Tehran University Medical Journal

Cancer is the major cause of death in the world and the rate of mortality is higher in developed countries. Therefore, lifestyle could be effective in promoting the cancer. The pancreatic tumors, are 8th cause of mortality due to cancer, which have several types, among them ductal adenocarcinoma is the most common and includes 85% of cases. Since, it is almost impossible to diagnosis the tumor in early stages of the disease, it contributes to high rates of mortality, although if it diagnosis in early stage and the surgery performed for them only 10-20% of patients will be survived. Metastasis occurs when the tumor is smaller than 2 cm in size and because the pancreas is located in the depth of abdomen, typically, it happens after tumor is spread to other organs. A combination of medical imaging, blood tests, and examination of tissue samples are usually made for diagnosis and based on the cancer stage, surgery, radiotherapy and chemotherapy are chosen as treatment options. Some rare genetic variations can cause pancreatic cancer and about 5-10% of cases are linked to inherited genes. However, major risk factors are including age, obesity, tobacco smoking and diabetes. Smoking counts for about 25% of cases, and the diabetes is the main symptoms of pancreatic cancer, which observed in about 80% of cases. But, it is still unclear whether diabetes is a predisposing factor in pancreatic cancer, or the outcome of tumor progression. Recent studies have shown that, diabetes is unique in pancreatic cancer which is not related to common types. Currently, CA 19-9 is the only reliable tumor marker for pancreatic cancer that its frequency also increases in non-bad conditions, such as pancreatitis and obstructive jaundice, so is not sensitive and specific enough for diagnosis of this cancer. Due to researches continue to find more specific markers. In this review the etiology of pancreatic cancer, diabetes associated with this type of cancer and significant biomarkers for diagnosis will be considered.

Infertility influences an estimated 20% of couples worldwide. The factors that can affect the fertility potential are equally distributed between men and women. Despite extensive research in male infertility, the etiology in majority of infertile men is unknown. In 2010, there was an opinion published in Nature asking a selection of leading researchers and policy-makers about what their future focuses will be in 2020. Metabolomics was mentioned as the leading omics technology by them. The word metabolomics has been defined almost 20 years ago. However, the clinical metabolomics history goes back to more than 1,000 years ago. The great Persian physician and philosopher Avicenna observed an individual urine changes during illness. Today, the color or smell changes are known to be caused by metabolites deregulation indicating metabolic diseases. Metabolomics approach is a systematic analysis of the unique pattern followed by a specific biochemical pathway that uses a biological material, e.g. spermatozoa or human seminal plasma. For the diagnosis of infertile men, the typical parameters of semen analysis are: sperm motility, sperm morphology, concentration and count. Human seminal plasma is a valuable biological source which was not used in the diagnosis of infertile men, unfortunately. To the best of our knowledge, there is no parameter for analysis of the human seminal plasma. Thus, the need for a novel parameter to diagnose infertile men is urgently needed. We recommend the use of seminal plasma in order to diagnose infertile men according to our previous research. Only a handful studies have used metabolomics approaches in the male infertility. In this study, we summarize the current research and our contribution to the field of male infertility and metabolomics. One of our main contributions has been to use metabolic profiling of seminal plasma from non-obstructive azoospermia to find 36 potentials biomarkers for detection of spermatogenesis. A search in the PubMed using keywords “metabolomics” and “infertility” shows only 59 publications. This demonstrates how newborn the metabolomics in its application for male infertility is. In this review article we have tried to have a comprehensive and specific approach to male infertility from a metabolomics perspective and related techniques.

Gastric cancer (GC) is the second leading cause of cancer-related deaths worldwide. It has been proposed that the specific genotypes of Helicobacter pylori (H. pylori) are the causative agents in the development of gastroduodenal diseases, such as chronic atrophic gastritis, peptic ulcerations, and GC. However, disease progression to GC occurs in only a small proportion of infected patients. Recently, we identified a novel polymorphic site in the 3ʹ-end region of H. pylori vacA gene. The vacA c1 genotype increased the risk of GC. This association was independent of and larger than the associations of the m-, i-, and d-type of vacA or cagA status with GC. Therefore, treatment of H. pylori infection may be an effective way to prevent GC. Expression of cytokines and their associations with inflammatory responses has been shown. Several cytokine polymorphisms, such as IL-1B, IL-8, IL-10, and TNF-α have been considered as risk factors for GC. It has been shown that the interaction of bacterial genotypes and host factors plays an essential role in developing GC. Several altered molecular pathways are involved in the pathogenesis of GC. Micro-RNAs are small, non-coding RNAs of 18-25 nucleotides in length that regulate the expression of target mRNAs. Expression pattern of cancer cells is different compared with the normal cells. Micro-RNAs plays a critical role in apoptosis and classified in two groups: pro- and anti-apoptotic agents. Recent studies have confirmed the oncogenic or tumor suppression role of micro-RNAs in cancer cells. They play a significant role in the GC cell physiology and tumor progression, by translational suppression of target genes. These small RNAs have therefore emerged as a new type of GC biomarker with immeasurable clinical potential. Generally, a variety of micro-RNAs involved in different stages of cancer, including tumorigenesis, angiogenesis, and metastasis. Considering to this issue more than 50% of cancers can be cured, if they were diagnosed in the early stages. Hence, identifying the biomarkers of GC could play an important role in prevention, early diagnosis and rapid treatment of patients. In this review article, we have reviewed the latest findings about bacterial and tissue biomarkers of GC

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: 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.