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1.
Cipher: ЕУ12/2020/42/3
   Journal
Экспериментальная онкология [Text]
2020year Т. 42 № 3 . - 51.52, р.
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2.


   
    Suboptimal molecular response to tyrosine kinase inhibition associated with acquisition of a T240A ABL1 kinase domain mutation in a patient with chronic myeloid leukemia [Text] / S. E. Langabeer [та ін.] // Экспериментальная онкология. - 2019. - Т. 41, № 1. - С. 82-83. - Bibliogr. at the end of the art.

Annotation: Over the last twenty years, chronic myeloid leukemia (CML) has come to be considered a paradigm for rationally selected, targeted inhibition of the disease-specific, BCR-ABL1 tyrosine kinase activity. However, a minor but significant numbers of patients either fail, or have suboptimal responses to first line tyrosine kinase inhibitor (TKI) therapy. The causes of a suboptimal response are many, with the acquisition of ABL1 kinase domain mutations (KDMs) contributing to resistance being widely studied. These ABL1 KDMs usually become apparent within the first two years of starting TKI therapy and their discovery has led to the development of second and third generation TKIs [1]. ABL1 KDMs have been detected throughout the kinase domain with ten common mutations accounting for the majority of those observed [2]. However, rare and novel mutations continue to be detected in TKI-resistant patients with reporting of such cases necessary for future understanding of real-world CML patient management
A 44 year-old man presented with fatigue, weight loss, night sweats, abdominal discomfort, and a hemoglobin of 9.9 g/dl, white cell count of 353.9•109/l and platelet count of 130•109/l. The patient had a marked splenomegaly detected 17 cm below the costal margin. Bone marrow aspirate showed hypercellularity, myeloid metaplasia, only 1% basophils and no myeloblasts with cytogenetics detecting the t(9;22) translocation in all metaphases analysed. Quantitative reverse-transcription polymerase chain reaction detected e13a2 BCR-ABL1 transcripts at a high level, all consistent with a diagnosis of high-risk (Sokal score 1.5; EUTOS score 88), chronic phase CML. The patient commenced nilotinib 300 mg twice daily with BCR-ABL1 transcript levels decreasing very slowly (Figure). Within the first year of treatment he experienced intermittent eye irritation, conjunctival hyperemia which required occasional steroid eye drops and ocular lubricant, and a persistent sensation of asthenia with regular myalgias. His peripheral blood BCR-ABL1 transcript level (Internationally Standardised) at twelve months was a suboptimal 4.87% prompting switch to dasa­tinib 100 mg once daily increased to 140 mg once daily. At twenty months post-diagnosis, the BCR-ABL1 transcript level was 2.12% triggering analysis for an ABL1 KDM as previously described [4] and of which no mutation was detected (Figure). Despite a continued slow decline in BCR-ABL1 transcripts, a major molecular response was never achieved with re-analysis for an ABL1 KDM at 47 months detecting an ABL1 T240A mutation (c.718AG, p.Thr240Ala; reference sequence NM_005157.5). The patient is currently well with persistent thrombocytopenia secondary to dasatinib and occasional myalgias. He continues attending for regular close molecular monitoring with a most recent BCR-ABL1 level of 0.15% five years post diagnosis
Additional Access Points:
Langabeer, S. E.
Haslam, K.
Crampe, M.
MacDonagh, B.
McHugh, J.

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3.


    Brieieva, O.
    Scientific and Practical Conference of Young Scientists “Fundamental Medicine: Integrated Approaches to Cancer Therapy” [Text] / O. Brieieva // Экспериментальная онкология. - 2019. - Т. 41, № 1. - С. 84-86. - Bibliogr. at the end of the art.

Annotation: On February 4–5, 2019, the R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of the National Academy of Sciences of Ukraine (IEPOR NASU) hosted the Scientific-Practical Conference of Young Scientists “Fundamental Medicine: Integrated Approaches to Cancer Therapy” dedicated to the World Cancer Day. The event took place by the initiative and support of the Council of Young Scientists of IEPOR NASU
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4.


   
    Tumor and Host: Novel Aspects of Old Problem [Text] // Экспериментальная онкология. - 2019. - Т. 41, № 1. - С. 87

Annotation: II International Conference "Tumor and Host: Novel Aspects of Old Problem"dedicated to the 120-th anniversary of the birth of Academician R.E. Kavetsky. The Conference is timed with the 25-th anniversary of R.E. Kavetsky IEPOR membership in the OECI
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5.


   
    Parathyroid carcinoma: a case report [Text] / R. Tkachenko [та ін.] // Экспериментальная онкология. - 2019. - Т. 41, № 1. - С. 72-75. - Bibliogr. at the end of the art.

