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Impact of oxaliplatin and trastuzumab combination therapy on tumor markers and T lymphocyte subsets for advanced gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第9期16卷 3905-3912页

作者： Cheng-Wan Zheng Yun-Mo Yang Hui Yang department of Thyroid Surgery The Affiliated Hospital of Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina

BACKGROUND Advanced gastric cancer(AGC)remains a challenging malignancy with poor *** combination of oxaliplatin and trastuzumab has shown promising results in AGC *** study aimed to investigate the effects of oxaliplatin and trastuzumab combination therapy on serum tumor markers and T lymphocyte subsets in patients with AGC and to explore their potential as predictive biomarkers for treatment *** To investigate the impact of oxaliplatin and trastuzumab combination therapy on serum markers and T cell subsets in patients with *** This prospective study enrolled 60 patients with *** patients received oxaliplatin(130 mg/m^(2),every 3 weeks)and trastuzumab(8 mg/kg loading dose,followed by 6 mg/kg every 3 weeks)for six *** carcinoembryonic antigen(CEA),cancer antigen 19-9(CA19-9),and cancer antigen 72-4(CA72-4)were measured before and after treatment.T-lymphocyte subsets,including CD3+,CD4+,CD8+,and CD4+/CD8+ratios,were also *** clinical response was assessed using the Response Evaluation Criteria in Solid Tumors version *** After six cycles of treatment,the CEA,CA19-9,and CA72-4 serum levels significantly decreased compared to baseline levels(P<0.001).The percentages of CD3+and CD4+T lymphocytes increased significantly(P<0.05),whereas the percentage of CD8+T lymphocytes decreased(P<0.05).The CD4+/CD8+ratio also significantly increased after treatment(P<0.05).Patients with a higher decrease in serum tumor markers(≥50%reduction)and a higher increase in CD4+/CD8+ratio(≥1.5-fold)showed better clinical response rates(P<0.05).CONCLUSION Oxaliplatin and trastuzumab combination therapy effectively reduced serum tumor marker levels and modulated T lymphocyte subsets in patients with *** therapy not only has a direct antitumor effect,but also enhances the immune response in patients with *** tumor markers and T lymphocyte subsets may serve as potential predictive biomarkers for treatment respon

关键词： Advanced gastric cancer Oxaliplatin Trastuzumab Serum tumor markers T lymphocyte subsets Predictive biomarkers

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New therapeutic target NCF1-directed multi-bioactive conjugate therapies prevent preterm birth and adverse pregnancy outcomes

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Science Bulletin 2024年第16期69卷 2604-2621页

作者： Juan Cheng Xiaoyan Jia Limei Yang Siqi Zhang Zhiyu Chen Qian Gui Ting Li Zedan Pu Hongbo Qi Jianxiang Zhang Chongqing Key Laboratory of Maternal and Fetal Medicine The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Women and Children’s hospital of Chongqing medical university Chongqing 401147China department of Obstetrics The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China department of Pharmaceutics College of PharmacyThird Military Medical University(Army Medical University)Chongqing 400038China department of Orthopedics The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Yu-Yue Pathology Scientific Research Center Chongqing 400039China State Key Laboratory of Trauma and Chemical Poisoning Third Military Medical University(Army Medical University)Chongqing 400038China

Preterm birth(PTB)is a leading cause of neonatal morbidity and mortality worldwide,yet the cellular and molecular mechanisms driving this condition remain undeciphered,thus limiting discovery of new ***-depth analyses of human and mouse tissues associated with PTB,in combination with cellular studies,indicated that aberrantly high-expressed neutrophil cytoplasmic factor(NCF)1 leads to oxidative distress,recruitment,and pro-inflammatory activation of neutrophils and macrophages,while sequentially overexpressed pro-inflammatory mediators induce contractions of uterine smooth muscle cells(USMCs)as well as apoptosis of USMCs and amniotic epithelial cells,thereby causing *** to these new findings,we rationally engineered an amphiphilic macromolecular conjugate LPA by covalently integrating low-molecular-weight heparin,a reactive oxygen species-responsive/scavenging component,and an anti-inflammatory *** bioengineered macromolecular conjugate can selfassemble into multi-bioactive nanoparticles(LPA NP).In a mouse model of PTB,LPA NP effectively delayed PTB and inhibited adverse pregnancy outcomes,by regulating NCF1-mediated oxidativeinflammatory cascades,i.e.,attenuating oxidative stress,inhibiting inflammatory cell activation,reducing local inflammation,and decreasing contraction/apoptosis of myometrial *** LPA NP into temperature-responsive,self-healing,and bioadhesive hydrogel further potentiated its in vivo efficacies after intravaginal delivery,by prolonging retention time,sustaining nanotherapy release,and increasing bioavailability in the placenta/***,both the conjugate/nanotherapy and hydrogel formulations exhibited excellent safety profiles in pregnant mice,with negligible side effects on the mother and offspring.

