Tehran University Medical Journal

---

Breast cancer is one of the most common types of cancer in women. Screening mammography is a low‑dose X‑ray examination of breasts, which is conducted to detect breast cancer at early stages when the cancerous tumor is too small to be felt as a lump. Screening mammography is conducted for women with no symptoms of breast cancer, for early detection of cancer when the cancer is most treatable and consequently greatly reduce the death rate from the breast cancer. Screening mammography should be performed every year for women age 45-54, and every two years for women age 55 and older who are in good health. A mammogram is read by a radiologist to diagnose cancer.
To assist radiologists in reading mammograms, computer-aided detection (CAD) systems have been developed which can identify suspicious lesions on mammograms. CADs can improve the accuracy and confidence level of radiologists in decision making and have been approved by FDA for clinical use. Traditional CAD systems work based on conventional machine learning (ML) and image processing algorithms. With recent advances in software and hardware resources, a great breakthrough in deep learning (DL) algorithms was followed, which revolutionized various engineering areas including medical technologies. Recently, DL models have been applied in CAD systems in mammograms and achieved outstanding performance. In contrast to conventional ML, DL algorithms eliminate the need for the tedious task of human-designed feature engineering, as they are capable of learning useful features automatically from the raw data (mammogram). One of the most common DL frameworks is the convolutional neural network (CNN). To localize lesions in a mammogram, a CNN should be applied in region‑based algorithms such as R‑CNN, Fast R‑CNN, Faster R‑CNN, and YOLO.

Proper training of a DL‑based CAD requires a large amount of annotated mammogram data, where cancerous lesions have been marked by an experienced radiologist. This highlights the importance of establishing a large, annotated mammogram dataset for the development of a reliable CAD system. This article provides a brief review of the state‑of‑the‑art techniques for DL‑based CAD in mammography.

---

The recording of electrophysiological activities of brain neurons in the last half-century has been considered as one of the effective tools for the development of neuroscience. One of the techniques for recording the activity of nerve cells is the multi-electrode arrays (MEAs). Microelectrode arrays (MEAs) are usually employed to record electrical signals from electrogenic cells like neurons or cardiomyocytes. MEAs consist of an array of planar or three-dimensional electrodes that act as electrical interfaces and record cellular signals or stimulate cells. These platforms can be used in different applications including neuroscience studies, prostheses and rehabilitation, deep brain stimulation (DBS), cardiac pacemakers, retinal and cochlear implants, or for brain-computer interfaces (BCI) in general. Multi-electrode arrays are known as long-term recording and non-invasive devices. The MEA structure includes arrays of electrodes with micrometer and nanometer dimensions which are designed to stimulate and record the electrical activity of cells, and are fabricated using micromachining technologies. MEAs should be biocompatible to serve as a substrate for cell growth. On the other hand, they must have low impedance to be able to provide a high signal-to-noise ratio, and small size to offer a suitable spatial resolution for recording. MEAs are usually fabricated on glass substrates patterned with high-conductivity metals such as gold, iridium or platinum, which are insulated with a biocompatible layer. Despite fast progress, current multi-electrode arrays for neural applications still face limitations such as low signal-to-noise ratio and spatial resolution. To achieve better spatial resolution and lower noise levels and therefore more accurate signal, it is necessary to develop arrays with smaller sizes and lower impedance. Meanwhile, many nanostructures such as graphene, carbon nanotubes, gold nanoparticles, and also conductive polymers have become attractive candidates for this application due to their interesting properties. In this paper, the technology of multi-electrode arrays, how it works and its various parts are introduced, and finally, the challenges and developments in this field are investigated. Multi-electrode array technology is used for neuroscience research, neural network analysis, drug effects screening, and neural prosthesis studies.

---

Glioma is the most common type of brain tumor and according to the 2016 WHO classification, based on invasion level, it is divided into four categories. The most severe and invasive type is grade IV glioma or glioblastoma (GBM), which has a very poor prognosis and a survival rate of only 15 months. However, the molecular pathway of invasion in malignant glioma tumors has not yet been clearly elucidated. Like other cancers, brain tumors are thought to migrate and metastasize to other tissues via epithelial-to-mesenchymal transition (EMT). EMT is a process by which epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties to become mesenchymal stem cells. Studies have shown that EMT and angiogenesis can help brain tumors to migrate to other parts of the brain as well as surrounding tissues. Thus they can induce metastasis. EMT is controlled by three gene families, including SNAIL, TWIST, and ZEB. During EMT, the expression of epithelial-related genes is silenced, and, conversely, the expression of mesenchymal-related genes is increased. In this way, the cells acquire the mesenchymal tissue’s features and can be prepared for invasion and metastasis. On the other hand, only about 1% of the genome can take its role in the translation of functional proteins, and the large remaining part of the genome is made up of non-coding sequences. Therefore, much attention has recently been paid to the role of such noncoding transcripts, at the top of them, long non-coding RNAs (lncRNAs), in regulating the expression of genes involved in important molecular pathways such as apoptosis, proliferation, invasion, and migration in cancer progression and metastasis. Any interference in regulating the expression of genes involved in each of these molecular pathways leads to cancer in different ways. Understanding and identifying lncRNAs involved in tumorigenesis and invasion of brain tumors, while helping to better identify the molecular mechanisms of metastasis in glioma, can also be effective as biomarkers in the diagnosis, prognosis, treatment, and drug resistance of glioma. Therefore, in this review study, the most important lncRNAs involved in EMT in glioma have been investigated.

