Diffusionless-Like Transformation Unlocks Pseudocapacitance with Bulk Utilization: Reinventing Fe_(2)O_(3) in Alkaline Electrolyte

Energy density can be substantially raised and even maximized if the bulk of an electrode material is fully utilized.Transition metal oxides based on conversion reaction mechanism are the imperative choice due to either constructing nanostructure or intercalation pseudocapacitance with their intrinsic limitations.However,the fully bulk utilization of transition metal oxides is hindered by the poor understanding of atomic-level conversion reaction mechanism,particularly it is largely missing at clarifying how the phase transformation(conversion reaction)determines the electrochemical performance such as power density and cyclic stability.Herein,α-Fe_(2)O_(3) is a case provided to claim how the diffusional and diffusionless transformation determine the electrochemical behaviors,as of its conversion reaction mechanism with fully bulk utilization in alkaline electrolyte.Specifically,the discharge productα-FeOOH diffusional from Fe(OH)2 is structurally identified as the atomic-level arch criminal for its cyclic stability deterioration,whereas the counterpartδ-FeOOH is theoretically diffusionless-like,unlocking the full potential of the pseudocapacitance with fully bulk utilization.Thus,such pseudocapacitance,in proof-of-concept and termed as conversion pseudocapacitance,is achieved via diffusionless-like transformation.This work not only provides an atomic-level perspective to reassess the potential electrochemical performance of the transition metal oxides electrode materials based on conversion reaction mechanism but also debuts a new paradigm for pseudocapacitance.

Gastric cancer secreted miR 214-3p inhibits the anti-angiogenesis effect of apatinib by suppressing ferroptosis in vascular endothelial cells

Diferent from necrosis,apoptosis,autophagy and other forms of cell death,ferroptosis is a mechanism that catalyzes lipid peroxidation of polyunsaturated ftty acids under the action of iron divalent or lipoxygenase,leading to cell death.Apatinib is currently used in the third line standard treatment of advanced gastric cancer,targeting the anti-angiogenesis pathway.However,Apatinib mediated ferroptosis in vascular endothelial cells has not been reported yet.Tumor.secreted exosomes can be taken up into target cells to regulate tumor development,but the mechanism related to vascular endothelial cell ferroptosis has not yet been discovered.Here,we show that exosomes secreted by gastric cancer cells carry miR-214.3p into vascular endothelial cells and directdy target zinc finger protein A20 to negatively regulate ACSL4,a key enzyme of lipid peroxidation during frroptosis thereby inhibiting ferroptosis in vascular endothelial cells and reducing the eficiency of Apatinib.In conclusion,inhibition of miR-214-3p can increase the sensitivity of vascular endothelial cells to Apatinib,thereby promoting the antiangiogenic efect of Apatinib,suggesting a potential combination therapy for advanced gastric cancer.

The design and engineering strategies of metal tellurides for advanced metal-ion batteries

Owning various crystal structures and high theoretical capacity,metal tellurides are emerging as promising electrode materials for high-performance metal-ion batteries(MBs).Since metal telluride-based MBs are quite new,fundamental issues raise regarding the energy storage mechanism and other aspects affecting electrochemical performance.Severe volume expansion,low intrinsic conductivity and slow ion diffusion kinetics jeopardize the performance of metal tellurides,so that rational design and engineering are crucial to circumvent these disadvantages.Herein,this review provides an in-depth discussion of recent investigations and progresses of metal tellurides,beginning with a critical discussion on the energy storage mechanisms of metal tellurides in various MBs.In the following,recent design and engineering strategies of metal tellurides,including morphology engineering,compositing,defect engineering and heterostructure construction,for high-performance MBs are summarized.The primary focus is to present a comprehensive understanding of the structural evolution based on the mechanism and corresponding effects of dimension control,composition,electron configuration and structural complexity on the electrochemical performance.In closing,outlooks and prospects for future development of metal tellurides are proposed.This work also highlights the promising directions of design and engineering strategies of metal tellurides with high performance and low cost.