关键词： Preterm birth Neutrophil cytoplasmic factor Bioactive conjugate Nanotherapy Hydrogel therapy

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ZYX promotes invasion and metastasis of gastric cancer cells via WNK1/SNAI1axis

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Genes & Diseases 2024年第2期11卷 564-567页

作者： Yi Jiang Dongfang Xiang Xianmei Wen Mingmin He Yan Qin Xiaoxue Yao Zexuan Yan Xiuli Geng Yong Ren Xiongwei Cai Youhong Cui Yan Wang Institute of Pathology and southwest Cancer Center Southwest HospitalArmy Medical University (Third Military Medical University)Chongqing 400038China department of Pathology General Hospital of Central Theater Command of PLAWuhanHubei 430070China department of Obstetrics and Gynecology Southwest HospitalArmy Medical University (Third Military Medical University)Chongqing 400038China department of pharmacy The Hospital of 83rd Group of PLAXinxiangHenan 453000China department of Gynecology Chongqing Health Center for Women and ChildrenWomen and Children's Hospital of Chongqing Medical UniversityChongqing 400013China

Gastric cancer(GC)is the third most common cause of cancer death globally and a large portion of patients are diagnosed at advanced stages with cancer invasion and metastasis1,***,the mechanisms underlying the invasion and metastasis of GC remain to be *** plays critical roles in cell mobility via cytoskeleton regulation in various cell types.3 In this study,we further reported that ZYX promoted migration,invasion,and metastasis of GC ***,ZYX promoted WNK1 activation and SNAl1 up-regulation,inducing epithelial-mesenchymal transition(EMT)to enhance the mobility of GC *** of WNK1 impaired the mobility of GC ***,ZYX/WNK1 could be potential therapeutic targets for GC treatment.

关键词： WNK1 invasion metastasis

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Trametinib boosts palbociclib’s efficacy in breast cancer via autophagy inhibition

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Oncology Research 2024年第7期32卷 1197-1207页

作者： ANGUO WU JIAO YAN TING SU CHI FENG XIN LONG YIRU PAN RUPEI YE TIAN XIA HANAN LONG JIANMING WU XIULI XIAO Sichuan Key medical Laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia MedicaKey Laboratory of Medical Electrophysiology of Ministry of EducationSchool of PharmacySouthwest Medical UniversityLuzhou646000China The department of Pathology The Affiliated Hospital of Southwest Medical UniversityLuzhou646000China The department of Pathology Mianyang Central HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaMianyang621000China The department of Pathology Yongchuan Hospital of Chongqing Medical UniversityChongqing402160China School of Basic medical Sciences Southwest Medical UniversityLuzhou646000China School of Clinical medical Sciences Southwest Medical UniversityLuzhou646000China

Breast cancer,a predominant global health issue,requires ongoing exploration of new therapeutic ***(PAL),a well-known cyclin-dependent kinase(CDK)inhibitor,plays a critical role in breast cancer *** its efﬁcacy is recognized,the interplay between PAL and cellular autophagy,particularly in the context of the RAF/MEK/ERK signaling pathway,remains insufﬁciently *** study investigates PAL’s inhibitory effects on breast cancer using both in vitro(MCF7 and MDA-MB-468 cells)and in vivo(tumor-bearing nude mice)*** at elucidating the impact of PAL on autophagic processes and exploring the potential of combining it with trametinib(TRA),an MEK inhibitor,our research seeks to address the challenge of PAL-induced drug ***ﬁndings reveal that PAL signiﬁcantly decreases the viability of MCF7 and MDA-MB-468 cells and reduces tumor size in mice while showing minimal cytotoxicity in MCF10A ***,PAL also induces protective autophagy,potentially leading to drug resistance via the RAF/MEK/ERK pathway *** TRA effectively neutralized this autophagy,enhancing PAL’s anti-tumor efﬁcacy.A combination of PAL and TRA synergistically reduced cell viability and proliferation,and in vivo studies showed notable tumor size *** conclusion,the PAL and TRA combination emerges as a promising strategy for overcoming PAL-induced resistance,offering a new horizon in breast cancer treatment.

