Publications by authors named "Siqi Han"

31 Publications

Clinical Effects of Stereotactic Body Radiation Therapy Targeting the Primary Tumor of Liver-Only Oligometastatic Pancreatic Cancer.

Front Oncol 2021 27;11:659987. Epub 2021 May 27.

Department of Medical Oncology, Jinling Hospital, Nanjing Clinical School of Nanjing Medical University, Nanjing, China.

Aim: To investigate the efficacy and safety of stereotactic body radiotherapy (SBRT) targeting the primary tumor for liver-only oligometastatic pancreatic cancer.

Methods: We compared the efficacy and safety of SBRT plus chemotherapy with chemotherapy alone in patients with liver-only oligometastatic pancreatic cancer. The populations were balanced by propensity score-weighted and propensity score-matched analyses based on baseline variables. The primary outcome was overall survival (OS). The secondary outcomes included progression free survival (PFS), local progression, metastatic progression and symptomatic local control.

Results: This is a retrospective study of 89 pancreatic cancer patients with liver-only oligometastasis. Overall, 34 (38.2%) and 55 (61.8%) patients received SBRT plus chemotherapy and chemotherapy alone, respectively. After propensity score matching, 1-year OS rate was 34.0% (95%CI, 17.8-65.1%) in the SBRT plus chemotherapy group and 16.5% (95%CI, 5.9-46.1%) in chemotherapy alone group (P=0.115). The 6-month PFS rate was 29.4% (95%CI, 15.4-56.1) in SBRT plus chemotherapy and 20.6% (95%CI, 8.8-48.6) in chemotherapy alone group (P=0.468), respectively. Further subgroup analysis indicated that the addition of SBRT improved OS in patients with primary tumor located in the head of pancreas (stratified HR, 0.28; 95% CI, 0.09 to 0.90) or good performance status (stratified HR, 0.24; 95% CI, 0.07 to 0.86). In terms of disease control, SBRT delayed local progression of pancreas (P=0.008), but not distant metastatic progression (P=0.56). Besides, SBRT offered significant abdominal/back pain relief (P=0.016) with acceptable toxicities.

Conclusions: The addition of SBRT to chemotherapy in patients with liver-only oligometastatic pancreatic cancer improves the OS of those with primary tumor located in the head of pancreas or good performance status. In addition, it is a safe and effective method for local progression control and local symptomatic palliation in patients with metastatic pancreatic cancer.
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http://dx.doi.org/10.3389/fonc.2021.659987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190391PMC
May 2021

CRISPR screen in cancer: status quo and future perspectives.

Am J Cancer Res 2021 15;11(4):1031-1050. Epub 2021 Apr 15.

Department of Medical Oncology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University Nanjing 210002, China.

Clustered regularly interspaced short palindromic repeats (CRISPR) system offers a powerful platform for genome manipulation, including protein-coding genes, noncoding RNAs and regulatory elements. The development of CRISPR screen enables high-throughput interrogation of gene functions in diverse tumor biologies, such as tumor growth, metastasis, synthetic lethal interactions, therapeutic resistance and immunotherapy response, which are mostly performed or in transplant models. Recently, direct CRISPR screens have been developed to identify drivers of tumorigenesis in native microenvironment. Key parameters of CRISPR screen are constantly being optimized to achieve higher targeting efficiency and lower off-target effect. Here, we review the recent advances of CRISPR screen in cancer studies both and , with a particular focus on identifying cancer immunotherapy targets, and propose optimizing strategies and future perspectives for CRISPR screen.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085856PMC
April 2021

TriBAFF-CAR-T cells eliminate B-cell malignancies with BAFFR-expression and CD19 antigen loss.

Cancer Cell Int 2021 Apr 17;21(1):223. Epub 2021 Apr 17.

Department of Hematology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong Province, 510317, China.

Background: To investigate the effect of TriBAFF-CAR-T cells on hematological tumor cells.

Methods: TriBAFF-CAR-T and CD19-CAR-T cells were co-cultured with BAFFR-bearing B-cell malignancies at different effector/target ratios to evaluate the anti-tumor effects. In vivo, TriBAFF-CAR-T and CD19-CAR-T cells were intravenously injected into Raji-luciferase xenograft mice. CD19 antigens losing lymphoblasts was simulated by Raji knocking out CD19 (CD19) to investigate the effect of TriBAFF-CAR-T cells on CD19 Raji.

Results: Both TriBAFF-CAR-T and CD19-CAR-T cells significantly induced the lysis of Raji, BALL-1, and Jeko-1. Moreover, when CD19-CAR-T cells specifically caused the lysis of K562 with overexpressed CD19, the lethal effect of TriBAFF-CAR-T cells was also specific for BAFFR-bearing K562 with increasing levels of interleukin-2 and INF-γ. The TriBAFF-CAR-T have the same effect with CD19-CAR-T cells in treating Raji xenofraft mice. TriBAFF-CAR-T cells also have great effect in CD19 Raji cells.

Conclusions: In this study, we successfully constructed novel TriBAFF-CAR-T cells to eliminate BAFFR-bearing and CD19 antigen loss in hematological tumor cells.
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http://dx.doi.org/10.1186/s12935-021-01923-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052726PMC
April 2021

Hydrogen sulfide triggered molecular agent for imaging and cancer therapy.

Chem Commun (Camb) 2021 Feb;57(15):1931-1934

School of Chemistry and Materials Science, Jiangsu Key Laboratory of Biofunctional Materials, Nanjing Normal University, Nanjing, 210023, P. R. China.

