Original Article

Monomethyl auristatin E Exhibits Potent Cytotoxic Activity against Human Cancer Cell Lines SKBR3 and HEK293

Meghdad Abdollahpour-Alitappeh, Sepand Razavi-vakhshourpour, Majid Lotfinia, Saeed Jahandideh, Hamid Najminejad, Saeed Balalaie, Reza Moazzami, Elnaz Shams, Mahdi Habibi-Anbouhi, Mohsen Abolhassani

Novelty in Biomedicine, Vol. 5 No. 4 (2017), , Page 145-151

Background: Monomethyl auristatin E (MMAE) is a synthetic analog of dolastatin 10, a compound originally isolated from the marine mollusk. MMAE, as a highly potent microtubule inhibitor, exerts its potent cytotoxic effect by inhibiting microtubule assembly, tubulin-dependent GTP hydrolysis and microtubes polymerization. This molecule, by itself, lacks the tumor specificity required to elicit therapeutic benefit. Nevertheless, the extremely cytotoxic potential of MMAE could be harnessed in the form of MMAE-antibody conjugates. The aim of the present study was to evaluate the cytotoxic activity of MMAE against breast (SKBR3) and kidney (HEK293) cancer cell lines in an in vitro cell-based assay.

Materials and Methods: SKBR3 and HEK293 cells were treated with different concentrations ranging from 0.002048, 0.01024, 0.0512, 0.256, 1.28, 6.4, 32, 160, 800 and 4000 nM of MMAE, and cell viability was determined after 72 hours using an MTT colorimetric assay. The effect of MMAE was regularly monitored by direct observation using an invert microscope.

Results: Microscopic observation showed that there was a concentration-dependent increase in cell death. Results from the MTT assay revealed a statistically significant loss of viability (P<0.0001) at concentrations ranging from 0.01024 to 4000 nM in SKBR3 cells, and 0.0512 to 4000 nM in HEK293 cells. Our findings showed that MMAE inhibited the growth of SKBR3 and HEK293 cells in a concentration-dependent manner, with IC50 values of 3.27 ± 0.42 and 4.24 ± 0.37 nM, respectively.

Conclusion: MMAE was able to significantly inhibit cell growth at nanomolar concentrations, emphasizing its great potential for the development of antibody-drug conjugates.

Seroprevalence of Toxoplasma gondii in Military Personnel and their Families Referred to the Military Hospital in Tehran, Iran

Hamid Reza Bitaraf, Zahra Arab-Mazar, Mohamad Ghanimatdan, Mostafa Mohammadi, Mahdi Mohseni, Sadjjad Parsipour, Aliyar Mirzapour, Mohsen Rahimi

Novelty in Biomedicine, Vol. 5 No. 4 (2017), , Page 152-157

Background: Toxoplasmosis is one of the world's most common infections in human and other warm-blooded vertebrates and has the most extensive universal spread. The purpose of this study is determining the seroprevalence of human Toxoplasma gondii infection, in the military personnel and their families referred to Baqiyatallah hospital, 2011-2015.

Materials and Methods: In this cross-sectional study, the serum of 3370 person contain 770 men and 2600 women attending the laboratories were selected and after completing the questionnaires and also by implementing Chemiluminescence method, these serums were examined for the presence of IgM and IgG immunoglobulins of the Toxoplasma gondii.

Results: The results were analyzed using the chi-square test. They showed that there were no statistical relationships between the prevalence of IgG and gender in 2011, 2013, (P>0.05) but there were significant relationships between them in 2012, 2014 and 2015 (P<0.05), also there were no statistical relationships between the prevalence of IgM and gender in all years (P>0.05). The results showed that there were statistical relationships among IgG and age (P<0.01) but there was no statistical relationships between IgM and age in all cases (P>0.05).

Conclusion: The results showed high prevalence of Toxoplasmosis in the military personnel and their families in Baqiyatallah hospital. The prevalence of IgG was somehow in the range and positive IgG titer was somewhat higher than what was reported in other studies in the North-West of the country; this could be partly due to the sensitivity and specificity of Chemiluminescence method compared to other methods of serology in diagnosis of Toxoplasmosis.

Breast Incidental Lesions at 18 F FDG PET/CT: Diagnostic Performance of PET-derived Metabolic Parameters

Mehrdad Bakhshayeshkaram, Farahnaz Aghahosseini, Razieh Hashemi, Maryam Hassanzad, Hamid Reza Jamaati

Novelty in Biomedicine, Vol. 5 No. 4 (2017), , Page 158-165

Background: Breast incidental lesion at 18 F FDG PET/CT are occasionally encountered in cancer patients, which may represent a second primary malignancy. The aim of the present study was to investigate the diagnostic performance of PET metabolic parameters to characterize breast incidentaloma.

Materials and Methods: All the images of patients with cancers other than breast with breast incidental lesion underwent PET/CT scan at Masih Daneshvari Hospital between May 2012 and May 2016 were retrieved and reviewed. SUVmax, SUVmean, MTV and TLG in addition to associated morphologic features on CT and demographics were recorded and correlated with final diagnosis defined by histophatologic confirmation or an at least 1-year clinical formal follow up.

Results: Of a total 58 from 51 patients (51/5029, 1.01%), 10 (19.60%) were histopathologically verified as second primary breast cancers. There was a statistically significant difference in SUVmax, SUVmean, MTV and TLG between benign and malignant group (1.64 vs. 5.32 (p=0.009), 1.34 vs. 3.69 (p=0.027), 0.96 vs. 2.62 (p=0.035), 1.54 vs 8.89 (p=0.006). Using cut off 2, 1.35, 1.16 and 1.75, sensitivity and specificity of SUVmax, SUVmean, MTV and TLG were calculated as 77% and 62%, 92% and 66.5%, 77% and 75% 77% and 67%, respectively.

