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A phase Ⅰ study of Hemay022, an irreversible dual EGFR/HER2 tyrosine kinase inhibitor in Chinese patients with HER2-positive advanced breast cancer

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Chinese Journal of Cancer Research 2024年第1期36卷 46-54页

作者： Pin Zhang Lin Wang Yueying Zhen Zhihong Wang Hesheng Zhang Richard Jones binghe Xu Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Tianjin Hemay Pharmaceutical Co. LTDTianjin 300308China

Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor(EGFR)/human epidermal growth factor receptor 2(HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics,tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer ***: Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg QD and 300 mg BID. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day *** samples were obtained on d 1 and d 28. Clinical responses were assessed every eight ***: Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea(85.7%), vomiting(28.6%), nausea(25.0%) and decreased appetite(17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response(CR), and three achieved partial response(PR). The objective response rate(ORR) and disease control rate(DCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival(PFS) was3.98 ***: Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase Ⅲ trial(No. NCT05122494).

关键词： Advanced breast cancer HER2-positive Hemay022 first-in-human trial

An immunogenic cell death-related signature for prediction of prognosis and response to immunotherapy in breast cancer

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Chinese Medical Journal 2024年第4期137卷 487-489页

作者： Cong Li Fengzhu Guo Jingtong Zhai Xiaohan Liu Zhijun Li binghe Xu Department of Medical Oncology National Cancer CenterNational Clinical Research Center for CancerCancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Medical Oncology Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060China Department of Medical Oncology Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Department of Histology and Embryology Basic Medical CollegeChina Medical UniversityShenyangLiaoning 110122China

To the Editor:Tumor immune microenvironment plays a key role in breast cancer development and progression,which determines the long-term survival of breast cancer *** data have revealed that the application of cancer immunotherapy has some limitations,including generating weak immune responses due to inadequate delivery of immunostimulants to the immune cells.^([1])Thus,current clinical efforts are primarily focused on developing immune-based chemotherapy that can convert non-responders to responders.^([2])Immunogenic cell death(ICD)is a form of regulated cell death that is sufficient to activate an adaptive immune response.

关键词： breast immunotherapy chemotherapy

重思维、多途径促核心素养的形成——以“测量电源电动势和内阻的误差分析”为例

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物理教学 2024年第9期46卷 24-27页

作者：陈炳河福建省泉州市培元中学福建362000

科学探究是一种综合能力,也是学习物理的主要方式,而误差分析作为科学探究的重要环节,是促进学生核心素养形成的有效途径之一。在测量电源电动势和内阻的常规实验方案中,系统误差的主要来源为电压表分流或电流表分压。在进行具体的误差... 详细信息

科学探究是一种综合能力,也是学习物理的主要方式,而误差分析作为科学探究的重要环节,是促进学生核心素养形成的有效途径之一。在测量电源电动势和内阻的常规实验方案中,系统误差的主要来源为电压表分流或电流表分压。在进行具体的误差分析时,可以采用不同的分析方法,不同分析方法对学生的能力要求各有侧重,对促进学生核心素养形成的作用也不同。文章就解析法、图象法、等效电源法三种误差分析方法进行详细阐述。

关键词：系统误差解析法图象法等效电源

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早发性胃癌的研究进展与未来方向

中华胃肠外科杂志 2024年第5期27卷 521-526页

作者：赵冰鹤王鑫鑫解放军总医院第一医学中心普通外科医学部北京100853 南开大学医学院天津300071

早发性胃癌(EOGC)是指发病年龄较为年轻的胃癌。EOGC分化较差,恶性程度较高。遗传物质和环境暴露因素可能是胃癌早发的主要原因。延长EOGC患者的生存期和提高患者的生活质量是我们未来主要的研究目标。本文将从EOGC的临床病理学特征、... 详细信息

早发性胃癌(EOGC)是指发病年龄较为年轻的胃癌。EOGC分化较差,恶性程度较高。遗传物质和环境暴露因素可能是胃癌早发的主要原因。延长EOGC患者的生存期和提高患者的生活质量是我们未来主要的研究目标。本文将从EOGC的临床病理学特征、分子遗传学、微生态环境、预测方法、治疗方案及预后等方面阐述目前EOGC的研究现状与进展,并探讨未来的研究方向。

关键词：胃癌,早发性研究进展诊疗方向

温度效应对斜拉桥拉索张拉过程中索力损失的影响研究

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市政技术 2024年第6期42卷 112-117页

作者：薛炳贺中铁十八局集团有限公司勘察设计院天津300222

为研究温度效应对斜拉桥拉索张拉过程中索力损失的影响,依托浙江省嵊州市小砩桥工程,采用Midas civil软件建立全桥有限元模型,结合拉索张拉过程中的索力和塔梁位移等实测数据对斜拉桥拉索张拉过程中的索力损失进行了研究,分析了温度对... 详细信息

为研究温度效应对斜拉桥拉索张拉过程中索力损失的影响,依托浙江省嵊州市小砩桥工程,采用Midas civil软件建立全桥有限元模型,结合拉索张拉过程中的索力和塔梁位移等实测数据对斜拉桥拉索张拉过程中的索力损失进行了研究,分析了温度对于张拉索力损失的影响机理。研究结果表明,温度效应会导致斜拉桥主塔、主梁、索体三者的变形不协调,进而导致拉索索力的不均匀损失。基于研究结果提出了斜拉桥拉索张拉的适用环境条件建议,为同类型斜拉桥的设计和建造提供了重要参考。

