Chemotherapy: a double-edged sword in cancer treatment.

Chemotherapy is a well-known and effective treatment for different cancers; unfortunately, it has not been as efficient in the eradication of all cancer cells as been expected. The mechanism of this failure was not fully clarified, yet. Meanwhile, alterations in the physiologic conditions of the tumor microenvironment (TME) were suggested as one of the underlying possibilities. Chemotherapy drugs can activate multiple signaling pathways and augment the secretion of inflammatory mediators. Inflammation may show two opposite roles in the TME. On the one hand, inflammation, as an innate immune response, tries to suppress tumor growth but on the other hand, it might be not powerful enough to eradicate the cancer cells and even it can provide appropriate conditions for cancer promotion and relapse as well. Therefore, the administration of mild anti-inflammatory drugs during chemotherapy might result in more successful clinical results. Here, we will review and discuss this hypothesis. Most chemotherapy agents are triggers of inflammation in the tumor microenvironment through inducing the production of senescence-associated secretory phenotype (SASP) molecules. Some chemotherapy agents can induce systematic inflammation by provoking TLR4 signaling or triggering IL-1B secretion through the inflammasome pathway. NF-kB and MAPK are key signaling pathways of inflammation and could be activated by several chemotherapy drugs. Furthermore, inflammation can play a key role in cancer development, metastasis and exacerbation.

The prevalence of ataxia telangiectasia mutated (ATM) variants in patients with breast cancer patients: a systematic review and meta-analysis.

Breast cancer is the most common cancer in women, and its high mortality has become one of the biggest health problems globally. Several studies have reported an association between breast cancer and ATM gene variants. This study aimed to demonstrate and analyze the relationship between ATM gene polymorphisms and breast cancer prevalence rate. A systematic literature review was undertaken using the following databases: Medline (PubMed), Web of sciences, Scopus, EMBASE, Cochrane, Ovid, and CINHAL to retrieve all cross-sectional studies between January 1990 and January 2020, which had reported the frequency of ATM variants in patients with breast cancer. A random-effects model was applied to calculate the pooled prevalence with a 95% confidence interval. The pooled prevalence of ATM variants in patients with breast cancer was 7% (95% CI: 5-8%). Also, the pooled estimate based on type of variants was 6% (95% CI: 4-8%; I square: 94%; P: 0.00) for total variants¸ 0% (95% CI: 0-1%; I square: 0%; P: 0.59) for deletion variants, 12% (95% CI: 7-18%; I square: 99%; P: 0.00) for substitution variants, and 2% (95% CI: 4-9%; I square: 67%; P: 0.08) for insertion variants. This meta-analysis showed that there is a significant relationship between ATM variants in breast cancer patients. Further studies are required to determine which of the variants of the ATM gene are associated with BRCA mutations.

Analysis of KRT5 and KRT14 gene mutations and mode of inheritance in Iranian patients with clinical suspicion of Epidermolysis bullosa simplex.

Background: Epidermolysis bullosa simplex is a hereditary skin disorder caused by mutations in several genes such as KRT5 and KRT14 . Skin fragility in basal keratinocytes presence regions led to the cytolysis of epidermis and blistering. Aim of this study was to detect the molecular defects in KRT5 and KRT14 genes hot spots in patients with clinical suspicion of EBS and investigation of their probable genotype-phenotype correlations. Methods: Exons 1 and 6-7 of KRT5 and exons 1 and 4-7 of KRT14 amplification and mutation detection were performed by polymerase chain reaction and Sanger sequencing, respectively. Novel variants pathogenicity evaluated by bioinformatics tools. Results: Nine important variants detected in seven different patients within 6 Iranian families affected by Epidermolysis bullosa simplex, of which four variants were novel. Three patients had a mottled pigmentation phenotype [G96D (p.Gly96Asp) and F97I (p.Phe97Ile) in KRT5 ]. One of them showed a Dowling-Meara phenotype [A417P (p.Ala417Pro) and E477D (p.Glu477Asp) in KRT5 ] and another had a Koebner type phenotype [R397I (p.Arg397Ile) and Q444* (p.Gln444Ter) in KRT5 ]. A novel variant [G92E (p.Gly92Glu) in KRT5 ] in a double heterozygous state with a challenging variant [A413T (p.Ala413Thr) in KRT14 ] identified in one patient with Koebner type phenotype. Also, a previously reported mutation [I377T (p.Ile377Thr) in KRT14 gene] identified in this study. Conclusion: The results of molecular data analysis showed that the most severe phenotypes were associated with mutations in highly conserved regions. In some cases, different inheritance modes were observed.