---

Cancer is the second leading cause of death in the United States and has become a health problem worldwide. The reported incidence of new cancer cases is estimated at 19.3 million, with a mortality rate of 10 million in the world in 2020. There are several therapeutic approaches for cancer, including chemotherapy. Chemotherapy is consuming anti-neoplastic drugs, alone or in combination. However, it causes damages to the normal cells and has many side effects. Cardiac complications are common side effects of some chemotherapy agents. Cardiac myocytes are potentially more susceptible to the long-term adverse effects of chemotherapy agents due to the less regeneration ability in cardiac cells. Moreover, heart muscle dysfunction (cardiomyopathy) and cardiovascular complications may occur in cancer survivors even a year after chemotherapy or radiation therapy and influence their quality of life. Anthracyclines are commonly used in chemotherapy; especially doxorubicin is the most widely used drug of this family. Doxorubicin is an effective anti-malignant agent prescribed for the treatment of some solid tumors (e.g. ovary, breast, and gastrointestinal cancers). Doxorubicin can cause several side effects, ranging from cancer treatment’s common side effects such as fever, nausea, and vomiting to lethal cardiac side effects. Assumed that doxorubicin has many therapeutic and cytotoxic mechanisms, cardiotoxicity induced by doxorubicin is very common and there is no reliable treatment for this problem. The cardiac side effects of doxorubicin during a chemotherapy regimen can be acute, chronic, or even gradually progressive and persistent after the termination of doxorubicin therapy. In patients undergoing doxorubicin therapy, reported symptoms are cardiac rhythm and blood pressure changes, pericarditis, myocarditis, cardiomyopathy, and congestive heart failure. The pathophysiology of doxorubicin-induced cardiotoxicity is very wide. Disruption of normal mitochondrial function, decreased amount of antioxidant factors, production of reactive oxygen species (ROS), an imbalance in calcium hemostasis, activation of inflammatory cytokines, targeting topoisomerase-IIβ (Top2b), and induced DNA damage are associated with doxorubicin-induced cardiotoxicity. Increased doxorubicin in mitochondria activates the redox cycle that ultimately leads to the production of reactive oxygen species in both normal and tumor cells. The present review aims to investigate the cardiotoxic mechanisms of doxorubicin and explain different types of doxorubicin-induced cardiotoxicity.

---

---

Medullary thyroid cancer accounts for 5-10% of thyroid carcinomas. RET proto-oncogene mutations occur in all of the hereditary MTCs and about 66% of the sporadic MTCs. So, the detection of the RET mutations is necessary for rapid and proper diagnosis and treatment. This systematic review seeks to find a comprehensive list of RET gene mutations in the diagnosis of medullary thyroid cancer.
The previous studies on RET proto-oncogene mutations in the diagnosis of medullary thyroid cancer were searched in the major databases including PubMed, Scopus, Medline, Embase and NCBI between 2010 and 2021.
Missense mutations in exons 10, 11, 13, 14, 15, and 16 of the RET proto-oncogene have the highest frequency in MTCs. The most common mutations in FMTC, are in codons 609, 611, 618, and 620 in exon 10, codon 768 in exon 13, codon 804 in exon 14, and codon 634 in exon 11. In the case of MEN2A, RET gene mutations have been observed in exons 5, 8, 10, 11, with the highest mutations in exons 10 (codons 609, 611, 618, and 620) and exon 11 (codons 630 and 634). Moreover, M918T mutation in exon 16 and A883F mutation in exon 15 have been detected in 95% and 5% of the patients with MEN2B respectively. In the case of MTC, the M918T mutation in exon 16 is the most common mutation, which is associated with a poor prognosis. RET genetic screening is crucial for an exact approach to the diagnosis and treatment of MTC. Anyone with MTC, even without a family history of MEN2, should be genetically tested for the RET mutations to confirm or rule out the inherited disease and, if necessary, preventive thyroidectomy. This systematic review provided a comprehensive list of the reported mutations in the RET gene for the diagnosis of medullary thyroid cancer.

---

Prostate cancer is the most common and second leading cause of death among men in the world. Nowadays, radiotherapy has been known as one of the most affecting methods for prostate cancer treatment. Nevertheless, radiotherapy is accompanied by the concern of developing secondary cancers by the scattered radiation to the neighbor  organs at risk. Several studies have shown that secondary cancers after the radiotherapy of prostate cancer treatment, occur in tissues such as the bladder and rectum which have been exposed to direct or indirect radiations. Therefore, this review study aimed to evaluate the influencing factors for developing secondary cancers after the radiotherapy of prostate cancer. To access the previously validated published studies, Persian and English keywords such as prostate cancer, secondary cancers, radiotherapy and organs at risk have been searched in ISID, Google Scholar, Science Direct, PubMed, and World Health Organization, between 1997 and 2021. Totally 246 pieces of literature have been selected which finally, by ignoring the similar and overlapping studies, only 40 studies were reviewed. In the present study, the most affecting factors for developing secondary malignancies including the anatomical status changes, dose variations, smoking and the impact of the various treatment techniques, have been studied. The results of the reviewed studies showed a reduction of secondary cancer risks with performing the modern modalities such as proton therapy to treat prostate cancer. Moreover, organ movements and anatomical status changes which vary from one patient to others, have been reported to make a significant difference in the relative risk of secondary cancers. It has been shown that smoking may increase the risk of secondary cancers after the radiotherapy of prostate cancer, so radiotherapy and smoking may cause genetic mutations. Despite the advantages of radiotherapy for prostate cancer treatment, developing secondary cancers after the radiotherapy should not be ignored. Assessments of the affecting factors for secondary cancers after the radiotherapy of prostate cancer require social and comprehensive studies which can result in an accurate modality with fewer side effects.

---

---

---

---

---

---

---

---

---

---

---

---

---