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Three-dimensional models:from cell culture to Patient-Derived Organoid and its application to future liposarcoma research

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Oncology Research 2025年第1期33卷 1-13页

作者： SAYUMI TAHARA SYDNEY RENTSCH FERNANDA COSTAS CASAL DE FARIA PATRICIA SARCHET ROMA KARNA FEDERICA CALORE RAPHAEL E.POLLOCK department of Surgery Division of Surgical OncologyThe James Comprehensive Cancer CenterThe Ohio State University Wexner Medical CenterColumbusOH 43210USA department of cancer biology and Genetics The James Comprehensive Cancer CenterThe Ohio State University Wexner Medical CenterColumbusOH 43210USA

Liposarcoma is one of the most common soft tissue sarcomas,however,its occurrence rate is still rare compared to other *** to its rarity,in vitro experiments are an essential approach to elucidate liposarcoma *** cell culture-based research(2D cell culture)is still playing a pivotal role,while several shortcomings have been recently under *** vivo,mouse models are usually adopted for pre-clinical analyses with expectations to overcome the issues of 2D cell ***,they do not fully recapitulate human dedifferentiated liposarcoma(DDLPS)***,three-dimensional(3D)culture systems have been the recent research focus in the cell biology field with the expectation to overcome at the same time the disadvantages of 2D cell culture and in vivo animal models and fill in the gap between *** the liposarcoma rarity,we believe that 3D cell culture techniques,including 3D cell cultures/co-cultures,and Patient-Derived tumor Organoids(PDOs),represent a promising approach to facilitate liposarcoma investigation and elucidate its molecular mechanisms and effective therapy *** this review,we first provide a general overview of 3D cell cultures compared to 2D cell *** then focus on one of the recent 3D cell culture applications,Patient-Derived Organoids(PDOs),summarizing and discussing several PDO ***,we discuss the current and future applications of PDOs to sarcoma,particularly in the field of liposarcoma.

关键词： Cell culture Liposarcoma Patient-Derived Organoid(PDO) Spheroid Three-dimensional(3D)cell culture

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E3 Ligases and COVID-19:Insights into Viral Control andTherapeutic Potential

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BIOCELL 2025年第1期49卷 127-147页

作者： Mukul Mishra Deeba Khan Sehbanul Islam department of cancer biology Abramson Family Cancer Research InstitutePerelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA department of Pathology Jawaharlal Nehru Medical CollegeAligarh Muslim UniversityAligarh202002Uttar PradeshIndia

The COVID-19 pandemic,caused by the newly emerged coronavirus SARS-CoV-2,has resulted in unprecedented global health challenges,including millions of infections and *** the direct effects of the virus are critical,the interplay between SARS-CoV-2 and cellular host factors significantly impacts the replication cycle of the virus and the clinical severity of *** review provides a comprehensive analysis of hostpathogen interactions,focusing on the functional roles and regulatory mechanisms of SARS-CoV-2 viral *** systematically review the literature to detail how SARS-CoV-2 engages with host cellular machinery,with a specific emphasis on their modulation by E3 ubiquitin *** dissecting these intricate interactions and the impact of E3 ligases on SARS-CoV-2 infection,we aimto uncover novel therapeutic opportunities and strategies to effectively combat COVID-19.

关键词： SARS-CoV-2 COVID-19 viral proteins host-pathogen interaction E3 ubiquitin ligases ubiquitination targeted protein degradation

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Integrating artificial intelligence into radiological cancer imaging: from diagnosis and treatment response to prognosis

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cancer biology & Medicine 2025年第1期22卷 6-13页

作者： Sunyi Zheng Xiaonan Cui Zhaoxiang Ye Tianjin Medical University cancer Institute and Hospital National Clinical Research Center for Cancer Tianjin's Clinical Research Center for Cancer State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine Tianjin Key Laboratory of Digestive Cancer Key Laboratory of Cancer Prevention and Therapy Department of Radiology

cancer poses a serious threat to human health worldwide and is a leading cause of death1. The analysis of radiological imaging is crucial in early detection, accurate diagnosis, effective treatment planning, and ongoing monitoring of patients with cancer. However, several challenges impede the effectiveness of cancer imaging analysis in clinical practice.

