Dual-frequency ultrasound activation of nanomicellar doxorubicin in targeted tumor chemotherapy.

INTRODUCTION: This study investigated the therapeutic effect of dual-frequency sonication (3 MHz and 28 kHz) at low intensity levels in combination with micellar doxorubicin in the treatment of a tumor model of spontaneous breast adenocarcinoma in Balb/c mice. METHODS: We used sonication frequencies 28 kHz and 3 MHz and their dual combinations in the progressive wave mode to enhance acoustic cavitation. Then, the antitumor effect of the simultaneous dual-frequency ultrasound (28 kHz and 3 MHz) at low intensity levels in combination with doxorubicin and micellar doxorubicin injection was investigated in a spontaneous model of breast adenocarcinoma in Balb/c mice. Sixty-three tumor-bearing mice were randomly divided into seven groups: control, sham, sonication with dual frequency, doxorubicin without sonication, doxorubicin with dual-frequency sonication, micellar doxorubicin without sonication, and micellar doxorubicin with dual-frequency sonication. The tumor volume change relative to the initial volume, tumor growth inhibition ratio, the required times for each tumor to reach two (T 2) and five (T 5) times its initial volume, and survival period were the tumor growth delay parameters which were calculated and recorded at various times after treatment. RESULTS: The results of the combination of frequencies 28 kHz (0.04 W/cm(2)) and 3 MHz (2.00 W/cm(2)) showed remarkable enhancement of the cavitation activity compared with single-frequency sonication (P < 0.05). The micellar doxorubicin injection with sonication group showed a significant difference in the relative volume percent parameter compared with the other groups (P < 0.05). Additionally, the T 2 and T 5 times in the micellar doxorubicin with sonication group were significantly higher than in the other groups (P < 0.05). Also, the survival period of the mice in the micellar doxorubicin with sonication group was significantly longer than in the other groups (P < 0.05). These findings were verified histopathologically. CONCLUSION: This study shows that simultaneous combined dual-frequency ultrasound sonication in continuous mode is effective in producing cavitation activity at low intensity. We conclude that dual-frequency sonication with micellar doxorubicin injection extends survival in a murine breast adenocarcinoma model.

Effect of fractionation on treatment outcome in local dual-frequency sonication and Dox-encapsulated nanomicelles.

PURPOSE: The goal of this study was to localize drug release from nanomicelles using dual-frequency sonication at low levels of acoustic intensity. METHODS: In this study, the antitumor effect of simultaneous dual-frequency sonication (28 kHz and 3 MHz) at low levels of acoustic intensity in combination with doxorubicin and micellar doxorubicin injection was assessed in a spontaneous model of breast adenocarcinoma in female Balb/c mice. Sixty-three tumor-bearing mice were randomly grouped into control, sham, dual-frequency sonication, doxorubicin injection with and without dual-frequency sonication, and micellar doxorubicin injection with and without dual-frequency sonication groups. RESULTS: The results of volume change relative to initial volume showed that in the micellar doxorubicin injection with sonication group, this parameter was significantly different from that of the control, sham, sonication, and doxorubicin injection groups (P < 0.05). In addition, the volume began to increase on the 15th day after the start of treatment, which is a good indication to repeat treatment; therefore, another group received an extra treatment on day 15. The animal life span in the micellar doxorubicin with sonication and repeated treatment groups was significantly higher than that in all the other experimental groups except for the micellar doxorubicin injection group (P < 0.05). CONCLUSION: It was concluded that dual-frequency sonication with micellar doxorubicin injection extends the life span relative to doxorubicin injection or dual-frequency sonication alone, and that repeating this treatment on day 15 decreases the rate of tumor growth significantly.

Morphometric and volumetric study of caudate and putamen nuclei in normal individuals by MRI: Effect of normal aging, gender and hemispheric differences.