We developed an activatable molecular reagent, PNF, triggered by intracellular H2S in the lysosome to release the therapeutic drug amonafide, which can escape from the lysosome into the nucleus to induce autophagy of cancer cells. PNF exhibits potent inhibitory activity against cisplatin-resistant tumor cell lines.
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http://dx.doi.org/10.1039/d0cc07982kDOI Listing
February 2021

Highly sensitive qualitative and quantitative detection of saturated fatty aldehydes in edible vegetable oils using a "turn-on" fluorescent probe by high performance liquid chromatography.

J Chromatogr A 2020 Jun 9;1621:461063. Epub 2020 Apr 9.

School of Pharmacy, Jining Medical University, Jining 272000, PR China. Electronic address:

A new turn-on fluorescent probe, based on a hydrazine group placed in the meso-position of the BODIPY molecule, was synthesized. It was then used for detecting long-chain fatty aldehydes, which can be harmful to human health, in edible vegetable oils. In acetonitrile, the probe produced strong "turn on" and 100-fold fluorescence enhancement with high sensitivity and rapid response to saturated fatty aldehydes. A highly sensitive detection method for long-chain fatty aldehydes was established using pre-column derivation fluorescence procedure by high-performance liquid chromatography. The chromatographic method established provided satisfactory precision (1.91%-5.93%), good linearity (R ≥ 0.999), an acceptable accuracy (83.7%-108%) and a low limit of detection (6.4-12.4 ng/mL). The experimental results indicated that the probe could qualitatively and quantitatively detect six fatty aldehydes in vegetable oils, thus providing the potential for use in routine analysis for identifying the type of vegetable oil and for controlling its quality and safety.
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http://dx.doi.org/10.1016/j.chroma.2020.461063DOI Listing
June 2020

MiRNAs and E2F3: a complex network of reciprocal regulations in human cancers.

Oncotarget 2017 Sep 21;8(36):60624-60639. Epub 2017 Apr 21.

Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, PR China.

E2F transcription factor 3 (E2F3) is oncogenic in tumorigenesis. Alterations in E2F3 functions correspond with poor prognosis in various cancers, underscoring their status for the clinical cancer phenotype. Latest reports discovered intricate networks between microRNAs (miRNAs) and E2F3 in regulating the balance of these events, including proliferation, apoptosis, metastasis, as well as drug resistance. miRNAs are non-coding small RNAs which negatively regulate gene expressions post-transcriptionally mainly through 3'-UTR binding of target mRNAs. Increasing evidence shows that E2F3 can be activated/inhibited by numerous miRNAs whose dysregulation has been implicated in malignancy. In turn, miRNAs themselves can be transcriptionally regulated by E2F3, thus forming a negative feedback loop. These findings add a new challenging layer of complexity to E2F3 network. Current understanding of the reciprocal link between E2F3 and miRNAs in human cancers were summarized, which could help to develop potential therapeutic strategies.
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http://dx.doi.org/10.18632/oncotarget.17364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601167PMC
September 2017

The lincRNA-ROR/miR-145 axis promotes invasion and metastasis in hepatocellular carcinoma via induction of epithelial-mesenchymal transition by targeting ZEB2.

Sci Rep 2017 07 5;7(1):4637. Epub 2017 Jul 5.

Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu Province, China.

Emerging evidence show that long noncoding RNAs (lncRNAs) play critical roles in tumor development. LincRNA-ROR (linc-ROR) is known to promote tumor progress in several human cancers, including hepatocellular carcinoma (HCC). Nevertheless, the roles of linc-ROR in HCC metastasis and its underlying mechanisms remain fully unclear. In the present study, we showed that linc-ROR was upregulated in HCC tissues and high linc-ROR expression level predicted poor prognosis. Functionally, linc-ROR significantly induced epithelial-mesenchymal transition (EMT), and increased in vitro invasion and in vivo metastasis of HCC cells. Mechanistically, linc-ROR acted as a sponge for miR-145 to de-repress the expression of target gene ZEB2, thereby inducing EMT and promoting HCC metastasis. Collectively, our research indicates the potential of linc-ROR as a vital therapeutic target for the treatment of aggressive and metastatic HCC.
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http://dx.doi.org/10.1038/s41598-017-04113-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498629PMC
July 2017

Proteasome beta-4 subunit contributes to the development of melanoma and is regulated by miR-148b.

Tumour Biol 2017 Jun;39(6):1010428317705767

3 Department of Medical Oncology, Jinling Hospital, Nanjing, China.

The proteasome beta-4 subunit is required for the assembly of 20S proteasome complex, forming a pivotal component for the ubiquitin-proteasome system. Emerging evidence indicates that proteasome beta-4 subunit may be involved in underlying progression and mechanisms of malignancies. However, the role of proteasome beta-4 subunit in melanoma is currently unknown. Here, we reported that proteasome beta-4 subunit was markedly upregulated in human melanoma tissues and cells, compared with normal skin samples. High proteasome beta-4 subunit levels were significantly associated with poor overall survival in patients with melanoma. Proteasome beta-4 subunit knockdown strongly decreased melanoma cell growth in vitro and in vivo. We further identified miR-148b as a negative regulator of proteasome beta-4 subunit. Enforced expression of miR-148b resulted in vitro growth inhibition of melanoma cells, whereas this inhibition was further abolished by enforced expression of proteasome beta-4 subunit. Our findings, for the first time, indicated that the miR-148b/proteasome beta-4 subunit axis contributed to the development of melanoma, revealing novel therapeutic targets for the treatment of melanoma.
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http://dx.doi.org/10.1177/1010428317705767DOI Listing
June 2017

Non-coding RNAs as emerging regulators of epithelial to mesenchymal transition in non-small cell lung cancer.

