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Primary malignant peritoneal mesothelioma mimicking tuberculous peritonitis:A case report

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World Journal of Clinical Cases 2022年第10期10卷 3156-3163页

作者： Li-Cheng Lin Wen-Yen Kuan Bei-Hao Shiu Yu-Ting Wang Wan-Ru Chao Chi-Chih Wang Department of Education Chung Shan Medical University HospitalTaichung 402Taiwan Department of Surgery Chung Shan Medical University HospitalTaichung 402Taiwan Department of Pathology Chung Shan Medical University HospitalTaichung 402Taiwan Division of Endoscopy Gastroenterology and HepatologyDepartment of Internal MedicineChung Shan Medical University HospitalTaichung 402Taiwan School of Medicine Chung Shan Medical UniversityTaichung 402Taiwan

BACKGROUND Malignant peritoneal mesothelioma(MPM)is a rare malignancy arising in mesothelial cells in the peritoneum.It can be mistaken for many other diseases,such as peritoneal carcinomatosis and tuberculous peritonitis(TBP),because its clinical manifestations are often nonspecific.Therefore,the diagnosis of MPM is often challenging and delayed.CASE SUMMARY A 42-year-old man was referred to our hospital with lower abdominal pain for 1 wk and ascites observed under abdominal sonography.His laboratory findings revealed an isolated elevated tumor marker of carcinoma antigen 125(167.4 U/m L;normal,mesothelioma invasion into soft tissue composed of a papillary,tubular,single-cell arrangement of epithelioid cells.In addition,immunohistochemical staining was positive for mesothelioma markers and negative for adenocarcinoma markers.Based on the above findings,TBP was excluded,and the patient was diagnosed with MPM.CONCLUSION It is important to distinguish MPM from TBP because they have similar symptoms and blood test findings.

关键词： Peritoneal neoplasms Peritoneal diseases mesothelioma Malignant ascites Tuberculous peritonitis Laparoscopy Case report

Current status and progress in immunotherapy for malignant pleural mesothelioma

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Chronic Diseases and Translational Medicine 2022年第2期8卷 91-99页

作者： Boyang Sun Yiting Dong Jiachen Xu Zhijie Wang State Key Laboratory of Molecular Oncology Department of Medical OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100021China

Malignant pleural mesothelioma(MPM)is a rare and aggressive malignant disease.Currently,the platinum doublet of pemetrexed and cisplatin is the standard first-line treatment for unresectable MPM.However,recent promising results of immunotherapy have markedly changed the landscape of MPM treatment.Further,the ongoing innovative therapeutic strategies are expected to expand the range of treatment options;however,several questions remain unanswered.First,establishing predictive biomarkers with high potency is urgently needed to optimize the patient selection process.Second,further exploration of the combination algorithm is expected to unveil more effective and safe regimens.Moreover,other dilemmas,such as the resistance mechanism of immunotherapy and the role of immunotherapy in perioperative settings,still warrant further exploration.

关键词： immunotherapy mesothelioma predictive biomarker

Butein-instigated miR-186-5p-dependent modulation of TWIST1 affects resistance to cisplatin and bioenergetics of Malignant Pleural mesothelioma cells

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Cancer Drug Resistance 2022年第3期5卷 814-828页

作者： Mario Cioce Daniela Rutigliano Annamaria Puglielli Vito Michele Fazio Department of Medicine Laboratory of Molecular Medicine and BiotechnologyUniversity Campus Bio-Medico of RomeRome 00128Italy Institute of Translational Pharmacology National Research Council of Italy(CNR)Rome 00133Italy

