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Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy

Cancer Communications 2024年第3期44卷 297-360页

作者： Bin Song Ping Yang Shuyu Zhang laboratory of Radiation medicine West China Second University HospitalSichuan UniversityChengduSichuanP.R.China The Second Affiliated Hospital of Chengdu medical College China National Nuclear Corporation 416 HospitalChengduSichuanP.R.China laboratory of Radiation medicine NHC Key Laboratory of Nuclear Technology Medical TransformationWest China School of Basic Medical Sciences&Forensic MedicineSichuan UniversityChengduSichuanP.R.China

Cancer is a leading cause of death worldwide.Targeted therapies aimed at key oncogenic driver mutations in combination with chemotherapy and radiother-apy as well as immunotherapy have benefited cancer patients considerably.Tumor protein p53(TP53),a crucial tumor suppressor gene encoding p53,reg-ulates numerous downstream genes and cellular phenotypes in response to various stressors.The affected genes are involved in diverse processes,includ-ing cell cycle arrest,DNA repair,cellular senescence,metabolic homeostasis,apoptosis,and autophagy.However,accumulating recent studies have contin-ued to reveal novel and unexpected functions of p53 in governing the fate of tumors,for example,functions in ferroptosis,immunity,the tumor microenvi-ronment and microbiome metabolism.Among the possibilities,the evolutionary plasticity of p53 is the most controversial,partially due to the dizzying array of biological functions that have been attributed to different regulatory mechanisms of p53 signaling.Nearly 40 years after its discovery,this key tumor suppressor remains somewhat enigmatic.The intricate and diverse functions of p53 in reg-ulating cell fate during cancer treatment are only the tip of the iceberg with respect to its equally complicated structural biology,which has been painstak-ingly revealed.Additionally,TP53 mutation is one of the most significant genetic alterations in cancer,contributing to rapid cancer cell growth and tumor pro-gression.Here,we summarized recent advances that implicate altered p53 in modulating the response to various cancer therapies,including chemotherapy,radiotherapy,and immunotherapy.Furthermore,we also discussed potential strategies for targeting p53 as a therapeutic option for cancer.

关键词： cancer chemotherapy drug targeting immunotherapy p53 tumor suppressor

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Unexpected focal fluorodeoxyglucose uptake in main organs;pass through or pass by?

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World Journal of Clinical Cases 2024年第11期12卷 1885-1899页

作者： Haejun Lee Kyung-Hoon Hwang Department of nuclear medicine Gachon University College of MedicineGil Medical CenterIncheon 21565South Korea

Since the inception of fluorine-18 fluorodeoxyglucose(F-18 FDG),positron emission tomography/computed tomography(PET/CT)utilizing F-18 FDG has become widely accepted as a valuable imaging modality in the field of oncology,with global prevalence in clinical practice.Given that a single Torso PET/CT scan encompasses the anatomical region from the skull base to the upper thigh,the detection of incidental abnormal focal hypermetabolism in areas of limited clinical interest is both feasible and not uncommon.Numerous investigations have been undertaken to delineate the distinctive features of these findings,yet the outcomes have proven inconclusive.The incongruent results of these studies present a challenge for physicians,leaving them uncertain about the appropriate course of action.This article provides a succinct overview of the characteristics of fluorodeoxyglucose,followed by a comprehensive discussion of the imaging findings and clinical significance associated with incidental focal abnormal F-18 FDG activity in several representative organs.In conclusion,while the prevalence of unrecognized malignancy varies across organs,malignancies account for a substantial proportion,ranging from approximately one-third to over half,of incidental focal uptake.In light of these rates,physicians are urged to exercise vigilance in not disregarding unexpected uptake,facilitating more assured clinical decisions,and advocating for further active evaluation.

关键词： Incidental Focal Incidentaloma Fluorodeoxyglucose Positron emission tomography Hypermetabolism

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Focal incidental colorectal fluorodeoxyglucose uptake:Should it be spotlighted?

