Tehran University Medical Journal

In recent years, the use of gold nanoparticles (GNPs) in radiation therapy has been studied by experimentation and Monte Carlo simulation repeatedly. Although the idea of increasing doses has been raised by high-atomic elements since decades ago, but due to the adaptation of gold nanoparticles with the biological system, scientists have incited more about the various uses of these materials in radiation therapy. The results of all studies in this field are consistent with the increase in tumor-derived doses with gold nanoparticles in radiotherapy. But the results of the interaction of radiation energy are still controversial with the size of gold nanoparticles. In other words, in the Monte Carlo simulations the gold nanoparticles with a size of about 10 to 100 nm, and in biological studies, the nanoparticles with a dimension of 1.9 nm were used. On the other hand, some studies of energy dependence have been developed in dose enhancement, and in some other studies the effect of the size of gold nanoparticles has been investigated on photon energy. However, in some respects, the results of radiation therapy using by gold nanoparticles does not appear to be definitive, although the photoelectric effect in low energies is considered to be the dominant phenomenon. The main idea behind the GNP dose enhancement in some studies is not able to explain the results especially in recent investigation on cell lines and animal models radiation therapy using GNPs. With the rapid development of nanotechnology in the biomedical field, GNPs have been widely used in the diagnosis and treatment for disease. Numerous pre-clinical studies in vitro and in vivo have proved the potential value of metal-based GNPs as radio sensitizers in cancer treatment. Various studies have indicated that radio sensitizing ability could be influenced by nanomaterial size, concentration, surface coating, and the radiation energy. Hence, gold nanostructures provide a versatile platform to integrate many therapeutic options leading to effective combinational therapy in the fight against cancer. In this review article, the recent progress in the development of gold-based NPs towards improved therapeutics will be discussed. A multifunctional platform based on gold nanostructures with targeting ligands, therapeutic molecules, and imaging contrast agents, holds an array of promising directions for cancer research.

Background: Diffusion-weighted imaging (DWI) is one of methods in evaluation of breast lesions. We aimed to investigate the apparent diffusion coefficient (ADC) values in breast tumors and their accuracy in differentiating benign versus malignant lesions.
Methods: In this cross-sectional study, 72 patients with 88 breast lesions were investigated by 1.5-T breast MRI from 2015 to 2017 in Athari Imaging Center in Tehran, Iran. Nearly all patients has undergone histopathology evaluation. One small region of interest (ROI) were placed on the most restricted region inside the solid part on the ADC map. Care was taken to avoid cystic or necrotic, fatty regions and hematoma inside the mass. A large round ROIs were placed in healthy fibroglandular tissue of contralateral breast ADC values were measured and compared in normal breast tissue and in most restricted parts of breast lesions (mass and non-mass). After determining cut-off for differentiation of benign and malignant lesions, sensitivity, specificity, accuracy, positive predictive value and negative predictive value were calculated.
Results: Mean age of patients was 43.3 years. The average tumor size of benign and malignant lesions were calculated 26.0 mm, 35.3 mm respectively and 23 mm and 46 mm in mass and non-mass respectively. Invasive ductal carcinoma include the majority of pathology result (in 37.5% of the patients). Our results revealed that the measured ADC values in normal breast tissue were higher than breast lesions (P≤0.01). Mean ADC value in benign lesions was 1.40×10-3 mm²/s and for malignant lesion was 1.08×10-3 mm²/s. ADC value in the normal breast tissue was 1.79×10-3 mm2/s and was significantly higher than ADC value of breast lesions (benign and malignant). Cut-off value in non-mass was not valid, but in mass was 1.19×10-3 mm²/s with sensitivity, specificity, positive predictive value, negative predictive and accuracy of 89.7%, 83.8%, 87.5%, 86.6%, and 87.1% respectively.
Conclusion: In DWI imaging, ADC value can differentiate benign and malignant masses with high sensitivity and specificity but not helpful in non-mass lesions.

