive (p < .001), which is different from previous research. All models show similar results on scoring, and support the usual simple sum score in most practice.
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http://dx.doi.org/10.1017/sjp.2016.66DOI Listing
October 2016

Correlation between mucin biology and tumor heterogeneity in lung cancer.

Semin Cell Dev Biol 2017 04 26;64:73-78. Epub 2016 Aug 26.

Zhongshan Hospital Institute of Clinical Science, Fudan University, Shanghai Institute of Clinical Bioinformatics, Biomedical Research Center, Shanghai, China. Electronic address:

Mucins (MUC) are a family consisting of large O-glycoproteins whose primary functions are to protect and lubricate cell epithelial surfaces and contribute to intra- and inter-cellular signal pathways, cell proliferation, growth and apotosis. With the development of new technologies, MUCs begin to be identified as an effective marker in evaluating the tumor heterogeneity in lung cancer. MUCs' diverse expressions in subtypes of lung cancer indicate the inter-tumor heterogeneity. MUCs' mutation may also contribute to the development of intra-heterogeneity and evolution of lung cancer. Understanding MUCs' association with lung cancer heterogeneity and its molecular regulatory mechanism will benefit the development of diagnosis, therapy choice, and prognosis prediction of lung cancer.
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http://dx.doi.org/10.1016/j.semcdb.2016.08.027DOI Listing
April 2017

Variations of chromosome 2 gene expressions among patients with lung cancer or non-cancer.

Cell Biol Toxicol 2016 10 15;32(5):419-35. Epub 2016 Jun 15.

Zhongshan Hospital, Shanghai Institute of Clinical Bioinformatics, Fudan University Medical School, Shanghai, China.

Lung cancer is one of the most common malignancies worldwide. The present study aimed to investigate specific genotypes of different subtypes or stages of lung cancer through gene expression variations of chromosome 2 genes, trying to identify predictors for diagnosis or prognosis of lung cancer. About 537 patients with lung adenocarcinoma (ADC), 140 patients with lung squamous carcinoma (SQC), 9 patients with lung large cell carcinoma (LCC), 56 patients with small cell lung cancer (SCLC), and 590 patients without cancer were analyzed in present study. Co-expressed, subtype-specific, and stage-specific chromosome 2 genes were identified and further analyzed by bioinformatic methods. As a result, 15 or 10 genes were significantly up- or down-regulated in all four subtypes of lung cancer. GKN1, LOC100131510, prominin-2 (PROM2), IL37, and SNORA41 were identified as ADC-specific up-regulated genes; SQC-specific up-regulated genes included HOXD family (HOXD1, HOXD3, HOXD4, HOXD8, and HOXD9) and UGT1A family (UGT1A1, UGT1A3, UGT1A4, UGT1A5, UGT1A7, UGT1A8, UGT1A9, and UGT1A10); and LCC- or SCLC-specific genes were also identified. Nine genes were significantly up-expressed at all four stages of ADC while 230 genes at all three stages of SQC. MFSD2B, CCL20 and STAT1, or STARD7 and ZNF512 genes may be risk or protect factors in prognosis of ADC, while HTR2B, DPP4, and TGFBRAP1 genes may be risk factors in prognosis of SQC. Our results suggested that a number of altered chromosome 2 genes have the subtype or stage specificities of lung cancer and may be considered as diagnostic and prognostic biomarkers.
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http://dx.doi.org/10.1007/s10565-016-9343-zDOI Listing
October 2016

Global analyses of subtype- or stage-specific genes on chromosome 7 in patients with lung cancer.

Cancer Metastasis Rev 2015 Jun;34(2):333-45

Zhongshan Hospital, Fudan University Medical School, Shanghai Institute of Clinical Bioinformatics, Shanghai, China.

Lung cancer is the most common cancer and becomes the leading cause of cancer mortality. Genetic and epigenetic alterations and variations are important to identify target genes in lung cancer and demonstrate the potential association of the chromosome 7 aberration with tumorigenesis. The present article integrated the independent and scattered global datasets to detect significant genes, co-expressed, type-special and stage-special genes in lung cancer with a special focus on chromosome 7 with bioinformatics analysis methods. About 60, 214, 26, or 49 up-regulated type-special genes, and 67, 35, 114, or 141 down-regulated type-special genes were identified in adenocarcinoma (ADC), squamous cell carcinoma (SCC), large cell carcinoma (LCC) or small-cell lung cancer (SCLC), respectively. About 5, 2, 8, or 1 stage-specific genes were up-regulated, while 23, 8, 2, or 90 stage-specific genes were down-regulated in ADC at stage I, II, III, or IV, respectively. Two stage-specific genes were significantly up-regulated in SCC at stage II, while 2 or 18 stage-specific genes in SCC at stage I or III were down-regulated, respectively. Lung cancer prognostic prediction rates of subtype- or stage-specific genes were further evaluated. The present study globally analyzed and identified subtype- or stage-specific target genes of lung cancer on chromosome 7 by combining 16 GSE datasets for the first time, although there are still needs to furthermore validate the clinical values of those identified genes in a large population of patients with lung cancer.
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http://dx.doi.org/10.1007/s10555-015-9568-yDOI Listing
June 2015
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