Oncotarget 2017 May;8(22):36787-36799

Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, PR China.

Non-small cell lung cancer (NSCLC) remains a major health problem that patients suffer from around the world. The epithelial to mesenchymal transition (EMT) has attractive roles in increasing malignant potential and reducing sensitivity to conventional therapeutics in NSCLC cells. Meanwhile, it is now evident that non-coding RNAs (ncRNAs), primarily microRNAs and long non-coding RNAs contribute to tumorigenesis partially via regulating EMT. This article briefly summarizes current researches about EMT-related ncRNAs in NSCLC and discusses their crucial roles in the complex regulatory network. Also, the authors will show the evidence that ncRNAs not only contribute to cancer cells migration and invasion, but also take charge of the resistance of chemotherapy, radiotherapy and EGFR-TIKs. Then, we will further discuss the potential of inhibition of EMT via manipulating relevant ncRNAs to change our current treatment of NSCLC patients.
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http://dx.doi.org/10.18632/oncotarget.16375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482698PMC
May 2017

Hepatitis B virus X protein-mediated non-coding RNA aberrations in the development of human hepatocellular carcinoma.

Exp Mol Med 2017 02 10;49(2):e293. Epub 2017 Feb 10.

Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.

Hepatitis B virus (HBV) has an important role in the development of human hepatocellular carcinoma (HCC). Accumulated evidence has shown that HBV-encoded X protein (HBx) can induce both genetic alterations in tumor suppressor genes and oncogenes, as well as epigenetic aberrations in HCC pathogens. Non-coding RNAs (ncRNAs) mainly include microRNAs and long non-coding RNAs (lncRNAs). Although ncRNAs cannot code proteins, growing evidence has shown that they have various important biological functions in cell proliferation, cell cycle control, anti-apoptosis, epithelial-mesenchymal transition, tumor invasion and metastasis. This review summarizes the current knowledge regarding the mechanisms and emerging roles of ncRNAs in the pathogenesis of HBV-related HCC. Accumulated data have shown that ncRNAs regulated by HBx have a crucial role in HBV-associated hepatocarcinogenesis. The findings of these studies will contribute to more clinical applications of HBV-related ncRNAs as potential diagnostic markers or as molecular therapeutic targets to prevent and treat HBV-related HCC.
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http://dx.doi.org/10.1038/emm.2016.177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5336563PMC
February 2017

MicroRNA-129 in Human Cancers: from Tumorigenesis to Clinical Treatment.

Cell Physiol Biochem 2016 2;39(6):2186-2202. Epub 2016 Nov 2.

Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.

Emerging evidence has shown that microRNAs (miRNAs) play essential roles in regulating human cancers development and progression. However, the underlying mechanisms remain to be further explored. MiRNAs are a class of endogenous, non-coding, 18-24 nucleotide length single-strand RNAs that moderate gene expression primarily at post-transcriptional level. There is a growing body of literature that recognizes the importance of microRNA (miR)-129 during the development of cancers. Aberrant expression of miR-129 has been detected in various types of human cancers and the validated target genes are involved in cancer-related biological processes such as DNA methylation, cell proliferation, apoptosis, cell cycle, and metastasis. In this review, we summarized the roles of miR-129 family members and their target genes in tumorigenesis and clinical treatment of human cancers, highlighting the potential roles of miR-129 as biomarkers for cancer diagnosis and prognosis, and promising tools for cancer treatment.
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http://dx.doi.org/10.1159/000447913DOI Listing
February 2017

Health service utilisation of rural-to-urban migrants in Guangzhou, China: does employment status matter?

Trop Med Int Health 2017 01 17;22(1):82-91. Epub 2016 Nov 17.

Faculty of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China.

Objective: To describe the self-reported health status and service utilisation of employed, retired and unemployed migrants in Guangzhou, a megacity in southern China.

Methods: A cross-sectional study adapted from the National Health Service Survey was conducted between September and December in 2014. Based on the distribution of occupation of migrants, multistage sampling was used to recruit individuals. Logistic regression was applied to explore the factors influencing their service utilisation.

Results: Of 2906 respondents, 76.6% were employed, 9.2% retired and 14.2% unemployed. Only 8.1% reported having an illness in the previous 2 weeks, and 6.5% reported having been hospitalised in the previous year. Employed migrants had the lowest recent physician consultation rate (3.4%) and the lowest annual hospitalisation rate (4.5%) (P < 0.05); unemployed migrants had the highest rates (6.8% and 14.5% respectively, P < 0.05). Retired migrants were more likely to return to their hometown for health care (8.6%) than employed (1.5%) and unemployed migrants (3.4%) (P < 0.05). After adjusting for age and gender, employment status remained significant in explaining the recent two-week treatment-seeking behaviour of migrants (P < 0.05).

Conclusion: Disparity of service utilisation continues to be a problem for migrants due to the poor health awareness, lack of time and inconvenience of medical insurance reimbursement. Employed migrants make the least use of health services.
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http://dx.doi.org/10.1111/tmi.12801DOI Listing
January 2017

MicroRNA-215 suppresses cell proliferation, migration and invasion of colon cancer by repressing Yin-Yang 1.

Biochem Biophys Res Commun 2016 Oct 20;479(3):482-488. Epub 2016 Sep 20.

Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. Electronic address:

Colorectal cancer is one of the most common malignant tumors worldwide with rising incidence. MicroRNAs are small non-coding RNAs that implicate in multiple physiological or pathological processes. The aberrant expression of miRNA-215 (miR-215) has been illustrated in various types of cancers. However, the expression of miR-215 in human colon cancer and the biological roles of it remain largely unknown. We conducted this study to explore the expression and the function of miR-215 in human colon cancer. The results showed that miR-215 was remarkably downregulated in colon cancer tissues and cell lines. Overexpression of miR-215 by miR-215 mimic significantly inhibited colon cancer cell proliferation, migration and invasion while knockdown of miR-215 by miR-215 inhibitor exerted reverse effects. Furthermore, we newly identified Yin-Yang 1(YY1) as a direct target of miR-215 which could rescue the effects of miR-215 on colon cancer cells. In summary, our investigation revealed that miR-215 was downregulated in colon cancer and it suppressed colon cancer cell proliferation, migration and invasion by directly targeting YY1.
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http://dx.doi.org/10.1016/j.bbrc.2016.09.089DOI Listing
October 2016

MiR-630 inhibits invasion and metastasis in esophageal squamous cell carcinoma.

Acta Biochim Biophys Sin (Shanghai) 2016 Sep 25;48(9):810-9. Epub 2016 Aug 25.

Department of Medical Oncology, Jinling Hospital, Nanjing 210002, China

Esophageal squamous cell carcinoma (ESCC) is among the most aggressive malignancies and has a high incidence in China. MicroRNAs (miRNAs) are small endogenous RNAs that regulate multiple tumorigenic processes, including proliferation, invasion, metastasis and prognosis. Using miRNA expression profiling analysis, we found that miR-630 was markedly down-regulated in three ESCC tissue samples compared with that in paired normal esophageal tissues. Differential miR-630 expression was subsequently confirmed using quantitative real-time PCR. To determine whether miR-630 down-regulation could be considered as a diagnostic indicator and adverse prognostic factor, we investigated the association between miR-630 and clinicopathological characteristics in patients with ESCC. It was found that decreased miR-630 expression was associated with poor overall survival in these patients. In addition, we also explored the biological function of miR-630 by targeting Slug and investigated the correlation between miR-630 expression and epithelial-mesenchymal transition (EMT) progression in vivo and in vitro Ectopic miR-630 expression could inhibit proliferation, invasion and metastasis, whereas miR-630 knockdown induced proliferation, invasion, metastasis and EMT traits. Overall, our study supports a role for miR-630 as a critical novel modulator in ESCC.
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http://dx.doi.org/10.1093/abbs/gmw073DOI Listing
September 2016

A systematic review: perivascular epithelioid cell tumor of gastrointestinal tract.

Medicine (Baltimore) 2016 Jul;95(28):e3890

Department of Gastrointestinal Surgery, The First Affiliated Hospital,Sun Yat-Sen University Faculty of Medical Statistics and Epidemiology, School of Public Health,Sun Yat-Sen University Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, Guangdong, China.

Perivascular epithelioid cell tumor (PEComa) is a rare entity with distinctive morphology and of expressing myomelanocytic markers. Gastrointestinal tract (GI) is one of the most common anatomic sites of origin and counts for 20% to 25% of all reported cases of perivascular epithelioid cell tumors not otherwise specified (PEComas-NOS). However, the biologic behavior of perivascular epithelioid cell tumors of gastrointestinal tract (GI PEComas-NOS) is still unclear. The aim of conducting this systematic review is to sum up what is known so far of the epidemiology, natural history, management and prognosis of GI PEComas-NOS.A systematic research was performed on PubMed and EMBASE using the following terms: ("perivascular epithelioid cell tumor" or "PEComa") and ("gastrointestinal tract" or "GI" or "oral " or "mouth" or "esophagus" or "gullet" or "gastric" or "stomach" or "duodenum" or "jejunum" or "ileum" or "cecum" or "colon" or "colorectal" or "sigmoid" or "rectum" or "anus" or "mesentery") up to December 1, 2015. Retrieved GI PEComas-NOS publications, which included these terms, contains case reports, case series to case characteristic researches.A total of 168 articles were reviewed, 41 GI PEComa-NOS English studies among which were retrieved for analysis. We reviewed epidemiology, natural history, management and prognosis of GI PEComa-NOS. Generally GI PEComa-NOS is believed to have women predomination. The most frequently involved location is colon with non-specific clinical signs. Pathologically, GI PEComas-NOS shows epithelioid predominance (70%), meanwhile coexpresses melanocytic and muscle markers characteristically, while immunohistochemistry is a useful tool for identify, which indicates that HMB-45 is regarded as the most sensitive reagent. Complete resection served as mainstay of treatment, while chemotherapy should be unanimously considered to apply in malignant cases. Eventually, it is necessary for closed and long-term follow-up with endoscope and imaging for ruling out local recurrence or distant metastasis of this tumor.GI PEComas-NOS lives with unclear behavior. There are still many unverified clinicopathological issues of GI PEComas-NOS that needs to be clarified. Further studies and analyses concerning this rare entity should be brought out. Thus, the randomized clinical researches (RCTs) are required to be conducted.
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http://dx.doi.org/10.1097/MD.0000000000003890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4956776PMC
July 2016

Study protocol: a cluster randomized controlled trial to assess the effectiveness of a multi-pronged behavioural intervention to improve use of personal protective equipment among migrant workers exposed to organic solvents in small and medium-sized enterprises.

BMC Public Health 2016 07 16;16:580. Epub 2016 Jul 16.

Faculty of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou, 510080, People's Republic of China.

