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  • 1
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    Online Resource
    Clinical definition of secondary resistance to immunotherapy in non‐small cell lung cancer
    Wiley ; 2023
    In:  Thoracic Cancer Vol. 14, No. 34 ( 2023-12), p. 3421-3429
    Details
    In: Thoracic Cancer, Wiley, Vol. 14, No. 34 ( 2023-12), p. 3421-3429
    Abstract: Immune checkpoint inhibitors (PD‐1/PD‐L1 and CTLA‐4 blockade) have revolutionized the treatment landscape in non‐small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO‐IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    URL: Article
    DOI: 10.1111/tca.v14.34
    DOI: 10.1111/1759-7714.15157
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2559245-2
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  • 2
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    The G143A /S substitution of mitochondrially encoded cytochrome b (Cytb) in Magnaporthe oryzae confers resistance to quinone outside inhibitors
    Wiley ; 2022
    In:  Pest Management Science Vol. 78, No. 11 ( 2022-11), p. 4850-4858
    Details
    In: Pest Management Science, Wiley, Vol. 78, No. 11 ( 2022-11), p. 4850-4858
    Abstract: Rice blast, caused by Magnaporthe oryzae , is a destructive disease threatening the production of staple foods worldwide. Quinone outside inhibitors (QoIs) are a group of chemicals exhibiting excellent activity against a majority of plant pathogens, with the disadvantage that pathogens can easily develop resistance to QoIs. RESULTS Here, we investigated the activity of picoxystrobin against M. oryzae , which showed a great inhibitory effect on 100 strains of M. oryzae with half‐maximal effective concentrations (EC 50 ) ranging from 0.0251 to 0.1337 μg ml −1 . The EC 50 values showed a continuous unimodal distribution that was identical to the normal distribution, suggesting the potency of our study to represent baseline sensitivity. In addition, nine resistant mutants were obtained by exposing M. oryzae to a high dosage of picoxystrobin in the laboratory; all of them showed cross‐resistance to the other five QoI fungicides. Although some mutants showed a decreased resistance factor after ten successive cultures on fungicide‐free medium, the resistance to picoxystrobin was still inheritable. Amino acid substitution of G143S was detected in eight of nine picoxystrobin‐resistant mutants, and G143A was detected in only one of nine mutants. A fitness penalty was found in the mutants carrying G143S rather than G143A. CONCLUSION Our findings suggested that M. oryzae had a mid to high risk of resistance to picoxystrobin. Considering this, we should be vigilant to the resistance risk and apply picoxystrobin sensibly in the field. © 2022 Society of Chemical Industry.
    Type of Medium: Online Resource
    ISSN: 1526-498X , 1526-4998
    URL: Issue
    URL: Article
    DOI: 10.1002/ps.v78.11
    DOI: 10.1002/ps.7106
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2003455-6
    SSG: 12
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  • 3
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    Risk assessment and molecular mechanism of Fusarium incarnatum resistance to phenamacril
    Wiley ; 2022
    In:  Pest Management Science Vol. 78, No. 8 ( 2022-08), p. 3394-3403
    Details
    In: Pest Management Science, Wiley, Vol. 78, No. 8 ( 2022-08), p. 3394-3403
    Abstract: Cucumber fruit rot (CFR) caused by Fusarium incarnatum is a devastating fungal disease in cucumber. In recent years, CFR has occurred frequently, resulting in serious yield and quality losses in China. Phenamacril exhibits a specific antifungal activity against Fusarium species. However, no data for phenamacril against F. incarnatum is available. RESULTS The sensitivity of 80  F. incarnatum strains to phenamacril was determined. The half maximal effective concentration (EC 50 ) values ranged from 0.1134 to 0.3261 μg mL −1 with a mean EC 50 value of 0.2170 ± 0.0496 μg mL −1 . A total of seven resistant mutants were obtained from 450 mycelial plugs by phenamacril‐taming on potato dextrose agar (PDA) plates with 10 μg mL −1 of phenamacril, and the resistant frequency was 1.56%. Phenamacril‐resistant mutants showed decreased mycelial growth, conidiation and virulence as compared with the corresponding wild‐type strains, indicating that phenamacril resistance suffered a fitness penalty in F. incarnatum . In addition, using sequence analysis, the point mutations of S217P or I424S were discovered in Fimyosin‐5 (the target of phenamacril). The site‐directed mutagenesis of the S217P, P217S, I424S and S424I substitutions were constructed to reveal the relationship between the point mutations and phenamacril resistance. The results strongly demonstrated that the mutations of S217P and I424S in Fimyosin‐5 conferred phenamacril‐resistance in F. incarnatum . CONCLUSION Phenamacril‐resistant mutants were easily induced and their resistance level was high. The S217P or I424S substitutions in Fimyosin‐5 conferring phenamacril resistance were detected and futherly verified by transformation assay with site‐directed mutagenesis. Thus, we proposed that the resistance development of F. incarnatum to phenamacril is high risk. © 2022 Society of Chemical Industry.