关键词： Palbociclib Trametinib Protective autophagy RAF/MEK/ERK MCF7 MDA-MB-468

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Development and validation of a nomogram for predicting in-hospital mortality of intensive care unit patients with liver cirrhosis

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World Journal of Hepatology 2024年第4期16卷 625-639页

作者： Xiao-Wei Tang Wen-Sen Ren Shu Huang Kang Zou Huan Xu Xiao-Min Shi Wei Zhang Lei Shi Mu-Han Lü department of Gastroenterology The Affiliated Hospital of Southwest Medical UniversityLuzhou 646099Sichuan ProvinceChina Nuclear Medicine and Molecular Imaging Key Laboratory The Affiliated Hospital of Southwest Medical UniversityLuzhou 646099Sichuan ProvinceChina department of Gastroenterology Lianshui People’Hospital of Kangda College Affiliated to Nanjing Medical UniversityHuaian 223499Jiangsu ProvinceChina

BACKGROUND Liver cirrhosis patients admitted to intensive care unit(ICU)have a high mortality *** To establish and validate a nomogram for predicting in-hospital mortality of ICU patients with liver *** We extracted demographic,etiological,vital sign,laboratory test,comorbidity,complication,treatment,and severity score data of liver cirrhosis patients from the medical Information Mart for Intensive Care IV(MIMIC-IV)and electronic ICU(eICU)collaborative research database(eICU-CRD).Predictor selection and model building were based on the MIMIC-IV *** variables selected through least absolute shrinkage and selection operator analysis were further screened through multivariate regression analysis to obtain final *** final predictors were included in the multivariate logistic regression model,which was used to construct a ***,we conducted external validation using the *** area under the receiver operating characteristic curve(AUC),decision curve,and calibration curve were used to assess the efficacy of the *** Risk factors,including the mean respiratory rate,mean systolic blood pressure,mean heart rate,white blood cells,international normalized ratio,total bilirubin,age,invasive ventilation,vasopressor use,maximum stage of acute kidney injury,and sequential organ failure assessment score,were included in the multivariate logistic *** model achieved AUCs of 0.864 and 0.808 in the MIMIC-IV and eICU-CRD databases,*** calibration curve also confirmed the predictive ability of the model,while the decision curve confirmed its clinical *** The nomogram has high accuracy in predicting in-hospital *** the included predictors may help improve the prognosis of patients.

关键词： Liver cirrhosis Intensive care unit Nomogram Predicting model Mortality

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Shuxuening Injection Inhibits Apoptosis and Reduces Myocardial Ischemia-Reperfusion Injury in Rats through PI3K/AKT Pathway

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Chinese Journal of Integrative Medicine 2024年第5期30卷 421-432页

作者： YUE Tong-tong CAO Ying-jie CAO Ya-xuan LI Wei-xia WANG Xiao-yan SI Chun-ying XIA Han ZHU Ming-jun TANG Jin-fa WANG He The First Clinical medical College of Henan university of Chinese Medicine Zhengzhou 450046China department of pharmacy the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou 451200China department of Cardiovascular Diseases the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou 451200China

