Genetic Variants in the PI3K/PTEN/AKT/mTOR Pathway Predict Platinum-based Chemotherapy Response of Advanced Non-small Cell Lung Cancers in a Chinese Population

Xu, Jia-Li,Wang, Zhen-Wu,Hu, Ling-Min,Yin, Zhi-Qiang,Huang, Ming-De,Hu, Zhi-Bin,Shen, Hong-Bing,Shu, Yong-Qian Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Objective: The PI3K/PTEN/AKT/mTOR signaling pathway has been implicated in resistance to cisplatin. In the current study, we determined whether common genetic variations in this pathway are associated with platinum-based chemotherapy response and clinical outcome in advanced non-small cell lung cancer (NSCLC) patients. Methods: Seven common single nucleotide polymorphisms (SNPs) in core genes of this pathway were genotyped in 199 patients and analyzed for associations with chemotherapy response, progression-free survival (PFS) and overall survival (OS). Results: Logistic regression analysis revealed an association between AKT1 rs2494752 and response to treatment. Patients carrying heterozygous AG had an increased risk of disease progression after two cycles of platinum-based chemotherapy compared to those with AA genotype (Adjusted odds ratio (OR)=2.18, 95% confidence interval (CI): 1.00-4.77, which remained significant in the stratified analyses). However, log-rank test and cox regression detected no association between these polymorphisms in the PI3K pathway genes and survival in advanced NSCLC patients. Conclusions: Our findings suggest that genetic variants in the PI3K/PTEN/AKT/mTOR pathway may predict platinum-based chemotherapy response in advanced NSCLC patients in a Chinese population.

Genetic Variants of NBS1 Predict Clinical Outcome of Platinum-based Chemotherapy in Advanced Non-small Cell Lung Cancer in Chinese

Xu, Jia-Li,Hu, Ling-Min,Huang, Ming-De,Zhao, Wan,Yin, Yong-Mei,Hu, Zhi-Bin,Ma, Hong-Xia,Shen, Hong-Bing,Shu, Yong-Qian Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.3

Objective: NBS1 plays a key role in the repair of DNA double-strand break (DSB). We conducted this study to investigate the effect of two critical polymorphisms (rs1805794 and rs13312840) in NBS1 on treatment response and prognosis of advanced non-small cell lung cancer (NSCLC) patients with platinum-based chemotherapy. Methods: Using TaqMan methods, we genotyped the two polymorphisms in 147 NSCLC patients. Odds ratios (ORs) and their 95% confidential intervals (CIs) were calculated as a measure of difference in the response rate of platinum-based chemotherapy using logistic regression analysis. The Kaplan-Meier and log-rank tests were used to assess the differences in progression-free survival (PFS) and overall survival (OS). Cox proportional hazards model was applied to assess the hazard ratios (HRs) for PFS and OS. Results: Neither of the two polymorphisms was significantly associated with treatment response of platinum-based chemotherapy. However, patients carrying the rs1805794 CC variant genotype had a significantly improved PFS compared to those with GG genotype (16.0 vs. 8.0 months, P = 0.040). Multivariable cox regression analysis further showed that rs1805974 was a significantly favorable prognostic factor for PFS [CC/CG vs. GG: Adjusted HR = 0.62, 95% CI: 0.39-0.99; CC vs. CG/GG: Adjusted HR = 0.56, 95% CI: 0.32-0.97). Similarly, rs13312840 with a small sample size also showed a significant association with PFS (CC vs. CT/TT: Adjusted HR = 25.62, 95% CI: 1.53-428.39). Conclusions: Our findings suggest that NBS1 polymorphisms may be genetic biomarkers for NSCLC prognosis especially PFS with platinum-based chemotherapy in the Chinese population.

