Journal articles on the topic 'Jian zhu xue yuan'
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Li, Zhuo, Liang Qu, Xin Chen, Liu Xue, Jie Li, Qi Liu, Jian Sun, et al. "Abstract 2371: BGB-B167, a first-in-class 4-1BB/CEACAM5 bispecific antibody, exhibits potent in vitro and < for vivo antitumor activity and < for superior safety profile in preclinical models." Cancer Research 84, no. 6_Supplement (March 22, 2024): 2371. http://dx.doi.org/10.1158/1538-7445.am2024-2371.
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Abstract 4-1BB (CD137) is a key costimulatory immunoreceptor and a promising therapeutic target in cancer. CEACAM5 (CEA) is a well-established tumor associated antigen overexpressed in many cancers, including colorectal, gastric, lung, pancreatic cancer, liver, breast and thyroid cancers. BGB-B167 is a novel immunoglobulin G (IgG)-based bispecific antibody targeting 4-1BB and CEA and is under clinical development for the treatment of advanced or metastatic solid tumors in humans. BGB-B167 binds to its target proteins with high specificity and affinity. Potent and CEA-dependent functional activities were demonstrated using peripheral blood mononuclear cell (PBMC)-based immune cell activation and cytotoxicity assays. In humanized 4-1BB knock-in mice bearing human CEA-expressing tumors, BGB-B167 exhibited potent, dose-associated single-agent efficacy as well as synergistic antitumor activity in combination with anti-PD-1 antibody. BGB-B167 was well tolerated in 1-month repeat-dose toxicology study in cynomolgus monkeys. Here, we describe the characterization of BGB-B167 with regard to preclinical proof-of-concept and basic drug-like properties. The combined dataset provides an overview on the design, mode of action, preclinical pharmacology and safety profile of BGB-B167. Citation Format: Zhuo Li, Liang Qu, Xin Chen, Liu Xue, Jie Li, Qi Liu, Jian Sun, Hanzi Sun, Yun Chen, Yuanyuan Xie, Wanyi Wang, Lin Zhu, Penghao Wang, Xiaosui Zhou, Hongjia Hou, Jie Chen, Xinyi Liu, Yilu Zhang, Ning Liu, Xinyi Liang, Shuo Zhang, Xiaoyan Tang, Jing Song, Tong Zhang, Xiaomin Song, Xuesong Liu, Kang Li, Chichi Huang. BGB-B167, a first-in-class 4-1BB/CEACAM5 bispecific antibody, exhibits potent in vitro and < for vivo antitumor activity and < for superior safety profile in preclinical models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2371.
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지준호. "A Study on the differentiation and development aspects of Zhu-zi xue - centering around the connection between Huang Gan and Jin-hua school in Yuan period." JOURNAL OF KOREAN PHILOSOPHICAL HISTORY ll, no. 23 (March 2008): 317–47. http://dx.doi.org/10.35504/kph.2008..23.011.
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Ma, Xiaowei, Bryan D. Wood, and Brian Way. "Application of Tetraethylsulfamide (TES) As a Cathode Additive in Cylindrical Cells." ECS Meeting Abstracts MA2022-01, no. 2 (July 7, 2022): 357. http://dx.doi.org/10.1149/ma2022-012357mtgabs.
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Recently, sulfonamides have been shown to be promising electrolyte components due to their high chemical and electrochemical stability in lithium batteries [1, 2]. The electrolyte stability becomes critical when applying high voltage and/or utilizing Ni-rich layered oxides in high energy density lithium-ion batteries. Another approach to successful Ni-rich cathode performance is to develop a stable and effective cathode electrolyte interphase (CEI). Given the success of sultones and sulfates in this regard [3, 4], it is hypothesized that nitrogen analogs, like sulfonamides, could be tailored to provide a similar benefit. Indeed, Yim et al. [5, 6] have shown that N,N,N’,N’-tetraethylsulfamide (TES) forms a CEI on NMC811 that imparts high voltage cycling stability and less cathode corrosion. Our earlier studies of TES with Ni-rich NCA also formed a favorable CEI and these results are the topic of this presentation. Herein, we examine the performance of 0 - 4 wt.% TES in our commercially available, high power INR18650-P28A. These cells contain a composite SiO/graphite anode in addition to a Ni-rich cathode. As shown in Fig 1, TES significantly decreased the impedance of the cathode interface after conditioning compared to the control electrolyte. Thereafter, cells containing up to 2%TES show improved capacity retention during long-term high-rate cycling (+1C/-80W). Part of this success was due to a suppression of resistance growth during cycling by TES. Fast charge cycling (+3C/-2C), however, was moderately impaired with increased TES. Considering the largely reduced impedance of the cathode, fast-charge performance may have suffered due to anode rate limitations. These results will be discussed as well as gas generation, storage performance, and additional rate and cycling tests. [1] Shuting Feng, Mingjun Huang, Jessica R. Lamb, Wenxu Zhang, Ryoichi Tatara, Yirui Zhang, Yun Guang Zhu, Collin F. Perkinson, Jeremiah A. Johnson, Yang Shao-Horn. Chem, 5, 2630-2641 (2019) [2] Weijiang Xue, Mingjun Huang, Yutao Li, Yun Guang Zhu, Rui Gao, Xianghui Xiao, Wenxu Zhang, Sipei Li, Guiyin Xu, Yang Yu, Peng Li, Jeffrey Lopez, Daiwei Yu, Yanhao Dong, Weiwei Fan, Zhe Shi, Rui Xiong, Cheng-Jun Sun, Inhui Hwang, Wah-Keat Lee, Yang Shao-Horn, Jeremiah A. Johnson, Ju Li. Nature Energy, 6, 495-505 (2021) [3] Koji Abe, Manuel Colera, Kei Shimamoto, Masahide Kondo, Kazuhiro Miyoshi. Journal of Electrochemical Society, 161 (6) A863-A870 (2014) [4] Jian Xia, N. N. Sinha, L. P. Chen, J. R. Dahn. Journal of Electrochemical Society, 161 (3) A264-A274 (2014) [5] Kwangeun Jung, Taeeun Yim. Journal of Alloys and Compounds, 834,155155 (2020) [6] Ji Won Kim, Kwangeun Jung, Taeeun Yim. Journal of Mater. Sci & Tech. 86, 70-76 (2021) Figure 1
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Төрбат, Цагаан. "Ашина овгийн хатны эртний геном нь Хөх түрэгийн хаант улсыг Зүүн хойд Азийн гаралтай болохыг харуулжээ." Mongolian Journal of Anthropology, Archaeology and Ethnology 13, no. 1 (May 10, 2024): 141–45. http://dx.doi.org/10.22353/mjaae.20241301013.
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Xiao‐Min Yang, Hai‐Liang Meng, Jian‐Lin Zhang, Yao Yu, Edward Allen, Zi‐Yang Xia, Kong‐Yang Zhu, Pan‐Xin Du, Xiao‐Ying Ren, Jian‐Xue Xiong, Xiao‐Yu Lu, Yi Ding, Sheng Han, Wei‐Peng Liu, Li Jin, Chuan‐Chao Wang, and Shao‐Qing Wen. Ancient genome of Empress Ashina reveals the Northeast Asian origin of Göktürk Khanate. – Journal of Systematic and Evolution. Institute of Botany, Chinese Academy of Sciences. 2023. Volume 00 (0) 1-9.
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Zhou, Lin, Jianguo Sun, Conghua Xie, Youling Gong, Meijuan Huang, Zhiyong Yuan, Lin Wu, et al. "Abstract CT219: Efficacy and safety of Low dose radiotherapy (LDRT) concurrent Atezolizumab (Atezo) plus chemotherapy as first line (1L) therapy for ES-SCLC: Primary analysis of Phase II MATCH study." Cancer Research 83, no. 8_Supplement (April 14, 2023): CT219. http://dx.doi.org/10.1158/1538-7445.am2023-ct219.
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Abstract Background: The IMpower133 represented the current standard of care in the 1L setting for patients (pts) with ES-SCLC (extensive-stage small cell lung cancer). However, there are still unmet needs for ES-SCLC treatment. LDRT could play a key role in the priming effect of immune system by acting as an immune adjuvant and having sensitive cytotoxic activity to SCLC. The interim analysis of MATCH study after stage I showed promising benefit and tolerability of combination of Atezo + chemotherapy + LDRT in pts with ES-SCLC. Here we report the primary efficacy and safety results of this study. Methods: The MATCH study was a single-arm phase II trial conducted in 8 centers across China. Previously untreated ES-SCLC pts with measureable disease per RECIST v1.1 at baseline, age≥18, ECOG 0-1 were eligible. Atezo (1200 mg IV, D1) + Cisplatin (75 mg/m2 IV, D1)/Carboplatin (AUC = 5 IV, D1) +Etoposide (100 mg/m2 IV, D1-D3) were administrated on a 21-day cycle for four cycles. Concurrent LDRT (15 Gy/5f) were conducted from D1-D5 in the first cycle. Then pts received Atezo maintenance until loss of clinical benefit or unacceptable toxicity. The primary endpoint was objective response rate (ORR), defined as the proportion of patients with a complete response or partial response on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. A Simon’s minimax 2-stage design was adopted. Results: As the cutoff date of 30th Nov. 2022, 56 pts have been enrolled. 49 (87.5%) were males; mean age was 58.9 years with 78.6% pts had ECOG PS of 1. 80.4% pts had smoking history. Most pts were staged T4 (n = 33, 58.9%), N3 (n = 37, 66.1%) and M1(n = 40, 71.4%). Median follow-up was 14.8 months (range: 11.6-17.8 m). The confirmed ORR was 87.5% (95% CI: 75.9%-94.8%), all partial response. DCR was 94.6% (95% CI: 85.1%-98.9%). Median PFS was 6.9 m (95% CI: 5.4-9.3 m). The 6-month and 12-month PFS rate were 56.5% and 27.7%. Median OS was not reached (NR, 95% CI: 13.3m, NR). The 12-month OS rate was 71.9%. The safety profile, analyzed in all 56 pts, was consistent with the previous reports. Neutrophil count decreased (60.7%), white blood cell count decreased (58.9%) and platelet count decreased (23.2%) were the most common grade (G) 3-4 adverse events (AE). G5 AE occurred in 1 pt (pneumonia and pulmonary embolism). 4 pts experienced AEs leading to treatment discontinuation. IrAEs were reported in 21 (37.5%) pts, most common irAEs were hyperthyroidism (5.4%) and rash (5.4%). Radiation pneumonitis (G1) was observed in 1 pt. Conclusions: Adding LDRT to Atezo + chemotherapy shows impressive antitumor activity, potential survival benefit and well tolerability in 1L treatment of ES-SCLC. Clinical registration: NCT04622228. Citation Format: Lin Zhou, Jianguo Sun, Conghua Xie, Youling Gong, Meijuan Huang, Zhiyong Yuan, Lin Wu, Hui Wang, Nan Bi, Yaping Xu, Jiang Zhu, Yongmei Liu, Yan Zhang, Min Fan, Bingwen Zou, Min Yu, Yanying Li, Feifei Na, Weigang Xiu, Yong Xu, Jin Wang, Xuanwei Zhang, Jianxin Xue, You Lu. Efficacy and safety of Low dose radiotherapy (LDRT) concurrent Atezolizumab (Atezo) plus chemotherapy as first line (1L) therapy for ES-SCLC: Primary analysis of Phase II MATCH study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT219.