Genetic and epigenetic contribution to astrocytic gliomas pathogenesis.

Astrocytic gliomas are the most common and lethal form of intracranial tumors. These tumors are characterized by a significant heterogeneity in terms of cytopathological, transcriptional, and (epi)genomic features. This heterogeneity has made these cancers one of the most challenging types of cancers to study and treat. To uncover these complexities and to have better understanding of the disease initiation and progression, identification, and characterization of underlying cellular and molecular pathways related to (epi)genetics of astrocytic gliomas is crucial. Here, we discuss and summarize molecular and (epi)genetic mechanisms that provide clues as to the pathogenesis of astrocytic gliomas.

Keratins and epidermolysis bullosa simplex.

Keratin intermediate filaments play an important role in maintaining the integrity of the skin structure. Understanding the importance of this subject is possible with the investigation of keratin defects in epidermolysis bullosa simplex (EBS). Nowadays, in addition to clinical criteria, new molecular diagnostic methods, such as next generation sequencing, can help to distinguish the subgroups of EBS more precisely. Because the most important and most commonly occurring molecular defects in these patients are the defects of keratins 5 and14 (KRT5 and KRT14), comprehending the nature structure of these proteins and their involved processes can be very effective in understanding the pathophysiology of this disease and providing new and effective therapeutic platforms to treat it. Here, we summarized the various aspects of the presence of KRT5 and KRT14 in the epidermis, their relation to the incidence and severity of EBS phenotypes, and the processes with which these proteins can affect them.

Genetic and epigenetic effects on couple adjustment in context of romantic relationship: A scoping systematic review.

Introduction: Couples' relationships defined by a complex interaction between the two partners and their intrapersonal traits. Romantic; relationships and love are associated with marital satisfaction and stability, as well as couples' happiness and health. Personality traits influence romantic relationships and, personality influenced by genetical and non-genetically factors. The roles of non-genetically factors such as socioeconomic position and external appearance have revealed in determining the quality of romantic relationships. Methods: We; performed a scoping systematic review to assess the association between genetics and epigenetic factors and romantic relationship. Relevant articles were identified by PubMed, EMBASE, Web of Science, Scopus, and the APA PsycInfo searching between inception and 4 June 2022. Results: Different studies evaluated the associated polymorphisms in 15 different genes or chromosomal regions. In the first step; we classified them into four groups: (1) Oxytocin-related signaling pathway (OXTR, CD38, and AVPR1A); (2) Serotonin-related signaling pathway (SLC6A4, HTR1A, and HTR2A); (3) Dopamine and catecholamine-related signaling pathway (DRD1, DRD2, DRD4, ANKK1, and COMT); and (4) other genes (HLA, GABRA2, OPRM1, and Y-DNA haplogroup D-M55). Then, we evaluated and extracted significant polymorphisms that affect couple adjustment and romantic relationships. Discussion: Overall, the findings suggest that genetic and epigenetics variants play a key role in marital adjustment and romantic relationships over time.

The Effect of LINC01296 Expression in Patients with Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Recently has been suggested that LINC01296 has an important role in tumor-promoting in different malignancies. We performed first meta-analysis to assess the association between the LINC01296 expression and clinicopathological criteria and the survival of patients with cancers. METHODS: Relevant articles Identified by PubMed, EMBASE, Web of Science, and Scopus searching between December 2000 and 28 December 2018. Binomial data were evaluated by the odds ratio (OR) as the rapid statistic. The association between overall survival (OS) and the LINC01296 expression was evaluated using pooling the hazard ratio (HR) with its corresponding 95% confidence interval (CI). RESULTS: Finally, 9 studies with 720 patients with cancer were included. The expression of LINC01296 showed a significant positive association with TNM stage (OR = 2.67, 95% CI = 1.83-3.88), tumor stage (OR= 2.22, 95% CI= 1.34-3.66) and lymph node metastasis (OR = 3.07, 95% CI = 2.23-4.21). A shorter OS was significantly associated with the expression of LINC01296 (HR = 3.95, 95% CI = 2.65-5.25) and lymph node metastasis (HR = 2.39, 95% CI =1.16-3.63). The OS did not show significant association with gender (HR = 0.83, 95% CI = -0.63-2.30) and tumor stage (HR= 2.66, 95% CI= -0.22-5.54). CONCLUSION: In conclusion, the results of this meta-analysis suggest that the expression of LINC01296 might be considered as a potential biomarker in patients with cancer.