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Magnetic resonance imaging-based lymph node radiomics for predicting the metastasis of evaluable lymph nodes in rectal cancer

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1849-1860页

作者： Yong-Xia Ye Liu Yang Zheng Kang Mei-Qin Wang Xiao-Dong Xie Ke-Xin Lou Jun Bao Mei Du Zhe-Xuan Li Department of Radiology The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer ResearchNanjing 210011Jiangsu ProvinceChina Department of Colorectal Surgery Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing 210000Jiangsu ProvinceChina1 Department of Pathology The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer ResearchNanjing 210011Jiangsu ProvinceChina Colorectal Center The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer ResearchNanjing 210011Jiangsu ProvinceChina

BACKGROUND Lymph node(LN)staging in rectal cancer(RC)affects treatment decisions and patient prognosis.For radiologists,the traditional preoperative assessment of LN metastasis(LNM)using magnetic resonance imaging(MRI)poses a challenge.AIM To explore the value of a nomogram model that combines Conventional MRI and radiomics features from the LNs of RC in assessing the preoperative metastasis of evaluable LNs.METHODS In this retrospective study,270 LNs(158 nonmetastatic,112 metastatic)were randomly split into training(n=189)and validation sets(n=81).LNs were classified based on pathology-MRI matching.Conventional MRI features[size,shape,margin,T2-weighted imaging(T2WI)appearance,and CE-T1-weighted imaging(T1WI)enhancement]were evaluated.Three radiomics models used 3D features from T1WI and T2WI images.Additionally,a nomogram model combining conventional MRI and radiomics features was developed.The model used univariate analysis and multivariable logistic regression.Evaluation employed the receiver operating characteristic curve,with DeLong test for comparing diagnostic performance.Nomogram performance was assessed using calibration and decision curve analysis.RESULTS The nomogram model outperformed conventional MRI and single radiomics models in evaluating LNM.In the training set,the nomogram model achieved an area under the curve(AUC)of 0.92,which was significantly higher than the AUCs of 0.82(P<0.001)and 0.89(P<0.001)of the conventional MRI and radiomics models,respectively.In the validation set,the nomogram model achieved an AUC of 0.91,significantly surpassing 0.80(P<0.001)and 0.86(P<0.001),respectively.CONCLUSION The nomogram model showed the best performance in predicting metastasis of evaluable LNs.

关键词： Radiomics Lymph node metastasis Rectal cancer Magnetic resonance imaging

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Neoantigen cancer vaccines:a new star on the horizon

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cancer Biology & Medicine 2024年第4期21卷 274-311页

作者： Xiaoling Li Jian You Liping Hong Weijiang Liu Peng Guo Xishan Hao Cell Biotechnology Laboratory Tianjin Cancer Hospital Airport HospitalTianjin 300308China National Clinical Research Center for cancer Tianjin 300060China Haihe Laboratory of Synthetic Biology Tianjin 300090China Department of Thoracic Oncology Tianjin Cancer Hospital Airport HospitalTianjin 300308China Department of Thoracic Oncology Surgery Tianjin Medical University Cancer Institute&HospitalTianjin 300060China Tianjin Medical University cancer institute&hospital Tianjin 300060China

Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer cells.One of the most exciting advances within this field is the targeting of neoantigens,which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal cells.Although neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment,early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint inhibitors.Progress made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of neoantigens.Consequently,personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents recurrences.This review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines,and also discusses challenges and future perspectives for this innovative approach,particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors.

关键词： Immunotherapy neoantigen cancer vaccine solid tumors high-throughput sequencing bioinformatics PDOs AI HLA TCR

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Prognostic significance of grade of malignancy based on histopathological differentiation and Ki-67 in pancreatic ductal adenocarcinoma

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cancer Biology & Medicine 2024年第5期21卷 416-432页

作者： Yuexiang Liang Guannan Sheng Yu Guo Yiping Zou Hanhan Guo Zhifei Li Shaofei Chang Quan Man Song Gao Jihui Hao Department of Pancreatic cancer Tianjin Medical University Cancer Institute & Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and TherapyTianjin Tianjin's Clinical Research Center for Cancer Department of Gastrointestinal Oncology The First Affiliated Hospital of Hainan Medical University Department of Gastrointestinal Pancreatic Surgery Shanxi Provincial People's Hospital

