MicroRNAs as Predictors of Lung-Cancer Resistance and Sensitivity to Cisplatin.

BACKGROUND: Platinum-based chemotherapy, cisplatin (DDP) specifically, is the main strategy for treating lung cancer (LC). However, currently, there is a lack of predictive drug-resistance markers, and there is increased interest in the development of a reliable and sensitive panels of markers for DDP chemotherapy-effectiveness prediction. MicroRNAs represent a perspective pool of markers for chemotherapy effectiveness. OBJECTIVES: Data on miRNAs associated with LC DDP chemotherapy response are summarized and analyzed. MATERIALS AND METHODS: A comprehensive review of the data in the literature and an analysis of bioinformatics resources were performed. The gene targets of miRNAs, as well as their reciprocal relationships with miRNAs, were studied using several databases. RESULTS AND DISCUSSION: The complex analysis of bioinformatics resources and the literature indicated that the expressions of 12 miRNAs have a high predictive potential for LC DDP chemotherapy responses. The obtained information was discussed from the point of view of the main mechanisms of LC chemoresistance. CONCLUSIONS: An overview of the published data and bioinformatics resources, with respect to the predictive microRNA markers of chemotherapy response, is presented in this review. The selected microRNAs and gene panel have a high potential for predicting LC DDP sensitiveness or DDP resistance as well as for the development of a DDP co-therapy.

Soil organic matter turnover: Global implications from δ13C and δ15N signatures.

The turnover and residence time of carbon (C) and nitrogen (N) in soil is a fundamental parameter reflecting the rates of soil organic matter (SOM) transformation and the contribution of soils to greenhouse gases fluxes. Based on the global database of the stable isotope composition of C (δ13C) and N (δ15N) depending on soil depth (171 profiles), we assessed С and N turnover and related them to climate, biome types and soil properties. The 13C and 15N discrimination between the litter horizon and mineral soil was evaluated to explain the key processes of litter transformation. The 13C and 15N discrimination by microbial utilization of litter and SOM, as well as the continuous increase of δ13C and δ15N with depth, enabled to assess C and N turnover within SOM. N turnover was two times faster than that of C, which reflects i) repeated N recycling by microorganisms accelerating N turnover, ii) C loss as CO2 and input of new C atoms to cycling, which reduces the C turnover within soil, and iii) generally slower turnover of N free persistent organic compounds (e.g. lignin, suberin, cellulose) compared to the N containing compounds (e.g. amino acids, ribonucleic acids). An increase in temperature and precipitation accelerated C and N turnover because: i) higher microbial activity and SOM decomposition rate, ii) larger soil moisture and fast diffusion of dissolved organics towards exoenzymes, iii) downward transport of 13C-enriched organic matter (e.g. sugars, amino acids), and iii) leaching of 15N-depleted nitrates from the topsoil into subsoil and losses from the whole soil profile. Temperature accelerates SOM turnover stronger than precipitation. The temperature increase by 10 °C accelerates the C and N turnover for 40 %. SOM turnover is boosted by decreasing C/N ratio because: i) SOM with a high C/N ratio originated from litter is converted to microbially-derived SOM in mineral soil characterized by a low C/N ratio; ii) litter with a low C/N ratio is decomposed faster than litter with a high C/N; iii) microbial carbon-use efficiency increases with N availability. The biome type affects SOM decomposition by i) climate: slower turnover under wet and cold conditions, and ii) by litter quality: faster utilization of leaves than needles. Thus, the fastest C turnover is common under evergreen forests and the lowest under mixed and coniferous ones, whereas temperature and C/N ratio are the main factors controlling SOM turnover. Concluding, the assessment of SOM turnover by δ13C and δ15N approach showed two times faster N turnover compared to C, and specifics of SOM turnover depending on the biomes as well as climate conditions.

Cervicovaginal-Microbiome Analysis by 16S Sequencing and Real-Time PCR in Patients from Novosibirsk (Russia) with Cervical Lesions and Several Years after Cancer Treatment.

Disturbed cervicovaginal-microbiome (CVM) structure promotes human papillomavirus (HPV) persistence and reflects risks of cervical lesions and cancer onset and recurrence. Therefore, microbiomic biomarkers may be useful for cervical disease screening and patient management. Here, by 16S rRNA gene sequencing and commercial PCR-based diagnostic kits, we profiled CVM in cytological preparations from 140 HPV-tested women (from Novosibirsk, Russia) with normal cytological findings, cervical lesions, or cancer and from 101 women who had recently received different cancer therapies. An increase in lesion severity was accompanied by higher HPV prevalence and elevated CVM biodiversity. Post-treatment CVM was found to be enriched with well-known microbial biomarkers of dysbiosis, just as in cervical disease. Nonetheless, concentrations of some skin-borne and environmental species (which gradually increased with increasing lesion severity)-especially Cutibacterium spp., Achromobacter spp., and Ralstonia pickettii-was low in post-treatment patients and depended on treatment types. Frequency of Lactobacillus iners dominance was high in all groups and depended on treatment types in post-treatment patients. Microbiome analysis via PCR-based kits revealed statistically significant differences among all groups of patients. Thus, microbiome profiling may help to find diagnostic and prognostic markers for management of cervical lesions; quantitative PCR-based kits may be suitable for these purposes.

