Nucleolus as an emerging hub in maintenance of genome stability and cancer pathogenesis

The nucleolus is the major site for synthesis of ribosomes, complex molecular machines that are responsible for protein synthesis. A wealth of research over the past 20 years has clearly indicated that both quantitative and qualitative alterations in ribosome biogenesis can drive the malignant phenotype via dysregulation of protein synthesis. However, numerous recent proteomic, genomic, and functional studies have implicated the nucleolus in the regulation of processes that are unrelated to ribosome biogenesis, including DNA-damage response, maintenance of genome stability and its spatial organization, epigenetic regulation, cell-cycle control, stress responses, senescence, global gene expression, as well as assembly or maturation of various ribonucleoprotein particles. In this review, the focus will be on features of rDNA genes, which make them highly vulnerable to DNA damage and intra- and interchromosomal recombination as well as built-in mechanisms that prevent and repair rDNA damage, and how dysregulation of this interplay affects genome-wide DNA stability, gene expression and the balance between euchromatin and heterochromatin. We will also present the most recent insights into how malfunction of these cellular processes may be a central driving force of human malignancies, and propose a promising new therapeutic approach for the treatment of cancer

Макрофагальная активность в коже больных псориазом при NB-UVB (311 нм) терапии

Досліджено 55 пацієнтів хворих на псоріаз. Пацієнти були розділені на 2 групи. Група 1 – 27 пацієнтів, які отримували тільки стандартне лікування і група 2 – 28 пацієнтів, які отримували стандартну і NB-UVB терапію. NB-UVB призначалась 3 рази в тиждень, при цьому використовували стартову дозу 0,1-0,3 J/cm2 , середня кумулятивна доза від 30 до 60 J/cm2 . Рівень макрофагальної активності в біоптатах шкіри досліджували за допомогою імуногістохімічного методу на 1 і 21 добу. NB-UVB терапія призовдить до зниження рівня експресії CD68 – маркера макрофагів, більшою часткою якої є функціонально-активні клітини, що свідчить про адекватність імуної відповіді і зниження запальної реакції.There were researched 55 psoriasis patients. Patients were divided in two groups. Group 1 – 27 patients who received only standard therapy and Group 2 – 28 patients who received standard and NB-UVB therapy. NB-UVB treatment was applied three times weekly. Starting UVB dose 0.1-0.3 J/cm2 , the mean cumulative UVB dose was 42.0 J/cm2 . The level of macrophage activity in skin biopsy was investigated by an immunohistochemical method on 1 and 21 days. NB-UVB therapy is linked to decline of level of CD68 expression with predominant of functionally active cells which testifies to adequacy of immune reactions and decline of inflammatory reaction

Polymorphisms of estrogen receptors and risk of biliary tract cancers and gallstones: a population-based study in Shanghai, China

Biliary tract cancer encompasses tumors of the gallbladder, bile duct and ampulla of Vater. Gallbladder cancer is more common in women, whereas bile duct cancer is more common in men, suggesting that sex hormones may play a role in the etiology of these cancers. The intracellular action of estrogens is regulated by the estrogen receptor (ESR); thus, we examined the role of common genetic variants in ESR genes on the risk of biliary tract cancers and stones in a population-based case–control study in Shanghai, China (411 cancer cases, 895 stone cases and 786 controls). We genotyped six single-nucleotide polymorphisms (SNPs), four in ESR1 (rs2234693, rs3841686, rs2228480 and rs1801132) and two in ESR2 (rs1256049 and rs4986938). In all participants, the ESR1 rs1801132 (P325P) G allele was associated with excess risks of bile duct [odds ratio (OR) = 1.7, 95% confidence interval (CI) 1.1–2.8] and ampulla of Vater cancers (OR = 2.1, 95% CI 0.9–4.9) compared with the CC genotype. The association with bile duct cancer was apparent among men (OR = 2.8, 95% CI 1.4–5.7) but not among women (P-heterogeneity = 0.01). Also, the ESR2 rs4986938 (38 bp 3′ of STP) GG genotype was associated with a higher risk of bile duct cancer (OR = 3.3, 95% CI 1.3–8.7) compared with the AA genotype, although this estimate was based on a small number of subjects. None of the other SNPs examined was associated with biliary tract cancers or stones. False discovery rate-adjusted P-values were not significant (P > 0.1). No association was found for ESR1 haplotype based on four SNPs. These preliminary results suggest that variants in ESR genes could play a role in the etiology of biliary tract cancers, especially bile duct cancer in men