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Circulating tumor DNA genomic profiling reveals the complicated olaparib-resistance mechanism in prostate cancer salvage therapy: A case report

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World Journal of Clinical Cases 2022年第11期10卷 3461-3471页

作者： Fang Yuan Nan Liu Ming-Zhen Yang Xiao-Tian Zhang Hong Luo Hong Zhou Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment Chongqing University Cancer HospitalChongqing 400044China Department of Clinical Biochemistry College of Medical LaboratoryArmy Military Medical UniversityChongqing 400038China Department of Medicine BGI GenomicsShenzhen 518083Guangdong ProvinceChina

BACKGROUND The poly(ADP-ribose)polymerase(PARP)inhibitor olaparib has displayed superior clinical effect in metastatic castration-resistant prostate cancer(mCRPC)patients with the homologous recombination repair(HRR)genes ***,when a patient’s tumor tissue volume is insufficient for genomic profiling of HRR gene mutations,circulating tumor DNA(ctDNA)may be useful in helping to determine and monitor the efficacy of olaparib,as well as in abiraterone-combination treatment,and for understanding any resistance mechanism related to such *** SUMMARY A 61-year-old man who was diagnosed with metastatic prostate adenocarcinoma was initially hormone sensitivity,showing high Gleason score(5+5=10)and absolute positive rate(14/14 biopsied specimens).Following failure of several standard therapies,the patient progressed to ***,the patient showed good response to olaparib-abiraterone-prednisone combination treatment(an androgen-deprivation therapy,provided as the‘final choice’in China).Serum total prostate-specific antigen(TPSA)level reduced and symptoms remitted for 4 ***,thereafter,serum TPSA levels began slowly increasing,indicating development of olaparib *** comprehensive genomic profiling of ctDNA, screening 508 cancer-related genes by next-generation sequencing,identified 10 somatic variants as well as 3 copy number alterations. Two identified reversemissense mutations in partner and localizer of BRCA2 (PALB2) may have recovered the readingframe, restoring function of the primary germline PALB2 mutation and causing resistance to thePARP inhibitor *** mutations in PALB2, discovered via genomic profiling of ctDNA, may represent apotential resistance mechanism against olaparib in mCRPC.

关键词： mCRPC Olaparib Circulating tumor DNA Partner and localizer of BRCA2 resistance mechanism Reverse missense mutations

Evaluation of Rice Germplasm for resistance to the Small Brown Planthopper (Laodelphax striatellus) and Analysis of resistance mechanism

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Rice science 2008年第1期15卷 36-42页

作者： DUAN Can-xing ZHANG Shi-xian LEI Cai-lin CHENG Zhi-jun CHEN Qing ZHAI Hu-qu WAN Jian-min Institute of Crop Sciences Chinese Academy of Agricultural Sciences / The National Key Facility for Crop Gene Resources and Genetic Improvement Beijing 100081 China Institute of Plant Protection Chinese Academy of Agricultural Sciences Beijing100094 China Chinese Academy of Agricultural Sciences Beijing 100081 China）

One hundred and thirty-eight rice accessions were screened for resistance to the small brown planthopper （SBPH）（Laodelphax striatellus Fallen） by the modified seedbox screening test. Twenty-five rice accessions with different levels of resistance to SBPH were detected, accounting for 18.1% of the total accessions, which included 2 highly resistant, 9 resistant and 14 moderately resistant varieties. Compared with indica rice, japonica rice was more susceptible to SBPH. Antixenosis test, antibiosis test and correlation analysis were performed to elucidate the resistance mechanism. The resistant check Rathu Heenati （RHT）, highly resistant varieties Mudgo and Kasalath, and resistant variety IR36 expressed strong antixenosis and antibiosis against SBPH, indicating the close relationship between resistance level and these two resistance mechanisms in the four rice varieties. Antibiosis was the dominant resistance pattern in the resistant varieties Daorenqiao and Yangmaogu due to their high antibiosis but low antixenosis. Dular, ASD7 and Milyang 23 had relatively strong antixenosis and antibiosis, indicating the two resistance mechanisms were significant in these three varieties. The resistant DV85 expressed relatively high level of antixenosis but low antibiosis, whereas Zhaiyeqing 8 and Guiyigu conferred only moderate antibiosis and antixenosis to SBPH, suggesting tolerance in these three varieties. Antibiosis and antixenosis governed the resistance to SBPH in the moderately resistant accession 9311. Antixenosis was the main resistance type in V20A. Tolerance was considered to be an important resistance mechanism in Minghui 63 and Yangjing 9538 due to their poor antibiosis and antixenosis resistance. The above accessions with strong antibiosis or antixenosis were the ideal materials for the resistance breeding.

