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        Calculation of Jaws-only IMRT (JO-IMRT) dose distributions based on the AAPM TG-119 test cases using Monte Carlo simulation and Prowess Panther treatment planning system

        Luong Thi Oanh,Duong Thanh Tai,Truong Thi Hong Loan,James CL Chow 한국원자력학회 2021 Nuclear Engineering and Technology Vol.53 No.12

        The aim of this study is to calculate the JO-IMRT dose distributions based on the AAPM TG-119 usingMonte Carlo (MC) simulation and Prowess Panther treatment planning system (TPS) (Panther, ProwessInc., Chico, CA). JO-IMRT dose distributions of AAPM TG-119 were calculated by the TPS and wererecalculated by MC simulation. The DVHs and 3D gamma index using global methods implemented inthe PTW-VeriSoft with 3%/3 mm were used for evaluation. JO-IMRT dose distributions calculated by TPSand MC were matched the TG-119 goals. The gamma index passing rates with 3%/3 mm were 98.7% formulti-target, 96.0% for mock prostate, 95.4% for mock head-and-neck, and 96.6% for C-shape. The dose inthe planning target volumes (PTV) for TPS was larger than that for the MC. The relative dose differencesin D99 between TPS and MC for multi-target are 1.52%, 0.17% and 1.40%, for the center, superior andinferior, respectively. The differences in D95 are 0.16% for C-shape; and 0.06% for mock prostate. Mockhead-and-neck difference is 0.40% in D99. In contrast, the organ curve for TPS tended to be smaller thanMC values. JO-IMRT dose distributions for the AAPM TG-119 calculated by the TPS agreed well with theMC.

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        Novel Anti-Mesothelin Nanobodies and Recombinant Immunotoxins with Pseudomonas Exotoxin Catalytic Domain for Cancer Therapeutics

        Han Choe,Minh Quan Nguyen,Do Hyung Kim,Hye Ji Shim,Huynh Kim Khanh Ta,Thi Luong Vu,Thi Kieu Oanh Nguyen,Jung Chae Lim 한국분자세포생물학회 2023 Molecules and cells Vol.46 No.12

        Recombinant immunotoxins (RITs) are fusion proteins consisting of a targeting domain linked to a toxin, offering a highly specific therapeutic strategy for cancer treatment. In this study, we engineered and characterized RITs aimed at mesothelin, a cell surface glycoprotein overexpressed in various malignancies. Through an extensive screening of a large nanobody library, four mesothelin-specific nanobodies were selected and genetically fused to a truncated Pseudomonas exotoxin (PE24B). Various optimizations, including the incorporation of furin cleavage sites, maltose-binding protein tags, and tobacco etch virus protease cleavage sites, were implemented to improve protein expression, solubility, and purification. The RITs were successfully overexpressed in Escherichia coli, achieving high solubility and purity post-purification. In vitro cytotoxicity assays on gastric carcinoma cell lines NCI-N87 and AGS revealed that Meso(Nb2)-PE24B demonstrated the highest cytotoxic efficacy, warranting further characterization. This RIT also displayed selective binding to human and monkey mesothelins but not to mouse mesothelin. The competitive binding assays between different RIT constructs revealed significant alterations in IC50 values, emphasizing the importance of nanobody specificity. Finally, a modification in the endoplasmic reticulum retention signal at the C-terminus further augmented its cytotoxic activity. Our findings offer valuable insights into the design and optimization of RITs, showcasing the potential of Meso(Nb2)-PE24B as a promising therapeutic candidate for targeted cancer treatment.

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