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Recent Advances in Pd-Catalyzed Reactions Involving the “On-Water” Mechanism

Chinese Journal of Chemistry 2024年第5期42卷 533-542页

作者： Dong Wei Guo-Qiang Lin State Key Laboratory of Systems Medicine for cancer Shanghai Cancer InstituteShanghai Key Laboratory of Systems Regulation and Clinical Translation for CancerRen Ji HospitalShanghai Jiao Tong University School of MedicineShanghai200127 China State Key Laboratory of Chemical Biology Shanghai Institute of Organic ChemistryUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai200032 China

As the chemical industry grapples with the need for more eco-friendly practices,the use of water as a reaction medium is gaining attraction in organic *** mini-review delves into Pd-catalyzed reactions that utilize the "on-water" mechanism,spanning from 2019 to late *** reactions are neatly categorized into several types: (A) Catalytic C—H activations,(B) Mizoroki- Heck-type reactions,(C) Suzuki-Miyaura reactions,and (D) Cyclization *** showcasing the potential of water as a sustainable reaction medium for organic transformations,these reactions leave no doubt about the importance of embracing eco-friendly practices in the chemical *** Scientists In 1980,a seminal work by Breslow et *** an acceleration of reaction rate in the Diels-Alder *** and co-workers noted a significant increase in the rate of the [2σ+2σ+2π] cycloaddition of quadricyclane and dimethyl azodicarboxylate (DMAD) when the reaction was conducted in water,as opposed to when it was carried out in organic *** term "on-water" was then coined to describe this *** strategy was further expanded to transition-metal catalyzed transformations by Ackermann in ***,Varma and Leazer disclosed a Pd-catalyzed Mizoroki-Heck type arylation of alkenes with diaryliodonium salts “on-water”.The enantioselective version of "on-water" process was not realized until 2014 by the Zhou *** on,the Schaub group described a Pd-catalyzed Suzuki–Miyaura coupling reaction of electron-poor aryl chlorides with water,using only 50 ppm of catalyst *** recently,Liu and Lin extended the "on-water" strategy to Pd-catalyzed double Mizoroki-Heck *** mini-review has focused on Pd-catalyzed reactions involving the “on-water” mechanism.

关键词： Pd-catalyzed “On-water” Green chemistry Aqueous reactions Mechanism Methodology and reactions Mizoroki-Heck reaction Cross-coupling

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Assessment of HER2 status in extramammary Paget disease and its implication for disitamab vedotin,a novel humanized anti-HER2 antibody-drug conjugate therapy

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Frontiers of Medicine 2024年第3期18卷 565-569页

作者： Jia Jia Lili Mao Jing Lin Wenyu Li Pei Yuan Lei Guo Jie Dai Caili Li Xue Bai Zhongwu Li Yu Chen Jun Guo Jianming Ying Lu Si State Key Laboratory of Molecular Oncology Department of PathologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100021China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Melanoma and SarcomaPeking University Cancer Hospital&InstituteBeijing100142China Department of Medical Oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou350014China Department of Pathology Peking University Cancer Hospital&InstituteBeijing100142China

Dear Editor,Extramammary Paget disease(EMPD)is a rare adenocarcinoma that originates in the apocrine gland-rich skin and usually affects the perineal skin(primary EMPD)or represents the intraepithelial spread of an underlying visceral carcinoma(secondary EMPD).Approximately half of EMPD cases are confined to the epidermis,which was defined as intraepithelial EMPD.

关键词： Paget HER2 adenocarcinoma

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Phase Ib study of anti-EGFR antibody(SCT200) in combination with anti-PD-1 antibody(SCT-I10A) for patients with RAS/BRAF wild-type metastatic colorectal cancer

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cancer Biology & Medicine 2024年第7期21卷 636-650页

作者： Ming Bai Yao Lu Chunmei Shi Jianwei Yang Wei Li Xianli Yin Chenghui Huang Lin Shen Liangzhi Xie Yi Ba Department of GI Medical Oncology Tianjin Medical University Cancer Institute & Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and TherapyTianjin Tianjin's Clinical Research Center for Cancer Tianjin Key Laboratory of Digestive Cancer Fujian Medical University Union Hospital Fujian Provincial cancer Hospital cancer Center The First Hospital of Jilin University Department of Medical Oncology Gastroenterology and Urology Hunan Cancer Hospital Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Department of Oncology The Third Xiangya Hospital Central South University Department of Gastrointestinal Oncology Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Peking University Cancer Hospital and Institute Beijing Engineering Research Center of Protein and Antibody Sinocelltech Ltd. Department of cancer Center Peking Union Medical College Hospital Chinese Academy of Medical Sciences

