MicroRNA 345 (miR345) regulates KISS1-E-cadherin functional interaction in breast cancer brain metastases
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01.07.2020 |
Ulasov I.
Borovjagin A.
Fares J.
Yakushov S.
Malin D.
Timashev P.
Lesniak M.S.
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Cancer Letters |
10.1016/j.canlet.2020.03.025 |
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© 2020 Elsevier B.V. Brain metastases manifest the advanced stage of breast cancer disease with poor prognosis for patient survival. Recent reports demonstrate that some therapeutic agents can activate the expression of several breast cancer-associated genes, whose products are involved in the onset and development of brain metastases. In this study, we discovered a functional link between KISS1 and E-cadherin that could be observed in both primary brain metastatic lesions and paired cell lines, such as parental CN34TGL and MDA-MB-231 and their respective brain metastatic subclones CN34Brm2Ctgl and MDA-MB-231Br. Remarkably, expression of KISS1 and E-cadherin genes consistently showed an inverse correlation in all of the above cell/tissue types. While E-cadherin expression was strongly upregulated in metastatic clones isolated from blood and brain, the levels of this protein in parental MDA-MB-231 cell line was low. Furthermore, E-cadherin upregulation can be artificially induced in MDA-MB-231Br and CN34Brm2Ctgl cell populations by knocking down KISS1 expression directly or through overexpressing the miR345 mimic. In the aggregate, our data suggest that the tumor microenvironment, which controls breast cancer spreading via miR345-regulated KISS1 expression, might modulate metastatic spreading by a mechanism(s) involving upregulation of E-cadherin production.
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Combination of low-temperature electrosurgical unit and extractive electrospray ionization mass spectrometry for molecular profiling and classification of tissues
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15.08.2019 |
Sukhikh G.
Chagovets V.
Wang X.
Rodionov V.
Kometova V.
Tokareva A.
Kononikhin A.
Starodubtseva N.
Chingin K.
Chen H.
Frankevich V.
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Molecules |
10.3390/molecules24162957 |
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© 2019 by the authors. Real-time molecular navigation of tissue surgeries is an important goal at present. Combination of electrosurgical units and mass spectrometry (MS) to perform accurate molecular visualization of biological tissues has been pursued by many research groups. Determination of molecular tissue composition at a particular location by surgical smoke analysis is now of increasing interest for clinical use. However, molecular analysis of surgical smoke is commonly lacking molecular specificity and is associated with significant carbonization and chemical contamination, which are mainly related to the high temperature of smoke at which many molecules become unstable. Unlike traditional electrosurgical tools, low-temperature electrosurgical units allow tissue dissection without substantial heating. Here, we show that low-temperature electrosurgical units can be used for desorption of molecules from biological tissues without thermal degradation. The use of extractive electrospray ionization technique for the ionization of desorbed molecules allowed us to obtain mass spectra of healthy and pathological tissues with high degree of differentiation. Overall, the data indicate that the described approach has potential for intraoperative use.
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KISS1 tumor suppressor restricts angiogenesis of breast cancer brain metastases and sensitizes them to oncolytic virotherapy in vitro
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28.03.2018 |
Platonov M.
Borovjagin A.
Kaverina N.
Xiao T.
Kadagidze Z.
Lesniak M.
Baryshnikova M.
Ulasov I.
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Cancer Letters |
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3 |
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© 2017 Elsevier B.V. KISS1 tumor suppressor protein regulates cancer cell invasion via MMP9 metalloproteinase. Downregulation of KISS1 gene expression promotes progression of breast cancer and melanoma, resulting in the development of distant metastases. In the current study, we investigated whether restoration of KISS1 expression in KISS1-deficient human metastatic breast cancer cells holds potential as an advanced anticancer strategy. To this end we engineered an infectivity-enhanced conditionally-replicative human adenovirus type 5 encoding KISS1 as an “arming” transgene in the Ad5 E3 region for an ectopic KISS1 expression in transduced cancer cells. The oncolytic potential of the vector was examined using brain-invading metastatic clones of CN34 and MDA-MB-231 breast cancer cells, which supported high levels of AdKISS1 replication, correlating with a robust CRAd-mediated cytotoxicity. Secretion of cellular factors responsible for tumor angiogenesis, cell-to-cell communication and anti-tumoral immune responses upon KISS1 expression in breast cancer cells was analyzed by a RayBiotech Kiloplex Quantibody array. Overall, our results indicate that KISS1 transgene expression provides an important benefit for CRAd-mediated cytotoxicity in breast cancer cells and holds potential as an anticancer treatment in conjunction with oncolytic virotherapy of breast and other metastatic cancers.
