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Penpulimab,an anti-PD-1 antibody,for heavily pretreated metastatic nasopharyngeal carcinoma:a single-arm phase II study

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3056-3062页

作者： Xiaozhong Chen Wei Wang Qingfeng Zou Xiaodong Zhu Qin Lin Yi Jiang Yan Sun Liangfang Shen Lin Wang Guorong Zou Xiaoyan Lin Shaojun Lin Minying Li Ying Wang Ruilian Xu Rui Ao Rensheng Wang Haifeng Lin Shuang Huang Tingting Xu Wenting Li Mengying Xia Yu Xia Zhongmin Wang Baiyong Li Jingao Li Chaosu Hu Department of radiation oncology Cancer Hospital of the University of ChineseAcademy of Sciences(Zhejiang Cancer Hospital)HangzhouChina Gastroenterology and urology Department II Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaChina Clinical Research Center for Gastrointestinal Cancer in Hunan Province ChangshaChina Department of Medical oncology Affiliated Cancer Hospital&Institute of Guangzhou Medical UniversityGuangzhouChina Department of radiation oncology Guangxi Medical University Affiliated Tumor Hospital&Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University)Ministry of Education&Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency TumorGuangxi Medical UniversityNanningChina Department of radiation oncology Cancer CenterThe First Affiliated Hospital of Xiamen UniversityXiamenChina Department of Medical oncology Cancer Hospital of Shantou University Medical CollegeShantouChina Department of radiation oncology Peking University Cancer Hospital&InstituteBeijingChina Department of oncology Xiangya Hospital Central South UniversityChangshaChina Department of Medical oncology Hainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikouChina Department of oncology The Affiliated Panyu Central Hospital of Guangzhou Medical UniversityGuangzhouChina Department of Medical oncology Fujian Medical University Union HospitalFuzhouChina Department of radiation oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhouChina Department of radiation Therapy for Thoracic Tumors Zhongshan City People’s HospitalZhongshanChina Tumor Radiotherapy Center Chongqing University Cancer HospitalChongqing Cancer HospitalChongqing Cancer InstituteChongqingChina Department of oncology Shenzhen People’s Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSo

Penpulimab is an anti-programmed cell death-1(PD-1)IgG1 antibody with no Fc gamma receptor(FcγR)binding activity,and thus theoretically reduced immune-related adverse events(irAEs)while maintaining *** single-arm,phase II trial conducted across 20 tertiary care centers in China enrolled adult patients with metastatic nasopharyngeal carcinoma(NPC)who had failed two or more lines of previous systemic *** received 200-mg penpulimab intravenously every 2 weeks(4 weeks per cycle)until disease progression or intolerable *** primary endpoint was objective response rate(ORR)per RECIST(version 1.1),as assessed by an independent radiological review *** secondary endpoints included progression-free survival(PFS)and overall survival(OS).One hundred thirty patients were enrolled and 125 were efficacy *** the data cutoff date(September 28,2022),1 patient achieved complete response and 34 patients attained partial *** ORR was 28.0%(95%CI 20.3–36.7%).The response was durable,with 66.8%still in response at 9 ***-three patients(26.4%)were still on *** median PFS and OS were 3.6 months(95%CI=1.9–7.3 months)and 22.8 months(95%CI=17.1 months to not reached),***(7.6%)patients experienced grade 3 or higher *** has promising anti-tumor activities and acceptable toxicities in heavily pretreated metastatic NPC patients,supporting further clinical development as third-line treatment of metastatic NPC.

关键词： metastatic nasopharyngeal supporting

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Remodeling Tumor Immune Microenvironment by Using Polymer-Lipid-Manganese Dioxide Nanoparticles with radiation Therapy to Boost Immune Response of Castration-Resistant Prostate Cancer

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Research 2024年第3期2023卷 83-96页

作者： Abdulmottaleb E.Zetrini HoYin Lip Azhar Z.Abbasi Ibrahim Alradwan Taksim Ahmed Chunsheng He Jeffrey T.Henderson Andrew M.Rauth Xiao Yu Wu Advanced Pharmaceutics and Drug Delivery Laboratory Leslie Dan Faculty of PharmacyUniversity of TorontoM5S 3M2TorontoONCanada. departments of Medical Biophysics and radiation oncology University of TorontoM5G 1L7TorontoONCanada.

