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  • 1
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    Immunohistochemical evaluation of Cyclin D1 and β-Catenin expression in subtypes of triple-negative breast cancer.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e12553-e12553
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e12553-e12553
    Abstract: e12553 Background: The purpose of the study was to reveal characteristics of Cyclin D1 and β-Catenin expression in subtypes of triple negative breast cancer (TNBC). Methods: The study included 60 patients diagnosed with verified TNBC (T1N1M0/T2N0M0, ER-/PR-/Her2-). Immunohistochemical staining with CK5/6, EGFR, Cyclin D1, β-Catenin antibodies was performed. Basal-like (BL) subtype was identified when 〉 25% cells were CK5/6+ and/or EGFR+ (any staining). The expression of β-Catenin was assessed by its location: the membrane, cytoplasm, nucleus. Cells with negative staining on the membrane and cytoplasmic staining were counted and calculated as a percentage of the total number of tumor cells. Nuclear expression of β-Catenin was considered positive with at least 1 positively stained cell in the field of view at x200 magnification. Parametric statistical methods were used. Significance of the difference between the two means was assessed by the Student's t-test. Results: A number of TNBC samples showed Cyclin D1 overexpression. The loss of β-Catenin on the cell membrane and its abnormal accumulation in the cytoplasm was significantly more frequent in TNBC with Cyclin D1 overexpression. These processes were more pronounced in BL cancers. Loss of membrane expression in BL cancers: 29.6±6.1 and 58±7.4%; accumulation in the cytoplasm: 33.4±5.4 and 63.3±7.2%, with low and high Cyclin D1 respectively. Loss of membrane expression in non-BL cancers: 17.6±3.8 and 33.3±4.3%; accumulation in the cytoplasm: 27.3±6.3 and 49.5±8.2%, with low and high Cyclin D1 respectively. Only BL TNBC demonstrated β-catenin translocation to the nucleus (up to 20 stained cells in the field of view): in 33.3% tumors with Cyclin D1 overexpression and in 12% of tumors with its low expression. Conclusions: Levels of expression of β-catenin and Cyclin D1 in TNBC may have predictive value, and the choice of these biomarkers as targets will improve the treatment with new-generation medications.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e12553
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 2
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    Visualization of different anatomical parts of the enucleated human eye using X-ray micro-CT imaging
    Elsevier BV ; 2021
    In:  Experimental Eye Research Vol. 203 ( 2021-02), p. 108394-
    Details
    In: Experimental Eye Research, Elsevier BV, Vol. 203 ( 2021-02), p. 108394-
    Type of Medium: Online Resource
    ISSN: 0014-4835
    URL: Article
    DOI: 10.1016/j.exer.2020.108394
    RVK:
    XA 10000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 1466924-9
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  • 3
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    Expression of CD44 and CD133 markers in regional metastases from breast cancer.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e13087-e13087
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e13087-e13087
    Abstract: e13087 Background: High incidence and mortality of breast cancer (BC) require a constant search for the most informative and effective methods of diagnosis and treatment evaluation. The purpose of the study was to analyze phenotypic characteristics of cancer stem cells in tumor tissues and regional metastases of breast cancer (BC). Methods: The study included 20 BC patients with regional metastases (lymph nodes) aged 32-74 years, mean age 56.1±3.3 years. IHC analysis was performed on sections from paraffin blocks of tumors using monoclonal mouse antibodies to CD44 (156-3C11 Thermo Scientific) at a dilution of 1:2500 and polyclonal rabbit antibodies to CD133 (Cloud-Clone Corp.) at a dilution of 1:700 using the Thermo Scientific automated stainer. Membrane staining and staining intensity were evaluated: 0, 1+ weak, 2+ moderate, 3+ strong staining. CD44 expression was considered positive when staining was detected in more than 10% (cut-off) tumor cells. CD133 expression was considered positive when staining was detected in more than 5% (cut-off) of the tumor. Results: CD44 + expression was detected in 80% of breast tumor tissues (16 samples), while in 20% this marker was not determined. The average CD44 expression was 27.2±13.9%. The expression of CD44 in regional metastases (RM) from BC was 35% (from 0 to 30%), on average 17.0±6.8%. When distributed according to the χ2 criterion in the tumor and RM, an association between factorial and resultant signs was statistically significant (8.286, at p 〈 0.004). CD133+ expression in tumor tissues was detected in 80%, with an average expression level of 56.0±14.6%, with a predominance of positive cytoplasmic staining in 60%. Determination of this marker in BC RM gave a positive result in 15% (3 samples), with expression fluctuations from 0 to 60%, the average level was 33.0±15.4%. When distributed according to the χ2 criterion in the tumor and RM, an association between factorial and resultant signs was statistically significant (16.942, at p 〈 0.001). Conclusions: Determination of tumor cells with the stem phenotype directly in the tissue of primary BC tumors and in tissues of regional metastases demonstrated that the percentage of CD44+ and CD133+ cells in the primary BC tumor was higher.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e13087
