Journal of Arak University of Medical Sciences

Cancer and Radiotherapy

Mohamad Reza Bayatiani

Abnormal and uncontrolled growth of the cells can lead to cancer. In advanced countries, cancer is the second leading cause of death, and in our country, it is the third cause of death (after cardiovascular diseases and driving accidents). According to a report published by the Institute of Health and Evaluation (2015), for evaluating 32 cancers in 195 countries between 2005 and 2015, the prevalence of cancer has increased by 33% (1).
Radiotherapy is one of the most common cancer treatments that can be used alone or in combination with other therapies such as surgery, chemotherapy or hormone therapy. Approximately 52% of patients with cancer have to be treated by Radiotherapy with a 50% contribution to treatment (2). Radiation therapy uses gamma rays or x-rays or accelerated particles to destroy tumor cells (3). In the past, radiotherapy was done in a two-dimensional fashion, using rectangular fields based on conventional imaging that has now been replaced with 3D conformal radiotherapy. In Three‐dimensional treatment, based on CT or other imaging methods, the treatment volumes such as: GTV (Gross Tumor Volume), target with microscopic spread of tumor that is CTV (Clinical Tumor Volume), ITV (Internal Target Volume), PTV (Planning Target Volume) and also related organs at risk are defined with high accuracy for treatment planning (4). In recent years, with the advancement of computer sciences in treatment planning systems, as well as accelerator equipment for delivering the dose to the patient, treatment can be applied as Intensity Modulated Radiation Therapy (IMRT). In IMRT, each radiation field consists of a beamlets and produces different intensities. This treatment is especially useful for curved areas and when the organs at risk are in the vicinity of the tumor. IMRT can be delivered using linear accelerators with static or Dynamic MLCs, Intensity Modulated Arc Therapy (IMAT), Volumetric Arc Modulated Therapy (VMAT) or tomotherapy (5).
In determination of treatment volumes, the selection of appropriate margin is very important, because small margin may cause loos of the tumor and great margin can damage healthy tissues. The use of IGRT (Image Guide Radiotherapy) reduces these errors and increases the accuracy of treatment. Todays, in developed countries, SRT (Stereotactic Radiation Therapy) is used to destroy the non-surgical tumors, such as some of the brain tumors. In SRS, the prescribed dose is delivered to the tumor up to five sessions. In this method using imobilization devices is important, which usually involve the use of the relevant frames (6). In this regard, Cyber knife is actually a stereotactic system in which the x-ray source is mounted on a robot and can rotates in different angles. This treatment is based on three-dimentional imaging, so the tumor can be identified precisely with the guide of imaging. Cybernayev can be used to treat small tumors with high precision (7).
In addition to treatment with X-rays, ions such as proton can be used to kill cancer cells. One of the important features of treatment with proton is the deliver of the absorbed dose of the particles into the tissue. The absorbed dose curve of this beam in the tissue has a peak at a specified depth, depends on the energy used, called the Bragg peak which can give the highest dose of radiation in the tumor site (8).
There have been many advances in radiotherapy in Iran in recent years, but there is still lack of some advanced treatment equipment. On the other hand, with the regard of the significant cancer rate in the country, it is necessary to have proper information about the incidence of cancer at first. It should be noted that the use of registration systems based on just laboratory information (pathology) leads to a low number of cancer statistic, which this way is recorded in Iran. However, the cancer registry system in developed countries is based on clinical information and mortality in addition to collecting laboratory information.
Another factor causing errors in the cancer record statistics is the population coverage of cancer registries; for example, population coverage in the United States is 99%, Australia and New Zealand is 86%, and the European ::union:: is 57%, while coverage in South and central America is only 21% and in the African and Asian countries is 11 % and 8 %., respectively (1). Therefore, at first, it seems necessary to register the cancer properly in our country and then, based on the needs assessment for the different regions, establish and equipe radiotherapy centers.

