فهرست مطالب negin saffarzadeh

Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary kidney disease that can affect several organs. The clinical course of the disease varies among patients; some never become symptomatic, and others reach end-stage kidney disease (ESKD) in the 5th decade of their life.

This historical cohort study was conducted on ADPKD patients to investigate kidney and patient survival rates and related risk factors in Iran. Survival analysis and risk ratio calculation were performed using the Cox proportional hazards model, Kaplan– Meier method, and log-rank test.

Among the 145 participants, 67 developed ESKD, and 20 died before the end of the study period. Developing chronic kidney disease (CKD) at the age of ≤ 40, baseline serum creatinine level (SCr) of more than 1.5 mg/dL, and cardiovascular disease increased the risk of ESKD by 4, 1.8, and 2.4 times; respectively. Patient survival analysis revealed a fourfold increase in mortality if the glomerular filtration rate (GFR) declined more than 5 cc/min annually and if CKD was diagnosed at the age of ≤ 40. Vascular thrombotic events or ESKD in the course of disease increased the risk of death by approximately 6- and 7-fold, respectively. Kidney survival was 48% by the age of 60 and 28% by the age of 70. Patient survival was 86.05% at the age of 60 and 67.99% at the age of 70. Additionally, men had a significantly better renal function and survival than women.

Elevated baseline SCr and cardiovascular disease can increase ESKD risk in ADPKD patients. A rapid decline in GFR, ESKD development, and vascular thrombotic events increase the risk of death, but early CKD can affect both.

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.

Although several chemical and physical methods for gene delivery have been introduced, their cytotoxicity, non-specific immune responses and the lack of biodegradability remain the main issues. In this study, hydroxyapatite nanoparticles (NPs) and 1,2-dioleoyl-sn-glycero-3-phosphoethanol​amine (DOPE)-modified hydroxyapatite NPs was coated with antisense oligonucleotide of E6 mRNA, and their uptakes into the cervical cancer cell line were evaluated. Calcium nitrate and diammonium phosphate were used for the synthesis of the hydroxyapatite nanoparticle. Thus, they were coated with polyethylene glycol (PEG), DOPE and antisense oligonucleotide of E6 mRNA using a cross-linker. Then, hydroxyapatite NPs and DOPE-modified hydroxyapatite NPs were incubated 48 hours with cervical cancer cells and their uptakes were evaluated by fluorescent microscopy. The hydroxyapatite NPs had different shapes and some agglomeration with average size of 100 nm. The results showed DOPE-modified hydroxyapatite NPs had higher uptake than hydroxyapatite NPs (P<0.05). Hydroxyapatite NPs conjugated with DOPE are a good choice for gene delivery and silencing of viral genes in cervical cancer cells, but their efficacy should be addressed more in future studies.