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 4
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    Contrast-Enhanced Computed Tomography and Laboratory Parameters as Non-Invasive Diagnostic Markers of Pancreatic Fibrosis
    MDPI AG ; 2023
    In:  Diagnostics Vol. 13, No. 14 ( 2023-07-21), p. 2435-
    Details
    In: Diagnostics, MDPI AG, Vol. 13, No. 14 ( 2023-07-21), p. 2435-
    Abstract: Pancreatic fibrosis (PF) is a part of the pathogenesis in most pancreatic disorders and plays a crucial role in chronic pancreatitis development. The aim of our study was to investigate a relationship between PF grade and signs in resected pancreatic specimens, and the results of both multidetector computed tomography (MDCT) post-processing parameters and fibronectin (FN), hyaluronic acid (HA), matrix metalloproteinase (MMP)-1, and MMP-9 serum levels. The examination results of 74 patients were analyzed. The unenhanced pancreas density (UPD) value and contrast enhancement ratio (CER) showed statistically significant differences in groups with peri- and intralobular fibrosis grades, an integrative index of fibrosis, inflammation in pancreatic tissue, and pancreatic duct epithelium metaplasia, while the normalized contrast enhancement ratio in the venous phase (NCER VP) significantly differed with the perilobular fibrosis grade, integrative fibrosis index, and inflammation (p 〈 0.05). The blood FN level showed a weak positive correlation with the intralobular fibrosis grade (rho = 0.32, p = 0.008). The blood level of HA positively correlated with the presence of prominent and enlarged peripheral nerves (rho = 0.28, p = 0.02) and negatively correlated with the unenhanced pancreas density value (rho = −0.42, p = 0.0001). MMP-1 and MMP-9 values’ intergroup analysis and correlation did not show any statistical significance. The UPD value, NCER VP, and CER, as well as blood levels of FN and HA, could be used in non-invasive PF diagnosis.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics13142435
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662336-5
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  • 5
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    Comparison of the tumor cells proliferative activity in donor tissue and samples of xenograft generations.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e15619-e15619
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e15619-e15619
    Abstract: e15619 Background: Esophageal cancer is a common tumor of the mucous layer of the esophagus and the sixth most common cause of cancer deaths worldwide. Studying the mechanisms of its occurrence and development and the search for new approaches to its prevention and treatment are relevant. Such studies require a reliable experimental basis with such an important component as the use of animal models of cancer. In vivo models are an important tool both for testing new drugs and for studying the mechanisms of disease development. The purpose of the study was to create a patient-derived xenograft (PDX) model of esophageal cancer and to evaluate the proliferative activity of cells in the donor tumor and in xenograft samples in a series of successive generations. Methods: A PDX model of esophageal cancer was created by transplanting a tumor fragment from a patient with esophageal squamous cell carcinoma to the distal esophagus of BALB/c Nude athymic mice. The tumor histotype was confirmed histologically (hematoxylin and eosin staining). The proliferative activity of cells was evaluated by immunohistochemistry (IHC) with anti-Ki-67 antibodies. Results: Histological identity of xenograft samples and the donor tumor was confirmed. IHC showed an increase in the proliferative activity index in samples of transplanted tumors compared to the donor material: 12.4% in the primary tumor and 58%, 65.2%, 54.2% and 60.7% in generations 1, 3, 4 and 5, respectively. Conclusions: Histological characteristics of the donor tumor are preserved in all PDX models. The study demonstrated an increase of the proliferative activity in the first PDX generation compared to the primary tumor which persisted in the subsequent models.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e15619
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 6
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    Deep Learning Classification of Colorectal Lesions Based on Whole Slide Images
    MDPI AG ; 2022
    In:  Algorithms Vol. 15, No. 11 ( 2022-10-27), p. 398-
