Role of FUS-CHOP in Myxoid Liposarcoma via miR-486/CDK4 Axis

Author(s):  
Hao Wu ◽  
Liming Xia ◽  
Haichao Xu
Keyword(s):  
1998 ◽  
Vol 84 (5) ◽  
pp. 571-577 ◽  
Author(s):  
Silvana Pilotti ◽  
Cinzia Lavarino ◽  
Alessandra Mezzelani ◽  
Gabriella Della Torre ◽  
Fabiola Minoletti ◽  
...  

Aims Circumstantial evidence suggests that genetic changes may lead to tumor progression within the myxoid liposarcoma tumors (MLTs) carrying non-random chromosomal translocation t(12;16). Methods To address this subject an immunophenotypic analysis, applying antibodies against proteins encoded by TP53, MDM2 and CDK4 genes, complemented by molecular analysis of eight suitable cases, was performed on 104 consecutive cases. Chromosomal translocations were assessed either by cytogenetic analysis or by RT-PCR in 9 suitable cases and chimeric transcripts were found in all cases but two pleomorphic liposarcomas. Results Based on immunophenotyping and tumor site, the case material consisted of three groups. The first one was made up of 92 non-retroperitoneal cases carrying a null p53, mdm2, cdk4 immunophenotype, which remained unchanged over the time of recurrences and along the gamut of histologic subtypes. The second group was represented by five p53+, mdm2-, cdk4- non-retroperitoneal cases, 4 of which were further analysed by PCR-SSCP for p53 mutation. The im-munophenotipic profile of these cases, complemented by the molecular findings, supported a role of TP53 in tumor progression in three high-grade MLTs. The third group, consisting of 7 retroperitoneal cases, showed a heterogeneous immunophenotype, sharing immunophenotypic and molecular features with the well-differentiated/evoluted (dedifferentiated) liposarcoma group. Conclusions TP53 mutations seem to play a role in tumor progression in a few cases of MLTs (2.8%) showing more aggressive histologic characteristics. The unexpected finding that a number of retroperitoneal LMTs display the immunophenotypic profile of the well differentiated/evoluted (dedifferentiated) liposarcomas, deserves further investigation.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e23566-e23566
Author(s):  
Sonia Simonetti ◽  
Michele Iuliani ◽  
Francesco Pantano ◽  
Giulia Ribelli ◽  
Andrea Napolitano ◽  
...  

e23566 Background: Glyoxalase-1 (Glo1) is involved in the detoxification of the endogenous reactive metabolite, methylglyoxal (MG), whose abnormal accumulation increases adduct levels and induce cell apoptosis. Previous studies demonstrated that increased Glo-1 expression was associated with cancer chemotherapy resistance. We performed bioinformatics analyses finding that Glo-1 mRNA over-expression was correlated with worse prognosis in patients affected by Soft Tissue Sarcoma (STS). On the bases of these evidences, we investigated the potential role of Glo1 expression as biomarker of tumor growth and drug resistance in STS. Methods: Trabectedin and MG cytoxicity was evaluated by MTT viability assay measured at spectrofluorometer. Apoptosis was analyzed by flow cytometry using Annexin V antibody and propidium iodide. Glo-1 expression analysis was performed by Western Blot using a mouse monoclonal anti-human Glo-1 antibody (NBP1-19015). Synergy analysis was calculated using Combenefit software and statistical analysis was performed by Student-t test using the program GraphPad-Prism. Results: As STS trabectedin resistant model, we used a myxoid-liposarcoma cell line (402-91 ET cells) that are not responsive to clinical doses of trabectedin contrary to the parental sensitive cell line (402-91 WT cells). Intriguingly, we found higher Glo-1 protein levels in 402-91 ET cells compared to 402-91 WT cells. The treatment of 402-91 ET cells with the specific Glo1 inhibitor S-p-bromobenzylglutathione cyclopentyl diester (BBGC), in combination with trabectedin (PharmaMar), significantly inhibited cell viability and increased apoptosis than trabectedin alone. In particular, the addition of BBGC reduced trabectedin EC50 (half-maximal effective concentration) from 20.4nM to 5.92nM in 402-91 ET cells, similar to that observed in 402-91 WT cells (4.92nM). To investigate if cell death was induced by MG accumulation following Glo1 inhibition, we evaluated 402-91 ET cell viability after treatment with different doses of MG in combination with trabectedin. The addition of MG restored sensitivity to trabectedin in 402-91 ET cells as well as BBGC. Conclusions: Our results highlight a new potential mechanism of trabectedin resistance mediated by Glo-1 over-expression. The use of the specific Glo-1 inhibitor, BBGC, restores trabectedin sensitivity in resistant cells leading to MG accumulation that, in turn, promotes cell death and apoptosis. These data provide a strong rationale to investigate Glo-1 inhibition strategy, in combination with trabectedin, in STS in vivo models.