Objective: This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR) antibody(SCT200) and an anti-programmed cell death 1(PD-1) antibody(SCT-I10A) as third-line or subsequent therapies in patients with rat sarcoma viral oncogene(RAS)/v-raf murine sarcoma viral oncogene homolog B(BRAF) wild-type(wt) metastatic colorectal cancer(mCRC).Methods: We conducted a multicenter, open-label, phase Ib clinical trial. Patients with histologically confirmed RAS/BRAF wt m CRC with more than two lines of treatment were enrolled and treated with SCT-I10A and SCT200. The primary endpoints were the objective response rate(ORR) and safety. The secondary endpoints included disease control rate(DCR), progression-free survival(PFS), and overall survival(OS).Results: Twenty-one patients were enrolled in the study through January 28, 2023. The ORR was 28.57% and the DCR was 85.71%(18/21). The median PFS and OS were 4.14 and 12.84 months, respectively. The treatment-related adverse events(TRAEs) were tolerable. Moreover, compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt m CRC in a third-line setting, no significant improvements in PFS and OS were observed in the combination ***: SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt m CRC patients with an acceptable safety profile. Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting.(Registration No. NCT04229537).

关键词： Colorectal cancer SCT-I10A SCT200 epidermal growth factor receptor programmed cell death 1

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AKT2^(S128)/CCTα^(S315/319/323)-positive cancer-associated fibroblasts (CAFs) mediate focal adhesion kinase (FAK) inhibitors resistance via secreting phosphatidylcholines (PCs)

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Signal Transduction and Targeted Therapy 2024年第2期9卷 782-796页

作者： Jie Chen Lingyuan Zhang Yuheng Zhu Di Zhao Jing Zhang Yanmeng Zhu Jingyuan Pang Yuanfan Xiao Qingnan Wu Yan Wang Qimin Zhan Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital&Institute100142 BeijingChina Peking University International cancer institute Peking University100191 BeijingChina Research Unit of Molecular cancer Research Chinese Academy of Medical SciencesBeijingChina Soochow University cancer institute Suzhou 215000China institute of cancer Research Shenzhen Bay LaboratoryShenzhen 518107China

Abnormal metabolism is regarded as an oncogenic hallmark related to tumor progression and therapeutic *** study employed multi-omics,including phosphoproteomics,untargeted metabolomics and lipidomics,to demonstrate that the pAKT2 Ser128 and pCCTαSer315/319/323-positive cancer-associated fibroblasts(CAFs)substantially release phosphatidylcholines(PCs),contributing to the resistance of focal adhesion kinase(FAK)inhibitors in esophageal squamous cell carcinoma(ESCC)***,we observed extremely low levels of FAK Tyr397 expression in CAFs,potentially offering no available target for FAK inhibitors playing their anti-growth role in ***,FAK inhibitor increased the intracellular concentration of Ca2+in CAFs,promoting the formation of AKT2/CCTαcomplex,leading to phosphorylation of CCTαSer315/319/323 sites and eventually enhancing stromal PC *** activation could stimulate the intratumoral Janus kinase 2(JAK2)/Signal transducer and activator of transcription 3(STAT3)pathway,triggering resistance to FAK *** of clinical samples demonstrated that stromal pAKT2 Ser128 and pCCTαSer315/319/323 are related to the tumor malignancy and reduced patient ***-targeted lipidomics and further validation cohort quantitatively showed that plasma PCs enable to distinguish the malignant extent of ESCC *** conclusion,inhibition of stroma-derived PCs and related pathway could be possible therapeutic strategies for tumor therapy.

关键词： CAFs metabolism resistance

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Expert consensus on radiotherapy combined with immunotherapy for esophageal cancer(2024 edition)

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Radiation Medicine and Protection 2024年第2期5卷 59-67页

作者： Professional Committee of Radiation Oncology China Anti-cancer Association Branch ofRadiation Oncology Chinese Medical Association Branch of Radiation Oncology TreatmentPhysician Chinese Medical Doctor Association Qingsong Pang Jun Wang Zhouguang Hui 不详 Tianjin Medical University cancer institute&Hospital Tianjin 300060China the Fourth Hospital of Hebei Medical University Shijiazhuang 050011China National cancer Center National Clinical Research Center for CancerCancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China.

