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New roles of tumor-derived exosomes in tumor microenvironment

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Chinese Journal of Cancer Research 2024年第2期36卷 151-166页

作者： Shiqian Chen Jinzhe Sun Huan Zhou Hongbin Lei Dan Zang Jun Chen Department of oncology the Second Hospital of Dalian Medical UniversityDalian 116023China Department of radiotherapy the Second Hospital of Dalian Medical UniversityDalian 116023China

Throughout tumorigenesis, the co-evolution of tumor cells and their surrounding microenvironment leads to the development of malignant phenotypes. Cellular communication within the tumor microenvironment(TME) plays a critical role in influencing various aspects of tumor progression, including invasion and metastasis. The release of exosomes, a type of extracellular vesicle, by most cell types in the body, is an essential mediator of intercellular communication. A growing body of research indicates that tumor-derived exosomes(TDEs) significantly expedite tumor progression through multiple mechanisms, inducing epithelial-mesenchymal transition and macrophage polarization, enhancing angiogenesis, and aiding in the immune evasion of tumor cells. Herein, we describe the formation and characteristics of the TME, and summarize the contents of TDEs and their diverse functions in modulating tumor development. Furthermore, we explore potential applications of TDEs in tumor diagnosis and treatment.

关键词： Tumor-derived exosomes tumorigenesis tumor microenvironment diagnosis treatment

High-dose methotrexate and zanubrutinib combination therapy for primary central nervous system lymphoma

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World Journal of Clinical oncology 2024年第3期15卷 371-374页

作者： Budhi Singh Yadav Department of radiotherapy&oncology Post Graduate Institute of Medical Education&ResearchChandigarh 160012India

In this editorial I comment on the article,published in the current issue of the World Journal of Clinical oncology.Primary central nervous system lymphoma(PCNSL)is a disease of elderly and immunocompromised patients.The authors reported clinical results of 19 patients with PCNSL treated with zanubrutinib/high dose methotrexate(HD-MTX)until disease progression.They demonstrated that the combination of zanubrutinib with HD-MTX led to a marked clinical response and tolerability among these patients.They also observed that cerebrospinal fluid liquid biopsy to detect circulating tumor DNA may be a good option for evaluating treatment response and tumor burden in patients with PCNSL.PCNSL is a challenging disease for treatment as these patients present with different neurological states and comorbidities.Treatment has evolved over the years from whole brain radiotherapy to HD-MTX followed by autologous stem cell transplant.Gradually,treatment of patients with PCNSL is going to become individualized.

关键词： Primary central nervous system lymphoma High dose methotrexate Zanubrutinib Whole brain radiotherapy Liquid biopsy

Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma:a multicenter,single-arm,phase II trial

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Cancer Biology & Medicine 2024年第5期21卷 433-444页

作者： Shuzhen Lai Peijing Li Xiaohui Liu Guihong Liu Tieming Xie Xing Zhang Xiaoxuan Wang Jing Huang Yiqiang Tang Zhigang Liu Guoping Shen Chaoming Li Fangxiao Lu Lei Wang Fagui Jiang Caixing Sun Yuanyuan Chen Ming Chen Department of Radiation oncology The Second Affiliated Hospital of Soochow UniversitySuzhou 215000China Department of Radiation oncology Yuebei People’s Hospital Affiliated to the Medical College of Shantou UniversityShaoguan 512026China Chinese Academy of SciencesHangzhou 310022China Department of Radiation oncology The Second Clinical Medical College of Zhejiang Chinese Medical UniversityHangzhou 311403China Department of Radiation oncology The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221004China Chinese Academy of SciencesHangzhou 310022China State Key Laboratory of Translational Medicine and Innovative Drug Development Jiangsu Simcere Diagnostics Co.LtdNanjing 210000China Department of Radiation oncology The Affiliated Huai’an First People’s Hospital of Nanjing Medical UniversityHuai’an 223399China Department of Radiation oncology Jiangxi Cancer Hospital of Nanchang UniversityNanchang 330029China Department of radiotherapy Dongguan Institute of Clinical Cancer ResearchDongguan Key Laboratory of Precision Diagnosis and Treatment for TumorsAffiliated Dongguan HospitalSouthern Medical UniversityDongguan 523059China The Cancer Center The Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhai 519000China Department of Radiation oncology The First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510080China Department of oncology Maoming People’s HospitalMaoming 525000China Department of Radiation oncology Kecheng District People’s HospitalQuzhou 324003China Chinese Academy of SciencesHangzhou 310022China Department of Radiation oncology State Key Laboratory of Oncology in South ChinaSun Yat-sen University Cancer CenterGuangzhou 510060China United Laboratory of Frontier radiotherapy Technology of Sun Yat-sen University&Chinese Academy of Sciences Ion Medical Technology Co. LtdGuangzhou 510060China