Background: In China, most of migrant workers work in the small and medium-sized enterprises (SMEs) and are a vulnerable group for occupational health. Migrant workers are at increased risk of occupational health risks due to poor occupational health behaviours such as the low use of personal protective equipment (PPE). However, there is a lack of solid evidence regarding how to improve the use of PPE among migrant workers in SMEs. The current study will assess the effectiveness of a multi-pronged behavioural intervention designed to promote PPE utilization among migrant workers exposed to organic solvents in SMEs.

Methods/design: This is a single blind, three-arm cluster randomized trial with 60 SMEs equally randomized to receive a top-down intervention (i.e. general health education and mHealth intervention provided by researchers) or a comprehensive intervention (which includes both top-down intervention and peer education) or a control condition (participants will not receive the intervention, but study measures will be obtained). Interventions will be conducted at the SMEs level for 6 months and all eligible migrant workers in these SMEs will be enrolled into the trial. The primary outcome is effective use of PPE during the last week. The secondary outcomes are occupational health knowledge and attitude and participation in occupational health check-up. Data will be collected and assessed at baseline; 3 months post baseline and the end of the intervention.

Discussion: This theory- and evidence based intervention will contribute to the limited evidence of behaviour change intervention in improving PPE utilization of migrant workers in SMEs, and provide timely evidence for the development of basic occupational health services in China and elsewhere with similar industrialization contexts.

Trial Registration: ChiCTR-IOR-15006929 . Registered on 16 August 2015.
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http://dx.doi.org/10.1186/s12889-016-3268-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947353PMC
July 2016

MiR-143-3p functions as a tumor suppressor by regulating cell proliferation, invasion and epithelial-mesenchymal transition by targeting QKI-5 in esophageal squamous cell carcinoma.

Mol Cancer 2016 06 29;15(1):51. Epub 2016 Jun 29.

Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Nanjing, Jiangsu, 210002, People's Republic of China.

Background: Dysregulation of microRNAs (miRNAs) have been demonstrated to contribute to carcinogenesis. MiR-143-3p has been identified to function as a tumor suppressor in several tumors, but the role of miR-143-3p in esophageal squamous cell carcinoma (ESCC) has not been intensively investigated. Our aim was to evaluate the potential role of miR-143-3p in the progression of ESCC.

Methods: The expression levels of miR-143-3p and QKI-5 protein were measured in 80 resected ESCC tumor specimens and the clinicopathological significance of these levels determined. We also investigated the role of miR-143-3p in the regulation of QKI-5 expression in ESCC cell lines both in vivo and in vitro.

Results: MiR-143-3p levels were decreased in ESCC clinical samples and low expression of miR-143-3p was significantly associated with poor prognosis in ESCC patients. Ectopic expression of miR-143-3p suppressed proliferation and induced apoptosis in ESCC cells both in vivo and in vitro. Ectopic expression of miR-143-3p also reduced the metastatic potential of cells by selectively regulating epithelial-mesenchymal transition regulatory proteins. Furthermore, QKI-5 isoform was upregulated in ESCC tissues and was a direct target of miR-143-3p. Lastly, re-introduction of QKI-5 expression abrogated the inhibitory effects of miR-143-3p on ESCC cell proliferation and motility.

Conclusions: Our results demonstrate that miR-143-3p acts as a tumor-suppressor by targeting QKI-5 in ESCC, suggesting that miR-143-3p is a potential therapy for the treatment of ESCC.
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http://dx.doi.org/10.1186/s12943-016-0533-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4928305PMC
June 2016

Staying in STEM or changing course: Do natives and immigrants pursue the path of least resistance?

Authors:
Siqi Han

Soc Sci Res 2016 07 14;58:165-183. Epub 2016 Jan 14.

Department of Sociology, The Ohio State University, United States. Electronic address:

This paper examines why Science, Technology, Engineering and Math (STEM) fields are becoming "immigrant" fields of study as native students shift from STEM fields to law, medicine and business. Using data from the 2010 National Survey of College Graduates, the analyses find that foreign college-educated immigrants with STEM degrees tend to remain in STEM fields, while natives are more likely to shift from STEM fields to law, medicine and business in graduate school. Among those who moved into law, medicine and business, the gains in earnings are larger for natives than for foreign educated immigrants. These results have important implications for the social mobility of highly educated natives and immigrants.
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http://dx.doi.org/10.1016/j.ssresearch.2015.12.003DOI Listing
July 2016

The Emerging Role and Promise of Long Noncoding RNAs in Lung Cancer Treatment.

Cell Physiol Biochem 2016 17;38(6):2194-206. Epub 2016 May 17.

Lung cancer is the leading cause of cancer death around the world. The advanced discovery of numerous long noncoding RNAs (lncRNAs) has dramatically changed the understanding of biology of human cancers, including lung cancer. LncRNAs are a group of noncoding RNAs (ncRNAs) with a length greater than 200 nucleotides with limited or no protein-coding capacity. Increasing evidence has shown that specific lncRNAs may be implicated in the process of tumorigenesis. Because of their roles in the regulation of multiple molecular pathways associated with changes in gene expression, lncRNAs can serve as potential diagnostic biomarkers or therapeutic targets in lung cancer. Importantly, dysregulated lncRNAs is reported to be correlated with the sensitivity of lung cancer cells to anticancer therapies, including chemotherapy, molecular-targeted therapy, etc. Herein, we review the recent progress of lncRNAs in lung cancer, with a particular focus on the multiple molecular roles of regulatory lncRNAs on the molecular signaling pathways involved in tumorigenesis and the resistance to such therapies.
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http://dx.doi.org/10.1159/000445575DOI Listing
February 2017

Association between Social Integration and Health among Internal Migrants in ZhongShan, China.