Annotation: Parathyroid carcinoma (PC) is an uncommon cause of primary hyperparathyroidism (pHPT). The tumor is mostly functioning with following high serum calcium and parathyroid hormone (PTH) levels. Consideration of PC in differential diagnosis of pHPT is important because the mortality and the prognosis depend on early recognition and surgical approach. A case of PC in 51-year old female patient with persistent pHPT is reported. A patient, referred with anterior cervical hematoma, dysphagia, underwent neck ultrasound, barium X-ray swallow test and neck computed tomography. On the posterior surface of left thyroid lobe, close to the esophagus the heterogenic lesion with irregular margins was found. The preoperative calcemia was slightly elevated. The patient underwent cervical exploration with parathyroidectomy. Histological exam showed parathyroid lesion with immunohistochemical confirmation of PC. After 2 months follow-up there are no signs of a residual-recurrent disease. Although laboratory tests revealed pHPT preoperatively, no clinical effects of elevated calcium and PTH concentration levels were presented. As histological features are not specific for the differential diagnosis between the parathyroid adenoma and PC, the immunohistochemistry remains the only useful tool for the definite diagnosis
Additional Access Points:
Tkachenko, R.
Zakhartseva, L.
Golovko, A.
Kuryk, O.
Lazarenko, G.

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6.


   
    A case of synchronous bilateral calyx urothelial carcinoma: combined treatment approach [Text] / S. Semko [та ін.] // Экспериментальная онкология. - 2019. - Т. 41, № 1. - С. 76-79. - Bibliogr. at the end of the art.

Annotation: Upper urinary tract urothelial carcinoma is a rare tumor. Data about its correct management are controversial. Investigational technology development made it possible to diagnose asymptomatic small tumors, which can be successfully managed endoscopically. We report the case of bilateral urothelial cancer and hydronephrosis in patient aged 38. After management of acute post-renal kidney insufficiency, the neoadjuvant platinum-based chemotherapy was used followed by the kidney-sparing surgery split in two interventions on both sides. The patient does not have any relapse or further progression after one year of initial treatment with good performance status and high life quality level. We believe that the kidney preserving strategy can be considered as an option even in high-risk patients. The renal function in such cases is a crucial parameter affecting the outcome
Additional Access Points:
Semko, S.
Pikul, M.
Voylenko, O.
Stakhovskyi, O.
Kononenko, O.
Vitruk, Yu.
Stakhovsky, E.

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7.


   
    Cutaneous leiomyosarcoma: a clinical, dermoscopic, pathologic case study [Text] / Giorgi V. De [та ін.] // Экспериментальная онкология. - 2019. - Т. 41, № 1. - С. 80-81. - Bibliogr. at the end of the art.

Annotation: Cutaneous leiomyosarcoma is a rare malignant mesenchymal tumor of smooth muscle origin of unknown etiology. Leiomyosarcomas located on the skin include superficial leiomyosarcomas and metastatic leiomyosarcomas. Superficial leiomyosarcomas represent 7–10% of all cases of leiomyosarcoma and are subdivided into cutaneous and subcutaneous lesions based on skin location. We report a case of an 81-year-old woman who presented a slow growing tender single nodule on the left thigh and describe its clinical and dermoscopic features
Additional Access Points:
De, Giorgi V.
Scarfì, F.
Silvestri, F.
Maida, P.
Gori, A.
Trane, L.
Massi, D.

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8.


    Syvyk, A. E.
    Inducible dominant negative ErbB2 rat spermatogonial line for generation of transgenic rat model and dissecting ERBB2 tyrosine kinase mediated pathways [Text] / A. E. Syvyk, T. L. Syvyk // Экспериментальная онкология. - 2019. - Т. 41, № 2. - С. 95-105. - Bibliogr. at the end of the art.

Annotation: The ERBB2 receptors tyrosine kinase, also known as HER2/Neu, play an essential role in early organism development and modulation of cell behavior in varieties of tissue in an adult organism. Our aim was the generation of transgenic rat spermatogonial line capable of inducible expression of a dominant negative form of the ERBB2 protein in vitro and the transgenic rat as an animal model for dissection of the ERBB2 mediated signaling in vitro and in vivo. Materials and Methods: Donor derived rat spermatogonial stem cells that express green fluorescence protein and inducible ERT2CreERT2 recombinase were modified with Sleeping Beauty transposon-based vector that express truncated kinase deficient form of the ERBB2 receptor upon Cre mediated recombination. Clonally selected spermatogonial cell lines were extensively tested in vitro. Animals were generated via spermatogonia mediated transgenesis by transplantation of clonal cell line into testes of chemically sterilized recipients. Obtained progeny were tested for inducibility in vivo and served as donors of spermatogonia for downstream analysis. Results: We obtained animals and clonally derived spermatogonial stem cell lines that express an inducible dominant negative form of the ERBB2 protein. Isogenic nature of induced and uninduced cells allows most accurate morphological and molecular comparison of cells affected by the interruption of normal function of the ERBB2 receptor and cellular dynamics in vitro and in vivo. Conclusions: Clonally derived spermatogonial stem cell lines that express an inducible dominant negative form of ErbB2 demonstrated an obvious difference in morphological appearance and growth kinetics of induced cells comparing to uninduced ones. Western blot analysis of induced and uninduced cells revealed significant differences in presence and phosphorylation state of several tested important proteins involved in the ERBB2 mediated signal transduction, such as S6 ribosomal protein; AKT (the serine/threonine kinase also known as protein kinase B); and three protein kinases that participate in the RAS-RAF-MEK-ERK signal transduction cascade PRAS40, MEK, ERK1/2
Additional Access Points:
Syvyk, T. L.