关键词： intelligence prognosis imaging cancer from artificial diagnosis integrating into radiological

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Improved treatment of colorectal liver metastases by early response evaluation and regimen adjustment: a prospective study of clinical functional MR-based modeling

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cancer biology & Medicine 2025年第02期 166-176页

作者： Wenhua Li Huan Zhang Zhe Gong Yue Li Zhiyu Chen Xiaodong Zhu Mingzhu Huang Zhe Zhang Chenchen Wang Lixin Qiu Qirong Geng Jinjia Chang Xiaoying Zhao Xuedan Sheng Wen Zhang Tong Tong Weijian Guo department of Medical Oncology Fudan University Shanghai Cancer Center department of Oncology Shanghai Medical College Fudan University department of Radiology Fudan University Shanghai Cancer Center department of Radiation Oncology Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences

Objective: The aim of the study was to evaluate the feasibility of functional MR in predicting the clinical response to chemotherapy in patients with colorectal liver metastases(CLM).Methods: A total of 196 eligible patients were enrolled in the study between August 2016 and January 2023. Functional MR was performed at baseline and after one cycle of chemotherapy. The diffusion kurtosis radiomic texture features were extracted and a signature model was built using the R package. The initial 100 cases were designated as the training set, the following 48 cases were designated as the validation set, and the final 48 cases were designated as the intervention validation ***: Good performance for the response prediction(AUC = 0.818 in the training set and 0.755 in the validation set) was demonstrated. The objective response rates(ORRs) in the high-risk subgroup were significantly lower than the low-risk subgroup in the training and validation sets. Worse progression-free survival and overall survival rates were noted in the high-risk population. In the intervention set 22.9%(11/48) of the chemotherapy regimens for patients were changed in response to the model-predicted results and the ORR reached 77.1%(37/48), which was significantly higher than the training and validation sets [47.97%(71/148); P = 0.000].Conclusions: A functional MR signature effectively predicted the chemotherapy response and long-term survival. The adjustment of the regimen guided by the model significantly improved the ORR.

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Fighting hypoxia to improve photodynamic therapy-driven immunotherapy: Alleviating, exploiting and disregarding

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Chinese Chemical Letters 2025年第2期36卷 57-68页

作者： Liangliang Jia Ye Hong Xinyu He Ying Zhou Liujiao Ren Hongjun Du Bin Zhao Bin Qin Zhe Yang Di Gao The Key Laboratory of Biomedical Information Engineering of Ministry of Education School of Life Science and Technology Xi'an Jiaotong University center of Digestive Endoscopy Shaanxi Provincial Cancer Hospital department of Ophthalmology Xijing Hospital department of Epidemiology Shaanxi Provincial Cancer Hospital department of Gastroenterology Second Affiliated Hospital Xi'an Jiaotong University Research Institute of Xi'an Jiaotong University

Innovative anti-cancer therapies that activate the immune system show promise in combating cancers resistant to conventional treatments. Photodynamic therapy (PDT) is one such treatment, which not only directly eliminates tumor cells but also functions as an in situ tumor vaccine by enhancing tumor immunogenicity and triggering anti-tumor immune responses through immunogenic cell death (ICD). However, the effectiveness of PDT in enhancing immune responses is influenced by factors, such as photosensitizers and the tumor microenvironment, particularly hypoxia. Current clinically used PDT heavily relies on oxygen (O2) availability and can be limited by tumor hypoxia. Additionally, the tumor immunosuppressive microenvironment induced by hypoxia affects the anti-tumor immunity of tumor-infiltrating effector T cells. Meanwhile, the immunosuppressive myeloid-lineage cells are recruited to the hypoxic tumor tissue and exhibit higher immunosuppressive capabilities under hypoxia conditions. Consequently,numerous strategies have been developed to modulate tumor hypoxia or to create hypoxia-compatible PDT, aiming to reduce the effects of tumor hypoxia on PDT-driven immunotherapy. This review investigates these strategies, including approaches to alleviate, exploit, and disregard tumor hypoxia within the context of PDT/immunotherapy. It also emphasizes the role of advanced nanomedicine and its benefits in these strategies, while outlining current challenges and future prospects in the field.