QTL Analysis for Low-Temperature Requirement Vernalization in Brassica campestris

Yang Xu,Yu Yang Jun,Zhang Feng Lan,Zhao Xiu Yun,Zhang De Shuang,Xu Jia Bing 한국원예학회 2006 한국원예학회 기타간행물 Vol.- No.-

Transcriptome Analysis Reveals Molecular Mechanisms Underlying Methyl Jasmonate-mediated Biosynthesis of Protopanaxadiol-type Saponins in Panax notoginseng Leaves

Li Ying,Lin Yuan,Jia Bing,Chen Geng,Shi Huineng,Xu Rui,Li Xuejiao,Tang Junrong,Tang Qingyan,Zhang Guanghui,Yang Jianli,Fan Wei,Yang Shengchao 한국식물학회 2022 Journal of Plant Biology Vol.65 No.1

Methyl jasmonate (MeJA) has been widely used to improve the biosynthesis of secondary metabolites such as triterpenoid saponins in medicinal plants. However, the underlying molecular mechanisms remain poorly understood. Differing from roots that accumulate protopanaxatriol-type saponins, Panax notoginseng leaves with a lower biomass mainly contain protopanaxadiol (PPD)-type saponins. Therefore, it is interesting to explore whether MeJA can activate the biosynthesis of PPD-type saponins in P. notoginseng leaves. In this study, we found MeJA could effectively induce the accumulation of PPD-type saponins, including ginsenoside Rb1, Rc, Rb2, Rb3 and notoginsenoside Fa, Fe in P. notoginseng leaves based on a newly established high-performance liquid chromatography method. Transcriptome analysis showed that differentially expressed genes (DEGs) induced by MeJA were mainly enriched in “terpenoid backbone biosynthesis”, “biosynthesis of unsaturated fatty acids”, “sesquiterpenoid and triterpenoid biosynthesis”, “fatty acid metabolism”, and “phenylpropanoid biosynthesis”. Furthermore, the expression profile and quantitative real-time PCR analysis of DEGs showed that MeJA could positively induce the molecular response of endogenous jasmonic acid (JA) signaling pathway, and increased PPD-type saponins mediated by MeJA in P. notoginseng leaves may be related to the high expression of FPS, SS, SE, DS and UGTs, and the low expression of CYP716A53v2 and β-AS. The results provide a molecular understanding for MeJA-elicited biosynthesis of triterpenoid saponins and facilitate the further characterization of the genes responsible for biosynthesis of PPD-type saponins in P. notoginseng leaves.

DFT Studies on Two Novel Explosives Based on the Guanidine-Fused Bicyclic Structure

Jin, Xing-Hui,Hu, Bing-Cheng,Jia, Huan-Qing,Liu, Zu-Liang,Lu, Chun-Xu Korean Chemical Society 2014 Bulletin of the Korean Chemical Society Vol.35 No.4

Density functional theory (DFT) calculations at the B3LYP/6-31G(d,p) theoretical level were performed for two novel explosives (compounds B and C) based on the guanidine-fused bicyclic skeleton $C_4N_6H_8$ (A). The heats of formation (HOFs) were calculated via isodesmic reaction. The detonation properties were evaluated by using the Kamlet-Jacobs equations. The bond dissociation energies (BDEs) for the thermolysis initiation bond were also analyzed to investigate the thermal stability. The results show that the compounds have high positive HOF values (B, 1064.68 $kJ{\cdot}mol^{-1}$; C, 724.02 $kJ{\cdot}mol^{-1}$), high detonation properties (${\rho}$, D and P values of 2.04 $g{\cdot}cm^{-3}$ and 2.21 $g{\cdot}cm^{-3}$, 9.98 $km{\cdot}s^{-1}$ and 10.99 $km{\cdot}s^{-1}$, 46.44 GPa and 59.91 Gpa, respectively) and meet the basic stability requirement. Additionally, feasible synthetic routes of the these high energy density compounds (HEDCs) were also proposed via retrosynthetic analysis.

DFT Studies on Two Novel Explosives Based on the Guanidine-Fused Bicyclic Structure

Xing-Hui Ji,Bing-Cheng Hu,Huan-Qing Jia,Zu Liang Liu,Chun-Xu Lu 대한화학회 2014 Bulletin of the Korean Chemical Society Vol.35 No.4

Density functional theory (DFT) calculations at the B3LYP/6-31G(d,p) theoretical level were performed for two novel explosives (compounds B and C) based on the guanidine-fused bicyclic skeleton C4N6H8 (A). The heats of formation (HOFs) were calculated via isodesmic reaction. The detonation properties were evaluated by using the Kamlet-Jacobs equations. The bond dissociation energies (BDEs) for the thermolysis initiation bond were also analyzed to investigate the thermal stability. The results show that the compounds have high positive HOF values (B, 1064.68 kJ·mol−1; C, 724.02 kJ·mol−1), high detonation properties (ρ, D and P values of 2.04 g·cm−3 and 2.21 g·cm−3, 9.98 km·s−1 and 10.99 km·s−1, 46.44 GPa and 59.91 Gpa, respectively) and meet the basic stability requirement. Additionally, feasible synthetic routes of the these high energy density compounds (HEDCs) were also proposed via retrosynthetic analysis.