BACKGROUND: The aim of this study was to determine age, gender, and hemispheric differences in the volume of the human neostriatum (striatum) nucleus in healthy humans. MATERIAL/METHODS: This study was performed on 120 normal human subjects (60 males, 60 females, right-handed) 15-65 years old, divided into two groups: young (<40 yrs) and old (=≥40 yrs). Sectional brain images were obtained via magnetic resonance imaging (MRI), analyzed and processed using the Image-J software, and the striatum volume was calculated using the Cavalieri's principle, retrospectively. RESULTS: The analyses revealed bilateral age-related shrinkage of the putamen in both genders and the putamen and caudate nucleus were significantly smaller in older than in younger subjects (P-value <0.001). The age-related shrinkage of the caudate and putamen nucleus in men and women was about 5%, 5% and 4%, 4%, respectively, and there were statistically significant volume differences between males and females (P-value <0.05). In both genders, a significant rightward asymmetry was observed in the caudate and putamen nucleus (3.89%, 4.21% in men and 4.51%, 3.32% in women). CONCLUSIONS: Bilateral age-related shrinkage and rightward asymmetry of the striate nucleus was found in healthy adults and there were significant volume differences between men and women. Obtained results provide useful baseline data on age and gender-related changes of the volume of the striatum.

Comparing the in vivo sonodynamic effects of dual- and single-frequency ultrasound in breast adenocarcinoma.

INTRODUCTION: Dual-frequency ultrasound has recently been shown to extensively enhance the acoustic cavitation yield in water. METHODS: In this study, the in vivo antitumor effect of simultaneous, dual-frequency ultrasound at low-level intensity (I SATA = 2 W/cm(2) for 1 MHz and I SATA = 0.2 W/cm(2) for 150 kHz) in combination with an intravenous injection of 5 mg/kg hematoporphyrin (Hp) was investigated in a model of breast adenocarcinoma in Balb/c mice. Seventy-one tumor-bearing mice were divided into nine treatment groups: control, sham, Hp injection, and single- and dual-frequency sonication in the presence and absence of Hp. The tumor growth delay was then calculated based on the tumor volume at various times after treatment using the following parameters: relative volume percent, [Formula: see text] and [Formula: see text] times (to reach five and two times the initial volume), percent of tumor growth inhibition ratio, and survival period. RESULTS: Our results showed no significant difference between the 150 kHz and 1 MHz single-frequency groups when compared with the sham group after 9 days of treatment (p > 0.05). However, treatment with dual-frequency ultrasound significantly delayed tumor growth when compared with the sham group (p < 0.05) after 9 days of treatment. Furthermore, in vivo experiments showed that combined dual-frequency sonication controlled tumor growth more effectively than single-frequency sonication. Evaluation of the therapeutic effects of single- and dual-frequency ultrasound in sonodynamic therapy revealed that treatment with the combination of dual-frequency ultrasound and Hp resulted in a significant reduction in the relative volume percent of tumors after 3 days of treatment (p < 0.05) compared with the controls. Additionally, the T 5 time and the survival period in the group treated with the combination therapy was significantly longer than those in all the other groups (p < 0.05). These findings were further verified histopathologically. CONCLUSION: In conclusion, our results reveal that sonodynamic therapy using dual-frequency ultrasound is able to extend the survival time of animals compared with single-frequency sonication.

Gdn 3+@CNTs-PEG versus Gadovist®: In Vitro Assay.

OBJECTIVES: Carbon nanotubes (CNTs) are allotropes of carbon with a length-to-diameter ratio greater than 106 with the potential uses as medical diagnostic or therapeutic agents. In vitro studies have revealed that gadolinium (Gd) nanoparticle-catalyzed single-walled carbon nanotubes (SWCNTs) possess superparamagnetic properties, which enable them to be used as contrast agents in magnetic resonance imaging (MRI). Our study synthesized Gd-CNT for use as MRI contrast agents. METHODS: To reduce the toxicity and solubility of CNTs, it was functionalized, and after loading with Gd was coated with polyethylene glycols (PEG). We then synthesized different concentrations of Gdn 3+@CNTs-PEG and Gadovist® to be evaluated as MRI contrast agents. RESULTS: The analysis showed that the Gd concentration in Gadovist® was 12.18% higher than synthesized Gdn 3+@CNTs-PEG, but the mean signal intensity of the Gdn 3+@CNTs-PEG was approximately 3.3% times higher than Gadovist®. CONCLUSIONS: Our findings indicate that synthesized Gdn 3+@CNTs-PEG has the potential to be used as an MRI contrast agent in vitro, but in vivo assessment is necessary to determine the bio-distribution, kinetic, and signal enhancement characteristics.