    Type of Medium: Online Resource
    ISSN: 1526-498X , 1526-4998
    URL: Issue
    URL: Article
    DOI: 10.1002/ps.v78.8
    DOI: 10.1002/ps.6967
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2003455-6
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  • 4
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    TNF‐α‐induced NF‐κB activation promotes myofibroblast differentiation of LR‐MSCs and exacerbates bleomycin‐induced pulmonary fibrosis
    Wiley ; 2018
    In:  Journal of Cellular Physiology Vol. 233, No. 3 ( 2018-03), p. 2409-2419
    Details
    In: Journal of Cellular Physiology, Wiley, Vol. 233, No. 3 ( 2018-03), p. 2409-2419
    Abstract: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible lung disease of unknown cause. It has been reported that both lung resident mesenchymal stem cells (LR‐MSCs) and tumor necrosis factor‐α (TNF‐α) play important roles in the development of pulmonary fibrosis. However, the underlying connections between LR‐MSCs and TNF‐α in the pathogenesis of pulmonary fibrosis are still elusive. In this study, we found that the pro‐inflammatory cytokine TNF‐α and the transcription factor nuclear factor kappa B (NF‐κB) p65 subunit were both upregulated in bleomycin‐induced fibrotic lung tissue. In addition, we discovered that TNF‐α promotes myofibroblast differentiation of LR‐MSCs through activating NF‐κB signaling. Interestingly, we also found that TNF‐α promotes the expression of β‐catenin. Moreover, we demonstrated that suppression of the NF‐κB signaling could attenuate myofibroblast differentiation of LR‐MSCs and bleomycin‐induced pulmonary fibrosis which were accompanied with decreased expression of β‐catenin. Our data implicates that inhibition of the NF‐κB signaling pathway may provide a therapeutic strategy for pulmonary fibrosis, a disease that warrants more effective treatment approaches.
