The Dosimetric Performance of Volumetric Modulated Arc Therapy and Intensity Modulated Radiation Therapy in the Treatment of Locally Advanced Laryngeal Cancer

Background: This study aims to compare the performance of intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) in treating laryngeal cancer.Method: In this retrospective dosimetric study, 15 patients diagnosed with locally advanced laryngeal cancer (LALC) were selected. The dosimetric performance of the two techniques was analyzed using 6 MV X-rays, based on dose-volume histograms for primary and boost planning target volumes (PTVp and PTVb, respectively), relevant organs at risk (OARs), mean Dose (Dmean), maximum Dose (Dmax), 95% Dose (D95), 2% Dose (D2%), 5% Dose (D5%), monitor units per segment (MU/segment), number of MU/cGy, treatment delivery time, along with conformity and homogeneity indices.Results: Both techniques were able to achieve favorable equivalent uniform doses and low doses to OARs. The average total number of monitor units for IMRT was significantly greater than that for VMAT (1724.5 ± 249.5 and 475.3 ± 47.0, respectively for PTVp and 601.4 ± 81.7 and 458.0 ± 62.6, respectively for PTVb). The modulation factor (MU/cGy) of IMRT was significantly greater than that for VMAT for both the primary and the boost phases. The mean treatment delivery time for all cases of IMRT was significantly longer than that of VMAT.Conclusion: The primary distinction between IMRT and VMAT in the treatment of LALC is that VMAT requires significantly fewer monitor units (one-third) compared with IMRT. This reduction contributes to a decrease in treatment time, which in turn positively impacts patient comfort and the accuracy of treatment

Dose verification of intensity modulated radiotherapy in head and neck tumors

Purpose: To evaluate the agreement between measured and calculated doses for head and neck tumors using different gamma criteria and to establish quality assurance protocol for the delivery of IMRT in The National Cancer Institute in Cairo. Methods: The dose is calculated for 30 patients using CMS Treatment Planning System. The ionization chamber (0.6 cm3 Farmer type) is used for point dose measurements. The 2D-array (PTW 729) and GafChromic films (EBT2) are used for 2D graphical dose distribution. Four different gamma criteria of dose difference (DD) and distance to agreement (DTA) (3%/3 mm, 3%/5 mm, 4%/4 mm and 5%/5 mm DD / DTA) are selected. These criteria are evaluated while suppressing the dose of 10%, 20% or 30% from dose distribution. Results: Point dose evaluations using the ion chamber ranged from -2.6% to 3.7% (mean and standard deviation of 0.46 ± 1.7). Significant differences are observed between the films and 2D-array for all criteria except the 3%/5 mm criteria (96.89 ± 2.2% vs. 94.81 ± 4.2% (p < 0.01)). Conclusion: Differences may exceed about 3% when the ionization chamber is present in steep dose gradient regions. The present results suggest the gamma criteria of 3%/5 mm as the most suitable criteria for IMRT quality assurance. This gamma criterion of 3%/5 mm favorably exceeds 95% in case of maximum dose while suppressing the dose of 20%.The use of 2D-array can reduce the IMRT QA workload.------------------------------Cite this article as: Elawady RA, Attalla EM, Elshemey WM, Shouman T, Alsayed AA. Dose verification of intensity modulated radiotherapy in head and neck tumors. Int J Cancer Ther Oncol 2014; 2(3):02037. DOI: 10.14319/ijcto.0203.

IDX-184 is a superior HCV direct-acting antiviral drug : A QSAR study

Quantitative structure-activity relationship (QSAR) parameters are good indicators for the reactivity of direct-acting antiviral drugs. Since molecular structure is related to molecular function, careful selection of molecular substitutions will result in more drugs that are potent. In this work, QSAR parameters are selected in order to compare the four drugs used as nucleotide inhibitors (NIs) for non-structural 5B (NS5B) RNA-dependent RNA polymerase (RdRp) of hepatitis C virus (HCV). These drugs are: ribavirin (widely used over the last 20 years), sofosbuvir (approved on December 2013 by FDA), and finally IDX-184 and R7128 (phase IIb of clinical trial drugs). The nucleotide analogues uracil (U), guanine (G), and cytosine (C) from which these drugs are fabricated are also compared to that group of drugs. QSAR parameters suggested that the drug IDX-184 is the best among all of the studied NIs. It also shows that NIs are always more reactive than their parent nucleotide

Prediction of HCV E2 association with the host-cell chaperone, GRP78

Background: Hepatitis C Virus (HCV) is the main causative factor for liver cirrhosis and for the development of liver cancer. E2 is an HCV structural protein responsible for virus entry to the host cell. GRP78 is the master regulator of the unfolded protein response mechanism in the Endoplasmic Reticulum (ER) in normal conditions. Under the stress of HCV infection or carcinogenesis, GRP78 is upregulated. Consequently, it escapes the ER retention and translocates to the cytoplasm and over the plasma membrane. Aim: This study aims to predict the binding mode of HCV E2 to GRP78 protein. Methods: Due to the high sequence and structural conservation between the C554–C566 region of HCV E2 and the Pep42, cyclic peptide that is reported to target GRP78, we propose that this region of E2 can be the recognition site. We predict the possible binding mode between HCV E2 and GRP78 by implementing molecular docking and molecular dynamics simulation to test such proposed binding. Results: The simulations reveal a stable and highly potent (−111.2 docking score) binding of the HCV E2 C554–C566 peptide to GRP78 substrate-binding domain β (SBDβ). Moreover, the full-length HCV E2 also exhibits high binding affinity to GRP78 SBDβ (score = −107.5 ± 3.1), which is better than the association of GRP78 and Pep42. Conclusions: Defining the compulsory mode between HCV E2 and GRP78 is significant, so it would be possible to interfere with such binding to reduce the viral infection

Binding site prediction between lysozyme and glucose-regulated protein 78, a hope to fight amyloidosis

Amyloidosis is an extraordinarily vigorous and heterogeneous group of disorders that causes numerous organ failures due to the precipitation of misfolded proteins. Many of these damaged proteins are discarded before causing any fatal diseases due to the contribution of the protein quality control (PQC) system and its chaperons, including glucose-regulated protein (GRP78). One of the most important enzymatic proteins inside the body is lysozyme, which is reported to have many mutated variants that may cause amyloid fibrils. This study used structural bioinformatics and molecular dynamics simulations to test and suggest binding sites for the human lysozyme protein with GRP78. Multiple sequence alignment (MSA) shows that part of the lysozyme envelope protein (C65–C81 cyclic region) has high similarities (30.77% identity) with the cyclic Pep42. Additionally, the binding between the lysozyme cyclic region (C65–C81) and GRP78 substrate binding domain (SBD) is found favorable. The number and types of interactions vary between each of the mutant isoforms of lysozyme. The more significant the conformational changes in the mutation, the greater its probability of aggregation and the formation of amyloid fibrils. Each mutation leads to different interactions and binding patterns with GRP78. The present computational study suggests a lysozyme-GRP78 binding site, thus paving the way for drug designers to construct suitable carriers that can collect misfolded lysozyme proteins and eliminate them from the body, preventing their aggregation and amyloidogenesis. Communicated by Ramaswamy H. Sarma</p