Despite substantial progress in the treatment of castration-resistant prostate cancer (CRPC), including radiation therapy and immunotherapy alone or in combination, the response to treatment remains poor due to the hypoxic and immunosuppressive nature of the tumor microenvironment. Herein, we exploited the bioreactivity of novel polymer–lipid manganese dioxide nanoparticles (PLMDs) to remodel the tumor immune microenvironment (TIME) by increasing the local oxygen levels and extracellular pH and enhancing radiation-induced immunogenic cell death. This study demonstrated that PLMD treatment sensitized hypoxic human and murine CRPC cells to radiation, significantly increasing radiation-induced DNA double-strand breaks and ultimately cell death, which enhanced the secretion of damage-associated molecular patterns, attributable to the induction of autophagy and endoplasmic reticulum stress. Reoxygenation via PLMDs also polarized hypoxic murine RAW264.7 macrophages toward the M1 phenotype, enhancing tumor necrosis factor alpha release, and thus reducing the viability of murine CRPC TRAMP-C2 cells. In a syngeneic TRAMP-C2 tumor model, intravenous injection of PLMDs suppressed, while radiation alone enhanced recruitment of regulatory T cells and myeloid-derived suppressor cells. Pretreatment with PLMDs followed by radiation down-regulated programmed death-ligand 1 and promoted the infiltration of antitumor CD8+ T cells and M1 macrophages to tumor sites. Taken together, TIME modulation by PLMDs plus radiation profoundly delayed tumor growth and prolonged median survival compared with radiation alone. These results suggest that PLMDs plus radiation is a promising treatment modality for improving therapeutic efficacy in radioresistant and immunosuppressive solid tumors.

关键词： RAW264.7 alone treatment

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Alzheimer's disease and low-dose radiation therapy:A new hope

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radiation Medicine and Protection 2024年第1期5卷 1-6页

作者： Neal E.Dunlap Robert P.Friedland Lu Cai Department of radiation oncology University of Louisville School of MedicineLouisvilleKY40202USA Department of Neurology The University of Louisville School of MedicineLouisvilleKY40202USA Pediatric Research Institute Departments of PediatricsPharmacology and ToxicologyUniversity of Louisville School of MedicineLouisvilleKY40202USA

The concept of low-dose radiation(LDR)-induced hormetic responses was initially observed approximately 70 years ago and systematically reviewed along with the discovery of LDR-induced adaptive responses in a cytogenetic in vitro study in *** the end of the 1990s,discussions regarding the potential applications of LDRinduced hormesis and adaptive responses for preventing or treating chronic diseases,such as Alzheimer’s disease(AD)had taken *** 2016,reports on radiotherapy for the subjects with AD and for genetic AD model mice were ***,several preclinical studies with animal models of AD and clinical studies in AD subjects were conducted.A significant milestone was achieved with the online availability of a new Systematic Review based on qualified publications from these preclinical and clinical *** mini-review provides a concise historical introduction to LDR-induced hormesis and adaptive responses with discussion of AD radiotherapy with either LDR or relatively high dose *** of this Systematic Review cover promising outcomes,challenges,and new questions,followed by discussion of potential mechanisms.

关键词： Alzheimer’s disease Low-dose radiation radiation adaptive response radiation hormesis

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Antitumor efficacy and potential mechanism of FAP-targeted radioligand therapy combined with immune checkpoint blockade

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2936-2952页

作者： Liang Zhao Yizhen Pang Yangfan Zhou Jianhao Chen Hao Fu Wei Guo Weizhi Xu Xin Xue Guoqiang Su Long Sun Hua Wu Jingjing Zhang Zhanxiang Wang Qin Lin Xiaoyuan Chen Haojun Chen Department of Nuclear Medicine and Minnan PET Center Xiamen Key Laboratory of RadiopharmaceuticalsThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and College of Design and EngineeringNational University of SingaporeSingaporeSingapore Clinical Imaging Research Centre Centre for Translational MedicineYong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Department of radiation oncology Xiamen Cancer CenterXiamen Key Laboratory of Radiation OncologyThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina Department of Colorectal Tumor Surgery Xiamen Cancer CenterXiamen Key Laboratory of Radiation OncologyThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina Department of Cardiothoracic Surgery Zhongda HospitalSchool of MedicineSoutheast UniversityNanjingChina Nanomedicine Translational Research Program NUS Center for NanomedicineYong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Department of Neurosurgery and Department of Neuroscience Fujian Key Laboratory of Brain Tumors Diagnosis and Precision TreatmentXiamen Key Laboratory of Brain Centerthe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina Institute of Molecular and Cell Biology Agency for ScienceTechnology and Research(A*STAR)SingaporeSingapore Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials Xiamen Institute of Rare Earth MaterialsHaixi InstituteChinese Academy of SciencesXiamenChina