关键词： rice germplasm the small brown planthopper evaluation for resistance resistance mechanism antixenosis antibiosis

Understanding the resistance mechanism in Brassica napus to early infection by Plasmodiophora brassicae

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Understanding the resistance mechanism in Brassica napus to ...

Functional assessment of cadherin as a shared mechanism for cross/dual resistance to Cry1Ac and Cry2Ab in Helicoverpa zea

中国作物学会油料作物专业委员会第八次会员代表大会暨学术年会

作者： MEI Jia-qin GUO Zhen WANG Jin-hua FENG Yu-xia ZHANG Chun-yu SI Jun QIAN Wei CHEN Guo-kang College of Agronomy and Biotechnology Southwest University Academy of Agricultural Sciences Southwest University College of Plant Protection Southwest University College of Plant Science & Technology Huazhong Agricultural University College of Horticulture and Landscape Architecture Southwest University

Clubroot,caused by Plasmodiophora brassicae,is one of the most important diseases of Brassicas *** the mechanism of plant resistance has become the basis for resistance varieties *** this study,transcriptome analysis was conducted in a clubroot resistant *** breeding line ’ ZHE-226’ and a susceptible rapeseed variety ’ Zhongshuang 11’ at 0,3,6,9 and 12 days after inoculation(dai) to study their different defense response induced by *** alteration was detected specifically in ZHE-226 as soon as the root hair infection happened,with significant promotion on many processes in particular cell division/cell cycle,DNA repair and synthesis,protein synthesis,signaling,antioxidation and secondary ***,biochemical and histochemical assays were carried out between two genotypes at each time point,implying an effective signaling in ZHE-226 in resistance to ***,*** fast initiation of receptor kinases by unknown effectors of *** may activate intercellular G proteins which may,together with the enhanced Ca signalling,promote ROS,PCD and HR,and affect hormone mediated signal ***,the resistant rapeseed possibly possesses high ability on maintaining homeostasis of auxin and cytokinin thus may repress the development of clubs and galls on root and contribute to maintain root *** study is of great significance in understanding resistant mechanism of *** against ***.

关键词： Brassica napus Plasmodiophora brassicae resistance mechanism

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Journal of Integrative Agriculture 2024年第5期23卷 1604-1617页

作者： Jizhen Wei Min Zhang Pin Li Zhongyuan Deng Xinming Yin Shiheng An Xianchun Li State Key Laboratory of Wheat and Maize Crop Science/College of Plant Protection Henan Agricultural UniversityZhengzhou 450046China Department of Entomology and BIO5 Institute University of ArizonaTucsonAZ 85721USA School of Agricultural Sciences Zhengzhou UniversityZhengzhou 450001China

Helicoverpa zea is a major target pest of pyramided transgenic crops expressing Cry1,Cry2 and/or Vip3Aa proteins from Bacillus thuringiensis(Bt)in the United ***-selected Cry1Ac/Cry2Ab cross resistance and fieldevolved practical dual resistance of *** to these two toxins have been widely *** the widespread Cry1Ac/Cy2Ab dual resistance of *** has resulted from the selection of one shared or two independent resistance mechanisms by pyramided Bt crops remains *** is a well-confirmed receptor of Cry1Ac and a suggested receptor of Cry2Ab in at least three Lepidopteran *** test whether cadherin may serve as one shared mechanism for the cross and dual resistance of *** to Cry1Ac and Cry2Ab,we cloned *** cadherin(HzCadherin)cDNA and studied its functional roles in the mode of action of Cry1Ac and Cry2Ab by gain-and lossof-function *** expression of HzCadherin in *** midgut,*** fat body and Sf9 cells made all three of these cell lines more susceptible to activated Cry1Ac but not activated Cry2Ab,whereas silencing HzCadherin of *** midgut and fat body cells significantly reduced the susceptibility to Cry1Ac but not ***,suppressing HzCadherin with siRNA made *** larvae resistant to *** results clearly demonstrate that HzCadherin is not a receptor for Cry2Ab,and thus it is unlikely to serve as one shared mechanism for the cross and dual resistance of *** to Cry1Ac and Cry2Ab.

关键词： Bt crops cadherin Cry toxin receptor resistance mechanism

Identification of a novel planthopper resistance gene from wild rice(Oryza rufipogon Griff.)