Induction of Apoptosis and Inhibition of Invasion in Gastric Cancer Cells by Titanium Dioxide Nanoparticles.

OBJECTIVES: Nanoparticles induce oxidative stress in cells and damage them through the cell membrane and DNA damage, eventually resulting in cell death. This study aimed to evaluate the effect of titanium dioxide (TiO2) nanoparticles on apoptosis induction and invasion of gastric cancer cell line, MKN-45. METHODS: We used the MTT assay to assess proliferation of MKN-45 gastric cancer cells after exposure to different forms of TiO2 nanoparticles including amorph, brookite, anatase, and rutile coated with polyethylene glycol (PEG) and bovine serum albumin (BSA). Ethidium bromide and acridine orange staining were used to visualize cancer cell apoptosis, and the wound healing assay technique (migration test) was used to assay cancer cell invasion. RESULTS: Viability and proliferation of cancer cells in the presence of various forms of TiO2 nanoparticles were reduced (p ≤ 0.050). This reduction in cell proliferation and viability was directly related to concentration and duration of exposure to nanoparticles. Induction of cell death was seen in all groups (p ≤ 0.050). Increased cell invasion was seen in PEG-amorph TiO2 group compared to the control group. Cell invasion was decreased only in the brookite BSA group (p ≤ 0.050). CONCLUSIONS: Various forms of TiO2 nanoparticles reduced cell proliferation and induced apoptosis in cancer cells. Some forms of TiO2 nanoparticles such as brookite BSA also inhibited cell invasion. PEG-amorph TiO2 nanoparticles increased cell invasion. These differences seem to be due to the effects of different configurations of TiO2 nanoparticles. TiO2 may provide a new strategy for cancer treatment and more studies are needed.

Radiation Protection Knowledge, Attitude, and Practice (KAP) in Interventional Radiology.

OBJECTIVES: Due to increasing cardiac disease and its mortality rate, the frequency of cardiac imaging has grown and, as a result, interventional cardiologists potentially receive high radiation doses in cardiac examinations. This study aimed to assess the knowledge, attitude, and practice (KAP) level of radiation protection (RP) among interventional radiology staff in Iranian health care centers across the country. METHODS: We used a validated questionnaire survey consisting of 30 multiple-choice questions to perform a cross-sectional study. Participants were healthcare personnel working professionally with radiation at different levels (i.e., secretary, radiology technologists, nurse, and physician). The questionnaire was divided into three sections to assess KAP regarding RP. RESULTS: Significant differences exist in RP KAP mean scores based on educational age (p < 0.050). There was no significant difference in RP KAP mean scores when looking at sex, practice age, and hospital type (p > 0.050). We found a significant difference between RP KAP mean scores and different regions (p < 0.050). CONCLUSIONS: Educational and practice age, sex, type of hospital, and geographical region affect he KAP of interventional radiology staff regarding RP. Since many of the subjective radiation harms for both medical team and patients, this can be easily controlled and prevented; a checkup for personnel of interventional radiology departments, considering samples from different parts of the country with different levels of education, continuous training, and practical courses may help map the status of KAP. The results of this study may also help authorized health physics officers design strategic plans to enhance the quality of such services in radiation departments.

Proteomic Analysis of the Effect of Extremely Low-Frequency Electromagnetic Fields (ELF-EMF) With Different Intensities in SH-SY5Y Neuroblastoma Cell Line.

Introduction: During the last 3 decades, human is exposed to extremely low frequency electromagnetic fields (ELF-EMF) emitted by power lines and electronic devices. It is now well accepted that ELF-EMF are able to produce a variety of biological effects, although the molecular mechanism is unclear and controversial. Investigation of different intensities effects of 50 Hz ELF-EMF on cell morphology and protein expression is the aim of this study. Methods: SH-SY5Y human neuroblastoma cell line was exposed to 0.5 and 1 mT 50 Hz (ELF-EMF) for 3 hours. Proteomics techniques were used to determine the effects of these fields on protein expression. Bioinformatic and statistical analysis of proteomes were performed using Progensis SameSpots software. Results: Our results showed that exposure to ELF-EMF changes cell morphology and induces a dose-dependent decrease in the proliferation rate of the cells. The proteomic studies and bioinformatic analysis indicate that exposure to 50 Hz ELF-EMF leads to alteration of cell protein expression in both dose-dependent and intensity dependent manner, but the later is more pronounced. Conclusion: Our data suggests that increased intensity of ELF-EMF may be associated with more alteration in cell protein expression, as well as effect on cell morphology and proliferation.