    Type of Medium: Online Resource
    ISSN: 0021-9541 , 1097-4652
    URL: Issue
    URL: Article
    DOI: 10.1002/jcp.v233.3
    DOI: 10.1002/jcp.26112
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 1478143-8
    SSG: 12
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  • 5
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    A prognostic index for nasal‐type early‐stage extranodal natural killer/T‐cell lymphoma: A multicenter study
    Wiley ; 2019
    In:  American Journal of Hematology Vol. 94, No. 5 ( 2019-05)
    Details
    In: American Journal of Hematology, Wiley, Vol. 94, No. 5 ( 2019-05)
    Type of Medium: Online Resource
    ISSN: 0361-8609 , 1096-8652
    URL: Issue
    URL: Article
    DOI: 10.1002/ajh.v94.5
    DOI: 10.1002/ajh.25426
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 1492749-4
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  • 6
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    Monitoring treatment efficacy and resistance in breast cancer patients via circulating tumor DNA genomic profiling
    Wiley ; 2020
    In:  Molecular Genetics & Genomic Medicine Vol. 8, No. 2 ( 2020-02)
    Details
    In: Molecular Genetics & Genomic Medicine, Wiley, Vol. 8, No. 2 ( 2020-02)
    Abstract: One of the major challenges in managing invasive breast cancer (BC) is the lack of reliable biomarkers to track response. Circulating tumor DNA (ctDNA) from liquid biopsy, as a candidate biomarker, provides a valuable assessment of BC patients. In this retrospective study, we evaluated the utility of ctDNA to reflect the efficacy of treatment and to monitor resistance mechanisms. Methods Targeted next‐generation sequencing (NGS) of 416 cancer‐relevant genes was performed on 41 plasma biopsy samples of 19 HER2+ and 12 HER2‐ BC patients. Longitudinal ctDNA samples were analyzed in three BC patients over the treatment course for detecting acquired mutations. Results In HER2+ BC patients, ERBB2 somatic copy numbers in ctDNA samples were significantly higher in patients progressed on HER2‐targeted therapy than those who were still responding to the treatment. Recurrent acquired mutations were detected in genes including ERBB2, TP53, EGFR, NF1 , and SETD2 , which may contribute to trastuzumab resistance. In longitudinal analyses, the observed mutation allele frequencies were tracked closely in concordance with treatment responses. A novel ERBB2 p.(Leu869Arg) mutation was acquired in one patient upon resistant to trastuzumab therapy, which was further validated as an oncogenic mutation in vitro and contributed to resistance. In HER2‐ BC patients with chemotherapy resistance, genetic alterations on TP53, PIK3CA, and DNA damage repair genes were frequently observed. Conclusions In summary, ctDNA monitoring, particularly longitudinal analyses, provides valuable insights into the assessment of targeted therapy efficacy and gene alterations underlying trastuzumab resistance and chemotherapy resistance in HER2+ and HER2‐ BC patients, respectively.
    Type of Medium: Online Resource
    ISSN: 2324-9269 , 2324-9269
    URL: Issue
    URL: Article
    DOI: 10.1002/mgg3.v8.2
    DOI: 10.1002/mgg3.1079
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2734884-2
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  • 7
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    N 6 ‐methyladenosine modification changes during the recovery processes for Paulownia witches' broom disease under the methyl methanesulfonate treatment
    Wiley ; 2023
    In:  Plant Direct Vol. 7, No. 7 ( 2023-07)
    Details
    In: Plant Direct, Wiley, Vol. 7, No. 7 ( 2023-07)
    Abstract: Phytoplasmas induce diseases in more than 1000 plant species and cause substantial ecological damage and economic losses, but the specific pathogenesis of phytoplasma has not yet been clarified. N 6 ‐methyladenosine (m 6 A) is the most common internal modification of the eukaryotic Messenger RNA (mRNA). As one of the species susceptible to phytoplasma infection, the pathogenesis and mechanism of Paulownia has been extensively studied by scholars, but the m 6 A transcriptome map of Paulownia fortunei ( P. fortunei ) has not been reported. Therefore, this study aimed to explore the effect of phytoplasma infection on m 6 A modification of P. fortunei and obtained the whole transcriptome m 6 A map in P. fortunei by m 6 A‐seq. The m 6 A‐seq results of Paulownia witches' broom (PaWB) disease and healthy samples indicate that PaWB infection increased the degree of m 6 A modification of P. fortunei . The correlation analysis between the RNA‐seq and m 6 A‐seq data detected that a total of 315 differentially methylated genes were predicted to be significantly differentially expressed at the transcriptome level. Moreover, the functions of PaWB‐related genes were predicted by functional enrichment analysis, and two genes related to maintenance of the basic mechanism of stem cells in shoot apical meristem were discovered. One of the genes encodes the receptor protein kinase CLV2 (Paulownia_LG2G000076), and the other gene encodes the homeobox transcription factor STM (Paulownia_LG15G000976). In addition, genes F‐box (Paulownia_LG17G000760) and MSH5 (Paulownia_LG8G001160) had exon skipping and mutually exclusive exon types of alternative splicing in PaWB‐infected seedling treated with methyl methanesulfonate, and m 6 A modification was found in m 6 A‐seq results. Moreover, Reverse Transcription–Polymerase Chain Reaction (RT‐PCR) verified that the alternative splicing of these two genes was associated with m 6 A modification. This comprehensive map provides a solid foundation for revealing the potential function of the mRNA m 6 A modification in the process of PaWB. In future studies, we plan to verify genes directly related to PaWB and methylation‐related enzymes in Paulownia to elucidate the pathogenic mechanism of PaWB caused by phytoplasma invasion.