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Chao, Xue-lin, Shu-zhen Jiang, Jian-wen Xiong, Jin-qiong Zhan, Bo Wei, Chun-nuan Chen, and Yuan-jian Yang. "Erratum to: Changes of Serum Insulin-like Growth Factor-2 Response to Negative Symptom Improvements in Schizophrenia Patients Treated with Atypical Antipsychotics." Current Medical Science 40, no. 5 (October 2020): 997. http://dx.doi.org/10.1007/s11596-020-2256-3.
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The article “Changes of Serum Insulin-like Growth Factor-2 Response to Negative Symptom Improvements in Schizophrenia Patients Treated with Atypical Antipsychotics”, written by Xue-lin CHAO, Shu-zhen JIANG, Jian-wen XIONG, Jin-qiong ZHAN, Bo WEI, Chun-nuan CHEN, Yuan-jian YANG was originally published electronically on the publisher’s internet portal on June 2020 without open access. With the author(s)’ decision to opt for Open Choice, the copyright of the article is changed to © The Author(s) 2020 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
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Wei, Heyi, and Wenhua Jiang. "Translation of the ‘Landscape Architecture’ Into Chinese and How to Build the Discipline of Landscape Architecture in China?" International Research in Education 8, no. 1 (February 3, 2020): 104. http://dx.doi.org/10.5296/ire.v8i1.16381.
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The translation and connotation of landscape architecture (LA) caused a lot of controversy in academia when the term ‘LA’ was introduced to China. In this study, we summarized the different opinions of Chinese scholars based on the origin, evolution, and professional contents of LA, which can be divided into ‘Jing Guan Jian Zhu’ (Chinese Pinyin), ‘Jing Guan She Ji’, and ‘Feng Jing Yuan Lin’. Finally, this article provides strategies and suggestions for enhancing the development of LA when the first-level discipline is established in China, and the aim is to narrow the gap with the international community.
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Song, Runjie, and Lu Gao. "Daiwie Fu 傅大為, STS de yuan qi yu duo zhong jian gou - heng kan jin dai ke xue de yi zhong bian zhi yu da zao STS的緣起與多重建構—橫看近代科學的一種編織與打造 [A Genealogical History of STS and Its Multiple Constructions: To Weave an Extensive Network for Gazing upon the Modern Sciences]." East Asian Science, Technology and Society: An International Journal 15, no. 1 (January 2, 2021): 111–18. http://dx.doi.org/10.1080/18752160.2021.1877035.
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Yi, Guo, and Martin Lu. "Guodian Bamboo Texts and Pre-Qin Intellectual Thoughts (Guo Dian Zhu Jian Yu Xian Qin Xue Shu Si Xiang)a." Journal of Chinese Philosophy 31, no. 2 (June 2004): 297–301. http://dx.doi.org/10.1111/j.0301-8121.2004.155_1.x.
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Zhu, Xiu-Zhi, Xi Jin, Hu-Yun-Long Zhang, Xiyu Liu, Yi-Fan Zhou, Yi-Yu Chen, Tong Fu, et al. "Abstract PO1-15-07: Subtyping-directed precision treatment refines traditional one-size-fits-all therapy in HR+/HER2- breast cancer: a sub-study of the MULAN umbrella trial." Cancer Research 84, no. 9_Supplement (May 2, 2024): PO1–15–07—PO1–15–07. http://dx.doi.org/10.1158/1538-7445.sabcs23-po1-15-07.
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Abstract Background: The standard approach of using one-size-fits-all endocrine therapy for hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancers has faced significant challenges due to variations in treatment response among individuals. Consequently, there is still an urgent need to understand the molecular biology of HR+/HER2- breast cancer and explore precision treatment strategy. Methods: We established a multiomics cohort (n = 351), multicenter real-world clinical cohorts (n = 643), a prospective clinical cohort (MULAN trial), and a drug-testing platform containing patient-derived organoids (n = 126) and patient-derived tumor fragments (n = 49) of HR+/HER2- breast cancers. Integrating "bench" and “bedside” data, we conducted comprehensive preclinical and clinical translational research on precision strategies in HR+/HER2- breast cancer. Results: We implemented a comprehensive classification system for HR+/HER2- breast cancer, comprising four distinct subtypes. We further demonstrated the efficacy and mechanisms of subtyping-directed precision treatment strategies through clinical cohort studies, omics analysis and functional assays: endocrine therapy alone for the canonical luminal subtype; the addition of CDK4/6 inhibitor and PARP inhibitor for the proliferative subtype; the immunotherapy for the immunogenic subtype; and tyrosine kinase inhibitors for the receptor tyrosine kinase-driven subtype. Using clinically applicable subtyping methods, we validated that matched precision treatment strategies outperformed unmatched approaches in a real-world cohort, almost doubling the median progression-free survival time for patients with refractory advanced HR+/HER2- breast cancer (9.83 months [95% CI, 5.74-13.93] vs 4.77 months [95% CI, 3.35-6.18]; hazard ratio 0.64 [95% CI, 0.41-0.99]). Importantly, the first-stage analysis of the MULAN phase II umbrella clinical trial (NCT04355858) verified the higher objective response rate (88.9%, 95%CI: 51.7%-99.7%) of the subtyping-directed precision treatment. Conclusion: Our study emphasizes the superiority of subtyping-directed precision treatment strategies for HR+/HER2- breast cancer, refines traditional “one-size-fits-all” therapy, and facilitates the translation of precision treatment strategies from bench to bedside. Overall study design Part 1 Subtype Molecular Characteristics: Molecular features of the four subtypes of HR+/HER2- breast cancer. Part 2 Multidimensional Efficacy Validation: Integrating data from a multiomics cohort, real-world study, drug testing platform and prospective clinical research to validate the subtyping-directed precision treatment strategy in HR+/HER2- breast cancer. Part 3 Subtyping-directed Precision Treatment Strategy: Integrating clinical cohort studies, omics analysis and functional assays revealed the heterogeneity of treatment response in HR+/HER2- breast cancer, and proposed a subtyping-directed precision treatment strategy. CIN, chromosomal instability; RTK, receptor tyrosine kinase; CNA, copy-number alteration; ER, estrogen receptor; HR, hormone receptor; HER2, human epidermal growth factor receptor 2. Citation Format: Xiu-Zhi Zhu, Xi Jin, Hu-Yun-Long Zhang, Xiyu Liu, Yi-Fan Zhou, Yi-Yu Chen, Tong Fu, Ming-Liang Jin, Ya-Xin Zhao, Yi-Fan Xie, Ruo-Xi Wang, Zhong-Hua Wang, Lei Fan, Yi-Zhou Jiang, Zhi-Ming Shao. Subtyping-directed precision treatment refines traditional one-size-fits-all therapy in HR+/HER2- breast cancer: a sub-study of the MULAN umbrella trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-15-07.
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Lu, Martin. "Guodian Bamboo Texts and Pre-Qin Intellectual Thoughts (Guo Dian Zhu Jian Yu Xian Qin Xue Shu Si Xiang).a By Guo Yi. b (Shanghai: Shanghai Educational Publishing House, 2001. 859 pp.)." Journal of Chinese Philosophy 31, no. 2 (February 19, 2004): 297–301. http://dx.doi.org/10.1163/15406253-03102008.
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Wang, Xue, Feng Du, Jian Yue, Yiran Si, Lina Cui, Bei Zhang, Xiaochen Zhao, Binghe Xu, and Peng Yuan. "Abstract 5084: KMT2D and PIK3CA mutation as potential factors to predict adjuvant chemotherapy efficacy in surgical triple negative breast cancer." Cancer Research 82, no. 12_Supplement (June 15, 2022): 5084. http://dx.doi.org/10.1158/1538-7445.am2022-5084.
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Abstract Background: Chemotherapy is the most common treatment strategy for triple negative breast cancer (TNBC) patients. Nevertheless, due to adverse drug reactionsthe molecular high heterogeneity of TNBC and no appropriate meaningful efficacy markers, it is still difficult to establish preferred therapeutic strategies and predict the outcomes for TNBC. This study was to investigate the potential predictors and therapeutic targets based on genetic features. Methods: A total of 386 TNBC patients were randomized 1:1 to receive either six cycles of paclitaxel + cisplatin (TP) or four cycles of epirubicin + cyclophosphamide followed by four cycles of docetaxel (EC-T) adjuvant chemotherapy after surgery (NCT01150513), which were described previously. Finally, 149 TNBC patients with clinical and tumor sequencing data availability were retrospectively analysed by NGS for 733 cancer-related genes. All tumor samples were collected during the surgical operation and subjected to NGS for evaluating genomic mutations and the potential predictors. Cox regression model and Kaplan-Meier method were applied to evaluate disease-free survival (DFS). Results: In the surgical cohort receiving adjuvant chemotherapy, 74 patients received platinum and 75 received platinum-free chemotherapy as adjuvant chemotherapy. The most frequently mutated genes in this surgical TNBC cohort were TP53 (84%), BRCA1 (18%), BRCA2 (15%), POL1 (13%), PTEN (12%), REV3L (11%), FANCC (10%), and PARP4 (10%). We analyzed the associations between 733 cancer-related gene mutations and DFS after adjuvant chemotherapy. For the TP group, PIK3CA mutation (19%, 14/74) was discovered to correlate with poor DFS for patients treated with platinum-containing adjuvant therapy (HR=3.2, P=0.037), and KMT2D mutation (15%, 11/75) display worse DFS for patients treated with EC-T platinum-free group (HR=3.0, p=0.039). However, BRCA1/2 mutation (24%, 35/149) was found to be associated with poor prognosis (HR=2.1 (95% CI: 1-4.6), p=0.047), irrespective of therapeutic regimen. Conclusions: In this population of surgical TNBC patients, NGS analysis identified potential predictive markers. PIK3CA mutation in TP platinum-containing group and KMT2D mutation in EC-T platinum-free group were significantly associated to poor prognosis for adjuvant chemotherapy in triple negative breast cancer. Citation Format: Xue Wang, Feng Du, Jian Yue, Yiran Si, Lina Cui, Bei Zhang, Xiaochen Zhao, Binghe Xu, Peng Yuan. KMT2D and PIK3CA mutation as potential factors to predict adjuvant chemotherapy efficacy in surgical triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5084.
