IU Indianapolis ScholarWorks :: Browsing by Author "Chen, Meng"

Browsing by Author "Chen, Meng"

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Development of the Chronic Pain Coding System (CPCS) for Characterizing Patient-Clinician Discussions About Chronic Pain and Opioids
(Oxford Academic, 2016-10) Henry, Stephen G.; Chen, Meng; Matthias, Marianne S.; Bell, Robert A.; Kravitz, Richard L.; Communication Studies, School of Liberal Arts
Objective. To describe the development and initial application of the Chronic Pain Coding System., Design. Secondary analysis of data from a randomized clinical trial., Setting. Six primary care clinics in northern California., Subjects. Forty-five primary care visits involving 33 clinicians and 45 patients on opioids for chronic noncancer pain., Methods. The authors developed a structured coding system to accurately and objectively characterize discussions about pain and opioids. Two coders applied the final system to visit transcripts. Intercoder agreement for major coding categories was moderate to substantial (kappa = 0.5–0.7). Mixed effects regression was used to test six hypotheses to assess preliminary construct validity., Results. Greater baseline pain interference was associated with longer pain discussions (P = 0.007) and more patient requests for clinician action (P = 0.02) but not more frequent negative patient evaluations of pain (P = 0.15). Greater clinician-reported visit difficulty was associated with more frequent disagreements with clinician recommendations (P = 0.003) and longer discussions of opioid risks (P = 0.049) but not more frequent requests for clinician action (P = 0.11). Rates of agreement versus disagreement with patient requests and clinician recommendations were similar for opioid-related and non-opioid–related utterances., Conclusions. This coding system appears to be a reliable and valid tool for characterizing patient-clinician communication about opioids and chronic pain during clinic visits. Objective data on how patients and clinicians discuss chronic pain and opioids are necessary to identify communication patterns and strategies for improving the quality and productivity of discussions about chronic pain that may lead to more effective pain management and reduce inappropriate opioid prescribing.
Failure patterns of locoregional recurrence after reducing target volumes in patients with nasopharyngeal carcinoma receiving adaptive replanning during intensity-modulated radiotherapy: a single-center experience in China
(Springer Nature, 2023-11-16) Zhou, Xiate; Zhu, Jian; Zhou, Chao; Wang, Wei; Ding, Weijun; Chen, Meng; Chen, Kuifei; Li, Shuling; Chen, Xiaofeng; Yang, Haihua; Radiation Oncology, School of Medicine
Background: Previous researches have demonstrated that adaptive replanning during intensity-modulated radiation therapy (IMRT) could enhance the prognosis of patients with nasopharyngeal carcinoma (NPC). However, the delineation of replanning target volumes remains unclear. This study aimed to evaluate the feasibility of reducing target volumes through adaptive replanning during IMRT by analyzing long-term survival outcomes and failure patterns of locoregional recurrence in NPC. Methods: This study enrolled consecutive NPC patients who received IMRT at our hospital between August 2011 and April 2018. Patients with initially diagnosed, histologically verified, non-metastatic nasopharyngeal cancer were eligible for participation in this study. The location and extent of locoregional recurrences were transferred to pretreatment planning computed tomography for dosimetry analysis. Results: Among 274 patients, 100 (36.5%) received IMRT without replanning and 174 (63.5%) received IMRT with replanning. Five-year rates of locoregional recurrence-free survival (LRFS) were 90.1% (95%CI, 84.8% to 95.4%) and 80.8% (95%CI, 72.0% to 89.6%) for patients with and without replanning, P = 0.045. There were 17 locoregional recurrences in 15 patients among patients with replanning, of which 1 (5.9%) was out-field and 16 (94.1%) were in-field. Among patients without replanning, 19 patients developed locoregional recurrences, of which 1 (5.3%) was out-field, 2 (10.5%) were marginal, and 16 (84.2%) were in-field. Conclusions: In-field failure inside the high dose area was the most common locoregional recurrent pattern for non-metastatic NPC. Adapting the target volumes and modifying the radiation dose prescribed to the area of tumor reduction during IMRT was feasible and would not cause additional recurrence in the shrunken area.
