Risk Assessment of Secondary Primary Malignancies in Nasopharyngeal Carcinoma: A Big-Data Intelligence Platform-Based Analysis of 6,377 Long-term Survivors from an Endemic Area Treated with Intensity-Modulated Radiation Therapy during 2003-2013

Lu-Lu Zhang,Guo-Hong Li,Yi-Yang Li,Zhen-Yu Qi,Ai-Hua Lin,Ying Sun 대한암학회 2019 Cancer Research and Treatment Vol.51 No.3

Purpose The incidence, risk factors and survival impact of secondary primary malignancies (SPMs) among survivors of nasopharyngeal carcinoma (NPC) treated with definitive intensity-modulated radiation therapy (IMRT) with or without chemotherapy are poorly characterized. Materials and Methods Consecutive patients (n=6,377) from the big-data intelligence platform at Sun Yat-sen University Cancer Center, China (in a high-incidence area) with newly diagnosed non-metastatic pathologically proven non-keratinizing undifferentiated NPC treated with IMRT±chemotherapy between January 2003 and June 2013 were retrospectively analyzed. Cumulative incidence of SPMs was calculated using the Kaplan-Meier method. Cox proportional hazards model was used to identify potential risk factors for SPMs and assess whether SPMs affect overall survival. Results Of the 6,377 patients, 189 (3.0%) suffered SPMs (median follow-up, 62 months). One-, 2-, 3-, 4-, and 5-cumulative risks of SPMs were 0.4%, 0.9%, 1.6%, 2.2%, and 2.6%, respectively. Latency from start of IMRT to SPMs diagnosis was 37 months (range, 6 to 102 months). In patients with SPMs, 14.3% suffered SPMs within 1 year post-IMRT: 1-3 years, 38.1%; 3-5 years, 33.9%; and > 5 years, 13.7%. Lung cancer was the most common SPM (50/6,377, 0.78%). Multivariate analysis demonstrated sex (male, 64% increase), age (! 50 years, 68% increase), and smoking history (41% increase) were significant risk factors for SPMs, and SPMs were associated with poorer overall survival. Conclusion This large cohort study confirms SPMs a dreadful complication for long-term survivors of NPC treated with IMRT. SPMs negatively impact overall survival in NPC. Close follow-up is recommended for older male survivors with a smoking history.

Protein-based soft micro-optics fabricated by femtosecond laser direct writing

Sun, Yun-Lu,Dong, Wen-Fei,Niu, Li-Gang,Jiang, Tong,Liu, Dong-Xu,Zhang, Lu,Wang, Ying-Shuai,Chen, Qi-Dai,Kim, Dong-Pyo,Sun, Hong-Bo Nature Publishing Group 2014 Light, science & applications Vol.3 No.1

<P>In this work, we report a novel soft diffractive micro-optics, called 'microscale kinoform phase-type lens (micro-KPL)', which is fabricated by femtosecond laser direct writing (FsLDW) using bovine serum albumin (BSA) as building blocks and flexible polydimethylsiloxane (PDMS) slices as substrates. By carefully optimizing various process parameters of FsLDW (e. g., average laser power density, scanning step, exposure time on a single point and protein concentration), the as-formed protein micro-KPLs exhibit excellent surface quality, well-defined three-dimensional (3D) geometry and distinctive optical properties, even in relatively harsh operation environments (for instance, in strong acid or base). Laser shaping, imaging and other optical performances can be easily achieved. More importantly, micro-KPLs also have unique flexible and stretchable properties as well as good biocompatibility and biodegradability. Therefore, such protein hydrogel-based micro-optics may have great potential applications, such as in flexible and stretchable photonics and optics, soft integrated optical microsystems and bioimplantable devices.</P>

The Predictive Value of Pre-therapeutic Serum Gamma-glutamyl transferase in Efficacy and Adverse Reactions to Neoadjuvant Chemotherapy among Breast Cancer Patients

Lu Sun,Wenjin Yin,Ziping Wu,Yaohui Wang,Jinsong Lu 한국유방암학회 2020 Journal of breast cancer Vol.23 No.5

