فهرست مطالب akbar akbari

Head and neck squamous cell carcinoma (HNSCC) with a high mortality rate is among the most commontypes of cancer in the world. Human epidermal growth factor receptor 2 (HER2) is expressed higher than normal levelin the most HNSCC tumors, making them resistant to chemotherapy and radiotherapy. Therefore, HER2 has beenintroduced as a suitable target for anticancer drugs. The aim of this study is to examine the efficacy of a treatmentprotocol involving targeted delivery of idarubicin encapsulated in trastuzumab-decorated liposomes to HNSCC cells. In the current experimental study, efficacies of idarubicin, prepared liposomal idarubicin,and constructed immunoliposomal idarubicin (trastuzumab-decorated) were investigated in killing HN5 cells, a HER2-overexpressing HNSCC-originating cell line. Liposomal content of idarubicin and trastuzumab were qualified by UVVisiblespectroscopy and preparations were characterized for shape and size by atomic force microscopy (AFM) anddynamic light scattering (DLS). To clarify role of the missing parts of the available crystal structure (PDB ID: 1n8z)within trastuzumab-HER2 interactions, we used a 40 ns molecular dynamic simulation approach. Based on the obtained results, liposomal idarubicin showed higher toxicity of the encapsulated drug on HN5cells compared to the traditional free drug formulations. The immunoliposomal form of idarubicin was more effectivethan the liposomal formulation, in killing of HN5 cells. In addition, simulation of interactions between trastuzumab andHER2 revealed that the missing parts (in the crystal structure) of HER2 have critical interaction with trastuzumab,through salt-bridges and hydrogen bonds. It seems that the prepared immunoliposomes could attach more efficiently to HER2 overexpressingcells, which consequently leads to increasing cellular uptake of idarubicin through a receptor-mediated endocytosismechanism. Moreover, simulation of the interaction between HER2 and trastuzumab suggested considerablepossibilities for increasing trastuzumab affinity to HER2.

The worldwide incidence rate for cancer has been rising. However, the molecular mechanisms involved in tumor growth and metastasis are unclear. Autophagy is a cellular pathway that leads to cell death or survival depending on the specific condition of the tumor cells. The aim of this study was to evaluate the effects of activation or inhibition of the autophagy pathway using tunicamycin or N-acetylcysteine on cell viability in the MDA-MB-231 breast cancer cell line.

MDA-MB-231 cells were cultured in the presence of different doses of tunicamycin or N-acetylcysteine. Then, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was performed for the evaluation of tumor cell viability. Real-time PCR was carried out to evaluate the expression of the genes encoding for Becline-1 and the mammalian target of rapamycin (mTOR) (as autophagy markers) in the MDA-MB-231 cell line. The LC3-II to LC3-I ratio and p62 were measured with western blotting.

Tunicamycin significantly increased autophagy markers and inhibited cell viability in a time- and dose-dependent manner. A negative significant correlation was observed between the expression of autophagy markers and cell viability. However, N-acetylcysteine resulted in decreased autophagy and increased cell viability just at a concentration of 2mM.

Tunicamycin leads to activation of the autophagy pathway, resulting in a decrease in cell viability in breast cancer cells (MDA-MB-231); and N-acetylcysteine, at a low concentration, can inhibit autophagy and increase cell viability. Thus, the autophagy pathway can be considered a target in cancer treatment.

Most cancer studies focus on exploring non-invasive biomarkers for cancer detection. In the present study, we sought to investigate the expression level of microRNA-21 (miR-21), as a potential diagnostic marker, in serum and stool samples from 40 patients with colorectal cancer (CRC) and 40 healthy controls.
Quantitative real-time RT-PCR was applied to determine the relative expression level of miR-21 in serum and stool. At the same time, the sensitivity and specificity of this marker was evaluated by receiver operating characteristic (ROC) curve analysis.
miR-21 expression levels of serum and stool were up-regulated 12.1 (P The results of this study indicated that miR-21 expression levels in serum and stool can be considered as a potential diagnostic biomarker for the diagnosis of CRC patients. However, more studies are required to confirm the validity of miR-21 as a valuable non-invasive diagnostic tool for CRC.

Multiple sclerosis (MS) is a chronic autoimmune disease due to demyelination of the central nervous system. It is believed that cytokines are involved in the pathogenesis of MS. The interleukin-2 (IL2) gene is powerful functional candidate that is involved in immune regulation and operation. In this study, for the first time, we investigated the effect of -475 A/T and -631 G/A IL2 polymorphisms on MS disease in Iranian patients. In this case-control study, 100 MS patients (mean age: 32.95 ± 6.51 years, age range: 20-42 years) selected according to McDonald criteria, and 100 ethnically, sex and age matched healthy controls (mean age: 29 ± 7.8 years, age range: 20-52 years) with no personal or family history of autoimmune diseases were studied. The restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) method was applied to define different alleles and genotypes of IL2 promoter single nucleotide polymorphism -475 A/T as well as -631 G/A among individuals. χ2 was calculated and Fisher’s exact test was applied to analyze the obtained data. The value of p <0.05 was considered significantly. Evaluation of the -475 IL2 revealed that T allele and A/T genotype are present in 2% and 4% of MS patients, respectively, whereas T allele was absent in control samples. The comparison between alleles and genotypes in MS patients and healthy controls was not significant (p=0.1). For the -631 position, 1% and 2% of MS patients carried A allele and A/G heterozygote genotypes, respectively. All control samples had G allele and G/G genotype. The differences between patients and controls were not significant (p=0.4). Moreover, our results showed a very low frequency of T at -475 and A at -631 IL2 position in each of the two groups. Both -475 and -631 IL2 polymorphisms were higher in MS patients as compared to controls, but the frequency differences were not significant. Based on these data, it is suggested that the -475 and -631 IL2 polymorphisms as functional promoter position may be involved in IL2 expression and regulation. To find out the exact effect of the mentioned SNPs on susceptibility to MS, study on a larger sample size is suggested.

Patients with Thalassemia Major suffer from different skeletal deformities. This study was carried out to compare the rate of deformities between patients with Major and minor thalassemia.

This historical cohort study was done on 87 patients with major thalassemia (case group) and 87 patients with minor thalassemia (control group). Indices of skeletal abnormalities of the spine (inclined neck, forward head, asymmetry of shoulders, kyphosis, scoliosis, and lordosis) were measured in 2 groups and compared by chi-square test.

Comparison of inclined neck and asymmetry of shoulders between major and minor thalassemic patients showed no significant difference however the frequency of forward head deformity, kyphosis, scoliosis and lordosis between patients with major and minor thalassemia was significantly different (p<0.05).

Incidence of spinal abnormalities in patients with thalassemia major is significantly higher than individuals with minor thalassemia. We recommend that the effect of exercise on prevention and treatment of spine abnormalities should be evaluated.