The function of the 130kDa MLCK in regulating in vivo vascular permeability and angiogenesis
(Office of the Vice Chancellor for Research, 2011-04-08) Chen, Meng; Herring, Paul
Disruption of endothelial integrity is an essential component of vascular inflammation, angiogenesis, atherosclerosis, and tumor metastasis. Many studies have shown that activation of myosin light chain kinase (MLCK) in endothelial cell is correlated with increase in vascular permeability. Currently, most research in endothelial cells has focused on the 220kDa MLCK isoform which is the predominant isoform present in cultured endothelial cells. However, in freshly isolated uncultured endothelial cells, the 130kDa MLCK predominates. Yet nothing is known about the roles of the 130kDa MLCK isoform in endothelial cells. Therefore, our goal is to determine the role of the 130kDa MLCK in regulating vascular permeability and angiogenesis in vivo. To do this we will generate an endothelial cell-specific 130kDa MLCK knockout mice. As transcripts encoding the 130 and 220kDa MLCK isoforms are produced by independent promoters within the same mylk1 gene, I will selectively knockout the 130kDa MLCK by deleting unique cis-acting gene regulatory elements required for the expression of this transcript. A key element identified within the intron following the first exon of the 130kDa MLCK transcript has been flanked by LoxP sites such that Cre recombinase (Cre) mediated recombination will delete the element and attenuate expression of the 130kDa MLCK. By crossing these floxed mice with Tie2-Cre mice which express Cre specifically in endothelial cells, I will obtain endothelial cellspecific 130kDa MLCK knockout mice. In vivo vascular permeability and angiogenesis assays on these mice will allow me to determine the role played by the 130kDa MLCK in these processes. This study will not only help to identify specific functions of the 130kDa MLCK isoform, but also determine if this is a drug target for developing novel treatments of vascular diseases and cancer.
H19 Noncoding RNA, an Independent Prognostic Factor, Regulates Essential Rb-E2F and CDK8-β-Catenin Signaling in Colorectal Cancer
(Elsevier, 2016-11) Ohtsuka, Masahisa; Ling, Hui; Ivan, Cristina; Pichler, Martin; Matsushita, Daisuke; Goblirsch, Matthew; Stiegelbauer, Verena; Shigeyasu, Kunitoshi; Zhang, Xinna; Chen, Meng; Vidhu, Fnu; Bartholomeusz, Geoffrey A.; Toiyama, Yuji; Kusunoki, Masato; Doki, Yuichiro; Mori, Masaki; Song, Shumei; Gunther, Jillian R.; Krishnan, Sunil; Slaby, Ondrej; Goel, Ajay; Ajani, Jaffer A.; Radovich, Milan; Calin, George A.; Department of Surgery, IU School of Medicine
The clinical significance of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC) remains largely unexplored. Here, we analyzed a large panel of lncRNA candidates with The Cancer Genome Atlas (TCGA) CRC dataset, and identified H19 as the most significant lncRNA associated with CRC patient survival. We further validated such association in two independent CRC cohorts. H19 silencing blocked G1-S transition, reduced cell proliferation, and inhibited cell migration. We profiled gene expression changes to gain mechanism insight of H19 function. Transcriptome data analysis revealed not only previously identified mechanisms such as Let-7 regulation by H19, but also RB1-E2F1 function and β-catenin activity as essential upstream regulators mediating H19 function. Our experimental data showed that H19 affects phosphorylation of RB1 protein by regulating gene expression of CDK4 and CCND1. We further demonstrated that reduced CDK8 expression underlies changes of β-catenin activity, and identified that H19 interacts with macroH2A, an essential regulator of CDK8 gene transcription. However, the relevance of H19-macroH2A interaction in CDK8 regulation remains to be experimentally determined. We further explored the clinical relevance of above mechanisms in clinical samples, and showed that combined analysis of H19 with its targets improved prognostic value of H19 in CRC.
