Clinical Efficacy of Bevacizumab Concomitant with Pemetrexed in Patients with Advanced Non-small Cell Lung Cancer

Zhang, Yu-Mei,Li, Yong-Qiang,Liu, Zhi-Hui,Liao, Xiao-Li,Liang, Rong,Lin, Yan,Yuan, Chun-Ling,Liao, Si-Na,Liang, Chao-Yong,Li, Qian,Li, Le-Qun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.8

Objective: To observe the clinical efficacy of bevacizumab concomitant with pemetrexed in patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods: A total of 72 patients were randomly divided into a combination group (pemetrexed+bevacizumab, n=36) and a pemetrexed group (n=36) and assessed for disease control (CR+PR+SD) after 4-cycles of first-line GP chemotherapy (gemcitabine+cisplatin). Clinical efficacy, progression-free survival time (PFS), overall survival time (OS), overall response rate (ORR), disease control rate (DCR) and rate of adverse responses between two groups were observed and compared. Results: ORR and DCR were 27.8% and 83.4% in combination group, and 16.7% and 69.5% in the pemetrexed group, respectively, but there were no significant differences (P>0.05). PFS in combination group and pemetrexed group were 4.6 months and 3.9 months respectively (P=0.09), whereas OS in the combination group was 14 months, evidently higher than in the pemetrexed group (11 months, P=0.004). Adverse responses in both groups included high blood pressure, bleeding, thrombocytopenia, anemia, elevated transaminase, diarrhea, vomiting and proteinuria, but there were no significant differences (P>0.05). Conclusions: Bevacizumab concomitant with pemetrexed has better clinical efficacy and safety, giving rise to prolonged survival time in patients with advanced NSCLC.

Pituitary P62 deficiency leads to female infertility by impairing luteinizing hormone production

Li Xing,Zhou Ling,Peng Guiliang,Liao Mingyu,Zhang Linlin,Hu Hua,Long Ling,Tang Xuefeng,Qu Hua,Shao Jiaqing,Zheng Hongting,Long Min 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-

P62 is a protein adaptor for various metabolic processes. Mice that lack p62 develop adult-onset obesity. However, investigations on p62 in reproductive dysfunction are rare. In the present study, we explored the effect of p62 on the reproductive system. P62 deficiency-induced reproductive dysfunction occurred at a young age (8 week old). Young systemic p62 knockout (p62 -/- ) and pituitary-specific p62 knockout (p62 flox/flox αGSU cre ) mice both presented a normal metabolic state, whereas they displayed infertility phenotypes (attenuated breeding success rates, impaired folliculogenesis and ovulation, etc.) with decreased luteinizing hormone (LH) expression and production. Consistently, in an infertility model of polycystic ovary syndrome (PCOS), pituitary p62 mRNA was positively correlated with LH levels. Mechanistically, p62 -/- pituitary RNA sequencing showed a significant downregulation of the mitochondrial oxidative phosphorylation (OXPHOS) pathway. In vitro experiments using the pituitary gonadotroph cell line LβT2 and siRNA/shRNA/plasmid confirmed that p62 modulated LH synthesis and secretion via mitochondrial OXPHOS function, especially Ndufa2, a component molecule of mitochondrial complex I, as verified by Seahorse and rescue tests. After screening OXPHOS markers, Ndufa2 was found to positively regulate LH production in LβT2 cells. Furthermore, the gonadotropin-releasing hormone (GnRH)-stimulating test in p62 flox/flox αGSU cre mice and LβT2 cells illustrated that p62 is a modulator of the GnRH-LH axis, which is dependent on intracellular calcium and ATP. These findings demonstrated that p62 deficiency in the pituitary impaired LH production via mitochondrial OXPHOS signaling and led to female infertility, thus providing the GnRH-p62-OXPHOS(Ndufa2)-Ca 2+ /ATP-LH pathway in gonadotropic cells as a new theoretical basis for investigating female reproductive dysfunction.

HiF-1α siRNA and Cisplatin in Combination SuppressTumor Growth in a Nude Mice Model of Esophageal Squamous Cell Carcinoma

Liao, Hong-Ying,Wang, Gui-Ping,Gu, Li-Jia,Huang, Shao-Hong,Chen, Xiu-Ling,Li, Yun,Cai, Song-Wang Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.2

