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PubMed | Institute of Oncology, Oncological Hospital of the Republic of Bashkortostan, Tomsk Cancer Research Institute, City Oncological Hospital No 62 and 7 more.
Type: Journal Article | Journal: Molecular diagnosis & therapy | Year: 2016

This study was aimed to evaluate distribution of epidermal growth factor receptor (EGFR) mutations in a large series of Russian lung cancer (LC) patients.10,607 LC samples were considered for EGFR analysis; EGFR status was successfully determined in 10,426 cases (98.3%), indicating relatively low failure rate.EGFR mutations (ex19del and L858R) were detected in 1759/8716 (20.2%) adenocarcinomas, 28/669 (4.2%) squamous cell carcinomas (SCC) and 8/119 (6.7%) large cell carcinomas. The occurrence of EGFR mutations in adenocarcinomas gradually increased with age, being attributed mainly to the increment of the L858R frequency in non-smokers (patients aged 18-30years: 1/27 (3.7%); 31-40years: 5/98 (5.1%); 41-50years: 18/276 (6.5%); 51-60years: 102/944 (10.8%); 61-70years: 138/1011 (13.7%); 71-80years: 85/496 (17.1%); 81-100years: 5/27 (18.5%); p<0.0001). The EGFR mutation was detected in 804/2107 (38.2%) non-smoking women versus 125/806 (15.5%) non-smoking men (p<0.0001), while the corresponding figures for smokers were 60/273 (22.0%) versus 147/2214 (6.6%) (p<0.0001). The obtained gender-related data differ from the estimates obtained in Asian studies; they indicate that increased prevalence of EGFR mutations in white females may not be entirely attributed to the low prevalence of smoking, but is likely to be related to gender factors per se.Biological causes of distinct age- and gender-related distribution of EGFR mutations in LC deserve further investigation.


Litviakov N.V.,Tomsk State University | Cherdyntseva N.V.,Tomsk State University | Tsyganov M.M.,Tomsk State University | Slonimskaya Y.M.,Tomsk Cancer Research Institute | And 4 more authors.
Oncotarget | Year: 2016

Neoadjuvant chemotherapy (NAC) is intensively used for the treatment of primary breast cancer. In our previous studies, we reported that clinical tumor response to NAC is associated with the change of multidrug resistance (MDR) gene expression in tumors after chemotherapy. In this study we performed a combined analysis of MDR gene locus deletions in tumor DNA, MDR gene expression and clinical response to NAC in 73 BC patients. Copy number variations (CNVs) in biopsy specimens were tested using high-density microarray platform CytoScanTM HD Array (Affymetrix, USA). 75%-100% persons having deletions of MDR gene loci demonstrated the down-regulation of MDR gene expression. Expression of MDR genes was 2-8 times lower in patients with deletion than in patients having no deletion only in post-NAC tumors samples but not in tumor tissue before chemotherapy. All patients with deletions of ABCB1 ABCB3 ABCC5 gene loci - 7q21.1, 6p21.32, 3q27 correspondingly, and most patients having deletions in AVSS1 (16p13.1), AVSS2 (10q24), ABCG1 (21q22.3), ABCG2 (4q22.1), responded favorably to NAC. The analysis of all CNVs, including both amplification and deletion showed that the frequency of 13q14.2 deletion was 85% among patients bearing tumor with the deletion at least in one MDR gene locus versus 9% in patients with no deletions. Differences in the frequency of 13q14.2 deletions between the two groups were statistically significant (p = 2.03 kh 10-11, Fisher test, Bonferroni-adjusted p = 1.73 kh 10-8). In conclusion, our study for the first time demonstrates that deletion MDR gene loci can be used as predictive marker for tumor response to NAC.


PubMed | Tomsk State University, Kang & Park Medical Co., Seoul National University and Tomsk Cancer Research Institute
Type: Journal Article | Journal: Case reports in oncology | Year: 2016

Published reports on salvage treatment for trachea reconstruction after total thyroidectomy or partial tracheotomy are available, some of them using structures of the trachea itself, auricular cartilage, a musculocutaneous flap, or other methods. In our report, we emphasize the importance of a search for a new material and approach for sparing surgery. The purpose of this article is to describe a case of a successful sparing surgery in a patient with advanced thyroid papillary carcinoma invading the trachea. After total thyroidectomy in 2012, partial resection of the trachea was performed in 2014. The lesion defect was 5.5 2.3 cm in size, located between 4 (2nd-6th) tracheal cartilaginous rings and involving about a semicircumference. It was reconstructed with the aid of the knitted TiNi-based mesh endograft, which has been prefabricated in the sternocleidomastoid muscle and further covered with the skin draped over the wound. The tracheostoma was fully closed 6 weeks after the surgery. There were neither side effects nor complications. This kind of tracheal surgery for extensive lesions demonstrates good functional and cosmetic outcomes.


PubMed | Tomsk State University, Tomsk Polytechnic University, University of Heidelberg and Tomsk Cancer Research Institute
Type: Journal Article | Journal: Experimental oncology | Year: 2015

In recent years, the new direction such as identification of informative circulating markers reflecting molecular genetic changes in the DNA of tumor cells was actively developed. Smoking-related DNA adducts are very promising research area, since they indicate high pathogenetic importance in the lung carcinogenesis and can be identified in biological samples with high accuracy and reliability using highly sensitive mass spectrometry methods (TOF/TOF, TOF/MS, MS/MS). The appearance of DNA adducts in blood or tissues is the result of the interaction of carcinogenic factors, such as tobacco constituents, and the body reaction which is determined by individual characteristics of metabolic and repair systems. So, DNA adducts may be considered as a cumulative mirror of heterogeneous response of different individuals to smoking carcinogens, which finally could determine the risk for lung cancer. This review is devoted to analysis of the role of DNA adducts in lung carcinogenesis in order to demonstrate their usefulness as cancer associated markers. Currently, there are some serious limitations impeding the widespread use of DNA adducts as cancer biomarkers, due to failure of standardization of mass spectrometry analysis in order to correctly measure the adduct level in each individual. However, it is known that all DNA adducts are immunogenic, their accumulation over some threshold concentration leads to the appearance of long-living autoantibodies. Thus, detection of an informative pattern of autoantibodies against DNA adducts using innovative multiplex ELISA immunoassay may be a promising approach to find lung cancer at an early stage in high-risk groups (smokers, manufacturing workers, urban dwellers).