Objective:Glioblastomas are highly vascularized malignant tumors.We determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor,anlotinib,for a newly diagnosed glioblastoma.Methods:This multicenter,single-arm trial(NCT04119674)enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November 2020.Patients underwent treatment with the standard STUPP regimen[fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w×6 w(total=54-60 Gy)]or radiotherapy plus continuous daily temozolomide(TMZ)(75 mg/m^(2)of body surface area/d,7 d/w from the first to the last day of radiotherapy),followed by 6 cycles of adjuvant TMZ(150-200 mg/m^(2)×5 d during each 28-d cycle)plus anlotinib(8 mg/d on d 1-14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy,8 maximal cycles as adjuvant therapy,followed by maintenance at 8 mg/d.The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival(OS)and adverse events(AEs).Results:Thirty-three patients received the planned treatment.The median PFS was 10.9 months(95%CI,9.9-18.7 months)and the 12-month PFS rate was 48.5%.The median OS was 17.4 months(95%CI,14.5-21.1 months)and the 12-month OS rate was 81.8%.The most common AEs included hypertriglyceridemia[58%(n=19)],hypoalbuminemia[46%(n=15)],and hypercholesterolemia[46%(n=15)]during concurrent chemoradiotherapy and leukopenia[73%(n=24)],hypertriglyceridemia[67%(n=22)],and neutropenia[52%(n=17)]during adjuvant therapy.Five patients discontinued treatment due to AEs.HEG1(HR,5.6;95%CI,1.3-23.7;P=0.021)and RP1L1 alterations(HR,11.1;95%CI,2.2-57.2;P=0.004)were associated with a significantly shorter PFS.Conclusions:Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable toxicity.HEG1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.

关键词： Glioblastoma anti-angiogenesis multi-kinase inhibitor anlotinib temozolomide progression-free survival

Inflammatory myofibroblastic tumor from molecular diagnostics to current treatment

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oncology Research 2024年第7期32卷 1141-1162页

作者： PAULINA CHMIEL ALEKSANDRA SŁOWIKOWSKA ŁUKASZ BANASZEK ANNA SZUMERA-CIEĆKIEWICZ BARTŁOMIEJ SZOSTAKOWSKI MATEUSZ J.SPAŁEK TOMASZŚWITAJ PIOTR RUTKOWSKI ANNA M.CZARNECKA Department of Soft Tissue/Bone Sarcoma and Melanoma Maria Sklodowska-Curie National Research Institute of OncologyWarsaw02-781Poland Faculty of Medicine Medical University of WarsawWarsaw02-091Poland Department of Pathology Maria Sklodowska Curie National Research Institute of OncologyWarsaw02-781Poland Department of radiotherapy Maria Sklodowska-Curie National Research Institute of OncologyWarsaw02-781Poland

Inﬂammatory myoﬁbroblastic tumor(IMT)is a rare neoplasm with intermediate malignancy characterized by a propensity for recurrence but a low metastatic rate.Diagnostic challenges arise from the diverse pathological presentation,variable symptomatology,and lack of different imaging features.However,IMT is identiﬁed by the fusion of the anaplastic lymphoma kinase(ALK)gene,which is present in approximately 70%of cases,with various fusion partners,including ran-binding protein 2(RANBP2),which allows conﬁrmation of the diagnosis.While surgery is the preferred approach for localized tumors,the optimal long-term treatment for advanced or metastatic disease is difﬁcult to deﬁne.Targeted therapies are crucial for achieving sustained response to treatment within the context of genetic alteration in IMT.Crizotinib,an ALK tyrosine kinase inhibitor(TKI),was ofﬁcially approved by the US Food and Drug Administration(FDA)in 2020 to treat IMT with ALK rearrangement.However,most patients face resistance and disease progression,requiring consideration of sequential treatments.Combining radiotherapy with targeted therapy appears to be beneﬁcial in this indication.Early promising results have also been achieved with immunotherapy,indicating potential for combined therapy approaches.However,deﬁned recommendations are still lacking.This review analyzes the available research on IMT,including genetic disorders and their impact on the course of the disease,data on the latest targeted therapy regimens and the possibility of developing immunotherapy in this indication,as well as summarizing general knowledge about prognostic and predictive factors,also in terms of resistance to systemic therapy.