Background: Prostate cancer is currently the third malignant disease in Iran and fifth common cancer worldwide. The aim of this study was to determine the expression of GPRC6A, E.cadherin, and ZEB1 genes in prostate cancer in comparison with benign tumor. Since early detection of cancer plays an important role in treatment, this study aims to identify the role of GPRC6A, E.cadherin and ZEB1 genes in screening of prostate cancer.
Methods: In this case-control study, 30 samples including 15 samples of malignant prostate cancer and 15 samples of benign tumor were collected from the patients. RNA was extracted from the tissues, followed by cDNA preparation. In the last step, expression of GPRC6A, E.cadherin and ZEB1 genes was measured using the Real-time polymerase chain reaction (PCR) technique and the Relative expression software tool (REST), Version 2009 (http://rest.gene-quantification.info/).
Results: In this study, the expression of GPRC6A genes compared to its benign tumor increased 3-fold, ZEB1 expression in prostate cancer, compared to its benign tumor, increased 2-fold, and expression of E.cadherin gene in cancerous samples compared to benign tumor declines 10 was equal. In this study, there was no significant relationship between the expression of genes in benign and malignant samples with common diagnostic factors in this type of disease such as age, Prostate-specific antigen (PSA), pathologic stage and Gleason score.
Conclusion: According to this study and similar studies, increased expression of GPRC6A in prostate cancer cells can stimulate the progression of cancer cells by regulating cell proliferation and invasive response to various ligands. Increasing the expression of ZEB1 and decreasing the expression of E.cadherin is also due to the lack of binding of cells and spread of metastasis. As a result, tumors express ZEB1 with absence of E.cadherin is associated with advanced disease or metastases, which indicates that ZEB1 induces EMT and tumor progression in clinical cancers. Therefore examined genes have potential for screening prostate cancer and they can be used as a diagnostic marker for prostate cancer with further investigation.

Background: Differentiated thyroid cancer (DTC) frequently occurs in women at fertility age. One of the cornerstones in treating this malignancy is Radioactive Iodine (RAI) therapy following thyroid resection. In this study, we evaluated the effect of RAI therapy on the fertility rate and pregnancy complications.
Methods: This is a retrospective study on 41 patients with differentiated thyroid cancer, with at least one experience of pregnancy after standard treatment (thyroid resection followed by radioiodine therapy). All patients have been signed a written consent form in initial admission to our department. Furthermore, we asked our patients to fill in a questionnaire about their thyroid cancer and its treatment as well as pregnancy and its complication. As a control group with no different mean age, the same checklist has also been filled in for the patient’s healthy sister too, just related to gravidity and its complications. The complications of pregnancy were registered in these patients and compared with the control group consisted of their healthy sisters. Also, the association of abortion rate with other underlying factors has been assessed. All data has been included in SPSS software, version 22 (IBM SPSS, Armonk, NY, USA) and analyzed using logistic regression. This study conducted at the Nuclear Medicine Department of Ghaem Hospital in Mashhad, from May 2017 to February 2018 with the support of Mashhad University of Medical Sciences, Iran.
Results: No significant difference was noted in the mean age between case (differentiated thyroid cancer) and control groups (P=0.9). The two groups were also statistically similar in terms of pregnancy frequency (P=0.05) and number of alive children (P=0.8). Abortion seems to be the only item in DTC patients which was more than healthy sisters (0.2 versus 0.7) (P=0.003). However, this statistical difference showed no direct relationship with radioiodine treatment (RIT). As in DTC patients before and after RIT, no significant difference has been detected in DTC patients before and after RIT (P=0.48). Birth weight was not statistically different in DTC patients before and after RIT (P=0.66) and between DTC patients and their healthy sisters (P=0.2).
Conclusion: Radioiodine therapy for differentiated thyroid carcinoma has no considerable negative impact on pregnancy, whether on fertility rate or on gravity complications.

Background: Breast cancer is the most commonly diagnosed and the leading cause of cancer death among females worldwide. The rate of breast cancer incidence among Iranian women is 17% of all cancers, it has been ranked first in Iran. This study aimed to investigate the factors affecting axillary lymph node involvement in female patients with breast cancer.
Methods: A cross-sectional study was conducted on 167 patients with breast cancer diagnosed between March 2012 and March 2015 at Shahid Beheshti of Babol, Shahid Rajaei of Tonekabon and Imam Sajad of Ramsar hospitals. A researcher-made questionnaire was used to collect information on the patients and pathology report of tumor and lymph nodes was completed.
Results: The rate of axillary lymph node involvement was observed in 117 patients (70.1%). Mean age was 49.64±11.62 years in the patients with breast cancer. The highest frequency of lymph node involvement was observed in the 40-49 age group (24%). The average size of tumor was 3.39 cm and the majority of patients had a tumor 2-5 cm (T2) but the most involvement was related to T3 (>5cm). The most common type of cancer and grading were invasive ductal carcinoma (93.4%) and tumor grade 2 (52.1%), respectively. Most lymph node involvement was observed in invasive ductal carcinoma and 85.1% of patients had tumor degree 3. 22.2% of patients with vessels involvement had axillary lymph node involvement. 63% of patients’ tumors had receptors of estrogen and progesterone. A statistically significant association was observed between axillary lymph node involvement and tumor size (P=0.031), tumor type (P=0.007), tumor grade (P=0.011), estrogen receptor (P=0.008) and progesterone receptor (P=0.038).
Conclusion: There was a statistically significant association between axillary lymph node involvement and tumor size, type and grade, estrogen and progesterone receptor status, but there was no statistically significant association between axillary lymph node involvement and age and estrogen as well as progesterone receptor status.