关键词： Immunogenic cell death Immunotherapy Nanomedicine Photodynamic therapy Photosensitizers Tumor hypoxia

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Pattern-based rapid and robust profiling of gut microbiota and its metabolism with a single fluorescent probe

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Science China Chemistry 2025年第2期68卷 781-788页

作者： Hongli Tan Meizi Zeng Cong Fang Xiaohua Zhu Feng Liu Ying Long Ruijie Deng Peng Yin Meiling Liu Haitao Li Youyu Zhang Shouzhuo Yao Key Laboratory of Chemical biology and Traditional Chinese Medicine Research(Ministry of Education) College of Chemistry and Chemical EngineeringInstitute of Interdisciplinary StudiesHunan Normal UniversityChangsha 410081China Hunan cancer Hospital/The Affiliated cancer Hospital of Xiangya School of Medicine Central South UniversityChangsha 410013China College of Biomass Science and Engineering Healthy Food Evaluation Research CenterSichuan UniversityChengdu 610064China

The gut microbiota and the associated metabolism play a pivotal role in maintaining human health,yet their assessment is challenging due to their inherent diversity,variety,and ***,we developed a multichannel sensor array based on a single fluorescent probe,allowing for rapid and robust profiling gut microbiota and their key metabolites including cysteine(Cys),glutathione(GSH),and homocysteine(Hcy).The assay leverages the single fluorescent probe that is with multiple binding sites and the cross-reactive sensing principle to specifically recognize different biological *** analyzing the pattern of biological thiols,the assay is capable of rapidly identifying six gut-derived bacteria including probiotics,neutral,and pathogenic strains based on fluorescent fingerprints within 5 min,and also discriminating bacteria and their mixtures with different *** the assay that enables the simultaneous measurement of multiple gut-derived bacteria and their metabolites,the designed array achieved an accuracy of 0.99 when discriminating colorectal cancer(CRC)patient feces samples from healthy ***,the as-prepared sensor array can also be used to identify various stages of *** simplicity,rapidness,and cost-effectiveness of our approach render it a robust platform for the analysis of gut microbiota.

关键词： gut microbiota biological thiols sensor array fluorescent probe

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Attitude towards genetic testing for breast cancer susceptibility genes and choice of prevention strategies in Chinese women with or without breast cancer

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cancer biology & Medicine 2025年第1期22卷 28-32页

作者： Xue Yu Furong Kou Yuntao Xie department of Breast Surgery Peking University International Hospital Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Department of Comprehensive Clinical Trial WardPeking University Cancer Hospital & Institute Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Familial and Hereditary Cancer Center Peking University Cancer Hospital & Institute

Breast cancer (BC) is now the most common cancer and the fifth leading cause of cancer-associated mortality among women in China1. Germline pathogenic variants (PVs) of BC susceptibility genes, such as the well-known BRCA1/2 genes, increase the risk of BC and other cancers (ovarian and pancreatic cancer)2,3. Recent studies have demonstrated substantial benefits of poly (adenosine diphosphate ribose) polymerase inhibitors in the treatment of BC patients who carry BRCA1/2 PVs4.

关键词： strategies chinese attitude cancer genetic genes breast choice prevention susceptibility

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Acellular scaffold‑based approach for in situ genetic engineering of host T‑cells in solid tumor immunotherapy

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Military Medical Research 2025年第1期12卷 16-35页

作者： Hiren Y.Dandia Mamatha M.Pillai Deepak Sharma Meghna Suvarna Neha Dalal Ayush Madhok Arvind Ingle Shubhada V.Chiplunkar Sanjeev Galande Prakriti Tayalia department of Biosciences and Bioengineering Indian Institute of Technology BombayPowaiMumbai 400076India Radiation biology and Health Sciences Division Bhabha Atomic Research CentreMumbai 400085India Centre of Excellence in Epigenetics Department of BiologyIndian Institute of Science Education and ResearchPune 411008India Advanced Centre for Treatment Research and Education in Cancer(ACTREC)Tata Memorial CentreKhargharMumbai 410210India