Proliferation and differentiation of rat bone marrow stem cells by 400µT electromagnetic field.

The interaction between environment electromagnetic field (EMF) and cells can effect on various physiological processes. EMF as an external inducing factor, could effect on proliferation or differentiation of cells. The purpose of this study was to evaluate the influence of the electromagnetic field on the viability, proliferation and differentiation rate of bone marrow stem cells (BMSCs) to neuron. BMSCs were obtained from 42 adult male rats. The cells incubated and cultured in 96-wells and 6-wells plates and exposed to electromagnetic field (40 or 400µT) with a selected waveform: AC (alternative current), rectified half wave (RHW) and rectified full wave (RFW), for a week. To assess the viability and proliferation rate of treated cells, MTT assay was done, and then immunocytochemistry staining Neu N was used to evaluate cell differentiation to neuron. Results showed that EMF decreases the viability and proliferation in treated groups. But in AC group's reduction was significant. Minimum viability and proliferation rate was observed in RHW 400µT group compared with sham. Immunocytochemistry showed that EMF can induce BMSC differentiation into neuron in AC 400µT and RFW 400µT. Evidences of this research support the hypothesis that EMF can induce differentiation of BMSCs to neuron.

Effects of 3 Hz and 60 Hz Extremely Low Frequency Electromagnetic Fields on Anxiety-Like Behaviors, Memory Retention of Passive Avoidance and Electrophysiological Properties of Male Rats.

INTRODUCTION: The effects of electromagnetic fields on biological organisms have been a controversial and also interesting debate over the past few decades, despite the wide range of investigations, many aspects of extremely low frequency electromagnetic fields (ELF/EMFs) effects including mechanism of their interaction with live organisms and also their possible biological applications still remain ambiguous. In the present study, we investigated whether the exposures of ELF/EMF with frequencies of 3 Hz and 60 Hz can affect the memory, anxiety like behaviors, electrophysiological properties and brain's proteome in rats. METHODS: Male rats were exposed to 3 Hz and 60 Hz ELF/EMFs in a protocol consisting of 2 cycles of 2 h/day exposure for 4 days separated with a 2-day interval. Short term memory and anxiety like behaviors were assessed immediately, 1 and 2 weeks after the exposures. Effects of short term exposure were also assessed using electrophysiological approach immediately after 2 hours exposure. RESULTS: Behavioral test revealed that immediately after the end of exposures, locomotor activity of both 3 Hz and 60 Hz exposed groups significantly decreased compared to sham group. This exposure protocol had no effect on anxiety like behavior during the 2 weeks after the treatment and also on short term memory. A significant reduction in firing rate of locus coeruleus (LC) was found after 2 hours of both 3 Hz and 60 Hz exposures. Proteome analysis also revealed global changes in whole brain proteome after treatment. CONCLUSION: Here, some evidence regarding the fact that such exposures can alter locomotor activity and neurons firing rate in male rats were presented.

High-Dose-Rate (192)Ir Brachytherapy Dose Verification: A Phantom Study.

BACKGROUND: The high-dose-rate (HDR) brachytherapy might be an effective tool for palliation of dysphagia. Because of some concerns about adverse effects due to absorbed radiation dose, it is important to estimate absorbed dose in risky organs during this treatment. OBJECTIVES: This study aimed to measure the absorbed dose in the parotid, thyroid, and submandibular gland, eye, trachea, spinal cord, and manubrium of sternum in brachytherapy in an anthropomorphic phantom. MATERIALS AND METHODS: To measure radiation dose, eye, parotid, thyroid, and submandibular gland, spine, and sternum, an anthropomorphic phantom was considered with applicators to set thermoluminescence dosimeters (TLDs). A specific target volume of about 23 cm(3) in the upper thoracic esophagus was considered as target, and phantom planned computed tomography (CT) for HDR brachytherapy, then with a micro-Selectron HDR ((192)Ir) remote after-loading unit. RESULTS: Absorbed doses were measured with calibrated TLDs and were expressed in centi-Gray (cGy). In regions far from target (≥ 16 cm) such as submandibular, parotid and thyroid glands, mean measured dose ranged from 1.65 to 5.5 cGy. In closer regions (≤ 16 cm), the absorbed dose might be as high as 113 cGy. CONCLUSIONS: Our study showed similar depth and surface doses; in closer regions, the surface and depth doses differed significantly due to the role of primary radiation that had imposed a high-dose gradient and difference between the plan and measurement, which was more severe because of simplifications in tissue inhomogeneity, considered in TPS relative to phantom.