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9.


   
    Antitumor effects and hematotoxicity of C60-Cis-Pt nanocomplex in mice with Lewis lung carcinoma [Text] / S. V. Prylutska [та ін.] // Экспериментальная онкология. - 2019. - Т. 41, № 2. - С. 106-111. - Bibliogr. at the end of the art.

Annotation: Cisplatin (Cis-Pt) is a widely used anticancer drug but its therapeutic efficiency is limited by hemato-, cardio-, hepato-, nephro- and neurotoxicity. Complexation of Cis-Pt with C60 fullerene nanoparticle will allow to enhance the antitumor activity of the drug and to reduce its side toxic effects. Aim: To estimate the antitumor effects of С60-Cis-Pt nanocomplex in Lewis lung carcinoma (LLC) and analyze hematological toxicity in tumor-bearing mice. Materials and Methods: Complexation of C60 fullerene and Cis-Pt molecule was studied by computer simulation. С60-Cis-Pt nanocomplex was i.p. injected to LLC-bearing mice in a total dose of 7.5 mg/kg (C60:Cis-Pt as 3.75:3.75 mg/kg). The survival of tumor-bearing mice and the relative reduction of tumor weight was recorded. Blood indices were determined using the Particle Counter PCE­210 automatic hematology analyzer. Results: Computer simulation demonstrated the formation of С60-Cis-Pt nanocomplex in physiological medium and its stability due to the hydrophobic interactions. Treatment with C60-Cis-Pt nanocomplex increased survival time of LLC-bearing mice by 32%, normalized hemoglobin content (up to 100 g/l), erythrocyte and platelet count as compared to the untreated LLC-bearing mice. Tumor weight decreased by 35.5%; the mitotic index of tumor cells decreased by 78%, and apoptotic index increased by 75%. The revealed effects of the C60-Cis-Pt nanocomplex were more pronounced than the effects of Cis-Pt or C60 fullerene alone in equivalent dose. Conclusion: Treatment with C60-Cis-Pt nanocomplex prolonged the survival of LLC-bearing mice and reduced anemia in LLC-bearing mice
Additional Access Points:
Prylutska, S. V.
Lynchak, O. V.
Kostjukov, V. V.
Evstigneev, M. P.
Remeniak, O. V.
Rybalchenko, V. K.
Prylutskyy, Yu. I.
Ritter, U.
Scharff, P.

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10.


   
    Proinflammatory effects of photoactivated methylene blue on rat model of Walker 256 carcinosarcoma [Text] / M. C. Petrellis [та ін.] // Экспериментальная онкология. - 2019. - Т. 41, № 2. - С. 112-122. - Bibliogr. at the end of the art.

Annotation: Photodynamic therapy (PDT) is an anticancer therapy that associates the photosensitizer (PS), oxygen and light to destroy cancer cells. Methylene blue (MB) is considered a second generation phenothiazine dye with excellent photochemical properties. Aim: To evaluate whether MB-mediated PDT can induce oxidative stress and inflammation, therefore, interfering tumor growth. Materials and Methods: The study was conducted on Wistar rats transplanted with Walker 256 carcinosarcoma (W256). The proinflammatory interleukins levels (IL-1β, IL-6, IL-10, TNF-α) were determined by ELISA, mRNA expression of COX-1, COX-2, iNOS and eNOS by RT-PCR, lipid peroxidation was measured by the TBARS method. Moreover, myeloperoxidase (MPO) activity in neutrophils was determined by MPO activity assay. All indices mentioned above were determined in tumor tissue. Kaplan — Meier and Gehan — Breslow — Wilcoxon tests were used for survival analysis. Results: We found that the treatment of W256 with 0.1% MB + 1 J/cm2 provoked a significant increase in the interleukins levels (IL-1β, IL-6, IL-10, TNF-α), prostaglandin E2, the mRNA expression of COX-2, iNOS, lipid peroxidation and MPO activity in tumor tissue, which were statistically different (p 0.05) compared to other experimental and control groups. The results of the estimation of survival curves show a greater probability of survival in 0.1% MB + 1 J/cm2 (total energy dose
Additional Access Points:
Petrellis, M. C.
Frigo, L.
Ribeiro, W.
Leal-Junior, E. C. P.
Oliveira, F. R.
Maria, D. A.
Lopes-Martins, R. Á. B.

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