Tehran University Medical Journal

Background: Breast cancer is a common malignancy in which early breast cancer detection by the help of imaging can improve the treatment outcome. Thermography utilizes infrared beams which are fast, non-invasive, and non-contact and the output created images by this technique are flexible and useful to monitor the temperature of the human body.
Case presentation: Our patient is a 25-year-old woman who was referred to Tehran's Imam Khomeini Hospital, Tehran University of Medical Sciences, in October 2014 and June 2017 to perform clinical examinations of breast cancer at the Invasive and New Radiology Research Center of Tehran. The results of the sonography for the left breast and bilateral axillary regions and sonography guided biopsy from the left axillary region indicated that:  it was consistent with the tangential prominence at 11-12 O’ clock in the left breast tissue and echo gene was found without any suspected findings. Then, using the non-contact infrared imaging camera VisIR 640 (Thermoteknix Systems Ltd, Cambridge, UK), the feasibility of thermography method in the patient's follow-up was investigated.
Conclusion: Thermography can be used to detect abnormal areas in the breast tissue that may have cystic origin. The results indicated that the accuracy of the identification and matching of patient cysts in mammography and ultrasonography with the results of thermography in both periods of October 2014 and June 2017. Considering the results, it is noteworthy that the diagnostic clock of the breast cysts in the patient is consistent with the results of the clinical trials with the thermography. Moreover, in a 2 years intervals, the status of thermal morphology status of the cystic region did not considerably change which showed a relatively stable status.

Cancer immunotherapy refers to any intervention that leverages the immune system to eliminate a malignancy. Successful cancer immunotherapies generate an anti-cancer response that is systemic, specific, and durable and overcome to the primary limitations of traditional cancer treatment modalities. In this review paper, the effective methods in immune system to treat cancer, such as immunosuppression in tumor microenvironment (TME), cancer vaccines and T cell adaptive therapy are mentioned. Engineered T cells can use for destruction of the different cancer tissues to diagnose tumor surface antigens. Promotion in culture of T cell methods and their engineering with retroviral vectors that carry T cell receptors or chimeric antigen receptors (CAR) by co-stimulator domains, provide opportunity to treat tumor by T cells. The tumors with high genome mutation, such as lung and melanoma, have severe environmental mutagenesis that is induced by ultra violet light in melanoma and Tobacco in lung cancers. Expression of tumor specific receptors is increased by engineered T cells. The neo-antigens conduct the intensity of intra tumor T cell response. The present of CD8+ in tumor site with more mutation is higher and the mutation load is showed strong relation with the clinical response. In addition to the successful approaches to cancer immunotherapy, the other combination and molecular therapies by nanomaterials are listed. Nanomaterials as efficient modulators and diverse vaccine have been developed in the treatment of cancer. In recent cancer vaccine development has been on subunit vaccines that contain purified tumor antigens or antigenic epitopes as an antigen source. However, soluble bolus-based subunit vaccines typically induce weak cytotoxic T lymphocyte responses which limit their utility for cancer. To overcome this, nanoscale colloids can be used to promote more efficient antigen presentation by acting as phagocytic substrates. Nanomaterials are showed co-suppression and immunization in tumor microenvironment by multiple additive functions in preclinical models. In this manner, they exhibited good prospects because of the good results in overcoming the limitations of current therapies. In this review paper is tried to provide new prospect for therapies and hope it creates highest efficacy and lowest side effects for the treatment of patients in the near future.

