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Acta Pharmaceutica Sinica B 2024年第1期14卷 365-377页

作者： Dandan Ling Xueli Jia Ke Wang Qiucheng Yan Bochuan Yuan Lina Du Miao Li Yiguang Jin Anhui Medical University Hefei 230032China department of Pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer,although it is limited by the low tumor delivery efficacy of anticancer *** therapy is emerging for cancer treatment due to its high immune stimulation effect;however,excessively generated immunogenicity will cause serious inflammatory response ***,we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts(LP@BG@CCM)by layer-by-layer encapsulation for the treatment of metastatic lung *** preparation processes were simple,only involving film formation,electroporation,and pore ***@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer *** the 4T1 breast cancer metastatic lung cancer mouse models,the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance,the reduced lung weight,the clear lung tissue structure,and the enhanced cancer cell apoptosis compared to its ***,several major immune factors were improved after administration of LP@BG@CCM,including the CD4^(+)/CD8a^(+)T cells in the spleen and the TNF-α,IFN-γ,and IL-4 in the ***@BG@CCM exhibits the optimal synergistic chemo-immunotherapy,which is a promising medication for the treatment of metastatic lung cancer.

关键词： Apoptosis Bacterial ghost Cancer cell membrane Immune stimulation Liposome Lung targeting Metastatic lung cancer Paclitaxel

Molecular docking-aided AIEgen design: concept, synthesis and applications

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Science China Chemistry 2024年第8期67卷 2614-2628页

作者： Jian-Qing Zhang Xiao-Yu Xu Fu-Sheng Liu Shu-Qiang Cao Yu-Xin Gui Yi-Wen Su Xiao-Yu He Ji-Yuan Liang You-Quan Zou department of radiation and Medical oncology Zhongnan Hospital of Wuhan UniversitySchool of Pharmaceutical SciencesWuhan UniversityWuhan 430071China Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of EducationWuhan UniversityWuhan 430071China Tai Kang Center for Life and Medical Sciences Wuhan UniversityWuhan 430071China department of Hepatobiliary Pancreatic SurgeryZhongnan Hospital of Wuhan UniversityWuhan 430071China

Aggregate-induced emission luminogens(AIEgens) have been widely used in biological imaging, chemical sensing, and disease treatments. The rational design and construction of AIEgens have received considerable research interests during the last few years. Herein, molecular docking-aided AIEgen design has been reasonably proposed and AIEgen TBQZY with excellent ~1O_(2) generation ability has been synthesized. The newly developed TBQZY could efficiently kill S. epidermidis and methicillinresistant S. epidermidis(MRSE) by tightly binding to bacteria and triggering the accumulation of ~1O_(2) in bacteria. TBQZY specifically regulated the immune system and polarized macrophages from M1 to M2 to accelerate the elimination of biofilm in vivo. In addition, healing acceleration was observed in chronic wounds treated with TBQZY, and side effects were ***, TBQZY had extraordinary potential for combating drug-resistant bacteria in the clinical setting. This research not only provided new concepts for the design of AIEgens, but also shed some lights on the discovery of drugs against drug-resistant bacteria.

关键词： AIEgen molecular docking drug-resistant bacteria biofilm chronic wounds healing

Establishment of NaLuF_(4):15%Tb-based low dose X-PDT agent and its application on efficient antitumor therapy

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International Journal of Minerals,Metallurgy and Materials 2024年第3期31卷 599-610页

作者： Yi Tian Zhiguang Fu Xiaosheng Zhu Chunjing Zhan Jinwei Hu Li Fan Chaojun Song Qian Yang Yu Wang Mei Shi department of radiation oncology Xijing HospitalThe Fourth Military Medical UniversityXi’an 710032China department of oncology Air Force Medical CenterPLAThe Fourth Military Medical UniversityBeijing 100142China department of Tumor Radiotherapy Air Force Medical CenterPLAThe Fourth Military Medical UniversityBeijing 100142China department of Gastroenterology Air Force Hospital of Southern Theater CommandGuangzhou 510062China department of Pharmaceutical Chemistry and Analysis School of PharmacyThe Fourth Military Medical UniversityXi’an 710032China School of Life Sciences Northwestern Polytechnical UniversityXi’an 710072China Institue of Materia Medica School of PharmacyThe Fourth Military Medical UniversityXi’an 710032China

