fusion product
Recently Published Documents


TOTAL DOCUMENTS

256
(FIVE YEARS 26)

H-INDEX

32
(FIVE YEARS 3)

2022 ◽  
Vol 23 (1) ◽  
pp. 575
Author(s):  
Katharina Woess ◽  
Yuchen Sun ◽  
Hanae Morio ◽  
Anna Stierschneider ◽  
Anna Kaufmann ◽  
...  

Conventional anti-cancer therapies based on chemo- and/or radiotherapy represent highly effective means to kill cancer cells but lack tumor specificity and, therefore, result in a wide range of iatrogenic effects. A promising approach to overcome this obstacle is spliceosome-mediated RNA trans-splicing (SMaRT), which can be leveraged to target tumor cells while leaving normal cells unharmed. Notably, a previously established RNA trans-splicing molecule (RTM44) showed efficacy and specificity in exchanging the coding sequence of a cancer target gene (Ct-SLCO1B3) with the suicide gene HSV1-thymidine kinase in a colorectal cancer model, thereby rendering tumor cells sensitive to the prodrug ganciclovir (GCV). In the present work, we expand the application of this approach, using the same RTM44 in aggressive skin cancer arising in the rare genetic skin disease recessive dystrophic epidermolysis bullosa (RDEB). Stable expression of RTM44, but not a splicing-deficient control (NC), in RDEB-SCC cells resulted in expression of the expected fusion product at the mRNA and protein level. Importantly, systemic GCV treatment of mice bearing RTM44-expressing cancer cells resulted in a significant reduction in tumor volume and weight compared with controls. Thus, our results demonstrate the applicability of RTM44-mediated targeting of the cancer gene Ct-SLCO1B3 in a different malignancy.


2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii9-ii9
Author(s):  
N Kehl ◽  
M Friedrich ◽  
M Kilian ◽  
T Zheng ◽  
K Pajtler ◽  
...  

Abstract BACKGROUND The oncogenic gene fusion between ZFTA (formerly C11orf95) and RELA has in recent years been highlighted as oncogenic driver event ultimately leading to malignant transformation and progression of ependymoma. Representing a genetic hallmark in 17.6% of ependymomas, ZFTA-RELA fusion-positive tumors qualified as separate diagnostic entity in the 2016 revision of the WHO classification of CNS tumors. This tumor entity mainly occurs in pediatric patients and is characterized by poor prognosis and the lack of biology-driven therapy. RESULTS De novo prediction of putative gene fusion-derived neoepitopes in malignant CNS diseases yielded several potential candidates suitable for screening. Of these, vaccination of A2.DR1-transgenic major histocompatibility complex (MHC)-humanized mice with in silico compiled peptide vaccines encompassing the ZFTA-RELA fusion sequence elicited robust antigen-specific CD4+-restricted immune responses. We identified ZFTA-RELA-reactive T cell clones by multiplexed Interferon-γ / Interleukin-2 recall response. Single-cell VDJ-sequencing of reactive T cells demonstrated a highly clonal T cell receptor (TCR) repertoire and shared clonotypes among all vaccinated animals. Matching TCRα/β chains have been assembled from single-cell sequencing data and cloned for functional testing of neoepitope-reactive TCR-transgenic T cells in vitro as well as in vivo using a transposon system-based immunocompetent, MHC-humanized ZFTA-RELA fusion-positive ependymoma model. CONCLUSION Here we identify the oncogenic ZFTA-RELA gene fusion product as a novel tumor-specific neoepitope that is recognized by MHC class II-restricted TCRs. Therapeutic efficacy of TCR-transgenic cell therapy can be further investigated using an immunocompetent MHC-humanized mouse model of ZFTA-RELA fusion-positive ependymoma. Our findings provide initial evidence for neoepitope-specific immunotherapy in pediatric CNS tumors.


2021 ◽  
Vol 19 (50) ◽  
pp. 9-19
Author(s):  
Rıdvan Baldık

The biggest problem of structural materials for fusion reactor is the damage caused by the fusion product neutrons to the structural material. If this problem is overcomed, an important milestone will be left behind in fusion energy. One of the important problems of the structural material is that nuclei forming the structural material interacting with fusion neutrons are transmuted to stable or radioactive nuclei via (n, x) (x; alpha, proton, gamma etc.) reactions. In particular, the concentration of helium gas in the structural material increases through deuteron- tritium (D-T) and (n, α) reactions, and this increase significantly changes the microstructure and the properties of the structural materials. Therefore, in this study, the effects of the different nuclear level density models on the excitation functions of the (n, α) reactions on 46-50Ti isotopes, an attractive candidate for the structural material for fusion reactors, have been investigated for the first time. Also, the differential cross-sections with respect to alpha energy for the emission of alpha particles of the 46-50Ti (n, xα) reactions have been investigated at 14.1 MeV incident neutron energy. The calculations are performed using the two-component exciton model in the TALYS 1.9 code, and the results are compared with available experimental data. The results of this study will contribute to nuclear database as required for improving, design and operations of the important facilities as ITER (International Thermonuclear Experimental Reactor), DEMO (The demonstration power plant) and ENS (European Nuclear Society).