Background: The average age of women with breast cancer in Iran is at least 10 years lower in comparison to developed countries and the incidence of the disease in Iranian women is on a rise. According to studies, diets that are diverse in food groups can play a role in protecting against chronic diseases including cardiovascular diseases and cancer. Diet diversity score is an indicator used to measure diversity between and within food groups. This study aimed to assess the relationship between diet diversity score and breast cancer risk.
Methods: This case-control study was carried out from April 2014 to February 2015 at Shohada Hospital in Tajrish, Tehran. Demographic and anthropometric data of 298 participants including 149 breast cancer cases and 149 apparently healthy women were collected. A valid food frequency questionnaire containing 168 food items was completed to assess usual dietary intake through face to face interviews. Energy was calculated using Nutritionist 4 software (First Databank Inc., Hearst Corp., San Bruno, CA, USA) and diet diversity score was calculated using five food group scoring. Odds ratios with 95% confidence intervals were obtained using logistic regression test to evaluate the association between breast cancer risk and diet diversity score tertiles.
Results: There was no significant difference in weight, height, body mass index between the two groups, but physical activity level and daily energy intake showed a significant difference (P<0.001). After adjusting for the effect of confounding variables including energy, body mass index, physical activity, menopause status, family history of breast cancer, contraceptive use, number of pregnancy, age of menarche and smoking, the risk for developing breast cancer was 86% lower in those in the highest tertile of diet diversity score compared to those in the first tertile (OR=0.14, 95% CI=0.06-0.31). An inverse and significant association was found between breast cancer risk and diversity scores of fruits and milk groups (P<0.001).
Conclusion: Higher diet diversity score is associated with reduced risk of breast cancer.

Background: Gastric cancer is among the most common malignancies in certain parts of the world, such as northwest Iran. miRNAs are small and single-stranded noncoding RNAs with about 19-23 nucleotides. Several studies have shown that miRNAs play important roles in gastric tumorigenesis. The aim of this study was to determine the effect of miRNA-1266-5p repression on the cell survival and alterations of the cell cycle in gastric cancer cell line of AGS (NCBI Code: C131, Gastric epithelial cell line).
Methods: This experimental study was performed from April to December 2017 in Cellular-Molecular Research Center of Ardabil University of Medical Sciences, Iran. In this study, AGS cells were cultured in RPMI-1640 medium containing 10% serum and 1% antibiotic. The cells were transfected with miR-1266-5p mimic, miR-1266-5p inhibitor and HiPerFect reagent alone as negative control. The miR-1266-5p expression and transfection efficiency were analyzed by Stem-loop TaqMan qRT-PCR. The cell proliferation and cell cycle alterations were determined using MTT calorimetric assay and flow cytometry, respectively. The results were analyzed using SPSS 19.0 statistics software (SPSS Inc., Chicago, IL, USA) and presented as the means±standard deviation (SD).
Results: miR-1266-5p expression was increased in AGS cells transfected with miR-1266-5p mimic compared to control cells (P=0), while miR-1266-5p expression was decreased in transfected cells with the inhibitor compared to controls (P=0). Among different time points, the most effects of miR-1266-5p mimic and inhibitor were noticed after 48 hours of transfection. The upregulated miR-1266-5p significantly decreased cell growth, in contrast, inhibitor promoted cell proliferation (P=0). In addition, miR-1266-5p upregulation induced cell cycle arrest at the transition of G1 to S phase and led to G0/G1 entry (P=0), while of miR-1266-5p led to G2/M entry (P=0.001).
Conclusion: According to the results obtained from this study, miR-1266-5p can reduce cell survival and induce cell cycle arrest and act as a tumor suppressor in AGS cells. While its inhibition can increase cell survival and reduce apoptosis.

Background: Intensity-modulated radiotherapy (IMRT) is one of the most usable methods in prostate radiotherapy that is used with different techniques. The aim of this study was to evaluate and compare the dosimetric and radiobiological effects of prostate IMRT techniques regarding to joint volume between the target tissue and organs at risk as a patients anatomical parameter.
Methods: This research was a cross-sectional, analytical, and quantitative study that was carried out from April 2016 to June 2018 at the radiotherapy and oncology center of Shoheday-e-Tajrish Hospital and Medical Physics Department of Tarbiat Modarres University Tehran, Iran. Four various prostate IMRT techniques (9, 7 and 5 fields and automatic) were planned on 63 prostate cancer patients CT scans. Radiobiological effects were calculated using Relative Seriality model for the organs at risk (bladder and rectum) and target tissue. Results of mentioned prostate IMRT techniques were compared based on the patient’s anatomical parameter. 
Results: For the patients with joint volumes ranged from 0 to 15%, statistical differences were not observed among various IMRT techniques. The tumor control probability and complication free tumor control probability values decreased as a function of joint volume. The normal tissue complication probability value increased as a function of joint volume. The 9 and 7 fields IMRT techniques had not any significant differences (P=0.06) in all of the joint volume ranges. In patients with the joint volumes higher than 30%, the 9 and 7 fields techniques showed significantly better radiobiological values in comparison with 5 fields and automatic techniques (P=0.009).
Conclusion: In the patients with lower percentage of joint volume, all the mentioned prostate IMRT techniques showed same radiobiological effects; however, in the patients with higher joint volume percentages (> 30%), the 9 and 7 fields techniques have better results. It is proposed to use the 7 fields technique instead of the 9 fields technique, especially in prostate cancer cases with high uncertainty in patients’ setup.