PubMed | Tomsk State University and Tomsk Cancer Research Institute
Type: Journal Article | Journal: Oncotarget | Year: 2016

Neoadjuvant chemotherapy (NAC) is intensively used for the treatment of primary breast cancer. In our previous studies, we reported that clinical tumor response to NAC is associated with the change of multidrug resistance (MDR) gene expression in tumors after chemotherapy. In this study we performed a combined analysis of MDR gene locus deletions in tumor DNA, MDR gene expression and clinical response to NAC in 73 BC patients. Copy number variations (CNVs) in biopsy specimens were tested using high-density microarray platform CytoScanTM HD Array (Affymetrix, USA). 75%-100% persons having deletions of MDR gene loci demonstrated the down-regulation of MDR gene expression. Expression of MDR genes was 2-8 times lower in patients with deletion than in patients having no deletion only in post-NAC tumors samples but not in tumor tissue before chemotherapy. All patients with deletions of ABCB1 ABCB 3 ABCC5 gene loci--7q21.1, 6p21.32, 3q27 correspondingly, and most patients having deletions in ABCC1 (16p13.1), ABCC2 (10q24), ABCG1 (21q22.3), ABCG2 (4q22.1), responded favorably to NAC. The analysis of all CNVs, including both amplification and deletion showed that the frequency of 13q14.2 deletion was 85% among patients bearing tumor with the deletion at least in one MDR gene locus versus 9% in patients with no deletions. Differences in the frequency of 13q14.2 deletions between the two groups were statistically significant (p = 2.03 10(-11), Fisher test, Bonferroni-adjusted p = 1.73 10(-8)). In conclusion, our study for the first time demonstrates that deletion MDR gene loci can be used as predictive marker for tumor response to NAC.


Kostyuchenko E.,Tomsk State University of Control Systems and Radioelectronics | Roman M.,Tomsk State University of Control Systems and Radioelectronics | Ignatieva D.,Tomsk State University of Control Systems and Radioelectronics | Pyatkov A.,Tomsk State University of Control Systems and Radioelectronics | And 2 more authors.
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2016

In this paper, we propose the selection of parameters for quality evaluation criterion of pronunciation of certain phonemes. Is presented a comparison of the different options and criteria for the selection of the parameter metric serving their basis-the Minkowskian metric. This approach is used for the comparative assessment of the quality of their utterances in the process of voice rehabilitation of patients after surgical treatment of cancer of the oral cavity and oropharynx. The pronunciation before surgery, taken as a etalon, and after the operation in the course of employment with a speech therapist are compared. The proposed criterion is calculated based on a comparison of the Fourier spectra of these signals and detect differences on the basis of Minkowskian distance. Pre-signals are subjected to the procedure of normalization for the comparability of the spectra. At the end of the experiment the value of the Minkowskian distance parameter to ensure the greatest legibility signals in comparing the quality of pronunciation was suggested. Various approaches to the formation of the quality evaluation criteria pronouncing phonemes are presented. The applicability of the proposed approach for an objective comparative evaluation of the quality of pronouncing phonemes [k] and [t] in patients before and after surgery is confirmed. © Springer International Publishing Switzerland 2016.


PubMed | Tomsk Cancer Research Institute
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2016

Recurrences occur in 30% of lung cancer patients after radical therapy; however, known prognostic factors are not always effective. In this study, we investigated whether the frequency of squamous non-small cell lung cancer (NSCLC) recurrence depends on the presence of reactive lesions in tumor-adjacent bronchial epithelium. Specimens of adjacent lung tissue from 104 patients with squamous NSCLC were used for the determination of basal cell hyperplasia (BCH) and squamous metaplasia (SM) and for the analysis of the expression of Ki-67, p53, Bcl-2, and CD138. We found that recurrence was observed in 36.7% of patients with BCH combined with SM (BCH + SM+) in the same bronchus, compared with 1.8% in patients with isolated BCH (BCH + SM-; odds ratio (OR) 31.26, 95% confidence interval (CI) 3.77-258.60; p=0.00002). The percentage of Ki-67-positive cells was significantly higher in BCH + SM+ than in BCH + SM- (34.9 vs. 18.3%; effect size 2.86, 95% CI 2.23-3.47; p=0.003). P53 expression was also more significant in BCH + SM+ than in BCH + SM- (14.4 vs. 9.6%; effect size 1.22, 95% CI 0.69-1.76; p=0.0008). In contrast, CD138 expression was lower in BCH + SM+ than in BCH + SM- (21.8 vs. 38.5%; effect size -6.26, 95% CI -7.31 to -5.22; p=0.003). Based on our results, we concluded that the co-presence of reactive bronchial lesions is associated with the development of recurrent squamous NSCLC and may be a negative prognostic indicator. In addition, significant differences in Ki-67, p53, and CD138 expression exist between isolated BCH and BCH combined with SM that probably reflect part of biological differences, which could relate to the mechanism of lung cancer recurrence.

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