Radiotherapy combined with immune checkpoint blockade holds great promise for synergistic antitumor *** radionuclide therapy delivers radiation directly to tumor ***1004 is a fibroblast activation protein(FAP)-targeting radiopharmaceutical,conjugated with the albumin binder Evans Blue,which has demonstrated enhanced tumor uptake and retention in previous preclinical and clinical ***,we demonstrate that^(68)Ga/^(177)Lu-labeled LNC1004 exhibits increased uptake and prolonged retention in MC38/NIH3T3-FAP and CT26/NIH3T3-FAP tumor *** therapy with^(177)Lu-LNC1004 induced a transient upregulation of PD-L1 expression in tumor *** combination of^(177)Lu-LNC1004 and anti-PD-L1 immunotherapy led to complete eradication of all tumors in MC38/NIH3T3-FAP tumor-bearing mice,with mice showing 100%tumor rejection upon ***,single-cell RNA sequencing(scRNA-seq),and TCR sequencing revealed that combination therapy reprogrammed the tumor microenvironment in mice to foster antitumor immunity by suppressing malignant progression and increasing cell-to-cell communication,CD8^(+)T-cell activation and expansion,M1 macrophage counts,antitumor activity of neutrophils,and T-cell receptor diversity.A preliminary clinical study demonstrated that^(177)Lu-LNC1004 was well-tolerated and effective in patients with refractory ***,scRNA-seq of peripheral blood mononuclear cells underscored the importance of addressing immune evasion through immune checkpoint blockade *** was emphasized by the observed increase in antigen processing and presentation juxtaposed with T cell *** conclusion,our data supported the efficacy of immunotherapy combined with^(177)Lu-LNC1004 for cancer patients with FAP-positive tumors.

关键词： immunity retention holds

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A preliminary study on rectal dose reduction associated with hyaluronic acid implantation in brachytherapy for prostate cancer

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Asian Journal of urology 2024年第2期11卷 286-293页

作者： Tairo Kashihara Yuka Urago Hiroyuki Okamoto Mihiro Takemori Hiroki Nakayama Shohei Mikasa Tetsu Nakaichi Kotaro Iijima Takahito Chiba Junichi Kuwahara Satoshi Nakamura Weishan Chang Yoshiyuki Matsui Hiroshi Igaki Department of radiation oncology National Cancer Center Hospital5-1-1 TsukijiChuo-kuTokyoJapan radiation Safety and Quality Assurance Division National Cancer Center Hospital5-1-1 TsukijiChuo-kuTokyoJapan Department of Radiological Sciences Graduate School of Human Health SciencesTokyo Metropolitan University7-2-10 Higashi-OguArakawa-kuTokyoJapan Department of Radiological Technology National Cancer Center Hospital5-1-1 TsukijiChuo-kuTokyoJapan Department of Urological oncology National Cancer Center Hospital5-1-1 TsukijiChuo-kuTokyoJapan

Objectives: Hydrogel spacer (HS) was developed to reduce rectal toxicities caused by radiotherapy, but has been reported to cause major adverse events. Our institute has attempted to introduce a hyaluronic acid (HA) as an alternative spacer. This study aimed to compare rectal doses and geometric distributions between the HS and HA implantation in prostate ***: HS and HA were inserted in 20 and 18 patients undergoing high-dose brachytherapy, respectively. The rectum spacer volumes injected were 10 mL and 22 mL, respectively. In the treatment planning system, 13.5 Gy was administered with common catheter positions. The rectal dose indices were assessed between the spacer groups for dosimetry evaluation. Distances between the prostate and rectum and configurations of the spacers were ***: The mean doses irradiated to 0.1 and 2 mL of the rectum were 10.45 Gy and 6.71 Gy for HS, and 6.73 Gy and 4.90 Gy for HA (p<0.001). The mean minimum distances between the prostate and rectum were 1.23 cm and 1.79 cm for HS and HA, respectively (p<0.05). Geometrical configuration comparisons revealed that HA has a higher ability to expand the space than ***: The rectal dose reduction ability of HA is significantly greater than that of HS, suggesting its potential as a new spacer.

