Radiation-induced Non-targeted Effect and Carcinogenesis; Implications in Clinical Radiotherapy.

Bystander or non-targeted effect is known to be an interesting phenomenon in radiobiology. The genetic consequences of bystander effect on non-irradiated cells have shown that this phenomenon can be considered as one of the most important factors involved in secondary cancer after exposure to ionizing radiation. Every year, millions of people around the world undergo radiotherapy in order to cure different types of cancers. The most crucial aim of radiotherapy is to improve treatment efficiency by reducing early and late effects of exposure to clinical doses of radiation. Secondary cancer induction resulted from exposure to high doses of radiation during treatment can reduce the effectiveness of this modality for cancer treatment. The perception of carcinogenesis risk of bystander effects and factors involved in this phenomenon might help reduce secondary cancer incidence years after radiotherapy. Different modalities such as radiation LET, dose and dose rate, fractionation, types of tissue, gender of patients, etc. may be involved in carcinogenesis risk of bystander effects. Therefore, selecting an appropriate treatment modality may improve cost-effectiveness of radiation therapy as well as the quality of life in survived patients. In this review, we first focus on the carcinogenesis evidence of non-targeted effects in radiotherapy and then review physical and biological factors that may influence the risk of secondary cancer induced by this phenomenon.

Use of Magnetic Resonance Imaging in Food Quality Control: A Review.

Modern challenges of food science require a new understanding of the determinants of food quality and safety. Application of advanced imaging modalities such as magnetic resonance imaging (MRI) has seen impressive successes and fast growth over the past decade. Since MRI does not have any harmful ionizing radiation, it can be considered as a magnificent tool for the quality control of food products. MRI allows the structure of foods to be imaged noninvasively and nondestructively. Magnetic resonance images can present information about several processes and material properties in foods. This review will provide an overview of the most prominent applications of MRI in food research.

Melatonin as an anti-inflammatory agent in radiotherapy.

Radiotherapy is one of the most relevant treatment options for cancer therapy with or without other treatment modalities including immunotherapy, surgery and chemotherapy. Exposure to heavy doses of ionizing radiation during radiotherapy results in short and long term side effects. It appears that many of these side effects are linked to inflammatory responses during treatment or after prolonged use. Inflammation is mediated by various genes and cytokines related to immune system responses caused by massive cell death following radiotherapy. This phenomenon is more obvious, particularly after exposure to clinical doses of radiotherapy. Inflammation is involved in the amplification of acute responses, genomic instability and also long term pathological changes in normal tissues. Moreover, inflammation attenuates responses of the tumor to radiotherapy through some mechanisms such as angiogenesis. Thus, the management of inflammation is one of the most interesting aims in cancer radiotherapy. Melatonin, known as a natural product in the body, has been of much interest for its anti-inflammatory properties. Some studies have proposed melatonin as a novel anti-inflammation agent. This literature review will concentrate on the anti-inflammatory properties of melatonin that may help the management of different inflammatory signaling pathways in both tumor and normal tissues.

Evaluating Radioprotective Effect of Hesperidin on Acute Radiation Damage in the Lung Tissue of Rats.

BACKGROUND: Oxidative stress plays an important role in the pathogenesis and progression of γ-irradiation-induced cellular damage, Lung is a radiosensitive organ and its damage is a dose-limiting factor in radiotherapy. The administration of dietary antioxidants has been suggested to protect against the succeeding tissue damage. The present study aimed to evaluate the radioprotective efficacy of Hesperidin (HES) against γ-irradiation-induced tissue damage in the lung of male rats. MATERIALS AND METHODS: Thirty two rats were divided into four groups. Rats in Group 1 received PBS and underwent sham irradiation. Rats in Group 2 received HES and underwent sham irradiation. Rats in Group 3 received PBS and underwent γ-irradiation. Rats in Group 4 received HES and underwent γ-irradiation. These rats were exposed to γ-radiation 18 Gy using a single fraction cobalt-60 unit, and were administered HES (100 mg/kg/d, b.w, orally) for 7 days prior to irradiation. Rats in each group were sacrificed 24 hours after radiotherapy (RT) for the determination of superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) and histopathological evaluations. RESULTS: Compared to group 1, the level of SOD and GSH significantly decreased and MDA level significantly increased in group 3 at 24 h following irradiation, (p=0.001, p<0.001, p=0.001), respectively. A statistically significant difference in all parameters was observed for rats in group 4 as compared to group 3 (p<0.05). Histopathological results 24 hours after RT showed that radiation has increased inflammation, lymphocyte, macrophage and neutrophil compared to group 1 ( p<0.0125). Oral administration of HES before RT significantly decreased macrophage and neutrophil when compared to group 3 (p<0.0125), but partly there was inflammation and lymphocyte that indicated there was no significant difference when compared to group 3 (p>0.0125). CONCLUSION: Oral administration of HES was found to offer protection against γ-irradiation- induced pulmonary damage and oxidative stress in rats, probably by exerting a protective effect against inflammatory disorders via its free radical scavenging and membrane stabilizing ability.

BRAF inhibitors: From the laboratory to clinical trials.