Exosomal miR-155 from gastric cancer induces cancerassociated cachexia by suppressing adipogenesis and promoting brown adipose differentiation via C/EPBβ

Objective:The aim of this research was to identify whether exosomes were involved in impairing adipogenesis in cancer-associated cachexia(CAC)by detecting the adipodifferentiation capacity and the expressions of adipogenic proteins in gastric cancer(GC)-associated adipocytes.Methods:Western blotting and RT-PCR were used to investigate the expressions of C/EPBβ,C/EPBα,PPARγ,and UCP1 in adipose mesenchymal stem cells(A-MSCs)to evaluate the function of exosomal miR-155.BALB/c nude mice were intravenously injected in vivo with GC exosomes with different levels of miR-155 to determine changes in adipodifferentiation of A-MSCs.Results:Exosomes derived from GC cells suppressed adipogenesis in A-MSCs as characterized by decreased lipid droplets.Similarly,A-MSCs co-cultured with GC exosomes exhibited increased ATP production through brown adipose differentiation characterized by highly dense mitochondria and enhanced UCP1 expression(P<0.05).Mechanistically,exosomal miR-155 secreted from GC cells suppressed adipogenesis and promoted brown adipose differentiation by targeting C/EPBβ,accompanied by downregulated C/EPBαand PPARγand upregulated UCP1(P<0.05).Moreover,overexpression of miR-155 in GC exosomes improved CAC in vivo,which was characterized by fat loss,suppressed expressions of C/EPBβ,C/EPBα,and PPARγin A-MSCs,and high expression of UCP1(P<0.05).Decreasing the level of miR-155 in injected GC exosomes abrogated the improved CAC effects.Conclusions:GC exosomal miR-155 suppressed adipogenesis and enhanced brown adipose differentiation in A-MSCs by targeting C/EPBβof A-MSCs,which played a crucial role in CAC.

Reinventing the mechanism of high-performance Bi anode in aqueous K^+ rechargeable batteries

Increasing attention has been paid to rechargeable aqueous batteries due to their high safety and low cost.However,they remain in their infancy because of the limited choice of available anode materials with high specific capacity and satisfying cycling performance.Bi metal with layered structure can act as an ideal anode material with high capacity;however,the energy storage mechanism has not well elucidated.Herein,we demonstrate that Bi metal enables affording ultra-high specific capacity(254.3 mAh g^-1),superior rate capability and a capacity retention of 88.8%after 1600 cycles.Different from the previously-reported redox reaction mechanisms of Bi electrode,efficient(de)alloying of K+is responsible for its excellent performance.An excellent aqueous Bi battery is fabricated by matching Bi anode with Co(OH)2 cathode in KOH(1 M)electrolyte.Its outstanding performance is quite adequate and competitive for electrochemical energy storage devices.

Integrated Co3O4/carbon fiber paper for high-performance anode of dual-ion battery

In dual-ion batteries (DIBs), energy storage is achieved by intercalation/de-intercalation of both cations and anions. Due to the mismatch between ion diameter and layer space of active materials, however, volume expansion and exfoliation always occur for electrode materials. Herein, an integrated electrode Co3O4/carbon fiber paper (CFP) is prepared as the anode of DIB. As the Co3O4 nanosheets grow on CFP substrate vertically, it promotes the immersion of electrolyte and shortens the pathway for ionic transport. Besides, the strong interaction between Co3O4 and CFP substrate reduces the possibility of sheet exfoliation. An integrated-electrode-based DIB is therefore packaged using Co3O4/CFP as anode and graphite as cathode. As a result, a high energy density of 72 Wh/kg is achieved at a power density of 150 W/kg. The design of integrated electrode provides a new route for the development of high-performance DIBs.

