scholarly journals Aminopeptidase N (CD13): Expression, Prognostic Impact, and Use as Therapeutic Target for Tissue Factor Induced Tumor Vascular Infarction in Soft Tissue Sarcoma

2018 ◽  
Vol 11 (6) ◽  
pp. 1271-1282 ◽  
Author(s):  
Torsten Kessler ◽  
Ariane Baumeier ◽  
Caroline Brand ◽  
Michael Grau ◽  
Linus Angenendt ◽  
...  
Author(s):  
Dennis Strassmann ◽  
Bennet Hensen ◽  
Viktor Grünwald ◽  
Katharina Stange ◽  
Hendrik Eggers ◽  
...  

Abstract Introduction Advanced or metastatic soft tissue sarcoma (a/mSTS) is associated with a dismal prognosis. Patient counseling on treatment aggressiveness is pivotal to avoid over- or undertreatment. Recently, evaluation of body composition markers like the skeletal muscle index (SMI) became focus of interest in a variety of cancers. This study focuses on the prognostic impact of SMI in a/mSTS, retrospectively. Methods 181 a/mSTS patients were identified, 89 were eligible due to prespecified criteria for SMI assessment. Baseline CT-Scans were analyzed using an institutional software solution. Sarcopenia defining cut-off values for the SMI were established by optimal fitting method. Primary end point was overall survival (OS) and secondary endpoints were progression free survival (PFS), disease control rate (DCR), overall response rate (ORR). Descriptive statistics as well as Kaplan Meier- and Cox regression analyses were administered. Results 28/89 a/mSTS patients showed sarcopenia. Sarcopenic patients were significantly older, generally tended to receive less multimodal therapies (62 vs. 57 years, P = 0.025; respectively median 2.5 vs. 4, P = 0.132) and showed a significantly lower median OS (4 months [95%CI 1.9–6.0] vs. 16 months [95%CI 8.8–23.2], Log-rank P = 0.002). Sarcopenia was identified as independent prognostic parameter of impaired OS (HR 2.40 [95%-CI 1.4–4.0], P < 0.001). Moreover, DCR of first palliative medical treatment was superior in non-sarcopenic patients (49.2% vs. 25%, P = 0.032). Conclusion This study identifies sarcopenia as a prognostic parameter in a/mSTS. Further on, the data suggest that sarcopenia shows a trend of being associated with first line therapy response. SMI is a promising prognostic parameter, which needs further validation.


2017 ◽  
Vol 24 (6) ◽  
pp. 1596-1605 ◽  
Author(s):  
Maria Anna Smolle ◽  
Per-Ulf Tunn ◽  
Elisabeth Goldenitsch ◽  
Florian Posch ◽  
Joanna Szkandera ◽  
...  

2020 ◽  
Author(s):  
Alberto Gualtieri ◽  
Valerio Licursi ◽  
Chiara Mozzetta

AbstractRhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood characterized by the inability to exit the proliferative myoblast-like stage. The alveolar fusion positive subtype (FP-ARMS) is the most aggressive and is mainly caused by the expression of PAX3/7-FOXO1 oncoproteins, which are challenging pharmacological targets. Thus, other therapeutic vulnerabilities resulting from gene expression changes are progressively being recognized. Here, we identified the DEAD box RNA helicase 5 (DDX5) as a potential therapeutic target to inhibit FP-ARMS growth. We show that DDX5 is overexpressed in alveolar RMS cells, demonstrating that its depletion drastically decreases FP-ARMS viability and slows tumor growth in xenograft models. Mechanistically, we provide evidence that DDX5 functions upstream the G9a/AKT survival signalling pathway, by modulating G9a protein stability. Finally, we show that G9a interacts with PAX3-FOXO1 and regulates its activity, thus sustaining FP-ARMS myoblastic state. Together, our findings identify a novel survival-promoting loop in FP-ARMS and highlight DDX5 as potential therapeutic target to arrest rhabdomyosarcoma growth.


2017 ◽  
Vol 123 ◽  
pp. S21
Author(s):  
A. Cortesi ◽  
A. Arcelli ◽  
R. Frakulli ◽  
L. Giaccherini ◽  
S. Bisello ◽  
...  

2014 ◽  
Vol 53 (9) ◽  
pp. 1188-1196 ◽  
Author(s):  
Katja Maretty-Nielsen ◽  
Ninna Aggerholm-Pedersen ◽  
Akmal Safwat ◽  
Steen Baerentzen ◽  
Alma B. Pedersen ◽  
...  

2008 ◽  
Vol 14 (16) ◽  
pp. 5033-5042 ◽  
Author(s):  
Zeming Jin ◽  
Guy Lahat ◽  
Borys Korchin ◽  
Theresa Nguyen ◽  
Quan-Sheng Zhu ◽  
...  

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11014-11014 ◽  
Author(s):  
Sophie Cousin ◽  
Amandine Crombe ◽  
Eberhard Stoeckle ◽  
Véronique Brouste ◽  
Francois Le Loarer ◽  
...  

11014 Background: Two large phase III studies have shown an improved overall survival in soft-tissue sarcoma (STS) pts treated with neoadjuvant chemotherapy. The prognostic impact of pathologic response is not known neither the clinical, radiological and genetic features associated with response. Methods: Data from pts with localized STS of the extremities or trunk wall and treated with anthracyline-based NAC at Institut Bergonie (Bordeaux, France) were reviewed. Central pathology (diagnosis, histological response) and radiology (MRI, DCE-MRI) reviews were performed for all the cases. A good histological response (GR) was defined as <10% residual viable tumor. Exome and RNA sequencing of pre-treatment tumor samples was performed in order to identify genetic aberrations predictive of response. Results: 150 patients (88 male) were included in the study. Median age was 60 years (17-84). 40 pts (26.7%) were good responders. GR was associated with undifferentiated pleomorphic sarcomas and very large tumors (> 20 cm). Median OSwas 10.3 year [IC95 : 5.8 ; 14.9]. On multivariate analysis, only GR (HR= 0.36, 95%CI 0.184-0.703, p=0.0028) and performance status (PS) (HR= 3.799, 95%CI 1.72-8.387, p=0.001 for PS=2-3) were prognostic factors for OS. Early DCE- MRI parameters (after 2 cycles of treatment) such as, area under the contrast concentration vs. time curve for 90 seconds after contrast injection ( IAUC90) were strongly associated with histological response (p=0.027) whereas RECIST 1.1 was not. Conclusions: As for bone sarcomas, histological response to NAC is a crucial prognostic factor in STS. Multiparametric MRI parameters obtained post-2nd cycle of NAC are predictive of histological response and should be considered to adjust the therapeutic strategy. Genetic features (including the CINSARC signature) associated with response to NAC will be presented at the meeting.


PLoS ONE ◽  
2020 ◽  
Vol 15 (2) ◽  
pp. e0229271 ◽  
Author(s):  
Caroline Brand ◽  
Burkhard Greve ◽  
Tobias Bölling ◽  
Hans T. Eich ◽  
Normann Willich ◽  
...  

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