Evaluation the Efficacy of Sodium Valproate and Low Frequency Stimulation During CA1 Hippocampal Kindling on Anxiety-Like Behavior in Adult Male Rat

Ahmad Ali Moazedi

Background and Aim: Emotional disorders are prevalent in many epileptic patients. So, in this research, we have studied the efficacy of two treatment methods of seizure on anxiety-like behavior during kindling in adult male rat.
Materials and Methods: 42 male rats were randomly divided into 6 groups: Control, Sham operation, saline-kindled and drug-kindled groups which have received saline or drug 15 minutes before kindling stimulations, and saline-kindled-LFS or drug-kindled-LFS group which have received saline or drug 15 minutes before kindling stimulations and LFS applied after termination of kindling stimulations. Anxiety-like behavior was assessed on the 6th day by using elevated plus maze and open field apparatus.
Findings: kindling significantly increased open arms (OAs) entries percentage, OAs exploration percentage, increasing jumping from elevated plus maze (p<0.001) and rearing frequency in open field apparatus (p<0.05) compared to the sham group. Sodium valproate increased OAs entries percentage and OAs exploration percentage in drug-kindled group compared to sham group (p<0.001). But, there wasn’t any significant difference in jumping from elevated plus maze and rearing in open field compared to sham group. Also, there was no significant change in these parameters in Saline-kindled-LFS, drug-kindled and drug–kindled-LFS groups.
Conclusion: Sodium valproate and LFS, as two therapies controlling epilepsy, decrease anxiety induced by kindling stimulation.

Evaluation Risk Factors of Coronary Artery Disease Through Competing Risk Tree

Ebrahim Hagizadeh

Background and Aim: Advances in the field of medicine over the past few decades enabled the identification of risk factors that may contribute toward the development of coronary artery disease (CHD). However, this knowledge has not yet helped in the significant reduction of CHD incidence. The purpose of this study is to assess the risk factors of coronary artery heart events, after receiving stent, by competing risks with composite events tree. We can reduce CHD incidence with control of this risk factors.
Materials and Methods: This sectional study includes the Coronary Artery Disease (CAD) patients that received Percutaneous Coronary Intervention (PCI) cure with at least planting one stent from May 21, 2007 to May 22, 2009 in Tehran heart center. We followed patients for three years. Revascularization, nonfatal myocardial infarction, and cardiac death are considered as major acute cardiovascular events (outcome). We used decision tree with competing risks with composite events model for classification of patients. The data were analyzed by IBM SPSS Statistics 24 and R 3.3.3 softwares.
Findings: Four factors including fasting blood sugar, diabetes mellitus, body mass index and age established six homogeneous subgroups of patients for nonfatal myocardial infarction and revascularization. Maximum Revascularization incidence after 50 months was 17.8% and Maximum Nonfatal myocardial infarction was 9.7%.
Conclusion: CAD patients can reduce serious cardiac events by controling their weight and diabetes status, after receiving stent.

Evaluation of Promoter Methylation Pattern of the Vascular Endothelial Growth Factor (VEGF) Gene in Metabolic Syndrome Patients of East Azerbaijan Province

Saeid Ghorbian

Background and Aim: Metabolic syndrome (MS) was committed multiple disorders including diabetes, hypertension, and obesity, which were played influential effects on the mortality rates of patients suffering from of cardiovascular disorders. Vascular endothelial growth factor (VEGF) is a protein that stimulates vascular and angiogenesis. One of the most common epigenetic changes is methylation of the promoter regions of genes, which leads to the regulation of gene expression. We aimed to assess the methylation pattern of promoter regions of VEGF gene which may act a critical role in the pathogenesis of MS.
Materials and Methods: In this descriptive-analytical investigation, we have assessed a total of 100 subjects, which were included 50 of cases diagnosed as MS and 50 healthy individuals as a control group. Methyl specific polymerase chain reaction (MS–PCR) method was performed to analyzing of VEGF gene promoter methylatin patterns and data analysis was performed using Chi Square test and SPSS 23 software.
Findings: The frequencies of VEGF gene promoter methylation observed in 32% and 20% of case and control individuals, respectively. Our findings revealed that the frequencies of the gene methylated were not statistically different between two groups (p=0.239). In other hand, our findings revealed a statistically significant difference regarding to the clinical parametrics including, triglycired (p=0.050), cholesterol (p=0.046), suger blood (p=0.025) and HbA1C (p=0.016) between cases and control groups (p=0.05).
Conclusion: According to our findings, methylation alteration in VEGF gene did not show any critical role in the pathogenesis of MS and it is suggested that more evidence will be needed to approve the present results.