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Therapeutic and prophylactic effects of vitamin d in gynecological diseases associated with excessive proliferation
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01.01.2018 |
Kuznetsova I.
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Akusherstvo i Ginekologiya (Russian Federation) |
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© Bionika Media Ltd. Objective. To carry out a systems analysis of the data available in the current literature on the impact of vitamin D deficiency on the risk of endometriosis and reproductive cancer, as well as on the possibilities of vitamin D supplementation in order to treat and prevent these diseases. Material and methods. The review includes the data of foreign and Russian articles published in the past 10 years and found in Pubmed on this topic. Results. The paper describes the mechanisms by which vitamin D is involved in the processes of inflammation, immunomodulation, and proliferation, as well as the role of its deficiency in pathogenesis of pathological proliferation and inflammation in endometriosis, breast cancer, and ovarian cancer. It gives the data of clinical trials confirming the role of vitamin D deficiency in the progression and negative effects of endometriosis and carcinogenesis, the possibility of vitamin D supplementation for the prevention and adjunct therapy of reproductive cancer and endometriosis. Conclusion. It is necessary to conduct further studies to experimentally and clinically evaluate vitamin D deficiency in endometriosis and cancer. Currently, vitamin D supplements should be prescribed to patients with this pathology if they have been found to have a low blood level of 25(OH)D3.
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PET/CT and whole body MRI in diagnosis of sarcoid reaction
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01.01.2018 |
Subbotin Y.
Plaksa I.
Bakhtiozin R.
Volkonskiy M.
Shipuleva I.
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Russian Electronic Journal of Radiology |
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0 |
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© 2018 Russian Electronic Journal of Radiology. All Rights Reserved. Purpose. To present abilities and limitations of Whole body MRI and FDG-PET/CT in the setting of sarcoid reaction and to stress the importance of use of broader differential diagnosis during interpreting its results. Materials and methods. The observation is introduced from clinical practice, examination was performed on 1.5 Tesla MRI scanner with the acquisition of four regions of interest: head and neck, thorax, abdomen, pelvis and upper thigh. Scanning protocol included diffusion-weighted imaging sequence. Results. The examination has let us exclude the presence of the active tumor tissue in breast cancer patient after systemic neoadjuvant treatment and drew our attention to false positive PET/CT result, which in turn led to change of further treatment strategy. Conclusions. Interpretation of FDG-PET/CT should be done in a complex manner with clinical, laboratory and radiological data correlation.
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Scintigraphy and SPECT/CT of sentinel lymph nodes for planning of operative intervention in breast cancer
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01.01.2018 |
Ryzhkov A.
Bilik M.
Krylov A.
Afanaseva K.
Goncharov M.
Shiryaev S.
Petrovsky A.
Litvinov R.
Khakurinova N.