Objective: Tumor cell malignancy is indicated by histopathological differentiation and cell proliferation. Ki-67, an indicator of cellular proliferation, has been used for tumor grading and classification in breast cancer and neuroendocrine tumors. However, its prognostic significance in pancreatic ductal adenocarcinoma(PDAC) remains uncertain.Methods: Patients who underwent radical pancreatectomy for PDAC were retrospectively enrolled, and relevant prognostic factors were examined. Grade of malignancy(GOM), a novel index based on histopathological differentiation and Ki-67, is proposed, and its clinical significance was evaluated.Results: The optimal threshold for Ki-67 was determined to be 30%. Patients with a Ki-67 expression level > 30% rather than ≤ 30% had significantly shorter 5-year overall survival(OS) and recurrence-free survival(RFS). In multivariate analysis, both histopathological differentiation and Ki-67 were identified as independent prognostic factors for OS and RFS. The GOM was used to independently stratify OS and RFS into 3 tiers, regardless of TNM stage and other established prognostic factors. The tumor-nodemetastasis-GOM stage was used to stratify survival into 5 distinct tiers, and surpassed the predictive performance of TNM stage for OS and RFS.Conclusions: Ki-67 is a valuable prognostic indicator for PDAC. Inclusion of the GOM in the TNM staging system may potentially enhance prognostic accuracy for PDAC.

关键词： Ki-67 Pancreatic ductal adenocarcinoma TNM stage differentiation prognosis

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Targeting lncRNA16 by GalNAc-siRNA conjugates facilitates chemotherapeutic sensibilization via the HBB/NDUFAF5/ROS pathway

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Science China(Life Sciences) 2024年第4期67卷 663-679页

作者： Yanfang Liu Yan Wang Bing Liu Wenzhong Liu Yuanyuan Ma Yiren Cao Shi Yan Panpan Zhang Lixin Zhou Qimin Zhan Nan Wu Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Thoracic Surgery IIPeking University Cancer Hospital and InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital and InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Thoracic Oncology IIPeking University Cancer Hospital and InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of PathologyPeking University Cancer Hospital and InstituteBeijing 100142China Peking University International cancer institute Beijing 100191China institute of cancer Research Shenzhen Bay LaboratoryShenzhen 518132China

Chemoresistance is a significant barrier to effective cancer treatment.Potential mechanisms for chemoresistance include reactive oxygen species(ROS)accumulation and expression of chemoresistance-promoting genes.Here,we report a novel function of lncRNA16 in the inhibition of ROS generation and the progression of chemoresistance.By analyzing the serum levels of lncRNA16 in a cohort of 35 patients with non-small cell lung cancer(NSCLC)and paired serum samples pre-and post-treatment from 10 NSCLC patients receiving neoadjuvant platinum-based chemotherapy,performing immunohistochemistry(IHC)assays on 188 NSCLC tumor samples,using comprehensive identification of RNA-binding proteins by mass spectrometry(ChIRP-MS)assays,as well as RNA immunoprecipitation(RIP)and RNA pull-down analyses,we discovered that patients with increased serum levels of lncRNA16 exhibited a poor response to platinum-based chemotherapy.The expression of hemoglobin subunit beta(HBB)and NDUFAF5 significantly increases with the development of chemoresistance.LncRNA16 binds to HBB and promotes HBB accumulation by inhibiting autophagy.LncRNA16 can also inhibit ROS generation via the HBB/NDUFAF5 axis and function as a scaffold to facilitate the colocalization of HBB and NDUFAF5 in the mitochondria.Importantly,preclinical studies in mouse models of chemo-resistant NSCLC have suggested that lncRNA16 targeting by trivalent N-acetylgalactosamine(GalNAc)-conjugated siRNA restores chemosensitivity and results in tumor growth inhibition with no detectable toxicity in vivo.Overall,lncRNA16 is a promising therapeutic target for overcoming chemoresistance,and the combination of first-line platinum-based chemotherapy with lncRNA16 intervention can substantially enhance anti-tumor efficacy.

关键词： chemoresistance lncRNARNA interference ROs chemosensitizer

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PCK1 attenuates tumor stemness via activating the Hippo signaling pathway in hepatocellular carcinoma

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Genes & Diseases 2024年第4期11卷 340-352页

作者： Rui Liu Yi Liu Wenlu Zhang Guiji Zhang Zhirong Zhang Luyi Huang Ni Tang Kai Wang Key Laboratory of Molecular Biology for Infectious Diseases(Ministry of Education) Institute for Viral HepatitisDepartment of Infectious DiseasesThe Second Affiliated HospitalChongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory Sichuan Clinical Research Center for CancerSichuan Cancer Hospital&InstituteSichuan Cancer CenterAffiliated Cancer Hospital of University of Electronic Science and Technology of ChinaChengduSichuan 610041China