X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration ***,high X-ray irradiation dose caused organ lesions and side effects became the major barrier to X-PDT *** address this issue,this work employed a classic-al co-precipitation reaction to synthesize NaLuF_(4):15%Tb^(3+)(NLF)with an average particle size of(23.48±0.91)nm,which was then coupled with the photosensitizer merocyanine 540(MC540)to form the X-PDT system NLF-MC540 with high production of singlet *** system could induce antitumor efficacy to about 24%in relative low dose X-ray irradiation range(0.1-0.3 Gy).In vivo,when NLF-MC540 irradiated by 0.1 Gy X-ray,the tumor inhibition percentage reached 89.5%±5.7%.The therapeutic mechanism of low dose X-PDT was found.A significant increase of neutrophils in serum was found on the third day after *** immunohistochemical staining of tumor sections,the Ly6G^(+),CD8^(+),and CD11c^(+)cells infiltrated in the tumor microenvironment were *** the bilat-eral tumor model,the NLF-MC540 with 0.1 Gy X-ray irradiation could inhibit both the primary tumor and the distant tumor ***-tected by enzyme linked immunosorbent assay(ELISA),two cytokines IFN-γand TNF-αin serum were upregulated 7 and 6 times than negative control,*** by enzyme linked immune spot assay(ELISPOT),the number of immune cells attributable to the IFN-γand TNF-αlevels in the group of low dose X-PDT were 14 and 6 times greater than that in the negative control group,***,it conclude that low dose X-PDT system could successfully upregulate the levels of immune cells,stimulate the secretion of cy-tokines(especially IFN-γand TNF-α),activate antitumor immunity,and finally inhibit colon tumor growth.

关键词： X-ray excited photodynamic therapy singlet oxygen low dose X-Ray irradiation efficient antitumor therapy anti-tumor immunity

Pharmacological methods for ovarian function and fertility preservation in women with cancer:A literature review

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oncology Research 2024年第8期32卷 1309-1322页

作者： ANA S.CVETANOVIC MATTEO LAMBERTINI KEVIN PUNIE GORANA G.MATOVINA BRKO NIKOLA D.ZIVKOVIC MAJA J.POPOVIC MARIJANA M.MILOVIC KOVACEVIC LAZAR S.POPOVIC department for oncology Medical Faculty NisUniversity of NisNis18000Serbia Clinic of oncology University Clinical Centre NisNis18000Serbia department of Internal Medicine and Medical Sciences(DiMI) School of MedicineUniversity of GenovaGenova16100Italy department of Medical oncology U.O.C Clinica di Oncologia MedicaIRCCS Ospedale Policlinico San MartinoGenova16100Italy department of General Medical oncology and Multidisciplinary Breast Centre Leuven Cancer InstituteUniversity Hospitals LeuvenLeuven3001Belgium department of Medical oncology Oncology Institute of VojvodinaSremska Kamenica21208Serbia department for Pathology Medical Faculty NisUniversity of NisNis18000Serbia Center for Pathology University Clinical Centre NisNis18000Serbia Faculty of Medicine University of Novi SadNovi Sad21000Serbia department of Medical oncology Institute of Oncology and Radiology SerbiaBelgrade11000Serbia

Oncofertility is an extremely signiﬁcant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but signiﬁcantly contributes to preserving life *** effect of chemotherapy can range from minimal effects to complete ovarian *** data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and *** ovarian suppression by administering a gonadotropin-releasing hormone agonist(GnRHa)during chemotherapy decreases the gonadotoxic effect of chemotherapy,thereby diminishing the chance of developing premature ovarian insufﬁciency(POI).At present,the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian ***,most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer,with a considerably small number of studies on patients with hematological ***,most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk,regardless of the hormone receptor *** addition,studies on hematological malignancies have yielded negative results;nevertheless,theﬁndings must be interpreted with caution owing to numerous *** guidelines from the American Society of Clinical oncology and ESMO Clinical Practice Guidelines recommend sperm,oocyte,and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not *** this manuscript,we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data,as well as future perspectives in thisﬁeld

关键词： Gonadotropin-releasing hormone agonists(GnRHa) Fertility preservation Premature ovarian insufficiency(POI) Premenopausal patients