Background: Breast cancer is one of the most common diseases in women and causes more deaths rather than other cancers. The increasing trend of breast cancer in Iran makes clear the need of extensive breast cancer research in this area. Some studies showed that in the variety countries and even in the different areas in one country has different risk of breast cancer incidence and this is a reason that there is a correlation between region of life and risk of breast cancer. The purpose of this study was to determine the spatial structure associated with the incidence of breast cancer based on statistical models and identification of areas with high incidence of breast cancer in Iran.
Methods: This ecological study was conducted in Kermanshah University of Medical Sciences, Iran, from February to July 2018. Data on breast cancer patients in all provinces of Iran (30 provinces) were investigated since 2004 to 2009. Risk factors in this study included fruit and vegetable consumption, physical activity, overweight or obesity, and human development index. In this study, we have used routine and spatial Poisson's generalized linear mixed models for data analysis.
Results: In both routine and spatial models, direct and significant correlation was found between the incidence of breast cancer and the human development index (P<0.05). In addition to human development index, overweight or obesity factors were also had direct and significant relationship to the incidence of breast cancer in the spatial Poisson's generalized linear mixed model (P<0.05). In the spatial Poisson's generalized linear mixed model with correlation structure of Besag Yorg Molie (BYM), two provinces of Gilan and East Azerbaijan had the highest risk of breast cancer incidence and province of Kohgiluyeh and Boyer Ahmad had the lowest risk of breast cancer incidence.
Conclusion: The results showed that the distribution of breast cancer incidence in Iran has a spatial structure. That is, the adjacent provinces have similar incidences of this disease.

Background: Due to the incidence and recurrence of bladder cancer (BC), it could be categorized as a clinical and social problem that often occurs at an advanced age. This study was designed to determine the incidence of BC in Isfahan, Iran.
Methods: A retrospective descriptive survey of information based on bladder cancer (ICD-O, third edition; C67) was obtained from the Isfahan Deputy of Health. The study was in conducted to the department of Urology and Kidney Transplantation Research Center and approved by the University Ethics Committee. The Isfahan Cancer Program is intended to record all cancer cases in the Isfahan. From 20 March 2016 to 19 March 2017, records with linkage to using of pathology, demographic and clinical information were recorded in Microsoft Excel 2013 (Microsoft Corp., Redmond, WA, USA) and analyzed by SPSS statistical software, version 22 (IBM, Armonk, NY, USA). The incidence rates (Irs) were calculated by dividing new cases of BC during the year of study to the population at risk during the same time period×100000.
Results: A total of 417 patients that corresponded to Irs of 8 per 100000 persons were studied. The overall recorded number was comprised of 361 males (IRs of 13.9 per 100000) and 56 females (Irs of 2.2 per 100000). The mean±SD age of patients was 64.7±13 years. The minimum age in males versus females was 12 versus 25 years old respectively. Age in the most patients (80% of cases) was more than 50 years old. The invasion of the muscle was recorded in 44% of cases. Geographical distribution in 65% of cases was related to Isfahan City as a place of birth-residence and in the next categories were Khomeinishahr (7.6%), Najafabad (6.8%), Lenjan (4.5%), Mobarekeh (3.7%) and Felavarjan (2.8%) respectively.
Conclusion: Comparison of BC incidence rate between the year 2014 and 2016 showed that incidence rates decreased by 18.2%. In the 44%, invasive neoplasm of BC was recorded for the population studied. The highest frequency of BC was associated with Isfahan City and then Khomeinshahr, Najaf abad, Lenjan, Mobarakeh and Falavarjan.

