Weight Loss Correlates with Macrophage Inhibitory Cytokine-1 Expression and Might Influence Outcome in Patients with Advanced Esophageal Squamous Cell Carcinoma

Lu, Zhi-Hao,Yang, Li,Yu, Jing-Wei,Lu, Ming,Li, Jian,Zhou, Jun,Wang, Xi-Cheng,Gong, Ji-Fang,Gao, Jing,Zhang, Xiao-Tian,Li, Jie,Li, Yan,Shen, Lin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

Background: Weight loss during chemotherapy has not been exclusively investigated. Macrophage inhibitory cytokine-1 (MIC-1) might play a role in its etiology. Here, we investigated the prognostic value of weight loss before chemotherapy and its relationship with MIC-1 concentration and its occurrence during chemotherapy in patients with advanced esophageal squamous cell carcinoma (ESCC). Materials and Methods: We analyzed 157 inoperable locally advanced or metastatic ESCC patients receiving first-line chemotherapy. Serum MIC-1 concentrations were assessed before chemotherapy. Patients were assigned into two groups according to their weight loss before or during chemotherapy:>5% weight loss group and ${\leq}5%$ weight loss group. Results: Patients with weight loss>5% before chemotherapy had shorter progression-free survival period (5.8 months vs. 8.7 months; p=0.027) and overall survival (10.8 months vs. 20.0 months; p=0.010). Patients with weight loss >5% during chemotherapy tended to have shorter progression-free survival (6.0 months vs. 8.1 months; p=0.062) and overall survival (8.6 months vs. 18.0 months; p=0.022), and if weight loss was reversed during chemotherapy, survival rates improved. Furthermore, serum MIC-1 concentration was closely related to weight loss before chemotherapy (p=0.001) Conclusions: Weight loss both before and during chemotherapy predicted poor outcome in advanced ESCC patients, and MIC-1 might be involved in the development of weight loss in such patients.

Changes in Activity of Key Enzymes related with N and S Assimilation in Response to S-Availability in Rape (Brassica napus L.)

Lu-Shen Li,Sang-Hyun Park,An-Na Cho,Tae-Hwan Kim 한국초지조사료학회 2009 한국초지조사료학회 학술대회논문집 Vol.2009 No.08

To investigate the effect of S-availability on N and S assimilations, Enzymatic activity of nitrate reductase (NR), glutamine synthetase (GS), ATP sulfurylase (ATPS) and O-acetylserine(thiol)lyase (OASTL) was measured, and also followed by their activity staining in forage rape (Brassica napus L.) fed with three different SO₄²? levels (0, 0.1 and 2.0 mM) for 25 hours. NR activity decreased as S-availability decreased, especially in young and middle leaves. S-limited conditions (0 and 0.1 mM sot) resulted in a reduction of GS activity. The activity of ATPS tended to increase with decreasing the exogenous SO₄²? supplying level. The activity of OASTL also increased as S-availability decreased for all leaf tissues, while tended to decrease in root. The results indicated t㏊t N assimilation was restricted by the limited S-nutrition especially in the developing leaf tissues, but S assimilation was stimulated except for OASTL activity in the roots.

Sulfur Deficiency Effects on Sulfate Uptake and Assimilatory Enzymes Activity in Rape Plants

Lu-Shen Li(이노신),Yu-Lan Jin(김옥란),Bok-Rye Lee(이복례),Tae-Hwan Kim(김태환) 한국초지조사료학회 2009 한국초지조사료학회지 Vol.29 No.2

유채 (Brassica napus L.)에서 외생적 황 공급이 SO₄²⁻ 흡수와 동화에 대한 영향을 알아보고자 SO₄²⁻ 농도를 세가지 수준 (1 mM SO₄²⁻, 대조구; 0.1 mM SO₄²⁻, 결핍; 0 mM SO₄²⁻, 무공급)으로 25시간 처리한 후 식물조직내에서의 SO₄²⁻ 농도, ATP sulfurylase와 APS reductase 활성을 측정하였다. SO₄²⁻의 흡수와 식물조직내에서의 SO₄²⁻의 농도는 결핍과 무공급 조건하에서 현저하게 감소하였다. ATP sulfurylase 활성은 외부 황 공급의 감소에 따라 증가한 반면, APS reductase 활성은 감소하였다. 황 무공급에 따른 이 두 효소 활력의 유의적인 차이는 어린잎과 중간잎에서만 고찰되었다. 이러한 결과는 한정된 황 조건하에서 특히 어린잎에서 SO₄²⁻ 동화는 더욱 민감하게 반응한다는 것을 제시한다.

