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1.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Lifsics A., Rate E., Ivanova A., Tars J., Murovska M., Groma V.
Заглавие : Survival analysis of oropharyngeal squamous cell carcinoma patients linked to histopathology, disease stage, tumor stage, risk factors, and received therapy
Место публикации : Experimental Oncology. - К., 2020. - Том 42, N 1. - С. 51-59 (Шифр ЕУ12/2020/42/1)
MeSH-главная: РОТОВОЙ ПОЛОСТИ НОВООБРАЗОВАНИЯ -- MOUTH NEOPLASMS
ГЛОТКИ НОВООБРАЗОВАНИЯ -- PHARYNGEAL NEOPLASMS
Аннотация: Survival of oropharyngeal squamous cell carcinoma (OSCC) patients depends on the risk and environmental factors, tumor biology, achievements in diagnostics and treatment approaches. Aim: To perform a survival analysis of the patients with OSCC treated over a 10-year period in a single hospital in Latvia linking these data to histopathological findings, risk factors and received therapy. Materials and Methods: The main outcome measures were overall and disease-specific survival (OS and DS) along with histopathology analysis. Results: Kaplan – Meier survival analysis showed better survival for females, younger patients lacking bad habits, operated and received radiotherapy, with lower T grade and disease stage. Cox regression showed diminished early death risk in patients with lower T grade, no regional metastases (N0) and bad habits, operated and received radiotherapy. A vast majority of tumors were localized in palatine tonsils and the base of the tongue. The localization did not correlate with mean survival time/survival. Lower OS (p = 0.03) and DS (p = 0.026) were estimated for patients with pharyngeal wall and tonsillar involvement compared to tumors localized in the soft palate. A histological variant of tumor seemed irrelevant estimating OS and DS, whereas therapeutic modalities significantly affected survival. Conclusions: OSCC patients with lower T grade, N0 status, lacking bad habits, and surgically treated had better survival
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2.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Sarnatskaya V. V., Yushko L. A., Prokopenko I. V., Hudenko N. V., Maslenny V. N., Paziuk L. M., Bubnovskaya L. N., Nikolaev V. G.
Заглавие : Structural changes of serum albumin in response to oxidative stress caused by Walker-256 carcinosarcoma growth
Место публикации : Experimental Oncology. - К., 2020. - Том 42, N 1. - С. 40-45 (Шифр ЕУ12/2020/42/1)
MeSH-главная: КАРЦИНОМА 256 УОКЕРА -- CARCINOMA 256, WALKER
АЛЬБУМИН СЫВОРОТОЧНЫЙ -- SERUM ALBUMIN
ОКСИДАТИВНЫЙ СТРЕСС -- OXIDATIVE STRESS
Аннотация: To assess oxidative stress and structural changes of the serum albumin in rats with transplanted Walker-256 carcinosarcoma (W256) strains with varying sensitivity to doxorubicin (Dox). Materials and Methods: The study was performed on female Wistar rats with transplanted W256. On the 9th day after tumor cell transplantation an analysis of peripheral blood, oxidative stress para­meters, and structural changes of serum albumin of experimental animals was performed. Results: On the 9th day after W256 transplantation a significant increase in the leukocyte counts was observed in the groups of animals with the Dox-resistant and parental (Dox-sensitive) W256 tumors compared with the group of the intact animals: up to 14.24 ± 1.92 • 103/μl and 9.78 ± 1.03 • 103/μl, vs 8.92 ± 1.04 • 103/μl, respectively, due to the increase of granulocyte and monocyte counts. The number of lymphocytes was within the normal range. The level of hemoglobin and the erythrocyte counts were also within normal limits, but hematocrit in both groups of animals with tumors somewhat increased against the background of 1.2-fold elevation of the mean erythrocyte volume. In the group of rats with Dox-resistant W256, there was observed a decrease in the plateletcrit by almost 22% and thrombocyte counts — by 28%. Analysis of oxidative stress indices revealed a significant increase in the level of reactive oxygen species, 2-fold increase of malonic dialdehyde level and the degree of oxidative damage of blood plasma proteins, as well as a decrease in the activity of catalase in hemolysates (by 12–15%) in both groups of tumor-bearing rats. With the use of differential scanning calorimetry, UV and fluorescence spectroscopy we have revealed anomalous conformational changes of albumin caused by tumor development: structural rearrangements in the region of its first drug binding site located in the IIA domain, separation of globular parts of albumin molecule, and partial “opening” in a protein molecular three-domain structure resulting a loss of its thermal resistance. Conclusion: The development of transplanted Walker-256 carcinosarcoma, especially its Dox-resistant variant, results in severe metabolic intoxication reflected in alteration of hematological parameters, and indices of oxidative stress, as well as architectonic changes of serum albumin
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3.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Shcherbina V., Gordiienko I., Shlapatska L., Ivanivska T., Sidorenko S.