Purpose: Gamma-glutamyl transferase (GGT) has been reported as being involved in tumor progression. Previous studies documented a potential relationship between serum GGT level and survival outcome in several types of human malignancies. However, the association between serum GGT levels and response to neoadjuvant chemotherapy (NAC) has not yet been reported. The present study aimed to evaluate the association between pre-therapeutic serum GGT level and the efficacy, long-term survival, and adverse reactions of NAC and to investigate its role in predicting NAC sensitivity in patients with breast cancer. Methods: A total of 129 patients were recruited and stratified into 2 groups according to serum GGT level (< 29 U/L and ≥ 29 U/L). The association between pre-therapeutic serum GGT levels and clinicopathological parameters was examined. The correlation between pre-therapeutic serum GGT levels and pathological complete response (pCR) was analyzed using univariate and multivariate logistic regression. Survival analyses of relapse-free survival (RFS) and disease-free survival (DFS) were performed. Pearson's χ2 test and multivariate logistic regression model were used to analyze the correlation between pre-therapeutic serum GGT levels and adverse reactions. Results: Pre-therapeutic serum GGT levels were associated with pCR among breast cancer patients treated with NAC. Multivariate analysis showed that low-level GGT significantly increased pCR rate. Patients in the high-level GGT group had poorer survival than those in the low-level GGT group. Subgroup analysis demonstrated that serum GGT level was potentially related to RFS and DFS in the hormone receptor-positive group. Low levels of GGT are significantly associated with a higher incidence of neutropenia. Conclusion: Pre-therapeutic serum GGT level is an independent and novel biomarker for predicting the efficiency, prognosis, and adverse reactions to NAC in breast cancer patients. Patients with low pre-therapeutic serum GGT levels are more likely to have higher pCR rates, better RFS and DFS, and higher hematologic toxicity.

Circ_0026359 induces HOXA9 to regulate gastric cancer malignant progression through miR‑140‑3p

Lu Shuirong,Lu Jinlai,Liu Lang,Sun Yilong,Zhao Yixuan,Tan Xi,Li Jingze 한국응용생명화학회 2022 Applied Biological Chemistry (Appl Biol Chem) Vol.65 No.4

Recent researches indicate the key role of circRNA in gastric cancer (GC) progression. However, the role of circ_0026359 in GC progression remains unclear. This study aims to analyze the role of circ_0026359 in GC development and the underlying mechanism. The results showed that compared with controls, GC tissues and cells displayed high circ_0026359 and HOXA9 expression, and low miR-140-3p expression. Depletion of circ_0026359 repressed cell proliferation, migration, invasion and glycolysis, and induced cell apoptosis. Circ_0026359 knockdown inhibited neoplasm growth in vivo. Under-expression of miR-140-3p, a target miRNA of circ_0026359, relieved the effects of circ_0026359 knockdown on GC progression. Additionally, HOXA9 was regulated by the circ_0026359/miR-140-3p axis. Thus, circ_0026359 absence inhibited GC progression by miR-140-3p/HOXA9 pathway, which provided an effective therapeutic target for GC.

Ginsenoside compound K protects human umbilical vein endothelial cells against oxidized low-density lipoprotein-induced injury via inhibition of nuclear factor-κB, p38, and JNK MAPK pathways

Lu, Shan,Luo, Yun,Zhou, Ping,Yang, Ke,Sun, Guibo,Sun, Xiaobo The Korean Society of Ginseng 2019 Journal of Ginseng Research Vol.43 No.1

Background: Oxidized low-density lipoprotein (ox-LDL) causes vascular endothelial cell inflammatory response and apoptosis and plays an important role in the development and progression of atherosclerosis. Ginsenoside compound K (CK), a metabolite produced by the hydrolysis of ginsenoside Rb1, possesses strong anti-inflammatory effects. However, whether or not CK protects ox-LDL-damaged endothelial cells and the potential mechanisms have not been elucidated. Methods: In our study, cell viability was tested using a 3-(4, 5-dimethylthiazol-2yl-)-2,5-diphenyl tetrazolium bromide (MTT) assay. Expression levels of interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor-${\alpha}$, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 were determined by enzyme-linked immunosorbent assay and Western blotting. Mitochondrial membrane potential (${\Delta}{\Psi}m$) was detected using JC-1. The cell apoptotic percentage was measured by the Annexin V/ propidium iodide (PI) assay, lactate dehydrogenase, and caspase-3 expression. Apoptosis-related proteins, nuclear factor $(NF)-{\kappa}B$, and mitogen-activated protein kinases (MAPK) signaling pathways protein expression were quantified by Western blotting. Results: Our results demonstrated that CK could ameliorate ox-LDL-induced human umbilical vein endothelial cells (HUVECs) inflammation and apoptosis, $NF-{\kappa}B$ nuclear translocation, and the phosphorylation of p38 and c-Jun N-terminal kinase (JNK). Moreover, anisomycin, an activator of p38 and JNK, significantly abolished the anti-apoptotic effects of CK. Conclusion: These results demonstrate that CK prevents ox-LDL-induced HUVECs inflammation and apoptosis through inhibiting the $NF-{\kappa}B$, p38, and JNK MAPK signaling pathways. Thus, CK is a candidate drug for atherosclerosis treatment.

