Butylcycloheptylprodigiosin and undecylprodigiosin are potential photosensitizer candidates for photodynamic cancer therapy.

BACKGROUND: Prodiginines are bacterial red polypyrrole pigments and multifaceted secondary metabolites. These agents have anti-proliferative, immunosuppressive, antimicrobial, and anticancer effects. Recent analysis revealed that prodigiosin hypersensitizes Serratia marcescens to gamma radiation. In the present study, we report the cytotoxicity and genotoxicity properties of undecylprodigiosin and butylcycloheptylprodigiosin in the presence and absence of radiation through the MTT and alkaline comet experiments. METHODS AND RESULTS: Findings demonstrated that undecylprodigiosin was at least a fivefold more cytotoxic at low radiation doses (1 and 3 Gy) on both MCF7 and HDF lines rather than in the absence or high radiation doses (5 Gy) (P value < 0.05). Although butylcycloheptylprodigiosin toxicity on MCF7 and HDF was dose-dependent, it was not influenced by any radiation doses (P value > 0.05). Comet findings confirmed that these compounds' genotoxicity is only dose-dependent. Radiation had no significant effects on DNA damage on any of the cells (P value > 0.05). CONCLUSIONS: In general, it can be concluded that the prodiginines are cytotoxic agents that act as a double-edged sword, radiosensitizers and radio-protective, respectively at low and high radiation doses in cancer treatment process. As the results they could be used in antitumor therapies very soon.

Introduction of a Simple Algorithm to Create Synthetic-computed Tomography of the Head from Magnetic Resonance Imaging.

BACKGROUND: Recently, magnetic resonance imaging (MRI)-based radiotherapy has become a favorite science field for treatment planning purposes. In this study, a simple algorithm was introduced to create synthetic computed tomography (sCT) of the head from MRI. METHODS: A simple atlas-based method was proposed to create sCT images based on the paired T1/T2-weighted MRI and bone/brain window CT. Dataset included 10 patients with glioblastoma multiforme and 10 patients with other brain tumors. To generate a sCT image, first each MR from dataset was registered to the target-MR, the resulting transformation was applied to the corresponding CT to create the set of deformed CTs. Then, deformed-CTs were fused to generate a single sCT image. The sCT images were compared with the real CT images using geometric measures (mean absolute error [MAE] and dice similarity coefficient of bone [DSCbone]) and Hounsfield unit gamma-index (ГHU) with criteria 100 HU/2 mm. RESULTS: The evaluations carried out by MAE, DSCbone, and ГHU showed a good agreement between the synthetic and real CT images. The results represented the range of 78-93 HU and 0.80-0.89 for MAE and DSCbone, respectively. The ГHU also showed that approximately 91%-93% of pixels fulfilled the criteria 100 HU/2 mm for brain tumors. CONCLUSION: This method showed that MR sequence (T1w or T2w) should be selected depending on the type of tumor. In addition, the brain window synthetic CTs are in better agreement with real CT relative to bone window sCT images.

Role of CT scan in theranostic and management of traumatic spinal cord injury.

Traumatic spinal cord injury (TSCI) is a condition with suffering of neural structures from acute trauma with short-term or permanent sensory and motor problems. This study was conducted with the aim of determining the prevalence of TSCI in Tehran with emphasis on demographic characteristics of patients and to evaluate the effect of computed tomography (CT) in determining fracture type and severity grade of injury among TSCI patients. In a cross-sectional study, all TSCI and spinal fracture patients (N = 520) who referred to the main trauma center in Tehran, Iran, in 2013 and 2014 were selected. Radiography and CT scan were prepared and reported blindedly by two radiologists. Majority of the patients was 21-30 years male, married and their most common occupation was car driver. A significant difference was observed between gender and etiology (P = 0.001). The main etiology was traffic accident followed by falling from height. While the most common location of injury for males was thoracic vertebrae followed by lumbar vertebrae; for females it was lumbar followed by thoracic. Majority of patients had ASIA (American Spinal Injury Association) impairment scale of E (normal), followed by B (sensory incomplete). Most of the cases were hospitalized less than one week. Age of the patient and duration of hospitalization had a significant association (P = 0.015). The results showed that in traumatic spinal cord events, traffic accident and falling from height are the main etiologies; hence, authorities in Iranian health system could consider preventive policies to decline the load and TSCI effects in hospitals and population.