Concomitance of P-gp/LRP Expression with EGFR Mutations in Exons 19 and 21 in Non-Small Cell Lung Cancers

Shen Lu,Hong Wei,Weipeng Lu,Mei Li,Qiuping Zhang 연세대학교의과대학 2016 Yonsei medical journal Vol.57 No.1

Purpose: Traditional chemotherapy is the main adjuvant therapy for the treatment of non-small cell lung cancer (NSCLC). However,the emergence of multi-drug resistance (MDR) has greatly restricted the curative effect of chemotherapy. Therefore, it isnecessary to find a method to treat MDR NSCLC clinically. It is worth investigating whether NSCLCs that are resistant to traditionalchemotherapy can be effectively treated with tyrosine kinase inhibitors targeting epidermal growth factor receptor (EGFR). Materials and Methods: The expression of P-glycoprotein (P-gp) and lung resistance-related protein (LRP) was detected by immunohistochemistry,and mutations in EGFR (exons 19 and 21) and Kirsten rat sarcoma viral oncogene homolog (KRAS) (exon 2)were detected by high-resolution melting analysis (HRMA) of surgical NSCLC specimens from 127 patients who did not undergotraditional chemotherapy or radiotherapy. A Pearson chi-square test was performed to analyze the correlations between the expressionof P-gp and LRP and mutations in EGFR and KRAS. Results: The expression frequencies of P-gp and LRP were significantly higher in adenocarcinomas from non-smoking patients;the expression frequency of LRP was significantly higher in cancer tissue from female patients. The frequency of EGFR mutationswas significantly higher in well to moderately differentiated adenocarcinomas from non-smoking female patients. The frequencyof EGFR mutations in the cancers that expressed P-gp, LRP, or both P-gp and LRP was significantly higher than that in cancersthat did not express P-gp or LRP. Conclusion: NSCLCs expressing P-gp/LRP bear the EGFR mutation in exon 19 or 21 easily.

Glutathione Concentration as Affected by Sulfate Supply Level and its Relationship with Sulfate Uptake and Assimilatory Enzymes Activity in Rape Plants

Lu-Shen Li(이노신),Tae-Hwan Kim(김태환) 한국초지조사료학회 2011 한국초지조사료학회지 Vol.31 No.1

유채 (Brassica napus L.)에서 황 공급수준에 따른 글루타치온 함량의 변화가 황 흡수 및 동화관련 효소 활력에 미치는 영향을 규명하고자, SO₄²? 농도를 4수준 (0, 0.1, 1.0 및 2.0 mM)으로 25시간 처리한 후 식물조직 내 글루타치온 함량을 측정하고, SO₄²? 흡수, ATP sulfurylase (ATPS) 및 Oacteylserine (thiol) lyase (OASTL) 효소 활력과의 상관관계를 분석하였다. SO₄²? 흡수는 황 공급수준에 따라 평행적인 증가를 보였으나 잎과 뿌리 조직의 단백질 함량은 유의적인 차이가 없었다. ATPS 활력은 황 공급수준이 0 mM에서 2.0 mM로 증가함에 따라 유의적으로 감소 (p<0.05) 하였으며, OASTL 활력은 황 결핍수준인 0 및 0.1 mM에서만 유의적인 감소 (p<0.05)를 보였다. 어린잎, 중간잎 및 뿌리 조직에서는 황 결핍수준이 증가함에 따라 글루타치온 함량은 유의적으로 증가 (p<0.05) 하였으나, 뿌리에서는 처리간 유의적인 차이가 없었다. 황 공급수준의 감소에 따른 글루타치온 함량과 SO₄²? 흡수 간에는 고도의 정의 상관관계 (p<0.01)가 인정되었으며, 잎과 뿌리내의 ATPS 및 잎조직의 OASTL 효소활력 간에는 각각 부의 상관관계 (p<0.05)가 인정되었다. The glutathione (GSH) concentration in leaves of different maturities and roots of forage rape (Brassica napus L.) supplied with four levels of external SO₄²? (0, 0.1, 1.0 and 2.0 mM) supply were measured. The relationships of GSH concentration with SO₄²? uptake, ATP sulfurylase (ATPS) and O-acteylserine (thiol) lyase (OASTL) activity were also assessed. The SO₄²? uptake increased in parallel with the external SO₄²? supply, while protein concentration was not significantly changed. The ATPS activity increased continuously with decreasing SO₄²? supply from 2.0 to 0 mM, while the OASTL activity decreased significantly only at S-deficient conditions (0 and 0.1 mM). The GSH concentration in the young leaves, middle leaves and roots continuously increased (except for between 1.0 and 2.0 mM in the middle leaves and roots) as the external S supply was increased, but no significant changes occurred in the old leaves. The increased endogenous GSH concentration, affected by the SO₄²? supply level, was significantly related with the decrease in ATPS activity in both leaves and roots, and the decrease in OASTL activity only in leaves..