A study of hydroelastic behavior of hinged VLFS

Sun, Yonggang,Lu, Da,Xu, Jin,Zhang, Xiantao The Society of Naval Architects of Korea 2018 International Journal of Naval Architecture and Oc Vol.10 No.2

This paper introduces a new method to study the hydroelastic behavior of hinged Very Large Floating Structures (VLFSs). A hinged two-module structure is used to confirm the present approach. For each module, the hydroelasticity theory proposed by Lu et al. (2016) is adopted to consider the coupled effects of wave dynamics and structural deformation. The continuous condition at the connection position between two adjacent modules is also satisfied. Then the hydroelastic motion equation can be established and numerically solved to obtain the vertical displacement, force and bending moment of the hinged structure. The results calculated by the present new method are compared with those obtained using three-dimensional hydroelasticity theory (Fu et al., 2007), which shows rather good agreement.

MMP-2-responsive fluorescent nanoprobes for enhanced selectivity of tumor cell uptake and imaging

Sun, Lu,Xie, Shuping,Ji, Xiuru,Zhang, Jingming,Wang, Dongmei,Lee, Seung Jin,Lee, Hyukjin,He, Huining,Yang, Victor C. The Royal Society of Chemistry 2018 Biomaterials Science Vol.6 No.10

<P>It is difficult to develop highly selective substrate-based fluorescent nanoprobes for specific matrix metalloproteinases (MMPs) due to overlapping substrate specificities among the family of MMP enzymes. To resolve this issue, we have developed novel fluorescent nanoprobes that are highly selective for soluble MMP-2. Herein, MMP-2-responsive nanoprobes were prepared by immobilizing fluorescent fusion proteins on nickel ferrite nanoparticles <I>via</I> the His-tag nickel chelation mechanism. The fusion protein consisted of a fluorescent mCherry protein with a cell penetrating peptide (CPP) moiety. An MMP-2 cleavage site was also introduced within the fusion protein, which was directly linked to the nickel ferrite nanoparticles. The selectivity of nanoprobes was modulated by hiding the cleavage site of MMP-2 substrates deeply inside the system, which could result in strong steric hindrance between the nanoprobes and MMPs, especially for membrane-tethered MMPs such as MMP-14. A cell-based assay demonstrated that the nanoprobes could only be activated by tumor cells secreting soluble MMP-2, but not membrane-tethered MMP-14. To further evaluate the contribution of the steric hindrance effect on the nanoprobes, a truncated recombinant MMP-14 was employed to confer their cleavage activity as compared to native membrane-tethered MMP-14. Furthermore, a designed probe with a diminished steric hindrance effect was proved to be activated by membrane-tethered type MMP-14. The results indicated that the design of fluorescent nanoprobes employing the steric hindrance effect can greatly enhance the selectivity of MMP-responsive nanoprobes realizing the specific detection of soluble MMP-2 in a tumor microenvironment. We believe that highly selective MMP-2-responsive fluorescent nanoprobes have broad impacts on biomedical applications including molecular imaging and labeling for tumor detection.</P>

Wood anatomy of Tectona grandis L.

( Sun Lu ),( Su Kyoung Chun ) 한국임학회 2006 한국임학회 학술발표논문집 Vol.2006 No.-

Proposal of a Pretreatment Nomogram for Predicting Local Recurrence after Intensity-Modulated Radiation Therapy in T4 Nasopharyngeal Carcinoma: A Retrospective Review of 415 Chinese Patients

Lu-Lu Zhang,Yi-Yang Li,Jiang Hu,Guan-Qun Zhou,Lei Chen,Wen-Fei Li,Ai-Hua Lin,Jun Ma,Zhen-Yu Qi,Ying Sun 대한암학회 2018 Cancer Research and Treatment Vol.50 No.4

Purpose Local relapse-free survival (LRFS) differs widely among patients with T4 category nasopharyngeal carcinoma (NPC). We aimed to build a nomogram incorporating clinicopathological information to predict LRFS in T4 NPC after definitive intensity-modulated radiation therapy (IMRT). Materials and Methods Retrospective study of 415 Chinese patients with non-metastatic T4 NPC treated with definitive IMRT with or without chemotherapy at our cancer center between October 2009 and September 2013. The nomogram for LRFS at 3 and 5 years was generated based on multivariate Cox proportional hazards regression, and validated using bootstrap resampling, assessing discriminative performance using the concordance index (C-index) and determining calibration ability via calibration curves. Results Five-year LRFS was 88.8%. We identified and incorporated four independent prognostic factors for LRFS: ethmoid sinus invasion, primary gross tumor volume, age, and pretreatment body mass index. The C-index of the nomogram for local recurrence was 0.732 (95% confidence interval, 0.726 to 0.738), indicating excellent predictive accuracy. The calibration curve revealed excellent agreement between nomogram-predicted and observed LRFS probabilities. Risk subgroups based on total point score cutoff values enabled effective discrimination of LRFS. Conclusion This pretreatment nomogram enables clinicians to accurately predict LRFS in T4 NPC after definitive IMRT, and could help to facilitate personalized patient counselling and treatment strategies.

Wood anatomy of Samanea saman (Jacq.) Merr

( Sun Lu ),( Su Kyoung Chun ) 한국임학회 2006 한국임학회 학술발표논문집 Vol.2006 No.-