2021 ◽  
Vol 13 (12) ◽  
pp. 2402
Author(s):  
Weifu Sun ◽  
Jin Wang ◽  
Yuheng Li ◽  
Junmin Meng ◽  
Yujia Zhao ◽  
...  

Based on the optimal interpolation (OI) algorithm, a daily fusion product of high-resolution global ocean columnar atmospheric water vapor with a resolution of 0.25° was generated in this study from multisource remote sensing observations. The product covers the period from 2003 to 2018, and the data represent a fusion of microwave radiometer observations, including those from the Special Sensor Microwave Imager Sounder (SSMIS), WindSat, Advanced Microwave Scanning Radiometer for Earth Observing System sensor (AMSR-E), Advanced Microwave Scanning Radiometer 2 (AMSR2), and HY-2A microwave radiometer (MR). The accuracy of this water vapor fusion product was validated using radiosonde water vapor observations. The comparative results show that the overall mean deviation (Bias) is smaller than 0.6 mm; the root mean square error (RMSE) and standard deviation (SD) are better than 3 mm, and the mean absolute deviation (MAD) and correlation coefficient (R) are better than 2 mm and 0.98, respectively.


2020 ◽  
Vol 12 (19) ◽  
pp. 3209
Author(s):  
Yunan Luo ◽  
Kaiyu Guan ◽  
Jian Peng ◽  
Sibo Wang ◽  
Yizhi Huang

Remote sensing datasets with both high spatial and high temporal resolution are critical for monitoring and modeling the dynamics of land surfaces. However, no current satellite sensor could simultaneously achieve both high spatial resolution and high revisiting frequency. Therefore, the integration of different sources of satellite data to produce a fusion product has become a popular solution to address this challenge. Many methods have been proposed to generate synthetic images with rich spatial details and high temporal frequency by combining two types of satellite datasets—usually frequent coarse-resolution images (e.g., MODIS) and sparse fine-resolution images (e.g., Landsat). In this paper, we introduce STAIR 2.0, a new fusion method that extends the previous STAIR fusion framework, to fuse three types of satellite datasets, including MODIS, Landsat, and Sentinel-2. In STAIR 2.0, input images are first processed to impute missing-value pixels that are due to clouds or sensor mechanical issues using a gap-filling algorithm. The multiple refined time series are then integrated stepwisely, from coarse- to fine- and high-resolution, ultimately providing a synthetic daily, high-resolution surface reflectance observations. We applied STAIR 2.0 to generate a 10-m, daily, cloud-/gap-free time series that covers the 2017 growing season of Saunders County, Nebraska. Moreover, the framework is generic and can be extended to integrate more types of satellite data sources, further improving the quality of the fusion product.


2020 ◽  
Vol 18 (10) ◽  
pp. 1300-1304
Author(s):  
Sanjeev Kumar Gupta ◽  
Nitin Jain ◽  
Guilin Tang ◽  
Andrew Futreal ◽  
Sa A. Wang ◽  
...  

RNA-seq was used to identify the partner gene and confirm the presence of a BCR-PDGFRB fusion. Identification of this fusion product resulted in successful treatment and long-term remission of this myeloid neoplasm. Based on our results, we suggest that despite current WHO recommendations, screening for PDGFRB rearrangement in cases of leukocytosis with eosinophilia and no other etiologic explanation is necessary, even if the karyotype is normal.


2020 ◽  
pp. 1-5
Author(s):  
Debora Lana ◽  
Debora Lana ◽  
Marina Pacheco ◽  
Federico Ostetto ◽  
Stefania Benini ◽  
...  

Clear cell sarcoma is a rare mesenchymal tumor with melanocytic differentiation, firstly described by Enziger in 1965. It accounts for less than 1% of all soft tissue sarcomas and occurs predominantly in the extremities of adults. Primary clear cell sarcoma of bone is even rarer; current literature consists of only 13 cases with a mean age of presentation of 45-year-old, ranging from 18 to 81. Because of the overlapping expression of melanocytic markers, the differential diagnosis should be addressed with metastatic malignant melanoma and metastasis from clear cell sarcoma of soft parts. Essential for the diagnosis is the evidence of translocations t (12;22) or t (2;22) resulting respectively in EWSR1/ATF1 and EWSR1-CREB1 gene fusion. Clinical history and radiological assessment could help discriminate between bone or soft parts origin. We report an unusual case of clear cell sarcoma of distal femur involving a 13-year-old patient. Histological sections showed a malignant neoplasm composed of nests of uniform cells separated by fibrous septa, showing strong immunoreactivity for melanoma triple cocktail. Real Time-Polymerase Chain Reaction revealed the presence of the fusion product EWSR1-ATF1, confirming the diagnosis of clear cell sarcoma of bone. Our purpose was to revise the current literature in order to find common clinicalradiological features to this rare entity. To the best of our knowledge, our case is the first bone clear cell sarcoma arising from the distal femur in a pediatric patient described in the literature: it highlights the importance of considering this rare entity in the differential diagnosis of primary bone tumor, although extremely rare and of the use of molecular means to confirm the diagnosis.


Sign in / Sign up

Export Citation Format

Share Document