Synthesis, characterization and antimicrobial studies of imine derivatives of amoxicillin

Some novel imine derivatives (1-14) of a broad spectrum antibiotic amoxicillin were prepared by condensation with different carbonyl compounds. The amoxicillin imine derivatives were characterized using elemental analysis and spectroscopic techniques such as FT-IR and 1H NMR. The prepared imine derivatives were evaluated for antimicrobial activities against some pathogens using disc diffusion method. The results of present studies demonstrate enhanced antimicrobial activity of the novel imine derivatives of amoxicillin as compared to the parent drug

A High-Throughput In Vitro Radiobiology Platform for Megavoltage Photon Linear Accelerator Studies

We designed and developed a multiwell tissue culture plate irradiation setup, and intensity modulated radiotherapy plans were generated for 96-, 24-, and 6-well tissue culture plates. We demonstrated concordance between planned and measured/imaged radiation dose profiles using radiochromic film, a 2D ion chamber array, and an electronic portal-imaging device. Cell viability, clonogenic potential, and γ-H2AX foci analyses showed no significant differences between intensity-modulated radiotherapy and open-field, homogeneous irradiations. This novel platform may help to expedite radiobiology experiments within a clinical environment and may be used for wide-ranging ex vivo radiobiology applications

Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial

Background: Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence. Patients and methods: Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.5?mg/kg i.v. 3 weekly for 1?year) or standard observation. The primary end point was detection of an 8% difference in 5-year overall survival (OS) rate; secondary end points included disease-free interval (DFI) and distant metastasis-free interval (DMFI). Tumour and blood were analysed for prognostic and predictive markers. Results: Patients (n=1343) recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56?years (range 18-88?years). With 6.4-year median follow-up, 515 (38%) patients had died [254 (38%) bevacizumab; 261 (39%) observation]; 707 (53%) patients had disease recurrence [336 (50%) bevacizumab, 371 (55%) observation]. OS at 5?years was 64% for both groups [hazard ratio (HR) 0.98; 95% confidence interval (CI) 0.82-1.16, P?=?0.78). At 5?years, 51% were disease free on bevacizumab versus 45% on observation (HR 0.85; 95% CI 0.74-0.99, P?=?0.03), 58% were distant metastasis free on bevacizumab versus 54% on observation (HR 0.91; 95% CI 0.78-1.07, P?=?0.25). Forty four percent of 682 melanomas assessed had a BRAFV600 mutation. In the observation arm, BRAF mutant patients had a trend towards poorer OS compared with BRAF wild-type patients (P?=?0.06). BRAF mutation positivity trended towards better OS with bevacizumab (P?=?0.21). Conclusions: Adjuvant bevacizumab after resection of high-risk melanoma improves DFI, but not OS. BRAF mutation status may predict for poorer OS untreated and potential benefit from bevacizumab. Clinical Trial Information: ISRCTN 81261306; EudraCT Number: 2006-005505-64

Gene-directed enzyme prodrug therapy with CPG2-ZD2767P : novel vaccina vectors and combination with radiotherapy

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Biological effects of static magnetic field exposure in the context of MR-guided radiotherapy

The clinical introduction of magnetic resonance imaging guided radiotherapy has prompted consideration of the potential impact of the static magnetic field on biological responses to radiation. This review provides an introduction to the mechanisms of biological interaction of radiation and magnetic fields individually, in addition to a description of the magnetic field effects on megavoltage photon beams at the macroscale, microscale and nanoscale arising from the Lorentz force on secondary charged particles. A relatively small number of scientific studies have measured the impact of combined static magnetic fields and ionising radiation on biological endpoints of relevance to radiotherapy. Approximately half of these investigations found that static magnetic fields in combination with ionising radiation produced a significantly different outcome compared with ionising radiation alone. MRI strength static magnetic fields appear to modestly influence the radiation response via a mechanism distinct from modification to the dose distribution. This review intends to serve as a reference for future biological studies, such that understanding of static magnetic field plus ionising radiation synergism may be improved, and if necessary, accounted for in magnetic resonance imaging guided radiotherapy treatment planning.</p

Textural Analysis and Lung Function study: Predicting lung fitness for radiotherapy from a CT scan

Objectives This study tested the hypothesis that shows advanced image analysis can differentiate fit and unfit patients for radical radiotherapy from standard radiotherapy planning imaging, when compared to formal lung function tests (FEV1, Forced Expiratory Volume in 1 second) and TLCO (Transfer Factor of Carbon Monoxide). Methods An apical region of interest (ROI) of lung parenchyma was extracted from a standard radiotherapy planning CT scan. Software using a grey level co-occurrence matrix (GLCM) assigned an entropy score to each voxel, based on its similarity to the voxels around it. Density and entropy scores were compared between a cohort of fit patients (defined as FEV1 and TLCO above 50% predicted value) and unfit patients (FEV1 or TLCO below 50% predicted). Results 29 fit and 32 unfit patients were included. Mean and median density and mean and median entropy were significantly different between fit and unfit patients (p= 0.0021, 0.0019, 0.0357 and 0.0363 respectively, 2 sided t-test). Conclusions Density and entropy assessment can differentiate between fit and unfit patients for radical radiotherapy, using standard CT imaging. Advances in knowledge This study shows that a novel intervention can generate further data from standard CT imaging. This data could be combined with existing studies to form a multi-organ patient fitness assessment from a single CT scan.</p

Textural Analysis and Lung Function study: Predicting lung fitness for radiotherapy from a CT scan

Objectives This study tested the hypothesis that shows advanced image analysis can differentiate fit and unfit patients for radical radiotherapy from standard radiotherapy planning imaging, when compared to formal lung function tests (FEV1, Forced Expiratory Volume in 1 second) and TLCO (Transfer Factor of Carbon Monoxide). Methods An apical region of interest (ROI) of lung parenchyma was extracted from a standard radiotherapy planning CT scan. Software using a grey level co-occurrence matrix (GLCM) assigned an entropy score to each voxel, based on its similarity to the voxels around it. Density and entropy scores were compared between a cohort of fit patients (defined as FEV1 and TLCO above 50% predicted value) and unfit patients (FEV1 or TLCO below 50% predicted). Results 29 fit and 32 unfit patients were included. Mean and median density and mean and median entropy were significantly different between fit and unfit patients (p= 0.0021, 0.0019, 0.0357 and 0.0363 respectively, 2 sided t-test). Conclusions Density and entropy assessment can differentiate between fit and unfit patients for radical radiotherapy, using standard CT imaging. Advances in knowledge This study shows that a novel intervention can generate further data from standard CT imaging. This data could be combined with existing studies to form a multi-organ patient fitness assessment from a single CT scan.</p

Educational Activity Corner Improving the efficiency of image guided brachytherapy in cervical cancer

Abstract Brachytherapy is an essential component of the treatment of locally advanced cervical cancers. It enables the dose to the tumor to be boosted whilst allowing relative sparing of the normal tissues. Traditionally, cervical brachytherapy was prescribed to point A but since the GEC-ESTRO guidelines were published in 2005, there has been a move towards prescribing the dose to a 3D volume. Image guided brachytherapy has been shown to reduce local recurrence, and improve survival and is optimally predicated on magnetic resonance imaging. Radiological studies, patient workflow, operative parameters, and intensive therapy planning can represent a challenge to clinical resources. This article explores the ways, in which 3D conformal brachytherapy can be implemented and draws findings from recent literature and a well-developed hospital practice in order to suggest ways to improve the efficiency and efficacy of a brachytherapy service. Finally, we discuss relatively underexploited translational research opportunities