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The Crop Journal 2020年第6期8卷 1057-1070页

作者： Meng Yang Jiebin Lin Ling Cheng Hailian Zhou Shu Chen Fang Liu Rongbai Li Yongfu Qiu State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources Agricultural CollegeGuangxi UniversityNanning 530005GuangxiChina College of Agriculture Yangtze UniversityJingzhou 434025HubeiChina

Rice planthoppers,including brown planthopper(BPH)and white-backed planthopper(WBPH),are the most destructive pests in Asian rice cultivation *** resistance genes that have been mapped and characterized advance our understanding of underlying resistance mechanisms and facilitate the breeding of resistant varieties,thereby contributing to an efficient pest management *** this study,a novel resistance gene Bph38 derived from the wild rice species Oryza rufipogon *** found to confer high resistance to BPH and *** mapping was performed to identify regions associated with BPH and WBPH resistance,and two mapping efforts led to the same region on chromosome 4 flanked by markers RM16563 and ***-segregant analysis and next-generation sequencing were performed using the same population to detect the resistance *** mapping narrowed the region to a 12.3-Mb segment,and fine mapping using BC1 F2 recombinants identified a 79-kb segment flanked by markers YM112 and ***-isogenic lines(NILs)carrying Bph38 in the 9311(indica)and BR54(japonica)genetic backgrounds were developed by crossing and backcrossing with marker-assisted *** agronomic traits and BPH and WBPH resistance of the NILs were similar to those of the recurrent *** feeding and host-choice tests revealed that Bph38 showed both antibiotic and antixenotic effects in both insects,with stronger effects in indica-background *** fine mapping and characterization of the major gene may result in map-based cloning of the gene and allow its application in breeding insectresistant rice varieties.

关键词： Oryza rufipogon Griff. Planthopper resistance Next-generation sequencing-based bulked-segregant analysis Gene mapping resistance mechanism

High basal defense gene expression determines sorghum resistance to the whorl-feeding insect southwestern corn borer

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Insect Science 2013年第3期20卷 307-317页

作者： Wei-Ning Cheng Jia-Xin Lei William L. Rooney Tong-Xian Liu Keyan Zhu-Salzman Key Laboratory of Integrated Pest Management on Crops in Northwestern Loess Plateau Ministry of Agriculture Northwest A&F Uni- versity Yangling Shaanxi China Department of Entomology Department of Soil and Crop Sciences Vegetable & Fruit Improvement Center Texas A&M University College Station Texas United States

Southwestern corn borer （SWCB, Diatraea grandiosella） and fall armyworm （FAW, Spodopterafrugiperda） are major pests of sorghum in the southern United States. Host plant resistance is a desirable means for reducing plant damage and yield losses from both insects. In this study, we evaluated 12 sorghum lines for whorl-stage resistance to leaf-feeding SWCB and FAW in greenhouse and laboratory bioassays. Differential plant responses were detected against the two insects. Among 12 lines tested, CM1821, Della and PI196583 were resistant to both insects, while BTx2752 was largely susceptible. Line R.09110 was resistant to SWCB, but susceptible to FAW, whereas Redbine-60 was suscep- tible to SWCB, but not to FAW. In addition, we quantified various chemical components in the plants and determined their association with insect resistance. Tannin and chloro- phyll in leaves did not show any significant correlation with resistance to either insects, but contents of soluble protein in general were negatively correlated with resistance to both insects. Endogenous soluble sugar and dhurrin were only positively correlated with resistance to SWCB, but not with FAW resistance. To gain some molecular insight into resistance mechanism of sorghum to SWCB, we performed qPCR reactions for key genes encoding enzymes involved in dhurrin and jasmonic acid （JA） biosynthesis on selected resistant or susceptible lines. Although these genes were rapidly and strongly induced by insect feeding in all lines, the observed resistance is likely explained by higher constitutive dhurrin contents in some resistant lines and higher basal JA biosynthesis in others. Our results suggest that sorghum utilizes multiple strategies to defend itself against SWCB.