关键词： Inﬂammatory myoﬁbroblastic tumor(IMT) Epithelioid inﬂammatory myoﬁbroblastic sarcoma Tyrosine kinase inhibitors(TKI) Anaplastic lymphoma kinase(ALK)

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

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World Journal of Gastroenterology 2024年第9期30卷 1237-1249页

作者： Yue-Hong Kong Mei-Ling Xu Jun-Jun Zhang Guang-Qiang Chen Zhi-Hui Hong Hong Zhang Xiao-Xiao Dai Yi-Fu Ma Xiang-Rong Zhao Chen-Yang Zhang Rong-Zheng Chen Peng-Fei Xing Li-Yuan Zhang Center for Cancer Diagnosis and Treatment The Second Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina Department of radiotherapy&oncology The Second Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina Institution of radiotherapy&oncology Soochow UniversitySuzhou 215000Jiangsu ProvinceChina Department of Radiology The Second Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina Department of Nuclear Medicine The Second Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina Department of Clinical Laboratory The Second Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina Department of Pathology The Second Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

关键词： Pancreatic ductal adenocarcinoma PRaG 3.0 therapy Human epidermal growth factor receptor 2 Novel combination therapy Case report

Anaplastic thyroid cancer: Unveiling advances in diagnosis andmanagement

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World Journal of Clinical oncology 2024年第7期15卷 786-789页

作者： Treshita Dey Budhi Singh Yadav Department of radiotherapy&oncology Post-Graduate Institute of Medical Education&ResearchChandigarh 160012India

The review article by Pavlidis et al published in World J Clin Oncol provides a meticulous analysis of the intricacies surrounding anaplastic carcinoma of the thyroid.Thyroid carcinoma encompasses a spectrum of diseases,each charac-terized by distinct behaviors and outcomes.Diagnostic approaches encompass a diverse array of tools.Surgery remains the pivotal treatment for anaplastic thyroid carcinoma.radiotherapy and chemotherapy offer the best overall sur-vival in aggressive disease.Combinations of immunotherapy with targeted the-rapies,such as dabrafenib-trametinib,demonstrate potential for enhanced effect-iveness and improved survival outcomes.Multifaceted approach fuelled by precision medicine and interdisciplinary collaboration is imperative in charting a course toward improved outcomes in this formidable malignancy.

关键词： Anaplastic thyroid cancer Surgery radiotherapy Chemotherapy Targeted therapy Immunotherapy

Preoperative prediction of lymphovascular and perineural invasion in gastric cancer using spectral computed tomography imaging and machine learning

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World Journal of Gastroenterology 2024年第6期30卷 542-555页

作者： Hui-Ting Ge Jian-Wu Chen Li-Li Wang Tian-Xiu Zou Bin Zheng Yuan-Fen Liu Yun-Jing Xue Wei-Wen Lin Department of Radiology Fujian Medical University Union HospitalFuzhou 350001Fujian ProvinceChina Fujian Key Laboratory of Intelligent Imaging and Precision radiotherapy for Tumors Fujian Medical UniversityFuzhou 350001Fujian ProvinceChina Digestive Hematological and Breast MalignanciesClinical Research Center for Radiology and Radiotherapy of Fujian ProvinceFuzhou 350001Fujian ProvinceChina Department of Radiation oncology Fujian Medical University Union HospitalFuzhou 350001Fujian ProvinceChina Department of Diagnostic Radiology Fujian Medical University Union HospitalFuzhou 350001Fujian ProvinceChina School of Electrical and Computer Engineering University of OklahomaOklahomaOK 73019United States

BACKGROUND Lymphovascular invasion(LVI)and perineural invasion(PNI)are important prognostic factors for gastric cancer(GC)that indicate an increased risk of metastasis and poor outcomes.Accurate preoperative prediction of LVI/PNI status could help clinicians identify high-risk patients and guide treatment deci-sions.However,prior models using conventional computed tomography(CT)images to predict LVI or PNI separately have had limited accuracy.Spectral CT provides quantitative enhancement parameters that may better capture tumor invasion.We hypothesized that a predictive model combining clinical and spectral CT parameters would accurately preoperatively predict LVI/PNI status in GC patients.AIM To develop and test a machine learning model that fuses spectral CT parameters and clinical indicators to predict LVI/PNI status accurately.METHODS This study used a retrospective dataset involving 257 GC patients(training cohort,n=172;validation cohort,n=85).First,several clinical indicators,including serum tumor markers,CT-TN stages and CT-detected extramural vein invasion(CT-EMVI),were extracted,as were quantitative spectral CT parameters from the delineated tumor regions.Next,a two-step feature selection approach using correlation-based methods and information gain ranking inside a 10-fold cross-validation loop was utilized to select informative clinical and spectral CT parameters.A logistic regression(LR)-based nomogram model was subsequently constructed to predict LVI/PNI status,and its performance was evaluated using the area under the receiver operating characteristic curve(AUC).RESULTS In both the training and validation cohorts,CT T3-4 stage,CT-N positive status,and CT-EMVI positive status are more prevalent in the LVI/PNI-positive group and these differences are statistically significant(P<0.05).LR analysis of the training group showed preoperative CT-T stage,CT-EMVI,single-energy CT values of 70 keV of venous phase(VP-70 keV),and the ratio of standardized iodine concentration of equilibrium phase(EP-NIC)were ind