关键词： Brachytherapy Hyaluronicacid Hydrogel Prostaticneoplasm Radiotherapy

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Diabetic cardiomyopathy:Importance of direct evidence to support the roles of NOD-like receptor protein 3 inflammasome and pyroptosis

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World Journal of Diabetes 2024年第8期15卷 1659-1662页

作者： Lu Cai Yi Tan Md Shahidul Islam Michael Horowitz Kupper A Wintergerst Pediatric Research Institute Departments of PediatricsRadiation OncologyPharmacology and ToxicologyUniversity of LouisvilleWendy Novak Diabetes InstituteNorton Children’s HospitalLouisvilleKY 40202United States Department of Biochemistry School of Life SciencesUniversity of KwaZulu-NatalDurban 4000KwaZulu-NatalSouth Africa Department of Medicine University of AdelaideAdelaide 5005Australia Pediatric Research Institute Division of EndocrinologyDepartment of PediatricsWendy Novak Diabetes InstituteNorton Children’s HospitalUniversity of LouisvilleLouisvilleKY 40202United States

Recently,the roles of pyroptosis,a form of cell death induced by activated NODlike receptor protein 3(NLRP3)inflammasome,in the pathogenesis of diabetic cardiomyopathy(DCM)have been extensively ***,most studies have focused mainly on whether diabetes increases the NLRP3 inflammasome and associated pyroptosis in the heart of type 1 or type 2 diabetic rodent models,and whether various medications and natural products prevent the development of DCM,associated with decreased levels of cardiac NLRP3 inflammasome and *** direct link of NLRP3 inflammasome and associated pyroptosis to the pathogenesis of DCM remains unclear based on the limited evidence derived from the available studies,with the approaches of NLRP3 gene silencing or pharmaceutical application of NLRP3 specific *** thus emphasize the requirement for more systematic studies that are designed to provide direct evidence to support the link,given that several studies have provided both direct and indirect evidence under specific *** editorial emphasizes that the current investigation should be circumspect in its conclusion,i.e.,not overemphasizing its role in the pathogenesis of DCM with the fact of only significantly increased expression or activation of NLRP3 inflammasome and pyroptosis in the heart of diabetic rodent *** clear-cut evidence-based causative roles of NLRP3 inflammasome and pyroptosis in the pathogenesis of DCM can help to develop effective and safe medications for the clinical management of DCM,targeting these biomarkers.

关键词： Diabetic cardiomyopathy Nucleotide oligomerization domain NOD-like receptor protein 3 inflammasome Cardiac cell death Pyroptosis

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Fo screen or not to screen： the prostate cancer dilemma

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Asian Journal of Andrology 2015年第1期17卷 44-45页

作者： Nelson N Stone E David Crawford departments of urology and radiation oncology The Icahn School of Medicine at Mount Sinai New York NY USA Department of Surgery Division of Urology and Radiation Oncology The Anschutz Cancer Center The University of Colorado Health Sciences Center. Aurora. CO. USA.

The European Randomized Study of Screening for Prostate （ERSPC） has updated their previous seminal report on prostate cancer mortality comparing screened men to controls. Now with 13 years follow-up, the rate ratio of prostate cancer mortality was 0.79 favoring the screened population. The authors concluded that there was a ＂substantial reduction in prostate cancer mortality attributable to testing with prostate-specific antigen （PSA）＂ but they also stated that a＂quantification of harms＂ needed to be addressed. The issue of harms was not addressed by the ERSPC （at least not in this report） and hence this additional statement most likely reflects the controversy currently surrounding the risks associated with over-diagnosis and treatment of indolent diseases inadvertently detected by a screening protocol, In addition, the positive results from this trial conflict with those of the prostate, lung, colorectal and ovarian （PLCO）2 study and reouire further elaboration.

关键词： ACTIVE SURVEILLANCE BIOPSY ANTIGEN

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High-dose-rate intraluminal brachytherapy during preoperative chemoradiation for locally advanced rectal cancers

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World Journal of Gastroenterology 2010年第35期16卷 4436-4442页

作者： Mutahir Ali Tunio Mansoor Rafi Altaf Hashmi Rehan Mohsin Abdul Qayyum Mujahid Hasan Amjad Sattar Muhammad Mubarak Department of radiation oncology Sindh Institute of Urology and Transplantation Department of Surgical oncology Sindh Institute of Urology and Transplantation Department of Medical oncology Sindh Institute of Urology and Transplantation Department of Gastroenterology Sindh Institute of Urology and Transplantation Department of Radiology Sindh Institute of Urology and Transplantation Department of Pathology Sindh Institute of Urology and Transplantation

AIM:To determine the feasibility and safety of high dose rate intraluminal brachytherapy(HDR-ILBT) boost during preoperative chemoradiation for rectal ***:Between 2008 and 2009,thirty-six patients with locally advanced rectal cancer(≥ T3 or N+),were treated initially with concurrent capecitabine(825 mg/m2 oral twice daily) and pelvic external beam radiotherapy(EBRT)(45 Gy in 25 fractions),then were randomized to group A;HDR-ILBT group(n = 17) to receive 5.5-7 Gy×2 to gross tumor volume(GTV) and group B;EBRT group(n = 19) to receive 5.4 Gy×3 fractions to GTV with *** patients underwent total mesorectal ***:Grade 3 acute toxicities were registered in 12 patients(70.6%) in group A and in 8(42.1%) in group *** pathologic response of T stage(ypT0) in group A was registered in 10 patients(58.8%) and in group B,3 patients(15.8%) had ypT0(P radiation for rectal cancers,with higher response rates,downstaging and with manageable acute toxicities.