Заглавие : Sensitivity of chronic lymphocytic leukemia cells to chemotherapeutic drugs ex vivo depends on expression staus of cell surface receptors
Место публикации : Experimental Oncology. - К., 2020. - Том 42, N 1. - С. 16-24 (Шифр ЕУ12/2020/42/1)
MeSH-главная: ЛЕЙКОЗ-ЛИМФОМА ПРЕ-КЛЕТОЧНЫЙ ЛИМФОБЛАСТНЫЙ -- PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA
Аннотация: Response of chronic lymphocytic leukemia (CLL) patients to classical chemoimmunotherapy that remains the main strategy in treatment of this disease is strikingly variable. This issue requires the finding of biomarkers which could predict efficiency of drug administration and choose the best treatment option for each patient individually. The aim of this study was to find out association between cell surface receptors expression levels and CLL B cells sensitivity to chemotherapeutic drugs ex vivo. Materials and Methods: The study was performed on malignant B cells isolated from peripheral blood of primary CLL patients. Flow cytometry, qPCR, ex vivo drug sensitivity assay, and cell viability assay were used in this study. Results: The high CD5 expression level was linked to better bendamustine (BEN) and cyclophosphamide (CP) CLL B cells response in contrast to B cells with low CD5 expression. Sensitivity of CLL B cells to CP also could be predicted by high level of CD20 expression. Expression of CD38 and high levels of CD37 and CD40 showed CLL B cells resistance to BEN ex vivo. CLL B cells sensitivity to analyzed chemotherapeutic drugs was not dependent on CD22 expression status. The CD180 expression was detected in CLL B cells which were more susceptible to fludarabine and cyclophosphamide (FC) combinatory action. CLL B cells that coexpressed CD150 and CD180 on the cell surface were characterized by significantly decreased cell viability under fludarabine (FLU) exposure alone or FC in comparison with CD150-CD180- B cells. Cell surface expression level of CD150 was not associated with CLL B cells chemosensitivity. However, high mRNA expression level of mCD150 isoform in CLL B cells was linked to their FLU sensitivity and CP resistance, while high nCD150 mRNA expression level showed resistance to FLU. Simultaneous CD150 and CD180 ligation increased FLU resistance, but BEN susceptibility of CLL B cells. CD150 and CD180 alone or in combination are involved in upregulation of CD20 cell surface expression. Conclusion: Expression status of the CD5, CD20, CD37, CD38, CD40, CD150, and CD180 cell surface receptors could be used in prediction CLL B cells sensitivity to FLU, CP, BEN and FC ex vivo. Moreover, CD150 and CD180 receptors are involved in regulation of CLL B cells susceptibility to FLU and BEN. The CD150 and CD180 are positive regulators of CD20 expression that could make CD150+CD180+ CLL B cells more responsive to CD20-based immunotherapy
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4.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Gong Y., Wu J., Yang R., Zhang L., Ma Z.