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World Journal of Clinical Cases 2024年第15期12卷 2466-2474页

作者： Haejun Lee Kyung-Hoon Hwang Department of nuclear medicine Gachon University College of MedicineGil Medical CenterIncheon 21565South Korea

Fluorine-18 fluorodeoxyglucose(F-18 FDG)positron emission tomography/computed tomography(PET/CT)has emerged as a cornerstone in cancer evaluation imaging,with a well-established history spanning several years.This imaging modality,encompassing the examination of the body from the base of the skull to the upper thighs,comprehensively covers the chest and abdominopelvic regions in a singular scan,allowing for a holistic assessment of nearly the entire body,including areas of marginal interest.The inherent advantage of this expansive scan range lies in its potential to unveil unexpected incidental abnormal hypermetabolic areas.The identification of incidental focal FDG uptake within colorectal regions during PET/CT scans is not an uncommon occurrence,albeit fraught with challenges associated with non-specific FDG uptake.The presence of benign colorectal lesions or physiological uptake poses a particular obstacle,as these may manifest with FDG uptake levels that mimic malignancy.Consequently,physicians are confronted with a diagnostic dilemma when encountering abnormal FDG uptake in unexpected colorectal areas.Existing studies have presented divergent results concerning these uptakes.Standardized uptake value and its derivatives have served as pivotal metrics in quantifying FDG uptake in PET images.In this article,we aim to succinctly explore the distinctive characteristics of FDG,delve into imaging findings,and elucidate the clinical significance of incidental focal colorectal uptake.This discussion aims to contribute valuable insights into the nuanced interpretation of such findings,fostering a comprehensive understanding.

关键词： Focal Incidental Colorectal Fluorodeoxyglucose Positron emission tomography Hypermetabolism

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Metal-Free Photocatalytic[4+2]Annulation of Acrylamides with 2-Benzyl-2-bromocarbonyls to Assemble Tetralin-1-carboxamides

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Chinese Journal of Chemistry 2024年第2期42卷 157-163页

作者： Weicai Li Lu Tan Yijun Chen Rui Liu Zhongyu Qi Shixuan Yuan Zhanwen Huang Siping Wei Xi Du Dong Yi nuclear medicine and Molecular Imaging Key laboratory of Sichuan Province School of PharmacySouthwest Medical UniversityLuzhouSichuan 646000China Department of Chemistry School of Basic Medical ScienceSouthwest Medical UniversityLuzhouSichuan 646000China Department of Pharmacy Affiliated HospitalSouthwest Medical UniversityLuzhouSichuan 646000China

Tetralin-1-carboxamides are frequently incorporated in myriad medicinally important molecules.However,their existing synthetic routes not only suffer from some drawbacks such as tedious procedures,harsh reaction conditions,narrow substrate scope,low yields,and environmental problems,but are also based upon the elaboration of uneasily available non-linear tetralin derivatives.Herein,we describe a metal-and additive-free visible light-induced[4+2]annulation of two simple linear starting materials,namely acrylamides and 2-benzyl-2-bromocarbonyls,through a cascade C(sp^(3))-Br/C(sp^(2))-H bond cleavage,double C-C bond formation,and aromatization sequence.The developed protocol provides a convenient,efficient,and green approach to a variety of tetralin-1-carboxamide derivatives with good functional group compatibility.Importantly,the resulting products could also undergo the Licl-mediated mono-decarboxylative cyclization process to further furnish the architecturally novel bridged polycyclic imides with excellentcis-diastereoselectivities.