Long-term outcomes of replanning during intensity-modulated radiation therapy in patients with nasopharyngeal carcinoma: An updated and expanded retrospective analysis
(Elsevier, 2022-05) Zhou, Xiate; Wang, Wei; Zhou , Chao; Zhu , Jian; Ding , Weijun; Chen, Meng; Chen, Kuifei; Shi, Yangyang; Chen , Xiaofeng; Kong, Feng-Ming; Yang , Haihua; Radiation Oncology, School of Medicine
Background and purpose Recent studies show that adaptive replanning for patients with nasopharyngeal carcinoma (NPC) during intensity-modulated radiation therapy (IMRT) improve the short-term local–regional recurrence-free survival (LRFS), and quality of life (QoL). We aimed to assess the long-term survival outcomes and QoL in patients with non-metastatic NPC who received IMRT with replanning compared to those who received IMRT without replanning. Methods and materials We conducted an updated and expanded retrospective analysis from an existing prospective cohort for non-metastatic NPC patients undergoing IMRT in our institution. Non-metastatic NPC patients receiving IMRT from June 2007 to December 2015 were consecutively enrolled based on electronic medical record. Patients who were still alive were eligible for the QoL study. The survival outcomes and QoL were compared between patients with and without replanning. Results Among 290 patients, 147 (50.7%) received IMRT without replanning and 143 (49.3%) received IMRT with replanning. Replanning group had a higher 8-year LRFS rate (87.4% vs. 75.6%, P = 0.025). However, 8-year overall survival rate was not statistically significant. Patients with replanning compared to those who without replanning had significant improvements in social functioning (P = 0.016), insomnia (P = 0.048), dry mouth (P = 0.004), and sticky saliva (P = 0.005). Additionally, the score of the role functioning was marginally higher in patients treated with IMRT replanning (P = 0.063). Conclusion This extended follow-up study demonstrates the long-term security and validity for adaptive radiotherapy in IMRT for non-metastatic NPC patients. We highly recommend that adaptive replanning should be routinely implemented for non-metastatic NPC patients.
The prognostic value of circulating lymphocyte counts and ABO blood group in lung cancer stereotactic body radiation therapy: a retrospective study
(AME, 2022) Chen, Meng; Chen, Kuifei; Li, Shuling; Meng, Yinnan; Shi, Yangyang; Chen, Xiaofeng; Yang, Haihua; Radiation Oncology, School of Medicine
Background: Clinically, there is a lack of simple and feasible indicators to predict the efficacy of stereotactic body radiation therapy (SBRT). Circulating lymphocyte counts (CLCs) is considered to be related to curative effect in conventional radiotherapy of lung cancer, and blood groups are also associated with the survival. In this study, we investigate the prognostic value of CLCs and ABO blood groups in lung cancer patients treated with SBRT. Methods: We retrospectively analyzed 191 patients who were treated with lung cancer SBRT in Taizhou Hospital of Zhejiang Province from September 2014 to December 2018. The medical record system of Taizhou Hospital was used to collect relevant clinical data, such as stage, CLC, ABO blood groups and other important clinical co-variates. The effects of SBRT were evaluated by patient reexamination image data and telephone follow-up. The RECIST 1.1 standard was used to evaluate the short-term efficacy in the first, third, and sixth months after SBRT. Progression-free survival (PFS) was defined as the time from the day of SBRT to disease progression or death from any cause. Overall survival (OS) was measured from the day of SBRT until the last follow-up or death. Survival curves and univariate, multivariate logistic-regression analyses were used to expound the prognostic factors for local control (LC), PFS, and OS of lung cancer SBRT patients. Results: Univariate and multivariate analysis results showed that post-SBRT CLCs were independent factors for the short-term efficacy 3 and 6 months after lung cancer SBRT [hazard ratio (HR) =0.249, P=0.037; HR =0.347, P=0.012]. Survival analyses showed that the PFS and OS of lung cancer SBRT patients with A blood type was significantly shorter than that in the other three non-A blood groups (PFS: 6.5 vs. 10 months, HR =1.535, P=0.020; OS: 24 vs. 41 months, HR =1.578, P=0.048). Moreover, the patients with high post-SBRT CLCs in the non-A blood group had the longest PFS and OS after lung cancer SBRT (HR =0.551, P=0.043). Conclusions: Lung cancer SBRT patients with high-post-SBRT CLCs and non-A blood groups seem to exhibits best curative effect, which represent a potential opportunity to improve the clinical management of these patients. The mechanisms of this association deserve further verification and investigation.