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Medical Radiology and Radiation Safety |
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0 |
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© 2018 State Research Center, Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency. All rights reserved. Purpose: To increase the effectiveness and quality of surgery treatment for patients with early stages of breast cancer. Material and methods: Since 2016, 25 patients with breast cancer were examined and went through surgery. A lymphotropic colloidal radiopharmaceutical labeled with 99mTc was used; it was administered (150 MBq) the day before the operation. 20 patients received this injection intradermally into periareolar zone, 4 patients received it peritumourally (under control of ultrasound), 1 - paratumorally. Lymphoscintigraphy was performed 3 hours after injection, the images were acquired using dualhead gamma camera Symbia E (Siemens, Germany). A static multiplanar imaging (scintigraphy) (anterior, posterior, lateral projections) was performed for the sentinel nodes (SN) mapping. 25 planar examinations were performed. In 3 cases additional SPECT/CT study was performed using a hybrid SPECT/CT Symbia T2 (Siemens, Germany). Surgical intervention was done on the next day after scintigraphy. During the surgery the handheld gamma probe NEO 2000 (Johnson & Johnson, USA) was used to localize radioactivity. The lymph nodes with the highest count (hot lymph nodes) were removed and sent for immediate histological examination. The results of immediate histological examination were evaluated again during next studies of gross specimen and slides. Results: During scintigraphy studies planar and SPECT/CT, 26 SN were detected in 20 women (80 %). In 15 patients only one SN lymph node was found, in 4 patients - 2, and in one case 3 SN were found. Intraoperative search of SN and immediate histological examination was conducted in 22 cases, 33 SN were found, while during planar scintigraphy only 26. In three cases, after histological examination (after obtaining examination results), patient surveillance was changed, these patients did not undergo through intraoperative radiometry and a decision was to conduct a onestage mastectomy with regional lymphadenectomy. 10 out of 22 patients which underwent intraoperative radiometry and sentinel node biopsy, with immediate histological examination had metastases in the removed nodes, therefore lymphadenectomy had been performed. In the rest 12 patients after immediate histological examination of SN no evidence of tumor growth was found, thus lymphadenectomy was not performed. In case of three patients which did not undergo through intraoperative radiometry, lymphadenectomy was performed and after histological examination only two patients had tumorinvolved SN, and one patient was clear. All intraoperative results were confirmed with next followup histological examinations. In 5 out of 25 patients (20 %) sentinel nodes were not founded. In these 5 cases during follow up period metastases were found in regional lymph nodes, and one patient had tumor emboli in lymphatic vessels, this considered being the cause of negative scintigraphy result. In 12 cases out of 25 (48 %) it was possible to minimize surgical management, and 13 (52 %) undergo lymphadenectomy. Conclusion: 1) The integration of SPECT/CT method of sentinel nodes search allows to plan an optimal surgical management, and can positively affect the longterm followup result of treatment of patients with breast cancer, and improve the quality of life. 2) The sensitivity and positive prognostic value (PPV) of planar scintigraphy and intraoperative radiometry of searching for SN are 80, 100 and 73.3, 100 %, respectively. 3) Thanks to the method of lymphoscintigraphy, 12 (48 %) of 25 women it was possible to minimize surgical management without lymphadenectomy.
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Modern trends in the breast cancer conserving surgery and oncoplastic breast surgery
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01.01.2018 |
Zikiryahodjaev A.
Ermoshchenkova M.
Kaprin A.
Chissov V.
Zapirov G.
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Medical Radiology and Radiation Safety |
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© 2018 Medical Radiology and Radiation Safety. All rights reserved. Introduction: The highest priority for modern clinical oncology is functionally-sparing and organ-conserving treatment. In Russia, breast cancer (BC), among all malignant tumors, accounted for 21.1 % of women in 2017. Oncoplastic radical resections (OPS-BCS = oncoplastic surgery – breast conserving surgery) have been widely used. This term means resection of the breast for cancer using plastic surgery to restore the shape of the breast, in most cases with one-stage correction of the contralateral breast. Purpose: It was the creation of various techniques of oncoplastic breast surgery, applicable for the appropriate localization of breast cancer and the evaluation of surgical, oncological and aesthetic results. Methods: From 2013 to 2017, in the P.A. Hertsen Moscow Oncology Research Center, organ-conserving surgery were performed in 570 patients with BC with an average age of 54.2. Stage 0 was diagnosed in 4.6 %, I – 5.9 %, IIA – 28.7 %, IIB – 6 %, IIIA – 5.1 %, IIIC – 3.3 %, IIIB – 0.2 %, IV – 0.2 %. Radical resection in the standard version was performed in 290 patients with breast cancer, oncoplastic breast surgery in various modifications – in 280. All patients after the organ-conserving surgical treatment received radiation therapy. Patients received chemotherapy, targeted therapy and hormone therapy according to the indications in depending the disease stage and the immunohistochemical type of the tumor. Results: After an urgent and planned morphological study positive margins of resection were revealed in 10 patients, which required reresection of the edges to a negative state of them in case of an urgent intraoperative response and mastectomy – in case of a planned response. Within 4 years, local recurrences were detected in 4 patients (0.7 %), which required a mastectomy with a one-stage reconstruction. In 1 patient (0.2 %), the disease progressed as metastases to the lung – in this case lobectomy and a necessary chemotherapy were conducted. Cosmetic results were defined as excellent in 70 % cases, good – 25 %, satisfactory – 5 %. Conclusion: If there are indications for organ-conserving treatment of breast cancer and the patient’s decision concerning this surgery, the patient should be offered methods of oncoplastic surgery for the prevention of psychological and emotional stress, effective rehabilitation, and a quick return to active social life.