关键词： Annulation Metal-free Photoredox catalysis Tetralin-1-carboxamide Cyclic imides Synthetic methods C-C coupling Radical reactions Reaction mechanisms

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Chinese consensus on the diagnosis and treatment of immunoglobulin light-chain cardiac amyloidosis

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Chinese medical Journal 2024年第2期137卷 127-129页

作者： Kaini Shen Zhuang Tian Yajuan Gao Yining Wang Li Huo Jian Li Yun Zhang Shuyang Zhang On behalf of Chinese Society of Rare Diseases and Rare Diseases Branch of China Research Hospital Association Department of Hematology State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Cardiology State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Clinical medicine Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Radiology State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of nuclear medicine Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear MedicineState Key Laboratory of Complex Severe and Rare DiseasesCenter for Rare Diseases ResearchPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Cardiology The Key Laboratory of Cardiovascular Remodeling and Function ResearchChinese Ministry of EducationChinese National Health Commission and Chinese Academy of Medical SciencesThe State and Shandong Province Joint Key Laboratory of Translational Cardiovascular MedicineQilu HospitalCheeloo College of MedicineShandong UniversityJinanShandong 250012China Cardiovascular Disease Research Center of Shandong First medical University Central Hospital Affiliated to Shandong First Medical UniversityJinanShandong 250013China 不详

Epidemiology of Amyloid Light-Chain Cardiac Amyloidosis(AL-CA)The annual incidence of amyloid light-chain(AL)amyloidosis is 3-5/million,and the incidence in men is slightly higher than that in women.Approximately,70%o... 详细信息

关键词： amyloid cardiac diagnosis

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Engineering biomimetic nanosystem targeting multiple tumor radioresistance hallmarks for enhanced radiotherapy

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Science China(Life Sciences) 2024年第7期67卷 1398-1412页

作者： Shuxiang Wang Hongmei Cao Cui-Cui Zhao Qian Wang Dianyu Wang Jinjian Liu Lijun Yang Jianfeng Liu State Key laboratory of Advanced medical Materials and Devices Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear MedicineKey Laboratory of Radiopharmacokinetics for Innovative DrugsTianjin Institutes of Health ScienceInstitute of Radiation MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China Tianjin medical University Cancer Institute and Hospital National Clinical Research Center for CancerTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Prevention and Therapy(Tianjin)Key Laboratory of Breast Cancer Prevention and TherapyTianjin Medical UniversityMinistry of EducationTianjin 300060China

Tumor cells establish a robust self-defense system characterized by hypoxia,antioxidant overexpression,DNA damage repair,and so forth to resist radiotherapy.Targeting one of these features is insufficient to overcome radioresistance due to the feedback mechanisms initiated by tumor cells under radiotherapy.Therefore,we herein developed an engineering biomimetic nanosystem(M@HHPt)masked with tumor cell membranes and loaded with a hybridized protein-based nanoparticle carrying oxygens(O_(2))and cisplatin prodrugs(Pt(Ⅳ))to target multiple tumor radioresistance hallmarks for enhanced radiotherapy.After administration,M@HHPt actively targeted and smoothly accumulated in tumor cells by virtue of its innate homing abilities to realize efficient co-delivery of O_(2)and Pt(Ⅳ).O_(2)introduction induced hypoxia alleviation cooperated with Pt(Ⅳ)reduction caused glutathione consumption greatly amplified radiotherapy-ignited cellular oxidative stress.Moreover,the released cisplatin effectively hindered DNA damage repair by crosslinking with radiotherapy-produced DNA fragments.Consequently,M@HHPt-sensitized radiotherapy significantly suppressed the proliferation of lung cancer H1975 cells with an extremely high sensitizer enhancement ratio of 1.91 and the progression of H1975 tumor models with an excellent tumor inhibition rate of 94.7%.Overall,this work provided a feasible strategy for tumor radiosensitization by overcoming multiple radioresistance mechanisms.

关键词： biomimetic nanosystem hypoxia alleviation glutathione consumption oxidative stress amplification DNA damage fixation radiosensitization

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Eudragit^®-PEG Nanoparticles: Physicochemical Characterization and Interfacial Tension Measurements

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Open Journal of biophysics 2024年第2期14卷 121-131页

作者： Papa Mady Sy Sidy Mouhamed Dieng Alphonse Rodrigue Djiboune Louis Augustin Diaga Diouf Boucar Ndong Gora Mbaye Mounibé Diarra laboratory of Physics and Pharmaceutical biophysics Faculty of Medicine Pharmacy and Odontology UCAD Dakar Senegal laboratory of Galenic Pharmacy Faculty of Medicine Pharmacy and Odontology UCAD Dakar Senegal laboratory of medical biophysics and nuclear medicine Faculty of Medicine Pharmacy and Odontology UCAD Dakar Senegal