Radiotherapy represents an essential treatment approach for esophageal *** recent years,immunotherapy combined with chemotherapy has become the first-line standard treatment for patients with advanced esophageal *** phase III studies on immunotherapy combined with radiotherapy for locally advanced esophageal cancer are currently *** evidence-based medical data are urgently needed to support the integration of immunotherapy and chemoradiotherapy as a new treatment strategy for patients with locally advanced esophageal *** consensus,formulated based on the latest study results,in-depth research,and thorough discussions,provides a comprehensive set of *** document extensively covers treatment strategies and evaluation methods for radiotherapy combined with immunotherapy across patients with operable esophageal cancer,inoperable locally advanced esophageal cancer,and advanced esophageal ***,common complications and radiation-related issues associated with radiotherapy combined with immunotherapy are discussed,serving as clinical *** expert group comprised members from the Professional Committee of Radiation Oncology,China Anti-cancer Association,the Branch of Radiation Oncology,Chinese Medical Association,and the Branch of Radiation Oncology Treatment Physician,Chinese Medical Doctor Association.

关键词： Esophageal squamous cell carcinoma Esophageal adenocarcinoma Immunotherapy Chemoradiotherapy Radiotherapy Expert consensus

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Long noncoding RNAs HAND2-AS1 ultrasound microbubbles suppress hepatocellular carcinoma progression by regulating the miR-873-5p/tissue inhibitor of matrix metalloproteinase-2 axis

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1547-1563页

作者： Qiang Zou Hao-Wen Wang Xi-Liang Di Yuan Li Hui Gao Department of Interventional Therapy Tianjin Medical University Cancer Institute and HospitalTianjin 300060China National clinical Research Center for cancer Key Laboratory of Cancer Prevention and TherapyTianjin’s Clinical Research Center for CancerTianjin 300060China College of Animal Science and Technology Northeast Agricultural UniversityHarbin 150030Heilongjiang ProvinceChina Department of Hematology and Oncology Linyi People’s HospitalLinyi 251500Shandong ProvinceChina Department of Comprehensive Oncology Baotou Cancer HospitalBaotou 014030Inner Mongolia Autonomous RegionChina

BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is *** targeted microbubble destruction mediated gene transfection is a new method to overexpress *** To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of *** In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,*** addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell ***,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and *** vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation *** We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of ***,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of *** miR-873-5p mimic counteracted the impact of ***,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to *** discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/*** vivo results showed that HAND2-AS1 silencing sig

关键词： Hepatocellular carcinoma Ultrasound microbubbles Long noncoding RNA HAND2-AS1 miR-873-5p Tissue inhibitor of matrix metalloproteinase-2

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PIM1-HDAC2 axis modulates intestinal homeostasis through epigenetic modification

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3049-3067页

作者： Jianming Yang Yawen Xiao Ningning Zhao Geng Pei Yan Sun Xinyu Sun Kaiyuan Yu Chunhui Miao Ran Liu Junqiang Lv Hongyu Chu Lu Zhou Bangmao Wang Zhi Yao Quan Wang Key Laboratory of Immune Microenvironment and Disease(Ministry of Education) Tianjin Institute of ImmunologyState Key Laboratory of Experimental Hematologythe Province and Ministry Co-sponsored Collaborative Innovation Center for Medical EpigeneticsDepartment of ImmunologySchool of Basic Medical SciencesTianjin Institute of Urologythe Second Hospital of Tianjin Medical UniversityTianjin Key Laboratory of Cellular and Molecular ImmunologyTianjin Medical UniversityTianjin 300070China Department of Pathology Tianjin Medical University Cancer Institute and Hospital/National Clinical Research Center of Cancer/Key Laboratory of Cancer Prevention and TherapyTianjin/Tianjin’s Clinical Research Center of CancerTianjin 30060China Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300070China

The mucosal barrier is crucial for intestinal homeostasis,and goblet cells are essential for maintaining the mucosal barrier *** proviral integration site for Moloney murine leukemia virus-1(PIM1)kinase regulates multiple cellular functions,but its role in intestinal homeostasis during colitis is ***,we demonstrate that PIM1 is prominently elevated in the colonic epithelia of both ulcerative colitis patients and murine models,in the presence of intestinal *** PIM1 leads to decreased goblet cells,thus impairing resistance to colitis and colitis-associated colorectal cancer(CAC)in ***,PIM1 modulates goblet cell differentiation through the Wnt and Notch signaling ***,PIM1 interacts with histone deacetylase 2(HDAC2)and downregulates its level via phosphorylation,thereby altering the epigenetic profiles of Wnt signaling pathway ***,these findings investigate the unknown function of the PIM1-HDAC2 axis in goblet cell differentiation and ulcerative colitis/CAC pathogenesis,which points to the potential for PIM1-targeted therapies of ulcerative colitis and CAC.