Заглавие : Rapamycin-induced autophagy plays a pro-survival role by enhancing up-regulation of intracellular ferritin expression in acute lymphoblastic leukemia
Место публикации : Experimental Oncology. - К., 2020. - Том 42, N 1. - С. 11-15 (Шифр ЕУ12/2020/42/1)
MeSH-главная: ЛЕЙКОЗ-ЛИМФОМА ПРЕ-КЛЕТОЧНЫЙ ЛИМФОБЛАСТНЫЙ -- PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA
Аннотация: Elevated mammalian target of rapamycin (mTOR) signaling has been reported to correlate with poor prognosis in acute lymphoblastic leukemia (ALL) patients. Rapamycin, an mTOR kinase inhibitor, and also a potent autophagy inducer, could not only effectively reverse glucocorticoid resistance, but also promote autophagy in the ALL cells. Autophagy has been suggested to play a paradoxical role in cancer treatment. The aim of this study was to address the role of the rapamycin-induced autophagy in the leukemia treatment. Materials and Methods: Cell proliferation was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in ALL cell lines of CEM-C1 and CEM-C7. Western Blot analysis was performed to test protein expressions. Results: Inhibition of mTOR by rapamycin could reverse glucocorticoid resistance in CEM-C1 cells, and also induce autophagy in these cells by up-regulation of LC3-II and Beclin-1 expressions. This autophagy played a pro-survival role since its inhibition by 6-amino-3-methylpurine or chroloquine could enhance rapamycin-induced cell death. Rapamycin increased the expression of intracellular ferritin, and this effect could be totally blocked by 6-amino-3-methylpurine and chroloquine, suggesting that the protective role of autophagy might be mediated through up-regulation of ferritin, the major iron-binding stress protein. Ciclopirox olamine, an iron chelator, could enhance rapamycin’s anti-leukemia effect by down-regulation of intracellular ferritin expression. Conclusions: All these findings would suggest that rapamycin-induced autophagy plays a pro-survival role in leukemia cells and this effect might be mediated by up-regulation of intracellular ferritin expression. We hypothesize that the combination of mTOR pathway inhibitors and autophagy inhibition is rational and would induce strong anti-leukemia effects in ALL
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5.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Bilous N., Abramenko I., Chumak A., Dyagil I., Martina Z.
Заглавие : MYC copy number and mRNA expression in chronic lymphocytic leukemia patients exposed to ionizing radiation due to the Chornobyl NPP accident
Место публикации : Experimental Oncology. - К., 2020. - Том 42, N 1. - С. 60-65 (Шифр ЕУ12/2020/42/1)
MeSH-главная: ЛЕЙКОЗ ЛИМФОИДНЫЙ -- LEUKEMIA, LYMPHOID
Аннотация: Some clinical and biological features indicating an unfavorable course of the disease were found in ionizing radiation (IR) — related chronic lymphocytic leukemia (CLL) patients. The MYC proto-oncogene is considered to contribute to CLL pathogenesis. Increased MYC copy number is associated with poor prognosis in CLL. Aim: To investigate the frequency of MYC gene copy number amplification in IR-exposed CLL patients and relate the findings to the MYC mRNA levels, the presence of unfavourable prognosis mutations (TP53, SF3B1, NOTCH1), and patient’s outcome. Materials and Methods: The analysis of MYC copy number was carried out by real-time quantitative polymerase chain reaction (PCR) in 70 IR-exposed CLL patients. The MYC mRNA expression was measured by real-time quantitative reverse transcription PCR. Results: Increased MYC gene copy number was present in 5.7% of cases. There was a statistically significant association between increased MYC copy number and increased MYC mRNA (p 0.014). Additionally, somatic deletion in MYC locus was found in one patient. Most of patients (80%) with detected MYC aberrations were previously untreated, suggesting that these lesions might occur early in the course of the disease. The MYC aberrations were found mutually exclusive with high risk TP53 and SF3B1 mutations, while one case was identified, where MYC amplification and NOTCH1 mutation coincided simultaneously. Regarding clinical outcome, the MYC aberrations were associated with a shorter time to first treatment (3 vs 25 months, p
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6.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Kolesnik D. L., Pyaskovskaya O. N., Gorbach O., Solyanik G. I.