SRT1720, a potential sensitizer for radiotherapy and cytotoxicity effects of NVB-BEZ235 in metastatic breast cancer cells.

BACKGROUND: Chemo-radio therapy (CRT) resistance is a main barrier in treating the triple negative breast cancer (TNBC). The success of conventional treatment may be ameliorated by elevating the responsiveness of the cancer cells to CRT. NVP-BEZ235 as a PI3K/AKT/mTOR dual inhibitor has been shown promising results in treating breast cancer cells. However, potential radiation-sensitizing effect of NVP-BEZ235 in TNBC remained unclear. In addition, SIRT-1 activation state and environmental cytokine were identified as being responsible for cancer cells responses to CRT. Herein, we investigate the role of interleukin 6 (IL-6) as a tumor environmental cytokine and SIRT1 in the effectiveness of NVP-BEZ235 plus radiotherapy. MATERIAL AND METHODS: TNBC cells were pre-treated with/without IL-6 and were exposed to single and combination of SRT1720 (SIRT1 activator)/EX-527 (SIRT1 inhibitor) and/or NVP-BEZ235 and/or gamma radiation. The effect of our treatments on cellular growth was determined by MTT and the cellular death and CSCs percentage were determined by Flow cytometry. Senescence detection kit was used to assay the effect of our treatments on cellular senescence induction. RESULTS: Activation of SIRT1 via SRT1720 increased the efficacy of CRT in TNBC cells, especially when IL-6 exists in tumor microenvironment. Additionally, IL-6 pre-treatment followed by exposure to SRT1720 and NVP-BEZ235 significantly increased sensitivity of the cancer stem cells to radiation (p < 0.05). CONCLUSION: Our result shows that combination of NVP-BEZ235 and SRT1720 may effectively improve late stage breast cancer cells therapeutics approach. Activation of SIRT1 and STAT3 in resistance breast cancer cells improves the in-vitro therapeutic efficacy of CRT.

Radioprotective effects of Silymarin on the sperm parameters of NMRI mice irradiated with γ-rays.

Free radicals and reactive oxygen species (ROS) are generated using various endogenous systems or from external sources such as exposure to different physiochemicals. Ionizing radiation damage to the cell can be caused by the direct or indirect effects of radiotherapy processes. Silymarin (SM), a flavanolignan compound, has been identified as a natural potent antioxidant with cytoprotection activities due to scavenging free radicals. The aim of the present study was to evaluate the radioprotective effect of SM on sperm parameters of mice induced by γ-rays. A total number of 40 adult, male NMRI mice were randomly divided into four equal groups. The control group was neither treated with SM nor irradiated by γ-rays. The second group was only irradiated with 2Gy of γ-rays. The third group was firstly treated with 50mg/kg of SM for 7 consecutive days, and one day later, last injections were irradiated by 2Gy of γ-rays. The fourth groups received only 50mg/kg of SM for 7 consecutive days. All the animals were treated intraperitoneally. Histopathological and morphometrical examinations were performed. The data were analyzed using ANOVA and Tukey post hoc test. A value of p<0.05 was considered significant. The results showed that in the radiation-only group when compared with those treated with SM and irradiated, a significant different was observed in testicular parameters and DNA damage (p<0.05). In conclusion, SM can be considered as a promising herbal radioprotective agent in complementary medicine which may play an important role to protect normal spermatocytes against possible effects of γ-radiation-induced cellular damage.

Effects of gamma rays on rat testis tissue according to the morphological parameters and immunohistochemistry: radioprotective role of silymarin.