Optimizing the micropore-to-mesopore ratio of carbon-fiber-cloth creates record-high specific capacitance

The application of commercial carbon fiber cloth(CFC) in energy storage equipment is limited by its low specific capacitance and energy density. By a simple one-step activation treatment, the specific surface area of CFCs with porous structure can be increased considerably from 3.9 up to 875 m^2/g and the electrochemical properties of CFCs can be improved by three orders of magnitude(1324 mF/cm^2). Moreover,the hydrophobicity of CFCs can be transformed into superhydrophilicity. However, the electrochemical performance of CFCs does not show a positive correlation with specific surface area but have a strong relationship with the hierarchical pore distribution forged by the annealing treatment. Only moderate micropore and mesoporous ratio enables optimizing the electrochemical performance of CFCs.

Unlock the potential of Li4Ti5O(12) for high-voltage/long-cycling-life and high-safety batteries: Dual-ion architecture superior to lithium-ion storage

Li4Ti5O(12)(LTO)has drawn great attention due to its safety and stability in lithium-ion batteries(LIBs).However,high potential plateau at 1.5 V vs.Li reduces the cell voltage,leading to a limited use of LTO.Dual-ion batteries(DIBs)can achieve high working voltage due to high intercalation potential of cathode.Herein,we propose a DIB configuration in which LTO is used as anode and the working voltage was 3.5 V.This DIB achieves a maximum specific energy of 140 Wh/kg at a specific power of 35 W/kg,and the specific power of 2933 W/kg can be obtained with a remaining specific energy of 11 Wh/kg.Traditional LIB material shows greatly improved properties in the DIB configuration.Thus,reversing its disadvantage leads to upgraded performance of batteries.Our configuration has also widened the horizon of materials for DIBs.

Safety and efficacy of anti-EGFR monoclonal antibody (SCT200) as second-line therapy in advanced esophageal squamous cell carcinoma

Objective:The mainstay treatment of esophageal squamous cell carcinoma(ESCC)involves chemotherapy and immunotherapy.However,alternative therapies are required for patients who are refractory or intolerant to existing therapies.Methods:In this single-arm,multicenter,open-label phase Ib study,30 patients received an intravenous infusion of SCT200,an antiepidermal growth factor receptor(EGFR)monoclonal antibody,6.0 mg/kg once a week for 6 weeks,followed by 8.0 mg/kg once every 2 weeks until disease progression or intolerable toxicity.The primary endpoint was the objective response rate(ORR).The secondary endpoints were progression-free survival(PFS),overall survival(OS),and safety.Results:Thirty patients were enrolled between July 2018 and May 2019.The ORR was 16.7%(95%CI:5.6%–34.7%).The median PFS and OS were 3.1 months(95%CI:1.5–4.3)and 6.8 months(95%CI:4.7–10.1),respectively.A numerical difference without any statistical significance in ORR was observed in patients with different EGFR expressions(≥50%:25.0%vs.<50%:0%,P=0.140)or TP53 mutation abundance(<10%:23.8%vs.≥10%:0%,P=0.286).Improved median PFS(3.4 vs.1.4 months,P=0.006)and OS(8.0 vs.4.2 months,P=0.027)were associated with TP53 mutation abundance of<10%.The most common treatment-related adverse events of grade 3 or 4(occurring in≥2 patients)were hypomagnesemia[7(23.3%)]and rash[2(6.7%)].No treatmentrelated death occurred.Conclusions:SCT200 monotherapy as the second-or further-line treatment for advanced ESCC showed favorable efficacy,with an acceptable safety profile.TP53 mutation abundance might serve as a potential predictive biomarker.