Establishing a Nomogram for Stage IA-IIB Cervical Cancer Patients after Complete Resection

Zhou, Hang,Li, Xiong,Zhang, Yuan,Jia, Yao,Hu, Ting,Yang, Ru,Huang, Ke-Cheng,Chen, Zhi-Lan,Wang, Shao-Shuai,Tang, Fang-Xu,Zhou, Jin,Chen, Yi-Le,Wu, Li,Han, Xiao-Bing,Lin, Zhong-Qiu,Lu, Xiao-Mei,Xing, H Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.9

Background: This study aimed to establish a nomogram by combining clinicopathologic factors with overall survival of stage IA-IIB cervical cancer patients after complete resection with pelvic lymphadenectomy. Materials and Methods: This nomogram was based on a retrospective study on 1,563 stage IA-IIB cervical cancer patients who underwent complete resection and lymphadenectomy from 2002 to 2008. The nomogram was constructed based on multivariate analysis using Cox proportional hazard regression. The accuracy and discriminative ability of the nomogram were measured by concordance index (C-index) and calibration curve. Results: Multivariate analysis identified lymph node metastasis (LNM), lymph-vascular space invasion (LVSI), stromal invasion, parametrial invasion, tumor diameter and histology as independent prognostic factors associated with cervical cancer survival. These factors were selected for construction of the nomogram. The C-index of the nomogram was 0.71 (95% CI, 0.65 to 0.77), and calibration of the nomogram showed good agreement between the 5-year predicted survival and the actual observation. Conclusions: We developed a nomogram predicting 5-year overall survival of surgically treated stage IA-IIB cervical cancer patients. More comprehensive information that is provided by this nomogram could provide further insight into personalized therapy selection.

Preoperative Prealbumin Level as an Independent Predictor of Long-Term Prognosis after Curative Liver Resection of Hepatocellular Carcinoma (a Multicenter Study of 1,483 Patients)

( Ju-dong Li ),( Xin-fei Xu ),( Jiong-jie Yu ),( Jia-he Wang ),( Li- Yang Sun ),( Wen-tao Yan ),( Bing Quan ),( Jian-hong Zhong ),( Yi-sheng Huang ),( Ya-hao Zhou ),( Ting-hao Chen ),( Hong Wang ),( W 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Serum prealbumin is more sensitive to profile nutritional status and liver function than albumin, which could hardly be affected by infusion supplement. This study aims: to identify the relationship between preoperative prealbumin level and the long-term prognosis after curative resection of hepatocellular carcinoma (HCC). Methods: Patients undergone HCC curative resection between 2001 and 2014 at six institutions in China were enrolled. By using 170 mg/dl as cut-off value of serum prealbumin level, these patients were divided into the low and normal preoperative prealbumin groups. The overall survival (OS) and recurrence-free survival (RFS) were analyzed and compared. Univariable and multivariable Cox-regression analyses were performed to identify predictive factors of OS and RFS. Results: Among 1,483 patients, 437 (29.5%) had a low prealbumin level within a week before surgery. The 1-, 3-, and 5-year OS and RFS rates of patients in the low prealbumin group were 83.8, 57.0, and 31.1%, and 67.0, 39.8, and19.9%, respectively, which was significantly poorer than those in the normal group (93.0, 75.5, and 42.6%, and 77.0, 56.4, and 28.4%, both P<0.001). Multivariable analyses revealed that preoperative prealbumin level, but not albumin level, was an independent predictor of OS (HR, 1.789; 95% CI: 1.544 -2.072, P<0.001) and RFS (HR, 1.420; 95% CI: 232-1.636, P<0.001). Conclusions: Preoperative prealbumin level is useful for predicting long-term prognosis in patients undergoing liver resection for HCC. Prealbumin may be suitable to displace albumin, yielding to an updated Child-Pugh grade for accessing liver function.