Introduction: The esophagus squamous cell carcinoma (ESCC) is one of the most deadly malignances, and a current challenge is the development of effective therapeutic agents. Our present work addressed the effect of HIF-$1{\alpha}$ siRNA alone or in combination with cisplatin on the growth of ESCC in nude mice. Materials and Methods: Xenografts were established by inoculating ESCC TE-1 cells in nude mice, and transplanted tumors were treated with HIF-$1{\alpha}$ siRNA, cisplatin alone or together. Growth was assessed by measuring tumor volume. HIF-$1{\alpha}$ mRNA and protein expression were detected using RT-PCR and immunohistochemistry, respectively. Apoptosis of ESCC TE-1 cells was analyzed by flow cytometry. Results: In our nude mice model, HIF-$1{\alpha}$ siRNA effectively inhibited the growth of transplanted ESCC, downregulating HIF-$1{\alpha}$ mRNA and protein expression, and inducing ESCC TE-1 cell apoptosis. Notably when combinated with cisplatin, HIF-$1{\alpha}$ siRNA showed synergistic interaction in suppressing tumor growth. Furthermore, the proportion of apoptotic cells in HIF-$1{\alpha}$ siRNA plus cisplatin group was significantly higher than that in cisplatin or HIF-$1{\alpha}$ siRNA-treated groups (P<0.05). Conclusions: Down-regulated HIF-$1{\alpha}$ expression induced by siRNA could effectively suppress the growth of transplanted ESCC $in$ $vivo$. HIF-$1{\alpha}$ siRNA could enhance the cytotoxicity of cisplatin, which suggests that a combination of these two agents may have potential for therapy of advanced ESCC.

Identification of Key Genes and Pathways in Peripheral Blood Mononuclear Cells of Type 1 Diabetes Mellitus by Integrated Bioinformatics Analysis

Xing Li,Mingyu Liao,Jiangheng Guan,Zhou Ling,Rufei Shen,Long Min,Shao Jiaqing 대한당뇨병학회 2022 Diabetes and Metabolism Journal Vol.46 No.3

Background: The onset and progression of type 1 diabetes mellitus (T1DM) is closely related to autoimmunity. Effective monitoring of the immune system and developing targeted therapies are frontier fields in T1DM treatment. Currently, the most available tissue that reflects the immune system is peripheral blood mononuclear cells (PBMCs). Thus, the aim of this study was to identify key PBMC biomarkers of T1DM.Methods: Common differentially expressed genes (DEGs) were screened from the Gene Expression Omnibus (GEO) datasets GSE9006, GSE72377, and GSE55098, and PBMC mRNA expression in T1DM patients was compared with that in healthy participants by GEO2R. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) network analyses of DEGs were performed using the Cytoscape, DAVID, and STRING databases. The vital hub genes were validated by reverse transcription-polymerase chain reaction using clinical samples. The disease-gene-drug interaction network was built using the Comparative Toxicogenomics Database (CTD) and Drug Gene Interaction Database (DGIdb).Results: We found that various biological functions or pathways related to the immune system and glucose metabolism changed in PBMCs from T1DM patients. In the PPI network, the DEGs of module 1 were significantly enriched in processes including inflammatory and immune responses and in pathways of proteoglycans in cancer. Moreover, we focused on four vital hub genes, namely, chitinase-3-like protein 1 (CHI3L1), C-X-C motif chemokine ligand 1 (CXCL1), matrix metallopeptidase 9 (MMP9), and granzyme B (GZMB), and confirmed them in clinical PBMC samples. Furthermore, the disease-gene-drug interaction network revealed the potential of key genes as reference markers in T1DM.Conclusion: These results provide new insight into T1DM pathogenesis and novel biomarkers that could be widely representative reference indicators or potential therapeutic targets for clinical applications.

Mineralogy and geochemistry of three weathered Lower Cambrian black shale profiles in Northeast Chongqing, China

Sixiang Ling,Xiyong Wu,Chunwei Sun,Xin Liao,Yong Ren,Xiaoning Li 한국지질과학협의회 2016 Geosciences Journal Vol.20 No.6

This paper reports a geochemical study on the mineralogy and major elements of mid-ridge (A), near mountaintop (B), and valley (C) profiles developed in the Lower Cambrian black shale in Northeast Chongqing, China. The primary objective was to understand the elemental mobility, mineralogical transformation, and weathering progression during black shale chemical weathering in a subtropical climate. Profiles A, B, and C are characterized as weak, weak to moderate, and moderate to intense in terms of weathering intensity, respectively, by the Chemical Index of Alteration (CIA). Results indicate that most elements were mobilized by acidic solutions produced during the oxidation of pyrite and organic matter (OM). Among the major elements, Si was slightly enriched in profile A, but depleted through desilication in profile B and C. Al was enriched in the regolith zone in profile A and C, and Fe was enriched at the oxic front because of secondary clay and sesquioxide formation. The addition and depletion of major elements and the depth of the oxic front increased with the degree of weathering. Gypsum and Fe- (hydro-) oxides were observed to form and re-precipitate in the saprock and fractured shale zones. Clay minerals formed from dissolution of plagioclase and the transformation of other labile clay minerals during weathering. The progressive changes in mineralogical composition of weathered material from profile A to C showed the sequence of mineral decomposition with degree of weathering: first, oxidation of pyrite and OM; then Ca and Mg were removed during dissolution of carbonatite; followed by removal of Na from dissolution of plagioclase; lastly, transformation of clay minerals during weathering; meanwhile, desilication occurs at moderate to intense weathering stages.

