مجله دانشکده پزشکی دانشگاه علوم پزشکی تهران
سال هفتاد و ششم شماره 8 (پیاپی 212، آبان 1397)

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.

Pseudomonas aeruginosa is an opportunistic pathogen and one of the important factors of hospital infection. It causes many issues such as urinary tract infections, respiratory infection in cystic fibrosis patients, and wound infection in burn patients, septicemia and meningitis. Antibiotic resistance through various mechanisms is one of the challenges for the treatment of pseudomonad-caused infections. According to the inherent and acquired capacity of this bacterium in creating resistance against the antimicrobial factors, it is very important to identify a pattern for its antibiotic resistance. The aim of this study was to deliberate the frequency of pattern antibiotic resistance of pseudomonas aeruginosa strains. In this cross-sectional study, 200 pseudomonas aeruginosa isolations (from 86 males and 114 females) were collected from different samples such as urine, blood, wound, catheter and other samples from teaching hospitals in Zahedan City during nine-month period in 2017. After conducting biochemical tests and confirming bacterium type, based on Clinical Laboratory Standards Institute (CLSI), the antibiotic resistance of strains for 10 antibiotics was determined using disk diffusion method. In addition, the minimum inhibitory concentration of three antibiotics such as imipenem, piperacillin/tazobactam and ceftazidime were determined through E-test. The Chi-square test was used for statistical analysis through the SPSS software, version 16 (IBM SPSS, Armonk, NY, USA). Out of 200 pseudomonas aeruginosa isolations (from 86 males and 114 females), the maximum resistance was related to ciprofloxacin (37%) and gentamicin (28.5%). The minimum resistance was related to piperacillin/tazobactam (6.5%) and ceftazidime (6%). The highest separated strain was from urine sample (54%), blood sample (23.5%) and wound sample (10.5%). Additionally all strains were sensitive to colistin. In this study, the percentage of multidrug-resistance (MDR) and extensively drug-resistant (XDR) strains were investigated, which were 13% and 5.5%, respectively. In this study, pseudomonas aeruginosa isolates had the lowest resistance to ceftazidime which this antibiotic could be the main treatment option. The high prevalence of MDR strains is a serious warning.

Estrogen-negative breast cancers have different clinical course, prognostic features and treatment response in comparison to estrogen receptor-positive (ER-positive) breast cancers. Human epidermal growth factor receptor 2 (HER2) oncoprotein has found to have a pivotal role in natural cell growth and cell division and is suggested to be directly related to tumor invasiveness in breast cancer patients. The purpose of this study was to retrospectively assess the mammography, ultrasound, and magnetic resonance imaging (MRI) features of estrogen negative breast cancers with and without overexpression of HER2/neu receptor. In this cross-sectional retrospective study, mammographic, ultrasound and MRI features as well as HER2 status were assessed in patients with ER-negative breast cancer that were referred to Cancer Institute of Imam Khomeini Hospital Complex in Tehran from October 2015 to October 2017. Clinicopathologic data and mammography, ultrasound, and MRI features were reviewed and were correlated with HER2 status of estrogen-negative tumors. Of the 172 patients with ER-negative breast cancer, 101 patients were positive for HER2/neu receptor (58.8%). There was a significant correlation between HER2-positivity and tumor type (P=0.004). Among estrogen negative breast cancers, significant association were found between HER2 and tumor histologic grade (P=0.024) and TNM stage (P=0.021). HER2-positive tumors were more likely to present with microcalcification (P=0.007) and have irregular shapes (P=0.034) in mammography than HER2-negative tumors. No association was found between HER-2 status and tumor size, shape, margin, posterior feature, halo or orientation of the tumor in ultrasound. We also found no correlation between HER2 status and MRI features including mass shape or margin, internal enhancement pattern or curve type among estrogen-negative breast cancers. Findings of this study showed that among estrogen-negative breast cancers, HER2/neu positive tumors are more likely to be diagnosed at higher stage and have higher histologic grade at the time of diagnosis. Tumor mass shape and microcalcification in mammography are found to be associated with HER2 status among patients with estrogen-negative breast cancer.