Effect of Hormone Therapy on Long-term Outcomes of Patients with Human Epidermal Growth Factor Receptor 2-and Hormone Receptor-Positive Metastatic Breast Cancer: Real World Experience in China

Du, Feng,Yuan, Peng,Wang, Jia-Yu,Ma, Fei,Fan, Ying,Luo, Yang,Xu, Bing-He Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.3

Background: Among human epidermal growth factor receptor 2 (HER2)-positive breast cancer, more than half are also hormone receptor (HR)-positive. Although HR is a predictive factor for the efficacy of hormone therapy, there are still some uncertainties in regard to the effects on patients with HR-positive and HER2-positive metastatic breast cancers due to the potential resistance to hormone therapy caused by co-expression of HR and HER2. There are no clinical trials directly comparing the efficacy of hormonal therapy with chemotherapy. Materials and Methods: To examine the real-world effect of hormone therapy on patients with HR-positive and HER2-positive metastatic breast cancers, a cross-sectional study of a representative sample of the Chinese population was conducted. The study included 113 patients who received first-line and second-line palliative treatment between 2005 and 2010 in the Cancer Institute and Hospital, Chinese Academy of Medical Science. The effect of hormone therapy on overall survival (OS) was studied. Results: The patients who received hormone therapy (n=51) had better overall survival in contrast to those who received chemotherapy with anti-HER2 therapy (n=62) in first- or second-line treatment. The difference was of borderline statistical significance (51.8m vs 31.9m, p=0.065). In addition, the effect of hormone therapy did not differ significantly with other prognostic factors, including age (${\leq}50$ years or >50 years), disease free survival (${\geq}2$ years or < 2 years) and site of metastasis (visceral or bone/soft tissue). On multivariate analysis, administration of hormone therapy was associated with a trend toward a favorable prognosis (p=0.148, HR=0.693, 95%CI 0.422-1.139). Age more than 50 years was the sole independent harmful prognostic factor (p<0.001, HR=2.797, 95%CI 1.676-4.668). Conclusions: Our data suggest that hormonel therapy may improve outcomes of the patients with ER-positive and HER2-positive metastatic breast cancer.

Apoptosis induction by alantolactone in breast cancer MDA-MB- 231 cells through reactive oxygen species-mediated mitochondrion-dependent pathway

Li Cui,Weiquan Bu,Jie Song,Liang Feng,Tingting Xu,Dan Liu,Wenbo Ding,Jianhua Wang,Changyang Li,Binge Ma,Yi Luo,Ziyu Jiang,Chengcheng Wang,Juan Chen,Jian Hou,Hong-mei Yan,Lei Yang,Xiao-bin Jia 대한약학회 2018 Archives of Pharmacal Research Vol.41 No.3

Alantolactone is a sesquiterpene lactone isolatedfrom Inula helenium L. Although alantolactone possessesanti-inflammation and apoptosis-induction activities, theunderlying mechanism of anti-cancer effect on humanbreast cancer cells remains largely unknown. In this study,we explored the possibility of alantolactone as an apoptosis-inducing cytotoxic agent using MDA-MB-231 cells asin vitro model. Alantolactone significantly induced itsapoptosis, demonstrated by cell cycle analysis, annexinV-APC/7-AAD double staining and dUTP nick end labeling. Additionally, alantolactone triggered the mitochondrial-mediated caspase cascade apoptotic pathway, whichwas confirmed by increased Bax/Bcl-2 ratio, loss of MMP,release of cytc from mitochondria to cytoplasm, activationof caspase 9/3, and subsequent cleavage of PARP. Z-VADFMKpartially prevented apoptosis induced by alantolactone. Alantolactone provoked the production of ROS, whileNAC (a scavenger of ROS) reversed alantolactone-mediateddepolarization of MMP and apoptosis. Alantolactonemodulated the activities of MAPKs. As expected, cotreatmentwith SB203580, SP600125 or U0126 could reducedthe apoptotic rate. Furthermore, alantolactone decreasedthe protein expressions of p-NF-kB p65 and p-STAT3,increased p-c-Jun level in a dose-dependent manner. Thesefindings suggested that alantolactone possessed anticanceractivity via ROS-mediated mitochondrial dysfunctioninvolving MAPK pathway, and had an effect on the transcriptionfactors of NF-kB, AP-1 and STAT3.