OBJECTIVE: To determine the radioprotective effects of Silymarin in adult male Sprague-Dawley rats irradiated with γ-rays. METHODS: The present experimental study was performed in Tehran University of Medical Sciences, Tehran, Iran from December 2009 to March 2010. The study was performed on 40 rats, which were randomly and equally divided into four groups: 1) control group: neither received Silymarin nor irradiated with γ-rays; 2) γ-irradiation group: testis region exposed to 2Gy of γ-rays; 3) Silymarin & γ-irradiation: rats received 100 mg/kg of Silymarin 24hrs before exposure to 2Gy of γ-rays; 4) Silymarin & γ-irradiation: rats received 200 mg/kg of Silymarin 24hrs before exposure to 2Gy of γ-rays. After animal experiments and preparing the tissue sections, different histological and histomorphological parameters of seminiferous tubules and the biological characteristics of Leydig cells were evaluated applying quantitative assessment, Johnson scoring, and Leydig cell apoptosis assay by TUNEL method. The data were analyzed applying ANOVA and Tukey's post hoc test, using SPSS software (V.19). RESULTS: Irradiation of 2 Gy γ-rays to the testis of the rats significantly affected the frequency of spermatogonia, primary spermatocyte, round spermatid, spermatozoa, seminiferous tube and lumen diameters, thickness of the epithelium, Leydig cell nuclear diameter and volume, epithelium height, and apoptotic cells (p<0.05). However, administration of Silymarin improved the mentioned parameters specifically in 200 mg/kg of dosage. CONCLUSION: Silymarin could act as a potent radioprotector and it can be used in modulation as well as improvement to radiation therapy to prevent male reproductive function, specifically seminiferous tubules in an animal model; however, its molecular mechanism is still not clear and needs more molecular researches.

Color doppler indices of proximal and distal parts of middle cerebral artery in fetuses with intrauterine growth restriction.

INTRODUCTION: Intrauterine growth restriction (IUGR) is a major clinical issue for pregnant women. The purpose of this study was to evaluate color Doppler indices of the proximal and distal parts of the middle cerebral artery (MCA) of the fetus. METHODS: In this cross-sectional study, 350 pregnant patients, with gestation age of 32-40 who were suspected to have intrauterine growth restriction, participated. The patients were referred for color Doppler sonography at the Imam Reza Hospital (Kermanshah, Iran) from May 2011 to September 2012. The following indices were measured for the proximal and distal part of the MCA: pulsatility index (PI), resistive index (RI), fetal heart rate (FHR), systolic to diastolic (S/D) ratio, and peak systolic velocity (PSV). The data were analyzed applying Tukey's-test, Paired-Samples t-test, and simple linear regression analysis using SPSS 19. RESULTS: Average age of the mother, the frequency of pregnancy, and fetus gestational age were 27.79±0.17 years, 2.09±1.3, and 34.19±2.52 weeks, respectively. For gestation age of <36weeks, all Doppler indices of the distal part of the fetus MCA were significantly different from those of proximal part (p<0.05). Comparing indices of gestation age <36 weeks with those of >36 weeks, significant difference was found between the Doppler indices of the proximal parts as well as for the distal parts (p<0.05). CONCLUSION: Measurement of fetus MCA indices may depend to the sampling location; however, this needs further investigation in order to find a clear probe location.

Efficacy of Multidetector-Row Computed Tomography as a Practical Tool in Comparison to Invasive Procedures for Visualization of the Biliary Obstruction.

INTRODUCTION: Recently, multidetector computed tomography (MDCT) has been introduced into clinical practice. MDCT has become the noninvasive diagnostic test of choice for detailed evaluation of biliary obstruction. AIM: the main objective of the present study was to evaluate the diagnostic value of MDCT compared to invasive procedures for detecting biliary obstruction causes. MATERIAL AND METHODS: Since February 2009 until May 2011 fifty biliary obstruction patients based on clinical, laboratory or ultrasonographic findings, were evaluated by Multidetector-row computed tomography. The causes of biliary obstruction, which was identified using. MDCT were classified into three categories: calculus, benign stricture, and malignancy. Final diagnosis was conducted based on percutaneous transhepatic cholangiography (PTC), endoscopic retrograde cholangiopancreatography, biopsy, or surgery. The MDCT diagnosis and were compared with the final diagnosis. RESULTS: A correct diagnosis of causes of biliaryobstruction was made on the basis of MDCT findings for 44 of the total 50 patients. Two patients with chronic pancreatitis were incorrectly diagnosed with a pancreatic head adenocarcinoma on the basis of MDCT findings. One patient with biliary stone was incorrectly diagnosed with a periampullary adenocarcinoma on the basis of MDCT findings. The Sensitivity, specificity and accuracy of MDCT in the diagnosis of causes of biliary obstruction were 94.12% and87.87% and94.6% respectively. CONCLUSION: Based on the findings of this study MDCT has an excellent image quality, providing valuable information about the biliary tree and other abdominal organs. The use of advanced image processing, including maximum intensity projection and multiplanar reconstruction (especially coronal or sagittal reformatted images), allows superior visualization of the biliary tree and vascular structures. Three-dimensional reconstruction images complement axial images by providing a more anatomically meaningful display of the lesion and its relationship to adjacent structures, and accurate determining the craniocaudal extent of the lesion. High accuracy, wide availability and ease of use, make the MDCT the imaging modality of choice for evaluation of biliary obstruction.