Aim:Malignant pleural mesothelioma is a chemoresistant tumor,and biphasic and sarcomatoid histologies portend the worst prognosis for malignant pleural mesothelioma(MPM)patients.We obtained the microRNA expression profile of three biphasic-sarcomatoid MPM cell lines to identify commonly expressed microRNAs and evaluate the effect of butein,a chemo-sensitizing compound,on this microRNA subset.Methods:Nanostring-based microRNA profiling and analysis through the ROSALIND platform were employed to identify the commonly modulated microRNAs and their targets.MicroRNA-mimic transfection,Luciferase assay,and Western blotting were employed to show specific perturbation of TWIST1 levels by miR-186-5p.Sphere-forming assays,invasion assay,and metabolic profiling were used to assess the biological consequences of the butein-instigated miR-186-5p-mediated perturbation of TWIST1 levels.TGCA analysis was used to search for the correlation between TWIST1 and miR-186-5p levels in biphasic and epithelioid MPM specimens.Results:We identified a set of perturbed microRNAs,common to three biphasic/sarcomatoid MPM cell lines,after butein treatment.When focusing on miR-186-5p,we unraveled a butein-ignited and miR-186-5p-mediated modulation of TWIST1 levels which affected the 3D anchorage-independent growth,cisplatin resistance,invasion,and bioenergetics of the MPM cell lines tested.We showed that miR-186-5p and TWIST1 levels are anti-correlated in biphasic MPM specimens from TCGA.Conclusion:We unraveled a novel mechanism of action of butein,which attenuated the pro-tumorigenic features of MPM at least through a miR-186-5p-TWIST1 axis.We suggest that those activities converge into the chemo-sensitizing effect of this compound and may be of translational relevance.

关键词： mesothelioma butein miR-186-5p TWIST1 pithelial-to-mesenchymal transition(EMT) chemoresistance cancer metabolism invasion anchorage-independent growth

Updates on the pathologic diagnosis and classification of mesothelioma

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Journal of Cancer Metastasis and Treatment 2022年第1期8卷 197-209页

作者： Julia R.Farkas Mark Sharobim Jefree J.Schulte Department of Pathology and Laboratory Medicine University of WisconsinMadisonWI 53792USA

mesothelioma is a rare malignant tumor of the serosal membranes that can be challenging to diagnose,especially on small biopsy specimens.There are updated guidelines on the diagnosis and classification of mesothelioma,which incorporate advancements in understanding mesothelioma biology published in the literature over recent years.This review will discuss marked developments and/or improvements that have been made,including:(1)to the histologic classifications of mesothelioma;(2)the use of such classifications and nuclear grading in prognosis;(3)the indispensability of ancillary studies in the diagnosis of mesothelioma;(4)the application of these pleural based classifications and diagnostic schemes in peritoneal mesothelioma;and(5)the potential for diagnosis of mesothelioma in situ.

关键词： mesothelioma BRCA associated peptide 1(BAP1) methylthioadenosine phosphorylase(MTAP) nuclear grading mesothelioma in situ

Overcoming tumor antigen heterogeneity in CAR-T cell therapy for malignant mesothelioma(MM)

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Journal of Cancer Metastasis and Treatment 2022年第1期8卷 302-316页

作者： Reena R.D'Souza Paraskevi Dimou Reyisa Bughda Elizabeth Hawkins Clara Leboreiro Babe Astero Klampatsa Division of Cancer Therapeutics The Institute of Cancer ResearchLondon SM25NGUK Division of Radiotherapy and Imaging The Institute of Cancer ResearchLondon SM25NGUK

Malignant mesothelioma(MM)is a rare,aggressive solid tumor with limited therapeutic options and poor therapeutic response.The role of immunotherapy in MM is now well established and therapeutic options,such as checkpoint inhibitors,are increasingly being approved.Chimeric antigen receptor(CAR)-T cell therapy is successfully implemented in several hematologic cancers,but currently has inadequate effect in solid tumors,owing to several limitations,such as trafficking and infiltration,limited T cell persistence and exhaustion,the immunosuppressive TME and tumor antigen heterogeneity.The lack of uniform and universal expression of tumor-associated antigens(TAAs)on tumor cells,as well as TAA heterogeneity following tumor editing post-therapy,are issues of significant importance to CAR-T cell and associated antigen-targeting therapies.Our review discusses the concept of tumor antigen heterogeneity in MM,the consequences for CAR-T cell therapies and the strategies to overcome it.