Заглавие : Metformin enhances cytotoxic action of dichloroacetate against lewis lung carcinoma cells in vitro
Место публикации : Experimental Oncology. - К., 2020. - Том 42, N 1. - С. 35-39 (Шифр ЕУ12/2020/42/1)
MeSH-главная: КАРЦИНОМА ЛЬЮИС ЛЕГКОГО -- CARCINOMA, LEWIS LUNG
Аннотация: Tumor cell metabolism is considered one of the hallmarks of cancer. This concept is exploited in the development of new ways of anticancer therapy based on the use of substances capable of changing drastically bioenergetic metabolism of tumor cells. Among them, sodium dichloroace­tate (DCA), an inhibitor of pyruvate dehydrogenase kinase, and metformin (MTF), an antidiabetic hypoglycemic drug, an inhibitor of the mitochondrial respiratory chain (complex I), both have been long used in clinical non-oncological practice, and presently are considered promising candidates in oncology. Aim: To study the capability of MTF to enhance the antitumor action of DCA against Lewis lung carcinoma cells in vitro. Materials and Methods: LLC/R9, a low metastatic variant of Lewis lung carcinoma cells, was used. Effects of 30 mM DCA in combination with 2 mM MTF on cell survival, cell cycle distribution, apoptosis, mitochondrial potential, intracellular ATP level, glucose consumption, and lactate production rates were determined in vitro. Results: MTF was shown to enhance the cytotoxic/cytostatic action of DCA against LLC/R9 cells in vitro. Treatment of LLC/R9 cells with 30 mM DCA in combination with 2 mM MTF resulted in a 39% decrease in the number of viable cells (p 0.05), a 2.8-fold increase of the number of dead cells (p 0.05), a near 2-fold decrease in the proportion of cells at the S-phase (p 0.05), a 4-fold increase in the apoptosis (p 0.05) and significant reduction (p 0.05) of the mitochondrial membrane potential of tumor cells as compared to corresponding values in control. DCA alone reduced glucose consumption and lactate production rates by more than 26% (p 0.05) and 34% (p 0.05), respectively, whereas MTF counteracted these effects. Nevertheless, in the cells treated with both DCA and DCA in combination with MTF, the intracellular adenosine triphosphate increased by 33–35% compared with that in the control (p 0.05). Conclusion: MTF enhanced the cytotoxic/cytostatic action of DCA against LLC/R9 cells in vitro, which points on their possible synergistic antitumor action in vivo
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7.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Kearney L., Grampe M., Langabeer S. E.
Заглавие : Frequency and spectrum of atypical BCR-ABL1 transcripts in chronic myeloid leukemia
Место публикации : Experimental Oncology. - К., 2020. - Том 42, N 1. - С. 78-79 (Шифр ЕУ12/2020/42/1)
MeSH-главная: ЛЕЙКОЗ МОНОЦИТАРНЫЙ ОСТРЫЙ -- LEUKEMIA, MONOCYTIC, ACUTE
Аннотация: The BCR-ABL1 oncogene is the molecular hallmark of chronic myeloid leukemia (CML) with the majority of patients possessing a fusion between BCR exon 13 or 14 and ABL1 exon a2 (e13a2 and e14a2 respectively). However, a minority of patients express atypical transcripts usually as due to splicing of alternative BCR or ABL1 exons. These variants become apparent upon discordant diagnostic cytogenetic and molecular testing and may be resolved by multiplex, reverse transcription polymerase chain reaction (RT-PCR) or sequencing approaches [1]. In a recent international survey of BCR-ABL1 transcript types in more than 34,000 CML patients, 1.93% of cases expressed these atypical forms [2]. It is therefore likely that any laboratory performing molecular dia­gnosis or monitoring of more than 50 CML patients will have encountered a variant BCR-ABL1 transcript. We sought to review the incidence and type of atypical BCR-ABL1 transcripts in CML patients from the National molecular dia­gnostic centre in order to inform appropriate dia­gnostic and monitoring techniques. New or existing CML patients were identified from January 2005 to June to 2019 inclusive at the National center for the molecular diagnosis and monitoring of CML in Ireland. All patients had cytogenetic or fluorescence in situ hybridization confirmation of a t(9;22) translocation or BCR-ABL1 fusion signal respectively. BCR-ABL1 detection and quantitative RT-PCR were performed using standardized approaches throughout this period with Sanger sequencing used for confirmation of an atypical fusion transcript [3, 4]. Of 706 CML patients, atypical BCR-ABL1 transcripts were detected in 16 (2.3%). These variants comprised e1a2 (n = 4), e6a2 (n = 2), e8a1 (n = 1), e13a3 (n = 1), atypical e13a2 with a deletion and insertion (n = 2), and e19a2 (n = 6). The above demonstrates that the frequency and spectrum of atypical BCR-ABL1 transcripts in the Irish CML population is similar to that seen elsewhere. The clinical importance of correct identification of the atypical BCR-ABL1 transcripts is two-fold. Firstly, there is accumulating evidence for a BCR-ABL1 genotype-tyrosine kinase inhibitor (TKI) response correlation: patients expressing the shorter transcript types such as e1a2 and e6a2 have an aggressive disease with higher rates of blast crisis transformation [5, 6] whereas TKI responses in patients with longer BCR-ABL1 trans­cript types such as the e19a2 are generally favorable [7, 8]: establishing the transcript type will therefore inform selection of TKI. Secondly, monitoring the molecular response by quantitation of BCR-ABL1 transcripts is now an integral part of CML patient management with significant advances made towards harmonization of diffe­rent methodological approaches: characterization of a variant transcript type therefore allows selection of correct primers and probes for quantitative RT-PCR. However, to date, quantitation of atypical BCR-ABL1 transcript has only been performed on an ad hoc basis [9]. Given that the survival of CML patients receiving TKI therapy is similar to that of the normal population, more patients with these atypical BCR-ABL1 transcripts will require monitoring. Furthermore, given the possibility for treatment-free remission in which important criteria for TKI discontinuation are the length and depth of molecular remission, consensus standards and methodologies are now required for this small but expanding population of CML patients
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8.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Fedorenko Z. P., Mikchailovich Yu. I., Goulak L. O., Ryzhov A. Yu., Gorokh Ye. L., Soumkina O. V.
Заглавие : Incidence and long-term effects of treatment of malignant germ cell neoplasms in Ukraine
Место публикации : Experimental Oncology. - К., 2020. - Том 42, N 1. - С. 66-74 (Шифр ЕУ12/2020/42/1)
MeSH-главная: ГЕРМИНОМА -- GERMINOMA
Аннотация: To describe incidence of malignant germ cell neoplasms (GCNs) in Ukraine and assess the medical care to patients with GCNs and its efficacy. Materials and Methods: Records on 6495 males and 1038 females with malignant GCNs diagnosed in 2000–2013 extracted from the database of National Cancer Registry of Ukraine have been analyzed using methods of descriptive epidemiology and survival evaluation. Results: In Ukraine, GCNs covered 79.1% of testicular cancers and 48.9% of ovarian cancers in patients aged 0–19 years, while their proportions in total cancer incidence did not exceed 0.7% in males and 0.1% in females. Most of GCNs in males (75.9%) were diagnosed at the reproductive age (20–49) and in females 72.2% of GCNs were diagnosed at the age of 0–44 years. Female gonadal GCNs were divided by germinomatous and nongerminomatous as 49.3% vs 50.7% while in males this proportion was 65.3% vs 34.7%. Age-specific incidence of genital GCNs in Ukraine reached peak values in males aged 25–39 years and in females aged 10–24 years. Nonseminomatous testicular GCN cases were more common than seminomatous cases in males until the age of 30 years with an incidence of seminomas peaked 10 years later than non-seminomas. Ovarian germinomas were more common than non-germinomas in females aged 15–29. Total GCN incidence rate in 2013 was 1.99 ± 0.090/0000 in males and 0.32 ± 0.040/0000 in females, being closer to that in the countries of Eastern Europe and Asia. In Ukraine, 5-year survival of patients with testicular GCN of stage I who received surgery combined with chemotherapy or radiotherapy was lower than that reported for Europe and USA, and substantially lower in patients with stages II–IV. Five-year survival of patients with ovarian GCN treated with surgery plus chemotherapy was close to that reported in a study for populations of European countries. Conclusion: The trends and patterns of GCN incidence in Ukraine are similar to those in other European countries, while patterns of treatment and survival in Ukraine are closer to that in countries in transition. Further research and analysis are impossible without due registration of both the diagnosis and the treatment undertaken as well as close follow-up of patients’ life status
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9.