The Effect of Atorvastatin on Inflammatory Markers in Patients with Type Two Diabetes

afsaneh talaei

Background and Aim: Regarding to paradoxical results of the studies about the effects of atorvastatin on inflammatory markers and metabolism, we aimed to evaluate the effects of atorvastatin on inflammatory markers in diabetic patients.
Materials and Methods: Through a double blind randomized clinical trial, placebo control, 88 type two diabetic patients (T2DP), were treated with anti-diabetes oral agents, were randomly classified into two 44 cases groups. The intervention group took atorvastatin 40 mg daily and control group took placebo for three months and adiponectin, hsCRP, leptin, TNF-α, lipid profile and fasting blood glucose (FBS) were measured and compared at the beginning and the end of the study. The data were analyzed using student t test and paired t test.
Findings: After three months, adiponectin was significantly increased in intervention group in comparison to control group, but leptin had not a significant change in two groups. Total cholesterol, hsCRP and LDL cholesterol (Low density Lipoprotein) were decreased significantly in the intervention group than control group, while FBS was
non-significantly decreased.
Conclusion: It seems atorvastatin is effective to decrease inflammatopry markers in diabetic patients.

Evaluation of Anticancer Effect of Aqueous and Hydroalcoholic Extracts of Quercusin Fectoria Leaf against Colon Cancer HT29 Cell Line

Fahimeh Baghbani-Arani

Background and Aim: In traditional medicine and previous studies, Quercus infectoria plants have been suggested as a cancer treatment. The aim of the current study was to investigate the cytotoxic effect of aqueous and hydro alcoholic extracts of Quercus infectoria leaf against colon cancer HT29 cell line and to evaluate the Bax and Bcl-2 gene expression in treated cells.
Materials and Methods: In this study, aqueoFus and hydro alcoholic extracts of Quercus infectoria leaf were prepared. Then, the HT29 and HEK293 cell lines were treated by various concentrations of extracts for 24 hours and the cytotoxicity effect of extracts was estimated by colorimetric MTT (methyl thiazolyl tetrazolium) assay. Finally, the pro-apoptotic Bax and anti-apoptotic Bcl-2 gene expression in treated cells compared to GAPDH reference gene expression was evaluated using real time PCR technique.
Findings: According to the MTT results, the cytotoxic activity of aqueous extract has dose-dependent manner against both cell lines, therefore, the Bax and Bcl-2 gene expression levels in treated cells by aqueous extract were changed 2.8 (p˂0.05) and 2.2-fold (p˃0.05) compared to reference gene, respectively.
Conclusion: According to the results, it seems that the aqueous extract of Quercus infectoria leaf has the potential for apoptosis induction in colon cancer HT29 cell line and based on more studies, it can be used as a colon cancer treatment.

Effect of Niacin on Side Effects of Bleomycin in Patients under Chemotherapy in Khansari Hospital of Arak

Iraj Javadi

Background and Aim: The history of using bleomycin in a hospital indicates a series of vast reactions in biological systems caused by direct and indirect effects. The biological responses of the biological system make this process more complicated. Increasing the prevalence and the incidence of cancerous diseases that are treated with bleomycin is of paramount importance. The aim of this study was to evaluate the effect of niacin on reducing the complications of bleomycin consumption in human model.
Materials and Methods: This experimental study was done as case-control and double-blind clinical trial. Of the cancer patients referred to Khansari hospital in Arak that underwent the bleomycin monotherapy, 20 subjects were randomly selected and divided into two groups. Each person in the first group (control) received 2 placebos per day (every 12 hours) and the second group (treatment) were given two pills of niacin (each pill: 100 mg) daily, and the results were recorded and analyzed.
Findings: A comparison between treatment and control groups showed a reduction in nausea and vomiting in the treatment group compared to the control group. The sense of taste disorder complication was reduced in the treatment group compared with the control group and this difference was statistically significant (p <0.05).
Conclusion: The results suggest that niacin can decrease the side effects of cancer treatment from different directions, including side effects, nausea, vomiting, loss of sense of taste, but its impact on respiratory problems probably because of the damage caused by bleomycin was not significant.