Objective: To investigate the main components and potential mechanism of Shuxuening Injection(SXNI) in the treatment of myocardial ischemia-reperfusion injury(MIRI) through network pharmacology and in vivo research. Methods: The Traditional Chinese Medicine Systems Pharmacology(TCMSP) and Pharm Mapper databases were used to extract and evaluate the effective components of Ginkgo biloba leaves, the main component of SXNI. The Online Mendelian Inheritance in Man(OMIM) and Gene Cards databases were searched for disease targets and obtain the drug target and disease target intersections. The active ingredient-target network was built using Cytoscape 3.9.1 software. The STRING database, Metascape online platform, and R language were used to obtain the key targets and signaling pathways of the anti-MIRI effects of SXNI. In order to verify the therapeutic effect of different concentrations of SXNI on MIRI in rats, 60 rats were first divided into 5 groups according to random number table method: the sham operation group, the model group, SXNI low-dose(3.68 mg/kg), medium-dose(7.35 mg/kg), and high-dose(14.7 mg/kg) groups, with 12 rats in each group. Then, another 60 rats were randomly divided into 5 groups: the sham operation group, the model group, SXNI group(14.7 mg/kg), SXNI+LY294002 group,and LY294002 group, with 12 rats in each group. The drug was then administered intraperitoneally at body weight for 14 days. The main biological processes were validated using in vivo testing. Evans blue/triphenyltetrazolium chloride(TTC) double staining, hematoxylin-eosin(HE) staining, terminal deoxynucleotidyl transferase d UTP nick end labeling(TUNEL) assay, enzyme-linked immunosorbent assay(ELISA), and Western blot analysis were used to investigate the efficacy and mechanism of SXNI in MIRI rats. Results: Eleven core targets and 30 Kyoto Encyclopedia of Genes and Genomes(KEGG) pathways were selected. Among these, the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) pathway was

关键词： myocardial ischemia reperfusion injury PI3K/AKT signaling pathway Shuxuening Injection apoptosis Ginkgo biloba leaves

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mTORC2:The“Ace in the Hole”for a Broader Control of Epileptic Seizures?

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Neuroscience Bulletin 2024年第5期40卷 677-679页

作者： Shuo Zhang Xiongfeng Guo Wei Huang Cenglin Xu department of pharmacy The First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine)Hangzhou310006China The Second affiliated hospital of Zhejiang Chinese medical university(Zhejiang Xinhua hospital) Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang ProvinceSchool of Pharmaceutical SciencesZhejiang Chinese Medical UniversityHangzhou310053China

Over 70 million people worldwide suffer from epilepsy-one of the most prevalent chronic neurological disorders[1].Despite the availability of over thirty anti-seizure drugs(ASDs)that mainly act on voltage-gated ion channels or inhibitory GABAergic receptors,the effectiveness of these drugs in achieving seizure freedom remains unsatisfactory due to pharmacoresistance and the inevitable occurrence of side-effects.

关键词： drugs spite epilepsy

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Fine-tuning the structure-tolerance-antitumor efficacy axis of prodrug nanoassemblies via branched aliphatic functionalization

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Nano Research 2024年第4期17卷 2908-2918页

作者： Guanting Li Fengli Xia Hongying Xiao Shunzhe Zheng Shuwen Fu Han Qiao Qianhui Jin Xuanbo Zhang Dun Zhou Chutong Tian Jin Sun Zhonggui He Bingjun Sun department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China department of Pharmaceutics College of PharmacyShenyang Pharmaceutical UniversityShenyang 110016China Emergency department The First Affiliated Hospital of Jinzhou Medical UniversityJinzhou 121001China

Small-molecule prodrug nanoassemblies have emerged as efficient antitumor drug delivery ***,in the case of camptothecins-based prodrug nanoassemblies,linear aliphatic side chain modification often results in rod-shaped or irregularly shaped nanoassemblies,which are highly unfavorable for sterilization through filtration,and may cause capillary blockage upon intravenous *** rational design of camptothecins-based prodrug nanoassemblies remains a ***,we propose that branched aliphatic alcohol(BAA)functionalization could fine-tune the structure-tolerance-antitumor efficacy axis of prodrug ***,four SN38-BAA prodrugs were synthesized by conjugating 7-ethyl-10-hydroxycamptothecin(SN38)with BAAs of varying lengths via a tumor redox-responsive disulfide bond,which self-assemble into uniform spherical *** length of BAA was found to significant impact the multiple drug delivery process,including colloidal stability,drug release profiles and ***,SN38-C21 NPs(SN38-11-heneicosanol nanoparticles),featuring the longest BAA,showcased multiple therapeutic advantages,ultimately culminating the optimal antitumor efficacy and *** findings underscore the potential of BAA functionalization in strengthening the therapeutic outcomes of prodrug nanoassemblies,and provide valuable insights for developing translational camptothecins-based nanomedicines.