Regulation of 130kDa smooth muscle myosin light chain kinase expression by an intronic CArG element
(2013) Chen, Meng; Zhang, Wenwu; Lu, Xiao; Hoggatt, April M.; Gunst, Susan J.; Kassab, Ghassan S.; Tune, Johnathan D.; Herring, B. Paul; Department of Cellular & Integrative Physiology, IU School of Medicine
The mylk1 gene encodes a 220-kDa nonmuscle myosin light chain kinase (MLCK), a 130-kDa smooth muscle MLCK (smMLCK), as well as the non-catalytic product telokin. Together, these proteins play critical roles in regulating smooth muscle contractility. Changes in their expression are associated with many pathological conditions; thus, it is important to understand the mechanisms regulating expression of mylk1 gene transcripts. Previously, we reported a highly conserved CArG box, which binds serum response factor, in intron 15 of mylk1. Because this CArG element is near the promoter that drives transcription of the 130-kDa smMLCK, we examined its role in regulating expression of this transcript. Results show that deletion of the intronic CArG region from a β-galactosidase reporter gene abolished transgene expression in mice in vivo. Deletion of the CArG region from the endogenous mylk1 gene, specifically in smooth muscle cells, decreased expression of the 130-kDa smMLCK by 40% without affecting expression of the 220-kDa MLCK or telokin. This reduction in 130-kDa smMLCK expression resulted in decreased phosphorylation of myosin light chains, attenuated smooth muscle contractility, and a 24% decrease in small intestine length that was associated with a significant reduction of Ki67-positive smooth muscle cells. Overall, these data show that the CArG element in intron 15 of the mylk1 gene is necessary for maximal expression of the 130-kDa smMLCK and that the 130-kDa smMLCK isoform is specifically required to regulate smooth muscle contractility and small intestine smooth muscle cell proliferation.
The Regulation of MicroRNAs by Brahma-Related Gene 1 in Smooth Muscle Cells
(Office of the Vice Chancellor for Research, 2013-04-05) Chen, Meng; Herring, Paul
MicroRNAs (miRs) regulate the phenotypic switch of smooth muscle cells (SMCs) that occurs under several pathological conditions such as atherosclerosis. However, little is known about the transcriptional and epigenetic regulation of miR expression in SMCs. To identify miRs that are regulated by the Brahmarelated gene 1 (Brg1)-containing SWI/SNF chromatin remodeling complex we performed a microRNA array screen of RNA isolated from colonic SMCs of mice harboring a smooth muscle-specific knockout of Brg1. Quantitative RT-PCR confirmed changes in expression of several miRs, including miRs-143/145 and miR-133. Expression of dominant negative Brg1 in wild-type SMCs led to decreased expression of miRs-143/145 but not miR-133. The dominant negative Brg1 also blocked the myocardin-mediated induction of miRs-143/145 in 10T1/2 cells. Knockdown of SRF or myocardin decreased expression of miRs-143/145 in SMCs, whereas miR-133 expression was only repressed following SRF knockdown. In Brg1-null SW13 cells, miRs-143/145 but not miR-133 were dramatically induced by myocardin only in the presence of Brg1. Chromatin immunoprecipitation assays revealed that Brg1 is important for myocardin-mediated SRF binding to the miRs-143/145 promoter. Together these data show that Brg1- dependent chromatin remodeling regulates the expression of miRs-143/145 and miR-133 through distinct pathways in SMCs. This implies that chromatin remodeling complexes modulate smooth muscle phenotypes and functions not only through protein coding genes but also non-coding genes.