The objectives of this study are to understand the mechanisms involved in the stabilization of water/oil interfaces by polymeric nanoparticles (NPs) (Eudragit®). Eudragit L100 NPs of various sizes and Zeta potentials were studied and compared at a water/cyclohexane model interface using a droplet tensiometer (Tracker Teclis, Longessaigne, France). The progressive interfacial adsorption of the NPs in the aqueous phase was monitored by tensiometry. The model interface was maintained and observed in a drop tensiometer, analyzed via axisymmetric drop shape analysis (ADSA), to determine the interfacial properties. Given the direct relationship between the stability of Pickering emulsions (emulsions stabilized by solid nanoparticles) and the interfacial properties of these layers, different nanoparticle systems were compared. Specifically, Eudragit NPs of different sizes were examined. Moreover, the reduction of the Zeta potential with PEG-6000 induces partial aggregation of the NPs (referred to as NP flocs), significantly impacting the stability of the interfacial layer. Dynamic surface tension measurements indicate a significant decrease in interfacial tension with Eudragit® nanoparticles (NPs). This reduction correlates with the size of the NPs, highlighting that this parameter does not operate in isolation. Other factors, such as the contact angle and wettability of the nanoparticles, also play a critical role. Notably, larger NPs further diminished the interfacial tension. This study enhances our understanding of the stability of Pickering emulsions stabilized by Eudragit® L100 polymeric nanoparticles.

关键词： Nanoparticles Eudragit® PEG Interfacial Tension Pickering Emulsion

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Asymptomatic recurrence in patients with pulmonary embolism

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中华医学杂志(英文版) 2024年第9期137卷 1118-1120页

作者： Hu Song Wang Lei Tan Jiangshan Fang Wei Ma Xinghong Guo Tingting Gao Xin Wu Yan Zhou Yuzi Wang Li Hua Lu State Key laboratory of Cardiovascular Disease National Center for Cardiovascular Diseases Fuwai Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Department of nuclear medicine National Center for Cardiovascular Diseases Fuwai Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Key laboratory of Pulmonary Vascular medicine Department of Cardiology National Clinical Research Center of Cardiovascular Diseases National Center for Cardiovascular Diseases Fuwai Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Fuwai Shenzhen Hospital Chinese Academy of Medical Sciences Shenzhen Guangdong China

To the Editor:Pulmonary embolism (PE) is the third most common cause of cardiovascular-related death worldwide after stroke and heart attack.As a consequence of hemodynamic differences,patients with PE present a wide spectrum of clinical manifestations,ranging from asymptomatic to life-threatening conditions.There are high rates of recurrence in PE patients,and although most patients survive after the initial phase of the disease,the risk of recurrence remains throughout life.Similar to patients experiencing their first PE episodes,patients with recurrent PE may be asymptomatic.To date,much of our knowledge about recurrent PE has come from clinical trials or registry studies in which symptomatic recurrence was a major endpoint,while asymptomatic recurrence is rarely reported.Moreover,current guidelines suggest treating patients with asymptomatic PE similarly to those with symptomatic PE,but do not recommend routine follow-up of asymptomatic patients by imaging methods after PE diagnosis.

