BRCA1 Reversion Mutation Confers Resistance to Olaparib and Camrelizumab in a Patient with Breast Cancer Liver Metastasis

Jia-Ni Pan,Lei Lei,Wei-Wu Ye,Xiao-Jia Wang,Wen-Ming Cao 한국유방암학회 2021 Journal of breast cancer Vol.24 No.5

Reversion mutations are associated with clinical resistance to poly(ADP-ribose) polymerase inhibitors (PARPi). Here, we describe the detection of a BRCA1 reversion mutation in a 39-year-old woman with metastatic breast cancer harboring a heterozygous germline BRCA1 exons 7–8 deletion who received PARPi olaparib combined with immune checkpoint inhibitor camrelizumab as third-line therapy. During progression from the olaparib and camrelizumab combination therapy, we identified via genomic sequencing a novel 7-base pair somatic deletion in BRCA1 (c.617_623delACAAATC). Sequence analyses indicated that this mutation realigned the reading frame of BRCA1, which potentially led to the reversal of its normal function and conferred resistance to PARPi.

LncRNA TMPO-AS1 promotes esophageal squamous cell carcinoma progression by forming biomolecular condensates with FUS and p300 to regulate TMPO transcription

Luo Xiao-Jing,He Ming-Ming,Liu Jia,Zheng Jia-Bo,Wu Qi-Nian,Chen Yan-Xing,Meng Qi,Luo Kong-Jia,Chen Dong-Liang,Xu Rui-Hua,Zeng Zhao-Lei,Liu Ze-Xian,Luo Hui-Yan 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Esophageal squamous cell carcinoma (ESCC) is one of the most life- and health-threatening malignant diseases worldwide, especially in China. Long noncoding RNAs (lncRNAs) have emerged as important regulators of tumorigenesis and tumor progression. However, the roles and mechanisms of lncRNAs in ESCC require further exploration. Here, in combination with a small interfering RNA (siRNA) library targeting specific lncRNAs, we performed MTS and Transwell assays to screen functional lncRNAs that were overexpressed in ESCC. TMPO-AS1 expression was significantly upregulated in ESCC tumor samples, with higher TMPOAS1 expression positively correlated with shorter overall survival times. In vitro and in vivo functional experiments revealed that TMPO-AS1 promotes the proliferation and metastasis of ESCC cells. Mechanistically, TMPO-AS1 bound to fused in sarcoma (FUS) and recruited p300 to the TMPO promoter, forming biomolecular condensates in situ to activate TMPO transcription in cis by increasing the acetylation of histone H3 lysine 27 (H3K27ac). Targeting TMPO-AS1 led to impaired ESCC tumor growth in a patient-derived xenograft (PDX) model. We found that TMPO-AS1 is required for cell proliferation and metastasis in ESCC by promoting the expression of TMPO, and both TMPO-AS1 and TMPO might be potential biomarkers and therapeutic targets in ESCC.

Effect of Fluorescence Light on Phenolic Compounds and Antioxidant Activities of Soybeans (Glycine max L. Merrill) during Germination

Ming Yuan,Xuejing Jia,ChunBang Ding,Haiqiong Zeng,Lei Du,Shu Yuan,Zhongwei Zhang,Qi Wu,Chao Hu,Jing Liu 한국식품과학회 2015 Food Science and Biotechnology Vol.24 No.5

Effects of light on phenolic compounds and antioxidant activities during germination of soybean seeds were studied. Soybean seeds were germinated in the presence and absence of light. Chlorophylls and morphological characteristics of sprouts were evaluated daily. Antioxidant activities were determined using 2,2-diphenyl-1-picryl-hydrazyl (DPPH) and ferric reducing activity power methods. Morphological characteristics of light-grown sprouts were superior to dark-grown sprouts and the metabolism of phenolic compounds was regulated by light. Light treatment improved accumulation of phenolic compounds in soybean sprouts and increased antioxidant activities. The optimum harvest time of light-grown sprouts was on the seventh day when sprouts achieved the best nutraceutical value. Green sprouts can serve as a good vegetable source for the human diet.

Associations Between Three Polymorphisms in the Interleukin-4 Receptor Gene and Risk of Cancer: a Meta-analysis

Wang, Jia-Yi,Zhou, Yu-Qiao,Li, Xiao-Xu,Jin, Xin,Wang, Li-Li,Lei, Lei,Zhou, Yu,Lu, Jiang,Zeng, Xin,Dan, Hong-Xia,Liao, Ga,Chen, Qian-Ming Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12

