Background/Aim: Two-thirds of head and neck squamous cell carcinoma (HNSCC) patients present with locally advanced (LA) stages and have a poor survival rate. The aim of this study was to investigate the roles of the long non-coding RNAs MALAT1 on radiation and cisplatin sensitivity of HNSCC cells. Materials and Methods: Clonogenic, cell viability, and apoptosis assays were performed in cells following MALAT1 knockdown using CRISPR/Cas9 system. Results: MALAT1 was overexpressed in HNSCC cell lines as compared to a non-tumorigenic cell line. The number of colonies formed after radiation was significantly reduced in MALAT1 knockdown cells. The IC 50 value of cisplatin in MALAT1 knockdown cells was lower than that of the control cells. MALAT1 knockdown resulted in cell cycle arrest at G 2 /M phase, DNA damage and apoptotic cell death. Conclusion: MALAT1 knockdown enhanced the sensitivity of HNSCC cells to radiation and cisplatin partly through the induction of G 2 /M cell cycle arrest resulting in DNA damage and apoptosis.Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumors arising from epithelial cells of the oral cavity, nasal cavity, pharynx, larynx, and hypopharynx. HNSCC is the sixth most common cancer worldwide in which two-third of patients are diagnosed with locally advanced stage. Annually, approximately 700,000 new HNSCC cases and 350,000 death are reported (1). Concurrent chemoradiotherapy (CRT) using platinum-based chemotherapy (e.g. cisplatin or carboplatin) and/or surgery are considered a standard treatment for locally advanced (LA) HNSCC patients. Cisplatin is considered as the mainstay chemotherapy agent for CRT in patients with LA-HNSCC. Nevertheless, the majority of LA-HNSCC patients suffer from locoregional recurrence due to CRT resistance, and the overall survival (OS) rate remains poor (2, 3). Therefore, understanding the mechanism of radiotherapy and cisplatin sensitivity in HNSCC is essential to improve survival outcome of LA-HNSCC patients.Long non-coding RNAs (lncRNAs) are a novel class of non-protein coding transcripts containing >200 nucleotides (4). Increasing evidence has reported the critical roles of lncRNAs in the regulation of multiple cellular processes (5). The molecular mechanism relies on the interaction of lncRNAs with other biomolecules including chromatin, protein and RNA (6). They also play a role in epigenetic regulation through the recruitment of chromatin-modifying complexes to specific genomic DNA targets (7). Moreover, lncRNA can also function as endogenous sponge for other RNAs, such as mRNAs and miRNAs to regulate their stability and translation (8). Alteration of lncRNA functions has been shown to associate with treatment sensitivity of cancer cells through multiple cellular processes, such as chromatin modification, DNA damage and repair mechanism, cell cycle 2645
Abstract. The study aimed to determine appropriate detectors for output factor measurement of small fields in 6 and 10 MV flattening filter free photon beams using five different detectors. Field sizes were varied between 0.6 × 0.6 and 4.0 × 4.0 cm 2 . An indirect method (daisy-chaining) was applied to normalize the output factors. For the smallest field size, the variations of output factors compared among the detectors were 13%. Exradin A16 had the lowest output factor and increasing in sequence with CC01, microDiamond, microLion and EDGE detectors, respectively, for both energies. The similarity between CC01 and microDiamond output factor values were within 1.6% and 1% for all field sizes of 6 and 10 MV FFF, respectively. EDGE and microLion presented the highest values while ExradinA16 gave lowest values. In conclusion, IBACC01, Exradin A16, microLion, microDiamond and EDGE detectors seem to be the detectors of choices for small field output factor measurement of FFF beams down to 1.6×1.6 cm 2 . However, we could not guarantee which detector is the most suitable for output factor measurement in small field less than 1.6 × 1.6 cm 2 of FFF beams. Further studies are required to provide reference information for validation purposes.
The Varian millennium 120 multileaf collimator has curved leaf ends. Transmission through the leaf ends generates a small asymmetric penumbral dose effect. This design can lead to hot spots between neighbouring beam segments during step and shoot IMRT dose delivery. We have observed some matchlines with film for clinical beams optimized using the pinnacle radiotherapy treatment planning system; hence we sought to verify the optimum leaf offset required to minimize the matchline effect. An in-house program was created to control the MLC leaf banks in 2 cm steps with a 2 cm gap. The gap was varied by the following offset values from 0.0 to 0.1 cm. Two types of radiographic films (Kodak EDR and XV films) and a radiochromic film (Gafchromic MD-55-2) were used to measure the optical density maps. The films were positioned in a solid water phantom perpendicular to the beam axis and irradiated at d(max) using a 6 MV photon beam. An ion chamber (IC4) was used to measure point doses for normalization in a beam umbral minima position. The relative mean peak to valley dose ratios measured with no leaf offset were 1.31, 1.30 and 1.31 for the XV, EDR2 and Gafchromic films, respectively. For a 0.07 cm gap per leaf and a performance of end leaf repeatability of 0.01 cm, the central matchline was reduced to about 1.0 for all dosimeters, with two mini-peaks measured as 1.05, 1.05 and 1.08 each side of the matchline, for XV, EDR2 and Gafchromic, respectively. The average relative dose across the umbra for this offset was XO-mat V = 1.01, EDR = 1.01 and radiochromic film = 1.02, respectively. While we expected the beam penumbral tails from segment neighbours to cause overprediction of the dose in the central valley regions due to the energy response of radiographic films, by normalizing all dosimeters to an ion chamber reading in the minimum we could not observe any major shape distortion between the radiographic film and radiochromic film results. In conclusion, relative doses measured by radiographic and radiochromic films agree well with IC4 within +/-2%.
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