The role of Brahma-related gene 1 in regulating the expression of microRNAs in colonic smooth muscle cells
(Office of the Vice Chancellor for Research, 2012-04-13) Chen, Meng; Herring, Paul
Previous work by our group has shown that mice harboring null mutation of Brahma-related gene 1 (Brg1)-an ATPase subunit of SWI/SNF (SWItch/Sucrose NonFermentable) chromatin remodeling complex have reduced smooth muscle contractility and disorganized smooth muscle cells (SMCs) in colon, which are similar defects to those of microRNA maturation enzyme Dicer-deficient mice. Recently microRNAs (miRs) such as miR-143/145 have been implicated in the regulation of gene expression essential for smooth muscle cell proliferation and differentiation. Thus we aimed to identify the microRNAs that were involved in regulating the phenotypic changes in Brg1-deficient colonic smooth muscle cells and determine how Brg1 regulated them. The microRNA array screens of colonic smooth muscle and quantitative reverse transcription-polymerase chain reaction assays identified 6 miRs were down-regulated and 6 were up-regulated in smooth muscle specific Brg1 knockout tissue compared with control. Inactivation of endogenous Brg1 by introducing dominant negative Brg1 into wild type SMCs in vitro decreased miR-143/145 expression in smooth muscle cells. In Brg1 null SW13 cells, miR-143/145 were dramatically induced by myogenic transcriptional co-factor myocardin only in the presence of Brg1. Chromatin immunoprecipitation assays demonstrated that myocardin together with Brg1 increased the binding of transcription factor serum response factor (SRF) to the promoter region of miR-143/145 gene cluster. In conclusion, Brg1 together with myocardin can induce the transcription of miR-143/145 through enhancing the binding of SRF to the promoter region in SMCs. Together this suggests that SWI/SNF mediated chromatin remodeling regulates the phenotype of colonic smooth muscle by regulating expression of microRNAs that further modulate expression of their targets.
Serum response factor-dependent regulation of smooth muscle gene transcription
(2014-07-07) Chen, Meng; Herring, B. Paul; Gallagher, Patricia J.; Petrache, Irina; Rhodes, Simon J.; Tune, Johnathan D.
Several common diseases such as atherosclerosis, post-angioplasty restenosis, and graft vasculopathies, are associated with the changes in the structure and function of smooth muscle cells. During the pathogenesis of these diseases, smooth muscle cells have a marked alteration in the expression of many smooth muscle-specific genes and smooth muscle cells undergo a phenotypic switch from the contractile/differentiated status to the proliferative/dedifferentiated one. Serum response factor (SRF) is the major transcription factor that plays an essential role in coordinating a variety of transcriptional events during this phenotypic change. The first goal of my thesis studies is to determine how SRF regulates the expression of smooth muscle myosin light chain kinase (smMLCK) to mediate changes in contractility. Using a combination of transgenic reporter mouse and knockout mouse models I demonstrated that a CArG element in intron 15 of the mylk1 gene is necessary for maximal transcription of smMLCK. SRF binding to this CArG element modulates the expression of smMLCK to control smooth muscle contractility. A second goal of my thesis work is to determine how SRF coordinates the activity of chromatin remodeling enzymes to control expression of microRNAs that regulate the phenotypes of smooth muscle cells. Using both mouse knockout models and in vitro studies in cultured smooth muscle cells I showed how SRF acts together with Brg1-containing chromatin remodeling complexes to regulate expression of microRNAs-143, 145, 133a and 133b. Moreover, I found that SRF transcription cofactor myocardin acts together with SRF to regulate expression of microRNAs-143 and 145 but not microRNAs-133a and 133b. SRF can, thus, further modulate gene expression through post-transcriptional mechanisms via changes in microRNA levels. Overall my research demonstrates that through direct interaction with a CArG box in the mylk1 gene, SRF is important for regulating expression of smMLCK to control smooth muscle contractility. Additionally, SRF is able to harness epigenetic mechanisms to modulate expression of smooth muscle contractile protein genes directly and indirectly via changes in microRNA expression. Together these mechanisms permit SRF to coordinate the complex phenotypic changes that occur in smooth muscle cells.

Browsing by Author "Chen, Meng"

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