关键词：斜拉桥拉索索力损失温度效应

维普期刊数据库博看期刊

HER2阳性晚期乳腺癌靶向治疗药物分类及临床研究进展

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中国肿瘤 2024年第7期33卷 583-595页

作者：姜明霞李俏徐兵河国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院北京100021

人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)是乳腺癌已知的重要分子靶点。HER2作为原癌基因之一,通常与侵袭性、复发转移及较差预后相关。抗HER2药物曲妥珠单抗的临床应用,大大改善了HER2阳性乳腺癌的诊疗模... 详细信息

人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)是乳腺癌已知的重要分子靶点。HER2作为原癌基因之一,通常与侵袭性、复发转移及较差预后相关。抗HER2药物曲妥珠单抗的临床应用,大大改善了HER2阳性乳腺癌的诊疗模式和预后,并成为乳腺癌抗HER2靶向治疗的里程碑。HER2阳性晚期乳腺癌患者除存在禁忌情况外,应尽早进行抗HER2治疗。全文就HER2阳性晚期乳腺癌靶向治疗的药物分类及其研究进展作一综述,以期为晚期乳腺癌靶向治疗研究提供新思路。

关键词：晚期乳腺癌人表皮生长因子受体2 靶向治疗单克隆抗体抗体偶联药物

Overcoming resistance to endocrine therapy in hormone receptorpositive human epidermal growth factor receptor 2-negative(HR^(+)/HER2^(-))advanced breast cancer:a meta-analysis and systemic review of randomized clinical trials

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Frontiers of Medicine 2021年第2期15卷 208-220页

作者： Wenjie Zhu binghe Xu National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciencesand Peking Union Medical CollegeBeijing 100021China

New targeted therapies have been developed to overcome resistance to endocrine therapy(ET)and improve the outcome of HR^(+)/HER2^(-)advanced breast cancer(ABC).We conducted a meta-analysis and systemic review on randomized controlled trials evaluating various targeted therapies in combination with ET in HR^(+)/HER2^(-)*** and EMBASE databases were searched for eligible *** ratios(HRs)for progression-free survival(PFS),odds ratios(ORs)for objective response rate(ORR),clinical benefit rate(CBR),and toxicity were ***-six studies with data on 10347 patients were included and *** addition of cyclin-dependent kinase 4/6 inhibitors to ET significantly improved median PFS(pooled HR=0.547,P<0.001),overall survival(pooled HR=0.755,P<0.001),and tumor response rates(ORR,pooled OR=1.478,P<0.001;CBR,pooled OR=1.201,P<0.001)with manageable toxicities(pooled OR=3.280,P<0.001).The mammalian targets of rapamycin inhibitors and exemestane were not clinically beneficial for this pooled population including ET-naïve and ET-resistant *** improvement in PFS(pooled HR=0.686,P<0.001)yet pronounced toxicities(pooled OR=2.154,P<0.001)were noted in the combination of phosphatidylinositol-4,5-bisphosphate 3-kinase inhibitors with *** studies are warranted to optimize the population and the dosing sequence of these available options.

关键词： endocrine-resistant HR^(+)/HER2^(-)advanced breast cancer randomized clinical trials meta-analysis targeted therapy

Nature’s marvels endowed in gaseous molecules Ⅰ:Carbon monoxide and its physiological and therapeutic roles

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Acta Pharmaceutica Sinica B 2021年第6期11卷 1434-1445页

作者： Xiaoxiao yang Wen Lu Christopher P.Hopper Bowen Ke binghe Wang Department of Chemistry and Center for Diagnostics and Therapeutics Georgia State UniversityAtlantaGA 30303USA Institut für Experimentelle Biomedizin Universit?tsklinikum WürzburgBavaria 97080Germany Department of Anesthesiology West China HospitalChengdu 610041China

Nature has endowed gaseous molecules such as O_(2),CO_(2),CO,NO,H2 S,and N2 with critical and diverse roles in sustaining life,from supplying energy needed to power life and building blocks for life ’s physical structure to mediating and coordinating cellular *** this article,we give a brief introduction of the complex functions of the various gaseous molecules in life and then focus on carbon monoxide as a specific example of an endogenously produced signaling molecule to highlight the importance of this class of *** past twenty years have seen much progress in understanding CO’s mechanism(s) of action and pharmacological effects as well as in developing delivery methods for easy *** remarkable trait of CO is its pleiotropic effects that have few parallels,except perhaps its sister gaseous signaling molecules such as nitric oxide and hydrogen *** review will delve into the sophistication of CO-mediated signaling as well as its validated pharmacological functions and possible therapeutic applications.

关键词： Carbon monoxide Gasotransmitter Gaseous signaling molecule CO releasing molecule Organic CO prodrug Homeostasis Pleiotropic effect Yin and yang

Evaluation of the transfer function of human pulse system based on signal detection

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Chinese Science Bulletin 1999年第17期44卷 1566-1571页

作者： binghe Wang Jinglin Xiang Yong yang Liqin Zhi Wei Zheng Northwestern Polytech Univ Coll Marine Engn Xian 710072 Peoples R China Xian Tradit Chinese Med Hosp Cardiovasc Sect Xian 710005 Peoples R China

On the basis of the pulse source-system model, a convenient and effective method used to evaluate the transfer function of human pulse system has been proposed by using the principle of signal detection and system analysis. The experimental results show that the pulse system of the normal pulse has 3 formants; the smooth pulse, 2 formants; the wiry pulse, 4 formants; and the thready pulse, only 1 formant. Formant frequencies reflect the resonance behaviour of the arterial system.

关键词： human pulse system (HPS) signal detection transfer function frequency characteristics formants.