Background: Prostate cancer has been reported as a worldwide important kind of cancer and the second most common cause of cancer-related mortality among men. Prostate-specific antigen (PSA) serum level is one of the most important markers of prostate cancer diagnosis. While PSA level helps predict the risk of prostate cancer development, researchers still looking for ways to increase the accuracy of prognostic models. To increase the specificity of PSA and decrease of unnecessary biopsies and morbidity, PSA-related parameters such as PSA doubling time (PSADT) have been used. In this study, the relationship between this factor and the severity of prostate cancer was evaluated.
Methods: In this retrospective study, the data of patients who were subjected to transrectal ultrasound-guided (TRUS) biopsy of the prostate and referred to Imam Khomeini Hospital, Tehran, between 2009 and 2017 were reviewed. We enrolled the men with at least two consecutive elevated PSA level within three months to calculate PSADT. Based on the pathology report, primary and secondary Gleason score (GS) were determined. Correspondingly, considering GS, the patients were divided into two groups with high-grade and low-grade tumor (GS<7 considered as low-grade and GS>7 considered as high-grade tumor).
Results: Totally, 1712 cases of TRUS biopsy of the prostate were studied. Among them, 547 (32.3%) had prostate cancer, of whom 73 cases were eligible based on inclusion criteria and were consented to enroll in the study. According to the data obtained, we found a significant difference in PSADT between the two groups of patients with high-grade and low-grade malignancy (mean±SD PSADT, 9.8±14.2 vs. 16.1±14.9 respectively, P=0.004). Considering the seven months as the cut-off point for PSADT in determining malignancy, there was a significant difference between the two groups according to Fisher's exact test (P=0.01).
Conclusion: In our study, PSADT cut-off of 7 months provided the greatest accuracy for differentiation between low-grade and high-grade malignancy, and PSADT has acceptable accuracy for the diagnosis of high-grade tumors.

Background: Gastric cancer (GC) is considered as one of the most common types of cancer worldwide with poor prognosis and generally limited treatment options. Recent studies have indicated that HER2, MDM2, MYC, MET, and TP53 play an important role in the development of gastric cancer. Therefore, the aim of this study was to evaluate the incidence of amplification/deletion of these genes in patients with gastric cancer.
Methods: In this descriptive study, a total of 37 gastric cancer tissue samples from GC patients including 23 males (62.2%) and 14 females (37.8%) referred to the Hematology-Oncology and Stem Cell Research Center of Shariati Hospital, Tehran, from March 2015 to February 2016 were evaluated. The patient's age at diagnosis ranged from 33 to 85 years (median: 65 years). The amplification pattern of HER2, MDM2, MYC and MET genes and TP53 deletion were investigated by fluorescence in situ hybridization (FISH) technique performed on 3 to 5 micron section obtained from formalin-fixed and paraffin-embedded cancer tissues.
Results: The tumors were preferably identified at the distal stomach (54.05%) in comparison to tumors arising from the gastric cardia. The tumor size varied between 2 and 5 cm (average, 3.5 cm). Seven of the cases (19%) had advanced tumors at the time of diagnosis. HER2, MDM2, MYC, MET and TP53 copy number alteration were successfully determined in all samples obtained from the GC patients. HER2, MDM2, and c-MYC genes were amplified in 2 (5.41%), 1 (2.7%) and 3 (8.11%) of 37 patient samples, however, MET gene amplification and TP53 deletion were not observed in the obtained GC tissue samples. Co-amplification of HER2, MDM2, and MYC genes, and co-amplification of HER2 and MYC genes were detected in one patient.
Conclusion: The results of this study indicate the low frequency of MDM2, HER2 and MYC genes in gastric cancer patient and their copy number alterations may provide diagnostic and prognostic marker for GC patients.