关键词： Spectral computed tomography Gastric cancer Lymphovascular invasion Perineural invasion

CircMYBL2 facilitates hepatocellular carcinoma progression by regulating E2F1 expression

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oncology Research 2024年第6期32卷 1129-1139页

作者： JUNZHE YI BINBIN LI XIAOMIN YIN LINGRUI LIU CAILU SONG YING ZHAO MANBO CAI HAILIN TANG DONG CHEN NING LYU State Key Laboratory of oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou510060China Department of Medical oncology The Third People’s Hospital of YongzhouYongzhou425000China Department of radiotherapy The First Affiliated HospitalHengyang Medical SchoolUniversity of South ChinaHengyang421001China Center of Hepato-Pancreato-Biliary Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhou510080China

Circular RNAs(circRNAs)have been recognized as pivotal regulators in tumorigenesis,yet the biological functions as well as molecular mechanisms of the majority of circRNAs in hepatocellular carcinoma(HCC)remain elusive.We sought to unveil the expression profile and biological role of circMYBL2 in HCC.Initial microarray analyses were conducted to probe the expression profile of circMYBL2 in HCC cells,and qRT‒PCR analysis was then performed in HCC cell lines and tissues,revealing significant upregulation of circMYBL2.Subsequent experiments were conducted to evaluate the biological function of circMYBL2 in HCC progression.Furthermore,bioinformatics analysis,qRT‒PCR analysis,luciferase reporter assays,and western blot analysis were employed to investigate the interplay among circMYBL2,miR-1205,and E2F1.CircMYBL2 was found to exhibit marked upregulation in tumor tissues as well as HCC cell lines.Elevated expression of circMYBL2 increased the proliferation and migration of HCC cells,whereas circMYBL2 knockdown elicited contrasting effects.Mechanistically,our results indicated that circMYBL2 promoted E2F1 expression and facilitated HCC progression by sponging miR-1205.Our findings revealed that circMYBL2 contributed to HCC progression through the circMYBL2/miR-1205/E2F1 axis,suggesting the potential of circMYBL2 as a novel target for HCC treatment or a prognostic biomarker for HCC.

关键词： Circular RNAs circMYBL2 miR-1205 E2F1 Hepatocellular carcinoma

Management of Testicular Cancers in Brazzaville

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Open Journal of Urology 2024年第5期14卷 324-332页

作者： Roland Bertile Banga-Mouss Yanick Dimi Nyanga Brice Nkoua Epala Armel Melvin Atipo Ondongo Steve Aristid Ondziel-Opara Eliane Ndounga Alexis Bolenga Louis Constant Mbele Mantsouaka Judith Nsonde Malanda Aanani Séverin Wencesl Odzébé Prosper Alain Bouya Departement of Urology and Andrology University Hospital of Brazzaville Brazzaville Republic of the Congo Departement of Medicale oncology and radiotherapy University Hospital of Brazzaville Brazzaville Republic of the Congo

Introduction: Testicular cancer accounts for 5% of urological tumors, predominantly affecting young men. The aim of our study was to report the diagnostic and evolutionary aspects of testicular cancer cases treated in our center. Patients and Methods: A retrospective study conducted over a 15-year period involving 12 patients treated for testicular cancer at the University Hospital of Brazzaville. Results: The median age was 31 years (range 11 to 49 years), with a median consultation delay of 10.6 months (range 3 to 27 months). Scrotal mass was the most common reason for consultation. Cancer was bilateral in two patients. Two patients were admitted with metastatic disease. Histopathological examination favored germ cell tumors in 7 cases, two cases of non-Hodgkin’s malignant lymphoma, and one case of epididymo-testicular adenocarcinoma. Adjuvant chemotherapy resulted in complete remission in patients with germ cell tumors. However, neoadjuvant chemotherapy was not effective in patients admitted with advanced-stage disease. Conclusion: Testicular cancer is a rare condition that is curable in the majority of cases, but its management is often complicated in our setting due to delayed diagnosis caused by taboos surrounding genital organ pathologies.

关键词： Testicular Cancer Germ Cell Tumor Cisplatin Testicular Lymphoma Testicular Adenocarcinoma