Background:Targeted T-cell therapy has emerged as a promising strategy for the treatment of hematological ***,its application to solid tumors presents significant challenges due to the limited accessibility and *** delivery of tumor-specific T-cells using biomaterials has shown promise,however,procedures required for genetic modification and generation of a sufficient number of tumor-specific T-cells ex vivo remain major obstacles due to cost and time ***:Polyethylene glycol(PEG)-based three-dimensional(3D)scaffolds were developed and conjugated with positively charged poly-L-lysine(PLL)using carbamide chemistry for efficient loading of lentiviruses(LVs)carrying tumor antigen-specific T-cell receptors(TCRs).The physical and biological properties of the scaffold were extensively ***,the scaffold loaded with OVA-TCR LVs was implanted in B16F10 cells expressing ovalbumin(B16-OVA)tumor model to evaluate the anti-tumor response and the presence of transduced ***:Our findings demonstrate that the scaffolds do not induce any systemic inflammation upon subcutaneous implantation and effectively recruit T-cells to the *** B16-OVA melanoma tumor-bearing mice,the scaffolds efficiently transduce host T-cells with OVA-specific *** genetically modified T-cells exhibit homing capability towards the tumor and secondary lymphoid organs,resulting in a significant reduction of tumor size and systemic increase in anti-tumor *** cell profiling revealed a significantly high percentage of transduced T-cells and a notable reduction in suppressor immune cells within the tumors of mice implanted with these ***:Our scaffold-based T-cell therapy presents an innovative in situ localized approach for programming T-cells to target solid *** approach offers a viable alternative to in vitro manipulation of T-cells,circumventing the need for large-scale in vitro generat

关键词： Polyethylene glycol diacrylate Poly-L-lysine Lentiviruses T-cell therapy B16F10-OVA melanoma

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Plasma metabolomics combined with mass spectrometry imaging reveals crosstalk between tumor and plasma in gastric cancer genesis and metastasis

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Chinese Chemical Letters 2025年第1期36卷 506-512页

作者： Yanhua Chen Xian Ding Jun Zhou Zhaoying Wang Yunhai Bo Ying Hu Qingce Zang Jing Xu Ruiping Zhang Jiuming He Fen Yang Zeper Abliz Key Laboratory of Mass Spectrometry Imaging and Metabolomics(State Ethnic Affairs Commission) Center for Imaging and Systems BiologyCollege of Life and Environmental SciencesMinzu University of ChinaBeijing 100081China State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100050China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Center of Drug Clinical TrialPeking University Cancer Hospital and InstituteBeijing 100142China Beijing Engineering Research center of Food Environment and Public Health Minzu University of ChinaBeijing 100081China Key laboratory of Ethnomedicine of Ministry of Education School of PharmacyMinzu University of ChinaBeijing 100081China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of BioBankPeking University Cancer Hospital and InstituteBeijing 100142China Pharmacy department of Beijing Chao–Yang Hospital Capital Medical UniversityBeijing 100020China

Gastric Carcinoma(GC)is a highly fatal malignant tumor with a poor *** elevated mortality rates are primarily due to its proclivity for late-stage *** the metabolic interactions between tumor microenvironment and the systemic bloodstream could help to clearly understand the mechanisms and identify precise biomarkers of tumor growth,proliferation,and *** this study,an integrative approach that combines plasma metabolomics with mass spectrometry imaging of tumor tissue was developed to investigate the global metabolic landscape of GC tumorigenesis and *** results showed that the oxidized glutathione to glutathione ratio(GSSH/GSH)became increased in non-distal metastatic GC(M0),which means an accumulation of oxidative stress in tumor ***,it was found that the peroxidation of polyunsaturated fatty acids,such as 9,10-EpOMe,9-HOTrE,etc.,were accelerated in both plasma and tumor tissues of distal metastatic GC(M1).These changes were further confirmed the potential effect of CYP2E1 and GGT1 in metastatic potential of GC by mass spectrometry imaging(MSI)and immunohistochemistry(IHC).Collectively,our findings reveal the integrated multidimensional metabolomics approach is a clinical useful method to unravel the bloodtumor metabolic crosstalk,illuminate reprogrammed metabolic networks,and provide reliable circulating biomarkers.