PLoS One 2016 10;11(2):e0148397. Epub 2016 Feb 10.

Faculty of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China.

Internal migrants are the individuals who migrate between regions in one country. The number of internal migrants were estimated at 245 million in China in 2013. Results were inconsistent in the literature about the relationship between their health statuses and social integration. The main difference exists on how to measure the social integration and whether health statuses of internal migrants improve with years of residence. To complement the existing literature, this study measured social integration more comprehensively and estimated the internal migrants' health statuses with varying years of residence, and explored the associations between the migrants' social integration and health. We used the data from 2014 Internal Migrant Dynamic Monitoring Survey of Health and Family Planning in ZhongShan, China. Health status was measured from four aspects: self-reported health, subjective well-being, perception of stress, mental health. We measured social integration through four dimensions: economy, social communication, acculturation, and self-identity. The analyses used multiple linear regressions to examine the associations between self-reported health, subjective well-being, and perception of stress, mental health and social integration. The analytical sample included 1,999 households of the internal migrants and 1,997 local registered households, who were permanent residents in ZhongShan. Among the internal migrants, Adults in the labor force, who were aged 25 to 44 years old, accounted for 91.2% of the internal migrant population, while 74.6% of the registered population were in that age group. Median residential time among migrants was 2.8 (1.3-6.2) years, and 20.2% of them were migrating in the same Guangdong province. Except for mental health, other health statuses among migrants had significant differences compared with local registered population, e.g. self-reported health was better, but subjective well-being was worse. However, these health measurements were improved with more years of residence. Moreover, our results show that two aspects of social integration, economic integration and self-identity, were significantly associated with health status. Subjective feeling of relative social status levels were more associated with health, which prompted the attention to social fairness and the creation of a fair and respectful culture. More interventions could be experimented, such as encouraging internal migrants to participate in community activities more actively, educating local registered residents to treat internal migrants more equally, and developing self-identity among internal migrants. Better social, economic, and cultural environment can benefit internal migrants' health statuses.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0148397PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749174PMC
July 2016

The Roles of MicroRNA-141 in Human Cancers: From Diagnosis to Treatment.

Cell Physiol Biochem 2016 1;38(2):427-48. Epub 2016 Feb 1.

Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.

Cancer remains one of the most threatening causes of human health impairment, and the mechanisms underlying tumorigenesis have not been completely characterized. MicroRNAs (miRNAs) are a group of endogenous, small (18∼25 nucleotides) non-coding RNAs which negatively regulate gene expressions by directly binding to the 3'-untranslated regions (3'-UTRs) of the target messenger RNAs (mRNAs). Increasing evidence has demonstrated abnormal miRNA profiles and confirmed their involvement in tumor initiation and progression. As one important member of the miR-200 family, microRNA (miR)-141 is aberrantly expressed in many human malignant tumors, participating in various cellular processes including epithelial-mesenchymal transition (EMT), proliferation, migration, invasion, and drug resistance. In the present review, we briefly describe the mechanisms underlying miR-141-mediated tumorigenesis and the possible future of miR-141 as a potential diagnostic and prognostic parameter as well as therapeutic target in clinical applications.
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http://dx.doi.org/10.1159/000438641DOI Listing
November 2016

Gendered transitions to adulthood by college field of study in the United States.

Demogr Res 2016 28;35:929-960. Epub 2016 Sep 28.

Brown University, USA.

Background: Field of study may influence the timing of transitions to the labor market, marriage, and parenthood among college graduates. Research to date has yet to study how field of study is associated with the interweaving of these transitions in the USA.

Objective: The current study examines gendered influences of college field of study on transitions to a series of adult roles, including full-time work, marriage, and parenthood.

Methods: We use Cox proportional hazards models and multinomial logistic regression to examine gendered associations between field of study and the three transitions among college graduates of the NLSY97 (National Longitudinal Survey of Youth) cohort.

Results: Men majoring in STEM achieve early transitions to full-time work, marriage, and parenthood; women majoring in STEM show no significant advantage in finding full-time work and delayed marriage and childbearing; women in business have earlier transitions to full-time work and marriage than women in other fields, demonstrating an advantage similar to that of men in STEM.

Conclusions: The contrast between men and women in STEM shows that transition to adulthood remains gendered; the contrast between women in STEM and women in business illustrates that a prestigious career may not necessarily delay family formation.
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http://dx.doi.org/10.4054/DemRes.2016.35.31DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5654611PMC
September 2016

Multiple Roles of MicroRNA-100 in Human Cancer and its Therapeutic Potential.

Cell Physiol Biochem 2015 26;37(6):2143-59. Epub 2015 Nov 26.

MicroRNAs (miRNAs) are a recently discovered class of endogenous, small (about 22 nucleotides) non-coding RNAs, which play important roles in cancer development and progression. Emerging evidence shows that microRNAs exert their regulatory effects by directly binding to the 3'- untranslated regions (UTRs) of their target genes. MicroRNA-100 (miR-100) is aberrantly expressed and functions in many human cancers by regulating multiple cell processes, such as cell cycle, proliferation, differentiation, migration, invasion and apoptosis, via post-transcriptionally regulating various target genes. A better understanding of the molecular mechanisms involved in miR-100-mediated tumor progression will provide an opportunity for exploring novel miR-100-based targeted therapies for human cancers. This review aims to summarize the recently published literature on the roles of miR-100 in regulating tumorigenesis, and explore its potential clinical applications for cancer diagnosis, prognosis and clinical treatment.
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http://dx.doi.org/10.1159/000438572DOI Listing
October 2016

PSMB4 promotes multiple myeloma cell growth by activating NF-κB-miR-21 signaling.