Interleukin-4 receptor (IL-4R) gene single nucleotide polymorphisms (SNPs) are implicated in cancer development. However, results from the published reports have remained inconclusive. The objective of this study was to conduct a meta-analysis investigating the association between polymorphisms in IL-4R gene and cancer risk. Pubmed, EMBASE and China National Knowledge Infrastructure (CNKI) were searched for case-control studies published up to October 30, 2012 that investigated IL-4R polymorphisms and cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of any associations. Three IL-4R polymorphisms (Q576R, rs1801275; I75V, rs1805010; S503P, rs1805015) in 21 case-control studies were analyzed. Our meta-analysis indicated that these three polymorphisms are not associated with cancer risk when all studies were pooled together. In the subgroup analysis by tumor site, the results showed that Q576R G allele carriers were associated with a significantly decreased cervical cancer risk (recessive model: OR = 0.77, 95%CI = 0.60-0.98; homozygote comparison: OR = 0.76, 95%CI = 0.58-0.98). I75V G allele carriers were associated with a decreased risk of renal cancer (dominant model = 0.71, 95%CI = 0.57-0.89, heterozygote comparison: OR = 0.69, 95%CI = 0.55-0.87). When stratified by ethnicity, Q576R G allele carriers were associated with a decreased cancer risk in Caucasians (dominant model: OR = 0.90, 95%CI = 0.83-0.98; heterozygote comparison: OR = 0.89, 95%CI = 0.82-0.98). I75V G allele carriers were associated with a decreased cancer risk in Asians (heterozygote comparison: OR = 0.76, 95%CI = 0.62-0.94). S503P C allele carriers were also associated with a decreased cancer risk in Asians (CC VS TT: OR = 0.29, 95%CI = 0.08-0.99). Our results suggest that Q576R, I75V and S503P may be associated with a decreased cancer risk for certain types of cancers and in some specific ethnic groups. Future case-control studies with large sample size are needed to evaluate these associations in detail.

MiR-221 promotes trastuzumab-resistance and metastasis in HER2-positive breast cancers by targeting PTEN?

( Xing Ming Ye ),( Wen Dong Bai ),( Hua Yu Zhu ),( Xiao Zhang ),( Ying Chen ),( Lei Wang ),( An Gang Yang ),( Jing Zh Ao ),( Lin Tao Jia ) 생화학분자생물학회 2014 BMB Reports Vol.47 No.5

HER2-overexpressing breast cancers are characterized byfrequent distant metastasis and often develop resistance aftershort-term effective treatment with the monoclonal antibodydrug, trastuzumab. Here, we found that the oncogenic miRNA,miR-221, inhibited apoptosis, induced trastuzumab resistanceand promoted metastasis of HER2-positive breast cancers. Thetumor suppressor PTEN was identified as a miR-221 target;overexpression of PTEN abrogated the aforementionedmiR-221-induced malignant phenotypes of the cells. Thesefindings indicate that miR-221 may promote trastuzumabresistance and metastasis of HER2-positive breast cancers bytargeting PTEN, suggesting its role as a potential biomarker forprogression and poor prognosis, and as a novel target fortrastuzumab-combined treatment of breast cancers.[BMB Reports 2014; 47(5): 268-273]

Knockout of the EgriBLOS2 gene results in the transparent integuments of Ectropis grisescens larvae

Li Jia-Li,Zhuang Xiang-Lin,Yuan Ting-Ting,Cai Xiao-Ming,Luo Zong-Xiu,Bian Lei,Chen Zong-Mao,Li Zhao-Qun,Liu Nai-Yong 한국응용곤충학회 2022 Journal of Asia-Pacific Entomology Vol.25 No.1

The body colors of insects have evolved specialized roles in body protection, signaling and physiology. In some case, the larvae can camouflage their body colors to adapt the habitants and protect themselves. However, the genetic and molecular basis on larval body colors of the tea geometrid, Ectropis grisescens, remains poorly known. Here, we reported an effect of the lysosome-related organelles complex-1, subunit 2 (EgriBLOS2) gene knockout on larval integuments of E. grisescens, by using a clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system. Combining transcriptomic data and PCR approaches, we first identified the EgriBLOS2 gene from E. grisescens, which encoded 137 amino acids and comprised 3 introns. In the phylogenetic analysis, EgriBLOS2 clustered in the Lepidoptera clade with high conservation to members in other lepidopteran species. Developmental expression profiles revealed that EgriBLOS2 was constantly tran scribed at each stage, in which its expression was significantly lower in 2nd instar larvae than that of other instars. After injecting EgriBLOS2-specific guide RNA and Cas9 messenger RNA into eggs, 70% of larvae showed the translucent integuments in G0 generation, with an emphasis on black splayed patterns in the 2nd and 8th segments of abdomens. However, some typical characteristics of larvae were not obviously changed in mutant instars, such as ocelli, mouthparts and other appendants. This study has unraveled the roles of EgriBLOS2 in the formation of larval integument colors, and provides an alternative strategy for pest management based on the colors in this species.