Intra-patient comparison between two annular phased array applicators, Sigma-60 and Sigma-Eye: Applied RF powers and intraluminally measured temperatures.

PURPOSE: To investigate whether one can replace the Sigma-60 with the Sigma-Eye applicator (or vice versa) during a deep hyperthermia treatment series without a loss in quality of the treatment. PATIENTS AND METHODS: Hyperthermia data of all 48 patients with locally advanced cervical cancer who were treated with both applicators were analysed. In this study no use was made of the longitudinal SAR steering option of the Sigma-Eye. Hence, the Sigma-Eye was used as a Sigma-60 with a modified shape and water bolus. Power and intraluminal temperature were analysed. Sub-group analyses were performed for six groups, categorised according to the reasons for switching between the applicators. RESULTS: The 'all patient' analysis showed a significant difference for radio frequency (RF) power indices as applied to the two applicators, but for temperatures no difference between applicators was found. Sub-group analyses showed a consistent difference for RF power indices, i.e. the RF power for the Sigma-Eye was 8-29% higher than that for Sigma-60. In contrast, in about 90% of patients the number of switch-offs was 8-62% lower when the Sigma-Eye was applied. Similarly, in 73% of patients total switch-off time was 18-150% lower for the Sigma-Eye than for the Sigma-60. For the largest sub-group (n = 23), patients treated with the Sigma-Eye all had temperature indices slightly lower (ΔT = 0.2-0.5°C) than those for the Sigma-60 (p < 0.028). For the other five sub-groups no relevant difference was found between temperatures obtained by the two applicators. CONCLUSION: In the case of severe patient discomfort with the Sigma-60 or Sigma-Eye applicator, or if achieved temperatures are not satisfactory, one can freely switch between both applicators without loss of hyperthermia treatment quality.

Hyperthermia dose-effect relationship in 420 patients with cervical cancer treated with combined radiotherapy and hyperthermia.

Adding hyperthermia to standard radiotherapy (RT+HT) improves treatment outcome for patients with locally advanced cervical cancer (LACC). We investigated the effect of hyperthermia dose on treatment outcome for patients with LACC treated with RT+HT. We collected treatment and outcome data of 420 patients with LACC treated with hyperthermia at our institute from 1990 to 2005. Univariate and multivariate analyses were performed on response rate, local control, disease-specific survival and toxicity for these patients to search for a thermal dose response relationship. Besides commonly identified prognostic factors in LACC like tumour stage, performance status, radiotherapy dose and tumour size, thermal parameters involving both temperature and duration of heating emerged as significant predictors of the various end-points. The more commonly used CEM43T90 (cumulative equivalent minutes of T90 above 43 degrees C) was less influential than TRISE (based on the average T50 increase and the duration of heating, normalised to the scheduled duration of treatment). CEM43T90 and TRISE measured intraluminally correlate significantly and independently with tumour control and survival. These findings stimulate further technological development and improvement of deep hyperthermia, as they strongly suggest that it might be worthwhile to increase the thermal dose for LACC, either by treatment optimisation or by prolonging the treatment time. These results also confirm the beneficial effects from hyperthermia as demonstrated in our earlier randomised trial, and justify applying radiotherapy and hyperthermia as treatment of choice for patients with advanced cervical cancer.