关键词： High dose rate Intraluminal brachytherapy boost Locally advanced rectal cancer Preoperative chemoradiation

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Adaptive ultra-hypofractionated whole-pelvic radiotherapy in high-risk and very high-risk prostate cancer on 1.5-Tesla MR-Linac:Estimated delivered dose and early toxicity results

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Chronic Diseases and Translational Medicine 2024年第1期10卷 51-61页

作者： Linrui Gao Ran Wei Shirui Qin Yuan Tian Wenlong Xia Yongwen Song Shulian Wang Hui Fang Yu Tang Hao Jing Yueping Liu Yuan Tang Shunan Qi Bo Chen Yexiong Li Nianzeng Xing Ningning Lu Department of radiation oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina GCP Center/Clinical Research Center National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of urology State Key Laboratory of Molecular OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Background: Magnetic resonance(MR)-guided ultra-hypofractionated radiotherapy with whole-pelvic irradiation(UHF-WPRT)is a novel approach to radiotherapy for patients with high-risk(HR)and very high-risk(VHR)prostate cancer(PCa).However,the inherent complexity of adaptive UHF-WPRT might inevitably result in longer on-couch *** aimed to estimate the delivered dose,study the feasibility and safety of adaptive UHF-WPRT on a 1.5-Tesla ***: Ten patients with clinical stage T3a-4N0-1M0-1c PCa,who consecutively received UHF-WPRT,were enrolled *** contours of the target and organ-at-risks on the position verification-MR(PV-MR),beam-on 3D-MR(Bn-MR),and post-MR(after radiotherapy delivery)were derived from the pre-MR data by deformable image *** physician then manually adjusted them,and dose recalculation was performed *** Prism 9(GraphPad Prism Software Inc.)was utilized for conducting statistical ***: In total,we collected 188 MR scans(50 pre-MR,50 PV-MR,44 Bn-MR,and 44 post-MR scans).With median 59 min,the mean prostate clinical target volume(CTV)-V_(100%)was 98.59%±2.74%,and the mean pelvic CTVp-V_(100%)relative percentages of all scans was 99.60%±1.18%.The median V29 Gy change in the rectal wall was−2%(−18%to 20%).With a median follow-up of 9 months,no patient had acute Common Terminology Criteria for Adverse Events(CTCAE)grade 2 or more severe genitourinary(GU)or gastrointestinal(GI)toxicities(0%).Conclusion: UHF-RT to the prostate and the whole pelvis with concomitant boost to positive nodes using an Adapt-To-Shape(ATS)workflow was technically feasible for patients with HR and VHR PCa,presenting only mild GU and GI *** estimated target dose during the beam-on phase was clinically acceptable based on the 3D-MR-based dosimetry *** trial registration Chinese Clinical Trial Registry ChiCTR2000033382.

关键词： dosimetry hypofractionation magnetic resonance imaging prostate cancer radiation dose radiotherapy

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Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk

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Genes & Diseases 2024年第1期11卷 103-134页

作者： Kevin Qin Michael Yu Jiaming Fan Hongwei Wang Piao Zhao Guozhi Zhaoo Wei Zeng Connie Chen Yonghui Wang Annie Wang Zander Schwartz Jeffrey Hong Lily Song William Wagstaff Rex C.Haydon Hue H.Luu Sherwin H.Ho Jason Strelzow Russell R.Reid Tong-Chuan He Lewis L.Shi Chicago Medical School Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China departments of Orthopaedic Surgery and urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China School of Biomedical Engineering Vanderbilt UniversityNashvilleTN 37235USA Laboratory of Craniofacial Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Wnt signaling plays a major role in regulating cell proliferation and *** Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical *** of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body,establishing the complex interplay between Wnt signaling and other signaling *** crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ ***-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic *** complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic ***,both stimulatory and inhibitory treatments come with potential risks that need to be *** review synthesized much of the current knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt *** thoroughly described the different variants of Wnt signaling,including canonical,noncanonical Wnt/PCP,and the noncanonical Wnt/Ca2+*** description involved each of its components and their involvement in other cellular ***,this review explained the various other pathways and processes that crosstalk with Wnt signaling.

关键词： β-catenin Canonical Wnt Noncanonical Wnt Signal transduction Signaling crosstalk

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