    Type of Medium: Online Resource
    ISSN: 2475-4455 , 2475-4455
    URL: Issue
    URL: Article
    DOI: 10.1002/pld3.v7.7
    DOI: 10.1002/pld3.508
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2912669-1
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  • 8
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    Real‐world clinical outcomes of olaparib therapy in Chinese patients with advanced serous ovarian cancer treated in Macau
    Wiley ; 2019
    In:  Cancer Reports Vol. 2, No. 5 ( 2019-10)
    Details
    In: Cancer Reports, Wiley, Vol. 2, No. 5 ( 2019-10)
    Abstract: Olaparib has been approved as an active and maintenance therapy for patients with platinum‐sensitive, BRCA‐mutated high‐grade serous ovarian cancer (SOC). However, the efficacy and safety data is lack among Chinese ovarian cancer patients. Aim This real‐world study aimed to evaluate the effectiveness and safety profile of olaparib in patients from mainland China, where olaparib is currently unavailable. Methods and results This single‐center, observational study included 65 patients with pathologically confirmed advanced serous ovarian cancer from Kiang Wu Hospital in Macau between December 2015 and September 2017. Progression‐free survival (PFS) and other endpoints (treatment response, disease progression, and adverse events) were evaluated. PFS was estimated using the Kaplan‐Meier method. The median treatment duration was 4 months (range, 1‐15). The median PFS for the overall population was 4.2 months (95% CI 2.7‐5.2), while those for patients with wild‐type BRCA1/2 and BRCA1/2 mutations were 3.1 months (95% CI 1.3‐4.6) and 5.3 months (95% CI 2.8‐7.1), respectively. The median PFS tended to be longer for patients on maintenance therapy (between 9.0 months [95% CI 1.4‐17.5] and 10.0 months [95% CI 2.5‐18.1] ) than for those on active therapy (between 3.1 months [95% CI 2.1‐3.8] and 3.0 months [95% CI 1.4‐4.5] ). Most patients (87.0%) experienced low‐grade adverse events; the most common of which were fatigue (49.0%) and nausea (35.0%). Conclusion Our findings demonstrate clinical benefit of olaparib to mainland Chinese patients with high‐grade SOC, particularly for patients with BRCA mutations and who require maintenance therapy.
    Type of Medium: Online Resource
    ISSN: 2573-8348 , 2573-8348
    URL: Issue
    URL: Article
    DOI: 10.1002/cnr2.v2.5
    DOI: 10.1002/cnr2.1180
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2920367-3
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  • 9
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    Obstetric outcomes for twins from different conception methods – A multicenter cross‐sectional study from China
    Wiley ; 2021
    In:  Acta Obstetricia et Gynecologica Scandinavica Vol. 100, No. 6 ( 2021-06), p. 1061-1067
    Details
    In: Acta Obstetricia et Gynecologica Scandinavica, Wiley, Vol. 100, No. 6 ( 2021-06), p. 1061-1067
    Abstract: The effects of assisted reproductive technology on the outcomes of twin pregnancies are controversial. Therefore, the purpose of this study was to compare the maternal and perinatal outcomes of twin pregnancies conceived spontaneously and those conceived by assisted reproductive technology. Material and methods This was a cross‐sectional study performed at Peking Union Medical College Hospital (PUMCH). Data on twin pregnancies (conceived spontaneously and by in vitro fertilization [IVF]/intracytoplasmic sperm injection [ICSI] ) were obtained from the National Birth Registry of China for the period between 1 October 2016, and 30 September 2017. The primary obstetric outcomes were compared between twin pregnancies conceived by different methods. Logistic regression analysis with 95% confidence intervals (95% CI) was used for the multivariate analysis. Results A total of 3270 twin pregnancies (2003 and 1209 conceived spontaneously and by IVF/ICSI, respectively) were