Quality of Life in Cancer Patients undergoing Chemotherapy.

OBJECTIVES: The objective of this study is to describe the quality of life (QoL) in cancer patients with solid tumors and at different chemotherapy (CT) cycles. METHODS: A total of 200 cancer patients were included. With some modification, the European Organization for Research and Treatment of Cancer QoL Questionnaire (EORTC QLQ-C30) was used to measure QoL in the student patients. RESULTS: There was no correlation between the QoL and variables such as age, sex, marital status, duration of disease, economic conditions, and occupational function. Furthermore, no correlation was found between QoL and the patients' educational level (literate or illiterate). Nevertheless, a significant difference was found between the level of QoL in patients with ≤ 2 CT cycles and/or with 3-5 cycles (p< 0.001). CONCLUSION: This study suggests that encouraging cancer patients to complete a CT course plays an important role in the treatment outcome and the QoL in cancer patients undergoing CT.

SAR characteristics of the Sigma-60-Ellipse applicator.

PURPOSE: To characterize the basic performance of the Sigma-60-Ellipse applicator. MATERIALS AND METHODS: The E-field distributions were measured using Schottky diode sheets in a cylindrical phantom (diameter 26 cm, length 50 cm), filled with saline-water (2 g NaCl/L). The phantom was positioned symmetrically in the Sigma-60-Ellipse applicator. The stability of the SAR distribution was assessed as a function of power and frequency. Furthermore, the accuracy of target steering was evaluated at various frequencies. Finally, the SAR characteristics were compared with those of the Sigma-60 and the Sigma-Eye applicators. The average 50% iso-SAR area increased from 241 to 296 cm(2) when the RF power increased from 100 to 1600 W. The SAR maximum was located in the centre of the applicator for the frequencies of 75-80 MHz and it moves towards the feet for higher frequencies (up to 3.5 cm at 120 MHz). The average 50% iso-SAR area decreased from 268 to 161 cm(2) with increasing frequency from 75 to 120 MHz. The 50% iso-SAR longitudinal length was almost stable (mean 21.3 cm) at 75-120 MHz for both power outputs of 400 and 800 W. As expected the 50% iso-SAR radial length decreased with frequency from 14.9 cm at 75 MHz to 8.4 cm at 120 MHz. There was a fair agreement between requested and measured target settings. At the lower frequencies of 75-90 MHz and at 100 MHz the SAR characteristics were almost identical to those of the Sigma-60 and Sigma-Eye applicators, respectively. CONCLUSION: At the frequency range of 75-90 MHz the Sigma-60 and at 100 MHz the Sigma-Eye can safely replaced by the Sigma-60-Ellipse applicator.

RF-power and temperature data analysis of 444 patients with primary cervical cancer: deep hyperthermia using the Sigma-60 applicator is reproducible.

Treatment reproducibility is important to guarantee reproducible treatment-outcome, a low-complication rate and efficient treatment procedures. This study evaluated the performance of loco-regional deep hyperthermia with four BSD-2000 configurations during 1990-2005 using the direct available parameters, i.e., temperature and power. Primary cervical cancer patients (n = 444) were all treated within the Sigma-60. Patients were grouped in three weight-groups: <61 kg, 61-70 kg, >70 kg. Different temperature and power indices were extensively analyzed per BSD configuration, per weight-group, and over the time-period. No substantial variations were found for temperature/power indices over the four BSD configurations or for the temperature doses in similar weight-groups. The 'bare' power indices were increased with weight; however, the derivative power-related (W/kg, W/cm(2)) and temperature indices decreased. Large variations were found in the power-related parameters during 1991-1996 (1st time-period), whereas they were much smaller during 1997-2005 (2nd time-period). The most relevant change noted was the adaptation of the treatment strategy with respect to power modulation. The average frequency of switched-off was 3.4 and 8.9 times/treatment session for the 1st and 2nd time-period, respectively, while the average duration of each switched-off time was 78.2 vs. 38.3 s. The yearly average of vagina T(50) was in the range of 39.3-40.2 degrees C (1st time-period) and 40.0-40.5 degrees C (2nd time-period). In 40% of the patients, a positive correlation was found between normalized net integrated power per pelvic area and vagina T(50). Good reproducible heating is achieved with the BSD-2000 Sigma-60 irrespective of the regular technological upgrades of the system and variation of trained staff-members.