Systemic Inflammation Response Index and weight loss as prognostic factors in metastatic pancreatic cancer: A concept study from the PANTHEIA-SEOM trial

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World Journal of Gastrointestinal oncology 2024年第2期16卷 386-397页

作者： Vilma Pacheco-Barcia Sara Custodio-Cabello Fatima Carrasco-Valero Magda Palka-Kotlowska Axel Mariño-Mendez Alberto Carmona-Bayonas Javier Gallego A J Muñoz Martín Paula Jimenez-Fonseca Luis Cabezon-Gutierrez department of Medical oncology Hospital Universitario de TorrejonMadrid 28850Spain department of Internal Medicine Hospital Universitario de TorrejonMadrid 28850Spain department of Medical oncology Hospital Universitario Central de AsturiasOviedo 33011Spain department of Medical oncology Hospital Universitario Morales MeseguerUniversity of MurciaMurcia 30001Spain department of Medical oncology Hospital General Universitario de ElcheElche 03202Spain department of Medical oncology Hospital General Universitario Gregorio MarañónUniversidad Complutense MadridMadrid 28007Spain Universidad Francisco de Vitoria Madrid 28223Spain

BACKGROUND The prognostic value of the Systemic Inflammation Response Index(SIRI)in advanced pancreatic cancer is recognized,but its correlation with patients´nutritional status and outcomes remains *** To study the prognostic significance of SIRI and weight loss in metastatic pancreatic *** The PANTHEIA-Spanish Society of Medical oncology(SEOM)study is a multicentric(16 Spanish hospitals),observational,longitudinal,non-interventional initiative,promoted by the SEOM Real World-Evidence work *** pilot study sought to analyze the association between weight loss and inflammatory status as defined by *** cohort stems from a proof-of-concept pilot study conducted at one of the coordinating *** with pathologically confirmed metastatic pancreatic adenocarcinoma,treated from January 2020 to January 2023,were *** index was calculated using the product of neutrophil and monocyte counts,divided by lymphocyte counts,obtained within 15 days before initiation *** study evaluated associations between overall survival(OS),SIRI and weight *** A total of 50 patients were included.66%of these patients were male and the median age was 66 *** sites:36%liver,12%peritoneal carcinomatosis,10%lung,and 42%multiple *** the first line palliative chemotherapy treatments:50%received gemcitabine plus nab-paclitaxel;28%,modified fluorouracil,leucovorin,irinotecan and oxaliplatin,and 16%were administered gemcitabine.42%had a weight loss>5%in the three months(mo)preceding diagnosis.21 patients with a SIRI≥2.3×10^(3)/L exhibited a trend towards a lower median OS compared to those with a SIRI5%weight loss before diagnosis,the median OS was 6 mo,in contrast to 19 mo for those who did not experience such weight loss(P=0.003).Patients with a weight loss>5%showed higher SIRI *** difference was statistically significant(P<0.000).For pat

关键词： Pancreatic cancer Nutrition Prognostic factor Inflammation Advanced cancer Systemic inflammatory response index Weight loss

Study on the Impact of Post-Mastectomy Radiotherapy on Immediate Breast Reconstruction and Complications: A Meta-Analysis

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Journal of Clinical and Nursing Research 2024年第6期8卷 64-76页

作者： Wen Li Manman Sun Lihao Zheng Yibo Jiang Nan Ba department of radiation oncology Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhou CityHenan Province 450000China

Background and objective:Immediate breast reconstruction not only reduces the number of surgeries for patients after mastectomy but also decreases psychological and physical trauma,making it increasingly ***,there is currently no consensus on the integration of post-mastectomy radiotherapy(PMRT)with reconstruction *** review evaluates the impact of PMRT on complications following immediate breast reconstruction,providing guidance for clinical treatment ***:PubMed,Web of Science,Embase,and other databases were searched for studies published in the past 15 years on outcomes of implant-based breast reconstruction in the context of radiotherapy to identify articles for *** 5.4 software was used to analyze the risks of seroma,infection,wound dehiscence,flap necrosis,implant exposure,capsule contracture,and reconstruction ***:A total of 1l relevant studies were included,comprising 6323 cases of immediate breast *** was found that breasts receiving postoperative irradiation had a significantly increased risk of complications,with statistically significant differences in seroma(P=0.004),infection(P<0.00001),wound dehiscence(P=0.04),implant exposure(P<0.00001),capsule contracture(P<0.00001),and reconstruction failure(P<0.00001).There was no statistically significant difference in flap necrosis(P=0.88).Conclusion:The results indicate that postoperative radiotherapy significantly increases the risk of complications for patients undergoing immediate implant-based *** measures may be taken in advance with the assistance of healthcare providers if necessary.