    Details
    In: Algorithms, MDPI AG, Vol. 15, No. 11 ( 2022-10-27), p. 398-
    Abstract: Microscopic tissue analysis is the key diagnostic method needed for disease identification and choosing the best treatment regimen. According to the Global Cancer Observatory, approximately two million people are diagnosed with colorectal cancer each year, and an accurate diagnosis requires a significant amount of time and a highly qualified pathologist to decrease the high mortality rate. Recent development of artificial intelligence technologies and scanning microscopy introduced digital pathology into the field of cancer diagnosis by means of the whole-slide image (WSI). In this work, we applied deep learning methods to diagnose six types of colon mucosal lesions using convolutional neural networks (CNNs). As a result, an algorithm for the automatic segmentation of WSIs of colon biopsies was developed, implementing pre-trained, deep convolutional neural networks of the ResNet and EfficientNet architectures. We compared the classical method and one-cycle policy for CNN training and applied both multi-class and multi-label approaches to solve the classification problem. The multi-label approach was superior because some WSI patches may belong to several classes at once or to none of them. Using the standard one-vs-rest approach, we trained multiple binary classifiers. They achieved the receiver operator curve AUC in the range of 0.80–0.96. Other metrics were also calculated, such as accuracy, precision, sensitivity, specificity, negative predictive value, and F1-score. Obtained CNNs can support human pathologists in the diagnostic process and can be extended to other cancers after adding a sufficient amount of labeled data.
    Type of Medium: Online Resource
    ISSN: 1999-4893
    URL: Article
    DOI: 10.3390/a15110398
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2455149-1
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  • 7
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    Genomics-driven derivatization of the bioactive fungal sesterterpenoid variecolin: Creation of an unnatural analogue with improved anticancer properties
    Elsevier BV ; 2023
    In:  Acta Pharmaceutica Sinica B ( 2023-8)
    Details
    In: Acta Pharmaceutica Sinica B, Elsevier BV, ( 2023-8)
    Type of Medium: Online Resource
    ISSN: 2211-3835
    URL: Article
    DOI: 10.1016/j.apsb.2023.08.025
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2631779-5
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  • 8
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    X‐ray micro‐computed tomography in the assessment of penile cavernous fibrosis in a rabbit castration model
    Wiley ; 2021
    In:  Andrology Vol. 9, No. 5 ( 2021-09), p. 1467-1480
    Details
    In: Andrology, Wiley, Vol. 9, No. 5 ( 2021-09), p. 1467-1480
    Abstract: Current assessment methods of penile cavernous fibrosis in animal models have limitations due to the inability to provide complex and volume analysis of fibrotic alterations. Objective The aim was to evaluate micro‐computed tomography for assessment of cavernous fibrosis and compare it with histological, histochemical, immunohistochemical, and RT‐PCR analysis. Materials and methods A controlled trial was performed involving 25 New Zealand male rabbits with induced testosterone deficiency by orchidectomy. Penile samples were obtained before and after 7, 14, 21, and 84 days from orchidectomy. We consistently performed (a) gray value analysis of corpora cavernosa 3D models reconstructed after micro‐computed tomography, (b) morphometry of smooth muscles/connective tissue ratio, collagen type I/III ratio, and area of TGF‐beta‐1 expression in corpora cavernosa, and (c) RT‐PCR of TGF‐beta‐1 expression. Results Micro‐computed tomography allowed visualization of penile structures at a resolution comparable to light microscopy. Gray values of corpora cavernosa decreased from 1673 (1512–1773) on the initial day to 1184 (1089–1232) on the 21st day ( p   〈  0.005). However, on the 84th day, it increased to 1610 (1551–1768). On 21st and 84th days, there was observed a significant decrease in smooth muscle/connective tissue ratio and a significant increase in collagen type I/III ratio ( p   〈  0.05). TGF‐beta1 expression increased on the 84th day according to immunohistochemistry ( p   〈  0.005). RT‐PCR was impossible to conduct due to the absence of RNA in obtained samples after micro‐CT. Discussion and conclusions Micro‐computed tomography provided 3D visualization of entire corpora cavernosa and assessment of radiodensity alterations by gray value analysis in fibrosis progression. We speculate that gray value changes at early and late fibrosis stages could be related to tissue reorganization. RT‐PCR is impossible to conduct on tissue samples studied by micro‐CT due to RNA destruction. We also suggest that micro‐computed tomography could negatively affect the immunohistochemical outcome, as a significant increase of TGF‐beta‐1 expression occurs later than histological fibrotic signs.
