Publications by authors named "Anton Klimov"

3 Publications

  • Page 1 of 1

Haplotype analysis of APOE intragenic SNPs.

BMC Neurosci 2018 04 19;19(Suppl 1):16. Epub 2018 Apr 19.

The Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, Center of Neurobiology and Neurogenetics, Lavrentieva str. 10, Novosibirsk, Russia, 630090.

Background: APOE ε4 allele is most common genetic risk factor for Alzheimer's disease (AD) and cognitive decline. However, it remains poorly understood why only some carriers of APOE ε4 develop AD and how ethnic variabilities in APOE locus contribute to AD risk. Here, to address the role of APOE haplotypes, we reassessed the diversity of APOE locus in major ethnic groups and in Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset on patients with AD, and subjects with mild cognitive impairment (MCI), and control non-demented individuals.

Results: We performed APOE gene haplotype analysis for a short block of five SNPs across the gene using the ADNI whole genome sequencing dataset. The compilation of ADNI data with 1000 Genomes identified the APOE ε4 linked haplotypes, which appeared to be distant for the Asian, African and European populations. The common European ε4-bearing haplotype is associated with AD but not with MCI, and the Africans lack this haplotype. Haplotypic inference revealed alleles that may confer protection against AD. By assessing the DNA methylation profile of the APOE haplotypes, we found that the AD-associated haplotype features elevated APOE CpG content, implying that this locus can also be regulated by genetic-epigenetic interactions.

Conclusions: We showed that SNP frequency profiles within APOE locus are highly skewed to population-specific haplotypes, suggesting that the ancestral background within different sites at APOE gene may shape the disease phenotype. We propose that our results can be utilized for more specific risk assessment based on population descent of the individuals and on higher specificity of five site haplotypes associated with AD.
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April 2018

Technical success and short-term results of surgical treatment of gastrointestinal stromal tumors: an experience of three centers.

Transl Gastroenterol Hepatol 2017 2;2:56. Epub 2017 Jun 2.

Federal State-Funded Budgetary Public Health Facility L.G. Sokolov' Hospital N 122 of the Federal Medical and Biological Agency, Saint-Petersburg, Russia.

Background: Gastrointestinal stromal tumors (GIST) comprise about 80% of gastrointestinal sarcomas. In patients with localized disease, surgery is considered as "Gold Standard" treatment. Organ-sparing radical en-block resection is widely accepted practice. Since lymph node dissection is not routinely indicated, minimally invasive approach is of particular interest. The aim of this study is to investigate the short-term outcomes of different surgical treatment of GISTs.

Methods: We analyzed data of 116 patients who received surgical treatment for localized forms of GIST. Tumors were located in the stomach in 87 (75%) cases, in the small intestine in 26 (22.4%) cases, and extragastrointestinal GISTs were found in 3 (2.6%) patients. Four different approaches were used-open surgery (OpS, n=48), laparoscopic surgery (LS, n=40), endoscopic procedures (EP, n=22) and hybrid rendezvous (HR, n=6). Patient demographics, clinical presentation of tumors, characteristics of operation procedures (duration, intraoperative blood loss, frequency of R0-resection and fragmentation of tumor), postoperative complications and length of hospital stay were examined in all these groups.

Results: Radical treatment (R0-resection) was performed in all patients. There were no cases of tumor ruptures during surgical procedure. Mean size of GIST in OpS was 9.1±2.0 [2-35] cm; in LS: 4.9±0.8 (1.5-15) cm; in HR: 3.5±0.8 (2-4.5) cm and in EP: 2.3±0.3 (0.4-3.5) cm. Intraoperative blood loss in OpS was 369.7±209.5 [0-4,000] mL; LS: 63.9±16.0 [0-150] mL; in HR: 96.7±44.3 [50-200] mL; in EP: 33.3±11.0 [0-150] mL. Duration of operation in OpS was 160±20.4 [50-310] min; in LS: 104.7±12.7 [50-185]; in HR: 176.7±44.0 [110-260] min and in EP: 89.8±15.5 [25-190] min. Complication rate in OpS was 5 (10.4%); in LS: 3 (7.5%); in HR: 0% and in EP: 3 (13.6%). Length of hospital stay in OpS was 13.8±2.2 [7-52] days; in LS: 11, 4±2.2 [4-21] days; in HR: 11±3.2 [7-15] days and in EP: 11, 9±2.1 [5-22] days. There were no postoperative deaths.

Conclusions: There is a diversity of surgical approaches for GISTs treatment. From our point of view, the main selection criteria for certain procedure are size, localization, growth type of the tumor and status of overlying mucosa. Nevertheless, due to relative rarity and heterogeneity of this pathology, individualization is necessary in each specific case. Laparoscopic and endoscopic surgery is proved to be safe and feasible for resection of the gastric GISTs, with a reasonable operation time, low blood loss, and an acceptable complication rate. Immediate results indicate that all interventions were performed radically without mortality or serious morbidity.
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June 2017

Is hyperthermia combined with radiotherapy adequate in elderly patients with muscle-invasive bladder cancers? Thermo-radiobiological implications from an audit of initial results.

Int J Hyperthermia 2016 06 22;32(4):390-7. Epub 2016 Jan 22.

c Centre for Radiation Oncology , KSA-KSB , Kantonsspital Aarau , Switzerland , and.

Purpose: The aim of this study was to evaluate the outcomes of loco-regional hyperthermia (HT) with radiotherapy (RT) and/or chemotherapy (CT) in elderly patients with muscle-invasive bladder cancers (MIBC).

Material And Methods: Twenty consecutive MIBC patients were treated with HTRT (n = 8) or HTCTRT (n = 12) following transurethral resection of their bladder tumours. Weekly HT was administered prior to RT to a mean temperature of 40.6-42.7 °C for 60 min. A mean RT dose of 54.6 Gy (SD ± 4.2) was delivered. Single-agent cisplatin (n = 2) or carboplatin (n = 10) was used in HTCTRT patients.

Results: The median age was 81 years. HTRT patients received a mean RT dose of 51.0 Gy compared to 57.1 Gy with HTCTRT (p < 0.001) in a shorter overall treatment time (OTT) (30.8 ± 6.9 versus 43.9 ± 4.0 days, p < 0.001). All HTRT patients had long-term local disease control, while 41.6% of HTCTRT recurred during follow-up. None of the HTRT patients experienced grade III/IV acute and late toxicities, while these were evident in two and one HTCTRT patients respectively. Taken together, the 3-year bladder preservation, local disease-free survival, cause-specific survival and overall survival were 86.6%, 60.7%, 55% and 39.5% respectively. Even though the mean biological effective dose (BED) for both groups was similar (57.8 Gy15), the thermo-radiobiological BED estimated from HT-induced reduction of α/β was significantly higher for HTRT patients (91 ± 4.4 versus 85.8 ± 4.3 Gy3, p = 0.018).

Conclusions: Thermal radiosensitisation with consequent reduction in α/β results in a higher thermo-radiobiological BED with a relatively higher RT dose/fraction and shorter OTT. This translates into a favourable outcome in elderly MIBC patients. Any benefit of CT in these patients needs further investigation.
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June 2016