Comparison of intratumor and intraluminal temperatures during locoregional deep hyperthermia of pelvic tumors.

PURPOSE: To investigate whether intraluminal thermometry provides sufficient information to apply high quality deep hyperthermia in pelvic tumors. PATIENTS AND METHODS: The intratumor and intraluminal temperatures of 48 patients were analyzed per cancer type: rectum (21 male, 14 female), cervix (n=8), and bladder (n=5). Temperature-dose parameters were calculated, temperature curves within each treatment session were compared, and correlation between intratumor and intraluminal temperatures was analyzed. RESULTS: Intratumor and intraluminal temperatures at the same time points during individual treatments were highly correlated (mean correlation coefficient: 0.93). However, the quantitative level differed from 0.1 to 1.1 degrees C and the differences of the time-temperature graphs varied per tumor group. Average intratumor and intraluminal temperatures were not different in the four groups. Intratumor thermometry was found not superior over intraluminal thermometry to improve tumor temperature level and homogeneity by SAR steering. CONCLUSION: Intraluminal thermometry provides sufficient information to apply deep hyperthermia to individual patients with centrally located rectum, cervix or bladder cancer.

Weekly systemic cisplatin plus locoregional hyperthermia: an effective treatment for patients with recurrent cervical carcinoma in a previously irradiated area.

PURPOSE: Patients with recurrent cervical carcinoma within a previously irradiated area respond poorly to chemotherapy. We have treated these patients with simultaneous cisplatin and hyperthermia (CDDP + HT) and investigated response, toxicity, palliative effect and survival. MATERIALS AND METHODS: Between 1992 and 2005 47 patients received CDDP + HT. Response was evaluated by gynaecologic examination and CT-scan. The Common Toxicity Criteria (CTC) were used for evaluation of toxicity and palliative effect. The Kaplan-Meier method was used to estimate survival, and Cox regression analysis to evaluate the influence of prognostic factors. RESULTS: The objective response rate was 55%, palliation was achieved in 74% and operability in 19% of patients. Two patients are currently disease free at 9 years and 18 + months following treatment and 2 remained disease free until death by other causes. The median survival was 8 months and was influenced by duration of disease free interval and tumour diameter. Grade 3-4 haematological toxicity was observed in 36% of patients and renal toxicity was maximum grade 2. CONCLUSION: CDDP + HT results in a high response rate and acceptable toxicity in patients with recurrent cervical cancer.

RHyThM, a tool for analysis of PDOS formatted hyperthermia treatment data generated by the BSD2000/3D system.

One of the systems used by hyperthermia (HT) groups for heating tumours in the pelvic region is the BSD2000 system. Previous versions of the BSD2000 operate on a PDOS machine and the majority of the currently installed BSD2000/3D systems are still running under PDOS. Availability of the PDOS formatted treatment data provided by the BSD2000/3D has some difficulties. To facilitate analysis of the PDOS formatted treatment data generated by the BSD2000/3D a programme, called RHyThM (Rotterdam Hyperthermia Thermal Modulator) has been created. The purpose of RHyThM is first to read and check the integrity and validity of the treatment data for each measurement in time and space as provided by the BSD2000/3D and secondly to register a tissue type, based on computer tomography information, for each temperature probe position. Prior to any analyses, RHyThM shows the temperature profiles enabling the user to check on probe movement and to correct for unrealistically high temperature gradients in time and space. Subsequently, this approved data set is saved in a 'mother-file' for future on-demand thermal dose analyses. A unique feature of RHyThM is that it also shows all radiofrequency (RF) power signals for inspection. Finally, to make a quick assessment of the quality of the applied HT-treatment, RHyThM reports several temperature indices for bladder, vagina and rectum as well as RF-power related quantities. In summary, RHyThM is considered a valuable tool as it quickly provides a quality index per treatment, which serves as input for the preparation of the next treatment. Further, it makes verified and improved primary data sets accessible for further analysis with advanced statistical programmes.