Effects of Stress Related Acute Exercise on Reconsolidation of Implicit Motor Memory in Women

Asma Mahmoodi

Background and Aim: Stress is a powerful modulator of memory performance. Emotional arousal affects the various aspects of learning and memory through stimulation of the amygdala or the hippocampus. The aim of the present study was to investigate the effects of stress related acute exercise on reconsolidation of dart throwing task learned with errorless method.
Materials and Methods: Participants of the study included 60 girls with an average age of 20.5 who were randomly assigned to three groups including: target (n = 20), control (n=20), and control 2 (n = 20). On the first day, all three groups under the same conditions acquired the skill of throwing darts in an errorless method and immediately after that performed the immediate retrieval. On the second day, after memory reactivation, the target group was exposed to stress resulting of acute exercise while the control 1 group did rest. The acute stress was presented to control 2 group without memory reactivation. During the experiment, changes in salivary cortisol were measured. On the third day, the delayed memory retrieval for each of the three groups was implemented.
Findings: the results showed that while the control 1 and control 2 groups did not show enhancement of dart throwing learning across delayed memory retrieval than immediate retrieval, the target group showed substantial enhancement across the same time (p<0.05).
Conclusion: Our findings indicate that acute stress after memory reactivation can facilitate the implicit motor memory reconsolidation in women.

Comparison of Detection of Clinical Isolates of Mycobacterium Tuberculosis by Flash PCR and Conventional Culture Method

Mohammad Arjomandzadegan

Background and Aim: Ziehl Nelson staining, fluorescent and also culture are the standard methods for the diagnosis of tuberculosis. In this study, the performance of conventional cultivation methods was compared with Flash PCR.
Materials and Methods: A total of 56 sputum samples from patients with suspected tuberculosis in Tuberculosis Center of Arak city were collected and Ziehl–Neelsen and culture in Löwenstein–Jensen medium were accomplished. Moreover, DNA from all of the 56 sputum samples was extracted by Chelex100 method. Molecular evaluation was accomplished by Flash PCR kit containing probes and primers for gene amplification IS6110. Positive and negative controls together with samples were used in a MTC410 apparatus for amplification. FD-12 apparatus was used to evaluate the results. In addition, electrophoresis on agarose was used for confirmation of the results.
Findings: From 56 sputum samples of suspected TB patients, 20 samples were positive and 36 samples were negative on microscopic evaluation and culture methods. FLASH-PCR molecular analysis showed that all of 20 positive samples were positive in molecular methods, too. On the other hand, three of sputum samples that were negative by culture and staining were positive in FLASH-PCR method. One of these 3 patients, received Isoniazid, pyrazinamide and ethambutol antibiotic by responsible medicine. All results were confirmed using conventional electrophoresis.
Conclusion: In some negative samples, possibly because of the small number of bacteria in sample or a defect in the sampling, the Flash PCR may due good advantages. Therefore, due to the low cost, this method is recommended for routine use.

