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Breast cancer:an up-to-date review and future perspectives

Cancer Communications 2022年第10期42卷 913-936页

作者： ruoxi hong Binghe Xu Department of Medical Oncology Sun Yat-Sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdong 510060P.R.China State Key Laboratory of Molecular Oncology and Department of Medical Oncology Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100006P.R.China

Breast cancer is the most common cancer worldwide.The occurrence of breast cancer is associated with many risk factors,including genetic and hereditary predisposition.Breast cancers are highly heterogeneous.Treatment strategies for breast cancer vary by molecular features,including activation of human epidermal growth factor receptor 2(HER2),hormonal receptors(estrogen receptor[ER]and progesterone receptor[PR]),gene mutations(e.g.,mutations of breast cancer 1/2[BRCA1/2]and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha[PIK3CA])and markers of the immune microenvironment(e.g.,tumor-infiltrating lymphocyte[TIL]and programmed death-ligand 1[PDL1]).Early-stage breast cancer is considered curable,for which local-regional therapies(surgery and radiotherapy)are the cornerstone,with systemic therapy given before or after surgery when necessary.Preoperative or neoadjuvant therapy,including targeted drugs or immune checkpoint inhibitors,has become the standard of care for most early-stage HER2-positive and triple-negative breast cancer,followed by risk-adapted post-surgical strategies.For ER-positive early breast cancer,endocrine therapy for 5-10 years is essential.Advanced breast cancer with distant metastases is currently considered incurable.Systemic therapies in this setting include endocrine therapy with targeted agents,such as CDK4/6 inhibitors and phosphoinositide 3-kinase(PI3K)inhibitors for hormone receptor-positive disease,anti-HER2 targeted therapy for HER2-positive disease,poly(ADP-ribose)polymerase inhibitors for BRCA1/2 mutation carriers and immunotherapy currently for part of triple-negative disease.Innovation technologies of precision medicine may guide individualized treatment escalation or de-escalation in the future.In this review,we summarized the latest scientific information and discussed the future perspectives on breast cancer.

关键词： PIK3CA Breast cancer

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CPSF4 promotes triple negative breast cancer metastasis by upregulating MDM4

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Signal Transduction and Targeted Therapy 2021年第6期6卷 1675-1677页

作者： Kaping Lee Qiufan Zheng Qianyi Lu Fei Xu Ge Qin Qinglian Zhai ruoxi hong Miao Chen Wuguo Deng Shusen Wang Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouChina The Sixth Affiliated Hospital of Sun Yat-Sen University GuangzhouChina

Dear Editor,Breast cancer(BrC)is the most common cancer in women.Triple negative BrC(TNBC)is the subtype with highly aggressive clinical behaviors and heterogeneity.Metastasis is the leading cause of TNBC-related deaths,but its mechanism is not well-understood.Apart from PIK3CA,TP53,and PTEN,few recurrent mutations have been identified in TNBC so far,suggesting that TNBC phenotype could be driven by nongenetic alterations such as aberrant expression of oncogenes.

关键词： PIK3CA cancer alterations

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Defect of SLC38A3 promotes epithelial-mesenchymal transition and predicts poor prognosis in esophageal squamous cell carcinoma

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Chinese Journal of Cancer Research 2020年第5期32卷 547-563页

作者： Rui Liu ruoxi hong Yan Wang Ying Gong Danna Yeerken Di Yang Jinting Li Jiawen Fan Jie Chen Weimin Zhang Qimin Zhan Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital&InstituteBeijing 100142China State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhou 510060China

Objective: Solute carrier family 38(SLC38 s) transporters play important roles in amino acid transportation and signaling transduction. However, their genetic alterations and biological roles in tumors are still largely unclear.This study aimed to elucidate the genetic signatures of SLC38 s transporters and their implications in esophageal squamous cell carcinoma(ESCC).Methods: Analyses on somatic mutation and copy number alterations(CNAs) of SLC38 A3 were performed as described. Immunohistochemistry(IHC) assay and Western blot assay were used to detect the protein expression level. MTS assay, colony formation assay, transwell assay and wound healing assay were used to explore the malignant phenotypes of ESCC cells. Immunofluorescence assay was used to verify the colocalization of two indicated proteins and immunopreciptation assay was performed to confirm the interaction of proteins.Results: Our findings revealed that SLC38 s family was significantly disrupted in ESCC, with high frequent CNAs and few somatic mutations. SLC38 A3 was the most frequent loss gene among them and was linked to poor survival and lymph node metastasis. The expression of SLC38 A3 was lower in tumor tissues compared to that in normal tissues, which was also significantly associated with worse clinical outcome. Further experiments revealed that depletion of SLC38 A3 could promote EMT in ESCC cell lines, and the interaction of SLC38 A3 and SETDB1 might lead to the reduced transcription of Snail. Pharmacogenomic analyses demonstrated that fifteen inhibitors were showed significantly correlated with SLC38 A3 expression.Conclusions: Our investigations have provided insights that SLC38 A3 could act as a suppressor in EMT pathway and serve as a prognostic factor and predictor of differential drug sensitivities in ESCC.