Conclusion: Despite a significantly higher value in malignant breast incidental lesion, PET-derivative metabolic parameters provided only modest sensitivity and specificity and hence may not be considered as the sole criteria for risk stratification in this clinical setting.

Morphological Study of Fasciola Parasites Isolated from Cattle and Sheep in Golestan Province (Iran)

Ahmad Halakou, Hooshang Khazan, Mojgan Bendehpour, Bahram Kazemi

Novelty in Biomedicine, Vol. 5 No. 4 (2017), , Page 166-171

Background: The genus Fasciola parasite causes fascioliasis infection. Fascioliasis is widespread all around the world and it is finding in abundance in the northern provinces of Iran. Cattle and sheep are the main hosts of the Fasciola parasite and intermediate hosts are lymnaeid snails such as Galba and Fossaria. Two main species of this genus are F. hepatica and F. gigantica. One of the most important methods of diagnosing this worm is morphological method. The aim of this study is to identify Fasciola through the morphological method in Golestan province.

Materials and Methods: Fasciola worms taken from infected livestock livers were washed three times with PBS and were stained with carmine alum. After staining using Valero و and Periago Periago methods, the worms were measured morphologically by و   بcalibrated میکروسکوپ microscope, واستریومیکstereomicroscope, and True Chrome II camera. SPSS version 19 was used for analysis of the data.

Results: A total of 45 livers from infected sheep and cattle with Fasciola worms were taken out of 228 samples, including 84 Fasciola hepatica (36.18%), 117 Fasciola gigantica (51.31%) and 27 Fasciola  sp. (11.84%).

Conclusion: This مطالعه study نشان showed داد کهthat هر the two main species of worms that isگ شاخصF.hepatica وand F. gigantica were foundژیگانتیکا inبه فراوانیabundance یافتin Golestan province. The current study was unable to identify 11.84% genus Fasciola showed as Fasciola sp.

Background: Hepatitis C infection is a worldwide problem. In Iran, hepatitis C virus (HCV) infection prevalence is about 1-2%. A combination therapy of pegylated interferon alfa-2a and ribavirin (PEG-IFNa/RBV) is a standard treatment, but our aim was to determine the efficacy and safety of dual PEG-IFNa/RBV therapy in treating patients infected with HCV in Iranian context.

Materials and Methods: This study is a cross sectional conducted among 98 HCV infected patients who were admitted to Labbafinezhad Hospital (Tehran, Iran) for treatment from April 2014 to September 2016. Patients were medicated with Peg Interferon Alfa (INFα) and Ribavirin (RBV). Lab tests were monitored through the study and dose modification was done. We also assessed treatment responses at the defined time points. The incidences of adverse events were determined either. We investigated independent predictors of sustained virologic response (SVR) in the participants. Finally, data were gathered and statistical analysis was completed.

Results: Eighty-eight percent of patients were male and 11.2% were female. Mean age was 43.44 years. Patients were mostly male, single, with nongovernmental business and low level of education. Risk factors were known to be addiction with non-injectable substances and phlebotomy. Myalgia, fatigue and malaises were the most common complications and suicide intention was the least one. SVR was estimated 76.7%. AST and ALT were significantly reduced in treatment period.

Conclusion: Peg INFα and RBV are effective in treating HCV infection.

Effect of Moderate Treadmill Exercise on hip Osteoarthritis in Male and Female Wistar Rats

Ramona Mosavian Naeini, Mansour Sahebalzamani, Mohammad Naser Nazem

Novelty in Biomedicine, Vol. 5 No. 4 (2017), , Page 177-184

Background: Osteoarthritis (OA) is a slowly progressive degenerative disease characterized by gradual loss of articular cartilage. The influence of excessive running load on the development of knee OA was investigated in male Wistar rats. This study was done to test the sex-related difference in the risk of OA of the hip joint after moderate running exercise.

Materials and Methods: Forty male and female Wistar rats were randomly assigned to four equal groups (2 male and 2 female groups) in a same condition. Ten of each sex were selected as control groups and kept separately while running exercises were performed in remained 20 male and female rats using a motor treadmill to motivate rats to run daily distances of 1 km at 5 days/week within six weeks. The treadmill incline was zero. On day 43, all control and training animals were killed and the hip articular cartilage and its synovial layer were evaluated microscopically.

Results: The appearance of hip articular cartilage was normal and similar in all male, female and also male running groups while female running group showed some changes. Obtained results showed a mild OA only in the female running group. There wasn’t seen synovitis in both male and female running groups in comparison with control groups (P>0.05).

Conclusion: This study showed that the development of hip OA may be related to the sex differences as seen in the knee OA previously.

Case Report

Background: Septic Thrombophlebitis is one of the rare complications of hysterectomy, which is well known through an uncontrolled fever after wide spectrum antibiotic therapy. One of the very rare pathogens to cause bacteremia in this situation is Klebsiella pneumonia, which is a vaginal normal flora. Although it is accepted that the main treatment for thrombophlebitis is anticoagulant therapy, however, in cases with co morbid bacteremia antibiotic therapy remains a critical procedure.

Cases Report: We present a case with a history of recent hysterectomy who was admitted to the Vali-e-Asr hospital of Zanjan with uncontrolled high fever 72 hours after her surgical procedure.

Conclusion: Fever is one of the most common post-surgical complications which could be due to post- operative infections. Thrombophlebitis of pelvic veins is one of the very rare complications which can alternatively cause bacteremia. Although uncommon, Klebsiella could be the leading cause of bacteremia. So it is important to consider a thorough work up in patients presenting with fever after hysterectomy.

Letter to editor