Background: Metalloproteinase enzymes can lead to the digestion of the extracellular matrix and its compounds and ultimately facilitate the metastasis of cancer cells to other tissues. This study aimed to evaluate the activity of matrix metalloproteinases (MMPs) 1 and 13 in the tissue and plasma samples of the patients with breast cancer and their relationship with clinical features of the disease.
Methods: In this experimental study, twenty-five patients with the diagnosis of non-metastatic luminal A breast cancer in the stage 2 or 3 from the patients referred to the Cancer Institute of Iran, as well as eight healthy subjects which was performed in the Cancer Research Center of Tehran University of Medical Sciences from March 2017 to September 2017, were entered into the study. After obtaining written consent, a few biopsies of breast tumor tissues and 10 cc of the whole blood were collected from all the subjects. Then, the collagen zymography assay was used to evaluate the activity of MMPs 1 and 13.
Results: The results of the present study showed that the activity of MMPs 1 and 13 in the plasma samples was significantly increased in comparison with the healthy group (respectively P=0.0055 and P=0.0263). Unlike the MMP-13, the activity level of the MMP-1 in the tumor and plasma samples was significantly different (P=0.0227). Plasma activity levels of MMP-1 (P=0.0037) and MMP-13 (P=0.0311) were also significantly different in stages 2 and 3 of the disease. Unlike the MMP-13, the activity level of MMP-1 was significantly different in lymph nodes between the tissue and plasma samples (respectively P=0.03 and P=0.015). Moreover, there was no significant difference in the activity level of MMPs 1 and 13 with menopausal and non-menopausal status between the tissue and plasma samples.
Conclusion: The results of the present study showed that plasma concentrations of the MMPs 1 and 13 in comparison with their tissue concentrations could be an appropriate diagnostic tool for breast cancer patients.

Background: Micro-Ribonocellic Acids (miRNA) are non-coding nucleic acids that are evolutionally protected and have a length of 24-20 nucleotides. MiRNAs control the expression of genes after transcription by mRNA degradation or translation inhibition. By blocking the oncogenic miRNAs and creating the necessary and functional miRNAs (tumor suppressor), these small regulatory RNAs can have therapeutic applications in cancer. The high mortality from lung cancer highlights the fact that the majority of patients are diagnosed at an advanced stage of the disease. The use of serum biomarkers can help early detection. MiRNA is more stable than mRNA. MiRNA expression in tissue, plasma, sputum, and urine samples can be detected by fixed formulation. In addition, miRNAs are important modulators of gene expression, diagnostic markers, and prognosis. Therefore, in the present study, the expression of miR-137 in the serum of patients with lung cancer was investigated.
Methods: In this descriptive and analytical study, 100 serum samples were collected from patients referring to Masih Daneshvari Hospital in Tehran from August 2017 to May 2018. Also, individual and clinical information were collected by a questionnaire and real-time polymerase chain reaction (RT-PCR) was used for the qualitative evaluation of changes in expression of miR-137.
Results: Data showed that there was no significant difference between the expression of miR-137 in serum samples of the first and second stages of the disease. While in the serum of patients with lung cancer who metastasized in the third and fourth stages, miR-137 expression decreased by 3.2 (P=0.42) and 6.8 times (P=0.003), respectively. Based on the results, it can be inferred that the measurement of miR-137 expression in lung cancer patients with concomitant reduction can be a sign of the progression of the disease.
Conclusion: Based on the results of this study, there was a significant relationship between miR-137 expression and lung cancer.