Neutrophil Count and the Inflammation-based Glasgow Prognostic Score Predict Survival in Patients with Advanced Gastric Cancer Receiving First-line Chemotherapy

Li, Qing-Qing,Lu, Zhi-Hao,Yang, Li,Lu, Ming,Zhang, Xiao-Tian,Li, Jian,Zhou, Jun,Wang, Xi-Cheng,Gong, Ji-Fang,Gao, Jing,Li, Jie,Li, Yan,Shen, Lin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.2

Purpose: To explore the value of systemic inflammatory markers as independent prognostic factors and the extent these markers improve prognostic classification for patients with inoperable advanced or metastatic gastric cancer (GC) receiving palliative chemotherapy. Methods: We studied the prognostic value of systemic inflammatory factors such as circulating white blood cell count and its components as well as that combined to form inflammation-based prognostic scores (Glasgow Prognostic Score (GPS), Neutrophil-Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Prognostic Index (PI) and Prognostic Nutritional Index (PNI)) in 384 patients with inoperable advanced or metastatic gastric cancer (GC) receiving first-line chemotherapy. Univariate and multivariate analyses were performed to examine the impact of inflammatory markers on overall survival (OS). Results: Univariate analysis revealed that an elevated white blood cell, neutrophil and/or platelet count, a decreased lymphocyte count, a low serum albumin concentration, and high CRP concentration, as well as elevated NLR/PLR, GPS, PI, PNI were significant predictors of shorter OS. Multivariate analysis demonstrated that only elevated neutrophil count (HR 3.696, p=0.003) and higher GPS (HR 1.621, p=0.01) were independent predictors of poor OS. Conclusion: This study demonstrated elevated pretreatment neutrophil count and high GPS to be independent predictors of shorter OS in inoperable advanced or metastatic GC patients treated with first-line chemotherapy. Upon validation of these data in independent studies, stratification of patients using these markers in future clinical trials is recommended.

The type II histidine triad protein HtpsC facilitates invasion of epithelial cells by highly virulent Streptococcus suis serotype 2

Lu Yunjun,Li Shu,Shen Xiaodong,Zhao Yan,Zhou Dongming,Hu Dan,Cai Xushen,Lu Lixia,Xiong Xiaohui,Li Ming,Cao Min 한국미생물학회 2021 The journal of microbiology Vol.59 No.10

Streptococcus suis serotype 2 (S. suis 2) is an important zoonotic pathogen that presents a significant threat both to pigs and to workers in the pork industry. The initial steps of S. suis 2 pathogenesis are unclear. In this study, we found that the type II histidine triad protein HtpsC from the highly virulent Chinese isolate 05ZYH33 is structurally similar to internalin A (InlA) from Listeria monocytogenes, which plays an important role in mediating listerial invasion of epithelial cells. To determine if HtpsC and InlA function similarly, an isogenic htpsC mutant (ΔhtpsC) was generated in S. suis by homologous recombination. The htpsC deletion strain exhibited a diminished ability to adhere to and invade epithelial cells from different sources. Double immunofluorescence microscopy also revealed reduced survival of the ΔhtpsC mutant after cocultivation with epithelium. Adhesion to epithelium and invasion by the wild type strain was inhibited by a monoclonal antibody against E-cadherin. In contrast, the htpsC-deficient mutant was unaffected by the same treatment, suggesting that E-cadherin is the host-cell receptor that interacts with HtpsC and facilitates bacterial internalization. Based on these results, we propose that HtpsC is involved in the process by which S. suis 2 penetrates host epithelial cells, and that this protein is an important virulence factor associated with cell adhesion and invasion.

Oxymatrine Causes Hepatotoxicity by Promoting the Phosphorylation of JNK and Induction of Endoplasmic Reticulum Stress Mediated by ROS in LO2 Cells

Li-li Gu,Zhe-lun Shen,Yang-Lei Li,Yi-Qi Bao,Hong Lu 한국분자세포생물학회 2018 Molecules and cells Vol.41 No.5

Oxymatrine (OMT) often used in treatment for chronic hepatitis B virus infection in clinic. However, OMT–induced liver injury has been reported. In this study, we aim to investigate the possible mechanism of OMT-induced hepatotoxicity in human normal liver cells (L02). Exposed cells to OMT, the cell viability was decreased and apoptosis rate increased, the intracellular markers of oxidative stress were changed. Simultaneously, OMT altered apoptotic related proteins levels, including Bcl-2, Bax and pro-caspase-8/-9/-3. In addition, OMT enhanced the protein levels of endoplasmic reticulum (ER) stress makers (GRP78/Bip, CHOP, and cleaved-Caspase-4) and phosphorylation of c-Jun N-terminal kinase (p-JNK), as well as the mRNA levels of GRP78/Bip, CHOP, caspase-4, and ER stress sensors (IREI, ATF6, and PERK). Pre-treatment with Z-VAD-fmk, JNK inhibitor SP600125 and N-acetyl-l-cysteine (NAC), a ROS scavenger, partly improved the survival rates and restored OMT-induced cellular damage, and reduced caspase-3 cleavage. SP600125 or NAC reduced OMT-induced p-JNK and NAC significantly lowered caspase-4. Furthermore, 4-PBA, the ER stress inhibitor, weakened inhibitory effect of OMT on cells, on the contrary, TM worsen. 4-PBA also reduced the levels of p-JNK and cleaved-caspase-3 proteins. Therefore, OMT-induced injury in L02 cells was related to ROS mediated p-JNK and ER stress induction. Antioxidant, by inhibition of p-JNK or ER stress, may be a feasible method to alleviate OMT-induced liver injury.