关键词： SOCIETY

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Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer

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Chinese Journal of Cancer Research 2024年第1期36卷 25-35页

作者： Zhuanzhuan Mu Xin Zhang Dongquan Liang Jugao Fang Ge Chen Wenting Guo Di Sun Yuqing Sun Zhentian Kai Lisha Huang Jun Liang Yansong Lin Department of nuclear medicine State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College(PUMC)HospitalChinese Academy of Medical Sciences&PUMCBeijing 100730China Beijing Key laboratory of Molecular Targeted Diagnosis and Therapy in nuclear medicine Beijing 100730China Pepperdine University Graduate School of Education and Psychology Los Angeles 90045USA Department of Head and Neck Surgery Affiliated Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Department of General Surgery State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College(PUMC)HospitalChinese Academy of Medical Sciences&PUMCBeijing 100730China Central laboratory State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College(PUMC)HospitalChinese Academy of Medical Sciences&PUMCBeijing 100730China Department of Bioinformatics Zhejiang Shaoxing Topgen Biomedical Technology Co.LtdShanghai 201321China Department of medicine Zhejiang Shaoxing Topgen Biomedical Technology Co.LtdShanghai 201321China Department of Oncology Peking University International HospitalBeijing 102206China

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(P<0.001), with an odds ratio(OR) of high to low MRS of 7.52 [95%confidence interval(95% CI), 3.96-14.28;P<0.001] and an OR of intermediate to low MRS of 3.20(95% CI,1.01-10.14;P=0.041).Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.

关键词： Differentiated thyroid cancer distant metastases genetic alterations RAI refractoriness molecular risk stratification

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Activation of autophagy by Citri Reticulatae Semen extract ameliorates amyloid-beta-induced cell death and cognition deficits in Alzheimer’s disease

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Neural Regeneration Research 2024年第11期19卷 2467-2479页

作者： Yong Tang Jing Wei Xiao-Fang Wang Tao Long Xiaohong Xiang Liqun Qu Xingxia Wang Chonglin Yu Xingli Xiao Xueyuan Hu Jing Zeng Qin Xu Anguo Wu Jianming Wu Dalian Qin Xiaogang Zhou Betty Yuen-Kwan Law Dr.Neher’s biophysics laboratory for Innovative Drug Discovery State Key Laboratory of Quality Research in Chinese MedicineMacao University of Science and TechnologyMacao Special Administrative RegionChina Sichuan Key medical laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica Southwest Medical UniversityLuzhouSichuan ProvinceChina Eye School and Key laboratory of Sichuan Province Ophthalmopathy Prevention&Cure and Visual Function Protection of Chengdu University of TCM ChengduSichuan ProvinceChina School of Basic medical Sciences Southwest Medical UniversityLuzhouSichuan ProvinceChina Department of Ophthalmology The Affiliated Hospital of Southwest Medical UniversityLuzhouSichuan ProvinceChina Department of Neurology The First People’s Hospital of NeijiangNeijiangSichuan ProvinceChina

Amyloid-beta-induced neuronal cell death contributes to cognitive decline in Alzheimer’s disease.Citri Reticulatae Semen has diverse beneficial effects on neurodegenerative diseases,including Parkinson’s and Huntington’s diseases,however,the effect of Citri Reticulatae Semen on Alzheimer’s disease remains unelucidated.In the current study,the anti-apoptotic and autophagic roles of Citri Reticulatae Semen extract on amyloid-beta-induced apoptosis in PC12 cells were first investigated.Citri Reticulatae Semen extract protected PC12 cells from amyloid-beta-induced apoptosis by attenuating the Bax/Bcl-2 ratio via activation of autophagy.In addition,Citri Reticulatae Semen extract was confirmed to bind amyloid-beta as revealed by biolayer interferometry in vitro,and suppress amyloid-beta-induced pathology such as paralysis,in a transgenic Caenorhabditis elegans in vivo model.Moreover,genetically defective Caenorhabditis elegans further confirmed that the neuroprotective effect of Citri Reticulatae Semen extract was autophagy-dependent.Most importantly,Citri Reticulatae Semen extract was confirmed to improve cognitive impairment,neuronal injury and amyloid-beta burden in 3×Tg Alzheimer’s disease mice.As revealed by both in vitro and in vivo models,these results suggest that Citri Reticulatae Semen extract is a potential natural therapeutic agent for Alzheimer’s disease via its neuroprotective autophagic effects.

关键词： Alzheimer’s disease amyloid-beta apoptosis autophagy Caenorhabditis elegans Citri Reticulatae Semen

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