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Ma, Rulan, Dangcheng Xue, Yong Zhang, Kun Zhu, Dawei Yuan, Tuanhe Sun, Caijing Mo, Xiaoyuan Deng, Fujun Qin, and Kang Li. "Abstract 2207: The prognostic role of γδ T cells in colorectal cancer and the establishment of related nomogram for predicting overall survival of the patients." Cancer Research 83, no. 7_Supplement (April 4, 2023): 2207. http://dx.doi.org/10.1158/1538-7445.am2023-2207.
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Abstract Objective: The aim of the present study was to explore the prognostic role of γδ T cells in colorectal cancer, and establish a nomogram for predicting the overall survival of the patients. Methods: Immunohistochemistry was performed to analyze the infiltration degree of γδ T cells in tumor and normal tissues of colorectal cancer. The relationship between γδ T cells infiltration in tumor tissues and the prognosis of patients with colorectal cancer were determined by survival analysis. Cox regression analysis was performed to detect the factors related to the prognosis of patients with colorectal cancer. R software was used to establish and verify a nomogram for predicting the prognosis of patients with colorectal cancer. Results: The degree of γδ T cell infiltration in tumor tissues and normal tissues of CRC was not different (t=0.35, P=0.731). However, the infiltration of γδ T cell was related to the survival status of the patients (x2=4.88, P=0.027). Besides, the infiltrating degree of γδ T cells in tumor tissue was obviously related to the prognostic improvement of the patients with colorectal cancer (Log-rank P=0.016) and could reflect the benefit of adjuvant chemotherapy (Log-rank P=0.003). Cox regression analysis showed that tumor stage (HR:3.14, 95%CI:1.25-7.89, P=0.015), serum CEA level (HR:3.67, 95%CI:1.48-9.10, P=0.005) and γδ T cell infiltration (HR:0.38, 95%CI:0.14-0.99, P=0.049) were independent prognostic factors of overall survival in patients with colorectal cancer. A nomogram based on tumor stage, serum CEA level and γδ T cell infiltration was established and showed a good prediction ability for survival of patients with colorectal cancer. Conclusion: γδ T cell infiltration degree in tumor tissue was an important factor to improve the outcome of patients with colorectal cancer, and could predict the benefit of adjuvant chemotherapy. The nomogram had a good ability for predicting overall survival of the patients with colorectal cancer. Citation Format: Rulan Ma, Dangcheng Xue, Yong Zhang, Kun Zhu, Dawei Yuan, Tuanhe Sun, Caijing Mo, Xiaoyuan Deng, Fujun Qin, Kang Li. The prognostic role of γδ T cells in colorectal cancer and the establishment of related nomogram for predicting overall survival of the patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2207.
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Lavanya, Maruthasalam, Duraisamy Thiruarul, Karuppaiya Balasundaram Rajesh, and Zbigniew Jaroszewicz. "Generating novel focal patterns for radial variant vector beam focusing through a dielectric interface." Photonics Letters of Poland 15, no. 1 (April 2, 2023): 7–9. http://dx.doi.org/10.4302/plp.v15i1.1198.
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Electric and magnetic energy densities as well as energy flux (Poynting vector) for radial variant vector beam focusing through a dielectric interface is analyzed numerically based on vector diffraction theory. The electric and magnetic energy densities are tailored by properly manipulating the radial as well as initial phases to generates novel focal patterns in the focal area. These peculiar properties may find applications in fields such as optical trapping, optical recording, magnetic recording, and magnetic resonance microscopy and semiconductor inspection. Full Text: PDF References S.N. Khonina, I. Golub, "Optimization of focusing of linearly polarized light ", Opt. Lett. 36 352 (2011). CrossRef V.V. Kotlyar, S.S. Stafeev, Y. Liu, L. O'Faolain, A. A. Kovalev, "Analysis of the shape of a subwavelength focal spot for the linearly polarized light", Appl. Opt. 52 330 (2013). CrossRef S. Sen, M.A. Varshney, D. Varshney, "Relativistic Propagation of Linearly/Circularly Polarized Laser Radiation in Plasmas", ISRN Optics. 2013 1 (2013). CrossRef M. Martínez-Corral, R. Martínez-Cuenca, I. Escobar, G. Saavedra, "Reduction of focus size in tightly focused linearly polarized beams", Appl. Phys. Lett. 85 4319 (2004) . CrossRef J. Lekner, "Polarization of tightly focused laser beams", Opt. A: Pure Appl. Opt. 5, 6 (2003). CrossRef H. Guo, X. Weng, M. Jiang, Y. Zhao, G. Sui, Q. Hu, Y. Wang, S. Zhuang, "Tight focusing of a higher-order radially polarized beam transmitting through multi-zone binary phase pupil filters", Opt.Express 21, 5363 (2013). CrossRef C.-C. Sun, C.-K. Liu, "Ultrasmall focusing spot with a long depth of focus based on polarization and phase modulation", Opt. Lett. 28, 99 (2003). CrossRef G.H. Yuan, S.B. Wei, X.-C. Yuan, "Nondiffracting transversally polarized beam", Opt. Lett. 36, 3479 (2011). CrossRef P. Yu, S. Chen, J. Li, H. Cheng, Z. Li, W. Liu, B. Xie, Z. Liu, J. Tian, "Generation of vector beams with arbitrary spatial variation of phase and linear polarization using plasmonic metasurfaces", Opt. Lett. 40, 3229 (2015). CrossRef Z. Chen, T. Zeng, B. Qian, "Complete shaping of optical vector beams", J. Ding, Opt. Express 23, 17701 (2015). CrossRef Z. Liu, Y. Liu, Y. Ke, Y. Liu, W. Shu, H. Luo, S. Wen, "Generation of arbitrary vector vortex beams on hybrid-order Poincaré sphere", Photon. Res. 5, 15 (2017). CrossRef Z. Man, Z. Bai, S. Zhang, J. Li, X. Li, X. Ge, Y. Zhang, S. Fu, "Focusing properties of arbitrary optical fields combining spiral phase and cylindrically symmetric state of polarization", J. Opt. Soc. Am. A 35, 1014 (2018). CrossRef Z. Man, S. Fu, G. Wei, "Focus engineering based on analytical formulae for tightly focused polarized beams with arbitrary geometric configurations of linear polarization", J. Opt. Soc. Am. A 34, 1384 (2017). CrossRef Z. Man et al, "Optical cage generated by azimuthal- and radial-variant vector beams", Appl. Opt. 57 (2018). CrossRef S.S. Stafeev, V.V Kotlyar, A.G. Nalimov, E.S. Kozlova, "The Non-Vortex Inverse Propagation of Energy in a Tightly Focused High-Order Cylindrical Vector Beam", IEEE Photon. J., 11, 1 (2019). CrossRef S.S. Stafeev, V.V. Kotlyar, "Elongation of the area of energy backflow through the use of ring apertures", Opt. Commun.450 (2019) 67-71. CrossRef S.S. Stafeev, V.V. Kotlyar, A.G. Nalimov, "Energy backflow in in a tightly focused high-order cylindrical vector beam", Proc. SPIE 11025, 1102518 (2019). CrossRef N.G. Orji, M. Badaroglu, B.M. Barnes, "Metrology for the next generation of semiconductor devices", Nat. Electron. 1, 532 (2018). CrossRef P. Torok, P. Varga, G.R. Booker, "Electromagnetic diffraction of light focused through a planar interface between materials of mismatched refractive indices: structure of the electromagnetic field. I", I, J. Opt. Soc. Am. A 12, 2136 (1995). CrossRef P. Torok, P. Varga, Z. Laczik, G.R. Booker, "Electromagnetic diffraction of light focused through a planar interface between materials of mismatched refractive indices: an integral representation", J. Opt. Soc. Am. A., 12, 325 (1995). CrossRef Z. Zhou, L. Zhu, "Tight focusing of high order axially symmetric polarized beams through a dielectric interface", Optik, 124, 2219 (2013). CrossRef J. Shu, Z. Chen, J. Pu, Y. Liu "Tight focusing of a double-ring-shaped, azimuthally polarized beam through a dielectric interface", J. Opt. Soc. Am. A 31, 1180 (2014). CrossRef K. Hu, Z. Chen, J. Pu., "Generation of super-length optical needle by focusing hybridly polarized vector beams through a dielectric interface", Opt. Lett. 37, 3303 (2012). CrossRef B. Richards, E. Wolf, "Electromagnetic diffraction in optical systems, II. Structure of the image field in an aplanatic system", Proc. R. Soc. London A 253, 358 (1959). CrossRef
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Yue, Jian, Xue Wang, Jie Ju, Zixiang Yang, Tong Wei, Peng Yuan, Min Gao, Ling Xu, and Yin Guan. "Abstract PO4-05-04: Comparative effectiveness of Palbociclib plus Aromatase inhibitor versus fulvestrant alone as initial endocrine therapy for HR+/HER2- advanced breast cancer in Chinese clinical practice: a real-world study." Cancer Research 84, no. 9_Supplement (May 2, 2024): PO4–05–04—PO4–05–04. http://dx.doi.org/10.1158/1538-7445.sabcs23-po4-05-04.
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Abstract Background: In the real world, there are still a large number of HR+/HER2- advanced breast cancer patients receiving initial endocrine therapy with fulvestrant monotherapy in China, especially patients with bone metastases only. It is due to lack of data comparing the effective between Palbociclib combined with AI and fulvestrant monotherapy as initial endocrine therapy. On the other hand, there are economic factors and access issues. According to the National Cancer Center's previous clinical experience, Palbociclib combined with AI is superior to fulvestrant monotherapy in HR+/HER2- advanced breast cancer patients receiving initial endocrine therapy. Therefore, we collected and summarized the previous clinical data in our center to compare the effective of Palbociclib combined with AI and fulvestrant monotherapy for HR+/HER2-advanced breast cancer patients receiving initial endocrine therapy in China. Patients and methods: This is a retrospective real-world study of multicenter studies. It aimed at verifying the effective of Palbociclib combined with AI and fulvestrant monotherapy for HR+/HER2-advanced breast cancer patients receiving initial endocrine therapy in China. A total of 392 patients with ≥3 months of follow-up received Palbociclib plus AI or fulvestrant alone in the first-line setting between April 1, 2015 and February 1, 2023. Stabilized inverse probability treatment weighting (sIPTW) was used to balance baseline demographic and clinical characteristics. Real-world progression-free survival (rwPFS) and overall survival (OS) were analyzed. Results: After sIPTW adjustment, a median follow-up of 37 months (range 34-40) in the Palbociclib group and 59 months (range 56-61) in those taking fulvestrant alone. Palbociclib combination regiment was associated with significantly longer median rwPFS compared to fulvestrant alone (22.0 vs 14.0 months; HR,0.469;95% CI 0.370–0.594, p< 0·0001). Median OS was not reached in the Palbociclib group and was 57 months (95% CI 54.0–66.0) in the fulvestrant group(HR,0.666; 95% CI 0.437–1.017, p< 0·94). Conclusion: In the real-world population of patients, palbociclib combined with AI endocrine therapy is superior to fulvestrant monotherapy in HR+/HER2- advanced breast cancer patients receiving initial endocrine therapy. PFS and OS before IPTW PFS and OS after IPTW Table patient characteristics Citation Format: Jian Yue, Xue Wang, Jie Ju, Zixiang Yang, Tong Wei, Peng Yuan, Min Gao, Ling Xu, Yin Guan. Comparative effectiveness of Palbociclib plus Aromatase inhibitor versus fulvestrant alone as initial endocrine therapy for HR+/HER2- advanced breast cancer in Chinese clinical practice: a real-world study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-05-04.