Huge cerebral pial arteriovenous fistula in a newborn: illustrative case.

BACKGROUND: Pediatric arteriovenous malformations (AVMs) and pial/dural arteriovenous fistulas (AVFs) are rare but life-threatening complications that can lead to congestive heart failure and hemorrhagic stroke in newborns and pediatric patients. The pronounced shunting in these conditions is associated with early complications and necessitates aggressive surgical management. Here, the authors describe endovascular treatment of an atypical cerebral pial AVF in a newborn. OBSERVATIONS: This AVF formed direct communication between a major cerebral artery (basilar artery) and a large draining vein (dilated deep cerebral vein). The authors performed earlier subtotal embolization of the AVF using 0.020-inch coils, which led to progressive thrombosis of the fistula with restoration of normal arterial blood flow. The patient was discharged 18 days after surgery, examination at 1.5 and 6 months showed magnetic resonance imaging signs of blood flow absence through the fistula and satisfactory condition of the infant without physical and mental developmental delay. LESSONS: Subtotal coiling of a high-flow pial AVF in a newborn can result in a good clinical outcome.

Detection of Cervical Lesions and Cancer in Air-Dried Cytologic Smears by Combined Analysis of mRNA and miRNA Expression Levels.

Cervical cancer screening is based on cytologic analysis and high-risk human papillomavirus (HR-HPV) testing, each having their drawbacks. Implementation of new biomarker-based methods may improve screening accuracy. Here, the levels of 25 microRNAs (miRNAs, miRs) and 12 mRNAs involved in cervical carcinogenesis in 327 air-dried Papanicolaou-stained cervical smears from patients with cervical precancerous lesions, cancer, or without the disease were estimated by real-time PCR. Using logistic regression analysis, small-scale miRNA-based, mRNA-based, and combined molecular classifiers were built based on paired ratios of miRNA or mRNA concentrations; their ability to detect high-grade cervical lesions and cancer was then compared. Combined mRNA-miRNA classifiers manifested a better combination of sensitivity and specificity than miRNA- and mRNA-based classifiers. The best classifier, combining miR-375, miR-20, miR-96, CDKN2A, TSP4, and ECM1, predicted high-grade lesions with diagnostic sensitivity of 89.0%, specificity of 84.2%, and a receiver-operating characteristic area under the curve of 0.913. Additionally, in a subsample of the same specimens, the levels of MIR124-2 and MAL promoter methylation, HR-HPV genotypes, and viral loads were analyzed. The relative high-grade lesion risk estimated by the classifier correlated with the frequency of MAL and MIR124-2 methylation but not with the HR-HPV genotype or viral load. The results support the feasibility of cellular biomarker-based methods for cervical screening and patient management.

Comparative analysis of SNP in estrogen-metabolizing enzymes for ovarian, endometrial, and breast cancers in Novosibirsk, Russia.

We estimated the frequency of CYP1A1, CYP1A2, CYP1B1, CYP19, and SULT1A1 allelic variants in a female population of the Novosibirsk district and their association with the elevated risk of breast (BC), ovarian (OC), and endometrial (EC) cancers. Significant differences (OR = 2.34, p = 0.0002) in the allele distributions for CYP1A1 M1 polymorphism between patients with BC (n = 118) and controls (n = 180) were found. No significant difference in both genotype and allele distributions for CYP1A1 polymorphisms in patients with OC (n = 96) and EC (n = 154) was observed. Remarkable differences in the allele and genotype distributions for CYP1A2*1F polymorphism in patients with BC or OC were found (OR = 0.26, p = 0.0000005 and OR = 0.34, p = 0.00000002). There were no differences for this polymorphism in women with EC. In patients with BC no significant differences were found in genotype and allele distributions for R264C polymorphism in the CYP19 gene. The frequency of a mutant CYP19 heterozygote genotype C/T was higher in patients with OC and EC compared with healthy women (OR = 3.87, p = 0.001 and OR = 3.73, p = 0.0004, respectively). Comparison of allele frequencies revealed a deficiency of an allele A of SULT1A1*2 in patients with OC (OR = 0.64, p = 0.019) compared with controls. No differences were found in the genotype and allele distributions for SULT1A1 polymorphism between patients with BC and EC and controls. In addition, there were no difference in allele and genotype distributions for CYP1B1 119G-->T polymorphism between BC and control. In conclusion, these results support the hypothesis that susceptibility gene alleles of estrogen-metabolizing enzymes may differentially influence risk for woman hormone-dependent cancers.