关键词： Antigen heterogeneity chimeric antigen receptor(CAR)T cells mesothelioma tumor-associated antigens(TAAs) bystander effect epitope spreading tumor microenvironment

Tsunami of immunotherapy reaches mesothelioma

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World Journal of Clinical Oncology 2022年第4期13卷 267-275页

作者： Xabier Mielgo-Rubio Ana Cardena Gutierrez Veronica Sotelo Pena Maria Virginia Sanchez Becerra Andrea Maria Gonzalez Lopez Adriana Rosero Juan Carlos Trujillo-Reyes Felipe Counago Department of Medical Oncology Hospital Universitario Fundacion AlcorconAlcorcon 28922MadridSpain Department of Medical Oncology Hospital Universitario Nuestra Senora de CandelariaSanta Cruz de TenerifeCanarias 38010Spain Department of Medical Oncology Hospital Virgen de La LuzCuenca 16002Spain Department of Medical Oncology Hospital Universitario Del HenaresCoslada 28822MadridSpain Department of Thoracic Surgery Hospital Universitari de la Santa Creu i Sant PauUniversitat Autonoma de BarcelonaBarcelona 08029Spain Department of Radiation Oncology Hospital Universitario Quironsalud MadridPozuelo de Alcorcon 28223MadridSpain Department of Radiation Oncology Hospital La LuzMadrid 28003Spain Medicine Department Universidad Europea de MadridVillaviciosa de Odon 28670MadridSpain

Malignant pleural mesothelioma(MPM) is the most common type of malignant mesothelioma. It is a rare tumor linked to asbestos exposure and is associated with a poor prognosis. Until very recently, patients with advanced or unresectable disease had limited treatment options, primarily based on doublet chemotherapy with cisplatin and pemetrexed. In 2020 and 2021, after more than a decade with no major advances or new drugs, two phase Ⅲ clinical trials published results positioning immunotherapy as a promising option for the first-and second-line treatment of MPM. Immunotherapy has revolutionized the treatment of many cancers and is also showing encouraging results in malignant mesothelioma. Both immune checkpoint inhibition and dual cytotoxic T-lymphocyte–associated antigen 4 and programmed death-ligand 1 pathway blockade resulted in significantly improved overall survival in randomized phase Ⅲ trials. In the Check Mate 743 trial, first-line therapy with nivolumab plus ipilimumab outperformed standard chemotherapy, while in the CONFIRM trial, nivolumab outperformed placebo in patients previously treated with chemotherapy. These two trials represent a major milestone in the treatment of MPM and are set to position immunotherapy as a viable alternative for treatment-naive patients and patients with progressive disease after chemotherapy.

关键词： mesothelioma Malignant pleural mesothelioma Immunotherapy Immune checkpoint inhibitors Cytotoxic T-lymphocyte–associated antigen 4 Programmed cell death protein 1 Nivolumab Ipilimumab Immunotherapy combo Check Mate 743 CONFIRM

In-vitro proliferation assay with recycled ascitic cancer cells in malignant pleural mesothelioma: A case report

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World Journal of Clinical Cases 2019年第23期7卷 4036-4043页

作者： Takashi Anayama Mai Taguchi Takehiro Tatenuma Hironobu Okada Ryohei Miyazaki KentaroHirohashi Motohiko Kume Keisuke Matsusaki Kazumasa Orihashi Department of SurgeryⅡ Kochi Medical SchoolKochi UniversityKochi 783-8505Japan Japanese CART Study Group Kaname Second ClinicKanamecho HospitalTokyo 171-0043Japan

BACKGROUND We report the first case,to the best of our knowledge,of massive ascites due to recurrent malignant pleural mesothelioma that was controlled using KM-cell-free and concentrated ascites reinfusion therapy(KM-CART).The tumor cells derived via KM-CART were utilized secondarily in an in vitro cell growth assay using the collagen gel droplet-embedded culture drug sensitivity test(CD-DST)to investigate anticancer drug susceptibility.CASE SUMMARY A 56-year-old man presented with recurrent malignant mesothelioma with massive ascites;more than 4000 mL of ascitic fluid was removed,filtered,and concentrated using KM-CART,and the cell-free ascitic fluid was reinfused into the patient to improve quality of life.Cancer cells isolated secondarily in an in vitro proliferation assay using CD-DST exhibited low sensitivity to pemetrexed and high sensitivity to gemcitabine.Treatment with gemcitabine maintained stable disease for 4 mo.CONCLUSION The combination of KM-CART and CD-DST may be a promising treatment option for malignant ascites associated with malignant mesothelioma.