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Wang, Xue, Jian Yue, Jiayu Wang, Pin Zhang, Fei Ma, Binghe Xu, and Peng Yuan. "Abstract P3-02-07: Combined Chemo-endocrine Therapy Maybe a New Option for HR+/HER2− Advanced Breast Cancer: A Prospective, Single-center Clinical Study of Fulvestrant plus Oral Vinorelbine." Cancer Research 83, no. 5_Supplement (March 1, 2023): P3–02–07—P3–02–07. http://dx.doi.org/10.1158/1538-7445.sabcs22-p3-02-07.
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Abstract Background Fulvestrant have demonstrated synergistic antitumor effect with chemotherapy regimen. This study evaluates the efficacy and safety of Fulvestrant with Vinorelbine in patients with hormone receptor positive (HR+)/human epidermal growth factor receptor-2-negative (HER2−) recurrent or metastatic breast cancer. Methods In this prospective, single-arm and investigator-initiated clinical study, patients with recurrent or metastatic HR+/HER2− breast cancer after the first line adjuvant endocrine therapy for > 1 year were eligible, in which the subjects of the first line was defined as the patients with recurrence and metastasis after adjuvant endocrine therapy for over 1 year and did not receive treatment for the recurrence and metastasis and the second-line defined as the patients who had disease progression after receiving first-line endocrine therapy or first-line chemotherapy). Patients were administered i.m. Fulvestrant 500mg (day 1 per cycle for 28 days) and oral Vinorelbine (60 mg/m2 on day 1, 8 and 15 of each cycle). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), and safety. The Kaplan–Meier method and log-rank test were used to evaluate PFS and OS. Results Total 38 HR+/HER2- advanced breast cancer patients with median follow-up time (25.1 months) were enrolled in, and median PFS [9.86 months (95% CI: 7.2, 23.13)] were discovered. The median PFS of the first-line and the second-line treatment population were 20.73 months (95% CI: 9.82, NR) and 4.27 months (95% CI: 3.68, NR), respectively. The median OS of the intent-to-treat (ITT) and the first-line treatment population were not reached, and the OS of the second-line treatment was 28.2 months (95% CI: 11.5, NR). The ORR of the ITT population was 39.47% (95% CI: 23.93, 55.01). The ORR of the patients receiving first-line and second-line treatments were 44.44% (95% CI: 25.70, 63.19) and 27.27% (95% CI: 0.95, 53.59), respectively. The DCR of ITT population was 92.11% (95% CI: 83.54, 100.00)], and the median DoR was approximately 15.33 months (95% CI: 7.23, 22.54)]. In the safety analysis, most of the adverse events were grade of 1/2, and none of grade 4/5 adverse events were reported. Conclusion This is the first exploratory study of Fulvestrant with oral Vinorelbine regimen in the treatment of HR+/HER2− recurrent and metastatic breast cancer conducted worldwide. The combinative chemo-endocrine therapy was efficacious, safe and promising for patients with HR+/HER2− advanced breast cancer. Citation Format: Xue Wang, Jian Yue, Jiayu Wang, Pin Zhang, Fei Ma, Binghe Xu, Peng Yuan. Combined Chemo-endocrine Therapy Maybe a New Option for HR+/HER2− Advanced Breast Cancer: A Prospective, Single-center Clinical Study of Fulvestrant plus Oral Vinorelbine [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-02-07.
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Ravindranathan, Sruthi, Passang Tenzin, Jian Ming Li, Rohan Dhamsania, Michael Ware, Mohammad Zaidi, Shuhua Wang, et al. "Abstract PO-072: Inhibiting vasoactive intestinal peptide receptor signaling elicits T cell dependent anti-tumor response of pancreatic ductal adenocarcinoma to immune checkpoint therapy." Cancer Research 81, no. 22_Supplement (November 15, 2021): PO—072—PO—072. http://dx.doi.org/10.1158/1538-7445.panca21-po-072.
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Abstract Pancreatic ductal adenocarcinoma (PDAC) is unresponsive to immune checkpoint therapy largely due to a paucity of T cells within the tumor microenvironment (TME) and abundant immunosuppressive signaling pathways. In this study we show that human PDAC tumors over-express vasoactive intestinal peptide (VIP), an immunosuppressive neuropeptide that suppresses T cell effector properties and promotes the generation of regulatory T cells (Tregs). Therefore, we treated tumor-bearing mice with VIP receptor peptide antagonists and measured T cell homing, activation, and anti-tumor responses in preclinical murine models of PDAC. Pharmacological inhibition of VIP receptor (VIP-R) signaling using daily subcutaneous injections of peptide antagonists had no discernable toxicity in healthy and tumor-bearing mice. Treatment with VIP-R antagonists in combination with anti-PD-1 checkpoint blockade significantly decreased tumor burden, and improved survival in subcutaneous and orthotopic murine PDAC models. Combination therapy significantly enhanced T cell activation and proliferation and decreased frequencies of Tregs within the TME. Anti-tumor responses were T cell dependent, as the combination therapy failed to improve survival in CD4 or CD8 deficient mice using knock-out strains and antibody depletion. Furthermore, combination therapy significantly increased frequencies of tumor specific T cells (measured with a tetramer reagent) and provided protective immunity against tumor rechallenge. Combination therapy led to significant increases in the infiltration of adoptively transferred GFP+ T cells into PDAC tumors and decreased CXCR4 expression levels on T cells. Encouragingly, peptide-based VIP-R antagonists enhanced the in vitro activation of human T cells isolated from peripheral blood of PDAC patients. Human T cells cultured with VIP-R antagonists had increased proliferation, activation, and decreased proportions of T regs and exhausted T cells co-expressing PD-1, Tim-3 and Lag-3. Taken together, our findings show that VIP is a targetable mechanism of immune escape in PDAC. Inhibiting VIP receptor signaling improves T cell effector properties and synergistically improves anti-tumor responses to checkpoint inhibitors in mouse PDAC models. Additionally, as the VIP sequence is identical between human and mice, and since VIP-R antagonists have similar effects on human and murine T cells in culture, clinical translation is highly feasible. Citation Format: Sruthi Ravindranathan, Passang Tenzin, Jian Ming Li, Rohan Dhamsania, Michael Ware, Mohammad Zaidi, Shuhua Wang, Jingru Zhu, Maria Cardenas, Yuan Liu, Gaurav Joshi, Sanjeev Gumber, Brian Robinson, Anish Sen-Majumdar, Shanmuganathan Chandrakasan, Haydn Kissick, Alan Frey, Susan Thomas, Bassel El-Rayes, Gregory Lesinski, Edmund K. Waller. Inhibiting vasoactive intestinal peptide receptor signaling elicits T cell dependent anti-tumor response of pancreatic ductal adenocarcinoma to immune checkpoint therapy [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-072.
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Wang, Xue, Yimeng Chen, Feng Du, Jian Yue, Yiran Si, Xiaochen Zhao, Lina Cui, et al. "Abstract 5689: Effects of homologous recombination-related gene mutation subtypes on gene instability and the efficacy of platinum-containing regiments in triple-negative breast cancer." Cancer Research 82, no. 12_Supplement (June 15, 2022): 5689. http://dx.doi.org/10.1158/1538-7445.am2022-5689.
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Abstract Background: Platinum-containing chemotherapy is treatment with high efficacy in homologous recombination (HR) deficient cancers that arise in carriers of mutations in the BRCA1/2 genes. However, previous reports have shown that TNBC patients carrying no BRCA1/2 mutations also could benefit from platinum therapy. This study aimed to explore the association between HR-related gene mutations and genomic instability, and further evaluate the effectiveness of platinum-containing chemotherapy preliminarily. Methods: A total of 386 TNBC patients were screened from a surgical cohort (NCT01150513) and a metastatic cohort. Finally, 189 TNBC patients with clinical and tumor sequencing data availability were included, including 149 patients treated with radical surgery and adjuvant chemotherapy. All tumor samples were collected during the surgical operation and subjected to NGS for evaluating homologous recombination deficiency (HRD) score and 15 HR-related gene pathogenic or likely pathogenic mutations (including ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51D, RAD51C, RAD54L). HRD score was an algorithmic assessment of three biomarkers of genomic instability as loss of heterozygosity, telomeric-allelic imbalance, large-scale state transitions and based on over 10,000 single-nucleotide polymorphisms in the human genome. Results: In 189 TNBC cohort, 40 patients (21.1%) had BRCA1/2 deleterious mutations, with additional 26 patients (13.8%) carrying mutations in HR-related genes other than BRCA1/2. Compared with BRCA1/2-intact patients, those carrying BRCA1/2m displayed a significantly higher HRD score (median, 35.5 vs 20.0; P=0.02). However, patients with HRm obtained a similar HRD score with HRwt patients (median, 28.0 vs 21.0, P=0.83). TNBC patients with PALB2m (n=8) had a small trend higher HRD score compared with BRCA1/2m (median HRD score 39.0 and 35.5), and TNBC patients with RAD51 family (n=7), ATM (n=5) and other HR-related gene mutations had a numerical trend lower HRD score compared with BRCA1/2m (median HRD score 22.0, 4.0, 14.5 and 35.5). Of the 149 patients in surgical cohort, 74 received platinum-containing, and 75 underwent platinum-free adjuvant chemotherapy. We analyzed the associations between HR-related gene mutations and disease-free survival (DFS), and found that patients with RAD51Bm (n=3), RAD51Cm (n=1) or PPP2R2Am (n=1) displayed worse DFS for patients treated with adjuvant chemotherapy (P =0.012, P<0.0001 or P<0.0001, respectively). Conclusions: In this study, we found that different HR-related genes mutation subtypes may exert distinct effects on genomic instability, and mutations in HR-related genes beyond the context of BRCA1/2 may serve as a biomarker for platinum-based adjuvant therapy for TNBC patients, which warrants further studies. Citation Format: Xue Wang, Yimeng Chen, Feng Du, Jian Yue, Yiran Si, Xiaochen Zhao, Lina Cui, Bei Zhang, Ting Bei, Peng Yuan, Binghe Xu. Effects of homologous recombination-related gene mutation subtypes on gene instability and the efficacy of platinum-containing regiments in triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5689.
