Genetic Polymorphism of GSTP1: Prediction of Clinical Outcome to Oxaliplatin/5-FU-based Chemotherapy in Advanced Gastric Cancer

Qing-Fang Li,Ru-Yong Yao,Ke-wei Liu,Hong-Ying Lv,Tao Jiang,Jun Liang 대한의학회 2010 Journal of Korean medical science Vol.25 No.6

The aim of this study was to evaluate the predictive value of the polymorphism Glutathione S-transferase P1 (GSTP1) Ile105Val on oxaliplatin/5-FU-based chemotherapy in advanced gastric cancer. Patients with advanced gastric cancer accepted oxaliplatin/5-FU-based chemotherapy as first-line chemotherapy were investigated. GSTP1 Ile105Val polymorphism was detected by TaqMan-MGB probe allelic discrimination method. Response to treatment was assessed by disease controlled rate. Time to progression, overall survival and toxicities were recorded. Final patient outcomes were as follows: the allele frequencies of GSTP1 were 105Ile/105Ile 52%, 105Ile/105Val 41% and 105Val/105Val 7%. For patients with 105Ile/105Ile and those with at least one 105Val allele, disease control rate was 39% and 71% (P=0.026), respectively;median time to progression was 4.0 and 7.0 months (P=0.002); median overall survival time was 7.0 and 9.5 months (P=0.002). Neurological toxicity was more frequently occurred in patients with two 105Ile alleles (P=0.005). In conclusion, patients with at least one 105Val allele have better prognosis and response to oxaliplatin/5-FUbased regimen as first-line treatment for patients with advanced gastric cancer.

Protective Effect of Astragalus polysaccharides on Liver Injury Induced by Several Different Chemotherapeutics in Mice

Liu, Wen,Gao, Fang-Fang,Li, Qun,Lv, Jia-Wei,Wang, Ying,Hu, Peng-Chao,Xiang, Qing-Ming,Wei, Lei Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.23

Side effects are an unavoidable consequence of chemotherapy drugs, during which liver injury often takes place. The current study was designed to investigate the protective effect of Astragalus polysaccharides (APS) against the hepatotoxicity induced by frequently-used chemical therapy agents, cyclophosphamide (CTX), docetaxel (DTX) and epirubicin (EPI)) in mice. Mice were divided into five groups, controls, low or high dose groups ($DTX_L$, $CTX_L$, $EPI_L$ or $DTX_H$, $CTX_H$, $EPI_H$), and low or high dose chemotherapeutics+APS groups ($DTX_L$+APS, $CTX_L$+APS, $EPI_L$+APS or $DTX_H$+APS, $CTX_H$+APS, $EPI_H$+APS). Controls were treated with equivalent normal saline for 28 days every other day; low or high dose group were intraperitoneal (i.p) injected with low or high doses of CTX, DTX and EPI for 28 days every other day; low or high dose chemotherapeutics+APS group were separately intraperitoneal (i.p) injected with chemotherapeutics for 28 days every other day and i.p with APS (100 mg/kg) for 7 days continually from the 22th to the 28th days. The body weight, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), histopathological features, and ultrastructure morphological change of liver tissues, protein expression level of caspase-3 were estimated at different time points. With high dose treatment of DTX, CTX and EPI, weight gain was inhibited and serum levels of ALT and AST were significantly increased. Sections of liver tissue showed massive hepatotoxicity in $CTX_H$ group compared to the control group, including hepatic lobule disorder, granular and vacuolar degeneration and necrosis in hepatic cells. These changes were confirmed at ultrastructural level, including obvious pyknosis, heterochromatin aggregation, nuclear membrane resolution, and chondrosome crystal decrease. Western blotting revealed that the protein levels of caspase-3 increased in $CTX_H$ group. The low dose groups exhibited trivial hepatotoxicity. More interestingly, after 100 mg/kg APS, liver injury was redecued not only regarding serum transaminase activities (low or high dose chemotherapeutics+APS group), but also from pathological and ultrastructural changes and the protein levels of caspase-3 ($CTX_H$+APS group). In conclusion, DTX, CTX and EPI induce liver damage in a dose dependent manner, whereas APS exerted protective effects.

Juvenile hormone-mediated reproduction induced by a sublethal concentration of imidacloprid in Cyrtorhinus lividipennis (Hemiptera: Miridae)

Jun Zhu,Yao Li,Ying-Ying Tang,Jian-Qi Liu,Yi-Yu Chen,Zhongxian LV,Fang Liu 한국응용곤충학회 2020 Journal of Asia-Pacific Entomology Vol.23 No.1