关键词： Ascites Cancer Malignant mesothelioma Pemetrexed Palliative therapy Case report

Experience with peritoneal mesothelioma at the Milan National Cancer Institute

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World Journal of Gastrointestinal Oncology 2010年第2期2卷 76-84页

作者： Marcello Deraco Dario Baratti Antonello Domenico Cabras Nadia Zaffaroni Federica Perrone Raffaella Villa Jenny Jocollè Maria Rosaria Balestra Shigeki Kusamura Barbara Laterza Silvana Pilotti Department of Surgery National Cancer Institute Department of Pathology National Cancer Institute Department of Experimental Oncology National Cancer Institute

Diffuse malignant peritoneal mesothelioma (DMPM) is an uncommon and rapidly fatal tumor.Therapeutic options have traditionally been limited and ineffective.The biologic and molecular events correlated with poor responsiveness to therapy are still poorly understood.In recent years,an innovative treatment approach involving aggressive cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy has reportedly resulted in improved outcome,as compared to historical controls.Since 1995,at the National Cancer Institute (NCI) of Milan (Italy),patients with DMPM have been treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC).In the present paper,clinical experiences and basic science investigations on DMPM at Milan NCI are reviewed.Perioperative and long-term outcome results with CRS and HIPEC are presented.Clinico-pathological prognostic factors were investigated by multivariate analysis.The pathologic features and immunohistochemical markers related to DMPM biologic behavior were assessed in a large case-series uniformly treated at our institution.The prevalence and prognostic role of telomere maintenance mechanisms,which account for the limitless cell replicative potential of many malignancies,were studied.The dysregulation of the apoptotic pathways may play a role in the relative chemo-resistance of DMPM and a better understanding of apoptosis-related mechanisms could result in novel targeted therapeutic strategies.On this basis,the expression of survivin and other IAP family members (IAP-1,IAP-2,and X-IAP),the pro-apoptotic protein Smac/DIABLO,and antigens associated with cell proliferation (Ki-67) and apoptosis (caspase-cleaved cytokeratin-18) were analyzed.Finally,analyses of EGFR,PDGFRA and PDGFRB were performed to ascertain if deregulation of RTK could offer useful alternative therapeutic targets.

关键词： Peritoneal mesothelioma Cytoreductive surgery Hyperthermic intraperitoneal chemotherapy Telomerase Surviving Apoptosis Receptor tyrosin kinase

In vivo formation of Cu(DDC)2 complex induced by nanomedicine for mesothelioma chemotherapy

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Chinese Chemical Letters 2020年第12期31卷 3168-3172页

作者： Yixin Zhang Shunjie Ding Junhua Li Xinyu Peng Jing Li Jing Chang Wenxia Gao Bin He National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610064China Army Logistics University of PLA Chongqing 401331China College of Marine Life Science Ocean University of ChinaQingdao 266003China College of Chemistry and Materials Engineering Wenzhou UniversityWenzhou 325027China

The copper(Ⅱ)diethyldithiocarbamate(Cu(DDC)2)complex exhibited excellent inhibition to cancer cells.The usual administration is intravenous injection for disulfram and oral for copper.A new strategy was reported to improve the administration efficiency of the Cu(DDC)2 drug.Poly(lactide-co-glycolide)(PLGA)nanoparticles were used to trap disulfram and copper gluconate separately,the two types of drug loaded nanoparticles were injected in mesothelioma-bearing nude mice via intraperitoneal injection.The in vivo formation of Cu(DDC)2 complex was induced by disulfiram and Cu^2+ released from PLGA nanoparticles.This stra tegy avoided many obstacles in the use of Cu(DDC)2 complex as chemothe rapeutic and exhibited excellent anticancer activity to mesothelioma.

关键词： mesothelioma Nanoparticles In vivo formation PLGA Cu(DDC)2 complex