ABSTRACT
AIM: To evaluate dose calculation accuracy of various algorithms in lung equivalent inhomogeneity comprising tumor within it and comparison with Gafchromic film data. MATERIALS AND METHODS: Gafchromic film measured central axis absorbed dose in lung insert (-700 Hounsfield unit [HU]), in racemosa wood cylindrical inhomogeneity (-725 HU) and at three surfaces of tumor (-20 HU) created in cylindrical inhomogeneity, put in the cavity of computerized imaging reference systems (CIRS) thorax phantom were compared with convolution (CON), superposition (SP), fast SP (FSP), and X-ray voxel Monte Carlo (XVMC) algorithms calculated dose using 6 MV beams of field size 2 cm × 2 cm, 3 cm × 3 cm, 4 cm × 4 cm, 5 cm × 5 cm, and 8 cm × 8 cm. RESULTS: XVMC was in good agreement with film measured results for all selected field sizes except 3 cm × 3 cm. SP under estimated by 5.7% at the center of the lung insert while deviation up to 6% was found at the cent of wood inhomogeneity in 2 cm × 2 cm. Except CON, increase in dose from proximal to the central surface of the tumor and then dose falloff from central to the distal surface for field size 2 cm × 2 cm to 4 cm × 4 cm was recorded. The change in film measured percentage depth dose from 2 cm × 2 cm to 3 cm × 3 cm field sizes was found -8% however for consecutive field size(s) larger than 3 cm × 3 cm this difference was less. CON and FSP produced overestimated results. CONCLUSION: Out of four algorithms, XVMC found consistent with measured data. The electronic disequilibrium within and at the interface of inhomogeneity make the accurate dose predictions difficult. These limitations results in deviations from the expected results of the treatments.
Subject(s)
Lung Neoplasms/radiotherapy , Lung/diagnostic imaging , Radiometry/methods , Radiotherapy Planning, Computer-Assisted/methods , Algorithms , Humans , Lung/pathology , Lung Neoplasms/pathology , Monte Carlo Method , Phantoms, Imaging , Radiotherapy DosageABSTRACT
Chronic ultraviolet radiation (UV-R) exposure causes skin disorders like erythema, edema, hyperpigmentation, photoaging and photocarcinogenesis. Recent research trends of researchers have focused more attention on the identification and use of photo stable natural agents with photoprotective properties. Piperine (PIP), as a plant alkaloid, is an important constituent present in black pepper (Piper nigrum), used widely in ayurvedic and other traditional medicines and has broad pharmacological properties. The study was planned to photoprotective efficacy of PIP in human keratinocyte (HaCaT) cell line. We have assessed the UV-R induced activation of transcription factor NF-κB in coordination with cell death modulators (Bax/Bcl-2 and p21). The LC-MS/MS analysis revealed that PIP was photostable under UV-A/UV-B exposure. PIP (10µg/ml) attenuates the UV-R (A and B) induced phototoxicity of keratinocyte cell line through the restoration of cell viability, inhibition of ROS, and malondialdehyde generation. Further, PIP inhibited UV-R mediated DNA damage, prevented micronuclei formation, and reduced sub-G1 phase in cell cycle, which supported against photogenotoxicity. This study revealed that PIP pretreatment strongly suppressed UV-R induced photodamages. Molecular docking studies suggest that PIP binds at the active site of NF-κB, and thus, preventing its translocation to nucleus. In addition, transcriptional and translational analysis advocate the increased expression of NF-κB and concomitant decrease in IkB-α expression under UV-R exposed cells, favouring the apoptosis via Bax/Bcl-2 and p21 pathways. However, PIP induced expression of IkB-α suppress the NF-κB activity which resulted in suppression of apoptotic marker genes and proteins that involved in photoprotection. Therefore, we suggest the applicability of photostable PIP as photoprotective agent for human use.
Subject(s)
Alkaloids/pharmacology , Benzodioxoles/pharmacology , Piperidines/pharmacology , Polyunsaturated Alkamides/pharmacology , Radiation-Protective Agents/pharmacology , Signal Transduction/drug effects , Ultraviolet Rays , Alkaloids/chemistry , Benzodioxoles/chemistry , Binding Sites , Catalytic Domain , Cell Cycle Checkpoints/drug effects , Cell Cycle Checkpoints/radiation effects , Cell Line , Cell Survival/drug effects , Cell Survival/radiation effects , Comet Assay , DNA Damage/drug effects , Humans , Keratinocytes/cytology , Keratinocytes/drug effects , Keratinocytes/metabolism , Lipid Peroxidation/drug effects , Lipid Peroxidation/radiation effects , Microscopy, Fluorescence , Molecular Docking Simulation , NF-kappa B/chemistry , NF-kappa B/metabolism , Piperidines/chemistry , Polyunsaturated Alkamides/chemistry , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Radiation-Protective Agents/chemistry , Reactive Oxygen Species/metabolism , Signal Transduction/radiation effects , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolismABSTRACT
INTRODUCTION: Cyclin-D1, p53 and EGFR are molecular markers that regulate the cell cycle and play an important role in tumor progression and development. The present study evaluates the prognostic significance of these markers with chemoradiation response in patients of locally advanced oral squamous cell carcinoma (OSCC). MATERIAL AND METHOD: A total of 97 OSCC patients (females = 19 and males = 78), aged 20-67 years and stage III/IV were recruited. Treatment response was assessed according to WHO criteria. Cyclin-D1, p53 and EGFR expressions in tumor tissue was estimated by immunohistochemical (IHC) method and quantified as percentage positive nuclei. RESULTS: The positive expression rates of molecular markers were 86.6% for Cyclin-D1, 92.8% for EGFR and 85.6% for p53. The strong positive expressions of both Cyclin-D1 and p53 showed significant association with poor response. The Cox multivariate regression analysis showed coexpressions of Cyclin-D1 and p53 a significant and independent predictor of overall survival (OR = 1.90, 95% CI = 1.45-4.82, p = 0.046) after adjusting the demographic, clinicopathological and radiological response. The strong positive expressions of Cyclin-D1 and p53 and coexpressions of Cyclin-D1, EGFR and p53 showed significant (p < 0.05 or p < 0.01 or p < 0.001) and lower survival as compared to negative or moderate positive expressions and coexpressions, respectively. CONCLUSION: Expressions and coexpressions of Cyclin-D1 and p53 may serve as a prognostic marker in OSCC patients.
ABSTRACT
This study compared the efficacy and toxicity of Gefitinib, Methotrexate and Methotrexate plus 5-Fluorouracil (5-FU) in patients of recurrent squamous cell carcinoma of head and neck (SCCHN) treated with palliative intent. Patients with recurrent SCCHN not amenable to curative treatment were randomly assigned to Gefitinib, Methotrexate or Methotrexate plus 5-FU arm. The primary end point was overall survival. Secondary end points of interest were objective response rate, toxicity and quality of life. Total 117 patients were analyzed. Median overall survival and objective response rates were 8.8 months, 7.8 months and 8.1 months and 7.7%, 5.0% and 7.9% in Gefitinib, Methotrexate and Methotrexate plus 5-FU arms respectively with no statistically significant difference between 3 arms. Gefitinib had different toxicity profile compared with other arms. Majority of toxicities were Grade 1 or Grade 2. Gefitinib had significant improvement in quality of life during initial months over Methotrexate. There was no suggestion that Gefitinib significantly prolonged overall survival compared with Methotrexate and Methotrexate plus 5-FU. However, improved Quality of Life with manageable toxicities was observed.