The Hemipteran predator, Cyrtorhinus lividipennis, feeds on the eggs and nymphs of rice planthoppers and leafhoppers. We previously demonstrated that sublethal concentrations of imidacloprid stimulated the reproduction of C. lividipennis. Considering the essential roles of juvenile hormone (JH) in insect reproduction, we speculated that sublethal concentrations of imidacloprid may stimulate the reproduction of C. lividipennis by regulating JH level. To test this, we cloned C. lividipennis JH acid methyl transferase (ClJHAMT) and JH esterase (ClJHE), which are responsible for JH biosynthesis and degradation genes, respectively. We then knocked down ClJHAMT by injecting dsRNA into C. lividipennis nymphs and found that emerging female adults exhibited 88.8% lower expression of the vitellogenin gene (ClVg) and the number of eggs was reduced by 41.5% as compared with controls. Silencing ClJHE increased ClVg mRNA expression by 275.0% but did not affect fecundity. A sublethal concentration of imidacloprid (LC 20 ) increased the JH titer in females by 35.3% and 60.6% at 24 and 48 h post-emergence, respectively. In treatments containing both imidacloprid and dsJHAMT, the silencing of CLJHAMT reduced the number of eggs produced by adult females by 21.4% as compared to the control (imidacloprid + dsGFP). Our results indicated that sublethal concentration of imidacloprid may induce C. lividipennis reproduction by upregulating JH level via JHAMT. The finding could provide valuable information for improved integration of C. lividipennis and insecticides in pest management.

Expression of RUNX2/LAPTM5 in the Induction of MC3T3-e1 Mineralization and Its Possible Relationship with Autophagy

Xing Lei,Li Yanqin,Li Wenhao,Liu Rong,Geng Yuanming,Ma Weiqun,Qiao Yu,Li Jianwen,Lv Yingtao,Fang Ying,Xu Pingping 한국조직공학과 재생의학회 2022 조직공학과 재생의학 Vol.19 No.6

BACKGROUND: The study aims to correlate osteogenesis with autophagy during the mineralization induction of MC3T3-e1 through exploring the expression of runt-related transcription factor 2 (RUNX2)/lysosomal-associated transmembrane protein 5 (LAMPT5). METHODS: The induction of mineralization in MC3T3-e1 was followed by detecting the expressions of osteogenesisrelated indexes such as RUNX2, alkaline phosphatase (ALP), osteocalcin (OCN), and LAPTM5 using RT-qPCR and Western blot from 0 to 14 days. Transmission electron microscope was utilised in visualizing the alterations of autophagosomes, which was followed by immunofluorescence detecting the subcellular localization of autophagy-related index sequestosome 1 (P62) and microtubule-associated protein 1 light 3 (LC3) protein and scrutinising the expression of P62 mRNA and P62 and LC3 proteins. RESULTS: Induction of MC3T3-e1 mineralization demonstrated an increased expression of osteogenesis-related indicators such as RUNX2, ALP, OCN, and LAPTM5 (p\0.05), as evident from the results of RT-qPCR and Western blot. Meanwhile, the expression of autophagosomes increased one day after mineralization induction and then experienced a gradual decline, and enhanced expression of LC3 protein was noted on days 1–2 of mineralization induction but was then followed by a corresponding reduce. In contrast, a continuous increase was reported in the expression of P62 mRNA and protein, respectively (p\0.05). Up- and down-regulating RUNX2/LAPTM5 expression alone confirmed the aforementioned results. CONCLUSION: It was therefore proposed that RUNX2 may be responsible for an early increase and then a gradual decrease in LAPTM5-mediated autophagy through the regulation of its high expression. Meanwhile, increased LAPTM5 expression in osteogenic mineralization presumed that RUNX2/LAPTM5 promoted autophagy and osteogenic expression, which may play a bridging role in the regulation of autophagy and osteogenesis.

Beneficial effects of natural Jeju groundwaters on lipid metabolism in high-fat diet-induced hyperlipidemic rats

Yan-chao Wang,Jin-miao Lu,Hui-zi Jin,Ai-niu Ma,Jin-yang Zhang,Nian Gong,Qi Xiao,Bin Zhu,Ying-fang Lv,Na Yu,Wei-dong Zhang,Yong-xiang Wang 한국영양학회 2014 Nutrition Research and Practice Vol.8 No.2

BACKGROUND: Groundwater is believed to possess many beneficial effects due to its natural source of various minerals. In this study, we examined the effects of natural Jeju groundwater S1 (SamdasooTM), S2 and S3 pumped up from different locations of Jeju Island, Korea, along with local tap water, on body weight gain, serum lipids and lipoproteins, and liver histopathology in high-fat diet-induced hyperlipidemic rats. MATERIALS/METHODS: Rats were randomly and equally divided into 6 groups. Different water samples were supplied to the hyperlipidemic rats as their daily drinking water and the widely-used anti-hyperlipidemic drug simvastatin was used as a positive control. Body weight, serum lipids and lipoproteins were measured weekly. Liver weight, liver index and liver histopathology were examined after the execution of the rats. RESULTS: After drinking Jeju groundwaters for two months, S2 but not S3 significantly reduced weight growth and serum triglycerides levels and increased high density lipoprotein-C (HDL-C) without affecting total cholesterol or LDL-C. S1 and particularly S2 significantly reduced the severity of liver hypertrophy and steatosis. All Groundwaters had much higher contents of vanadium (S3>S2>S1>>tap water) whereas S1 and S2 but not S3 markedly blocked autoxidation of ferrous ions. CONCLUSION: Jeju Groundwater S1 and particularly S2 exhibit protective effects against hyperlipidemia and fatty liver and hypothesize that the beneficial effect of Jeju Groundwaters may be contributed from blockade of autoxidation of ferrous ions rather than their high contents of vanadium.