Osteoporosis is the most common metabolic disease of the bone in the world, and has hit about 200 million people around the world and it increases the risk of fractures. More than 5 million osteoporotic fractures occur annually in the world. Bone mineral density is the standard method of diagnosis of this disease. In this method, proximal of femur (neck) and lumbar vertebra bones (L2, L3, L4, L5) are typically evaluated. The aim of this study was determine the bone density profile of one third of distal radial bone in patients with primary osteoporosis. This cross-sectional study conducted at Shahid Beheshi hospital in Hamadan city, from October 2015 to October 2016. Among of the patients, those over the age of 50 years old, 71 patients were selected by convenience sampling method taking into account if they have inclusion criteria (such as: age> 50 years, no systemic diseases, no history of corticosteroid use). For all patients that enter the study, lumbar, femoral neck and one third of distal radial bone densitometry was done by dual X-ray absorptiometry (DXA) method. Osteopenia and normal bone density the World Health Organization criteria were used to determine osteoporosis. In this research 71 people entered the study. The mean age of the patients was 62.25±9.36 (51-92) years. In term of gender 5.63% of patients were male and 94.37% female. Pearson correlation coefficient showed a positive and significant correlation between the results of one third of distal radius with neck and total femur bone and lumbar bones (P<0.05). Correlation between the T-score of one third of distal radius and total femoral neck was statistically significant (P<0.05). The mean age of patients was 62.25±9.36 years. According to the findings of this study one third of distal radial bone mineral density has an acceptable sensitivity to detect osteoporosis. Radius bone density decreases much faster than lumbar, vertebra and femoral neck.

The transverse abdominis (TrA) muscle is one of the most important muscles that contribute to the stability of the lumbar spine. Strengthening of trunk muscles that have a significant role in trunk stability is very important in the field of professional sport, sport medicine and rehabilitation of patient with low back pain (LBP). Identifying the exercises that can improve the strength and endurance of these muscles in the efficient way is an important challenge in rehabilitation of LBP patients. The aim of this study was to investigate the effect of maximum voluntary isometric contraction of upper and lower limb muscles on ultrasonic thickness of the TrA muscle. This is a pre-test post-test study. Thirty healthy young male subjects with mean age of 23 years were recruited from the university staff and student population (non probability sample). Ultrasonic thickness of the right and left TrA muscle (as an indirect measure of muscle activity) was taken at rest and during maximum isometric contraction of six muscle groups: shoulder and hip flexor, extensor and abductor muscles. Mixed-model ANOVA with repeated measures design were used to analyze data. To further analyses post hoc comparisons were performed with paired t-tests adjusted with the Bonferroni method. The significance level was set at P<0.05. The result showed that mean TrA thickness on right and left sides during maximum isometric contraction of the upper and lower limb muscles was significantly thicker than in resting position (P<0.001). The type of isometric contraction had a significant effect on the thickness of the TrA muscle on dominant side (P<0.05). As a result, the greatest change in the thickness of TrA muscle on dominant side was observed in hip isometric extension (P<0.05). There was a significant difference between the thickness of TrA during upper limb isometric contraction of dominant and non-dominant side (P<0.001). Isometric contraction of upper and lower limb muscles especially in hip extension can increase the ultrasonic thickness of the transversus abdominis muscle.

Re-epithelialization has an important role in skin wound healing. Delays in re-epithelialization are more likely to create the chronic wound. Impaired wound healing leads to a large burden of morbidity and mortality. Current treatments based on the use of autografts, allografts and xenografts, suffer from limitations such as, quantity of donor skin available, donor-site infection, potential risk of disease transmission and rejection of the graft. Given this problems, nanomaterial such as copper nanoparticles has attracted considerable research interest because of their high surface area to volume ratio, high stability, clinical safety, and antibacterial effects. Epithelialization involves keratinocyte migration and proliferation to the wound site. Therefore, this study was conducted to investigate the effect of copper nanoparticles on keratinocyte cell migration and proliferation. This experimental study was performed in Royan Institute, Tehran in 2016. In this study we investigated the effect of copper nanoparticles on viability, migration and proliferation of keratinocyte cells. Cultured human foreskin Keratinocyte cells were exposed to various concentration (1, 10 and 100 µmol) and sizes (40 and 80 nm) of copper nanoparticles for 24, 48 and 72 hours. The copper nanoparticles toxicity was examined by MTS assay. Cell migration has also been investigated with the Scratch assay. The results showed that the 1, 10 and 100 µmol concentrations of 40 and 80 nm copper nanoparticles were not toxic for cultured human foreskin keratinocyte cells after 24h. It was also found keratinocyte cell proliferation was increased by 1 µmol concentration of 80 nm copper nanoparticles after 72h. The results of the Scratch assay showed that the 1 µmol concentration of 80 nm copper nanoparticles significantly (P<0.05) increased keratinocyte cell migration compared to deionized water as of control group after 24h. It seems the 1 µmol concentration of 80 nm copper nanoparticle could stimulate keratinocyte cell migration and proliferation. However, in vivo studies conducted on animal model wound healing subjects are needed for determining re-epithelialization.