Background: Colorectal cancer is the second most common cancer in the world which is mainly caused by epigenetic and environmental factors. Among these epigenetic factors, gut microbiota is an important one. Although it has not been proved a unique group of bacteria correlated with colorectal cancer, these findings have generally demonstrated differences between healthy and disease gut microbiome in population. Actually, the identification and investigation of intestinal microbiota in early detection of colorectal cancer have been highlighted in new researches and studies. Herein, in the current study, we aimed to evaluate the number of selected gut bacteria including Lactobacillus and Escherichia coli and Prevotella in the fecal specimens of adenomatous polyposis patients, colorectal cancerous cases in compared to normal participants in terms of estimating important role of gut microbiota during colorectal cancer initiation and progression.
Methods: The current research was a case-control study. Fecal samples were provided from 31 healthy individuals, 42 adenomatous polyposis patients and 20 colorectal cancer cases that were referred to Taleghani Hospital, Tehran, Iran, from August 2016 to August 2017 for colorectal cancer screening tests. Fecal samples were collected to analyze intestinal bacteria including, Lactobacillus, Escherichia coli, and Prevotella by absolute quantitative real-time polymerase chain reaction (PCR). The number of these gut bacteria was precisely determined by this method of real-time PCR.
Results: Higher number of Prevotella with 24.6 CT number (P<0.005) and E.coli with 20.4 CT number (P<0.015) were achieved in colorectal cancer cases and adenomatous polyposis patients in contrast to samples from normal individuals. On the contrary, the opposite range was observed for the quantification of Lactobacillus and greater numbers of bacteria (CT=28.6) were detected in normal, compared to the colorectal cancer cases and adenomatous polyposis (P<0.001).
Conclusion: The gut microbiota composition of individuals with colorectal cancer and adenomatous polyposis differs from that of healthy individuals, and the higher numbers of pathogenic microbiota versus beneficial microbiota present in those with colorectal cancer and adenomatous polyposis. In contrast, healthy individuals have higher numbers of beneficial gut microbiota than pathogenic microbes. These findings need more experimental analysis and investigation to better clarify.

Background: Skin cancer is one of the most common forms of cancer in the world and melanoma is the deadliest type of skin cancer. Both melanoma and melanocytic nevi begin in melanocytes (cells that produce melanin). However, melanocytic nevi are benign whereas melanoma is malignant. This work proposes a deep learning model for classification of these two lesions.   
Methods: In this analytic study, the database of HAM10000 (human against machine with 10000 training images) dermoscopy images, 1000 melanocytic nevi and 1000 melanoma images were employed, where in each category 900 images were selected randomly and were designated as the training set. The remaining 100 images in each category were considered as the test set. A deep learning convolutional neural network  (CNN) was deployed with AlexNet (Krizhevsky et al., 2012) as a pretrained model. The network was trained with 1800 dermoscope images and subsequently was validated with 200 test images. The proposed method removes the need for cumbersome tasks of lesion segmentation and feature extraction. Instead, the CNN can automatically learn and extract useful features from the raw images. Therefore, no image preprocessing is required. Study was conducted at Shahid Beheshti University of Medical Sciences, Tehran, Iran from January to February, 2020.
Results: The proposed model achieved an area under the receiver operating characteristic (ROC) curve of 0.98. Using a confidence score threshold of 0.5, a classification accuracy of 93%, sensitivity of 94%, and specificity of 92% was attained. The user can adjust the threshold to change the model performance according to preference. For example, if sensitivity is the main concern; i.e. false negative is to be avoided, then the threshold must be reduced to improve sensitivity at the cost of specificity. The ROC curve shows that to achieve sensitivity of 100%, specificity is decreased to 83%.
Conclusion: The results show the strength of convolutional neural networks in melanoma detection in dermoscopy images. The proposed method can be deployed to help dermatologists in identifying melanoma. It can also be implemented for self diagnosis of photographs taken from skin lesions. This may facilitate early detection of melanoma, and hence substantially reduce the mortality chance of this dangerous malignancy.

Background: The most common types of non-melanoma skin cancer are basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). AKIEC -Actinic keratoses (Solar keratoses) and intraepithelial carcinoma (Bowen’s disease)- are common non-invasive precursors of SCC, which may progress to invasive SCC, if left untreated. Due to the importance of early detection in cancer treatment, this study aimed to propose a computer-based model for identification non-melanoma malignancies.
Methods: In this analytic study, 327 AKIEC, 513 BCC, and 840 benign keratosis images from human against machine with 10000 training dermoscopy images (HAM10000) were extracted. From each of these three types, 90% of the images were designated as the training set and the remaining images were considered as the test set. A deep learning convolutional neural network (CNN) was developed for skin cancer detection by using AlexNet (Krizhevsky, et al., 2012) as a pretrained network. First, the model was trained on the training images to discriminate between benign and malignant lesions. In comparison with conventional methods, the main advantage of the proposed approach is that it does not need cumbersome and time-consuming procedures of lesion segmentation and feature extraction. This is because CNNs have the capability of learning useful features from the raw images. Once the system was trained, it was validated with test data to assess the performance. Study was carried out at Shahid Beheshti University of Medical Sciences, Tehran, Iran, in January and February, 2020.