Biochem Biophys Res Commun 2015 Mar 3;458(2):328-33. Epub 2015 Feb 3.

Department of Hematology, Navy General Hospital, Beijing 100048, China. Electronic address:

Proteasomal subunit PSMB4, was recently identified as potential cancer driver genes in several tumors. However, the regulatory mechanism of PSMB4 on carcinogenesis process remains unclear. In this study, we investigated the expression and roles of PSMB4 in multiple myeloma (MM). We found a significant up-regulation of PSMB4 in MM plasma and cell lines. Ectopic overexpression of PSMB4 promoted cell growth and colony forming ability of MM cells, whereas inhibition of PSMB4 led to a decrease of such events. Furthermore, our results demonstrated the up-regulation of miR-21 and a positive correlation between the levels of miR-21 and PSMB4 in MM. Re-expression of miR-21 markedly rescued PSMB4 knockdown-mediated suppression of cell proliferation and clone-formation. Additionally, while enforced expression of PSMB4 profoundly increased NF-κB activity and the level of miR-21, PSMB4 knockdown or NF-κB inhibition suppressed miR-21 expression in MM cells. Taken together, our results demonstrated that PSMB4 regulated MM cell growth in part by activating NF-κB-miR-21 signaling, which may represent promising targets for novel specific therapies.
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http://dx.doi.org/10.1016/j.bbrc.2015.01.110DOI Listing
March 2015

MiR-203 inhibits melanoma invasive and proliferative abilities by targeting the polycomb group gene BMI1.

Biochem Biophys Res Commun 2015 Jan 2;456(1):361-6. Epub 2014 Dec 2.

Department of Dermatology and Venereal Disease, Capital Medical University, Beijing 100069, China. Electronic address:

Metastasis is the major problem in malignant melanoma, posing a therapeutic challenge to clinicians. The investigation of the underlying mechanism driving this progress remains a large unmet need. In this study, we revealed a miR-203-BMI1 axis that regulated melanoma metastasis. We found significantly deregulation of miR-203 and up-regulation of BMI1 in melanoma, particularly in metastatic melanoma. An inverse correlation between the levels of miR-203 and BMI1 was further observed in melanoma tissues and cell lines. We also identified BMI1 as a downstream target gene of miR-203, which bound to the 3'UTR of BMI1. Overexpression of miR-203 was associated with decreased BMI1 expression and impaired cell invasion and tumor sphere formation activities. Re-expression of BMI1 markedly rescued miR-203-mediated suppression of these events. Taken together, our results demonstrated that miR-203 regulated melanoma invasive and proliferative abilities in part by targeting BMI1, providing new insights into potential mechanisms of melanoma metastasis.
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http://dx.doi.org/10.1016/j.bbrc.2014.11.087DOI Listing
January 2015

Aurora-A promotes chemoresistance in hepatocelluar carcinoma by targeting NF-kappaB/microRNA-21/PTEN signaling pathway.

Oncotarget 2014 Dec;5(24):12916-35

Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.

Hepatocellular carcinoma (HCC) is highly resistant to chemotherapy. Previously, we have shown that Aurora-A mRNA is upregulated in HCC cells or tissues and silencing of Aurora-A using small interfering RNA (siRNA) decreases growth and enhances apoptosis in HCC cells. However, the clinical significance of Aurora-A protein expression in HCC and association between Aurora-A expression and HCC chemoresistance is unclear. Here, we showed that Aurora-A protein is upregulated in HCC tissues and significantly correlated with recurrence-free and overall survival of patients and multivariate analysis indicated that immunostaining of Aurora-A will be an independent prognostic factor for patients. Silencing of Aurora-A significantly increased the chemosensitivity of HCC cells both in vitro and in vivo, while overexpression of Aurora-A induced the opposite effects. Furthermore, overexpression of Aurora-A reduces chemotherapy-induced apoptosis by promoting microRNA-21 expression, which negatively regulates PTEN and then inhibits caspase-3-mediated apoptosis induction. Mechanically, we demonstrated that Aurora-A promotes expression of nuclear Ikappaβ-alpha (Iκβα) protein and enhances NF-kappa B (NF-κB) activity, thus promotes the transcription of miR-21. This study first reported the involvement of Aurora-A/NF-κB/miR-21/PTEN/Akt signaling axis in chemoresistance of HCC cells, suggesting that targeting this signaling pathway would be helpful as a therapeutic strategy for the reversal of chemoresistance in HCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350360PMC
http://dx.doi.org/10.18632/oncotarget.2682DOI Listing
December 2014

The CCL2/CCR2 axis enhances IL-6-induced epithelial-mesenchymal transition by cooperatively activating STAT3-Twist signaling.

Tumour Biol 2015 Feb 16;36(2):973-81. Epub 2014 Oct 16.

Department of Respiratory, Navy General Hospital, Beijing, 100048, China.