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. 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. 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). Higher diet diversity score is associated with reduced risk of breast cancer.

In forensic anthropological identification, we usually use body remains. Accurate sex estimation from these remains is very important and needs the knowledge of specific population standards of that area. Sometimes, human remains are damaged by environmental circumstances. So, we must examine single bones for sex estimation. One of the relatively resistant bones to environmental conditions are hand bones. Specific hand phalanges and metacarpals have significantly different dimensions in two sexes depending to each population and can be a helpful tool to estimate the gender of individuals. The aim of this study was to investigate the possibility of estimating gender using phalanges and metacarpals dimensions in Iranian people. This prospective study was conducted on the X-ray images of adult people hands between the months of March and September 2017. They referred to Shafayahyaian Hospital, the educational and referral center of orthopedic disease of Iran University of Medical Sciences, in Iran. 200 adult persons (100 male and 100 female) without any background of specific disease, entered in our study. In each case, the length of D: distal phalanx, M: middle phalanx, P: proximal phalanx, MC: metacarpal, Fl: finger length, and T: total (Distal phalanx+middle phalanx+proximal phalanx+soft tissue of the finger tip) were measured in millimeter and reported in ratio. All analyses were done using SPSS software, version 20 (SPSS Inc., Chicago, IL, USA). Student t-test showed that many ratios were significantly different between two genders. It is concluded that the length ratio of metacarpals and phalanges could be used for sex determination. The most valuable ratios were FL1/FL3 and MC4/MC5. Multivariate logistic regression test reported an equation by which the gender is predictable. Z= 5.856+ -3.904 X FL1/FL3+ -1.865 X MC4/MC5. If “Z=0”, the gender is male and if “Z=1”, it is female without any doubt. In our knowledge, this study provides the first population sex estimation formulae from the hand bones in Iranian population. However, we need further studies in larger groups to use this equation for sex determination in forensic contexts.

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). 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). 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). 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.

Sexually transmitted infections are the most common human infections that lead to severe complications. Mycoplasma genitalium (MG) and Ureaplasma urealyticum (UU) are common and important cause of genitourinary tract infections. MG is a member of genital mycoplasmas which is emerging as an important causative agent of sexually transmitted infections both in males and females. This study aimed to determine the prevalence of UU and MG in pregnant women and to assess the risk factors which may contribute to the predisposition of the individuals to the infection. In this cross-sectional study, The population of 210 pregnant women admitted to the Rasoul Akram Hospital in Tehran, were selected for the study using non-random sampling. The urine specimens were collected from 194 pregnant women from May to December, 2015. The samples were transferred to the Infectious Disease Research Center of Rasoul Akram Hospital under sterile condition. Samples were exposed to DNA extraction followed by multiplex polymerase chain reaction (PCR) to detect the infection. Data including sex, age, history of abortion, history of genitourinary tract infections were collected subsequently. The prevalence of MG and UU infections in urine samples was 5.6%, 11.2%, respectively. The mean and standard deviation of the risk of UU was 2.08 (3.56-1.22) in women with a history of abortion and 0.70 (1.03-0.47) in women without a history of abortion. There was a significant relationship between the history of sexually transmitted diseases and the frequency of UU (P<0.022). From 22 patients with UU infection, six patients had a history of sexually transmitted diseases. A significant correlation was found between prevalence of MG and UU infections. The History of abortion was significantly related with the frequency of UU and MG infections. The prevalence of MG infection is negatively correlated with pregnancy trimesters. The History of genitourinary tract infections was significantly associated with the frequency of UU. The presence of UU and MG could be associated with abortion.