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Zhang, Jian, Yu Fang, Lei Sun, Hongling Yuan, Mao Shang, Xiaoyan Zhang, Honglin Zhu, and Tonghui Ma. "Abstract 5292: Investigating the potential relationship between BRAF mutations and tumor mutation burden (TMB) in lung cancer (LC)." Cancer Research 82, no. 12_Supplement (June 15, 2022): 5292. http://dx.doi.org/10.1158/1538-7445.am2022-5292.
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Abstract BackgroundCurrently, BRAF inhibitors are primarily effective in LC patients with BRAF V600E mutation, while with limited benefit for patients with BRAF non-V600E mutation. Additionally, it is unclear whether immunotherapy is effective in LC patients with BRAF mutations, and the relationship between BRAF mutations and immune biomarkers, such as TMB, is also unclear. Here, we retrospectively investigated the relationship with BRAF mutation and TMB in Chinese LC patients.MethodsSamples were extracted from 3,136 our cohort samples of LC, which from OncoPanscan࣪ (Genetron Health) based sequencing of tissue. Because of the significantly different cohort characteristics, propensity score matching was used to resolve potential confounding by a nearest neighbor algorithm. The use of a multivariable logistic regression model to estimate the propensity score was based on age, sex, cancer type and detail panels. The samples after propensity score matching was used to investigate the relationship with TMB. ResultsIn our cohort, 171 samples had BRAF mutations and 2,965 samples had non-BRAF mutations. After propensity score analysis, 165 samples of BRAF mutations were screened with 165 paired samples of non-BRAF mutations.In the 165 samples of BRAF mutations, 83 samples of them had TMB information, while 83 samples of the 165 paired samples of non-BRAF mutations had TMB information. Patients with BRAF mutation had a higher median TMB than the patients with non-BRAF mutation (9.39 vs. 7.51 Muts/Mb, p=0.0545). Similarly, in these two groups, there was slightly higher ratio of samples with TMB ≥10muts/Mb (43.37% vs. 31.32%, P=0.0788). Among BRAF mutation group, when compared to BRAF V600E group (N=26), the median TMB was much higher in non-V600E group (N=57) (7.38 vs. 9.86 muts/Mb, P=0.0270). The proportion of TMB ≥10muts/Mb in BRAF non-V600E group was much higher than V600E group (49.12% vs. 30.77%, P=0.0094). Additionally, we analyzed the samples that had high TMB (TMB≥10 muts/Mb) and high PD-L1 (TPS≥50%). The BRAF mutation group had more proportion than non-BRAF mutation (14.46% vs.6.02%, p=0.0593), and the BRAF non-V600E group was higher than BRAF V600E group (15.79% vs. 11.54%, P=0.4150).ConclusionsCompared with non-BRAF mutation, BRAF mutation was associated with higher TMB, and it was also higher in BRAF non-V600E than BRAF V600E. These results suggested that patients with driver mutation of BRAF V600E had lower TMB and they always had good response to BRAF inhibitors. While LC patients with BRAF non-V600E always with higher TMB, thus, they may be more suitable for immunotherapy. However, more clinical research are needed to evaluate the effectiveness of immunotherapy. Citation Format: Jian Zhang, Yu Fang, Lei Sun, Hongling Yuan, Mao Shang, Xiaoyan Zhang, Honglin Zhu, Tonghui Ma. Investigating the potential relationship between BRAF mutations and tumor mutation burden (TMB) in lung cancer (LC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5292.
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Sharma, Kirti, Xue Fei, Yatao Shi, Christopher Browne, Dirk Walther, Caroline Daigle, Anand Ramanathan, et al. "Abstract LB037: E3 pairing and structural mechanisms underlying anti-tumor activity of clinical STAT3 degrader KT-333." Cancer Research 84, no. 7_Supplement (April 5, 2024): LB037. http://dx.doi.org/10.1158/1538-7445.am2024-lb037.
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Abstract To elucidate the underlying mechanisms of STAT3 degradation and the suitability of VHL as an E3 ligase partner for targeting STAT3 in cancer using our clinical degrader, KT-333. Signal transducer and activator of transcription 3 (STAT3) is an undrugged oncogenic transcription factor and its role as cancer driver and tumor microenvironment modulator has been validated in a multitude of studies. Based on it’s potential as a target for cancer therapeutics and limitations of prior approaches, we developed KT-333, a first-in-class, potent, highly selective, heterobifunctional STAT3 degrader currently in Phase 1 clinical trials. Here, based on STAT3 degradation by multiple E3s based degraders, structure of STAT3-KT333-VHL and a lysine site-resolved target ubiquitination model, we provide evidence for VHL as the ideal partner E3 for targeting STAT3 in cancer. We successfully identified potent and selective STAT3 degraders using either CRBN or VHL as the E3 ligase, but ultimately preferred VHL based degraders for their increased potency, and consistent STAT3 degradation across multiple cancer lines. KT-333, our VHL based clinical STAT3 degrader, induces a strong ternary complex between STAT3 and VHL. We present a high resolution cryo-electron microscopy based ternary complex structure of STAT3-KT333-VHL which provides mechanistic insights further validating VHL as the E3 of choice for deep, selective and fast STAT3 degradation. Specifically, KT-333 enables favorable protein-protein interactions between STAT3 and VHL, burying a large protein interface in the ternary complex to the extent typically observed only in native protein complexes. Additionally, the residues forming the STAT3-VHL interface are not conserved in other STAT family members corroborating with degradation selectivity observed with KT-333. Next, we leveraged this structure and generated a ubiquitination super-complex model by deploying a combination of biochemical and proteomics techniques and reveal that KT-333-induced ubiquitination occurs by precise targeting of specific lysine resides on STAT3. Furthermore, to decode the mechanism for KT-333 activity against SUDHL1 cell line both in vitro and in a mouse xenograft model, we measured temporal changes at protein level by discovery proteomics. Reduced expression of canonical STAT3 targets and down-regulation of cytokine-mediated signaling and cell cycle signature genes indicated that cell cycle arrest and subsequent apoptosis are the main drivers of efficacy in vitro and in vivo. In summary, we show that our clinical STAT3 degrader, KT-333, is designed and optimally paired with VHL resulting in a very stable ternary complex exhibiting properties of native protein complexes. Our data provides precise structural and molecular mechanisms behind potent, selective, consistent, and fast degradation of STAT3, and downstream mechanism of action observed in vitro and in vivo. Citation Format: Kirti Sharma, Xue Fei, Yatao Shi, Christopher Browne, Dirk Walther, Caroline Daigle, Anand Ramanathan, Richard Miller, Karen Yuan, Kiran Mahasenan, Sean Zhu, Xin Huang, Bin Yang. E3 pairing and structural mechanisms underlying anti-tumor activity of clinical STAT3 degrader KT-333 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB037.
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Chen, Yimeng, Xue Wang, Feng Du, Jian Yue, Yiran Si, Lina Cui, Bei Zhang, Binghe Xu, and Peng Yuan. "Abstract P1-08-12: The status of homologous recombination deficiency is a potential biomarker for platinum-based chemotherapy in triple-negative breast cancer." Cancer Research 82, no. 4_Supplement (February 15, 2022): P1–08–12—P1–08–12. http://dx.doi.org/10.1158/1538-7445.sabcs21-p1-08-12.
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Abstract BackgroundTriple-negative breast cancer (TNBC) is a subtype of breast cancer that is highly susceptible to recurrence and metastasis. The therapeutic drugs are limited due to the lack of effective biomarkers predicting the therapeutic efficacy and prognosis of disease. Previous studies have shown that platinum-containing regimens are effective for both early and advanced TNBC, therefore, it is particularly important to explore biomarkers for predicting the efficacy of platinum drugs and to screen the population sensitive to platinum drugs. Methods All patients with available tumor specimens from National Cancer Center in China were eligible for this prospective-retrospective study (n=189), including 149 patients with early TNBC (NCT01150513, CH-BC-007) and 40 patients with advanced TNBC (12-123/657, CH-BC-018) who are treated with or without platinum. The primary endpoint is disease-free survival (DFS) for early TNBC and progression free survival (PFS) for advanced TNBC. For HRD status and genomic signatures, indexed libraries were subjected to probe-based hybridization with a customized NGS panel targeting 733 cancer-related genes. 3DMed-HRD algorithm was evaluated based on loss of heterozygosity score (LOH), telomeric allelic imbalance score (TAI) and large-scale state transition score (LST) to characterize genomic instability using over 10,000 single-nucleotide polymorphisms distributed across human genome, adjusted by tumor ploidy and purity. HRD positive is defined by HRD score above the threshold (cut-off ≥30) and/or deleterious mutation in BRCA1/2. ResultsDeleterious BRCA1/2 mutations were detected in 21.2% (40/189) of TNBC patients and 48.1% (91/189) were defined as HRD positive. In advanced TNBC cohort, 21 patients received platinum-containing and 19 received platinum-free chemotherapy regimens for first-line chemotherapy. The progression-free survival (PFS) of the platinum-containing group was longer than that of the platinum-free group (median PFS 9.13 vs 2.97 months, HR 0.39, 95%CI, 0.19-0.81, P=0.011), and the PFS of patients with HRD positive was significantly longer than HRD negative patients (median PFS 13.6 vs 6.80 months, HR 0.38, 95%CI, 0.15-0.99, P=0.048) in platinum-containing group. Interestingly, HRD-positive patients have a significantly shorter PFS than HRD-negative in platinum-free group (median PFS 1.97 vs 4.52 months, HR 3.67, 95%CI, 1.20-11.22, P=0.023). For the HRD-positive patients, median PFS was significantly better in platinum-based group than platinum-free group (median PFS 13.6 vs 1.97 months, HR 0.12, 95%CI, 0.03-0.43, P=0.001). In early-stage TNBC cohort (n=149), 74 patients received platinum-containing and 75 received platinum-free chemotherapy regimens for adjuvant chemotherapy. In platinum-containing group, no statistically significant difference was found in DFS between HRD-positive and HRD-negative patients (P=0.118). High-risk TNBC group (Ki-67 ≥ 15%) analysis revealed that HRD-positive patients had a numerical better DFS than HRD-negative patients (HR 0.43, 95%CI, 0.12-1.50, P=0.180). Among patients with HRD-positive, patients in platinum-containing group had a tendency to benefit more than those in platinum-free group (HR 0.35, 95%CI, 0.11-1.10, P=0.062). Conclusions: We developed a novel algorithm to evaluate 3DMed-HRD status and highlights the potential utility of HRD in guiding chemotherapy for TNBC patients in this retrospective analysis. In comparison to platinum-free chemotherapy, the advanced TNBC HRD positive patients with advanced TNBC receiving platinum-based chemotherapy is a preferable regimen, and the HRD negative patients might be on the contrary. Prospective validation with larger sample size is needed. Citation Format: Yimeng Chen, Xue Wang, Feng Du, Jian Yue, Yiran Si, Lina Cui, Bei Zhang, Binghe Xu, Peng Yuan. The status of homologous recombination deficiency is a potential biomarker for platinum-based chemotherapy in triple-negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-08-12.