肿瘤患者支持治疗的进展

肿瘤支持治疗是与肿瘤放疗、化疗和手术并重的治疗手段。肿瘤支持治疗包括从肿瘤诊断开始一直到生命结束的全程,其内容相当宽泛,且对于延长患者生存期,改善生存质量,节约医疗成本等均具有重要意义。随着研究的不断深入,肿瘤支持治疗在各领域均取得了一系列重要进展,其作用也越来越受到重视。尤为重要的是,医患认知从传统治疗理念发生根本性转变,使肿瘤支持治疗的发展前景焕发蓬勃生机。目前,肿瘤支持治疗逐渐向多学科整合、以患者为中心的个体化、全程化的管理及数字化方向发展。未来,随着学科分支的精细化和基础转化研究的不断深入,肿瘤患者的支持治疗必将形成一个完整的学科,造福广大的癌症患者。

改良FOLFIRINOX方案一线化疗中国转移性胰腺癌患者的疗效与安全性研究

背景与目的奥沙利铂(oxaliplatin)、伊立替康(irinotecan)、5-氟尿嘧啶(5-fluorouracil)和1-醛氢叶酸(l-leucovorin)联合用药(即FOLFIRINOX方案)已成为晚期胰腺癌(pancreatic cancer,PC)的一线治疗方案之一。然而,与FOLFIRINOX标准剂量相关的3级或4级不良事件的较高发生率限制了该方案在临床上的广泛应用。在本研究中,我们对改良FOLFIRINOX方案一线化疗中国转移性PC患者的疗效和安全性进行了评价。方法将组织学证实为原发转移性胰腺癌,且东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)体能状态评分为0-2的患者纳入本研究。所有患者均接受改良FOLFIRINOX方案治疗(静脉滴注奥沙利铂65 mg/m^2、伊立替康150 mg/m^2、l-醛氢叶酸200 mg/m^2、5-氟尿嘧啶2400 mg/m^2,每2周重复1次)。治疗持续12个周期,除非患者出现疾病进展(progressive disease,PD)、症状恶化的疾病稳定(stable disease,SD)、不可耐受的不良事件或要求提前终止治疗。主要终点为客观缓解率(objective response rate,ORR)。结果2012年7月至2017年4月期间,共有来自3个机构的65例患者被纳入本研究。所有患者均接受了至少1个周期化疗,化疗周期中位数为8个周期(范围:1-12个周期)。本研究中未观察到完全缓解。21(32.3%)例患者为部分缓解,27(41.5%)例表现为SD。总体人群的ORR和疾病控制率(diseasecontrol rate,DCR)分别为32.3%和73.8%。中位总生存期和无进展生存期分别为11.60[95%置信区间(confidence interval,CI):8.76-14.44]个月和5.77(95%CI:5.00-6.54)个月。主要的3级或4级不良事件包括中性粒细胞减少(12.3%)和腹泻(6.2%)。未观察到与治疗相关的死亡。结论改良FOLFIRINOX具有良好的耐受性,可作为中国转移性PC中国患者的一线治疗方案。

