Oropharyngeal carcinoma in fanconi anemia patient - Radiation treatment, toxicity, and a year follow-up: Case report.

Fanconi anemia (FA) is an inherited bone marrow failure disorder. In patients with FA, there is a high incidence of head and neck squamous cell carcinoma (HNSCC). As there is a defective DNA repair mechanism, radiotherapy (RT) or chemotherapy has an increased risk of toxicity in FA patients with HNSCC. We report the radiation treatment for oropharyngeal carcinoma in a FA patient. Our patient was treated with RT to a total dose of 60 Gy in 30 fractions. She developed grade 3 oral mucositis, grade 3 neutropenia, and thrombocytopenia at 20 Gy which resulted in treatment break of 11 days. She again developed grade 3 mucositis, grade 2 dermatitis, grade 3 thrombocytopenia, worsening of odynophagia at 44 Gy which resulted in a treatment break of 19 days. She completed RT and is now disease-free for 1 year with a good quality of life.

Effectiveness of abdominal compression in reducing internal target motion during conformal radiotherapy for carcinoma stomach - A pilot study.

AIM: : To assess the effectiveness of abdominal compression in reducing internal target motion during conformal radiotherapy for stomach cancer. MATERIALS AND METHODS: A pilot study was conducted on five patients who received adjuvant radiotherapy for stomach cancer. All the patients had surgical clips and were offered radiotherapy and concurrent chemotherapy as per the institutional protocol. An abdominal compression device was developed consisting of a triangular Styrofoam's plate and an inflatable air bladder that was positioned over the patients' abdomen. The pneumatic pressure was set according to the patients' comfort. On the simulation day, patients had two computed tomography (CT)-scanning sessions, with and without abdominal compression. Target volumes and organs at risk (OAR) were delineated on the CT images without compression. On the treatment day, fluoroscopy was acquired with onboard imager (OBI) and movements of surgical clips with and without compression analyzed with the help of a tracker software. Observed values with and without abdominal compression were compared. RESULTS: Abdominal compression usage has reduced the mean breathing excursion (MBE) in medio lateral(ML) direction from 5.92mm to 4.15 mm and in cranio caudal direction (CC) from 11.3mm to 7.2mm. The range of reduction by 29.85% in the ML and 36.86% in CC direction. The average residual breathing excursion was 1.766 mm (SD = 1.33 mm) in the ML and 4.02 mm (SD = 2.18 mm) in the CC direction, respectively. CONCLUSION: Abdominal compression was useful in reducing internal target motion during stomach cancer conformal radiotherapy. The device we developed is patient friendly and cost-effective.

Experimental Probing and Molecular Dynamics Simulation of the Molecular Recognition of DNA Duplexes by the Flavonoid Luteolin.

Luteolin (C15H10O6) is an important flavonoid found in many fruits, plants, medicinal herbs, and vegetables exhibiting many pharmacological properties. The anticancer, antitumor, antioxidant, and anti-inflammatory activities of luteolin have been reported. The pharmacological action of small molecules is dependent upon its interaction with biomacromolecules. The interactions of small molecules with DNA play a major role in the transcription and translation process. In this work, we explored the energetic profile of DNA-luteolin interaction by isothermal titration calorimetry (ITC). The effect of temperature and salt concentration on DNA binding was examined by UV-Vis method. The mode of interaction was further probed by UV melting temperature analysis and differential scanning calorimetry. An atomic level insight on the recognition of luteolin with DNA was achieved by employing molecular dynamics (MD) simulation on luteolin in complex with AT- and GC-rich DNA sequences. AMBER force field proves to be appropriate in providing an understanding on the binding mode and specificity of luteolin with duplex DNA. MD results suggest a minor groove binding of luteolin with DNA and the binding free energy obtained is in agreement with the experimental results.

Conformational features of benzo-homologated yDNA duplexes by molecular dynamics simulation.

yDNA is a base-modified nucleic acid duplex containing size-expanded nucleobases. Base-modified nucleic acids could expand the genetic alphabet and thereby enhance the functional potential of DNA. Unrestrained 100 ns MD simulations were performed in explicit solvent on the yDNA NMR sequence [5'(yA T yA yA T yA T T yA T)2 ] and two modeled yDNA duplexes, [5'(yC yC G yC yC G G yC G G)2 ] and [(yT5' G yT A yC yG C yA yG T3')•(yA5' C T C yG C G yT A yC A3')]. The force field parameters for the yDNA bases were derived in consistent with the well-established AMBER force field. Our results show that DNA backbone can withstand the stretched size of the bases retaining the Watson-Crick base pairing in the duplexes. The duplexes retained their double helical structure throughout the simulations accommodating the strain due to expanded bases in the backbone torsion angles, sugar pucker and helical parameters. The effect of the benzo-expansion is clearly reflected in the extended C1'-C1' distances and enlarged groove widths. The size expanded base modification leads to reduction in base pair twist resulting in larger overlapping area between the stacked bases, enhancing inter and intra strand stacking interactions in yDNA in comparison with BDNA. This geometry could favour enhanced interactions with the groove binders and DNA binding proteins., 2016. © 2015 Wiley Periodicals, Inc. Biopolymers 105: 55-64, 2016.

Molecular dynamics simulations of xDNA.

xDNA is a modified DNA, which contains natural as well as expanded bases. Expanded bases are generated by the addition of a benzene spacer to the natural bases. A set of AMBER force-field parameters were derived for the expanded bases and the structural dynamics of the xDNA decamer (xT5' G xT A xC xG C xA xG T3').(xA5' C T xG C G xT A xC A3') was explored using a 22 ns molecular dynamics simulation in explicit solvent. During the simulation, the duplex retained its Watson-Crick base-pairing and double helical structure, with deviations from the starting B-form geometry towards A-form; the deviations are mainly in the backbone torsion angles and in the helical parameters. The sugar pucker of the residues were distributed among a variety of modes; C2' endo, C1' exo, O4' endo, C4' exo, C2' exo, and C3' endo. The enhanced stacking interactions on account of the modification in the bases could help to retain the duplex nature of the helix with minor deviations from the ideal geometry. In our simulation, the xDNA showed a reduced minor groove width and an enlarged major groove width in comparison with the NMR structure. Both the grooves are larger than that of standard B-DNA, but major groove width is larger than that of A-DNA with almost equal minor groove width. The enlarged groove widths and the possibility of additional hydration in the grooves makes xDNA a potential molecule for various applications.