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Wu, C. Y., Q. Wang, J. Shi, X. Zhang, R. Du, J. Gu, Q. H. Liu, et al. "AB0455 BARICITINIB IN THE TREATMENT OF PATIENTS WITH MODERATE TO SEVERE ACTIVE RHEUMATOID ARTHRITIS IN CHINA: 24-WEEK RESULTS OF POST-MARKETING SAFETY STUDY." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 1418. http://dx.doi.org/10.1136/annrheumdis-2023-eular.2148.
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BackgroundBaricitinib, an orally selective inhibitor of JAK1 and JAK2, was approved for adult patients with moderate-to-severe rheumatoid arthritis (RA) in China. The recommended dose is 2mg once daily and 4mg once daily in patients who have inadequately responded to baricitinib 2mg once daily (for 3 months) or TNF inhibitors. A single-arm, prospective, non-interventional post-marketing safety study (PMSS) was conducted in Chinese RA patients to describe the safety and effectiveness of baricitinib at 24 weeks.ObjectivesTo describe the safety and effectiveness of baricitinib in real-world setting of treating patients with moderate to severe active RA.MethodsThis PMSS (starting July 2020) included 667 patients with RA treated with baricitinib (2 mg or/and 4mg/day) and followed up for 24 weeks. Safety and effectiveness (disease activity) were assessed for 24 weeks. All statistical analyses are descriptive.ResultsSafety analyses included 667 patients (females=82.3%, mean age=53.3 years, mean RA duration 86.9 months). 106 (15.9%) were ≥65 and <75years and 19 (2.8%) were ≥75 years. 29 (4.3%) had previously received biologic therapy. Baricitinib dose regimen was as follows: 2 mg/day, n = 580 (87.0%); 4 mg/day, n = 53 (7.9%); 2/4 mg, n = 34 (5.1%). Concomitant use of MTX and leflunomide occurred in 54.3% and 35.5%, respectively. The overall exposure of baricitinib was 262.1 patient-years; 197 (29.5%) patients withdrew from the study, mostly for patient’s decision (n = 101). Adverse events (AEs) occurred in 250 (37.5%) patients [serious: 28 (4.2%)]. Two patients (0.3%) died: one of pneumonia and one with no cause reported. The incidence of serious infection, herpes zoster and hepatotoxicity was 0.6%, 1.0%, and 3.4%, respectively. No case met laboratory criteria for potential Hy’s Law (ALT/AST ≥3 x ULN and TBL ≥2 x ULN). Malignancy occurred in one patient (thyroid cancer). No venous thromboembolism (VTE) or major adverse cardiovascular event (MACE) were reported during the study observation period (Table 1).In the effectiveness analysis at Week 24, the proportions of patients achieving remission/ low disease activity were 66.6% (235/353) for DAS28-CRP, 64.6% (228/353) for SDAI, and 63.5% (242/381) for CDAI (Figure 1).ConclusionIn conclusion, the safety and effectiveness profile of baricitinib in this Chinese PMSS was generally similar to that in the global RA population with no VTEs or MACE reported and no new safety signals.ReferencesNIL.Table 1.Safety summary among patients with RA treated with baricitinibn (%) PYE [EAIR]Safety Population (N=667)12 weeks24 weeksAE214 (32.08)124.04 [172.52]250 (37.48)198.58 [125.89]AEs related to study treatmentas judged by the investigator95 (14.24)139.99 [67.86]120 (17.99)236.65 [50.71]Death/2 (0.30)261.30 [0.77]SAE22 (3.30)147.03 [14.96]28 (4.20)256.72 [10.91]SAEs related to study treatmentas judged by the investigator8 (1.20)148.32 [5.39]10 (1.50)260.30 [3.84]Treatment discontinuation due to AEs20 (3.00)148.18 [13.50]24 (3.60)260.79 [9.20]AESISerious infection3 (0.45)148.52 [2.02]4 (0.60)260.99 [1.53]Hepatotoxicity16 (2.40)147.13 [10.87]23 (3.45)256.76 [8.96]VTE0148.63 [0.00]0261.30 [0.00]Herpes zoster, n (%)3 (0.45)7 (1.05)Malignancy, n (%)1 (0.15)1 (0.15)MACE, n (%)00Abbreviations: AE= adverse event; AESI= adverse event with special interest; EAIR= exposure-adjusted incidence rate; MACE= major adverse cardiovascular events; N= number of patients in the safety analysis set; n= number of patients in the specified category; PYE= patient-years of exposure; RA= rheumatoid arthritis; SAE= serious adverse event; VTE= venous thromboembolismUsed EAIR per 100 PYE (patient exposure censored at the event).AESI was based on the judgement of investigator recorded in eCRF (electronic case report form)MACE included myocardial infarction, cardiovascular death, and stroke.Acknowledgements:NIL.Disclosure of InterestsChan-yuan Wu: None declared, Qian Wang: None declared, Jian Shi: None declared, XIUYING ZHANG: None declared, Rong Du: None declared, Jieruo Gu: None declared, Qi-huan Liu: None declared, Jiao Yu Employee of: Eli Lilly and Company, Jia-wei Xu Employee of: Eli Lilly and Company, Yan-jie Zhang Employee of: Eli Lilly and Company, Hao Zhu Employee of: Eli Lilly and Company, Mengtao Li: None declared, Xiaofeng Zeng: None declared.
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Wu, Guodong, Haishun Du, Doohee Lee, Wonhyeong Kim, Yoolim Cha, Xinyu Zhang, and Dong-Joo Kim. "Wearable Conductive Polymer Matrix Composites for Breath Monitoring with Ammonia Detection." ECS Meeting Abstracts MA2022-02, no. 62 (October 9, 2022): 2284. http://dx.doi.org/10.1149/ma2022-02622284mtgabs.
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Conductive polymers, such as polyaniline (PANI), Polythiophene (PTh), polypyrrole (PPy), etc., are widely used for gas sensors due to their excellent electrical conductivity and low cost to manufacture [1]. In particular, PANI has attracted more attention due to its ease of synthesis, high environmental stability, and high reactivity with ammonia gas. In addition, the selection of acid-base dopant during the preparation process of polyaniline can adjust carrier concentrations for the change in electrical conduction or resistance to improve sensing properties. There have been many reports on the fabrication of flexible gas sensors using PANI [2-4]. Bandgar et al. [5] synthesized a low-temperature flexible polyaniline gas sensor by in-situ chemical oxidation polymerization of aniline on a polyethylene terephthalate (PET) substrate, showing 99% reproducibility, rapid response and recovery. Still, the response value was only 26% in 100 ppm ammonia atmosphere. Qi et al. [6] prepared a gas sensor by in-situ polymerization of aniline on non-woven fabric. The high air permeability of the fabric effectively improved the performance of the polyaniline-based gas sensor. Due to the outbreak of the COVID-19 pandemic, the use of face masks in public has become essential to reduce the spread of the virus. Some reports claim that the increased carbon dioxide in the mask over time may cause medical issues related to the respiratory system. Therefore, monitoring breathing air quality can help detect the wearer's vital conditions. In this study, we used a disposable mask as a flexible substrate to prepare polypropylene/carbon nanotube/polyaniline composite film through a layer-by-layer method. The polypropylene/carbon nanotube composite films were prepared by applying the carbon nanotube aqueous solution with surfactants evenly on the surface of a mask filter layer by a drop-coating method. Then, the in-situ polyaniline polymerization was performed on the surface of the polypropylene/carbon nanotube composite film through ammonium sulfate. The polypropylene/carbon nanotube /polyaniline composite film exhibits high sensitivity, fast sensing response/recovery time, room temperature operation, reliable flexibility, and cycle stability. The synthesized and wearable masks have demonstrated real-time detection respiratory rate and other breathing conditions such as CO2 and humidity. The ammonia gas sensing can also be used as a potential biomarker for health screening. The design and integration of multiple gas sensing materials in masks will help wearers better understand their own body conditions. References [1] Y. Jiang, N. Tang, C. Zhou, Z.Y. Han, H. Qu, X.X. Duan, et al., A chemiresistive sensor array from conductive polymer nanowires fabricated by nanoscale soft lithography, Nanoscale, 10(2018) 20578-86. [2] T.F. Wu, E. Gray, B.Q. Chen, A self-healing, adaptive and conductive polymer composite ink for 3D printing of gas sensors, J Mater Chem C, 6(2018) 6200-7. [3] D.Z. Zhang, Z.L. Wu, X.Q. Zong, et al., Flexible and highly sensitive H2S gas sensor based on in-situ polymerized SnO2/rGO/PANI ternary nanocomposite with application in halitosis diagnosis, Sensor Actuators B: Chem, 289(2019) 32-41. [4] C.H. Liu, H.L. Tai, P. Zhang, Z. Yuan, X.S. Du, G.Z. Xie, et al., A high-performance flexible gas sensor based on self-assembled PANI-CeO2 nanocomposite thin film for trace-level NH3 detection at room temperature, Sensor Actuators B: Chem, 261(2018) 587-97. [5] D.K. Bandgar, S.T. Navale, S.R. Nalage, R.S. Mane, F.J. Stadler, D.K. Aswal, et al., Simple and low-temperature polyaniline-based flexible ammonia sensor: a step towards laboratory synthesis to economical device design, J Mater Chem C, 3(2015) 9461-8. [6] J. Qi, X. Xu, X. Liu, K.T. Lau, Fabrication of textile based conductometric polyaniline gas sensor, Sensors and Actuators B: Chemical, 202(2014) 732-40.
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Wu, Jiong, Jian Zhang, Qingyuan Zhang, Yuping Sun, Hongtao Li, Yongmei Yin, Yehui Shi, et al. "Abstract PS15-01: A first-in-human phase 1 study of SIM0270, a brain-penetrant oral selective estrogen receptor degrader (SERD), in patients with ER+/HER2- locally advanced or metastatic breast cancer." Cancer Research 84, no. 9_Supplement (May 2, 2024): PS15–01—PS15–01. http://dx.doi.org/10.1158/1538-7445.sabcs23-ps15-01.