关键词： PIM1 HDAC2 Goblet cell Gut microbiota Intestinal homeostasis Epigenetic modification Ulcerative colitis CAC

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The E3 ubiquitin ligase TRAF6 controls CTLA-4 turnover and promotes T-cell-mediated antitumor immunity

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Cellular & Molecular Immunology 2024年第1期21卷 97-99页

作者： Xiao-Liang Jie Hua Guo Guang-Biao Zhou State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College100021 BejingChina

Yu et al.[1]reported that the tumor necrosis factor(TNF)receptor OX40(CD134)-TNF receptor-associated factor 6(TRAF6)axis mediates Lys63-linked ubiquitination and subsequent lysosomal degradation of cytotoxic T-lymphocyte antigen 4(CTLA-4),leading to the enhancement of CD8^(+)T-cell-mediated antitumor *** findings unveil a previously unknown mechanism in controlling the stability of the immune checkpoint CTLA-4 and provide a potential therapeutic target for the improvement of Tcell-based immunotherapy.

关键词： immunity OX40 ubiquitin

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Heavy-atom engineered hypoxia-responsive probes for precisive photoacoustic imaging and cancer therapy

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Chinese Chemical Letters 2024年第4期35卷 316-320页

作者： Ling-Ling Wu Xiangchuan Meng Qingyang Zhang Xiaowan Han Feiya Yang Qinghua Wang Hai-Yu Hu Nianzeng Xing Department of Urology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Bioactive Substances and Function of Natural Medicine Institute of Materia MedicaPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100050China

Photoacoustic agents combining photodynamic therapy(PDT) and photothermal therapy(PTT) functions have emerged as potent theranostic agents for combating cancer. The molecular approaches for enhancing the near-infrared(NIR)-absorption and maximizing non-radiative energy transfer are essential for effective photoacoustic imaging(PAI) and therapy applications. In addition, such molecules with high specificity and affinity to cancer cells are urgently needed, which would further decrease the side effect during treatments. In this study, we applied a heavy-atom engineering strategy and introduced p-aminophenol,-thio, and-seleno moieties into NIR heptamethine cyanine(Cy7) skeleton(Cy7-X-NH_(2), X = O, S, Se) to significantly increase photothermal conversion efficiency for PTT and promote intersystem crossing for ***, we designed a series of nitroreductase(NTR)-activated photoacoustic probes(Cy7-X-NO_(2),X = O, S, Se), and target hypoxic tumors with NTR overexpression. Our prostate cancer targeting probe,Cy7-Se-NO_(2)-KUE, exhibited specific tumor photoacoustic signals and effective tumor killing through outstanding synergistic PTT/PDT in vivo. These findings highlighted a versatile strategy for cancer photoacoustic diagnosis and enhanced phototherapy.

关键词： Heavy-atom effect Phototherapy Photoacoustic imaging Hypoxia-responsive Prostate cancer

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Flurbiprofen microneedle patches for the management of acute postoperative pain

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Nano Research 2024年第8期17卷 7493-7503页

作者： Huaqing Chu Yanyan Zhang Yuan Yang Jiangtao Xue Cong Li Wei Zhang Zhou Li Hui Zheng National cancer Center/National clinical Research Center for cancer/cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Beijing institute of Nanoenergy and Nanosystems Chinese Academy of SciencesBeijing 101400China Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases School of Integrated Chinese and Western MedicineHunan University of Chinese MedicineChangsha 410208China School of Life Science Institute of Engineering MedicineBeijing Institute of TechnologyBeijing 100081China institute of Process Engineering Chinese Academy of SciencesBeijing 100190China

Acute postoperative pain is commonly treated with flurbiprofen(FBP),but conventional delivery methods are *** study prepared a new non-burst release microneedles(MNs)using genipin cross-linked gelatin(cGel).By adding varying amounts of genipin to modulate the crosslinking degree of cGel,the drug release behavior of the drug-loaded MNs in the skin can be *** crosslinking parameters that meet therapeutic requirements are selected,thus providing rapid and longlasting analgesic *** solutions were successfully cross-linked,altering matrix material microstructure,confirmed by scanning electron microscope imaging and fourier transform infrared *** demonstrated increasing mechanical strength with higher *** release rates were rapid initially,then slowed,exhibiting a characteristic of decreased release rates with increasing degrees of *** vivo,FBP/cGel MNs significantly reduced allodynia and hyperalgesia post-surgery,with the greatest effect observed at 2–3 h post-surgery,and can maintain analgesia for up to 6 *** tests confirmed good ***/cGel MNs effectively penetrate the stratum corneum,safely delivering drugs with significant analgesic effects,excellent mechanical properties,and good biocompatibility,representing a promising strategy for managing acute postoperative pain.

关键词： microneedle postoperative pain flurbiprofen non-steroid anti-inflammatory drug cross-linked gelatin

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