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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      Whole-exome sequencing insights into pulmonary artery sarcoma mimicking pulmonary embolism: a case report and review

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          Abstract

          Pulmonary artery sarcoma (PAS) is a rare and aggressive mesenchymal tumor that often mimics thromboembolic disease. Due to its rare and fatal nature, patients are often underdiagnosed or misdiagnosed. There is still no consensus regarding the diagnosis and treatment of PAS. We present a case of a 63 year old male misdiagnosed with pulmonary thromboembolism who received anticoagulant therapy. 18FDG positron emission tomography (PET) integrated with computed tomography (PET/CT) and subsequent surgery led to the final diagnosis of PAS. Whole exome sequencing of the tissue identified the genetic alterations profile of PAS: copy number variation (CNV) of KIT and mutations of TP53, PIK3CA, IL7R and  ATR. Treated with chemotherapy followed by anlotinib, the patient’s survival time was 8 months after firm diagnosis. To our knowledge, anlotinib used as a treatment for PAS has not been reported.

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          MDM2 small-molecule antagonist RG7112 activates p53 signaling and regresses human tumors in preclinical cancer models.

          F J Podlaski, Mingxuan Xia, L Vassilev … (2013)
          MDM2 negatively regulates p53 stability and many human tumors overproduce MDM2 as a mechanism to restrict p53 function. Thus, inhibitors of p53-MDM2 binding that can reactivate p53 in cancer cells may offer an effective approach for cancer therapy. RG7112 is a potent and selective member of the nutlin family of MDM2 antagonists currently in phase I clinical studies. RG7112 binds MDM2 with high affinity (K(D) ~ 11 nmol/L), blocking its interactions with p53 in vitro. A crystal structure of the RG7112-MDM2 complex revealed that the small molecule binds in the p53 pocket of MDM2, mimicking the interactions of critical p53 amino acid residues. Treatment of cancer cells expressing wild-type p53 with RG7112 activated the p53 pathway, leading to cell-cycle arrest and apoptosis. RG7112 showed potent antitumor activity against a panel of solid tumor cell lines. However, its apoptotic activity varied widely with the best response observed in osteosarcoma cells with MDM2 gene amplification. Interestingly, inhibition of caspase activity did not change the kinetics of p53-induced cell death. Oral administration of RG7112 to human xenograft-bearing mice at nontoxic concentrations caused dose-dependent changes in proliferation/apoptosis biomarkers as well as tumor inhibition and regression. Notably, RG7112 was highly synergistic with androgen deprivation in LNCaP xenograft tumors. Our findings offer a preclinical proof-of-concept that RG7112 is effective in treatment of solid tumors expressing wild-type p53. ©2013 AACR.
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            Management of primary pulmonary artery sarcomas.

            Ara Vaporciyan, Jon-Cecil Walkes, Reza Mehran … (2009)
            The objective of this review is to determine the outcome of patients with sarcomas involving the main pulmonary artery, pulmonic valve, or right ventricular outflow tract. Survival data were analyzed using an aggregate series derived from the published literature in conjunction with a current series. Median survival was 36.5 +/- 20.2 months for patients undergoing an attempt at curative resection compared with 11 +/- 3 months for those undergoing incomplete resection. Median survival was 24.7 +/- 8.5 months for patients undergoing multimodality treatment compared with 8.0 +/- 1.7 months for patients having single-modality therapy. A complete review of diagnosis, evaluation, treatment, and surveillance of primary pulmonary artery sarcomas follows.
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              Intimal sarcoma is the most frequent primary cardiac sarcoma: clinicopathologic and molecular retrospective analysis of 100 primary cardiac sarcomas.

              Pauline Lagarde, Agnès Neuville, Jean-Michel Coindre … (2014)
              We report novel molecular and pathologic features of sarcomas involving the heart. Intimal sarcoma appears as the most frequent primary cardiac sarcoma within the largest described series of 100 primary cardiac sarcomas. Immunohistochemical analysis, fluorescence in situ hybridization, real-time polymerase chain reaction, and array-comparative genomic hybridization were performed on materials from 65 women and 35 men, aged 18 to 82 years (mean 50 y), retrieved from the French Departments of Pathology, between 1977 and early 2013. Right and left heart was involved in 44 and 56 cases, respectively. There were 42 intimal sarcomas, 26 angiosarcomas, 22 undifferentiated sarcomas, 7 synovial sarcomas, 2 leiomyosarcomas, and 1 peripheral neuroectodermal tumor. All but 1 angiosarcomas originated from the right heart, whereas 83% of the intimal sarcomas and 72% of the undifferentiated sarcomas were from the left heart. MDM2 overexpression was immunohistochemically observed in all intimal sarcomas, as well as in 10 of the 22 undifferentiated sarcomas and in 5 of the 26 angiosarcomas. MDM2 amplification was only demonstrated in intimal sarcomas. Genomic analysis showed a complex profile, with recurrent 12q13-14 amplicon involving MDM2, 4q12 amplicon involving KIT and PDGFRA, 7p12 gain involving EGFR, and 9p21 deletion targeting CDKN2A. Immunohistochemical detection of MDM2 overexpression can easily detect intimal sarcoma, provided that molecular aberration is proved. As resections are limited to the left atrium, this histologic subtype could benefit from therapies targeting PDGFRA or MDM2.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Onco Targets Ther
                Journal ID (iso-abbrev): Onco Targets Ther
                Journal ID (publisher-id): OTT
                Journal ID (pmc): ott
                Title: OncoTargets and therapy
                Publisher: Dove
                ISSN (Electronic): 1178-6930
                Publication date (Electronic): 07 August 2019
                Publication date Collection: 2019
                Volume: 12
                Pages: 6227-6235
                Affiliations
                [1 ]Department of Respiratory Medicine, Zhongda Hospital, School of Medicine, Southeast University , Nanjing 210009, People’s Republic of China
                [2 ]Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine , Nanjing 210002, People’s Republic of China
                Author notes
                Correspondence: Xihua WangDepartment of Respiratory Medicine, Zhongda Hospital, School of Medicine, Southeast University , 87 Dingjiaqiao, Nanjing210009, People’s Republic of ChinaTel +86 258 326 2803Email wangxihua@126.com
                Hongbing LiuDepartment of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine , 305 East Zhongshan Road, Nanjing210002, People’s Republic of ChinaTel +86 258 086 0592Email netlhb@126.com
                Article
                Publisher ID: 212416
                DOI: 10.2147/OTT.S212416
                PMC ID: 6689559
                PubMed ID: 31496726
                SO-VID: 1dd27051-ed02-4988-95fc-008505635f24
                Copyright © © 2019 Wu et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 16 April 2019
                Date accepted : 17 July 2019
                Page count
                Figures: 4, Tables: 1, References: 26, Pages: 9
                Categories
                Subject: Case Report

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: pulmonary artery sarcoma,whole exome sequencing,anlotinib
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: pulmonary artery sarcoma, whole exome sequencing, anlotinib

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