Increasing the range of non-noble-metal single-atom catalysts

由于良好的催化活性和稳定性,贵金属催化剂已经被广泛应用于各种异相催化反应中,但是贵金属的稀有性和高成本无法满足未来日益增长的催化需求.2011年,张涛课题组成功地制备了高效、稳定的铂单原子催化剂.高效的单原子催化剂利用单个活性位点作为催化活性中心,可能会成为连接同相催化和异相催化的桥梁.然而从经济适用的长远角度考虑,将非贵金属催化剂缩小到原子尺度是否也会展现出优良的催化活性;是否有潜力替代目前已被广泛应用的贵金属催化剂?虽然现阶段非贵金属催化剂的催化性能仍无法达到贵金属催化剂的标准,但是已有相关研究从理论和实验上报道了非贵金属单原子催化剂及其优异的性能表明了其在未来发展中极其重要,因而,可以预见这两个疑问的答案都是肯定的.单原子概念的出现不仅为提高贵金属的催化性能及成本的降低指明了方向,同时也为制备具有高催化活性、甚至可与贵金属催化剂相媲美的非贵金属催化剂提供了可能性.我们在上述背景下,阐述了对单原子的概念日益加深的机制认知,并从理论和实验上概述了非贵金属单原子催化剂近期的发展情况,指出了目前的在单原子催化剂领域需要解决的一些问题,最后,针对研究现状,我们对未来单原子的发展提出了相应的展望.单原子催化剂具有较高的表面能,因而,如何寻找合适的基体与单原子相互作用,进而,使基体材料像一只手一样稳固地"抓紧"单原子,因而,降低其高表面能则是发挥优良催化性能的基础.强金属–基体相互作用(SMSI)不仅可以将单原子限制在基体表面,亦会影响整个催化过程.目前应用于单原子催化剂的基体种类很多,如金属氧化物、金属以及其他材料,而对SMSI认知则主要分两大类,一类是源自于基体表面的结构缺陷,另一类是源于其电子缺陷.从目前的发展状况来看SMSI机制仍有很多疑惑尚未解决,例如对电子转移影响的认知等.理论研究表明,在某些反应中非贵金属单原子展示出可替代贵金属的催化性质.比如,在一氧化碳优先反应(PROX)中,单原子钴和钛展示出的催化性能可与贵金属相媲美;理论计算同样证明单原子镍在一氧化碳还原中的催化活性比单原子铱优秀,甚至与单原子铂类似.大量的实验进展也报道了非贵金属单原子同样能在其他反应中展现出优异的性能,如氧析出反应(OER)、氢析出反应(HER)和氧还原反应(ORR).对于单原子催化剂,还有很多问题需要我们去解决,例如基体对于催化过程的具体影响、非贵金属的电子结构对于其催化性能的影响,以及单原子在基体上产生相互作用的位点等问题.纵然有许多问题需要更加深入的研究,但是单原子概念的出现,使得非贵金属催化剂材料取代传统贵金属催化剂成为了可能.

Architecture of Co-layered double hydroxide nanocages/graphene composite electrode with high electrochemical performance for supercapacitor

A facile hydrolysis method was applied to fabricate high-performance Co-layered double hydroxide（LDH）nanocages/graphene composites for supercapacitors. The materials exhibit enhanced rate capability than the counterpart electrode free of graphene while maintaining a high specific capacitance. In addition,such Co-LDH nanocages/graphene composites display an excellent cycling stability; the capacitance retention of Co-LDH nanocages/graphene composite electrode remains 90.4% after 10000 cycles at a current density of 2 A g（-1）. The integration of high capacity of double hydroxide and outstanding conductivity of graphene makes the delicately-designed composites promising candidates for electrode materials for supercapacitors.

Change of SPARC expression after chemotherapy in gastric cancer

Objective： The expression of tumor biomarkers may change after chemotherapy. However, whether secreted protein acidic and rich in cysteine （SPARC） expression changes after chemotherapy in gastric cancer （GC） is unclear, qqais study investigated the influence of chemotherapy on SPARC expression in GC. Methods： Immunohistochemistry was used to analyze SPARC expression in 132 GC cases （including 54 cases with preoperative chemotherapy and 78 cases without preoperative chemotherapy）. SPARC expression of postoperative specimens with and without preoperative chemotherapy was assessed to analyze the influence of chemotherapy on SPARC expression. Results： SPARC was highly expressed in GC compared with the desmoplastic stroma surrounding tumor cells and noncancerous tissues. High SPAKC expression was correlated with invasion depth, lymph node, and TNM stage. After chemotherapy, a lower proportion of high SPARC expression was observed in patients with preoperative chemotherapy than in the controls. For 54 patients with preoperative chemotherapy; gross type, histology, depth of invasion, lymph node, TNM stage, and SPARC expression were related to overall survival. Further multivariate analysis showed that lymph node, histology, and SPARC expression after chemotherapy were independent prognostic factors. Conclusiou： SPARC expression may change after chemotherapy in GC. SPARC expression should be reassessed for patients with GC after chemotherapy.

