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| 1 | Safety,tolerability,and pharmacokinetics of BAT8001 in patients with HER2-positive breast cancer:An open-label,dose-escalation,phase I study显示文摘Background:The introductions of anti-human epidermal growth factor receptor-2(HER2)agents have significantly improved the treatment outcome of patients with HER2-positive breast cancer.BAT8001 is a novel antibodydrug conjugate targeting human epidermal growth factor receptor-2(HER2)-expressing cells composed of a trastuzumab biosimilar linked to the drug-linker Batansine.This dose-escalation,phase I study was designed to assess the safety,tolerability,pharmacokinetics,and preliminary anti-tumor activity of BAT8001 in patients with HER2-positive locally advanced or metastatic breast cancer.Methods:This trial was conducted in subjects with histologically confirmed HER2-positive breast cancer(having evaluable lesions and an Eastern Cooperative Oncology Group performance status of 0 or 1)using a 3+3 design of escalating BAT8001 doses.Patients received BAT8001 intravenously in a 21-day cycle,with dose escalation in 5 cohorts:1.2,2.4,3.6,4.8,and 6.0 mg/kg.The primary objective was to evaluate the safety and tolerability of BAT8001.Preliminary activity of BAT8001 was also assessed as a secondary objective.Results:Between March 2017 to May 2018,29 HER2-positive breast cancer patients were enrolled.The observed dose-limiting toxicities were grade 4 thrombocytopenia and grade 3 elevated transaminase.The maximum tolerated dose was determined to be 3.6 mg/kg.Grade 3 or greater adverse events(AEs)occurred in 14(48.3%)of 29 patients,including thrombocytopenia in 12(41.4%)patients,aspartate aminotransferase increased in 4(13.8%)patients,γ-glutamyl transferase increased in 2(6.9%)patients,alanine aminotransferase increased in 2(6.9%)patients,diarrhea in 2(6.9%)patients.Objective response was observed in 12(41.4%,95%confidence interval[CI]=23.5%-61.1%)and disease control(including patients achieving objective response and stable disease)was observed in 24(82.8%,95%CI=64.2%-94.2%)patients.Conclusions:BAT8001 demonstrated favorable safety profiles,with promising anti-tumor activity in patients with HER2-positive locally advanced or metastatic breast cancer.BAT8001 has the potential to provide a new therapeutic option in patients with metastatic HER2-positive breast cancer. | Ruoxi Hong Wen Xia Liye Wang Kaping Lee Qianyi Lu Kuikui Jiang Shengfeng Li Jinquan Yu Jin Wei Weijia Tang Danyang Zhou Xin An Jiajia Huang Cong Xue Xiwen Bi Yanxia Shi Zhongyu Yuan Fei Xu Shusen Wang | 2021 | Cancer Communications2021，41，2： | 2 |
| 2 | Geochronology and Geochemistry of Late Devonian I- and A-Type Granites from the Xing’an Block,NE China:Implications for Slab Break-off during Subduction of the Hegenshan-Heihe Ocean显示文摘We present detailed geochronological,geochemical,and zircon Hf isotopic data for Late Paleozoic granitic rocks from Handagai and Zhonghe plutons in the Xing’an Block,NE China,aiming to provide constraints on their origin and tectonic implications.New zircon U-Pb ages indicate they were formed in the Late Devonian(ca.379 Ma) immediately after a striking 50 Ma magmatic lull(ca.430-380 Ma) in the Xing ’ an Block.Petrological and geochemical features suggest that the Handagai monzogranites and Zhonghe alkali-feldspar granites are I- and A-type granites,respectively,although both of them have high-K calc-alkaline features and positive zircon ε_(Hf)(t) values(+3.47 to +10.77).We infer that the Handagai monzogranites were produced by partial melting of juvenile basaltic crustal materials under a pressure of <8-10 kbar,whereas the Zhonghe alkali-feldspar granites were generated by partial melting of juvenile felsic crustal materials at shallower depths(P ≤ 4 kbar).Our results,together with published regional data,indicate their generation involves a subduction-related extensional setting.Slab break-off of the Hegenshan-Heihe oceanic plate may account for the subduction-related extensional setting,as well as the transformation of arc magmatism from the Early-Middle Devonian lull to the Late Devonian-Early Carboniferous flare-up in the Xing’an Block. | Zheng Ji Wenchun Ge Hao Yang Yanlong Zhang Yu Dong Junhui Bi Xiwen Liu | 2022 | Journal of Earth Science2022，33，1： | 1 |