关键词： prodrug nanoassembly self-assembly antitumor efficacy tolerance 7-ethyl-10-hydroxycamptothecin(SN_(3)8)

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Curcumin inhibits colorectal cancer development by blocking the YAP/TAZ signaling axis

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BIOCELL 2024年第3期48卷 443-451页

作者： FEI SHA DAISHAN XIN JUN XU ZHIWEI ZHENG WENXIN LIN XIAORUI CAI FEI LIN MINGHAO ZHENG JIAOLING CHEN department of pharmacy Affiliated Cancer Hospital of Shantou University School of MedicineShantouChina department of pharmacy Shantou University Mental Health CenterShantouChina Static Distribution Center Affiliated Cancer Hospital of Shantou University School of MedicineShantouChina

Background:Curcumin is a plant polyphenol with antitumor properties and inhibits the development of colorectal cancer(CRC).However,as the molecular mechanism associated is still unclear,our study aimed to explore the underlying molecular mechanisms by which curcumin inhibits ***:HT29 and SW480 cells were treated with curcumin or/and Doxycycline(DOX),and cell viability,colony forming ability,migration and invasion were conﬁrmed by cell counting kit-8(CCK-8),colony forming,Transwell *** Yes-associated protein 1(YAP)and PDZ-binding motif(TAZ)signaling-related genes or proteins were analyzed using reverse transcription quantitative real-time PCR(RT-qPCR),western blot,and immunoﬂuorescence *** nude mice xenograft tumor model was constructed,YAP and Ki67 expressions were tested by immunohistochemistry(IHC)***:In our study,we proved that curcumin signiﬁcantly inhibited the CRC cell viability,cell migration,and cell invasion *** addition,curcumin inhibited YAP and Transcriptional coactivator with TAZ or the YAP/TAZ signaling axis in CRC ***,in the nude mice model,curcumin treatment signiﬁcantly decreased the size and weight of xenotransplant ***:Therefore,curcumin signiﬁcantly inhibited CRC development and invasion by regulating the YAP/TAZ signaling axis.

关键词： Curcumin Colorectal cancer YAP/TAZ signaling axis

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Platelet-derived microparticles and their cargos: The past, present and future

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 72-88页

作者： Jingwen Guo Bufeng Cui Jie Zheng Chang Yu Xuran Zheng Lixin Yi Simeng Zhang Keke Wang department of pharmacy The First Hospital of China Medical UniversityShenyang 110001 China School of pharmacy China Medical UniversityShenyang 110122China Key Laboratory of medical Cell Biology of Ministry of Education Key Laboratory of Major Chronic Diseases of Nervous System of Liaoning ProvinceHealth Sciences Institute of China Medical UniversityShenyang 110122China department of pharmacy The Fourth Affiliated Hospital of China Medical UniversityShenyang 110032China department of medical Oncology the First Hospital of China Medical UniversityShenyang 110001China

All eukaryotic cells can secrete extracellular vesicles, which have a double-membrane structure and are important players in the intercellular communication involved in a variety of important biological processes. Platelets form platelet-derived microparticles (PMPs) in response to activation, injury, or apoptosis. This review introduces the origin, pathway, and biological functions of PMPs and their importance in physiological and pathological processes. In addition, we review the potential applications of PMPs in cancer, vascular homeostasis, thrombosis, inflammation, neural regeneration, biomarkers, and drug carriers to achieve targeted drug delivery. In addition, we comprehensively report on the origin, biological functions, and applications of PMPs. The clinical transformation, high heterogeneity, future development direction, and limitations of the current research on PMPs are also discussed in depth. Evidence has revealed that PMPs play an important role in cell-cell communication, providing clues for the development of PMPs as carriers for relevant cell-targeted drugs. The development history and prospects of PMPs and their cargos are explored in this guidebook.

关键词： Platelet-derived particles Application Heter ogeneity Potential and limitations

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