Background: Granular cell tumor (Abrikossoff’s tumor) is a rare and slow-growing tumor of the soft tissue. Originated from the Schwann cells, it is often a benign tumor, but it can be malignant in 1-3% of the cases. Malignant cases can cause significant morbidity and mortality. It may develop in many anatomic locations, especially in the head and neck region, and also in skin and subcutaneous tissue.

Background: Prostate cancer is the most common malignancy in men and the second leading cause of death in all countries of the world. The exact mechanism of prostate cancer is not known. On the other hand, early detection of prostate cancer can lead to a complete cure. Several clinical experiments including Digital Rectum Examination (DRE), biochemistry such as Prostate Specific Antigen (PSA), and pathology such as Trans Rectal Ultra Sonography (TRUS) are used to assess the size and spread of prostate cancer. In this study, the relationship between mean serum PSA and Gleason score as a standard method in patients with prostate cancer was compared using the parameters extracted from DCE MRI.

Background: In addition to heart disease, ECG also changes in non-heart disease, which due to its similarity, can lead to misdiagnosis of heart disease in patients. ECG changes in brain lesions such as ischemic and hemorrhagic strokes, brain traumas, etc. and have been studied in many articles, but the effects of brain midline shift on ECG changes have not been studied. In this study, we want to examine these changes.
Methods: This is a prospective cross-sectional descriptive study. Patients with brain tumors who were referred to Al-Zahra and Kashani hospitals in Isfahan from April 2019 to March 2021 were selected. Patients with a history of heart disease, patients receiving medications that cause ECG changes, patients with ECG changes due to non-cardiac and cerebral causes, and individuals under 15 years of age were not included in the study. Patients whose ECG changes were due to electrolyte disturbances or acute heart problems were also excluded from the study. After obtaining informed consent from patients, a CT scan or brain MRI was taken and patients were divided into two groups with and without midline shift. Then the ECG was taken and ECG changes (T wave, ST segment, QTc Interval, QRS prolongation) were compared in two groups of brain tumors with and without midline shift.
Results: 136 patients were included in the study. Of these, 69 patients were in the without midline shift group and 67 patients were in the midline shift group. In the midline shift group, 3% of patients had ST segment changes and 23.9% had T wave changes, which were 1.4% and 10.1% in the without midline shift group, respectively. The mean QTc Interval in the two groups without and with midline shift was 338.26 (4 28.438) and 388.66 (37.855), respectively, and the mean QRS in the without midline shift group was 86.09 (88.9.88) ms and in the midline shift group was 94.63 (±12.83) ms.
Conclusion: Brain midline shifts can cause QRS widening, QTc interval prolongation, and T-wave changes in patients' ECGs.

Methods: This cross-sectional study was conducted on all files of patients admitted to Qaem Hospital in Mashhad City, Iran, in a period of 10 years from March 2009 to February 2018 with a definitive diagnosis of benign or malignant tumors of the CNS, including tumors of the brain, cerebellum, spinal cord, or meningeal membranes. Information sources included the patients' physical files and the hospital information system (HIS). The statistical software SPSS version 28.0 for Windows (IBM SPSS, Armonk, New York, USA) was used for the statistical analysis. Results: In total, 775 patients with benign and 771 patients with malignant CNS tumors were included in the study. Regarding epidemiological aspects of benign tumors, the incidence rate of women was almost twice that of men (68.47% versus 31.53%), with an overall average age of 45.31±19.81 years. The most common benign tumors were meningioma (72.77%), followed by schwannoma (13.67%). Regarding malignant brain tumors, the mean age of affected patients was 36.64±19.67 years, with males accounting for 53.04% of cases and females for 46.96%. The most frequent type of tumor was glioblastoma (32.68%), followed by diffuse astrocytoma (16.47%). Both benign and malignant CNS tumors were associated with significant hospital mortality; in-hospital mortality rates for benign and malignant tumors were 10.1% and 17.5%, respectively. Tumor type and its grade were the main determinants of early death in malignant CNS tumors. Conclusion: The epidemiological characteristics of benign and malignant tumors in our study community were similar to the reports presented in other communities. Knowledge of these characteristics provides the possibility of managing patients and reducing morbidity and mortality related to these tumors.