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Biological materials in breast cancer reconstructive surgery
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01.01.2018 |
Zikiryahodjaev A.
Ermoshchenkova M.
Chissov V.
Shirokih I.
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Biomedical Photonics |
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© 2018 Russian Photodynamic Association. All rights reserved. Currently, reconstructive-plastic surgery is becoming the standard for surgical and combined treatment of breast cancer (BC) patients. With a one-stage reconstruction of the breast, the use of biological implants that can replace muscle autografts and, consequently, reduce trauma, blood loss and operation time, and also to avoid defects in the donor zones is becoming topical. From 2014 to 2017, 151 reconstructive operations on 121 patients with BC (average age 41.5 years) using synthetic and biological materials were carried out in P.Herzen Moscow Oncology Research Institute. 0 stage of BC TisN0M0 was diagnosed in 11 (9.1%) patients, I stage - in 52 (42.9%), IIA - in 41 (33.9%), IIB - in 9 (7.4%), IIIA - in 4 (3.3%), IIIB - in 2 (1.7%), IIIC - in 2 (1.7%). To strengthen the lower slope, a biological implant - Permacol acellular dermal matrix, was used in 34 cases. Cosmetic result was rated as excellent in 20 (58.9%) cases, good in 11 (32.3%), unsatisfactory in 3 (8,8%). Biological materials are an important addition to various options for breast reconstruction. The criterion for selecting the material for strengthening the lower slope of the breast with subcutaneous or cutaneous mastectomy for cancer with a one-stage reconstruction using a silicone endoprosthesis is the pinch-test value.
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Exosome-mediated transfer of cancer cell resistance to antiestrogen drugs
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01.01.2018 |
Semina S.
Scherbakov A.
Vnukova A.
Bagrov D.
Evtushenko E.
Safronova V.
Golovina D.
Lyubchenko L.
Gudkova M.
Krasil’nikov M.
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Molecules |
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6 |
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© 2018 by the authors. Exosomes are small vesicles which are produced by the cells and released into the surrounding space. They can transfer biomolecules into recipient cells. The main goal of the work was to study the exosome involvement in the cell transfer of hormonal resistance. The experiments were performed on in vitro cultured estrogen-dependent MCF-7 breast cancer cells and MCF-7 sublines resistant to SERM tamoxifen and/or biguanide metformin, which exerts its anti-proliferative effect, at least in a part, via the suppression of estrogen machinery. The exosomes were purified by differential ultracentrifugation, cell response to tamoxifen was determined by MTT test, and the level and activity of signaling proteins were determined by Western blot and reporter analysis. We found that the treatment of the parent MCF-7 cells with exosomes from the resistant cells within 14 days lead to the partial resistance of the MCF-7 cells to antiestrogen drugs. The primary resistant cells and the cells with the exosome-induced resistance were characterized with these common features: decrease in ERα activity and parallel activation of Akt and AP-1, NF-κB, and SNAIL1 transcriptional factors. In general, we evaluate the established results as the evidence of the possible exosome involvement in the transferring of the hormone/metformin resistance in breast cancer cells.
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