The pattern of secreted factors in the tumor microenvironment has been shown to initiate tumor epithelial-mesenchymal transition (EMT); however, little is known about their interplay undergoing this phenotypic switch. In this study, we revealed obvious coactions of cytokine IL-6 and chemokine CCL2 during EMT induction. We found that IL-6 effectively induced EMT and promoted tumor cell invasion, which could be markedly enhanced by addition of CCL2 in a CCR2-dependent manner. IL-6 and CCL2 induced each other and cooperatively elicited STAT3 phosphorylation; conversely, STAT3 regulated the production of IL-6 and CCL2, thus constituting a positive feedback loop to maintain and amplify STAT3 signaling, consequently promoting additional EMT events. Furthermore, CCL2 greatly enhanced IL-6-induced EMT events mainly by upregulating the expression of Twist. Genetic or pharmacological inhibition of STAT3 disrupted STAT3-centered loop and markedly suppressed Twist expression as well as IL-6/CCL2-mediated EMT induction. Thus, our findings highlighted the synergy of the two secreted factors of tumor microenvironment, in regulating transformed properties of non-small cell lung cancer (NSCLC).
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http://dx.doi.org/10.1007/s13277-014-2717-zDOI Listing
February 2015

An IL6-STAT3 loop mediates resistance to PI3K inhibitors by inducing epithelial-mesenchymal transition and cancer stem cell expansion in human breast cancer cells.

Biochem Biophys Res Commun 2014 Oct 5;453(3):582-7. Epub 2014 Oct 5.

Department of Burn and Plastic Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, China. Electronic address:

Recently, a new generation of PI3K-specific inhibitors, such as GDC0941 and BKM120, are being investigated in clinical trials for treatment against tumors harboring PIK3CA mutations. Nevertheless, not all patients benefit from such treatment, suggesting that their tumors may be resistant to PI3K inhibitors. The investigation of the underlying mechanisms and efficacious personalized treatment remain a large unmet need. In this study, we revealed an IL6-STAT3 positive feedback loop that mediated the resistance to PI3K inhibitors. We found that breast cancer cells with acquired resistance to PI3K inhibitors displayed epithelial-mesenchymal transition (EMT) features and an highly enriched cancer stem cells (CSCs), secreting ∼1000-fold more IL6 than parental cells. Further studies elucidated that activation of the IL6-STAT3 signaling effectively triggered EMT action, expanded the CSCs population, and reduced sensitivity to PI3K inhibitors. Pharmacological inhibition of STAT3 disrupted the IL6-STAT3 signaling and overcome resistance to PI3K inhibitors partially due to increased apoptosis induction. Taken together, our results demonstrated that feedback activation of the IL6-STAT3 loop lead to acquired resistance to PI3K inhibitors by promoting EMT and CSC-like features, and suggested that targeting this loop may be an efficient strategy to overcome resistance to PI3K inhibitors.
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http://dx.doi.org/10.1016/j.bbrc.2014.09.129DOI Listing
October 2014

Blocking the PI3K pathway enhances the efficacy of ALK-targeted therapy in EML4-ALK-positive nonsmall-cell lung cancer.

Tumour Biol 2014 Oct 29;35(10):9759-67. Epub 2014 Jun 29.

Department of Clinical Laboratory, Hubei Maternal and Child Health Hospital, Wuhan, 430070, China.

Targeted therapy based on ALK tyrosine kinase inhibitors (ALK-TKIs) has made significant achievements in individuals with EML4-ALK (echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene) fusion positive nonsmall-cell lung cancer (NSCLC). However, a high fraction of patients receive inferior clinical response to such treatment in the initial therapy, and the exact mechanisms underlying this process need to be further investigated. In this study, we revealed a persistently activated PI3K/AKT signaling that mediates the drug ineffectiveness. We found that genetic or pharmacological inhibition of ALK markedly abrogated phosphorylated STAT3 and ERK, but it failed to suppress AKT activity or induce apoptosis, in EML4-ALK-positive H2228 cells. Furthermore, targeted RNA interference of PI3K pathway components restored sensitivity to TAE684 treatment at least partially due to increased apoptosis. Combined TAE684 with PI3K inhibitor synergistically inhibited the proliferation of EML4-ALK-positive cells in vitro and significantly suppressed the growth of H2228 xenografts in vivo, suggesting the potential clinical application of such combinatorial therapy regimens in patients with EML4-ALK positive lung cancer.
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http://dx.doi.org/10.1007/s13277-014-2252-yDOI Listing
October 2014

A bispecific antibody against two different epitopes on hepatitis B surface antigen has potent hepatitis B virus neutralizing activity.

MAbs 2013 Nov-Dec;5(6):946-55

Shanghai Institute of Immunology; Institutes of Medical Sciences; Shanghai Jiao Tong University School of Medicine; Shanghai, China; International Joint Cancer Institute; Second Military Medical University; Shanghai, China; PLA General Hospital Cancer Center; PLA School of Medical Sciences; Beijing, China.

Treatment of chronic hepatitis B virus (HBV) infection with interferon and viral reverse transcriptase inhibitor regimens results in poor viral clearance, loss of response, and emergence of drug-resistant mutant virus strains. These problems continue to drive the development of new therapeutic approaches to combat HBV. Here, we engineered a bispecific antibody using two monoclonal antibodies cloned from hepatitis B surface antigen (HBsAg)-specific memory B cells from recombinant HBsAg-vaccinated healthy volunteers. Next, we evaluated its efficacy in neutralizing HBV in HepaRG cells. This bispecific antibody, denoted as C4D2-BsAb, had superior HBV-neutralizing activity compared with the combination of both parental monoclonal antibodies, possibly through steric hindrance or induction of HBsAg conformational changes. Moreover, C4D2-BsAb has superior endocytotic characteristics into hepatocytes, which inhibits the secretion of HBsAg. These results suggest that the anti-HBsAg bispecific antibody may be an effective treatment method against HBV infection.
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http://dx.doi.org/10.4161/mabs.26390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896608PMC
January 2015