Вид документа : Статья из журнала
Шифр издания :
Заглавие : In commemoration of Dmitriy Vladimirovich Myasoyedov
Место публикации : Experimental Oncology. - К., 2020. - Том 42, N 1. - С. 80 (Шифр ЕУ12/2020/42/1)
MeSH-главная: ОНКОЛОГИЯ МЕДИЦИНСКАЯ -- MEDICAL ONCOLOGY
Аннотация: On the 24th January 2020, a famous Ukrainian oncologist-surgeon, the Honored Master Of Science and Technology of Ukraine, Doctor of Medical Sciences, Professor Dmitriy Vladimirovich Myasoyedov has passed away on the 89th year of his life. He was born in the city of Pryluky, Chernigov Region of Ukraine in a family cherishing the traditions of intelligence. The impact of his mother, a clinical physician-neurologist, influenced professional choice of Dmitriy Myasoyedov. In 1955, he graduated from Kishinev Medical Institute (Moldavia Republic), wherein Dr. Myasoyedov became one of the best students in theoretical and clinical disciplines. After graduation from the Institute, he was assigned to work as a surgeon in the Regional Hospital of Ryshkany. Through subsequent 5 years of his career as a surgeon and the Head of the Hospital, Dr. Myasoyedov gained wide experience in general surgery and the health organization in the district of his supervision. For the achievements in his practice, Dr. Myasoyedov was awarded The Medal “For Honor in Trade” and the Certificate of Commendation from the local Power. In 1960, Dr. Myasoyedov came to Ukraine where he started his career as an assistant fellow of the Oncology Department in Kyiv Institute for Advanced Training of Physicians (now Shupyk National Medical Academy of Postgraduate Education), where he worked until his death
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10.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Kozirovskis V., Zandberga E., Magone M., Purkalne G., Line A., Vikmanis U.
Заглавие : High expression of GLI1 is associated with better survival in advanced SCLC
Место публикации : Experimental Oncology. - К., 2020. - Том 42, N 1. - С. 75-77 (Шифр ЕУ12/2020/42/1)
MeSH-главная: ЛЕГКИХ НОВООБРАЗОВАНИЯ -- LUNG NEOPLASMS
Аннотация: Aberrant Sonic hedgehog (Shh) pathway signaling has been described in small cell lung cancer (SCLC), as well discrepancies, when analyzing expression of pathway components in SCLC cell lines vs tumor biopsies. Shh key component GLI1 was evaluated in advanced SCLC and data correlated with patient survival. Materials and methods: GLI1 expression was analyzed by quantitative real-time polymerase chain reaction in pre-treatment fresh frozen tumor biopsies of 12 advanced SCLC patients and mRNA level of GLI1 was compared in short-term vs long-term survivor’s samples (stratified by median survival, independent samples t-test). Results: Expression of GLI1 mRNA was significantly higher in long-term ( 9.6 months, n = 6) survivor’s biopsies than in short-term (≤ 9.6 months, n = 6) survivors (p = 0.0196, 95% CI: 0.000016 to 0.000147, two-tailed independent samples t-test). Conclusion: High GLI1 mRNA expression in SCLC was found to be positive prognostic marker associated with longer survival. Further research is needed for validation of these results due to the small number of patients in the study
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11.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Burlaka A. A., Burlaka A. P., Krotevych M. S., Rudiuk T. O., Orel V. E.