Background: The rate of recurrence and mortality in high-risk prostate cancer remains high. On the other hand, the use of chemotherapy in metastatic prostate cancer has improved overall survival of patients. The aim of this study was to evaluate the effect of neoadjuvant chemotherapy alone on increasing survival of patients with high risk localized prostate cancer
Methods: This is a systematic review study. Databases including Scopus, Medline, PubMed, Google Scholar, Cochrane, Embase were searched. The terms used include prostate cancer, adenocarcinoma, neoadjuvant, chemotherapy, chemotherapy alone, systemic therapy. Of the various types of articles, only oiginal research studies that specifically focused on neoadjuvant chemotherapy (not chemotherapy with target therapy, immunotherapy, or hormone therapy) were identified. Inclusion criteria included study type (original research studies) and sample type (high-risk localized prostate cancer patients) and outcome type (patient survival).
Results: A total of 17 original research studies were identified. All of these studies were phase one or phase two. Docetaxel was the most commonly used chemotherapy drug. Also, the most common regimen used was the use of docetaxel alone. The rate of decrease in prostate-specific antigen (PSA) (>50%) after neoadjuvant chemotherapy was reported in 24 to 58% of patients. PSA declines of less than 50% after neoadjuvant chemotherapy occurred in 40 to 100% of patients. No studies reported a complete pathologic response following neoadjuvant chemotherapy. However, the relative pathologic response and reduced tumor volume were seen in the majority of patients. All of these studies showed that neoadjuvant chemotherapy alone, in high-risk prostate cancer patients, was almost well tolerated and that the complications were mostly mild (grade 1 and 2). Grade 3 and 4 complications were negligible. A 2-year recurrence-free survival of up to 68.5% and a 5-year recurrence-free survival of up to 49% were reported. The overall 5-year survival also ranged from 35 to 48%.
Conclusion: The use of neoadjuvant chemotherapy alone has not clearly increased the survival of patients with high-risk localized prostate cancer, and there is controversy in studies.

Background: Melatonin is one of the drugs which are used in the treatment of sleep problems, including insomnia and sleep deprivation. The aim of the present study was to evaluate the melatonin effect on sleep quality in patients with cancer.
Methods: This quasi-experimental study was performed on cancer patients with trouble sleeping who were treated with melatonin (3 mg per day) for a month. Sleep quality according to the Pittsburgh sleep quality index (PSQI) questionnaire was evaluated before and after taking melatonin. This study was conducted in the Oncology Clinic of Imam Reza Hospital, Kermanshah City in Iran from August 2016 to February 2018.
Results: There was a significant difference between the sleep quality of patients with cancer before and after taking melatonin (P<0.05). In other words, before taking melatonin, sleep quality of none of the patients was not optimal but after taking melatonin, the sleep quality of 52% of patients was satisfactory. Also, there was a significant difference between the components of subjective sleep quality (P<0.001), sleep latency (P<0.001), sleep duration (P<0.001), sleep efficiency rate (P<0.001), sleep disturbances (P=0.001), and daytime dysfunction (P<0.001) of patients with cancer before and after taking melatonin. There was no significant difference between the components of subjective sleep quality, sleep latency, sleep duration, sleep efficiency rate, sleep disturbances, and daytime dysfunction of cancer patients with age, sex, kind of cancer, and kind of metastasis before and after taking melatonin (P˃0.05).
Conclusion: According to the mentioned findings, it seems that the administration of melatonin to enhance sleep quality in patients with cancer is effective.

Background: Ovarian cancer is the fifth leading cancer-related cause of death in women worldwide and is often diagnosed at advanced stages. Regarding the low sensitivity and specificity of the currently available diagnostic techniques, in the present study, we aimed to evaluate the accuracy of RMI and ROMA indexes and comparing these two indexes with CA-125 and HE4 parameters for the diagnosis and differentiation between benign and malignant ovarian tumors. Also, we determined the optimal cut-off level of these markers in patients who attended Arash Women’s Hospital.
Methods: In this cross-sectional study, we included 137 women with ovarian mass who were attended the gynecology clinic of Arash Women's Hospital, Tehran, Iran (April 2017-April 2019), and were eligible according to the inclusion criteria. We included patients with an adnexal mass over 3 cm. Our exclusion criteria were as the following: pregnancy, age under 18 and over 90 years, taking hormonal agents, renal failure, suspected ovarian torsion, ovarian cancer and taking antibiotics, nitric oxide compounds, and heavy metals. Based on serum CA125, HE4, and ultrasound findings, ROMA and RMI indexes were determined for each patient, and the sensitivity and specificity of HE4, RMI, ROMA, and CA125 were compared with the result of the operative histopathologic assessment.

Conclusion: Measurement of HE4 before menopause and CA125 during menopause seems to be helpful in the early detection of ovarian cancers in women with ovarian masses.