Apoptosis/Necrosis Induction by Ultraviolet, in ER Positive and ER Negative Breast Cancer Cell Lines.

BACKGROUND: Ultraviolet (UV) light exposure has been one of the major inducers of apoptosis. UV exposure has caused pyrimidine dimers and DNA fragmentation which might lead to cell cycle arrest and apoptosis signals activation. UV induced apoptosis has investigated in MDA-MB 468 as an ER negative breast adenocarcinoma and MCF-7 as an ER positive breast cancer cell line. Apoptosis induction rate by UV might be different in these two types of cells due to different biological characteristics of the cell. OBJECTIVES: In this paper we have evaluated serial dose of UV-B exposure on ER positive and ER negative breast cancer cell lines and its effect on apoptosis or necrosis induction in these cells. MATERIALS AND METHODS: MDA-MB468 and MCF-7 cell lines have cultured for 24 hours and UV exposure has carried out at 290 nm at dose of 154 J/m(2) to 18 KJ/m(2) using UV lamp. UV exposed cells have incubated in cell culture condition for 24 or 48 hours following UV exposure and the cells have stained and analyzed by flow cytometry for apoptosis evaluation by Annexin V/PI method. RESULTS: Apoptosis rate (PI and Annexin V double positive cells) after 24 hours incubation was higher in 24 hours in comparison with 48 hours incubation in both cell lines. The frequency of PI positive MDA-MB 468 cells was higher than PI and Annexin V double positive cells after 48 hours. PI positive MDA-MB 468 cells were significantly higher than MCF-7 cells in 24 hours incubation time. CONCLUSIONS: The results have shown that MDA-MB 468 cells were more sensitive to UV exposure and DNA fragmentation and necrosis pathway was dominant in these cells.

Introducing biomarker panel in esophageal, gastric, and colon cancers; a proteomic approach.

Cancer research is an attractive field in molecular biology and medicine. By applying large-scale tools such as advanced genomics and proteomics, cancer diagnosis and treatment have been improved greatly. Cancers of esophagus, gastric, and colon accounted for major health problem globally. Biomarker panel could bring out the accuracy for cancer evaluation tests as it can suggest a group of candidate molecules specified to particular malignancy in a way that distinguishing malignant tumors from benign, differentiating from other diseases, and identifying each stages with high specificity and sensitivity. In this review, a systematic search of unique protein markers reported by several proteomic literatures are classified in their specific cancer type group as novel panels for feasible accurate malignancy diagnosis and treatment. About thousands of introduced proteins were studied; however, a small number of them belonged to a specific kind of malignancy. In conclusion, despite the fact that combinatorial biomarkers appear to be hopeful, more evaluation of them is crucial to achieve the suitable biomarker panel for clinical application. This effort needs more investigations and researches for finding a specific and sensitive panel.

Protein-Protein Interaction Network could reveal the relationship between the breast and colon cancer.