Заглавие : Drag reducing polymers attenuate adverse effects of ischemia-reperfusion upon resection of liver metastases modeled by MC38 mouse colon adenocarcinoma
Место публикации : Experimental Oncology. - К., 2020. - Том 42, N 1. - С. 46-50 (Шифр ЕУ12/2020/42/1)
MeSH-главная: КОЛОРЕКТАЛЬНЫЕ НОВООБРАЗОВАНИЯ -- COLORECTAL NEOPLASMS
НОВООБРАЗОВАНИЙ МЕТАСТАЗЫ -- NEOPLASM METASTASIS
ПЕЧЕНИ НОВООБРАЗОВАНИЯ -- LIVER NEOPLASMS
Аннотация: The resection of metastases within healthy parenchyma improves significantly the long-term outcome in metastatic colorectal cancer. Until now, the resection technique involves Pringle maneuver, which allows reducing blood loss during transsection of liver parenchyma. However, the classical Pringle maneuver has restrictions due to ischemia/reperfusion (I/R) effect, in particular increasing risk of tumor recurrence after liver surgery. Aim: To study the pathological impact of surgical intervention and I/R effect on healthy liver tissue in the experimental setting by evaluating the markers of redox-homeostasis and oxidatively induced mutage­nesis, and also to assess the current possibilities of their correction by application of drag-reducing polymers (DRPs). Materials and Methods: MC38 mouse colon adenocarcinoma cells were transplanted intrahepatically to C57Bl/6 mice. The influence of warm ischemia on metastatic potential of MC38 cells, the speed of superoxide radicals (SR) generation and 8-hydroxydeoxyguanosine content were studied. Results: In case of modeled liver metastases, the surgery initiates an increase in the rate of SR generation into the remaining liver tissue and, consequently, provokes its ischemic injury. The application of DRPs protects liver tissue under I/R conditions. Conclusions: The warm I/R can promotes metastatic lesions in the healthy part of the organ with underlying increase in the rate of SR generation and oxidatively induced damage of guanine in DNA. The hemorheological effects of DRPs ensure increase of microcirculatory perfusion and oxygenation of liver tissues with the reduction of the rate of SR generation and decrease of 8-hydroxydeoxyguanosine as a marker of oxidatively induced mutations in DNA of hepatocytes. The intraperitoneal administration of nanomolar doses of DRPs prevents the activation of the growth of dormant metastatic MC38 cells in the liver. Further experimental and clinical study of these substances will allow reducing the risks of activation of uncontrolled tumor growth in the liver due to the pathological effect of post-operative I/R
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12.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Bubnovskaya L., Osinsky D.
Заглавие : Tumor microenvironment and metabolic factors: contribution to gastric cancer
Место публикации : Experimental Oncology. - К., 2020. - Том 42, N 1. - С. 2-10 (Шифр ЕУ12/2020/42/1)
MeSH-главная: ЖЕЛУДКА НОВООБРАЗОВАНИЯ -- STOMACH NEOPLASMS
Аннотация: Malignancy may be characterized as a state formed in the setting of specific tumor-host relationships at the molecular and cellular microenvironment levels. R.E. Kavetsky and his collaborators distinctly outlined the concept of tumor-host interaction. Tumor is a complicated biological system closely connected with the organism, where it arises and develops. Tumor cells are in the environment of different factors that form tumor microenvironment playing an active role in the disease progression. There are two types of tumor microenvironment: the metabolic microenvironment mediated by factors of tumor microphysiology (blood flow, vascular permeability, oxygenation, extracellular рН, interstitial fluid pressure, etc.) and the cellular-molecular microenvironment comprising interactions between tumor cells and non-tumor cells and the factors of the stromal compartment. Factors of tumor microphysio­logy can modify the interaction between tumor cells and surrounding non-tumor cells and molecular components and they form the tumor profile that influences the pressure of tumor on the host. The review presents the data concerning the role of metabolic microenvironment of tumor cells from the point of tumor-host interaction in order to employ these parameters to working out the methods of diagnosis and prognosis of disease outcome in patients with gastric cancer. Special attention has been paid to hypoxia as a key factor of metabolic microenvironment that positively affects tumor progression, stimulating its aggressiveness, metastasis and resistance to therapy and is regarded as a factor of unfavorable prognosis. It was shown that there is possible clinical relevance of tumor classification based on the level of tumor oxygenation that may be advantageous for selection of patients for individualized therapy that may give the hope for enhancement of treatment efficacy
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13.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Siromolot A. A., Krynina O. I., Kolybo D. V., Komisarenko S. V.