The Effect of Increasing Resistance Training on Testicular Oxidative Stress and Quality of Spermatogenesis in Male Rats

Amin Mombeyni

Background and Aim: Following physical activity in various tissues of the body, oxidative stress occurs and affects the antioxidant capacity and consequently the fertility of men negatively. The aim of this study was to investigate the effects of resistance training on oxidative stress and spermatogenesis quality.
Materials and Methods: 20 male rats of Sprague Dawley (weight 200-250, 4 months old) were randomly divided into two groups of resistance training and control group (n = 10). The exercise program included climbing a ladder by hanging the load to the tail for 8 weeks (5 days a week, 3 times 4 repetitions). During the program, the load gradually was increased, and in the last week, it reached to 200% of the animal body weight. After intervention, the mice were anesthetized in separate groups and testicular tissue was isolated to evaluate Malondialdehyde index as an oxidative stress marker and to determine antioxidant capacity by Frap method. Fixation, processing, cutting of testicular tissue and eventually coloring steps were examined by Hematoxylin and Eosin (H & E). The spermatogenesisqualitywas calculated based on Johnson method. The data were analyzed by independent t-test was used and significance level was considered p <0.05.
Findings: Increased Malondialdehyde levels were observed in the treatment group compared to control group (p =0.01). In the training group, the spermatogenesis quality was lower (p =0.013), the antioxidant capacity in the training group was significantly higher than the control group (p‏=0.83) and there isn’t any significant difference.
Conclusion: The findings indicate thatdue to increased oxidative stress, increasing resistance training may have negative effects on the quality of spermatogenesis and men's fertility.

The Effect of Exercise with Different Intensity on Glucose Transporter 4 (GLUT4) Gene Expression in Skeletal Muscle of Obese Male Rats

Mostafa Rahimi

Background and Aim: The aim of study was to investigate the effect of 8 weeks of moderate-intensity continuous training (MICT) and high intensity interval training (HIIT) on the GLUT4 gene expression in skeletal muscle of obese male rats.
Materials and Methods: Twenty-eight male Wistar rats with 150 ± 25 grams body weight were divided into base control (n = 6), obese control (n = 6), MICT (n = 8), and (n = 8) HIIT groups as study sample. At the beginning of the study, base control group rats were sacrificed. In other groups, rats underwent high fat regime diet for 8 weeks. After one week of familiarization, rats in training groups run on treadmill for 8 weeks and 5 days per week. Forty-eight hours after the last session, the rats were scarified and gastrocnemius muscle tissue sample were removed. GLUT4 gene expression was measured by Real-Time PCR methods.
Findings: Results indicated that high fat diet for 8 weeks significantly increased rats body weight (p= 0.001), whereas both of MICT and HIIT training significantly decreased body weight (p= 0.001). Moreover, the MICT and HIIT had significant increase in GLUT4 gene expression in gastrocnemius muscle of obese rats (p = 0.001). Although, there were no differences between two experimental groups (p = 0.99).
Conclusion: According to the results, the MICT and HIIT increase gene expression of GLUT4 in mixed muscle fibers in obese rats.

The Evaluation of Antimicrobial Effect of Alpha-Cellulose Nanofibers Based on Wheat Bran with Ciprofloxacin Hydrochloride on Staphylococcus Aureus

Aboo Saeed Rashidi

Background and Aim: The purpose of this research is to provide nanofibers from cellulose with Wheat bran as an agricultural residue and its antimicrobial activity by dipping ciprofloxacin hydrochloride on Staphylococcus aureus.
Materials and Methods: In this experimental study, cellulose disks were prepared from nano-impregnated fiber. Subsequently, these disks were placed on Staphylococcus aureus with standard paper disks and the results were measured as a non-growth zone after 24 hours. The amount of ciprofloxacin hydrochloride adsorbed in cellulose by comparing the effect of cellulosic discs containing different concentrations of antibiotics and standard ciprofloxacin disks was determined. Subsequently, the evaluation of the time of recovery of the ulcer in the skin of the rats was carried out with the drug-mediated formulation and without drug.
Findings: The disk (nano alpha-cellulosic) dipped by ciprofloxacin hydrochloride created a non-growth zone in Staphylococcus aureus. Measuring the size of the wound was done by digital imaging and the ImageJ software. The results of the recovery process were analyzed by ANOVA and pathological tests in five days.
Conclusion: The results showed that the nano-fibers disk could be useful in controlling bacteria in the culture medium, and the area of the wounds in rats (rats) dressed with nano-fibers impregnated with the drug was significantly less than the control group (p <0.05).