Liver cancer stem cells were found to rely on glycolysis as the preferred metabolic program.Phosphoenolpyruvate carboxylase 1(PCK1),a gluconeogenic metabolic enzyme,is down-regulated in hepatocellular carcinoma and is closely related to poor prognosis.The onco-genesis and progression of tumors are closely related to cancer stem cells.It is not completely clear whether the PCK1 deficiency increases the stemness of hepatoma cells and promotes the oncogenesis of hepatocellular carcinoma.Herein,the results showed that PCK1 inhibited the self-renewal property of hepatoma cells,reduced the mRNA level of cancer stem cell markers,and inhibited tumorigenesis.Moreover,PCK1 increased the sensitivity of hepatocellular carci-noma cells to sorafenib.Furthermore,we found that PCK1 activated the Hippo pathway by enhancing the phosphorylation of YAP and inhibiting its nuclear translocation.Verteporfin reduced the stemness of hepatoma cells and promoted the pro-apoptotic effect of sorafenib.Thus,combined treatment with verteporfin and sorafenib may be a potential anti-tumor strat-egy in hepatocellular carcinoma.

关键词： cancer stem cells Chemoresistance Gluconeogenesis Hepatocellular carcinoma YAP

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Curcumin Interferes with TGF-β1-Induced Fibrosis in NRK-49F Cells by Reversing ADAMTS18 Gene Methylation

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Chinese Journal of Integrative Medicine 2024年第7期30卷 600-607页

作者： XU Ben ZHANG Jia-en YE Lin YUAN Chang-wei Department of Urology Peking University First Hospital and Institute of Urology Peking UniversityNational Urological Cancer Center

Objective: To explore the molecular mechanism by which curcumin affects renal interstitial fibrosis（RIF） progression by regulating ADAM metallopeptidase with thrombospondin type 1 motif 18（ADAMTS18） methylation. Methods: NRK-49F cells RIF model were induced with transforming growth factor β1（TGF-β1）. Effects of different concentrations of curcumin（0, 10, 20, and 30 μmol/L） on cell proliferation, cell cycle, cell apoptosis as well as cyclin D1 expression were analyzed by cell counting kit-8, flow cytometry and Western blot, respectively. ADAMTS18 methylation levels were determined by methylation-specific polymerase chain reaction. ADAMTS18, fibronectin（FN）, type Ⅰ collagen（Col-Ⅰ） and alpha-smooth muscle actin（α-SMA） mRNA and protein expressions were analyzed by real-time PCR（RT-PCR） and Western blot, respectively. Meanwhile, cells were treated with 50 mmol/L 5-aza-2'-deoxycytidine（5-aza-dC, demethylation agent） for 72 h. Effect of curcumin on extracellular matrix（ECM） deposition was evaluated by immunochemical staining and Western blot. NRK-49F cells were transfected with ADAMTS18 small interfering RNA and grouped into a normal control, ADAMTS18-knock-out（KO）, and ADAMTS18-KO+ 30 μmol/L curcumin groups, and whether curcumin can reverse the effect of ADAMTS18 knockdown on RIF was evaluated. Results: Compared with the control group, TGF-β1 significantly inhibited the proliferation of NRK-49F cells, blocked the G1/G0phase, promoted cell apoptosis and inhibited cyclin D1 expression（P<0.01）. Among the different concentrations of curcumin, 30 μmol/L curcumin significantly reversed these processes（P<0.01）. Immunochemical staining and Western blot results showed that curcumin significantly inhibited the deposition of FN, Col-Ⅰ and α-SMA（P<0.01）. Curcumin and 5-zaz-dC had synergistic effects, promoting ADAMTS18 expression, removing ADAMTS18 methylation, and reducing ECM deposition. ADAMTS18 knockdown promoted ECM accumulation, and curcumin reversed this process（P<0.01）. Conclusion: TGF-β1 induced fibrosis in NRK-49F cells.

关键词： renal fibrosis curcumin Chinese medicine ADAMTS18 methylation modification

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Subsequent strategies and underlying mechanism of acquired resistance to PD-1 axis inhibitors in advanced non-small cell lung cancer

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中华医学杂志(英文版) 2024年第7期137卷 880-882页

作者： Wang Huilan Cheng Xinyu Yang Fan Chen Lu Zhang Anmei Zhong Liangzhi Long Haixia Zhu Bo Wang Zhongyu institute of cancer Xinqiao hospital Third Military Medical University Chongqing 400037 China

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Advances in regional nodal management of early-stage breast cancer

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Chinese Journal of cancer Research 2024年第2期36卷 215-225页

作者： Zhao Bi Yongsheng Wang Breast cancer Center Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinan 250017China