Background: Neck mass is one of the most common clinical findings in all age groups. Differential diagnosis of masses includes a range of pathologies from congenital to infectious or neoplasm. Understanding the risk factors of neck masses can help us to assess them properly. The purpose of this study is to obtain the epidemiological and clinical features of different neck masses in Kerman, Iran.
Methods: This research was a descriptive, retrospective and cross-sectional study. 120 Patients that have been biopsied from neck masses during March 2014 to March 2018  in the otorhinolaryngology department of Shafa hospital of Kerman (referral center of otorhinolaryngology disease of southeastern Iran), were the participants of the study. Data regarding age, sex, history of addiction, smoking and definite pathologic diagnosis were collected and analyzed with SPSS 20^th version.
Results: Of 120 cases, 57.5 % were male and 42.5% were female. In the malignant masses group, the male to female ratio was 4.1 to 1. The average age of patients was 39.44 years old. From them, 20.83 percent had a history of smoking but 79.17 percent had never experienced smoking. In addition, 77.5% of the patients have not experienced opium consumption and 22.5% were addicted to opium regularly. There was a significant relationship between smoking and opium consumption and the incidence of malignant cervical masses (P<0.05). In the pathological study, inflammatory and infectious masses with 48.33 percent were in the head of pathology; malignant neoplasm with 25 percent, benign neoplasms with a prevalence of 12.5 percent and congenital masses with a prevalence of 9.7 percent were in the next ranks.

Background: Skin cancer is the most prevalent type of cancer and melanoma is the deadliest kind of skin cancer in the world. Due to enhanced induction of apoptosis and ROS levels, low-level lasers can be utilized to destroy skin cancer cells. Lasers are used to treat some skin lesions. Vitamin A is beneficial in the prevention and treatment of skin cancer. Vitamin A inhibits the pathway of cancer signals in the skin and suppresses tumor growth. In this study, the combined effect of low-level laser radiation (LLL) and vitamin A on cellular factors of skin melanoma cancer cells was investigated.
Methods: An in-vitro interventional laboratory study was performed in the cell culture laboratory of Medical Laser Research Center, Yara Institute in 2020-2021 (July 2020 to July 2021). First, A375 skin cancer cells were cultured in DMEM with 10% FBS. After preparation and culture of A375 cell lines, different concentrations of vitamin A (1, 5, 50, 100 μM) and LLL energy doses (1, 2, 5, 10 J/cm²) as treatments were done. Combination research of these treatments was performed to eliminate skin melanoma cancer cells. The rate of viability was determined using the MTT test, and the rate of apoptosis was determined using flow cytometry.

Background: Breast cancer is the second leading cause of cancer death in women, after lung cancer. Due to the importance of predicting this disease, the use of data mining methods in medical research is more significant than before. Data mining algorithms can be a great help in preventing the development of lymphedema in patients. The aim Of this study was to create a diagnosis system that can predict the probability of lymphedema in breast cancer patients.
Methods: In the present study, the factors of lymphedema in 1117 patients with breast cancer have been collected. The likelihood of developing lymphedema is predicted using ensemble learning via 5 heterogeneous classification algorithms, feature selection and the genetic algorithm (The Two-layer Ensemble Feature Selection method). After collecting the data of patients with breast cancer from 2009 to 2018, and data preprocessing using the optimized ensemble learning algorithm and feature selection, we will examine the likelihood of developing lymphedema for the new patient. Finally, the factors affecting the disease have been extracted. Excluding the time of collecting statistical data, the period of the study was from September 2019 to February 2021. This study is performed at Seyed Khandan Rehabilitation Center, Tehran, Iran.
Results: The results of algorithms showed that the accuracy of the ensemble learning method with selected classification algorithms (SVM with RBF kernel) is 87% and the accuracy of the ensemble learning with feature selection method is 90%. According to the final evaluation of the proposed method, the most effective risk factors for lymphedema have been extracted.
Conclusion: Unfortunately, treatment and diagnosis are not without complications, and one of the most important of these complications in breast cancer is lymphedema in the upper extremities, which can affect the quality of life in patients. It is essential to have a method that can accurately suggest to a specialist whether a new patient will develop lymphedema in the future or how likely it is to develop it, using patient’s own clinical and demographic characteristics.