Psychometric Testing of Behavior Assessment for Children

Hsiao-Ling Chuang,Ching-Pyng Kuo,Chia-Ying Li,Wen-Chun Liao 한국간호과학회 2016 Asian Nursing Research Vol.10 No.1

Purpose: The purpose of this study was to test the reliability and validity of the Behavior Assessment for Children (BAC) in a community of school-aged children in Taiwan. Method: A school-based sample comprising third grade and fourth grade students was recruited from Taichung City in Taiwan. The parents (n = 248) and teachers (n = 15) of these students completed structured questionnaires, including the Child Behavior Checklist (CBCL) and the proposed BAC. Content validity, concurrent validity, construct validity, internal consistency, and inter-rater reliability of the BAC were assessed. Results: The BAC comprised three subscales (attention, emotion, and self-control) that included 17 items. The content validity index (CVI) score was 0.98. The result of the confirmatory factor analysis (goodness of fit = .90, root mean square of residual = .03, root mean square error of approximation = .06, and comparative fit index = .94) supported the construct validity of the three BAC subscales. The concurrent validity of the BAC subscales significantly correlated with the compatible CBCL subscales (r = .59-.78, p < .001). Cronbach a of the subscales of the BAC ranged from .78 to .92. The intraclass correlation coefficient between the parents and teachers ranged from .31 to .44, and the joint probability of agreement ranged from 31.4% to 92.2%. Conclusions: The BAC is a valid and reliable instrument for evaluating behavioral problems in schoolaged children.

New Insights into mTOR Signal Pathways in Ovarian-Related Diseases: Polycystic Ovary Syndrome and Ovarian Cancer

Liu, Ai Ling,Liao, Hong Qing,Li, Zhi Liang,Liu, Jun,Zhou, Cui Lan,Guo, Zi Fen,Xie, Hong Yan,Peng, Cui Ying Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.12

mTOR, the mammalian target of rapamycin, is a conserved serine/threonine kinase which belongs to the phosphatidyl-linositol kinase-related kinase (PIKK) family. It has two complexes called mTORC1 and mTORC2. It is well established that mTOR plays important roles in cell growth, proliferation and differentiation. Over-activation of the mTOR pathway is considered to have a relationship with the development of many types of diseases, including polycystic ovary syndrome (PCOS) and ovarian cancer (OC). mTOR pathway inhibitors, such as rapamycin and its derivatives, can directly or indirectly treat or relieve the symptoms of patients suffering from PCOS or OC. Moreover, mTOR inhibitors in combination with other chemical-molecular agents may have extraordinary efficacy. This paper will discuss links between mTOR signaling and PCOS and OC, and explore the mechanisms of mTOR inhibitors in treating these two diseases, with conclusions regarding the most effective therapeutic approaches.

The Study on Stress in Clinical Practice Internship and Professional Commitment among Graduating Nursing Students of a 5-year Junior College in Southern Taiwan

Su Hui Cheng,Li-Ling Liao,I-Ju Lai 한국간호과학회 2015 한국간호과학회 학술대회 Vol.2015 No.10

On/off Switch Mediated by Exo+ Polymerases: Experimental Analysis for Its Physiological and Technological Implications

( Jia Zhang ),( Lin Ling Chen ),( Zi Fen Guo ),( Cui Ying Peng ),( Duan Fang Liao ),( Kai Li ) 생화학분자생물학회 2003 BMB Reports Vol.36 No.6

The potential physiological role and technological application of the premature termination of DNA polymerization through the off-switch of exo+ polymerases were studied using 3` phosphorothioate-modified or unmodified primers with single base mismatch distal to the 3` terminus. With exonuclease-digestible unmodified primers, a gradient premature termination of DNA polymerization was observed when amplified with exo+ polymerases. With 3` allele specific phosphorothioate-modified primers, an efficient off-switch effect occurred in the discrimination of a single nucleotide polymorphism when directly using genomic DNA. Clearly, the off-switch of exo+polymerases is useful in biomedical research.

On/off Switch Mediated by Exo+ Polymerases: Experimental Analysis for Its Physiological and Technological Implications

Zhang, Jia,Chen, Lin-Ling,Guo, Zi-Fen,Peng, Cui-Ying,Liao, Duan-Fang,Li, Kai Korean Society for Biochemistry and Molecular Biol 2003 Journal of biochemistry and molecular biology Vol.36 No.6

The potential physiological role and technological application of the premature termination of DNA polymerization through the off-switch of exo+ polymerases were studied using 3' phosphorothioate-modified or unmodified primers with single base mismatch distal to the 3' terminus. With exonuclease-digestible unmodified primers, a gradient premature termination of DNA polymerization was observed when amplified with exo+ polymerases. With 3' allele specific phosphorothioate-modified primers, an efficient off-switch effect occurred in the discrimination of a single nucleotide polymorphism when directly using genomic DNA. Clearly, the off-switch of exo+ polymerases is useful in biomedical research.