Cancer is one of the main causes of death all over the world, accounting for about 10 million deaths in 2020. On the other hand, a lot of money, time and energy are spent in the treatment process of this disease. In fact, cancer is a big challenge that we have been facing for years, but there is still no method that can definitively cure this disease. For years, we have mainly used surgery, chemotherapy and radiation therapy to treat cancer. Although many advances have been made in these methods, these methods are not a definitive cure for all types of cancer and also have many complications and impose high costs on patients. By the high success of Chimeric Antigen Receptor (CAR) T cell therapy in the treatment of leukemia, hopes for effective treatment for various types of cancer increased, but by testing this method in solid tumors, it was found that this method has low efficiency in solid tumors. In this review article, I consider the challenges and mechanisms that cancer cells apply to resist different main therapies, and finally, by comparing the challenges of different therapies, I conclude that virus therapy has a higher potential than other methods to end the problem of cancer and become a definitive cure for cancer.

Abstract

Background: PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome is a rare autosomal dominant autoinflammatory disorder caused by mutations in the PSTPIP1/CD2BP1 gene. We systematically reviewed 93 patients with PAPA and PAPA-like syndrome.Most patients were male (65.9%) mainly born to non-consanguineous parents. The median (IQR) age at the onset of symptoms and diagnosis was 6.0 (2.0-8.0)  and 25.0 (7.0-32.0) years, respectively. 62.5% of patients were presented with arthropathies and septic arthritis was the most common (54.2%) initial diagnosis. Joint disorders were the most common findings (n=71, 78.9%) starting at the median (IQR) age of 4.0 (2.0-8.0) years, mainly in the knee (56.5%), ankle (36.9%), and elbow (47.8%).

Skin involvement (62 (66.7%)) initially presented at a median (IQR) age of 12.0 (20.-10.0) years and included pyoderma gangrenosum (n=41, 44.1%), acne (n=43, 46.2%), and nodulocystic acne (n=19, 20.4%).

There was a stronger association between skin manifestations and the development of classic triad (P<0.001) compared to joint disorders (P=0.05) and patients with lower age of onset were more prone to the progression of the complete triad (p=0.18). Corticosteroids (n=45, 50.0%) with or without anakinra (33.3%) were the treatments applied in the majority of patients.

Conclusion: PAPA/PAPA-like syndromes involve mainly non-axial joints in early childhood and later skin in the second decade of life. Only 26.4% of the patients manifested the classical triad of PAPA syndrome. There is no clear genotype-phenotype association in these disorders. More studies are required to investigate the therapeutic options in PAPA/PAPA-like syndromes.

Immune system has a critical tumor suppressor function via detection and elimination of the tumor cells. Tumor cells immune escaping is commonly observed during neoplastic transformations. Immune response suppression or aberrations facilitate immune escape that promotes tumor progression in distant or primary locations via epithelial-mesenchymal transition and angiogenesis, respectively. It has been reported that there is a rising trend of cancer incidence among Iranian population. Since, aberrant immune responses are involved in tumorigenesis; immunotherapeutic methods can be efficient for the tumor cells elimination. In the present review, we discussed all of the immune related genes that have been associated with tumor progression among Iranian population to clarify the genetics of immune deficiency during tumor progression in this population. T regulatory and T helper related genes were the most frequent deregulated genes during tumor progression in Iranian population. This review paves the way to suggest an immune specific panel of genetic markers for diagnostic and immunotherapeutic purposes among Iranian cancer patients.

Background: Graves’ disease(GD) is an autoimmune disease that is associated with increased thyroid gland irritation and, consequently, hyperthyroidism. Autoimmune diseases are common in general population which is influenced by both genetic and environmental factors. PTPN22 that was reported as a susceptible locus for GD in several populations, acts as a negative regulator for activation of primary T-cells, and LYP polymorphism could potentially increase susceptibility to Graves' disease which may play a role in other autoimmune conditions as well. In this study we investigated the association of several PTPN22 single nucleotide polymorphisms (SNPs) with Graves patients.

Methods: After DNA extraction from peripheral blood cells, SNP Genotyping was performed through real-time PCR with allelic discrimination TaqMan genotyping assays (ABI Applied Biosystems, 7300 Real-Time PCR System, USA) based on manufacturer protocols. The frequencies of alleles and genotypes of PTPN22 SNPs (rs12760457, rs2476601, rs1310182 and rs1217414) were recorded.

Results: In our study, the rs1310182 was found to be significantly more frequent in patients with GD compared to healthy individuals. While the C allele of rs1310182 was 1.78 times more frequent in GD patients (95%CI: 1.18-2.69, P=0.005), the T allele was more frequent in healthy subjects (OR=0.56, 95% CI: 0.37-0.84, P=0.005). In addition, the CC genotype of this SNP was 1.86 times more common in patients (P=0.05).  No significant differences were observed between the other SNPs of this gene in case and control.

Conclusion: The results demonstrate that one SNP (rs1310182) of the PTPN22 gene is associated with susceptibility to GD in an Iranian population. Further studies including functional analyses are required.

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