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Abstract Background: ER+/HER2- breast cancer is the most prevalent subtype, and endocrine-based therapy is the standard treatment. SIM0270 is a brain-penetrant and highly potent oral SERD that has demonstrated ER degradation and robust antitumor activity across various preclinical models, including those with intracranial xenograft tumors. Methods: This Phase 1 study evaluates the safety, pharmacokinetics and preliminary anti-tumor activity of SIM0270 as monotherapy and/or in combination with palbociclib or everolimus in patients with HR+/HER2- advanced or metastatic breast cancer. The primary objective of the phase 1a study, which consisted of the dose escalation stage and the dose expansion stage, is to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of SIM0270 as monotherapy. A Bayesian Optimal Interval design (BOIN) was adopted. SIM0270 was administered orally daily in 28-day cycles. Here we report preliminary monotherapy data. Results: As of May 22nd 2023, 45 female patients were enrolled, receiving SIM0270 at dose levels of 10 mg (n=4), 30 mg (n=4), 60 mg (n=9), 90 mg (n=6), 120 mg (n=11), 200 mg (n=5), or 300 mg (n=6). The median age was 56 years (range, 40-73) and ECOG performance status was 0 (18%) or 1 (82%). Most patients were heavily pretreated, with a median of 2 prior endocrine-based therapies (range, 0-5) and a median of 2 prior chemotherapies (range, 0-8). Thirty-one patients (69%) received prior fulvestrant, 42 (93%) received prior aromatase inhibitors, and 28 (62%) received prior CDK4/6 inhibitors. Visceral metastases were present in 33 patients (72%), and brain metastases in 7 patients (16%). The most common TEAEs were sinus bradycardia (51%), anemia (38%), hypalbuminaemia (31%), hypercholesterolaemia (24%), urinary tract infection (24%), asthenia (24%), electrocardiogram (ECG) QT prolonged (24%), and dizziness (22%). Most of the TEAEs were Grade 1-2. Grade 3 TRAEs were ECG QT prolonged, gamma-glutamyltransferase(γ-GT) increased and dizziness in 2 patients each. All AEs were manageable with dose interruption or reduction, except only 1 patient discontinued treatment of SIM0270 due to TRAE (Grade 3 γ-GT increased). Four patients experienced dose-limiting toxicities (DLTs): 1 with Grade 3 ECG QT prolonged at 200mg dose level, 1 with Grade 3 ECG QT prolonged and 2 with Grade 3 dizziness at 300mg dose level. All DLTs were resolved with dose interruption then reduction. The MTD of single-agent SIM0270 was established as 200mg QD. Pharmacokinetic analysis revealed a T1/2 of approximately 70 hours, and the AUC and Cmax increased in an approximately linear manner with dose escalation. Concentration in cerebrospinal fluid was measured in 1 patient after 41 days treatment of SIM0270, which is consistent with preclinical data and suggested high concentration of SIM0270 in the brain of patients. Among 31 response evaluable patients (per RECIST 1.1 criteria), 4 PRs (3 unconfirmed) were observed, yielding an ORR of 12.9%. Brain lesions were all stable in 4 evaluable patients per RANO-BM criteria. In patients with ESR1 mutations at baseline and samples available for analysis, 4/6(67%) exhibited a reduction or loss of mutant ESR1 upon SIM0270 treatment. Conclusions: Single-agent SIM0270 was well tolerated and showed favorable antitumor activity in heavily pretreated advanced or metastatic ER+/HER2- breast cancer patients, including those previously treated with CDK4/6 inhibitors and fulvestrant. Phase 1a dose expansion with single-agent SIM0270 is ongoing, and the RP2D will be determined based on further accumulative data of tolerability and efficacy. (NCT05293964) Citation Format: Jiong Wu, Jian Zhang, Qingyuan Zhang, Yuping Sun, Hongtao Li, Yongmei Yin, Yehui Shi, Wenfeng Li, Yunjiang Liu, Min Yan, Chen Yang, Lili Zhu, Yang Yang, Liting Xue. A first-in-human phase 1 study of SIM0270, a brain-penetrant oral selective estrogen receptor degrader (SERD), in patients with ER+/HER2- locally advanced or metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS15-01.
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Yao, Herui, Min Yan, Zhongsheng Tong, Xinhong Wu, Min-Hee Ryu, Jee Hyun Kim, John Park, et al. "Abstract CT175: Safety, tolerability, pharmacokinetics, and antitumor activity of SHR-A1811 in HER2-expressing/mutated advanced solid tumors: A global phase 1, multi-center, first-in-human study." Cancer Research 83, no. 8_Supplement (April 14, 2023): CT175. http://dx.doi.org/10.1158/1538-7445.am2023-ct175.
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Abstract Background: SHR-A1811 is an ADC comprised of a humanized anti-HER2 monoclonal antibody (trastuzumab), a cleavable linker, and a DNA topoisomerase I inhibitor payload. Here we assessed SHR-A1811 in HER2-expressing/mutated unresectable, advanced, or metastatic solid tumors. Methods: Pts were eligible if they had HER2 positive breast cancer (BC), HER2 positive gastric/GEJ carcinoma, HER2 low-expressing BC, HER2-expressing/mutated NSCLC, or other HER2-expressing/mutated solid tumors, and were refractory or intolerant to standard therapy. SHR-A1811 at doses of 1.0-8.0 mg/kg was given Q3W (IV). The primary endpoints were DLT, safety, and the RP2D. Results: From Sep 7, 2020 to Sep 28, 2022, 250 pts who had undergone a median of 3 prior treatment lines in the metastatic setting received at least one dose of SHR-A1811 in dose escalation, PK expansion, and indication expansion part. As of data cutoff on Sep 28, 2022, 1 pt experienced DLT. Treatment-related adverse events (TRAEs) were reported in 243 (97.2%) pts. Grade ≥3 TRAEs, serious TRAEs, and treatment-related deaths were reported in 131 (52.4%), 31 (12.4%), and 3 (1.2%) pts, respectively. Interstitial lung disease (AESI) was reported in 8 (3.2%) pts. Exposures of SHR-A1811, total antibody, and the payload were generally proportional to dose from 3.2 to 8.0 mg/kg. ORR was 61.6% (154/250, 95% CI 55.3-67.7) in all pts. Objective responses were observed in pts with HER2 positive BC (88/108, ORR 81.5%, 95% CI 72.9-88.3), HER2-low BC (43/77, ORR 55.8%, 95% CI 44.1-67.2), urothelial carcinoma (7/11), colorectal cancer (3/10), gastric/GEJ carcinoma (5/9), biliary tract cancer (5/8), NSCLC (1/3), endometrial cancer (1/2), and H&N cancer (1/1). Subgroup analyses of ORR are shown in Table 1. The 6-month PFS rate was 73.9% in all pts. Conclusions: SHR-A1811 was well-tolerated and showed promising antitumor activity in heavily pretreated advanced solid tumors. Table 1. Subgroup analyses of ORR No. of prior treatment lines in metastatic setting in all pts (N=250) HER2 positive BC (N=108) HER2-low BC (N=77) Other tumor types (N=65) ≤3 81.8% (45/55) 58.7% (27/46) 36.7% (18/49) >3 81.1% (43/53) 51.6% (16/31) 31.3% (5/16) Prior anti-HER2 therapies in pts with BC (N=185)* HER2 positive BC (N=108) HER2-low BC (N=77) All BC (N=185) Any 82.2% (88/107, 73.7-89.0) 68.8% (11/16, 41.3-89.0) 80.5% (99/123, 72.4-87.1) Trastuzumab 81.9% (86/105, 73.2-88.7) 75.0% (9/12, 42.8-94.5) 81.2% (95/117, 72.9-87.8) Pertuzumab 83.0% (39/47, 69.2-92.4) 100% (5/5, 47.8-100) 84.6% (44/52, 71.9-93.1) Pyrotinib 86.9% (53/61, 75.8-94.1) 71.4% (5/7, 29.0-96.3) 85.3% (58/68, 74.6-92.7) Lapatinib 80.0% (28/35, 63.1-91.6) 100% (1/1, 2.5-100) 80.6% (29/36, 64.0-91.8) T-DM1 82.4% (14/17, 56.6-96.2) 100% (3/3, 29.2-100) 85.0% (17/20, 62.1-96.8) Other HER2-ADC (except T-DM1)** 60.0% (9/15, 32.3-83.7) 50.0% (2/4, 6.8-93.2) 57.9% (11/19, 33.5-79.8) ORR in pts with tumor types other than BC (N=65) HER2 IHC3+ or IHC2+/ISH+ (N=36) HER2 IHC2+/ISH- or IHC1+ or unknown (N=29) All other tumor types (N=65) % (n/N) 38.9% (14/36) 31.0% (9/29) 35.4% (23/65) ORR was shown as % (n/N, 95% CI) or % (n/N). *ORR is calculated using the number of subjects previously treated with anti-HER2 cancer therapy in advanced/metastatic setting as denominator; 2-sided 95% CIs are estimated using Clopper-Pearson method. **Includes RC48-ADC, A166, DP303c, MRG002, ARX788, TAA013, DX126-262, PF-06804103, and BAT8001. Citation Format: Herui Yao, Min Yan, Zhongsheng Tong, Xinhong Wu, Min-Hee Ryu, Jee Hyun Kim, John Park, Yahua Zhong, Weiqing Han, Caigang Liu, Mark Voskoboynik, Qun Qin, Jian Zhang, Minal Barve, Ana Acuna-Villaorduna, Vinod Ganju, Seock-Ah Im, Changsheng Ye, Yongmei Yin, Amitesh C. Roy, Li-Yuan Bai, Yung-Chang Lin, Chia-Jui Yen, Hui Li, Ki Young Chung, Shanzhi Gu, Jun Qian, Yuee Teng, Yiding Chen, Yu Shen, Kaijing Zhao, Shangyi Rong, Xiaoyu Zhu, Erwei Song. Safety, tolerability, pharmacokinetics, and antitumor activity of SHR-A1811 in HER2-expressing/mutated advanced solid tumors: A global phase 1, multi-center, first-in-human study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT175.
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Thanh Huyen, Le, Dao Sy Duc, Nguyen Xuan Hoan, Nguyen Huu Tho, and Nguyen Xuan Viet. "Synthesis of Fe3O4-Reduced Graphene Oxide Modified Tissue-Paper and Application in the Treatment of Methylene Blue." VNU Journal of Science: Natural Sciences and Technology 35, no. 3 (September 20, 2019). http://dx.doi.org/10.25073/2588-1140/vnunst.4883.