BRAF is one of the most commonly mutated proto-oncogenes and plays a significant role in the development of numerous cancers of high clinical impact. Due to the commonality of BRAF mutations, a number of BRAF inhibitors have been developed as tools in the management of patients with cancers dependent on the action of mutant BRAF to drive cellular proliferation. In this review, we examine the current state of clinical trials and laboratory research concerning BRAF inhibitors in development and available for clinical use. We contrast the effectiveness of type-I and type-II BRAF inhibitors, the former typically showing much more restricted inhibitory selectivity and greater patient response rates.

B-Raf mutation: a key player in molecular biology of cancer.

B-Raf is one of the more commonly mutated proto-oncogenes implicated in the development of cancers. In this review, we consider the mechanisms and clinical impacts of B-Raf mutations in cancer and discuss the implications for the patient in melanoma, thyroid cancer and colorectal cancer, where B-Raf mutations are particularly common.

Single nucleotide polymorphisms and mRNA expression of VEGF-A in papillary thyroid carcinoma: potential markers for aggressive phenotypes.

BACKGROUND AND OBJECTIVES: Polymorphisms of the VEGF gene are known to affect the biological behaviour of cancers but have seldom been studied in thyroid cancer. The aim of the current study is to evaluate the prevalence and relevance of VEGF-A polymorphisms and mRNA expression in papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: Genomic DNA and total RNA were isolated from paraffin-embedded tissue from 91 PTC (51 conventional PTC and 40 follicular variant) and 78 control thyroid tissues. Three DNA polymorphisms (+936C > T, +405C > G and -141A > C) in the 3' and 5' untranslated region (3'-UTR, 5'-UTR) of VEGF-A were studied using PCR and RFLP. Also, the mRNA expression of VEGF-A in these tissues was studied by real-time PCR. RESULTS: Distribution of polymorphisms in the 5'-UTR (VEGF-VEGF -141A > C and +405C > G) and 3'-UTR (VEGF +936C > T) were all significantly different in PTC and benign thyroid tissue (p = 0.0001, 0.001 and 0.028 respectively). The VEGF -141 C allele was more common in PTC with lymph node metastases (p = 0.026). VEGF + 405 Galleles andVEGF +936 CC genotype were more common in PTC of advanced pathological staging (p = 0.018 and 0.017 respectively). Also, increased expression of VEGF-A mRNA was noted in PTC compared to control (p = 0.009). Within the group of patients with conventional PTC, those with lymph nodal metastases had a higher level of VEGF-A mRNA expression than other patients (p = 0.0003). CONCLUSION: These findings suggest that VEGF polymorphisms and mRNA expression may predict the aggressiveness behaviour of thyroid cancer.

Follicular variant of papillary thyroid carcinoma: a diagnostic challenge for clinicians and pathologists.

The follicular variant of papillary thyroid carcinoma (FVPTC) presents a type of papillary thyroid cancer that has created continuous diagnosis and treatment controversies among clinicians and pathologists. In this review, we describe the nomenclature, the clinical features, diagnostic problems and the molecular biology of FVPTC. It is important for clinicians to understand this entity as the diagnosis and management of this group of patient may be different from other patients with conventional PTC. The literature suggests that FVPTC behaves in a way similar, clinically, to conventional papillary thyroid carcinoma. However, there are some genotypic differences which may characterise this neoplasm. These parameters may account for the phenotypic variation described by some scientists in this type of cancer. Further understanding can only be achieved by defining strict pathological criteria, in-depth study of the molecular biology and long term follow-up of the optional patients with FVPTC.

A template-free approach for determining the latency of single events of auditory evoked M100.

The phase of the complex output of a narrow band Gaussian filter is taken to define the latency of the auditory evoked response M100 recorded by magnetoencephalography. It is demonstrated that this definition is consistent with the conventional peak latency. Moreover, it provides a tool for reducing the number of averages needed for a reliable estimation of the latency. Single-event latencies obtained by this procedure can be used to improve the signal quality of the conventional average by latency adjusted averaging.

Systematic latency variation of the auditory evoked M100: from average to single-trial data.

Standard analyses of neurophysiologically evoked response data rely on signal averaging across many epochs associated with specific events. The amplitudes and latencies of these averaged events are subsequently interpreted in the context of the given perceptual, motor, or cognitive tasks. Can such critical timing properties of event-related responses be recovered from single-trial data? Here, we make use of the M100 latency paradigm used in previous magnetoencephalography (MEG) research to evaluate a novel single-trial analysis approach. Specifically, the latency of the auditory evoked M100 varies systematically with stimulus frequency over a well-defined time range (lower frequencies, e.g., 125 Hz, yield up to 25 ms longer latencies than higher frequencies, e.g., 1000 Hz). Here, we show that the complex filtering approach to single-trial analysis recovers this key characteristic of the M100 response, as well as some other important response properties relating to lateralization. The results illustrate (i) the utility of the complex filtering method and (ii) the potential of the M100 latency to be used for stimulus encoding, since the relevant variation can be observed in single trials.

Multiple nucleation in the precipitation of nickel dimethylglyoximate from homogeneous solution.

Spectrophotometric measurements of undissociated nickel dimethylglyoximate molecules in solution and electron-microscope observations of the precipitated particles have confirmed and extended previous information on the nucleation of nickel dimethylglyoximate precipitated from homogeneous solution. Supersaturated concentrations several hundred times the equilibrium solubility may persist for as long as 2 hr. Nucleation occurs not all at one initial time but rather in multiple "bursts" spread out over several hours.