Preparation and Characterization of Anti-GP73 Monoclonal Antibodies and Development of Double-antibody Sandwich ELISA

Li, Qi-Wen,Chen, Hong-Bing,Li, Zhi-Yang,Shen, Peng,Qu, Li-Li,Gong, Lai-Ling,Xu, Hong-Pan,Pang, Lu,Si, Jin Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.5

Background: Serum Golgi protein 73 (GP73) as a novel and potential marker for diagnosing hepatocellular carcinoma (HCC) have been found to be elevated in HCC patients and associated with clinical variables representing tumor growth and invasiveness. The aim of this study was to prepare a pair of monoclonal antibodys (mAbs) against GP73 and develop a newly designed double-antibody sandwich enzyme-linked immunosorbent assay (s-ELISA), which would be used in the detection of serum GP73 (sGP73) as well as in the diagnosis of HCC. Materials and Methods: Produced by prokaryotic expression, the purified recombinant GP73 (rGP73), produced by prokaryotic expression, was used to immunize the Balb/c mice. Two hybridoma cell lines against GP73 were obtained by fusing mouse Sp2/0 myeloma cells with spleen cells from the immunized mice. The titers of anti-GP73 mAb reached 1:243,000. Western blotting analysis and Immunohistochemistry staining revealed that anti-GP73 mAb could recognize GP73 protein. The double-antibody s-ELISA was successfully established and validated by 119 HCC and 103 normal serum samples. Results: showed that the detection limit of this method could reach 1.56 ng/ml, and sGP73 levels in HCC group (mean=190.6 ng/ml) were much higher than those of in healthy controls (mean=70.92 ng/ml). Conclusions: Results of our study not only showed that sGP73 levels of HCC patients were significantly higher than those of healthy controls, but also indicated that the laboratory homemade anti-GP73 mAbs could be the optimal tool used in evaluating sGP73 levels, which would provide a solid foundation for subsequent clinical applications.

Sulfur Deficiency Effects on Nitrate Uptake and Assimilatory Enzyme Activities in Rape Plants

Lu-Shen Li(이노신),Yu-Lan Jin(김옥란),Bok-Rye Lee(이복례),Tae-Hwan Kim(김태환) 한국초지조사료학회 2009 한국초지조사료학회지 Vol.29 No.2

유채 (Brassica napus L.)에서 황 결핍이 NO₃⁻ 흡수와 동화에 대한 영향을 알아보고자 SO₄²⁻ 농도를 세가지 수준 (1 mM SO₄²⁻, 대조구; 0.1 mM SO₄²⁻, 결핍; 0 mM SO₄²⁻, 무공급)으로 25시간 처리한 후 NO₃⁻ 흡수량, 식물조직내의 nitrate reductase (NR) 및 glutamine syntheetase (GS) 활성을 분석하였다. 25시간 처리과정에서 황결핍 조건하에서의 NO₃⁻의 흡수는 대조구와 큰 차이를 나타내지 않은 반면, 황 무공급구에서는 NO₃⁻의 흡수는 유의적으로 감소하였다. NR 활성은 잎과 뿌리 조직에서 공히 SO₄²⁻ 농도가 감소됨에 따라 감소하였다. 특히 어린잎과 중간 잎의 황 결핍 처리구에서 각각 35% 및 황 무공급구에서 70%의 뚜렸한 감소를 보였다. 뿌리에서는 오직 황 무공급구에서 유의적인 감소(-29%)를 보였다. SO₄²⁻ 농도에 따른 잎 조직에서 GS 활성은 잎의 성숙 정도에 따라 차이를 보였으며, 전반적으로 황 결핍과 황 무공급구에서 감소하는 경향을 보였다. 뿌리조직에서 GS 활성은 황 무공급구에서만 유의적인 감소를 보였다. 이러한 결과들은 황 공급이 제한을 받는 조건에서 질산염의 흡수가 감소되며, 식물조직체내의 질산염환원과 아미노산 합성관련 효소의 활성이 제한을 받았다는 것을 보여준다.