Toripalimab combined with targeted therapy and chemotherapy achieves pathologic complete response in gastric carcinoma:A case report

BACKGROUND Neoadjuvant or perioperative chemotherapy combined with surgery can reduce postoperative recurrence and improve the long-term survival rate of patients with locally advanced resectable gastric carcinoma.Nivolumab combined with chemotherapy has been recommended by the National Comprehensive Cancer Network guidelines as a first-line therapy for advanced gastric carcinoma/adenocarcinoma of the gastroesophageal junction and serves as the basis for immunotherapy combined with chemotherapy to become a neoadjuvant therapy.Herein,we report a case in which pathologic complete response was achieved by neoadjuvant administration of toripalimab,Herceptin,and docetaxel,oxaliplatin,calcium folinate,and fluorouracil(FLOT)chemotherapy followed by surgery for human epidermal growth factor receptor 2(HER2)-and programmed deathligand 1(PD-L1)-positive locally advanced gastric carcinoma.We hope that this case will shed some light on neoadjuvant therapy for gastric carcinoma.CASE SUMMARY The patient was diagnosed with locally advanced adenocarcinoma of the cardia.Immunohistochemistry of the baseline tissues suggested that the tissues were HER2-(fluorescent in situ hybridization)and PD-L1-positive(combined positive score=1).The patient underwent surgery following a four-cycle neoadjuvant therapy comprising Herceptin,toripalimab,and FLOT chemotherapy.The postoperative pathological findings showed mild atypical hyperplasia of the local glands with chronic mucosal inflammation(proximal stomach),no clear residual tumor(tumor regression grade 0),no regional lymph node metastasis,and negative upper and lower cut ends.The levels of tumor markers were reduced to normal levels after re-examination.With good postoperative recovery,the four-cycle preoperative chemotherapy was continued at the same dosage as that previously administered.After the treatment,the patient was monitored every 3 mo with a follow-up of 12 mo(4 times).As of February 27,2022,he was in a good condition without disease progression.The clinical trial registration number is E2019401.CONCLUSION There are many ongoing studies on neoadjuvant immunotherapy combined with chemotherapy or radiotherapy;however,most of these studies are phase II studies with small cohorts.According to the results of some current studies,these combined regimens have shown promising results in terms of efficacy and safety.However,the clinical efficacy and safety of the neoadjuvant therapies used in these combined regimens need to be confirmed by additional prospective phase III clinical trials,and further exploration of molecular markers for effective populations is required.

Electrochemical CO_(2)reduction to C_(2+)products over Cu/Zn intermetallic catalysts synthesized by electrodeposition

Electrocatalytic CO_(2)reduction(ECR)offers an attractive approach to realizing carbon neutrality and producing valuable chemicals and fuels using CO_(2)as the feedstock.However,the lack of cost-effective electrocatalysts with better performances has seriously hindered its application.Herein,a one-step co-electrodeposition method was used to introduce Zn,a metal with weak^(*)CO binding energy,into Cu to form Cu/Zn intermetallic catalysts(Cu/Zn IMCs).It was shown that,using an H-cell,the high Faradaic efficiency of C_(2+)hydrocarbons/alcohols()could be achieved in ECR by adjusting the surface metal components and the applied potential.In suitable conditions,FEC_(2+)and current density could be as high as 75%and 40 mA/cm^(2),respectively.Compared with the Cu catalyst,the Cu/Zn IMCs have a lower interfacial charge transfer resistance and a larger electrochemically active surface area(ECSA),which accelerate the reaction.Moreover,the^(*)CO formed on Zn sites can move to Cu sites due to its weak binding with*CO,and thus enhance the C–C coupling on the Cu surface to form C_(2+)products.

Onco-miR-24 regulates cell growth and apoptosis by targeting BCL2L11 in gastric cancer

Gastric cancer is one of the most common malignancies worldwide; however, the molecular mechanism in tumorigenesis still needs exploration. BCL2L11 belongs to the BCL-2 family, and acts as a central regulator of the intrinsic apoptotic cascade and mediates cell apoptosis. Although miRNAs have been reported to be involved in each stage of cancer development, the role of miR-24 in GC has not been reported yet. In the present study, miR- 24 was found to be up-regulated while the expression of BCL2L11 was inhibited in tumor tissues of GC. Studies from both in vitro and in vivo shown that miR-24 regulates BCL2L11 expression by directly binding with 3＇UTR of mRNA, thus promoting cell growth, migration while inhibiting cell apoptosis. Therefore, miR-24 is a novel onco-miRNA that can be potential drug targets for future clinical use.