AIM: This study is aimed to elicit the possible correlation between breast and colon cancer from molecular prospective by analyzing and comparing pathway-based biomarkers. BACKGROUND: Breast and colon cancer are known to be frequent causes of morbidity and mortality in men and women around the world. There is some evidence that while the incident of breast cancer in young women is high, it is reported lower in the aged women. In fact, aged women are more prone to colorectal cancer than older men. . In addition, many studies showed that several biomarkers are common among these malignancies. PATIENTS AND METHODS: The genes were retrieved and compared from KEGG database and WikiPathway, and subsequently, protein-protein interaction (PPI) network was constructed and analyzed using Cytoscape v:3.2.1 software and related algorithms. RESULTS: More than forty common genes were identified among these malignancies; however, by pathways comparison, twenty genes are related to both breast and colon cancer. Centrality and cluster screening identified hub genes, including SMAD2, SMAD3, (SMAD4, MYC), JUN, BAD, TP53. These seven genes are enriched in regulation of transforming growth factor beta receptor signaling pathway, positive regulation of Rac protein signal transduction, positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway, and positive regulation of mitotic metaphase/anaphase transition respectively. CONCLUSION: As there are numerous genes frequent between colorectal cancer and breast cancer, there may be a common molecular origin for these malignancies occurrences. It seems that breast cancer in females interferes with the rate of colorectal cancer incidence.

Evaluation of Organs at Risk's Dose in External Radiotherapy of Brain Tumors.

BACKGROUND: Radiotherapy plays an important role in the management of most malignant and many benign primary central nervous system (CNS) tumors. Radiotherapy affects both tumor cells and uninvolved normal cells; so, it is important to estimate absorbed dose to organs at risk in this kind of treatment. The aim of this study was to determine the absorbed dose to chiasma, lens, optic nerve, retina, parotid, thyroid and submandibular gland in frontal lobe brain tumors radiotherapy based on treatment planning system (TPS) calculation and direct measurement on the phantom. METHODS: A head and neck phantom was constructed using natural human bone and combination of paraffin wax and Sodium Chloride (NaCl) as tissue-equivalent material. Six cylinders were made of phantom material which had cavities to insert Thermoluminescent Dosimeters (TLDs) at several depths in order to measure absorbed dose to chiasma, lens, optic nerve, retina, parotid, thyroid and submandibular gland. Three routine conventional plans associated with tumors of this region and a new purposed technique were performed on the phantom and dose distribution and absorbed dose to critical organs were compared using treatment planning system (TPS) calculation and direct measurement on the phantom. RESULTS: Absorbed doses were measured with calibrated TLDs and are expressed in centigray (cGy). In all techniques absorbed dose to all organs except the lenses were at their tolerance dose levels and in the new purposed technique, absorbed dose to chiasma was significantly reduced. CONCLUSION: Our findings showed differences in the range of 1-5% in all techniques between TPS calculation and direct measurements for all organs except submandibular glands and thyroid. Because submandibular glands and thyroid are far from primary radiation field, TLD reading in these regions although small but differs from TPS calculation which shows very smaller doses. This might be due to scattered radiation which is not well considered in the TPS. In the new technique, because the chiasma is out of the radiation field, absorbed dose was reduced significantly.

Effect of ELF-EMF Exposure on Human Neuroblastoma Cell Line: a Proteomics Analysis.

BACKGROUND: Extremely low frequency electromagnetic fields (ELF-EMF) have been common in daily life all over the world. They have produced by power lines and electrical appliances, but higher levels of them have raised a lot of concerns about their carcinogenesis. Both epidemiological and laboratory studies have suggested that EMFs might increase cancer incidence, including acute childhood leukemia, brain and breast cancer. METHODS: In the present study, SH-SY5Y human neuroblastoma cell line has exposed to 2mT, 50 Hz magnetic field for 3 h. Next, effect of this exposure on protein expression including over-expression or under-expression has assessed by proteomics. RESULTS: Bioinformatics and statistical analysis using progenesis same spot software on the obtained 2D electrophoresis has shown that expression of 189 proteins in exposed group has changed relative to control. Besides, PCA analysis has verified results of clustering, and has shown that protein data has clustered according to experimental conditions. CONCLUSION: The results of this study have shown that ELF-EMF changes cell morphology via altering protein expression, but more profound studies have needed to determine the kind of proteins altered.

Saffron Aqueous Extract Inhibits the Chemically-induced Gastric Cancer Progression in the Wistar Albino Rat.