Distinctions Between Clinicopathological Factors and Prognosis of Alpha-fetoprotein Negative and Positive Hepatocelluar Carcinoma Patients

Xu, Jia,Liu, Chang,Zhou, Lei,Tian, Feng,Tai, Ming-Hui,Wei, Ji-Chao,Qu, Kai,Meng, Fan-Di,Zhang, Ling-Qiang,Wang, Zhi-Xin,Zhang, Jing-Yao,Chang, Hu-Lin,Liu, Si-Nan,Xu, Xin-Shen,Song, Yan-Zhou,Liu, Jun,Z Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.2

Serum alpha-fetoprotein (AFP) is a significant marker for clinical diagnosis and prognosis evaluation in hepatocellular carcinoma (HCC) patients. However, some proportion of liver cancer patients are AFP-negative (AFP ${\leq}$20ng/ml). In order to study the differences between clinicopathological factors and prognosis of alpha-fetoprotein negative and positive patients, a total of 114 cases (41 AFP-negative and 73 AFP-positive) were selected for our research. By systematically statistical analysis, the results demonstrated that compared with AFP-negative patients, AFP-positive examples were more likely to feature cirrhosis nodules, non-complete neoplasm capsules, and a poor Edmondson-steiner grade. Furthermore, AFP-negative patients demonstrated a favorable long-term prognosis. By univariate analysis and multivariate analysis with Cox's proportional hazards model, multiple tumors were found to be independent risk factors for worse survival of AFP negative patients; however, less tumor-free margins, multiple tumors and Edmondson-steiner grades III/IV, proved to be independent risk factors leading to a poor prognosis of AFP positive cases. Finally, we can infer that high levels of AFP signify a highly malignant tumor and unfavorable prognosis.

Vitamin D3 and Beta-carotene Deficiency is Associated with Risk of Esophageal Squamous Cell Carcinoma - Results of a Case-control Study in China

Huang, Gui-Ling,Yang, Lei,Su, Ming,Wang, Shao-Kang,Yin, Hong,Wang, Jia-Sheng,Sun, Gui-Ju Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.2

Objective: The aim was to evaluate roles of vitamin D3 (VD3) and beta-carotene (BC) in the development of esophageal squamous cell carcinoma (ESCC) in a high-risk area, Huai'an District, Huai'an City, China. Methods: 100 new ESCC diagnosed cases from 2007 to 2008 and 200 residency- age-, and sex-matched healthy controls were recruited. Data were collected from questionnaires, including a food frequency questionnaire (FFQ) to calculate the BC intake, and reversed phase high-performance liquid chromatography (RP-HPLC) was used to measure the serum concentrations of BC and VD3. Odds ratios (OR) and 95% confidence intervals (CI) were calculated in conditional logistic regression models. Results: The average dietary intake of BC was $3322.9{\mu}g$ (2032.4-5734.3) in the case group and $3626.8{\mu}g$ (1961.9-5827.9) in control group per capita per day with no significant difference by Wilcoxon test (p>0.05). However, the levels of VD3 and BC in the case group were significantly lower than in the control group (p<0.05). The OR values of the highest quartile and the lowest quartile of VD3 and BC in serum samples were both 0.13. Conclusion: Our results add to the evidence that high circulating levels of VD3 and BC are associated with a reduced risk of ESCC in this Chinese population.

Numerical Study on the Damage Characteristics of Layered Shale Using 3D DEM

Juan Huang,Yintao Song,Ming-feng Lei,Cheng-hua Shi,Chaojun Jia,Jian Zhang 대한토목학회 2023 KSCE Journal of Civil Engineering Vol.27 No.12

Layered shale is a kind of rock with obvious anisotropy, which is significantly influenced by the inclination angle of the rock. In this study, the influence of bedding dip on the strength characteristics, failure mode, and internal fracture evolution of layered shale was investigated through laboratory triaxial compression tests and three-dimensional discrete element numerical simulations. Results show that the numerical model of layered shale constructed using the bonded block model can simulate the layered shale in terms of U-shaped strength variation and failure modes very well. Based on the distribution of cracks and failure characteristics of layered rocks, the failure modes of layered rocks are classified as follows: Shear failure across the bedding plane, slip failure along bedding planes, combined tensile splitting and shear failure. The development of microcracks damage in the slip failure model is controlled by interlayer joints, while in other failure modes, it is jointly controlled by the rock matrix and interlayer joints. The relationship between microscopic joint parameters and the variations of Young's modulus and peak strength has been proposed.

Large Eddy Simulation of Fuel Sprays in Diesel Engines

( Mao Zhao Xie ),( Ming Jia ),( Lei Zhou ) 한국액체미립화학회 2010 한국액체미립화학회 학술강연회 논문집 Vol.2010 No.-

A brief introduction of the recent research at Dalian University of Technology (DUT) on the applications of the large eddy simulation (LES) approach to fuel sprays in a constant volume vessel and in a real engine configuration is presented. Firstly the fundamental of the LES approach and related mathematical models are briefly described. Then, some aspects concerning applications of LES to the fuel spray in the engine environment are discussed, including comparisons between RANS (Reynolds Averaged Navier-Stokes equations) and LES models; an examination of the influence of different subgrid scale (SGS) models on fuel sprays and their applicability to IC engines; a performance assessment of four breakup models in connection with the LES simulations; as well as an example of the LES application to a Ford 2.0 liter high-speed direct-injection (HSDI) diesel engine. Finally, suggestions to the further LES study in the engine area are proposed.