identified. The proportion of twin pregnancies among all pregnancies was 3.4% (3332/97 278). Multiple regression analysis indicated that the incidences of gestational diabetes mellitus (adjusted odds ratio [AOR] = 1.42, 95% CI 1.10–1.83, p  = 0.007), preterm premature rupture of membranes (AOR = 1.65, 95% CI 1.21–2.25, p  = 0.002), placenta accreta spectrum (AOR = 2.12, 95% CI 1.42–3.17, p   〈  0.001) and postpartum hemorrhage (AOR = 1.38, 95% CI 1.02–1.86, p  = 0.037) were significantly higher in the IVF/ICSI group than in the natural pregnancy group. Multivariate analysis also revealed that conception mode was not an independent risk factor for neonate outcomes. Conclusions In twin pregnancies, IVF/ICSI is independently associated with multiple maternal complications, including gestational diabetes mellitus, preterm premature rupture of membranes and placenta accreta spectrum compared with spontaneous conception, although potential residual confounders due to indications for assisted reproductive technology exist.
    Type of Medium: Online Resource
    ISSN: 0001-6349 , 1600-0412
    URL: Issue
    URL: Article
    DOI: 10.1111/aogs.v100.6
    DOI: 10.1111/aogs.14116
    RVK:
    YM 6500
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2024554-3
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  • 10
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    Everolimus‐containing therapy vs conventional therapy in the treatment of refractory breast cancer patients with PI3K/AKT/mTOR mutations: A retrospective study
    Wiley ; 2019
    In:  Cancer Medicine Vol. 8, No. 12 ( 2019-09), p. 5544-5553
    Details
    In: Cancer Medicine, Wiley, Vol. 8, No. 12 ( 2019-09), p. 5544-5553
    Abstract: Previous case reports have shown the promising antitumor activity of everolimus in solid tumors containing molecular aberrations in PI3K/ATK/mTOR pathway, however, whether it is effective in patients with breast cancer remains unknown. Therefore, we conducted this retrospective cohort study to compare the efficacy of molecularly matched targeted therapy with everolimus to conventional therapy in refractory breast cancer patients harboring PI3K/ATK/mTOR pathway activating mutations. Methods Refractory metastatic breast cancer patients who have received molecular screening using next‐generation sequencing (NGS) between September 8, 2015 and October 30, 2017 in two sites were screened for this study. The primary outcome was progression‐free survival (PFS). The secondary outcomes were overall response rate (ORR), disease control rate (DCR), and safety profile. Results A total of 78 patients were screened for analysis, amongst all, 52 (66.7%) had at least one gene mutation in PI3K/AKT/mTOR pathway. The most common mutation fell in PIK3CA (76.9%, 40/52) with a mutational prevalence of 51.3%. Of the 32 patients who were eligible for efficacy analysis, patients in the everolimus group (n = 19) exhibited shorter PFS than those in the conventional group (n = 13) (median, 1.9 vs 6.1 months; HR, 3.6; 95% CI, 1.48‐8.81; P  = .0005). ORR was 15.4% (2/13) in the everolimus group and 23.1% (3/13) in the conventional group ( P  = 1.000), and DCR was 30.8% (4/13) and 100% (13/13) for each group, respectively ( P  = .000). The incidence of grade 3‐5 adverse events was relatively higher in the conventional group (38.5%, 5/13) than that in the everolimus group (26.3%, 5/19). Conclusions Our findings suggested that everolimus might not be effective for cancer patients harboring mutations in PI3K/ATK/mTOR pathway and physicians should be cautious about its off‐label use in clinical practice.
    Type of Medium: Online Resource
    ISSN: 2045-7634 , 2045-7634
    URL: Issue
    URL: Article
    DOI: 10.1002/cam4.v8.12
    DOI: 10.1002/cam4.2460
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2659751-2
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