关键词： Diatraea grandiosella host plant resistance resistance mechanism sorghum,Spodoptera frugiperda

Epidemiology and mechanisms of Ceftazidime-Avibactam resistance in Gram-Negative Bacteria

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Engineering 2022年第4期8卷 138-145页

作者： Tingting Xu Yuqi Guo Yang Ji Baohong Wang Kai Zhou Shenzhen Institute of Respiratory Diseases Shenzhen People’s Hospital&2nd Clinical Medical College of Jinan University&1st Affiliated Hospital of Southern University of Science and TechnologyShenzhen 518020China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310003China

Carbapenem resistance presents a major challenge for the global public health network, as clinical infections caused by carbapenem-resistant organisms(CRO) are frequently associated with significant morbidity and mortality. Ceftazidime–avibactam(CAZ–AVI) is a novel cephalosporin/β-lactamase inhibitor combination offering an important advance in the treatment of CRO infections. CAZ–AVI has been reported to inhibit the activities of Ambler classes A, C, and some class D enzymes. However, bacterial resistance has been emerging shortly after the introduction of this combination in clinical use, with an increasing trend. Understanding these resistance mechanisms is crucial for guiding the development of novel treatments and aiding in the prediction of underlying resistance mechanisms. This review aims to systematically summarize the epidemiology of CAZ–AVI-resistant strains and recently identified resistance mechanisms of CAZ–AVI, with a focus on the production of β-lactamase variants, the hyperexpression of β-lactamases, reduced permeability, and overexpressed efflux pumps. The various mechanisms of CAZ–AVI resistance that have emerged within a short timescale emphasize the need to optimize the use of current agents, as well as the necessity for the surveillance of CAZ–AVI-resistant pathogens.

关键词： Ceftazidime-avibactam resistance mechanism Carbapenem-resistant b-lactam/b-lactamase inhibitor

mechanisms of inducible resistance against Bacillus thuringiensis endotoxins in invertebrates

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Insect Science 2005年第5期12卷 319-330页

作者： GANG MA MUHAMMAD SARJAN CHRISTOPHER PRESTON SASSAN ASGARI OTTO SCHMIDT Plant and Pest Science Faculty of Sciences the University of Adelaide Glen Osmond South Australia Australia Faculty of Agriculture University of Mataram Lombok Indonesia School of Integrative Biology University of Queensland St Lucia Queensland Australia

resistance in insect pests against the endotoxin of Bacillus thuringiensis （Berliner）（Bt） is a major threat to the usefulness of this biopesticide, both used as traditional formulations and in transgenic crops. A crucial requirement for the development of successful resistance management strategies is a molecular understanding of the nature and inheritance of resistance mechanisms. This information can be used to design management strategies that will delay or counteract Bt resistance. The best known Bt resistance mechanism is inactivation of brush border membrane receptors. This type of resistance has a largely recessive mode of inheritance, which has enabled the design of resistance management approaches involving high dose and refuge strategies. Recent observations suggest that other resistance mechanisms are possible, including a mechanism that sequesters the toxin in the gut lumen through inducible immune reactions. The elevated immune status associated with tolerance to the toxin can be transmitted to subsequent generations by a maternal effect, which has implications for resistance management in the field. The high dose/refuge strategy may not be appropriate for the management of these alternative resistance mechanisms and other strategies have to be developed if inducible dominant resistance or tolerance mechanisms occur frequently in the field.

关键词： Bacillus thuringiensis crystal toxin innate immunity melanization resistance mechanism

Relationship Between Several Biochemical Indexes and resistance of Aegilops Species to Oat-Bird Cherry Aphids(Homoptera:Aphididae)

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Agricultural Sciences in China 2003年第9期2卷 994-999页

作者： LI Qing, YE Hua zhi, YANG Qun fang and JIANG Su rong (College of Agronomy, Sichuan Agricultural University, Yaan 625014, P.R.China) College of Agronomy Sichuan Agricultural University Yaan 625014 P.R.China

The biochemical mechanism of resistance of 9 Aegilops species including ***,***, ***, *** var. varianilis, ***, ***, ***, *** and *** in Triticeae to oat bird cherry aphid ( Rhopalosiphum padi ) were reported for the first time. The results showed that the content of total phenols in seedling was not associated with resistance to this aphid. The level of DIMBOA was negatively related to intrinsic innate rate of increase ( r m ) of R. padi. Neither of soluable sugar nor total phenols in adult stage was associated with resistance level. However, concentrations of free proline and serine in leaf were positively related to r m of R. padi ( r m =0.0636+0.23x pro ** +1.982x ser *). The content of DIMBOA was high negatively related to r m of R. padi ( r =0.819 ** ). The low level of free proline and serine and high concentration of DIMBOA could be regarded as important elements for resistance of Aegilops species to R. padi.

关键词： Aegilops resistance mechanism Rhopalosiphum padi