Sarcoma ◽  
2004 ◽  
Vol 8 (2-3) ◽  
pp. 91-96 ◽  
Author(s):  
A. Mitra ◽  
C. Fisher ◽  
P. Rhys-Evans ◽  
C. Harmer

Liposarcoma of the thyroid gland is rare with only 3 cases reported in the English literature. We present a further two patients whom we have recently treated: a 49 year old lady with a myxoid liposarcoma and a 71 year old man with a pleomorphic liposarcoma. Both underwent macroscopic excision of tumour but had positive margins, so were then treated with external beam radiotherapy. The former patient died from metastases 10 months after presentation, the latter remains alive but has developed metastatic disease on follow up at 24 months.We recommend the use of high dose radiotherapy following radical surgery as margins of excision are usually narrow in this most difficult region. The role of chemotherapy is yet to be established.


2013 ◽  
Vol 4 (4) ◽  
pp. 28-32
Author(s):  
Chen Niu ◽  
Netra Rana ◽  
Zhi Gang Min ◽  
Ming Zhang

Liposarcomas are common malignant soft-tissue tumors, which come from primitive mesenchymal cells and differentiate into adipose tissue. These tumors are more commonly found in lower limbs and retroperitoneal region but also reported in pharynx, lung, liver, digestive tract, diaphragm, as well as in the spermatic cord. We reported a case of primary orbital myxoid liposarcoma in a 20-year-old female patient presented with a painless proptosis of the right eye. The mass was pathologically diagnosed as a myxoid liposarcoma. The tumor recurred in 9 months after surgical intervention. The second surgery was performed and followed by postoperative local radiotherapy. No recurrence has been reported after one year of follow-up. We highlighted the role of CT and MRI findings in the tumor diagnosis and the importance of local radiotherapy after surgery. Asian Journal of Medical Science, Volume-4 (2013), Pages 28-32 DOI: http://dx.doi.org/10.3126/ajms.v4i4.8311 


JAMA ◽  
1966 ◽  
Vol 195 (12) ◽  
pp. 1005-1009 ◽  
Author(s):  
D. J. Fernbach
Keyword(s):  

JAMA ◽  
1966 ◽  
Vol 195 (3) ◽  
pp. 167-172 ◽  
Author(s):  
T. E. Van Metre

2018 ◽  
Vol 41 ◽  
Author(s):  
Winnifred R. Louis ◽  
Craig McGarty ◽  
Emma F. Thomas ◽  
Catherine E. Amiot ◽  
Fathali M. Moghaddam

AbstractWhitehouse adapts insights from evolutionary anthropology to interpret extreme self-sacrifice through the concept of identity fusion. The model neglects the role of normative systems in shaping behaviors, especially in relation to violent extremism. In peaceful groups, increasing fusion will actually decrease extremism. Groups collectively appraise threats and opportunities, actively debate action options, and rarely choose violence toward self or others.


2018 ◽  
Vol 41 ◽  
Author(s):  
Kevin Arceneaux

AbstractIntuitions guide decision-making, and looking to the evolutionary history of humans illuminates why some behavioral responses are more intuitive than others. Yet a place remains for cognitive processes to second-guess intuitive responses – that is, to be reflective – and individual differences abound in automatic, intuitive processing as well.


2020 ◽  
Vol 43 ◽  
Author(s):  
Stefen Beeler-Duden ◽  
Meltem Yucel ◽  
Amrisha Vaish

Abstract Tomasello offers a compelling account of the emergence of humans’ sense of obligation. We suggest that more needs to be said about the role of affect in the creation of obligations. We also argue that positive emotions such as gratitude evolved to encourage individuals to fulfill cooperative obligations without the negative quality that Tomasello proposes is inherent in obligations.


2020 ◽  
Vol 43 ◽  
Author(s):  
Andrew Whiten

Abstract The authors do the field of cultural evolution a service by exploring the role of non-social cognition in human cumulative technological culture, truly neglected in comparison with socio-cognitive abilities frequently assumed to be the primary drivers. Some specifics of their delineation of the critical factors are problematic, however. I highlight recent chimpanzee–human comparative findings that should help refine such analyses.


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