    Type of Medium: Online Resource
    ISSN: 2047-2919 , 2047-2927
    URL: Issue
    URL: Article
    DOI: 10.1111/andr.v9.5
    DOI: 10.1111/andr.13077
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2693844-3
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  • 9
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    Prognostic significance of Musashi 2 (MSI2) RNA-binding protein expression in precancerous polyps and during colorectal cancer (CRC) progression.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e16009-e16009
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e16009-e16009
    Abstract: e16009 Background: The RNA-binding protein Musashi-2 (MSI2) controls the translation of proteins that support stem cell identity and lineage determination. Elevated expression of MSI2 plays an important role during progression, dissemination, and drug resistance in numerous solid and hematological malignancies. This study assessed MSI2 as potential clinical biomarker in colorectal cancer (CRC) and pre-malignant disorders of colon mucosa. Methods: This study included 125 patients, of whom 20 had tubulovillous adenomas (TAs) of the colon, and 105 had verified colorectal cancer. Of the 105 patients with CRC, 45 had locoregional invasion (stages I-III). The remaining 60 patients had liver metastases (mCRC), with 31 patients diagnosed with synchronous and 29 with metachronous metastases. We used immunohistochemical (IHC) approach to measure MSI2 expression in matching specimens of normal versus TA tissues, normal versus primary CRC tumor, and normal versus metastatic CRC, followed by correlative analysis in relation to clinical outcomes. In parallel, the biological effects of overexpressing or depleting MSI2 expression in human CRC cells were analyzed in vitro using qRT-PCR, western blot, proliferation and clonogenic assays. Results: MSI2 expression in patient samples was significantly elevated in TAs versus primary tissue (p 〈 0.002), and was further elevated in primary tumor, and in metastatic sites (p 〈 0.0001 versus normal tissue, p 〈 0.003 versus TAs). MSI2 expression positively correlated with decreased progression free survival (PFS) and overall survival (OS), lower tumor grade, and right-side localization (p = 0.004) of tumors. In vitro knockdown of MSI2 in CRC cells suppressed of proliferation, survival and clonogenic capacities of the cells. Conclusions: Elevated expression of MSI2 is associated with pre-cancerous polyps (TAs) in the colonic mucosa, indicating it is an early event in transformation. MSI2 is further elevated during, CRC progression, and associated with poor prognosis, and loss of MSI2 reduces multiple growth properties of CRC cell models. These data imply a causative role of MSI2 overexpression at multiple stages of CRC formation and progression.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e16009
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 10
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    Combination treatment for giant cell tumors of the bone.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e22504-e22504
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e22504-e22504
    Abstract: e22504 Background: Positive effect of the monoclonal antibody denosumab in cancer treatment has been reported in recent years. Since surgical treatment is considered the main method of treatment for giant-cell tumors of the bone (GCTB), the purpose of our study was to improve treatment outcomes using denosumab. Methods: The study included 10 patients with verified GCTB (5 men, 5 women, mean age 36±3.14 years). Tumors were located in the upper third of the tibia (3 patients), the lower third of the tibia (3), iliac bone (1), heel bone - 1, the lower third of the femur - 1, the lower third of the humerus - 1.Patients received 2 cycles of neoadjuvant denosumab treatment (120 mg subcutaneously once every 4 weeks) with further tumor resection. The bone defect was reconstructed with bone grafting in marginal resections and endoprosthetics in segmental resections. The effect of neoadjuvant therapy was assessed morphologically by optical light microscopy; histological and histochemical methods were used. Results: Neoadjuvant treatment reduced pain syndrome and restored the support ability. X-ray and spiral X-ray CT showed sclerotic sites in the lytic foci. Consolidation of pathological fractures in the tumor area was registered, as well as fibrosis of the tumor focus. The tissue on the sections of removed material appeared dryish and whitish, it replaced the medullary canal. Microscopic examination of tumors revealed areas of extensive sclerosis foci, and a slight lymphohistiocytic infiltration in some cases. Osteoclasts and osteoblasts were absent in the histological preparations. Conclusions: Neoadjuvant denosumab in GCTB with the following surgery has a pronounced positive effect. This was confirmed by the morphological picture of the operative material demonstrating the development of extensive foci of loose and dense fibrous connective tissue with a small amount of lymphohistiocytic elements.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e22504
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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