CACA guidelines for holistic integrative management of esophageal carcinoma

Esophageal carcinoma(EC)is a common malignant tumor of the upper digestive tract worldwide.An analysis of the latest data from cancer centers in China showed that the incidence of EC and the number of deaths due to EC in China in 2015 were 266,000 and 188,000,respectively,ranking sixth(6.3%)and fourth(8.0%)among all malignant tumors.The early diagnosis and treatment of EC and standardized diagnosis and treatment are important tasks for EC healthcare professionals in various centers across the country.At present,the 8th edition of the EC staging system jointly released by Union for International Cancer Control(UICC)and American Joint Committee on Cancer(AJCC)is the most recent,authoritative and widely used EC staging standard.The EC professional committee of the Chinese Anti-Cancer Association also organizes the"EC Standardization Campaign in China"every year to promote the development of EC diagnostic and treatment norms throughout the country.Since 2011,the EC Committee of the Chinese Anti-Cancer Association has published the Guidelines for Standardized Diagnosis and Treatment of EC.Considering the increasing number of EC clinical studies and the continuous progress in diagnostic and treatment technologies in recent years,the updated Guidelines will include the latest progress in the diagnosis and treatment of EC,with a goal of promoting the forward development of EC diagnosis and treatment in clinical practice.

Advances in medical treatment of advanced hepatobiliary and pancreatic cancer in 2022

This article summarizes the drug therapy progress of advanced hepatocellularcarcinoma, biliary tract cancer, and pancreatic cancer in 2022, includingchemotherapy, molecular targeted therapy, and immunotherapy, to providereference information for current clinical treatment and future clinicalresearch, and to better improve prognosis and quality of life in patients withhepatobiliary and pancreatic cancer.

Efficacy and safety of a novel anti-HER2 therapeutic antibody RC48 in patients with HER2-overexpressing,locally advanced or metastatic gastric or gastroesophageal junction cancer:a single-arm phase II study

Background:Current treatment options for human epidermal growth factor receptor 2(HER2)-overexpressing gastric cancer at third-line have shown limited clinical benefit.Further,there is no specific treatment for HER2 immunohistochemistry(IHC)2+and fluorescence in-situ hybridization-negative patients.Here,we report the efficacy and safety of a novel anti-HER2 antibody RC48 for patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer.Methods:Patients with HER2-overexpressing(IHC 2+or 3+),locally advanced or metastatic gastric or gastroesophageal junction cancer who were under at least second-line therapy were eligible and received RC482.5 mg/kg alone every 2 weeks.The primary endpoint was the objective response rate(ORR)assessed by an independent review committee.Secondary endpoints included progressionfree survival(PFS),overall survival(OS),duration of response,time to progression,disease control rate,and safety.Results:Of 179 patients screened,125 were eligible and received RC48 treatment.The ORR was 24.8%(95%confidence interval[CI]:17.5%-33.3%).The median PFS and OS were 4.1 months(95%CI:3.7-4.9 months)and 7.9 months(95%CI:6.7-9.9 months),respectively.The most frequently reported adverse events were decreased white blood cell count(53.6%),asthenia(53.6%),hair loss(53.6%),decreased neutrophil count(52.0%),anemia(49.6%),and increased aspartate aminotransferase level(43.2%).Serious adverse events(SAEs)occurred in 45(36.0%)patients,and RC48-related SAEs were mainly decreased neutrophil count(3.2%).Seven patients had adverse events that led to death were not RC48-related.Conclusions:RC48 showed promising activity with manageable safety,suggesting potential application in patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer who have previously received at least two lines of chemotherapy.