With the continuous improvement of systemic treatment, reasonable local regional control of early-stage breast cancer can be translated into survival benefits. The optimization of regional nodal management in patients with limited sentinel lymph node(SLN) metastasis needs to be weighed by surgical complications, regional recurrence risk, and lymph node status, as well as other escalating treatment(systemic/radiotherapy) that may result from deescalating surgery. With the effective support and supplementation of systemic therapy and radiotherapy, the management of axillary surgery is developing in a de-escalating trend. The widespread application of neoadjuvant therapy has contributed to optimizing the management of patients with clinically node-negative/imaging nodepositive disease. In clinical practice, it is necessary to consider the residual tumor burden of regional lymph nodes when formulating the optimal irradiation fields in patients with limited positive SLN without axillary lymph node dissection. The combined application of genomic tests and American College of Surgeons Oncology Group Z0011/AMAROS criteria could provide patients with a better strategy of dual de-escalation treatment, which includes the de-escalation of both axillary surgery and systemic treatment. In the era of sentinel lymph node biopsy(SLNB), the regional nodal management of breast cancer should adhere to the concept of “updating ideas, making bold assumptions, and carefully seeking proof”, make full use of the benefits of systemic therapy and radiotherapy to reduce the scope of surgery and complications, and expand the “net benefit” of efficacy and quality of life. This review discusses the optimization of regional nodal management in the era of SLNB, in order to provide reference information for clinicians.

关键词： Breast cancer sentinel lymph node biopsy internal mammary lymph node radiotherapy surgery

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Ferroptosis:a critical mechanism of N^(6)-methyladenosine modification involved in carcinogenesis and tumor progression

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Science China(Life Sciences) 2024年第6期67卷 1119-1132页

作者： Qingqing Wei Changning Xue Mengna Li Jianxia Wei Lemei Zheng Shipeng Chen Yumei Duan Hongyu Deng Faqing Tang Wei Xiong Ming Zhou NHC Key Laboratory of Carcinogenesis Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410013China cancer Research institute and School of Basic Medical Sciences Central South UniversityChangsha 410078China The Key Laboratory of Carcinogenesis and cancer Invasion of the Chinese Ministry of Education Central South UniversityChangsha 410078China Hunan Key Laboratory of Oncotarget Gene Hunan Key Laboratory of Cancer MetabolismHunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410013China

Ferroptosis is an iron-dependent regulatory cell necrosis induced by iron overload and lipid peroxidation.It occurs when multiple redoxactive enzymes are ectopically expressed or show abnormal function.Hence,the precise regulation of ferroptosis-related molecules is mediated across multiple levels,including transcriptional,posttranscriptional,translational,and epigenetic levels.N^(6)-methyladenosine(m^(6)A)is a highly evolutionarily conserved epigenetic modification in mammals.The m^(6)A modification is commonly linked to tumor proliferation,progression,and therapy resistance because it is involved in RNA metabolic processes.Intriguingly,accumulating evidence suggests that dysregulated ferroptosis caused by the m^(6)A modification drives tumor development.In this review,we summarized the roles of m^(6)A regulators in ferroptosis-mediated malignant tumor progression and outlined the m^(6)A regulatory mechanism involved in ferroptosis pathways.We also analyzed the potential value and application strategies of targeting m^(6)A/ferroptosis pathway in the clinical diagnosis and therapy of tumors.

关键词： ferroptosis m6A modification RNA methylation m^(6)A regulator tumor progression

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Reducing the global cancer burden with gastrointestinal screening: China's 30 years practice

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cancer Biology & Medicine 2024年第3期21卷 204-212页

作者： Lei Yang Li Feng Yong Zhu Ning Wang Xinpu Lu Fanghui Gu Xiaotian Zhang Jiafu Ji Peking University cancer hospital(Inner Mongolia Campus)/Affiliated cancer hospital of Inner Mongolia Medical University Inner Mongolia Cancer CenterHohhot 010020China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Bejing) Bejing Office for Cancer Prevention and ControlPeking University Cancer Hospital&InstituteBejing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Peking University Cancer Hospital&InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Bejing) Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China State Key Laboratory of Holistic Integrative Management of Gastrointestinal cancers Bejing Key Laboratory of Carcinogenesis and Translational ResearchGastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China

Gastrointestinal(GI) cancers include esophageal [EC(International Classification of Disease 10^(th) revision: C15)], gastric [GC(C16)], and colorectal [CRC(C18-C21)] cancers. China is a high-incidence country of GI ca... 详细信息

关键词： esophageal colorectal gastrointestinal

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