Full textAbstract:
Graphene-based composites have received a great deal of attention in recent year because the presence of graphene can enhance the conductivity, strength of bulk materials and help create composites with superior qualities. Moreover, the incorporation of metal oxide nanoparticles such as Fe3O4 can improve the catalytic efficiency of composite material. In this work, we have synthesized a composite material with the combination of reduced graphene oxide (rGO), and Fe3O4 modified tissue-paper (mGO-PP) via a simple hydrothermal method, which improved the removal efficiency of the of methylene blue (MB) in water. MB blue is used as the model of contaminant to evaluate the catalytic efficiency of synthesized material by using a Fenton-like reaction. The obtained materials were characterized by SEM, XRD. The removal of materials with methylene blue is investigated by UV-VIS spectroscopy, and the result shows that mGO-PP composite is the potential composite for the color removed which has the removal efficiency reaching 65% in acetate buffer pH = 3 with the optimal time is 7 h.
Keywords
Graphene-based composite, methylene blue, Fenton-like reaction.
References
[1] Ma Joshi, Rue Bansal, Reng Purwar, Colour removal from textile effluents, Indian Journal of Fibre & Textile Research, 29 (2004) 239-259 http://nopr.niscair.res.in/handle/123456789/24631.[2] Kannan Nagar, Sundaram Mariappan, Kinetics and mechanism of removal of methylene blue by adsorption on various carbons-a comparative study, Dyes and pigments, 51 (2001) 25-40 https://doi.org/10.1016/S0143-7208(01)00056-0.[3] K Rastogi, J. N Sahu, B. C Meikap, M. N Biswas, Removal of methylene blue from wastewater using fly ash as an adsorbent by hydrocyclone, Journal of hazardous materials, 158 (2008) 531-540.https://doi.org/10.1016/j.jhazmat.2008.01. 105.[4] Qin Qingdong, Ma Jun, Liu Ke, Adsorption of anionic dyes on ammonium-functionalized MCM-41, Journal of Hazardous Materials, 162 (2009) 133-139 https://doi.org/10.1016/j.jhazmat. 2008.05.016.[5] Mui Muruganandham, Rps Suri, Sh Jafari, Mao Sillanpää, Lee Gang-Juan, Jaj Wu, Muo Swaminathan, Recent developments in homogeneous advanced oxidation processes for water and wastewater treatment, International Journal of Photoenergy, 2014 (2014). http://dx. doi.org/10.1155/2014/821674.[6] Herney Ramirez, Vicente Miguel , Madeira Luis Heterogeneous photo-Fenton oxidation with pillared clay-based catalysts for wastewater treatment: a review, Applied Catalysis B: Environmental, 98 (2010) 10-26 https://doi.org/ 10.1016/j.apcatb.2010.05.004.[7] Guo Rong, Jiao Tifeng, Li Ruifei, Chen Yan, Guo Wanchun, Zhang Lexin, Zhou Jingxin, Zhang Qingrui, Peng Qiuming, Sandwiched Fe3O4/carboxylate graphene oxide nanostructures constructed by layer-by-layer assembly for highly efficient and magnetically recyclable dye removal, ACS Sustainable Chemistry & Engineering, 6 (2017) 1279-1288 https://doi.org/10.1021/acssuschemeng.7b03635.[8] Sun Chao, Yang Sheng-Tao, Gao Zhenjie, Yang Shengnan, Yilihamu Ailimire, Ma Qiang, Zhao Ru-Song, Xue Fumin, Fe3O4/TiO2/reduced graphene oxide composites as highly efficient Fenton-like catalyst for the decoloration of methylene blue, Materials Chemistry and Physics, 223 (2019) 751-757 https://doi.org/ 10.1016/j.matchemphys.2018.11.056.[9] Guo Hui, Ma Xinfeng, Wang Chubei, Zhou Jianwei, Huang Jianxin, Wang Zijin, Sulfhydryl-Functionalized Reduced Graphene Oxide and Adsorption of Methylene Blue, Environmental Engineering Science, 36 (2019) 81-89 https://doi. org/10.1089/ees.2018.0157.[10] Zhao Lianqin, Yang Sheng-Tao, Feng Shicheng, Ma Qiang, Peng Xiaoling, Wu Deyi, Preparation and application of carboxylated graphene oxide sponge in dye removal, International journal of environmental research and public health, 14 (2017) 1301 https://doi.org/10.3390/ijerph14111301.[11] Yu Dandan, Wang Hua, Yang Jie, Niu Zhiqiang, Lu Huiting, Yang Yun, Cheng Liwei, Guo Lin, Dye wastewater cleanup by graphene composite paper for tailorable supercapacitors, ACS applied materials & interfaces, 9 (2017) 21298-21306 https://doi.org/10.1021/acsami.7b05318.[12] Wang Hou, Yuan Xingzhong, Wu Yan, Huang Huajun, Peng Xin, Zeng Guangming, Zhong Hua, Liang Jie, Ren MiaoMiao, Graphene-based materials: fabrication, characterization and application for the decontamination of wastewater and wastegas and hydrogen storage/generation, Advances in Colloid and Interface Science, 195 (2013) 19-40 https://doi. org/10.1016/j.cis.2013.03.009.[13] Marcano Daniela C, Kosynkin Dmitry V, Berlin Jacob M, Sinitskii Alexander, Sun Zhengzong, Slesarev Alexander, Alemany Lawrence B, Lu Wei, Tour James M, Improved synthesis of graphene oxide, ACS nano, 4 (2010) 4806-4814 https://doi.org/10.1021/nn1006368.[14] Zhang Jiali, Yang Haijun, Shen Guangxia, Cheng Ping, Zhang Jingyan, Guo Shouwu, Reduction of graphene oxide via L-ascorbic acid, Chemical Communications, 46 (2010) 1112-1114 http://doi. org/10.1039/B917705A [15] Gong Ming, Zhou Wu, Tsai Mon-Che, Zhou Jigang, Guan Mingyun, Lin Meng-Chang, Zhang Bo, Hu Yongfeng, Wang Di-Yan, Yang Jiang, Nanoscale nickel oxide/nickel heterostructures for active hydrogen evolution electrocatalysis, Nature communications, 5 (2014) 4695 https:// doi.org/10.1038/ncomms5695.[16] Wu Zhong-Shuai, Yang Shubin, Sun Yi, Parvez Khaled, Feng Xinliang, Müllen Klaus, 3D nitrogen-doped graphene aerogel-supported Fe3O4 nanoparticles as efficient electrocatalysts for the oxygen reduction reaction, Journal of the American Chemical Society, 134 (2012) 9082-9085 https://doi.org/10.1021/ja3030565.[17] Nguyen Son Truong, Nguyen Hoa Tien, Rinaldi Ali, Nguyen Nam Van, Fan Zeng, Duong Hai Minh, Morphology control and thermal stability of binderless-graphene aerogels from graphite for energy storage applications, Colloids and Surfaces A: Physicochemical and Engineering Aspects, 414 (2012) 352-358 https://doi.org/ 10.1016/j.colsurfa.2012.08.048.[18] Deng Yang, Englehardt James D, Treatment of landfill leachate by the Fenton process, Water research, 40 (2006) 3683-3694 https://doi.org/ 10.1016/j.watres.2006.08.009.
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Thinh, Nguyen Hong, Tran Hoang Tung, and Le Vu Ha. "Depth-aware salient object segmentation." VNU Journal of Science: Computer Science and Communication Engineering 36, no. 2 (October 7, 2020). http://dx.doi.org/10.25073/2588-1086/vnucsce.217.
Full textAbstract:
Object segmentation is an important task which is widely employed in many computer vision applications such as object detection, tracking, recognition, and retrieval. It can be seen as a two-phase process: object detection and segmentation. Object segmentation becomes more challenging in case there is no prior knowledge about the object in the scene. In such conditions, visual attention analysis via saliency mapping may offer a mean to predict the object location by using visual contrast, local or global, to identify regions that draw strong attention in the image. However, in such situations as clutter background, highly varied object surface, or shadow, regular and salient object segmentation approaches based on a single image feature such as color or brightness have shown to be insufficient for the task. This work proposes a new salient object segmentation method which uses a depth map obtained from the input image for enhancing the accuracy of saliency mapping. A deep learning-based method is employed for depth map estimation. Our experiments showed that the proposed method outperforms other state-of-the-art object segmentation algorithms in terms of recall and precision.
KeywordsSaliency map, Depth map, deep learning, object segmentation
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"Correction to: Suppression of Lipogenesis via Reactive Oxygen Species–AMPK Signaling for Treating Malignant and Proliferative Disease, by Fan XX, Leung ELH, Xie Y, Liu ZQ, Zheng YF, Yao ZJ, Lu LL, Wu JL, He JX, Yuan ZW, Fu J, Wei CL, Huang J, Xiao DK, Luo LX, Jiang ZB, Zhou YL, Kam RKT, and Liu L. Antioxid Redox Signal 28: 339–357, 2018. DOI: 10.1089/ars.2017.7090." Antioxidants & Redox Signaling 30, no. 4 (February 2019): 710. http://dx.doi.org/10.1089/ars.2017.7090.correx.
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Thi Thu Hoai, Nguyen, Nguyen Thuy Duong, Bui Thanh Tung, Dao Thi Vui, and Dang Kim Thu. "Comparing Acetylcholinesterase and Butyrylcholinesterase Inhibition Effect of Total Extract and Fractions with Alcaloid-Rich Extract of Huperzia Serrata (Thunb.) Trevis." VNU Journal of Science: Medical and Pharmaceutical Sciences 36, no. 1 (March 24, 2020). http://dx.doi.org/10.25073/2588-1132/vnumps.4214.
Full textAbstract:
Herbal extract, rich with natural compounds, has been used for medicinal purpose such as treating neurological disorders such as cognitive defection for a long period of time, often without significant adverse effects. We compared AChE and BuChE – inhibition effect of total extracts and fractions of Huperzia serrata (Thunb.) Trevis. with alcaloid-rich extract. Our samples were subjected under supersonic extraction with ethanol 50o as solvent and fractionally extracted with n-hexane, EtOAc and n-butanol, respectively; alcaloid-rich extract was collected simutaneously. Ellman’s method was used to assay AChE and BuChE inhibition activity. Results: Alcaloid-rich extraction proved to be the superior AChE inhibiting agent, its activity nearly 6 fold of the most active Huperzia serrata extraction with IC50 value of 7.93 (5.43-10.98) µg/ml. While the fractions as well as the total extract did not provide any BuChE inhibition activity, alcaloid-rich extract showed weak ability (IC50 at 76.67 (64.78 – 91.84) µg/ml). Overall, the superior enzyme inhibition effect of alcaloid-rich extract might open a new approach in preventing and treating neurological disorders such as alzheimer’s.
Keywords
Huperzia serrata (Thunb.) Trevis, alcaloid, Acetylcholinesrerase inhibitors (AChE); butyrylcholinesterase (BuChE), Alzheimer.
References
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