关键词： Breast cancer Immediate breast reconstruction Radiotherapy Post-mastectomy Complications

Reconceptualization of immune checkpoint inhibitor-associated gastritis

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World Journal of Gastroenterology 2024年第36期30卷 4031-4035页

作者： Ying-Fang Deng Xian-Shu Cui Liang Wang department of oncology Affiliated Hospital of Qinghai UniversityXining 810000Qinghai ProvinceChina department of Gastrointestinal oncology Surgery Affiliated Hospital of Qinghai UniversityXining 810000Qinghai ProvinceChina

In recent years,with the extensive application of immunotherapy in clinical practice,it has achieved encouraging therapeutic *** enhancing clinical efficacy,however,it can also cause autoimmune damage,triggering immunerelated adverse events(irAEs).Reports of immunotherapy-induced gastritis have been increasing annually,but due to its atypical clinical symptoms,early diagnosis poses a certain ***,it can lead to severe complications such as gastric bleeding,elevating the risk of adverse outcomes for solid tumor patients if immunotherapy is ***,gaining a thorough understanding of the pathogenesis,clinical manifestations,diagnostic criteria,and treatment of immune-related gastritis is of utmost importance for early identification,diagnosis,and ***,the treatment of immune-related gastritis should be personalized according to the specific condition of each *** patients with grade 2-3 irAEs,restarting immune checkpoint inhibitors(ICIs)therapy may be considered when symptoms subside to grade *** restarting ICIs therapy,it is often recommended to use different types of *** grade 4 irAEs,permanent discontinuation of the medication is necessary.

关键词： Programmed cell death receptor-1 Programmed cell death-ligand 1 Cytotoxic T lymphocyte-associated antigen 4 Immune-related adverse events Immune-related gastritis

Development and Characterization of Novel FAP-Targeted Theranostic Pairs: A Bench-to-Bedside Study

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Research 2024年第3期2023卷 473-485页

作者： Wei Huang Yizhen Pang Qiufang Liu Chenyi Liang Shuxian An Qianyun Wu You Zhang Gang Huang Haojun Chen Jianjun Liu Weijun Wei department of Nuclear Medicine Institute of Clinical Nuclear MedicineRenj HospitalSchool of Medicine Shanghai Jiao Tong UniversityShanghai 200127China department of Nuclear Medicine and Minnan PET Center Xiamen Cancer CenterXiamen Key Laboratory of Radiation OncologyThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361003China department of Nuclear Medicine Fudan University Shanghai Cancer CenterFudan UniversityShanghai 200032China

Fibroblast activation protein (FAP) is among the most popular targets in nuclear medicine imaging and cancer theranostics. Several small-molecule moieties (FAPI-04, FAPI-46, etc.) are used for developing FAP-targeted theranostic agents. Nonetheless, the circulation time of FAP inhibitors is relatively short, resulting in rapid clearance via kidneys, low tumor uptake, and associated unsatisfactory treatment efficacy. To address the existing drawbacks, we engineered 3 peptides named FD1, FD2, and FD3 with different circulation times through solid-phase peptide synthesis. All the 3 reported peptides bind to human and murine FAP with single-digit nanomolar affinity measured by surface plasmon resonance. The diagnostic and therapeutic potential of the agents labeled with 68Ga and 177Lu was assessed in several tumor models exhibiting different levels of FAP expression. While radiolabeled FD1 was rapidly excreted from kidneys, radiolabeled FD2/FD3 have significantly prolonged circulation, increased tumor uptake, and decreased kidney accumulation. Our findings indicated that [68Ga]Ga-DOTA-FD1 positron emission tomography (PET) effectively detected FAP dynamics, whereas [177Lu]Lu-DOTA-FD2 and [177Lu]Lu-DOTA-FD3 exhibited remarkable therapeutic efficacy in FAP-overexpressing tumor models, including pancreatic cancer cell models characterized by abundant stroma. Moreover, a pilot translational investigation demonstrated that [68Ga]Ga-DOTA-FD1 had the capability to identify both primary and metastatic tumors with precision and distinction. In summary, we developed [68Ga]Ga-DOTA-FD1 for same-day PET imaging of FAP dynamics and [177Lu]Lu-DOTA-FD2 and [177Lu]Lu-DOTA-FD3 for effective radioligand therapy of FAP-overexpressing tumors.