Заглавие : Antiproliferative and apoptotic effects of anti-human HB-EGF neutralizing polyclonal antibodies in vitro
Место публикации : Experimental Oncology. - К., 2020. - Том 42, N 1. - С. 25-30 (Шифр ЕУ12/2020/42/1)
MeSH-главная: АНТИТЕЛА НЕЙТРАЛИЗУЮЩИЕ -- ANTIBODIES, NEUTRALIZING
НОВООБРАЗОВАНИЯ -- NEOPLASMS
Аннотация: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the epidermal growth factor family and has a variety of physiological and pathophysiological functions. Also, HB-EGF plays a pivotal role in progression of different tumors. So, HB-EGF seems to be a target molecule for the treatment of some cancer types. Aim: To obtain HB-EGF neutralizing polyclonal antibodies and test their anti-proliferative properties in vitro. Materials and Methods: Lab rabbits and mice were used for immunization with recombinant HB-EGF. The effect of generated polyclonal antibodies on viability and apoptosis of human epidermoid carcinoma derived A431 cell line was assessed using MTT and Annexin V-propidium iodide assays. Results: Rabbit polyclonal anti-HB-EGF serum could block binding of soluble HB-EGF to epidermal growth factor receptor/human epidermal growth factor receptor. Also, anti-HB-EGF antibodies could bind to surface of A431 cells which express abnormally high levels of membrane bound proHB-EGF and its receptor. It has been shown that immune serum with polyclonal antibodies against HB-EGF was able to block the mitogenic activation of the cells with HB-EGF and cause apoptotic cell death. Conclusion: Inhibition of HB-EGF activity with neutralizing polyclonal antibodies can effectively inhibit mitogenic activation and cause apoptosis of cancer cells with significant epidermal growth factor receptor overexpression
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14.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Shvachko L. P., Zavelevich M. P., Gluzman D. F., Telegeev G. D.
Заглавие : Aberrant expression of placental-like alkaline phosphatase in chronic myeloid leukemia cells in vitro and its modulation by vitamin E
Место публикации : Experimental Oncology. - К., 2020. - Том 42, N 1. - С. 31-34 (Шифр ЕУ12/2020/42/1)
MeSH-главная: ЛЕЙКОЗ МИЕЛОИДНЫЙ -- LEUKEMIA, MYELOID
ВИТАМИН E -- VITAMIN E
Аннотация: Placental-like alkaline phosphatase (PLAP) is expressed by many tumors and can be detected in sera of patients with various cancers. Its aberrant expression has been considered to be potentially useful as tumor marker. However, the biological background of the role of this aberrant alkaline phosphatase (AP) in cancer is still unclear. The expression of various forms of AP in cells of chronic myeloid leukemia (CML) has not yet been studied. Aim: To analyze the expression patterns of various AP forms in cells originated from CML patients in blast crisis and to modify their expression by vitamin E. Materials and Methods: RNA extracted from leukemic cells was converted to cDNA and real-time reverse transcription polymerase chain reaction was performed using SYBR Green protocol with primers to tissue non-specific alkaline phosphatase (TNAP), intestinal alkaline phosphatase and CCAAT-enhancer-binding proteins alpha (C/EBPα). To analyze the modulation of expression of APs and C/EBPα, CML cells were incubated with 100 µM vitamin E. Results: We have observed the aberrant expression of mRNA intestinal alkaline phosphatase in CML cells that upon sequencing demonstrated the significant alignment with PLAP sequence while no gene homology with tissue placental alkaline phosphatase (PAP) was revealed. Vitamin E decreases mRNA PLAP expression and increases mRNA TNAP expression. Moreover, along with down-regulation of aberrant PLAP and up-regulation of TNAP, vitamin E increases C/EBPα mRNA expression. Conclusion: The loss of TNAP in CML may contribute to pathogenesis of this disease. PLAP may be considered as a putative target in differentiation therapies in myeloid neoplasms. Our findings suggest the potential role of vitamin E as the inducer of differentiation potential of leukemic cells in CML
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