| 3 | SYK-mediated epithelial cell state is associated with response to c-Met inhibitors in c-Met-overexpressing lung cancer显示文摘Genomic MET amplification and exon 14 skipping are currently clinically recognized biomarkers for stratifying subsets of non-small cell lung cancer(NSCLC)patients according to the predicted response to c-Met inhibitors(c-Metis),yet the overall clinical benefit of this strategy is quite limited.Notably,c-Met protein overexpression,which occurs in approximately 20–25%of NSCLC patients,has not yet been clearly defined as a clinically useful biomarker.An optimized strategy for accurately classifying patients with c-Met overexpression for decision-making regarding c-Meti treatment is lacking.Herein,we found that SYK regulates the plasticity of cells in an epithelial state and is associated with their sensitivity to c-Metis both in vitro and in vivo in PDX models with c-Met overexpression regardless of MET gene status.Furthermore,TGF-β1 treatment resulted in SYK transcriptional downregulation,increased Sp1-mediated transcription of FRA1,and restored the mesenchymal state,which conferred resistance to c-Metis.Clinically,a subpopulation of NSCLC patients with c-Met overexpression coupled with SYK overexpression exhibited a high response rate of 73.3%and longer progression-free survival with c-Meti treatment than other patients.SYK negativity coupled with TGF-β1 positivity conferred de novo and acquired resistance.In summary,SYK regulates cell plasticity toward a therapy-sensitive epithelial cell state.Furthermore,our findings showed that SYK overexpression can aid in precisely stratifying NSCLC patients with c-Met overexpression regardless of MET alterations and expand the population predicted to benefit from c-Met-targeted therapy. | Ji Zhou Xu-Chao Zhang Shan Xue Mengdi Dai Yueliang Wang Xia Peng Jianjiao Chen Xinyi Wang Yanyan Shen Hui Qin Bi Chen Yu Zheng Xiwen Gao Zuoquan Xie Jian Ding Handong Jiang Yi-Long Wu Meiyu Geng Jing Ai | 2023 | Signal Transduction and Targeted Therapy2023，8，6： | 0 |
| 4 | Nail pigmentation induced by chemotherapy:an observational study of patients with early-stage breast cancer显示文摘Purpose:Chemotherapy-induced nail pigmentation is a common adverse efect,but prospective studies focussing on its onset,recovery,and severity are few.We aim to evaluate the pattern of chemotherapy-induced nail pigmentation in early-stage breast cancer patients by calculating the comprehensive score based on hyperpigmentation area and color depth of the nail plate.Methods:This prospective,observational study was conducted between February 2019 and December 2019.Early-stage breast cancer patients scheduled to receive anthracyclines combined with cyclophosphamide or taxanecontaining regimens were enrolled.The clinicopathologic characteristics and treatment protocols were collected.The onset,patterns,and duration of nail changes were photographed and recorded regularly.Results:A total of 90 patients were enrolled.The most common nail change was nail pigmentation(n=81,90.0%),followed by onycholysis(n=39,43.3%),Beau’s lines(n=19,21.1%),Mees’lines(n=16,17.8%),Muehrcke’s lines(n=7,7.8%),and hemorrhage(n=1,1.1%).Forty-four(48.9%)patients developed severe nail pigmentation.The median onset time of nail pigmentation was 37 days after the initiation of chemotherapy.At the latest follow-up,55(67.9%)patients achieved remission of melanonychia with the median recovery time of 118 days.The median duration of nail pigmentation was 214 days.Conclusion:Our study revealed the specifc pattern of chemotherapy-induced nail pigmentation,which onsets early and recovers slowly with a high incidence of severe nail pigmentation,in early-stage breast cancer patients.The results provide reference for further intervention studies.Trial Registration:ClinicalTrials.gov Identifer:NCT04215744.Registered 30 December 2019—Retrospectively registered. | Kuikui Jiang Simei Shi Qiulian Lin Peng Sun Luan Zhang Zhongyu Yuan Ruoxi Hong Yanxia Shi Xia Liu Jingmin Zhang Jiajia Huang Xiwen Bi Wen Xia Qianyi Lu Qiufan Zheng Shusen Wang Fei Xu | 2022 | Holistic Integrative Oncology2022，1，1： | 0 |
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