关键词： DOTA expressing labeled

Planning Target Volume Margin in Linac-Based Stereotactic Radiosurgery for Brain Metastases

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Journal of Cancer Therapy 2024年第7期15卷 265-272页

作者： Hany S. Attallah Radwa M. Hamed Khaled M. EL-Shahat Aliaa Mahmoud Mahmoud Abdallah Ibraheem Haggag Emad Moustafa Adel Yassin department of radiation oncology International Medical Center (IMC) Cairo Egypt department of radiation oncology Armed Forces Medical Collogue (AFCM) Cairo Egypt department of Medical Physics Al Azhar University Cairo Egypt department of Medical Physics International Medical Center (IMC) Cairo Egypt department of Medical Physics Department of Clinical Oncology Faculty of Medicine Zagazig University Zagazig Egypt

Background: The treatment of brain metastases with radiotherapy has shifted to the use of Stereotactic Radio-surgery (SRS). The technical issue of expanding the treatment volume around the Gross Tumor Volume (GTV) is a current debate. Radiotherapy centers use variable GTV-PTV margins, ranging from one to 2 mm. Material and Methods: We performed a dosimetric comparison in plans of twenty patients using three margins: PTV zero, PTV1, and PTV2. We also developed imaginary Peel volumes. These volumes are described as follows: Peel1 = PTV1 − GTV, Peel2 = PTV2 − GTV. Results: Our results showed that the mean PTV volume differed significantly across the different margins (p = 0.000). The V12 of the brain significantly varied as a function of PTV margin (p = 0.000). The target coverage and plan quality indices were not significantly different. The Peel volume dosimetric analysis showed that the mean dose was significantly higher in the nearby normal brain tissue: Peel1 (p = 0.022) and Peel 2 (p = 0.013). Conclusion: According to our dosimetric analysis, expanding the GTV into a PTV by 1 mm margin is more convenient than 2 mm.

关键词： SRS Brain Metastases PTV

Strategy for Detecting Systemic Treatment Sensitivity of Primary Liver Cancer Based on a Novel Infrared-emissive Organic Nanoparticle

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Chemical Research in Chinese Universities 2024年第1期40卷 145-152页

作者： WU Jun LI Yongzhi QIN Hanjiao GAO Ying YANG Bing SHENG Jiyao ZHANG Xuewen department of Hepatobiliary and Pancreatic Surgery the Second Hospital of Jilin UniversityChangchun130022P.R.China department of radiation oncology the Second Hospital of Jilin UniversityChangchun130022P.R.China State Key Laboratory of Supramolecular Structure and Materials Institute of Theoretical ChemistryCollege of ChemistryJilin UniversityChangchun130012P.R.China

In this study,we synthesized an organic material with near-infrared emission capabilities:4-(2-(4-(9-(4-(diphenylamino)phenyl)naphtho[2,3-c][1,2,5]thiadiazol-4-yl)phenyl)-1H-phenol-1-ylidene)malononitrile(TPA).Furthermore,TPA-PEG2000 fluorescent nanoparticles were prepared via coating the shells with ***-PEG2000 exhibited strong near-infrared emission near 700 nm,with a photoluminescence quantum yield of 15.09%,indicating a high emission *** biology experiments have confirmed its low toxicity and excellent *** cholesterol and phospholipid levels in liver cancer cell membranes with low sensitivity or high drug resistance lead to increased rigidity,reduced membrane fluidity,reduced endocytic efficiency,and reduced ***,the uptake of TPA-PEG2000 nanoparticles into cells and the near-infrared fluorescence intensity can be used to evaluate the sensitivity of systemic liver cancer treatment in a simple and efficient manner.

关键词： Nanoparticle Near-infrared Fluorescence Systemic treatment sensitivity Cell membrane fluidity