关键词： Amino acid transporter esophageal squamous cell carcinoma epithelial-mesenchymal transition genomic alterations SLC38A3 SETDB1 Snail

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Metronomic chemotherapy of cyclophosphamide plus methotrexate for advanced breast cancer:Real-world data analyses and experience of one center

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Cancer Communications 2020年第5期40卷 222-233页

作者： Qianyi Lu Kaping Lee Fei Xu Wen Xia Qiufan Zheng ruoxi hong Kuikui Jiang Qinglian Zhai Yuan Li Yanxia Shi Zhongyu Yuan Shusen Wang Department of Medical Oncology State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhouGuangdong510060P.R.China

Background:Real-world data of the CM regimen[cyclophosphamide(CTX)plus methotrexate(MTX)]in metronomic pattern for advanced breast cancer is limited to small-sample or retrospective studies.This study was aimed to determine the effectiveness and safety of CM regimen in treating advanced breast cancer and to identify which patients are most likely to benefit from metronomic CM regimen.Methods:Patients with advanced breast cancer who received the metronomic CM regimen at least once between January 2009 and February 2019 in Sun Yat-sen University Cancer Center were included.Clinicopathological characteristics were collected.Overall survival(OS)and progression-free survival(PFS)were assessed using Kaplan-Meier estimates.Characteristics between patients with PFS<6 months and≥6 months were compared using the Chi-square test.Univariate and multivariate Cox regression model was used to estimate the prognostic factors for PFS and OS.Results:A total of 186 patients were included.The median age and follow-up were 49 years and 13.3 months,respectively.Over 50%of the patients were estrogen receptor/progesterone receptor-positive,and 60.8%had been heavily treated(≥3 lines).The objective response rate was 3.8%,the disease control rate at 12 weeks was 41.4%,and the clinical benefit rate at 24 weeks was 31.2%(58/186).The median PFS was 4.0 months[95%confidence interval(CI):3.6-4.7 months],the median duration of clinical benefit was 9.5 months(95%CI:8.2-10.8 months),and the median OS was 26.8 months(95%CI:20.9-37.7 months).Multivariate analysis for PFS revealed the CM regimen as maintenance therapy and no liver metastasis as favorable prognostic factors.Furthermore,patients without liver metastasis were more likely to have a PFS over 6 months than those with liver involvement(P=0.022).Liver,lymph node,and brain metastases were unfavorable prognostic factors for OS.The CM regimen was well-tolerated without newly reported adverse events.Conclusions:The CM regimen was effective in selected patients.In clinical practice,it would be be

关键词： metronomic chemotherapy advanced breast cancer cyclophosphamide methotrexate real-world

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Safety,tolerability,and pharmacokinetics of BAT8001 in patients with HER2-positive breast cancer:An open-label,dose-escalation,phase I study

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Cancer Communications 2021年第2期41卷 171-182页

作者： 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 Department of Medical Oncology Sun Yat-Sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdong 510060P.R.China Biology Research Department Bio-Thera SolutionsLtd.GuangzhouGuangdong 510060P.R.China Clinical Development Department Bio-Thera SolutionsLtd.GuangzhouGuangdong 510060P.R.China

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

关键词： BAT8001 antibody-drug conjugate HER2-postive breast cancer dose escalation maximum tolerated dose

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Nail pigmentation induced by chemotherapy:an observational study of patients with early-stage breast cancer

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Holistic Integrative Oncology 2022年第1期1卷 145-153页

作者： 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 State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine651 Dongfeng Road EastGuangzhou 510060People’s Republic of China Department of Pathology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhou 510060People’s Republic of China

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.

关键词： Nail pigmentation Chemotherapy Nail toxicity Breast cancer

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A Solution-Processed n-Type Conducting Polymer Without Side Chains Formed via Nonmetal-Participated Polymerization and in Situ n-Doping

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CCS Chemistry 2023年第11期5卷 2534-2544页

作者： Haoran Tang Houji Cai Haiyang Zhao Ziyang Liu ruoxi Tan Fei Huang Institute of Polymer Optoelectronic Materials and Devices State Key Laboratory of Luminescent Materials and DevicesSouth China University of Technology(SCUT)Guangzhou 510640