关键词： Metabolomics Spatial-resolved metabolomics Gastric cancer Blood-tumor metabolic crosstalk Lipid peroxidation

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Fibrotic liver extracellular matrix induces cancerous phenotype in biomimetic micro-tissues of hepatocellular carcinoma model

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Hepatobiliary & Pancreatic Diseases International 2025年第1期24卷 92-103页

作者： Kosar Nouri Abbas Piryaei Homeyra Seydi Ibrahim Zarkesh Ibrahim Ghoytasi Bahare Shokouhian Mustapha Najimi Massoud Vosough department of Developmental biology University of Science and CultureACECR 14155-4364 TehranIran department of Regenerative Medicine Cell Science Research CenterRoyan Institute for Stem Cell Biology and TechnologyACECR 14155-4364 TehranIran department of Stem Cells and Developmental biology Cell Science Research CenterRoyan Institute for Stem Cell Biology and TechnologyACECR 14155-4364 TehranIran department of biology and Anatomical Sciences School of MedicineShahid Beheshti University of Medical SciencesTehranIran department of Tissue Engineering and Applied Cell Sciences School of Advanced Technologies in MedicineShahid Beheshti University of Medical SciencesTehranIran department of Cell Engineering Cell Science Research CenterRoyan Institute for Stem Cell Biology and TechnologyACECR 14155-4364 TehranIran department of Medical Biotechnology School of Advanced Technologies in MedicineTehran University of Medical SciencesTehranIran Laboratory of Pediatric Hepatology and Cell Therapy Institute of Experimental and Clinical Research(IREC)UCLouvainBrusselsBelgium Experimental cancer Medicine Institution for Laboratory MedicineKarolinska InstituteStockholmSweden

Background: Despite considerable advancements in identifying factors contributing to the development of hepatocellular carcinoma(HCC), the pathogenesis of HCC remains unclear. In many cases, HCC is a consequence of prolonged liver fibrosis, resulting in the formation of an intricate premalignant microenvironment. The accumulation of extracellular matrix(ECM) is a hallmark of premalignant microenvironment. Given the critical role of different matrix components in regulating cell phenotype and function, this study aimed to elucidate the interplay between the fibrotic matrix and malignant features in HCC. Methods: Liver tissues from both control(normal) and carbon tetrachloride(CCl_(4))-induced fibrotic rats were decellularized using sodium dodecyl sulfate(SDS) and Triton X-100. The resulting hydrogel from decellularized ECM was processed into micro-particles via the water-in-oil emulsion method. Microparticles were subsequently incorporated into three-dimensional liver biomimetic micro-tissues(MTs) comprising Huh-7 cells, human umbilical vein endothelial cells(HUVECs), and LX-2 cells. The MTs were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS) assay at day 11, immunofluorescence staining, immunoblotting, and spheroid migration assay at day 14 after co-culture. Results: Fibrotic matrix from CCl4-treated rat livers significantly enhanced the growth rate of the MTs and their expression of CCND1 as compared to the normal one. Fibrotic matrix, also induced the expression of epithelial-to-mesenchymal transition(EMT)-associated genes such as TWIST1, ACTA2, MMP9, CDH2, and VIMENTIN in the MTs as compared to the normal matrix. Conversely, the expression of CDH1 and hepatic maturation genes HNF4A, ALB, CYP3A4 was decreased in the MTs when the fibrotic matrix was used. Furthermore, the fibrotic matrix increased the migration of the MTs and their secretion of alpha-fetoprotein. Conclusions: Our findings suggest a

关键词： Liver fibrosis Decellularized extracellular matrix Spheroid Epithelial-to-mesenchymal transition Cell differentiation Hepatocellular carcinoma

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