OBJECTIVE(S): Gastric cancer is the first and second leading cause of cancer related death in Iranian men and women, respectively. Gastric cancer management is based on the surgery, radiotherapy and chemotherapy. In the present study, for the first time, the beneficial effect of saffron (Crocus sativus L.) aqueous extract (SAE) on the 1-Methyl -3- nitro -1- nitrosoguanidine (MNNG)-induced gastric cancer in rat was investigated. MATERIALS AND METHODS: MNNG was used to induce gastric cancer and then, different concentrations of SAE were administered to rats. After sacrificing, the stomach tissue was investigated by both pathologist and flow cytometry, and several biochemical parameters was determined in the plasma (or serum) and stomach of rats. RESULTS: Pathologic data indicated the induction of cancer at different stages from hyperplasia to adenoma in rats; and the inhibition of cancer progression in the gastric tissue by SAE administration; so that, 20% of cancerous rats treated with higher doses of SAE was completely normal at the end of experiment and there was no rat with adenoma in the SAE treated groups. In addition, the results of the flow cytometry/ propidium iodide staining showed that the apoptosis/proliferation ratio was increased due to the SAE treatment of cancerous rats. Moreover, the significantly increased serum LDH and decreased plasma antioxidant activity due to cancer induction fell backwards after treatment of rats with SAE. But changes in the other parameters (Ca(2+), tyrosine kinase activity and carcino-embryonic antigen) were not significant. CONCLUSION: SAE inhibits the progression of gastric cancer in rats, in a dose dependent manner.

A simple calculation method for determination of equivalent square field.

Determination of the equivalent square fields for rectangular and shielded fields is of great importance in radiotherapy centers and treatment planning software. This is accomplished using standard tables and empirical formulas. The goal of this paper is to present a formula based on analysis of scatter reduction due to inverse square law to obtain equivalent field. Tables are published by different agencies such as ICRU (International Commission on Radiation Units and measurements), which are based on experimental data; but there exist mathematical formulas that yield the equivalent square field of an irregular rectangular field which are used extensively in computation techniques for dose determination. These processes lead to some complicated and time-consuming formulas for which the current study was designed. In this work, considering the portion of scattered radiation in absorbed dose at a point of measurement, a numerical formula was obtained based on which a simple formula was developed to calculate equivalent square field. Using polar coordinate and inverse square law will lead to a simple formula for calculation of equivalent field. The presented method is an analytical approach based on which one can estimate the equivalent square field of a rectangular field and may be used for a shielded field or an off-axis point. Besides, one can calculate equivalent field of rectangular field with the concept of decreased scatter radiation with inverse square law with a good approximation. This method may be useful in computing Percentage Depth Dose and Tissue-Phantom Ratio which are extensively used in treatment planning.

Effect of local dual frequency sonication on drug distribution from polymeric nanomicelles.

To overcome the side effects caused by systemic administration of doxorubicin, nanosized polymeric micelles were used in combination with dual frequency ultrasonic irradiation. These micelles release the drug due to acoustic cavitation, which is enhanced in dual frequency ultrasonic fields. To form the drug-loaded micelles, Pluronic P-105 copolymer was used, and doxorubicin was physically loaded into stabilized micelles with an average size of 14 nm. In this study, adult female Balb/C mice were transplanted with spontaneous breast adenocarcinoma tumors and were injected with a dose of 1.3 mg/kg doxorubicin in one of three forms: free doxorubicin, micellar doxorubicin without sonication and micellar doxorubicin with sonication. To increase cavitation yield, the tumor region was sonicated for 2.5 min at simultaneous frequencies of 3 MHz (I(SATA)=2 W/cm(2)) and 28 kHz (I(SATA)=0.04 W/cm(2)). The animals were sacrificed 24h after injection, and their tumor, heart, spleen, liver, kidneys and plasma were separated and homogenized. The drug content in the tissues was determined using tissue fluorimetry (350 nm excitation and 560 nm emission), and standard drug dose curves were obtained for each tissue. The results show that in the group that received micellar doxorubicin with sonication, the drug concentration in the tumor tissue was significantly higher than in the free doxorubicin injection group (8.69 times) and the micellar doxorubicin without sonication group (2.60 times). The drug concentration in other tissues was significantly lower in the micellar doxorubicin with sonication group relative to the free doxorubicin (3.35 times) and the micellar drug without sonication (2.48 times) groups (p<0.05). We conclude that dual frequency sonication improves drug release from micelles and increases the drug uptake by tumors due to sonoporation. The proposed drug delivery system creates an improved treatment capability while reducing systemic side effects caused by drug uptake in other tissues.