Solution-processed conducting polymers(CPs)are emerging as promising multifunctional materials and are motivating the development of several electronic applications.However,there are fewer highperformance electron conduction-dominated n-type CPs than p-types.Thus,the exploration of other material designs and synthesis methods is required.Accordingly,we developed a facile metal catalystfree method by combining polymerization and in situ n-doping to produce an n-type conducting polymer,poly(benzodithiophenedione)(PBTDO).The doping procedure enabled interaction between the charged conjugated backbones and solvent,dimethyl sulfoxide,making the doped conducting polymer soluble without the assistance of side chains or surfactants.PBTDO exhibited an extremely low-lying reduction level,moderate conductivity,and good air stability with potential applications in n-type organic thermoelectric devices.Moreover,it was found that the in situ doping efficiency in the reaction was highly dependent on the energy level and backbone planarity.Doping cannot occur for polymers with a high lowest unoccupied molecular orbital level and distorted conjugated chains prevent a high doping efficiency from being obtained.This study gains deeper insight into the n-doping mechanisms of conjugated polymers,with guidance for the design of highperformance n-type CPs.

关键词： conducting polymer nonmetalparticipated polymerization n-type in situ doping solution processability solvent interaction

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Synthesis of (±)-Bakuchiol via a Pot-Economy Approach

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Chinese Journal of Chemistry 2014年第8期32卷 715-720页

作者： Meng-Yuan Huang Long Chen ruoxi Li Xueshun Jia Ran hong Department of Chemistry Shanghai UniversityShanghai 200444China CAS Key Laboratory of Synthetic Chemistry of Natural Substances Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 200032China

A rapid synthetic route toward(±)-Bakuchiol is presented in 29%overall yield.After the sole all-carbon quaternary carbon center is created via allylboration of 2-aryl acetaldehyde,a“Pot-Economy”approach including mesylation,elimination,and desilylation was realized in the presence of ^(t)BuOK under ambient temperature to provide(±)-Bakuchiol.

关键词： allylboration bukuchiol meroterpenoid pot-economy quaternary carbon

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A Positive Correlation between Elevated Altitude and Frequency of Mutant Alleles at the EPAS1 and HBB Loci in Chinese Indigenous Dogs

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Journal of Genetics and Genomics 2015年第4期42卷 173-177页

作者： ruoxi Fan Fei Liu hong Wu Shifang Wu Chunling Zhu Yan Li Guodong Wang Yaping Zhang Laboratory for Conservation and Utilization of Bio-resources Yunnan University State Key Laboratory of Genetic Resources and Evolution and Yunnan Laboratory of Molecular Biology of Domestic AnimalsKunming Institute of ZoologyChinese Academy of Sciences

Hypoxia represents one of the most extreme environmental conditions for both human beings and animals living at high al- titudes （Zhao et al., 2009）. Over the past few years, great attention has been focused on the genetic bases of adaption to high-altitude environments （Bigham et al., 2010; Simonson et al., 2010）. The domestic dog （Canisfamiliaris） is the first animal that developed an intimate relationship with human beings. Dogs migrated with human beings and have adapted to variety of ecological niches （Savolainen et al., 2002）. Our previous research revealed parallel evolution and convergent evolution in the adaptation of dogs and humans to the high-altitude environment of the Tibetan plateau （Wang et al., 2013, 2014）, suggesting that exploring the adaption of domestic dogs to high-altitude hypoxia is an interesting and important question.

关键词： HBB PAS A Positive Correlation between Elevated Altitude and Frequency of Mutant Alleles at the EPAS1 and HBB Loci in Chinese Indigenous Dogs

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抗大开展思想政治工作的四条经验

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党的文献 2023年第4期 122-127页

作者：洪若曦韩华首都师范大学马克思主义学院北京100089

抗大是抗日战争时期我们党着眼于培养军政干部的迫切需要而创办的。抗大始终高度重视思想政治工作,把“坚定正确的政治方向”作为教育方针的第一条,并颁布政治工作暂行条例,使思想政治工作有章可循;把思想政治教育贯穿教育教学全过程,... 详细信息

抗大是抗日战争时期我们党着眼于培养军政干部的迫切需要而创办的。抗大始终高度重视思想政治工作,把“坚定正确的政治方向”作为教育方针的第一条,并颁布政治工作暂行条例,使思想政治工作有章可循;把思想政治教育贯穿教育教学全过程,在教学内容中突出思想政治教育,教育学员克服非无产阶级思想意识,加强教员队伍建设;通过结合革命形势进行教育,因时制宜、因材施教,发扬艰苦奋斗作风,参加生产劳动实践等方法,把干部培养同革命需要紧密结合起来;通过开展文体、革命宣传等活动,寓思想政治教育于学员文化生活之中,发挥出以文化人、以文育人的重要作用。抗大开展的思想政治工作卓有成效,培养了一大批德才兼备的军政干部,为党领导的抗日军队的发展壮大和抗战的胜利提供了可靠的人才支撑。

关键词：抗大思想政治工作政治方向

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