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Background/aim: The aim of this study was to evaluate the mechanical performance and the effect on dose distribution and deliverability of volumetric modulated arc therapy (VMAT) plans for prostate cancer created with the commercial knowledge-based planning (KBP) system (RapidPlan™)., Materials and Methods: Three institutions, A, B, and C were enrolled in this study. Each institution established and trained a KBP model with their own cases. CT data and structures for 45 patients at institution B were utilized to validate the dose-volume parameters (D 2(%) , D 95(%) , and D 98(%) for target, and V 50(%) , V 75(%) , and V 90(%) for rectum and bladder), and the following mechanical performance parameters and gamma passing rates of each KBP model: leaf sequence variability (LSV), aperture area variability (AAV), total monitor unit (MU), modulation complexity score for VMAT (MCSv), MU/control point (CP), aperture area (AA)/CP, and MU×AA/CP., Results: Significant differences (p<0.01) in dosimetric parameters such as D 2 and D 98 for target and V 50 , V 75 , and V 90 for bladder were observed among the three institutions. The means and standard deviations of MCSv were 0.31±0.03, 0.29±0.02, and 0.32±0.03, and the angles of maximum and minimum MU×AA/CP were 269° and 13°, 269° and 13°, and 273° and 153° at institutions A, B, and C, respectively. The mean gamma passing rate (1%/1 mm.) was >95% for all cases in each institution. Dose distribution and mechanical performance significantly differed between the three models., Conclusion: Each KBP model had different dose distributions and mechanical performance but could create an acceptable plan for deliverability regardless of mechanical performance., (Copyright© 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

MTG8 (RUNX1T1) is a fusion partner of AML1 (RUNX1) in the leukemic chromosome translocation t(8;21). The AML1-MTG8 fusion gene encodes a chimeric transcription factor. One of the highly conserved domains of MTG8 is TAFH which possesses homology with human TAF4 [TATA-box binding protein-associated factor]. To obtain specific inhibitors of the AML1-MTG8 fusion protein, we isolated RNA aptamers against the MTG8 TAFH domain using systematic evolution of ligands by exponential enrichment. All TAF aptamers contained guanine-rich sequences. Analyses of a TAF aptamer by NMR, CD, and mutagenesis revealed that it forms a parallel G-quadruplex structure in the presence of K + . Furthermore, the aptamer could bind to the AML1-MTG8 fusion protein and dissociate the AML1-MTG8/DNA complex, suggesting that it can inhibit the dominant negative effects of AML1-MTG8 against normal AML1 function and serve as a potential therapeutic agent for leukemia., (© 2020 Federation of European Biochemical Societies.)

Background: Insulin-derived amyloidosis is a skin-related complication of insulin therapy that interferes with insulin therapy. Although toxicities of in vitro-formed insulin amyloid fibrils have been well studied, the toxicity of insulin-derived amyloidosis remains to be clarified., Case Presentation: A 58-year-old man with type 2 diabetes mellitus underwent a lower limb amputation due to diabetic gangrene. Several antibiotics including minocycline were administered for infection and sepsis. A hard mass at the insulin injection sites in the lower abdomen was discovered by chance four months later. Although no abnormal findings in the surface skin of the mass were observed, necrotic tissue was seen around the mass when a biopsy was performed. Histological and toxicity studies were performed for this patient and four other patients with abdominal masses at insulin injection sites. Histological and immunohistochemical studies showed that the masses had typical characteristics of amyloid deposits in all cases, whereas necrotic findings were seen adjacent to the amyloid deposit only in the case presented. Toxicity studies indicated that the amyloid tissue from the present case had significant cell toxicity compared to the control skin tissue or the amyloid tissues from the other four cases., Conclusions: This report showed that toxic insulin-derived amyloidosis can occur. In addition, this report suggested that toxic insulin-derived amyloidosis may cause necrosis in the surrounding tissue. Although the toxic amyloid deposit of insulin-derived amyloidosis was found in only one patient, no structural differences between toxic and non-toxic deposits were seen on histological and immunohistochemical studies.

The present study compares dosimetric parameters between volumetric-modulated arc therapy (VMAT) and 3D conformal radiation therapy (3D-CRT) in lung tumors adjacent to the chest wall treated with stereotactic body radiation therapy (SBRT). The study focused on the radiation dose to the chest wall of 16 patients who had developed radiation-induced rib fractures (RIRF) after SBRT using 3D-CRT. The targets in all patients were partially overlapping with the fractured ribs, and the median overlapping rib-PTV distance was 0.4 cm. Stereotactic body radiation therapy was re-planned for all patients. The prescribed dose was 48 Gy in four fractions to cover at least 95% of the planning target volume (PTV). Evaluated dosimetric factors included D98% and the conformation number (CN) of the PTV, the D2cm3, V40 and V30 of the fractured ribs, the V30 of the chest wall, and the Dmean, V20 and V5 of the lung. A comparison of 3D-CRT with the VMAT plan for PTV revealed that CN was significantly improved in the VMAT plan, whereas D98% did not significantly differ between the two plans. Regarding organs at risk (OARs), the D2cm3, V40 and V30 of fractured ribs, the V30 of the chest wall, and the Dmean, V20 and V5 of the lung, were significantly decreased in the VMAT plan. We concluded that the dose to OARs such as ribs and chest wall could be reduced with improved target conformity using VMAT instead of 3D-CRT for SBRT to treat peripheral lung tumors.

AML1 (RUNX1) is a key transcription factor for hematopoiesis that binds to the Runt-binding double-stranded DNA element (RDE) of target genes through its N-terminal Runt domain. Aberrations in the AML1 gene are frequently found in human leukemia. To better understand AML1 and its potential utility for diagnosis and therapy, we obtained RNA aptamers that bind specifically to the AML1 Runt domain. Enzymatic probing and NMR analyses revealed that Apt1-S, which is a truncated variant of one of the aptamers, has a CACG tetraloop and two stem regions separated by an internal loop. All the isolated aptamers were found to contain the conserved sequence motif 5'-NNCCAC-3' and 5'-GCGMGN'N'-3' (M:A or C; N and N' form Watson-Crick base pairs). The motif contains one AC mismatch and one base bulged out. Mutational analysis of Apt1-S showed that three guanines of the motif are important for Runt binding as are the three guanines of RDE, which are directly recognized by three arginine residues of the Runt domain. Mutational analyses of the Runt domain revealed that the amino acid residues used for Apt1-S binding were similar to those used for RDE binding. Furthermore, the aptamer competed with RDE for binding to the Runt domain in vitro. These results demonstrated that the Runt domain of the AML1 protein binds to the motif of the aptamer that mimics DNA. Our findings should provide new insights into RNA function and utility in both basic and applied sciences.

During upper endoscopic screening, a 71-year-old asymptomatic woman was found to have a small, yellowish, superficial elevated lesion in the upper third of her stomach, without any signs of atrophic mucosa. The patient underwent endoscopic follow-up once a year for approximately five years; however, changes in the tumor were barely detectable. Endoscopic mucosal resection was performed, and a histological examination confirmed the diagnosis of gastric adenocarcinoma with chief cell differentiation (GA-CCD). GA-CCD is rare; therefore, its clinicopathological features remain unknown. This case suggests that only barely detectable endoscopic changes may be observed in GA-CCD during long-term follow-up.